TW202233679A - 選擇性地與cldn6和cd3結合的多肽構建體 - Google Patents
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Abstract
本發明關於多肽或多肽構建體，該多肽或多肽構建體包含結合緊密連接蛋白6（CLDN6）的結構域和結合CD3的另一個結構域。此外，本發明提供了編碼該構建體的多核苷酸、包含所述多核苷酸的載體、以及用所述多核苷酸或載體轉化或轉染的宿主細胞。此外，本發明提供了用於產生本發明之構建體之方法、所述構建體的醫學用途、以及包含所述構建體的套組。
Description
本發明關於多肽/多肽構建體，該多肽/多肽構建體包含含有與緊密連接蛋白6（CLDN6）結合的互補位的結構域和含有與CD3結合的互補位的另一個結構域。此外，本發明提供編碼該等多肽/多肽構建體的多核苷酸、包含所述多核苷酸的載體和用所述多核苷酸或載體轉化或轉染的宿主細胞。此外，本發明提供了用於產生本發明之多肽/多肽構建體之方法、所述多肽/多肽構建體的醫學用途以及包含所述構建體的套組。
緊密連接蛋白係位於兩個相鄰細胞之間的上皮緊密連接的關鍵結構和功能組分，其調節細胞-細胞通透性、維持離子穩態、並且支持細胞黏附和極性。緊密連接蛋白係22-27 kDa的四分子交聯體（tetraspan）跨膜蛋白，其在細胞膜內或跨細胞膜進行多聚化以形成保護屏障。已經報導的24種緊密連接蛋白依據它們的組織定位和表現以及由於它們與其他蛋白的相互作用而不同。
緊密連接蛋白6（CLDN6）最初係在對屬於基因和蛋白的緊密連接蛋白家族的其他基因和蛋白進行的相似性研究中鑒定的（Morita等人, Proc. Natl. Acad. Sci. USA [美國科學院院報], 第96卷, 第511-516頁, 1999）。在成年組織中未檢測到緊密連接蛋白6 mRNA的表現，而只在胚胎組織檢測到。隨後，在多種腫瘤和腫瘤細胞系中檢測到mRNA和蛋白表現。與這一發現一致，緊密連接蛋白6被認為係癌胚跨膜蛋白，其在正常成人組織中不存在。CLDN6表現在各種癌症類型（諸如卵巢癌、肺癌、胃癌、乳腺癌、生殖細胞癌和兒科癌症）中被異常活化（Stadler等人, Oncoimmunology [腫瘤免疫學] 2016, 第5卷, 第3期, e1091555及其引用的參考文獻，例如，Micke等人, Int. J. Cancer [國際癌症雜誌] 2014:2206-14；Rendón-Huerta等人, J. Gastrointest.Cancer [胃腸道癌雜誌] 2010; 41: 52-59；Ushiku等人, Histopathology [組織病理學] 2012, 61:1043-56；Ben-David等人, Nat. Commun. [自然通訊]2013; 4:1992；Birks等人, BRAIN PATHOL. [腦病理學]2010; 20:140-50；Sullivan等人, Am. J. Surg.Pathol. [美國外科病理學雜誌]2012; 36:73-80）。
CLDN6係具有兩個細胞外環（ECL）的220個胺基酸的蛋白，其與CLDN9具有高度的序列同一性，僅在這兩個ECL中有三個胺基酸殘基不同。
CLDN6在多種腫瘤類型中的表現（正常組織表現僅限於胎兒發育）導致考慮將CLDN6作為各種癌症類型（例如，卵巢癌和非小細胞肺癌（NSCLC）及其他適應症）的治療靶標。
卵巢癌和NSCLC癌仍然是有著高度未滿足的醫療需求的適應症。
卵巢癌係全世界第七大最常見的癌症。2018年，全球新增病例295,414例，且死亡184,799例，北半球國家的死亡率高於亞洲或非洲（Bray等人, CA Cancer J Clin [臨床腫瘤雜誌] 2018）。典型的一線治療包括外科手術和組合化學療法（包括鉑和紫杉醇或多西紫杉醇）。最近，抗VEGF抗體貝伐單抗和PARP抑制劑已被批准作為一線化療後的維持治療。然而，儘管最初有反應，但高達70%的患者由於產生化療耐藥性和/或腫瘤免疫逃避而經歷疾病復發。卵巢腫瘤的特徵在於高度免疫抑制的腫瘤微環境；雖然有證據表明卵巢腫瘤具有免疫原性，但改變了其他實性瘤類型治療標準的免疫檢查點療法在卵巢癌中的持久性有限（Rodriguez等人, Cancers [癌症] 2018）。儘管在卵巢癌的臨床試驗中，多種新療法和聯合療法取得了進展，但5年生存率仍然很低，迫切需要能夠產生持久反應的療法。
肺癌係全世界最常見的癌症之一，2018年報告了超過200萬新病例和170萬例死亡（Bray等人, CA: A Cancer Journal for Clinicians [臨床醫師癌症雜誌] 2018）。非小細胞肺癌（NSCLC）占肺癌病例的大多數（85%），並且通常與吸煙和諸如石棉等環境暴露有關（Zappa和Mousa, Transl Lung Cancer Res [肺癌轉化研究] 2016）。對於腫瘤表現PD-L1的患者而言，推薦的NSCLC一線治療係免疫檢查點阻斷和鉑雙藥化療，儘管對於具有驅動突變的腫瘤的初始治療可能首選靶向治療（Ettinger等人, JNCCN, 2019）。雖然該等進展係有希望的，並且在免疫檢查點阻斷的情況下，一些患者實現了長期持久的反應（Santini and Hellman, Cancer J [癌症雜誌] 2018），但需要對免疫治療組合進行進一步評估，並且大多數患者的治療需要有另外的新療法的進展。
因此，卵巢癌和/或NSCLC的治療，特別是表現CLDN6的任何類型的癌症的治療，更特別是處於二線治療或更高的癌症患者（諸如以前接受過化療或免疫療法的患者和有復發性疾病患者）的治療，仍然需要有可能對更大的患者群體提供持久反應的新療法。
包含一個與T細胞上的CD3結合的抗原結合（更準確地說，表位結合）結構域和一個與靶細胞上表現的蛋白質結合的抗原結合（更準確地說，表位結合）結構域的雙特異性（和多特異性）構建體將T細胞直接連接到靶細胞以誘導T細胞定向溶解。這種作用機制不同於化學療法、靶向療法和其他免疫療法，因為它可以與任何CD3陽性T細胞一起工作，而不依賴共刺激活化信號（Klinger等人, Immunol Reviews [免疫學評論] 2016）。
生殖細胞腫瘤、卵巢癌和非小細胞肺癌細胞表面CLDN6的表現為用CLDN6 x CD3多肽/多肽構建體靶向該等腫瘤類型提供了基礎。此外，CLDN6 x CD3多肽/多肽構建體有潛力靶向表現CLDN6的另外的腫瘤類型，特別是表現CLDN6的任何類型的癌症，更特別地用於處於二線治療或更高的癌症患者（諸如以前接受過化療或免疫療法的患者和有復發性疾病患者）的治療。
本發明提供了作為選擇性地且較佳的是與CLDN6（SEQ ID NO: 1）或其任何亞型特異性結合的化合物的新的多肽/多肽構建體，包含此類化合物的組成物，使用本文揭露的產品治療和預防腫瘤疾病之方法，包含本文揭露的產品的套組，用作藥物的產品，特別是用於治療和預防腫瘤疾病的產品。人CLDN6的胺基酸序列和相關資訊可在UniProt數據庫中找到，登錄號為P56747。
本發明之化合物
在一個方面，本發明提供了一種多肽/多肽構建體，該多肽/多肽構建體包含與靶細胞表面上的CLDN6（SEQ ID NO: 1或其片段或胺基酸序列變體）結合的結構域和與T細胞表面上的CD3結合的結構域或由其組成，與CLDN6和CD3兩者的結合允許T細胞的活化。根據本發明之多肽構建體的結合接合T細胞，即與CD3結合，並使T細胞和靶細胞緊密接觸，以允許活化的T細胞誘導細胞毒性/細胞溶解機制，導致靶細胞的破壞（T細胞依賴性細胞毒性）。
進一步地，本發明提供了一種多肽/多肽構建體，該多肽/多肽構建體包含含有與CLDN6結合的互補位（即抗原結合結構域，更特別是表位結合結構）的結構域或由其組成，其中視需要，本發明之多肽/多肽構建體的包含互補位（即抗原結合（表位結合）結構）的結構域能夠與表現CLDN6的細胞的表面上的CLDN6結合，該多肽/多肽構建體與CLDN6（SEQ ID NO: 1）的E1A和/或E2B區域結合。 因此，本發明提供了一種多肽/多肽構建體，該多肽/多肽構建體包含與CLDN6結合的結構域或由其組成，其中視需要，該結構域能夠與表現CLDN6的細胞的表面上的CLDN6結合，該多肽/多肽構建體與E1A和/或E2B區域結合，其序列對應於SEQ ID NO: 9和10中描繪的該等環的E1A和/或E2B區域。
在本發明之實施方式中，包含含有與CLDN6結合的互補位（即抗原結合結構域，更特別是表位結合結構）的結構域或由其組成的多肽/多肽構建體與CLDN6（SEQ ID NO: 1）的E1A和/或E2B區域結合，不與SEQ ID NO: 1中描繪的CLDN6的胺基酸138 - 150結合，其中視需要，本發明之多肽/多肽構建體的包含互補位（即抗原結合（表位結合）結構）的結構域能夠與表現CLDN6的細胞的表面上的CLDN6結合。在本發明之另外的實施方式中，包含與CLDN6結合的結構域或由其組成的多肽/多肽構建體與CLDN6（SEQ ID NO: 1）的E1A和/或E2B區域結合，不與SEQ ID NO: 1中描繪的CLDN6的胺基酸138 - 150結合。
因此，本發明提供了多肽/多肽構建體，該多肽/多肽構建體包含含有互補位（即抗原結合結構域，更特別是表位結合結構）的結構域或由其組成，該互補位與靶細胞表面上包含CLDN6的細胞外環1（ECL1）的胺基酸（較佳的是包含SEQ ID NO: 1的胺基酸29-39）的表位區域和/或包含CLDN6的細胞外環2（ECL2）的對應於SEQ ID NO: 1的胺基酸151-160的胺基酸的表位區域結合。因此，本發明提供了多肽/多肽構建體，該多肽/多肽構建體包含以下結構域或由其組成，該結構域與靶細胞表面上包含CLDN6的細胞外環1（ECL1）的胺基酸（較佳的是包含SEQ ID NO: 1的胺基酸29-39）的表位區域和/或包含CLDN6的細胞外環2（ECL2）的對應於SEQ ID NO: 1的胺基酸151-160的胺基酸的表位區域結合。
因此，本發明提供了如前述段落中任一項所定義的多肽/多肽構建體，該等多肽/多肽構建體包含識別CD3ε鏈（較佳的是，人和獼猴CD3ε鏈）的細胞外表位和/或與其結合的互補位（即抗原結合結構（表位結合結構））的另一結構域和向個體投與後延長多肽半衰期（HLE結構域）的結構域，該延長多肽半衰期的結構域視需要包含兩個多肽單體，每個單體均包含鉸鏈、CH2結構域和CH3結構域。因此，本發明提供了如前述段落中任一項所定義的多肽/多肽構建體，該等多肽/多肽構建體包含識別CD3ε鏈（較佳的是，人和獼猴CD3ε鏈）的細胞外表位和/或與其結合的另一結構域和向個體投與後延長多肽半衰期（HLE結構域）的結構域，該延長多肽半衰期的結構域視需要包含兩個多肽單體，每個單體均包含鉸鏈、CH2結構域和CH3結構域。
根據本發明，提供了多肽/多肽構建體，其中該構建體的結構域免疫選擇性地與包含在以下a) 至s)中提及的任一個序列中的互補位（抗原結合或表位結合結構）識別和/或結合的CLDN6的表位結合：a) 至d)、n) 和s) 係較佳的，a) 至c)、e) 和s) 係非常較佳的：
a) 包含SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區；
b) 包含SEQ ID NO: 27中描繪的CDR-H1、SEQ ID NO: 28中描繪的CDR-H2和SEQ ID NO: 29中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 30中描繪的CDR-L1、SEQ ID NO: 31中描繪的CDR-L2和SEQ ID NO: 32中描繪的CDR-L3的VL區；
c) 包含SEQ ID NO: 41中描繪的CDR-H1、SEQ ID NO: 42中描繪的CDR-H2和SEQ ID NO: 43中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 44中描繪的CDR-L1、SEQ ID NO: 45中描繪的CDR-L2和SEQ ID NO: 46中描繪的CDR-L3的VL區；
d) 包含SEQ ID NO: 55中描繪的CDR-H1、SEQ ID NO: 56中描繪的CDR-H2和SEQ ID NO: 57中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 58中描繪的CDR-L1、SEQ ID NO: 59中描繪的CDR-L2和SEQ ID NO: 60中描繪的CDR-L3的VL區；
e) 包含SEQ ID NO: 69中描繪的CDR-H1、SEQ ID NO: 70中描繪的CDR-H2和SEQ ID NO: 71中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 72中描繪的CDR-L1、SEQ ID NO: 73中描繪的CDR-L2和SEQ ID NO: 74中描繪的CDR-L3的VL區；
f) 包含SEQ ID NO: 83中描繪的CDR-H1、SEQ ID NO: 84中描繪的CDR-H2和SEQ ID NO: 85中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 86中描繪的CDR-L1、SEQ ID NO: 87中描繪的CDR-L2和SEQ ID NO: 88中描繪的CDR-L3的VL區；
g) 包含SEQ ID NO: 97中描繪的CDR-H1、SEQ ID NO: 98中描繪的CDR-H2和SEQ ID NO: 99中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 100中描繪的CDR-L1、SEQ ID NO: 101中描繪的CDR-L2和SEQ ID NO: 102中描繪的CDR-L3的VL區；
h) 包含SEQ ID NO: 111中描繪的CDR-H1、SEQ ID NO: 112中描繪的CDR-H2和SEQ ID NO: 113中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 114中描繪的CDR-L1、SEQ ID NO: 115中描繪的CDR-L2和SEQ ID NO: 116中描繪的CDR-L3的VL區；
i) 包含SEQ ID NO: 125中描繪的CDR-H1、SEQ ID NO: 126中描繪的CDR-H2和SEQ ID NO: 127中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 128中描繪的CDR-L1、SEQ ID NO: 129中描繪的CDR-L2和SEQ ID NO: 130中描繪的CDR-L3的VL區；
j) 包含SEQ ID NO: 139中描繪的CDR-H1、SEQ ID NO: 140中描繪的CDR-H2和SEQ ID NO: 141中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 142中描繪的CDR-L1、SEQ ID NO: 143中描繪的CDR-L2和SEQ ID NO: 144中描繪的CDR-L3的VL區；
k) 包含SEQ ID NO: 153中描繪的CDR-H1、SEQ ID NO: 154中描繪的CDR-H2和SEQ ID NO: 155中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 156中描繪的CDR-L1、SEQ ID NO: 157中描繪的CDR-L2和SEQ ID NO: 158中描繪的CDR-L3的VL區；
l) 包含SEQ ID NO: 167中描繪的CDR-H1、SEQ ID NO: 168中描繪的CDR-H2和SEQ ID NO: 169中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 170中描繪的CDR-L1、SEQ ID NO: 171中描繪的CDR-L2和SEQ ID NO: 172中描繪的CDR-L3的VL區；
m) 包含SEQ ID NO: 181中描繪的CDR-H1、SEQ ID NO: 182中描繪的CDR-H2和SEQ ID NO: 183中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 184中描繪的CDR-L1、SEQ ID NO: 185中描繪的CDR-L2和SEQ ID NO: 186中描繪的CDR-L3的VL區；
n) 包含SEQ ID NO: 195中描繪的CDR-H1、SEQ ID NO: 196中描繪的CDR-H2和SEQ ID NO: 197中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 198中描繪的CDR-L1、SEQ ID NO: 199中描繪的CDR-L2和SEQ ID NO: 200中描繪的CDR-L3的VL區；
o) 包含SEQ ID NO: 209中描繪的CDR-H1、SEQ ID NO: 210中描繪的CDR-H2和SEQ ID NO: 211中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 212中描繪的CDR-L1、SEQ ID NO: 213中描繪的CDR-L2和SEQ ID NO: 214中描繪的CDR-L3的VL區；
p) 包含SEQ ID NO: 223中描繪的CDR-H1、SEQ ID NO: 224中描繪的CDR-H2和SEQ ID NO: 225中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 226中描繪的CDR-L1、SEQ ID NO: 227中描繪的CDR-L2和SEQ ID NO: 228中描繪的CDR-L3的VL區；
q) 包含SEQ ID NO: 237中描繪的CDR-H1、SEQ ID NO: 238中描繪的CDR-H2和SEQ ID NO: 239中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 240中描繪的CDR-L1、SEQ ID NO: 241中描繪的CDR-L2和SEQ ID NO: 242中描繪的CDR-L3的VL區；
r) 包含SEQ ID NO: 251中描繪的CDR-H1、SEQ ID NO: 252中描繪的CDR-H2和SEQ ID NO: 253中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 254中描繪的CDR-L1、SEQ ID NO: 255中描繪的CDR-L2和SEQ ID NO: 256中描繪的CDR-L3的VL區，
s) 包含SEQ ID NO: 265中描繪的CDR-H1、SEQ ID NO: 266中描繪的CDR-H2和SEQ ID NO: 267中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 268中描繪的CDR-L1、SEQ ID NO: 269中描繪的CDR-L2和SEQ ID NO: 270中描繪的CDR-L3的VL區，以及
t) 包含SEQ ID NO: 680中描繪的CDR-H1、SEQ ID NO: 681、682或683的任一項中描繪的CDR-H2和SEQ ID NO: 684、685、686或687的任一項中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 688或689的任一項中描繪的CDR-L1、SEQ ID NO: 690中描繪的CDR-L2和SEQ ID NO: 691、692、693或694的任一項中描繪的CDR-L3的VL區，以及與本文所述之重鏈和輕鏈的CDR的任何可能的組合。
前述段落的構建體相應地較佳的是包含至少一個結構域，該結構域包含如 (a) 至 (s) 部分中定義的結合CLDN6的互補位，視需要進一步包含含有與CD3結合的結構域的結構域，例如，前述段落的構建體相應地較佳的是結合CLDN6並具有包含如 (a) 至 (s) 部分中定義的CDR的VL和/或VH區，視需要進一步包含含有與CD3結合的結構域的結構域。
根據本發明，提供了多肽/多肽構建體，該多肽/多肽構建體包含含有與表位結合（免疫選擇性地）的互補位（抗原結合（表位結合）結構）的結構域，該表位藉由包含含有SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區以及含有SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區的結構域識別。因此，根據本發明，提供了多肽/多肽構建體，該多肽/多肽構建體包含與表位結合（免疫選擇性地）的結構域，該表位藉由包含含有SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區以及含有SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區的結構域識別。
根據本發明，提供了多肽/多肽構建體，該多肽/多肽構建體包含含有與表位結合（免疫選擇性地）的互補位（抗原結合（表位結合）結構）的結構域，該表位藉由包含含有SEQ ID NO: 27中描繪的CDR-H1、SEQ ID NO: 28中描繪的CDR-H2和SEQ ID NO: 29中描繪的CDR-H3的VH區以及含有SEQ ID NO: 30中描繪的CDR-L1、SEQ ID NO: 31中描繪的CDR-L2和SEQ ID NO: 32中描繪的CDR-L3的VL區的結構域識別。換言之，根據本發明，提供了多肽/多肽構建體，該多肽/多肽構建體包含與表位結合（免疫選擇性地）的結構域，該表位藉由包含含有SEQ ID NO: 27中描繪的CDR-H1、SEQ ID NO: 28中描繪的CDR-H2和SEQ ID NO: 29中描繪的CDR-H3的VH區以及含有SEQ ID NO: 30中描繪的CDR-L1、SEQ ID NO: 31中描繪的CDR-L2和SEQ ID NO: 32中描繪的CDR-L3的VL區的結構域識別。
根據本發明，提供了多肽/多肽構建體，該多肽/多肽構建體包含含有與表位結合（免疫選擇性地）的互補位（抗原結合（表位結合）結構）的結構域，該表位藉由包含含有SEQ ID NO: 41中描繪的CDR-H1、SEQ ID NO: 42中描繪的CDR-H2和SEQ ID NO: 43中描繪的CDR-H3的VH區以及含有SEQ ID NO: 44中描繪的CDR-L1、SEQ ID NO: 45中描繪的CDR-L2和SEQ ID NO: 46中描繪的CDR-L3的VL區的結構域識別。因此，根據本發明，提供了多肽/多肽構建體，該多肽/多肽構建體包含與表位結合（免疫選擇性地）的結構域，該表位藉由包含含有SEQ ID NO: 41中描繪的CDR-H1、SEQ ID NO: 42中描繪的CDR-H2和SEQ ID NO: 43中描繪的CDR-H3的VH區以及含有SEQ ID NO: 44中描繪的CDR-L1、SEQ ID NO: 45中描繪的CDR-L2和SEQ ID NO: 46中描繪的CDR-L3的VL區的結構域識別。
根據本發明，提供了多肽/多肽構建體，該多肽/多肽構建體包含含有與表位結合（免疫選擇性地）的互補位（抗原結合（表位結合）結構）的結構域，該表位藉由包含含有SEQ ID NO: 69中描繪的CDR-H1、SEQ ID NO: 70中描繪的CDR-H2和SEQ ID NO: 71中描繪的CDR-H3的VH區以及含有SEQ ID NO: 72中描繪的CDR-L1、SEQ ID NO: 73中描繪的CDR-L2和SEQ ID NO: 74中描繪的CDR-L3的VL區的結構域識別。因此，根據本發明，提供了多肽/多肽構建體，該多肽/多肽構建體包含與表位結合（免疫選擇性地）的結構域，該表位藉由包含含有SEQ ID NO: 69中描繪的CDR-H1、SEQ ID NO: 70中描繪的CDR-H2和SEQ ID NO: 71中描繪的CDR-H3的VH區以及含有SEQ ID NO: 72中描繪的CDR-L1、SEQ ID NO: 73中描繪的CDR-L2和SEQ ID NO: 74中描繪的CDR-L3的VL區的結構域識別。
根據本發明，提供了多肽/多肽構建體，該多肽/多肽構建體包含含有與表位結合（免疫選擇性地）的互補位（抗原結合（表位結合）結構）的結構域，該表位藉由包含含有SEQ ID NO: 195中描繪的CDR-H1、SEQ ID NO: 196中描繪的CDR-H2和SEQ ID NO: 197中描繪的CDR-H3的VH區以及含有SEQ ID NO: 198中描繪的CDR-L1、SEQ ID NO: 199中描繪的CDR-L2和SEQ ID NO: 200中描繪的CDR-L3的VL區的結構域識別。因此，根據本發明，提供了多肽/多肽構建體，該多肽/多肽構建體包含與表位結合（免疫選擇性地）的結構域，該表位藉由包含含有SEQ ID NO: 195中描繪的CDR-H1、SEQ ID NO: 196中描繪的CDR-H2和SEQ ID NO: 197中描繪的CDR-H3的VH區以及含有SEQ ID NO: 198中描繪的CDR-L1、SEQ ID NO: 199中描繪的CDR-L2和SEQ ID NO: 200中描繪的CDR-L3的VL區的結構域識別。
根據本發明，提供了多肽/多肽構建體，該多肽/多肽構建體包含含有與表位結合（免疫選擇性地）的互補位（抗原結合（表位結合）結構）的結構域，該表位藉由包含含有SEQ ID NO: 237中描繪的CDR-H1、SEQ ID NO: 238中描繪的CDR-H2和SEQ ID NO: 239中描繪的CDR-H3的VH區以及含有SEQ ID NO: 240中描繪的CDR-L1、SEQ ID NO: 241中描繪的CDR-L2和SEQ ID NO: 242中描繪的CDR-L3的VL區的結構域識別。因此，根據本發明，提供了多肽/多肽構建體，該多肽/多肽構建體包含與表位結合（免疫選擇性地）的結構域，該表位藉由包含含有SEQ ID NO: 237中描繪的CDR-H1、SEQ ID NO: 238中描繪的CDR-H2和SEQ ID NO: 239中描繪的CDR-H3的VH區以及含有SEQ ID NO: 240中描繪的CDR-L1、SEQ ID NO: 241中描繪的CDR-L2和SEQ ID NO: 242中描繪的CDR-L3的VL區的結構域識別。
根據本發明，提供了多肽/多肽構建體，其中
(i) 結構域包含互補位（抗原結合（表位結合）結構），該互補位與表位區域結合（免疫選擇性地），該表位區域包含CLDN6（如SEQ ID NO: 1中描繪）的第一細胞外環的胺基酸，該第一細胞外環也稱為細胞外環1（ECL1）；所述表位區域在SEQ ID NO: 9中描繪，並且該結構域視需要包含以下a) 至s) 中提及的任一個序列，和/或
(ii) 結構域包含互補位（抗原結合（表位結合）結構），該互補位與表位區域結合（免疫選擇性地），該表位區域包含CLDN6（如SEQ ID NO: 1中描繪）的第二細胞外環的胺基酸，該第二細胞外環也稱為細胞外環2（ECL2）；所述表位區域在SEQ ID NO: 10中描繪，並且該結構域視需要包含以下a) 至s) 中提及的任一個序列；和/或
(iii) 結構域包含互補位（抗原結合（表位結合）結構），該互補位與包含CLDN6的ECL1和ECL2的胺基酸的表位區域結合（免疫選擇性地），較佳的是為包含含有SEQ ID NO: 9和10的表位區域的胺基酸的那些，並且該結構域視需要包含以下a) 至s) 中提及的任何一種結構；和/或
(iv) 結構域包含互補位（抗原結合（表位結合）結構），該互補位與包含結合靶細胞表面上的CLDN6的互補位的抗體或多肽構建體結合（免疫選擇性地）CLDN6上相同的表位，並且該結構域包括以下a) 至s) 中提及的任一個序列：
a) 包含SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區；
b) 包含SEQ ID NO: 27中描繪的CDR-H1、SEQ ID NO: 28中描繪的CDR-H2和SEQ ID NO: 29中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 30中描繪的CDR-L1、SEQ ID NO: 31中描繪的CDR-L2和SEQ ID NO: 32中描繪的CDR-L3的VL區；
c) 包含SEQ ID NO: 41中描繪的CDR-H1、SEQ ID NO: 42中描繪的CDR-H2和SEQ ID NO: 43中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 44中描繪的CDR-L1、SEQ ID NO: 45中描繪的CDR-L2和SEQ ID NO: 46中描繪的CDR-L3的VL區；
d) 包含SEQ ID NO: 55中描繪的CDR-H1、SEQ ID NO: 56中描繪的CDR-H2和SEQ ID NO: 57中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 58中描繪的CDR-L1、SEQ ID NO: 59中描繪的CDR-L2和SEQ ID NO: 60中描繪的CDR-L3的VL區；
e) 包含SEQ ID NO: 69中描繪的CDR-H1、SEQ ID NO: 70中描繪的CDR-H2和SEQ ID NO: 71中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 72中描繪的CDR-L1、SEQ ID NO: 73中描繪的CDR-L2和SEQ ID NO: 74中描繪的CDR-L3的VL區；
f) 包含SEQ ID NO: 83中描繪的CDR-H1、SEQ ID NO: 84中描繪的CDR-H2和SEQ ID NO: 85中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 86中描繪的CDR-L1、SEQ ID NO: 87中描繪的CDR-L2和SEQ ID NO: 88中描繪的CDR-L3的VL區；
g) 包含SEQ ID NO: 97中描繪的CDR-H1、SEQ ID NO: 98中描繪的CDR-H2和SEQ ID NO: 99中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 100中描繪的CDR-L1、SEQ ID NO: 101中描繪的CDR-L2和SEQ ID NO: 102中描繪的CDR-L3的VL區；
h) 包含SEQ ID NO: 111中描繪的CDR-H1、SEQ ID NO: 112中描繪的CDR-H2和SEQ ID NO: 113中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 114中描繪的CDR-L1、SEQ ID NO: 115中描繪的CDR-L2和SEQ ID NO: 116中描繪的CDR-L3的VL區；
i) 包含SEQ ID NO: 125中描繪的CDR-H1、SEQ ID NO: 126中描繪的CDR-H2和SEQ ID NO: 127中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 128中描繪的CDR-L1、SEQ ID NO: 129中描繪的CDR-L2和SEQ ID NO: 130中描繪的CDR-L3的VL區；
j) 包含SEQ ID NO: 139中描繪的CDR-H1、SEQ ID NO: 140中描繪的CDR-H2和SEQ ID NO: 141中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 142中描繪的CDR-L1、SEQ ID NO: 143中描繪的CDR-L2和SEQ ID NO: 144中描繪的CDR-L3的VL區；
k) 包含SEQ ID NO: 153中描繪的CDR-H1、SEQ ID NO: 154中描繪的CDR-H2和SEQ ID NO: 155中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 156中描繪的CDR-L1、SEQ ID NO: 157中描繪的CDR-L2和SEQ ID NO: 158中描繪的CDR-L3的VL區；
l) 包含SEQ ID NO: 167中描繪的CDR-H1、SEQ ID NO: 168中描繪的CDR-H2和SEQ ID NO: 169中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 170中描繪的CDR-L1、SEQ ID NO: 171中描繪的CDR-L2和SEQ ID NO: 172中描繪的CDR-L3的VL區；
m) 包含SEQ ID NO: 181中描繪的CDR-H1、SEQ ID NO: 182中描繪的CDR-H2和SEQ ID NO: 183中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 184中描繪的CDR-L1、SEQ ID NO: 185中描繪的CDR-L2和SEQ ID NO: 186中描繪的CDR-L3的VL區；
n) 包含SEQ ID NO: 195中描繪的CDR-H1、SEQ ID NO: 196中描繪的CDR-H2和SEQ ID NO: 197中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 198中描繪的CDR-L1、SEQ ID NO: 199中描繪的CDR-L2和SEQ ID NO: 200中描繪的CDR-L3的VL區；
o) 包含SEQ ID NO: 209中描繪的CDR-H1、SEQ ID NO: 210中描繪的CDR-H2和SEQ ID NO: 211中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 212中描繪的CDR-L1、SEQ ID NO: 213中描繪的CDR-L2和SEQ ID NO: 214中描繪的CDR-L3的VL區；
p) 包含SEQ ID NO: 223中描繪的CDR-H1、SEQ ID NO: 224中描繪的CDR-H2和SEQ ID NO: 225中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 226中描繪的CDR-L1、SEQ ID NO: 227中描繪的CDR-L2和SEQ ID NO: 228中描繪的CDR-L3的VL區；
q) 包含SEQ ID NO: 237中描繪的CDR-H1、SEQ ID NO: 238中描繪的CDR-H2和SEQ ID NO: 239中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 240中描繪的CDR-L1、SEQ ID NO: 241中描繪的CDR-L2和SEQ ID NO: 242中描繪的CDR-L3的VL區；
r) 包含SEQ ID NO: 251中描繪的CDR-H1、SEQ ID NO: 252中描繪的CDR-H2和SEQ ID NO: 253中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 254中描繪的CDR-L1、SEQ ID NO: 255中描繪的CDR-L2和SEQ ID NO: 256中描繪的CDR-L3的VL區，以及
s) 包含SEQ ID NO: 265中描繪的CDR-H1、SEQ ID NO: 266中描繪的CDR-H2和SEQ ID NO: 267中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 268中描繪的CDR-L1、SEQ ID NO: 269中描繪的CDR-L2和SEQ ID NO: 270中描繪的CDR-L3的VL區。
因此，根據本發明，提供了多肽/多肽構建體，其中
(i) 結構域與表位區域結合（免疫選擇性地），該表位區域包含CLDN6（如SEQ ID NO: 1中描繪）的第一細胞外環的胺基酸，該第一細胞外環也稱為細胞外環1（ECL1）；所述表位區域在SEQ ID NO: 9中描繪，並且該結構域視需要包含以下a) 至s) 中提及的任一個序列，和/或
(ii) 結構域與表位區域結合（免疫選擇性地），該表位區域包含CLDN6（如SEQ ID NO: 1中描繪）的第二細胞外環的胺基酸，該第二細胞外環也稱為細胞外環2（ECL2）；所述表位區域在SEQ ID NO: 10中描繪，並且該結構域視需要包含以下a) 至s) 中提及的任一個序列；和/或
(iii) 結構域與包含CLDN6的ECL1和ECL2的胺基酸的表位區域結合（免疫選擇性地），較佳的是為包含含有SEQ ID NO: 9和10的表位區域的胺基酸的那些，並且該結構域視需要包含以下a) 至s) 中提及的任何一種結構；和/或
(iv) 結構域與包含結合靶細胞表面上的CLDN6的互補位的抗體或多肽構建體結合（免疫選擇性地）CLDN6上相同的表位，並且該結構域包括以下a) 至s) 中提及的任一個序列：
a) 包含SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區；
b) 包含SEQ ID NO: 27中描繪的CDR-H1、SEQ ID NO: 28中描繪的CDR-H2和SEQ ID NO: 29中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 30中描繪的CDR-L1、SEQ ID NO: 31中描繪的CDR-L2和SEQ ID NO: 32中描繪的CDR-L3的VL區；
c) 包含SEQ ID NO: 41中描繪的CDR-H1、SEQ ID NO: 42中描繪的CDR-H2和SEQ ID NO: 43中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 44中描繪的CDR-L1、SEQ ID NO: 45中描繪的CDR-L2和SEQ ID NO: 46中描繪的CDR-L3的VL區；
d) 包含SEQ ID NO: 55中描繪的CDR-H1、SEQ ID NO: 56中描繪的CDR-H2和SEQ ID NO: 57中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 58中描繪的CDR-L1、SEQ ID NO: 59中描繪的CDR-L2和SEQ ID NO: 60中描繪的CDR-L3的VL區；
e) 包含SEQ ID NO: 69中描繪的CDR-H1、SEQ ID NO: 70中描繪的CDR-H2和SEQ ID NO: 71中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 72中描繪的CDR-L1、SEQ ID NO: 73中描繪的CDR-L2和SEQ ID NO: 74中描繪的CDR-L3的VL區；
f) 包含SEQ ID NO: 83中描繪的CDR-H1、SEQ ID NO: 84中描繪的CDR-H2和SEQ ID NO: 85中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 86中描繪的CDR-L1、SEQ ID NO: 87中描繪的CDR-L2和SEQ ID NO: 88中描繪的CDR-L3的VL區；
g) 包含SEQ ID NO: 97中描繪的CDR-H1、SEQ ID NO: 98中描繪的CDR-H2和SEQ ID NO: 99中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 100中描繪的CDR-L1、SEQ ID NO: 101中描繪的CDR-L2和SEQ ID NO: 102中描繪的CDR-L3的VL區；
h) 包含SEQ ID NO: 111中描繪的CDR-H1、SEQ ID NO: 112中描繪的CDR-H2和SEQ ID NO: 113中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 114中描繪的CDR-L1、SEQ ID NO: 115中描繪的CDR-L2和SEQ ID NO: 116中描繪的CDR-L3的VL區；
i) 包含SEQ ID NO: 125中描繪的CDR-H1、SEQ ID NO: 126中描繪的CDR-H2和SEQ ID NO: 127中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 128中描繪的CDR-L1、SEQ ID NO: 129中描繪的CDR-L2和SEQ ID NO: 130中描繪的CDR-L3的VL區；
j) 包含SEQ ID NO: 139中描繪的CDR-H1、SEQ ID NO: 140中描繪的CDR-H2和SEQ ID NO: 141中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 142中描繪的CDR-L1、SEQ ID NO: 143中描繪的CDR-L2和SEQ ID NO: 144中描繪的CDR-L3的VL區；
k) 包含SEQ ID NO: 153中描繪的CDR-H1、SEQ ID NO: 154中描繪的CDR-H2和SEQ ID NO: 155中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 156中描繪的CDR-L1、SEQ ID NO: 157中描繪的CDR-L2和SEQ ID NO: 158中描繪的CDR-L3的VL區；
l) 包含SEQ ID NO: 167中描繪的CDR-H1、SEQ ID NO: 168中描繪的CDR-H2和SEQ ID NO: 169中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 170中描繪的CDR-L1、SEQ ID NO: 171中描繪的CDR-L2和SEQ ID NO: 172中描繪的CDR-L3的VL區；
m) 包含SEQ ID NO: 181中描繪的CDR-H1、SEQ ID NO: 182中描繪的CDR-H2和SEQ ID NO: 183中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 184中描繪的CDR-L1、SEQ ID NO: 185中描繪的CDR-L2和SEQ ID NO: 186中描繪的CDR-L3的VL區；
n) 包含SEQ ID NO: 195中描繪的CDR-H1、SEQ ID NO: 196中描繪的CDR-H2和SEQ ID NO: 197中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 198中描繪的CDR-L1、SEQ ID NO: 199中描繪的CDR-L2和SEQ ID NO: 200中描繪的CDR-L3的VL區；
o) 包含SEQ ID NO: 209中描繪的CDR-H1、SEQ ID NO: 210中描繪的CDR-H2和SEQ ID NO: 211中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 212中描繪的CDR-L1、SEQ ID NO: 213中描繪的CDR-L2和SEQ ID NO: 214中描繪的CDR-L3的VL區；
p) 包含SEQ ID NO: 223中描繪的CDR-H1、SEQ ID NO: 224中描繪的CDR-H2和SEQ ID NO: 225中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 226中描繪的CDR-L1、SEQ ID NO: 227中描繪的CDR-L2和SEQ ID NO: 228中描繪的CDR-L3的VL區；
q) 包含SEQ ID NO: 237中描繪的CDR-H1、SEQ ID NO: 238中描繪的CDR-H2和SEQ ID NO: 239中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 240中描繪的CDR-L1、SEQ ID NO: 241中描繪的CDR-L2和SEQ ID NO: 242中描繪的CDR-L3的VL區；
r) 包含SEQ ID NO: 251中描繪的CDR-H1、SEQ ID NO: 252中描繪的CDR-H2和SEQ ID NO: 253中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 254中描繪的CDR-L1、SEQ ID NO: 255中描繪的CDR-L2和SEQ ID NO: 256中描繪的CDR-L3的VL區，以及
s) 包含SEQ ID NO: 265中描繪的CDR-H1、SEQ ID NO: 266中描繪的CDR-H2和SEQ ID NO: 267中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 268中描繪的CDR-L1、SEQ ID NO: 269中描繪的CDR-L2和SEQ ID NO: 270中描繪的CDR-L3的VL區。
根據本發明，提供了多肽/多肽構建體，其中：
(i) 結構域包含互補位（抗原結合（表位結合）結構），該互補位與表位區域結合（免疫選擇性地），該表位區域包含CLDN6（如SEQ ID NO: 1中描繪）的第一細胞外環的胺基酸，該第一細胞外環也稱為細胞外環1（ECL1）；所述表位區域在SEQ ID NO: 9中描繪，並且該結構域視需要包含以下a-1) 至s-1) 中提及的任一個序列，和/或
(ii) 結構域包含互補位（抗原結合（表位結合）結構），該互補位與表位區域結合（免疫選擇性地），該表位區域包含CLDN6（如SEQ ID NO: 1中描繪）的第二細胞外環的胺基酸，該第二細胞外環也稱為細胞外環2（ECL2）；所述表位區域在SEQ ID NO: 10中描繪，並且該結構域視需要包含以下a-1) 至s-1) 中提及的任一個序列；和/或
(iii) 結構域包含互補位（抗原結合（表位結合）結構），該互補位與包含CLDN6的ECL1和ECL2的胺基酸的表位區域結合（免疫選擇性地），較佳的是為包含含有SEQ ID NO: 9和10的表位區域的胺基酸的那些，並且該互補位視需要包含以下a-1) 至s-1) 中提及的任何一種結構；和/或
(iv) 結構域包含互補位（抗原結合（表位結合）結構），該互補位與包含結合靶細胞表面上的CLDN6的互補位的抗體或多肽構建體結合（免疫選擇性地）CLDN6上相同的表位，並且該互補位包括以下a-1) 至s-1) 中提及的任一個序列：
a-1) SEQ ID NO: 11中描繪的VH區，和/或SEQ ID NO: 12中描繪的VL區；
b-1) SEQ ID NO: 25中描繪的VH區，和/或SEQ ID NO: 26中描繪的VL區；
c-1) SEQ ID NO: 39中描繪的VH區，和/或SEQ ID NO: 40中描繪的VL區；
d-1) SEQ ID NO: 53中描繪的VH區，和/或SEQ ID NO: 54中描繪的VL區；
e-1) SEQ ID NO: 67中描繪的VH區，和/或SEQ ID NO: 68中描繪的VL區；
f-1) SEQ ID NO: 81中描繪的VH區，和/或SEQ ID NO: 82中描繪的VL區；
g-1) SEQ ID NO: 95中描繪的VH區，和/或SEQ ID NO: 96中描繪的VL區；
h-1) SEQ ID NO: 109中描繪的VH區，和/或SEQ ID NO: 110中描繪的VL區；
i-1) SEQ ID NO: 123中描繪的VH區，和/或SEQ ID NO: 124中描繪的VL區；
j-1) SEQ ID NO: 137中描繪的VH區，和/或SEQ ID NO: 138中描繪的VL區；
k-1) SEQ ID NO: 151中描繪的VH區，和/或SEQ ID NO: 152中描繪的VL區；
l-1) SEQ ID NO: 165中描繪的VH區，和/或SEQ ID NO: 166中描繪的VL區；
m-1) SEQ ID NO: 179中描繪的VH區，和/或SEQ ID NO: 180中描繪的VL區；
n-1) SEQ ID NO: 193中描繪的VH區，和/或SEQ ID NO: 194中描繪的VL區；
o-1) SEQ ID NO: 207中描繪的VH區，和/或SEQ ID NO: 208中描繪的VL區；
p-1) SEQ ID NO: 221中描繪的VH區，和/或SEQ ID NO: 222中描繪的VL區；
q-1) SEQ ID NO: 235中描繪的VH區，和/或SEQ ID NO: 236中描繪的VL區；
r-1) SEQ ID NO: 249中描繪的VH區，和/或SEQ ID NO: 250中描繪的VL區；和
s-1) SEQ ID NO: 263中描繪的VH區，和/或SEQ ID NO: 264中描繪的VL區。
因此，根據本發明，提供了多肽/多肽構建體，其中:
(i) 結構域與表位區域結合（免疫選擇性地），該表位區域包含CLDN6（如SEQ ID NO: 1中描繪）的第一細胞外環的胺基酸，該第一細胞外環也稱為細胞外環1（ECL1）；所述表位區域在SEQ ID NO: 9中描繪，並且該結構域視需要包含以下a-1) 至s-1) 中提及的任一個序列，和/或
(ii) 結構域與表位區域結合（免疫選擇性地），該表位區域包含CLDN6（如SEQ ID NO: 1中描繪）的第二細胞外環的胺基酸，該第二細胞外環也稱為細胞外環2（ECL2）；所述表位區域在SEQ ID NO: 10中描繪，並且該結構域視需要包含以下a-1) 至s-1) 中提及的任一個序列；和/或
(iii) 結構域與包含CLDN6的ECL1和ECL2的胺基酸的表位區域結合（免疫選擇性地），較佳的是為包含含有SEQ ID NO: 9和10的表位區域的胺基酸的那些，並且該結構域視需要包含以下a-1) 至s-1) 中提及的任何一種結構；和/或
(iv) 結構域與包含結合靶細胞表面上的CLDN6的互補位的抗體或多肽構建體結合（免疫選擇性地）CLDN6上相同的表位，並且該互補位包含以下a-1) 至s-1) 中提及的任一個序列：
a-1) SEQ ID NO: 11中描繪的VH區，和/或SEQ ID NO: 12中描繪的VL區；
b-1) SEQ ID NO: 25中描繪的VH區，和/或SEQ ID NO: 26中描繪的VL區；
c-1) SEQ ID NO: 39中描繪的VH區，和/或SEQ ID NO: 40中描繪的VL區；
d-1) SEQ ID NO: 53中描繪的VH區，和/或SEQ ID NO: 54中描繪的VL區；
e-1) SEQ ID NO: 67中描繪的VH區，和/或SEQ ID NO: 68中描繪的VL區；
f-1) SEQ ID NO: 81中描繪的VH區，和/或SEQ ID NO: 82中描繪的VL區；
g-1) SEQ ID NO: 95中描繪的VH區，和/或SEQ ID NO: 96中描繪的VL區；
h-1) SEQ ID NO: 109中描繪的VH區，和/或SEQ ID NO: 110中描繪的VL區；
i-1) SEQ ID NO: 123中描繪的VH區，和/或SEQ ID NO: 124中描繪的VL區；
j-1) SEQ ID NO: 137中描繪的VH區，和/或SEQ ID NO: 138中描繪的VL區；
k-1) SEQ ID NO: 151中描繪的VH區，和/或SEQ ID NO: 152中描繪的VL區；
l-1) SEQ ID NO: 165中描繪的VH區，和/或SEQ ID NO: 166中描繪的VL區；
m-1) SEQ ID NO: 179中描繪的VH區，和/或SEQ ID NO: 180中描繪的VL區；
n-1) SEQ ID NO: 193中描繪的VH區，和/或SEQ ID NO: 194中描繪的VL區；
o-1) SEQ ID NO: 207中描繪的VH區，和/或SEQ ID NO: 208中描繪的VL區；
p-1) SEQ ID NO: 221中描繪的VH區，和/或SEQ ID NO: 222中描繪的VL區；
q-1) SEQ ID NO: 235中描繪的VH區，和/或SEQ ID NO: 236中描繪的VL區；
r-1) SEQ ID NO: 249中描繪的VH區，和/或SEQ ID NO: 250中描繪的VL區；和
s-1) SEQ ID NO: 263中描繪的VH區，和/或SEQ ID NO: 264中描繪的VL區。
根據本發明，提供了多肽/多肽構建體，該等多肽/多肽構建體與包含以下結構域或由其組成的多肽構建體競爭結合：
(i) 結構域包含互補位（抗原結合（表位結合）結構），該互補位與表位區域結合（免疫選擇性地），該表位區域包含CLDN6（如SEQ ID NO: 1中描繪）的第一細胞外環的胺基酸，該第一細胞外環也稱為細胞外環1（ECL1）；所述表位區域在SEQ ID NO: 9中描繪，並且該結構域視需要包含以下a-1) 至s-1) 中提及的任一個序列，和/或
(ii) 結構域包含互補位（抗原結合（表位結合）結構），該互補位與表位區域結合（免疫選擇性地），該表位區域包含CLDN6（如SEQ ID NO: 1中描繪）的第二細胞外環的胺基酸，該第二細胞外環也稱為細胞外環2（ECL2）；所述表位區域在SEQ ID NO: 10中描繪，並且該結構域視需要包含以下a-1) 至s-1) 中提及的任一個序列；和/或
(iii) 結構域包含互補位（抗原結合（表位結合）結構），該互補位與包含CLDN6的ECL1和ECL2的胺基酸的表位區域結合（免疫選擇性地），較佳的是為包含含有SEQ ID NO: 9和10的表位區域的胺基酸的那些，並且該互補位視需要包含以下a-1) 至s-1) 中提及的任何一種結構；和/或
(iv) 結構域包含互補位（抗原結合（表位結合）結構），該互補位與包含結合靶細胞表面上的CLDN6的互補位的抗體或多肽構建體結合（免疫選擇性地）CLDN6上相同的表位，並且該互補位包括以下a-1) 至s-1) 中提及的任一個序列：
a-1) SEQ ID NO: 11中描繪的VH區，和/或SEQ ID NO: 12中描繪的VL區；
b-1) SEQ ID NO: 25中描繪的VH區，和/或SEQ ID NO: 26中描繪的VL區；
c-1) SEQ ID NO: 39中描繪的VH區，和/或SEQ ID NO: 40中描繪的VL區；
d-1) SEQ ID NO: 53中描繪的VH區，和/或SEQ ID NO: 54中描繪的VL區；
e-1) SEQ ID NO: 67中描繪的VH區，和/或SEQ ID NO: 68中描繪的VL區；
f-1) SEQ ID NO: 81中描繪的VH區，和/或SEQ ID NO: 82中描繪的VL區；
g-1) SEQ ID NO: 95中描繪的VH區，和/或SEQ ID NO: 96中描繪的VL區；
h-1) SEQ ID NO: 109中描繪的VH區，和/或SEQ ID NO: 110中描繪的VL區；
i-1) SEQ ID NO: 123中描繪的VH區，和/或SEQ ID NO: 124中描繪的VL區；
j-1) SEQ ID NO: 137中描繪的VH區，和/或SEQ ID NO: 138中描繪的VL區；
k-1) SEQ ID NO: 151中描繪的VH區，和/或SEQ ID NO: 152中描繪的VL區；
l-1) SEQ ID NO: 165中描繪的VH區，和/或SEQ ID NO: 166中描繪的VL區；
m-1) SEQ ID NO: 179中描繪的VH區，和/或SEQ ID NO: 180中描繪的VL區；
n-1) SEQ ID NO: 193中描繪的VH區，和/或SEQ ID NO: 194中描繪的VL區；
o-1) SEQ ID NO: 207中描繪的VH區，和/或SEQ ID NO: 208中描繪的VL區；
p-1) SEQ ID NO: 221中描繪的VH區，和/或SEQ ID NO: 222中描繪的VL區；
q-1) SEQ ID NO: 235中描繪的VH區，和/或SEQ ID NO: 236中描繪的VL區；
r-1) SEQ ID NO: 249中描繪的VH區，和/或SEQ ID NO: 250中描繪的VL區；和
s-1) SEQ ID NO: 263中描繪的VH區，和/或SEQ ID NO: 264中描繪的VL區。
因此，根據本發明，提供了多肽/多肽構建體，該等多肽/多肽構建體與包含以下結構域或由其組成的多肽構建體競爭結合：
(i) 結構域與表位區域結合（免疫選擇性地），該表位區域包含CLDN6（如SEQ ID NO: 1中描繪）的第一細胞外環的胺基酸，該第一細胞外環也稱為細胞外環1（ECL1）；所述表位區域在SEQ ID NO: 9中描繪，並且該結構域視需要包含以下a-1) 至s-1) 中提及的任一個序列，和/或
(ii) 結構域與表位區域結合（免疫選擇性地），該表位區域包含CLDN6（如SEQ ID NO: 1中描繪）的第二細胞外環的胺基酸，該第二細胞外環也稱為細胞外環2（ECL2）；所述表位區域在SEQ ID NO: 10中描繪，並且該結構域視需要包含以下a-1) 至s-1) 中提及的任一個序列；和/或
(iii) 結構域與包含CLDN6的ECL1和ECL2的胺基酸的表位區域結合（免疫選擇性地），較佳的是為包含含有SEQ ID NO: 9和10的表位區域的胺基酸的那些，並且該結構域視需要包含以下a-1) 至s-1) 中提及的任何一種結構；和/或
(iv) 結構域與包含結合靶細胞表面上的CLDN6的互補位的抗體或多肽構建體結合（免疫選擇性地）CLDN6上相同的表位，並且該互補位包含以下a-1) 至s-1) 中提及的任一個序列：
a-1) SEQ ID NO: 11中描繪的VH區，和/或SEQ ID NO: 12中描繪的VL區；
b-1) SEQ ID NO: 25中描繪的VH區，和/或SEQ ID NO: 26中描繪的VL區；
c-1) SEQ ID NO: 39中描繪的VH區，和/或SEQ ID NO: 40中描繪的VL區；
d-1) SEQ ID NO: 53中描繪的VH區，和/或SEQ ID NO: 54中描繪的VL區；
e-1) SEQ ID NO: 67中描繪的VH區，和/或SEQ ID NO: 68中描繪的VL區；
f-1) SEQ ID NO: 81中描繪的VH區，和/或SEQ ID NO: 82中描繪的VL區；
g-1) SEQ ID NO: 95中描繪的VH區，和/或SEQ ID NO: 96中描繪的VL區；
h-1) SEQ ID NO: 109中描繪的VH區，和/或SEQ ID NO: 110中描繪的VL區；
i-1) SEQ ID NO: 123中描繪的VH區，和/或SEQ ID NO: 124中描繪的VL區；
j-1) SEQ ID NO: 137中描繪的VH區，和/或SEQ ID NO: 138中描繪的VL區；
k-1) SEQ ID NO: 151中描繪的VH區，和/或SEQ ID NO: 152中描繪的VL區；
l-1) SEQ ID NO: 165中描繪的VH區，和/或SEQ ID NO: 166中描繪的VL區；
m-1) SEQ ID NO: 179中描繪的VH區，和/或SEQ ID NO: 180中描繪的VL區；
n-1) SEQ ID NO: 193中描繪的VH區，和/或SEQ ID NO: 194中描繪的VL區；
o-1) SEQ ID NO: 207中描繪的VH區，和/或SEQ ID NO: 208中描繪的VL區；
p-1) SEQ ID NO: 221中描繪的VH區，和/或SEQ ID NO: 222中描繪的VL區；
q-1) SEQ ID NO: 235中描繪的VH區，和/或SEQ ID NO: 236中描繪的VL區；
r-1) SEQ ID NO: 249中描繪的VH區，和/或SEQ ID NO: 250中描繪的VL區；和
s-1) SEQ ID NO: 263中描繪的VH區，和/或SEQ ID NO: 264中描繪的VL區。
進一步地，本發明之多肽構建體與包含如下結構域的構建體競爭結合，該結構域與靶細胞表面上的CLDN6選擇性結合且包含以下a) 至s) 中提及的序列組的任何一個：a) 至d)、n) 和s) 係較佳的，a) 至c)、e) 和s) 係非常較佳的，並且本發明之多肽構建體與包含如下結構域的構建體競爭結合，該結構域包含選擇性地與靶細胞表面上的CLDN6結合的互補位（即，抗原結合（表位結合）結構，且該互補位包含以下a) 至s) 中提及的任一個序列組：a) 至d)、n) 和s) 係較佳的，a) 至c)、e) 和s) 係特別較佳的：
a) 包含SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區；
b) 包含SEQ ID NO: 27中描繪的CDR-H1、SEQ ID NO: 28中描繪的CDR-H2和SEQ ID NO: 29中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 30中描繪的CDR-L1、SEQ ID NO: 31中描繪的CDR-L2和SEQ ID NO: 32中描繪的CDR-L3的VL區；
c) 包含SEQ ID NO: 41中描繪的CDR-H1、SEQ ID NO: 42中描繪的CDR-H2和SEQ ID NO: 43中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 44中描繪的CDR-L1、SEQ ID NO: 45中描繪的CDR-L2和SEQ ID NO: 46中描繪的CDR-L3的VL區；
d) 包含SEQ ID NO: 55中描繪的CDR-H1、SEQ ID NO: 56中描繪的CDR-H2和SEQ ID NO: 57中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 58中描繪的CDR-L1、SEQ ID NO: 59中描繪的CDR-L2和SEQ ID NO: 60中描繪的CDR-L3的VL區；
e) 包含SEQ ID NO: 69中描繪的CDR-H1、SEQ ID NO: 70中描繪的CDR-H2和SEQ ID NO: 71中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 72中描繪的CDR-L1、SEQ ID NO: 73中描繪的CDR-L2和SEQ ID NO: 74中描繪的CDR-L3的VL區；
f) 包含SEQ ID NO: 83中描繪的CDR-H1、SEQ ID NO: 84中描繪的CDR-H2和SEQ ID NO: 85中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 86中描繪的CDR-L1、SEQ ID NO: 87中描繪的CDR-L2和SEQ ID NO: 88中描繪的CDR-L3的VL區；
g) 包含SEQ ID NO: 97中描繪的CDR-H1、SEQ ID NO: 98中描繪的CDR-H2和SEQ ID NO: 99中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 100中描繪的CDR-L1、SEQ ID NO: 101中描繪的CDR-L2和SEQ ID NO: 102中描繪的CDR-L3的VL區；
h) 包含SEQ ID NO: 111中描繪的CDR-H1、SEQ ID NO: 112中描繪的CDR-H2和SEQ ID NO: 113中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 114中描繪的CDR-L1、SEQ ID NO: 115中描繪的CDR-L2和SEQ ID NO: 116中描繪的CDR-L3的VL區；
i) 包含SEQ ID NO: 125中描繪的CDR-H1、SEQ ID NO: 126中描繪的CDR-H2和SEQ ID NO: 127中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 128中描繪的CDR-L1、SEQ ID NO: 129中描繪的CDR-L2和SEQ ID NO: 130中描繪的CDR-L3的VL區；
j) 包含SEQ ID NO: 139中描繪的CDR-H1、SEQ ID NO: 140中描繪的CDR-H2和SEQ ID NO: 141中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 142中描繪的CDR-L1、SEQ ID NO: 143中描繪的CDR-L2和SEQ ID NO: 144中描繪的CDR-L3的VL區；
k) 包含SEQ ID NO: 153中描繪的CDR-H1、SEQ ID NO: 154中描繪的CDR-H2和SEQ ID NO: 155中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 156中描繪的CDR-L1、SEQ ID NO: 157中描繪的CDR-L2和SEQ ID NO: 158中描繪的CDR-L3的VL區；
l) 包含SEQ ID NO: 167中描繪的CDR-H1、SEQ ID NO: 168中描繪的CDR-H2和SEQ ID NO: 169中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 170中描繪的CDR-L1、SEQ ID NO: 171中描繪的CDR-L2和SEQ ID NO: 172中描繪的CDR-L3的VL區；
m) 包含SEQ ID NO: 181中描繪的CDR-H1、SEQ ID NO: 182中描繪的CDR-H2和SEQ ID NO: 183中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 184中描繪的CDR-L1、SEQ ID NO: 185中描繪的CDR-L2和SEQ ID NO: 186中描繪的CDR-L3的VL區；
n) 包含SEQ ID NO: 195中描繪的CDR-H1、SEQ ID NO: 196中描繪的CDR-H2和SEQ ID NO: 197中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 198中描繪的CDR-L1、SEQ ID NO: 199中描繪的CDR-L2和SEQ ID NO: 200中描繪的CDR-L3的VL區；
o) 包含SEQ ID NO: 209中描繪的CDR-H1、SEQ ID NO: 210中描繪的CDR-H2和SEQ ID NO: 211中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 212中描繪的CDR-L1、SEQ ID NO: 213中描繪的CDR-L2和SEQ ID NO: 214中描繪的CDR-L3的VL區；
p) 包含SEQ ID NO: 223中描繪的CDR-H1、SEQ ID NO: 224中描繪的CDR-H2和SEQ ID NO: 225中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 226中描繪的CDR-L1、SEQ ID NO: 227中描繪的CDR-L2和SEQ ID NO: 228中描繪的CDR-L3的VL區；
q) 包含SEQ ID NO: 237中描繪的CDR-H1、SEQ ID NO: 238中描繪的CDR-H2和SEQ ID NO: 239中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 240中描繪的CDR-L1、SEQ ID NO: 241中描繪的CDR-L2和SEQ ID NO: 242中描繪的CDR-L3的VL區；
r) 包含SEQ ID NO: 251中描繪的CDR-H1、SEQ ID NO: 252中描繪的CDR-H2和SEQ ID NO: 253中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 254中描繪的CDR-L1、SEQ ID NO: 255中描繪的CDR-L2和SEQ ID NO: 256中描繪的CDR-L3的VL區，以及
s) 包含SEQ ID NO: 265中描繪的CDR-H1、SEQ ID NO: 266中描繪的CDR-H2和SEQ ID NO: 267中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 268中描繪的CDR-L1、SEQ ID NO: 269中描繪的CDR-L2和SEQ ID NO: 270中描繪的CDR-L3的VL區。
進一步地，本發明之多肽構建體與包含互補位（即抗原結合或表位結合結構）的抗體或多肽構建體結合或與其競爭結合，該互補位與靶細胞表面上的CLDN6結合（免疫選擇性地）且包含以下序列組的任何一個，並且本發明之多肽構建體與結合靶細胞表面上的CLDN6（免疫選擇性地）並包含以下序列組的任何一個的抗體或多肽構建體結合或與其競爭結合：
a-1) SEQ ID NO: 11中描繪的VH區，和/或SEQ ID NO: 12中描繪的VL區；
b-1) SEQ ID NO: 25中描繪的VH區，和/或SEQ ID NO: 26中描繪的VL區；
c-1) SEQ ID NO: 39中描繪的VH區，和/或SEQ ID NO: 40中描繪的VL區；
d-1) SEQ ID NO: 53中描繪的VH區，和/或SEQ ID NO: 54中描繪的VL區；
e-1) SEQ ID NO: 67中描繪的VH區，和/或SEQ ID NO: 68中描繪的VL區；
f-1) SEQ ID NO: 81中描繪的VH區，和/或SEQ ID NO: 82中描繪的VL區；
g-1) SEQ ID NO: 95中描繪的VH區，和/或SEQ ID NO: 96中描繪的VL區；
h-1) SEQ ID NO: 109中描繪的VH區，和/或SEQ ID NO: 110中描繪的VL區；
i-1) SEQ ID NO: 123中描繪的VH區，和/或SEQ ID NO: 124中描繪的VL區；
j-1) SEQ ID NO: 137中描繪的VH區，和/或SEQ ID NO: 138中描繪的VL區；
k-1) SEQ ID NO: 151中描繪的VH區，和/或SEQ ID NO: 152中描繪的VL區；
l-1) SEQ ID NO: 165中描繪的VH區，和/或SEQ ID NO: 166中描繪的VL區；
m-1) SEQ ID NO: 179中描繪的VH區，和/或SEQ ID NO: 180中描繪的VL區；
n-1) SEQ ID NO: 193中描繪的VH區，和/或SEQ ID NO: 194中描繪的VL區；
o-1) SEQ ID NO: 207中描繪的VH區，和/或SEQ ID NO: 208中描繪的VL區；
p-1) SEQ ID NO: 221中描繪的VH區，和/或SEQ ID NO: 222中描繪的VL區；
q-1) SEQ ID NO: 235中描繪的VH區，和/或SEQ ID NO: 236中描繪的VL區；
r-1) SEQ ID NO: 249中描繪的VH區，和/或SEQ ID NO: 250中描繪的VL區；和
s-1) SEQ ID NO: 263中描繪的VH區，和/或SEQ ID NO: 264中描繪的VL區。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的互補位（即抗原結合（表位結合）結構）由一對VH和VL區域組成，以及如前述段落中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域由一對VH和VL區域組成，其包含以下中描繪的胺基酸序列：SEQ ID NO: 11+12、SEQ ID NO: 25+26、SEQ ID NO: 39+40、SEQ ID NO: 53+54、SEQ ID NO: 67+68、SEQ ID NO: 81+82、SEQ ID NO: 95+96、SEQ ID NO: 109+110、SEQ ID NO: 123+124、SEQ ID NO: 137+138、SEQ ID NO: 151+152、SEQ ID NO: 165+166、SEQ ID NO: 179+180、SEQ ID NO: 193+194、SEQ ID NO: 207+208、SEQ ID NO: 221+222、SEQ ID NO: 235+236、SEQ ID NO: 249+250、或SEQ ID NO: 263+264，或該等多肽或多肽構建體與該結合CLDN6的多肽構建體競爭。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含以下中描繪的胺基酸序列或由其組成：SEQ ID NO: 19、SEQ ID NO: 22、SEQ ID NO: 33、SEQ ID NO: 36、SEQ ID NO: 47、SEQ ID NO: 50、SEQ ID NO: 61、SEQ ID NO: 64、SEQ ID NO: 75、SEQ ID NO: 78、SEQ ID NO: 89、SEQ ID NO: 92、SEQ ID NO: 103、SEQ ID NO: 106、SEQ ID NO: 117、SEQ ID NO: 120、SEQ ID NO: 131、SEQ ID NO: 134、SEQ ID NO: 145、SEQ ID NO: 148、SEQ ID NO: 159、SEQ ID NO: 162、SEQ ID NO: 173、SEQ ID NO: 176、SEQ ID NO: 187、SEQ ID NO: 190、SEQ ID NO: 201、SEQ ID NO: 204、SEQ ID NO: 215、SEQ ID NO: 218、SEQ ID NO: 229、SEQ ID NO: 232、SEQ ID NO: 243、SEQ ID NO: 246、SEQ ID NO: 257、或SEQ ID NO: 260、SEQ ID NO: 271或SEQ ID NO: 274，或該等多肽或多肽構建體與該結合CLDN6的多肽構建體競爭。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含或由選自以下中描繪的那些的群組的胺基酸序列組成：
- SEQ ID NO: 19、SEQ ID NO: 20、SEQ ID NO: 21、SEQ ID NO: 22、SEQ ID NO: 23和SEQ ID NO: 24；
- SEQ ID NO: 33、SEQ ID NO: 34、SEQ ID NO: 35、SEQ ID NO: 36、SEQ ID NO: 37和SEQ ID NO: 38；
- SEQ ID NO: 47、SEQ ID NO: 48、SEQ ID NO: 49、SEQ ID NO: 50、SEQ ID NO: 51和SEQ ID NO: 52；
- SEQ ID NO: 61、SEQ ID NO: 62、SEQ ID NO: 63、SEQ ID NO: 64、SEQ ID NO: 65和SEQ ID NO: 66；
- SEQ ID NO: 75、SEQ ID NO: 76、SEQ ID NO: 77、SEQ ID NO: 78、SEQ ID NO: 79和SEQ ID NO: 80；
- SEQ ID NO: 89、SEQ ID NO: 90、SEQ ID NO: 91、SEQ ID NO: 92、SEQ ID NO: 93和SEQ ID NO: 94；
- SEQ ID NO: 103、SEQ ID NO: 104、SEQ ID NO: 105、SEQ ID NO: 106、SEQ ID NO: 107和SEQ ID NO: 108；
- SEQ ID NO: 117、SEQ ID NO: 118、SEQ ID NO: 119、SEQ ID NO: 120、SEQ ID NO: 121和SEQ ID NO: 122；
- SEQ ID NO: 131、SEQ ID NO: 132、SEQ ID NO: 133、SEQ ID NO: 134、SEQ ID NO: 135和SEQ ID NO: 136；
- SEQ ID NO: 145、SEQ ID NO: 146、SEQ ID NO: 147、SEQ ID NO: 148、SEQ ID NO: 149和SEQ ID NO: 150；
- SEQ ID NO: 159、SEQ ID NO: 160、SEQ ID NO: 161、SEQ ID NO: 162、SEQ ID NO: 163和SEQ ID NO: 164；
- SEQ ID NO: 173、SEQ ID NO: 174、SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177和SEQ ID NO: 178；
- SEQ ID NO: 187、SEQ ID NO: 188、SEQ ID NO: 189、SEQ ID NO: 190、SEQ ID NO: 191和SEQ ID NO: 192；
- SEQ ID NO: 201、SEQ ID NO: 202、SEQ ID NO: 203、SEQ ID NO: 204、SEQ ID NO: 205和SEQ ID NO: 206；
- SEQ ID NO: 215、SEQ ID NO: 216、SEQ ID NO: 217、SEQ ID NO: 218、SEQ ID NO: 219和SEQ ID NO: 220；
- SEQ ID NO: 229、SEQ ID NO: 230、SEQ ID NO: 231、SEQ ID NO: 232、SEQ ID NO: 233和SEQ ID NO: 234；
- SEQ ID NO: 243、SEQ ID NO: 244、SEQ ID NO: 245、SEQ ID NO: 246、SEQ ID NO: 247和SEQ ID NO: 248；
- SEQ ID NO: 257、SEQ ID NO: 258、SEQ ID NO: 259、SEQ ID NO: 260、SEQ ID NO: 261和SEQ ID NO: 262；以及
- SEQ ID NO: 271、SEQ ID NO: 272、SEQ ID NO: 273、SEQ ID NO: 274、SEQ ID NO: 275、和SEQ ID NO: 276，或與CLDN6競爭結合的多肽構建體。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含SEQ ID NO: 21中描繪的胺基酸序列或由其組成。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含SEQ ID NO: 24中描繪的胺基酸序列或由其組成。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含SEQ ID NO: 35中描繪的胺基酸序列或由其組成。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含SEQ ID NO: 38中描繪的胺基酸序列或由其組成。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含SEQ ID NO: 49中描繪的胺基酸序列或由其組成。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含SEQ ID NO: 52中描繪的胺基酸序列或由其組成。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含SEQ ID NO: 63中描繪的胺基酸序列或由其組成。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含SEQ ID NO: 66中描繪的胺基酸序列或由其組成。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含SEQ ID NO: 77中描繪的胺基酸序列或由其組成。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含SEQ ID NO: 80中描繪的胺基酸序列或由其組成。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含SEQ ID NO: 234中描繪的胺基酸序列或由其組成。
本發明關於根據前述段落中任一項所述之多肽或多肽構建體，該等多肽/多肽構建體包含SEQ ID NO: 276中描繪的胺基酸序列或由其組成。
根據前述實施方式中任一項所述之多肽/多肽構建體，其中如在使用表現SEQ ID NO: 1中描繪的野生型CLDN6突變體的細胞進行的體外測定中確定的，該多肽/多肽構建體誘導的細胞毒性比使用表現SEQ ID NO:1中描繪的CLDN6的細胞進行的體外測定中測量的T細胞依賴性細胞毒性低至少100倍、至少250倍、至少500倍或至少1000倍，該突變體包含以下突變中至少一個或多個：M29X，其中X較佳的是L；R145X，其中X較佳的是Q；和/或Q156X，其中X較佳的是L。
根據本發明，提供了多肽/多肽構建體，
-其中本發明之多肽構建體的結構域（包含互補位，即抗原結合（表位結合）結構））能夠結合和區分表現SEQ ID NO: 1中描繪的CLDN6的細胞的表面上的CLDN6和表現所述CLDN6突變體的細胞的表面上的CLDN6突變體，其中所述CLDN6突變體包含SEQ ID NO: 1中描繪的序列，其中殘基31、38和39中的至少一個被另一個胺基酸殘基替代，特別地，其中殘基31係R和/或殘基38係S和/或殘基39係N，和/或其中殘基31、38和39中的至少一個被另一個胺基酸殘基替代，特別地，其中殘基156不是Q，
-其中視需要，本發明之多肽構建體的結構域（包括互補位（即抗原結合（表位結合）結構））結合CD3（特別是人或非人靈長類CD3），
-其中當所述多肽/多肽構建體（互補位（即，抗原結合（表位結合）結構））與表現CLDN6的細胞的表面上的CLDN6結合時，並且當另一個抗原結合（表位結合）結構域包含與CD3結合的互補位時，所述多肽/多肽構建體能夠接合、活化T細胞並誘導T細胞依賴性細胞毒性，並且
-其中結合CLDN6的結構域（包含互補位（即，抗原結合（表位結合）結構））包含重鏈CDR3區，其包含以下序列： X1LIVX2APX3（SEQ ID NO.667），其中X1係A或N；X2係V或E；並且X3係V或A，
-其中視需要，該多肽構建體不選擇性地與CLDN1、CLDN2、CLDN3、CLDN4、CLDN9和/或CLDN18.1結合，
-其中較佳的是，該多肽/多肽構建體與SEQ ID NO: 9和10中描繪的CLDN6（SEQ ID NO: 1）的E1A和/或E2B區域結合，並且
其中較佳的是，該多肽/多肽構建體不與包含CLDN6（SEQ ID NO: 1）的胺基酸138-150的表位結合。
根據本發明，提供了多肽/多肽構建體，
其中本發明之多肽構建體的結構域（包含互補位，即抗原結合（表位結合）結構））能夠結合和區分表現SEQ ID NO: 1中描繪的CLDN6的細胞的表面上的CLDN6和表現所述CLDN6突變體的細胞的表面上的CLDN6突變體，其中所述CLDN6突變體包含SEQ ID NO: 1中描繪的序列，其中殘基31、38和39中的至少一個被另一個胺基酸殘基替代，特別地，其中殘基31係R和/或殘基38係S和/或殘基39係N，
其中視需要，本發明之構建體的結構域（包括互補位（即抗原結合（表位結合）結構））結合CD3（特別是人或非人靈長類CD3），
進一步地，其中當所述多肽/多肽構建體（例如，互補位（即，抗原結合（表位結合）結構））與表現CLDN6的細胞的表面上的CLDN6結合時，並且當另一個抗原結合（表位結合）結構域（包含互補位）與CD3結合時，所述多肽/多肽構建體能夠接合、活化T細胞並誘導T細胞依賴性細胞毒性，並且
其中該結合CLDN6的結構域（包含互補位（即，抗原結合（表位結合）結構））包含重鏈CDR3區，該重鏈CDR3區包含以下序列：DX1LIVX2APX3T（SEQ ID NO.668），其中X1係A或N；X2係V或E；並且X3係V或A，
其中視需要，結構域（包括互補位（即抗原結合（表位結合）結構））不免疫特異性或免疫選擇性地與CLDN1、CLDN2、CLDN3、CLDN4、CLDN9和/或CLDN18.1結合，
其中視需要，本發明之多肽構建體的結構域（包含互補位（即，抗原結合（表位結合）結構））能夠結合和區分表現CLDN6的細胞的表面上的CLDN6，與CLDN6（SEQ ID NO: 1）的E1A和/或E2B區域結合。
根據本發明，提供了多肽/多肽構建體，
其中所述多肽/多肽構建體的結構域（包含互補位，即抗原結合（表位結合）結構））能夠結合和區分表現SEQ ID NO: 1中描繪的CLDN6的細胞的表面上的CLDN6和表現所述CLDN6突變體的細胞的表面上的CLDN6突變體，其中所述CLDN6突變體包含SEQ ID NO: 1中描繪的序列，其中殘基31、38和39中的至少一個被另一個胺基酸殘基替代，特別地，其中殘基31係R和/或殘基38係S和/或殘基39係N，
其中視需要，本發明之構建體的結構域（包括互補位（即抗原結合（表位結合）結構））結合CD3（特別是人或非人靈長類CD3），
進一步地，其中當所述多肽/多肽構建體（例如，互補位（即，抗原結合（表位結合）結構））與表現CLDN6的細胞的表面上的CLDN6結合時，並且當另一個抗原結合（表位結合）結構域包含與CD3結合的互補位時，所述多肽/多肽構建體能夠接合、活化T細胞並誘導T細胞依賴性細胞毒性，並且
其中該結合CLDN6的結構域（包含互補位（即，抗原結合（表位結合）結構））包含重鏈CDR3區，該重鏈CDR3區包含以下序列： DX
1LIVX
2APX
3TRDYYYYGMDV（SEQ ID NO.669），其中X
1係A或N；X
2係V或E；並且X
3係V或A，
其中視需要，該結合CLDN6的結構域（包括互補位（即抗原結合（表位結合）結構））不（免疫特異性或免疫選擇性地）與CLDN1、CLDN2、CLDN3、CLDN4、CLDN9、CLDN18.1和/或CLDN18.2結合，
其中視需要，本發明之多肽構建體的結構域（包含互補位（即，抗原結合（表位結合）結構））能夠結合和區分表現CLDN6的細胞的表面上的CLDN6，與CLDN6（SEQ ID NO: 1）的E1A和/或E2B區域結合。在實施方式中，該多肽/多肽構建體能夠結合表現CLDN6的細胞的表面上的CLDN6，其與CLDN6（SEQ ID NO: 1）的E1A和/或E2B區域結合，但不與SEQ ID NO: 1中描繪的CLDN6的胺基酸138 - 150結合。
根據本發明，提供了多肽/多肽構建體，
- 其中所述多肽/多肽構建體的結構域（包含互補位，即抗原結合（表位結合）結構））能夠結合和區分表現SEQ ID NO: 1中描繪的CLDN6的細胞的表面上的CLDN6和表現所述CLDN6突變體的細胞的表面上的CLDN6突變體，其中所述CLDN6突變體包含SEQ ID NO: 1中描繪的序列，其中殘基31、38和39中的至少一個被另一個胺基酸殘基替代，特別地，其中殘基31係R和/或殘基38係S和/或殘基39係N，
- 其中視需要，本發明之構建體的結構域（包括互補位（即抗原結合（表位結合）結構））結合CD3（特別是人或非人靈長類CD3），
- 進一步地，其中當該多肽/多肽構建體（藉由互補位（即，抗原結合（表位結合）結構））結合到表現CLDN6的細胞的表面上的CLDN6時，並且當另一個抗原結合（表位結合）結構域包含與CD3結合的互補位時，該多肽/多肽構建體能夠接合、活化T細胞並誘導T細胞依賴性細胞毒性，
- 其中該能夠結合和區分表現SEQ ID NO: 1中描繪的CLDN6的細胞的表面上的CLDN6的結構域（包含互補位（即，抗原結合（表位結合）結構））包含含有重鏈CDR3區的重鏈片段，該重鏈CDR3區包含選自SEQ ID No: 15、23、31、39、47、55、63、71、79、87、95、103、111、119、127、135、143和151的任一項中描繪的序列的組，特別是包含SEQ ID No: 15、23、31和47中描繪的序列的群組的序列，非常特別地，該重鏈CDR3區包含SEQ ID NO: 15或由其組成；
- 其中視需要，該多肽構建體不選擇性地與CLDN2（SEQ ID NO: 5）、CLDN3（SEQ ID NO: 6）、CLDN4（SEQ ID NO: 7）、CLDN9（SEQ ID NO: 8）、CLDN18.1（SEQ ID NO: 2）和/或CLDN18.2（SEQ ID NO: 3）結合，和/或
- 其中該構建體與CLDN6（SEQ ID NO: 1）的E1A和/或E2B區域結合，但不與SEQ ID NO: 1中描繪的CLDN6的胺基酸138 - 150結合。
根據本發明，提供了如貫穿說明書和申請專利範圍所定義的多肽/多肽構建體，其包含與人CLDN6（SEQ ID NO: 1）結合的結構域、和與人CD3結合的結構域、以及延長該多肽的半衰期的結構域。該與CLDN6結合的結構域包含可變輕（VL）鏈結構域，該可變輕鏈結構域包含在以下序列RASQSVX
1SX
2YLA（SEQ ID NO: 695）中描繪的CDR1區域，其中X
1選自S和R，較佳的是S，並且其中X
2選自S和T，較佳的是S：和/或在以下序列QQYX
1X
2SPX
3T（SEQ ID NO: 696）中描繪的CDR3區域，其中X
1選自G、D和Q，較佳的是G，並且其中X
2選自S、A和T，較佳的是S，並且X
3選自L和I，較佳的是L。在一個特定實施方式中，該等多肽/多肽構建體具有如下的V鏈，該V鏈包含SEQ ID NO: 16中描繪的CDR1區和SEQ ID NO: 18中描繪的CDR3區，進一步較佳的是與SEQ ID NO: 17中描繪的VL CDR2區組合，進一步特別地與SEQ ID NO: 13、14和/或15中描繪的可變重（VH）鏈結構域的CDR1、CDR2、CDR3區組合；該等多肽/多肽與SEQ ID NO: 9和/或10中描繪的CLDN6區，如結構域交換實驗中所確定的（參考實例部分）。發現本發明之多肽或多肽構建體特別適於區分CLDN6和CLDN9，並且較佳的是與CLDN6細胞（例如用編碼CLDN6和/或CLDN9的核酸轉化的CHO細胞）結合和有效地體外殺傷它們。不僅是細胞毒性活性更佳，而且該等多肽或多肽構建體還顯示出令人驚訝的蛋白質穩定性，如當它們具有以上標題所說的CDR時在1 mg/ml下DLS °C聚集熱穩定性測試中確定的。該等特性對用於免疫腫瘤學（T細胞接合）治療方法以及藥物配製劑的製備和存儲中的多肽和/或多肽很重要。
根據本發明，提供了多肽/多肽構建體，其中結構域（包含互補位（即抗原結合（表位結合）結構））與如以上任一部分中所定義的CLDN6結合，該等多肽/多肽構建體進一步包含與CD3、特別是與CD3結合互補位結合的結構域（包含互補位（即，抗原結合（表位結合）結構）），如例如WO2019/133961中所揭露的，多肽/多肽構建體僅顯示對於人和獼猴、或普通狨（Callithrix jacchus）、絨頂檉柳猴（Saguinus Oedipus）或松鼠猴（Saimiri sciureus）CD3ε鏈的跨物種特異性，而且由於識別此特定表位（而不是先前描述的雙特異性T細胞接合分子中CD3結合物的表位），未證明與對前一代T細胞接合抗體觀察到的相同的程度的T細胞非特異性活化。可在本發明之抗體和構建體的上下文中使用的CD3結合結構域/互補位的序列在以下各個段落中描述。
有利地，靶向被本發明之構建體識別的CLDN6的表位（還參見實例部分）提供以下益處：
(1) CLDN6xCD3構建體相對於CLDN9的免疫特異性/免疫選擇性（實例1和5），以及
(2) 對CLDN6xCD3構建體的出乎意料的高細胞毒性效力（實例4、6和7）。
根據本發明，本發明之多肽/多肽構建體包含如下抗原結合（表位結合）結構域（包含互補位（即抗原結合（表位結合）結構）），該結構域特異性地和選擇性地與通常在T細胞上表現的CD3結合。
由當前結構域/互補位結合的CD3ε細胞外結構域的實例分別在SEQ ID NO: 442和443中示出。進一步地，CD3ε結合結構域/互補位胺基酸、包含它們的scFv、VH和VL鏈的實例在SEQ ID NO: 444至562中以及在SEQ ID NO: 670至678中示出。
本發明還關於根據前述段落中任一項所述之多肽，其中與人CD3ε鏈的胞外表位結合的結合結構域包含與VL區連接的VH區或由其組成，其中
- i) 該VH區包含：
● X1YAX2N的CDR-H1序列，其中X1係K、V、S、G、R、T或I；且X2係M或I；
● RIRSKYNNYATYYADX1VK X2的CDR-H2序列，其中X1係S或Q；且X2係D、G、K、S或E；和
● HX1NFGNSYX2SX3X4AY的CDR-H3序列，其中X1係G、R或A；X2係I、L、V或T；X3係Y、W或F；並且X4係W、F或Y；並且
- ii) 其中該VL區包含：
● X1SSTGAVTX2X3X4YX5N的CDR-L1序列，其中X1係G、R或A；X2係S或T；X3係G或S；X4係N或Y；並且X5係P或A；
● X1TX2X3X4X5X6的CDR-L2序列；其中X1係G或A；X2係K、D或N；X3係F、M或K；X4係L或R；X5係A、P或V；並且X6係P或S；和
● X1LWYSNX2WV的CDR-L3序列，其中X1係V、A或T；並且X2係R或L；並且
- iii) 其中i) 和/或ii) 的CDR序列包含選自以下的一種或多種胺基酸取代：CDR-H1中的X24V或X24F；
● CDR-H2中的D15（較佳的是E）、X116A；
● CDR-H3中的H1（較佳的是A或N）、X12E、F4（較佳的是I）和/或N6（較佳的是S或T）；和
● CDR-L3中的W93（較佳的是Y）。
本發明關於可具有連接子（linker）、半衰期延長肽和分別在SEQ ID NO: 563至575和SEQ ID NO: 576至666中揭露的其他結構部分的化合物。有關該等結構的功能的詳細資訊在實例部分後的序列表中找到。
設想了根據本發明之多肽/多肽構建體，與T細胞表面上的CD3結合的結構域（包含互補位）包含如下VL區，該VL區選自由序列表中示例的相應SEQ ID號444至562和677中（特別是在SEQ ID號507-512和534-541和677中）描繪的VL區組成之群組。
在另一個實施方式中，根據本發明之多肽/多肽構建體，與T細胞表面上的CD3結合的結構域（包含互補位）包含SEQ ID NO: 677中描繪的VL區。
設想了根據本發明之多肽/多肽構建體，與T細胞表面上的CD3結合的結構域（包含互補位）包含如下VH區，該VH區選自由序列表中示例的相應SEQ ID號444至562和676中（特別是在SEQ ID號513-533和676中）描繪的VH區組成之群組。
在另一個實施方式中，根據本發明之多肽/多肽構建體，與T細胞表面上的CD3結合的結構域（包含互補位）包含SEQ ID NO: 676中描繪的VH區。
更較佳的是，包含與T細胞表面上的CD3結合的結構域（包含互補位）的根據本發明之多肽/多肽構建體包含選自由序列表中示例的相應SEQ ID號中描繪的VL區和VH區組成之群組的VL區和VH區，特別是以下VL區和VH區對特別是SEQ ID號507+514、508+519、509+521、510+525、511+528、512+532、534+513、535+515、536+516、537+517、538+518、539+520、540+522和541+523中描繪的，並且非常特別是VL區和VH區對特別是SEQ ID號676+677中描繪的。
根據本發明之上述多肽/多肽構建體的較佳的實施方式的特徵在於與T細胞表面上的CD3結合的結構域（包含互補位），其包含選自由SEQ ID NO: 542-562和SEQ ID NO: 678組成之群組的胺基酸序列。
根據本發明之上述多肽/多肽構建體的一個特定實施方式的特徵在於與T細胞表面上的CD3結合的結構域（包含互補位），其包含SEQ ID NO: 678中描繪的胺基酸序列。
根據本發明之上述多肽/多肽構建體的一個特定實施方式的特徵在於與T細胞表面上的CD3結合的結構域（包含互補位），該結構域包含SEQ ID NO: 678中描繪的胺基酸序列，並且其中該與CLDN6結合的結構域（包括互補位（即抗原結合（表位結合）結構））（或競爭與CLDN6結合的結構域）由包含以下中描繪的胺基酸序列的一對VH和VL區組成：SEQ ID NO: 11+12、SEQ ID NO: 25+26、SEQ ID NO: 39+40、SEQ ID NO: 53+54、SEQ ID NO: 67+68、SEQ ID NO: 81+82、SEQ ID NO: 95+96、SEQ ID NO: 109+110、SEQ ID NO: 123+124、SEQ ID NO: 137+138、SEQ ID NO: 151+152、SEQ ID NO: 165+166、SEQ ID NO: 179+180、SEQ ID NO: 193+194、SEQ ID NO: 207+208、SEQ ID NO: 221+222、SEQ ID NO: 235+236、SEQ ID NO: 249+250、或SEQ ID NO: 263+264。
根據本發明之上述多肽/多肽構建體的一個特定實施方式的特徵在於與T細胞表面上的CD3結合的結構域（包含互補位），其包含SEQ ID NO: 678中描繪的胺基酸序列，並且其中該與CLDN6結合的結構域（包含互補位（即抗原結合（表位結合）結構））由以下SEQ ID NO中描繪的胺基酸序列組成，或競爭與CLDN6結合的結構域包含以下SEQ ID NO中描繪的胺基酸序列：SEQ ID NO: 19、SEQ ID NO: 22、SEQ ID NO: 33、SEQ ID NO: 36、SEQ ID NO: 47、SEQ ID NO: 50、SEQ ID NO: 61、SEQ ID NO: 64、SEQ ID NO: 75、SEQ ID NO: 78、SEQ ID NO: 89、SEQ ID NO: 92、SEQ ID NO: 103、SEQ ID NO: 106、SEQ ID NO: 117、SEQ ID NO: 120、SEQ ID NO: 131、SEQ ID NO: 134、SEQ ID NO: 145、SEQ ID NO: 148、SEQ ID NO: 159、SEQ ID NO: 162、SEQ ID NO: 173、SEQ ID NO: 176、SEQ ID NO: 187、SEQ ID NO: 190、SEQ ID NO: 201、SEQ ID NO: 204、SEQ ID NO: 215、SEQ ID NO: 218、SEQ ID NO: 229、SEQ ID NO: 232、SEQ ID NO: 243、SEQ ID NO: 246、SEQ ID NO: 257、or SEQ ID NO: 260、SEQ ID NO: 271或SEQ ID NO: 274。
根據本發明之上述多肽/多肽構建體的一個特定實施方式的特徵在於與T細胞表面上的CD3結合的結構域（包含互補位），其包含SEQ ID NO: 678中描繪的胺基酸序列，並且其中該與CLDN6結合的結構域（包含互補位（即抗原結合（表位結合）結構））在選自以下群組的SEQ ID號中描繪，該群組包括SEQ ID NO: 19、22、33、36、47、50、75、78、201和204，特別是SEQ ID NO: 19和22，非常特別是SEQ ID NO: 22。
根據本發明之上述多肽/多肽構建體的另一個特定實施方式的特徵在於與T細胞表面上的CD3結合的結構域（包含互補位），其包含SEQ ID NO: 678中描繪的胺基酸序列，並且其中該與CLDN6結合的結構域（包含互補位（即抗原結合（表位結合）結構））在SEQ ID NO: 22中描繪。
根據本發明之上述多肽/多肽構建體的一個非常特定實施方式的特徵在於與T細胞表面上的CD3結合的結構域（包含互補位），所述結構域包含SEQ ID NO: 670、671和/或672中描繪的VH CDR序列HCDR1、HCDR2和/或HCDR3，和/或其中該與T細胞表面上的CD3結合的結構域（包含互補位）包含SEQ ID NO: 673、674和/或675中描繪的VL CDR序列LCDR1、LCDR2和/或LCDR3，並且其中該與CLDN6結合的結構域（包含互補位（即抗原結合（表位結合）結構））在SEQ ID NO: 22、36、50、78和204中描繪的序列的任一項中描繪。
根據本發明之上述多肽/多肽構建體的另一個非常特定實施方式的特徵在於與T細胞表面上的CD3結合的結構域（包含互補位），其中所述結構域包含SEQ ID NO: 670、671和/或672中描繪的VH CDR序列HCDR1、HCDR2和/或HCDR3，和/或其中該結構域包含SEQ ID NO: 673、674和/或675中描繪的VL CDR序列LCDR1、LCDR2和/或LCDR3，並且其中所述與CLDN6結合的結構域（包含互補位（即抗原結合（表位結合）結構））包含SEQ ID NO: 13、14和/或15中描繪的VH CDR序列HCDR1、HCDR2和/或HCDR3，和/或其中該結構域（包含互補位（即抗原結合（表位結合）結構））包含SEQ ID NO: 16、17和/或18中所示序列的任一項中描繪的VL CDR序列LCDR1、LCDR2和/或LCDR3。
根據本發明之上述多肽/多肽構建體的又一個非常特定實施方式的特徵在於與T細胞表面上的CD3結合的結構域（包含互補位），其中所述結構域包含SEQ ID NO: 670、671和/或672中所示序列的任一項中描繪的VH CDR序列HCDR1、HCDR2和/或HCDR3，和/或其中該結構域包含SEQ ID NO: 673、674和/或675中所示序列的任一項中描繪的VL CDR序列LCDR1、LCDR2和/或LCDR3，並且其中所述與CLDN6結合的結構域（包含互補位（即抗原結合（表位結合）結構））包含SEQ ID NO: 27、28和/或29中所示序列的任一項中描繪的VH CDR序列HCDR1、HCDR2和/或HCDR3，和/或其中該結構域（包含互補位（即抗原結合（表位結合）結構））包含SEQ ID NO: 30、31和/或32中所示序列的任一項中描繪的VL CDR序列LCDR1、LCDR2和/或LCDR3。
根據本發明之上述多肽/多肽構建體的仍然另一個非常特定實施方式的特徵在於與T細胞表面上的CD3結合的結構域（包含互補位），其中所述結構域包含SEQ ID NO: 670、671和/或672中所示序列的任一項中描繪的VH CDR序列HCDR1、HCDR2和/或HCDR3，和/或其中該結構域包含SEQ ID NO: 673、674和/或675中所示序列的任一項中描繪的VL CDR序列LCDR1、LCDR2和/或LCDR3，並且其中所述與CLDN6結合的結構域（包含互補位（即抗原結合（表位結合）結構））包含SEQ ID NO: 41、42和/或42中描繪的序列的任一項中描繪的VH CDR序列HCDR1、HCDR2和/或HCDR3，和/或其中該結構域（包含互補位（即抗原結合（表位結合）結構））包含SEQ ID NO: 44、45和/或46中所示序列的任一項中描繪的VL CDR序列LCDR1、LCDR2和/或LCDR3。
根據本發明之上述多肽/多肽構建體的仍然另一個非常特定實施方式的特徵在於與T細胞表面上的CD3結合的結構域（包含互補位），其中所述結構域包含SEQ ID NO: 670、671和/或672中所示序列的任一項中描繪的VH CDR序列HCDR1、HCDR2和/或HCDR3，和/或其中該結構域包含SEQ ID NO: 673、674和/或675中所示序列的任一項中描繪的VL CDR序列LCDR1、LCDR2和/或LCDR3，並且其中所述與CLDN6結合的結構域（包含互補位（即抗原結合（表位結合）結構））包含SEQ ID NO: 69、70和/或71中所示序列的任一項中描繪的VH CDR序列HCDR1、HCDR2和/或HCDR3，和/或其中該結構域（包含互補位（即抗原結合（表位結合）結構））包含SEQ ID NO: 72、73和/或74中所示序列的任一項中描繪的VL CDR序列LCDR1、LCDR2和/或LCDR3。
根據本發明之上述多肽/多肽構建體的仍然另一個非常特定實施方式的特徵在於與T細胞表面上的CD3結合的結構域（包含互補位），其中所述結構域包含SEQ ID NO: 670、671和/或672中所示序列的任一項中描繪的VH CDR序列HCDR1、HCDR2和/或HCDR3，和/或其中該結構域包含如SEQ ID NO: 673、674和/或675中所示序列的任一項中描繪的VL CDR序列LCDR1、LCDR2和/或LCDR3，並且其中所述與CLDN6結合的結構域（包含互補位（即抗原結合（表位結合）結構））包含SEQ ID NO: 195、196和/或197中所示序列的任一項中描繪的VH CDR序列HCDR1、HCDR2和/或HCDR3，和/或其中該結構域（包含互補位（即抗原結合（表位結合）結構））包含SEQ ID NO: 198、199和/或200中所示序列的任一項中描繪的VL CDR序列LCDR1、LCDR2和/或LCDR3。
核酸、宿主細胞和產生本發明化合物之方法
在第二方面，在本發明之上下文中進一步設想提供一種多核苷酸，該多核苷酸編碼如前述部分中任一項所描繪的本發明之多肽構建體。
在本發明之上下文中還設想提供一種載體，該載體包含本發明之多核苷酸。
進一步地，本發明提供了宿主細胞，該宿主細胞用本發明之多核苷酸或載體轉化或轉染。
在本發明之上下文中還設想提供一種用於產生本發明之多肽構建體之方法，所述方法包括在允許表現該構建體的條件下培養本發明之宿主細胞並且從該培養物中回收所產生的多肽構建體。
本發明之藥物組成物
在另一個方面，本發明提供了一種藥物組成物，該藥物組成物包含本發明之多肽化合物或根據本發明之方法產生的多肽化合物。
在所述方面內，在本發明之上下文中還設想該藥物組成物在約-20°C下穩定至少四週。
本發明之治療用途/方法
在本發明之上下文中進一步設想提供本發明之多肽化合物和包含根據本發明之方法產生的多肽化合物的藥物組成物，其用作藥物，特別是用於預防、治療或緩解選自增殖性疾病、腫瘤性疾病、癌症或免疫學障礙的疾病的藥物。
在本發明之上下文中進一步設想提供一種用於治療或緩解增殖性疾病、腫瘤性疾病、癌症或免疫學病症之方法，該方法包括向有需要的受試者投與本發明之多肽化合物或藥物組成物的步驟，其中視需要，該化合物根據本發明之方法產生。
較佳的是，該疾病選自以下群組，該群組包括選自由以下組成之群組的各種類型的表現CLDN6的癌症：尿膀胱癌、卵巢癌（特別是卵巢腺癌和卵巢畸胎癌）、肺癌（包括小細胞肺癌（SCLC）和非小細胞肺癌（NSCLC），特別是鱗狀細胞肺癌和腺癌）、胃癌、乳腺癌、肝癌、胰臟癌、皮膚癌（特別是基底細胞癌和鱗狀細胞癌）、惡性黑色素瘤、頭頸癌（特別是惡性多形性腺瘤）、肉瘤（特別是滑膜肉瘤和癌肉瘤）、膽管癌、尿膀胱癌（特別是移行細胞癌和乳頭狀癌）、腎癌（特別是腎細胞癌，包括透明細胞腎細胞癌和乳頭狀癌腎細胞癌）、大腸癌、小腸癌（包括回腸癌，特別是小腸腺癌和回腸腺癌）、睾丸胚胎癌、胎盤絨毛膜癌、宮頸癌、睾丸癌（特別是睾丸精原細胞瘤、睾丸畸胎瘤和胚胎睾丸癌）、子宮癌、生殖細胞腫瘤（如畸胎癌或胚胎癌，特別是睾丸的生殖細胞腫瘤及其轉移形式，非常特別是睾丸生殖細胞癌）、卵巢癌（特別是卵巢漿液性囊腺癌）和子宮癌（例如子宮體子宮內膜癌）、肺癌（包括小細胞肺癌（SCLC）和非小細胞肺癌（NSCLC），如肺腺癌）、三陰性乳腺癌、胃癌、膽管癌、食道癌、威爾姆氏瘤（Wilms tumor）、橫紋肌樣瘤，特別是卵巢癌、子宮癌和/或肺癌，並且更特別是卵巢漿液性囊腺癌、子宮癌肉瘤、子宮體子宮內膜癌，和/或特別是鱗狀細胞肺癌和肺腺癌。
還提供了本文所述之化合物在製備用於治療或預防或改善腫瘤疾病，特別是卵巢癌、子宮癌和/或肺癌的藥物中的用途。
在本發明之上下文中進一步設想提供一種用於治療或緩解胃腸癌之方法，該方法包括向有需要的受試者投與針對CLDN6和CD3的構建體的步驟。
在本發明之上下文中還設想提供針對CLDN6和CD3的多肽/多肽構建體，其用作藥物，特別是用於治療或改善例如卵巢癌、子宮癌、肺癌（特別是卵巢癌，特別是卵巢腺癌和卵巢畸胎癌）、肺癌（包括小細胞肺癌（SCLC）和非小細胞肺癌（NSCLC），特別是鱗狀細胞肺癌和腺癌）的藥物。
本發明之套組
在另一方面，在本發明之上下文中還設想提供一種套組，該套組包含本發明之多肽構建體或根據本發明之方法產生的抗體構建體、本發明之多核苷酸、本發明之載體、和/或本發明之宿主細胞。
根據本發明之術語定義
術語「多肽構建體」（可替代地簡稱為「化合物」）係指包含自身含有互補位的結構域的抗原結合（或表位結合）分子。在本發明之上下文中，多肽構建體被理解為一種有機聚合物，其包含至少一條天然不存在但經工程化的連續的、無分支的胺基酸鏈。作為單一多肽的多肽構建體的一個實例係包含核心結構的BiTE
®分子，該核心結構在單一多肽鏈上包含至少一個功能性靶標結合結構域以及至少一個完整的功能性CD3結合結構域，其中該等結構域經由柔性肽（「連接子」）在沒有任何進一步插入的結構域的情況下直接連接，這與Xmab不同，該Xmab在不同的多肽鏈上包含靶標結合物和CD3結合物。在本發明之上下文中，同樣設想包含多於一條胺基酸鏈的此類多肽構建物。較佳的是，術語「多肽」與本發明之化合物的單鏈形式結合使用，而「多肽構建體」可較佳的是也更適合描述包含多於一條多肽鏈（例如兩條、三條或四條多肽鏈）的多肽。此外，術語「多肽構建體」也適於描述包含一種或多種非基於胺基酸的成分的本發明化合物，例如人血清白蛋白等（HSA）。多肽胺基酸鏈典型地包含至少50個胺基酸，較佳的是至少100、200、300、400或500個胺基酸。在本發明之上下文中還設想，聚合物的胺基酸鏈與不由胺基酸組成的實體連接。
多肽包括基於抗體（例如全長免疫球蛋白分子）的結構和/或功能的結構和/或功能特徵。因此，多肽構建體特異性地且較佳的是、選擇性地或免疫特異性地與其靶標或抗原結合，更準確地說與所述靶標或靶抗原的表位結合，和/或它包含天然存在於抗體中的重鏈可變區（VH）和/或輕鏈可變區（VL），或包含由其衍生的結構域。因此，該構建體可替代地被認為包含互補位結構化（即互補位結構形成）和表位結合結構，如在天然抗體或其片段中發現的那些。根據本發明之多肽構建體包含允許免疫特異性靶標結合的最低抗體結構要求，即免疫特異性地或免疫選擇性地識別靶抗原上的表位的互補位。這種最低要求可以例如藉由至少三個輕鏈CDR（即VL區的CDR1、CDR2和CDR3）和/或三個重鏈CDR（即VH區的CDR1、CDR2和CDR3）、較佳的是全部六個CDR的存在來定義。因此，多肽構建體的特徵可能在於在一個或兩個結合結構域中存在三個或六個CDR，並且技術人員知道那些CDR在互補位結合結構內位於哪裡（以什麼順序）。 如本文所用，術語「抗原結合結構」係指包含抗原結合結構的任何多肽或對抗原具有結合活性的任何分子。肽和蛋白不限於衍生自活著的生物體的那些，例如，它們可以是由人工設計的序列產生的多肽。它們也可以是天然存在的多肽、合成多肽、重組多肽等中的任一種。由於根據本發明之抗原結合結構與抗原的部分特異性結合，即它們與表位特異性結合，因此抗原（表位）結合結構也可以定義為「互補位結構」。因此，根據本發明之多肽/多肽構建體也可定義為包含較佳的是與靶抗原/靶表位免疫特異性或免疫選擇性結合的互補位的結構域和較佳的是免疫特異性或免疫選擇性地與如本文定義的CD3分子的另一個靶抗原/靶表位結合的另一個互補位結構域。因此，每當本說明書提及本發明之構建體或分子的結構域時，該構建體包含至少一個如本文所定義（特別是根據所附請求項中任一項）的結合CLDN6的互補位結構（或互補位），以及如本文所定義的結合CD3的另一個互補位結構。
如根據本發明所使用的術語「抗體」包含全長抗體，還包括藉由生物技術或蛋白質工程方法或過程產生的駱駝抗體和其他免疫球蛋白。該等全長抗體可以是例如單株抗體、重組抗體、嵌合抗體、去免疫化（deimmunized）抗體、人源化抗體和人抗體，以及來自其他物種（如小鼠、倉鼠、兔、大鼠、山羊或非人靈長類動物）的抗體。
本發明之「多肽/多肽構建體」還可以包含天然存在的全長免疫球蛋白結構。例如，它們可以包含（至少）兩條全長抗體重鏈和兩條全長抗體輕鏈。然而，鑒於根據本發明之多肽/多肽構建體包含與CLDN6結合的互補位的一個結構域和與CD3結合的互補位的另一個結構域，它們不是天然存在的，並且它們在其功能方面與天然存在的產物明顯不同。因此，本發明之多肽或多肽構建體係包含具有不同特異性和/或選擇性的不同結合結構域的人工「雜交」分子。
如上所述，本發明之多肽可以包含多於一條多肽鏈，即包含兩條或更多條多肽鏈的多肽也受本發明之約束，特別是形成允許與CLDN6和CD3免疫特異性結合的三維蛋白質樣結構的多肽。因此，術語「多肽構建體」的定義包括僅由一條多肽鏈組成的分子以及由兩條、三條、四條、或更多條多肽鏈組成的分子，該等鏈可以是相同的（同源二聚體、同源三聚體或同源寡聚物）或不同的（異源二聚體、異源三聚體或異源寡聚物）。上述鑒定的抗體及其片段、變體、衍生物和由其衍生的構建體的實例尤其描述於Harlow和Lane, Antibodies: A laboratory manual [抗體：實驗室手冊], CSHL Press [冷泉港實驗室出版社] (1988)；Kontermann和Dübel, Antibody Engineering [抗體工程], Springer [斯普林格出版社], 第2版 2010；以及Little, Recombinant Antibodies for Immunotherapy [用於免疫療法的重組抗體], Cambridge University Press [劍橋大學出版社] 2009
本發明之「多肽/多肽構建體」還可以包含全長抗體的片段，如VH、VHH、VL、(s)dAb、Fv、輕鏈（VL-CL）、Fd（VH-CH1）、重鏈、Fab、Fab’、F(ab')2或「rIgG」（由重鏈和輕鏈組成的「半抗體」）。根據本發明之多肽/多肽構建體還可以包含抗體的修飾的片段，也稱為抗體變體或抗體衍生物。實例包括但不限於scFv、di-scFv或bi(s)-scFv、scFv-Fc、scFv-拉鍊（zipper）、scFab、Fab2、Fab3、雙抗體、單鏈雙抗體、串聯雙抗體（Tandab）、串聯di-scFv、串聯tri-scFv、„微型抗體「，其由如下結構示例：(VH-VL-CH3)2、(scFv-CH3)2、((scFv)2-CH3 + CH3)、((scFv)2-CH3)或(scFv-CH3-scFv)2、多體抗體如三抗體（triabody）或四抗體（tetrabody）、和單結構域抗體（如奈米抗體或僅包含一個可變區的單可變結構域抗體，該結構域可以是VHH、VH或VL，它獨立於其他可變區或結構域而選擇性和較佳的是特異性結合抗原或靶標）。根據本發明之多肽/多肽構建體的其他可能形式係交叉體、最大體、異Fc構建體、單Fc構建體和scFc構建體。那些形式的實例將在下文進行描述。
此外，術語「多肽構建體」的定義包括藉由不同的結合結構域選擇性和較佳的是特異性地結合兩個、三個或更多個抗原結構（表位）的二價和多價（polyvalent/multivalent）多肽/多肽構建體以及雙特異性和多特異性（polyspecific/multispecific）多肽/多肽構建體。多肽構建體可以具有比特異性更多的結合價，例如在其中兩個結合結構域針對一個靶標（CLDN6）並且一個結合結構域針對另一個靶標（CD3）或反之亦然的情況下，在這種情況下，多肽構建體係三價的和雙特異性的。通常，術語「雙特異性」包括多肽構建體結合（至少）兩種不同抗原（如CLDN6和CD3）的含義。
術語「互補位」、「抗原結合結構域」、「表位結合結構域」、「結合結構域」或「與……結合的結構域」與本發明相關地表徵構建體的結構域，其選擇性和較佳的是特異性或免疫特異性地與在靶標或抗原（此處：在第一結構域的情況下為CLDN6，以及在第二結構域的情況下為CD3）上的表位結合/相互作用/識別該表位。就關於本文所述之「構建體」而言，術語「結合結構域」或「與……結合的結構域」或「結構域」與本發明相關地表徵構建體的結構域，其免疫特異性地與在靶標或抗原上的表位結合/相互作用/識別表位（即選擇性地與某些胺基酸相互作用）。第一結構域（結合靶抗原）的結構和功能，以及較佳的是第二結構域（結合CD3）的結構和/或功能基於抗體（例如全長免疫球蛋白多肽）的結構和/或功能。因此，「結合結構域」或「與……結合的結構域」可以包含允許免疫特異性靶結合的抗體的最小結構要求。第一結構域的這種最小結構要求可以例如藉由至少三個輕鏈CDR（即VL區的CDR1、CDR2和CDR3）和/或三個重鏈CDR（即VH區的CDR1、CDR2和CDR3）、較佳的是全部六個CDR的存在來定義。設想第二結構域還包含允許免疫特異性靶標結合的這種抗體最小結構要求。更較佳的是，第二結構域還包含至少三個輕鏈CDR（即VL區的CDR1、CDR2和CDR3）和/或三個重鏈CDR（即VH區的CDR1、CDR2和CDR3）、較佳的是全部六個CDR。「與……結合的結構域」（或「結合結構域」）典型地可以包含抗體輕鏈可變區（VL）和抗體重鏈可變區（VH）；然而，它不必須包含兩者，但可以包含VH或VL中的僅一者。例如，Fd片段通常保留完整抗原結合結構域的一些抗原結合功能。如本文所用，術語「互補位」、「抗原結合結構」和「表位結合結構」還指抗體（或根據本發明之分子）的一部分，其包含特異性結合抗原或其一部分的全部或部分並與之互補的區域，即抗體只能與抗原的特定部分結合。該特定部分稱為「表位」。抗原結合域可以由一個或多個抗體可變結構域提供。較佳的是，抗原結合結構域包含抗體可變區，其包含抗體輕鏈可變區（VL）和抗體重鏈可變區（VH）。這種較佳的抗原結合結構域包括例如「單鏈Fv（scFv）」、「單鏈抗體」、「Fv」、「單鏈Fv2（scFv2）」、「Fab」和「F(ab')2」。「互補位」的特徵還在於與表位（抗原/靶標）側面的特定胺基酸發生化學相互作用的特定胺基酸。
「與……結合的結構域」、「包含互補位的結構域」（或「結合結構域」、「抗原結合結構」、「表位結合結構」）的形式的實例包括但不限於全長抗體、全長抗體的片段（如VH、VHH、VL）、(s)dAb、Fv、輕鏈（VL-CL）、Fd（VH-CH1）、重鏈、Fab、Fab’、F(ab')2或「r IgG」（「半抗體」））、抗體變體或衍生物（如scFv、二-scFv或聯(s)-scFv、scFv-Fc、scFv-拉鍊、scFab、Fab2、Fab3、雙抗體、單鏈雙抗體、串聯雙抗體（Tandab）、串聯二-scFv、串聯三-scFv、「微型抗體」（選自形式如(VH-VL-CH3)2、(scFv-CH3)2、((scFv)2-CH3 + CH3))、((scFv)2-CH3)或(scFv-CH3-scFv)2、多抗體（如三抗體或四抗體）、以及單結構域抗體（如奈米抗體或單可變結構域抗體）（僅包含一個可變區，其可以是VHH、VH或VL）。「與……結合的結構域」（或「結合結構域」）的形式的其他實例包括 (1) 包含VL、VH、CL和CH1的抗體片段或變體（如Fab）；(2) 包含兩個連接的Fab片段的抗體片段或變體（如F(ab')2）；(3) 包含VH和CH1的抗體片段或變體（如Fd）；(4) 包含VL和CL的抗體片段或變體（如輕鏈）；(5) 包含VL和VH的抗體片段或變體（如Fv）；(5) 具有VH結構域的dAb片段（Ward等人, (1989) Nature [自然] 341 : 544-546）；(6) 包含重鏈和/或輕鏈的至少三個分離的CDR的抗體變體；和 (7) 單鏈Fv（scFv）。根據本發明之構建體或結合結構域的實施方式的實例例如描述於以下中：WO 00/006605、WO 2005/040220、WO 2008/119567、WO 2010/037838、WO 2013/026837、WO 2013/026833、US 2014/0308285、US 2014/0302037、WO 2014/144722、WO 2014/151910和WO 2015/048272。在本發明之上下文中，互補位理解為作為如本文所述之多肽的一部分並且識別抗原並與其結合的抗原結合位點。互補位典型地是約至少5個胺基酸的小區域。如本文理解的互補位典型地包含抗體衍生的重鏈（VH）和輕鏈（VL）序列的部分。根據本發明之多肽的各個結合結構域提供了包含一組6個互補決定區（CDR環）（其中每三個分別包含在抗體衍生的VH和VL序列內）的互補位。
對於化合物，特別是對於本發明之構建體，設想a) 構建體係單鏈多肽或單鏈構建體，b) 第一結構域係scFv的形式，c) 第二結構域係scFv的形式，d) 第一和第二結構域經由連接子連接，較佳的是肽連接子，更較佳的是甘胺酸/絲胺酸連接子，和/或e) 構建體包含提供延長的血清半衰期的結構域，如基於Fc的結構域或人血清白蛋白（HSA）。在後一種情況下，如下是較佳的實施方案，其中術語「多肽構建體」明確表示它包含多於一條肽鏈。
本發明之構建體較佳的是「體外產生的構建體」和/或「重組構建體」。在本發明之上下文中，術語「體外產生的」係指根據上述定義的構建體，其中結合結構域或可變區的全部或部分（例如，至少一個CDR）在非免疫細胞選擇中（例如，在體外噬菌體展示中、在蛋白質晶片上或在其中可以測試候選胺基酸序列結合抗原的能力的任何其他方法中）產生。因此，這個術語較佳的是排除僅由動物免疫細胞中的基因組重排產生的序列。設想構建體的第一和/或第二結構域係藉由噬菌體展示或文庫篩選方法產生或可藉由其獲得的，而不是藉由將來自預先存在的（單株）抗體的CDR序列移植到支架中產生或可藉由其獲得的。「重組構建體」係使用（尤其）重組DNA技術或基因工程產生或生產的構建體。
設想本發明之構建體係單株的。如本文使用的，命名為「單株」（mAb）的多肽或構建體獲得自基本上同質的抗體/構建體的群體，即除了可以以少量存在的可能的天然發生的突變和/或翻譯後修飾（例如，異構化、醯胺化）之外，在群體中包含的各個抗體/構建體係相同的（具體地，關於它們的胺基酸序列）。與典型地包括針對不同決定簇（或表位）的不同抗體的多株抗體製劑相比，單株抗體/構建體針對抗原內的單一表位具有高度特異性。除了它們的特異性之外，單株抗體還在它們藉由雜交瘤培養物合成，因此不被其他免疫球蛋白污染方面係有優勢的。修飾語「單株」指示獲得自基本上均質的抗體群體的抗體/構建體的特徵，並且不應理解為要求藉由任何特定方法產生抗體。
對於單株抗體的製備，可以使用提供由連續細胞系培養物產生的抗體的任何技術。例如，有待使用的單株抗體可以藉由Koehler等人, Nature [自然], 256: 495 (1975)首次描述的雜交瘤方法，或可以藉由重組DNA方法（參見，例如美國專利案號4,816,567）製備。用於產生人單株抗體的另外技術的實例包括三源雜交瘤技術、人B細胞雜交瘤技術（Kozbor, Immunology Today [今日免疫學] 4 (1983), 72）和EBV-雜交瘤技術（Cole等人, Monoclonal Antibodies and Cancer Therapy [單株抗體和癌症治療], Alan R. Liss公司 (1985), 77-96）。
然後可以使用標準方法（如酶聯免疫吸附測定（ELISA）和表面電漿共振（BIACORE™）分析篩選雜交瘤，以鑒定一種或多種產生與指定抗原選擇性和較佳的是特異性或免疫特異性結合的抗體的雜交瘤。任何形式的相關抗原可用作免疫原，例如重組抗原、天然存在的形式、其任何變體或片段及其抗原肽。如在BIAcore™系統中採用的表面電漿共振可以用於增加與靶抗原的表位結合的噬菌體抗體/構建體的效率（Schier, Human Antibodies Hybridomas [人抗體雜交瘤] 7 (1996), 97-105；Malmborg, J. Immunol. Methods [免疫學方法雜誌] 183 (1995), 7-13）。
另一種製備構建體或結合結構域的示例性方法包括篩選蛋白質表現文庫，例如噬菌體展示或核糖體展示文庫。噬菌體展示例如描述於以下中：Ladner等人, 美國專利案號5,223,409；Smith (1985) Science [科學] 228:1315-1317、Clackson等人, Nature [自然], 352: 624-628 (1991)和Marks等人, J. Mol. Biol. [分子生物學雜誌], 222: 581-597 (1991)。
除了使用展示文庫之外，還可以使用相關抗原來免疫非人動物，例如齧齒動物（諸如小鼠、倉鼠、兔或大鼠）。在一個實施方式中，非人動物包括人免疫球蛋白基因的至少一部分。例如，可能利用人Ig（免疫球蛋白）基因座的大片段來工程化小鼠抗體產生缺陷的小鼠品系。使用雜交瘤技術，可以產生並選擇衍生自具有所希望的特異性的基因的抗原特異性單株抗體。參見，例如Xenomouse™；Green等人 (1994) Nature Genetics [自然遺傳學] 7:13-21；US 2003-0070185；WO 96/34096和WO 96/33735。
單株抗體也可以從非人動物獲得，然後使用本領域已知的重組DNA技術進行修飾，例如人源化、去免疫、呈現嵌合等。經修飾的構建體或結合結構域的實例包括非人抗體/構建體的人源化變體、「親和力成熟」構建體或結合結構域（參見，例如Hawkins等人 J. Mol. Biol. [分子生物學雜誌] 254, 889-896 (1992) 以及Lowman等人, Biochemistry [生物化學] 30, 10832-10837 (1991)）以及具有改變的效應子功能的抗體變體或突變體（參見，例如美國專利5,648,260；Kontermann和Dübel (2010), 上述引文；以及Little (2009), 上述引文）。
在免疫學中，親和力成熟係這樣的過程：藉由該過程，在免疫反應的過程中B細胞產生與抗原的親和力增加的抗體。反復暴露於相同的抗原後，宿主會產生親和力依次更大的抗體。與天然原型類似，體外親和力成熟係基於突變和選擇的原理。體外親和力成熟已成功用於優化抗體、抗體片段、抗體變體、構建體或結合結構域。使用輻射、化學誘變劑或易錯PCR在CDR內引入隨機突變。此外，遺傳多樣性可以藉由鏈改組來增加。使用展示方法（如噬菌體展示）進行兩輪或三輪突變和選擇通常產生具有低納莫耳範圍內的親和力的抗體、抗體片段、抗體變體、構建體或結合結構域。
本發明之構建體或結合結構域的胺基酸取代變化的較佳的類型關於取代親本抗體結構（例如人源化或人抗體結構）的高變區內的一個或多個殘基。一般來講，選擇用於進一步開發的一種或多種所得變體相對於產生它們的親本抗體結構將具有改善的生物特性。用於產生此類取代變體的便利方式關於使用噬菌體展示的親和力成熟。簡言之，將高變區的幾個位點（例如6-7個位點）突變以在每個位點產生所有可能的胺基酸取代。由此產生的變體以單價方式從絲狀噬菌體顆粒展示為與每個顆粒內包裝的M13的基因III產物的融合物。然後如本文所揭露那樣篩選噬菌體展示的變體的生物活性（例如結合親和力）。為了鑒定對抗原結合有顯著貢獻的候選高變區位點（修飾候選物），還可以進行丙胺酸掃描誘變。可替代地或另外地，分析在抗原與構建體或結合結構域之間的複合物的晶體結構以鑒定在結合結構域與其特異性抗原之間的接觸點可能是有益的。根據本文闡述的技術，此類接觸殘基和相鄰殘基係用於取代的候選者。一旦產生了此類變體，就如本文所述對這組變體進行篩選，並且可以選擇在一種或多種相關測定中具有優異特性的抗體、其抗原結合片段、構建體或結合結構域用於進一步的開發。
本發明之構建體和結合結構域具體地包括「嵌合」形式（其中重鏈和/或輕鏈的一部分與衍生自特定物種或屬於特定抗體類別或亞類的抗體中的相應序列相同或同源，而一條或多條鏈的其餘部分與衍生自另一物種或屬於另一抗體類別或亞類的抗體中的相應序列相同或同源），以及此類抗體的片段或變體，只要它們表現出期望的生物活性即可（美國專利案號4,816,567；Morrison等人, Proc. Natl. Acad. Sci. USA [美國國家科學院院刊] 81: 6851-6855 (1984)）；本文感興趣的嵌合構建體或結合結構域包括「靈長類化」構建體，該等抗體構建體包含衍生自非人靈長類動物（例如，舊大陸猴、猿等）的可變結構域抗原結合序列、和人恒定區序列。已經描述了多種用於製備嵌合抗體或構建體之方法。參見，例如Morrison等人, Proc. Natl. Acad. ScL U.S.A. [美國國家科學院院刊] 81:6851, 1985；Takeda等人, Nature [自然] 314:452, 1985；Cabilly等人, 美國專利案號4,816,567；Boss等人, 美國專利案號4,816,397；Tanaguchi等人, EP 0171496；EP 0173494；和GB 2177096。
抗體、多肽構建體、抗體片段、抗體變體或結合結構域還可以藉由使用例如在WO 98/52976或WO 00/34317中所揭露之方法將人T細胞表位特異性缺失（稱為「去免疫」之方法）來進行修飾。簡言之，可以針對與MHC II類結合的肽分析抗體、構建體或結合結構域的重鏈和輕鏈可變區；該等肽代表潛在的T細胞表位（如例如在WO 98/52976和WO 00/34317中所定義的）。為了檢測潛在T細胞表位，可以應用稱為「肽穿線」的電腦建模方法，並且此外針對VH和VL序列中存在的模體，可以搜索人MHC II類結合肽的數據庫，如WO 98/52976和WO 00/34317中所述。該等模體與18種主要的MHC II類DR同種異型中的任一種結合，並且因此構成潛在T細胞表位。檢測到的潛在T細胞表位可以藉由取代可變結構域或可變區中的少量胺基酸殘基，或者較佳的是藉由單個胺基酸取代來消除。典型地，進行保守取代。通常但不排他地，可以使用與人種系抗體序列中的位置共有的胺基酸。人種系序列例如揭露於以下中：Tomlinson等人 (1992) J. MoI.Biol. [分子生物學雜誌] 227:776-798；Cook, G.P.等人 (1995) Immunol. Today [今日免疫學] 第16卷 (5): 237-242；和Tomlinson等人 (1995) EMBO J. [歐洲分子生物學學會雜誌] 14: 14:4628-4638。V BASE目錄（www2.mrc-lmb.cam.ac.uk/vbase/list2.php）提供了人免疫球蛋白可變區序列的綜合目錄（由Tomlinson, LA.等人彙編 MRC Centre for Protein Engineering, Cambridge, UK [英國劍橋MRC蛋白質工程中心]）。該等序列可用作例如框架區和CDR的人序列的來源。也可以使用共有的人框架區，例如如美國專利案號6,300,064中所述。
「人源化」抗體、其變體或片段、構建體和結合結構域係基於主要人序列的免疫球蛋白，該等主要人序列含有一種或多種衍生自非人免疫球蛋白的最小序列。在大多數情況下，人源化抗體、其變體或片段、構建體和結合結構域基於人免疫球蛋白（受體抗體），其中來自高變區或CDR的殘基被來自非人物種（供體抗體）（如具有所希望的特異性、親和力、能力和/或生物活性的齧齒動物（例如，小鼠、倉鼠、大鼠、或兔））的高變區或CDR的殘基替代。在一些情況下，人免疫球蛋白的Fv框架區（FR）殘基被相應的非人類殘基替代。此外，如本文使用的，「人源化」抗體、變體或其片段、抗體、構建體和結合結構域還可以包含在受體抗體或供體抗體中均未發現的殘基。進行該等修飾以進一步改善和優化抗體性能。人源化抗體、變體或其片段、構建體和結合結構域還可以至少包含免疫球蛋白恒定區（如Fc）的一部分，典型地人免疫球蛋白的恒定區的一部分。對於更多的細節，參見Jones等人, Nature [自然], 321: 522-525 (1986)；Reichmann等人, Nature [自然], 332: 323-329 (1988)；和Presta, Curr.Op.Struct.Biol. [結構生物學新見], 2: 593-596 (1992)。
人源化抗體、其變體或片段、構建體和結合結構域可以藉由用人（Fv）可變區的等效序列替代不直接參與抗原結合的（Fv）可變區的序列來產生。用於產生此類分子的示例性方法由以下提供：Morrison (1985) Science [科學] 229:1202-1207；Oi等人 (1986) BioTechniques [生物技術] 4:214；以及US 5,585,089；US 5,693,761；US 5,693,762；US 5,859,205；以及US 6,407,213。該等方法包括分離、操縱和表現編碼來自重鏈或輕鏈中的至少一者的全部或部分免疫球蛋白（Fv）可變區的核酸序列。此類核酸可以獲自如上所述之產生針對預定靶的抗體的雜交瘤，以及其他來源。然後可以將編碼人源化抗體、其變體或片段、構建體或結合結構域的重組DNA選殖到合適的表現載體中。
人源化抗體、其變體或片段、構建體和結合結構域還可以使用轉基因動物（如表現人重鏈和輕鏈基因但不能表現內源性小鼠免疫球蛋白重鏈和輕鏈基因的小鼠）來產生。Winter描述了可用於製備本文所述之人源化分子的示例性CDR移植方法（美國專利案號5,225,539）。給定人序列的全部CDR可以用至少一部分非人CDR替代，或者僅一些CDR可以用非人CDR替代。僅需要替代用於將人源化分子與預定抗原結合所需的CDR數量。
可以藉由引入保守取代、共有序列取代、種系取代和/或回復突變來優化人源化抗體、其變體或片段、構建體或結合結構域。此類改變的免疫球蛋白分子可以藉由本領域已知的幾種技術中的任何一種來製備（例如，Teng等人, Proc. Natl. Acad. Sci. U.S.A. [美國國家科學院院刊], 80: 7308-7312, 1983；Kozbor等人, Immunology Today [今日免疫學], 4: 7279, 1983；Olsson等人, Meth. Enzymol. [酶學方法], 92: 3-16, 1982，以及EP 239 400）。
人抗小鼠抗體（HAMA）反應已經導致該行業製備嵌合或其他人源化抗體/構建體。然而，據預期，特別是在抗體或構建體的長期或多劑量利用中，會觀察到某些人抗嵌合抗體（HACA）反應。因此，期望提供構建體，該等抗體構建體包含針對CLDN6的人結合結構域和/或針對CD3的人結合結構域，以消除HAMA或HACA反應的問題和/或效應。
因此，根據一個實施方式，多肽構建體、第一結合結構域和/或另一個結合結構域係「人」的。術語「人抗體」、「人構建體」和「人結合結構域」分別包括具有抗體衍生區域的抗體、構建體和結合結構域，該等抗體衍生區域係如基本上對應於本領域中已知的人種系免疫球蛋白序列的可變和恒定區或結構域，包括例如由Kabat等人 (1991)（上述引文）描述的那些。本發明之人構建體或結合結構域可以包含例如CDR中且特別是CDR3中不由人種系免疫球蛋白序列編碼的胺基酸殘基（例如，藉由體外隨機或位點特異性誘變或藉由體內體細胞突變引入的突變）。人構建體或結合結構域可以具有至少1個、2個、3個、4個、5個或更多個被不由人種系免疫球蛋白序列編碼的胺基酸殘基替代的位置。然而，如本文使用的人抗體、構建體和結合結構域的定義還涵蓋僅包括非人工和/或遺傳改變的人抗體序列（如可以藉由使用技術或系統（如Xenomouse）衍生的那些）的完全人抗體、構建體和結合結構域。
包含至少一個人結合結構域的多肽/多肽構建體避免了與具有非人（如齧齒動物（例如鼠、大鼠、倉鼠或兔））可變區和/或恒定區的抗體或構建體相關的一些問題。此類齧齒動物衍生的蛋白質的存在可以導致抗體或構建體的快速清除或可以導致患者產生針對抗體或構建體的免疫反應。為了避免使用齧齒動物衍生的構建體，可以藉由將人抗體功能引入齧齒動物中以便使齧齒動物產生完全人抗體來產生人源化或完全人構建體。
在YAC中選殖和重組兆鹼基大小的人基因座並將它們引入到小鼠種系中的能力為闡明非常大或粗略定位的基因座的功能組分以及產生有用的人疾病模型提供了強有力之方法。此外，使用這種技術將小鼠基因座取代為其人等效物，可以提供關於人基因產物在發育過程中的表現和調控、其與其他系統的通信以及其參與疾病誘導和進展的獨特見解。
這種策略的重要實際應用係小鼠體液免疫系統的「人源化」。將人免疫球蛋白（Ig）基因座引入到其中內源性Ig基因已經失活的小鼠中，提供了研究抗體的程式化表現和組裝的根本機制以及其在B細胞發育中的作用的機會。此外，這種策略可以為完全人單株抗體（mAb）的產生提供理想來源 - 這係有助於實現抗體療法在人疾病中的前景的重要里程碑。預期完全人抗體或由其衍生的構建體將小鼠或小鼠衍生的mAb所固有的免疫原性和變應性反應最小化，並且由此增加投與的抗體/構建體的功效和安全性。可以預期使用完全人抗體或構建體在治療需要重複投與化合物的慢性和復發性人類疾病（如炎症、自體免疫和癌症）中提供大量的優勢。
實現這一目標的一種方法係用人Ig基因座的大片段工程化小鼠抗體產生缺陷的小鼠品系，預期這種小鼠在不存在小鼠抗體的情況下將產生大的人抗體組庫。大的人Ig片段將保持大的可變基因多樣性以及對抗體產生和表現的適當調控。藉由利用小鼠機構實現抗體多樣化和選擇以及缺乏對人蛋白質的免疫耐受性，在該等小鼠品系中再生的人抗體組庫應產生針對任何目的抗原（包括人抗原）的高親和力抗體。使用雜交瘤技術，可以容易地產生和選擇具有所希望特異性的抗原特異性人mAb。結合第一種XenoMouse小鼠品系的產生證明了這個一般策略（參見Green等人 Nature Genetics [自然遺傳學] 7:13-21 (1994)）。用酵母人工染色體（YAC）工程化XenoMouse品系，該等酵母人工染色體分別含有人重鏈基因座和κ輕鏈基因座的245 kb和190 kb大小的種系構型片段，該等片段含有核心可變區和恒定區序列。證明含有人Ig的YAC與小鼠系統相容以重排和表現抗體，並且能夠取代失活的小鼠Ig基因。這藉由其誘導B細胞發育、產生完全人抗體的成人樣人組庫和產生抗原特異性人mAb的能力來證明。該等結果還表明，引入含有更多數量的V基因、另外的調控元件和人Ig恒定區的更大部分的人Ig基因座可以實質上再現作為對感染和免疫的人體液反應的特徵的完整組庫。Green等人的工作擴展到藉由分別引入兆鹼基大小的人重鏈基因座和κ輕鏈基因座的種系構型YAC片段來引入大於約80%的人抗體組庫。參見Mendez等人 Nature Genetics [自然遺傳學] 15:146-156 (1997)和美國專利申請序號08/759,620。
XenoMouse模型的產生進一步論述和描述於以下中：美國專利申請序號07/466,008、序號07/610,515、序號07/919,297、序號07/922,649、序號08/031,801、序號08/112,848、序號08/234,145、序號08/376,279、序號08/430,938、序號08/464,584、序號08/464,582、序號08/463,191、序號08/462,837、序號08/486,853、序號08/486,857、序號08/486,859、序號08/462,513、序號08/724,752、序號08/759,620；和美國專利案號6,162,963；6,150,584；6,114,598；6,075,181和5,939,598以及日本專利案號3 068 180 B2、3 068 506 B2、和3 068 507 B2。還參見Mendez等人 Nature Genetics [自然遺傳學] 15:146-156 (1997) 以及Green和Jakobovits J. Exp. Med. [實驗醫學雜誌] 188:483-495 (1998)、EP 0 463 151 B1、WO 94/02602、WO 96/34096、WO 98/24893、WO 00/76310和WO 03/47336。
在一個可替代之方法中，包括真藥物國際公司（GenPharm International, Inc.）的其他公司利用了「微基因座」方法。在微基因座方法中，藉由包含來自Ig基因座的碎片（單獨的基因）來模擬外源性Ig基因座。因此，將一個或多個VH基因、一個或多個DH基因、一個或多個JH基因、mu恒定區和第二恒定區（較佳的是γ恒定區）形成為用於插入到動物中的構建體。此方法描述於以下中：Surani等人的美國專利案號5,545,807和美國專利案號5,545,806；5,625,825；5,625,126；5,633,425；5,661,016；5,770,429；5,789,650；5,814,318；5,877,397；5,874,299；和6,255,458（各自為Lonberg和Kay）、Krimpenfort和Berns的美國專利案號5,591,669和6,023.010、Berns等人的美國專利案號5,612,205；5,721,367；和5,789,215、以及Choi和Dunn的美國專利案號5,643,763、以及真藥物（GenPharm）國際美國專利申請序號07/574,748、序號07/575,962、序號07/810,279、序號07/853,408、序號07/904,068、序號07/990,860、序號08/053,131、序號08/096,762、序號08/155,301、序號08/161,739、序號08/165,699、序號08/209,741。還參見EP 0 546 073 B1、WO 92/03918、WO 92/22645、WO 92/22647、WO 92/22670、WO 93/12227、WO 94/00569、WO 94/25585、WO 96/14436、WO 97/13852和WO 98/24884以及美國專利案號5,981,175。進一步參見Taylor等人 (1992)，Chen等人 (1993)，Tuaillon等人 (1993)，Choi等人 (1993)，Lonberg等人 (1994)，Taylor等人 (1994)，以及Tuaillon等人 (1995)，Fishwild等人 (1996)。
Kirin也展示了從藉由微細胞融合引入大段染色體或整個染色體的小鼠產生人抗體。參見歐洲專利申請號773 288和843 961。Xenerex Biosciences正在開發用於人抗體的潛在產生的技術。在這種技術中，用人淋巴細胞（例如B和/或T細胞）重構SCID小鼠。然後將小鼠用抗原免疫並且可產生針對抗原的免疫反應。參見美國專利案號5,476,996；5,698,767；和5,958,765。
在一些實施方式中，本發明之構建體係「分離的」或「實質上純的」構建體。在用於描述本文所揭露的構建體時，「分離的」或「基本上純的」意味著構建體已經從其產生環境的組分鑒定、分離和/或回收。較佳的是，構建體不與或實質上不與來自其產生環境的所有其他組分締合。其產生環境的污染組分，諸如由重組轉染細胞產生的污染組分，係可能干擾構建體的診斷或治療用途的物質，並且可能包括酶、激素和其他蛋白質或非蛋白質化合物。應當理解，根據情況，分離的或基本上純的構建體可以構成給定樣本中總蛋白質/多肽含量的以重量計從5%至99.9%。使用誘導型啟動子或高表現啟動子，可以以顯著更高的濃度生產所期望的構建體。該定義包括在本領域已知的多種生物體和/或宿主細胞中產生構建體。在某些實施方式中，構建體 (1) 藉由使用旋杯式序列分析儀純化至足以獲得至少15個N末端或內部胺基酸序列的殘基的程度，或 (2) 藉由SDS-PAGE在非還原或還原條件下使用考馬斯藍或較佳的是銀染色純化至均質。然而，通常藉由至少一個純化步驟來製備分離的構建體。
根據一個實施方式，整個構建體和/或結合結構域呈一種或多種多肽的形式或處於蛋白質的形式。除了蛋白質部分以外，此類多肽或蛋白質可以包括非蛋白質部分（例如化學連接子或化學交聯劑如戊二醛）。
肽係經由共價肽（醯胺）鍵連接的胺基酸單體的短鏈。因此，肽屬於生物寡聚物和聚合物的廣泛化學類別。作為肽或多肽鏈的一部分的胺基酸被稱為「殘基」並且可以被連續編號。除環肽外的所有肽在肽的一端具有N-末端殘基，並且在另一端具有C-末端殘基。寡肽僅由少數胺基酸（通常在兩個至二十個之間）組成。多肽係更長、連續和無支鏈的肽鏈。基於尺寸，肽與蛋白質不同；並且作為任意基準，肽可以理解為含有大約50個或更少的胺基酸。蛋白質由一種或多種多肽組成，通常以生物功能方式排列。雖然應用於肽與多肽和蛋白質的實驗室技術的各方面不同（例如，電泳、層析等的特性），但是區分肽與多肽和蛋白質的尺寸邊界不是絕對的。因此，在本發明之上下文中，術語「肽」、「多肽」和「蛋白質」可互換地使用，並且術語「多肽」通常是較佳的。
如上面所提及，多肽可以進一步形成多聚體（如二聚體、三聚體和更高級的寡聚物），由多於一個多肽分子組成。形成此類二聚體、三聚體等的多肽分子可以是相同的或不相同的。因此，此類多聚體的相應高階結構被稱為同或異二聚體、同或異三聚體等。異多聚體的實例係抗體或免疫球蛋白分子，其天然存在形式由兩條相同的輕多肽鏈和兩條相同的重多肽鏈組成。術語「肽」、「多肽」和「蛋白質」還是指天然修飾的肽/多肽/蛋白質，其中修飾例如藉由翻譯後修飾（如糖基化、乙醯化、磷酸化等）來實現。當在本文中提及時，「肽」、「多肽」或「蛋白質」也可以是化學修飾的，如聚乙二醇化的。此類修飾在本領域中是熟知的並且在下文描述。
術語「選擇性地」和「較佳的是選擇性地」、「（特異性地或免疫特異性地）結合」、「（特異性地或免疫特異性地）識別」、或「與……（特異性或免疫特異性地）反應」根據本發明意指構建體或結合結構域與靶分子（抗原）（此處：分別為CLDN6和CD3）上的給定表位選擇性地相互作用或（免疫）特異性地相互作用。這種相互作用或結合在特定靶（此處的CLDN6）上的表位中比在替代性物質（非靶分子，例如此處的CLDN4、CLDN9、CLDN3等）中更頻繁、更快速地發生，具有更長的持續時間、具有更大的親和力、或者具有該等參數的一些組合。但是，由於不同物種中同源蛋白質之間的序列相似性，選擇性地和/或免疫特異性地結合其靶標（如人靶標）的構建體或結合結構域可能與來自不同物種（如，來自非人靈長類動物）的同源靶分子交叉反應。因此，術語「特異性地結合」、「特異性/免疫特異性結合」等可以包括構建體或結合結構域與多於一個物種中的表位或結構相關表位的結合。在本發明之上下文中，本發明之多肽以特定的方式與其對應的靶結構結合。較佳的是，根據本發明之多肽的每個結合結構域包含一個互補位，該結合結構域「特異性地或免疫特異性地」結合其對應的靶結構、「（特異性地或免疫特異性地）識別」其對應的靶結構、或與其對應的靶結構「（特異性地或免疫特異性地）反應」。根據本發明，這意指多肽或其結合結構域分別與靶分子（抗原）和CD3上的給定表位相互作用或（免疫）特異性地相互作用。這種相互作用或結合在特定靶上的表位中比在替代性物質（非靶分子）中更頻繁、更快速地發生，具有更長的持續時間、具有更大的親和力、或者具有該等參數的一些組合。但是，由於不同物種中同源蛋白質之間的序列相似性，免疫特異性地結合其靶標（如人靶標）的抗體構建體或結合結構域可能與來自不同物種（如，來自非人靈長類動物）的同源靶分子交叉反應。因此，術語「特異性/免疫特異性結合」可以包括抗體構建體或結合結構域與多於一種物種中的表位和/或結構相關表位的結合。術語（免疫）選擇地結合不包括與結構相關表位的結合。
在本發明之上下文中，術語「表位」係指由結合結構（即互補位）選擇性地識別/免疫特異性地識別的抗原的部分或區域。「表位」係抗原性的，並且因此術語表位有時也稱為「抗原結構」或「抗原決定簇」。與表位結合的結合結構域部分被稱為互補位（paratope）。認為特異性結合係藉由結合結構域和抗原的胺基酸序列中的特定模體實現的。因此，由於它們的一級、二級和/或三級結構以及所述結構的潛在二次修飾，結合得以實現。互補位與其抗原決定簇的特異性相互作用可以導致所述位點與抗原的簡單結合。在一些情況下，特異性相互作用可以替代地或另外地導致信號的引發，例如由於誘導抗原構象的變化、抗原的寡聚化等。
基於蛋白抗原的結構和與互補位的相互作用，蛋白抗原的表位分為兩類（構象表位和線性表位）。構象表位由抗原胺基酸序列的不持續部分組成。該等表位基於抗原的三維表面特徵和形狀或三級結構（折疊）與互補位相互作用。確定表位構象之方法包括但不限於x射線晶體學、二維核磁共振（2D-NMR）光譜學和定點自旋標記和電子順磁共振（EPR）光譜學。相反，線性表位基於其一級結構與互補位相互作用。線性表位由來自抗原的持續胺基酸序列形成，並且典型地在獨特的序列中包含至少3個或至少4個、且更通常地至少5個或至少6個或至少7個，例如約8個至約10個胺基酸。
以下描述了用於CLDN6表位定位之方法：在人CLDN6蛋白的細胞外環內的預定義區域（連續胺基酸延伸）與CLDN6旁系同源物（如人CLDN4或人CLDN18.2，但也可以想到其他旁系同源物，只要結合結構域不與所使用的旁系同源物發生交叉反應即可）的相應區域交換/替代。該等人CLDN6/旁系同源嵌合體在宿主細胞（如CHO細胞）的表面上表現。可以經由FACS分析測試抗體或構建體的結合。當完全消除抗體或構建體與嵌合分子的結合時，或當觀察到顯著的結合降低時，可以得出結論，從此嵌合分子中除去的人CLDN6區與免疫特異性表位-互補位識別相關。與人（野生型）CLDN6的結合相比，所述結合降低較佳的是為至少10%、20%、30%、40%或50%；更較佳的是為至少60%、70%或80%，並且最較佳的是為90%、95%或甚至100%，由此，與人CLDN6的結合被設定為100%。替代性地，可以藉由將一個或幾個點突變引入到CLDN6的序列中，特別是在細胞外環1或環2的序列中，更特別是對應於SEQ ID NO: 9和10中描繪的該等環的E1A和/或E2B區域的序列中，來修改上述表位作圖分析。該等點突變可以例如反映在CLDN6與其密切相關的旁系同源物CLDN4之間的差異。
確定靶抗原的特定殘基對構建體或結合結構域的識別的貢獻的另一種方法係丙胺酸掃描（參見，例如Morrison KL和Weiss GA.Cur Opin Chem Biol. [化學生物學新見] 2001年6月; 5(3):302-7），其中有待分析的每個殘基例如經由定點誘變被丙胺酸替代。丙胺酸的使用係因為其具有非巨大的、化學惰性的甲基官能基，但仍然模仿許多其他胺基酸所具有的二級結構參考。在需要保守突變殘基的大小的情形下，有時可以使用巨大的胺基酸（如纈胺酸或白胺酸）。
在結合結構域與靶抗原的表位之間的相互作用意味著結合結構域對表位/靶抗原（此處：分別為CLDN6和CD3）表現出相當可觀或顯著的親和力，並且通常對除靶抗原（此處：CLDN6/CD3）以外的蛋白質或抗原不表現出顯著的親和力 - 儘管上面論述過與例如來自其他物種的同源靶標、或同一物種的CLDN9（特別是人CLDN6和CLDN9）的交叉反應。「顯著的親和力」包括以≤10-6 M的親和力（解離常數，KD）結合。較佳的是，當結合親和力為≤10-7 M、≤10-8 M、≤10-9 M、≤10-10 M、或甚至≤10-11 M、或≤10-12 M時，結合被認為係特異性的。例如藉由比較所述結合結構域對其期望的靶蛋白質或抗原的親和力與所述結合結構域對非靶蛋白質或抗原（此處：分別為CLDN6或CD3以外的蛋白質）的親和力，可以容易地測試結合結構域是否與靶標（免疫）特異性地反應或結合。較佳的是，本發明之構建體不分別與除CLDN6或CD3以外的蛋白質或抗原顯著結合（即，第一結構域不與除CLDN6以外的蛋白質結合，並且第二結構域不與除CD3以外的蛋白質結合） - 除非針對另外的靶標的任何一個或多個另外的結合結構域被刻意引入本發明之構建體中，在這種情況下，本發明還提供該結合結構域與其特異性靶標的結合。
設想第一結構域對CLDN6（例如人CLDN6）的親和力為≤100 nM、≤90 nM、≤80 nM、≤70 nM、≤60 nM、≤50 nM、≤40 nM、≤30 nM或≤20 nM。較佳的是在基於細胞的測定（如Scatchard測定）中測量該等值。確定親和力的其他方法也是熟知的。進一步設想第二結構域對CD3（例如人CD3）的親和力為≤100 nM、≤90 nM、≤80 nM、≤70 nM、≤60 nM、≤50 nM、≤40 nM、≤30 nM、≤20 nM或≤10 nM。較佳的是在表面電漿共振測定（如Biacore測定）中測量該等值。
術語「不顯著結合」和「不選擇性地結合」意指當所述蛋白質或抗原在細胞表面上表現時，本發明之構建體或結合結構域不與除CLDN6或CD3以外的蛋白質或抗原結合。因此，構建體顯示出≤30%、較佳的是≤20%、更較佳的是≤10%、特別較佳的是≤9%、≤8%、≤7%、≤6%、≤5%、≤4%、≤3%、≤2%或≤1%的與除CLDN6或CD3以外的蛋白質或抗原（當所述蛋白質或抗原在細胞表面上表現時）的反應性，由此，分別與CLDN6或CD3的結合被設定為100%。「反應性」可以例如以親和力值表現（參見上文）。
設想本發明之構建體（並且更具體地，包含與CLDN6結合的互補位的結構域）不結合或不顯著結合CLDN6旁系同源物、更具體地人CLDN6旁系同源物和/或獼猴/食蟹猴CLDN6旁系同源物。還設想構建體不結合或不顯著結合在靶細胞表面上的（人或獼猴/食蟹猴）CLDN6旁系同源物。CLDN6旁系同源物包括 - 但不限於 - CLDN1、CLDN2、CLDN3、CLDN4、CLDN18.1、CLDN18.2和特別是CLDN9。根據一個實施方式，CLDN6的人旁系同源物具有如SEQ ID NO: 2-8所描述的序列。因此，設想本發明之構建體的第一結構域不結合或不顯著選擇性地與（在細胞的表面上的）CLDN1、CLDN2、CLDN3、CLDN4、CLDN18.1、CLDN18.2和/或CLDN9結合。設想本發明之構建體基本上不與在各種器官上表現的CLDN9結合。選擇性地與CLDN6結合，並且基本上不與CLDN9結合，避免了可能由脫靶結合引起的潛在不良事件。
包含本發明之多肽構建體的互補位（抗原結合（表位結合）結構）的一個結構域特異性地和/或選擇性地結合靶細胞表面上的CLDN6。「靶細胞」可以是在其表面表現CLDN6的任何原核或真核細胞；較佳的是，靶細胞係作為人或動物體一部分的細胞，如特定的表現CLDN6的癌細胞或腫瘤細胞或CLDN6陽性贅生物的細胞或人工產生的表現CLDN6的細胞（可以使用後者，例如，在離體測定中）。應當理解，在本發明之上下文中，術語「在表面上」意指構建體的第一抗原結合結構域選擇性地和較佳的是特異性地與在第一CLDN6細胞外環（CLDN6 ECL1）內、在第二CLDN6細胞外環（CLDN6 ECL2）內包含的表位結合，特別是它與在兩個環的組合內形成的表位結合。因此設想本發明之構建體的包含互補位（抗原結合（表位結合）結構）的結構域與由CLDN6（較佳的是人CLDN6）的一個或兩個細胞外環形成的表位結合。細胞外環可以是第一環和/或第二環。還設想兩個環都有助於結合。在這種情況下，有可能一個環（如第一環）代表構建體的主要結合配偶體，而另一個環（如第二環）例如作為穩定化配偶體有助於結合，但對於結合並非必要的。因此，當CLDN6被天然表現細胞或細胞系（如人癌細胞系OVCAR-3、OAW28、LCLC97TM1和NCI-H1435）和/或被用CLDN6轉化或（穩定地/暫態地）轉染的細胞或細胞系表現時，根據本發明之包含互補位（抗原結合（表位結合）結構）的結構域可以與CLDN6結合。在一個實施方式中，當將CLDN6在基於細胞的結合測定如Scatchard中用作靶分子時，結構域包含與CLDN6結合的互補位（抗原結合（表位結合）結構）。此外，設想構建體/其第一結構域與靶細胞表面上的人CLDN6結合。人CLDN6的較佳的胺基酸序列描述於SEQ ID NO: 1中。
設想根據本發明之多肽構建體（並且更具體地，該結構域包含結合所述構建體的CLDN6的互補位（即抗原結合（表位結合）結構））與CLDN6的第一細胞外環（ECL1，環1）結合。這並不一定排除第二細胞外環也促成互補位-表位相互作用位點，儘管不同例如程度較小。術語「CLDN6 ECL」（ECL = 細胞外環）係指CLDN6的那些部分，其基本上不含CLDN6的跨膜和細胞質結構域。應當理解，按照本領域常規使用的用於鑒定該疏水結構欄位型別的標準來鑒定針對本發明之CLDN6結合多肽所鑒定的跨膜結構域。跨膜結構域的確切邊界可以改變，但最有可能的是在本文明確提及的結構域的任一末端改變不多於約5個胺基酸。在SEQ ID NO: 9中顯示出較佳的人CLDN6 ECL1，並且在SEQ ID NO: 10中顯示出較佳的人CLDN6 ECL2。在一個非常具體的實施方式中，根據本發明之構建體（並且更具體地，所述構建體的第一結構域）與CLDN6（較佳的是人CLDN6）的第一細胞外環（ECL1，環1）的E1A結構域和第二細胞外環（ECL2，環2）的E2B結構域結合，其有利地在癌細胞或已被誘導（藉由轉化或轉染）表現CLDN6（例如人CLDN6）的細胞的表面上表現，並且不與SEQ ID NO: 1中描繪的CLDN6的胺基酸138-150結合。
本發明進一步提供，本發明之構建體的包含互補位（抗原結合（表位結合）結構）的結構域較佳的是選擇性地與包含結合靶細胞表面上的CLDN6的結構域的抗體或構建體結合CLDN6上相同的表位，並且本發明之構建體的該結構域包含：
a) 包含SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區；
b) 包含SEQ ID NO: 27中描繪的CDR-H1、SEQ ID NO: 28中描繪的CDR-H2和SEQ ID NO: 29中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 30中描繪的CDR-L1、SEQ ID NO: 31中描繪的CDR-L2和SEQ ID NO: 32中描繪的CDR-L3的VL區；
c) 包含SEQ ID NO: 41中描繪的CDR-H1、SEQ ID NO: 42中描繪的CDR-H2和SEQ ID NO: 43中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 44中描繪的CDR-L1、SEQ ID NO: 45中描繪的CDR-L2和SEQ ID NO: 46中描繪的CDR-L3的VL區；
d) 包含SEQ ID NO: 55中描繪的CDR-H1、SEQ ID NO: 56中描繪的CDR-H2和SEQ ID NO: 57中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 58中描繪的CDR-L1、SEQ ID NO: 59中描繪的CDR-L2和SEQ ID NO: 60中描繪的CDR-L3的VL區；
e) 包含SEQ ID NO: 69中描繪的CDR-H1、SEQ ID NO: 70中描繪的CDR-H2和SEQ ID NO: 71中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 72中描繪的CDR-L1、SEQ ID NO: 73中描繪的CDR-L2和SEQ ID NO: 74中描繪的CDR-L3的VL區；
f) 包含SEQ ID NO: 83中描繪的CDR-H1、SEQ ID NO: 84中描繪的CDR-H2和SEQ ID NO: 85中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 86中描繪的CDR-L1、SEQ ID NO: 87中描繪的CDR-L2和SEQ ID NO: 88中描繪的CDR-L3的VL區；
g) 包含SEQ ID NO: 97中描繪的CDR-H1、SEQ ID NO: 98中描繪的CDR-H2和SEQ ID NO: 99中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 100中描繪的CDR-L1、SEQ ID NO: 101中描繪的CDR-L2和SEQ ID NO: 102中描繪的CDR-L3的VL區；
h) 包含SEQ ID NO: 111中描繪的CDR-H1、SEQ ID NO: 112中描繪的CDR-H2和SEQ ID NO: 113中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 114中描繪的CDR-L1、SEQ ID NO: 115中描繪的CDR-L2和SEQ ID NO: 116中描繪的CDR-L3的VL區；
i) 包含SEQ ID NO: 125中描繪的CDR-H1、SEQ ID NO: 126中描繪的CDR-H2和SEQ ID NO: 127中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 128中描繪的CDR-L1、SEQ ID NO: 129中描繪的CDR-L2和SEQ ID NO: 130中描繪的CDR-L3的VL區；
j) 包含SEQ ID NO: 139中描繪的CDR-H1、SEQ ID NO: 140中描繪的CDR-H2和SEQ ID NO: 141中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 142中描繪的CDR-L1、SEQ ID NO: 143中描繪的CDR-L2和SEQ ID NO: 144中描繪的CDR-L3的VL區；
k) 包含SEQ ID NO: 153中描繪的CDR-H1、SEQ ID NO: 154中描繪的CDR-H2和SEQ ID NO: 155中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 156中描繪的CDR-L1、SEQ ID NO: 157中描繪的CDR-L2和SEQ ID NO: 158中描繪的CDR-L3的VL區；
l) 包含SEQ ID NO: 167中描繪的CDR-H1、SEQ ID NO: 168中描繪的CDR-H2和SEQ ID NO: 169中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 170中描繪的CDR-L1、SEQ ID NO: 171中描繪的CDR-L2和SEQ ID NO: 172中描繪的CDR-L3的VL區；
m) 包含SEQ ID NO: 181中描繪的CDR-H1、SEQ ID NO: 182中描繪的CDR-H2和SEQ ID NO: 183中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 184中描繪的CDR-L1、SEQ ID NO: 185中描繪的CDR-L2和SEQ ID NO: 186中描繪的CDR-L3的VL區；
n) 包含SEQ ID NO: 195中描繪的CDR-H1、SEQ ID NO: 196中描繪的CDR-H2和SEQ ID NO: 197中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 198中描繪的CDR-L1、SEQ ID NO: 199中描繪的CDR-L2和SEQ ID NO: 200中描繪的CDR-L3的VL區；
o) 包含SEQ ID NO: 209中描繪的CDR-H1、SEQ ID NO: 210中描繪的CDR-H2和SEQ ID NO: 211中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 212中描繪的CDR-L1、SEQ ID NO: 213中描繪的CDR-L2和SEQ ID NO: 214中描繪的CDR-L3的VL區；
p) 包含SEQ ID NO: 223中描繪的CDR-H1、SEQ ID NO: 224中描繪的CDR-H2和SEQ ID NO: 225中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 226中描繪的CDR-L1、SEQ ID NO: 227中描繪的CDR-L2和SEQ ID NO: 228中描繪的CDR-L3的VL區；
q) 包含SEQ ID NO: 237中描繪的CDR-H1、SEQ ID NO: 238中描繪的CDR-H2和SEQ ID NO: 239中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 240中描繪的CDR-L1、SEQ ID NO: 241中描繪的CDR-L2和SEQ ID NO: 242中描繪的CDR-L3的VL區；
r) 包含SEQ ID NO: 251中描繪的CDR-H1、SEQ ID NO: 252中描繪的CDR-H2和SEQ ID NO: 253中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 254中描繪的CDR-L1、SEQ ID NO: 255中描繪的CDR-L2和SEQ ID NO: 256中描繪的CDR-L3的VL區，或
s) 包含SEQ ID NO: 265中描繪的CDR-H1、SEQ ID NO: 266中描繪的CDR-H2和SEQ ID NO: 267中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 268中描繪的CDR-L1、SEQ ID NO: 269中描繪的CDR-L2和SEQ ID NO: 270中描繪的CDR-L3的VL區，
或
a-1) SEQ ID NO: 11中描繪的VH區，和SEQ ID NO: 12中描繪的VL區；
b-1) SEQ ID NO: 19中描繪的VH區，和SEQ ID NO: 20中描繪的VL區；
c-1) SEQ ID NO: 27中描繪的VH區，和SEQ ID NO: 28中描繪的VL區；
d-1) SEQ ID NO: 35中描繪的VH區，和SEQ ID NO: 36中描繪的VL區；
e-1) SEQ ID NO: 43中描繪的VH區，和SEQ ID NO: 44中描繪的VL區；
f-1) SEQ ID NO: 51中描繪的VH區，和SEQ ID NO: 52中描繪的VL區；
g-1) SEQ ID NO: 59中描繪的VH區，和SEQ ID NO: 60中描繪的VL區；
h-1) SEQ ID NO: 67中描繪的VH區，和SEQ ID NO: 68中描繪的VL區；
i-1) SEQ ID NO: 75中描繪的VH區，和SEQ ID NO: 76中描繪的VL區；
j-1) SEQ ID NO: 83中描繪的VH區，和SEQ ID NO: 84中描繪的VL區；
k-1) SEQ ID NO: 91中描繪的VH區，和SEQ ID NO: 92中描繪的VL區；
l-1) SEQ ID NO: 99中描繪的VH區，和SEQ ID NO: 100中描繪的VL區；
m-1) SEQ ID NO: 107中描繪的VH區，和SEQ ID NO: 108中描繪的VL區；
n-1) SEQ ID NO: 115中描繪的VH區，和SEQ ID NO: 116中描繪的VL區；
o-1) SEQ ID NO: 123中描繪的VH區，和SEQ ID NO: 124中描繪的VL區；
p-1) SEQ ID NO: 131中描繪的VH區，和SEQ ID NO: 132中描繪的VL區；
q-1) SEQ ID NO: 139中描繪的VH區，和SEQ ID NO: 140中描繪的VL區；或
r-1) SEQ ID NO: 147中描繪的VH區，和SEQ ID NO: 148中描繪的VL區，或s-1) SEQ ID NO: 263中描繪的VH區，和/或SEQ ID NO: 264中描繪的VL區。
在另外的實施方式中，本發明之多肽構建體包含結合CLDN6的結構域，其包含SEQ ID NO: 680至694中描繪的任何CDR區，例如SEQ ID NO: 680中描繪的重鏈CDR1，或重鏈SEQ ID NO: 681中描繪的CDR2，或SEQ ID NO: 682中描繪的重鏈CDR2，或SEQ ID NO: 683中描繪的重鏈CDR2，或SEQ ID NO: 684中描繪的重鏈CDR3，或SEQ ID NO: 685中描繪的重鏈CDR3，或SEQ ID NO: 686中描繪的重鏈CDR3，或SEQ ID NO: 687中描繪的重鏈CDR3，和/或SEQ ID NO: 688中描繪的輕鏈CDR1，或SEQ ID NO: 689中描繪的輕鏈CDR1，SEQ ID NO: 690中描繪的輕鏈CDR2，SEQ ID NO: 691中描繪的輕鏈CDR3，SEQ ID NO: 692中描繪的輕鏈CDR3，SEQ ID NO: 693中描繪的輕鏈CDR3，和SEQ ID NO: 694中描繪的輕鏈CDR3，或它們的包含SEQ ID NO: 680至687中描繪的重鏈序列的任何組合和/或它們的包含SEQ ID NO: 688至694中描繪的輕鏈序列的組合。熟悉該項技術者知道結合CLDN6的結合結構域可以僅包含HCDR1、HCDR2、HCDR3、LCDR1、LCDR2和LCDR3中的一個，其可以存在於根據本發明之組合中。
在表位定位中還分析了其他抗CLDN6結合物的CLDN6結合特異性（參見實例2）。發現該等CLDN6xCD3構建體具有不同的表位特異性，並且同時顯示出，與本發明之構建體相比具有顯著較差的細胞毒性潛力。在實例4中，證明了儘管對CLDN6具有相似的親和力，本發明之構建體顯示在2位元數皮莫耳範圍內的EC50值，而比較構建體顯示在3位元數至5位數皮莫耳範圍內的EC50值。顯示後一範圍的細胞毒性活性的構建體可能不夠有效用於在指導患者的免疫系統（更具體地T細胞對癌細胞的細胞毒性活性）中的治療用途。另一方面，根據本發明之構建體以非常有利的表位-活性關係存在，因此支持有效的構建體介導的細胞毒性活性。
抗體、多肽構建體或包含互補位（抗原結合（表位結合）結構）的結構域是否與另一種給定抗體、構建體或結合結構域一樣結合在靶細胞表面上的相同的CLDN6表位，可以藉由如本文所述之不同分析（例如，藉由用嵌合或突變的CLDN6分子進行表位定位）來測量，如本文上面或在實例1和2中所述之。本文描述了確定表位的其他方法，如丙胺酸掃描。
可以在競爭性測定如競爭性ELISA中測量抗體或多肽構建體或包含互補位（抗原結合（表位結合）結構）的結構域是否與另一種給定抗體或構建體競爭與靶細胞表面上的抗原（如CLDN6）結合。也可以使用抗生物素蛋白偶聯的微粒（珠粒）。與抗生物素蛋白塗覆的ELISA板類似，當與生物素化蛋白質反應時，該等珠粒中的每一個都可用作可在其上進行測定的底物。將抗原塗覆在珠粒上，並且然後用第一抗體預塗覆。添加第二抗體並且確定任何另外的結合。經由流動式細胞測量術進行讀出。較佳的是使用基於細胞的競爭測定，使用天然表現CLDN6的細胞或用CLDN6穩定地或暫態地轉化的細胞。在本發明之上下文中，術語「競爭結合」意指在至少20%、至少30%、至少40%、至少50%、至少60%、至少70%、至少80%或至少90%的兩種測試抗體之間發生競爭，如藉由上文揭露的任何一種測定（較佳的是基於細胞的測定）確定的。當然，相同的分析可以應用於其他靶標，如CD3。
競爭性抗體/多肽構建體結合測定包括確定兩種抗體/構建體與細胞表面結合抗原的競爭性結合的測定。旨在檢測兩種抗體/構建體A和B與細胞表面上的相同抗原的結合的常用方法可以包括以下步驟：
a) 藉由將細胞與抗體/多肽構建體A一起預孵育、隨後次最大程度地添加標記的抗體/多肽構建體B來阻斷細胞表面抗原，並檢測與在不存在A的情況下的結合相比B的結合；
b) 在次最大量的標記的抗體/多肽構建體B的存在下滴定（即添加不同量的）抗體/多肽構建體A，並檢測對B的結合的影響；或
c) 共滴定A和B，其中兩種抗體/多肽/多肽構建體以最大濃度一起孵育，並檢測總結合是否等於或超過單獨的A或B的結合，即不受添加的順序或抗體/構建體的相對量影響之方法。
當兩種抗體/多肽/多肽構建體A和B競爭細胞表面結合的抗原時，抗體將經常在不依賴於添加抗體的順序的阻斷測定中競爭。換句話說，如果在任一方向上進行測定，則競爭得以檢測。然而，情況並非總是如此，並且在某些情況下，抗體添加的順序或測定的方向可能影響產生的信號。這可能是由於潛在競爭性抗體/構建體的親和力或親合力的差異。如果添加的順序對產生的信號具有顯著影響，則推斷如果在至少一個順序中檢測到競爭，則兩種抗體/構建體確實有競爭。
在本發明之上下文中，術語「可變」係指抗體或免疫球蛋白結構域表現出其序列可變性並且參與確定特定抗體的特異性和結合親和力的那些部分（即「一個或多個可變區」）。通常，重鏈可變區（VH）和輕鏈可變區（VL）的配對在一起形成單個抗原結合位點。
可變性在整個抗體的可變區中並非均勻分佈；它集中在重鏈可變區和輕鏈可變區中的每一個的子結構域中。該等子結構域稱為「超變區」或「互補決定區」（CDR）。可變區的更保守的（即非超變）部分被稱為「框架」（FR）區，並且為三維空間中的六個CDR提供支架以形成抗原結合表面。天然存在的抗體重鏈和輕鏈的可變區各自包含主要採用β-折疊構型的四個FR區（FR1、FR2、FR3和FR4）。它們與CDR一起在可變重鏈或輕鏈內形成以下序列：FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4。每條鏈中的高變區藉由框架區靠近在一起，並通常與來自另一條鏈的高變區一起有助於抗原結合位點的形成（參見Kabat等人, 上述引文）。如本文所用，本發明之多肽/多肽構建體可在框架區中具有修飾。該等修飾可以是本文揭露序列的一個或多個胺基酸殘基被其他胺基酸殘基取代。如果該等修飾不阻止多肽/多肽構建體與CLDN6的選擇性結合和/或只要該等修飾不阻止多肽/多肽構建體與表現CLDN6的靶細胞的選擇性結合以及構建體接合和活化T細胞並誘導T細胞介導的細胞毒性的能力，則可能的進一步修飾係胺基酸殘基的缺失、倒位、添加。因此，當與非框架修飾的抗體比較時，本文揭露的構建體的框架區的修飾仍然允許至少100%、至少99%、至少98%、至少97%、至少96%、至少95%、至少94%、至少93%、至少92%、至少91%、至少90%、至少89%、至少88%、至少87%、至少86%、至少85%、至少84%、至少83%、至少82%、至少81%、至少80%、至少79%、至少78%、至少77%、至少76%、至少75%、至少74%、至少73%、至少72%、至少71%、至少70%、至少65%、至少60%、至少55%、至少50%、至少45%、至少40%、至少35%、至少30%、至少25%、至少20%、至少15%、至少10%、至少5%的接合T細胞並誘導T細胞介導的細胞毒性的能力。框架區中的修飾也可能與比未修飾的構建體更高的活性相關。 還考慮為了諸如增加構建體在給定介質中的溶解度、增加構建體的穩定性等目的而修飾本發明之構建體的框架區。
術語「CDR」及其複數「CDR」係指其中三個構成輕鏈可變區的結合特徵（CDR-L1、CDR-L2和CDR-L3）並且三個構成重鏈可變區的結合特徵（CDR-H1、CDR-H2和CDR-H3）的互補決定區。CDR包含大多數負責抗體（或構建體或結合結構域）與抗原的特異性相互作用的殘基，並且因此有助於抗體分子的功能活性：它們係抗原特異性的主要決定簇。
CDR邊界和長度的準確定義受制於不同的分類和編號系統。因此，CDR可以藉由Kabat、Chothia、contact或任何其他邊界定義（包括本文所述之編號系統）來引用。儘管有不同的邊界，但該等系統中的每一者在構成可變序列內所謂的「高變區」的方面具有一定程度的重疊。因此，根據該等系統的CDR定義可以相對於相鄰框架區在長度和邊界區域方面不同。參見，例如Kabat（一種基於跨物種序列變異性之方法）、Chothia（一種基於抗原-抗體複合物的晶體學研究之方法）和/或MacCallum（Kabat等人, 上述引文；Chothia等人, J. MoI.Biol [分子生物學雜誌], 1987, 196: 901-917；和MacCallum等人, J. MoI.Biol [分子生物學雜誌], 1996, 262: 732）。表徵抗原結合位點的還另一標準係由牛津大學分子公司（Oxfbrd Molecular）的AbM抗體建模軟體使用的AbM定義。參見例如，Protein Sequence and Structure Analysis of Antibody Variable Domains [抗體可變結構域的蛋白質序列和結構分析]在：Antibody Engineering Lab Manual [抗體工程實驗室手冊]（編輯：Duebel, S.和Kontermann, R.，施普林格出版社（Springer-Verlag），海德爾堡）。就兩種殘基鑒定技術定義重疊區而非相同區而言，可以將它們組合以定義雜合CDR。然而，根據所謂的Kabat系統進行編號係較佳的。
典型地，CDR形成可以分類為規範結構的環結構。術語「規範結構」係指由抗原結合（CDR）環所使用的主鏈構象。從比較結構研究中，已經發現六個抗原結合環中的五個僅具有有限的可用構象組庫。每個規範結構可以藉由多肽骨架的扭轉角來表徵。因此，在抗體之間的相應環可以具有非常相似的三維結構，儘管在環的大部分中具有高的胺基酸序列可變性（Chothia和Lesk, J. Mol. Biol. [分子生物學雜誌], 1987, 196: 901；Chothia等人, Nature [自然], 1989, 342: 877；Martin和Thornton, J. Mol. Biol [分子生物學雜誌], 1996, 263: 800）。此外，所使用的環結構與其周圍的胺基酸序列之間存在關係。特定規範類別的構象由環的長度和位於環內關鍵位置以及保守框架內（即，環外）的胺基酸殘基決定。因此，可以基於該等關鍵胺基酸殘基的存在來進行對特定規範類別的分配。
術語「規範結構」還可以包括關於抗體的線性序列的考慮因素，例如，如藉由Kabat（Kabat等人, 上述引文）編目的。Kabat編號方案（系統）係以一致方式對抗體可變區的胺基酸殘基進行編號的廣泛採用的標準，並且是本發明應用的較佳的方案，也如本文其他地方所提及。另外的結構考慮因素也可以用於確定抗體的規範結構。例如，Kabat編號未完全反映的那些差異可以藉由Chothia等人的編號系統來描述，並且/或者藉由其他技術（例如結晶學和二維或三維計算建模）來揭示。因此，可以將給定的抗體序列置於規範的類別中，該類別尤其允許鑒定適當的類別序列（例如，基於在文庫中包括多種規範結構的期望）。文獻中描述了抗體胺基酸序列的Kabat編號和如由Chothia等人, 上述引文所述之結構考慮因素以及其參與解釋抗體結構的規範方面。不同類別的免疫球蛋白的亞單位結構和三維構型在本領域中是熟知的。有關抗體結構的綜述，參見Antibodies: A Laboratory Manual [抗體：實驗室手冊], Cold Spring Harbor Laboratory [冷泉港實驗室],Harlow等人編輯, 1988。
輕鏈的CDR3以及特別是重鏈的CDR3可以構成輕鏈可變區和重鏈可變區內抗原結合中最重要的決定簇。在一些抗體或構建體/結合結構域中，重鏈CDR3似乎構成抗原與抗體之間的主要接觸區域。其中僅僅改變CDR3的體外選擇方案可以用於改變抗體或構建體/結合結構域的結合特性或確定哪些殘基有助於抗原的結合。因此，CDR3典型地是抗體結合位點內分子多樣性的最大來源。例如，CDR-H3可以短至兩個胺基酸殘基或大於26個胺基酸。
在經典的全長抗體或免疫球蛋白中，每條輕（L）鏈藉由一個共價二硫鍵與重（H）鏈連接，而兩條H鏈藉由一個或多個二硫鍵彼此連接，這取決於H鏈同種型。通常將最靠近VH的重鏈恒定（CH）結構域命名為CH1。恒定（「C」）結構域不直接參與抗原結合，但表現出各種效應子功能，如抗體依賴性細胞介導的細胞毒性（ADCC）和補體活化（補體依賴性細胞毒性，CDC）。抗體的Fc區係經典抗體的「尾部」區域，其與被稱為Fc受體的細胞表面受體和補體系統的一些蛋白質相互作用。在IgG、IgA和IgD抗體同種型中，Fc區由從抗體的兩條重鏈的第二和第三恒定結構域（CH2和CH3）衍生的兩個相同的蛋白質片段構成。IgM和IgE Fc區在每條多肽鏈中含有三個重鏈恒定結構域（CH2、CH3和CH4）。Fc區還含有藉由一個或多個二硫鍵和非共價相互作用保持在一起的所謂「鉸鏈」區的部分。天然存在的IgG的Fc區具有高度保守的N-糖基化位點。Fc片段的糖基化係Fc受體介導的活性所必需的。
ADCC係細胞介導的免疫防禦機制，由此免疫系統的效應細胞主動裂解靶細胞，該靶細胞的膜表面抗原已被特異性抗體結合。ADCC需要免疫效應細胞，其通常已知係典型地與IgG抗體相互作用的天然殺傷（NK）細胞。然而，ADCC也可以由巨噬細胞、中性粒細胞和嗜酸性粒細胞介導。天然發生的ADCC關於藉由表現Fc部分的抗體活化表現Fc受體的效應細胞。例如，NK細胞表面上最常見的Fc受體被稱為CD16或FcγRIII。一旦Fc受體結合IgG的Fc區，NK細胞就釋放導致靶細胞死亡的細胞毒性因子。同樣，嗜酸性粒細胞的Fc受體（FceRI）將識別IgE。相比之下，在CDC中，由於經典途徑補體活化，補體系統的分子「C1q」與抗體Fc區結合，並且這種結合觸發補體級聯，其導致在靶細胞表面形成膜攻擊複合物（MAC）。在治療性抗體中，ADCC和CDC兩者都可以藉由Fc同種型工程、Fc基因突變或Fc糖基化譜修飾來調節。如本文所用，本發明之多肽/多肽構建體不誘導通常理解的ADCC。相反，多肽可以接合T細胞並誘導T細胞介導的細胞毒性，例如藉由分泌穿孔素和/或誘導細胞凋亡。
組裝和體細胞突變後的抗體基因的序列高度改變，並且估計該等改變的基因編碼1010種不同抗體分子（Immunoglobulin Genes [免疫球蛋白基因], 第2版,Jonio等人編輯, Academic Press [學術出版社], San Diego, CA [加利福尼亞州聖地牙哥], 1995）。因此，免疫系統提供了免疫球蛋白組庫。術語「組庫」係指完全或部分衍生自至少一種編碼至少一種免疫球蛋白的序列的至少一種核苷酸序列。一個或多個序列可以藉由重鏈的V、D和J區段以及輕鏈的V和J區段的體內重排來產生。可替代地，一種或多種序列可以響應於發生重排（例如體外刺激）而從細胞產生。可替代地，部分或全部的一種或多種序列可以藉由DNA剪接、核苷酸合成、誘變和其他方法獲得，參見例如美國專利5,565,332。組庫可以僅包括一種序列或可以包括多種序列，包括遺傳多樣性集合中的序列。
設想本發明之多肽構建體在第一結構域內具有半胱胺酸夾具（cysteine clamp）。可以引入這種半胱胺酸夾具以改善構建體的穩定性。參見例如US 2016/0193295。
在本發明之一個實施方式中，本發明之構建體的一個結構域的CLDN6結合互補位（抗原結合（表位結合）結構）包含具有以下中描繪的胺基酸序列的VH區：SEQ ID NO: 11、SEQ ID NO: 25、SEQ ID NO: 39、SEQ ID NO: 67或SEQ ID NO: 193。
在另一個實施方式中，本發明之構建體的CLDN6特異性互補位（即抗原結合（表位結合）結構域）包含具有以下中描繪的胺基酸序列的VL區：SEQ ID NO: 12、SEQ ID NO: 26、SEQ ID NO: 40、SEQ ID NO: 68或SEQ ID NO: 194。
在另一個實施方式中，本發明之構建體的CLDN6特異性互補位（即抗原結合（表位結合）結構域）包含具有以下中描繪的胺基酸序列的VH區和VL區：SEQ ID NO: 11+12（VH+VL）、SEQ ID NO: 25+26、SEQ ID NO: 39+40、SEQ ID NO: 67+68或SEQ ID NO: 193+194（VH+VL）。
在又另一個實施方式中，本發明之構建體的CLDN6特異性互補位（即抗原結合（表位結合）結構域）包含具有以下中描繪的胺基酸序列的多肽：SEQ ID NO: 19、SEQ ID NO: 22、SEQ ID NO: 33、SEQ ID NO: 36、SEQ ID NO: 47、SEQ ID NO: 50、SEQ ID NO: 76、SEQ ID NO: 78、SEQ ID NO: 201或SEQ ID NO: 204，特別SEQ ID NO: 19和22。
如本文上面所述，本發明提供了如下實施方式，其中多肽構建體處於選自以下群組的形式，該組由以下組成：(scFv)2、scFv-單結構域mAb、任何上述形式的雙抗體和寡聚物。如本文所述之術語「處於……形式」並不排除可以被進一步修飾的構建體（例如藉由附接或融合到其他部分）。根據本發明之多肽構建體的一個實施方式，包含如本文所述之互補位的結構域處於scFv的形式。在scFv中，VH區和VL區以VH-VL或VL-VH的順序排列（從N末端至C末端）。設想包含如本文所述之互補位的結構域的VH和VL區經由連接子、較佳的是肽連接子連接。根據包含如本文所述之互補位的結構域的一個實施方式，該VH區位於連接子的N末端，並且該VL區位於連接子的C末端。換句話說，在包含如本文所述之互補位的結構域的一個實施方式中，該scFv從N末端至C末端包含：VH-連接子-VL。進一步設想，包含構建體的如本文所述之互補位的結構域經由連接子、較佳的是肽連接子連接。構建體可以例如包含以一個結構域 - 連接子 - 第二其他結構域的順序（從N末端至C末端）的結構域。逆序（其他結構域 - 連接子 - 第一結構域）也是可能的。
連接子較佳的是肽連接子，更較佳的是短肽連接子。根據本發明，「肽連接子」包含將構建體的一個結構域的胺基酸序列與另一個（可變和/或結合）結構域（例如可變結構域或結合結構域）連接的胺基酸序列。這種肽連接子的基本技術特徵在於它不包含任何聚合活性。合適的肽連接子係在美國專利4,751,180和4,935,233或WO 88/09344中描述的那些。肽連接子也可用於將其他結構域或模組或區（如半衰期延長結構域）附接到本發明之構建體。在SEQ ID NO: 563-575和SEQ ID NO: 679中顯示了有用的肽連接子的實例。在本發明之上下文中，「短」連接子具有在2個與50個之間的胺基酸，較佳的是在3個與35個之間、在4個與30個之間、在5個與25個之間、在6個與20個之間或在6個與17個之間的胺基酸。在一個結合結構域的兩個可變區之間的連接子可以具有與在兩個結合結構域之間的連接子不同的長度（例如可以更長）。例如，在一個結合結構域的兩個可變區之間的連接子可以具有在7個與15個之間（較佳的是在9個與13個之間）的胺基酸的長度，並且在兩個結合結構域之間的連接子可以具有在3個與10個（較佳的是在4個與8個之間）的胺基酸的長度。進一步設想，肽連接子係甘胺酸/絲胺酸連接子，如SEQ ID NO: 563-575和SEQ ID NO: 679中描繪的那些。甘胺酸/絲胺酸連接子中的大多數胺基酸選自甘胺酸和絲胺酸。
如果使用連接子，則該連接子較佳的是具有確保第一結構域和第二結構域中的每一者均可以彼此獨立地保留其差異結合特異性的長度和序列。對於連接構建體中的至少兩個結合結構域（或形成一個結合結構域的兩個可變區）的肽連接子，設想包含僅少數胺基酸殘基（例如12個胺基酸殘基或更少）的那些肽連接子。因此，12、11、10、9、8、7、6或5個胺基酸殘基的肽連接子係較佳的。設想的具有少於5個胺基酸的肽連接子包含4、3、2或1個胺基酸，其中富含Gly的連接子係較佳的。在所述「肽連接子」的上下文中的「單個胺基酸」連接子係Gly。肽連接子的另一個實施方式的特徵在於胺基酸序列Gly-Gly-Gly-Gly-Ser（即Gly4Ser（SEQ ID NO: 563））或其聚合物（即(Gly4Ser)x，其中x係1或更大（例如2或3）的整數）。在SEQ ID NO: 563-575和SEQ ID NO: 679中描繪了有用的連接子。所述肽連接子的特徵在本領域中是已知的並且描述於例如Dall’Acqua等人（Biochem. [生物化學] (1998) 37, 9266-9273）、Cheadle等人（Mol Immunol [分子免疫學] (1992) 29, 21-30）以及Raag和Whitlow（FASEB [美國實驗生物學聯合會會誌] (1995) 9(1), 73-80）中。不促進任何二級結構的肽連接子係較佳的。所述結構域彼此的連接可以例如藉由基因工程提供。用於製備融合的且可操作地連接的雙特異性單鏈構建體並在哺乳動物細胞或細菌中表現它們之方法係本領域中熟知的（例如WO 99/54440或Sambrook等人, Molecular Cloning: A Laboratory Manual [分子選殖：實驗室手冊], Cold Spring Harbor Laboratory Press [冷泉港實驗室出版社], Cold Spring Harbor, New York [紐約冷泉港], 2001）。
根據本發明之一個實施方式，本發明之多肽構建體係「單鏈構建體」。還設想第一結合結構域或第二結合結構域或兩個結合結構域可以處於「單鏈Fv」（scFv）的形式。儘管Fv片段的兩個結構域VL和VH由獨立的基因編碼，但使用重組方法可以將這兩個結構域藉由人工連接子接合，如上文所述，該人工連接子使它們能夠製成單條蛋白質鏈，其中VL和VH區配對以形成單價分子；參見例如，Huston等人 (1988) Proc. Natl. Acad. Sci USA [美國國家科學院院刊] 85:5879-5883。使用熟悉該項技術者已知的常規技術獲得該等抗體片段，並且按照與全長抗體或IgG相同的方式評價片段的功能。因此，單鏈可變片段（scFv）係免疫球蛋白的重鏈（VH）和輕鏈（VL）可變區的融合蛋白，通常用短連接子肽連接。為了靈活性，連接子通常富含甘胺酸，以及為了溶解性通常富含絲胺酸或還有蘇胺酸，並且可以連接VH的N末端和VL的C末端，或反之亦然。儘管去除了恒定區並引入了連接子，但該蛋白質保留了原始免疫球蛋白的特異性。
雙特異性單鏈分子在本領域中是已知的並描述於以下中：WO 99/54440；Mack, J. Immunol. [免疫學雜誌] (1997), 158, 3965-3970；Mack, PNAS [美國國家科學院院刊], (1995), 92, 7021-7025；Kufer, Cancer Immunol. Immunother. [癌症免疫學免疫治療], (1997), 45, 193-197；Löffler, Blood [血液], (2000), 95, 6, 2098-2103；Brühl, Immunol. [免疫學], (2001), 166, 2420-2426；Kipriyanov, J. Mol. Biol. [分子生物學雜誌], (1999), 293, 41-56。描述的用於產生單鏈構建體的技術（尤其參見美國專利4,946,778；Kontermann和Dübel (2010), 上述引文，以及Little (2009), 上述引文）可以適用於產生選擇性且較佳的是特異性識別一種或多種所選擇的靶標的單鏈構建體。
二價（bivalent）（也稱為雙價（divalent））或雙特異性單鏈可變片段（具有(scFv)2形式的聯-scFv或二-scFv）可以藉由連接兩個scFv分子（例如利用如上文所述之連接子）來工程化。連接可以藉由產生具有兩個VH區和兩個VL區的單一多肽鏈從而產生串聯scFv來進行（參見，例如Kufer P.等人, (2004) Trends in Biotechnology [生物技術趨勢] 22(5):238-244）。另一種可能性係產生具有連接子肽的scFv分子，該等連接子肽對於兩個可變區來說太短以致於不能折疊在一起（例如約五個胺基酸），從而迫使scFv二聚化。在這種情況下，結合結構域（與靶抗原CLDN6或CD3結合）的VH和VL不經由肽連接子直接連接。因此，CD3結合結構域的VH可以例如經由肽連接子與CLDN6結合結構域的VL融合，並且CLDN6結合結構域的VH經由這種肽連接子與CD3結合結構域的VL融合。這種類型被稱為雙抗體（參見，例如Hollinger, Philipp等人, (1993年7月) Proceedings of the National Academy of Sciences of the United States of America [美國國家科學院院刊] 90 (14): 6444-8）。
命名為「單結構域構建體」（或偶爾稱為「抗體構建體」）的構建體包含一個（單體）抗體可變區，該抗體可變區可以獨立於其他可變區選擇性地結合特定抗原。第一單結構域抗體係從駱駝中發現的重鏈抗體工程化而來，並且該等被稱為VHH片段。軟骨魚類也具有重鏈抗體（IgNAR），可以從該等重鏈抗體中獲得稱為VNAR片段的單結構域抗體。替代性方法係將來自常見免疫球蛋白的二聚體可變區分裂成單體，因此獲得VH或VL作為單結構域Ab。儘管對單結構域抗體的大多數研究目前皆為基於重鏈可變區，但衍生自輕鏈的奈米抗體也顯示出與靶表位特異性地結合。單結構域抗體的實例係所謂的sdAb、奈米抗體或單可變結構域抗體。因此，(單結構域mAb)2係由（至少）兩個單結構域單株建體構成的單株構建體，該等單結構域單株抗體單獨地選自包括VH、VL、VHH和VNAR的組。連接子較佳的是呈肽連接子的形式。類似地，「scFv-單結構域mAb」係由至少一個如上所述之單結構域抗體和一個如上所述之scFv分子構成的單株構建體。同樣，連接子較佳的是呈肽連接子的形式。
還設想本發明之多肽構建體除了具有與靶分子CLDN6和CD3結合的功能外，還具有另外的功能。在這種形式中，藉由CLDN6結合靶向靶細胞，藉由CD3結合介導細胞毒性T細胞活性，並且提供另外的功能（如增強或延長血清半衰期的手段或結構域、藉由募集效應細胞介導細胞毒性的完全功能或經修飾的Fc恒定結構域、標記（螢光等）、治療劑如毒素或放射性核素等），構建體可以是三功能或多功能構建體。
延長本發明之多肽/多肽構建體的血清半衰期的手段或結構域的實例包括與多肽/多肽構建體融合或以其他方式附接的肽、蛋白質或蛋白質的結構域。肽、蛋白質或蛋白質的結構域的組包括在人體中以較佳的藥物動力學特徵與其他蛋白質結合的肽，如血清白蛋白（參見WO 2009/127691）。此類半衰期延長的肽的替代性概念包括與新生兒Fc受體（FcRn，參見WO 2007/098420）結合的肽，其也可用於本發明之構建體中。附接較大蛋白質結構域或完整蛋白質的概念包括人血清白蛋白、人血清白蛋白的變體或突變體（參見WO 2011/051489、WO 2012/059486、WO 2012/150319、WO 2013/135896、WO 2014/072481、WO 2013/075066）或其結構域的融合，以及免疫球蛋白恒定區（Fc結構域）及其變體的融合。Fc結構域的此類變體被稱為基於Fc的結構域，並且可以例如被優化/修飾以允許期望的二聚體或多聚體配對，以消除Fc受體結合（例如避免ADCC或CDC）或出於其他原因。在本領域中已知延長物質或分子在人體中的半衰期的另外的概念係那些分子（如本發明之構建體）的聚乙二醇化。
在一個實施方式中，例如為了延長構建體的血清半衰期，根據本發明之多肽或多肽構建體與融合配偶體（如蛋白質、多肽或肽）連接（例如經由肽鍵）。該等融合配偶體可以選自人血清白蛋白（「HSA」或「HALB」）以及其序列變體、與HSA結合的肽、與FcRn結合的肽（「FcRn BP」）、或包含（抗體衍生的）Fc區的構建體。在SEQ ID NO: 576-637中描述了該等融合配偶體的示例性序列。通常，融合配偶體可以直接（例如經由肽鍵）或藉由肽連接子如(GGGGS)n（其中「n」係2或更大的整數，例如2或3或4）與根據本發明之構建體的N末端或C末端連接。在SEQ ID NO: 563-575中所示和討論了合適的肽連接子。
因此，設想根據本發明之多肽構建體以下的多肽，該多肽從N末端至C末端按以下順序包含：
a) VL（包含CLDN6結合互補位的一部分） - (G4S)3-VH（包含CLDN6結合互補位的一部分） - 肽連接子（SG4S） - VH（包含CD3結合互補位的一部分） - (G4S)3 - VL（包含CD3結合互補位的一部分） - 肽連接子（G4） - Fc單體（HLE結構域的一部分） - (G4S)6 - Fc單體（HLE結構域的一部分）；或
b) VH（包含CLDN6結合互補位的一部分） - (G4S)3 - VL（包含CLDN6結合互補位的一部分） - 肽連接子（SG4S） - VH（包含CD3結合互補位的一部分） - (G4S)3 - VL（包含CD3結合互補位的一部分） - 肽連接子（G4） - Fc單體（HLE結構域的一部分） - (G4S)6 - Fc單體（HLE結構域的一部分）。
因此，設想根據本發明之多肽構建體包含：
(a) 從N末端至C末端按以下順序構成的多肽：
● 多肽，該多肽具有選自由SEQ ID NO: 12、SEQ ID NO: 26、SEQ ID NO: 40、SEQ ID NO: 68和SEQ ID NO: 194組成之群組的胺基酸序列；
● 肽連接子，該肽連接子具有選自由SEQ ID NO: 563組成之群組的胺基酸序列，其可被以下中的任一個替代：SEQ ID NO: 564-575；或679；和
● 多肽，該多肽具有選自由SEQ ID NO: 11、SEQ ID NO: 25、SEQ ID NO: 39、SEQ ID NO: 67和SEQ ID NO: 193組成之群組的胺基酸序列；
(b) 從N末端至C末端按以下順序構成的多肽：
● 多肽，該多肽具有選自由SEQ ID NO: 11、SEQ ID NO: 25、SEQ ID NO: 39、SEQ ID NO: 67和SEQ ID NO: 193組成之群組的胺基酸序列
● 肽連接子，該肽連接子具有選自由SEQ ID NO: 563組成之群組的胺基酸序列，其可被以下中的任一個替代：SEQ ID NO: 564-575；或679；和
● 多肽，該多肽具有選自由SEQ ID NO: 12、SEQ ID NO: 26、SEQ ID NO: 40、SEQ ID NO: 68和SEQ ID NO: 194組成之群組的胺基酸序列；
(c) 從N末端至C末端按以下順序構成的多肽：
● 多肽，該多肽具有選自由SEQ ID NO: 12和SEQ ID NO: 194組成之群組特別是SEQ ID NO: 12的胺基酸序列；
● 肽連接子，該肽連接子具有選自由SEQ ID NO: 563組成之群組的胺基酸序列，其可被以下中的任一個替代：SEQ ID NO: 564-575；或679；和
● 多肽，該多肽具有選自由SEQ ID NO: 11和SEQ ID NO: 193組成之群組特別是SEQ ID NO: 11的胺基酸序列；
(d) 從N末端至C末端按以下順序構成的多肽：
● 多肽，該多肽具有選自由SEQ ID NO: 25、SEQ ID NO: 39和SEQ ID NO: 67組成之群組的胺基酸序列，
● 肽連接子，該肽連接子具有選自由SEQ ID NO: 563組成之群組的胺基酸序列，其可被以下中的任一個替代：SEQ ID NO: 564-575；和679；和
● 多肽，該多肽具有選自由SEQ ID NO: 26、SEQ ID NO: 40和SEQ ID NO: 68組成之群組的胺基酸序列；
(e) 從N末端至C末端按以下順序構成的多肽：
● 多肽，該多肽具有選自由SEQ ID NO: 12、SEQ ID NO: 26、SEQ ID NO: 40、SEQ ID NO: 68和SEQ ID NO: 194組成之群組的胺基酸序列；
● 肽連接子，該肽連接子具有選自由SEQ ID NO: 563組成之群組的胺基酸序列，其可被以下中的任一個替代：SEQ ID NO: 564-575；或679；和
● 多肽，該多肽具有選自由SEQ ID NO: 11、SEQ ID NO: 25、SEQ ID NO: 39、SEQ ID NO: 67和SEQ ID NO: 193組成之群組的胺基酸序列；
(f) 從N末端至C末端按以下順序構成的多肽：
● 多肽，該多肽具有選自由SEQ ID NO: 12、SEQ ID NO: 26、SEQ ID NO: 40、SEQ ID NO: 68和SEQ ID NO: 194組成之群組的胺基酸序列；
● 肽連接子，該肽連接子具有選自由SEQ ID NO: 563組成之群組的胺基酸序列，其可被以下中的任一個替代：SEQ ID NO: 564-575；或679；和
● 多肽，該多肽具有選自由SEQ ID NO: 11、SEQ ID NO: 25、SEQ ID NO: 39、SEQ ID NO: 67和SEQ ID NO: 193組成之群組的胺基酸序列；
● 肽連接子，該肽連接子具有選自由SEQ ID NO: 565組成之群組的胺基酸序列，其可被以下中的任一個替代：SEQ ID NO: 563、564、566-575；或679；和
● 多肽，該多肽具有選自由SEQ ID NO: 19、22、33、36、47、50、75、78、201和204，特別是19和22組成之群組的胺基酸序列；
(g) 從N末端至C末端按以下順序構成的多肽：
● 多肽，該多肽具有選自由SEQ ID NO: 11、SEQ ID NO: 25、SEQ ID NO: 39、SEQ ID NO: 67和SEQ ID NO: 193組成之群組的胺基酸序列
● 肽連接子，該肽連接子具有選自由SEQ ID NO: 563組成之群組的胺基酸序列，其可被以下中的任一個替代：SEQ ID NO: 564-575；或679；和
● 多肽，該多肽具有選自由SEQ ID NO: 12、SEQ ID NO: 26、SEQ ID NO: 40、SEQ ID NO: 68和SEQ ID NO: 194組成之群組的胺基酸序列；
● 肽連接子，該肽連接子具有選自由SEQ ID NO: 565組成之群組的胺基酸序列，其可被以下中的任一個替代：SEQ ID NO: 563、564、566-575；或679；和
● 多肽，該多肽具有選自由SEQ ID NO: 19、22、33、36、47、50、75、78、201和204，特別是19和22組成之群組的胺基酸序列。
根據另一個實施方式，本發明之構建體包含（除了包含結合CLDN6和CD3的本文所述之互補位的結構域以外）另外的結構域，該另外的結構域包含兩個多肽單體，每個多肽單體包含鉸鏈、CH2和CH3結構域，其中所述兩個多肽單體經由肽連接子彼此融合。設想所述第三結構域按N末端至C末端的順序包含：鉸鏈-CH2-CH3-連接子-鉸鏈-CH2-CH3。在SEQ ID NO: 581-637中描繪了可以用於所述第三結構域的胺基酸序列。所述多肽單體中的每一種可以具有選自由SEQ ID NO: 630-637組成之群組、或與那些序列至少90%相同的胺基酸序列。
SEQ ID NO: 622中描繪的一個較佳的多肽單體，和SEQ ID NO: 630中描繪的較佳的第三結構域。
在另一個實施方式中，本發明之構建體的第一和第二結構域經由肽連接子與第三結構域融合，所述肽連接子例如選自由SEQ ID NO: 563、564、565、566、567、568、569、570、571、572、573、574和575和SEQ ID NO: 679組成之群組。
根據本發明，「鉸鏈」係IgG鉸鏈區。該區域可以使用Kabat編號藉由模擬來鑒定，參見例如Kabat位置223-243。與上述一致，對於「鉸鏈」的最低要求係與根據Kabat編號的D231至P243的IgG1序列延伸物對應的胺基酸殘基。術語「CH2」和「CH3」係指免疫球蛋白重鏈恒定區2和3。該等區域也可以使用Kabat編號藉由模擬來鑒定，參見例如Kabat位置244-360（對於CH2）和Kabat位置361-478（對於CH3）。應當理解，在免疫球蛋白之間在其IgG1 Fc區、IgG2 Fc區、IgG3 Fc區、IgG4 Fc區、IgM Fc區、IgA Fc區、IgD Fc區和IgE Fc區方面存在一些變化（參見例如，Padlan, Molecular Immunology [分子免疫學], 31(3), 169-217 (1993)）。術語Fc區係指IgA、IgD和IgG的最後兩個重鏈恒定區、以及IgE和IgM的最後三個重鏈恒定區。Fc區還可以包括該等結構域的N末端的柔性鉸鏈。對於IgA和IgM，Fc區可以包括J鏈。對於IgG，Fc區包含免疫球蛋白結構域CH2和CH3、以及在前兩個結構域與CH2之間的鉸鏈。儘管免疫球蛋白的Fc區的邊界可以改變，但是包含功能鉸鏈、CH2和CH3結構域的人IgG重鏈Fc部分的實例可以定義為例如分別對於IgG4包含殘基D231（鉸鏈結構域的殘基）至P476（CH3結構域的C末端的殘基）、或D231至L476，其中編號係根據Kabat。
因此，本發明之多肽構建體按N末端至C末端的順序可以包含：
(a) 一個結構域，該結構域包含結合CLDN6表位的互補位（抗原結合（表位結合）結構）；
(b) 肽連接子，該肽連接子具有選自由SEQ ID NO: 563-575，特別是563、568、570至575，更特別是SEQ ID NO: 570組成之群組的胺基酸序列；
(c) 另一個結構域，該結構域包含結合CD3表位的互補位（抗原結合（表位結合）結構）；
(d) 肽連接子，該肽連接子具有選自由SEQ ID NO: 563-575和SEQ ID NO: 679組成之群組特別是SEQ ID NO: 679的胺基酸序列；
(e) 一種半衰期延長結構域（包括鉸鏈、CH2和CH3結構域）的多肽單體，具有選自由SEQ ID NO: 630-637，特別是SEQ ID NO: 630組成之群組的胺基酸序列；
(f) 肽連接子，該肽連接子具有選自由SEQ ID NO: 563-575組成之群組特別是SEQ ID NO: 573的胺基酸序列；和
(g) 另一種半衰期延長結構域（包括鉸鏈、CH2和CH3結構域）的多肽單體，具有選自由SEQ ID NO: 630-637，特別是SEQ ID NO: 630組成之群組的胺基酸序列。
還設想本發明之多肽構建體按N末端至C末端的順序包含：
● 包含結合CLDN6的表位的互補位（抗原結合（表位結合）結構）的一個結構域，其具有選自由以下組成之群組的胺基酸序列：SEQ ID NO: 19、SEQ ID NO: 22、SEQ ID NO: 33、SEQ ID NO: 36、SEQ ID NO: 47、SEQ ID NO: 50、SEQ ID NO: 75、SEQ ID NO: 78、SEQ ID NO: 201、SEQ ID NO: 204，特別是SEQ ID NO: 19、SEQ ID NO: 22、SEQ ID NO: 33、SEQ ID NO: 36、SEQ ID NO: 47，更特別是SEQ ID NO: 19、SEQ ID NO: 22；其中包含在那些序列中並具有SEQ ID NO: 570的肽連接子可以被SEQ ID NO: 563-575中的任何一個替代；
● 肽連接子，該肽連接子具有選自由SEQ ID NO: 563、565、566、569、570，特別是SEQ ID NO: 565組成的胺基酸序列；
● 包含結合CD3的表位的互補位（抗原結合（表位結合）結構）的另一個結構域，其具有選自由以下組成之群組的胺基酸序列：SEQ ID NO: 542-562和678；其中包含在那些序列中的肽連接子選自具有SEQ ID NO: 563-575和679的胺基酸；
● 肽連接子，該肽連接子具有選自由SEQ ID NO: 563-575組成之群組的胺基酸序列；和
● 包含選自由SEQ ID NO: 630-637、特別是SEQ ID NO: 630組成之群組的一個或多個胺基酸序列的另一個結構域，以及具有選自由SEQ ID NO: 563-575、特別是SEQ ID NO: 573組成之群組的胺基酸序列的肽連接子。
因此，在一個實施方式中，本發明之多肽構建體包含具有選自由以下各項組成的群組的胺基酸序列的多肽或由其組成：SEQ ID NO: 21、24、35、38、49、52、63、66、77、80、91、94、105、108、119、122、133、136、147、150、161、164、175、178、189、192、203、206、217、220、231、234、245、148、259、262、273、276、287、290、301、304、315、318、329、332、343、346、357、360、371、374、385、388、399、402、413、416、427和430，特別是21、24、35、38、49、52、63、66、77、80、91、94，更特別是21、24、35、38、49、52、77和80，特別是21、35、49和77。
多肽/多肽構建體的共價修飾也包括在本發明之範圍內，並且通常但不總是在翻譯後進行。例如，藉由使構建體的特定胺基酸殘基與可以與選擇的側鏈或與N末端或C末端殘基反應的有機衍生劑反應，將構建體的若干種類型的共價修飾引入到分子中。用雙功能劑衍生化可用於將本發明之構建體交聯到水不溶性載體基質或表面以用於多種方法中。麩醯胺酸醯殘基和天冬醯胺醯殘基通常分別脫醯胺成相應的麩胺醯殘基和天冬胺醯殘基。可替代地，該等殘基在弱酸性條件下脫醯胺。該等殘基的任一形式都屬於本發明之範圍。其他修飾包括對脯胺酸和離胺酸的羥基化、對絲胺醯或蘇胺醯殘基的羥基的磷酸化、對離胺酸、精胺酸和組胺酸側鏈的α-胺基的甲基化（T. E. Creighton, Proteins: Structure and Molecular Properties [蛋白質：結構和分子特性], W. H. Freeman & Co. [W.H.弗裡曼公司], 三藩市, 1983, 第79-86頁）、對N末端胺的乙醯化和對任何C末端羧基的醯胺化。
包括在本發明範圍內的構建體的另一物種型的共價修飾包括改變蛋白質的糖基化模式。如本領域中已知的，糖基化模式可以取決於蛋白質的序列（例如，下文論述的特定糖基化胺基酸殘基的存在或不存在）或其中產生蛋白質的宿主細胞或生物體。下面論述特定表現系統。多肽的糖基化典型地是N-連接或O-連接的。N-連接係指碳水化合物部分附接至天冬醯胺殘基的側鏈。三肽序列天冬醯胺-X-絲胺酸和天冬醯胺-X-蘇胺酸（其中X為除脯胺酸以外的任何胺基酸）係將碳水化合物部分酶促附接至天冬醯胺側鏈的識別序列。因此，在多肽中該等三肽序列中的任一個的存在產生潛在的糖基化位點。O-連接糖基化係指將糖N-乙醯半乳糖胺、半乳糖或木糖中的一種附接至羥基胺基酸，最常見的是絲胺酸或蘇胺酸，儘管也可使用5-羥基脯胺酸或5-羥基離胺酸。
藉由改變胺基酸序列以使得它含有上述三肽序列中的一者或多者，從而方便地完成向構建體添加糖基化位點（用於N-連接的糖基化位點）。還可以藉由向起始序列（對於O-連接的糖基化位點）添加或取代為一個或多個絲胺酸或蘇胺酸殘基來作出改變。為了方便起見，構建體的胺基酸序列可以藉由DNA水平的變化來改變，特別是藉由在預選鹼基處突變編碼多肽的DNA，以使得產生將翻譯成所希望胺基酸的密碼子。
增加構建體上的碳水化合物部分的數量的另一種手段係藉由將糖苷化學或酶促偶聯至蛋白質。該等程序的有利之處在於，它們不需要在具有用於N-和O-連接的糖基化的糖基化能力的宿主細胞中產生蛋白質。取決於所使用的偶聯方式，一種或多種糖可附接至 (a) 精胺酸和組胺酸，(b) 游離羧基基團，(c) 游離巰基基團，諸如半胱胺酸的那些，(d) 游離羥基基團，諸如絲胺酸、蘇胺酸或羥基脯胺酸的那些，(e) 芳香族殘基，諸如苯丙胺酸、酪胺酸或色胺酸的那些，或 (f) 麩醯胺酸的醯胺基團。該等方法描述於WO 87/05330以及Aplin和Wriston, 1981, CRC Crit. Rev. Biochem. [CRC生物化學關鍵評論], 第259-306頁中。
存在於起始構建體上的碳水化合物部分的去除可以藉由化學或酶促方式完成。化學去糖基化要求將蛋白質暴露於化合物三氟甲磺酸，或等效化合物。該處理導致除連接糖（N-乙醯葡糖胺或N-乙醯半乳糖胺）以外的大多數或所有糖裂解，同時使多肽保持完整。化學去糖基化由Hakimuddin等人, 1987, Arch. Biochem. Biophys. [生物化學與生物物理學集刊] 259:52以及Edge等人, 1981, Anal. Biochem. [分析生物化學] 118:131描述。多肽上碳水化合物部分的酶促裂解可以使用多種內切糖苷酶和外切糖苷酶實現，如由Thotakura等人, 1987, Meth. Enzymol. [酶學方法]138:350所述之。可以使用化合物衣黴素預防潛在糖基化位點處的糖基化，如由Duskin等人, 1982, J. Biol. Chem. [生物化學雜誌] 257:3105所述之。衣黴素阻斷蛋白質-N-糖苷鍵的形成。
本文還考慮構建體的其他修飾。例如，構建體的另一種類型的共價修飾包括以在美國專利案號4,640,835、4,496,689；4,301,144；4,670,417；4,791,192或4,179,337中所述之方式將構建體與各種非蛋白質聚合物（包括多元醇）連接。此外，如本領域中已知的，可以在構建體內的不同位置進行胺基酸取代，例如以有利於添加聚合物如聚乙二醇（PEG）。
在一些實施方式中，本發明之構建體的共價修飾包括添加一個或多個標記。標記基團可以經由各種長度的間隔臂與構建體偶聯以減少潛在的空間位阻。用於標記蛋白質的各種方法在本領域中是已知的並且可以用於進行本發明。術語「標記」或「標記基團」係指任何可檢測的標記。通常，標記屬於多種類別，這取決於將檢測它們的測定-以下實例包括但不限於：
a) 同位素標記，該等同位素標記可以是放射性同位素或重同位素，如放射性同位素或放射性核素（例如
3H、
14C、
15N、
35S、
89Zr、
90Y、
99Tc、
111In、
125I、
131I）
b) 磁性標記（例如磁性顆粒）
c) 氧化還原活性部分
d) 光學染料（包括但不限於，生色團、磷光體和螢光團），如螢光基團（例如FITC、羅丹明、鑭系元素磷光體）、化學發光基團和螢光團，該等螢光團可以是「小分子」螢光劑或蛋白質螢光劑
e) 酶促基團（例如辣根過氧化物酶、β-半乳糖苷酶、螢光素酶、鹼性磷酸酶）
f) 生物素化基團
g) 由第二報導基因識別的預定多肽表位（例如，白胺酸拉鍊對序列、第二抗體的結合位點、金屬結合結構域、表位標籤等）。
「螢光標記」意指可經由其固有螢光特性加以檢測的任何分子。適合的螢光標記包括但不限於螢光素、羅丹明、四甲基羅丹明、伊紅、赤蘚紅、香豆素、甲基-香豆素、芘、孔雀石綠、二苯乙烯、螢光黃、瀑布藍J、德克薩斯紅、IAEDANS、EDANS、BODIPY FL、LC紅640、Cy5、Cy5.5、LC紅705、俄勒岡綠、Alexa-Fluor染料（Alexa Fluor 350、Alexa Fluor 430、Alexa Fluor 488、Alexa Fluor 546、Alexa Fluor 568、Alexa Fluor 594、Alexa Fluor 633、Alexa Fluor 660、Alexa Fluor 680）、瀑布藍、瀑布黃和R-藻紅蛋白（PE）（俄勒岡州尤金市的分子探針公司（Molecular Probes, Eugene, OR））、FITC、羅丹明和德克薩斯紅（伊利諾州羅克福德的皮爾斯公司（Pierce, Rockford, IL））、Cy5、Cy5.5、Cy7（賓夕法尼亞州匹茲堡市的阿默舍姆生命科學公司（Amersham Life Science, Pittsburgh, PA））。適合的光學染料（包括螢光團）描述於Richard P. Haugland的Molecular Probes Handbook [分子探針手冊]中。
合適的蛋白質螢光標記還包括但不限於，綠色螢光蛋白，包括GFP的Renilla、Ptilosarcus、或Aequorea種類（Chalfie等人, 1994, Science [科學] 263:802-805）、EGFP（Clontech實驗室公司，Genbank®登錄號U55762）、藍色螢光蛋白（BFP，量子生物技術公司（Quantum Biotechnologies, Inc.），加拿大魁北克省蒙特利爾市邁松納夫大道西1801號第8層（郵編：H3H 1J9）（1801 de Maisonneuve Blvd. West, 8th Floor, Montreal, Quebec, Canada H3H 1J9）；Stauber, 1998, Biotechniques [生物技術] 24:462-471；Heim等人, 1996, Curr.Biol. [當代生物學] 6:178-182）、增強型黃色螢光蛋白（EYFP，克羅泰克實驗室有限公司）、螢光素酶（Ichiki等人, 1993, J. Immunol. [免疫學雜誌] 150:5408-5417）、β半乳糖苷酶（Nolan等人, 1988, Proc. Natl. Acad. Sci. U.S.A. [美國國家科學院院刊] 85:2603-2607）和海腎（Renilla）（WO 92/15673、WO 95/07463、WO 98/14605、WO 98/26277、WO 99/49019、美國專利案號5,292,658；5,418,155；5,683,888；5,741,668；5,777,079；5,804,387；5,874,304；5,876,995；5,925,558）。
白胺酸拉鍊結構域係促進在其中發現它們的蛋白質的寡聚化的肽。白胺酸拉鍊最初在幾種DNA結合蛋白中被鑒定（Landschulz等人, 1988, Science [科學] 240:1759），並且自此以後已經在多種不同的蛋白質中發現。已知的白胺酸拉鍊包括天然存在的肽及其二聚化或三聚化的衍生物。適合用於產生可溶性寡聚蛋白質的白胺酸拉鍊結構域的實例描述於PCT申請WO 94/10308中，並且從肺表面活性蛋白D（SPD）衍生的白胺酸拉鍊描述於Hoppe等人, 1994, FEBS Letters [歐洲生物化學會聯盟通訊] 344:191中。允許與其融合的異源蛋白質的穩定三聚化的經修飾的白胺酸拉鍊的使用描述於Fanslow等人, 1994, Semin.Immunol. [免疫學研討文輯] 6:267-78中。
本發明之多肽構建體還可以包含另外的結構域，該等結構域例如有助於分離分子或關於分子的適應性藥物動力學分佈。有助於分離構建體的結構域可以選自肽模體或輔助性地引入的部分，該等部分可以在分離方法（例如分離柱）中捕獲。此類另外的結構域的非限制性實施方式包括稱為Myc-標籤、HAT-標籤、HA-標籤、TAP-標籤、GST-標籤、幾丁質結合結構域（CBD-標籤）、麥芽糖結合蛋白（MBP-標籤）、Flag-標籤、Strep-標籤以及其變體（例如StrepII-標籤）和His-標籤的肽模體。本文揭露的所有構建體（以鑒定的CDR為特徵）可以包含His-標籤結構域，該His-標籤結構域通常被稱為分子的胺基酸序列中的連續His殘基的重複序列，例如五個His殘基的重複序列（SEQ ID NO: 638）或六個His殘基的重複序列（六組胺酸，SEQ ID NO: 639）。His-標籤可以位於例如構建體的N末端或C末端。在一個實施方式中，六組胺酸標籤（HHHHHH）經由肽鍵連接至根據本發明之構建體的C末端。
還設想本發明之多肽構建體包含以下多肽或由其組成，該多肽具有選自由SEQ ID NO: 22和24中描繪的那些胺基酸序列組成之群組的胺基酸序列並且在其N末端或其C末端與蛋白質純化標籤連接（較佳的是經由肽鍵（醯胺鍵））。蛋白質純化標籤在多肽的C末端的連接係較佳的。設想蛋白質純化標籤係短肽。例如，短肽的長度可以是2個-30個胺基酸、4個-25個胺基酸、5個-20個胺基酸或6個-19個胺基酸。蛋白質純化標籤的實例包括但不限於AU1表位（例如，SEQ ID NO: 644中描繪的）、AU5表位（例如，SEQ ID NO: 645中描繪的）、T7-標籤（例如，SEQ ID NO: 646中描繪的）、V5-標籤（例如，SEQ ID NO: 647中描繪的）、B-標籤（例如，SEQ ID NO: 648中描繪的）、E2表位（例如，SEQ ID NO: 649中描繪的）、FLAG表位/FLAG標籤（例如，SEQ ID NO: 650中描繪的）、Glu-Glu標籤（例如，SEQ ID NO: 651或652中描繪的）、HA標籤、組胺酸親和力標籤（例如，SEQ ID NO: 653中描繪的）、HSV表位（例如，SEQ ID NO: 654中描繪的）、KT3表位（例如，SEQ ID NO: 655中描繪的）、Myc表位（例如，SEQ ID NO: 656中描繪的）、聚精胺酸標籤（5個-6個Arg殘基）、聚天冬胺酸標籤（5個-16個Asp殘基）、聚組胺酸標籤（2個-10個His殘基，通常6個His殘基，參見例如，SEQ ID NO: 639）、聚苯丙胺酸標籤（通常11個Phe殘基）、S1標籤（例如，SEQ ID NO: 659中描繪的）、S-標籤（例如，SEQ ID NO: 660中描繪的）、Strep-標籤（例如，SEQ ID NO: 661或662中描繪的）、通用標籤（例如，SEQ ID NO: 663中描繪的）、VSV-G（例如，SEQ ID NO: 664中描繪的）、蛋白質C（例如，SEQ ID NO: 665中描繪的）和蛋白質A。組胺酸標籤係較佳的，尤其是6x His標籤（SEQ ID NO: 639）。因此，進一步設想本發明之構建體由如下多肽組成：該多肽具有選自由SEQ ID NO: 22和24中描繪的那些胺基酸序列組成之群組的胺基酸序列並且在其C末端經由肽鍵與6x His標籤連接。
T細胞或T淋巴細胞係在細胞介導的免疫中發揮核心作用的一類淋巴細胞（其本身係一類白血球）。有若干個T細胞亞組，每個亞組具有不同的功能。T細胞可以藉由細胞表面上存在T細胞受體（TCR）而與其他淋巴細胞（諸如B細胞和NK細胞）區分開。TCR負責識別與主要組織相容性複合物（MHC）分子結合的抗原，並且由兩種不同的蛋白質鏈構成。在95%的T細胞中，TCR由阿爾法（α）和貝塔（β）鏈組成。當TCR與抗原肽和MHC（肽/MHC複合物）接合時，T淋巴細胞藉由一系列由相關酶、共受體、特化銜接分子和活化或釋放的轉錄因子介導的生物化學事件而被活化。
本發明之多肽構建體包含與T細胞表面上的CD3結合的結構域。「CD3」（分化簇3）係由四條鏈構成的T細胞共受體。在哺乳動物中，CD3蛋白質複合物含有CD3γ（伽馬）鏈、CD3δ（德爾塔）鏈和兩條CD3ε（伊蒲賽龍）鏈。這四條鏈與T細胞受體（TCR）和所謂的ζ（截塔）鏈締合以形成「T細胞受體複合物」並在T淋巴細胞中產生活化信號。CD3γ（伽馬）、CD3δ（德爾塔）和CD3ε（伊蒲賽龍）鏈係免疫球蛋白超家族的高度相關的細胞表面蛋白，並且每一種都含有單一細胞外免疫球蛋白結構域。CD3分子的細胞內尾含有對於TCR的信號傳導能力所必需的單一保守模體，稱為基於免疫受體酪胺酸的活化模體（ITAM）。CD3ε分子係多肽，該多肽在人中由位於染色體11上的CD3ε基因編碼。在本發明之上下文中，CD3被理解為參與活化細胞毒性T細胞（CD8+原始T細胞）和T輔助細胞（CD4+原始T細胞）的蛋白質複合物和T細胞共受體。它通常由四條不同的鏈組成。特別在哺乳動物中，複合物含有CD3γ鏈、CD3δ鏈和兩條CD3ε鏈。該等鏈與T細胞受體（TCR）和ζ鏈（zeta-鏈）締合，在T淋巴細胞中產生活化信號。TCR、ζ鏈和CD3分子共同構成了TCR複合物。
藉由與T細胞上的CD3和與靶細胞上的靶蛋白結合的構建體募集T細胞來將靶細胞重定向溶解通常關於溶細胞突觸形成以及穿孔素和顆粒酶的遞送。接合的T細胞能夠進行連續靶細胞溶解，並且不受干擾肽抗原加工和呈遞或選殖T細胞分化的免疫逃逸機制的影響；參見例如WO 2007/042261。
可以按多種方式測量由CLDN6xCD3構建體介導的細胞毒性。「半數最大有效濃度」（EC50）通常用作生物活性分子（如本發明之構建體）的效力的量度。它可以按莫耳單位表示。在測量細胞毒性的當前情況下，EC50值係指在基線和最大值之間的中途誘導細胞毒性反應（靶細胞溶解）的構建體的濃度。細胞毒性測定中的效應細胞可以例如是刺激的富集的（人）CD8陽性T細胞或未刺激的（人）外周血單核細胞（PBMC）。與未刺激的PBMC相比，當將刺激的/富集的CD8+ T細胞用作效應細胞時，典型地預期EC50值較低。如果靶細胞係獼猴起源或表現的或用獼猴CLDN6轉染的，則效應細胞也應係獼猴起源的，如獼猴T細胞系，例如4119LnPx。靶細胞應在細胞表面上表現CLDN6，如人或獼猴CLDN6。較佳的是，靶細胞應在細胞表面上至少表現CLDN6的一個或多個細胞外環，如CLDN6環1和/或環2。靶細胞可以是用CLDN6（例如人或獼猴CLDN6）穩定或暫態轉染的細胞系（如CHO）。可替代地，靶細胞可以是CLDN6陽性自然表現細胞系，如人癌細胞系。通常，與具有較低靶標表現率的靶細胞相比，當使用在細胞表面上表現較高的CLDN6水平的靶細胞時，預期EC50值較低。
在細胞毒性測定中效應細胞與靶細胞（E:T）比率通常為約10:1，但也可以改變。CLDN6xCD3構建體的細胞毒性活性可以在鉻51釋放測定（例如，具有約18小時的孵育時間）中或在基於FACS的細胞毒性測定（例如，具有約48小時的孵育時間）中測量。還設想了孵育時間（細胞毒性反應）的修飾。其他測量細胞毒性之方法係熟知的，並且包括MTT或MTS測定、基於ATP的測定（包括生物發光測定）、磺基羅丹明B（SRB）測定、WST測定、選殖生成測定和ECIS技術。
根據一個實施方式，在基於細胞的細胞毒性測定中測量由本發明之CLDN6xCD3構建體介導的細胞毒性活性。它也可以在51-鉻釋放測定中進行測量。設想本發明之構建體的EC50值為≤300 pM、≤280 pM、≤260 pM、≤250 pM、≤240 pM、≤220 pM、≤200 pM、≤180 pM、≤160 pM、≤150 pM、≤140 pM、≤120 pM、≤100 pM、≤90 pM、≤80 pM、≤70 pM、≤60 pM、≤50 pM、≤40 pM、≤30 pM、≤20 pM、≤15 pM、≤10 pM或≤5 pM。
可以在不同的測定中和在不同條件下測量上述給定的EC50值。例如，當將人PBMC用作效應細胞並且將CLDN6轉染細胞如CHO細胞用作靶細胞時，設想CLDN6xCD3構建體的EC50值為≤500 pM、≤400 pM、≤300 pM、≤280 pM、≤260 pM、≤250 pM、≤240 pM、≤220 pM、≤200 pM、≤180 pM、≤160 pM、≤150 pM、≤140 pM、≤120 pM、≤100 pM、≤90 pM、≤80 pM、≤70 pM、≤60 pM、≤50 pM、≤40 pM、≤30 pM、≤20 pM、≤15 pM、≤10 pM或≤5 pM。當將人PBMC用作效應細胞時，並且當靶細胞係如CLDN6陽性細胞系時，可以設想CLDN6xCD3構建體的EC50值為≤300 pM、≤280 pM、≤260 pM、≤250 pM、≤240 pM、≤220 pM、≤200 pM、≤180 pM、≤160 pM、≤150 pM、≤140 pM、≤120 pM、≤100 pM、≤90 pM、≤80 pM、≤70 pM、≤60 pM、≤50 pM、≤40 pM、≤30 pM、≤20 pM、≤15 pM、≤10 pM或≤5 pM。
根據一個實施方式，本發明之CLDN6xCD3多肽/多肽構建體不誘導/介導不在其表面上表現CLDN6的細胞（CLDN6陰性細胞）如CHO細胞的溶解或基本上不誘導/介導溶解。術語「不誘導溶解」、「基本上不誘導溶解」、「不介導溶解」或「基本不介導溶解」意指本發明之構建體不誘導或介導多於30%、較佳的是不多於20%、更較佳的是不多於10%、特別較佳的是不多於9%、8%、7%、6%或5%的CLDN6陰性細胞的溶解，由此表現CLDN6的靶細胞（如用CLDN6轉化或轉染的細胞或天然表現細胞系如人癌細胞系）的溶解被設定為100%。這通常適用於濃度高達500 nM的構建體。細胞溶解測量係常規技術。此外，本說明書教導了如何測量細胞溶解的具體說明。
單個的CLDN6xCD3多肽/多肽構建體的單體與二聚體同種型之間的細胞毒性活性的差異被稱為「效力差距」。該效力差距可以例如計算為分子的單體與二聚體形式的EC50值之間的比率。在確定該差距的一種方法中，如下文所述用純化的構建體單體和二聚體進行了18小時51-鉻釋放測定或48 h基於FACS的細胞毒性測定。效應細胞係刺激的富集的人CD8+ T細胞或未刺激的人PBMC。靶細胞係hu CLDN6轉染的CHO細胞。效應細胞與靶細胞（E:T）的比率為10:1。本發明之CLDN6xCD3構建體的效力差距較佳的是≤5、更較佳的是≤4、甚至更較佳的是≤3、甚至更較佳的是≤2，並且最較佳的是≤1。
本發明之多肽構建體的結構域較佳的是對於靈長類哺乳動物目的成員（如獼猴）具有跨物種特異性。跨物種特異性CD3結合結構域例如描述於WO 2008/119567中。根據一個實施方式，除了與人CD3結合之外，該結構域還將與靈長類動物的CD3結合，該靈長類動物包括（但不限於）新大陸靈長類動物（如普通狨（Callithrix jacchus）、絨頂檉柳猴（Saguinus Oedipus）或松鼠猴（Saimiri sciureus））、舊大陸靈長類動物（如狒狒和獼猴）、長臂猿、猩猩和非人類人亞科（homininae）。設想與在T細胞表面上的人CD3結合的結構域還至少與獼猴CD3結合。較佳的獼猴係食蟹猴（Macaca fascicularis）。還設想了獼猴（Macaca mulatta）（恒河猴）。本發明之一種構建體包含與在靶細胞表面上的人CLDN6結合的結構域和與在T細胞表面上的人CD3和至少獼猴CD3結合的另一個結構域。
在一個實施方式中，根據本發明之構建體對於結合獼猴CD3與人CD3的親和力差距[KD ma CD3: KD hu CD3]（如藉由例如BiaCore或Scatchard分析確定的）為在0.01與100之間、較佳的是在0.1與10之間、更較佳的是在0.2與5之間、更較佳的是在0.3與4之間、甚至更較佳的是在0.5與3之間或在0.5與2.5之間，並且最較佳的是在0.5與1之間。
本發明之構建體的一個結構域與CD3結合。更較佳的是，它與T細胞表面上的CD3結合。此外，設想所述結構域與人CD3結合，較佳的是與T細胞表面上的人CD3結合。還設想所述結構域與CD3ε結合。更較佳的是，它與人CD3ε結合，例如與T細胞表面上的人CD3ε結合。人CD3ε的細胞外結構域的較佳的胺基酸序列在SEQ ID NO: 442中描繪。
在本發明之一個實施方式中，構建體的所述結構域與人CD3ε（或T細胞表面上的人CD3ε）和與普通狨（Callithrix jacchus）或松鼠猴（Saimiri sciureus）CD3ε結合。還設想所述結構域與CD3ε的細胞外表位結合、較佳的是與人CD3 ε的細胞外表位結合。還設想所述結構域與人和獼猴屬（Macaca）CD3ε鏈的細胞外表位結合。CD3ε的一個較佳的表位包含在人CD3ε細胞外結構域的胺基酸殘基1-27內（參見SEQ ID NO: 443）。甚至更特別地，表位至少包含胺基酸序列Gln-Asp-Gly-Asn-Glu。普通狨係屬於狨猴科（Callitrichidae）的新大陸靈長類動物，而松鼠猴係屬於懸猴科（Cebidae）的新大陸靈長類動物。具有此類特徵的結合物在WO 2008/119567中有詳細描述。
針對（人）CD3或選擇性和較佳的特異性針對CD3ε的抗體或雙特異性構建體在本領域中是已知的，並且它們的CDR、VH和VL序列可以作為本發明之多肽構建體的結合結構域的基礎。例如，Kung等人在1979年報導了OKT3（Ortho Kung T3）的開發，這係識別人T細胞上的CD3（特別是CD3的ε鏈）的第一個mAb。OKT3（莫羅單抗（muromonab））係第一種可用於人療法的鼠源性單株抗體。更新的抗CD3單株抗體包括奧特昔珠單抗（otelixizumab）（TRX4）、特普利珠單抗（teplizumab）（MGA031）、弗雷魯單抗（foralumab）和威司利珠單抗（visilizumab），均靶向CD3的ε鏈。針對（癌症）靶標和CD3的雙特異性構建體也正在進行開發和（預）臨床測試，並且它們的CD3結合結構域（CDR、VH、VL）可以用作本發明之構建體的第二結合結構域的基礎。實例包括但不限於博納吐單抗、索利托單抗（MT110、AMG 110）、卡妥索單抗（Catumaxomab）、度妥昔珠單抗（Duvortuxizumab）、厄妥瑪索單抗（Ertumaxomab）、洛莫索珠單抗（Mosunetuzumab）、FBTA05（Bi20、TPBs05）、CEA-TCB（RG7802、RO6958688）、AFM11、和MGD006（S80880）。例如在US 7,994,289 B2、US 7,728,114 B2、US 7,381,803 B1、US 6,706,265 B1中揭露了CD3結合結構域的其他實例。
對於根據本發明使用的多肽構建體，設想與T細胞表面上的CD3結合的結構域包含含有CDR-L1、CDR-L2和CDR-L3的VL區，其中CDR-L1的序列在SEQ ID NO: 673中描繪，CDR-L2的序列在SEQ ID NO: 674中描繪，並且CDR-L3的序列在SEQ ID NO: 675中描繪；或含有CDR-L1、CDR-L2和CDR-L3的VL區，CDR-L1序列如SEQ ID NO: 673中描繪，CDR-L2如SEQ ID NO: 674中描繪，並且CDR-L3如SEQ ID NO: 675中描繪，其中該等CDR中的一個或多個具有至少一個胺基酸殘基修飾。
對於根據本發明使用的多肽構建體，還設想與T細胞表面上的CD3結合的結構域包含含有CDR-H1、CDR-H2和CDR-H3的VH區，其中CDR-H1的序列如SEQ ID NO: 670中描繪，CDR-H2的序列如SEQ ID NO: 671中描繪，並且CDR-H3的序列如SEQ ID NO: 672中描繪；或含有CDR-H1、CDR-H2和CDR-H3的VH區，其中CDR-H1的序列如SEQ ID NO: 670中描繪，CDR-H2的序列如SEQ ID NO: 671中描繪，並且CDR-H3的序列如SEQ ID NO: 672中描繪，其中該等CDR中的一個或多個具有至少一個胺基酸殘基修飾。
對於根據本發明使用的多肽構建體，進一步設想與CD3結合的結構域包含含有CDR-L1、CDR-L2和CDR-L3的VL區和含有CDR-H1、CDR-H2和CDR-H3的VH區，其中CDR-L1的序列如SEQ ID NO: 673中描繪，CDR-L2的序列如SEQ ID NO: 674中描繪，CDR-L3的序列如SEQ ID NO: 675中描繪，其中CDR-H1的序列如SEQ ID NO: 670中描繪，CDR-H2的序列如SEQ ID NO: 671中描繪，並且CDR-H3的序列如SEQ ID NO: 672中描繪；或與CD3結合的結構域包含含有CDR-L1、CDR-L2和CDR-L3的VL區和含有CDR-H1、CDR-H2和CDR-H3的VH區，其中CDR-L1的序列如SEQ ID NO: 673中描繪，CDR-L2的序列如SEQ ID NO: 674中描繪，並且CDR-L3的序列如SEQ ID NO: 675中描繪，其中CDR-H1的序列如SEQ ID NO: 670中描繪，CDR-H2的序列如SEQ ID NO: 671中描繪，並且CDR-H3的序列如SEQ ID NO: 672中描繪，其中該等CDR中的一個或多個具有至少一個胺基酸殘基修飾。
對於根據本發明使用的多肽構建體，設想與T細胞表面上的CD3結合的結構域包含SEQ ID NO: 677中描繪的VL區，或其中該VL區包含至少一個胺基酸殘基修飾。
對於根據本發明使用的多肽構建體，設想與T細胞表面上的CD3結合的結構域包含SEQ ID NO: 676中描繪的VH區，或其中該VH區包含至少一個胺基酸殘基修飾。
更較佳的是，根據本發明使用的多肽構建體的特徵在於與T細胞表面上的CD3結合的結構域，該結構域包含VL區和VH區，該VL區和該VH區選自由SEQ ID NO: 677中描繪的VL區和SEQ ID NO: 676中描繪的VH區組成之群組；或其中該VL區或該VH區包含至少一個胺基酸殘基修飾。
根據本發明使用的上述多肽構建體的較佳的實施方式的特徵在於該與T細胞表面上的CD3結合的結構域包含SEQ ID NO: 678中描繪的胺基酸序列，或其中該與T細胞表面上的CD3結合的包含SEQ ID NO: 678中描繪的胺基酸序列的結構域包含至少一個胺基酸殘基修飾。
對於根據本發明使用的多肽構建體，設想與T細胞表面上的CD3結合的結構域包含VL區（例如，SEQ ID NO: 540中描繪的VL區）或VH區（例如，SEQ ID NO: 522或533中描繪的VL區），或SEQ ID NO: 444至506中描繪的CDR，特別是SEQ ID NO: 480至482和504至506中描繪的CDR，或例如SEQ ID NO: 551或562中或SEQ ID NO: 542-561任一項中描繪的scFv。
還考慮了本文描述的多肽/多肽構建體的胺基酸序列修飾。例如，可能需要改善多肽構建體的結合親和力和/或其他生物特性。多肽/多肽構建體的胺基酸序列變體藉由肽合成或藉由將適當的核苷酸改變引入編碼該多肽/多肽構建體的核酸分子中來製備。所有下面描述的胺基酸序列修飾應產生保留了未經修飾的親本分子的期望的生物活性（如結合CLDN6和CD3，誘導針對CLDN6陽性靶細胞的細胞毒性）的多肽構建體。
術語「胺基酸」或「胺基酸殘基」典型地是指具有其本領域公認的定義的胺基酸，如選自由以下組成之群組的胺基酸：丙胺酸（Ala或A）；精胺酸（Arg或R）；天冬醯胺（Asn或N）；天冬胺酸（Asp或D）；半胱胺酸（Cys或C）；麩醯胺酸（Gln或Q）；麩胺酸（Glu或E）；甘胺酸（Gly或G）；組胺酸（His或H）；異白胺酸（Ile或I）；白胺酸（Leu或L）；離胺酸（Lys或K）；蛋胺酸（Met或M）；苯丙胺酸（Phe或F）；脯胺酸（Pro或P）；絲胺酸（Ser或S）；蘇胺酸（Thr或T）；色胺酸（Trp或W）；酪胺酸（Tyr或Y）；以及纈胺酸（Val或V），儘管可以根據需要使用修飾的、合成的或稀有的胺基酸。基本上存在由不同的側鏈決定的四種不同類別的胺基酸：(1) 非極性和中性（不帶電荷）：Ala、Gly、Ile、Leu、Met、Phe、Pro、Val；(2) 極性和中性（不帶電荷）：Asn、Cys（僅微極性）、Gln、Ser、Thr、Trp（僅微極性）、Tyr； (3) 酸性和極性（帶負電荷）：Asp和Glu；(4) 鹼性和極性（帶正電荷）：Arg、His、Lys。
疏水性胺基酸可以根據它們是否具有脂肪族或芳香族側鏈來分開。Phe和Trp（非常大的疏水性）、Tyr和His（較小疏水性）被分類為芳香族胺基酸。嚴格地說，脂肪族意指側鏈僅含有氫原子和碳原子。藉由這種嚴格的定義，具有脂肪族側鏈的胺基酸係丙胺酸、異白胺酸、白胺酸（也是正白胺酸）、脯胺酸和纈胺酸。丙胺酸的側鏈非常短，意味著它不是特別具有疏水性，並且脯胺酸具有不尋常的幾何形狀，使其在蛋白質中起特殊作用。通常方便地將甲硫胺酸考慮為與異白胺酸、白胺酸和纈胺酸在同一類別，儘管它還含有硫原子。統一的主題係該等胺基酸主要含有非反應性和柔性側鏈。通常將胺基酸丙胺酸、半胱胺酸、甘胺酸、脯胺酸、絲胺酸和蘇胺酸分組在一起，因此它們全部都很小。Gly和Pro可能影響鏈取向。
胺基酸修飾包括，例如，多肽/多肽構建體的胺基酸序列內殘基的缺失、殘基的插入和/或殘基的取代。進行缺失、插入和/或取代的任何組合以獲得最終的構建體，條件係最終的構建體擁有所期望的特徵，例如，未經修飾的親本分子的生物活性（如結合CLDN6和CD3，誘導針對CLDN6陽性靶細胞的細胞毒性）。胺基酸變化還可以改變構建體的翻譯後過程，如改變糖基化位點的數目或位置。
例如，可以在每個CDR中插入、缺失和/或取代1個、2個、3個、4個、5個或6個胺基酸（當然，取決於它們各自的長度），而可以在每個框架區（FR）中插入、缺失和/或取代1個、2個、3個、4個、5個、6個、7個、8個、9個、10個、11個、12個、13個、14個、15個、16個、17個、18個、19個、20個或25個胺基酸。胺基酸序列插入還包括N末端和/或C末端胺基酸添加，其長度範圍為例如從1個、2個、3個、4個、5個、6個、7個、8個、9個或10個殘基至含有多於10個例如一百個或更多個殘基的多肽，以及單個或多個胺基酸殘基的序列內插入。本發明之構建體的插入變體包括將增加或延長構建體的血清半衰期的多肽融合至構建體的N末端或C末端。還可以想到，這樣的插入發生在構建體內，例如在第一結構域與第二結構域之間。
對於胺基酸修飾（特別是對於胺基酸取代）最感興趣的位點包括高變區，特別是重鏈和/或輕鏈的各個CDR，但是也考慮重鏈和/或輕鏈中的FR變化。取代可以是如本文所述之保守取代。較佳的是，可以在CDR中取代1個、2個、3個、4個、5個、6個、7個、8個、9個或10個胺基酸，而可以在框架區（FR）中取代1個、2個、3個、4個、5個、6個、7個、8個、9個、10個、11個、12個、13個、14個、15個、16個、17個、18個、19個、20個或25個胺基酸，這分別取決於CDR或FR的長度。例如，如果CDR序列涵蓋6個胺基酸，則設想該等胺基酸中的1個、2個或3個被取代。類似地，如果CDR序列涵蓋15個胺基酸，則設想該等胺基酸中的1個、2個、3個、4個、5個或6個被取代。
用於鑒定作為較佳的誘變位置的構建體內的某些殘基或區域的有用方法被稱為「丙胺酸掃描誘變」，並且描述於例如Cunningham B.C.和Wells J.A.（Science [科學].1989年6月2日; 244(4908):1081-5）中。此處，鑒定構建體內的殘基或殘基組（例如帶電殘基，如Arg、His、Lys、Asp和Glu），並將其用中性或非極性胺基酸（最較佳的是丙胺酸或聚丙胺酸）替代，以影響各個胺基酸與靶蛋白表位的相互作用。丙胺酸掃描係用於確定特定殘基對給定蛋白的穩定性或功能的貢獻的技術。丙胺酸的使用係因為其具有非巨大的、化學惰性的甲基官能基，但仍然模仿許多其他胺基酸所具有的二級結構偏好。在需要突變殘基大小保守的情況下，有時可以使用巨大的胺基酸（如纈胺酸或白胺酸）。該技術還可以用於確定特定殘基的側鏈是否在生物活性中起重要作用。丙胺酸掃描通常藉由定點誘變或隨機藉由創建PCR文庫完成。此外，已經開發了基於理論丙胺酸取代來估計熱力學參數的計算方法。數據可以藉由IR、NMR波譜法、數學方法、生物測定等進行測試。
然後，藉由在取代位點處或為取代位點引入另外的或其他變體來精確對取代展示功能敏感性的那些胺基酸位置（如例如藉由丙胺酸掃描確定的）。因此，雖然用於引入胺基酸序列變化的位點或區域係預定的，但突變本身的性質無需預定。例如，為了分析或優化給定位點處突變的性能，可以在靶密碼子或區域處進行丙胺酸掃描或隨機誘變，並且篩選所表現的構建體變體以獲得所希望活性的最優組合。用於在具有已知序列的DNA中的預定位點進行取代突變的技術係熟知的，例如，M13引物誘變和PCR誘變。例如使用抗原（例如CLDN6或CD3）結合活性和/或細胞毒性活性的測定來進行突變體篩選。
一般來講，如果在重鏈和/或輕鏈的一個或多個或所有CDR中胺基酸被取代，則設想當時獲得的「經取代的」序列與「原始」或「親本」CDR序列係至少60%或65%、更較佳的是70%或75%、甚至更較佳的是80%或85%並且特別較佳的是90%或95%相同的/同源的。這意味著原始序列與經取代的序列之間的同一性/同源性程度取決於CDR的長度。例如，總共具有5個胺基酸並且包含一個胺基酸取代的CDR與「原始」或「親本」CDR序列係80%相同的，而總共具有10個胺基酸並且包含一個胺基酸取代的CDR與「原始」或「親本」CDR序列係90%相同的。因此，本發明之構建體的經取代的CDR可以與其原始序列具有不同的同一性程度，例如，CDRL1可以具有80%的同源性，而CDRL3可以具有90%的同源性。相同的考慮適用於框架區和整個VH和VL區。
「變體CDR」係與本發明之親本CDR具有特定序列同源性、相似性或同一性的CDR，並且與親本CDR共用生物學功能，包括但不限於至少60%、65%、70%、75%、80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%或99%的親本CDR的特異性和/或活性。一般來講，各個變體CDR之間的胺基酸同源性、相似性或同一性為本文所描述的親本序列的至少60%，並且更典型地具有至少65%或70%、較佳的是至少75%或80%、更較佳的是至少85%、90%、91%、92%、93%、94%、並且最較佳的是95%、96%、97%、98%、99%、和幾乎100%的漸增的同源性、相似性或同一性。這同樣適用於「變體VH」和「變體VL」。根據一個實施方式，「變體VH」和/或「變體VL」內的序列變化不延伸至CDR。因此，本發明關於如本文所定義的構建體，該抗體構建體包含與本文所定義的特定序列（「親本」VH和VL）具有某些序列同源性（參見上文）的VH和VL序列，其中該等CDR序列與本文所定義的特定CDR序列（「親本」CDR）係100%相同的。
較佳的取代（或替代）係保守取代。然而，設想了任何取代（包括非保守取代或來自下表1中列出的「示例性取代」中的一個或多個），只要構建體保留其經由第一結構域與CLDN6結合並且經由第二結構域與CD3或CD3ε結合的能力，和/或只要其CDR、FR、VH和/或VL序列與原始或親本序列具有至少60%或65%、更較佳的是至少70%或75%、甚至更較佳的是至少80%或85%、並且特別較佳的是至少90%或95%的同一性程度即可。
保守替代（也稱為保守突變或保守取代）係將給定胺基酸改變為具有相似的生物化學特性（例如電荷、疏水性、大小）的不同胺基酸的胺基酸取代。與非保守替代相比，蛋白質中的保守替代通常對蛋白質功能具有較小的影響。在表1中顯示了保守取代。示例性保守取代顯示為「示例性取代」。如果此類取代導致生物活性的變化，那麼可以引入如本文中參考胺基酸類別進一步描述的更多實質性變化，並篩選產物的期望特徵。
[ 表 1] ：胺基酸取代（aa = 胺基酸）
| 原始aa | 保守取代 | 示例性取代 |
| Ala（A） | 小aa | Gly、Ser、Thr |
| Arg（R） | 極性aa，特別是Lys | Lys、Gln、Asn |
| Asn（N） | 極性aa，特別是Asp | Asp、Gln、His、Lys、Arg |
| Asp（D） | Glu或其他極性aa，特別是Asn | Glu、Asn |
| Cys（C） | 小aa | Ser、Ala |
| Gln（Q） | 極性aa，特別是Glu | Glu、Asn |
| Glu（E） | Asp或其他極性aa，特別是Gln | Asp、Gln |
| Gly（G） | 小aa，如Ala | Ala |
| His（H） | Asn、Gln、Arg、Lys、Tyr | |
| Ile（I） | 疏水性，特別是脂肪族aa | Ala、Val、Met、Leu、Phe |
| Leu（L） | 疏水性，特別是脂肪族aa | 正白胺酸、Ile、Ala、Val、Met |
| Lys（K） | 極性aa，特別是Arg | Arg、Gln、Asn |
| Met（M） | 疏水性，特別是脂肪族aa | Leu、Ala、Ile、Val、Phe |
| Phe（F） | 芳香族或疏水性aa，特別是Tyr | Tyr、Trp、Leu、Val、Ile、Ala |
| Pro（P） | 小aa | Ala |
| Ser（S） | 極性或小aa，特別是Thr | Thr |
| Thr（T） | 極性aa，特別是Ser | Ser |
| Trp（W） | 芳香族aa | Tyr、Phe |
| Tyr（Y） | 芳香族aa，特別是Phe | Phe、Trp、Thr、Ser |
| Val（V） | 疏水性，特別是脂肪族aa | Leu、Ile、Ala、Met、Phe |
本發明之構建體的生物特性的實質性修飾係藉由選擇在保持以下的效應方面顯著不同的取代來完成：(a) 取代基周圍多肽骨架的結構，例如呈折疊或螺旋構象，(b) 分子在靶位點的電荷或疏水性，或 (c) 側鏈的大部分。非保守取代通常需要將上面所定義的胺基酸類別之一（如極性、中性、酸性、鹼性、脂肪族、芳香族、小……）的成員交換為另一種類別。任何不參與維持構建體的適當構象的半胱胺酸殘基通常可以被絲胺酸取代以改善該構建體的氧化穩定性。
胺基酸序列的序列同一性、同源性和/或相似性藉由使用在本領域中已知的標準技術，較佳的是使用預設設置或藉由檢驗來確定，該等標準技術包括但不限於Smith和Waterman, 1981, Adv.Appl. Math.[應用數學進展]2:482的局部序列同一性演算法，Needleman和Wunsch（J Mol Biol. [分子生物學雜誌] 1970年3月; 48(3):443-53）的序列同一性比對演算法，Pearson和Lipman（Proc Natl Acad Sci USA. [美國國家科學院院刊]1988年4月; 85(8):2444-8）的相似性搜索方法，該等演算法的電腦化實現（威斯康辛遺傳學套裝軟體（Wisconsin Genetics Software Package）中的GAP、BESTFIT、FASTA和TFASTA，威斯康辛州麥迪森市科學大道575號遺傳學電腦組（Genetics Computer Group, 575 Science Drive, Madison, Wis.）），由Devereux等人（Nucleic Acids Res. [核酸研究] 1984年1月11日;12(1 Pt 1):387-95）描述的最佳擬合序列程式。設想了百分比同一性藉由FastDB基於以下參數來計算：錯配罰分為1；空位罰分為1；空位大小罰分為0.33；以及連接罰分為30。還參見「Current Methods in Sequence Comparison and Analysis [序列比較和分析的當前方法]」, Macromolecule Sequencing and Synthesis [大分子定序與合成], Selected Methods and Applications [所選擇之方法與應用], 第127-149頁 (1988), Alan R. Liss公司。
有用的演算法的實例係PILEUP。PILEUP使用漸進式成對比對從一組相關序列中創建多序列比對。它還可以繪製顯示用於創建比對的聚類關係的樹狀圖。PILEUP使用Feng和Doolittle（J Mol Evol. [分子進化雜誌] 1987; 25(4):351-60）的漸進式比對方法的簡單化；該方法類似於由Higgins和Sharp（Comput Appl Biosci. [電腦在生物科學中的應用] 1989年4月; 5(2):151-3）所描述之方法。有用的PILEUP參數包括預設空位權重為3.00、預設空位長度權重為0.10、和加權末端空位。
有用的演算法的另一實例係BLAST演算法，描述於以下中：Altschul等人（J Mol Biol. [分子生物學雜誌] 1990年10月5日; 215(3):403-10.）；Altschul等人（Nucleic Acids Res. [核酸研究] 1997年9月1日; 25(17):3389-402）；以及Karlin和Altschul（Proc Natl Acad Sci U S A. [美國國家科學院院刊] 1993年6月15日; 90(12):5873-7）。特別有用的BLAST程式係從Altschul等人（Methods Enzymol. [酶學方法] 1996; 266:460-80）獲得的WU-Blast-2程式。WU-Blast-2使用多個搜索參數，其中大部分都設定為預設值。將可調整參數設置為以下值：重疊間隔=1，重疊分數=0.125，字閾值（T）=II。HSP S和HSP S2參數係動態值，並且由程式本身根據特定序列的組成和各自的數據庫的組成來確立，根據該特定數據庫來搜索感興趣的序列；然而，可以調整該等值以增加靈敏度。
另外的有用演算法係空位BLAST，如由Altschul等人（Nucleic Acids Res. [核酸研究] 1997年9月1日;25(17):3389-402）報導的。空位BLAST使用BLOSUM-62取代評分；閾值T參數設定為9；觸發非空位擴展的按兩下方法，對k的空位長度收取10+k的成本；Xu設定為16，並且Xg設定為40（用於數據庫搜索階段）以及67（用於演算法的輸出階段）。空位比對由對應於約22比特的評分觸發。
與此一致，關於編碼本文鑒定的構建體的核酸序列的術語「核酸序列同一性/同源性/相似性的百分比（%）」被定義為候選序列中與構建體的編碼序列中的核苷酸殘基相同的核苷酸殘基的百分比。比對兩個序列並從而確定它們的同源性的一種方法使用WU-Blast2（設定為預設參數）的BLASTN模組，其中重疊跨度和重疊分數分別設定為1和0.125。一般來講，編碼各個變體CDR的核苷酸序列與本文所描述的核苷酸序列之間的核酸序列同源性、相似性或同一性係至少60%，並且更典型地具有至少65%、70%、75%、80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%或99%和幾乎100%的漸增的同源性、相似性或同一性。再次，這同樣適用於編碼「變體VH」和/或「變體VL」的核酸序列。
在一個實施方式中，根據本發明之多肽/多肽構建體或包含該等構建體的互補位（抗原結合（表位結合）結構；（結合結構域））的結構域與人種系的同一性百分比係≥70%或≥75%，更較佳的是≥80%或≥85%，甚至更較佳的是≥90%，並且最較佳的是≥91%、≥92%、≥93%、≥94%、≥95%或甚至≥96%。與人抗體種系基因產物的同一性被認為係降低治療期間治療性蛋白引發患者中針對藥物的免疫反應的風險的重要特徵。Hwang W.Y.和Foote J.（Methods.[方法]2005年5月; 36(1):3-10）證明了藥物構建體的非人部分的減少導致治療期間患者中誘導抗藥物抗體的風險降低。藉由比較無數臨床評價的抗體藥物和對應的免疫原性數據，顯示以下趨勢：抗體/構建體的可變區的人源化使得蛋白質免疫原性（平均5.1 %的患者）比攜帶未改變的非人可變區的抗體/構建體（平均23.59 %的患者）更低。因此，基於可變區和呈多肽/多肽構建體的形式的蛋白質治療劑需要與人序列具有較高程度的同一性。為了確定種系同一性，可以使用Vector NTI軟體將VL的V區與人種系V區段和J區段（http://www2.mrc-lmb.cam.ac.uk/vbase/）的胺基酸序列進行比對並且藉由將相同的胺基酸殘基除以VL的胺基酸殘基總數計算胺基酸序列（以百分比計）。對於VH區段（http://www2.mrc-lmb.cam.ac.uk/vbase/）同樣可以進行，只係由於VH CDR3的高度多樣性和缺少現有人種系VH CDR3比對配偶體，可以將VH CDR3排除。然後可以使用重組技術來增加與人抗體種系基因的序列同一性。
在另一個實施方式中，本發明之多肽/多肽構建體在標準研究規模條件下，例如在標準的兩步純化過程中表現出高單體產率。設想根據本發明之構建體的單體產率為≥0.25 mg/L上清液（SN）、較佳的是≥0.5 mg/L SN、更較佳的是≥1 mg/L SN、甚至更較佳的是≥2 mg/L SN、並且最較佳的是≥3 mg/L SN。命名為「CL-1 x I2C-6His」的構建體的產率顯示為4.1 mg/L上清液，並且命名為「CL-1 x I2C-scFc」的構建體的產率顯示為36.5 mg/L上清液。
同樣，可以確定二聚體多肽構建體同種型的產量以及構建體的單體百分比（即單體：（單體+二聚體））。單體和二聚體構建體的生產率和計算的單體百分比可以例如在對來自在滾瓶中標準化研究規模生產的培養物上清液的SEC純化步驟中獲得。根據一個實施方式，本發明之構建體的單體百分比為≥80%、更較佳的是≥85%、甚至更較佳的是≥90%、並且最較佳的是≥95%。
根據一個實施方式，本發明之多肽/多肽構建體的血漿穩定性（具有血漿的EC50與不具有血漿的EC50的比率）為≤5或≤4、更較佳的是≤3.5或≤3、甚至更較佳的是≤2.5或≤2、並且最較佳的是≤1.5或≤1。可以藉由例如以2-20 µg/ml的濃度將純化的構建體在人血漿中於37°C下孵育24至96小時來測試構建體的血漿穩定性，隨後在18 h 51-鉻釋放或48 h FACS細胞毒性測定（例如，如在實例部分中所描述的測定）中進行EC50確定。細胞毒性測定中的效應細胞可以是刺激的富集的人CD8陽性T細胞（較佳的）或未刺激的人PBMC。靶細胞可以例如是用人CLDN6轉染的CHO細胞。效應細胞與靶細胞（E:T）的比率可以是10:1。細胞毒性測定中構建體的起始濃度可以是0.01-0.1 μg/ml。用於此目的的人血漿庫來源於由EDTA塗覆的注射器收集的健康供體的血液。藉由離心去除細胞組分，並且收集上層血漿相並隨後彙集。作為對照，在細胞毒性測定之前在適當的培養基如RPMI-1640中立即稀釋未孵育的構建體。血漿穩定性計算為EC50（血漿孵育後）與EC50（對照/未孵化）的比。
此外，設想本發明之構建體的單體與二聚體轉化較低。可以在不同條件下測量轉化並且藉由高性能尺寸排阻層析進行分析。參見實例8。例如，構建體的單體同種型的孵育可以在培養箱中在通用配製緩衝液中並且以例如100 μg/ml或250 μg/ml的濃度在37°C下進行7天，隨後進行高性能SEC以確定已轉化為二聚體構建體的最初單體構建體的百分比。在該等條件下，設想本發明之多肽/多肽構建體顯示出≤8%、較佳的是≤6%、更較佳的是≤5%、更較佳的是≤4%、甚至更較佳的是≤3%、甚至更較佳的是≤2.5%、甚至更較佳的是≤2%、甚至更較佳的是≤1.5%、並且最較佳的是≤1%或≤0.5%或甚至0%的二聚體百分比。
同樣，設想本發明之多肽/多肽構建體在幾次冷凍/解凍循環之後呈現非常低的二聚體轉化。例如，將構建體單體在例如通用配製緩衝液中調整至濃度為250 μg/ml，並且進行三個冷凍/解凍循環（在-80°C下冷凍30 min，之後在室溫下解凍30 min），之後進行高性能SEC以確定已經轉化成二聚體構建體的最初單體構建體的百分比。設想，例如在三次冷凍/解凍循環之後，構建體的二聚體百分比為≤8%、較佳的是≤6%、更較佳的是≤5%、更較佳的是≤4%、甚至更較佳的是≤3%、甚至更較佳的是≤2.5%、甚至更較佳的是≤2%、甚至更較佳的是≤1.5%、並且最較佳的是≤1%或≤0.5%或甚至0%。
根據一個實施方式，本發明之多肽/多肽構建體顯示出聚集溫度≥45°C或≥46°C、更較佳的是≥47°C或≥48°C、甚至更較佳的是≥49°C或≥50°C、並且最較佳的是≥51°C的有利熱穩定性。熱穩定性參數可以根據抗體聚集溫度如下確定：將濃度為250 μg/ml的抗體溶液轉移到一次性比色杯中並置於動態光散射（DLS）裝置中。將樣本以0.5°C/min的加熱速率從40°C加熱至70°C，恒定獲取測量的半徑。使用指示蛋白質和聚集物熔融的半徑增加來計算抗體的聚集溫度。
可替代地，可以藉由差示掃描量熱法（DSC）確定溫度熔融曲線以確定構建體的固有生物物理學蛋白質穩定性。該等實驗可以使用微凱爾有限公司（MicroCal LLC）VP-DSC裝置進行。與僅含有配製緩衝劑的樣本相比，從20°C至90°C記錄含有構建體的樣本的能量攝取。例如在SEC運行緩衝液中將構建體調整至終濃度為250 μg/ml。為了記錄相應熔融曲線，逐步升高整個樣本溫度。在每個溫度下記錄樣本和配製緩衝液參考物的能量吸收。將樣本的能量攝取Cp（千卡/莫耳/°C）減去參考物的差針對相應溫度作圖。熔融溫度被定義為第一次最大能量攝取時的溫度。
還設想本發明之多肽/多肽構建體具有≤0.2或≤0.15、較佳的是≤0.10或≤0.08、更較佳的是≤0.06或≤0.05、並且最較佳的是≤0.04或≤0.03的濁度。可以藉由在2.5 mg/ml的構建體濃度下的OD340和在5°C下孵育16 h來測量濁度。
可以測量隨著在不存在T細胞的情況下在靶細胞上的構建體的預孵育的變化，靶標 x CD3構建體的效力的變化。如果構建體被內化，則預期其將經歷溶酶體降解。因此，預期有效濃度隨時間降低，並因此表觀效力也應降低。已經觀察到一些靶標的效果，對於它們這係已知的現象。設想本發明之構建體不被靶細胞內化或不經歷顯著的靶細胞內化。可以測定內化率，例如如以下所述：將T細胞計數並在測定培養基中稀釋至1 x 105個/ml的濃度。將靶標陽性靶細胞計數並例如以2500個細胞/孔（cpw）鋪板。將構建體例如以100 nM的起始濃度以1:2連續稀釋。將構建體添加到培養測定板中，以允許在添加T細胞之前孵育0小時、1小時或2小時。然後將T細胞以25000 cpw（E:T = 10:1）鋪板，並將測定在37°C下孵育48小時。例如使用Steady-Glo®系統（25 µl/孔）分析靶細胞存活。較佳的是，在構建體與靶細胞（預）孵育2小時之後，內化率（例如，測量為細胞毒性的降低）為≤20%、更較佳的是≤15%、甚至更較佳的是≤10%、並且最較佳的是≤5%。
此外，對於本發明之多肽構建體，設想脫落的或可溶性靶標不會顯著損害其功效或生物活性。這可以例如在細胞毒性測定中測量，其中將可溶性靶標以漸增的濃度（例如，以0 nM – 0.3 nM – 0.7 nM – 1 nM – 3 nM – 7 nM – 12 nM）添加到測定中。示例性E: T值為10:1。在可溶性靶標的存在下，測試的構建體的EC50值不應顯著增加。
本發明之多肽/多肽構建體的EC50值可以在使用表現CLDN6的細胞（例如，表現CLDN6的CHO細胞，將其用作靶標）和表現CLDN9的細胞（例如，表現CLDN9的CHO細胞，將其用作靶標）的體外細胞毒性測定中進行比較，後者用作陰性對照。可以使用T細胞（例如，PBMC）作為效應細胞和上述CHO細胞作為靶標來確定本發明之多肽/多肽構建體的選擇性和特異性。可以確定本發明之多肽/多肽構建體的細胞毒性作用。根據本發明，本文所述之多肽/多肽構建體對CLDN6陽性靶細胞比對CLDN9陽性靶細胞有效至少500倍、至少1000倍、至少2000倍、並且較佳的是至少3000倍，其中靶標較佳的是屬於相同的細胞來源，例如CHO細胞，將其分別用編碼CLDN6和CLDN9的基因轉染或轉化並表現。當然，可以使用表現CLDN6的其他細胞類型，以及不表現CLDN6但表現CLDN9或CLDN4或根本不表現CLDN家族成員的對照細胞。該等細胞可以是天然表現感興趣的分子的細胞系，或者它們可能已經被遺傳修飾以表現CLDN6和/或其他CLDN分子，後者係對照。該等細胞可用於測定與本發明多肽/多肽構建體相關的T細胞依賴性細胞毒性之方法。
在另一個實施方式中，根據本發明之多肽構建體在酸性pH值下是穩定的。構建體在非生理pH（如pH 5.5）（運行例如陽離子交換層析所需的pH）下的表現越耐受，從離子交換柱洗脫的構建體相對於載入蛋白質總量的回收率越高。構建體從pH 5.5的離子（例如陽離子）交換柱的回收率較佳的是≥30%、更較佳的是≥40%、更較佳的是≥50%、甚至更較佳的是≥60%、甚至更較佳的是≥70%、甚至更較佳的是≥80%、並且最較佳的是≥95%。百分比代表主峰的曲線下面積（= AUC）。
此外，設想本發明之多肽/多肽構建體表現出治療功效，其表現為抗腫瘤活性或腫瘤生長抑制。這可以例如在實例13或14中所揭露的研究中進行評估。在一個實施方式中，本發明之構建體的腫瘤生長抑制T/C [%]為≤70、≤60、≤50、≤40、≤30、≤20、≤10、≤5、≤4、≤3或≤2。還設想修改或調整該等研究的某些參數（如注射的腫瘤細胞的數量、注射部位、移植的人T細胞的數量、待投與的構建體的數量和時間線），同時仍然獲得了有意義且可再現的結果。
本發明進一步提供了編碼本發明之多肽構建體的多核苷酸/核酸分子。核酸分子係由核苷酸構成的生物聚合物。多核苷酸係由共價鍵合在鏈中的13個或更多個核苷酸單體構成的生物聚合物。DNA（如cDNA）和RNA（如mRNA）係具有不同生物功能的多核苷酸/核酸分子的實例。核苷酸係充當核酸分子如DNA或RNA的單體或亞單位的有機分子。本發明之核酸分子或多核苷酸可以是雙股的或單股的、線性的或環狀的。設想核酸分子或多核苷酸被包含在載體中。此外，設想這樣的載體被包含在宿主細胞中。所述宿主細胞例如在用本發明之載體或多核苷酸/核酸分子轉化或轉染後能夠表現構建體。為此目的，將多核苷酸或核酸分子可操作地連接至控制序列。
遺傳密碼係將遺傳物質（核酸）內編碼的資訊翻譯成蛋白質的一組規則。活細胞中的生物解碼係藉由以由mRNA指定的順序連接胺基酸的核糖體，使用tRNA分子攜帶胺基酸並一次讀出mRNA三個核苷酸來完成。該密碼定義了該等核苷酸三聯體的序列（稱為密碼子）如何指定在蛋白質合成期間接下來將添加哪種胺基酸。除了一些例外，核酸序列中的三核苷酸密碼子指定單一胺基酸。因為絕大多數基因都使用完全相同的密碼進行編碼，所以該特定密碼通常稱為規範或標準遺傳密碼。
密碼子的簡並性係遺傳密碼的冗餘，表現為指定胺基酸的三鹼基對密碼子組合的多樣性。簡並性發生係因為存在比可編碼的胺基酸更多的密碼子。編碼一種胺基酸的密碼子在它們的三個位置中的任何一個都可以不同；然而，通常這種差異係在第二或第三位置。例如，密碼子GAA和GAG都指定麩胺酸並表現出冗餘；但是，沒有指定任何其他胺基酸，並因此沒有表現出歧義。不同生物體的遺傳密碼可能偏向於使用編碼相同胺基酸的幾個密碼子之一而不是其他密碼子 - 也就是說，將發現比偶然預期具有更大頻率的一個。例如，白胺酸由六種不同的密碼子指定，其中一些很少被使用。可獲得詳細說明大多數生物體的基因組密碼子使用頻率的密碼子使用表。重組基因技術通常藉由實施稱為密碼子優化的技術來利用這種效應，其中將那些密碼子用於設計被各自宿主細胞（如人倉鼠起源的細胞、大腸桿菌（Escherichia coli）細胞或釀酒酵母（Saccharomyces cerevisiae）細胞）偏好的多核苷酸，例如以增加蛋白質表現。因此，設想本揭露的多核苷酸/核酸分子係密碼子優化的。然而，可以使用編碼所希望的胺基酸的任何密碼子來設計編碼本發明之構建體的多核苷酸/核酸分子。
根據一個實施方式，編碼本發明之多肽構建體的本發明之多核苷酸/核酸分子呈一個單一分子的形式或兩個或更多個分開的分子的形式。如果本發明之構建體係單鏈構建體，則編碼這種構建體的多核苷酸/核酸分子將最可能也呈一個單一分子的形式。然而，還設想多肽構建體的不同組分（如不同結構域，例如包含與CLDN6結合的結構域的互補位（抗原結合（表位結合）結構、包含與CD3結合的結構域的互補位（抗原結合（表位結合）結構、和/或其他結構域如抗體恒定結構域）位於單獨的多肽鏈上，在這種情況下，多核苷酸/核酸分子最可能呈兩個或更多個分開的分子的形式。
這同樣適用於包含本發明之多核苷酸/核酸分子的載體。如果本發明之構建體係單鏈構建體，則一個載體可以在一個單一位置（作為一個單一開放閱讀框，ORF）包含編碼構建體的多核苷酸。一個載體還可以在分開的位置（具有單獨的ORF）包含兩個或更多個多核苷酸/核酸分子，它們中的每一個編碼本發明之構建體的不同組分。設想包含本發明之多核苷酸/核酸分子的載體呈一個單一載體的形式或處於兩個或更多個分開的載體的形式。在一個實施方式中，並且出於在宿主細胞中表現構建體的目的，本發明之宿主細胞應包含編碼構建體的多核苷酸/核酸分子或包含這種多核苷酸/核酸分子的載體全部，這意味著構建體的所有組分 - 無論是編碼為一個單一分子還是在單獨的分子/位置編碼 - 將在翻譯之後組裝並一起形成本發明之生物學活性的構建體。
本發明還提供了包含本發明之多核苷酸/核酸分子的載體。載體係用作將（外來）遺傳物質轉移到細胞中的媒介物的核酸分子（通常為了確保遺傳物質的複製和/或表現）。術語「載體」涵蓋但不限於質體、病毒、黏粒和人造染色體。一些載體專門設計用於選殖（選殖載體），其他載體設計用於蛋白質表現（表現載體）。所謂的轉錄載體主要用於擴增其插入物。通常在含有其在大腸桿菌中維持所需的元件的大腸桿菌載體上進行DNA操作。然而，載體也可以具有允許它們維持在另一種生物體如酵母、植物或哺乳動物細胞中的元件，並且該等載體被稱為穿梭載體。將載體插入靶標或宿主細胞中通常被稱為轉化（對於細菌細胞）和轉染（對於真核細胞），而病毒載體的插入通常被稱為轉導。
一般來講，工程化載體包含複製起點、多株位點和選擇性標記。載體本身通常是包含插入物（轉基因）和充當載體「骨架」的較大序列的核苷酸序列（通常為DNA序列）。雖然遺傳密碼決定了給定編碼區的多肽序列，但其他基因組區域可能會影響該等多肽產生的時間和地點。因此，現代載體可以涵蓋除轉基因插入物和骨架之外的額外特徵：啟動子、遺傳標記、抗生素抗性、報告基因、靶向序列、蛋白質純化標籤。稱為表現載體（表現構建體）的載體尤其用於在靶細胞中表現轉基因，並且通常具有控制序列。
術語「控制序列」係指在特定宿主生物體中表現可操作地連接的編碼序列所必需的DNA序列。例如，適用於原核生物的控制序列包括啟動子、視需要的操縱子序列和核糖體結合位點。已知真核細胞利用啟動子、聚腺苷酸化信號、Kozak序列和增強子。
當核酸與另一核酸序列處於功能關係時，該核酸係「可操作地連接的」。例如，如果將前序列或分泌前導序列的DNA表現為參與多肽分泌的前蛋白，則該前序列或分泌前導序列的DNA可操作地連接至該多肽的DNA；如果啟動子或增強子影響編碼序列的轉錄，則該啟動子或增強子可操作地連接至該序列；或者如果核糖體結合位點被定位成有助於翻譯，則該核糖體結合位點可操作地連接至編碼序列。一般來講，「可操作地連接」意指所連接的核苷酸序列係連續的，並且在分泌性前導序列的情形下是連續的並處於閱讀相（reading phase）中。然而，增強子不必是連續的。連接藉由在方便的限制性位點進行接合來完成。如果不存在此類位點，則根據常規實踐使用合成的寡核苷酸銜接子或連接子。
「轉染」係有意將核酸分子或多核苷酸（包括載體）引入到靶細胞中的過程。該術語主要用於真核細胞中的非病毒方法。轉導通常用於描述病毒介導的核酸分子或多核苷酸的轉移。動物細胞的轉染典型地關於打開細胞膜中的暫態孔或「洞」，以允許攝取物質。轉染可以使用生物粒子（如病毒轉染，也稱為病毒轉導）、基於化學之方法（如使用磷酸鈣、脂質轉染、Fugene、陽離子聚合物、奈米粒子）或物理處理（如電穿孔、顯微注射、基因槍、細胞擠壓、磁轉染、靜水壓力、穿刺轉染（impalefection）、超音波波、光學轉染、熱休克）進行。
術語「轉化」用於描述核酸分子或多核苷酸（包括載體）向細菌中，和向非動物真核細胞（包括植物細胞）中的非病毒轉移。因此，轉化係細菌或非動物真核細胞的基因改變，該基因改變係因通過一個或多個細胞膜從其周圍直接攝取並隨後併入外源遺傳物質（核酸分子）而產生。轉化可以藉由人為手段來實現。為了發生轉化，細胞或細菌必須處於感受態，這可能作為對諸如饑餓等環境條件和細胞密度的時間限制反應而發生，並且也可以被人工誘導。
此外，本發明提供了一種宿主細胞，該宿主細胞經本發明之多核苷酸/核酸分子或本發明之載體轉化或轉染。
如本文使用的，術語「宿主細胞」或「受體細胞」旨在包括可以是或已經係載體、外源性核酸分子和/或編碼本發明構建體的多核苷酸的受體、和/或構建體本身的受體的任何單個細胞或細胞培養物。藉由轉化、轉染等方式將對應的物質引入細胞中（參見上文）。術語「宿主細胞」還旨在包括單細胞的後代或潛在後代。因為某些改變可能由於天然的、意外的或有意的突變或由於環境影響而在隨後世代中發生，所以這種後代事實上可能不會與親本細胞完全相同（在形態或基因組或全部DNA補體中），但仍包括在本文所用術語的範圍內。合適的宿主細胞包括原核細胞或真核細胞，並且包括但不限於 - 細菌（如大腸桿菌）、酵母細胞、真菌細胞、植物細胞和動物細胞，諸如昆蟲細胞和哺乳動物細胞，例如倉鼠、鼠類、大鼠、獼猴或人。
除了原核生物之外，真核微生物（如絲狀真菌或酵母）係本發明之構建體的適合的選殖或表現宿主。釀酒酵母（Saccharomyces cerevisiae）或普通麵包酵母係低等真核宿主微生物中最常用的。然而，許多其他屬、物種和菌株通常可獲得並且可用於本文中，如粟酒裂殖酵母（Schizosaccharomyces pombe）、克魯維酵母屬（Kluyveromyce）宿主，如乳酸克魯維酵母（K. lactis）、脆壁克魯維酵母（K. fragilis）（ATCC 12424）、保加利亞克魯維酵母（K. bulgaricus）（ATCC 16045）、威克克魯維酵母（K. wickeramii）（ATCC 24178）、瓦爾提魯維酵母（K. waltii）（ATCC 56500）、果蠅克魯維酵母（K. drosophilarum）（ATCC 36906）、耐熱克魯維酵母（K. thermotolerans）和馬克斯克魯維酵母（K. marxianus）；耶氏酵母屬（EP 402 226）；畢赤酵母（EP 183 070）；假絲酵母屬（Candida）；瑞氏木黴（EP 244 234）；粗糙脈孢菌（Neurospora crassa）；許旺酵母屬（Schwanniomyces），如西方許旺酵母（Schwanniomyces occidentalis）；和絲狀真菌，如脈孢菌屬（Neurospora）、青黴屬（Penicillium）、彎頸黴屬（Tolypocladium）和麯黴屬（Aspergillus）宿主，如構巢麯黴（A. nidulans）和黑麯黴（A. niger）。
用於表現糖基化構建體的合適宿主細胞衍生自多細胞生物體。無脊椎動物細胞的實例包括植物細胞和昆蟲細胞。已經鑒定了來自如草地貪夜蛾（Spodoptera frugiperda）（毛蟲）、埃及伊蚊（Aedes aegypti）（蚊子）、白紋伊蚊（Aedes albopictus）（蚊子）、黑腹果蠅（Drosophila melanogaster）（果蠅）和家蠶（Bombyx mori）（蠶蛾（silkmoth））的宿主的許多桿狀病毒株和變體以及相應的許可性昆蟲宿主細胞。用於轉染的多種病毒株係公眾可獲得的，例如苜蓿銀紋夜蛾（Autographa californica）NPV的L-1變體和家蠶NPV的Bm-5株，並且根據本發明，此類病毒可以用作本文的病毒，特別是用於轉染草地貪夜蛾細胞。
棉花、玉米、馬鈴薯、大豆、矮牽牛、番茄、阿拉伯芥和煙草的植物細胞培養物也可以用作宿主。可用於在植物細胞培養物中產生蛋白質的選殖和表現載體係熟悉該項技術者已知的。參見，例如Hiatt等人, Nature [自然] (1989) 342: 76-78；Owen等人 (1992) Bio/Technology [生物/技術] 10: 790-794；Artsaenko等人 (1995) The Plant J [植物雜誌] 8: 745-750和Fecker等人 (1996) Plant Mol Biol [植物分子生物學] 32: 979-986。
然而，對脊椎動物細胞的興趣最大，並且培養物（細胞培養物）中脊椎動物細胞的繁殖已成為常規程序。有用的哺乳動物宿主細胞系的實例係由SV40（如COS-7，ATCC CRL 1651）轉化的猴腎CV1系；人胚胎腎系（如293細胞或亞選殖用於在懸浮培養中生長的293細胞，Graham等人, J. Gen Virol.[普通病毒學雜誌] 36:59(1977)）；幼倉鼠腎細胞（如BHK，ATCC CCL 10）；中國倉鼠卵巢細胞/-DHFR（如CHO，Urlaub等人, Proc. Natl. Acad. Sci. USA [美國國家科學院院刊] 77: 4216 (1980)）；小鼠塞托利細胞（如TM4, Mather, Biol. Reprod.[生殖生物學]23: 243-251 (1980)）；猴腎細胞（如CVI ATCC CCL 70）；非洲綠猴腎細胞（如VERO-76，ATCC CRL1587）；人宮頸癌細胞（如HELA，ATCC CCL 2）；犬腎細胞（如MDCK，ATCC CCL 34）；布法羅大鼠肝細胞（如BRL 3A，ATCC CRL 1442）；人肺細胞（如W138，ATCC CCL 75）；人肝細胞（如Hep G2,1413 8065）；小鼠乳腺腫瘤（如MMT 060562, ATCC CCL-51）；TRI細胞（Mather等人, Annals N. Y Acad. Sci. [紐約科學院年刊] (1982) 383: 44-68）；MRC 5細胞；FS4細胞；和人肝癌細胞系（如Hep G2）。
在另一個實施方式中，本發明提供了一種用於產生本發明之構建體之方法，所述方法包括在允許表現本發明之構建體的條件下培養本發明之宿主細胞並且從該培養中回收所產生的構建體。
如本文使用的，術語「培養」係指細胞在合適的條件下在培養基中的體外維持、分化、生長、增殖和/或繁殖。使細胞在適當的溫度和氣體混合物下在細胞生長培養基中生長並維持。對於每種細胞類型，培養條件變化很大。典型的生長條件係約37°C的溫度、約5%的CO2濃度和約95%的濕度。生長培養基的配方可以例如在pH值、碳源（如葡萄糖）濃度、生長因子的性質和濃度、以及其他營養素（如胺基酸或維生素）的存在方面變化。用於補充培養基的生長因子通常衍生自動物血液的血清，如胎牛血清（FBS）、牛小牛血清（FCS）、馬血清和豬血清。細胞可以在懸浮液中生長或作為貼壁培養物生長。還存在如下細胞系，該等細胞系已經被修飾以能夠在懸浮培養物中存活，因此它們可以按比貼壁條件將允許的更高密度生長。
術語「表現」包括關於產生本發明之構建體的任何步驟，包括但不限於轉錄、轉錄後修飾、翻譯、折疊、翻譯後修飾、靶向特定亞細胞或細胞外位置、和分泌。術語「回收」係指旨在從細胞培養物中分離構建體的一系列過程。「回收」或「純化」過程可以分離細胞培養物的蛋白質和非蛋白質部分，並最終將所希望的構建體與所有其他多肽和蛋白質分離。分離步驟通常利用蛋白質大小、物理化學特性、結合親和力和生物活性的差異。製備型純化旨在產生相對大量的純化蛋白質供後續使用，而分析型純化產生相對少量的蛋白質用於各種研究或分析目的。
當使用重組技術時，構建體可以在周質空間中細胞內產生，或直接分泌到培養基中。如果構建體係在細胞內產生，則作為第一步，例如藉由離心或超濾去除宿主細胞或溶解片段的微粒狀碎片。本發明之構建體可以例如在諸如大腸桿菌等細菌中產生。在表現之後，將構建體從可溶性級分中的細菌細胞糊中分離出來，並且可以例如經由親和層析和/或尺寸排阻進行純化。最終純化可以以與用於純化在哺乳動物細胞中表現並分泌到培養基中的構建體之方法類似的方式進行。Carter等人（Biotechnology [生物技術] (NY) 1992年2月; 10(2):163-7）描述了用於分離分泌到大腸桿菌的周質間隙中的抗體的程序。
在構建體分泌到培養基中的情況下，通常首先使用可商購的蛋白質濃縮濾器（例如，超濾單元）從此類表現系統的上清液進行濃縮。
可以使用例如羥基磷灰石層析法、凝膠電泳、透析和親和層析法回收或純化從宿主細胞製備的本發明之構建體。根據待回收的構建體，也可獲得用於蛋白質純化的其他技術，如離子交換柱上分級分離、混合模式離子交換、HIC、乙醇沈澱、尺寸排阻層析、反相HPLC、在二氧化矽上進行的層析、在肝素瓊脂糖上進行的層析、在陰離子或陽離子交換樹脂（如聚天冬胺酸柱）上進行的層析、免疫親和（如蛋白質A/G/L）層析、層析聚焦、SDS-PAGE、超速離心和硫酸銨沈澱。
蛋白酶抑制劑可以被包括在任何前述步驟中以便抑制蛋白水解，並且抗生素可以被包括來防止污染物的生長。
此外，本發明提供了一種藥物組成物或配製物，該藥物組成物或配製物包含本發明之構建體或根據本發明之方法產生的構建體。
如本文使用的，術語「藥物組成物」關於適合投與給患者，較佳的是人患者的組成物。本發明之特別較佳的藥物組成物包含較佳的是治療有效量的一種或多種本發明之構建體。較佳的是，藥物組成物進一步包含一種或多種（藥學上有效的）載劑、穩定劑、賦形劑、稀釋劑、增溶劑、表面活性劑、乳化劑、防腐劑和/或佐劑的適合配製物。組成物的可接受成分較佳的是在所使用的劑量和濃度下是對接受者無毒性的。本發明之藥物組成物包括但不限於液體、冷凍和凍乾組成物。
該等組成物可以包含藥學上可接受的載劑。通常，如本文使用的，「藥學上可接受的載劑」意指與藥物投與、特別是腸胃外投與相容的所有的水性和非水性溶液、無菌溶液、溶劑、緩衝液（例如磷酸鹽緩衝鹽水（PBS）溶液）、水、懸浮液、乳液（諸如油/水乳液）、各種類型的潤濕劑、脂質體、分散介質和包衣。此類介質和藥劑在藥物組成物中的使用在本領域中是熟知的，並且包含此類載劑的組成物可以藉由熟知的常規方法配製。
某些實施方式提供了藥物組成物，該等藥物組成物包含本發明之構建體和另外一種或多種賦形劑，如在本部分和本文其他地方說明性描述的那些賦形劑。賦形劑在本發明中可用於多種目的，諸如調整配製物的物理、化學或生物特性，諸如調整黏度和/或本發明之方法以改善有效性和/或穩定此類配製物和方法，以防止例如由於在製造、運輸、存儲、使用前製備、投與和其後過程中發生的壓力而導致的降解和腐壞。通常將賦形劑以其最低有效濃度使用。
在某些實施方式中，為了改變、保持或保存組成物的某些特徵（如pH、莫耳滲透壓濃度、黏度、透明度、顏色、等滲性、氣味、無菌性、穩定性、溶解或釋放速率、吸附性或滲透性），藥物組成物可以含有配製物質（參見Remington’s Pharmaceutical Sciences [雷明登氏藥學全書], 第18版, 1990, Mack Publishing Company [馬克出版公司]）。在此類實施方式中，適合的配製物質可以包括但不限於：
● 胺基酸
● 抗微生物劑，例如抗細菌劑和抗真菌劑
● 抗氧化劑
● 用於將組成物維持在生理pH或稍低的pH下（通常在約5至約8或9的範圍內）的緩衝液、緩衝系統和緩衝劑
● 非水性溶劑、植物油和可注射的有機酯
● 水性載劑包括水、醇/水性溶液、乳液或懸浮液，包括鹽水和緩衝介質
● 可生物降解聚合物，如聚酯
● 增積劑
● 螯合劑
● 等滲劑和吸收延遲劑
● 錯合劑
● 填充劑
● 碳水化合物
● （低分子量）蛋白質、多肽或蛋白質載劑，較佳的是人起源的
● 著色劑和調味劑
● 含硫還原劑
● 稀釋劑
● 乳化劑
● 親水性聚合物
● 成鹽抗衡離子
● 防腐劑
● 金屬錯合物
● 溶劑和助溶劑
● 糖和糖醇
● 懸浮劑
● 表面活性劑或潤濕劑
● 穩定性增強劑
● 張力增強劑
● 腸胃外遞送媒介物
● 靜脈內遞送媒介物
眾所周知，例如，藥物組成物的不同成分可以具有不同的效應，並且胺基酸可以充當緩衝液、穩定劑和/或抗氧化劑；甘露醇可以充當膨脹劑和/或張力增強劑；氯化鈉可以充當遞送媒介物和/或張力增強劑；等。
在本發明之上下文中，藥物組成物可以包含：
(a) 如本文所述之構建體，
(b) 至少一種緩衝劑，
(c) 至少一種糖，以及
(d) 至少一種表面活性劑；
其中該藥物組成物的pH在3.5至6的範圍內。
在上面所述之組成物中，第一結構域較佳的是具有在4至9.5的範圍內的等電點（pI）；第二結構域具有在8至10（較佳的是8.5至9.0）的範圍內的pI；並且構建體視需要包含第三結構域，該第三結構域包含兩個多肽單體，每個多肽單體包含鉸鏈、CH2結構域和CH3結構域，其中所述兩個多肽單體經由肽連接子彼此融合；
在上面所述之組成物中，進一步設想所述至少一種緩衝劑以5 mM至200 mM的濃度範圍、更較佳的是以10 mM至50 mM的濃度範圍存在。還設想所述至少一種糖選自由以下組成之群組：單糖、二糖、環狀多糖、糖醇、線性支鏈葡聚糖或線性非支鏈葡聚糖。還設想該二糖選自由以下組成之群組：蔗糖、海藻糖和甘露糖醇、山梨糖醇及其組合。進一步設想該糖醇係山梨糖醇。還設想所述至少一種糖以1%至15%（m/V）的範圍內的濃度存在，較佳的是以9%至12%（m/V）的濃度範圍存在。進一步設想該構建體以0.1 mg/ml至8 mg/ml、較佳的是0.2-2.5 mg/ml、更較佳的是0.25-1.0 mg/ml的濃度範圍存在。
根據上面所述之組成物的一個實施方式，所述至少一種表面活性劑選自由以下組成之群組：聚山梨醇酯20、聚山梨醇酯40、聚山梨醇酯60、聚山梨醇酯80、泊洛沙姆188、普朗尼克F68、曲拉通X-100、聚氧乙烯（polyoxyethylen）、PEG 3350、PEG 4000及其組合。進一步設想所述至少一種表面活性劑以在0.004%至0.5%（m/V）的範圍內（較佳的是在0.001%至0.01%（m/V）的範圍內）的濃度存在。設想該組成物的pH在4.0至5.0的範圍內，較佳的是4.2。還設想該藥物組成物具有150 mOsm至500 mOsm的莫耳滲透壓濃度。進一步設想該藥物組成物進一步包含選自以下群組的賦形劑，該組由以下組成：一種或多種多元醇和一種或多種胺基酸。在本發明之上下文中，設想所述一種或多種賦形劑以0.1%至15%（w/V）的濃度範圍存在。
本發明還提供了藥物組成物，該藥物組成物包含 (a) 如本文描述的抗體構建體，較佳的是在0.1 mg/ml至8 mg/ml、較佳的是0.2 mg/ml-2.5 mg/ml、更較佳的是0.25 mg/ml-1.0 mg/ml的濃度範圍內；(b) 10 mM麩胺酸鹽或乙酸鹽；(c) 9%（m/V）蔗糖或6%（m/V）蔗糖和6%（m/V）羥丙基-β-環糊精；(d) 0.01%（m/V）聚山梨醇酯80；其中該液體藥物組成物的pH為4.2。
設想除了本文定義的本發明之構建體之外，本發明之組成物可以包含另外的生物活性劑，這取決於組成物的預期用途。此類藥劑可以是作用於胃腸系統的藥物、充當細胞抑制劑的藥物、預防高尿酸血症的藥物、抑制免疫反應的藥物、調節炎症反應的藥物、作用於循環系統的藥物和/或本領域中已知的藥劑諸如細胞介素。還設想將本發明之多肽構建體應用於共療法中，即與另一種抗癌藥物組合。
在這個背景下，設想本發明之藥物組成物（其包含構建體，該構建體包含與靶細胞表面上的CLDN6結合的結構域和與T細胞表面上的CD3結合的另一個結構域，如本文上面更詳細描述的）此外包含與免疫檢查點途徑的蛋白質（如PD-1或CTLA-4）或與共刺激免疫檢查點受體（如4-1BB）結合的藥劑（較佳的是抗體或構建體）。本發明還關於根據本發明之多肽構建體（其包含多肽構建體，該多肽構建體包含與靶細胞表面上的CLDN6結合的互補位（抗原結合（表位結合）結構的結構域和包含與T細胞表面上的CD3結合的互補位（抗原結合（表位結合）結構的另一個結構域的組合和藥劑，較佳的是抗體或多肽構建體，其與免疫檢查點途徑的蛋白（如PD-1或CTLA-4）或與共刺激免疫檢查點受體（如4-1BB）的蛋白結合。由於該組合的至少兩種成分的性質，即它們的藥物活性，該組合也可以被稱為治療性組合。在一些實施方式中，該組合可以呈藥物組成物或套組的形式。根據一個實施方式，該藥物組成物或該組合包含本發明之構建體和與PD-1結合的抗體或構建體。例如在藉由引用併入本文的PCT/US 2019/013205中詳細描述了可用於該目的的抗PD-1結合蛋白。
在某些實施方式中，最佳藥物組成物將根據例如預期投與途徑、遞送形式和所希望的劑量來確定。參見，例如Remington’s Pharmaceutical Sciences [雷明登氏藥學全書]，同上。在某些實施方式中，此類組成物可以影響本發明之構建體的物理狀態、穩定性、體內釋放速率和體內清除速率。在某些實施方式中，藥物組成物中的主要媒介物或載劑本質上可以是水性的或非水性的。例如，合適的媒介物或載劑可以是注射用水或生理鹽水溶液，可能補充有用於腸胃外投與的組成物中常見的其他物質。在某些實施方式中，包含本發明之構建體的組成物可以藉由將具有所希望純度的選擇成分與視需要的配製劑（Remington’s Pharmaceutical Sciences [雷明登氏藥學全書]，同上）以凍乾餅或水性溶液的形式混合來製備用於儲存。進一步地，在某些實施方式中，可以使用合適的賦形劑將本發明之構建體配製成凍乾物。
當考慮腸胃外投與時，用於本發明之治療組成物能以無熱原的腸胃外可接受的水性溶液的形式提供，該水性溶液在藥學上可接受的媒介物中包含本發明之所希望構建體。用於腸胃外注射的特別適合的媒介物係無菌蒸餾水，其中將本發明之構建體配製成適當保存的無菌等滲溶液。在某些實施方式中，製劑可以包括用可以提供產品的控制釋放或持續釋放的試劑配製所希望的分子，該產品可以經由積存注射遞送，或者可以促進在循環中持久的持續時間。在某些實施方式中，可植入藥物遞送裝置可用於引入所希望的構建體。
另外的藥物組成物對於熟悉該項技術者將是明顯的，包括關於在持續或控制遞送配製物中包括本發明之構建體的配製物。用於配製各種持續或控制遞送手段的技術對熟悉該項技術者而言係已知的。構建體也可以包埋在例如藉由凝聚技術或藉由介面聚合製備的微膠囊中、在膠體藥物遞送系統中或在粗乳液中。在Remington’s Pharmaceutical Sciences [雷明登氏藥學全書]，同上中揭露了此類技術。
用於體內投與的藥物組成物典型地以無菌製劑提供。滅菌可以通過無菌濾膜過濾完成。當組成物凍乾時，可以在凍乾和重構之前或之後進行使用該方法的滅菌。用於腸胃外投與的組成物能以凍乾形式或於溶液中儲存。通常將腸胃外組成物置於具有無菌進入口的容器（例如具有可由皮下注射針刺穿的塞子的靜脈內溶液袋或小瓶）中。
本發明之另一個方面包括包含本發明之構建體的自緩衝配製物，該等自緩衝配製物可以用作藥物組成物，如在國際專利申請WO 2006/138181中所述。關於可用於這方面的蛋白質穩定化和配製材料和方法，有多種出版物可用，如Arawaka T.等人, Pharm Res. [藥物研究] 1991年3月; 8(3):285-91；Kendrick等人, 「Physical stabilization of proteins in aqueous solution [蛋白質在水溶液中的物理穩定]」,Rational Design of Stable Protein Formulations: Theory and Practice [穩定的蛋白質製劑的合理設計：理論與實踐], Carpenter and Manning編輯Pharmaceutical Biotechnology [藥物生物技術].13: 61-84 (2002)；以及Randolph和Jones, Pharm Biotechnol. [藥物生物技術] 2002; 13:159-75，尤其參見與用於自緩衝蛋白質配製物的賦形劑和方法有關的部分，特別是關於用於獸醫和/或人類醫學用途的蛋白質藥物產品和方法。
根據本發明之某些實施方式，可以使用鹽例如以調整組成物或配製物的離子強度和/或等滲性和/或改善根據本發明之組成物的構建體或其他成分的溶解度和/或物理穩定性。離子可以藉由與蛋白質表面上的帶電荷的殘基結合並藉由遮罩蛋白質中的帶電荷基團和極性基團並降低其靜電相互作用、吸引和排斥相互作用的強度來穩定蛋白質的天然狀態。離子還可以藉由特別地與蛋白質的變性肽鍵（--CONH）結合來穩定蛋白質的變性狀態。此外，與蛋白質中的帶電荷基團和極性基團的離子相互作用還可以減少分子間靜電相互作用，並且從而防止或減少蛋白質聚集和不溶解。
離子種類對蛋白質的作用顯著不同。已經開發了幾種對可用於配製根據本發明之藥物組成物的離子及其對蛋白質的作用的分類評級。一個實例係Hofmeister系列，該系列藉由對溶液中蛋白質的構象穩定性的作用來對離子和極性非離子溶質進行評級。穩定溶質稱為「親液的」。不穩定溶質稱為「離液的」。通常使用高濃度的親液劑以從溶液中沈澱蛋白質（「鹽析」）。通常使用離液劑來使蛋白質變性和/或溶解（「鹽溶」）。離子對「鹽溶」和「鹽析」的相對有效性限定了其在Hofmeister系列中的位置。
根據本發明之各種實施方式，游離胺基酸可用於包含本發明之構建體的配製物或組成物中，以作為增積劑、穩定劑和抗氧化劑以及用於其他標準用途。可以將某些胺基酸用於穩定配製物中的蛋白質，其他胺基酸可用於凍乾過程中以確保正確餅結構和活性成分的特性。可以將一些胺基酸用於抑制液體和凍乾配製物中的蛋白質聚集，而其他胺基酸可用作抗氧化劑。
多元醇係親液的，並且可用作液體和凍乾配製物中的穩定劑，以保護蛋白質免受物理和化學降解過程。多元醇還可用於調節配製物的張力並且用於防止在運輸過程中的冷凍-解凍應力或防止在製造過程中製備團塊。在本發明之上下文中多元醇也可以用作冷凍保護劑。
包含本發明之構建體的配製物或組成物的某些實施方式可以包含表面活性劑。蛋白質可能易於吸附在表面上並且易於變性和在空氣-液體、固體-液體和液體-液體介面處產生聚集。該等有害的相互作用通常與蛋白質濃度成反比，並且典型地因物理振盪（如在產品運輸和處理過程中產生的物理振盪）而加劇。常規使用表面活性劑來防止、最小化或減少表面吸附。表面活性劑也常用於控制蛋白質構象穩定性。在這方面使用表面活性劑係蛋白質特異性的，因為一種特定的表面活性劑典型地會穩定一些蛋白質並使其他蛋白質不穩定。
包含本發明之構建體的配製物或組成物的某些實施方式可以包含一種或多種抗氧化劑。藉由保持適當水平的環境氧氣和溫度並避免暴露於光下，可以在某種程度上防止藥物配製物中蛋白質的有害氧化。抗氧化賦形劑也可以用於防止蛋白質的氧化降解。設想用於根據本發明之治療性蛋白質配製物的抗氧化劑可以是水溶性的並且在產品（包含構建體的組成物）的整個保質期內保持其活性。抗氧化劑也可能破壞蛋白質，並且因此應該除了別的之外以一種方式選擇，以消除或充分降低抗氧化劑破壞配製物中的構建體或其他蛋白質的可能性。
包含本發明之構建體的配製物或組成物的某些實施方式可以包含一種或多種防腐劑。例如，當開發關於從相同容器中提取超過一次的多劑量腸胃外配製物時，防腐劑係必需的。其主要功能係抑制微生物生長並確保在藥物產品的整個保質期或使用期限內的產品無菌性。儘管防腐劑與小分子腸胃外藥物一起使用有很長的歷史，但是開發包括防腐劑的蛋白質配製物可能具有挑戰性。防腐劑通常對蛋白質具有不穩定效應（聚集），並且這已成為限制其在多劑量蛋白質製劑中使用的主要因素。迄今為止，大部分蛋白質藥物僅配製用於一次性使用。然而，當多劑量配製物係可能時，它們具有使患者方便的附加優勢和增加的可銷售性。一個良好的實例係人生長激素（hGH），其中防腐配製物的開發已經導致更方便、多次使用的注射筆展示的商業化。在防腐劑型的配製和開發期間需要考慮若干個方面。必須優化藥物產品中有效的防腐劑濃度。這需要以賦予抗微生物有效性而不損害蛋白質穩定性的濃度範圍測試劑型中給定的防腐劑。
正如可以預期的那樣，含有防腐劑的液體配製物的開發比凍乾配製物更具挑戰性。冷凍乾燥的產品可以在沒有防腐劑的情況下凍乾，並且在使用時用含有防腐劑的稀釋劑重構。這縮短了防腐劑與構建體接觸的時間，從而顯著最小化相關的穩定性風險。在液體配製物的情況下，應在整個產品保質期內保持防腐劑有效性和穩定性。要指出的重要點係，防腐劑有效性應在含有活性藥物和所有賦形劑組分的最終配製物中得到證實。一旦配製了藥物組成物，可以將它作為溶液、懸浮液、凝膠、乳液、固體、晶體或作為脫水或凍乾粉末儲存在無菌小瓶中。此類配製物能以即用形式或以在投與前重構的形式（例如凍乾形式）儲存。
本文定義的藥物組成物的生物活性可以例如藉由體內細胞毒性測定來確定，如以下實例、WO 99/54440或由Schlereth等人（Cancer Immunol. Immunother. [癌症免疫學免疫治療]20 (2005), 1-12）所述。如本文使用的，「功效」或「體內功效」係指使用例如標準化NCI反應標準對本發明之藥物組成物或配製物治療的反應。使用本發明之藥物組成物的療法的成功或體內功效係指組成物對於其預期用途的有效性，即組成物引起其所希望效應，即耗盡病理細胞（例如腫瘤細胞）的能力。可以藉由針對各個疾病實體的已建立的標準方法監測體內功效，該等標準方法包括但不限於白血球計數、差異、螢光活化細胞分選、骨髓抽吸。另外，可以使用各種疾病特異性臨床化學參數和其他建立的標準方法。此外，可以使用電腦輔助斷層攝影、X射線、核磁共振斷層攝影、正電子發射斷層攝影掃描、淋巴結活組織檢查/組織學和其他已建立的標準方法。
開發藥物（如本發明之藥物組成物）的另一主要挑戰係藥物動力學特性的可預測調節。為此，可以建立候選藥物的藥物動力學曲線，即影響特定藥物治療給定病狀的能力的藥物動力學參數的曲線。影響藥物治療某種疾病實體的能力的藥物的藥物動力學參數包括但不限於：半衰期、分佈容量、肝臟首過代謝和血清結合程度。給定藥劑的功效可以受到上文提及的每個參數的影響。
「半衰期」係將量減少到其初始值的一半所需的時間。醫學科學係指物質或藥物在人體內的半衰期。在醫學背景下，半衰期可以是指物質/藥物失去其活性（例如藥理學、生理學或放射學活性）的一半所花費的時間。半衰期還可以描述藥物或物質（例如，本發明之構建體）在血漿/血清中的濃度達到其穩態值的一半所花費的時間（「血清半衰期」）。典型地，所投與的物質/藥物的清除或去除係指藉由諸如代謝、排泄等生物過程（還關於腎臟和肝臟的功能）進行身體清潔。「首過代謝」係藥物代謝、由此在藥物到達循環之前使藥物濃度降低的現象。它係吸收過程中藥物損失的部分。因此，「肝臟首過代謝」意指藥物在首次與肝臟接觸時（即在其首次通過肝臟期間）被代謝的傾向。「分佈容量」（VD）意指藥物在身體組織而非血漿中分佈的程度，較高的VD表示較大的組織分佈量。藥物的保留可以發生在遍佈身體的各個隔室，如細胞內和細胞外空間、組織和器官等。「血清結合程度」意指藥物與血清蛋白（如白蛋白）相互作用並結合的傾向，從而導致藥物生物活性的降低或喪失。
藥物動力學參數還包括就所投與的給定量的藥物而言的生體可用率、滯後時間（T滯後）、Tmax、吸收速率、和/或Cmax。「生體可用率」係指到達體循環（血液隔室）的所投與藥物/物質劑量的分數。當靜脈內投與藥物時，其生體可用率被認為係100%。然而，當經由其他途徑（如口服地）投與藥物時，其生體可用率通常會降低。「滯後時間」意指藥物投與與其在血液或血漿中的檢測和可測量性之間的時間延遲。Cmax係藥物在其投與之後（以及在投與第二劑量之前）達到的最大血漿濃度。Tmax係達到Cmax的時間。達到其生物效應所需的藥物的血液或組織濃度的時間受到所有參數的影響。如上面所概述和例如在Schlereth等人（同上）中所示的，可以在非黑猩猩靈長類動物的臨床前動物測試中確定表現出跨物種特異性的構建體的藥物動力學參數。
一個實施方式提供了本發明之構建體（或根據本發明之方法產生的構建體），其用作藥物，特別是用於在預防、治療或緩解疾病（較佳的是贅生物）的藥物。另一個實施方式提供了本發明之構建體（或根據本發明之方法產生的構建體）在製造用於預防、治療或緩解疾病（較佳的是贅生物）的藥物中的用途。還設想提供用於預防、治療或緩解疾病（較佳的是贅生物）之方法，該方法包括向對其有需要的受試者投與本發明之構建體（或根據本發明之方法產生的構建體）的步驟。術語「有需要的受試者」、「患者」或「需要治療」的那些包括已經患有該疾病的那些，以及將要預防該疾病的那些。該等術語還包括接受預防性或治療性治療的人和其他哺乳動物受試者。
本發明之多肽/多肽構建體和本文描述的配製物/藥物組成物可用於治療、緩解和/或預防對其有需要的患者中的如本文所述之醫學病症。術語「治療」係指治療性治療和預防性（prophylactic）或阻止性（preventative）措施兩者。治療包括將多肽/多肽構建體/藥物組成物投與或投與至患有如本文所述之疾病/障礙、具有這種疾病/障礙的症狀或具有患這種疾病/障礙的傾向的患者或有需要的受試者的體內、分離組織或細胞，目的是治癒、痊癒、緩和、減輕、改變、補救、緩解、改善或影響該疾病、該疾病症狀或患該疾病的傾向。如本文使用的，術語「減輕（amelioration）」係指藉由將根據本發明之多肽構建體投與至此類患者或有此需要的受試者而對患者的疾病狀態的任何改善。這樣的改善可以被視為減緩或停止患者的疾病進展、和/或疾病症狀的嚴重程度降低、無疾病症狀期的頻率或持續時間增加、或由於疾病導致的損害或殘疾的防止。如本文使用的，術語「預防」意指藉由將根據本發明之構建體的投與至對其有需要的受試者來避免如本文所指定的疾病的發生或復發。
術語「疾病」係指將受益於用本文所述之構建體或藥物組成物治療的任何病症。這包括慢性和急性障礙或疾病，包括那些使哺乳動物易患所考慮疾病的病理病狀。該疾病較佳的是贅生物、癌症或腫瘤。該疾病、贅生物、癌症或腫瘤較佳的是CLDN6陽性的，即其特徵在於CLDN6的表現或過表現。CLDN6的過表現意指增加至少10%、特別是至少25%、至少50%、至少100%、至少250%、至少500%、至少750%、至少1000%、或甚至更多。僅在患病組織中發現表現，而在相應的健康組織中檢測不到或顯著檢測不到表現。根據本發明，與表現CLDN6的細胞相關的疾病包括癌症疾病。此外，根據本發明，癌症疾病較佳的是其中癌細胞表現CLDN6的那些癌症疾病。
「贅生物」係組織的異常生長，通常但不總是形成腫塊。當也形成腫塊時，通常稱之為「腫瘤」。贅生物或腫瘤可以是良性的、潛在惡性的（癌前）、或惡性的（癌性）。惡性贅生物/腫瘤通常被稱為癌症。它們通常侵入並破壞周圍組織，並可能形成轉移，即它們擴散到身體的其他部位、組織或器官。「原發性腫瘤」係在腫瘤進展開始並且繼續產生癌性腫塊的解剖部位生長的腫瘤。大多數癌症在其原發部位發展，但然後繼續轉移或擴散至身體的其他部分（例如組織和器官）。該等另外的腫瘤係「繼發性腫瘤」。大多數癌症在它們的原發部位之後、甚至在它們已經擴散到身體的其他部分之後繼續被調用。
淋巴瘤和白血病係淋巴贅生物。出於本發明之目的，它們也涵蓋在術語「腫瘤」和「癌症」中。出於本發明之目的，術語「贅生物」、「腫瘤」和「癌症」可以互換使用，並且它們既包含原發性腫瘤/癌症又包含繼發性腫瘤/癌症（或「轉移瘤」）、連同腫塊形成贅生物（腫瘤）和淋巴贅生物（如淋巴瘤和白血病）以及微小殘留病（MRD）。
術語「微小殘留病」（MRD）係指在癌症治療之後，例如當患者處於緩解期（沒有疾病症狀或體征）時，留在患者體內的少量殘留癌細胞存在的證據。藉由常規手段通常不能檢測到極少量的剩餘癌細胞，因為用於評估或檢測癌症的標準測試不夠敏感以檢測MRD。如今，對於MRD非常敏感的分子生物學測試係可用的，如流動式細胞測量術、PCR和下一代定序。該等測試可以測量組織樣本中最低水平的癌細胞，有時低至百萬個正常細胞中的一個癌細胞。在本發明之上下文中，設想術語癌症的「預防」、「治療」或「緩解」還涵蓋「MRD的預防、治療或緩解」，無論是否檢測到MRD。
在本發明之一個實施方式中，贅生物、癌症或腫瘤選自以下群組，該群組包括但不限於生殖細胞癌、卵巢癌和肺癌（或由其組成）。
根據本發明之一個實施方式，卵巢癌係卵巢上皮癌，選自包括黏液性子宮內膜樣癌、透明細胞癌和未分化卵巢癌的組；卵巢間質瘤，包括顆粒細胞瘤、顆粒泡膜瘤和Sertoli-Leydig腫瘤；卵巢生殖細胞腫瘤，包括畸胎瘤、無性細胞瘤卵巢生殖細胞癌、內胚竇瘤（卵黃囊瘤）和絨毛膜癌腫瘤；卵巢肉瘤、庫肯勃瘤或卵巢囊腫。根據另一個實施方式，卵巢癌係反復發生的或復發性卵巢癌，或鉑（plantinum）和/或標準化學療法難治性的卵巢癌。可以藉由測量CA-125來確定治療功效。CA-125係存在於血液中的蛋白。大量的CA-125可能指示卵巢癌、輸卵管癌，而減少的量可能指示所選治療的功效。可能導致卵巢癌發展的遺傳因素係稱為乳腺癌基因1（BRCA1）和乳腺癌基因2（BRCA2）的兩種基因之一的突變。有BRCA1突變的女性患卵巢癌的風險高出35%至70%。有BRCA2突變的女性的風險要高出10%至30%（www.cancercenter.com/cancer-types/ovarian-cancer/risk-factors）。然而，大多數被診斷出卵巢癌的女性沒有該等突變。
根據本發明之另一個實施方式，肺癌為非小細胞肺癌，其可進一步選自以下群組，該群組包括鱗狀細胞癌、大細胞癌和腺癌。腺癌的亞組可以藉由編碼表皮生長因子受體（EGFR）和下游絲裂原活化蛋白激酶（MAPK）和磷脂醯肌醇3-激酶（PI3K）信號傳導通路的組分的基因中的特定突變來定義。與治療決定潛在相關的遺傳異常包括關於對ALK抑制劑敏感的間變性淋巴瘤激酶（ALK）-酪胺酸激酶受體的易位，以及編碼肝細胞生長因子受體的MET（間充質上皮轉化因子）的擴增。MET擴增與對EGFR酪胺酸激酶抑制劑的繼發性耐藥相關。
本發明之構建體通常設計用於特定投與途徑和方法、特定投與劑量和投與頻率、特定疾病的特定治療、生體可用率和持久性範圍等。組成物的材料較佳的是以對於投與位點可接受的濃度配製。因此可以根據本發明設計配製物和組成物，以藉由任何適合的投與途徑遞送。在本發明之上下文中，投與途徑包括但不限於局部途徑、腸內途徑和腸胃外途徑。
如果已將藥物組成物凍乾，則在投與之前首先將凍乾物質在適當液體中重構。可以將凍乾物質在例如抑菌注射用水（BWFI）、生理鹽水、磷酸鹽緩衝鹽水（PBS）或與冷凍乾燥前蛋白質所處於的相同配製物中重構。本發明之藥物組成物和構建體特別可用於腸胃外投與，例如靜脈內遞送，例如藉由注射或輸注。藥物組成物可以使用醫療裝置來投與。用於藥物組成物投與的醫療裝置的實例描述在美國專利案號4,475,196；4,439,196；4,447,224；4,447,233；4,486,194；4,487,603；4,596,556；4,790,824；4,941,880；5,064,413；5,312,335；5,312,335；5,383,851；和5,399,163中。
本發明之組成物可以以合適的劑量投與至受試者，該劑量可以例如在劑量遞增研究中確定。如上所述，表現出本文所述之種間特異性的本發明之構建體還可以有利地用於非黑猩猩靈長類動物的臨床前測試。劑量方案將由主治醫師和臨床因素決定。如在醫學領域中熟知的，任何一個患者的劑量取決於許多因素，包括患者體型、體表面積、年齡、有待投與的具體化合物、性別、投與時間和途徑、一般健康狀況和同時投與的其他藥物。
「有效劑量」係足以實現或至少部分地實現所希望的效果的治療劑的量。「治療有效劑量」係足以治癒或至少部分地阻止患有疾病的患者的疾病及其併發症、體征和症狀的量。對此用途有效的量或劑量將取決於待治療的疾病（適應症）、遞送的構建體、治療背景和目標、疾病的嚴重程度、先前療法、患者的臨床病史和對治療劑的反應、投與途徑、患者的體型（體重、體表）和/或病狀（年齡和一般健康狀況）以及患者自體免疫系統的一般狀態。可以根據主治醫師的判斷調整適當的劑量，以獲得最佳治療效果。
治療有效量的本發明之構建體較佳的是導致疾病症狀的嚴重程度降低、無疾病症狀期的頻率或持續時間增加或預防由於疾病引起的損害或殘疾。相對於未經治療的患者，在表現CLDN6的腫瘤的治療中，治療有效量的本發明之構建體較佳的是將腫瘤細胞生長抑制了至少約20%、至少約40%、至少約50%、至少約60%、至少約70%、至少約80%或至少約90%。可以在預測在人腫瘤中的功效的動物模型中評價化合物抑制腫瘤生長的能力。
在另一個實施方式中，本發明提供了套組，該套組包含本發明之構建體、根據本發明之方法產生的構建體、本發明之多核苷酸、本發明之載體和/或本發明之宿主細胞。在本發明之上下文中，術語「套組」意指兩種或更多種組分（其中一種對應於本發明之構建體、藥物組成物、多核苷酸、載體或宿主細胞）一起包裝在容器、接受器或其他中。因此，套組可以被描述為足以實現特定目標的一組產品和/或器具，其可以作為單個單元銷售。
設想本發明之套組的另外的組分係與免疫檢查點途徑的蛋白質（如PD-1或CTLA-4）或與共刺激免疫檢查點受體（如4-1BB）結合的藥劑（較佳的是抗體或構建體）。該等藥劑在本文上面更詳細地描述。根據一個實施方式，該套組包含本發明之構建體和與PD-1結合的抗體或構建體。例如在PCT/US 2019/013205中詳細描述了可用於該目的的抗PD-1結合蛋白。在某些實施方式中，該套組允許組分的同時和/或依次投與。
套組可以包括一個或多個具有任何適當形狀、大小和材料（較佳的是防水的，例如塑膠或玻璃）的接受器（諸如小瓶、安瓿、容器、注射器、小瓶、袋），該一個或多個接收器含有適於投與的劑量的本發明之構建體或藥物組成物（參見上文）。套組可以另外含有使用說明（例如以小冊子或說明手冊的形式）、用於投與本發明之構建體或藥物組成物的裝置（如注射器、泵、輸注器等）、用於重構本發明之構建體的裝置和/或用於稀釋本發明之構建體的裝置。
本發明還提供了用於單劑量投與單元的套組。本發明之套組還可以含有包含乾燥/凍乾的構建體或藥物組成物的第一接受器和包含水性配製物的第二接受器。在本發明之某些實施方式中，提供了含有單室和多室預填充注射器的套組。
本發明係指以下項目：
i) 一種多肽或多肽構建體，該多肽或多肽構建體包含以下或由其組成：
● 與靶細胞的表面上的人CLDN6（SEQ ID NO: 1）結合的結構域（包含互補位），和
● 與人CD3結合的結構域（包含互補位），和
● 延長該多肽的半衰期的結構域。
ii) 根據項目i) 所述之多肽或多肽構建體，其中所述多肽構建體係T細胞活化構建體。
iii) 根據項目i) 和ii) 中任一項所述之多肽或多肽構建體，其中所述多肽構建體係如藉由選自包括確定CD69的表現量、確定CD25的表現量、確定分泌的IL-2的量、和確定該等T細胞的細胞毒性活性的群組的T細胞活化測定所確定的T細胞活化多肽。
iv) 根據項目i) 至iii) 中任一項所述之多肽或多肽構建體，其中該延長該多肽的半衰期的結構域包含兩個多肽單體或由其組成，每個多肽單體包含鉸鏈、CH2結構域和CH3結構域。
v) 根據項目i) 至iv) 中任一項所述之多肽或多肽構建體，其中該結合CLDN6的抗原結合（表位結合）結構域包含與人CLDN6內對應於SEQ ID NO. 1的胺基酸29-81（UniProt條目P56747）的表位結合的互補位或由其組成。
vi) 根據項目i) 至v) 中任一項所述之多肽或多肽構建體，其中結合CLDN6的第一抗原結合（表位結合）結構域包含與人CLDN6內對應於SEQ ID NO. 1的胺基酸138-160（UniProt條目P56747）的表位結合的互補位或由其組成。
vii) 根據項目i) 至vi) 中任一項所述之多肽或多肽構建體，其中所述包含與CLDN6結合的互補位或由其組成的結構域與SEQ ID NO: 9中描繪的CLDN6的細胞外環1（ECL1）中的SEQ ID NO: 1的胺基酸29-39和/或SEQ ID NO: 10中描繪的在靶細胞表面上的CLDN6的細胞外環2（ECL2）中的SEQ ID NO: 1的胺基酸151-160結合；很明顯，結合物不需要在SEQ ID NO: 9和10中描繪的序列內的直接化學相互作用，但該等序列中的至少一個或多個胺基酸與結合結構域的一個且通常多個胺基酸直接接觸，例如藉由氫鍵。結合結構域（即互補位）和靶結構域（即表位）之間相互作用的一般原理係本領域已知的（參見Janeway等人 Immunobiology [免疫生物學], 第9版, 2016）。
viii) 根據項目i) 至vii) 中任一項所述之多肽或多肽構建體，其中所述包含與CD3結合的互補位或由其組成的結構域與人和獼猴CD3ε鏈的胞外表位結合。
ix) 根據項目i) 至viii) 中任一項所述之多肽或多肽構建體，其中該結合CLDN6的互補位與包含含有結合靶細胞表面上的CLDN6的互補位的結構域的多肽構建體或抗體或其衍生物或片段結合CLDN6上相同的表位，其中該互補位包含可變重（VH）鏈的互補決定區CDR-H1、CDR-H2和CDR-H3和/或可變輕（VL）鏈的互補決定區CDR-L1、CDR-L2和CDR-L3，其選自以下a) 至s) 中描繪的組：a) 至d)、n) 和s) 係較佳的，a) 至c)、e) 和s) 係非常較佳的：
a) 包含SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區；
b) 包含SEQ ID NO: 27中描繪的CDR-H1、SEQ ID NO: 28中描繪的CDR-H2和SEQ ID NO: 29中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 30中描繪的CDR-L1、SEQ ID NO: 31中描繪的CDR-L2和SEQ ID NO: 32中描繪的CDR-L3的VL區；
c) 包含SEQ ID NO: 41中描繪的CDR-H1、SEQ ID NO: 42中描繪的CDR-H2和SEQ ID NO: 43中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 44中描繪的CDR-L1、SEQ ID NO: 45中描繪的CDR-L2和SEQ ID NO: 46中描繪的CDR-L3的VL區；
d) 包含SEQ ID NO: 55中描繪的CDR-H1、SEQ ID NO: 56中描繪的CDR-H2和SEQ ID NO: 57中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 58中描繪的CDR-L1、SEQ ID NO: 59中描繪的CDR-L2和SEQ ID NO: 60中描繪的CDR-L3的VL區；
e) 包含SEQ ID NO: 69中描繪的CDR-H1、SEQ ID NO: 70中描繪的CDR-H2和SEQ ID NO: 71中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 72中描繪的CDR-L1、SEQ ID NO: 73中描繪的CDR-L2和SEQ ID NO: 74中描繪的CDR-L3的VL區；
f) 包含SEQ ID NO: 83中描繪的CDR-H1、SEQ ID NO: 84中描繪的CDR-H2和SEQ ID NO: 85中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 86中描繪的CDR-L1、SEQ ID NO: 87中描繪的CDR-L2和SEQ ID NO: 88中描繪的CDR-L3的VL區；
g) 包含SEQ ID NO: 97中描繪的CDR-H1、SEQ ID NO: 98中描繪的CDR-H2和SEQ ID NO: 99中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 100中描繪的CDR-L1、SEQ ID NO: 101中描繪的CDR-L2和SEQ ID NO: 102中描繪的CDR-L3的VL區；
h) 包含SEQ ID NO: 111中描繪的CDR-H1、SEQ ID NO: 112中描繪的CDR-H2和SEQ ID NO: 113中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 114中描繪的CDR-L1、SEQ ID NO: 115中描繪的CDR-L2和SEQ ID NO: 116中描繪的CDR-L3的VL區；
i) 包含SEQ ID NO: 125中描繪的CDR-H1、SEQ ID NO: 126中描繪的CDR-H2和SEQ ID NO: 127中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 128中描繪的CDR-L1、SEQ ID NO: 129中描繪的CDR-L2和SEQ ID NO: 130中描繪的CDR-L3的VL區；
j) 包含SEQ ID NO: 139中描繪的CDR-H1、SEQ ID NO: 140中描繪的CDR-H2和SEQ ID NO: 141中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 142中描繪的CDR-L1、SEQ ID NO: 143中描繪的CDR-L2和SEQ ID NO: 144中描繪的CDR-L3的VL區；
k) 包含SEQ ID NO: 153中描繪的CDR-H1、SEQ ID NO: 154中描繪的CDR-H2和SEQ ID NO: 155中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 156中描繪的CDR-L1、SEQ ID NO: 157中描繪的CDR-L2和SEQ ID NO: 158中描繪的CDR-L3的VL區；
l) 包含SEQ ID NO: 167中描繪的CDR-H1、SEQ ID NO: 168中描繪的CDR-H2和SEQ ID NO: 169中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 170中描繪的CDR-L1、SEQ ID NO: 171中描繪的CDR-L2和SEQ ID NO: 172中描繪的CDR-L3的VL區；
m) 包含SEQ ID NO: 181中描繪的CDR-H1、SEQ ID NO: 182中描繪的CDR-H2和SEQ ID NO: 183中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 184中描繪的CDR-L1、SEQ ID NO: 185中描繪的CDR-L2和SEQ ID NO: 186中描繪的CDR-L3的VL區；
n) 包含SEQ ID NO: 195中描繪的CDR-H1、SEQ ID NO: 196中描繪的CDR-H2和SEQ ID NO: 197中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 198中描繪的CDR-L1、SEQ ID NO: 199中描繪的CDR-L2和SEQ ID NO: 200中描繪的CDR-L3的VL區；
o) 包含SEQ ID NO: 209中描繪的CDR-H1、SEQ ID NO: 210中描繪的CDR-H2和SEQ ID NO: 211中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 212中描繪的CDR-L1、SEQ ID NO: 213中描繪的CDR-L2和SEQ ID NO: 214中描繪的CDR-L3或由其組成的VL區；
p) 包含SEQ ID NO: 223中描繪的CDR-H1、SEQ ID NO: 224中描繪的CDR-H2和SEQ ID NO: 225中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 226中描繪的CDR-L1、SEQ ID NO: 227中描繪的CDR-L2和SEQ ID NO: 228中描繪的CDR-L3或由其組成的VL區；
q) 包含SEQ ID NO: 237中描繪的CDR-H1、SEQ ID NO: 238中描繪的CDR-H2和SEQ ID NO: 239中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 240中描繪的CDR-L1、SEQ ID NO: 241中描繪的CDR-L2和SEQ ID NO: 242中描繪的CDR-L3或由其組成的VL區；
r) 包含SEQ ID NO: 251中描繪的CDR-H1、SEQ ID NO: 252中描繪的CDR-H2和SEQ ID NO: 253中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 254中描繪的CDR-L1、SEQ ID NO: 255中描繪的CDR-L2和SEQ ID NO: 256中描繪的CDR-L3或由其組成的VL區，
s) 包含SEQ ID NO: 265中描繪的CDR-H1、SEQ ID NO: 266中描繪的CDR-H2和SEQ ID NO: 267中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 268中描繪的CDR-L1、SEQ ID NO: 269中描繪的CDR-L2和SEQ ID NO: 270中描繪的CDR-L3或由其組成的VL區。
x) 根據項目i) 至ix) 中任一項所述之多肽或多肽構建體，其中該與人CD3ε結合的結構域（包含互補位或由其組成）也與普通狨或松鼠猴CD3ε結合。
xi) 根據項目i) 至x) 中任一項所述之多肽或多肽構建體，其中
a) 該多肽或構建體係單鏈構建體，
b) 該與CLDN6結合的結構域（包含互補位）處於scFv的形式，
c) 該與CD3結合的結構域（包含互補位）處於scFv的形式，
d) 該等結構域（包含互補位）經由連接子連接，和/或
e) 該多肽或多肽構建體包含提供延長的血清半衰期的結構域。
xii) 根據項目i) 至xi) 中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域（包含互補位或由其組成）不與CLDN1、CLDN2、CLDN3、CLDN4、CLDN9和/或CLDN18.1/CLDN18.2結合。
xiii) 根據前述項目中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域（包含互補位或由其組成）包含含有CDR-H1、CDR-H2和CDR-H3的VH區和含有CDR-L1、CDR-L2和CDR-L3的VL區，其選自以下a) 至s) 中描繪的組：a) 至d)、n) 和s) 係較佳的，a) 至c)、e) 和s) 係非常較佳的：
a) 包含SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區；
b) 包含SEQ ID NO: 27中描繪的CDR-H1、SEQ ID NO: 28中描繪的CDR-H2和SEQ ID NO: 29中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 30中描繪的CDR-L1、SEQ ID NO: 31中描繪的CDR-L2和SEQ ID NO: 32中描繪的CDR-L3的VL區；
c) 包含SEQ ID NO: 41中描繪的CDR-H1、SEQ ID NO: 42中描繪的CDR-H2和SEQ ID NO: 43中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 44中描繪的CDR-L1、SEQ ID NO: 45中描繪的CDR-L2和SEQ ID NO: 46中描繪的CDR-L3的VL區；
d) 包含SEQ ID NO: 55中描繪的CDR-H1、SEQ ID NO: 56中描繪的CDR-H2和SEQ ID NO: 57中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 58中描繪的CDR-L1、SEQ ID NO: 59中描繪的CDR-L2和SEQ ID NO: 60中描繪的CDR-L3的VL區；
e) 包含SEQ ID NO: 69中描繪的CDR-H1、SEQ ID NO: 70中描繪的CDR-H2和SEQ ID NO: 71中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 72中描繪的CDR-L1、SEQ ID NO: 73中描繪的CDR-L2和SEQ ID NO: 74中描繪的CDR-L3的VL區；
f) 包含SEQ ID NO: 83中描繪的CDR-H1、SEQ ID NO: 84中描繪的CDR-H2和SEQ ID NO: 85中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 86中描繪的CDR-L1、SEQ ID NO: 87中描繪的CDR-L2和SEQ ID NO: 88中描繪的CDR-L3的VL區；
g) 包含SEQ ID NO: 97中描繪的CDR-H1、SEQ ID NO: 98中描繪的CDR-H2和SEQ ID NO: 99中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 100中描繪的CDR-L1、SEQ ID NO: 101中描繪的CDR-L2和SEQ ID NO: 102中描繪的CDR-L3的VL區；
h) 包含SEQ ID NO: 111中描繪的CDR-H1、SEQ ID NO: 112中描繪的CDR-H2和SEQ ID NO: 113中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 114中描繪的CDR-L1、SEQ ID NO: 115中描繪的CDR-L2和SEQ ID NO: 116中描繪的CDR-L3的VL區；
i) 包含SEQ ID NO: 125中描繪的CDR-H1、SEQ ID NO: 126中描繪的CDR-H2和SEQ ID NO: 127中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 128中描繪的CDR-L1、SEQ ID NO: 129中描繪的CDR-L2和SEQ ID NO: 130中描繪的CDR-L3的VL區；
j) 包含SEQ ID NO: 139中描繪的CDR-H1、SEQ ID NO: 140中描繪的CDR-H2和SEQ ID NO: 141中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 142中描繪的CDR-L1、SEQ ID NO: 143中描繪的CDR-L2和SEQ ID NO: 144中描繪的CDR-L3的VL區；
k) 包含SEQ ID NO: 153中描繪的CDR-H1、SEQ ID NO: 154中描繪的CDR-H2和SEQ ID NO: 155中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 156中描繪的CDR-L1、SEQ ID NO: 157中描繪的CDR-L2和SEQ ID NO: 158中描繪的CDR-L3的VL區；
l) 包含SEQ ID NO: 167中描繪的CDR-H1、SEQ ID NO: 168中描繪的CDR-H2和SEQ ID NO: 169中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 170中描繪的CDR-L1、SEQ ID NO: 171中描繪的CDR-L2和SEQ ID NO: 172中描繪的CDR-L3的VL區；
m) 包含SEQ ID NO: 181中描繪的CDR-H1、SEQ ID NO: 182中描繪的CDR-H2和SEQ ID NO: 183中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 184中描繪的CDR-L1、SEQ ID NO: 185中描繪的CDR-L2和SEQ ID NO: 186中描繪的CDR-L3的VL區；
n) 包含SEQ ID NO: 195中描繪的CDR-H1、SEQ ID NO: 196中描繪的CDR-H2和SEQ ID NO: 197中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 198中描繪的CDR-L1、SEQ ID NO: 199中描繪的CDR-L2和SEQ ID NO: 200中描繪的CDR-L3的VL區；
o) 包含SEQ ID NO: 209中描繪的CDR-H1、SEQ ID NO: 210中描繪的CDR-H2和SEQ ID NO: 211中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 212中描繪的CDR-L1、SEQ ID NO: 213中描繪的CDR-L2和SEQ ID NO: 214中描繪的CDR-L3的VL區；
p) 包含SEQ ID NO: 223中描繪的CDR-H1、SEQ ID NO: 224中描繪的CDR-H2和SEQ ID NO: 225中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 226中描繪的CDR-L1、SEQ ID NO: 227中描繪的CDR-L2和SEQ ID NO: 228中描繪的CDR-L3的VL區；
q) 包含SEQ ID NO: 237中描繪的CDR-H1、SEQ ID NO: 238中描繪的CDR-H2和SEQ ID NO: 239中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 240中描繪的CDR-L1、SEQ ID NO: 241中描繪的CDR-L2和SEQ ID NO: 242中描繪的CDR-L3的VL區；
r) 包含SEQ ID NO: 251中描繪的CDR-H1、SEQ ID NO: 252中描繪的CDR-H2和SEQ ID NO: 253中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 254中描繪的CDR-L1、SEQ ID NO: 255中描繪的CDR-L2和SEQ ID NO: 256中描繪的CDR-L3的VL區，
s) 包含SEQ ID NO: 265中描繪的CDR-H1、SEQ ID NO: 266中描繪的CDR-H2和SEQ ID NO: 267中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 268中描繪的CDR-L1、SEQ ID NO: 269中描繪的CDR-L2和SEQ ID NO: 270中描繪的CDR-L3的VL區。
xiv) 根據前述項目中任一項所述之多肽或多肽構建體，其中該包含與CLDN6結合的互補位或由組成的結構域包含具有選自以下群組的胺基酸序列的VH區，該群組包括SEQ ID NO: 11、SEQ ID NO: 25、SEQ ID NO: 39、SEQ ID NO: 53、SEQ ID NO: 67、SEQ ID NO: 81、SEQ ID NO: 95、SEQ ID NO: 109、SEQ ID NO: 123、SEQ ID NO: 137、SEQ ID NO: 151、SEQ ID NO: 165、SEQ ID NO: 179、SEQ ID NO: 193、SEQ ID NO: 207、SEQ ID NO: 221、SEQ ID NO: 235、SEQ ID NO: 249、或SEQ ID NO: 263中描繪的序列，
其中所述VH區胺基酸序列可以在構架區和/或高變區中具有一個或幾個胺基酸殘基的一個或多個修飾，條件係包含所述修飾的VH區的所述結構域選擇性地與CLDN6結合，並且
視需要，其中所述結構域係活化T細胞並保持誘導T細胞依賴性細胞毒性的能力的多肽或多肽構建體的一部分，
進一步視需要，其中所述結構域係活化T細胞並保持誘導效力為表現CLDN9但不表現CLDN6的相同細胞類型的1000倍的T細胞依賴性細胞毒性的能力的多肽或多肽構建體的一部分，以及
更進一步視需要，其中所述結構域係不能活化T細胞並在相同細胞類型的CLDN6陰性細胞中誘導T細胞依賴性細胞毒性的多肽或多肽構建體的一部分，較佳的是當在體外細胞毒性測定中測試時。
xv) 根據前述項目中任一項所述之多肽或多肽構建體，其中該包含與CLDN6結合的結構域（包含互補位或由其組成）包含具有選自以下群組的胺基酸序列的VL區，該群組包括SEQ ID NO: 12、SEQ ID NO: 26、SEQ ID NO: 40、SEQ ID NO: 54、SEQ ID NO: 68、SEQ ID NO: 82、SEQ ID NO: 96、SEQ ID NO: 110、SEQ ID NO: 124、SEQ ID NO: 138、SEQ ID NO: 152、SEQ ID NO: 166、SEQ ID NO: 180、SEQ ID NO: 194、SEQ ID NO: 208、SEQ ID NO: 222、SEQ ID NO: 236、SEQ ID NO: 250、或SEQ ID NO: 264中描繪的序列，
其中所述VL區胺基酸序列可以在構架區和/或高變區中具有一個或幾個胺基酸殘基的一個或多個修飾，條件係包含所述修飾的VL區的所述結構域選擇性地與CLDN6結合，並且
視需要，其中所述結構域係活化T細胞並保持在靶細胞中誘導T細胞依賴性細胞毒性的能力的多肽或多肽構建體的一部分，
進一步視需要，其中所述結構域係活化T細胞並保持誘導效力為不表現CLDN6的對照細胞的500倍的T細胞依賴性細胞毒性的能力的多肽或多肽構建體的一部分，其中該等細胞視需要表現CLDN9，但是
更進一步視需要，其中所述結構域係不能活化T細胞並在相同細胞類型的CLDN6陰性細胞中誘導T細胞依賴性細胞毒性的多肽或多肽構建體的一部分，較佳的是當在體外細胞毒性測定中測試時。
xvi) 根據前述項目中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域（包含或由互補位組成）包含具有以下中描繪的胺基酸序列的一對VH區和VL區：SEQ ID NO: 11+12、SEQ ID NO: 25+26、SEQ ID NO: 39+40、SEQ ID NO: 53+54、SEQ ID NO: 67+68、SEQ ID NO: 81+82、SEQ ID NO: 95+96、SEQ ID NO: 109+110、SEQ ID NO: 123+124、SEQ ID NO: 137+138、SEQ ID NO: 151+152、SEQ ID NO: 165+166、SEQ ID NO: 179+180、SEQ ID NO: 193+194、SEQ ID NO: 207+208、SEQ ID NO: 221+222、SEQ ID NO: 235+236、SEQ ID NO: 249+250、或SEQ ID NO: 263+264。
xvii) 根據前述項目中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域（包含或由互補位組成）包含以下中描繪的胺基酸序列：SEQ ID NO: 19、SEQ ID NO: 22、SEQ ID NO: 33、SEQ ID NO: 36、SEQ ID NO: 47、SEQ ID NO: 50、SEQ ID NO: 61、SEQ ID NO: 64、SEQ ID NO: 75、SEQ ID NO: 78、SEQ ID NO: 89、SEQ ID NO: 92、SEQ ID NO: 103、SEQ ID NO: 106、SEQ ID NO: 117、SEQ ID NO: 120、SEQ ID NO: 131、SEQ ID NO: 134、SEQ ID NO: 145、SEQ ID NO: 148、SEQ ID NO: 159、SEQ ID NO: 162、SEQ ID NO: 173、SEQ ID NO: 176、SEQ ID NO: 187、SEQ ID NO: 190、SEQ ID NO: 201、SEQ ID NO: 204、SEQ ID NO: 215、SEQ ID NO: 218、SEQ ID NO: 229、SEQ ID NO: 232、SEQ ID NO: 243、SEQ ID NO: 246、SEQ ID NO: 257、或SEQ ID NO: 260、SEQ ID NO: 271或SEQ ID NO: 274。
xviii) 根據前述項目中任一項所述之多肽或多肽構建體，所述多肽或多肽構建體包含如下多肽或由其組成，該多肽具有選自以下中描繪的那些的群組的胺基酸序列：SEQ ID NO: 19、SEQ ID NO: 20、SEQ ID NO: 21、SEQ ID NO: 22、SEQ ID NO: 23、和SEQ ID NO: 24、SEQ ID NO: 33、SEQ ID NO: 34、SEQ ID NO: 35、SEQ ID NO: 36、SEQ ID NO: 37、和SEQ ID NO: 38、SEQ ID NO: 47、SEQ ID NO: 48、SEQ ID NO: 49、SEQ ID NO: 50、SEQ ID NO: 51、和SEQ ID NO: 52、SEQ ID NO: 61、SEQ ID NO: 62、SEQ ID NO: 63、SEQ ID NO: 64、SEQ ID NO: 65、和SEQ ID NO: 66、SEQ ID NO: 75、SEQ ID NO: 76、SEQ ID NO: 77、SEQ ID NO: 78、SEQ ID NO: 79、和SEQ ID NO: 80、SEQ ID NO: 89、SEQ ID NO: 90、SEQ ID NO: 91、SEQ ID NO: 92、SEQ ID NO: 93、和SEQ ID NO: 94、SEQ ID NO: 103、SEQ ID NO: 104、SEQ ID NO: 105、SEQ ID NO: 106、SEQ ID NO: 107、和SEQ ID NO: 108、SEQ ID NO: 117、SEQ ID NO: 118、SEQ ID NO: 119、SEQ ID NO: 120、SEQ ID NO: 121、和SEQ ID NO: 122、SEQ ID NO: 131、SEQ ID NO: 132、SEQ ID NO: 133、SEQ ID NO: 134、SEQ ID NO: 135、和SEQ ID NO: 136、SEQ ID NO: 145、SEQ ID NO: 146、SEQ ID NO: 147、SEQ ID NO: 148、SEQ ID NO: 149、和SEQ ID NO: 150、SEQ ID NO: 159、SEQ ID NO: 160、SEQ ID NO: 161、SEQ ID NO: 162、SEQ ID NO: 163、和SEQ ID NO: 164、SEQ ID NO: 173、SEQ ID NO: 174、SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、和SEQ ID NO: 178、SEQ ID NO: 187、SEQ ID NO: 188、SEQ ID NO: 189、SEQ ID NO: 190、SEQ ID NO: 191、和SEQ ID NO: 192、SEQ ID NO: 201、SEQ ID NO: 202、SEQ ID NO: 203、SEQ ID NO: 204、SEQ ID NO: 205、和SEQ ID NO: 206、SEQ ID NO: 215、SEQ ID NO: 216、SEQ ID NO: 217、SEQ ID NO: 218、SEQ ID NO: 219、和SEQ ID NO: 220、SEQ ID NO: 229、SEQ ID NO: 230、SEQ ID NO: 231、SEQ ID NO: 232、SEQ ID NO: 233、和SEQ ID NO: 234、SEQ ID NO: 243、SEQ ID NO: 244、SEQ ID NO: 245、SEQ ID NO: 246、SEQ ID NO: 247、和SEQ ID NO: 248、SEQ ID NO: 257、SEQ ID NO: 258、SEQ ID NO: 259、SEQ ID NO: 260、SEQ ID NO: 261、和SEQ ID NO: 262、SEQ ID NO: 271、SEQ ID NO: 272、SEQ ID NO: 273、SEQ ID NO: 274、SEQ ID NO: 275、和SEQ ID NO: 276，或選自具有與所述序列具有至少90%、91%、92%、93%、94%、95%、96%、97%、98%或99%同一性的胺基酸的多肽/多肽構建體的胺基酸序列。
xix) 根據前述項目中任一項所述之多肽或多肽構建體，其中如在使用表現SEQ ID NO: 1中描繪的野生型CLDN6突變體的細胞進行的體外測定中確定的，該包含與CLDN6結合的互補位或由其組成的結構域誘導的細胞毒性比使用表現SEQ ID NO:1中描繪的CLDN6的細胞進行的體外測定中測量的T細胞依賴性細胞毒性低至少100倍、至少250倍、至少500倍或至少1000倍，該突變體包含以下突變中至少一個或多個：M29X，其中X較佳的是L；R145X，其中X較佳的是Q；和/或Q156X，其中X較佳的是L。
xx) 根據前述項目中任一項所述之多肽或多肽構建體，其中如在使用表現SEQ ID NO: 1中描繪的野生型CLDN6突變體的細胞進行的體外測定中確定的，該包含與CLDN6結合的互補位或由其組成的結構域誘導的細胞毒性比使用表現SEQ ID NO:1中描繪的CLDN6的細胞進行的體外測定中測量的T細胞依賴性細胞毒性低至少100倍、至少250倍、至少500倍或至少1000倍，該突變體包含以下突變中至少一個或多個：M29X，其中X較佳的是L；R145X，其中X較佳的是Q；和/或Q156X，其中X較佳的是L，其中所述構建體能夠活化T細胞並在表現CLDN6的靶細胞中誘導T細胞依賴性細胞毒性，並且其中所述構建體具有重鏈CDR3序列，其包含：X1LIVX2APX3（SEQ ID NO.667），其中X1係A或N；X2係V或E；並且X3係V或A。
xxi) 根據前述項目之一所述之多肽或多肽構建體，其中該構建體係單鏈構建體。
xxii) 根據前述項目之一所述之多肽或多肽構建體，其中所述包含兩個多肽單體或由其組成的半衰期延長結構包含鉸鏈、CH2結構域和CH3結構域，按胺基至羧基順序包含：
鉸鏈-CH2-CH3-連接子-鉸鏈-CH2-CH3。
xxiii) 根據前述項目之一所述之多肽或多肽構建體，其中該CH2結構域包含結構域內半胱胺酸二硫橋。
xxiv) 根據前述項目之一所述之多肽或多肽構建體，其中
(a) 包含結合CLDN6的互補位的抗原結合（表位結合）結構域包含或由兩個抗體可變結構域組成，並且包含結合CD3的互補位的抗原結合（表位結合）結構域包含或由兩個抗體可變結構域組成；
(b) 包含結合CLDN6的互補位的抗原結合（表位結合）結構域包含或由一個抗體可變結構域組成，並且包含結合CD3的互補位的抗原結合（表位結合）結構域包含或由兩個抗體可變結構域組成；
(c) 包含結合CLDN6的互補位的抗原結合（表位結合）結構域包含或由兩個抗體可變結構域組成，並且包含結合CD3的互補位的抗原結合（表位結合）結構域包含或由一個抗體可變結構域組成；或
(d) 包含結合CLDN6的互補位的抗原結合（表位結合）結構域包含或由一個抗體可變結構域組成，並且包含結合CD3的互補位的抗原結合（表位結合）結構域包含或由一個抗體可變結構域組成。
xxv) 根據前述項目之一所述之多肽或多肽構建體，其中該包含結合CLDN6的互補位或由其組成的抗原結合（表位結合）結構域和包含結合CD3的互補位或由其組成的抗原結合（表位結合）結構域藉由肽連接子與另一個結構域融合。
xxvi) 根據前述項目中任一項所述之多肽或多肽構建體，其中該多肽或多肽構建體按胺基至羧基順序，或按羧基至胺基順序包含以下或由其組成：
(a) 與CLDN6結合的抗原結合（表位結合）結構域（包含互補位）；
(b) 肽連接子，該肽連接子較佳的是具有選自由SEQ ID NO: 563-575組成之群組的胺基酸序列；
(c) 與CD3結合的抗原結合（表位結合）結構域（包含互補位）。
xxvii) 根據項目xxvi) 中所述之多肽或多肽構建體，其中所述多肽或多肽構建體按胺基至羧基順序，或按羧基至胺基順序，或介於包含與CLDN6結合的互補位的抗原結合（表位結合）結構域和與CD3結合的抗原結合（表位結合）結構域（包含互補位）之間，進一步包含：
(a) 肽連接子，該肽連接子具有選自由SEQ ID NO: 563-575組成之群組的胺基酸序列；
(b) 第三結構域的第一多肽單體；
(c) 肽連接子，該肽連接子具有選自由SEQ ID NO: 563-575組成之群組的胺基酸序列；和
(d) 所述第三結構域的第二多肽單體。
xxviii) 根據前述項目之一所述之多肽或多肽構建體，其中該構建體描繪於SEQ ID NO: 21、24、35、38、49、52、63、66、77、80、91、94、105、108、119、122、133、136、147、150、161、164、175、178、189、192、203、206、217、220、231、234、245、148、259、262、273、276、287、290、301、304、315、318、329、332、343、346、357、360、371、374、385、388、399、402、413、416、427和430，特別是21、24、35、38、49、52、63、66、77、80、91、94，更特別是21、24、35、38、49、52、77和80，並且甚至更特別是21、35、49和77中描繪的任一個序列中。
xxix) 根據前述項目之一所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域（包含互補位），該結構域包含含有以下SEQ ID NO: 670、671和/或672中描繪的CDR序列的至少一個、兩個或全部的VH結構域。
xxx) 根據前述項目之一所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域（包含互補位），該結構域包含含有以下SEQ ID NO: 673、674和/或675中描繪的CDR序列的至少一個、兩個或全部。
xxxi) 根據前述項目之一所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域（包含互補位），該結構域包含含有以下SEQ ID NO: 670、671、672、673、674和/或675中描繪的CDR序列的至少一個、兩個或全部的VH和VL結構域。
xxxii) 根據前述項目之一所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域（包含互補位），該結構域包含SEQ ID NO: 676中描繪的VH結構域。
xxxiii) 根據前述項目之一所述之多肽構建體，其中該構建體包含與CD3結合的結構域（包含互補位），該結構域包含SEQ ID NO: 677中描繪的VL結構域。
xxxiv) 根據前述項目之一所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域（包含互補位），該結構域包含SEQ ID NO: 676中描繪的VH結構域和SEQ ID NO: 677中描繪的VL結構域。
xxxv) 根據前述項目之一所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域（包含互補位），該結構域包含SEQ ID NO: 678中描繪的scFv結構域。
xxxvi) 一種多核苷酸，該多核苷酸編碼如前述項目中任一項所定義的多肽或多肽構建體。
xxxvii) 一種載體，其包含如項目xxxvi) 中所定義的多核苷酸。
xxxviii) 一種宿主細胞，其經如項目xxxvi) 中所定義的多核苷酸或如項目xxxvii) 中所定義的載體轉化或轉染。
xil) 一種用於產生如項目i) 至xxxv) 中任一項所定義的多肽或多肽構建體之方法，所述方法包括在允許所述多肽構建體表現的條件下培養如項目xxxviii) 中所定義的宿主細胞並從培養物中回收所產生的多肽或多肽構建體。
xl) 一種藥物組成物，其包含如項目i) 至xxxv) 中任一項所定義的或根據項目xxxix) 之方法產生的多肽或多肽構建體。
xli) 根據項目i) 至 xxxv) 中任一項所述之或根據項目xxxix) 之方法產生的多肽或多肽構建體，其用作藥物，特別是用於預防、治療或緩解疾病、較佳的是贅生物的藥物。
xlii) 根據項目xli) 中所述之多肽或多肽構建體，其用作藥物，特別是用於預防、治療或改善疾病的藥物，其中該疾病或贅生物選自由以下組成之群組：生殖細胞癌，特別是卵巢癌，特別是卵巢腺癌和卵巢畸胎癌；子宮癌；和肺癌，包括小細胞肺癌（SCLC）和非小細胞肺癌（NSCLC），特別是鱗狀細胞肺癌和腺癌。
xliii) 根據項目xli) 中所述之多肽或多肽構建體，其中該肺癌係非小細胞肺癌（NSCLC），特別是鱗狀細胞肺癌和腺癌。
xliv) 一種套組，其包含如項目i) 至xxxv) 中任一項所定義的多肽或多肽構建體、根據項目xil) 之方法產生的多肽或多肽構建體、如項目xxxvi) 中所定義的多核苷酸、如項目xxxvii) 中所定義的載體、和/或如項目xxxviii) 中所定義的宿主細胞。
xlv) 一種用於治療或改善增殖性疾病、腫瘤性疾病、癌症或免疫障礙之方法，該方法包括向有需要的受試者投與根據項目i) 至 xxxv) 中任一項所述之或根據項目xil) 之方法產生的多肽或多肽構建體的步驟，其中該疾病較佳的是選自由以下組成之群組：生殖細胞癌；卵巢癌，特別是卵巢腺癌和卵巢畸胎癌；子宮癌，更特別是卵巢漿液性囊腺癌、子宮癌肉瘤、子宮體子宮內膜癌；和肺癌，包括小細胞肺癌（SCLC）和非小細胞肺癌（NSCLC），特別是鱗狀細胞肺癌和腺癌。
xlvi) 一種多肽或多肽構建體，其包含
● 與人CLDN6（SEQ ID NO: 1）結合的結構域，和
● 與人CD3結合的結構域，以及
● 延長該多肽的半衰期的結構域。
xlvii) 根據項目xlvi) 所述之多肽或多肽構建體，其中所述多肽構建體係T細胞活化構建體。
xlviii) 根據項目xlvi) 和xlvii) 中任一項所述之多肽或多肽構建體，其中所述多肽構建體係如在選自包括確定CD69的表現量、確定CD25的表現量、確定分泌的IL-2的量、和確定該等T細胞的細胞毒性活性的群組的T細胞活化測定中確定的T細胞活化多肽。
xlix) 根據項目xlvi) 至xlviii) 中任一項所述之多肽或多肽構建體，其中延長該多肽的半衰期的結構域包含兩個多肽單體，每個多肽單體包含鉸鏈、CH2結構域和CH3結構域。
xlx) 根據項目xlvi) 和xlix) 中任一項所述之多肽或多肽構建體，其中該結合CLDN6的抗原結合結構域包含與人CLDN6內對應於SEQ ID NO. 1的胺基酸29-81（UniProt條目P56747）的表位結合。
xlxi) 根據項目xlvi) 和xlx) 中任一項所述之多肽或多肽構建體，其中結合CLDN6的第一抗原結合結構域包含與人CLDN6內對應於SEQ ID NO. 1的胺基酸138-160（UniProt條目P56747）的表位結合。
xlxii) 根據項目xlvi) 和xlxi)中任一項所述之多肽或多肽構建體，其中所述結構域與CLDN6結合，即與SEQ ID NO: 9中描繪的CLDN6的細胞外環1（ECL1）中的SEQ ID NO: 1的胺基酸29-39和/或SEQ ID NO: 10中描繪的CLDN6的細胞外環2（ECL2）中的SEQ ID NO: 1的胺基酸151-160結合。
xlxiii) 根據項目xlvi) 和xlxii) 中任一項所述之多肽或多肽構建體，其中所述與CD3結合的結構域與人和獼猴CD3ε鏈的胞外表位結合。
xlxiv) 根據項目xlvi) 和xlxiii)中任一項所述之多肽或多肽構建體，其中該結合CLDN6的結構域與包含結合CLDN6的結構域的多肽構建體或抗體或其衍生物或片段結合CLDN6上相同的表位，其中該結構域包含可變重（VH）鏈的互補決定區CDR-H1、CDR-H2和CDR-H3和/或可變輕（VL）鏈的互補決定區CDR-L1、CDR-L2和CDR-L3，其選自以下a) 至s) 中描繪的組：a) 至d)、n) 和s) 係較佳的，a) 至c)、e) 和s) 係非常較佳的：
a) 包含SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區；
b) 包含SEQ ID NO: 27中描繪的CDR-H1、SEQ ID NO: 28中描繪的CDR-H2和SEQ ID NO: 29中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 30中描繪的CDR-L1、SEQ ID NO: 31中描繪的CDR-L2和SEQ ID NO: 32中描繪的CDR-L3的VL區；
c) 包含SEQ ID NO: 41中描繪的CDR-H1、SEQ ID NO: 42中描繪的CDR-H2和SEQ ID NO: 43中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 44中描繪的CDR-L1、SEQ ID NO: 45中描繪的CDR-L2和SEQ ID NO: 46中描繪的CDR-L3的VL區；
d) 包含SEQ ID NO: 55中描繪的CDR-H1、SEQ ID NO: 56中描繪的CDR-H2和SEQ ID NO: 57中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 58中描繪的CDR-L1、SEQ ID NO: 59中描繪的CDR-L2和SEQ ID NO: 60中描繪的CDR-L3的VL區；
e) 包含SEQ ID NO: 69中描繪的CDR-H1、SEQ ID NO: 70中描繪的CDR-H2和SEQ ID NO: 71中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 72中描繪的CDR-L1、SEQ ID NO: 73中描繪的CDR-L2和SEQ ID NO: 74中描繪的CDR-L3的VL區；
f) 包含SEQ ID NO: 83中描繪的CDR-H1、SEQ ID NO: 84中描繪的CDR-H2和SEQ ID NO: 85中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 86中描繪的CDR-L1、SEQ ID NO: 87中描繪的CDR-L2和SEQ ID NO: 88中描繪的CDR-L3的VL區；
g) 包含SEQ ID NO: 97中描繪的CDR-H1、SEQ ID NO: 98中描繪的CDR-H2和SEQ ID NO: 99中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 100中描繪的CDR-L1、SEQ ID NO: 101中描繪的CDR-L2和SEQ ID NO: 102中描繪的CDR-L3的VL區；
h) 包含SEQ ID NO: 111中描繪的CDR-H1、SEQ ID NO: 112中描繪的CDR-H2和SEQ ID NO: 113中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 114中描繪的CDR-L1、SEQ ID NO: 115中描繪的CDR-L2和SEQ ID NO: 116中描繪的CDR-L3的VL區；
i) 包含SEQ ID NO: 125中描繪的CDR-H1、SEQ ID NO: 126中描繪的CDR-H2和SEQ ID NO: 127中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 128中描繪的CDR-L1、SEQ ID NO: 129中描繪的CDR-L2和SEQ ID NO: 130中描繪的CDR-L3的VL區；
j) 包含SEQ ID NO: 139中描繪的CDR-H1、SEQ ID NO: 140中描繪的CDR-H2和SEQ ID NO: 141中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 142中描繪的CDR-L1、SEQ ID NO: 143中描繪的CDR-L2和SEQ ID NO: 144中描繪的CDR-L3的VL區；
k) 包含SEQ ID NO: 153中描繪的CDR-H1、SEQ ID NO: 154中描繪的CDR-H2和SEQ ID NO: 155中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 156中描繪的CDR-L1、SEQ ID NO: 157中描繪的CDR-L2和SEQ ID NO: 158中描繪的CDR-L3的VL區；
l) 包含SEQ ID NO: 167中描繪的CDR-H1、SEQ ID NO: 168中描繪的CDR-H2和SEQ ID NO: 169中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 170中描繪的CDR-L1、SEQ ID NO: 171中描繪的CDR-L2和SEQ ID NO: 172中描繪的CDR-L3的VL區；
m) 包含SEQ ID NO: 181中描繪的CDR-H1、SEQ ID NO: 182中描繪的CDR-H2和SEQ ID NO: 183中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 184中描繪的CDR-L1、SEQ ID NO: 185中描繪的CDR-L2和SEQ ID NO: 186中描繪的CDR-L3的VL區；
n) 包含SEQ ID NO: 195中描繪的CDR-H1、SEQ ID NO: 196中描繪的CDR-H2和SEQ ID NO: 197中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 198中描繪的CDR-L1、SEQ ID NO: 199中描繪的CDR-L2和SEQ ID NO: 200中描繪的CDR-L3的VL區；
o) 包含SEQ ID NO: 209中描繪的CDR-H1、SEQ ID NO: 210中描繪的CDR-H2和SEQ ID NO: 211中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 212中描繪的CDR-L1、SEQ ID NO: 213中描繪的CDR-L2和SEQ ID NO: 214中描繪的CDR-L3的VL區；
p) 包含SEQ ID NO: 223中描繪的CDR-H1、SEQ ID NO: 224中描繪的CDR-H2和SEQ ID NO: 225中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 226中描繪的CDR-L1、SEQ ID NO: 227中描繪的CDR-L2和SEQ ID NO: 228中描繪的CDR-L3的VL區；
q) 包含SEQ ID NO: 237中描繪的CDR-H1、SEQ ID NO: 238中描繪的CDR-H2和SEQ ID NO: 239中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 240中描繪的CDR-L1、SEQ ID NO: 241中描繪的CDR-L2和SEQ ID NO: 242中描繪的CDR-L3的VL區；
r) 包含SEQ ID NO: 251中描繪的CDR-H1、SEQ ID NO: 252中描繪的CDR-H2和SEQ ID NO: 253中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 254中描繪的CDR-L1、SEQ ID NO: 255中描繪的CDR-L2和SEQ ID NO: 256中描繪的CDR-L3的VL區，
s) 包含SEQ ID NO: 265中描繪的CDR-H1、SEQ ID NO: 266中描繪的CDR-H2和SEQ ID NO: 267中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 268中描繪的CDR-L1、SEQ ID NO: 269中描繪的CDR-L2和SEQ ID NO: 270中描繪的CDR-L3的VL區。
xlxv) 根據項目xlvi) 和xlxiv) 中任一項所述之多肽或多肽構建體，其中該與人CD3ε結合的結構域也與普通狨或松鼠猴CD3ε結合。
xlxvi) 根據項目xlvi) 和xlxv) 中任一項所述之多肽或多肽構建體，其中
a) 該多肽係單鏈構建體，
b) 該與CLDN6結合的結構域處於scFv的形式，
c) 該與CD3結合的結構域處於scFv的形式，
d) 該結構域經由連接子連接，和/或
e) 該多肽或多肽構建體包含提供延長的血清半衰期的結構域。
xlxvii) 根據項目xlvi) 和xlxvi) 中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域不與CLDN1、CLDN2、CLDN3、CLDN4、CLDN9和/或CLDN18.1/CLDN18.2結合。
xlxviii) 根據項目xlvi) 和xlxvii) 中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域包含含有CDR-H1、CDR-H2和CDR-H3的VH區以及含有CDR-L1、CDR-L2和CDR-L3的VL區，其選自以下a) 至s) 中描繪的組：a) 至d)、n) 和s) 係較佳的，a) 至c)、e) 和s) 係非常較佳的：
a) 包含SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區；
b) 包含SEQ ID NO: 27中描繪的CDR-H1、SEQ ID NO: 28中描繪的CDR-H2和SEQ ID NO: 29中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 30中描繪的CDR-L1、SEQ ID NO: 31中描繪的CDR-L2和SEQ ID NO: 32中描繪的CDR-L3的VL區；
c) 包含SEQ ID NO: 41中描繪的CDR-H1、SEQ ID NO: 42中描繪的CDR-H2和SEQ ID NO: 43中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 44中描繪的CDR-L1、SEQ ID NO: 45中描繪的CDR-L2和SEQ ID NO: 46中描繪的CDR-L3的VL區；
d) 包含SEQ ID NO: 55中描繪的CDR-H1、SEQ ID NO: 56中描繪的CDR-H2和SEQ ID NO: 57中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 58中描繪的CDR-L1、SEQ ID NO: 59中描繪的CDR-L2和SEQ ID NO: 60中描繪的CDR-L3的VL區；
e) 包含SEQ ID NO: 69中描繪的CDR-H1、SEQ ID NO: 70中描繪的CDR-H2和SEQ ID NO: 71中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 72中描繪的CDR-L1、SEQ ID NO: 73中描繪的CDR-L2和SEQ ID NO: 74中描繪的CDR-L3的VL區；
f) 包含SEQ ID NO: 83中描繪的CDR-H1、SEQ ID NO: 84中描繪的CDR-H2和SEQ ID NO: 85中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 86中描繪的CDR-L1、SEQ ID NO: 87中描繪的CDR-L2和SEQ ID NO: 88中描繪的CDR-L3的VL區；
g) 包含SEQ ID NO: 97中描繪的CDR-H1、SEQ ID NO: 98中描繪的CDR-H2和SEQ ID NO: 99中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 100中描繪的CDR-L1、SEQ ID NO: 101中描繪的CDR-L2和SEQ ID NO: 102中描繪的CDR-L3的VL區；
h) 包含SEQ ID NO: 111中描繪的CDR-H1、SEQ ID NO: 112中描繪的CDR-H2和SEQ ID NO: 113中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 114中描繪的CDR-L1、SEQ ID NO: 115中描繪的CDR-L2和SEQ ID NO: 116中描繪的CDR-L3的VL區；
i) 包含SEQ ID NO: 125中描繪的CDR-H1、SEQ ID NO: 126中描繪的CDR-H2和SEQ ID NO: 127中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 128中描繪的CDR-L1、SEQ ID NO: 129中描繪的CDR-L2和SEQ ID NO: 130中描繪的CDR-L3的VL區；
j) 包含SEQ ID NO: 139中描繪的CDR-H1、SEQ ID NO: 140中描繪的CDR-H2和SEQ ID NO: 141中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 142中描繪的CDR-L1、SEQ ID NO: 143中描繪的CDR-L2和SEQ ID NO: 144中描繪的CDR-L3的VL區；
k) 包含SEQ ID NO: 153中描繪的CDR-H1、SEQ ID NO: 154中描繪的CDR-H2和SEQ ID NO: 155中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 156中描繪的CDR-L1、SEQ ID NO: 157中描繪的CDR-L2和SEQ ID NO: 158中描繪的CDR-L3的VL區；
l) 包含SEQ ID NO: 167中描繪的CDR-H1、SEQ ID NO: 168中描繪的CDR-H2和SEQ ID NO: 169中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 170中描繪的CDR-L1、SEQ ID NO: 171中描繪的CDR-L2和SEQ ID NO: 172中描繪的CDR-L3的VL區；
m) 包含SEQ ID NO: 181中描繪的CDR-H1、SEQ ID NO: 182中描繪的CDR-H2和SEQ ID NO: 183中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 184中描繪的CDR-L1、SEQ ID NO: 185中描繪的CDR-L2和SEQ ID NO: 186中描繪的CDR-L3的VL區；
n) 包含SEQ ID NO: 195中描繪的CDR-H1、SEQ ID NO: 196中描繪的CDR-H2和SEQ ID NO: 197中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 198中描繪的CDR-L1、SEQ ID NO: 199中描繪的CDR-L2和SEQ ID NO: 200中描繪的CDR-L3的VL區；
o) 包含SEQ ID NO: 209中描繪的CDR-H1、SEQ ID NO: 210中描繪的CDR-H2和SEQ ID NO: 211中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 212中描繪的CDR-L1、SEQ ID NO: 213中描繪的CDR-L2和SEQ ID NO: 214中描繪的CDR-L3的VL區；
p) 包含SEQ ID NO: 223中描繪的CDR-H1、SEQ ID NO: 224中描繪的CDR-H2和SEQ ID NO: 225中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 226中描繪的CDR-L1、SEQ ID NO: 227中描繪的CDR-L2和SEQ ID NO: 228中描繪的CDR-L3的VL區；
q) 包含SEQ ID NO: 237中描繪的CDR-H1、SEQ ID NO: 238中描繪的CDR-H2和SEQ ID NO: 239中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 240中描繪的CDR-L1、SEQ ID NO: 241中描繪的CDR-L2和SEQ ID NO: 242中描繪的CDR-L3的VL區；
r) 包含SEQ ID NO: 251中描繪的CDR-H1、SEQ ID NO: 252中描繪的CDR-H2和SEQ ID NO: 253中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 254中描繪的CDR-L1、SEQ ID NO: 255中描繪的CDR-L2和SEQ ID NO: 256中描繪的CDR-L3的VL區，
s) 包含SEQ ID NO: 265中描繪的CDR-H1、SEQ ID NO: 266中描繪的CDR-H2和SEQ ID NO: 267中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 268中描繪的CDR-L1、SEQ ID NO: 269中描繪的CDR-L2和SEQ ID NO: 270中描繪的CDR-L3的VL區。
xlxix) 根據前述項目中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的該結構域包含具有選自以下群組的胺基酸序列的VH區，該群組包括SEQ ID NO: 11、SEQ ID NO: 25、SEQ ID NO: 39、SEQ ID NO: 53、SEQ ID NO: 67、SEQ ID NO: 81、SEQ ID NO: 95、SEQ ID NO: 109、SEQ ID NO: 123、SEQ ID NO: 137、SEQ ID NO: 151、SEQ ID NO: 165、SEQ ID NO: 179、SEQ ID NO: 193、SEQ ID NO: 207、SEQ ID NO: 221、SEQ ID NO: 235、SEQ ID NO: 249、或SEQ ID NO: 263中描繪的序列，
其中所述VH區胺基酸序列可以在構架區和/或高變區中具有一個或幾個胺基酸殘基的一個或多個修飾，條件係包含所述修飾的VH區的所述結構域選擇性地與CLDN6結合，並且
視需要，其中所述結構域係活化T細胞並保持誘導T細胞依賴性細胞毒性的能力的多肽或多肽構建體的一部分，
進一步視需要，其中所述結構域係活化T細胞並保持誘導效力為表現CLDN9但不表現CLDN6的相同細胞類型的1000倍的T細胞依賴性細胞毒性的能力的多肽或多肽構建體的一部分，以及
更進一步視需要，其中所述結構域係不能活化T細胞並在相同細胞類型的CLDN6陰性細胞中誘導T細胞依賴性細胞毒性的多肽或多肽構建體的一部分，較佳的是當在體外細胞毒性測定中測試時。
xlxix) 根據前述項目中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域包含具有選自以下群組的胺基酸序列的VL區，該群組包括SEQ ID NO: 12、SEQ ID NO: 26、SEQ ID NO: 40、SEQ ID NO: 54、SEQ ID NO: 68、SEQ ID NO: 82、SEQ ID NO: 96、SEQ ID NO: 110、SEQ ID NO: 124、SEQ ID NO: 138、SEQ ID NO: 152、SEQ ID NO: 166、SEQ ID NO: 180、SEQ ID NO: 194、SEQ ID NO: 208、SEQ ID NO: 222、SEQ ID NO: 236、SEQ ID NO: 250、或SEQ ID NO: 264中描繪的序列，
其中所述VL區胺基酸序列可以在構架區和/或高變區中具有一個或幾個胺基酸殘基的一個或多個修飾，條件係包含所述修飾的VL區的所述結構域選擇性地與CLDN6結合，並且
視需要，其中所述結構域係活化T細胞並保持在靶細胞中誘導T細胞依賴性細胞毒性的能力的多肽或多肽構建體的一部分，
進一步視需要，其中所述結構域係活化T細胞並保持誘導效力為不表現CLDN6的對照細胞的500倍的T細胞依賴性細胞毒性的能力的多肽或多肽構建體的一部分，其中該等細胞視需要表現CLDN9，但是
更進一步視需要，其中所述結構域係不能活化T細胞並在相同細胞類型的CLDN6陰性細胞中誘導T細胞依賴性細胞毒性的多肽或多肽構建體的一部分，較佳的是當在體外細胞毒性測定中測試時。
xlxx) 根據前述項目中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域包含具有以下中描繪的胺基酸序列的一對VH區和VL區：SEQ ID NO: 11+12、SEQ ID NO: 25+26、SEQ ID NO: 39+40、SEQ ID NO: 53+54、SEQ ID NO: 67+68、SEQ ID NO: 81+82、SEQ ID NO: 95+96、SEQ ID NO: 109+110、SEQ ID NO: 123+124、SEQ ID NO: 137+138、SEQ ID NO: 151+152、SEQ ID NO: 165+166、SEQ ID NO: 179+180、SEQ ID NO: 193+194、SEQ ID NO: 207+208、SEQ ID NO: 221+222、SEQ ID NO: 235+236、SEQ ID NO: 249+250、或SEQ ID NO: 263+264。
xlxxi) 根據前述項目中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域包含以下中描繪的胺基酸序列：SEQ ID NO: 19、SEQ ID NO: 22、SEQ ID NO: 33、SEQ ID NO: 36、SEQ ID NO: 47、SEQ ID NO: 50、SEQ ID NO: 61、SEQ ID NO: 64、SEQ ID NO: 75、SEQ ID NO: 78、SEQ ID NO: 89、SEQ ID NO: 92、SEQ ID NO: 103、SEQ ID NO: 106、SEQ ID NO: 117、SEQ ID NO: 120、SEQ ID NO: 131、SEQ ID NO: 134、SEQ ID NO: 145、SEQ ID NO: 148、SEQ ID NO: 159、SEQ ID NO: 162、SEQ ID NO: 173、SEQ ID NO: 176、SEQ ID NO: 187、SEQ ID NO: 190、SEQ ID NO: 201、SEQ ID NO: 204、SEQ ID NO: 215、SEQ ID NO: 218、SEQ ID NO: 229、SEQ ID NO: 232、SEQ ID NO: 243、SEQ ID NO: 246、SEQ ID NO: 257、或SEQ ID NO: 260、SEQ ID NO: 271或SEQ ID NO: 274。
xlxxii) 根據前述項目中任一項所述之多肽或多肽構建體，該多肽或多肽構建體包含具有選自以下中描繪的那些的群組的胺基酸序列的多肽：SEQ ID NO: 19、SEQ ID NO: 20、SEQ ID NO: 21、SEQ ID NO: 22、SEQ ID NO: 23、和SEQ ID NO: 24、SEQ ID NO: 33、SEQ ID NO: 34、SEQ ID NO: 35、SEQ ID NO: 36、SEQ ID NO: 37、和SEQ ID NO: 38、SEQ ID NO: 47、SEQ ID NO: 48、SEQ ID NO: 49、SEQ ID NO: 50、SEQ ID NO: 51、和SEQ ID NO: 52、SEQ ID NO: 61、SEQ ID NO: 62、SEQ ID NO: 63、SEQ ID NO: 64、SEQ ID NO: 65、和SEQ ID NO: 66、SEQ ID NO: 75、SEQ ID NO: 76、SEQ ID NO: 77、SEQ ID NO: 78、SEQ ID NO: 79、和SEQ ID NO: 80、SEQ ID NO: 89、SEQ ID NO: 90、SEQ ID NO: 91、SEQ ID NO: 92、SEQ ID NO: 93、和SEQ ID NO: 94、SEQ ID NO: 103、SEQ ID NO: 104、SEQ ID NO: 105、SEQ ID NO: 106、SEQ ID NO: 107、和SEQ ID NO: 108、SEQ ID NO: 117、SEQ ID NO: 118、SEQ ID NO: 119、SEQ ID NO: 120、SEQ ID NO: 121、和SEQ ID NO: 122、SEQ ID NO: 131、SEQ ID NO: 132、SEQ ID NO: 133、SEQ ID NO: 134、SEQ ID NO: 135、和SEQ ID NO: 136、SEQ ID NO: 145、SEQ ID NO: 146、SEQ ID NO: 147、SEQ ID NO: 148、SEQ ID NO: 149、和SEQ ID NO: 150、SEQ ID NO: 159、SEQ ID NO: 160、SEQ ID NO: 161、SEQ ID NO: 162、SEQ ID NO: 163、和SEQ ID NO: 164、SEQ ID NO: 173、SEQ ID NO: 174、SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、和SEQ ID NO: 178、SEQ ID NO: 187、SEQ ID NO: 188、SEQ ID NO: 189、SEQ ID NO: 190、SEQ ID NO: 191、和SEQ ID NO: 192、SEQ ID NO: 201、SEQ ID NO: 202、SEQ ID NO: 203、SEQ ID NO: 204、SEQ ID NO: 205、和SEQ ID NO: 206、SEQ ID NO: 215、SEQ ID NO: 216、SEQ ID NO: 217、SEQ ID NO: 218、SEQ ID NO: 219、和SEQ ID NO: 220、SEQ ID NO: 229、SEQ ID NO: 230、SEQ ID NO: 231、SEQ ID NO: 232、SEQ ID NO: 233、和SEQ ID NO: 234、SEQ ID NO: 243、SEQ ID NO: 244、SEQ ID NO: 245、SEQ ID NO: 246、SEQ ID NO: 247、和SEQ ID NO: 248、SEQ ID NO: 257、SEQ ID NO: 258、SEQ ID NO: 259、SEQ ID NO: 260、SEQ ID NO: 261、和SEQ ID NO: 262、SEQ ID NO: 271、SEQ ID NO: 272、SEQ ID NO: 273、SEQ ID NO: 274、SEQ ID NO: 275、和SEQ ID NO: 276，或為具有與所述序列有至少90%、91%、92%、93%、94%、95%、96%、97%、98%或99%同一性的胺基酸的多肽/多肽構建體。
xlxxiii) 根據前述項目中任一項所述之多肽或多肽構建體，其中如在使用表現SEQ ID NO: 1中描繪的野生型CLDN6突變體的細胞進行的體外測定中確定的，該與CLDN6結合的結構域誘導的細胞毒性比使用表現SEQ ID NO:1中描繪的CLDN6的細胞進行的體外測定中測量的細胞毒性低至少100倍、至少250倍、至少500倍，該突變體包含以下突變中至少一個或多個：M29X，其中X較佳的是L；R145X，其中X較佳的是Q；和/或Q156X，其中X較佳的是L。
xlxxiv) 根據前述項目中任一項所述之多肽或多肽構建體，其中如在使用表現SEQ ID NO: 1中描繪的野生型CLDN6突變體的細胞進行的體外測定中確定的，該與CLDN6結合的結構域誘導的細胞毒性比使用表現SEQ ID NO:1中描繪的CLDN6的細胞進行的體外測定中測量的細胞毒性低至少100倍、至少250倍、至少500倍，該突變體包含以下突變中至少一個或多個：M29X，其中X較佳的是L；R145X，其中X較佳的是Q；和/或Q156X，其中X較佳的是L，其中所述構建體能夠活化T細胞並在表現CLDN6的靶細胞中誘導細胞毒性，並且其中所述構建體具有重鏈CDR3序列，其包含：X1LIVX2APX3（SEQ ID NO.667），其中X1係A或N；X2係V或E；並且X3係V或A。
xlxxv) 根據前述項目的任一項所述之多肽或多肽構建體，其中該構建體係單鏈構建體。
xlxxvi) 根據前述項目的任一項所述之多肽或多肽構建體，其中所述包含兩個多肽單體的半衰期延長結構域包含鉸鏈、CH2結構域和CH3結構域，按胺基至羧基順序包含：
鉸鏈-CH2-CH3-連接子-鉸鏈-CH2-CH3。
xlxxvii) 根據前述項目中任一項所述之多肽或多肽構建體，其中該CH2結構域包含結構域內半胱胺酸二硫橋。
xlxxviii) 根據前述項目中的任一項所述之多肽或多肽構建體，其中
(i) 該與CLDN6結合的抗原結合（表位結合）結構域包含兩個抗體可變結構域且該與CD3結合的抗原結合（表位結合）結構域包含兩個抗體可變結構域；
(ii) 該與CLDN6結合的抗原結合（表位結合）結構域包含一個抗體可變結構域且該與CD3結合的抗原結合（表位結合）結構域包含兩個抗體可變結構域；
(iii) 該與CLDN6結合的抗原結合（表位結合）結構域包含兩個抗體可變結構域且該與CD3結合的抗原結合（表位結合）結構域包含一個抗體可變結構域；或
(iv) 該與CLDN6結合的抗原結合（表位結合）結構域包含一個抗體可變結構域且該與CD3結合的抗原結合（表位結合）結構域包含一個抗體可變結構域。
xlxxix) 根據前述項目中任一項所述之多肽或多肽構建體，其中該結合CLDN6的抗原結合（表位結合）結構域和該結合CD3的抗原結合（表位結合）結構域藉由肽連接子與另一個結構域融合。
xlxxx) 根據前述項目中任一項所述之多肽或多肽構建體，其中該多肽或多肽構建體按胺基至羧基順序，或按羧基至胺基順序包含：
(a) 與CLDN6結合的抗原結合（表位結合）結構域；
(b) 肽連接子，特別是具有選自由SEQ ID NO: 563-575組成之群組的胺基酸序列的肽連接子；
(c) 與CD3結合的抗原結合（表位結合）結構域。
xlxxxi) 根據前述項目的任一項所述之多肽或多肽構建體，其中所述多肽或多肽構建體按胺基至羧基順序，或按羧基至胺基順序，或介於與CLDN6結合的抗原結合（表位結合）結構域和與CD3結合的抗原結合（表位結合）結構域之間，進一步包含：
(a) 肽連接子，該肽連接子具有選自由SEQ ID NO: 563-575組成之群組的胺基酸序列；
(b) 第三結構域的第一多肽單體；
(c) 肽連接子，該肽連接子具有選自由SEQ ID NO: 563-575組成之群組的胺基酸序列；和
(d) 所述第三結構域的第二多肽單體。
xlxxxii) 根據前述項目中任一項所述之多肽或多肽構建體，其中該構建體描繪於SEQ ID NO: 21、24、35、38、49、52、63、66、77、80、91、94、105、108、119、122、133、136、147、150、161、164、175、178、189、192、203、206、217、220、231、234、245、148、259、262、273、276、287、290、301、304、315、318、329、332、343、346、357、360、371、374、385、388、399、402、413、416、427和430，特別是21、24、35、38、49、52、63、66、77、80、91、94，更特別是21、24、35、38、49、52、77和80，並且甚至更特別是21、35、49和77中描繪的任一個序列中。
xlxxxiii) 根據前述項目中任一項所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含含有以下SEQ ID NO: 670、671和/或672中描繪的CDR序列的至少一個、兩個或全部的VH結構域。
xlxxxiv) 根據前述項目中任一項所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含含有以下SEQ ID NO: 673、674和/或675中描繪的CDR序列的至少一個、兩個或全部的VL結構域。
xlxxxv) 根據前述項目中任一項所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含含有以下SEQ ID NO: 670、671、672、673、674和/或675中描繪的CDR序列的至少一個、兩個或全部的VH和VL結構域。
xlxxxvi) 根據前述項目中任一項所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含SEQ ID NO: 676中描繪的VH結構域。
xlxxxvii) 根據前述項目中任一項所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含SEQ ID NO: 677中描繪的VL結構域。
xlxxxviii) 根據前述項目中任一項所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含SEQ ID NO: 676中描繪的VH結構域和SEQ ID NO: 677中描繪的VL結構域。
xlxxxix) 根據前述項目中任一項所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含SEQ ID NO: 678中描繪的scFv結構域。
xc) 一種多核苷酸，該多核苷酸編碼如前述項目中任一項所定義的多肽或多肽構建體。
ixc) 一種載體，其包含如項目xc) 中所定義的多核苷酸。
iiivc) 一種宿主細胞，其經如項目xc) 中所定義的多核苷酸或如項目ixc) 中所定義的載體轉化或轉染。
iivc) 一種用於產生如前述項目中任一項所定義的多肽或多肽構建體之方法，所述方法包括在允許所述多肽構建體表現的條件下培養如項目iiivc) 中所定義的宿主細胞並從培養物中回收所產生的多肽或多肽構建體。
ivc) 一種藥物組成物，其包含如前述項目中任一項所定義的或如請求項iivc) 之方法產生的多肽或多肽構建體。
vc) 根據前述項目中任一項所述之或如請求項iivc) 所述之方法產生的多肽或多肽構建體，其用作藥物，特別是用於預防、治療或緩解疾病、較佳的是贅生物的藥物。
vic) 如請求項vc) 所述之多肽或多肽構建體，其用作藥物，特別是用於預防、治療或緩解疾病的藥物，其中該疾病或贅生物選自由以下組成之群組：生殖細胞癌；卵巢癌，特別是卵巢腺癌和卵巢畸胎瘤；子宮癌；和肺癌，包括小細胞肺癌（SCLC）和非小細胞肺癌（NSCLC），特別是鱗狀細胞肺癌和腺癌。
viic) 如請求項vc) 所述之多肽或構建體，其中該肺癌係非小細胞肺癌(NSCLC)，特別是鱗狀細胞肺癌和腺癌。
viiic) 一種套組，其包含如前述項目中任一項所定義的多肽或多肽構建體、如請求項vc所述之方法產生的多肽或多肽構建體、如上述項目中所定義的多核苷酸、載體、和/或宿主細胞。
ic) 一種用於治療或改善增殖性疾病、腫瘤性疾病、癌症或免疫障礙之方法，該方法包括向有需要的受試者投與如前述項目中任一項所述之或根據前述項目之方法產生的多肽或多肽構建體的步驟，其中該疾病較佳的是選自由以下組成之群組：生殖細胞癌；卵巢癌，特別是卵巢腺癌和卵巢畸胎癌；子宮癌，更特別是卵巢漿液性囊腺癌、子宮癌肉瘤、子宮體子宮內膜癌；和肺癌，包括小細胞肺癌（SCLC）和非小細胞肺癌（NSCLC），特別是鱗狀細胞肺癌和腺癌。
每當圖中使用術語「構建體」時，所述術語係指所使用的本發明之多肽/多肽構建體或其所指示的對照。
如本文使用的，除非上下文另外明確指示，否則單數形式「一個」、「一種」和「該」也包括複數指示物。因此，例如，對「一種試劑」的提及包括此類不同試劑中的一種或多種，並且對「該方法」的提及包括提及熟悉該項技術者已知的可以修改或取代本文所述之方法的等效步驟和方法。
除非另外指示，否則在一系列元素前面的術語「至少」應被理解為指該系列中的每一個元素。熟悉該項技術者僅使用常規實驗就將認識到或能夠確定本文所述之本發明之具體實施方式的許多等效物。此類等效物旨在涵蓋在本發明中。
術語「和/或」在本文使用時包括「和」、「或」和「由所述術語連接的要素的全部或任何其他組合」的含義。
如本文使用的，術語「約」或「大約」意指在給定值或範圍的±20%內、較佳的是在15%內、更較佳的是在10%內、並且最較佳的是在5%內。它還包括具體值，例如，「約50」包括值「50」。
貫穿本說明書及申請專利範圍，除非上下文另外要求，否則詞語「包含/包括（comprise以及變型如comprises和comprising）」應當被理解成隱含包括所陳述的整體或步驟、或者整體或步驟的組，但不排除任何其他整體或步驟、或者整體或步驟的組。當在本文中使用時，術語「包含」可以用術語「含有」或「包括」來取代，或者有時在本文中使用時用術語「具有」取代。
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在本文的每個例子中，術語「包含/包括」、「基本上由……組成」和「由……組成」中的任何一個可以用其他兩個術語中的任一個替代。
以上描述和以下實例提供了示例性的佈置，但是本發明不限於本文描述的特定方法、技術、方案、材料、試劑、物質等，並且因此可以變化。本文使用的術語僅用於描述特定實施方式。本文使用的術語不旨在限制僅由申請專利範圍限定的本發明之範圍。在獨立請求項中提供了本發明之各個方面。在從屬請求項中提供了本發明之一些可選特性。
本說明書全文中引用的所有出版物和專利（包括所有專利、專利申請、科學出版物、製造商的說明書、說明書等），無論是上文還是下文，均藉由引用整體併入文中。本文沒有任何內容應解釋為承認本發明無權由於先前發明而早於該等揭露內容。藉由引用併入的材料在一定程度上與本說明書發生衝突或不一致時，本說明書將替代任何此類材料。
將從以下實例中獲得對本發明及其優點的更好理解，該等實例僅用於說明目的。該等實例並不打算並不應該被解釋為以任何方式限制本發明之範圍。
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[圖1]顯示了表位作圖分析的結果。最上面一行提供了CLDN4（虛線）和CLDN6（連續圖）和嵌合蛋白的結構表示，表明CLDN6的各個區域已被相應的CLDN4區域替代。上面的第二行和第三行顯示了使用同種型對照和抗CLDN4-Ab和抗CLDN6-Ab（5 µg/ml 同種型對照（R&D IC003P）+5 µg/ml抗CLDN4-ab（殖株382321 R&D MAB4219））的FACS分析結果。左側的兩個FACS結果顯示，既不表現CLDN4也不表現CLDN6的細胞不被免疫特異性檢測CLDN-4或CLDN-6的抗體識別。底部的四行顯示FACS分析結果，使用本發明之四種不同多肽/多肽構建體作為主要結合物（5μg/ml CLDN6-多肽/多肽構建體）或具有2% FCS的PBS作為對照，4個主要候選物：SEQ ID NO: 343、SEQ ID NO.35、SEQ ID NO.21和SEQ ID NO: 105（從上到下）。作為二級結合物，使用1:50-hu Fcy-PE（傑克遜免疫研究實驗室（Jacks.Imm.Res.）109-116-98）。E1A和E2B區域對於本發明之一些多肽/多肽構建體與CLDN6的結合特別重要。在縱坐標軸（x軸）上描繪了數字0、20、40、60、80和100。在橫坐標（y軸）上指示了值10
1、10
2、10
3、10
4和10
5。
[圖2]顯示了人類泛T細胞的實驗結果，該等細胞與靶細胞以10:1的比率和所示濃度的多肽/多肽構建體一起孵育。48小時後，用Cell Titer-gloassay測量細胞活力並計算細胞毒性百分比。圖表顯示了重複樣本的代表性數據（運行了＞2個獨立實驗）。使用GraphPad Prism分析數據。類似地，使用基於先前技術抗體（A3E-20；揭露於WO 2009/087978）的多肽構建體進行實驗。SEQ ID NO: 21、24、217、147、119和90中的CLDN6構建體比基於A3E-20的多肽構建體更有效；與CLDN9相比，根據本發明之CLDN6xCD3多肽/多肽構建體對CLDN6具有＞3000倍的選擇性。圖2A = PA-1細胞；圖2B = CHO-CLDN6；圖2C = CHO-CLDN9。
[圖3]顯示了選擇性結合CLDN6的、具有不同CD3結合部分（根據本發明之CLDN6XI2C和CLDN6XI2E分子（SEQ ID NO: 21和24））的構建體的等效活性；CLDN6依賴性細胞毒性活性。將人泛T細胞與靶細胞以10:1的比率和所示濃度的多肽構建體一起孵育。48小時後，用Cell Titer-gloassay測量細胞活力並計算細胞毒性百分比。圖表顯示了重複樣本的代表性數據（運行了＞2個獨立實驗）。使用GraphPad Prism分析數據。根據本發明之CLDN6xI2C分子和CLDN6xI2E分子（SEQ ID NO: 21和24）在體外具有相同的細胞毒性活性；兩種分子都顯示出殺死表現CLDN6的細胞的特異性（圖3A)和3B)）。
[圖4]顯示了與不同靶細胞以5:1的比率和指定濃度的多肽/多肽構建體一起孵育的人PBMC的結果。48小時後，用基於流動式細胞測量術的測定測量細胞活力並計算細胞毒性百分比。圖表顯示了來自三個PBMC供體的代表性數據（運行了＞2個獨立實驗）。使用GraphPad Prism分析數據。黑線，CLDN6xI2C（SEQ ID NO: 24）；灰線，CLDN6xI2E（SEQ ID NO: 21）。數字（#150、#156、#158）指的是人PBMC的三個不同供體（圖4A) 至4F)）。使用的細胞系在圖表上方示出（圖4A：COV-362，圖4B：LCLC-97TIM1，圖4C：NCI-H322，圖4D：NCI-H1435，圖4E：OV-90和圖4F：OVCAR-3）。
[圖5]顯示了不同濃度範圍的CLDN6 HLE BiTE（I2C）（SEQ ID NO: 24）與CHO-CLDN6和CHO-CLDN9細胞一起孵育的結果（圖5A) 和5B)）。藉由流動式細胞測量術評估CHO-CLDN6和CHO-On細胞結合。CHO-CLDN6（左）：虛線 = 小鼠同種型對照（BD生物科學公司（BD Biosciences）），實線 = 抗CLDN6抗體（創意生物實驗室（Creative Biolabs），TAB-510LC，基於AE3-20殖株）；CHO-CLDN9（右）：虛線 = 大鼠同種型對照（BD生物科學公司），實線 = 抗CLDN9抗體（艾博抗公司（Abcam），ab187116，YD4E9殖株）；二抗（BV421通道，BD生物科學公司）。圖5C) 顯示本發明之多肽/多肽構建體與CLDN6選擇性和特異性結合，但不結合CHO細胞表現的CLDN9。
[圖6至8]顯示了CLDN6 HLE多肽/多肽構建體對不同類型的靶細胞具有細胞毒性活性，該等靶細胞藉由IHC顯示低水平CLDN6表現。圖6A：CHO-CLDN6: 虛線 = 小鼠同種型對照（BD生物科學公司），實線 = 抗CLDN6抗體（創意生物實驗室，TAB-510LC，基於AE3-20殖株）；二抗（APC通道，傑克遜免疫研究實驗室（Jackson ImmunoResearch））；圖6B：OVCAR-3：虛線 = 小鼠同種型對照（BD生物科學公司），實線 = 抗CLDN6抗體（創意生物實驗室，TAB-510LC，基於AE3-20殖株）；二抗（APC通道，傑克遜免疫研究實驗室）；圖6C：COV-362: 虛線 = 小鼠同種型對照（BD生物科學公司），實線 = 抗CLDN6抗體（創意生物實驗室，TAB-510LC，基於AE3-20殖株）；二抗（APC通道，傑克遜免疫研究實驗室）；圖6D：NCI-H322: 虛線 = 小鼠同種型對照（BD生物科學公司），實線 = 抗CLDN6抗體（創意生物實驗室，TAB-510LC，基於AE3-20殖株）；二抗（BV421通道，BD生物科學公司）；圖7A和7B：PA-1：虛線 = 小鼠同種型對照（BD生物科學公司），實線 = 抗CLDN6抗體（創意生物實驗室，TAB-510LC，基於AE3-20殖株）；二抗（APC通道，傑克遜免疫研究實驗室）；圖7C和7D：OVCAR-3：虛線 = 小鼠同種型對照（BD生物科學公司），實線 = 抗CLDN6抗體（創意生物實驗室，TAB-510LC，基於AE3-20殖株）；二抗（APC通道，傑克遜免疫研究實驗室）；圖7E和7F：OAW28：虛線 = 小鼠同種型對照（BD生物科學公司），實線 = 抗CLDN6抗體（創意生物實驗室，TAB-510LC，基於AE3-20殖株）；二抗（APC通道，傑克遜免疫研究實驗室）；圖7G和7H：LCLC-97TM1：虛線 = 小鼠同種型對照（BD生物科學公司），實線 = 抗CLDN6抗體（創意生物實驗室，TAB-510LC，基於AE3-20殖株）；二抗（APC通道，傑克遜免疫研究實驗室）；圖7I和7J：NCI-H1435：虛線 = 小鼠同種型對照（BD生物科學公司），實線 = 抗CLDN6抗體（創意生物實驗室，TAB-510LC，基於AE3-20殖株）；二抗（APC通道，傑克遜免疫研究實驗室）；
[圖9] - 對已建立的OVCAR-3異種移植瘤的抗腫瘤功效。圖9A) 至9C) 顯示了隨時間變化（x軸上的天數）的腫瘤體積的測量結果、隨時間變化的體重的測量結果以及不同濃度下的藥物動力學數據（隨時間變化的血清濃度）。
[圖10]顯示在探索性毒理學研究中觀察到T細胞活化多肽/多肽構建體的接合特徵的標誌。
[圖11]證明根據本發明之CLDN6 HLE多肽構建體（SEQ ID NO: 24）在非人靈長類動物中具有延長的半衰期。
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實例 1 - CLDN6 結合物生成雜交瘤產生
來自脾臟和淋巴結的彙集淋巴細胞富集IgG+ B細胞，隨後與小鼠P3骨髓瘤細胞進行電細胞融合。融合的雜交瘤細胞在透明質酸（HA）選擇培養基中培養2-5天，然後鋪板到96孔培養板上並培養2週以產生耗盡的上清液（ESN）。
篩選和序列分析
在初步篩選中，使用螢光微量分析技術（FMAT）鑒定了837個人CLDN6細胞上結合雜交瘤。藉由流動式細胞測量術進行的第二次晚期初步篩選也證實了該等雜交瘤中有776個與暫態表現的食蟹猴CLDN6的293T結合。為了進一步表徵837個結合CLDN6的雜交瘤，藉由對PA-1細胞的抗體依賴性細胞毒性（ADCC）活性測試ESN，以篩選出具有最佳殺傷活性的288個雜交瘤的名單。大多數該等雜交瘤顯示出對表現CLDN6的OVCAR3細胞的ADCC殺傷。針對與在細胞表面暫態表現人CLDN3、CLDN4、CLDN8或CLDN9的293 T細胞的交叉反應性結合，進一步表徵該等雜交瘤的ESN。
總的來說，基於PA-1和OVCAR3細胞系中ADCC殺傷標準鑒定的20種雜交瘤顯示出與CLDN3、CLDN4和CLDN8沒有交叉反應性。對該等雜交瘤進行定序，隨後重組mAb生成和放大。該等抗體尤其包括三個殖株，它們顯示出合格的序列和結合特性並且被選擇用於轉化為scFv和多肽/多肽構建體。
抗CLDN6多肽構建體生成
藉由基因合成進行抗CLDN6靶向多肽/多肽構建體結合物的組裝。更詳細地：抗CLDN6重鏈的VH和抗CLDN6輕鏈DNA的VL源自雜交瘤殖株。VH中的胺基酸位置44和VL中的位置100（Kabat編號）更改為半胱胺酸，這導致穩定靶結合物的額外二硫鍵。連接子（例如由四個甘胺酸的三個重複組成）和絲胺酸(G4S1)3-連接子可以插入VL和VH之間，從而產生單鏈片段可變（scFv）。可以將包含嵌入Kozak共有序列中的起始密碼子的人IgG重鏈訊息肽添加到抗CLDN6結合物的N端。藉由與抗CD3ε特異性scFv結合物結合，組裝的抗CLDN6靶結合物轉化為重組雙特異性單鏈結合物形式，其為人序列，並與人和獼猴CD3ε交叉反應。在該等構建體中，抗CD3ε scFv與單鏈Fc（scFc）半衰期延長（HLE）部分融合，該部分具有附接在框架內的C末端終止密碼子。在哺乳動物表現載體中，人抗CLDN6結合物與抗CD3ε結合物和scFc結合。一些人抗CLDN6 HLE多肽/多肽構建體具有結構域排列VL CLDN6 - (G4S1)3 -VH CLDN6 - S1G4S1 - VHCD3 - 肽連接子 (G4S1)3 - VLCD3 - 肽連接子 (G4) - Fc - (G4S1 )6 - Fc；其他具有結構域排列VH (CLDN6) - (G4S)3 - VL (CLDN6) - 肽連接子 (SG4S) - VH (CD3) - (G4S)3 - VL (CD3) - 肽連接子 (G4) - Fc - (G4S)6 - Fc。
抗CLDN6結合物的示例性序列優化
在合理設計的基礎上，進行了序列優化方法。此外，使用899個結合CLDN6的殖株的選殖命中庫，進行了LC改組方法以進一步改善所選多肽構建體殖株的結合和蛋白特性。對於該庫，使用PCR引物構建了人輕鏈Vκ可變區文庫，並與含有所選多肽構建體殖株CLDN6的VH的噬菌粒pComb3H5BHis連接（WO 99/25818；
Sacl Spel消化）。然後將得到的組合Ig輕鏈可變抗體庫轉化到大腸桿菌TG1中，在瓊脂上鋪板，並在流動式細胞測量術測量中篩選單個殖株以與人CLDN6和人CLDN9結合。為此，將含有scFv分子的單個菌落的周質細胞提取物在CLDN6轉染的CHO細胞或CLDN9轉染的CHO細胞上孵育，並藉由小鼠抗Flag抗體和R-藻紅蛋白軛合的山羊抗小鼠IgG或抗小鼠Fcγ-Alexa488二抗檢測結合。在FACSCanto II（BD生物科學公司，海德堡，FRG）上測量樣本。
在篩選方法中，與上述合理設計優化方法組合鑒定了殖株，並產生了在例如SEQ ID NO: 21、24、35、38、49、52、63、66、77和80中描繪的靶結合多肽/多肽構建體。
對CLDN6雙特異性構建體體外親和力的評價
CLDN6雙特異性構建體的基於細胞的親和力藉由非線性回歸（單位點特異性結合）分析確定。在4°C下將表現人CLDN6的CHO細胞與濃度降低的CLDN6雙特異性構建體（400 nM，步驟1:2，11步）一起孵育16 h。用Alexa Fluor 488軛合的AffiniPure Fab片段山羊抗人IgG（H+L；傑克遜免疫研究實驗室）檢測結合的CLDN6雙特異性構建體。
用DRAQ5、遠紅色螢光活細胞滲透DNA染料染色已固定細胞，藉由螢光活化細胞分選（FACS）檢測信號。用GraphPad Prism軟體（圖板公司（Graph Pad））中的單位點特異性結合評價工具計算各平衡解離常數（Kd）值。
細胞毒性活性
藉由Ficoll密度梯度離心從富集的淋巴細胞製劑（血沈棕黃層，血庫收集用於輸血的血液的副產物）中製備人外周血單核細胞（PBMC）。血沈棕黃層由本地血庫提供並且在採血後的同一天製備PBMC。在Ficoll密度離心和用達爾伯克氏（Dulbecco`s）PBS（吉博科公司（Gibco））進行大量洗滌之後，經由與紅血球溶解緩衝液（155 mM NH
4Cl、10 mM KHCO
3、100 µM EDTA）一起孵育，從PBMC中除去剩餘的紅血球。在100 x g下離心PBMC後，經由上清液除去血小板。剩餘的淋巴細胞主要包括B和T淋巴細胞、NK細胞和單核細胞。將PBMC保持在含有10% FCS（吉博科公司）的RPMI培養基（吉博科公司）中於37°C/5% CO
2下培養。
CD14+和CD56+細胞的耗盡
為了耗盡CD14+細胞，使用人CD14微珠（美天旎生物技術有限公司，MACS，#130-050-201）耗盡NK細胞人CD56微珠（MACS，#130-050-401）。對PBMC進行計數並在室溫下以300 x g離心10分鐘。棄去上清液，將細胞沈澱重懸於MACS分離緩衝液 [80 µL/107個細胞；PBS（英傑公司（Invitrogen），#20012-043）、0.5% (v/v) FBS（吉博科公司，#10270-106）、2 mM EDTA（西格瑪奧德里奇公司（Sigma-Aldrich），#E-6511）]。添加CD14微珠和CD56微珠（20 µL/107個細胞）並且在4°C-8°C下孵育15 min。用MACS分離緩衝液（1 - 2 mL/107個細胞）洗滌細胞。在離心（參見上文）之後，棄去上清液並且將細胞重懸於MACS分離緩衝液（500 µL/108個細胞）中。然後使用LS柱（美天旎生物技術有限公司，#130-042-401）分離CD14/CD56陰性細胞。將PBMC w/o CD14+/CD56+細胞在培養箱中在RPMI完全培養基（即補充有10% FBS（柏楉有限公司（Biochrom AG），#S0115）、1x非必需胺基酸（柏楉有限公司，#K0293）、10 mM Hepes緩衝液（柏楉有限公司，#L1613）、1 mM丙酮酸鈉（柏楉有限公司，#L0473）和100 U/mL青黴素/鏈黴素（柏楉有限公司，#A2213）的RPMI1640（柏楉有限公司，#FG1215））中在37°C下培養直至需要時。
靶細胞標記
為了在流動式細胞測量術測定中分析細胞溶解，將螢光膜染料DiOC18（DiO）（分子探針公司（Molecular Probes），#V22886）用於標記人CLDN6-或獼猴CLDN6-轉染的CHO細胞（作為靶細胞）並且將它們與效應細胞區分開。簡而言之，將細胞收穫，用PBS洗滌一次，並且在含有2%（v/v）FBS和膜染料DiO（5 µL/106個細胞）的PBS中調整至106個細胞/mL。在37°C下孵育3 min之後，將細胞在完全RPMI培養基中洗滌兩次，並且將細胞數目調整至1.25 x 105個細胞/mL。使用NC-250細胞計數器（化學計量公司（Chemometec））測定細胞活力
基於流動式細胞測量術的分析
將此測定設計用於在CLDN6雙特異性構建體的連續稀釋液存在下定量食蟹猴或人CLDN6-轉染的CHO細胞的溶解。將等體積的DiO標記的靶細胞和效應細胞（即，沒有CD14+細胞的PBMC）混合，得到10:1的E:T細胞比。將80 μl該懸浮液轉移到96孔板的每個孔中。添加20 µL的CLDN6xCD3雙特異性構建體的連續稀釋液和雙特異性陰性對照（識別無關靶抗原的基於CD3的雙特異性構建體）或RPMI完全培養基（作為另外的陰性對照）。雙特異性抗體介導的細胞毒性反應在7% CO2加濕培養箱中進行48小時。然後將細胞轉移到新的96孔板中，並且藉由添加終濃度為1 µg/mL的碘化丙啶（PI）監測靶細胞膜完整性的喪失。在iQue Plus儀器上藉由流動式細胞測量術測量樣本，並藉由Forecyt軟體（均來自Intellicyt）進行分析。將靶細胞鑒定為DiO陽性細胞。PI陰性靶細胞被分類為活的靶細胞。根據下式計算細胞毒性的百分比：
n = 事件數
使用GraphPad Prism 5軟體（圖板軟體公司，聖地牙哥），將細胞毒性的百分比相對於相應的雙特異性構建體濃度繪圖。使用四個參數邏輯回歸模型來分析劑量反應曲線，用於評價具有固定坡面的S形劑量反應曲線，並計算EC50值。
雙特異性結合和種間交叉反應
為了確認與人CLDN6和CD3以及食蟹猴CLDN6和CD3的結合，藉由流動式細胞測量術測試本發明之多肽/多肽構建體，使用
● 分別轉染了人CLDN6、人CLDN6亞型（I143V）和獼猴CLDN6的中國倉鼠卵巢（CHO）細胞，
● 人CLDN6陽性人細胞系PA-1，
● 表現CD3的人T細胞白血病細胞系HPB-all（德國微生物菌種保藏中心（DSMZ），以及
● 表現食蟹猴CD3的T細胞系LnPx 4119
為了確認不與CHO結合，藉由流動式細胞測量術使用轉染了人CLDN1、-3、-4、-8和-17的CHO細胞測試本發明之CLDN1、-3、-4、-8、-17雙特異性構建體。對於流動式細胞測量術，將各自細胞系的200,000個細胞在4°C下與濃度為5 μg/ml的50 μl純化雙特異性構建體一起孵育60 min。將細胞在PBS/2% FCS中洗滌兩次，然後將與對雙特異性構建體的CD3結合部分具有特異性的內部小鼠抗體（2 μg/ml）一起在4°C下孵育30分鐘。洗滌後，在4°C下用山羊抗小鼠Fcγ-PE（傑克遜免疫研究實驗室；1:100）檢測結合的小鼠抗體30分鐘。藉由流動式細胞測量術測量樣本。將未轉染的CHO細胞（DSMZ）用作陰性對照。
產生表現CLDN6突變的CHO細胞
為了產生作為對照的表現hu-CLDN6、hu-CLDN9、hu-CLDN4（SEQ ID NO: 1、8和7）的CHO細胞，將各自的編碼序列選殖到命名為pEF-DHFR的質體中（pEF-DHFR描述於Raum等人 Cancer Immunol Immunother [癌症免疫學免疫治療] 50 (2001) 141-150中）。所有選殖程序均按照標準方案進行（Sambrook, Molecular Cloning; A Laboratory Manual [分子選殖；實驗室手冊], 第三版, 冷泉港實驗室出版社, 冷泉港, 紐約 (2001)）。對於每種構建體，將相應的質體轉染到DHFR缺陷的CHO細胞中用於真核表現，如由Kaufman R.J. (1990) Methods Enzymol.[酶學方法] 185, 537-566所述。分別使用以5 μg/ml濃度的針對CLDN4、CLDN6（R&D小鼠抗人CLDN6單株抗體MAB3656）和CLDN9（大鼠抗人CLDN9單株抗體ABIN1720917）的抗體，在FACS測定中驗證上述多肽/多肽構建體在CHO細胞上的表現。作為陰性對照，將細胞與代替第一抗體的同種型對照抗體（BD 553454 / R&D MAB0041 / R&D MAB0061）一起孵育。用二級抗小鼠/抗大鼠/抗人IgG Fc-γ-PE（傑克遜免疫研究公司115-116-071 / 112-116-071 / 109-116-098）檢測結合的單株抗體。藉由流動式細胞測量術測量該等樣本。
實例 2 - 抗 CLDN6 構建體的表位定位
為了表位定位，將CLDN6的E1（細胞外環1；ECL1）分成三個亞結構域（E1A、E1B和E1C），並且將E2（細胞外環2；ECL2）分成兩個亞結構域（E2A和E2B）。將人CLDN6（E1、E1A、E1B、E1C、E2、E2A和E2B）的相應表位區域（環/結構域或亞結構域）的胺基酸序列交換為人CLDN4的對應序列。經由FACS分析驗證了CHO細胞中所有嵌合構建體的表現。將用實例1中所描述的構建體轉染的CHO細胞用濃度為20 μg/ml的純化的CLDN6xCD3多肽構建體染色。用抗人IgG Fc-γ-PE（傑克遜免疫研究公司；1:100）檢測結合的構建體。將抗體在PBS/2% FCS中稀釋。作為陰性對照，將細胞與PBS/2% FCS一起孵育，隨後與抗人IgG Fc-γ-PE一起孵育。藉由流動式細胞測量術測量該等樣本。表位定位分析的結果顯示在圖1中。當觀察到表現某種CLDN6嵌合體或突變的細胞喪失FACS信號時，假定各自的CLDN6xCD3多肽構建體結合表位（環/結構域/亞結構域）或結合在該CLDN6嵌合或突變多肽構建體中被交換的特定胺基酸。換句話說，該表位區域或胺基酸係結合被分析的CLDN6xCD3多肽構建體所必需的。除了用於證明各自靶標的正確表現的對照抗體外，還在表位定位分析中特異性地測試了以下CLDN6xCD3多肽/多肽構建體。如圖1所示，根據本發明之CLDN6xCD3多肽/多肽構建體（例如，SEQ ID NO: 21、35、49、77、203等）需要區域E1A和/或E2B與CLDN6選擇性結合。因此並且同樣地，該等亞結構域與CLDN4對應序列的交換導致FACS信號喪失。
實例 3- 基於 Biacore 確定對人和食蟹猴 CD3 和 FcRn 的親和力
使用重組人/獼猴CD3-ECD（ECD = 細胞外結構域）融合蛋白與雞白蛋白進行Biacore分析實驗，以確定本發明之構建體的靶標結合。
實例 4 - 具有不同 CD3 特異性互補位的 CLDN6xCD3 HLE 多肽 / 多肽構建體和基於抗體 AE3-20 的多肽構建體的比較
比較SEQ ID NO: 21、24中描繪的CLDN6xCD3（變體I2C）、CLDN6xCD3（變體I2E）和根據本發明之其他CLDN6xCD3（變體I2C）多肽/多肽構建體以及基於單株抗體AE3-20的多肽構建體（在WO 2009/087978中揭露；在SEQ ID NO: 441中描繪）的細胞毒性活性和對CLDN6的特異性。
對CLDN6xI2C和CLDN6xI2E（如SEQ ID NO: 21和24中描繪）在卵巢癌細胞系和非小細胞肺癌細胞系中的細胞毒性進行額外比較。為了藉由流動式細胞測量術對AE3-20多肽構建體進行結合分析，使用用人CLDN6、hu CLDN4或人CLDN9轉染的CHO細胞。對於流動式細胞測量術，將相應的CHO細胞與AE3-20多肽構建體（5 μg/ml）或以下單株抗體（作為細胞表面表現的陽性對照）一起孵育：抗CLDN6（R&D系統公司（R&D Systems），MAB3656）、抗CLDN4（R&D系統公司，MAB4219）和抗CLDN9（奧利金公司（Origene），AM26751PU-N）。使用與R-藻紅蛋白（PE）結合的小鼠抗人IgG Fc抗體、與PE結合的山羊抗小鼠Fcγ特異性抗體（傑克遜免疫研究實驗室 115-116-071）或與PE結合的山羊抗大鼠Fcγ特異性抗體（傑克遜免疫研究實驗室 112-116-071）檢測AE-320多肽構建體或陽性對照抗體的結合。使用相應的同種型對照抗體作為陰性對照。
與靶向E1A/E2A+B或E2A/(E2B)（AE-320表位）的BiTE分子相比，靶向CLDN6表位簇E1A/E2B或E1A/(E2B)的多肽顯示出意想不到的更高效力。與靶向E2A/（E2B）（AE-3-20表位）的BiTE分子相比，靶向CLDN6表位簇E1A/E2B或E1A/（E2B）的多肽的效力更高，儘管候選物在相似的親和力範圍內。令人驚訝的是，應避免表位簇E2A以獲得足夠的效力，同時保持對CLDN9的選擇性。本文研究的多肽（特別是在SEQ ID NO: 21、24、35、38、49、52、63、66、77和80，更特別是在SEQ ID NO: 21和24中描繪的那些）也具有有利的蛋白質性質，特別是在以1 mg/ml的溶液儲存後以及在反復冷凍/解凍循環後單體轉化率達到有利的穩定性，在過夜溶液中蛋白質濃度較高時的最低渾濁度，和在保持對CLDN6+細胞系的有利效力的同時有熱穩定性，以及非常好的親和力。
CLDN6xCD3構建體的效力和特異性
在T細胞依賴性細胞毒性（TDCC）測定中，人泛T細胞（AllCells）與靶細胞以10:1的比率和所示濃度的多肽/多肽構建體一起孵育。48小時後，用Cell Titer-glo®測定法（普洛麥格公司（Promega））測量細胞活力並計算細胞毒性百分比。圖2中的圖表顯示了重複樣本的代表性數據（運行了＞2個獨立實驗）。使用GraphPad Prism分析數據。類似地，使用基於揭露於WO 2009/087978的先前技術抗體（AE3-20；中外製藥（Chugai））的多肽構建體進行實驗。SEQ ID NO: 21和24中的CLDN6多肽/多肽構建體比基於A3E-20的多肽構建體更有效；與CLDN9相比，CLDN6xCD3多肽/多肽構建體對CLDN6具有＞3000倍的選擇性。
CLDN6 HLE多肽/多肽構建體 - 與基於AE3-20的構建體的比較
TDCC測定：將表現CLDN6的卵巢癌細胞系PA-1和經轉染以穩定表現CLDN6或CLDN9的CHO細胞用作靶細胞以評價本發明之CLDN6構建體的體外細胞毒性。將細胞鋪板在384孔微孔板（珀金埃爾默公司（PerkinElmer））中含有10%胎牛血清的培養基中，並將來自兩個供體（奧賽爾斯公司（AllCells））的人泛T細胞以10:1的比率添加到靶細胞中。本發明之CLDN6構建體以22點劑量範圍（60 nM作為最高濃度）和5倍稀釋添加。在37°C下在5% CO2潮濕箱中孵育48小時後，根據製造商的說明，使用Cell Titer-glo®測定（普洛麥格公司）評估細胞活力。使用PerkinElmer Envision測量發光信號。在GraphPad Prism中使用非線性回歸-可變斜率（四個參數）分析數據。圖表顯示了重複樣本的劑量反應曲線的平均值和標準差。
選擇性結合具有不同CD3結合部分的CLDN6的多肽/多肽構建體的活性
將人泛T細胞與靶細胞以10:1的比率和所示濃度的多肽構建體一起孵育。48小時後，用Cell Titer-glo測定法測量細胞活力並計算細胞毒性百分比。圖3中的圖表顯示了重複樣本的代表性數據（運行了＞2個獨立實驗）。使用GraphPad Prism分析數據。使用了根據本發明之CLDN6xI2C分子和CLDN6xI2E分子（SEQ ID NO: 21和24）；CLDN6依賴性細胞毒性活性（圖3）。
根據本發明之CLDN6xI2C分子和CLDN6xI2E分子（SEQ ID NOs: 21和24）在體外具有相同的細胞毒性活性，並且兩種分子都顯示出殺死表現CLDN6的細胞的特異性。在另一組實驗中，人PBMC與靶細胞以5:1的比率和所示濃度的多肽/多肽構建體一起孵育。48小時後，用基於流動式細胞測量術的測定測量細胞活力並計算細胞毒性百分比。圖表顯示了來自三個PBMC供體的代表性數據（運行了＞2個獨立實驗）。
使用GraphPad Prism分析數據。黑線，CLDN6xI2C（SEQ ID NO: 24）；灰線，CLDN6xI2E（SEQ ID NO: 21）。數字（#150、#156、#158）指的是人PBMC的三個不同供體（圖4A) 至4F)）。使用的細胞系在圖表上方示出（圖4A：COV-362，圖4B：LCLC-97TIM1，圖4C：NCI-H322，圖4D：NCI-H1435，圖4E：OV-90和圖4F：OVCAR-3）。
實例 5 - CLDN6 HLE 多肽 / 多肽構建體對 CLDN6 的選擇性超過 CLDN9
將一個濃度範圍的CLDN6 HLE BiTE（I2C）（SEQ ID NO: 24）與CHO-CLDN6和CHO-CLDN9細胞一起孵育（圖5A) 和5B)）。藉由流動式細胞測量術評估CHO-CLDN6和CHO-CLDN9細胞上結合（圖5）。藉由流動式細胞測量術評估細胞上結合，使用與APC軛合的二抗。圖5C) 顯示本發明之多肽/多肽構建體與CLDN6選擇性和特異性結合，但不結合CHO細胞表現的CLDN9。使用FlowJo軟體（FlowJo，LLC）分析數據。使用Geneious軟體進行CLDN6和CLDN9的比對。
實例 6 - CLDN6 HLE 多肽 / 多肽構建體對藉由 IHC 顯示低水平 CLDN6 表現的細胞具有細胞毒性活性
對表現CLDN6和CLDN9的各種癌細胞系和CHO細胞進行了TDCC測定（圖6）。抗體結合位點（ABC）EC50值顯示在下表中。顯然，本發明之多肽/多肽構建體識別並殺死表現較低和較高數量的每細胞CLDN6位點的細胞（參見表2）。
[ 表 2] ：在各種細胞系中的細胞毒性測定的情況下的 TDCC EC
50pM
*ABC = 抗體結合位點。藉由流動式細胞測量術使用QIFIKit®（安捷倫公司（Agilent））評估CLDN6細胞表面表現。在TDCC測定中評估細胞毒性活性。將人T細胞與靶細胞以10:1的比率和所示濃度的根據本發明之不同多肽（參見圖7E）（SEQ ID NO: 21、35、49、77、203）一起孵育。在48小時後，使用Cell Titer-glo®測定（普洛麥格公司）評估細胞活力。在GraphPad Prism中分析數據。確定體外細胞毒性以選擇多肽/多肽構建體用於隨後的體內研究。如下表所示，CLDN6 HLE多肽/多肽構建體（SEQ ID NO: 21和24）具有有效的細胞毒性活性（圖6和7）。
實例 7 - CLDN6 HLE 多肽 / 多肽構建體誘導 T 細胞活化
| TDCC EC 50pM | |||||||
| 細胞系（CLDN6位點/細胞） | PA-1 (400,000) | OVCAR-3 (200,000) | OAW28 (65,000) | LCLC97TM1 (100,000) | NCI-H1435 (55,000) | CHO-CLDN6 (900,000) | CHO-CLDN9 (400,000) |
| EC 50 | 1.8 +0.7 | 10.4 +4.1 | 24.2 +14.7 | 3.6 ±1.0 | 1.9 ±0.3 | 9.1 ±10.4 | ＞30,000 |
將人泛T細胞與靶細胞以10:1比率和指示濃度的根據本發明之示例性多肽/多肽構建體（SEQ ID NO: 21）一起孵育。48小時後，藉由流動式細胞測量術評估T細胞活化（CD25、CD69和PD-1的上調）。使用Cell Titer-glo®測定評估細胞活力。顯示該等生物標誌物的表現的該等數據清楚地證明多肽/多肽構建體誘導T細胞活性（圖8A) 至8E)）。
實例 8 - 對已建立的 OVCAR-3 異種移植瘤的抗腫瘤功效
用5e6個細胞/小鼠皮下接種雌性NSG小鼠（每組10隻）。使用的T細胞係活化的人類泛T細胞，每隻小鼠2e7個細胞。一旦腫瘤形成200 mm3的大小，並且然後腹腔內注射人T細胞，就將小鼠用僅媒介物或用CLDN6xCD3 HLE（SEQ ID NO: 21）每週一次進行治療（圖9A) 至9C)）。圖9A) 至9C) 顯示了隨時間變化（x軸上的天數）的腫瘤體積的測量結果、隨時間變化的體重的測量結果以及不同濃度下的藥物動力學數據（隨時間變化的血清濃度）。
實例 9 - 耐受 ＜100 mg/kg 劑量的 CLDN6xCD3 HLE
進行了一項研究，目的是在非人靈長類動物（NHP）的探索性PK/tox研究中評估根據本發明之CLDN6xCD3 HLE（SEQ ID NO: 21）的耐受性。為此，對各組投與靈活且交錯的劑量；15 mg/kg、45 mg/kg、100 mg/kg（1隻動物）。結果顯示，在所有劑量下均觀察到T細胞依賴性活化的跡象。本發明之多肽構建體在臨床上耐受高達100 μg/kg。結果示於圖10中。對肝臟（膽管）在≥ 45 µg/kg劑量下；且對皮膚（靜脈內投與部位、肛門、乳腺、背部和後肢）在≥ 45 µg/kg下（在所有動物的所有部位都沒有發現）；以及對食管和間質肺的黏膜上皮在≥ 100 µg/kg下，觀察到治療相關的顯微鏡檢查發現（輕度到重度）。該研究表明，CLDN6作為多肽構建體係一個安全的靶標。
實例 10- 在探索性毒理學研究中觀察到 T 細胞活化多肽 / 多肽構建體的接合特徵的標誌
在第1天和第8天給藥後4小時，觀察到CD3+ T淋巴細胞絕對計數的CLDN6劑量依賴性下降。 在第8天觀察到的下降幅度通常與第1天不同。在所有組中都觀察到在投與後暫態淋巴細胞重新分佈，總T細胞計數短暫減少。圖10表明T細胞活化多肽/多肽構建體誘導增加的活性，例如，在中劑量組和高劑量組中觀察到的CD69表現。如上所述藉由流動式細胞測量術評估T細胞活化。進一步地，還分析了CD3+ T淋巴細胞計數的絕對數和CD3+ T淋巴細胞計數的百分比，並且還可顯示暫態細胞介素釋放（IFN-γ、TNF-α、MCP-1、IL-1β、IL-1rα、IL-2、IL-5和IL-6）與T細胞活化多肽/多肽構建體的活性一致。進一步地，根據本發明之CLDN6 HLE多肽構建體（SEQ ID NO: 24）在非人靈長類動物中具有延長的半衰期。在毒理學研究的樣本中評估了非人靈長類動物血清中T細胞活化多肽/多肽構建體的暴露水平。該構建體證明了劑量依賴性暴露和延長的半衰期（8.39天）（圖11）。
實例 11- 體外和體內細胞毒性研究
使用實例6中描述之方法，分析了本發明之不同HLE多肽/多肽構建體在各種細胞系中的細胞毒性。如表3所示，本發明之多肽/多肽構建體在各種細胞系中具有細胞毒性。
[ 表 3] ：本發明不同多肽在各種細胞系中的細胞毒性測定的 TDCC EC
50pM
實例 12 - 在雌性非肥胖糖尿病 / 嚴重聯合免疫缺陷（ NOD/SCID ）小鼠的皮下晚期 NSCLC 模型中評估了 AMG 794 的抗腫瘤活性。當使用混合效應模型，隨後使用Dunnett事後檢驗，在第17日和第27日之間，將腫瘤生長與組2的媒介物治療的小鼠進行比較時，用CLDN6xCD3 HLE（SEQ ID NO: 21）治療NCI-H1435-峰-1-1荷瘤小鼠在0.5、0.15和0.05 mg/kg的劑量下導致統計上顯著的TGI，p值＜ 0.001。觀察到在第22天後腫瘤再次生長，直到在第27天腫瘤生長測量結束。與研究開始時相比，靶標陰性細胞群體增加且在外植腫瘤中檢測到人淋巴細胞數量較低，這可以解釋在第22天後的腫瘤再次生長。在0.5、0.15和0.05 mg/kg CLDN6xCD3 HLE的劑量下，在第22天實現的TGI分別為91%、67%和82%。
| 多肽構建體 | TDCC EC50（pM） | ||||
| PA-1 | OVCAR-3 | OAW28 | LCLC97TM1 | NCI-H1435 | |
| S3N（SEQ ID NO: 77） | 3.1 + 1.2 | 25.7 + 11.4 | 35.2 + 14.2 | NT | NT |
| L4B（SEQ ID NO: 49） | 3.4 + 1.2 | 19.4 | 44.6 + 19.0 | 10.7 ± 6.3 | 11.6 ± 4.1 |
| X3S（SEQ ID NO: 35） | 2.8 + 1.3 | 19.1 + 6.6 | 30.1 + 10.8 | 5.6 ± 2.5 | 5.9 ± 2.4 |
| B6L（SEQ ID NO: 21） | 1.8 + 0.7 | 10.4 + 4.1 | 24.2 + 14.7 | 3.6 ± 1.8 | 1.9 ± 0.5 |
| A3S（SEQ ID NO: 203） | 4.7 + 1.6 | 28.1 + 12.9 | 65.3 + 37.0 | NT | NT |
| SEQ ID NO: | 唯一標識符/ 描述 | 天然/人工 | 序列/AA |
| 1 | 人 CLDN-6 UNIPROT P56747 | 天然 | MASAGMQILGVVLTLLGWVNGLVSCALPMWKVTAFIGNSIVVAQVVWEGLWMSCVVQSTGQMQCKVYDSLLALPQDLQAARALCVIALLVALFGLLVYLAGAKCTTCVEEKDSKARLVLTSGIVFVISGVLTLIPVCWTAHAIIRDFYNPLVAEAQKRELGASLYLGWAASGLLLLGGGLLCCTCPSGGSQGPSHYMARYSTSAPAISRGPSEYPTKNYV |
| 2 | 人 CLDN -18.1 UNIPROT P56856-1 | 天然 | MSTTTCQVVAFLLSILGLAGCIAATGMDMWSTQDLYDNPVTSVFQYEGLWRSCVRQSSGFTECRPYFTILGLPAMLQAVRALMIVGIVLGAIGLLVSIFALKCIRIGSMEDSAKANMTLTSGIMFIVSGLCAIAGVSVFANMLVTNFWMSTANMYTGMGGMVQTVQTRYTFGAALFVGWVAGGLTLIGGVMMCIACRGLAPEETNYKAVSYHASGHSVAYKPGGFKASTGFGSNTKNKKIYDGGARTEDEVQSYPSKHDYV |
| 3 | 人 CLDN -18.2 UNIPROT P56856-2 | 天然 | MAVTACQGLGFVVSLIGIAGIIAATCMDQWSTQDLYNNPVTAVFNYQGLWRSCVRESSGFTECRGYFTLLGLPAMLQAVRALMIVGIVLGAIGLLVSIFALKCIRIGSMEDSAKANMTLTSGIMFIVSGLCAIAGVSVFANMLVTNFWMSTANMYTGMGGMVQTVQTRYTFGAALFVGWVAGGLTLIGGVMMCIACRGLAPEETNYKAVSYHASGHSVAYKPGGFKASTGFGSNTKNKKIYDGGARTEDEVQSYPSKHDYV |
| 4 | CLDN1 UNIPROT O95832-1 | 天然 | MANAGLQLLGFILAFLGWIGAIVSTALPQWRIYSYAGDNIVTAQAMYEGLWMSCVSQSTGQIQCKVFDSLLNLSSTLQATRALMVVGILLGVIAIFVATVGMKCMKCLEDDEVQKMRMAVIGGAIFLLAGLAILVATAWYGNRIVQEFYDPMTPVNARYEFGQALFTGWAAASLCLLGGALLCCSCPRKTTSYPTPRPYPKPAPSSGKDYV |
| 5 | CLDN2 UNIPROT P57739 | 天然 | MASLGLQLVGYILGLLGLLGTLVAMLLPSWKTSSYVGASIVTAVGFSKGLWMECATHSTGITQCDIYSTLLGLPADIQAAQAMMVTSSAISSLACIISVVGMRCTVFCQESRAKDRVAVAGGVFFILGGLLGFIPVAWNLHGILRDFYSPLVPDSMKFEIGEALYLGIISSLFSLIAGIILCFSCSSQRNRSNYYDAYQAQPLATRSSPRPGQPPKVKSEFNSYSLTGYV |
| 6 | CLDN3 UNIPROT O15551 | 天然 | MSMGLEITGTALAVLGWLGTIVCCALPMWRVSAFIGSNIITSQNIWEGLWMNCVVQSTGQMQCKVYDSLLALPQDLQAARALIVVAILLAAFGLLVALVGAQCTNCVQDDTAKAKITIVAGVLFLLAALLTLVPVSWSANTIIRDFYNPVVPEAQKREMGAGLYVGWAAAALQLLGGALLCCSCPPREKKYTATKVVYSAPRSTGPGASLGTGYDRKDYV |
| 7 | CLDN4 UNIPROT O14493 | 天然 | MASMGLQVMGIALAVLGWLAVMLCCALPMWRVTAFIGSNIVTSQTIWEGLWMNCVVQSTGQMQCKVYDSLLALPQDLQAARALVIISIIVAALGVLLSVVGGKCTNCLEDESAKAKTMIVAGVVFLLAGLMVIVPVSWTAHNIIQDFYNPLVASGQKREMGASLYVGWAASGLLLLGGGLLCCNCPPRTDKPYSAKYSAARSAAASNYV |
| 8 | CLDN9 UNIPROT O95484 | 天然 | MASTGLELLGMTLAVLGWLGTLVSCALPLWKVTAFIGNSIVVAQVVWEGLWMSCVVQSTGQMQCKVYDSLLALPQDLQAARALCVIALLLALLGLLVAITGAQCTTCVEDEGAKARIVLTAGVILLLAGILVLIPVCWTAHAIIQDFYNPLVAEALKRELGASLYLGWAAAALLMLGGGLLCCTCPPPQVERPRGPRLGYSIPSRSGASGLDKRDYV |
| 9 | E1A 人 CLDN-6 E1A | 人工 | MWKVTAFIGNS |
| 10 | E2B人CLDN-6 | 人工 | LVAEAQKREL |
| 11 | B6L / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 12 | B6L / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIK |
| 13 | B6L / CDR-H1 | 人工 | GYYMH |
| 14 | B6L / CDR-H2 | 人工 | WINPNSGETNYAQKFQG |
| 15 | B6L / CDR-H3 | 人工 | DALIVVAPVTRDYYYYGMDV |
| 16 | B6L / CDR-L1 | 人工 | RASQSVSSSYLA |
| 17 | B6L / CDR-L2 | 人工 | GASSRAT |
| 18 | B6L / CDR-L3 | 人工 | QQYGSSPLT |
| 19 | B6L /SCFV I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 20 | B6L / 雙特異性分子I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 21 | B6L / HLE-BITE I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK6GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 22 | B6L / SCFV I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 23 | B6L / 雙特異性分子I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 24 | B6L / HLE BITE I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 25 | X3S / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSS |
| 26 | X3S / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 27 | X3S / CDR-H1 | 人工 | GYYVH |
| 28 | X3S / CDR-H2 | 人工 | WINPNSGATNYAQKFQG |
| 29 | X3S / CDR-H3 | 人工 | DALIVEAPATRDYYYYGMDV |
| 30 | X3S / CDR-L1 | 人工 | RASQSVRSTYLA |
| 31 | X3S / CDR-L2 | 人工 | GASSRAT |
| 32 | X3S / CDR-L3 | 人工 | QQYDASPIT |
| 33 | X3S / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 34 | X3S / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 35 | X3S / HLE BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 36 | X3S / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 37 | X3S / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 38 | X3S / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 39 | L4B / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSS |
| 40 | L4B / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 41 | L4B / CDR-H1 | 人工 | GYYVH |
| 42 | L4B / CDR-H2 | 人工 | WINPNSGATNYAQKFQG |
| 43 | L4B / CDR-H3 | 人工 | DRLIVEAPATRDYYYYGMDV |
| 44 | L4B / CDR-L1 | 人工 | RASQSVRSTYLA |
| 45 | L4B / CDR-L2 | 人工 | GASSRAT |
| 46 | L4B / CDR-L3 | 人工 | QQYDASPIT |
| 47 | L4B / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 48 | L4B / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 49 | L4B / HLE BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 50 | L4B / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 51 | L4B / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 52 | L4B / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 53 | I2P / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSS |
| 54 | I2P / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKS |
| 55 | I2P / CDR-H1 | 人工 | GYYVH |
| 56 | I2P / CDR-H2 | 人工 | WINPNSGATNYAQKFQG |
| 57 | I2P / CDR-H3 | 人工 | DALIVEAPATRDYYYYGMDV |
| 58 | I2P / CDR-L1 | 人工 | RASQSVRSTYLA |
| 59 | I2P / CDR-L2 | 人工 | GASSRAT |
| 60 | I2P / CDR-L3 | 人工 | QQYDASPIT |
| 61 | I2P / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKS |
| 62 | I2P / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 63 | I2P / HLE BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 64 | I2P / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 65 | I2P / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 66 | I2P / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 67 | S3N / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSS |
| 68 | S3N / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIK |
| 69 | S3N / CDR-H1 | 人工 | GYYVH |
| 70 | S3N / CDR-H2 | 人工 | WINPNSGATNYAQKFQG |
| 71 | S3N / CDR-H3 | 人工 | DALIVEAPATRDYYYYGMDV |
| 72 | S3N / CDR-L1 | 人工 | RASQSVRSTYLA |
| 73 | S3N / CDR-L2 | 人工 | GASSRAT |
| 74 | S3N / CDR-L3 | 人工 | QQYQTSPIT |
| 75 | S3N / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIK |
| 76 | S3N / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 77 | S3N / HLE BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 78 | S3N / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIK |
| 79 | S3N / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 80 | S3N / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 81 | H7I / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSS |
| 82 | H7I / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 83 | H7I / CDR-H1 | 人工 | GYYVH |
| 84 | H7I / CDR-H2 | 人工 | WINPNSGATNYAQKFQG |
| 85 | H7I / CDR-H3 | 人工 | DRLIVEAPATRDYYYYGMDV |
| 86 | H7I / CDR-L1 | 人工 | RASQSVRSTYLA |
| 87 | H7I / CDR-L2 | 人工 | GASSRAT |
| 88 | H7I / CDR-L3 | 人工 | QQYDASPIT |
| 89 | H7I / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 90 | H7I / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 91 | H7I / HLE-BITE I2E. | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 92 | H7I / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 93 | H7I / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 94 | H7I / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 95 | J2I / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSS |
| 96 | J2I / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIK |
| 97 | J2I / CDR-H1 | 人工 | GYYVH |
| 98 | J2I / CDR-H2 | 人工 | WINPNSGATNYAQKFQG |
| 99 | J2I / CDR-H3 | 人工 | DRLIVEAPATRDYYYYGMDV |
| 100 | J2I / CDR-L1 | 人工 | RASQSVRSTYLA |
| 101 | J2I / CDR-L2 | 人工 | GASSRAT |
| 102 | J2I / CDR-L3 | 人工 | QQYQTSPIT |
| 103 | J2I / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIK |
| 104 | J2I / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 105 | J2I / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 106 | J2I / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIK |
| 107 | J2I / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 108 | J2I / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDRLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 109 | A4K / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSS |
| 110 | A4K / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 111 | A4K / CDR-H1 | 人工 | GYYVH |
| 112 | A4K / CDR-H2 | 人工 | WINPNSGATNYAQKFQG |
| 113 | A4K / CDR-H3 | 人工 | DALIVEAPATRDYYYYGMDV |
| 114 | A4K / CDR-L1 | 人工 | RASQSVRSTYLA |
| 115 | A4K / CDR-L2 | 人工 | GASSRAT |
| 116 | A4K / CDR-L3 | 人工 | QQYDASPIT |
| 117 | A4K / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 118 | A4K / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 119 | A4K / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 120 | A4K / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 121 | A4K / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 122 | A4K / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 123 | E5B / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSS |
| 124 | E5B / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIK |
| 125 | E5B / CDR-H1 | 人工 | GYYVH |
| 126 | E5B / CDR-H2 | 人工 | WINPNSGATNYAQKFQG |
| 127 | E5B / CDR-H3 | 人工 | DALIVEAPATRDYYYYGMDV |
| 128 | E5B / CDR-L1 | 人工 | RASQSVRSTYLA |
| 129 | E5B / CDR-L2 | 人工 | GASSRAT |
| 130 | E5B / CDR-L3 | 人工 | QQYQTSPIT |
| 131 | E5B / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIK |
| 132 | E5B / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 133 | E5B / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 134 | E5B / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIK |
| 135 | E5B / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 136 | E5B / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYQTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 137 | R8B / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSS |
| 138 | R8B / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIIGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 139 | R8B / CDR-H1 | 人工 | GYYVH |
| 140 | R8B / CDR-H2 | 人工 | WINPNSGATNYAQKFQG |
| 141 | R8B / CDR-H3 | 人工 | DALIVEAPATRDYYYYGMDV |
| 142 | R8B / CDR-L1 | 人工 | RASQSVRSTYLA |
| 143 | R8B / CDR-L2 | 人工 | GASSRAT |
| 144 | R8B / CDR-L3 | 人工 | QQYDASPIT |
| 145 | R8B / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIIGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 146 | R8B / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIIGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 147 | R8B / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIIGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 148 | R8B / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIIGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIK |
| 149 | R8B / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIIGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 150 | R8B / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDALIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIIGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDASPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 151 | IX9/VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 152 | IX9 / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIK |
| 153 | IX9 / CDR-H1 | 人工 | GYYMH |
| 154 | IX9 / CDR-H2 | 人工 | WINPNSGETNYAQKFQG |
| 155 | IX9 / CDR-H3 | 人工 | DALIVVAPVTRDYYYYGMDV |
| 156 | IX9 / CDR-L1 | 人工 | RASQTVSSSYLV |
| 157 | IX9 / CDR-L2 | 人工 | GASSRAT |
| 158 | IX9 / CDR-L3 | 人工 | QQYGGSPIT |
| 159 | IX9 / SCFV I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 160 | IX9 / 雙特異性分子I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 161 | IX9 / HLE-BITE I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 162 | IX9 / SCFV I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 163 | IX9 / 雙特異性分子I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 164 | IX9 / HLE BITE I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 165 | G5X / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 166 | G5X / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIK |
| 167 | G5X / CDR-H1 | 人工 | GYYMH |
| 168 | G5X / CDR-H2 | 人工 | WINPNSGDANYAQKFQG |
| 169 | G5X / CDR-H3 | 人工 | DALIVVAPVTRDYYYYGMDV |
| 170 | G5X / CDR-L1 | 人工 | RASQTVSSSYLV |
| 171 | G5X / CDR-L2 | 人工 | GASSRAT |
| 172 | G5X / CDR-L3 | 人工 | QQYGGSPIT |
| 173 | G5X / SCFV I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 174 | G5X / 雙特異性分子I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 175 | G5X / HLE-BITE I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 176 | G5X / SCFV I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 177 | G5X / 雙特異性分子I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 178 | G5X / HLE BITE I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 179 | O1C / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 180 | O1C / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIK |
| 181 | O1C / CDR-H1 | 人工 | GYYMH |
| 182 | O1C / CDR-H2 | 人工 | WINPNSGETNYAQKFQG |
| 183 | O1C / CDR-H3 | 人工 | DNLIVVAPVTRDYYYYGMDV |
| 184 | O1C / CDR-L1 | 人工 | RASQTVSSSYLV |
| 185 | O1C / CDR-L2 | 人工 | GASSRAT |
| 186 | O1C / CDR-L3 | 人工 | QQYGGSPIT |
| 187 | O1C / SCFV I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 188 | O1C / 雙特異性分子I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 189 | O1C / HLE-BITE I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 190 | O1C / SCFV I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 191 | O1C / 雙特異性分子I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 192 | O1C / HLE BITE I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 193 | A3S / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 194 | A3S / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIK |
| 195 | A3S / CDR-H1 | 人工 | GYYMH |
| 196 | A3S / CDR-H2 | 人工 | WINPNSGETNYAQKFQG |
| 197 | A3S / CDR-H3 | 人工 | DNLIVVAPVTRDYYYYGMDV |
| 198 | A3S / CDR-L1 | 人工 | RASQSVSSSYLA |
| 199 | A3S / CDR-L2 | 人工 | GASSRAT |
| 200 | A3S / CDR-L3 | 人工 | QQYGSSPLT |
| 201 | A3S / SCFV I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 202 | A3S / 雙特異性分子I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 203 | A3S / HLE-BITE I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 204 | A3S / SCFV I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 205 | A3S / 雙特異性分子I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 206 | A3S / HLE BITE I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 207 | B2J / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 208 | B2J / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIK |
| 209 | B2J / CDR-H1 | 人工 | GYYMH |
| 210 | B2J / CDR-H2 | 人工 | WINPNSGDANYAQKFQG |
| 211 | B2J / CDR-H3 | 人工 | DNLIVVAPVTRDYYYYGMDV |
| 212 | B2J / CDR-L1 | 人工 | RASQTVSSSYLV |
| 213 | B2J / CDR-L2 | 人工 | GASSRAT |
| 214 | B2J / CDR-L3 | 人工 | QQYGGSPIT |
| 215 | B2J / SCFV I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 216 | B2J / 雙特異性分子I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 217 | B2J / HLE-BITE I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 218 | B2J / SCFV I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 219 | B2J / 雙特異性分子I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 220 | B2J / HLE BITE I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 221 | M5E / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 222 | M5E / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIK |
| 223 | M5E / CDR-H1 | 人工 | GYYMH |
| 224 | M5E / CDR-H2 | 人工 | WINPNSGDANYAQKFQG |
| 225 | M5E / CDR-H3 | 人工 | DNLIVVAPVTRDYYYYGMDV |
| 226 | M5E / CDR-L1 | 人工 | RASQSVSSSYLA |
| 227 | M5E / CDR-L2 | 人工 | GASSRAT |
| 228 | M5E / CDR-L3 | 人工 | QQYGSSPLT |
| 229 | M5E / SCFV I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 230 | M5E / 雙特異性分子I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 231 | M5E / HLE-BITE I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 232 | M5E / SCFV I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSS |
| 233 | M5E / 雙特異性分子I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 234 | M5E / HLE BITE I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDNLIVVAPVTRDYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 235 | X3A / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 236 | X3A / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIK |
| 237 | X3A / CDR-H1 | 人工 | GYYMH |
| 238 | X3A / CDR-H2 | 人工 | WINPNSGDANYAQKFQG |
| 239 | X3A / CDR-H3 | 人工 | DALIVVAPVTRDYYYYGMDV |
| 240 | X3A / CDR-L1 | 人工 | RASQTVSSSYLV |
| 241 | X3A / CDR-L2 | 人工 | GASSRAT |
| 242 | X3A / CDR-L3 | 人工 | QQYGGSPIT |
| 243 | X3A / SCFV I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 244 | X3A / 雙特異性分子I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 245 | X3A / HLE-BITE I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 246 | X3A / SCFV I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 247 | X3A / 雙特異性分子I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 248 | X3A / HLE BITE I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 249 | S9W / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 250 | S9W / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIK |
| 251 | S9W / CDR-H1 | 人工 | GYYMH |
| 252 | S9W / CDR-H2 | 人工 | WINPNSGDANYAQKFQG |
| 253 | S9W / CDR-H3 | 人工 | DALIVVAPVTRDYYYYGMDV |
| 254 | S9W / CDR-L1 | 人工 | RASQSVSSSYLA |
| 255 | S9W / CDR-L2 | 人工 | GASSRAT |
| 256 | S9W / CDR-L3 | 人工 | QQYGSSPLT |
| 257 | S9W / SCFV I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 258 | S9W / 雙特異性分子I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 259 | S9W / HLE-BITE I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 260 | S9W / SCFV I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 261 | S9W / 雙特異性分子I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 262 | S9W / HLE BITE I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 263 | I7L / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDGLIVEAPATRDYYYYGMDVWGQGTTVTVSS |
| 264 | I7L / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDTSPITFGCGTRLEIK |
| 265 | I7L / CDR-H1 | 人工 | GYYVH |
| 266 | I7L / CDR-H2 | 人工 | WINPNSGATNYAQKFQG |
| 267 | I7L / CDR-H3 | 人工 | DGLIVEAPATRDYYYYGMDV |
| 268 | I7L / CDR-L1 | 人工 | RASQSVRSTYLA |
| 269 | I7L / CDR-L2 | 人工 | GASSRAT |
| 270 | I7L / CDR-L3 | 人工 | QQYDTSPIT |
| 271 | I7L / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDGLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDTSPITFGCGTRLEIK |
| 272 | I7L / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDGLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 273 | I7L / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDGLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 274 | I7L / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDGLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDTSPITFGCGTRLEIK |
| 275 | I7L / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDGLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 276 | I7L / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQCLEWMGWINPNSGATNYAQKFQGRVTMTRDTSISTAYMELSRLRSVDTAVYYCVRDGLIVEAPATRDYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQTPGQAPRLLISGASSRATGIPDRFSGSGSGTDFILTISRLEPEDFAVYYCQQYDTSPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 277 | W5F / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGLIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 278 | W5F / VL | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIK |
| 279 | W5F / CDR-H1 | 人工 | GYYMH |
| 280 | W5F / CDR-H2 | 人工 | WINPNSGDTNYAQKFQG |
| 281 | W5F / CDR-H3 | 人工 | DGLIVVAPVTRDYYYYGMDV |
| 282 | W5F / CDR-L1 | 人工 | RASQTVSSSYLV |
| 283 | W5F / CDR-L2 | 人工 | GASSRAT |
| 284 | W5F / CDR-L3 | 人工 | QQYGGSPIT |
| 285 | W5F / SCFV I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGLIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 286 | W5F / 雙特異性分子I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGLIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 287 | W5F / HLE-BITE I2E | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGLIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 288 | W5F / SCFV I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPE DFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGLIVVAPVTRDYYYYGMDVWGQGTTVTASS |
| 289 | W5F / 雙特異性分子I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGLIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 290 | W5F / HLE BITE I2C | 人工 | EIVLTQSPGTLSLSPGERATLSCRASQTVSSSYLVWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLIISRLEPEDFAVYYCQQYGGSPITFGCGTRLEIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGLIVVAPVTRDYYYYGMDVWGQGTTVTASSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 291 | K4Y / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSYTLYYYYGMDVWGQGTTVTVSS |
| 292 | K4Y / VL | 人工 | QSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 293 | K4Y / CDR-H1 | 人工 | DYHMH |
| 294 | K4Y / CDR-H2 | 人工 | WIKPISGDANYAQKFQG |
| 295 | K4Y / CDR-H3 | 人工 | DYYSSSYTLYYYYGMDV |
| 296 | K4Y / CDR-L1 | 人工 | TGTSSDVGGYNYVS |
| 297 | K4Y / CDR-L2 | 人工 | EVSKRPS |
| 298 | K4Y / CDR-L3 | 人工 | SSYAGSNNFV |
| 299 | K4Y / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSYTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 300 | K4Y / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSYTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 301 | K4Y / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSYTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 302 | K4Y / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSYTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 303 | K4Y / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSYTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 304 | K4Y / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSYTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 305 | M4B / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSS |
| 306 | M4B / VL | 人工 | QSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 307 | M4B / CDR-H1 | 人工 | DYHMH |
| 308 | M4B / CDR-H2 | 人工 | WIKPISGDANYAQKFQG |
| 309 | M4B / CDR-H3 | 人工 | DAYSSSWTLYYYYGMDV |
| 310 | M4B / CDR-L1 | 人工 | TGTSSDVGGYNYVS |
| 311 | M4B / CDR-L2 | 人工 | EVSKRPS |
| 312 | M4B / CDR-L3 | 人工 | SSYAGSNNFV |
| 313 | M4B / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 314 | M4B / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 315 | M4B / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 316 | M4B / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 317 | M4B / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 318 | M4B / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 319 | B4G / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSS |
| 320 | B4G / VL | 人工 | QSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 321 | B4G / CDR-H1 | 人工 | DYHMH |
| 322 | B4G / CDR-H2 | 人工 | WIKPISGDANYAQKFQG |
| 323 | B4G / CDR-H3 | 人工 | DAYSSSWTLYYYYGMDV |
| 324 | B4G / CDR-L1 | 人工 | TGTSSDVGGYNYVS |
| 325 | B4G / CDR-L2 | 人工 | EVSKRPS |
| 326 | B4G / CDR-L3 | 人工 | SSYAGSNNFV |
| 327 | B4G / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 328 | B4G / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 329 | B4G / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 330 | B4G / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 331 | B4G / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 332 | B4G / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDAYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 333 | U8B / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSS |
| 334 | U8B / VL | 人工 | QSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 335 | U8B / CDR-H1 | 人工 | DYHMH |
| 336 | U8B / CDR-H2 | 人工 | WIKPISGDANYAQKFQG |
| 337 | U8B / CDR-H3 | 人工 | DYYSSSWTLYYYYGMDV |
| 338 | U8B / CDR-L1 | 人工 | TGTSSDVGGYNYVS |
| 339 | U8B / CDR-L2 | 人工 | EVSKRPS |
| 340 | U8B / CDR-L3 | 人工 | SSYAGSNNFV |
| 341 | U8B / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 342 | U8B / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 343 | U8B / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 344 | U8B / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 345 | U8B / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 346 | U8B / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 347 | Y8G / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSS |
| 348 | Y8G / VL | 人工 | QSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 349 | Y8G / CDR-H1 | 人工 | DYHMH |
| 350 | Y8G / CDR-H2 | 人工 | WIKPISGDANYAQKFQG |
| 351 | Y8G / CDR-H3 | 人工 | DGYSSSWTLYYYYGMDV |
| 352 | Y8G / CDR-L1 | 人工 | TGTSSDVGGYNYVS |
| 353 | Y8G / CDR-L2 | 人工 | EVSKRPS |
| 354 | Y8G / CDR-L3 | 人工 | SSYAGSNNFV |
| 355 | Y8G / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 356 | Y8G / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 357 | Y8G / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 358 | Y8G / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 359 | Y8G / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 360 | Y8G / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 361 | G8B / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSS |
| 362 | G8B / VL | 人工 | QSALTQPPSASGSPGQSVTIYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 363 | G8B / CDR-H1 | 人工 | DYHMH |
| 364 | G8B / CDR-H2 | 人工 | WIKPISGDANYAQKFQG |
| 365 | G8B / CDR-H3 | 人工 | DYYSSSWTLYYYYGMDV |
| 366 | G8B / CDR-L1 | 人工 | TGTSSDVGGYNYVS |
| 367 | G8B / CDR-L2 | 人工 | EVSKRPS |
| 368 | G8B / CDR-L3 | 人工 | SSYAGSNNFV |
| 369 | G8B / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTIYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 370 | G8B / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTIYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 371 | G8B / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTIYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 372 | G8B / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTIYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 373 | G8B / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTIYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 374 | G8B / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTIYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 375 | W9B / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGR VTMTRDTSISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSS |
| 376 | W9B / VL | 人工 | QSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSK SGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 377 | W9B / CDR-H1 | 人工 | DYHMH |
| 378 | W9B / CDR-H2 | 人工 | WIKPISGDTNYAQKFQG |
| 379 | W9B / CDR-H3 | 人工 | DGYSSSWTLYYYYGMDV |
| 380 | W9B / CDR-L1 | 人工 | TGTSSDVGGYNYVS |
| 381 | W9B / CDR-L2 | 人工 | EVSKRPS |
| 382 | W9B / CDR-L3 | 人工 | SSYAGSNNFV |
| 383 | W9B / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 384 | W9B / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALT LSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 385 | W9B / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 386 | W9B / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGRVTMTRDT SISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 387 | W9B / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 388 | W9B / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDGYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 389 | A9G / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSS |
| 390 | A9G / VL | 人工 | QSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 391 | A9G / CDR-H1 | 人工 | DYHMH |
| 392 | A9G / CDR-H2 | 人工 | WIKPISGDANYAQKFQG |
| 393 | A9G / CDR-H3 | 人工 | DYYSSSWTLYYYYGMDV |
| 394 | A9G / CDR-L1 | 人工 | TGTSSDVGGYNYVS |
| 395 | A9G / CDR-L2 | 人工 | EVSKRPS |
| 396 | A9G / CDR-L3 | 人工 | SSYAGSNNFV |
| 397 | A9G / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 398 | A9G / 雙特異性分子I2E. | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 399 | A9G / HLE-BITE I2E. | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 400 | A9G / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 401 | A9G / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 402 | A9G / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 403 | D3F / VH | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSS |
| 404 | D3F / VL | 人工 | QSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 405 | D3F / CDR-H1 | 人工 | DYHMH |
| 406 | D3F / CDR-H2 | 人工 | WIKPISGDTNYAQKFQG |
| 407 | D3F / CDR-H3 | 人工 | DYYSSSWTLYYYYGMDV |
| 408 | D3F / CDR-L1 | 人工 | TGTSSDVGGYNYVS |
| 409 | D3F / CDR-L2 | 人工 | EVSKRPS |
| 410 | D3F / CDR-L3 | 人工 | SSYAGSNNFV |
| 411 | D3F / SCFV I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 412 | D3F / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 413 | D3F / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 414 | D3F / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 415 | D3F / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 416 | D3F / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSWTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTSYCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 417 | E4N / VH. | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSFTLYYYYGMDVWGQGTTVTVSS |
| 418 | E4N / VL. | 人工 | QSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 419 | E4N / CDR-H1 | 人工 | DYHMH |
| 420 | E4N / CDR-H2 | 人工 | WIKPISGDANYAQKFQG |
| 421 | E4N / CDR-H3 | 人工 | DYYSSSFTLYYYYGMDV |
| 422 | E4N / CDR-L1 | 人工 | TGTSSDVGGYNYVS |
| 423 | E4N / CDR-L2 | 人工 | EVSKRPS |
| 424 | E4N / CDR-L3 | 人工 | SSYAGSNNFV |
| 425 | E4N / SCFV I2E. | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSFTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 426 | E4N / 雙特異性分子I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSFTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 427 | E4N / HLE-BITE I2E | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSFTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 428 | E4N / SCFV I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSFTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVL |
| 429 | E4N / 雙特異性分子I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSFTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 430 | E4N / HLE BITE I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQCLEWMGWIKPISGDANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYSSSFTLYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFVFGCGTKVTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 431 | CL6 AE3-20 X I2C X SCFC / HCDR1 | 人工 | SYTMS |
| 432 | CL6 AE3-20 / HCDR2 | 人工 | TISSGGGRTYYPDSVKG |
| 433 | CL6 AE3-20 / HCDR3 | 人工 | GDYRYDGFAY |
| 434 | CL6 AE3-20 / LCDR1 | 人工 | RASENIDSYLA |
| 435 | CL6 AE3-20 / LCDR2 | 人工 | ASTLLVD |
| 436 | CL6 AE3-20 / LCDR3 | 人工 | QHYYSIPYT |
| 437 | CL6 AE3-20 / VH | 人工 | EVKLVESGGGLVKPGGSLKLSCAASGFTFNSYTMSWVRQTPAKRLEWVVTISSGGGRTYYPDSVKGRFTISRDNARNTLYLQMSSLRSEDTAMYYCIRGDYRYDGFAYWGQGTLVTVST |
| 438 | CL6 AE3-20 / VL | 人工 | DIQMTQSPASLSASVGETVTITCRASENIDSYLAWYQQKQGKSPQLLVYASTLLVDGVPSRFSGSRSGTQFSLKINSLQSEDVARYYCQHYYSIPYTFGSGTKLEIK |
| 439 | CL6 AE3-20 / SCFV | 人工 | EVKLVESGGGLVKPGGSLKLSCAASGFTFNSYTMSWVRQTPAKRLEWVVTISSGGGRTYYPDSVKGRFTISRDNARNTLYLQMSSLRSEDTAMYYCIRGDYRYDGFAYWGQGTLVTVSTGGGGSGGGGSGGGGSDIQMTQSPASLSASVGETVTITCRASENIDSYLAWYQQKQGKSPQLLVYASTLLVDGVPSRFSGSRSGTQFSLKINSLQSEDVARYYCQHYYSIPYTFGSGTKLEIK |
| 440 | CL6 AE3-20 / 雙特異性分子 | 人工 | EVKLVESGGGLVKPGGSLKLSCAASGFTFNSYTMSWVRQTPAKRLEWVVTISSGGGRTYYPDSVKGRFTISRDNARNTLYLQMSSLRSEDTAMYYCIRGDYRYDGFAYWGQGTLVTVSTGGGGSGGGGSGGGGSDIQMTQSPASLSASVGETVTITCRASENIDSYLAWYQQKQGKSPQLLVYASTLLVDGVPSRFSGSRSGTQFSLKINSLQSEDVARYYCQHYYSIPYTFGSGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 441 | CL6 AE3-20 / HLE-BITE I2E | 人工 | EVKLVESGGGLVKPGGSLKLSCAASGFTFNSYTMSWVRQTPAKRLEWVVTISSGGGRTYYPDSVKGRFTISRDNARNTLYLQMSSLRSEDTAMYYCIRGDYRYDGFAYWGQGTLVTVSTGGGGSGGGGSGGGGSDIQMTQSPASLSASVGETVTITCRASENIDSYLAWYQQKQGKSPQLLVYASTLLVDGVPSRFSGSRSGTQFSLKINSLQSEDVARYYCQHYYSIPYTFGSGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 442 | 人CD3ε ECD / | 人工 | QDGNEEMGGITQTPYKVSISGTTVILTCPQYPGSEILWQHNDKNIGGDEDDKNIGSDEDHLSLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARVCENCMEMD |
| 443 | 人CD3ε ECD / pos. 1-27 | 人工 | QDGNEEMGGITQTPYKVSISGTTVILT |
| 444 | H2C的CDR-L1 | 人工 | GSSTGAVTSGYYPN |
| 445 | H2C的CDR-L2 | 人工 | GTKFLAP |
| 446 | H2C的CDR-L3 | 人工 | ALWYSNRWV |
| 447 | E2M的CDR-L1 | 人工 | RSSTGAVTSGYYPN |
| 448 | E2M的CDR-L2 | 人工 | ATDMRPS |
| 449 | E2M的CDR-L3 | 人工 | ALWYSNRWV |
| 450 | F12Q的CDR-L1 | 人工 | GSSTGAVTSGNYPN |
| 451 | F12Q的CDR-L2 | 人工 | GTKFLAP |
| 452 | F12Q的CDR-L3 | 人工 | VLWYSNRWV |
| 453 | F6A的CDR-H1 | 人工 | IYAMN |
| 454 | F6A的CDR-H2 | 人工 | RIRSKYNNYATYYADSVKS |
| 455 | F6A的CDR-H3 | 人工 | HGNFGNSYVSFFAY |
| 456 | H2C的CDR-H1 | 人工 | KYAMN |
| 457 | H2C的CDR-H2 | 人工 | RIRSKYNNYATYYADSVKD |
| 458 | H2C的CDR-H3 | 人工 | HGNFGNSYISYWAY |
| 459 | H1E的CDR-H1 | 人工 | SYAMN |
| 460 | H1E的CDR-H2 | 人工 | RIRSKYNNYATYYADSVKG |
| 461 | H1E的CDR-H3 | 人工 | HGNFGNSYLSFWAY |
| 462 | G4H的CDR-H1 | 人工 | RYAMN |
| 463 | G4H的CDR-H2 | 人工 | RIRSKYNNYATYYADSVKG |
| 464 | G4H的CDR-H3 | 人工 | HGNFGNSYLSYFAY |
| 465 | A2J的CDR-H1 | 人工 | VYAMN |
| 466 | A2J的CDR-H2 | 人工 | RIRSKYNNYATYYADSVKK |
| 467 | A2J的CDR-H3 | 人工 | HGNFGNSYLSWWAY |
| 468 | E1L的CDR-H1 | 人工 | KYAMN |
| 469 | E1L的CDR-H2 | 人工 | RIRSKYNNYATYYADSVKS |
| 470 | E1L的CDR-H3 | 人工 | HGNFGNSYTSYYAY |
| 471 | E2M的CDR-H1 | 人工 | GYAMN |
| 472 | E2M的CDR-H2 | 人工 | RIRSKYNNYATYYADSVKE |
| 473 | E2M的CDR-H3 | 人工 | HRNFGNSYLSWFAY |
| 474 | F7O的CDR-H1 | 人工 | VYAMN |
| 475 | F7O的CDR-H2 | 人工 | RIRSKYNNYATYYADSVKK |
| 476 | F7O的CDR-H3 | 人工 | HGNFGNSYISWWAY |
| 477 | F12Q的CDR-H1 | 人工 | SYAMN |
| 478 | F12Q的CDR-H2 | 人工 | RIRSKYNNYATYYADSVKG |
| 479 | F12Q的CDR-H3 | 人工 | HGNFGNSYVSWWAY |
| 480 | I2C的CDR-H1 | 人工 | KYAMN |
| 481 | I2C的CDR-H2 | 人工 | RIRSKYNNYATYYADSVKD |
| 482 | I2C的CDR-H3 | 人工 | HGNFGNSYISYWAY |
| 483 | H2C的CDR-L2 | 人工 | GTKFLAP |
| 484 | H2C的CDR-L3 | 人工 | ALWYSNRWV |
| 485 | H2C的CDR-H1 | 人工 | KYAMN |
| 486 | H1E的CDR-L1 | 人工 | GSSTGAVTSGYYPN |
| 487 | H1E的CDR-L2 | 人工 | GTKFLAP |
| 488 | H1E的CDR-L3 | 人工 | ALWYSNRWV |
| 489 | H1E的CDR-H1 | 人工 | SYAMN |
| 490 | H1E的CDR-H2 | 人工 | RIRSKYNNYATYYADSVKG |
| 491 | H1E的CDR-H3 | 人工 | HGNFGNSYLSFWAY |
| 492 | G4H的CDR-L1 | 人工 | GSSTGAVTSGYYPN |
| 493 | G4H的CDR-L2 | 人工 | GTKFLAP |
| 494 | G4H的CDR-L3 | 人工 | ALWYSNRWV |
| 495 | A2J的CDR-L1 | 人工 | RSSTGAVTSGYYPN |
| 496 | A2J的CDR-L2 | 人工 | ATDMRPS |
| 497 | A2J的CDR-L3 | 人工 | ALWYSNRWV |
| 498 | E1L的CDR-L1 | 人工 | GSSTGAVTSGYYPN |
| 499 | E1L的CDR-L2 | 人工 | GTKFLAP |
| 500 | E1L的CDR-L3 | 人工 | ALWYSNRWV |
| 501 | F7O的CDR-L1 | 人工 | GSSTGAVTSGYYPN |
| 502 | F7O的CDR-L2 | 人工 | GTKFLAP |
| 503 | F7O的CDR-L3 | 人工 | ALWYSNRWV |
| 504 | I2C的CDR-L1 | 人工 | GSSTGAVTSGNYPN |
| 505 | I2C的CDR-L2 | 人工 | GTKFLAP |
| 506 | I2C的CDR-L3 | 人工 | VLWYSNRWV |
| 507 | H2C的VL | 人工 | QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 508 | E2M的VL | 人工 | QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPSGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 509 | F12Q的VL | 人工 | QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 510 | H2C的VL變體 | 人工 | ELVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 511 | A2J的VL變體 | 人工 | ELVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPSGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 512 | F12Q的VL變體 | 人工 | ELVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 513 | F6A的VH | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWGQGTLVTVSS |
| 514 | H2C的VH | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSS |
| 515 | H1E的VH | 人工 | EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWGQGTLVTVSS |
| 516 | G4H的VH | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWGQGTLVTVSS |
| 517 | A2J的VH | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWGQGTLVTVSS |
| 518 | E1L的VH | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWGQGTLVTVSS |
| 519 | E2M的VH | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWGQGTLVTVSS |
| 520 | F7O的VH | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWGQGTLVTVSS |
| 521 | F12Q的VH | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSS |
| 522 | I2C的VH | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSS |
| 523 | F12q的VH | 人工 | EVQLVESGGGLVQPGGSLRLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNSLKTEDTAVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSS |
| 524 | F6A的VH變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWGQGTLVTVSS |
| 525 | H2C的VH變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSS |
| 526 | H1E的VH變體 | 人工 | EVQLLESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWGQGTLVTVSS |
| 527 | G4H的VH變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWGQGTLVTVSS |
| 528 | A2J的VH變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWGQGTLVTVSS |
| 529 | E1L的VH變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWGQGTLVTVSS |
| 530 | E2M的VH變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWGQGTLVTVSS |
| 531 | F7O的VH變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWGQGTLVTVSS |
| 532 | F12Q的VH變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSS |
| 533 | I2C的VH變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSS |
| 534 | F6A的VL | 人工 | QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 535 | H1E的VL | 人工 | QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 536 | G4H的VL | 人工 | QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 537 | A2J的VL | 人工 | QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPSGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 538 | E1L的VL | 人工 | QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 539 | F7O的VL | 人工 | QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 540 | I2C的VL | 人工 | QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 541 | F12q的VL | 人工 | QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 542 | F6A的scFv | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 543 | H2C的scFv | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 544 | H1E的scFv | 人工 | EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 545 | G4H的scFv | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 546 | A2J的scFv | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPSGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 547 | E1L的scFv | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 548 | E2M的scFv | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPSGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 549 | F7O的scFv | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 550 | F12Q的scFv | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 551 | I2C的scFv | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 552 | F12q的scFv | 人工 | EVQLVESGGGLVQPGGSLRLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNSLKTEDTAVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 553 | F6A的scFv變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWGQGTLVTVSSGGGGSGGGGSGGGGSELVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 554 | H2C的scFv變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSELVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 555 | H1E的scFv變體 | 人工 | EVQLLESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWGQGTLVTVSSGGGGSGGGGSGGGGSELVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 556 | G4H的scFv變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSELVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 557 | A2J的scFv變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSELVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPSGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 558 | E1L的scFv變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWGQGTLVTVSSGGGGSGGGGSGGGGSELVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 559 | E2M的scFv變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWGQGTLVTVSSGGGGSGGGGSGGGGSELVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPSGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 560 | F7O的scFv變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSELVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL |
| 561 | F12Q的scFv變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSELVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 562 | I2C的scFv變體 | 人工 | EVQLLESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSELVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 563 | 連接子2 | 人工 | GGGGS |
| 564 | 連接子3 | 人工 | GGGGQ |
| 565 | 連接子4 | 人工 | SGGGGS |
| 566 | 連接子5 | 人工 | PGGGGS |
| 567 | 連接子6 | 人工 | PGGDGS |
| 568 | 連接子7 | 人工 | GGGGSGGGS |
| 569 | 連接子8 = (G4S)2連接子 | 人工 | GGGGSGGGGS |
| 570 | 連接子9 = (G4S)3連接子 | 人工 | GGGGSGGGGSGGGGS |
| 571 | (G4S)4連接子 | 人工 | GGGGSGGGGSGGGGSGGGGS |
| 572 | (G4S)5連接子 | 人工 | GGGGSGGGGSGGGGSGGGGSGGGGS |
| 573 | (G4S)6連接子 | 人工 | GGGGSGGGGSGGGGSGGGGSGGGGSGGGGS |
| 574 | (G4S)7連接子 | 人工 | GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS |
| 575 | (G4S)8連接子 | 人工 | GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS |
| 576 | 線性FcRn BP | 人工 | QRFVTGHFGGLXPANG |
| 577 | 線性FcRn BP-Y | 人工 | QRFVTGHFGGLYPANG |
| 578 | 線性FcRn BP-H | 人工 | QRFVTGHFGGLHPANG |
| 579 | 核心FcRn BP-H | 人工 | TGHFGGLHP |
| 580 | 環狀FcRn BP-H | 人工 | QRFCTGHFGGLHPCNG |
| 581 | HALB | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL |
| 582 | HALB 變體1 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAGTFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAAMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL |
| 583 | HALB 變體2 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGPKLVAASQAALGL |
| 584 | HALB 變體3 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALDVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGPHLVAASKAALGL |
| 585 | HALB 變體4 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALGVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDKFAAFVEKCCKADDKETCFAEEGPKLVAASQAALGL |
| 586 | HALB 變體5 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALDVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDKFAAFVEKCCKADDKETCFAEEGPKLVAASQAALGL |
| 587 | HALB 變體6 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDKFAAFVEKCCKADDKETCFAEEGPHLVAASQAALGL |
| 588 | HALB 變體7 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGPHLVAASKAALGL |
| 589 | HALB 變體8 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDKFAAFVEKCCKADDKETCFAEEGPKLVAASKAALGL |
| 590 | HALB 變體9 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALDVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGPKLVAASKAALGL |
| 591 | HALB 變體10 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQSPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL |
| 592 | HALB 變體11 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQSPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAGTFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAAMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL |
| 593 | HALB 變體12 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQSPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGPKLVAASQAALGL |
| 594 | HALB 變體13 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQSPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALDVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGPHLVAASKAALGL |
| 595 | HALB 變體14 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQSPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALGVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDKFAAFVEKCCKADDKETCFAEEGPKLVAASQAALGL |
| 596 | HALB 變體15 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQSPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALDVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDKFAAFVEKCCKADDKETCFAEEGPKLVAASQAALGL |
| 597 | HALB 變體16 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQSPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDKFAAFVEKCCKADDKETCFAEEGPHLVAASQAALGL |
| 598 | HALB 變體17 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQSPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGPHLVAASKAALGL |
| 599 | HALB 變體18 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQSPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDKFAAFVEKCCKADDKETCFAEEGPKLVAASKAALGL |
| 600 | HALB 變體19 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQSPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALDVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGPKLVAASKAALGL |
| 601 | HALB 變體20 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQAPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL |
| 602 | HALB 變體21 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQAPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAGTFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAAMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL |
| 603 | HALB 變體22 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQAPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGPKLVAASQAALGL |
| 604 | HALB 變體23 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQAPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALDVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGPHLVAASKAALGL |
| 605 | HALB 變體24 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQAPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALGVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDKFAAFVEKCCKADDKETCFAEEGPKLVAASQAALGL |
| 606 | HALB 變體25 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQAPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALDVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDKFAAFVEKCCKADDKETCFAEEGPKLVAASQAALGL |
| 607 | HALB 變體26 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQAPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDKFAAFVEKCCKADDKETCFAEEGPHLVAASQAALGL |
| 608 | HALB 變體27 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQAPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGPHLVAASKAALGL |
| 609 | HALB 變體28 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQAPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDKFAAFVEKCCKADDKETCFAEEGPKLVAASKAALGL |
| 610 | HALB 變體29 | 人工 | DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQAPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALDVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGPKLVAASKAALGL |
| 611 | 交叉體（Cross body）1 HC | 人工 | ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYDTTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 612 | 交叉體1 LC | 人工 | GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRKEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 613 | 交叉體2 HC | 人工 | ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYDTTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 614 | 交叉體2 LC | 人工 | GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECSEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRKEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 615 | 異Fc結合物Fc | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRKEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 616 | 異Fc配偶體Fc | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYDTTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 617 | 最大體（Maxi-body）1靶標Fc | 人工 | EPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRKEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 618 | 最大體1 CD3 Fc | 人工 | EPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYDTTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 619 | 最大體（Maxi-body）2靶標Fc | 人工 | EPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRKEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 620 | 最大體2 CD3 Fc | 人工 | EPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYDTTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 621 | 單Fc | 人工 | APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVTTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYDTTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 622 | Fc單體-1 +c/-g | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 623 | Fc單體-2 +c/-g/ delGK | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP |
| 624 | Fc單體-3 -c/+g | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 625 | Fc單體-4 -c/+g/ delGK | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP |
| 626 | Fc單體-5 -c/-g | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 627 | Fc單體-6 -c/-g/ delGK | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP |
| 628 | Fc單體-7 +c/+g | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYNSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 629 | Fc單體-8 +c/+g/ delGK | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYNSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP |
| 630 | scFc-1 | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 631 | scFc-2 | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP |
| 632 | scFc-3 | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 633 | scFc-4 | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP |
| 634 | scFc-5 | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 635 | scFc-6 | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP |
| 636 | scFc-7 | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYNSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYNSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
| 637 | scFc-8 | 人工 | DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYNSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYNSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP |
| 638 | 5x his-標籤 | 人工 | HHHHH |
| 639 | 6x his-標籤 | 人工 | HHHHHH |
| 640 | CL-1 x I2C | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGGTKYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDRITVAGTYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGVNNWLAWYQQKPGKAPKLLIYTASSLQSGVPSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQANSFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 641 | CL-2 x I2C | 人工 | QVQMVQSGAEVKKHGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGGTKYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDRITVAGTYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGVNNWLAWYQQKPGKAPKLLIYTASSLQSGVPSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQANSFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL |
| 642 | CL-1 x I2C-6His | 人工 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGGTKYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDRITVAGTYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGVNNWLAWYQQKPGKAPKLLIYTASSLQSGVPSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQANSFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH |
| 643 | CL-2 x I2C-6His | 人工 | QVQMVQSGAEVKKHGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGGTKYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDRITVAGTYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGVNNWLAWYQQKPGKAPKLLIYTASSLQSGVPSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQANSFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH |
| 644 | AU1表位 | 人工 | DTYRYI |
| 645 | AU5表位 | 人工 | TDFYLK |
| 646 | T-7 標籤 | 人工 | MASMTGGQQMG |
| 647 | V-5 標籤 | 人工 | GKPIPNPLLGLDST |
| 648 | B-標籤 | 人工 | QYPALT |
| 649 | E2表位 | 人工 | SSTSSDFRDR |
| 650 | FLAG標籤 | 人工 | DYKDDDK |
| 651 | Glu-Glu標籤1 | 人工 | EYMPME |
| 652 | Glu-Glu標籤2 | 人工 | EFMPME |
| 653 | 組胺酸親和標籤 | 人工 | KDHLIHNVHKEFHAHAHNK |
| 654 | HSV表位 | 人工 | QPELAPED |
| 655 | KT3表位 | 人工 | KPPTPPPEPET |
| 656 | Myc表位 | 人工 | CEQKLISEEDL |
| 657 | 7x his-標籤 | 人工 | HHHHHHH |
| 658 | 8x his-標籤 | 人工 | HHHHHHHH |
| 659 | S1標籤 | 人工 | NANNPDWDF |
| 660 | S-標籤 | 人工 | KETAAAKFERQHMDS |
| 661 | Strep-標籤1 | 人工 | WSHPQFEK |
| 662 | Strep-標籤2 | 人工 | AWAHPQPGG |
| 663 | 通用標籤 | 人工 | HTTPHH |
| 664 | VSV-G | 人工 | YTDIEMNRLGK |
| 665 | 蛋白C | 人工 | EDQVDPRLIDGK |
| 666 | Ab156 | 人工 | RDWDFDVFGGGTPVGG |
| 667 | H-CDR3 | 人工 | X 1LIVX 2APX 3，其中X 1係A或N；X 2係V或E；並且X 3係V或A， |
| 668 | H-CDR3 | 人工 | DX 1LIVX 2APX 3T, 其中X 1係A或N；X 2係V或E；並且X 3係V或A， |
| 669 | H-CDR3 | 人工 | DX 1LIVX 2APX 3TRDYYYYGMDV, 其中X 1係A或N；X 2係V或E；並且X 3係V或A |
| 670 | CD3 BINDER / I2E - HCDR1 | 人工 | KYAIN |
| 671 | CD3 BINDER / I2E - HCDR2 | 人工 | RIRSKYNNYATYYADAVKD |
| 672 | CD3 BINDER / I2E - HCDR3 | 人工 | AGNFGSSYISYWAY |
| 673 | CD3 BINDER / I2E - LCDR1 | 人工 | GSSTGAVTSGNYPN |
| 674 | CD3 BINDER /I2E - LCDR2 | 人工 | GTKFLAP |
| 675 | CD3 BINDER I2E - LCDR3 | 人工 | VLWYSNRWV |
| 676 | CD3 BINDER / I2E - VH | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSS |
| 677 | CD3 BINDER / I2E - VL | 人工 | QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 678 | CD3 BINDER / I2E-SCFV (G4S)3 | 人工 | EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL |
| 679 | G4-連接子 | 人工 | GGGG |
| 680 | HCDR1 | 人工 | GYSFTGYT |
| 681 | HCDR2 | 人工 | INPYNGGT |
| 682 | HCDR2 | 人工 | INPYNGGS |
| 683 | HCDR2 | 人工 | INPYNGGI |
| 684 | HCDR3 | 人工 | ARDYGYVLDY |
| 685 | HCDR3 | 人工 | ARDFGYVLDY |
| 686 | HCDR3 | 人工 | ARDYGFVLDY |
| 687 | HCDR3 | 人工 | ARDYGYVFDY |
| 688 | LCDR1 | 人工 | SSVSY |
| 689 | LCDR1 | 人工 | SSVNY |
| 690 | LCDR2 | 人工 | STS |
| 691 | LCDR3 | 人工 | QQRSIYPPWT |
| 692 | LCDR3 | 人工 | QQRSNYPPWT |
| 693 | LCDR3 | 人工 | QQRSTYPPWT |
| 694 | LCDR3 | 人工 | QQRNNYPPWT |
| 695 | LCDR1 | 人工 | RASQSVX 1SX 2YLA，X 1選自S和R，X 2選自S和T |
| 696 | LCDR3 | 人工 | QQYX 1X 2SPX 3T，X 1選自G、D和Q，X 2選自S、A和T，X 3選自L和I |
無
<![CDATA[<110> 德商安美基研究(慕尼黑)公司，美商安進公司]]>
<![CDATA[<120> 選擇性地與CLDN6和CD3結合的多肽構建體]]>
<![CDATA[<130> AMG17318PCT]]>
<![CDATA[<140> TW 110141510]]>
<![CDATA[<141> 2021-11-08]]>
<![CDATA[<150> US 63/110,817]]>
<![CDATA[<151> 2020-11-06]]>
<![CDATA[<150> US 63/139,419]]>
<![CDATA[<151> 2021-01-20]]>
<![CDATA[<160> 696 ]]>
<![CDATA[<170> PatentIn 3.5 版本]]>
<![CDATA[<210> 1]]>
<![CDATA[<211> 220]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人]]>
<![CDATA[<400> 1]]>
Met Ala Ser Ala Gly Met Gln Ile Leu Gly Val Val Leu Thr Leu Leu
1 5 10 15
Gly Trp Val Asn Gly Leu Val Ser Cys Ala Leu Pro Met Trp Lys Val
20 25 30
Thr Ala Phe Ile Gly Asn Ser Ile Val Val Ala Gln Val Val Trp Glu
35 40 45
Gly Leu Trp Met Ser Cys Val Val Gln Ser Thr Gly Gln Met Gln Cys
50 55 60
Lys Val Tyr Asp Ser Leu Leu Ala Leu Pro Gln Asp Leu Gln Ala Ala
65 70 75 80
Arg Ala Leu Cys Val Ile Ala Leu Leu Val Ala Leu Phe Gly Leu Leu
85 90 95
Val Tyr Leu Ala Gly Ala Lys Cys Thr Thr Cys Val Glu Glu Lys Asp
100 105 110
Ser Lys Ala Arg Leu Val Leu Thr Ser Gly Ile Val Phe Val Ile Ser
115 120 125
Gly Val Leu Thr Leu Ile Pro Val Cys Trp Thr Ala His Ala Ile Ile
130 135 140
Arg Asp Phe Tyr Asn Pro Leu Val Ala Glu Ala Gln Lys Arg Glu Leu
145 150 155 160
Gly Ala Ser Leu Tyr Leu Gly Trp Ala Ala Ser Gly Leu Leu Leu Leu
165 170 175
Gly Gly Gly Leu Leu Cys Cys Thr Cys Pro Ser Gly Gly Ser Gln Gly
180 185 190
Pro Ser His Tyr Met Ala Arg Tyr Ser Thr Ser Ala Pro Ala Ile Ser
195 200 205
Arg Gly Pro Ser Glu Tyr Pro Thr Lys Asn Tyr Val
210 215 220
<![CDATA[<210> 2]]>
<![CDATA[<211> 261]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人]]>
<![CDATA[<400> 2]]>
Met Ser Thr Thr Thr Cys Gln Val Val Ala Phe Leu Leu Ser Ile Leu
1 5 10 15
Gly Leu Ala Gly Cys Ile Ala Ala Thr Gly Met Asp Met Trp Ser Thr
20 25 30
Gln Asp Leu Tyr Asp Asn Pro Val Thr Ser Val Phe Gln Tyr Glu Gly
35 40 45
Leu Trp Arg Ser Cys Val Arg Gln Ser Ser Gly Phe Thr Glu Cys Arg
50 55 60
Pro Tyr Phe Thr Ile Leu Gly Leu Pro Ala Met Leu Gln Ala Val Arg
65 70 75 80
Ala Leu Met Ile Val Gly Ile Val Leu Gly Ala Ile Gly Leu Leu Val
85 90 95
Ser Ile Phe Ala Leu Lys Cys Ile Arg Ile Gly Ser Met Glu Asp Ser
100 105 110
Ala Lys Ala Asn Met Thr Leu Thr Ser Gly Ile Met Phe Ile Val Ser
115 120 125
Gly Leu Cys Ala Ile Ala Gly Val Ser Val Phe Ala Asn Met Leu Val
130 135 140
Thr Asn Phe Trp Met Ser Thr Ala Asn Met Tyr Thr Gly Met Gly Gly
145 150 155 160
Met Val Gln Thr Val Gln Thr Arg Tyr Thr Phe Gly Ala Ala Leu Phe
165 170 175
Val Gly Trp Val Ala Gly Gly Leu Thr Leu Ile Gly Gly Val Met Met
180 185 190
Cys Ile Ala Cys Arg Gly Leu Ala Pro Glu Glu Thr Asn Tyr Lys Ala
195 200 205
Val Ser Tyr His Ala Ser Gly His Ser Val Ala Tyr Lys Pro Gly Gly
210 215 220
Phe Lys Ala Ser Thr Gly Phe Gly Ser Asn Thr Lys Asn Lys Lys Ile
225 230 235 240
Tyr Asp Gly Gly Ala Arg Thr Glu Asp Glu Val Gln Ser Tyr Pro Ser
245 250 255
Lys His Asp Tyr Val
260
<![CDATA[<210> 3]]>
<![CDATA[<211> 261]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人]]>
<![CDATA[<400> 3]]>
Met Ala Val Thr Ala Cys Gln Gly Leu Gly Phe Val Val Ser Leu Ile
1 5 10 15
Gly Ile Ala Gly Ile Ile Ala Ala Thr Cys Met Asp Gln Trp Ser Thr
20 25 30
Gln Asp Leu Tyr Asn Asn Pro Val Thr Ala Val Phe Asn Tyr Gln Gly
35 40 45
Leu Trp Arg Ser Cys Val Arg Glu Ser Ser Gly Phe Thr Glu Cys Arg
50 55 60
Gly Tyr Phe Thr Leu Leu Gly Leu Pro Ala Met Leu Gln Ala Val Arg
65 70 75 80
Ala Leu Met Ile Val Gly Ile Val Leu Gly Ala Ile Gly Leu Leu Val
85 90 95
Ser Ile Phe Ala Leu Lys Cys Ile Arg Ile Gly Ser Met Glu Asp Ser
100 105 110
Ala Lys Ala Asn Met Thr Leu Thr Ser Gly Ile Met Phe Ile Val Ser
115 120 125
Gly Leu Cys Ala Ile Ala Gly Val Ser Val Phe Ala Asn Met Leu Val
130 135 140
Thr Asn Phe Trp Met Ser Thr Ala Asn Met Tyr Thr Gly Met Gly Gly
145 150 155 160
Met Val Gln Thr Val Gln Thr Arg Tyr Thr Phe Gly Ala Ala Leu Phe
165 170 175
Val Gly Trp Val Ala Gly Gly Leu Thr Leu Ile Gly Gly Val Met Met
180 185 190
Cys Ile Ala Cys Arg Gly Leu Ala Pro Glu Glu Thr Asn Tyr Lys Ala
195 200 205
Val Ser Tyr His Ala Ser Gly His Ser Val Ala Tyr Lys Pro Gly Gly
210 215 220
Phe Lys Ala Ser Thr Gly Phe Gly Ser Asn Thr Lys Asn Lys Lys Ile
225 230 235 240
Tyr Asp Gly Gly Ala Arg Thr Glu Asp Glu Val Gln Ser Tyr Pro Ser
245 250 255
Lys His Asp Tyr Val
260
<![CDATA[<210> 4]]>
<![CDATA[<211> 211]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人]]>
<![CDATA[<400> 4]]>
Met Ala Asn Ala Gly Leu Gln Leu Leu Gly Phe Ile Leu Ala Phe Leu
1 5 10 15
Gly Trp Ile Gly Ala Ile Val Ser Thr Ala Leu Pro Gln Trp Arg Ile
20 25 30
Tyr Ser Tyr Ala Gly Asp Asn Ile Val Thr Ala Gln Ala Met Tyr Glu
35 40 45
Gly Leu Trp Met Ser Cys Val Ser Gln Ser Thr Gly Gln Ile Gln Cys
50 55 60
Lys Val Phe Asp Ser Leu Leu Asn Leu Ser Ser Thr Leu Gln Ala Thr
65 70 75 80
Arg Ala Leu Met Val Val Gly Ile Leu Leu Gly Val Ile Ala Ile Phe
85 90 95
Val Ala Thr Val Gly Met Lys Cys Met Lys Cys Leu Glu Asp Asp Glu
100 105 110
Val Gln Lys Met Arg Met Ala Val Ile Gly Gly Ala Ile Phe Leu Leu
115 120 125
Ala Gly Leu Ala Ile Leu Val Ala Thr Ala Trp Tyr Gly Asn Arg Ile
130 135 140
Val Gln Glu Phe Tyr Asp Pro Met Thr Pro Val Asn Ala Arg Tyr Glu
145 150 155 160
Phe Gly Gln Ala Leu Phe Thr Gly Trp Ala Ala Ala Ser Leu Cys Leu
165 170 175
Leu Gly Gly Ala Leu Leu Cys Cys Ser Cys Pro Arg Lys Thr Thr Ser
180 185 190
Tyr Pro Thr Pro Arg Pro Tyr Pro Lys Pro Ala Pro Ser Ser Gly Lys
195 200 205
Asp Tyr Val
210
<![CDATA[<210> 5]]>
<![CDATA[<211> 230]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人]]>
<![CDATA[<400> 5]]>
Met Ala Ser Leu Gly Leu Gln Leu Val Gly Tyr Ile Leu Gly Leu Leu
1 5 10 15
Gly Leu Leu Gly Thr Leu Val Ala Met Leu Leu Pro Ser Trp Lys Thr
20 25 30
Ser Ser Tyr Val Gly Ala Ser Ile Val Thr Ala Val Gly Phe Ser Lys
35 40 45
Gly Leu Trp Met Glu Cys Ala Thr His Ser Thr Gly Ile Thr Gln Cys
50 55 60
Asp Ile Tyr Ser Thr Leu Leu Gly Leu Pro Ala Asp Ile Gln Ala Ala
65 70 75 80
Gln Ala Met Met Val Thr Ser Ser Ala Ile Ser Ser Leu Ala Cys Ile
85 90 95
Ile Ser Val Val Gly Met Arg Cys Thr Val Phe Cys Gln Glu Ser Arg
100 105 110
Ala Lys Asp Arg Val Ala Val Ala Gly Gly Val Phe Phe Ile Leu Gly
115 120 125
Gly Leu Leu Gly Phe Ile Pro Val Ala Trp Asn Leu His Gly Ile Leu
130 135 140
Arg Asp Phe Tyr Ser Pro Leu Val Pro Asp Ser Met Lys Phe Glu Ile
145 150 155 160
Gly Glu Ala Leu Tyr Leu Gly Ile Ile Ser Ser Leu Phe Ser Leu Ile
165 170 175
Ala Gly Ile Ile Leu Cys Phe Ser Cys Ser Ser Gln Arg Asn Arg Ser
180 185 190
Asn Tyr Tyr Asp Ala Tyr Gln Ala Gln Pro Leu Ala Thr Arg Ser Ser
195 200 205
Pro Arg Pro Gly Gln Pro Pro Lys Val Lys Ser Glu Phe Asn Ser Tyr
210 215 220
Ser Leu Thr Gly Tyr Val
225 230
<![CDATA[<210> 6]]>
<![CDATA[<211> 220]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人]]>
<![CDATA[<400> 6]]>
Met Ser Met Gly Leu Glu Ile Thr Gly Thr Ala Leu Ala Val Leu Gly
1 5 10 15
Trp Leu Gly Thr Ile Val Cys Cys Ala Leu Pro Met Trp Arg Val Ser
20 25 30
Ala Phe Ile Gly Ser Asn Ile Ile Thr Ser Gln Asn Ile Trp Glu Gly
35 40 45
Leu Trp Met Asn Cys Val Val Gln Ser Thr Gly Gln Met Gln Cys Lys
50 55 60
Val Tyr Asp Ser Leu Leu Ala Leu Pro Gln Asp Leu Gln Ala Ala Arg
65 70 75 80
Ala Leu Ile Val Val Ala Ile Leu Leu Ala Ala Phe Gly Leu Leu Val
85 90 95
Ala Leu Val Gly Ala Gln Cys Thr Asn Cys Val Gln Asp Asp Thr Ala
100 105 110
Lys Ala Lys Ile Thr Ile Val Ala Gly Val Leu Phe Leu Leu Ala Ala
115 120 125
Leu Leu Thr Leu Val Pro Val Ser Trp Ser Ala Asn Thr Ile Ile Arg
130 135 140
Asp Phe Tyr Asn Pro Val Val Pro Glu Ala Gln Lys Arg Glu Met Gly
145 150 155 160
Ala Gly Leu Tyr Val Gly Trp Ala Ala Ala Ala Leu Gln Leu Leu Gly
165 170 175
Gly Ala Leu Leu Cys Cys Ser Cys Pro Pro Arg Glu Lys Lys Tyr Thr
180 185 190
Ala Thr Lys Val Val Tyr Ser Ala Pro Arg Ser Thr Gly Pro Gly Ala
195 200 205
Ser Leu Gly Thr Gly Tyr Asp Arg Lys Asp Tyr Val
210 215 220
<![CDATA[<210> 7]]>
<![CDATA[<211> 209]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人]]>
<![CDATA[<400> 7]]>
Met Ala Ser Met Gly Leu Gln Val Met Gly Ile Ala Leu Ala Val Leu
1 5 10 15
Gly Trp Leu Ala Val Met Leu Cys Cys Ala Leu Pro Met Trp Arg Val
20 25 30
Thr Ala Phe Ile Gly Ser Asn Ile Val Thr Ser Gln Thr Ile Trp Glu
35 40 45
Gly Leu Trp Met Asn Cys Val Val Gln Ser Thr Gly Gln Met Gln Cys
50 55 60
Lys Val Tyr Asp Ser Leu Leu Ala Leu Pro Gln Asp Leu Gln Ala Ala
65 70 75 80
Arg Ala Leu Val Ile Ile Ser Ile Ile Val Ala Ala Leu Gly Val Leu
85 90 95
Leu Ser Val Val Gly Gly Lys Cys Thr Asn Cys Leu Glu Asp Glu Ser
100 105 110
Ala Lys Ala Lys Thr Met Ile Val Ala Gly Val Val Phe Leu Leu Ala
115 120 125
Gly Leu Met Val Ile Val Pro Val Ser Trp Thr Ala His Asn Ile Ile
130 135 140
Gln Asp Phe Tyr Asn Pro Leu Val Ala Ser Gly Gln Lys Arg Glu Met
145 150 155 160
Gly Ala Ser Leu Tyr Val Gly Trp Ala Ala Ser Gly Leu Leu Leu Leu
165 170 175
Gly Gly Gly Leu Leu Cys Cys Asn Cys Pro Pro Arg Thr Asp Lys Pro
180 185 190
Tyr Ser Ala Lys Tyr Ser Ala Ala Arg Ser Ala Ala Ala Ser Asn Tyr
195 200 205
Val
<![CDATA[<210> 8]]>
<![CDATA[<211> 217]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人]]>
<![CDATA[<400> 8]]>
Met Ala Ser Thr Gly Leu Glu Leu Leu Gly Met Thr Leu Ala Val Leu
1 5 10 15
Gly Trp Leu Gly Thr Leu Val Ser Cys Ala Leu Pro Leu Trp Lys Val
20 25 30
Thr Ala Phe Ile Gly Asn Ser Ile Val Val Ala Gln Val Val Trp Glu
35 40 45
Gly Leu Trp Met Ser Cys Val Val Gln Ser Thr Gly Gln Met Gln Cys
50 55 60
Lys Val Tyr Asp Ser Leu Leu Ala Leu Pro Gln Asp Leu Gln Ala Ala
65 70 75 80
Arg Ala Leu Cys Val Ile Ala Leu Leu Leu Ala Leu Leu Gly Leu Leu
85 90 95
Val Ala Ile Thr Gly Ala Gln Cys Thr Thr Cys Val Glu Asp Glu Gly
100 105 110
Ala Lys Ala Arg Ile Val Leu Thr Ala Gly Val Ile Leu Leu Leu Ala
115 120 125
Gly Ile Leu Val Leu Ile Pro Val Cys Trp Thr Ala His Ala Ile Ile
130 135 140
Gln Asp Phe Tyr Asn Pro Leu Val Ala Glu Ala Leu Lys Arg Glu Leu
145 150 155 160
Gly Ala Ser Leu Tyr Leu Gly Trp Ala Ala Ala Ala Leu Leu Met Leu
165 170 175
Gly Gly Gly Leu Leu Cys Cys Thr Cys Pro Pro Pro Gln Val Glu Arg
180 185 190
Pro Arg Gly Pro Arg Leu Gly Tyr Ser Ile Pro Ser Arg Ser Gly Ala
195 200 205
Ser Gly Leu Asp Lys Arg Asp Tyr Val
210 215
<![CDATA[<210> 9]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CLDN-6的E1A]]>
<![CDATA[<400> 9]]>
Met Trp Lys Val Thr Ala Phe Ile Gly Asn Ser
1 5 10
<![CDATA[<210> 10]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CLDN-6的E2B]]>
<![CDATA[<400> 10]]>
Leu Val Ala Glu Ala Gln Lys Arg Glu Leu
1 5 10
<![CDATA[<210> 11]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L的VH]]>
<![CDATA[<400> 11]]>
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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 12]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L的VL]]>
<![CDATA[<400> 12]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys
100 105
<![CDATA[<210> 13]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L的CDR-H1]]>
<![CDATA[<400> 13]]>
Gly Tyr Tyr Met His
1 5
<![CDATA[<210> 14]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L的CDR-H2]]>
<![CDATA[<400> 14]]>
Trp Ile Asn Pro Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 15]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L的CDR-H3]]>
<![CDATA[<400> 15]]>
Asp Ala Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 16]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L的CDR-L1]]>
<![CDATA[<400> 16]]>
Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala
1 5 10
<![CDATA[<210> 17]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L的CDR-L2]]>
<![CDATA[<400> 17]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 18]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L的CDR-L3]]>
<![CDATA[<400> 18]]>
Gln Gln Tyr Gly Ser Ser Pro Leu Thr
1 5
<![CDATA[<210> 19]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L / scFv I2E]]>
<![CDATA[<400> 19]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
245 250
<![CDATA[<210> 20]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L / 雙特異性分子I2E]]>
<![CDATA[<400> 20]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 21]]>
<![CDATA[<211> 985]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L / HLE-BITE I2E]]>
<![CDATA[<400> 21]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala
260 265 270
Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala
275 280 285
Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn
290 295 300
Asn Tyr Ala Thr Tyr Tyr Ala Asp Ala Val Lys Asp Arg Phe Thr Ile
305 310 315 320
Ser Arg Asp Asp Ser Lys Asn Thr Val Tyr Leu Gln Met Asn Asn Leu
325 330 335
Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe
340 345 350
Gly Ser Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu
355 360 365
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
370 375 380
Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val
385 390 395 400
Ser Pro Gly Gly Thr Val Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala
405 410 415
Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Lys Lys Pro Gly Gln
420 425 430
Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr
435 440 445
Pro Ala Arg Phe Ser Gly Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr
450 455 460
Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu
465 470 475 480
Trp Tyr Ser Asn Arg Trp Val Phe Gly Ser Gly Thr Lys Leu Thr Val
485 490 495
Leu Gly Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
500 505 510
Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
515 520 525
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
530 535 540
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
545 550 555 560
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln
565 570 575
Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln
580 585 590
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
595 600 605
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
610 615 620
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr
625 630 635 640
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
645 650 655
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
660 665 670
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
675 680 685
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
690 695 700
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
705 710 715 720
Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly
725 730 735
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro
755 760 765
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
770 775 780
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
785 790 795 800
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
805 810 815
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu
820 825 830
Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His
835 840 845
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
850 855 860
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
865 870 875 880
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met
885 890 895
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
900 905 910
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
915 920 925
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
930 935 940
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
945 950 955 960
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
965 970 975
Lys Ser Leu Ser Leu Ser Pro Gly Lys
980 985
<![CDATA[<210> 22]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L / scFv I2C]]>
<![CDATA[<400> 22]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
245 250
<![CDATA[<210> 23]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L / 雙特異性分子I2C]]>
<![CDATA[<400> 23]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 24]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B6L / HLE BITE I2C]]>
<![CDATA[<400> 24]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 25]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S的VH]]>
<![CDATA[<400> 25]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 26]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S的VL]]>
<![CDATA[<400> 26]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 27]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S的CDR-H1]]>
<![CDATA[<400> 27]]>
Gly Tyr Tyr Val His
1 5
<![CDATA[<210> 28]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S的CDR-H2]]>
<![CDATA[<400> 28]]>
Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 29]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S的CDR-H3]]>
<![CDATA[<400> 29]]>
Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 30]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S的CDR-L1]]>
<![CDATA[<400> 30]]>
Arg Ala Ser Gln Ser Val Arg Ser Thr Tyr Leu Ala
1 5 10
<![CDATA[<210> 31]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S的CDR-L2]]>
<![CDATA[<400> 31]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 32]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S的CDR-L3]]>
<![CDATA[<400> 32]]>
Gln Gln Tyr Asp Ala Ser Pro Ile Thr
1 5
<![CDATA[<210> 33]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S / scFv I2E]]>
<![CDATA[<400> 33]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 34]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S / 雙特異性分子I2E]]>
<![CDATA[<400> 34]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 35]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S / HLE BITE I2E]]>
<![CDATA[<400> 35]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 36]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S / scFv I2C]]>
<![CDATA[<400> 36]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 37]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S / 雙特異性分子I2C]]>
<![CDATA[<400> 37]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 38]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3S / HLE BITE I2C]]>
<![CDATA[<400> 38]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 39]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B的VH]]>
<![CDATA[<400> 39]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 40]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B的VL]]>
<![CDATA[<400> 40]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 41]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B的CDR-H1]]>
<![CDATA[<400> 41]]>
Gly Tyr Tyr Val His
1 5
<![CDATA[<210> 42]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B的CDR-H2]]>
<![CDATA[<400> 42]]>
Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 43]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B的CDR-H3]]>
<![CDATA[<400> 43]]>
Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 44]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B的CDR-L1]]>
<![CDATA[<400> 44]]>
Arg Ala Ser Gln Ser Val Arg Ser Thr Tyr Leu Ala
1 5 10
<![CDATA[<210> 45]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B的CDR-L2]]>
<![CDATA[<400> 45]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 46]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B的CDR-L3]]>
<![CDATA[<400> 46]]>
Gln Gln Tyr Asp Ala Ser Pro Ile Thr
1 5
<![CDATA[<210> 47]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B / scFv I2E]]>
<![CDATA[<400> 47]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 48]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B / 雙特異性分子I2E]]>
<![CDATA[<400> 48]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 49]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B / HLE BITE I2E]]>
<![CDATA[<400> 49]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 50]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B / scFv I2C]]>
<![CDATA[<400> 50]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 51]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B / 雙特異性分子I2C]]>
<![CDATA[<400> 51]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 52]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> L4B / HLE BITE I2C]]>
<![CDATA[<400> 52]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 53]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P的VH]]>
<![CDATA[<400> 53]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 54]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P的VL]]>
<![CDATA[<400> 54]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser
100 105
<![CDATA[<210> 55]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P的CDR-H1]]>
<![CDATA[<400> 55]]>
Gly Tyr Tyr Val His
1 5
<![CDATA[<210> 56]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P的CDR-H2]]>
<![CDATA[<400> 56]]>
Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 57]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P的CDR-H3]]>
<![CDATA[<400> 57]]>
Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 58]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P的CDR-L1]]>
<![CDATA[<400> 58]]>
Arg Ala Ser Gln Ser Val Arg Ser Thr Tyr Leu Ala
1 5 10
<![CDATA[<210> 59]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P的CDR-L2]]>
<![CDATA[<400> 59]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 60]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P的CDR-L3]]>
<![CDATA[<400> 60]]>
Gln Gln Tyr Asp Ala Ser Pro Ile Thr
1 5
<![CDATA[<210> 61]]>
<![CDATA[<211> 253]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P / I2E的scFv]]>
<![CDATA[<400> 61]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser
245 250
<![CDATA[<210> 62]]>
<![CDATA[<211> 508]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P / 雙特異性分子I2E]]>
<![CDATA[<400> 62]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Ser Gly Gly
245 250 255
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
260 265 270
Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
275 280 285
Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
290 295 300
Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr
305 310 315 320
Tyr Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser
325 330 335
Lys Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr
340 345 350
Ala Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile
355 360 365
Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
370 375 380
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln
385 390 395 400
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
405 410 415
Val Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
420 425 430
Tyr Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu
435 440 445
Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser
450 455 460
Gly Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
465 470 475 480
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg
485 490 495
Trp Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 63]]>
<![CDATA[<211> 996]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P / HLE BITE I2E]]>
<![CDATA[<400> 63]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Ser Gly Gly
245 250 255
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
260 265 270
Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
275 280 285
Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
290 295 300
Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr
305 310 315 320
Tyr Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser
325 330 335
Lys Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr
340 345 350
Ala Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile
355 360 365
Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
370 375 380
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln
385 390 395 400
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
405 410 415
Val Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
420 425 430
Tyr Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu
435 440 445
Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser
450 455 460
Gly Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
465 470 475 480
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg
485 490 495
Trp Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly
500 505 510
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
515 520 525
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
530 535 540
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
545 550 555 560
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
565 570 575
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
580 585 590
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
595 600 605
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
610 615 620
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
625 630 635 640
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
645 650 655
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
660 665 670
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
675 680 685
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
690 695 700
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
705 710 715 720
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
725 730 735
Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
740 745 750
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
755 760 765
Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
770 775 780
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
785 790 795 800
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
805 810 815
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
820 825 830
Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr
835 840 845
Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
850 855 860
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
865 870 875 880
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
885 890 895
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
900 905 910
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
915 920 925
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
930 935 940
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
945 950 955 960
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
965 970 975
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
980 985 990
Ser Pro Gly Lys
995
<![CDATA[<210> 64]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P / scFv I2C]]>
<![CDATA[<400> 64]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 65]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P / 雙特異性分子I2C]]>
<![CDATA[<400> 65]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 66]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2P / HLE BITE I2C]]>
<![CDATA[<400> 66]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 67]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N的VH]]>
<![CDATA[<400> 67]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 68]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N的VL]]>
<![CDATA[<400> 68]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 69]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N的CDR-H1]]>
<![CDATA[<400> 69]]>
Gly Tyr Tyr Val His
1 5
<![CDATA[<210> 70]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N的CDR-H2]]>
<![CDATA[<400> 70]]>
Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 71]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N的CDR-H3]]>
<![CDATA[<400> 71]]>
Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 72]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N的CDR-L1]]>
<![CDATA[<400> 72]]>
Arg Ala Ser Gln Ser Val Arg Ser Thr Tyr Leu Ala
1 5 10
<![CDATA[<210> 73]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N的CDR-L2]]>
<![CDATA[<400> 73]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 74]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N的CDR-L3]]>
<![CDATA[<400> 74]]>
Gln Gln Tyr Gln Thr Ser Pro Ile Thr
1 5
<![CDATA[<210> 75]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N / scFv I2E]]>
<![CDATA[<400> 75]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 76]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N / 雙特異性分子I2E]]>
<![CDATA[<400> 76]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 77]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N / HLE BITE I2E]]>
<![CDATA[<400> 77]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 78]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N / scFv I2C]]>
<![CDATA[<400> 78]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 79]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N的 / 雙特異性分子I2C]]>
<![CDATA[<400> 79]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 80]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S3N / HLE BITE I2C]]>
<![CDATA[<400> 80]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 81]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I的VH]]>
<![CDATA[<400> 81]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 82]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I的VL]]>
<![CDATA[<400> 82]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 83]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I的CDR-H1]]>
<![CDATA[<400> 83]]>
Gly Tyr Tyr Val His
1 5
<![CDATA[<210> 84]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I的CDR-H2 ]]>
<![CDATA[<400> 84]]>
Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 85]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I的CDR-H3]]>
<![CDATA[<400> 85]]>
Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 86]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I的CDR-L1]]>
<![CDATA[<400> 86]]>
Arg Ala Ser Gln Ser Val Arg Ser Thr Tyr Leu Ala
1 5 10
<![CDATA[<210> 87]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I的CDR-L2]]>
<![CDATA[<400> 87]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 88]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I的CDR-L3]]>
<![CDATA[<400> 88]]>
Gln Gln Tyr Asp Ala Ser Pro Ile Thr
1 5
<![CDATA[<210> 89]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I / scFv I2E]]>
<![CDATA[<400> 89]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 90]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I / 雙特異性分子I2E]]>
<![CDATA[<400> 90]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 91]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I / HLE BITE I2E]]>
<![CDATA[<400> 91]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 92]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I / scFv I2C]]>
<![CDATA[<400> 92]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 93]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I / 雙特異性分子I2C]]>
<![CDATA[<400> 93]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 94]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H7I / HLE BITE I2C]]>
<![CDATA[<400> 94]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 95]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I的VH]]>
<![CDATA[<400> 95]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 96]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I的VL]]>
<![CDATA[<400> 96]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 97]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I的CDR-H1]]>
<![CDATA[<400> 97]]>
Gly Tyr Tyr Val His
1 5
<![CDATA[<210> 98]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I的CDR-H2]]>
<![CDATA[<400> 98]]>
Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 99]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I的CDR-H3]]>
<![CDATA[<400> 99]]>
Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 100]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I的CDR-L1]]>
<![CDATA[<400> 100]]>
Arg Ala Ser Gln Ser Val Arg Ser Thr Tyr Leu Ala
1 5 10
<![CDATA[<210> 101]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I的CDR-L2]]>
<![CDATA[<400> 101]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 102]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I的CDR-L3]]>
<![CDATA[<400> 102]]>
Gln Gln Tyr Gln Thr Ser Pro Ile Thr
1 5
<![CDATA[<210> 103]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I / scFv I2E]]>
<![CDATA[<400> 103]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 104]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I / 雙特異性分子I2E]]>
<![CDATA[<400> 104]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 105]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I / HLE BITE I2E]]>
<![CDATA[<400> 105]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 106]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I / scFv I2C]]>
<![CDATA[<400> 106]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 107]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I / 雙特異性分子I2C]]>
<![CDATA[<400> 107]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 108]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> J2I / HLE BITE I2C]]>
<![CDATA[<400> 108]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Arg Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 109]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A4K的VH]]>
<![CDATA[<400> 109]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 110]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A4K的VL]]>
<![CDATA[<400> 110]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 111]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A4K的CDR-H1]]>
<![CDATA[<400> 111]]>
Gly Tyr Tyr Val His
1 5
<![CDATA[<210> 112]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A4K的CDR-H2]]>
<![CDATA[<400> 112]]>
Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 113]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A4K的CDR-H3]]>
<![CDATA[<400> 113]]>
Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 114]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A4K的CDR-L1]]>
<![CDATA[<400> 114]]>
Arg Ala Ser Gln Ser Val Arg Ser Thr Tyr Leu Ala
1 5 10
<![CDATA[<210> 115]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> A4K的CDR-L2]]>
<![CDATA[<400> 115]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 116]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A4K的CDR-L3]]>
<![CDATA[<400> 116]]>
Gln Gln Tyr Asp Ala Ser Pro Ile Thr
1 5
<![CDATA[<210> 117]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A4K / scFv I2E]]>
<![CDATA[<400> 117]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 118]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A4K / 雙特異性分子I2E]]>
<![CDATA[<400> 118]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 119]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A4K / HLE-BITE I2E]]>
<![CDATA[<400> 119]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 120]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A4K / scFv I2C]]>
<![CDATA[<400> 120]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 121]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A4K / 雙特異性分子I2C]]>
<![CDATA[<400> 121]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 122]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A4K / HLE BITE I2C]]>
<![CDATA[<400> 122]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 123]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B的VH]]>
<![CDATA[<400> 123]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 124]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B的VL]]>
<![CDATA[<400> 124]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 125]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B的CDR-H1]]>
<![CDATA[<400> 125]]>
Gly Tyr Tyr Val His
1 5
<![CDATA[<210> 126]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B的CDR-H2]]>
<![CDATA[<400> 126]]>
Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 127]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B的CDR-H3]]>
<![CDATA[<400> 127]]>
Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 128]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B的CDR-L1]]>
<![CDATA[<400> 128]]>
Arg Ala Ser Gln Ser Val Arg Ser Thr Tyr Leu Ala
1 5 10
<![CDATA[<210> 129]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B的CDR-L2]]>
<![CDATA[<400> 129]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 130]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B的CDR-L3]]>
<![CDATA[<400> 130]]>
Gln Gln Tyr Gln Thr Ser Pro Ile Thr
1 5
<![CDATA[<210> 131]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B / scFv I2E]]>
<![CDATA[<400> 131]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 132]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B / 雙特異性分子I2E]]>
<![CDATA[<400> 132]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 133]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B / HLE-BITE I2E]]>
<![CDATA[<400> 133]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 134]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B / scFv I2C]]>
<![CDATA[<400> 134]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 135]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B / 雙特異性分子I2C]]>
<![CDATA[<400> 135]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 136]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E5B / HLE BITE I2C]]>
<![CDATA[<400> 136]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gln Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 137]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> RBB的VH]]>
<![CDATA[<400> 137]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 138]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> RBB的VL]]>
<![CDATA[<400> 138]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ile Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 139]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> RBB的CDR-H1]]>
<![CDATA[<400> 139]]>
Gly Tyr Tyr Val His
1 5
<![CDATA[<210> 140]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> RBB的CDR-H2]]>
<![CDATA[<400> 140]]>
Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 141]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> RBB的CDR-H3]]>
<![CDATA[<400> 141]]>
Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 142]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> RBB的CDR-L1]]>
<![CDATA[<400> 142]]>
Arg Ala Ser Gln Ser Val Arg Ser Thr Tyr Leu Ala
1 5 10
<![CDATA[<210> 143]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> RBB的CDR-L2 ]]>
<![CDATA[<400> 143]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 144]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> RBB的CDR-L3]]>
<![CDATA[<400> 144]]>
Gln Gln Tyr Asp Ala Ser Pro Ile Thr
1 5
<![CDATA[<210> 145]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> RBB / scFv I2E]]>
<![CDATA[<400> 145]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ile Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 146]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> RBB / 雙特異性分子I2E]]>
<![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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ile Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 147]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> RBB / HLE-BITE I2E]]>
<![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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ile Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 148]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> RBB / scFv I2C]]>
<![CDATA[<400> 148]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ile Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 149]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> RBB / 雙特異性分子I2C]]>
<![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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ile Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 150]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> RBB / HLE BITE I2C]]>
<![CDATA[<400> 150]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Ala Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ile Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Ala Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 151]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> IX9的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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser
115 120 125
Ser
<![CDATA[<210> 152]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> IX9的VL]]>
<![CDATA[<400> 152]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 153]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> IX9的CDR-H1]]>
<![CDATA[<400> 153]]>
Gly Tyr Tyr Met His
1 5
<![CDATA[<210> 154]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> IX9的CDR-H2]]>
<![CDATA[<400> 154]]>
Trp Ile Asn Pro Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 155]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> IX9的CDR-H3]]>
<![CDATA[<400> 155]]>
Asp Ala Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 156]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> IX9的CDR-L1]]>
<![CDATA[<400> 156]]>
Arg Ala Ser Gln Thr Val Ser Ser Ser Tyr Leu Val
1 5 10
<![CDATA[<210> 157]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> IX9的CDR-L2]]>
<![CDATA[<400> 157]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 158]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> IX9的CDR-L3]]>
<![CDATA[<400> 158]]>
Gln Gln Tyr Gly Gly Ser Pro Ile Thr
1 5
<![CDATA[<210> 159]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> IX9 / scFv I2E]]>
<![CDATA[<400> 159]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser
245 250
<![CDATA[<210> 160]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> IX9 / 雙特異性分子I2E]]>
<![CDATA[<400> 160]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 161]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> IX9 / HLE-BITE I2E]]>
<![CDATA[<400> 161]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 162]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> IX9 / scFv I2C]]>
<![CDATA[<400> 162]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser
245 250
<![CDATA[<210> 163]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> IX9 / 雙特異性分子I2C]]>
<![CDATA[<400> 163]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 164]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> IX9 / HLE BITE I2C]]>
<![CDATA[<400> 164]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 165]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X的VH]]>
<![CDATA[<400> 165]]>
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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 166]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X的VL]]>
<![CDATA[<400> 166]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 167]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X的CDR-H1]]>
<![CDATA[<400> 167]]>
Gly Tyr Tyr Met His
1 5
<![CDATA[<210> 168]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X的CDR-H2]]>
<![CDATA[<400> 168]]>
Trp Ile Asn Pro Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 169]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X的CDR-H3]]>
<![CDATA[<400> 169]]>
Asp Ala Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 170]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X的CDR-L1]]>
<![CDATA[<400> 170]]>
Arg Ala Ser Gln Thr Val Ser Ser Ser Tyr Leu Val
1 5 10
<![CDATA[<210> 171]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X的CDR-L2]]>
<![CDATA[<400> 171]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 172]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X的CDR-L3]]>
<![CDATA[<400> 172]]>
Gln Gln Tyr Gly Gly Ser Pro Ile Thr
1 5
<![CDATA[<210> 173]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X / scFv I2E]]>
<![CDATA[<400> 173]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
245 250
<![CDATA[<210> 174]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X / 雙特異性分子I2E]]>
<![CDATA[<400> 174]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 175]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X / HLE-BITE I2E]]>
<![CDATA[<400> 175]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 176]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X / scFv I2C]]>
<![CDATA[<400> 176]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
245 250
<![CDATA[<210> 177]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X / 雙特異性分子I2C]]>
<![CDATA[<400> 177]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 178]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G5X / HLE BITE I2C]]>
<![CDATA[<400> 178]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 179]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C的VH]]>
<![CDATA[<400> 179]]>
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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Asn Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser
115 120 125
Ser
<![CDATA[<210> 180]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C的VL]]>
<![CDATA[<400> 180]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 181]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C的CDR-H1]]>
<![CDATA[<400> 181]]>
Gly Tyr Tyr Met His
1 5
<![CDATA[<210> 182]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C的CDR-H2]]>
<![CDATA[<400> 182]]>
Trp Ile Asn Pro Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 183]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C的CDR-H3]]>
<![CDATA[<400> 183]]>
Asp Asn Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 184]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C的CDR-L1]]>
<![CDATA[<400> 184]]>
Arg Ala Ser Gln Thr Val Ser Ser Ser Tyr Leu Val
1 5 10
<![CDATA[<210> 185]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C的CDR-L2]]>
<![CDATA[<400> 185]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 186]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C的CDR-L3]]>
<![CDATA[<400> 186]]>
Gln Gln Tyr Gly Gly Ser Pro Ile Thr
1 5
<![CDATA[<210> 187]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C / scFv I2E]]>
<![CDATA[<400> 187]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser
245 250
<![CDATA[<210> 188]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C / 雙特異性分子I2E]]>
<![CDATA[<400> 188]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 189]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C / HLE-BITE I2E]]>
<![CDATA[<400> 189]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 190]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C / scFv I2C]]>
<![CDATA[<400> 190]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser
245 250
<![CDATA[<210> 191]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C / 雙特異性分子I2C]]>
<![CDATA[<400> 191]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser
245 250
<![CDATA[<210> 192]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> O1C的 / HLE-BITE I2C]]>
<![CDATA[<400> 192]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 193]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S的VH]]>
<![CDATA[<400> 193]]>
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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Asn Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 194]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S的VL]]>
<![CDATA[<400> 194]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys
100 105
<![CDATA[<210> 195]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S的CDR-H1]]>
<![CDATA[<400> 195]]>
Gly Tyr Tyr Met His
1 5
<![CDATA[<210> 196]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S的CDR-H2]]>
<![CDATA[<400> 196]]>
Trp Ile Asn Pro Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 197]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S的CDR-H3]]>
<![CDATA[<400> 197]]>
Asp Asn Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 198]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S的CDR-L1]]>
<![CDATA[<400> 198]]>
Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala
1 5 10
<![CDATA[<210> 199]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S的CDR-L2]]>
<![CDATA[<400> 199]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 200]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S的CDR-L3]]>
<![CDATA[<400> 200]]>
Gln Gln Tyr Gly Ser Ser Pro Leu Thr
1 5
<![CDATA[<210> 201]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S / scFv I2E]]>
<![CDATA[<400> 201]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
245 250
<![CDATA[<210> 202]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S / 雙特異性分子I2E]]>
<![CDATA[<400> 202]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 203]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S / HLE-BITE I2E]]>
<![CDATA[<400> 203]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 204]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S / scFv I2C]]>
<![CDATA[<400> 204]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
245 250
<![CDATA[<210> 205]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S / 雙特異性分子I2C]]>
<![CDATA[<400> 205]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 206]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A3S / HLE BITE I2C]]>
<![CDATA[<400> 206]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Glu Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 207]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J的VH]]>
<![CDATA[<400> 207]]>
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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Asn Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 208]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J的VL]]>
<![CDATA[<400> 208]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 209]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J的CDR-H1]]>
<![CDATA[<400> 209]]>
Gly Tyr Tyr Met His
1 5
<![CDATA[<210> 210]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J的CDR-H2]]>
<![CDATA[<400> 210]]>
Trp Ile Asn Pro Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 211]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J的CDR-H3]]>
<![CDATA[<400> 211]]>
Asp Asn Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 212]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J的CDR-L1]]>
<![CDATA[<400> 212]]>
Arg Ala Ser Gln Thr Val Ser Ser Ser Tyr Leu Val
1 5 10
<![CDATA[<210> 213]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J的CDR-L2]]>
<![CDATA[<400> 213]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 214]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J的CDR-L3]]>
<![CDATA[<400> 214]]>
Gln Gln Tyr Gly Gly Ser Pro Ile Thr
1 5
<![CDATA[<210> 215]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J / scFv I2E]]>
<![CDATA[<400> 215]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
245 250
<![CDATA[<210> 216]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J / 雙特異性分子I2E]]>
<![CDATA[<400> 216]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 217]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J / HLE-BITE I2E]]>
<![CDATA[<400> 217]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 218]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J / scFv I2C]]>
<![CDATA[<400> 218]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
245 250
<![CDATA[<210> 219]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J / 雙特異性分子I2C]]>
<![CDATA[<400> 219]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 220]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B2J / HLE BITE I2C]]>
<![CDATA[<400> 220]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 221]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E的VH]]>
<![CDATA[<400> 221]]>
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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Asn Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 222]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E的VL]]>
<![CDATA[<400> 222]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys
100 105
<![CDATA[<210> 223]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E的CDR-H1]]>
<![CDATA[<400> 223]]>
Gly Tyr Tyr Met His
1 5
<![CDATA[<210> 224]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E的CDR-H2]]>
<![CDATA[<400> 224]]>
Trp Ile Asn Pro Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 225]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E的CDR-H3]]>
<![CDATA[<400> 225]]>
Asp Asn Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 226]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E的CDR-L1]]>
<![CDATA[<400> 226]]>
Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala
1 5 10
<![CDATA[<210> 227]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E的CDR-L2]]>
<![CDATA[<400> 227]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 228]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E的CDR-L3]]>
<![CDATA[<400> 228]]>
Gln Gln Tyr Gly Ser Ser Pro Leu Thr
1 5
<![CDATA[<210> 229]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E / scFv I2E]]>
<![CDATA[<400> 229]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
245 250
<![CDATA[<210> 230]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E / 雙特異性分子I2E]]>
<![CDATA[<400> 230]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 231]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E / HLE-BITE I2E]]>
<![CDATA[<400> 231]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 232]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E / scFv I2C]]>
<![CDATA[<400> 232]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
245 250
<![CDATA[<210> 233]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E的 / 雙特異性分子I2C]]>
<![CDATA[<400> 233]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 234]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M5E / HLE BITE I2C]]>
<![CDATA[<400> 234]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Asn Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 235]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A的VH]]>
<![CDATA[<400> 235]]>
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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser
115 120 125
Ser
<![CDATA[<210> 236]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A的VL]]>
<![CDATA[<400> 236]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 237]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A的CDR-H1]]>
<![CDATA[<400> 237]]>
Gly Tyr Tyr Met His
1 5
<![CDATA[<210> 238]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A的CDR-H2 ]]>
<![CDATA[<400> 238]]>
Trp Ile Asn Pro Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 239]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A的CDR-H3]]>
<![CDATA[<400> 239]]>
Asp Ala Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 240]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A的CDR-L1]]>
<![CDATA[<400> 240]]>
Arg Ala Ser Gln Thr Val Ser Ser Ser Tyr Leu Val
1 5 10
<![CDATA[<210> 241]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A的CDR-L2]]>
<![CDATA[<400> 241]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 242]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A的CDR-L3]]>
<![CDATA[<400> 242]]>
Gln Gln Tyr Gly Gly Ser Pro Ile Thr
1 5
<![CDATA[<210> 243]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A / scFv I2E]]>
<![CDATA[<400> 243]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser
245 250
<![CDATA[<210> 244]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A / 雙特異性分子I2E]]>
<![CDATA[<400> 244]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 245]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A / HLE-BITE I2E]]>
<![CDATA[<400> 245]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 246]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A / scFv I2C]]>
<![CDATA[<400> 246]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser
245 250
<![CDATA[<210> 247]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A的 / 雙特異性分子I2C]]>
<![CDATA[<400> 247]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 248]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> X3A /HLE BITE I2C]]>
<![CDATA[<400> 248]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 249]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S9W的VH]]>
<![CDATA[<400> 249]]>
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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser
115 120 125
Ser
<![CDATA[<210> 250]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S9W的VL]]>
<![CDATA[<400> 250]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys
100 105
<![CDATA[<210> 251]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S9W的CDR-H1]]>
<![CDATA[<400> 251]]>
Gly Tyr Tyr Met His
1 5
<![CDATA[<210> 252]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S9W的CDR-H2]]>
<![CDATA[<400> 252]]>
Trp Ile Asn Pro Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 253]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S9W的CDR-H3]]>
<![CDATA[<400> 253]]>
Asp Ala Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 254]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S9W的CDR-L1]]>
<![CDATA[<400> 254]]>
Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala
1 5 10
<![CDATA[<210> 255]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S9W的CDR-L2]]>
<![CDATA[<400> 255]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 256]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S9W的CDR-L3]]>
<![CDATA[<400> 256]]>
Gln Gln Tyr Gly Ser Ser Pro Leu Thr
1 5
<![CDATA[<210> 257]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S9W / scFv I2E]]>
<![CDATA[<400> 257]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser
245 250
<![CDATA[<210> 258]]>
<![CDATA[<400> 258]]>
000
<![CDATA[<210> 259]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S9W / HLE-BITE I2E]]>
<![CDATA[<400> 259]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 260]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S9W / scFv I2C]]>
<![CDATA[<400> 260]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser
245 250
<![CDATA[<210> 261]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S9W / 雙特異性分子I2C]]>
<![CDATA[<400> 261]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 262]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S9W / HLE BITE I2C]]>
<![CDATA[<400> 262]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Leu Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ala Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 263]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L的VH]]>
<![CDATA[<400> 263]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Gly Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser
<![CDATA[<210> 264]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L的VL]]>
<![CDATA[<400> 264]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Thr Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 265]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L的CDR-H1]]>
<![CDATA[<400> 265]]>
Gly Tyr Tyr Val His
1 5
<![CDATA[<210> 266]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L的CDR-H2]]>
<![CDATA[<400> 266]]>
Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 267]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L的CDR-H3]]>
<![CDATA[<400> 267]]>
Asp Gly Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 268]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L的CDR-L1]]>
<![CDATA[<400> 268]]>
Arg Ala Ser Gln Ser Val Arg Ser Thr Tyr Leu Ala
1 5 10
<![CDATA[<210> 269]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L的CDR-L2]]>
<![CDATA[<400> 269]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 270]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L的CDR-L3]]>
<![CDATA[<400> 270]]>
Gln Gln Tyr Asp Thr Ser Pro Ile Thr
1 5
<![CDATA[<210> 271]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L / scFv I2E]]>
<![CDATA[<400> 271]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Gly Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 272]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L / 雙特異性分子I2E]]>
<![CDATA[<400> 272]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Gly Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 273]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L / HLE-BITE I2E]]>
<![CDATA[<400> 273]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Gly Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 274]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L / scFv I2C]]>
<![CDATA[<400> 274]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Gly Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
245 250
<![CDATA[<210> 275]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L / 雙特異性分子I2C]]>
<![CDATA[<400> 275]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Gly Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 276]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I7L / HLE BITE I2C]]>
<![CDATA[<400> 276]]>
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 Gly Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Val Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Gly Leu Ile Val Glu Ala Pro Ala Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
145 150 155 160
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Thr
165 170 175
Tyr Leu Ala Trp Tyr Gln Gln Thr Pro Gly Gln Ala Pro Arg Leu Leu
180 185 190
Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
195 200 205
Gly Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Ser Arg Leu Glu
210 215 220
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asp Thr Ser Pro
225 230 235 240
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 277]]>
<![CDATA[<211> 129]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F的VH]]>
<![CDATA[<400> 277]]>
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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr
100 105 110
Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser
115 120 125
Ser
<![CDATA[<210> 278]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F的VL]]>
<![CDATA[<400> 278]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys
100 105
<![CDATA[<210> 279]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F的CDR-H1]]>
<![CDATA[<400> 279]]>
Gly Tyr Tyr Met His
1 5
<![CDATA[<210> 280]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F的CDR-H2]]>
<![CDATA[<400> 280]]>
Trp Ile Asn Pro Asn Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 281]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F的CDR-H3]]>
<![CDATA[<400> 281]]>
Asp Gly Leu Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 282]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F的CDR-L1]]>
<![CDATA[<400> 282]]>
Arg Ala Ser Gln Thr Val Ser Ser Ser Tyr Leu Val
1 5 10
<![CDATA[<210> 283]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F的CDR-L2]]>
<![CDATA[<400> 283]]>
Gly Ala Ser Ser Arg Ala Thr
1 5
<![CDATA[<210> 284]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F的CDR-L3]]>
<![CDATA[<400> 284]]>
Gln Gln Tyr Gly Gly Ser Pro Ile Thr
1 5
<![CDATA[<210> 285]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F / SCFV I2E]]>
<![CDATA[<400> 285]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Gly Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser
245 250
<![CDATA[<210> 286]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F / 雙特異性分子I2E]]>
<![CDATA[<400> 286]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Gly Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 287]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F / HLE-BITE I2E]]>
<![CDATA[<400> 287]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Gly Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 288]]>
<![CDATA[<211> 252]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F / scFv I2C]]>
<![CDATA[<400> 288]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Gly Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser
245 250
<![CDATA[<210> 289]]>
<![CDATA[<211> 507]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F / 雙特異性分子I2C]]>
<![CDATA[<400> 289]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Gly Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 290]]>
<![CDATA[<211> 995]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W5F / HLE BITE I2C]]>
<![CDATA[<400> 290]]>
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Ser Ser
20 25 30
Tyr Leu Val Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ile Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Gly Ser Pro
85 90 95
Ile Thr Phe Gly Cys Gly Thr Arg Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Ile Asn Pro
165 170 175
Asn Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Gly Leu
210 215 220
Ile Val Val Ala Pro Val Thr Arg Asp Tyr Tyr Tyr Tyr Gly Met Asp
225 230 235 240
Val Trp Gly Gln Gly Thr Thr Val Thr Ala Ser Ser Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp
500 505 510
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
515 520 525
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
530 535 540
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
545 550 555 560
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
565 570 575
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
580 585 590
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
595 600 605
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
610 615 620
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
625 630 635 640
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
645 650 655
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
660 665 670
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
675 680 685
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
690 695 700
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
705 710 715 720
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
725 730 735
Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
770 775 780
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
785 790 795 800
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
805 810 815
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
820 825 830
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
835 840 845
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
850 855 860
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
865 870 875 880
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
885 890 895
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
900 905 910
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
915 920 925
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
930 935 940
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
945 950 955 960
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
965 970 975
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
980 985 990
Pro Gly Lys
995
<![CDATA[<210> 291]]>
<![CDATA[<211> 126]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y的VH]]>
<![CDATA[<400> 291]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Tyr Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 292]]>
<![CDATA[<211> 110]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y的VL]]>
<![CDATA[<400> 292]]>
Gln Ser Ala Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Val Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr
20 25 30
Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser
85 90 95
Asn Asn Phe Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
100 105 110
<![CDATA[<210> 293]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y的CDR-H1]]>
<![CDATA[<400> 293]]>
Asp Tyr His Met His
1 5
<![CDATA[<210> 294]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y的CDR-H2]]>
<![CDATA[<400> 294]]>
Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 295]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y的CDR-H3]]>
<![CDATA[<400> 295]]>
Asp Tyr Tyr Ser Ser Ser Tyr Thr Leu Tyr Tyr Tyr Tyr Gly Met Asp
1 5 10 15
Val
<![CDATA[<210> 296]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y的CDR-L1]]>
<![CDATA[<400> 296]]>
Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser
1 5 10
<![CDATA[<210> 297]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y的CDR-L2]]>
<![CDATA[<400> 297]]>
Glu Val Ser Lys Arg Pro Ser
1 5
<![CDATA[<210> 298]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y的CDR-L3]]>
<![CDATA[<400> 298]]>
Ser Ser Tyr Ala Gly Ser Asn Asn Phe Val
1 5 10
<![CDATA[<210> 299]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y / scFv I2E]]>
<![CDATA[<400> 299]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Tyr Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 300]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y / 雙特異性分子I2E]]>
<![CDATA[<400> 300]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Tyr Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 301]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y / HLE-BITE I2E]]>
<![CDATA[<400> 301]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Tyr Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 302]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y / scFv I2C]]>
<![CDATA[<400> 302]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Tyr Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 303]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y / 雙特異性分子I2C]]>
<![CDATA[<400> 303]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Tyr Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 304]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> K4Y / HLE BITE I2C]]>
<![CDATA[<400> 304]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Tyr Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 305]]>
<![CDATA[<211> 126]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B的VH]]>
<![CDATA[<400> 305]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 306]]>
<![CDATA[<211> 110]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B的VL]]>
<![CDATA[<400> 306]]>
Gln Ser Ala Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Val Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr
20 25 30
Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser
85 90 95
Asn Asn Phe Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
100 105 110
<![CDATA[<210> 307]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B的CDR-H1]]>
<![CDATA[<400> 307]]>
Asp Tyr His Met His
1 5
<![CDATA[<210> 308]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B的CDR-H2]]>
<![CDATA[<400> 308]]>
Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 309]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B的CDR-H3]]>
<![CDATA[<400> 309]]>
Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly Met Asp
1 5 10 15
Val
<![CDATA[<210> 310]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B的CDR-L1]]>
<![CDATA[<400> 310]]>
Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser
1 5 10
<![CDATA[<210> 311]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B的CDR-L2 ]]>
<![CDATA[<400> 311]]>
Glu Val Ser Lys Arg Pro Ser
1 5
<![CDATA[<210> 312]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B的CDR-L3 ]]>
<![CDATA[<400> 312]]>
Ser Ser Tyr Ala Gly Ser Asn Asn Phe Val
1 5 10
<![CDATA[<210> 313]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B / scFv I2E]]>
<![CDATA[<400> 313]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 314]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B / 雙特異性分子I2E]]>
<![CDATA[<400> 314]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 315]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B / HLE BITE I2E]]>
<![CDATA[<400> 315]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 316]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B / scFv I2C]]>
<![CDATA[<400> 316]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 317]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B / 雙特異性分子I2C]]>
<![CDATA[<400> 317]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 318]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> M4B / HLE BITE I2C]]>
<![CDATA[<400> 318]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 319]]>
<![CDATA[<211> 126]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G的VH]]>
<![CDATA[<400> 319]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 320]]>
<![CDATA[<211> 110]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G的VL]]>
<![CDATA[<400> 320]]>
Gln Ser Ala Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Val Thr Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr
20 25 30
Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser
85 90 95
Asn Asn Phe Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
100 105 110
<![CDATA[<210> 321]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G的CDR-H1]]>
<![CDATA[<400> 321]]>
Asp Tyr His Met His
1 5
<![CDATA[<210> 322]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G的CDR-H2 ]]>
<![CDATA[<400> 322]]>
Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 323]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G的CDR-H3 ]]>
<![CDATA[<400> 323]]>
Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly Met Asp
1 5 10 15
Val
<![CDATA[<210> 324]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G的CDR-L1 ]]>
<![CDATA[<400> 324]]>
Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser
1 5 10
<![CDATA[<210> 325]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G的CDR-L2 ]]>
<![CDATA[<400> 325]]>
Glu Val Ser Lys Arg Pro Ser
1 5
<![CDATA[<210> 326]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G的CDR-L3]]>
<![CDATA[<400> 326]]>
Ser Ser Tyr Ala Gly Ser Asn Asn Phe Val
1 5 10
<![CDATA[<210> 327]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G / scFv I2E]]>
<![CDATA[<400> 327]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 328]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G / 雙特異性分子I2E]]>
<![CDATA[<400> 328]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 329]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G / HLE-BITE I2E]]>
<![CDATA[<400> 329]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 330]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G / scFv I2C]]>
<![CDATA[<400> 330]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 331]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G / 雙特異性分子I2C]]>
<![CDATA[<400> 331]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 332]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B4G / HLE BITE I2C]]>
<![CDATA[<400> 332]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ala Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 333]]>
<![CDATA[<211> 126]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B的VH]]>
<![CDATA[<400> 333]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 334]]>
<![CDATA[<211> 110]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B的VL]]>
<![CDATA[<400> 334]]>
Gln Ser Ala Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Val Thr Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr
20 25 30
Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser
85 90 95
Asn Asn Phe Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
100 105 110
<![CDATA[<210> 335]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B的CDR-H1 ]]>
<![CDATA[<400> 335]]>
Asp Tyr His Met His
1 5
<![CDATA[<210> 336]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B的CDR-H2]]>
<![CDATA[<400> 336]]>
Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 337]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B的CDR-H3 ]]>
<![CDATA[<400> 337]]>
Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly Met Asp
1 5 10 15
Val
<![CDATA[<210> 338]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B的CDR-L1 ]]>
<![CDATA[<400> 338]]>
Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser
1 5 10
<![CDATA[<210> 339]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B的CDR-L2 ]]>
<![CDATA[<400> 339]]>
Glu Val Ser Lys Arg Pro Ser
1 5
<![CDATA[<210> 340]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B的CDR-L3]]>
<![CDATA[<400> 340]]>
Ser Ser Tyr Ala Gly Ser Asn Asn Phe Val
1 5 10
<![CDATA[<210> 341]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B 7 scFv I2E]]>
<![CDATA[<400> 341]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 342]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B / 雙特異性分子I2E]]>
<![CDATA[<400> 342]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 343]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B / HLE-BITE I2E]]>
<![CDATA[<400> 343]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 344]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B / scFv I2C]]>
<![CDATA[<400> 344]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 345]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B / 雙特異性分子I2C]]>
<![CDATA[<400> 345]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 346]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> U8B / HLE BITE I2C]]>
<![CDATA[<400> 346]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 347]]>
<![CDATA[<211> 126]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G的VH]]>
<![CDATA[<400> 347]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 348]]>
<![CDATA[<211> 110]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G的VL]]>
<![CDATA[<400> 348]]>
Gln Ser Ala Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Val Thr Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr
20 25 30
Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser
85 90 95
Asn Asn Phe Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
100 105 110
<![CDATA[<210> 349]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G的CDR-H1 ]]>
<![CDATA[<400> 349]]>
Asp Tyr His Met His
1 5
<![CDATA[<210> 350]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G的CDR-H2]]>
<![CDATA[<400> 350]]>
Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 351]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G的CDR-H3]]>
<![CDATA[<400> 351]]>
Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly Met Asp
1 5 10 15
Val
<![CDATA[<210> 352]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G的CDR-L1]]>
<![CDATA[<400> 352]]>
Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser
1 5 10
<![CDATA[<210> 353]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G的CDR-L2]]>
<![CDATA[<400> 353]]>
Glu Val Ser Lys Arg Pro Ser
1 5
<![CDATA[<210> 354]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G的CDR-L3 ]]>
<![CDATA[<400> 354]]>
Ser Ser Tyr Ala Gly Ser Asn Asn Phe Val
1 5 10
<![CDATA[<210> 355]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G / scFv I2E]]>
<![CDATA[<400> 355]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 356]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G / 雙特異性分子I2E]]>
<![CDATA[<400> 356]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 357]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G / HLE-BITE I2E]]>
<![CDATA[<400> 357]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 358]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G / scFv I2C]]>
<![CDATA[<400> 358]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 359]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G / 雙特異性分子I2C]]>
<![CDATA[<400> 359]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 360]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Y8G / HLE BITE I2C]]>
<![CDATA[<400> 360]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 361]]>
<![CDATA[<211> 126]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B的VH ]]>
<![CDATA[<400> 361]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 362]]>
<![CDATA[<211> 110]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B的VL ]]>
<![CDATA[<400> 362]]>
Gln Ser Ala Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Val Thr Ile Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr
20 25 30
Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser
85 90 95
Asn Asn Phe Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
100 105 110
<![CDATA[<210> 363]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B的CDR-H1 ]]>
<![CDATA[<400> 363]]>
Asp Tyr His Met His
1 5
<![CDATA[<210> 364]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B的CDR-H3 ]]>
<![CDATA[<400> 364]]>
Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 365]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B的CDR-H3 ]]>
<![CDATA[<400> 365]]>
Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly Met Asp
1 5 10 15
Val
<![CDATA[<210> 366]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B的CDR-L1]]>
<![CDATA[<400> 366]]>
Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser
1 5 10
<![CDATA[<210> 367]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B的CDR-L2 ]]>
<![CDATA[<400> 367]]>
Glu Val Ser Lys Arg Pro Ser
1 5
<![CDATA[<210> 368]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B的CDR-L3]]>
<![CDATA[<400> 368]]>
Ser Ser Tyr Ala Gly Ser Asn Asn Phe Val
1 5 10
<![CDATA[<210> 369]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B / scFv I2E]]>
<![CDATA[<400> 369]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 370]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B / 雙特異性分子I2E]]>
<![CDATA[<400> 370]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 371]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B / HLE BITE I2E]]>
<![CDATA[<400> 371]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 372]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B / scFv I2C]]>
<![CDATA[<400> 372]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 373]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B / 雙特異性分子I2C]]>
<![CDATA[<400> 373]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 374]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G8B / HLE BITE I2C]]>
<![CDATA[<400> 374]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 375]]>
<![CDATA[<211> 126]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B的VH]]>
<![CDATA[<400> 375]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 376]]>
<![CDATA[<211> 110]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B的VL]]>
<![CDATA[<400> 376]]>
Gln Ser Ala Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Val Thr Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr
20 25 30
Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser
85 90 95
Asn Asn Phe Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
100 105 110
<![CDATA[<210> 377]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B的CDR-H1]]>
<![CDATA[<400> 377]]>
Asp Tyr His Met His
1 5
<![CDATA[<210> 378]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B的CDR-H2]]>
<![CDATA[<400> 378]]>
Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 379]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B的CDR-H3]]>
<![CDATA[<400> 379]]>
Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly Met Asp
1 5 10 15
Val
<![CDATA[<210> 380]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B的CDR-L1]]>
<![CDATA[<400> 380]]>
Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser
1 5 10
<![CDATA[<210> 381]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B的CDR-L2]]>
<![CDATA[<400> 381]]>
Glu Val Ser Lys Arg Pro Ser
1 5
<![CDATA[<210> 382]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B的CDR-L3]]>
<![CDATA[<400> 382]]>
Ser Ser Tyr Ala Gly Ser Asn Asn Phe Val
1 5 10
<![CDATA[<210> 383]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B / scFv I2E]]>
<![CDATA[<400> 383]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 384]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B / 雙特異性分子I2E]]>
<![CDATA[<400> 384]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 385]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B / HLE BITE I2E]]>
<![CDATA[<400> 385]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 386]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B / scFv I2C]]>
<![CDATA[<400> 386]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 387]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B / 雙特異性分子I2C]]>
<![CDATA[<400> 387]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 388]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> W9B / HLE BITE I2C]]>
<![CDATA[<400> 388]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 389]]>
<![CDATA[<211> 126]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A9G的VH]]>
<![CDATA[<400> 389]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 390]]>
<![CDATA[<211> 110]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A9G的VL]]>
<![CDATA[<400> 390]]>
Gln Ser Ala Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Val Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr
20 25 30
Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser
85 90 95
Asn Asn Phe Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
100 105 110
<![CDATA[<210> 391]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CDR-H1 of A9G的]]>
<![CDATA[<400> 391]]>
Asp Tyr His Met His
1 5
<![CDATA[<210> 392]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A9G的CDR-H2]]>
<![CDATA[<400> 392]]>
Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 393]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A9G的CDR-H3]]>
<![CDATA[<400> 393]]>
Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly Met Asp
1 5 10 15
Val
<![CDATA[<210> 394]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A9G的CDR-L1]]>
<![CDATA[<400> 394]]>
Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser
1 5 10
<![CDATA[<210> 395]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A9G的CDR-L2]]>
<![CDATA[<400> 395]]>
Glu Val Ser Lys Arg Pro Ser
1 5
<![CDATA[<210> 396]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A9G的CDR-L3]]>
<![CDATA[<400> 396]]>
Ser Ser Tyr Ala Gly Ser Asn Asn Phe Val
1 5 10
<![CDATA[<210> 397]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A9G / scFv I2E]]>
<![CDATA[<400> 397]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 398]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A9G / 雙特異性分子I2E]]>
<![CDATA[<400> 398]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 399]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A9G / HLE-BITE I2E]]>
<![CDATA[<400> 399]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 400]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A9G / scFv I2C]]>
<![CDATA[<400> 400]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 401]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A9G的 / 雙特異性分子I2C]]>
<![CDATA[<400> 401]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 402]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A9G / HLE BITE I2C]]>
<![CDATA[<400> 402]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 403]]>
<![CDATA[<211> 126]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F的VH ]]>
<![CDATA[<400> 403]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 404]]>
<![CDATA[<211> 110]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F的VL]]>
<![CDATA[<400> 404]]>
Gln Ser Ala Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Val Thr Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr
20 25 30
Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser
85 90 95
Asn Asn Phe Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
100 105 110
<![CDATA[<210> 405]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F的CDR-H1]]>
<![CDATA[<400> 405]]>
Asp Tyr His Met His
1 5
<![CDATA[<210> 406]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F的CDR-H2]]>
<![CDATA[<400> 406]]>
Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 407]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F的CDR-H3]]>
<![CDATA[<400> 407]]>
Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly Met Asp
1 5 10 15
Val
<![CDATA[<210> 408]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F的CDR-L1 ]]>
<![CDATA[<400> 408]]>
Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser
1 5 10
<![CDATA[<210> 409]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F的CDR-L2]]>
<![CDATA[<400> 409]]>
Glu Val Ser Lys Arg Pro Ser
1 5
<![CDATA[<210> 410]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F的CDR-L3]]>
<![CDATA[<400> 410]]>
Ser Ser Tyr Ala Gly Ser Asn Asn Phe Val
1 5 10
<![CDATA[<210> 411]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F / scFv I2E]]>
<![CDATA[<400> 411]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 412]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F / 雙特異性分子I2E]]>
<![CDATA[<400> 412]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 413]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F / HLE-BITE I2E]]>
<![CDATA[<400> 413]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 414]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F / scFv I2C]]>
<![CDATA[<400> 414]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 415]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F / 雙特異性分子I2C]]>
<![CDATA[<400> 415]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 416]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> D3F / HLE BITE I2C]]>
<![CDATA[<400> 416]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Trp Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ser Tyr Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 417]]>
<![CDATA[<211> 126]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N的VH]]>
<![CDATA[<400> 417]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Phe Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 418]]>
<![CDATA[<211> 110]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N的VL]]>
<![CDATA[<400> 418]]>
Gln Ser Ala Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Val Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr
20 25 30
Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser
85 90 95
Asn Asn Phe Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
100 105 110
<![CDATA[<210> 419]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N的CDR-H1 ]]>
<![CDATA[<400> 419]]>
Asp Tyr His Met His
1 5
<![CDATA[<210> 420]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N的CDR-H2]]>
<![CDATA[<400> 420]]>
Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<![CDATA[<210> 421]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N的CDR-H3]]>
<![CDATA[<400> 421]]>
Asp Tyr Tyr Ser Ser Ser Phe Thr Leu Tyr Tyr Tyr Tyr Gly Met Asp
1 5 10 15
Val
<![CDATA[<210> 422]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N的CDR-L1]]>
<![CDATA[<400> 422]]>
Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser
1 5 10
<![CDATA[<210> 423]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N的CDR-L2]]>
<![CDATA[<400> 423]]>
Glu Val Ser Lys Arg Pro Ser
1 5
<![CDATA[<210> 424]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N的CDR-L3 ]]>
<![CDATA[<400> 424]]>
Ser Ser Tyr Ala Gly Ser Asn Asn Phe Val
1 5 10
<![CDATA[<210> 425]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N / scFv I2E]]>
<![CDATA[<400> 425]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Phe Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 426]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N / 雙特異性分子I2E]]>
<![CDATA[<400> 426]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Phe Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 427]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N / HLE BITE I2E]]>
<![CDATA[<400> 427]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Phe Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Ser Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 428]]>
<![CDATA[<211> 251]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N / scFv I2C]]>
<![CDATA[<400> 428]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Phe Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu
245 250
<![CDATA[<210> 429]]>
<![CDATA[<211> 506]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N / 雙特異性分子I2C]]>
<![CDATA[<400> 429]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Phe Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<![CDATA[<210> 430]]>
<![CDATA[<211> 994]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E4N / HLE BITE I2C]]>
<![CDATA[<400> 430]]>
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 Asp Tyr
20 25 30
His Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Lys Pro Ile Ser Gly Asp Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Ser Ser Ser Phe Thr Leu Tyr Tyr Tyr Tyr Gly
100 105 110
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala
130 135 140
Leu Thr Gln Pro Pro Ser Ala Ser Gly Ser Pro Gly Gln Ser Val Thr
145 150 155 160
Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val
165 170 175
Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr
180 185 190
Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Lys Ser Gly Asn Thr Ala Ser Leu Thr Val Ser Gly Leu Gln Ala Glu
210 215 220
Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser Asn Asn Phe
225 230 235 240
Val Phe Gly Cys Gly Thr Lys Val Thr Val Leu Ser Gly Gly Gly Gly
245 250 255
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
260 265 270
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
275 280 285
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
290 295 300
Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala
305 310 315 320
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
325 330 335
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
340 345 350
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
355 360 365
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val
385 390 395 400
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
405 410 415
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
420 425 430
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
435 440 445
Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Asp Lys
500 505 510
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
515 520 525
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
530 535 540
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
545 550 555 560
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
565 570 575
Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys
580 585 590
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
595 600 605
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
610 615 620
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
625 630 635 640
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
645 650 655
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
660 665 670
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
675 680 685
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
690 695 700
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
705 710 715 720
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
725 730 735
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
755 760 765
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
770 775 780
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
785 790 795 800
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
805 810 815
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
820 825 830
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
835 840 845
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
850 855 860
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
865 870 875 880
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
885 890 895
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
900 905 910
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
915 920 925
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
930 935 940
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
945 950 955 960
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
965 970 975
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
980 985 990
Gly Lys
<![CDATA[<210> 431]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL6 AE3-20 X I2C的 X SCFC / HCDR1]]>
<![CDATA[<400> 431]]>
Ser Tyr Thr Met Ser
1 5
<![CDATA[<210> 432]]>
<![CDATA[<211> 17]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL6 AE3-20 / HCDR2]]>
<![CDATA[<400> 432]]>
Thr Ile Ser Ser Gly Gly Gly Arg Thr Tyr Tyr Pro Asp Ser Val Lys
1 5 10 15
Gly
<![CDATA[<210> 433]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL6 AE3-20 / HCDR3]]>
<![CDATA[<400> 433]]>
Gly Asp Tyr Arg Tyr Asp Gly Phe Ala Tyr
1 5 10
<![CDATA[<210> 434]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL6 AE3-20 / LCDR1]]>
<![CDATA[<400> 434]]>
Arg Ala Ser Glu Asn Ile Asp Ser Tyr Leu Ala
1 5 10
<![CDATA[<210> 435]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL6 AE3-20 / LCDR2]]>
<![CDATA[<400> 435]]>
Ala Ser Thr Leu Leu Val Asp
1 5
<![CDATA[<210> 436]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL6 AE3-20 / LCDR3]]>
<![CDATA[<400> 436]]>
Gln His Tyr Tyr Ser Ile Pro Tyr Thr
1 5
<![CDATA[<210> 437]]>
<![CDATA[<211> 119]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL6 AE3-20 / VH]]>
<![CDATA[<400> 437]]>
Glu Val Lys Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Ser Tyr
20 25 30
Thr Met Ser Trp Val Arg Gln Thr Pro Ala Lys Arg Leu Glu Trp Val
35 40 45
Val Thr Ile Ser Ser Gly Gly Gly Arg Thr Tyr Tyr Pro Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ile Arg Gly Asp Tyr Arg Tyr Asp Gly Phe Ala Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Thr
115
<![CDATA[<210> 438]]>
<![CDATA[<211> 107]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL6 AE3-20 / VL]]>
<![CDATA[<400> 438]]>
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 Glu Asn Ile Asp Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro Gln Leu Leu Val
35 40 45
Tyr Ala Ser Thr Leu Leu Val Asp Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Arg Ser Gly Thr Gln Phe Ser Leu Lys Ile Asn Ser Leu Gln Ser
65 70 75 80
Glu Asp Val Ala Arg Tyr Tyr Cys Gln His Tyr Tyr Ser Ile Pro Tyr
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105
<![CDATA[<210> 439]]>
<![CDATA[<211> 241]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL6 AE3-20 / SCFV]]>
<![CDATA[<400> 439]]>
Glu Val Lys Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Ser Tyr
20 25 30
Thr Met Ser Trp Val Arg Gln Thr Pro Ala Lys Arg Leu Glu Trp Val
35 40 45
Val Thr Ile Ser Ser Gly Gly Gly Arg Thr Tyr Tyr Pro Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ile Arg Gly Asp Tyr Arg Tyr Asp Gly Phe Ala Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Thr Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ala Ser
130 135 140
Leu Ser Ala Ser Val Gly Glu Thr Val Thr Ile Thr Cys Arg Ala Ser
145 150 155 160
Glu Asn Ile Asp Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys
165 170 175
Ser Pro Gln Leu Leu Val Tyr Ala Ser Thr Leu Leu Val Asp Gly Val
180 185 190
Pro Ser Arg Phe Ser Gly Ser Arg Ser Gly Thr Gln Phe Ser Leu Lys
195 200 205
Ile Asn Ser Leu Gln Ser Glu Asp Val Ala Arg Tyr Tyr Cys Gln His
210 215 220
Tyr Tyr Ser Ile Pro Tyr Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile
225 230 235 240
Lys
<![CDATA[<210> 440]]>
<![CDATA[<211> 496]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL6 AE3-20 / 雙特異性MOL]]>
<![CDATA[<400> 440]]>
Glu Val Lys Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Ser Tyr
20 25 30
Thr Met Ser Trp Val Arg Gln Thr Pro Ala Lys Arg Leu Glu Trp Val
35 40 45
Val Thr Ile Ser Ser Gly Gly Gly Arg Thr Tyr Tyr Pro Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ile Arg Gly Asp Tyr Arg Tyr Asp Gly Phe Ala Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Thr Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ala Ser
130 135 140
Leu Ser Ala Ser Val Gly Glu Thr Val Thr Ile Thr Cys Arg Ala Ser
145 150 155 160
Glu Asn Ile Asp Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys
165 170 175
Ser Pro Gln Leu Leu Val Tyr Ala Ser Thr Leu Leu Val Asp Gly Val
180 185 190
Pro Ser Arg Phe Ser Gly Ser Arg Ser Gly Thr Gln Phe Ser Leu Lys
195 200 205
Ile Asn Ser Leu Gln Ser Glu Asp Val Ala Arg Tyr Tyr Cys Gln His
210 215 220
Tyr Tyr Ser Ile Pro Tyr Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile
225 230 235 240
Lys Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
245 250 255
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
260 265 270
Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro
275 280 285
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn
290 295 300
Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
305 310 315 320
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
325 330 335
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly
340 345 350
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
355 360 365
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
370 375 380
Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser
385 390 395 400
Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val
405 410 415
Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala
420 425 430
Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro
435 440 445
Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu
450 455 460
Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp
465 470 475 480
Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
485 490 495
<![CDATA[<210> 441]]>
<![CDATA[<211> 984]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL6 AE3-20 / HLE-BITE I2E]]>
<![CDATA[<400> 441]]>
Glu Val Lys Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Ser Tyr
20 25 30
Thr Met Ser Trp Val Arg Gln Thr Pro Ala Lys Arg Leu Glu Trp Val
35 40 45
Val Thr Ile Ser Ser Gly Gly Gly Arg Thr Tyr Tyr Pro Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ile Arg Gly Asp Tyr Arg Tyr Asp Gly Phe Ala Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Thr Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ala Ser
130 135 140
Leu Ser Ala Ser Val Gly Glu Thr Val Thr Ile Thr Cys Arg Ala Ser
145 150 155 160
Glu Asn Ile Asp Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys
165 170 175
Ser Pro Gln Leu Leu Val Tyr Ala Ser Thr Leu Leu Val Asp Gly Val
180 185 190
Pro Ser Arg Phe Ser Gly Ser Arg Ser Gly Thr Gln Phe Ser Leu Lys
195 200 205
Ile Asn Ser Leu Gln Ser Glu Asp Val Ala Arg Tyr Tyr Cys Gln His
210 215 220
Tyr Tyr Ser Ile Pro Tyr Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile
225 230 235 240
Lys Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
245 250 255
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
260 265 270
Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro
275 280 285
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn
290 295 300
Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
305 310 315 320
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
325 330 335
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly
340 345 350
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
355 360 365
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
370 375 380
Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser
385 390 395 400
Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val
405 410 415
Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala
420 425 430
Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro
435 440 445
Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu
450 455 460
Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp
465 470 475 480
Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
485 490 495
Gly Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
500 505 510
Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
515 520 525
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
530 535 540
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
545 550 555 560
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr
565 570 575
Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp
580 585 590
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
595 600 605
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
610 615 620
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys
625 630 635 640
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
645 650 655
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
660 665 670
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
675 680 685
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
690 695 700
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
705 710 715 720
Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly
725 730 735
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
755 760 765
Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
770 775 780
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
785 790 795 800
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
805 810 815
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln
820 825 830
Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln
835 840 845
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
850 855 860
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
865 870 875 880
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr
885 890 895
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
900 905 910
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
915 920 925
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
930 935 940
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
945 950 955 960
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
965 970 975
Ser Leu Ser Leu Ser Pro Gly Lys
980
<![CDATA[<210> 442]]>
<![CDATA[<211> 105]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人 CD3 ECD]]>
<![CDATA[<400> 442]]>
Gln Asp Gly Asn Glu Glu Met Gly Gly Ile Thr Gln Thr Pro Tyr Lys
1 5 10 15
Val Ser Ile Ser Gly Thr Thr Val Ile Leu Thr Cys Pro Gln Tyr Pro
20 25 30
Gly Ser Glu Ile Leu Trp Gln His Asn Asp Lys Asn Ile Gly Gly Asp
35 40 45
Glu Asp Asp Lys Asn Ile Gly Ser Asp Glu Asp His Leu Ser Leu Lys
50 55 60
Glu Phe Ser Glu Leu Glu Gln Ser Gly Tyr Tyr Val Cys Tyr Pro Arg
65 70 75 80
Gly Ser Lys Pro Glu Asp Ala Asn Phe Tyr Leu Tyr Leu Arg Ala Arg
85 90 95
Val Cys Glu Asn Cys Met Glu Met Asp
100 105
<![CDATA[<210> 443]]>
<![CDATA[<211> 27]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人 CD3 ECD / pos. 1-27]]>
<![CDATA[<400> 443]]>
Gln Asp Gly Asn Glu Glu Met Gly Gly Ile Thr Gln Thr Pro Tyr Lys
1 5 10 15
Val Ser Ile Ser Gly Thr Thr Val Ile Leu Thr
20 25
<![CDATA[<210> 444]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的CDR-L1]]>
<![CDATA[<400> 444]]>
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
1 5 10
<![CDATA[<210> 445]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的CDR-L2]]>
<![CDATA[<400> 445]]>
Gly Thr Lys Phe Leu Ala Pro
1 5
<![CDATA[<210> 446]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的CDR-L3]]>
<![CDATA[<400> 446]]>
Ala Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<![CDATA[<210> 447]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E2M的CDR-L1]]>
<![CDATA[<400> 447]]>
Arg Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
1 5 10
<![CDATA[<210> 448]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E2M的CDR-L2]]>
<![CDATA[<400> 448]]>
Ala Thr Asp Met Arg Pro Ser
1 5
<![CDATA[<210> 449]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E2M的CDR-L3]]>
<![CDATA[<400> 449]]>
Ala Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<![CDATA[<210> 450]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的CDR-L1]]>
<![CDATA[<400> 450]]>
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
1 5 10
<![CDATA[<210> 451]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的CDR-L2]]>
<![CDATA[<400> 451]]>
Gly Thr Lys Phe Leu Ala Pro
1 5
<![CDATA[<210> 452]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的CDR-L3]]>
<![CDATA[<400> 452]]>
Val Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<![CDATA[<210> 453]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F6A的CDR-H1]]>
<![CDATA[<400> 453]]>
Ile Tyr Ala Met Asn
1 5
<![CDATA[<210> 454]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F6A的CDR-H2]]>
<![CDATA[<400> 454]]>
Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Ser
<![CDATA[<210> 455]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F6A的CDR-H3]]>
<![CDATA[<400> 455]]>
His Gly Asn Phe Gly Asn Ser Tyr Val Ser Phe Phe Ala Tyr
1 5 10
<![CDATA[<210> 456]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的CDR-H1]]>
<![CDATA[<400> 456]]>
Lys Tyr Ala Met Asn
1 5
<![CDATA[<210> 457]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的CDR-H2]]>
<![CDATA[<400> 457]]>
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> 458]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的CDR-H3]]>
<![CDATA[<400> 458]]>
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
1 5 10
<![CDATA[<210> 459]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的CDR-H1 ]]>
<![CDATA[<400> 459]]>
Ser Tyr Ala Met Asn
1 5
<![CDATA[<210> 460]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的CDR-H2]]>
<![CDATA[<400> 460]]>
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> 461]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的CDR-H3]]>
<![CDATA[<400> 461]]>
His Gly Asn Phe Gly Asn Ser Tyr Leu Ser Phe Trp Ala Tyr
1 5 10
<![CDATA[<210> 462]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G4H的CDR-H1]]>
<![CDATA[<400> 462]]>
Arg Tyr Ala Met Asn
1 5
<![CDATA[<210> 463]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G4H的CDR-H2]]>
<![CDATA[<400> 463]]>
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> 464]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G4H的CDR-H3]]>
<![CDATA[<400> 464]]>
His Gly Asn Phe Gly Asn Ser Tyr Leu Ser Tyr Phe Ala Tyr
1 5 10
<![CDATA[<210> 465]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A2J的CDR-H1]]>
<![CDATA[<400> 465]]>
Val Tyr Ala Met Asn
1 5
<![CDATA[<210> 466]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A2J的CDR-H2 ]]>
<![CDATA[<400> 466]]>
Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Lys
<![CDATA[<210> 467]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A2J的CDR-H3]]>
<![CDATA[<400> 467]]>
His Gly Asn Phe Gly Asn Ser Tyr Leu Ser Trp Trp Ala Tyr
1 5 10
<![CDATA[<210> 468]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E1L的CDR-H1]]>
<![CDATA[<400> 468]]>
Lys Tyr Ala Met Asn
1 5
<![CDATA[<210> 469]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E1L的CDR-H2]]>
<![CDATA[<400> 469]]>
Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Ser
<![CDATA[<210> 470]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E1L的CDR-H3]]>
<![CDATA[<400> 470]]>
His Gly Asn Phe Gly Asn Ser Tyr Thr Ser Tyr Tyr Ala Tyr
1 5 10
<![CDATA[<210> 471]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E2M的CDR-H1]]>
<![CDATA[<400> 471]]>
Gly Tyr Ala Met Asn
1 5
<![CDATA[<210> 472]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E2M的CDR-H2 ]]>
<![CDATA[<400> 472]]>
Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Glu
<![CDATA[<210> 473]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E2M的CDR-H3]]>
<![CDATA[<400> 473]]>
His Arg Asn Phe Gly Asn Ser Tyr Leu Ser Trp Phe Ala Tyr
1 5 10
<![CDATA[<210> 474]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F7O的CDR-H1]]>
<![CDATA[<400> 474]]>
Val Tyr Ala Met Asn
1 5
<![CDATA[<210> 475]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F7O的CDR-H2]]>
<![CDATA[<400> 475]]>
Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Lys
<![CDATA[<210> 476]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F7O的CDR-H3]]>
<![CDATA[<400> 476]]>
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Trp Trp Ala Tyr
1 5 10
<![CDATA[<210> 477]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的CDR-H1]]>
<![CDATA[<400> 477]]>
Ser Tyr Ala Met Asn
1 5
<![CDATA[<210> 478]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的CDR-H2]]>
<![CDATA[<400> 478]]>
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> 479]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的CDR-H3]]>
<![CDATA[<400> 479]]>
His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Trp Ala Tyr
1 5 10
<![CDATA[<210> 480]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2C的CDR-H1]]>
<![CDATA[<400> 480]]>
Lys Tyr Ala Met Asn
1 5
<![CDATA[<210> 481]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2C的CDR-H2]]>
<![CDATA[<400> 481]]>
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> 482]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2C的CDR-H3 ]]>
<![CDATA[<400> 482]]>
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
1 5 10
<![CDATA[<210> 483]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的CDR-L2 ]]>
<![CDATA[<400> 483]]>
Gly Thr Lys Phe Leu Ala Pro
1 5
<![CDATA[<210> 484]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的CDR-L3 ]]>
<![CDATA[<400> 484]]>
Ala Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<![CDATA[<210> 485]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的CDR-H1]]>
<![CDATA[<400> 485]]>
Lys Tyr Ala Met Asn
1 5
<![CDATA[<210> 486]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的CDR-L1]]>
<![CDATA[<400> 486]]>
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
1 5 10
<![CDATA[<210> 487]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的CDR-L2]]>
<![CDATA[<400> 487]]>
Gly Thr Lys Phe Leu Ala Pro
1 5
<![CDATA[<210> 488]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的CDR-L3]]>
<![CDATA[<400> 488]]>
Ala Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<![CDATA[<210> 489]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的CDR-H1 ]]>
<![CDATA[<400> 489]]>
Ser Tyr Ala Met Asn
1 5
<![CDATA[<210> 490]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的CDR-H2 ]]>
<![CDATA[<400> 490]]>
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> 491]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的CDR-H3]]>
<![CDATA[<400> 491]]>
His Gly Asn Phe Gly Asn Ser Tyr Leu Ser Phe Trp Ala Tyr
1 5 10
<![CDATA[<210> 492]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G4H的CDR-L1 ]]>
<![CDATA[<400> 492]]>
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
1 5 10
<![CDATA[<210> 493]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G4H的CDR-L2 ]]>
<![CDATA[<400> 493]]>
Gly Thr Lys Phe Leu Ala Pro
1 5
<![CDATA[<210> 494]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G4H的CDR-L3 ]]>
<![CDATA[<400> 494]]>
Ala Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<![CDATA[<210> 495]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A2J的CDR-L1]]>
<![CDATA[<400> 495]]>
Arg Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
1 5 10
<![CDATA[<210> 496]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A2J的CDR-L2]]>
<![CDATA[<400> 496]]>
Ala Thr Asp Met Arg Pro Ser
1 5
<![CDATA[<210> 497]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A2J的CDR-L3]]>
<![CDATA[<400> 497]]>
Ala Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<![CDATA[<210> 498]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E1L的CDR-L1 ]]>
<![CDATA[<400> 498]]>
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
1 5 10
<![CDATA[<210> 499]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E1L的CDR-L2 ]]>
<![CDATA[<400> 499]]>
Gly Thr Lys Phe Leu Ala Pro
1 5
<![CDATA[<210> 500]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E1L的CDR-L3]]>
<![CDATA[<400> 500]]>
Ala Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<![CDATA[<210> 501]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F7O的CDR-L1 ]]>
<![CDATA[<400> 501]]>
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
1 5 10
<![CDATA[<210> 502]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F7O的CDR-L2 ]]>
<![CDATA[<400> 502]]>
Gly Thr Lys Phe Leu Ala Pro
1 5
<![CDATA[<210> 503]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F7O的CDR-L3 ]]>
<![CDATA[<400> 503]]>
Ala Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<![CDATA[<210> 504]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2C的CDR-L1 ]]>
<![CDATA[<400> 504]]>
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
1 5 10
<![CDATA[<210> 505]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2C的CDR-L2]]>
<![CDATA[<400> 505]]>
Gly Thr Lys Phe Leu Ala Pro
1 5
<![CDATA[<210> 506]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2C的CDR-L3 ]]>
<![CDATA[<400> 506]]>
Val Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<![CDATA[<210> 507]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的VL]]>
<![CDATA[<400> 507]]>
Gln Thr 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 Ser Gly
20 25 30
Tyr Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 508]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E2M的VL]]>
<![CDATA[<400> 508]]>
Gln Thr 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 Ser Gly
20 25 30
Tyr Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Ala Thr Asp Met Arg Pro Ser Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 509]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的VL ]]>
<![CDATA[<400> 509]]>
Gln Thr 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 Ser Gly
20 25 30
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 510]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的VL變體 ]]>
<![CDATA[<400> 510]]>
Glu Leu 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 Ser Gly
20 25 30
Tyr Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 511]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A2J的VL變體]]>
<![CDATA[<400> 511]]>
Glu Leu 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 Ser Gly
20 25 30
Tyr Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Ala Thr Asp Met Arg Pro Ser Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 512]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的VL變體 ]]>
<![CDATA[<400> 512]]>
Glu Leu 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 Ser Gly
20 25 30
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 513]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F6A的VH]]>
<![CDATA[<400> 513]]>
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 Ile 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 Ser 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 Phe Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 514]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的VH]]>
<![CDATA[<400> 514]]>
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 Lys 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 Ile Ser Tyr Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 515]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的VH]]>
<![CDATA[<400> 515]]>
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Glu Gln Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Ser 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 Leu Ser Phe Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 516]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G4H的VH]]>
<![CDATA[<400> 516]]>
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 Arg 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 Leu Ser Tyr Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 517]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A2J的VH]]>
<![CDATA[<400> 517]]>
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 Val 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 Lys 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 Leu Ser Trp Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 518]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E1L的VH]]>
<![CDATA[<400> 518]]>
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 Lys 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 Ser 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 Thr Ser Tyr Tyr
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 519]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E2M的VH]]>
<![CDATA[<400> 519]]>
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 Gly 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 Glu 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 Arg Asn Phe Gly Asn Ser Tyr Leu Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 520]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F7O的VH]]>
<![CDATA[<400> 520]]>
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 Val 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 Lys 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 Ile Ser Trp Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 521]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的VH]]>
<![CDATA[<400> 521]]>
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 Ser 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 Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 522]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2C的VH]]>
<![CDATA[<400> 522]]>
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 Lys 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 Ile Ser Tyr Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 523]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的VH]]>
<![CDATA[<400> 523]]>
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 Ser 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 Ser 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 Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 524]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F6A的VH變體]]>
<![CDATA[<400> 524]]>
Glu Val Gln Leu Leu 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 Ile 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 Ser 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 Phe Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 525]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的VH變體 ]]>
<![CDATA[<400> 525]]>
Glu Val Gln Leu Leu 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 Lys 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 Ile Ser Tyr Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 526]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的VH變體]]>
<![CDATA[<400> 526]]>
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Glu Gln Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Ser 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 Leu Ser Phe Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 527]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G4H的VH變體]]>
<![CDATA[<400> 527]]>
Glu Val Gln Leu Leu 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 Arg 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 Leu Ser Tyr Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 528]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A2J的VH變體]]>
<![CDATA[<400> 528]]>
Glu Val Gln Leu Leu 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 Val 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 Lys 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 Leu Ser Trp Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 529]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E1L的VH變體]]>
<![CDATA[<400> 529]]>
Glu Val Gln Leu Leu 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 Lys 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 Ser 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 Thr Ser Tyr Tyr
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 530]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E2M的VH變體]]>
<![CDATA[<400> 530]]>
Glu Val Gln Leu Leu 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 Gly 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 Glu 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 Arg Asn Phe Gly Asn Ser Tyr Leu Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 531]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F7O的VH變體]]>
<![CDATA[<400> 531]]>
Glu Val Gln Leu Leu 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 Val 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 Lys 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 Ile Ser Trp Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 532]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的VH變體 ]]>
<![CDATA[<400> 532]]>
Glu Val Gln Leu Leu 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 Ser 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 Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 533]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2C的VH變體]]>
<![CDATA[<400> 533]]>
Glu Val Gln Leu Leu 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 Lys 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 Ile Ser Tyr Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 534]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F6A的VL]]>
<![CDATA[<400> 534]]>
Gln Thr 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 Ser Gly
20 25 30
Tyr Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 535]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的VL]]>
<![CDATA[<400> 535]]>
Gln Thr 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 Ser Gly
20 25 30
Tyr Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 536]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G4H的VL]]>
<![CDATA[<400> 536]]>
Gln Thr 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 Ser Gly
20 25 30
Tyr Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 537]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A2J的VL]]>
<![CDATA[<400> 537]]>
Gln Thr 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 Ser Gly
20 25 30
Tyr Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Ala Thr Asp Met Arg Pro Ser Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 538]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E1L的VL]]>
<![CDATA[<400> 538]]>
Gln Thr 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 Ser Gly
20 25 30
Tyr Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 539]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F7O的VL ]]>
<![CDATA[<400> 539]]>
Gln Thr 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 Ser Gly
20 25 30
Tyr Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 540]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2C的VL]]>
<![CDATA[<400> 540]]>
Gln Thr 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 Ser Gly
20 25 30
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 541]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的VL]]>
<![CDATA[<400> 541]]>
Gln Thr 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 Ser Gly
20 25 30
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 542]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F6A的scFv]]>
<![CDATA[<400> 542]]>
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 Ile 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 Ser 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 Phe Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 543]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的scFv ]]>
<![CDATA[<400> 543]]>
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 Lys 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 Ile Ser Tyr Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 544]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的scFv ]]>
<![CDATA[<400> 544]]>
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Glu Gln Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Ser 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 Leu Ser Phe Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 545]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G4H的scFv]]>
<![CDATA[<400> 545]]>
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 Arg 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 Leu Ser Tyr Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 546]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A2J的scFv ]]>
<![CDATA[<400> 546]]>
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 Val 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 Lys 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 Leu Ser Trp Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Ala
180 185 190
Thr Asp Met Arg Pro Ser Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 547]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E1L的scFv ]]>
<![CDATA[<400> 547]]>
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 Lys 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 Ser 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 Thr Ser Tyr Tyr
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 548]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E2M的scFv ]]>
<![CDATA[<400> 548]]>
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 Gly 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 Glu 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 Arg Asn Phe Gly Asn Ser Tyr Leu Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Ala
180 185 190
Thr Asp Met Arg Pro Ser Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 549]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F7O的scFv]]>
<![CDATA[<400> 549]]>
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 Val 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 Lys 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 Ile Ser Trp Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 550]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的scFv ]]>
<![CDATA[<400> 550]]>
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 Ser 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 Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 551]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2C的scFv ]]>
<![CDATA[<400> 551]]>
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 Lys 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 Ile Ser Tyr Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 552]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的scFv ]]>
<![CDATA[<400> 552]]>
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 Ser 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 Ser 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 Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 553]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F6A的scFv變體 ]]>
<![CDATA[<400> 553]]>
Glu Val Gln Leu Leu 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 Ile 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 Ser 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 Phe Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 554]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H2C的scFv變體]]>
<![CDATA[<400> 554]]>
Glu Val Gln Leu Leu 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 Lys 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 Ile Ser Tyr Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 555]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H1E的scFv變體 ]]>
<![CDATA[<400> 555]]>
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Glu Gln Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Ser 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 Leu Ser Phe Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 556]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G4H的scFv變體]]>
<![CDATA[<400> 556]]>
Glu Val Gln Leu Leu 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 Arg 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 Leu Ser Tyr Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 557]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> A2J的scFv變體 ]]>
<![CDATA[<400> 557]]>
Glu Val Gln Leu Leu 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 Val 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 Lys 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 Leu Ser Trp Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Ala
180 185 190
Thr Asp Met Arg Pro Ser Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 558]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E1L的scFv變體]]>
<![CDATA[<400> 558]]>
Glu Val Gln Leu Leu 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 Lys 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 Ser 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 Thr Ser Tyr Tyr
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 559]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E2M的scFv變體]]>
<![CDATA[<400> 559]]>
Glu Val Gln Leu Leu 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 Gly 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 Glu 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 Arg Asn Phe Gly Asn Ser Tyr Leu Ser Trp Phe
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Ala
180 185 190
Thr Asp Met Arg Pro Ser Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 560]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F7O的scFv變體 ]]>
<![CDATA[<400> 560]]>
Glu Val Gln Leu Leu 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 Val 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 Lys 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 Ile Ser Trp Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 561]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> F12Q的scFv變體]]>
<![CDATA[<400> 561]]>
Glu Val Gln Leu Leu 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 Ser 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 Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 562]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> I2C的scFv變體]]>
<![CDATA[<400> 562]]>
Glu Val Gln Leu Leu 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 Lys 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 Ile Ser Tyr Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Leu Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
165 170 175
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Gly Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 563]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 接頭2]]>
<![CDATA[<400> 563]]>
Gly Gly Gly Gly Ser
1 5
<![CDATA[<210> 564]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 接頭3]]>
<![CDATA[<400> 564]]>
Gly Gly Gly Gly Gln
1 5
<![CDATA[<210> 565]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 接頭4]]>
<![CDATA[<400> 565]]>
Ser Gly Gly Gly Gly Ser
1 5
<![CDATA[<210> 566]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 接頭5]]>
<![CDATA[<400> 566]]>
Pro Gly Gly Gly Gly Ser
1 5
<![CDATA[<210> 567]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 接頭6]]>
<![CDATA[<400> 567]]>
Pro Gly Gly Asp Gly Ser
1 5
<![CDATA[<210> 568]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 接頭7]]>
<![CDATA[<400> 568]]>
Gly Gly Gly Gly Ser Gly Gly Gly Ser
1 5
<![CDATA[<210> 569]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 接頭8 = (G4S)2接頭]]>
<![CDATA[<400> 569]]>
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10
<![CDATA[<210> 570]]>
<![CDATA[<211> 15]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 接頭9 = (G4S)3接頭]]>
<![CDATA[<400> 570]]>
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<![CDATA[<210> 571]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> (G4S)4接頭]]>
<![CDATA[<400> 571]]>
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> 572]]>
<![CDATA[<211> 25]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> (G4S)5接頭]]>
<![CDATA[<400> 572]]>
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser Gly Gly Gly Gly Ser
20 25
<![CDATA[<210> 573]]>
<![CDATA[<211> 30]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> (G4S)6接頭]]>
<![CDATA[<400> 573]]>
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
20 25 30
<![CDATA[<210> 574]]>
<![CDATA[<211> 35]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> (G4S)7接頭]]>
<![CDATA[<400> 574]]>
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
20 25 30
Gly Gly Ser
35
<![CDATA[<210> 575]]>
<![CDATA[<211> 40]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> (G4S)8接頭]]>
<![CDATA[<400> 575]]>
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
20 25 30
Gly Gly Ser Gly Gly Gly Gly Ser
35 40
<![CDATA[<210> 576]]>
<![CDATA[<211> 16]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 線性FcRn BP]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (12)..(12)]]>
<![CDATA[<223> Xaa可以是任何天然存在的氨基酸]]>
<![CDATA[<400> 576]]>
Gln Arg Phe Val Thr Gly His Phe Gly Gly Leu Xaa Pro Ala Asn Gly
1 5 10 15
<![CDATA[<210> 577]]>
<![CDATA[<211> 16]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 線性FcRn BP-Y]]>
<![CDATA[<400> 577]]>
Gln Arg Phe Val Thr Gly His Phe Gly Gly Leu Tyr Pro Ala Asn Gly
1 5 10 15
<![CDATA[<210> 578]]>
<![CDATA[<211> 16]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 線性FcRn BP-H]]>
<![CDATA[<400> 578]]>
Gln Arg Phe Val Thr Gly His Phe Gly Gly Leu His Pro Ala Asn Gly
1 5 10 15
<![CDATA[<210> 579]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 核心FcRn BP-H]]>
<![CDATA[<400> 579]]>
Thr Gly His Phe Gly Gly Leu His Pro
1 5
<![CDATA[<210> 580]]>
<![CDATA[<211> 16]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 環狀FcRn BP-H]]>
<![CDATA[<400> 580]]>
Gln Arg Phe Cys Thr Gly His Phe Gly Gly Leu His Pro Cys Asn Gly
1 5 10 15
<![CDATA[<210> 581]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB]]>
<![CDATA[<400> 581]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Lys Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 582]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體1]]>
<![CDATA[<400> 582]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Gly Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Ala Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Lys Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 583]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體2]]>
<![CDATA[<400> 583]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 584]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體3]]>
<![CDATA[<400> 584]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Asp Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro His Leu Val
565 570 575
Ala Ala Ser Lys Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 585]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體4]]>
<![CDATA[<400> 585]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Gly Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Lys Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 586]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體5]]>
<![CDATA[<400> 586]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Asp Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Lys Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 587]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體6]]>
<![CDATA[<400> 587]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Lys Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro His Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 588]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體7]]>
<![CDATA[<400> 588]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro His Leu Val
565 570 575
Ala Ala Ser Lys Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 589]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體8]]>
<![CDATA[<400> 589]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Lys Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Lys Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 590]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體9]]>
<![CDATA[<400> 590]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Asp Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Lys Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 591]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體10]]>
<![CDATA[<400> 591]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Lys Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 592]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體11]]>
<![CDATA[<400> 592]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Gly Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Ala Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Lys Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 593]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體12]]>
<![CDATA[<400> 593]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 594]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體13]]>
<![CDATA[<400> 594]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Asp Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro His Leu Val
565 570 575
Ala Ala Ser Lys Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 595]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體14]]>
<![CDATA[<400> 595]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Gly Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Lys Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 596]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體15]]>
<![CDATA[<400> 596]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Asp Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Lys Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 597]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體16]]>
<![CDATA[<400> 597]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Lys Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro His Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 598]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體17]]>
<![CDATA[<400> 598]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro His Leu Val
565 570 575
Ala Ala Ser Lys Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 599]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體18]]>
<![CDATA[<400> 599]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Lys Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Lys Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 600]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體19]]>
<![CDATA[<400> 600]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Asp Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Lys Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 601]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體20]]>
<![CDATA[<400> 601]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ala Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Lys Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 602]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體21]]>
<![CDATA[<400> 602]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ala Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Gly Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Ala Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Lys Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 603]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體22]]>
<![CDATA[<400> 603]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ala Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 604]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體23]]>
<![CDATA[<400> 604]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ala Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Asp Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro His Leu Val
565 570 575
Ala Ala Ser Lys Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 605]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體24]]>
<![CDATA[<400> 605]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ala Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Gly Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Lys Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 606]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體25]]>
<![CDATA[<400> 606]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ala Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Asp Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Lys Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 607]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體26]]>
<![CDATA[<400> 607]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ala Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Lys Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro His Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 608]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體27]]>
<![CDATA[<400> 608]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ala Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro His Leu Val
565 570 575
Ala Ala Ser Lys Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 609]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體28]]>
<![CDATA[<400> 609]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ala Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Lys Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Lys Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 610]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HALB變體29]]>
<![CDATA[<400> 610]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ala Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Asp Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Pro Lys Leu Val
565 570 575
Ala Ala Ser Lys Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 611]]>
<![CDATA[<211> 330]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 交叉體1 HC]]>
<![CDATA[<400> 611]]>
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
Lys 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 Cys Glu
165 170 175
Glu Gln Tyr Gly Ser Thr Tyr Arg Cys 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 Asp Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
275 280 285
Leu Tyr Ser Asp 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> 612]]>
<![CDATA[<211> 333]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 交叉體1 LC]]>
<![CDATA[<400> 612]]>
Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser
1 5 10 15
Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp
20 25 30
Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro
35 40 45
Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn
50 55 60
Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys
65 70 75 80
Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val
85 90 95
Glu Lys Thr Val Ala Pro Thr Glu Cys Ser Asp Lys Thr His Thr Cys
100 105 110
Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu
115 120 125
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
130 135 140
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys
145 150 155 160
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
165 170 175
Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu
180 185 190
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
195 200 205
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
210 215 220
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
225 230 235 240
Arg Lys Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
245 250 255
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
260 265 270
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Lys Ser Asp Gly
275 280 285
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
290 295 300
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
305 310 315 320
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
325 330
<![CDATA[<210> 613]]>
<![CDATA[<211> 330]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 交叉體2 HC]]>
<![CDATA[<400> 613]]>
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 Asn Phe Gly Thr Gln Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Thr Val Glu Pro Lys Ser Ser 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 Asp Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
275 280 285
Leu Tyr Ser Asp 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> 614]]>
<![CDATA[<211> 338]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 交叉體2 LC]]>
<![CDATA[<400> 614]]>
Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser
1 5 10 15
Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp
20 25 30
Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro
35 40 45
Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn
50 55 60
Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys
65 70 75 80
Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val
85 90 95
Glu Lys Thr Val Ala Pro Thr Glu Cys Ser Glu Pro Lys Ser Ser Asp
100 105 110
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly
115 120 125
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
130 135 140
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
145 150 155 160
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
165 170 175
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
180 185 190
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
195 200 205
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
210 215 220
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
225 230 235 240
Thr Leu Pro Pro Ser Arg Lys Glu Met Thr Lys Asn Gln Val Ser Leu
245 250 255
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
260 265 270
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
275 280 285
Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
290 295 300
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
325 330 335
Gly Lys
<![CDATA[<210> 615]]>
<![CDATA[<211> 227]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 異Fc結合物Fc]]>
<![CDATA[<400> 615]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
65 70 75 80
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Lys Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Lys
225
<![CDATA[<210> 616]]>
<![CDATA[<211> 227]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 異Fc配偶體Fc]]>
<![CDATA[<400> 616]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
65 70 75 80
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Asp Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Asp Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Lys
225
<![CDATA[<210> 617]]>
<![CDATA[<211> 232]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Maxi-body 1靶標Fc]]>
<![CDATA[<400> 617]]>
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
20 25 30
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
35 40 45
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
50 55 60
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln
65 70 75 80
Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln
85 90 95
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
100 105 110
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
115 120 125
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Lys Glu Met Thr
130 135 140
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
145 150 155 160
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
165 170 175
Lys Thr Thr Pro Pro Val Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr
180 185 190
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
195 200 205
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
210 215 220
Ser Leu Ser Leu Ser Pro Gly Lys
225 230
<![CDATA[<210> 618]]>
<![CDATA[<211> 232]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Maxi-body 1 CD3 Fc]]>
<![CDATA[<400> 618]]>
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
20 25 30
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
35 40 45
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
50 55 60
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln
65 70 75 80
Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln
85 90 95
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
100 105 110
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
115 120 125
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr
130 135 140
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
145 150 155 160
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
165 170 175
Asp Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
180 185 190
Ser Asp Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
195 200 205
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
210 215 220
Ser Leu Ser Leu Ser Pro Gly Lys
225 230
<![CDATA[<210> 619]]>
<![CDATA[<211> 232]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Maxi-body 2靶標Fc]]>
<![CDATA[<400> 619]]>
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
20 25 30
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
35 40 45
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
50 55 60
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
65 70 75 80
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
85 90 95
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
100 105 110
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
115 120 125
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Lys Glu Met Thr
130 135 140
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
145 150 155 160
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
165 170 175
Lys Thr Thr Pro Pro Val Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr
180 185 190
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
195 200 205
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
210 215 220
Ser Leu Ser Leu Ser Pro Gly Lys
225 230
<![CDATA[<210> 620]]>
<![CDATA[<211> 232]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Maxi-body 2 CD3 Fc]]>
<![CDATA[<400> 620]]>
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
20 25 30
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
35 40 45
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
50 55 60
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
65 70 75 80
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
85 90 95
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
100 105 110
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
115 120 125
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr
130 135 140
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
145 150 155 160
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
165 170 175
Asp Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
180 185 190
Ser Asp Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
195 200 205
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
210 215 220
Ser Leu Ser Leu Ser Pro Gly Lys
225 230
<![CDATA[<210> 621]]>
<![CDATA[<211> 217]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Mono Fc]]>
<![CDATA[<400> 621]]>
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Thr Thr Leu Pro Pro Ser Arg Glu Glu Met
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Asp Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Asp Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<![CDATA[<210> 622]]>
<![CDATA[<211> 227]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Fc單體-1 +c/-g]]>
<![CDATA[<400> 622]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
65 70 75 80
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Lys
225
<![CDATA[<210> 623]]>
<![CDATA[<211> 225]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Fc單體-2 +c/-g/ delGK]]>
<![CDATA[<400> 623]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
65 70 75 80
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro
225
<![CDATA[<210> 624]]>
<![CDATA[<211> 227]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Fc單體-3 -c/+g]]>
<![CDATA[<400> 624]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Lys
225
<![CDATA[<210> 625]]>
<![CDATA[<211> 225]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Fc單體-4 -c/+g/ delGK]]>
<![CDATA[<400> 625]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro
225
<![CDATA[<210> 626]]>
<![CDATA[<211> 227]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Fc單體-5 -c/-g]]>
<![CDATA[<400> 626]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Gly Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Lys
225
<![CDATA[<210> 627]]>
<![CDATA[<211> 225]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Fc單體-6 -c/-g/ delGK]]>
<![CDATA[<400> 627]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Gly Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro
225
<![CDATA[<210> 628]]>
<![CDATA[<211> 227]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Fc單體-7 +c/+g]]>
<![CDATA[<400> 628]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Lys
225
<![CDATA[<210> 629]]>
<![CDATA[<211> 225]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Fc單體-8 +c/+g/ delGK]]>
<![CDATA[<400> 629]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro
225
<![CDATA[<210> 630]]>
<![CDATA[<211> 484]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> scFc-1]]>
<![CDATA[<400> 630]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
65 70 75 80
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
225 230 235 240
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
245 250 255
Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
260 265 270
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
275 280 285
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
290 295 300
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
305 310 315 320
Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr
325 330 335
Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
340 345 350
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
355 360 365
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
370 375 380
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
385 390 395 400
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
405 410 415
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
420 425 430
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
435 440 445
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
450 455 460
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
465 470 475 480
Ser Pro Gly Lys
<![CDATA[<210> 631]]>
<![CDATA[<211> 480]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> scFc-2]]>
<![CDATA[<400> 631]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr
65 70 75 80
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
260 265 270
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
275 280 285
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
290 295 300
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
305 310 315 320
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
325 330 335
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
340 345 350
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
355 360 365
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
370 375 380
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
385 390 395 400
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
405 410 415
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
420 425 430
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
435 440 445
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
450 455 460
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
465 470 475 480
<![CDATA[<210> 632]]>
<![CDATA[<211> 484]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> scFc-3]]>
<![CDATA[<400> 632]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
225 230 235 240
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
245 250 255
Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
260 265 270
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
275 280 285
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
290 295 300
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
305 310 315 320
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
325 330 335
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
340 345 350
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
355 360 365
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
370 375 380
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
385 390 395 400
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
405 410 415
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
420 425 430
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
435 440 445
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
450 455 460
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
465 470 475 480
Ser Pro Gly Lys
<![CDATA[<210> 633]]>
<![CDATA[<211> 480]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> scFc-4]]>
<![CDATA[<400> 633]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
260 265 270
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
275 280 285
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
290 295 300
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
305 310 315 320
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
325 330 335
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
340 345 350
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
355 360 365
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
370 375 380
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
385 390 395 400
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
405 410 415
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
420 425 430
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
435 440 445
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
450 455 460
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
465 470 475 480
<![CDATA[<210> 634]]>
<![CDATA[<211> 484]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> scFc-5]]>
<![CDATA[<400> 634]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Gly Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
225 230 235 240
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
245 250 255
Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
260 265 270
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
275 280 285
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
290 295 300
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
305 310 315 320
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Gly Ser Thr
325 330 335
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
340 345 350
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
355 360 365
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
370 375 380
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
385 390 395 400
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
405 410 415
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
420 425 430
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
435 440 445
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
450 455 460
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
465 470 475 480
Ser Pro Gly Lys
<![CDATA[<210> 635]]>
<![CDATA[<211> 480]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> scFc-6]]>
<![CDATA[<400> 635]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Gly Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
260 265 270
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
275 280 285
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
290 295 300
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
305 310 315 320
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Gly Ser Thr Tyr Arg
325 330 335
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
340 345 350
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
355 360 365
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
370 375 380
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
385 390 395 400
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
405 410 415
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
420 425 430
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
435 440 445
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
450 455 460
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
465 470 475 480
<![CDATA[<210> 636]]>
<![CDATA[<211> 484]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> scFc-7]]>
<![CDATA[<400> 636]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
225 230 235 240
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
245 250 255
Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
260 265 270
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
275 280 285
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
290 295 300
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
305 310 315 320
Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Asn Ser Thr
325 330 335
Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
340 345 350
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
355 360 365
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
370 375 380
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
385 390 395 400
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
405 410 415
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
420 425 430
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
435 440 445
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
450 455 460
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
465 470 475 480
Ser Pro Gly Lys
<![CDATA[<210> 637]]>
<![CDATA[<211> 480]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> scFc-8]]>
<![CDATA[<400> 637]]>
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
260 265 270
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
275 280 285
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
290 295 300
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
305 310 315 320
Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
325 330 335
Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
340 345 350
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
355 360 365
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
370 375 380
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
385 390 395 400
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
405 410 415
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
420 425 430
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
435 440 445
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
450 455 460
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
465 470 475 480
<![CDATA[<210> 638]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 5x his-標籤]]>
<![CDATA[<400> 638]]>
His His His His His
1 5
<![CDATA[<210> 639]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 6x his-標籤]]>
<![CDATA[<400> 639]]>
His His His His His His
1 5
<![CDATA[<210> 640]]>
<![CDATA[<211> 502]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL-1 x I2C]]>
<![CDATA[<400> 640]]>
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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Lys Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Arg Ile Thr Val Ala Gly Thr Tyr Tyr Tyr Tyr Gly Met
100 105 110
Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met
130 135 140
Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly Asp Arg Val Thr
145 150 155 160
Ile Thr Cys Arg Ala Ser Gln Gly Val Asn Asn Trp Leu Ala Trp Tyr
165 170 175
Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Thr Ala Ser
180 185 190
Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
195 200 205
Thr Asp Phe Thr Leu Thr Ile Arg Ser Leu Gln Pro Glu Asp Phe Ala
210 215 220
Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro Ile Thr Phe Gly Cys
225 230 235 240
Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly Gly Ser Glu Val Gln
245 250 255
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
260 265 270
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn
275 280 285
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
290 295 300
Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys
305 310 315 320
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
325 330 335
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
340 345 350
Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
355 360 365
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
385 390 395 400
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
405 410 415
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
420 425 430
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
435 440 445
Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
450 455 460
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
465 470 475 480
Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
485 490 495
Thr Lys Leu Thr Val Leu
500
<![CDATA[<210> 641]]>
<![CDATA[<211> 502]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL-2 x I2C]]>
<![CDATA[<400> 641]]>
Gln Val Gln Met Val Gln Ser Gly Ala Glu Val Lys Lys His Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Lys Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Arg Ile Thr Val Ala Gly Thr Tyr Tyr Tyr Tyr Gly Met
100 105 110
Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met
130 135 140
Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly Asp Arg Val Thr
145 150 155 160
Ile Thr Cys Arg Ala Ser Gln Gly Val Asn Asn Trp Leu Ala Trp Tyr
165 170 175
Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Thr Ala Ser
180 185 190
Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
195 200 205
Thr Asp Phe Thr Leu Thr Ile Arg Ser Leu Gln Pro Glu Asp Phe Ala
210 215 220
Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro Ile Thr Phe Gly Cys
225 230 235 240
Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly Gly Ser Glu Val Gln
245 250 255
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
260 265 270
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn
275 280 285
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
290 295 300
Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys
305 310 315 320
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
325 330 335
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
340 345 350
Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
355 360 365
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
385 390 395 400
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
405 410 415
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
420 425 430
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
435 440 445
Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
450 455 460
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
465 470 475 480
Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
485 490 495
Thr Lys Leu Thr Val Leu
500
<![CDATA[<210> 642]]>
<![CDATA[<211> 508]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL-1 x I2C-6His]]>
<![CDATA[<400> 642]]>
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 Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Lys Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Arg Ile Thr Val Ala Gly Thr Tyr Tyr Tyr Tyr Gly Met
100 105 110
Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met
130 135 140
Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly Asp Arg Val Thr
145 150 155 160
Ile Thr Cys Arg Ala Ser Gln Gly Val Asn Asn Trp Leu Ala Trp Tyr
165 170 175
Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Thr Ala Ser
180 185 190
Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
195 200 205
Thr Asp Phe Thr Leu Thr Ile Arg Ser Leu Gln Pro Glu Asp Phe Ala
210 215 220
Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro Ile Thr Phe Gly Cys
225 230 235 240
Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly Gly Ser Glu Val Gln
245 250 255
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
260 265 270
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn
275 280 285
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
290 295 300
Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys
305 310 315 320
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
325 330 335
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
340 345 350
Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
355 360 365
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
385 390 395 400
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
405 410 415
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
420 425 430
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
435 440 445
Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
450 455 460
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
465 470 475 480
Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
485 490 495
Thr Lys Leu Thr Val Leu His His His His His His
500 505
<![CDATA[<210> 643]]>
<![CDATA[<211> 508]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CL-2 x I2C-6His]]>
<![CDATA[<400> 643]]>
Gln Val Gln Met Val Gln Ser Gly Ala Glu Val Lys Lys His Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Lys Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Arg Ile Thr Val Ala Gly Thr Tyr Tyr Tyr Tyr Gly Met
100 105 110
Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met
130 135 140
Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly Asp Arg Val Thr
145 150 155 160
Ile Thr Cys Arg Ala Ser Gln Gly Val Asn Asn Trp Leu Ala Trp Tyr
165 170 175
Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Thr Ala Ser
180 185 190
Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
195 200 205
Thr Asp Phe Thr Leu Thr Ile Arg Ser Leu Gln Pro Glu Asp Phe Ala
210 215 220
Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro Ile Thr Phe Gly Cys
225 230 235 240
Gly Thr Arg Leu Glu Ile Lys Ser Gly Gly Gly Gly Ser Glu Val Gln
245 250 255
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
260 265 270
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn
275 280 285
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
290 295 300
Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys
305 310 315 320
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
325 330 335
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
340 345 350
Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
355 360 365
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
385 390 395 400
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
405 410 415
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
420 425 430
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
435 440 445
Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
450 455 460
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
465 470 475 480
Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
485 490 495
Thr Lys Leu Thr Val Leu His His His His His His
500 505
<![CDATA[<210> 644]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> AU1表位]]>
<![CDATA[<400> 644]]>
Asp Thr Tyr Arg Tyr Ile
1 5
<![CDATA[<210> 645]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> AU5表位]]>
<![CDATA[<400> 645]]>
Thr Asp Phe Tyr Leu Lys
1 5
<![CDATA[<210> 646]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> T-7標籤]]>
<![CDATA[<400> 646]]>
Met Ala Ser Met Thr Gly Gly Gln Gln Met Gly
1 5 10
<![CDATA[<210> 647]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> V-5標籤]]>
<![CDATA[<400> 647]]>
Gly Lys Pro Ile Pro Asn Pro Leu Leu Gly Leu Asp Ser Thr
1 5 10
<![CDATA[<210> 648]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> B-標籤]]>
<![CDATA[<400> 648]]>
Gln Tyr Pro Ala Leu Thr
1 5
<![CDATA[<210> 649]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> E2表位]]>
<![CDATA[<400> 649]]>
Ser Ser Thr Ser Ser Asp Phe Arg Asp Arg
1 5 10
<![CDATA[<210> 650]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> FLAG標籤]]>
<![CDATA[<400> 650]]>
Asp Tyr Lys Asp Asp Asp Lys
1 5
<![CDATA[<210> 651]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Glu-Glu標籤1]]>
<![CDATA[<400> 651]]>
Glu Tyr Met Pro Met Glu
1 5
<![CDATA[<210> 652]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Glu-Glu標籤2]]>
<![CDATA[<400> 652]]>
Glu Phe Met Pro Met Glu
1 5
<![CDATA[<210> 653]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 組胺酸親和力標籤]]>
<![CDATA[<400> 653]]>
Lys Asp His Leu Ile His Asn Val His Lys Glu Phe His Ala His Ala
1 5 10 15
His Asn Lys
<![CDATA[<210> 654]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HSV表位]]>
<![CDATA[<400> 654]]>
Gln Pro Glu Leu Ala Pro Glu Asp
1 5
<![CDATA[<210> 655]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> KT3表位]]>
<![CDATA[<400> 655]]>
Lys Pro Pro Thr Pro Pro Pro Glu Pro Glu Thr
1 5 10
<![CDATA[<210> 656]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Myc表位]]>
<![CDATA[<400> 656]]>
Cys Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu
1 5 10
<![CDATA[<210> 657]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 7x his-標籤]]>
<![CDATA[<400> 657]]>
His His His His His His His
1 5
<![CDATA[<210> 658]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 8x his-標籤]]>
<![CDATA[<400> 658]]>
His His His His His His His His
1 5
<![CDATA[<210> 659]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S1 標籤]]>
<![CDATA[<400> 659]]>
Asn Ala Asn Asn Pro Asp Trp Asp Phe
1 5
<![CDATA[<210> 660]]>
<![CDATA[<211> 15]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> S-標籤]]>
<![CDATA[<400> 660]]>
Lys Glu Thr Ala Ala Ala Lys Phe Glu Arg Gln His Met Asp Ser
1 5 10 15
<![CDATA[<210> 661]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Strep-標籤1]]>
<![CDATA[<400> 661]]>
Trp Ser His Pro Gln Phe Glu Lys
1 5
<![CDATA[<210> 662]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Strep-標籤2]]>
<![CDATA[<400> 662]]>
Ala Trp Ala His Pro Gln Pro Gly Gly
1 5
<![CDATA[<210> 663]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 通用標籤]]>
<![CDATA[<400> 663]]>
His Thr Thr Pro His His
1 5
<![CDATA[<210> 664]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> VSV-G]]>
<![CDATA[<400> 664]]>
Tyr Thr Asp Ile Glu Met Asn Arg Leu Gly Lys
1 5 10
<![CDATA[<210> 665]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> 蛋白C]]>
<![CDATA[<400> 665]]>
Glu Asp Gln Val Asp Pro Arg Leu Ile Asp Gly Lys
1 5 10
<![CDATA[<210> 666]]>
<![CDATA[<211> 16]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> Ab156]]>
<![CDATA[<400> 666]]>
Arg Asp Trp Asp Phe Asp Val Phe Gly Gly Gly Thr Pro Val Gly Gly
1 5 10 15
<![CDATA[<210> 667]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H-CDR3]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (1)..(1)]]>
<![CDATA[<223> 位置1處的Xaa可以是A或N ]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (5)..(5)]]>
<![CDATA[<223> 位置5處的Xaa可以是V或E]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (8)..(8)]]>
<![CDATA[<223> 位置8處的Xaa可以是V或A]]>
<![CDATA[<400> 667]]>
Xaa Leu Ile Val Xaa Ala Pro Xaa
1 5
<![CDATA[<210> 668]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H-CDR3]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (2)..(2)]]>
<![CDATA[<223> 位置2處的Xaa可以是A或N]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (6)..(6)]]>
<![CDATA[<223> 位置6處的Xaa可以是V或E]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (9)..(9)]]>
<![CDATA[<223> 位置9處的Xaa可以是V或A]]>
<![CDATA[<400> 668]]>
Asp Xaa Leu Ile Val Xaa Ala Pro Xaa Thr
1 5 10
<![CDATA[<210> 669]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> H-CDR3]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (2)..(2)]]>
<![CDATA[<223> 位置2處的Xaa可以是A或N]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (6)..(6)]]>
<![CDATA[<223> 位置6處的Xaa可以是V或E]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (9)..(9)]]>
<![CDATA[<223> 位置9處的Xaa可以是V或A]]>
<![CDATA[<400> 669]]>
Asp Xaa Leu Ile Val Xaa Ala Pro Xaa Thr Arg Asp Tyr Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 670]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CD3結合物/ I2E - HCDR1]]>
<![CDATA[<400> 670]]>
Lys Tyr Ala Ile Asn
1 5
<![CDATA[<210> 671]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CD3結合物/ I2E - HCDR2]]>
<![CDATA[<400> 671]]>
Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ala
1 5 10 15
Val Lys Asp
<![CDATA[<210> 672]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CD3結合物/ I2E - HCDR3]]>
<![CDATA[<400> 672]]>
Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr Trp Ala Tyr
1 5 10
<![CDATA[<210> 673]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CD3結合物/ I2E - LCDR1]]>
<![CDATA[<400> 673]]>
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
1 5 10
<![CDATA[<210> 674]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CD3結合物/I2E - LCDR2]]>
<![CDATA[<400> 674]]>
Gly Thr Lys Phe Leu Ala Pro
1 5
<![CDATA[<210> 675]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CD3結合物I2E - LCDR3]]>
<![CDATA[<400> 675]]>
Val Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<![CDATA[<210> 676]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CD3結合物/ I2E - VH]]>
<![CDATA[<400> 676]]>
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 Lys Tyr
20 25 30
Ala Ile 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
Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 677]]>
<![CDATA[<211> 109]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CD3結合物/ I2E - VL]]>
<![CDATA[<400> 677]]>
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Ile Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly
20 25 30
Asn Tyr Pro Asn Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Ser Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 678]]>
<![CDATA[<211> 249]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> CD3結合物/ I2E-SCFV (G4S)3]]>
<![CDATA[<400> 678]]>
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 Lys Tyr
20 25 30
Ala Ile 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
Ala Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Val Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Ala Arg Ala Gly Asn Phe Gly Ser Ser Tyr Ile Ser Tyr Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
115 120 125
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val
130 135 140
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Ile
145 150 155 160
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
165 170 175
Trp Val Gln Lys Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
180 185 190
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
195 200 205
Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
210 215 220
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
225 230 235 240
Gly Ser Gly Thr Lys Leu Thr Val Leu
245
<![CDATA[<210> 679]]>
<![CDATA[<211> 4]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> G4-接頭]]>
<![CDATA[<400> 679]]>
Gly Gly Gly Gly
1
<![CDATA[<210> 680]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HCDR1]]>
<![CDATA[<400> 680]]>
Gly Tyr Ser Phe Thr Gly Tyr Thr
1 5
<![CDATA[<210> 681]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HCDR2]]>
<![CDATA[<400> 681]]>
Ile Asn Pro Tyr Asn Gly Gly Thr
1 5
<![CDATA[<210> 682]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HCDR2]]>
<![CDATA[<400> 682]]>
Ile Asn Pro Tyr Asn Gly Gly Ser
1 5
<![CDATA[<210> 683]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HCDR2]]>
<![CDATA[<400> 683]]>
Ile Asn Pro Tyr Asn Gly Gly Ile
1 5
<![CDATA[<210> 684]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HCDR3]]>
<![CDATA[<400> 684]]>
Ala Arg Asp Tyr Gly Tyr Val Leu Asp Tyr
1 5 10
<![CDATA[<210> 685]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HCDR3]]>
<![CDATA[<400> 685]]>
Ala Arg Asp Phe Gly Tyr Val Leu Asp Tyr
1 5 10
<![CDATA[<210> 686]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HCDR3]]>
<![CDATA[<400> 686]]>
Ala Arg Asp Tyr Gly Phe Val Leu Asp Tyr
1 5 10
<![CDATA[<210> 687]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> HCDR3]]>
<![CDATA[<400> 687]]>
Ala Arg Asp Tyr Gly Tyr Val Phe Asp Tyr
1 5 10
<![CDATA[<210> 688]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> LCDR1]]>
<![CDATA[<400> 688]]>
Ser Ser Val Ser Tyr
1 5
<![CDATA[<210> 689]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> LCDR1]]>
<![CDATA[<400> 689]]>
Ser Ser Val Asn Tyr
1 5
<![CDATA[<210> 690]]>
<![CDATA[<211> 3]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> LCDR2]]>
<![CDATA[<400> 690]]>
Ser Thr Ser
1
<![CDATA[<210> 691]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> LCDR3]]>
<![CDATA[<400> 691]]>
Gln Gln Arg Ser Ile Tyr Pro Pro Trp Thr
1 5 10
<![CDATA[<210> 692]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> LCDR3]]>
<![CDATA[<400> 692]]>
Gln Gln Arg Ser Asn Tyr Pro Pro Trp Thr
1 5 10
<![CDATA[<210> 693]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> LCDR3]]>
<![CDATA[<400> 693]]>
Gln Gln Arg Ser Thr Tyr Pro Pro Trp Thr
1 5 10
<![CDATA[<210> 694]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> LCDR3]]>
<![CDATA[<400> 694]]>
Gln Gln Arg Asn Asn Tyr Pro Pro Trp Thr
1 5 10
<![CDATA[<210> 695]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> LCDR1]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (7)..(7)]]>
<![CDATA[<223> 位置7處的Xaa可以選自S和R]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (9)..(9)]]>
<![CDATA[<223> 位置9處的Xaa可以選自S和T]]>
<![CDATA[<400> 695]]>
Arg Ala Ser Gln Ser Val Xaa Ser Xaa Tyr Leu Ala
1 5 10
<![CDATA[<210> 696]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>
<![CDATA[<220>]]>
<![CDATA[<223> LCDR3]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (4)..(4)]]>
<![CDATA[<223> 位置4處的Xaa可以選自G、D和Q]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (5)..(5)]]>
<![CDATA[<223> 位置5處的Xaa可以選自S、A和T]]>
<![CDATA[<220>]]>
<![CDATA[<221> 尚未歸類的特徵]]>
<![CDATA[<222> (8)..(8)]]>
<![CDATA[<223> 位置8處的Xaa可以選自L和I]]>
<![CDATA[<400> 696]]>
Gln Gln Tyr Xaa Xaa Ser Pro Xaa Thr
1 5
Claims (50)
- 一種多肽或多肽構建體，其包含 ● 與人CLDN6（SEQ ID NO: 1）結合的結構域，和 ● 與人CD3結合的結構域，以及 ● 延長該多肽的半衰期的結構域，其中該與人CLDN6結合的結構域與SEQ ID NO: 9中描繪的CLDN6的細胞外環1（ECL1）中的SEQ ID NO: 1的胺基酸29-39和/或SEQ ID NO: 10中描繪的CLDN6的細胞外環2（ECL2）中的SEQ ID NO: 1的胺基酸151-160結合。
- 如請求項1所述之多肽或多肽構建體，其中所述多肽構建體係T細胞活化構建體。
- 如請求項1和2中任一項所述之多肽或多肽構建體，其中所述多肽構建體係如在選自包括確定CD69的表現量、確定CD25的表現量、確定分泌的IL-2的量、和確定該等T細胞的細胞毒性活性的群組的T細胞活化測定中確定的T細胞活化多肽。
- 如請求項1至3中任一項所述之多肽或多肽構建體，其中所述延長該多肽的半衰期的結構域包含兩個多肽單體，每個多肽單體包含鉸鏈、CH2結構域和CH3結構域。
- 如請求項1至4中任一項所述之多肽或多肽構建體，其中與CD3結合的所述結構域與人和獼猴CD3ε鏈的細胞外表位結合。
- 如請求項1至5中任一項所述之多肽或多肽構建體，其中該結合CLDN6的結構域與包含結合CLDN6的結構域的多肽構建體或抗體或其衍生物或片段結合CLDN6上相同的表位，其中該結構域包含選自以下a) 至s) 中描繪的群組的可變重（VH）鏈的互補決定區CDR-H1、CDR-H2和CDR-H3和/或可變輕（VL）鏈的互補決定區CDR-L1、CDR-L2和CDR-L3：a) 至d)、n) 和s) 係較佳的，a) 至c)、e) 和s) 係特別較佳的： a) 包含SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區； b) 包含SEQ ID NO: 27中描繪的CDR-H1、SEQ ID NO: 28中描繪的CDR-H2和SEQ ID NO: 29中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 30中描繪的CDR-L1、SEQ ID NO: 31中描繪的CDR-L2和SEQ ID NO: 32中描繪的CDR-L3的VL區； c) 包含SEQ ID NO: 41中描繪的CDR-H1、SEQ ID NO: 42中描繪的CDR-H2和SEQ ID NO: 43中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 44中描繪的CDR-L1、SEQ ID NO: 45中描繪的CDR-L2和SEQ ID NO: 46中描繪的CDR-L3的VL區； d) 包含SEQ ID NO: 55中描繪的CDR-H1、SEQ ID NO: 56中描繪的CDR-H2和SEQ ID NO: 57中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 58中描繪的CDR-L1、SEQ ID NO: 59中描繪的CDR-L2和SEQ ID NO: 60中描繪的CDR-L3的VL區； e) 包含SEQ ID NO: 69中描繪的CDR-H1、SEQ ID NO: 70中描繪的CDR-H2和SEQ ID NO: 71中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 72中描繪的CDR-L1、SEQ ID NO: 73中描繪的CDR-L2和SEQ ID NO: 74中描繪的CDR-L3的VL區； f) 包含SEQ ID NO: 83中描繪的CDR-H1、SEQ ID NO: 84中描繪的CDR-H2和SEQ ID NO: 85中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 86中描繪的CDR-L1、SEQ ID NO: 87中描繪的CDR-L2和SEQ ID NO: 88中描繪的CDR-L3的VL區； g) 包含SEQ ID NO: 97中描繪的CDR-H1、SEQ ID NO: 98中描繪的CDR-H2和SEQ ID NO: 99中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 100中描繪的CDR-L1、SEQ ID NO: 101中描繪的CDR-L2和SEQ ID NO: 102中描繪的CDR-L3的VL區； h) 包含SEQ ID NO: 111中描繪的CDR-H1、SEQ ID NO: 112中描繪的CDR-H2和SEQ ID NO: 113中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 114中描繪的CDR-L1、SEQ ID NO: 115中描繪的CDR-L2和SEQ ID NO: 116中描繪的CDR-L3的VL區； i) 包含SEQ ID NO: 125中描繪的CDR-H1、SEQ ID NO: 126中描繪的CDR-H2和SEQ ID NO: 127中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 128中描繪的CDR-L1、SEQ ID NO: 129中描繪的CDR-L2和SEQ ID NO: 130中描繪的CDR-L3的VL區； j) 包含SEQ ID NO: 139中描繪的CDR-H1、SEQ ID NO: 140中描繪的CDR-H2和SEQ ID NO: 141中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 142中描繪的CDR-L1、SEQ ID NO: 143中描繪的CDR-L2和SEQ ID NO: 144中描繪的CDR-L3的VL區； k) 包含SEQ ID NO: 153中描繪的CDR-H1、SEQ ID NO: 154中描繪的CDR-H2和SEQ ID NO: 155中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 156中描繪的CDR-L1、SEQ ID NO: 157中描繪的CDR-L2和SEQ ID NO: 158中描繪的CDR-L3的VL區； l) 包含SEQ ID NO: 167中描繪的CDR-H1、SEQ ID NO: 168中描繪的CDR-H2和SEQ ID NO: 169中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 170中描繪的CDR-L1、SEQ ID NO: 171中描繪的CDR-L2和SEQ ID NO: 172中描繪的CDR-L3的VL區； m) 包含SEQ ID NO: 181中描繪的CDR-H1、SEQ ID NO: 182中描繪的CDR-H2和SEQ ID NO: 183中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 184中描繪的CDR-L1、SEQ ID NO: 185中描繪的CDR-L2和SEQ ID NO: 186中描繪的CDR-L3的VL區； n) 包含SEQ ID NO: 195中描繪的CDR-H1、SEQ ID NO: 196中描繪的CDR-H2和SEQ ID NO: 197中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 198中描繪的CDR-L1、SEQ ID NO: 199中描繪的CDR-L2和SEQ ID NO: 200中描繪的CDR-L3的VL區； o) 包含SEQ ID NO: 209中描繪的CDR-H1、SEQ ID NO: 210中描繪的CDR-H2和SEQ ID NO: 211中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 212中描繪的CDR-L1、SEQ ID NO: 213中描繪的CDR-L2和SEQ ID NO: 214中描繪的CDR-L3的VL區； p) 包含SEQ ID NO: 223中描繪的CDR-H1、SEQ ID NO: 224中描繪的CDR-H2和SEQ ID NO: 225中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 226中描繪的CDR-L1、SEQ ID NO: 227中描繪的CDR-L2和SEQ ID NO: 228中描繪的CDR-L3的VL區； q) 包含SEQ ID NO: 237中描繪的CDR-H1、SEQ ID NO: 238中描繪的CDR-H2和SEQ ID NO: 239中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 240中描繪的CDR-L1、SEQ ID NO: 241中描繪的CDR-L2和SEQ ID NO: 242中描繪的CDR-L3的VL區； r) 包含SEQ ID NO: 251中描繪的CDR-H1、SEQ ID NO: 252中描繪的CDR-H2和SEQ ID NO: 253中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 254中描繪的CDR-L1、SEQ ID NO: 255中描繪的CDR-L2和SEQ ID NO: 256中描繪的CDR-L3的VL區， s) 包含SEQ ID NO: 265中描繪的CDR-H1、SEQ ID NO: 266中描繪的CDR-H2和SEQ ID NO: 267中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 268中描繪的CDR-L1、SEQ ID NO: 269中描繪的CDR-L2和SEQ ID NO: 270中描繪的CDR-L3的VL區。
- 如請求項1至6中任一項所述之多肽或多肽構建體，其中該與人CD3ε結合的結構域也與普通狨或松鼠猴CD3ε結合。
- 如請求項1至7中任一項所述之多肽或多肽構建體，其中 a) 該多肽係單鏈構建體， b) 該與CLDN6結合的結構域處於scFv的形式， c) 該與CD3結合的結構域處於scFv的形式， d) 該結構域經由連接子連接，和/或 e) 該多肽或多肽構建體包含提供延長的血清半衰期的結構域。
- 如請求項1至8中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域不與CLDN1、CLDN2、CLDN3、CLDN4、CLDN9和/或CLDN18.1/CLDN18.2結合。
- 如前述請求項中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域包含含有CDR-H1、CDR-H2和CDR-H3的VH區以及含有CDR-L1、CDR-L2和CDR-L3的VL區，其選自以下a) 至s) 中描繪的組：a) 至d)、n) 和s) 係較佳的，a) 至c)、e) 和s) 係特別較佳的： a) 包含SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區； b) 包含SEQ ID NO: 27中描繪的CDR-H1、SEQ ID NO: 28中描繪的CDR-H2和SEQ ID NO: 29中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 30中描繪的CDR-L1、SEQ ID NO: 31中描繪的CDR-L2和SEQ ID NO: 32中描繪的CDR-L3的VL區； c) 包含SEQ ID NO: 41中描繪的CDR-H1、SEQ ID NO: 42中描繪的CDR-H2和SEQ ID NO: 43中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 44中描繪的CDR-L1、SEQ ID NO: 45中描繪的CDR-L2和SEQ ID NO: 46中描繪的CDR-L3的VL區； d) 包含SEQ ID NO: 55中描繪的CDR-H1、SEQ ID NO: 56中描繪的CDR-H2和SEQ ID NO: 57中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 58中描繪的CDR-L1、SEQ ID NO: 59中描繪的CDR-L2和SEQ ID NO: 60中描繪的CDR-L3的VL區； e) 包含SEQ ID NO: 69中描繪的CDR-H1、SEQ ID NO: 70中描繪的CDR-H2和SEQ ID NO: 71中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 72中描繪的CDR-L1、SEQ ID NO: 73中描繪的CDR-L2和SEQ ID NO: 74中描繪的CDR-L3的VL區； f) 包含SEQ ID NO: 83中描繪的CDR-H1、SEQ ID NO: 84中描繪的CDR-H2和SEQ ID NO: 85中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 86中描繪的CDR-L1、SEQ ID NO: 87中描繪的CDR-L2和SEQ ID NO: 88中描繪的CDR-L3的VL區； g) 包含SEQ ID NO: 97中描繪的CDR-H1、SEQ ID NO: 98中描繪的CDR-H2和SEQ ID NO: 99中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 100中描繪的CDR-L1、SEQ ID NO: 101中描繪的CDR-L2和SEQ ID NO: 102中描繪的CDR-L3的VL區； h) 包含SEQ ID NO: 111中描繪的CDR-H1、SEQ ID NO: 112中描繪的CDR-H2和SEQ ID NO: 113中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 114中描繪的CDR-L1、SEQ ID NO: 115中描繪的CDR-L2和SEQ ID NO: 116中描繪的CDR-L3的VL區； i) 包含SEQ ID NO: 125中描繪的CDR-H1、SEQ ID NO: 126中描繪的CDR-H2和SEQ ID NO: 127中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 128中描繪的CDR-L1、SEQ ID NO: 129中描繪的CDR-L2和SEQ ID NO: 130中描繪的CDR-L3的VL區； j) 包含SEQ ID NO: 139中描繪的CDR-H1、SEQ ID NO: 140中描繪的CDR-H2和SEQ ID NO: 141中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 142中描繪的CDR-L1、SEQ ID NO: 143中描繪的CDR-L2和SEQ ID NO: 144中描繪的CDR-L3的VL區； k) 包含SEQ ID NO: 153中描繪的CDR-H1、SEQ ID NO: 154中描繪的CDR-H2和SEQ ID NO: 155中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 156中描繪的CDR-L1、SEQ ID NO: 157中描繪的CDR-L2和SEQ ID NO: 158中描繪的CDR-L3的VL區； l) 包含SEQ ID NO: 167中描繪的CDR-H1、SEQ ID NO: 168中描繪的CDR-H2和SEQ ID NO: 169中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 170中描繪的CDR-L1、SEQ ID NO: 171中描繪的CDR-L2和SEQ ID NO: 172中描繪的CDR-L3的VL區； m) 包含SEQ ID NO: 181中描繪的CDR-H1、SEQ ID NO: 182中描繪的CDR-H2和SEQ ID NO: 183中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 184中描繪的CDR-L1、SEQ ID NO: 185中描繪的CDR-L2和SEQ ID NO: 186中描繪的CDR-L3的VL區； n) 包含SEQ ID NO: 195中描繪的CDR-H1、SEQ ID NO: 196中描繪的CDR-H2和SEQ ID NO: 197中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 198中描繪的CDR-L1、SEQ ID NO: 199中描繪的CDR-L2和SEQ ID NO: 200中描繪的CDR-L3的VL區； o) 包含SEQ ID NO: 209中描繪的CDR-H1、SEQ ID NO: 210中描繪的CDR-H2和SEQ ID NO: 211中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 212中描繪的CDR-L1、SEQ ID NO: 213中描繪的CDR-L2和SEQ ID NO: 214中描繪的CDR-L3的VL區； p) 包含SEQ ID NO: 223中描繪的CDR-H1、SEQ ID NO: 224中描繪的CDR-H2和SEQ ID NO: 225中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 226中描繪的CDR-L1、SEQ ID NO: 227中描繪的CDR-L2和SEQ ID NO: 228中描繪的CDR-L3的VL區； q) 包含SEQ ID NO: 237中描繪的CDR-H1、SEQ ID NO: 238中描繪的CDR-H2和SEQ ID NO: 239中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 240中描繪的CDR-L1、SEQ ID NO: 241中描繪的CDR-L2和SEQ ID NO: 242中描繪的CDR-L3的VL區； r) 包含SEQ ID NO: 251中描繪的CDR-H1、SEQ ID NO: 252中描繪的CDR-H2和SEQ ID NO: 253中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 254中描繪的CDR-L1、SEQ ID NO: 255中描繪的CDR-L2和SEQ ID NO: 256中描繪的CDR-L3的VL區， s) 包含SEQ ID NO: 265中描繪的CDR-H1、SEQ ID NO: 266中描繪的CDR-H2和SEQ ID NO: 267中描繪的CDR-H3的VH區，以及包含SEQ ID NO: 268中描繪的CDR-L1、SEQ ID NO: 269中描繪的CDR-L2和SEQ ID NO: 270中描繪的CDR-L3的VL區。
- 如前述請求項中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域包含具有選自以下群組的胺基酸序列的VH區，該群組包括SEQ ID NO: 11、SEQ ID NO: 25、SEQ ID NO: 39、SEQ ID NO: 53、SEQ ID NO: 67、SEQ ID NO: 81、SEQ ID NO: 95、SEQ ID NO: 109、SEQ ID NO: 123、SEQ ID NO: 137、SEQ ID NO: 151、SEQ ID NO: 165、SEQ ID NO: 179、SEQ ID NO: 193、SEQ ID NO: 207、SEQ ID NO: 221、SEQ ID NO: 235、SEQ ID NO: 249、或SEQ ID NO: 263中描繪的序列， 其中所述VH區胺基酸序列可以在構架區和/或高變區中具有一個或幾個胺基酸殘基的一個或多個修飾，條件係包含所述修飾的VH區的所述結構域選擇性地與CLDN6結合，並且 視需要，其中所述結構域係活化T細胞並保持誘導T細胞依賴性細胞毒性的能力的多肽或多肽構建體的一部分， 進一步視需要，其中所述結構域係活化T細胞並保持誘導效力為表現CLDN9但不表現CLDN6的相同細胞類型的1000倍的T細胞依賴性細胞毒性的能力的多肽或多肽構建體的一部分，以及 更進一步視需要，其中所述結構域係不能活化T細胞並在相同細胞類型的CLDN6陰性細胞中誘導T細胞依賴性細胞毒性的多肽或多肽構建體的一部分，較佳的是當在體外細胞毒性測定中測試時。
- 如前述請求項中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域包含具有選自以下群組的胺基酸序列的VL區，該群組包括SEQ ID NO: 12、SEQ ID NO: 26、SEQ ID NO: 40、SEQ ID NO: 54、SEQ ID NO: 68、SEQ ID NO: 82、SEQ ID NO: 96、SEQ ID NO: 110、SEQ ID NO: 124、SEQ ID NO: 138、SEQ ID NO: 152、SEQ ID NO: 166、SEQ ID NO: 180、SEQ ID NO: 194、SEQ ID NO: 208、SEQ ID NO: 222、SEQ ID NO: 236、SEQ ID NO: 250、或SEQ ID NO: 264中描繪的序列， 其中所述VL區胺基酸序列可以在構架區和/或高變區中具有一個或幾個胺基酸殘基的一個或多個修飾，條件係包含所述修飾的VL區的所述結構域選擇性地與CLDN6結合，並且 視需要，其中所述結構域係活化T細胞並保持在靶細胞中誘導T細胞依賴性細胞毒性的能力的多肽或多肽構建體的一部分， 進一步視需要，其中所述結構域係活化T細胞並保持誘導效力為不表現CLDN6的對照細胞的500倍的T細胞依賴性細胞毒性的能力的多肽或多肽構建體的一部分，其中該等細胞視需要表現CLDN9，但是 更進一步視需要，其中所述結構域係不能活化T細胞並在相同細胞類型的CLDN6陰性細胞中誘導T細胞依賴性細胞毒性的多肽或多肽構建體的一部分，較佳的是當在體外細胞毒性測定中測試時。
- 如前述請求項中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域包含具有以下中描繪的胺基酸序列的一對VH區和VL區：SEQ ID NO: 11+12、SEQ ID NO: 25+26、SEQ ID NO: 39+40、SEQ ID NO: 53+54、SEQ ID NO: 67+68、SEQ ID NO: 81+82、SEQ ID NO: 95+96、SEQ ID NO: 109+110、SEQ ID NO: 123+124、SEQ ID NO: 137+138、SEQ ID NO: 151+152、SEQ ID NO: 165+166、SEQ ID NO: 179+180、SEQ ID NO: 193+194、SEQ ID NO: 207+208、SEQ ID NO: 221+222、SEQ ID NO: 235+236、SEQ ID NO: 249+250、或SEQ ID NO: 263+264。
- 如前述請求項中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域包含以下中描繪的胺基酸序列：SEQ ID NO: 19、SEQ ID NO: 22、SEQ ID NO: 33、SEQ ID NO: 36、SEQ ID NO: 47、SEQ ID NO: 50、SEQ ID NO: 61、SEQ ID NO: 64、SEQ ID NO: 75、SEQ ID NO: 78、SEQ ID NO: 89、SEQ ID NO: 92、SEQ ID NO: 103、SEQ ID NO: 106、SEQ ID NO: 117、SEQ ID NO: 120、SEQ ID NO: 131、SEQ ID NO: 134、SEQ ID NO: 145、SEQ ID NO: 148、SEQ ID NO: 159、SEQ ID NO: 162、SEQ ID NO: 173、SEQ ID NO: 176、SEQ ID NO: 187、SEQ ID NO: 190、SEQ ID NO: 201、SEQ ID NO: 204、SEQ ID NO: 215、SEQ ID NO: 218、SEQ ID NO: 229、SEQ ID NO: 232、SEQ ID NO: 243、SEQ ID NO: 246、SEQ ID NO: 257、或SEQ ID NO: 260、SEQ ID NO: 271或SEQ ID NO: 274。
- 如前述請求項中任一項所述之多肽或多肽構建體，其包含選自以下中描繪的那些的群組的胺基酸序列：SEQ ID NO: 19、SEQ ID NO: 20、SEQ ID NO: 21、SEQ ID NO: 22、SEQ ID NO: 23、和SEQ ID NO: 24、SEQ ID NO: 33、SEQ ID NO: 34、SEQ ID NO: 35、SEQ ID NO: 36、SEQ ID NO: 37、和SEQ ID NO: 38、SEQ ID NO: 47、SEQ ID NO: 48、SEQ ID NO: 49、SEQ ID NO: 50、SEQ ID NO: 51、和SEQ ID NO: 52、SEQ ID NO: 61、SEQ ID NO: 62、SEQ ID NO: 63、SEQ ID NO: 64、SEQ ID NO: 65、和SEQ ID NO: 66、SEQ ID NO: 75、SEQ ID NO: 76、SEQ ID NO: 77、SEQ ID NO: 78、SEQ ID NO: 79、和SEQ ID NO: 80、SEQ ID NO: 89、SEQ ID NO: 90、SEQ ID NO: 91、SEQ ID NO: 92、SEQ ID NO: 93、和SEQ ID NO: 94、SEQ ID NO: 103、SEQ ID NO: 104、SEQ ID NO: 105、SEQ ID NO: 106、SEQ ID NO: 107、和SEQ ID NO: 108、SEQ ID NO: 117、SEQ ID NO: 118、SEQ ID NO: 119、SEQ ID NO: 120、SEQ ID NO: 121、和SEQ ID NO: 122、SEQ ID NO: 131、SEQ ID NO: 132、SEQ ID NO: 133、SEQ ID NO: 134、SEQ ID NO: 135、和SEQ ID NO: 136、SEQ ID NO: 145、SEQ ID NO: 146、SEQ ID NO: 147、SEQ ID NO: 148、SEQ ID NO: 149、和SEQ ID NO: 150、SEQ ID NO: 159、SEQ ID NO: 160、SEQ ID NO: 161、SEQ ID NO: 162、SEQ ID NO: 163、和SEQ ID NO: 164、SEQ ID NO: 173、SEQ ID NO: 174、SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、和SEQ ID NO: 178、SEQ ID NO: 187、SEQ ID NO: 188、SEQ ID NO: 189、SEQ ID NO: 190、SEQ ID NO: 191、和SEQ ID NO: 192、SEQ ID NO: 201、SEQ ID NO: 202、SEQ ID NO: 203、SEQ ID NO: 204、SEQ ID NO: 205、和SEQ ID NO: 206、SEQ ID NO: 215、SEQ ID NO: 216、SEQ ID NO: 217、SEQ ID NO: 218、SEQ ID NO: 219、和SEQ ID NO: 220、SEQ ID NO: 229、SEQ ID NO: 230、SEQ ID NO: 231、SEQ ID NO: 232、SEQ ID NO: 233、和SEQ ID NO: 234、SEQ ID NO: 243、SEQ ID NO: 244、SEQ ID NO: 245、SEQ ID NO: 246、SEQ ID NO: 247、和SEQ ID NO: 248、SEQ ID NO: 257、SEQ ID NO: 258、SEQ ID NO: 259、SEQ ID NO: 260、SEQ ID NO: 261、和SEQ ID NO: 262、SEQ ID NO: 271、SEQ ID NO: 272、SEQ ID NO: 273、SEQ ID NO: 274、SEQ ID NO: 275、和SEQ ID NO: 276，或選自具有與所述序列具有至少90%、91%、92%、93%、94%、95%、96%、97%、98%或99%同一性的胺基酸的多肽/多肽構建體的胺基酸序列。
- 一種多肽或多肽構建體，其包含SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3以及含有SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區。
- 一種多肽或多肽構建體，其包含具有SEQ ID NO: 11+12中描繪的胺基酸序列的VH區和VL區。
- 一種多肽或多肽構建體，其包含SEQ ID NO: 19中描繪的胺基酸序列。
- 一種多肽或多肽構建體，其包含SEQ ID NO: 19、SEQ ID NO: 20、SEQ ID NO: 21、SEQ ID NO: 22、SEQ ID NO: 23或SEQ ID NO: 24中描繪的胺基酸序列。
- 一種多肽/多肽構建體，其包含與人CLDN6（SEQ ID NO: 1）結合的結構域、和與人CD3結合的結構域、以及延長該多肽的半衰期的結構域，其中該與CLDN6結合的結構域包含含有SEQ ID NO: 13中描繪的CDR-H1、SEQ ID NO: 14中描繪的CDR-H2和SEQ ID NO: 15中描繪的CDR-H3的VH區以及含有SEQ ID NO: 16中描繪的CDR-L1、SEQ ID NO: 17中描繪的CDR-L2和SEQ ID NO: 18中描繪的CDR-L3的VL區。
- 如前述請求項中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域包含具有SEQ ID NO: 11+12中描繪的胺基酸序列的VH區和VL區。
- 如前述請求項中任一項所述之多肽或多肽構建體，其中該與CLDN6結合的結構域包含SEQ ID NO: 19中描繪的胺基酸序列。
- 如前述請求項中任一項所述之多肽或多肽構建體，其包含SEQ ID NO: 19、SEQ ID NO: 20、SEQ ID NO: 21、SEQ ID NO: 22、SEQ ID NO: 23和SEQ ID NO: 24中描繪的胺基酸序列。
- 如前述請求項中任一項所述之多肽或多肽構建體，其中如在使用表現SEQ ID NO: 1中描繪的野生型CLDN6突變體的細胞進行的體外測定中確定的，該與CLDN6結合的結構域誘導的細胞毒性比使用表現SEQ ID NO:1中描繪的CLDN6的細胞進行的體外測定中測量的細胞毒性低至少100倍、至少250倍、至少500倍，該突變體包含以下突變中的至少一個或多個：M29X，其中X較佳的是L；R145X，其中X較佳的是Q；和/或Q156X，其中X較佳的是L。
- 如前述請求項中任一項所述之多肽或多肽構建體，其中如在使用表現SEQ ID NO: 1中描繪的野生型CLDN6突變體的細胞進行的體外測定中確定的，該與CLDN6結合的結構域誘導的細胞毒性比使用表現SEQ ID NO:1中描繪的CLDN6的細胞進行的體外測定中測量的細胞毒性低至少100倍、至少250倍、至少500倍，該突變體包含以下突變中至少一個或多個：M29X，其中X較佳的是L；R145X，其中X較佳的是Q；和/或Q156X，其中X較佳的是L，其中所述構建體能夠活化T細胞並在表現CLDN6的靶細胞中誘導細胞毒性，並且其中所述構建體具有重鏈CDR3序列，其包含：X1LIVX2APX3（SEQ ID NO.667），其中X1係A或N；X2係V或E；並且X3係V或A。
- 如前述請求項之一所述之多肽或多肽構建體，其中該構建體係單鏈構建體。
- 如前述請求項之一所述之多肽或多肽構建體，其中所述包含兩個多肽單體的半衰期延長結構域包含鉸鏈、CH2結構域和CH3結構域，按胺基至羧基順序包含： 鉸鏈-CH2-CH3-連接子-鉸鏈-CH2-CH3。
- 如前述請求項之一所述之多肽或多肽構建體，其中該CH2結構域包含結構域內半胱胺酸二硫橋。
- 如前述請求項之一所述之多肽或多肽構建體，其中 (i) 該與CLDN6結合的抗原結合（表位結合）結構域包含兩個抗體可變結構域且該與CD3結合的抗原結合（表位結合）結構域包含兩個抗體可變結構域； (ii) 該與CLDN6結合的抗原結合（表位結合）結構域包含一個抗體可變結構域且該與CD3結合的抗原結合（表位結合）結構域包含兩個抗體可變結構域； (iii) 該與CLDN6結合的抗原結合（表位結合）結構域包含兩個抗體可變結構域且該與CD3結合的抗原結合（表位結合）結構域包含一個抗體可變結構域；或 (iv) 該與CLDN6結合的抗原結合（表位結合）結構域包含一個抗體可變結構域且該與CD3結合的抗原結合（表位結合）結構域包含一個抗體可變結構域。
- 如前述請求項之一所述之多肽或多肽構建體，其中該與CLDN6結合的抗原結合（表位結合）結構域和該與CD3結合的抗原結合（表位結合）結構域經由肽連接子與另一個結構域融合。
- 如前述請求項中任一項所述之多肽或多肽構建體，其中該多肽或多肽構建體按胺基至羧基順序，或按羧基至胺基順序包含： (a) 與CLDN6結合的抗原結合（表位結合）結構域； (b) 肽連接子，特別是具有選自由SEQ ID NO: 563-575組成之群組的胺基酸序列的肽連接子； (c) 與CD3結合的抗原結合（表位結合）結構域。
- 如請求項31所述之多肽或多肽構建體，其中該多肽或多肽構建體按胺基至羧基順序，或按羧基至胺基順序，或介於與CLDN6結合的抗原結合（表位結合）結構域和與CD3結合的抗原結合（表位結合）結構域之間，進一步包含： (a) 肽連接子，該肽連接子具有選自由SEQ ID NO: 563-575組成之群組的胺基酸序列； (b) 第三結構域的第一多肽單體； (c) 肽連接子，該肽連接子具有選自由SEQ ID NO: 563-575組成之群組的胺基酸序列；和 (d) 所述第三結構域的第二多肽單體。
- 如前述請求項之一所述之多肽或多肽構建體，其中該構建體描繪於SEQ ID NO: 35、38、49、52、63、66、77、80、91、94、105、108、119、122、133、136、147、150、161、164、175、178、189、192、203、206、217、220、231、234、245、148、259、262、273、276、287、290、301、304、315、318、329、332、343、346、357、360、371、374、385、388、399、402、413、416、427和430，特別是35、38、49、52、63、66、77、80、91、94，更特別是35、38、49、52、77和80，並且甚至更特別是35、49和77中描繪的任一個序列中。
- 如前述請求項之一所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含含有以下SEQ ID NO: 670、671和/或672中描繪的CDR序列的至少一個、兩個或全部的VH結構域。
- 如前述請求項之一所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含含有以下SEQ ID NO: 673、674和/或675中描繪的CDR序列的至少一個、兩個或全部的VL結構域。
- 如前述請求項之一所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含含有以下SEQ ID NO: 670、671、672、673、674和/或675中描繪的CDR序列的至少一個、兩個或全部的VH和VL結構域。
- 如前述請求項之一所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含SEQ ID NO: 676中描繪的VH結構域。
- 如前述請求項之一所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含SEQ ID NO: 677中描繪的VL結構域。
- 如前述請求項之一所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含SEQ ID NO: 676中描繪的VH結構域和SEQ ID NO: 677中描繪的VL結構域。
- 如前述請求項之一所述之多肽或多肽構建體，其中該構建體包含與CD3結合的結構域，該結構域包含SEQ ID NO: 678中描繪的scFv結構域。
- 一種多核苷酸，該多核苷酸編碼如前述請求項中任一項所定義的多肽或多肽構建體。
- 一種載體，其包含如請求項41中所定義的多核苷酸。
- 一種宿主細胞，該宿主細胞經如請求項41中所定義的多核苷酸或如請求項42中所定義的載體轉化或轉染。
- 一種用於產生如請求項1至40中任一項所定義的多肽或多肽構建體之方法，所述方法包括：在允許表現所述多肽構建體的條件下培養如請求項43中所定義的宿主細胞並且從培養物中回收所產生的多肽或多肽構建體。
- 一種藥物組成物，其包含如請求項1至40中任一項所定義的或根據如請求項44所述之方法產生的多肽或多肽構建體。
- 如請求項1至40中任一項所述之或根據如請求項44所述之方法產生的多肽或多肽構建體，其用作藥物，特別是用於預防、治療或緩解疾病、較佳的是贅生物的藥物。
- 如請求項40所述之多肽或多肽構建體，其用作藥物，特別是用於預防、治療或緩解疾病的藥物，其中該疾病或贅生物選自由以下組成之群組：生殖細胞癌；卵巢癌，特別是卵巢腺癌和卵巢畸胎瘤；子宮癌；和肺癌，包括小細胞肺癌（SCLC）和非小細胞肺癌（NSCLC），特別是鱗狀細胞肺癌和腺癌，進一步地，其中該疾病係選自包括威爾姆氏瘤、顱外橫紋肌樣瘤或促結締組織增生性小圓細胞瘤的群組的小兒贅生物。
- 如請求項40所述之多肽或多肽構建體，其中該肺癌係非小細胞肺癌(NSCLC)，特別是鱗狀細胞肺癌和腺癌。
- 一種套組，其包含如請求項1至40中任一項所定義的多肽或多肽構建體、如請求項44所述之方法產生的多肽或多肽構建體、如請求項41中所定義的多核苷酸、如請求項42中所定義的載體、和/或如請求項43中所定義的宿主細胞。
- 一種用於治療或緩解增殖性疾病、腫瘤性疾病、癌症或免疫學障礙之方法，該方法包括向有需要的受試者投與如請求項1至40中任一項所述之或如請求項41所述之方法產生的多肽或多肽構建體的步驟，其中該疾病較佳的是選自由以下組成之群組：生殖細胞癌；卵巢癌，特別是卵巢腺癌和卵巢畸胎瘤；子宮癌，更特別是卵巢漿液性囊腺癌、子宮癌肉瘤、子宮體子宮內膜癌；和肺癌，包括小細胞肺癌（SCLC）和非小細胞肺癌（NSCLC），特別是鱗狀細胞肺癌和腺癌；或選自威爾姆氏瘤、顱外橫紋肌樣瘤或促結締組織增生性小圓細胞瘤的小兒贅生物。
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| US4475196A (en) | 1981-03-06 | 1984-10-02 | Zor Clair G | Instrument for locating faults in aircraft passenger reading light and attendant call control system |
| US4447233A (en) | 1981-04-10 | 1984-05-08 | Parker-Hannifin Corporation | Medication infusion pump |
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| IL302586A (en) | 2023-07-01 |
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| JP2023547662A (ja) | 2023-11-13 |
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| CA3199976A1 (en) | 2022-05-12 |
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