TW202206455A - 一種抗新型冠狀病毒的單克隆抗體及其應用 - Google Patents
一種抗新型冠狀病毒的單克隆抗體及其應用 Download PDFInfo
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Abstract
本文涉及免疫學領域和分子病毒學領域,特別是新型冠狀病毒的診斷、預防和治療領域。具體而言,本文涉及抗新型冠狀病毒的單克隆抗體,以及包含所述抗體的組合物(例如,診斷劑和治療劑)。此外,本文還涉及所述抗體的用途。本文所述的抗體可用於診斷、預防和/或治療新型冠狀病毒的感染和/或由所述感染引起的疾病(例如,新型冠狀病毒肺炎)。
Description
本文涉及免疫學領域和分子病毒學領域,特別是新型冠狀病毒的診斷、預防和治療領域。具體而言,本文涉及抗新型冠狀病毒的抗體,以及包含所述抗體的組合物(例如,診斷劑和治療劑)。此外,本文還涉及所述抗體的用途。本文所述的抗體可用於診斷、預防和/或治療新型冠狀病毒的感染和/或由所述感染引起的疾病(例如,新型冠狀病毒肺炎)。
新型冠狀病毒(Severe acute respiratory syndrome coronavirus 2,2019-nCoV或SARS-CoV-2),因2019年底在武漢出現的病毒性肺炎病例而被發現,新型冠狀病毒是以前從未在人體中發現的冠狀病毒新毒株,隨後被世界衛生組織命名。從2019年底至2020年4月27日,中國確診病例超8萬例,累計死亡病例超3000例;中國境外(韓國,伊朗,義大利,泰國、美國、德國、澳大利亞等213個國家)新冠肺炎確診病例增至2810325例,累計死亡193825例,對公眾的生命和健康造成重大威脅。截至目前,對於新型冠狀病毒的治療仍缺乏疫苗和特效治療藥物。
新型冠狀病毒SARS-CoV-2是導致新型冠狀病毒肺炎(COVID-19)的病原體,是一種單鏈RNA病毒,它與2002-2003年引發疫情的重症急性呼吸綜合征冠狀病毒(SARS-CoV)以及2012年引發疫情的中東呼吸綜合征冠狀病毒(MERS-CoV)同屬冠狀病毒科(Coronaviridae
)。冠狀病毒顆粒呈圓形或橢圓形,亦為多形性,直徑50-200 nm,屬於尺寸較大的病毒。冠狀病毒是包膜病毒,病毒衣殼外面包裹著脂質包膜,其上排列較寬的刺突蛋白(Spike, S蛋白, SEQ ID No: 1460),形狀如太陽光環。已有研究證實,新型冠狀病毒SARS-CoV-2的病毒表面具有S蛋白,其能夠在病毒感染宿主的過程中通過其包含的受體結合結構域(RBD)結合宿主細胞受體血管緊張素轉換酶2(ACE2)分子,從而啟動病毒膜與宿主細胞膜發生融合,導致宿主細胞感染病毒。
迄今為止,中和抗體已被證明是治療病毒性疾病的有效方法。一般來說,患者體內的B淋巴細胞受到抗原的刺激後,會被活化,進而轉變和分化成多種不同的細胞,並產生抗體。據現有的研究報導,新型冠狀病毒肺炎康復者的外周血內抗新型冠狀病毒的抗體,它們由經活化的B細胞產生和分泌。然而,康復者血漿記憶體在著多種B細胞,並且不同的B細胞所產生的抗體的結合活性和中和效價也有所不同。到目前為止,尚無研究報導具有高結合活性和/或高中和活性的抗新型冠狀病毒的抗體。
因此,需要開發能夠抗新型冠狀病毒SARS-CoV-2的具有高結合活性和/或高中和活性的抗體,以提供有效的診斷、預防和/或治療新型冠狀病毒感染的手段。
本文所提供的下述技術方案滿足了上述需求,並且提供了相關的優點。
一方面,本文提供一種抗原結合單元,其包含重鏈可變區(VH)和輕鏈可變區(VL),所述重鏈可變區包含VH CDR1、VH CDR2和VH CDR3,所述輕鏈可變區包含VL CDR1、VL CDR2和VL CDR3;其中所述VH CDR3包含選自SEQ ID NO: 1-360和2971-3005的序列或者與SEQ ID NO: 1-360和2971-3005相比包含一個或多個氨基酸添加、刪除、或取代的序列,和/或其中所述VL CDR3包含選自SEQ ID NO: 361-720和3076-3110的序列或者與SEQ ID NO: 361-720和3076-3110相比包含一個或多個氨基酸添加、刪除、或取代的序列。
在一些實施方案中,所述抗原結合單元以小於100nM、小於50nM、小於20nM、小於15nM、小於10 nM、小於5nM、小於4nM、小於3nM、小於2nM、小於1nM、小於0.5nM、小於0.1 nM、小於0.05 nM、或小於0.01 nM的平衡解離常數(KD)結合新型冠狀病毒(SARS-CoV-2)S蛋白的受體結合結構域(RBD)。
在一些實施方案中,所述的抗原結合單元以小於20 µg/ml、小於10 µg/ml、小於9 µg/ml、小於8 µg/ml、小於7 µg/ml、小於6 µg/ml、小於5 µg/ml、小於4 µg/ml、小於3 µg/ml、小於2 µg/ml、小於1 µg/ml、小於0.5µg/ml、小於0.25 µg/ml、小於0.2 µg/ml、小於0.1 µg/ml、小於0.05 µg/ml、或小於0.001 µg/ml的IC50
中和新型冠狀病毒(SARS-CoV-2)。
在一些實施方案中,所述抗原結合單元的所述VH CDR1包含選自SEQ ID NO: 1461-1820和2901-2935的序列或者與SEQ ID NO: 1461-1820和2901-2935相比包含一個或多個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VH CDR1包含選自SEQ ID NO: 1461-1820和2901-2935的序列。在一些實施方案中,所述抗原結合單元的所述VH CDR1包含與SEQ ID NO: 1461-1820和2901-2935相比包含5、4、3、2或1個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VH CDR1包含與SEQ ID NO: 721-1080和3111-3145中所包含的CDR1相同的序列。
在一些實施方案中,所述抗原結合單元的所述VH CDR2包含選自SEQ ID NO: 1821-2180和2936-2970的序列或者與SEQ ID NO: 1821-2180和2936-2970相比包含一個或多個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VH CDR2包含選自SEQ ID NO: 1821-2180和2936-2970的序列。在一些實施方案中,所述抗原結合單元的所述VH CDR2包含與SEQ ID NO: 1821-2180和2936-2970相比包含5、4、3、2或1個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VH CDR2包含與SEQ ID NO: 721-1080和3111-3145中所包含的CDR2相同的序列。
在一些實施方案中,所述抗原結合單元的所述VL CDR1包含選自SEQ ID NO: 2181-2540和3006-3040的序列或者與SEQ ID NO: 2181-2540和3006-3040相比包含一個或多個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VL CDR1包含選自SEQ ID NO: 2181-2540和3006-3040的序列。在一些實施方案中,所述抗原結合單元的所述VL CDR1包含與SEQ ID NO: 2181-2540和3006-3040相比包含5、4、3、2或1個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VL CDR1包含與SEQ ID NO: 1081-1440和3146-3180中所包含的CDR1相同的序列。
在一些實施方案中,所述抗原結合單元的所述VL CDR2包含選自SEQ ID NO: 2541-2900和3041-3075的序列或者與SEQ ID NO: 2541-2900和3041-3075相比包含一個或多個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VL CDR2包含選自SEQ ID NO: 2541-2900和3041-3075的序列。在一些實施方案中,所述抗原結合單元的所述VL CDR2包含與SEQ ID NO: 2541-2900和3041-3075相比包含5、4、3、2或1個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VL CDR2包含與SEQ ID NO: 1081-1440和3146-3180中所包含的CDR2相同的序列。
在一些實施方案中,所述抗原結合單元的所述VH包含選自SEQ ID NO: 721-1080和3111-3145的序列或者與SEQ ID NO: 721-1080和3111-3145相比包含一個或多個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VH包含選自SEQ ID NO: 721-1080和3111-3145的序列。在一些實施方案中,所述抗原結合單元的所述VH包含與SEQ ID NO: 721-1080和3111-3145相比包含10、9、8、7、6、5、4、3、2或1個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VH包含與選自SEQ ID NO: 721-1080和3111-3145的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
在一些實施方案中,所述抗原結合單元的所述VL包含選自SEQ ID NO: 1081-1440和3146-3180的序列或者與SEQ ID NO: 1081-1440和3146-3180相比包含一個或多個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VL包含選自SEQ ID NO: 1081-1440和3146-3180的序列。在一些實施方案中,所述抗原結合單元的所述VL包含與SEQ ID NO: 1081-1440和3146-3180相比包含10、9、8、7、6、5、4、3、2或1個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VL包含與選自SEQ ID NO: 1081-1440和3146-3180的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
另一方面,本文提供一種抗原結合單元,其包含重鏈可變區(VH)和輕鏈可變區(VL),所述重鏈可變區包含VH CDR1、VH CDR2和VH CDR3,所述輕鏈可變區包含VL CDR1、VL CDR2和VL CDR3;其中所述VH CDR1包含選自SEQ ID NO: 1461-1820和2901-2935的序列、與SEQ ID NO: 1461-1820和2901-2935相比包含一個或多個氨基酸添加、刪除、或取代的序列、或者與SEQ ID NO: 721-1080和3111-3145中所包含的CDR1相同的序列,其中所述VH CDR2包含選自SEQ ID NO: 1821-2180和2936-2970的序列、與SEQ ID NO: 1821-2180和2936-2970相比包含一個或多個氨基酸添加、刪除、或取代的序列、或者與SEQ ID NO: 721-1080和3111-3145中所包含的CDR2相同的序列,其中所述VH CDR3包含選自SEQ ID NO: 1-360和2971-3005的序列、與SEQ ID NO: 1-360和2971-3005相比包含一個或多個氨基酸添加、刪除、或取代的序列、或者與SEQ ID NO: 721-1080和3111-3145中所包含的CDR3相同的序列;和/或其中所述VL CDR1包含選自SEQ ID NO: 2181-2540和3006-3040的序列、與SEQ ID NO: 2181-2540和3006-3040相比包含一個或多個氨基酸添加、刪除、或取代的序列、或者與SEQ ID NO: 1081-1440和3146-3180中所包含的CDR1相同的序列,所述VL CDR2包含選自SEQ ID NO: 2541-2900和3041-3075的序列、與SEQ ID NO: 2541-2900和3041-3075相比包含一個或多個氨基酸添加、刪除、或取代的序列、或者與SEQ ID NO: 1081-1440和3146-3180中所包含的CDR2相同的序列,所述VL CDR3包含選自SEQ ID NO: 361-720和3076-3110的序列、與SEQ ID NO: 361-720和3076-3110相比包含一個或多個氨基酸添加、刪除、或取代的序列、或者與SEQ ID NO: 1081-1440和3146-3180中所包含的CDR3相同的序列。
另一方面,本文提供一種抗原結合單元,其包含重鏈可變區(VH)和輕鏈可變區(VL),所述重鏈可變區包含VH CDR1、VH CDR2和VH CDR3,所述輕鏈可變區包含VL CDR1、VL CDR2和VL CDR3;其中所述VH CDR1包含選自SEQ ID NO: 1461-1820和2901-2935的序列或者與SEQ ID NO: 1461-1820和2901-2935相比包含一個或多個氨基酸添加、刪除、或取代的序列,其中所述VH CDR2包含選自SEQ ID NO: 1821-2180和2936-2970的序列或者與SEQ ID NO: 1821-2180和2936-2970相比包含一個或多個氨基酸添加、刪除、或取代的序列,其中所述VH CDR3包含選自SEQ ID NO: 1-360和2971-3005的序列或者與SEQ ID NO: 1-360和2971-3005相比包含一個或多個氨基酸添加、刪除、或取代的序列;和/或其中所述VL CDR1包含選自SEQ ID NO: 2181-2540和3006-3040的序列或者與SEQ ID NO: 2181-2540和3006-3040相比包含一個或多個氨基酸添加、刪除、或取代的序列,所述VL CDR2包含選自SEQ ID NO: 2541-2900和3041-3075的序列或者與SEQ ID NO: 2541-2900和3041-3075相比包含一個或多個氨基酸添加、刪除、或取代的序列,所述VL CDR3包含選自SEQ ID NO: 361-720和3076-3110的序列或者與SEQ ID NO: 361-720和3076-3110相比包含一個或多個氨基酸添加、刪除、或取代的序列。
在一些實施方案中,所述抗原結合單元的所述VH包含選自SEQ ID NO: 721-1080和3111-3145的序列或者與SEQ ID NO: 721-1080和3111-3145相比包含一個或多個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VH包含選自SEQ ID NO: 721-1080和3111-3145的序列。在一些實施方案中,所述抗原結合單元的所述VH包含與SEQ ID NO: 721-1080和3111-3145相比包含10、9、8、7、6、5、4、3、2或1個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VH包含與選自SEQ ID NO: 721-1080和3111-3145的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
在一些實施方案中,所述抗原結合單元的所述VL包含選自SEQ ID NO: 1081-1440和3146-3180的序列或者與SEQ ID NO: 1081-1440和3146-3180相比包含一個或多個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VL包含選自SEQ ID NO: 1081-1440和3146-3180的序列。在一些實施方案中,所述抗原結合單元的所述VL包含與SEQ ID NO: 1081-1440和3146-3180相比包含10、9、8、7、6、5、4、3、2或1個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述VL包含與選自SEQ ID NO: 1081-1440和3146-3180的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
在一些實施方案中,所述的抗原結合單元以小於100nM、小於50nM、小於20nM、小於15nM、小於10 nM、小於5nM、小於4nM、小於3nM、小於2nM、小於1nM、小於0.5nM、小於0.1 nM、小於0.05 nM、或小於0.01 nM的平衡解離常數(KD)結合新型冠狀病毒(SARS-CoV-2)S蛋白的受體結合結構域(RBD)。
在一些實施方案中,所述的抗原結合單元以小於20 µg/ml、小於10 µg/ml、小於9 µg/ml、小於8 µg/ml、小於7 µg/ml、小於6 µg/ml、小於5 µg/ml、小於4 µg/ml、小於3 µg/ml、小於2 µg/ml、小於1 µg/ml、小於0.5µg/ml、小於0.25 µg/ml、小於0.2 µg/ml、小於0.1 µg/ml、小於0.05 µg/ml、或小於0.001 µg/ml的IC50中和新型冠狀病毒(SARS-CoV-2)。
另一方面,本文提供一種抗原結合單元,其包含重鏈可變區(VH)和輕鏈可變區(VL),其中所述VH包含與選自SEQ ID NO: 721-1080和3111-3145的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列,和/或其中所述VL包含與選自SEQ ID NO: 1081-1440和3146-3180的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
在一些實施方案中,所述的抗原結合單元以小於100nM、小於50nM、小於20nM、小於15nM、小於10 nM、小於5nM、小於4nM、小於3nM、小於2nM、小於1nM、小於0.5nM、小於0.1 nM、小於0.05 nM、或小於0.01 nM的平衡解離常數(KD)結合新型冠狀病毒(SARS-CoV-2)S蛋白的受體結合結構域(RBD)。
在一些實施方案中,所述的抗原結合單元以小於20 µg/ml、小於10 µg/ml、小於9 µg/ml、小於8 µg/ml、小於7 µg/ml、小於6 µg/ml、小於5 µg/ml、小於4 µg/ml、小於3 µg/ml、小於2 µg/ml、小於1 µg/ml、小於0.5µg/ml、小於0.25 µg/ml、小於0.2 µg/ml、小於0.1 µg/ml、小於0.05 µg/ml、或小於0.001 µg/ml的IC50中和新型冠狀病毒(SARS-CoV-2)。
在一些實施方案中,所述抗原結合單元進一步包含重鏈恒定區(CH)。 在一些實施方案中,所述抗原結合單元的所述CH包含SEQ ID NO: 1457 的序列或者與SEQ ID NO: 1457相比包含一個或多個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述CH包含選自SEQ ID NO: 1457的序列。在一些實施方案中,所述抗原結合單元的所述CH包含與SEQ ID NO: 1457相比包含10、9、8、7、6、5、4、3、2或1個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述CH包含與選自SEQ ID NO: 1457的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
在一些實施方案中,所述抗原結合單元進一步包含輕鏈恒定區(CL)。 在一些實施方案中,所述抗原結合單元的所述CL包含SEQ ID NO: 1458 的序列或者與SEQ ID NO: 1458相比包含一個或多個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述CL包含選自SEQ ID NO: 1458的序列。在一些實施方案中,所述抗原結合單元的所述CL包含與SEQ ID NO: 1458相比包含10、9、8、7、6、5、4、3、2或1個氨基酸添加、刪除、或取代的序列。在一些實施方案中,所述抗原結合單元的所述CL包含與選自SEQ ID NO: 1458的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
在另一個方面,本文提供了分離的核酸分子,其編碼如上文所定義的本文所述的抗原結合單元。
在另一個方面,本文提供了一種載體,其包含如上文所定義的分離的核酸分子。本文所述的載體可以是克隆載體,也可以是表達載體。在一些實施方案中,本文所述的載體是例如質粒、粘粒、或噬菌體等等。
在另一個方面,還提供了包含本文所述的分離的核酸分子或載體的宿主細胞。此類宿主細胞包括但不限於,原核細胞例如大腸桿菌細胞,以及真核細胞例如酵母細胞、昆蟲細胞、植物細胞和動物細胞(如哺乳動物細胞,例如小鼠細胞、人細胞等)。本文所述的細胞還可以是細胞系,例如HEK293細胞。
在另一個方面,還提供了製備本文所述的抗原結合單元的方法,其包括,在合適的條件下培養本文所述的宿主細胞,和從細胞培養物中回收本文所述的抗原結合單元。
在另一個方面,本文提供了一種組合物,其包含如上文所描述的抗原結合單元、分離的核酸分子、載體或宿主細胞。
在另一個方面,本文提供了一種試劑盒,其包括本文所述的抗原結合單元。在一些實施方案中,本文所述的抗原結合單元還包括可檢測的標記。在一些實施方案中,所述試劑盒還包括第二抗體,其特異性識別本文所述的抗原結合單元。優選地,所述第二抗體還包括可檢測的標記。此類可檢測的標記是本領域技術人員熟知的,包括但不限於,放射性同位素,螢光物質,發光物質,有色物質和酶(例如辣根過氧化物酶)等。
在另一個方面,本文提供了檢測新型冠狀病毒或其S蛋白或S蛋白的RBD在樣品中的存在或其水準的方法,其包括,使用本文所述的抗原結合單元。在一些實施方案中,本文所述的抗原結合單元還包括可檢測的標記。在另一個優選的實施方案中,所述方法還包括,使用攜帶可檢測的標記的第二抗體來檢測本文所述的抗原結合單元。所述方法可以用於診斷目的(例如,所述樣品是來自患者的樣品),或者非診斷目的(例如,所述樣品是細胞樣品,而非來自患者的樣品)。
在另一個方面,本文提供了診斷受試者是否感染了新型冠狀病毒的方法,其包括:使用本文所述的抗原結合單元檢測新型冠狀病毒或其S蛋白或S蛋白的RBD在來自所述受試者的樣品中的存在。在一些實施方案中,本文所述的抗原結合單元還包括可檢測的標記。在另一個優選的實施方案中,所述方法還包括,使用攜帶可檢測的標記的第二抗體來檢測本文所述的抗原結合單元。
在另一個方面,提供了本文所述的抗原結合單元在製備試劑盒中的用途,所述試劑盒用於檢測新型冠狀病毒或其S蛋白或S蛋白的RBD在樣品中的存在或其水準,或用於診斷受試者是否感染了新型冠狀病毒。
在另一個方面,本文提供了一種藥物組合物,其包含本文所述的抗原結合單元,以及藥學上可接受的載體和/或賦形劑。
在另一個方面,本文提供了用於中和樣品中新型冠狀病毒的毒力的方法,其包括,將包含新型冠狀病毒的樣品與本文所述的抗原結合單元接觸。此類方法可以用於治療目的,或非治療目的(例如所述樣品是細胞樣品,而不是患者或來自患者的樣品)。
在另一個方面,提供了本文所述的抗原結合單元用於製備藥物的用途,所述藥物用於中和樣品中新型冠狀病毒的毒力。在另一個方面,本文提供了如上文所描述的抗原結合單元,其用於中和樣品中新型冠狀病毒的毒力。
在另一個方面,提供了本文所述的抗原結合單元在製備藥物組合物中的用途,所述藥物組合物用於預防或治療受試者的新型冠狀病毒感染或與新型冠狀病毒感染相關的疾病(例如新型冠狀病毒肺炎)。在另一個方面,本文提供了如上文所描述的抗原結合單元,其用於預防或治療受試者的新型冠狀病毒感染或與新型冠狀病毒感染相關的疾病(例如新型冠狀病毒肺炎)。
在另一個方面,本文提供了用於預防或治療受試者的新型冠狀病毒感染或新型冠狀病毒感染相關的疾病(例如新型冠狀病毒肺炎)的方法,其包括,給有此需要的受試者施用預防或治療有效量的本文所述的抗原結合單元,或者本文所述的藥物組合物。
在一些實施方案中,所述受試者是哺乳動物,例如人。
可通過任何適當的施用途徑來將本文所述的抗原結合單元或者本文所述的藥物組合物施用給受試者。此類施用途徑包括但不限於,口服、口腔、舌下、局部、腸胃外、直腸、葉鞘內、或鼻腔途徑。
本文所提供的藥物和藥物組合物可以單獨使用或聯合使用,也可以與其他藥學活性劑(例如抗病毒藥物,如法匹拉韋、瑞德西韋和干擾素等)聯合使用。在一些實施方案中,所述藥物組合物還含藥學上可接受的載體和/或賦形劑。
在另一個方面,本文提供了綴合物,其其包含如上文所描述的抗原結合單元,其中所述抗原結合單元與化學功能部分綴合。在一些實施方案中,所述化學功能部分選自射性同位素、酶、螢光化合物、化學發光化合物、生物發光化合物底物輔因數和抑制劑。
雖然本文已經示出並描述了本文所述的優選實施方案,但對於本領域技術人員顯而易見的是,這樣的實施方案只是通過示例的方式提供的。本領域技術人員在不脫離本文所述的情況下現將想到許多變化、改變和替代。應當理解,在實施本文所述的過程中可以採用本文所述的本文實施方案的各種替代方案。旨在用以下請求項限定本文所述的範圍,因此涵蓋這些請求項範圍內的方法和結構及其等同物。
當提供數值範圍時,應當理解,在此範圍的上限與下限之間的每個中間值(精確到下限單位的十分之一,除非上下文另有明確規定)以及在所述範圍內的其它任何所指出的或中間的值都包含在本發明內。這些較小範圍的上限和下限可獨立地包括在較小範圍中,而且也包含在本發明內,除了所述範圍內任何具體排除的限值。當所述範圍包含一個或兩個限值時,除去任一或兩個包含在內的限值的範圍也包含在本發明中。
如本文中所使用的,術語“多肽”、“肽”和“蛋白質”在本文中可互換使用,以指任何長度的氨基酸聚合物。聚合物可以是直鏈、環狀或支鏈的,它可以包含修飾的氨基酸,並且可以被非氨基酸中斷。該術語還包括已經被修飾的氨基酸聚合物,該修飾例如是通過硫酸化、糖基化、脂化、乙醯化、磷酸化、碘化、甲基化、氧化、蛋白水解處理、磷酸化、異戊烯化、外消旋化、硒化、轉移RNA介導的氨基酸向蛋白質的添加(如精氨酸化)、遍在蛋白化,或其它任何操作,如與標記組分的綴合。如本文所用的,術語“氨基酸”是指天然和/或非天然或合成的氨基酸,包括甘氨酸和D或L光學異構體,以及氨基酸類似物和擬肽。由指定蛋白質“衍生”的多肽或氨基酸序列是指多肽的起源。優選地,多肽具有與序列中編碼的多肽的氨基酸序列基本相同的氨基酸序列,或其部分,其中該部分由至少10-20個氨基酸或至少20-30氨基酸或至少30-50個氨基酸組成,或者其可用序列中編碼的多肽免疫學地標識。該術語還包括從指定核酸序列表達的多肽。如本文中所使用的,術語“結構域”是指蛋白質的一部分,它在物理上或功能上與該蛋白質或肽的其它部分區分開。物理上定義的結構域包括極具疏水性或親水性的氨基酸序列,如那些膜結合的或細胞質結合的序列。結構域還可以通過例如由基因複製引起的內部同源性來定義。功能上定義的結構域具有不同的生物學功能。例如,抗原結合域是指抗原結合單元或抗體中與抗原結合的部分。功能上定義的結構域不需要由連續的氨基酸序列編碼,且功能上定義的結構域可以含有一個或多個物理上定義的結構域。
如本文中所使用的,術語“氨基酸”是指天然的和/或非天然的或合成的氨基酸,包括但不限於D或L旋光異構體,以及氨基酸類似物和擬肽。標準的單字母或三字母代碼用來指稱氨基酸。在本文中,氨基酸通常用本領域公知的單字母和三字母縮寫來表示。例如,丙氨酸可用A或Ala表示。
如本文中所使用的,術語“抗體”是指通常由兩對多肽鏈(每對具有一條“輕”(L)鏈和一條“重”(H)鏈)組成的免疫球蛋白分子。抗體輕鏈可分類為κ和λ輕鏈。重鏈可分類為μ、δ、γ、α或ε,並且分別將抗體的同種型定義為IgM、IgD、IgG、IgA和IgE。在輕鏈和重鏈內,可變區和恒定區通過大約12或更多個氨基酸的“J”區連接,重鏈還包含大約3個或更多個氨基酸的“D”區。各重鏈由重鏈可變區(VH)和重鏈恒定區(CH)組成。重鏈恒定區由3個結構域(CH1、CH2和CH3)組成。各輕鏈由輕鏈可變區(VL)和輕鏈恒定區(CL)組成。輕鏈恒定區由一個結構域CL組成。抗體的恒定區可介導免疫球蛋白與宿主組織或因數,包括免疫系統的各種細胞(例如,效應細胞)和經典補體系統的第一組分(C1q)的結合。VH和VL區還可被細分為具有高變性的區域(稱為互補決定區(CDR)),其間散佈有較保守的稱為構架區(FR)的區域。各VH和VL由按下列順序:FR1、CDR1、FR2、CDR2、FR3、CDR3、FR4從氨基末端至羧基末端排列的3個CDR和4個FR組成。各重鏈/輕鏈對的可變區(VH和VL)分別形成抗體結合部位。氨基酸至各區域或結構域的分配遵循Kabat Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987 and 1991)),或Chothia & Lesk (1987) J. Mol. Biol. 196:901-917; Chothia等人 (1989) Nature 342:878-883的定義。本申請中的各區域或結構域的分配亦可遵循IMGT、AbM或Contact進行定義。這樣的命名法對於本領域技術人員來說是熟知的,且各編號系統之間的對應關係也是本領域技術人員所熟知的。術語“抗體”不受任何特定的產生抗體的方法限制。例如,其包括,重組抗體、單克隆抗體和多克隆抗體。抗體可以是不同同種型的抗體,例如,IgG (例如,IgG1,IgG2,IgG3或IgG4亞型),IgA1,IgA2,IgD,IgE或IgM抗體。
如本文中所使用的,術語抗體的“抗原結合片段”是指包含全長抗體的片段的多肽,其保持特異性結合全長抗體所結合的相同抗原的能力,和/或與全長抗體競爭對抗原的特異性結合,其也被稱為“抗原結合部分”。通常參見,Fundamental Immunology, Ch. 7 (Paul, W., ed., 第2版,Raven Press, N.Y. (1989),其以其全文通過引用合併入本文,用於所有目的。可通過重組DNA技術或通過完整抗體的酶促或化學斷裂產生抗體的抗原結合片段。在一些情況下,抗原結合片段包括Fab、Fab'、F(ab')2
、Fd、Fv、dAb和互補決定區(CDR)片段、單鏈抗體(例如,scFv)、嵌合抗體、雙抗體(diabody)和這樣的多肽,其包含足以賦予多肽特異性抗原結合能力的抗體的至少一部分。在一些情況下,抗體的抗原結合片段是單鏈抗體(例如,scFv),其中VL和VH結構域通過使其能夠產生為單個多肽鏈的連接體配對形成單價分子(參見,例如, Bird等人, Science 242:423 426 (1988)和Huston等人, Proc. Natl. Acad. Sci. USA 85:5879 5883 (1988))。此類scFv分子可具有一般結構:NH2-VL-接頭-VH-COOH或NH2-VH-接頭-VL-COOH。合適的現有技術接頭由重複的GGGGS氨基酸序列或其變體組成。例如,可使用具有氨基酸序列(GGGGS)4
的接頭,但也可使用其變體(Holliger等人(1993),Proc. Natl. Acad. Sci. USA 90: 6444-6448)。可用于本文所述的其他接頭由Alfthan等人(1995),Protein Eng. 8:725-731,Choi等人(2001),Eur. J. Immunol. 31: 94-106,Hu等人(1996),Cancer Res. 56:3055-3061,Kipriyanov等人(1999),J. Mol. Biol. 293:41-56和Roovers等人(2001),Cancer Immunol.描述。
在一些情況下,抗體的抗原結合片段是雙抗體,即,雙價抗體,其中VH和VL結構域在單個多肽鏈上表達,但使用太短的連接體以致不允許在相同鏈的兩個結構域之間配對,從而迫使結構域與另一條鏈的互補結構域配對並且產生兩個抗原結合部位(參見,例如, Holliger P.等人, Proc. Natl. Acad. Sci. USA 90:6444 6448 (1993),和Poljak R. J.等人, Structure 2:1121 1123 (1994))。
可使用本領域技術人員已知的常規技術(例如,重組DNA技術或酶促或化學斷裂法)可從給定的抗體(例如本文提供的抗體)獲得抗體的抗原結合片段(例如,上述抗體片段),並且以與用於完整抗體的方式相同的方式就特異性篩選抗體的抗原結合片段。
在本文中,除非上下文明確指出,否則當提及術語“抗體”時,其不僅包括完整抗體,而且包括抗體的抗原結合片段。
在本文中,除非上下文明確指出,術語“抗原結合單元”包括上述定義的抗體及其抗原結合片段。
如本文中所使用的,術語“單克隆抗體”是指,來自一群高度同源的抗體分子中的一個抗體或抗體的一個片段,也即,除可能自發出現的自然突變外,一群完全相同的抗體分子。單抗對抗原上的單一表位具有高特異性。多克隆抗體是相對于單克隆抗體而言的,其通常包含至少2種或更多種的不同抗體,這些不同的抗體通常識別抗原上的不同表位。單克隆抗體通常可採用Kohler等首次報導的雜交瘤技術獲得(Nature, 256:495 ,1975),但也可採用重組DNA技術獲得(如參見Journal of virological methods, 2009, 158(1-2): 171-179)。
如本文中所使用的,“中和抗體”是指,能清除或顯著降低目標病毒的毒力(例如,感染細胞的能力)的抗體或抗體片段。
如本文中所使用的,在多肽的情況下,“序列”是多肽中的氨基酸在從氨基末端到羧基末端方向上的順序,其中該序列中彼此相鄰的殘基在該多肽的一級結構中是連續的。序列也可以是已知在一個或兩個方向上包含額外殘基的多肽的一部分的線性序列。
如本文中所使用的,“同一性”、“同源性”或“序列同一性”是指在兩個或更多個多核苷酸序列之間或在兩個或更多個多肽序列之間的序列相似性或可互換性。當使用諸如Emboss Needle或BestFit等程式確定兩個不同氨基酸序列之間的序列同一性、相似性或同源性時,可以使用默認設置,或者可以選擇適當的打分矩陣,例如blosum45或blosum80,來優化同一性、相似性或同源性得分。優選地,同源的多核苷酸是那些在如本文所定義的嚴格條件下雜交並且與這些序列相比具有至少70%、優選至少80%、更優選至少90%、更優選95%、更優選97%、更優選98%並且甚至更優選99%的序列同一性的多核苷酸。當對可比長度的序列進行最佳比對時,同源的多肽優選具有至少80%,或至少90%,或至少95%,或至少97%,或至少98%的序列同一性,或具有至少99%的序列同一性。
就本文所確定的抗原結合單元而言,“序列同一性百分比(%)”被定義為在比對序列並在必要情況下引入缺口以獲得最大序列同一性百分比後,並且不把任何保守置換視為序列同一性的一部分,查詢序列中與第二、參考多肽序列或其部分的氨基酸殘基相同的氨基酸殘基的百分比。可以以本領域技術內的各種方式,例如使用可公開獲得的電腦軟體,如BLAST、BLAST-2、ALIGN、NEEDLE或Megalign(DNASTAR)軟體,來實現旨在確定氨基酸序列同一性百分比的比對。本領域技術人員可以確定用於測量比對的合適的參數,包括在所比較的序列的全長上獲得最大比對所需的任何演算法。同一性百分比可以在整個定義的多肽序列的長度上進行測量,或者可以在較短的長度上,例如,在從較大的、定義的多肽序列取得的片段的長度上進行測量,該片段例如是至少5、至少10、至少15、至少20、至少50、至少100或至少200個連續殘基的片段。這些長度只是示例性的,並且應該理解,由本文的表格、附圖或序列表中所示的序列支持的任何片段長度可以用來描述在其上可以測量同一性百分比的長度。
本文所述的抗原結合單元可具有相對於參考序列的一個或多個修飾。所述修飾可以是缺失、插入或添加,或氨基酸殘基的取代或置換。“缺失”是指由於缺少一個或多個氨基酸殘基而導致的氨基酸序列變化。“插入”或“添加”是指導致與參考序列相比添加一個或多個氨基酸殘基的氨基酸序列變化。“取代”或“置換”是指一個或多個氨基酸被不同的氨基酸所取代。在本文中,可以通過將抗原結合單元與參考序列進行比較來確定抗原結合單元相對於參考序列的突變。用於比較的序列的最佳比對可以根據本領域的任何已知方法進行。
如本文中所使用的,術語“新型冠狀病毒”、“SARS-CoV-2”和“2019-nCov”是指,因2019年武漢病毒性肺炎病例而被發現的一類冠狀病毒,它們具有相同的含義,可互換使用。如本文中所使用的,術語“新型冠狀病毒肺炎”和“COVID-19”是指,因新型冠狀病毒感染而導致的肺炎,二者具有相同的含義,可互換使用。
如本文中所使用的,術語“抗原”是指被抗原結合單元識別並特異性結合的物質。抗原可以包括肽、蛋白質、糖蛋白、多糖和脂質;其部分,及其組合。非限制性的示例性抗原包括來自冠狀病毒如SARS-CoV-2的蛋白,以及它們的其它同源物。
如本文中所使用的,術語“分離的”是指與細胞的和其它方面的成分分離的,其中在自然界中,多核苷酸、肽、多肽、蛋白質、抗體或其片段在正常情況下與之相關聯。本領域技術人員知曉,非天然存在的多核苷酸、肽、多肽、蛋白質、抗體或其片段不需要“分離”來與其天然存在的對應物區分開來。另外,“濃縮的”、“分離的”或“稀釋的”多核苷酸、肽、多肽、蛋白質、抗體或其片段與其天然存在的對應物是可區分的,因為每單位體積的分子濃度或數目大於(“濃縮的”)或小於從其天然存在的對應物(“分離的”)。富集可基於絕對量來測量,例如每單位體積的溶液的重量,或者其可相對于來源混合物中存在的第二、可能干擾性的物質來測量。
術語“多核苷酸”、“核酸”、“核苷酸”和“寡核苷酸”可互換使用。它們是指任何長度的核苷酸(無論是去氧核糖核苷酸還是核糖核苷酸)或其類似物的聚合形式。多核苷酸可具有任何三維結構,並且可以執行任何已知或未知的功能。以下是多核苷酸的非限制性實例:基因或基因片段的編碼區或非編碼區、從連鎖分析確定的基因座、外顯子、內含子、信使RNA (mRNA)、轉移RNA、核糖體RNA、核酶、cDNA、重組多核苷酸、支鏈多核苷酸、質粒、載體、任意序列的分離的DNA、任意序列的分離的RNA、核酸探針、引物、寡核苷酸或合成的DNA。多核苷酸可以包含修飾的核苷酸,如甲基化核苷酸和核苷酸類似物。如果存在的話,對核苷酸結構的修飾可以在聚合物裝配之前或之後賦予。核苷酸的序列可以被非核苷酸組分中斷。多核苷酸可以在聚合後進一步修飾,例如通過與標記組分綴合。
當應用于多核苷酸時,“重組的”意味著該多核苷酸是克隆、限制酶切消化和/或連接步驟以及產生與自然界中發現的多核苷酸不同的構建體的其它程式的各種組合的產物。
術語“基因”或“基因片段”在本文中可互換使用。它們是指含有至少一個開放閱讀框的多核苷酸,該開放閱讀框能夠在轉錄和翻譯後編碼特定蛋白質。基因或基因片段可以是基因組的、cDNA或合成的,只要該多核苷酸含有至少一個開放閱讀框,該開放閱讀框可以覆蓋整個編碼區或其區段。
術語“可操作地連接”或“有效連接”是指並置,其中這樣描述的組件所處的關係允許它們以其預期方式發揮作用。例如,如果啟動子序列促進編碼序列的轉錄,則該啟動子序列與該編碼序列可操作地連接。
如本文所用的,“表達”是指多核苷酸被轉錄為mRNA的過程,和/或轉錄的mRNA (也稱為“轉錄物”)隨後被翻譯成肽、多肽或蛋白質的過程。轉錄物和被編碼的多肽統稱為基因產物。如果多核苷酸衍生自基因組DNA,則表達可以包括真核細胞中mRNA的剪接。
如本文中所使用的,術語“載體(vector)”是指,可將多聚核苷酸插入其中的一種核酸運載工具。當載體能使插入的多核苷酸編碼的蛋白獲得表達時,載體稱為表達載體。載體可以通過轉化,轉導或者轉染導入宿主細胞,使其攜帶的遺傳物質元件在宿主細胞中獲得表達。載體是本領域技術人員公知的,包括但不限於:質粒;噬菌粒;人工染色體,例如酵母人工染色體(YAC)、細菌人工染色體(BAC)或P1來源的人工染色體(PAC);噬菌體如λ噬菌體或M13噬菌體及動物病毒等。可用作載體的動物病毒包括但不限於,逆轉錄酶病毒(包括慢病毒)、腺病毒、腺相關病毒、皰疹病毒(如單純皰疹病毒)、痘病毒、杆狀病毒、乳頭瘤病毒、乳頭多瘤空泡病毒(如SV40)。一種載體可以含有多種控制表達的元件,包括但不限於,啟動子序列、轉錄起始序列、增強子序列、選擇元件及報告基因。另外,載體還可含有複製起始位點。
如本文中所使用的,術語“宿主細胞”是指,可用於導入載體的細胞,其包括但不限於,如大腸桿菌或枯草芽孢桿菌等的原核細胞,如酵母細胞或曲黴菌等的真菌細胞,如S2果蠅細胞或Sf9等的昆蟲細胞,或者如纖維原細胞,CHO細胞,COS細胞,NSO細胞,HeLa細胞,BHK細胞,HEK293細胞或人細胞等的動物細胞。
如本文中所使用的,術語“生物樣品”包括多種從生物體獲得的樣品類型,並且可以在診斷或監測試驗中使用。該術語包括血液和生物起源的其它液體樣品,固體組織樣品,如活檢標本或組織培養物,或由其衍生的細胞及其後代。該術語包括在獲得後已經以任何方式進行處理的樣品,例如通過用試劑處理、溶解或針對某些組分進行富集。該術語包括臨床樣品,並且還包括在細胞培養物、細胞上清液、細胞裂解物、血清、血漿、生物流體和組織樣品中的細胞。
如本文中所使用的,術語“接受者”、“個體”、“受試者”、“宿主”和“患者”在本文中可互換使用,並且是指希望對其進行診斷、處理或治療的任何哺乳動物受試者,特別是人類。
如本文中所使用的,術語“治療”、“處理”等在本文中用來泛指獲得所需的藥理學和/或生理學效果。該效果就完全或部分防止疾病或其症狀而言可以是預防性的,和/或就部分或完全穩定或治癒疾病和/或歸因於該疾病的不良反應而言可以是治療性的。如本文所用的“治療”涵蓋在哺乳動物中對疾病的任何治療,該哺乳動物例如是小鼠、大鼠、兔、豬、靈長類動物,包括人類和其它猿類,特別是人,並且該術語包括:(a)防止疾病或症狀在可能易患該疾病或症狀但尚未發生診斷的受試者中發生;(b)抑制疾病症狀;(C)阻止疾病的發展;(d)緩解疾病症狀;(e)引起疾病或症狀消退;或其任意組合。如本文中使用的,術語“特異性結合”是指,兩分子間的非隨機的結合反應,如抗體和其所針對的抗原之間的反應。在某些實施方式中,特異性結合某抗原的抗體(或對某抗原具有特異性的抗體)是指,抗體以小於大約10-5
M,例如小於大約10-6
M、10-7
M、10-8
M、10-9
M或10-10
M或更小的親和力(KD)結合該抗原。
如本文中所使用的,術語“KD”是指特定抗體-抗原相互作用的解離平衡常數,其用於描述抗體與抗原之間的結合親和力。在本文中,KD被定義為兩個動力學速率常數Ka/Kd的比率,其中“Ka”指抗體與抗原結合的速率常數,“Kd”指抗體從抗體/抗原複合物中解離的速率常數。平衡解離常數KD越小,抗體-抗原結合越緊密,抗體與抗原之間的親和力越高。通常,抗體以小於大約10-5
M的解離平衡常數(KD)結合抗原。兩分子間的特異性結合性質可使用本領域公知的方法進行測定,例如使用表面等離子體共振術(SPR)在BIACORE儀中測定。
如本文中所使用的,術語“中和活性”是指抗體或抗體片段具有與病毒上的抗原蛋白相結合,從而阻止病毒感染細胞和/或病毒子代的成熟和/或病毒子代的釋放的功能活性,具有中和活性的抗體或抗體片段可以阻止病毒的擴增,從而抑制或消除病毒的感染。在一些實施方案中,所述中和活性通過抗體或抗體片段對病毒抑制的IC50
表示。“半數最大抑制濃度”(IC50
)是藥物如抗體在抑制生物或生化功能等方面(如病毒效力)的量度。在本文中的IC50
根據抗原結合片段對病毒(例如假病毒或真病毒)感染細胞的中和抑制率,並利用Reed-Muench法計算。本文提供一種抗原結合單元,其能夠特異性識別和靶向新型冠狀病毒的S蛋白,特別是S蛋白的受體結合結構域(RBD),並且顯示出了高效的中和病毒的能力。因此,本文所述的抗原結合單元特別適合用於診斷、預防和治療新型冠狀病毒感染或與新型冠狀病毒感染相關的疾病(例如新型冠狀病毒肺炎)。抗原結合單元
一方面,本文所述的抗原結合單元包含重鏈可變區(VH)和輕鏈可變區(VL),所述重鏈可變區包含VH CDR1、VH CDR2和VH CDR3,且所述輕鏈可變區包含VL CDR1、VL CDR2和VL CDR3。
本文所述的抗原結合單元的VH可包含選自SEQ ID NO.: 721-1080和3111-3145的序列,與選自SEQ ID NO: 721-1080和3111-3145的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 721-1080和3111-3145的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。當本文所述的抗原結合單元的VH與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VH與參考多肽相比可存在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個或20個添加、刪除或取代。當本文所述的抗原結合單元的VH與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VH與參考多肽相比可存在多於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個或20個添加、刪除或取代。當本文所述的抗原結合單元的VH與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VH與參考多肽相比可存在少於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個或20個添加、刪除或取代。
本文所述的抗原結合單元的VH CDR1可包含選自SEQ ID NO.: 1461-1820和2901-2935的序列,與選自SEQ ID NO: 1461-1820和2901-2935的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 1461-1820和2901-2935的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。當本文所述的抗原結合單元的VH CDR1與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VH CDR1與參考多肽相比可存在1個、2個、3個、4個、或5個添加、刪除或取代。當本文所述的抗原結合單元的VH CDR1與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VH CDR1與參考多肽相比可存在多於1個、2個、3個、4個、或5個添加、刪除或取代。當本文所述的抗原結合單元的VH CDR1與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VH CDR1與參考多肽相比可存在少於2個、3個、4個、或5個添加、刪除或取代。
本文所述的抗原結合單元的VH CDR2可包含選自SEQ ID NO.: 1821-2180和2936-2970的序列,與選自SEQ ID NO: 1821-2180和2936-2970的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 1821-2180和2936-2970的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。當本文所述的抗原結合單元的VH CDR2與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VH CDR2與參考多肽相比可存在1個、2個、3個、4個、或5個添加、刪除或取代。當本文所述的抗原結合單元的VH CDR2與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VH CDR2與參考多肽相比可存在多於1個、2個、3個、4個、或5個添加、刪除或取代。當本文所述的抗原結合單元的VH CDR2與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VH CDR2與參考多肽相比可存在少於2個、3個、4個、或5個添加、刪除或取代。
本文所述的抗原結合單元的VH CDR3可包含選自SEQ ID NO.: 1-360和2971-3005的序列,與選自SEQ ID NO: 1-360和2971-3005的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 1-360和2971-3005的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。當本文所述的抗原結合單元的VH CDR3與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VH CDR3與參考多肽相比可存在1個、2個、3個、4個、或5個添加、刪除或取代。當本文所述的抗原結合單元的VH CDR3與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VH CDR3與參考多肽相比可存在多於1個、2個、3個、4個、或5個添加、刪除或取代。當本文所述的抗原結合單元的VH CDR2與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VH CDR3與參考多肽相比可存在少於2個、3個、4個、或5個添加、刪除或取代。
本文所述的抗原結合單元的VL可包含選自SEQ ID NO.: 1081-1440和3146-3180的序列,與選自SEQ ID NO: 1081-1440和3146-3180的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 1081-1440和3146-3180的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。當本文所述的抗原結合單元的VL與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VL與參考多肽相比可存在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個或20個添加、刪除或取代。當本文所述的抗原結合單元的VL與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VL與參考多肽相比可存在多於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個或20個添加、刪除或取代。當本文所述的抗原結合單元的VL與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VL與參考多肽相比可存在少於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個或20個添加、刪除或取代。
本文所述的抗原結合單元的VL CDR1可包含選自選自SEQ ID NO.: 2181-2540和3006-3040的序列,與選自SEQ ID NO: 2181-2540和3006-3040的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 2181-2540和3006-3040的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。當本文所述的抗原結合單元的VL CDR1與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VL CDR1與參考多肽相比可存在1個、2個、3個、4個、或5個添加、刪除或取代。當本文所述的抗原結合單元的VL CDR1與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VL CDR1與參考多肽相比可存在多於1個、2個、3個、4個、或5個添加、刪除或取代。當本文所述的抗原結合單元的VL CDR1與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VL CDR1與參考多肽相比可存在少於2個、3個、4個、或5個添加、刪除或取代。
本文所述的抗原結合單元的VL CDR2可包含選自SEQ ID NO.: 2541-2900和3041-3075的序列,與選自SEQ ID NO: 2541-2900和3041-3075的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 2541-2900和3041-3075的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。當本文所述的抗原結合單元的VL CDR2與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VL CDR2與參考多肽相比可存在1個、2個、3個、4個、或5個添加、刪除或取代。當本文所述的抗原結合單元的VL CDR2與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VL CDR2與參考多肽相比可存在多於1個、2個、3個、4個、或5個添加、刪除或取代。當本文所述的抗原結合單元的VL CDR2與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VL CDR2與參考多肽相比可存在少於2個、3個、4個、或5個添加、刪除或取代。
本文所述的抗原結合單元的VL CDR3可包含選自SEQ ID NO.: 361-720和3076-3110的序列,與選自SEQ ID NO: 361-720和3076-3110的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 361-720和3076-3110的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。當本文所述的抗原結合單元的VL CDR3與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VL CDR3與參考多肽相比可存在1個、2個、3個、4個、或5個添加、刪除或取代。當本文所述的抗原結合單元的VL CDR3與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VL CDR3與參考多肽相比可存在多於1個、2個、3個、4個、或5個添加、刪除或取代。當本文所述的抗原結合單元的VL CDR3與參考多肽序列相比存在氨基酸添加、刪除或取代時,本文所述的抗原結合單元的VL CDR3與參考多肽相比可存在少於2個、3個、4個、或5個添加、刪除或取代。
本文所述的抗原結合單元的VH CDR1可包含選自SEQ ID NO.: 1461-1820和2901-2935的序列,與選自SEQ ID NO: 1461-1820和2901-2935的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 1461-1820和2901-2935的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列;並且本文所述的抗原結合單元的VL CDR1 可包含選自SEQ ID NO.: 2181-2540和3006-3040的序列,與選自SEQ ID NO: 2181-2540和3006-3040的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 2181-2540和3006-3040的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
本文所述的抗原結合單元的VH CDR2可包含選自SEQ ID NO.: 1821-2180和2936-2970的序列,與選自SEQ ID NO: 1821-2180和2936-2970的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 1821-2180和2936-2970的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列;並且本文所述的抗原結合單元的VL CDR2 可包含選自SEQ ID NO.: 2541-2900和3041-3075的序列,與選自SEQ ID NO: 2541-2900和3041-3075的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 2541-2900和3041-3075的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
本文所述的抗原結合單元的VH CDR3可包含選自SEQ ID NO.: 1-360和2971-3005的序列,與選自SEQ ID NO: 1-360和2971-3005的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 1-360和2971-3005的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列;並且本文所述的抗原結合單元的VL CDR3 可包含選自SEQ ID NO.: 361-720和3076-3110的序列,與選自SEQ ID NO: 361-720和3076-3110的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 361-720和3076-3110的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
本文所述的抗原結合單元的VH可包含VH CDR1、VH CDR2和VH CDR3,其中所述VH CDR1選自SEQ ID NO.: 1461-1820和2901-2935的序列,與選自SEQ ID NO: 1461-1820和2901-2935的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 1461-1820和2901-2935的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列;其中所述VH CDR2 選自SEQ ID NO.: 1821-2180和2936-2970的序列,與選自SEQ ID NO: 1821-2180和2936-2970的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 1821-2180和2936-2970的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列;且其中所述VH CDR3 選自SEQ ID NO.: 1-360和2971-3005的序列,與選自SEQ ID NO: 1-360和2971-3005的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 1-360和2971-3005的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
本文所述的抗原結合單元的VL可包含VL CDR1、VL CDR2和VL CDR3,其中所述VL CDR1選自SEQ ID NO.: 2181-2540和3006-3040的序列,與選自SEQ ID NO: 2181-2540和3006-3040的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 2181-2540和3006-3040的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列;其中所述VL CDR2 選自SEQ ID NO.: 2541-2900和3041-3075的序列,與選自SEQ ID NO: 2541-2900和3041-3075的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 2541-2900和3041-3075的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列;且其中所述VL CDR3 選自SEQ ID NO.: 361-720和3076-3110的序列,與選自SEQ ID NO: 361-720和3076-3110的序列相比包含一個或多個氨基酸添加、刪除、或取代的序列,或者與選自SEQ ID NO: 361-720和3076-3110的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
本文所述的抗原結合單元的VH可包含選自下表A的CDR1、CDR2、和CDR3的組合的序列,其中所述VH的CDR1、CDR2、和CDR3序列遵循IMGT系統定義。
表A. 本申請示例性抗原結合單元的VH所包含的CDR1、CDR2、和CDR3的組合
HCDR1 | HCDR2 | HCDR3 | HCDR1 | HCDR2 | HCDR3 | HCDR1 | HCDR2 | HCDR3 | |||
1461 | 1821 | 1 | 1581 | 1941 | 121 | 1701 | 2061 | 241 | |||
1462 | 1822 | 2 | 1582 | 1942 | 122 | 1702 | 2062 | 242 | |||
1463 | 1823 | 3 | 1583 | 1943 | 123 | 1703 | 2063 | 243 | |||
1464 | 1824 | 4 | 1584 | 1944 | 124 | 1704 | 2064 | 244 | |||
1465 | 1825 | 5 | 1585 | 1945 | 125 | 1705 | 2065 | 245 | |||
1466 | 1826 | 6 | 1586 | 1946 | 126 | 1706 | 2066 | 246 | |||
1467 | 1827 | 7 | 1587 | 1947 | 127 | 1707 | 2067 | 247 | |||
1468 | 1828 | 8 | 1588 | 1948 | 128 | 1708 | 2068 | 248 | |||
1469 | 1829 | 9 | 1589 | 1949 | 129 | 1709 | 2069 | 249 | |||
1470 | 1830 | 10 | 1590 | 1950 | 130 | 1710 | 2070 | 250 | |||
1471 | 1831 | 11 | 1591 | 1951 | 131 | 1711 | 2071 | 251 | |||
1472 | 1832 | 12 | 1592 | 1952 | 132 | 1712 | 2072 | 252 | |||
1473 | 1833 | 13 | 1593 | 1953 | 133 | 1713 | 2073 | 253 | |||
1474 | 1834 | 14 | 1594 | 1954 | 134 | 1714 | 2074 | 254 | |||
1475 | 1835 | 15 | 1595 | 1955 | 135 | 1715 | 2075 | 255 | |||
1476 | 1836 | 16 | 1596 | 1956 | 136 | 1716 | 2076 | 256 | |||
1477 | 1837 | 17 | 1597 | 1957 | 137 | 1717 | 2077 | 257 | |||
1478 | 1838 | 18 | 1598 | 1958 | 138 | 1718 | 2078 | 258 | |||
1479 | 1839 | 19 | 1599 | 1959 | 139 | 1719 | 2079 | 259 | |||
1480 | 1840 | 20 | 1600 | 1960 | 140 | 1720 | 2080 | 260 | |||
1481 | 1841 | 21 | 1601 | 1961 | 141 | 1721 | 2081 | 261 | |||
1482 | 1842 | 22 | 1602 | 1962 | 142 | 1722 | 2082 | 262 | |||
1483 | 1843 | 23 | 1603 | 1963 | 143 | 1723 | 2083 | 263 | |||
1484 | 1844 | 24 | 1604 | 1964 | 144 | 1724 | 2084 | 264 | |||
1485 | 1845 | 25 | 1605 | 1965 | 145 | 1725 | 2085 | 265 | |||
1486 | 1846 | 26 | 1606 | 1966 | 146 | 1726 | 2086 | 266 | |||
1487 | 1847 | 27 | 1607 | 1967 | 147 | 1727 | 2087 | 267 | |||
1488 | 1848 | 28 | 1608 | 1968 | 148 | 1728 | 2088 | 268 | |||
1489 | 1849 | 29 | 1609 | 1969 | 149 | 1729 | 2089 | 269 | |||
1490 | 1850 | 30 | 1610 | 1970 | 150 | 1730 | 2090 | 270 | |||
1491 | 1851 | 31 | 1611 | 1971 | 151 | 1731 | 2091 | 271 | |||
1492 | 1852 | 32 | 1612 | 1972 | 152 | 1732 | 2092 | 272 | |||
1493 | 1853 | 33 | 1613 | 1973 | 153 | 1733 | 2093 | 273 | |||
1494 | 1854 | 34 | 1614 | 1974 | 154 | 1734 | 2094 | 274 | |||
1495 | 1855 | 35 | 1615 | 1975 | 155 | 1735 | 2095 | 275 | |||
1496 | 1856 | 36 | 1616 | 1976 | 156 | 1736 | 2096 | 276 | |||
1497 | 1857 | 37 | 1617 | 1977 | 157 | 1737 | 2097 | 277 | |||
1498 | 1858 | 38 | 1618 | 1978 | 158 | 1738 | 2098 | 278 | |||
1499 | 1859 | 39 | 1619 | 1979 | 159 | 1739 | 2099 | 279 | |||
1500 | 1860 | 40 | 1620 | 1980 | 160 | 1740 | 2100 | 280 | |||
1501 | 1861 | 41 | 1621 | 1981 | 161 | 1741 | 2101 | 281 | |||
1502 | 1862 | 42 | 1622 | 1982 | 162 | 1742 | 2102 | 282 | |||
1503 | 1863 | 43 | 1623 | 1983 | 163 | 1743 | 2103 | 283 | |||
1504 | 1864 | 44 | 1624 | 1984 | 164 | 1744 | 2104 | 284 | |||
1505 | 1865 | 45 | 1625 | 1985 | 165 | 1745 | 2105 | 285 | |||
1506 | 1866 | 46 | 1626 | 1986 | 166 | 1746 | 2106 | 286 | |||
1507 | 1867 | 47 | 1627 | 1987 | 167 | 1747 | 2107 | 287 | |||
1508 | 1868 | 48 | 1628 | 1988 | 168 | 1748 | 2108 | 288 | |||
1509 | 1869 | 49 | 1629 | 1989 | 169 | 1749 | 2109 | 289 | |||
1510 | 1870 | 50 | 1630 | 1990 | 170 | 1750 | 2110 | 290 | |||
1511 | 1871 | 51 | 1631 | 1991 | 171 | 1751 | 2111 | 291 | |||
1512 | 1872 | 52 | 1632 | 1992 | 172 | 1752 | 2112 | 292 | |||
1513 | 1873 | 53 | 1633 | 1993 | 173 | 1753 | 2113 | 293 | |||
1514 | 1874 | 54 | 1634 | 1994 | 174 | 1754 | 2114 | 294 | |||
1515 | 1875 | 55 | 1635 | 1995 | 175 | 1755 | 2115 | 295 | |||
1516 | 1876 | 56 | 1636 | 1996 | 176 | 1756 | 2116 | 296 | |||
1517 | 1877 | 57 | 1637 | 1997 | 177 | 1757 | 2117 | 297 | |||
1518 | 1878 | 58 | 1638 | 1998 | 178 | 1758 | 2118 | 298 | |||
1519 | 1879 | 59 | 1639 | 1999 | 179 | 1759 | 2119 | 299 | |||
1520 | 1880 | 60 | 1640 | 2000 | 180 | 1760 | 2120 | 300 | |||
1521 | 1881 | 61 | 1641 | 2001 | 181 | 1761 | 2121 | 301 | |||
1522 | 1882 | 62 | 1642 | 2002 | 182 | 1762 | 2122 | 302 | |||
1523 | 1883 | 63 | 1643 | 2003 | 183 | 1763 | 2123 | 303 | |||
1524 | 1884 | 64 | 1644 | 2004 | 184 | 1764 | 2124 | 304 | |||
1525 | 1885 | 65 | 1645 | 2005 | 185 | 1765 | 2125 | 305 | |||
1526 | 1886 | 66 | 1646 | 2006 | 186 | 1766 | 2126 | 306 | |||
1527 | 1887 | 67 | 1647 | 2007 | 187 | 1767 | 2127 | 307 | |||
1528 | 1888 | 68 | 1648 | 2008 | 188 | 1768 | 2128 | 308 | |||
1529 | 1889 | 69 | 1649 | 2009 | 189 | 1769 | 2129 | 309 | |||
1530 | 1890 | 70 | 1650 | 2010 | 190 | 1770 | 2130 | 310 | |||
1531 | 1891 | 71 | 1651 | 2011 | 191 | 1771 | 2131 | 311 | |||
1532 | 1892 | 72 | 1652 | 2012 | 192 | 1772 | 2132 | 312 | |||
1533 | 1893 | 73 | 1653 | 2013 | 193 | 1773 | 2133 | 313 | |||
1534 | 1894 | 74 | 1654 | 2014 | 194 | 1774 | 2134 | 314 | |||
1535 | 1895 | 75 | 1655 | 2015 | 195 | 1775 | 2135 | 315 | |||
1536 | 1896 | 76 | 1656 | 2016 | 196 | 1776 | 2136 | 316 | |||
1537 | 1897 | 77 | 1657 | 2017 | 197 | 1777 | 2137 | 317 | |||
1538 | 1898 | 78 | 1658 | 2018 | 198 | 1778 | 2138 | 318 | |||
1539 | 1899 | 79 | 1659 | 2019 | 199 | 1779 | 2139 | 319 | |||
1540 | 1900 | 80 | 1660 | 2020 | 200 | 1780 | 2140 | 320 | |||
1541 | 1901 | 81 | 1661 | 2021 | 201 | 1781 | 2141 | 321 | |||
1542 | 1902 | 82 | 1662 | 2022 | 202 | 1782 | 2142 | 322 | |||
1543 | 1903 | 83 | 1663 | 2023 | 203 | 1783 | 2143 | 323 | |||
1544 | 1904 | 84 | 1664 | 2024 | 204 | 1784 | 2144 | 324 | |||
1545 | 1905 | 85 | 1665 | 2025 | 205 | 1785 | 2145 | 325 | |||
1546 | 1906 | 86 | 1666 | 2026 | 206 | 1786 | 2146 | 326 | |||
1547 | 1907 | 87 | 1667 | 2027 | 207 | 1787 | 2147 | 327 | |||
1548 | 1908 | 88 | 1668 | 2028 | 208 | 1788 | 2148 | 328 | |||
1549 | 1909 | 89 | 1669 | 2029 | 209 | 1789 | 2149 | 329 | |||
1550 | 1910 | 90 | 1670 | 2030 | 210 | 1790 | 2150 | 330 | |||
1551 | 1911 | 91 | 1671 | 2031 | 211 | 1791 | 2151 | 331 | |||
1552 | 1912 | 92 | 1672 | 2032 | 212 | 1792 | 2152 | 332 | |||
1553 | 1913 | 93 | 1673 | 2033 | 213 | 1793 | 2153 | 333 | |||
1554 | 1914 | 94 | 1674 | 2034 | 214 | 1794 | 2154 | 334 | |||
1555 | 1915 | 95 | 1675 | 2035 | 215 | 1795 | 2155 | 335 | |||
1556 | 1916 | 96 | 1676 | 2036 | 216 | 1796 | 2156 | 336 | |||
1557 | 1917 | 97 | 1677 | 2037 | 217 | 1797 | 2157 | 337 | |||
1558 | 1918 | 98 | 1678 | 2038 | 218 | 1798 | 2158 | 338 | |||
1559 | 1919 | 99 | 1679 | 2039 | 219 | 1799 | 2159 | 339 | |||
1560 | 1920 | 100 | 1680 | 2040 | 220 | 1800 | 2160 | 340 | |||
1561 | 1921 | 101 | 1681 | 2041 | 221 | 1801 | 2161 | 341 | |||
1562 | 1922 | 102 | 1682 | 2042 | 222 | 1802 | 2162 | 342 | |||
1563 | 1923 | 103 | 1683 | 2043 | 223 | 1803 | 2163 | 343 | |||
1564 | 1924 | 104 | 1684 | 2044 | 224 | 1804 | 2164 | 344 | |||
1565 | 1925 | 105 | 1685 | 2045 | 225 | 1805 | 2165 | 345 | |||
1566 | 1926 | 106 | 1686 | 2046 | 226 | 1806 | 2166 | 346 | |||
1567 | 1927 | 107 | 1687 | 2047 | 227 | 1807 | 2167 | 347 | |||
1568 | 1928 | 108 | 1688 | 2048 | 228 | 1808 | 2168 | 348 | |||
1569 | 1929 | 109 | 1689 | 2049 | 229 | 1809 | 2169 | 349 | |||
1570 | 1930 | 110 | 1690 | 2050 | 230 | 1810 | 2170 | 350 | |||
1571 | 1931 | 111 | 1691 | 2051 | 231 | 1811 | 2171 | 351 | |||
1572 | 1932 | 112 | 1692 | 2052 | 232 | 1812 | 2172 | 352 | |||
1573 | 1933 | 113 | 1693 | 2053 | 233 | 1813 | 2173 | 353 | |||
1574 | 1934 | 114 | 1694 | 2054 | 234 | 1814 | 2174 | 354 | |||
1575 | 1935 | 115 | 1695 | 2055 | 235 | 1815 | 2175 | 355 | |||
1576 | 1936 | 116 | 1696 | 2056 | 236 | 1816 | 2176 | 356 | |||
1577 | 1937 | 117 | 1697 | 2057 | 237 | 1817 | 2177 | 357 | |||
1578 | 1938 | 118 | 1698 | 2058 | 238 | 1818 | 2178 | 358 | |||
1579 | 1939 | 119 | 1699 | 2059 | 239 | 1819 | 2179 | 359 | |||
1580 | 1940 | 120 | 1700 | 2060 | 240 | 1820 | 2180 | 360 | |||
2901 | 2936 | 2971 | 2913 | 2948 | 2983 | 2925 | 2960 | 2995 | |||
2902 | 2937 | 2972 | 2914 | 2949 | 2984 | 2926 | 2961 | 2996 | |||
2903 | 2938 | 2973 | 2915 | 2950 | 2985 | 2927 | 2962 | 2997 | |||
2904 | 2939 | 2974 | 2916 | 2951 | 2986 | 2928 | 2963 | 2998 | |||
2905 | 2940 | 2975 | 2917 | 2952 | 2987 | 2929 | 2964 | 2999 | |||
2906 | 2941 | 2976 | 2918 | 2953 | 2988 | 2930 | 2965 | 3000 | |||
2907 | 2942 | 2977 | 2919 | 2954 | 2989 | 2931 | 2966 | 3001 | |||
2908 | 2943 | 2978 | 2920 | 2955 | 2990 | 2932 | 2967 | 3002 | |||
2909 | 2944 | 2979 | 2921 | 2956 | 2991 | 2933 | 2968 | 3003 | |||
2910 | 2945 | 2980 | 2922 | 2957 | 2992 | 2934 | 2969 | 3004 | |||
2911 | 2946 | 2981 | 2923 | 2958 | 2993 | 2935 | 2970 | 3005 | |||
2912 | 2947 | 2982 | 2924 | 2959 | 2994 |
本文所述的抗原結合單元的VL可包含選自下表B的CDR1、CDR2、和CDR3的組合的序列,其中所述VL的CDR1、CDR2、和CDR3序列遵循IMGT系統定義。
表B. 本申請示例性抗原結合單元的VL所包含的CDR1、CDR2、和CDR3的組合
LCDR1 | LCDR2 | LCDR3 | LCDR1 | LCDR2 | LCDR3 | LCDR1 | LCDR2 | LCDR3 | ||
2181 | 2541 | 361 | 2301 | 2661 | 481 | 2421 | 2781 | 601 | ||
2182 | 2542 | 362 | 2302 | 2662 | 482 | 2422 | 2782 | 602 | ||
2183 | 2543 | 363 | 2303 | 2663 | 483 | 2423 | 2783 | 603 | ||
2184 | 2544 | 364 | 2304 | 2664 | 484 | 2424 | 2784 | 604 | ||
2185 | 2545 | 365 | 2305 | 2665 | 485 | 2425 | 2785 | 605 | ||
2186 | 2546 | 366 | 2306 | 2666 | 486 | 2426 | 2786 | 606 | ||
2187 | 2547 | 367 | 2307 | 2667 | 487 | 2427 | 2787 | 607 | ||
2188 | 2548 | 368 | 2308 | 2668 | 488 | 2428 | 2788 | 608 | ||
2189 | 2549 | 369 | 2309 | 2669 | 489 | 2429 | 2789 | 609 | ||
2190 | 2550 | 370 | 2310 | 2670 | 490 | 2430 | 2790 | 610 | ||
2191 | 2551 | 371 | 2311 | 2671 | 491 | 2431 | 2791 | 611 | ||
2192 | 2552 | 372 | 2312 | 2672 | 492 | 2432 | 2792 | 612 | ||
2193 | 2553 | 373 | 2313 | 2673 | 493 | 2433 | 2793 | 613 | ||
2194 | 2554 | 374 | 2314 | 2674 | 494 | 2434 | 2794 | 614 | ||
2195 | 2555 | 375 | 2315 | 2675 | 495 | 2435 | 2795 | 615 | ||
2196 | 2556 | 376 | 2316 | 2676 | 496 | 2436 | 2796 | 616 | ||
2197 | 2557 | 377 | 2317 | 2677 | 497 | 2437 | 2797 | 617 | ||
2198 | 2558 | 378 | 2318 | 2678 | 498 | 2438 | 2798 | 618 | ||
2199 | 2559 | 379 | 2319 | 2679 | 499 | 2439 | 2799 | 619 | ||
2200 | 2560 | 380 | 2320 | 2680 | 500 | 2440 | 2800 | 620 | ||
2201 | 2561 | 381 | 2321 | 2681 | 501 | 2441 | 2801 | 621 | ||
2202 | 2562 | 382 | 2322 | 2682 | 502 | 2442 | 2802 | 622 | ||
2203 | 2563 | 383 | 2323 | 2683 | 503 | 2443 | 2803 | 623 | ||
2204 | 2564 | 384 | 2324 | 2684 | 504 | 2444 | 2804 | 624 | ||
2205 | 2565 | 385 | 2325 | 2685 | 505 | 2445 | 2805 | 625 | ||
2206 | 2566 | 386 | 2326 | 2686 | 506 | 2446 | 2806 | 626 | ||
2207 | 2567 | 387 | 2327 | 2687 | 507 | 2447 | 2807 | 627 | ||
2208 | 2568 | 388 | 2328 | 2688 | 508 | 2448 | 2808 | 628 | ||
2209 | 2569 | 389 | 2329 | 2689 | 509 | 2449 | 2809 | 629 | ||
2210 | 2570 | 390 | 2330 | 2690 | 510 | 2450 | 2810 | 630 | ||
2211 | 2571 | 391 | 2331 | 2691 | 511 | 2451 | 2811 | 631 | ||
2212 | 2572 | 392 | 2332 | 2692 | 512 | 2452 | 2812 | 632 | ||
2213 | 2573 | 393 | 2333 | 2693 | 513 | 2453 | 2813 | 633 | ||
2214 | 2574 | 394 | 2334 | 2694 | 514 | 2454 | 2814 | 634 | ||
2215 | 2575 | 395 | 2335 | 2695 | 515 | 2455 | 2815 | 635 | ||
2216 | 2576 | 396 | 2336 | 2696 | 516 | 2456 | 2816 | 636 | ||
2217 | 2577 | 397 | 2337 | 2697 | 517 | 2457 | 2817 | 637 | ||
2218 | 2578 | 398 | 2338 | 2698 | 518 | 2458 | 2818 | 638 | ||
2219 | 2579 | 399 | 2339 | 2699 | 519 | 2459 | 2819 | 639 | ||
2220 | 2580 | 400 | 2340 | 2700 | 520 | 2460 | 2820 | 640 | ||
2221 | 2581 | 401 | 2341 | 2701 | 521 | 2461 | 2821 | 641 | ||
2222 | 2582 | 402 | 2342 | 2702 | 522 | 2462 | 2822 | 642 | ||
2223 | 2583 | 403 | 2343 | 2703 | 523 | 2463 | 2823 | 643 | ||
2224 | 2584 | 404 | 2344 | 2704 | 524 | 2464 | 2824 | 644 | ||
2225 | 2585 | 405 | 2345 | 2705 | 525 | 2465 | 2825 | 645 | ||
2226 | 2586 | 406 | 2346 | 2706 | 526 | 2466 | 2826 | 646 | ||
2227 | 2587 | 407 | 2347 | 2707 | 527 | 2467 | 2827 | 647 | ||
2228 | 2588 | 408 | 2348 | 2708 | 528 | 2468 | 2828 | 648 | ||
2229 | 2589 | 409 | 2349 | 2709 | 529 | 2469 | 2829 | 649 | ||
2230 | 2590 | 410 | 2350 | 2710 | 530 | 2470 | 2830 | 650 | ||
2231 | 2591 | 411 | 2351 | 2711 | 531 | 2471 | 2831 | 651 | ||
2232 | 2592 | 412 | 2352 | 2712 | 532 | 2472 | 2832 | 652 | ||
2233 | 2593 | 413 | 2353 | 2713 | 533 | 2473 | 2833 | 653 | ||
2234 | 2594 | 414 | 2354 | 2714 | 534 | 2474 | 2834 | 654 | ||
2235 | 2595 | 415 | 2355 | 2715 | 535 | 2475 | 2835 | 655 | ||
2236 | 2596 | 416 | 2356 | 2716 | 536 | 2476 | 2836 | 656 | ||
2237 | 2597 | 417 | 2357 | 2717 | 537 | 2477 | 2837 | 657 | ||
2238 | 2598 | 418 | 2358 | 2718 | 538 | 2478 | 2838 | 658 | ||
2239 | 2599 | 419 | 2359 | 2719 | 539 | 2479 | 2839 | 659 | ||
2240 | 2600 | 420 | 2360 | 2720 | 540 | 2480 | 2840 | 660 | ||
2241 | 2601 | 421 | 2361 | 2721 | 541 | 2481 | 2841 | 661 | ||
2242 | 2602 | 422 | 2362 | 2722 | 542 | 2482 | 2842 | 662 | ||
2243 | 2603 | 423 | 2363 | 2723 | 543 | 2483 | 2843 | 663 | ||
2244 | 2604 | 424 | 2364 | 2724 | 544 | 2484 | 2844 | 664 | ||
2245 | 2605 | 425 | 2365 | 2725 | 545 | 2485 | 2845 | 665 | ||
2246 | 2606 | 426 | 2366 | 2726 | 546 | 2486 | 2846 | 666 | ||
2247 | 2607 | 427 | 2367 | 2727 | 547 | 2487 | 2847 | 667 | ||
2248 | 2608 | 428 | 2368 | 2728 | 548 | 2488 | 2848 | 668 | ||
2249 | 2609 | 429 | 2369 | 2729 | 549 | 2489 | 2849 | 669 | ||
2250 | 2610 | 430 | 2370 | 2730 | 550 | 2490 | 2850 | 670 | ||
2251 | 2611 | 431 | 2371 | 2731 | 551 | 2491 | 2851 | 671 | ||
2252 | 2612 | 432 | 2372 | 2732 | 552 | 2492 | 2852 | 672 | ||
2253 | 2613 | 433 | 2373 | 2733 | 553 | 2493 | 2853 | 673 | ||
2254 | 2614 | 434 | 2374 | 2734 | 554 | 2494 | 2854 | 674 | ||
2255 | 2615 | 435 | 2375 | 2735 | 555 | 2495 | 2855 | 675 | ||
2256 | 2616 | 436 | 2376 | 2736 | 556 | 2496 | 2856 | 676 | ||
2257 | 2617 | 437 | 2377 | 2737 | 557 | 2497 | 2857 | 677 | ||
2258 | 2618 | 438 | 2378 | 2738 | 558 | 2498 | 2858 | 678 | ||
2259 | 2619 | 439 | 2379 | 2739 | 559 | 2499 | 2859 | 679 | ||
2260 | 2620 | 440 | 2380 | 2740 | 560 | 2500 | 2860 | 680 | ||
2261 | 2621 | 441 | 2381 | 2741 | 561 | 2501 | 2861 | 681 | ||
2262 | 2622 | 442 | 2382 | 2742 | 562 | 2502 | 2862 | 682 | ||
2263 | 2623 | 443 | 2383 | 2743 | 563 | 2503 | 2863 | 683 | ||
2264 | 2624 | 444 | 2384 | 2744 | 564 | 2504 | 2864 | 684 | ||
2265 | 2625 | 445 | 2385 | 2745 | 565 | 2505 | 2865 | 685 | ||
2266 | 2626 | 446 | 2386 | 2746 | 566 | 2506 | 2866 | 686 | ||
2267 | 2627 | 447 | 2387 | 2747 | 567 | 2507 | 2867 | 687 | ||
2268 | 2628 | 448 | 2388 | 2748 | 568 | 2508 | 2868 | 688 | ||
2269 | 2629 | 449 | 2389 | 2749 | 569 | 2509 | 2869 | 689 | ||
2270 | 2630 | 450 | 2390 | 2750 | 570 | 2510 | 2870 | 690 | ||
2271 | 2631 | 451 | 2391 | 2751 | 571 | 2511 | 2871 | 691 | ||
2272 | 2632 | 452 | 2392 | 2752 | 572 | 2512 | 2872 | 692 | ||
2273 | 2633 | 453 | 2393 | 2753 | 573 | 2513 | 2873 | 693 | ||
2274 | 2634 | 454 | 2394 | 2754 | 574 | 2514 | 2874 | 694 | ||
2275 | 2635 | 455 | 2395 | 2755 | 575 | 2515 | 2875 | 695 | ||
2276 | 2636 | 456 | 2396 | 2756 | 576 | 2516 | 2876 | 696 | ||
2277 | 2637 | 457 | 2397 | 2757 | 577 | 2517 | 2877 | 697 | ||
2278 | 2638 | 458 | 2398 | 2758 | 578 | 2518 | 2878 | 698 | ||
2279 | 2639 | 459 | 2399 | 2759 | 579 | 2519 | 2879 | 699 | ||
2280 | 2640 | 460 | 2400 | 2760 | 580 | 2520 | 2880 | 700 | ||
2281 | 2641 | 461 | 2401 | 2761 | 581 | 2521 | 2881 | 701 | ||
2282 | 2642 | 462 | 2402 | 2762 | 582 | 2522 | 2882 | 702 | ||
2283 | 2643 | 463 | 2403 | 2763 | 583 | 2523 | 2883 | 703 | ||
2284 | 2644 | 464 | 2404 | 2764 | 584 | 2524 | 2884 | 704 | ||
2285 | 2645 | 465 | 2405 | 2765 | 585 | 2525 | 2885 | 705 | ||
2286 | 2646 | 466 | 2406 | 2766 | 586 | 2526 | 2886 | 706 | ||
2287 | 2647 | 467 | 2407 | 2767 | 587 | 2527 | 2887 | 707 | ||
2288 | 2648 | 468 | 2408 | 2768 | 588 | 2528 | 2888 | 708 | ||
2289 | 2649 | 469 | 2409 | 2769 | 589 | 2529 | 2889 | 709 | ||
2290 | 2650 | 470 | 2410 | 2770 | 590 | 2530 | 2890 | 710 | ||
2291 | 2651 | 471 | 2411 | 2771 | 591 | 2531 | 2891 | 711 | ||
2292 | 2652 | 472 | 2412 | 2772 | 592 | 2532 | 2892 | 712 | ||
2293 | 2653 | 473 | 2413 | 2773 | 593 | 2533 | 2893 | 713 | ||
2294 | 2654 | 474 | 2414 | 2774 | 594 | 2534 | 2894 | 714 | ||
2295 | 2655 | 475 | 2415 | 2775 | 595 | 2535 | 2895 | 715 | ||
2296 | 2656 | 476 | 2416 | 2776 | 596 | 2536 | 2896 | 716 | ||
2297 | 2657 | 477 | 2417 | 2777 | 597 | 2537 | 2897 | 717 | ||
2298 | 2658 | 478 | 2418 | 2778 | 598 | 2538 | 2898 | 718 | ||
2299 | 2659 | 479 | 2419 | 2779 | 599 | 2539 | 2899 | 719 | ||
2300 | 2660 | 480 | 2420 | 2780 | 600 | 2540 | 2900 | 720 | ||
3006 | 3041 | 3076 | 3018 | 3053 | 3088 | 3030 | 3065 | 3100 | ||
3007 | 3042 | 3077 | 3019 | 3054 | 3089 | 3031 | 3066 | 3101 | ||
3008 | 3043 | 3078 | 3020 | 3055 | 3090 | 3032 | 3067 | 3102 | ||
3009 | 3044 | 3079 | 3021 | 3056 | 3091 | 3033 | 3068 | 3103 | ||
3010 | 3045 | 3080 | 3022 | 3057 | 3092 | 3034 | 3069 | 3104 | ||
3011 | 3046 | 3081 | 3023 | 3058 | 3093 | 3035 | 3070 | 3105 | ||
3012 | 3047 | 3082 | 3024 | 3059 | 3094 | 3036 | 3071 | 3106 | ||
3013 | 3048 | 3083 | 3025 | 3060 | 3095 | 3037 | 3072 | 3107 | ||
3014 | 3049 | 3084 | 3026 | 3061 | 3096 | 3038 | 3073 | 3108 | ||
3015 | 3050 | 3085 | 3027 | 3062 | 3097 | 3039 | 3074 | 3109 | ||
3016 | 3051 | 3086 | 3028 | 3063 | 3098 | 3040 | 3075 | 3110 | ||
3017 | 3052 | 3087 | 3029 | 3064 | 3099 |
在本文所述的抗原結合單元中,所述VH可包含選自以下表C的CDR1、CDR2、和CDR3的組合的序列,且所述VL可包含選自以下表D的CDR1、CDR2、和CDR3的組合的序列,其中表C和表D中所述VH的CDR1、CDR2、和CDR3以及VL的CDR1、CDR2、和CDR3的序列遵循IMGT系統定義。
表C
表D
HCDR1 | HCDR2 | HCDR3 | HCDR1 | HCDR2 | HCDR3 | HCDR1 | HCDR2 | HCDR3 | ||
1461 | 1821 | 1 | 1581 | 1941 | 121 | 1701 | 2061 | 241 | ||
1462 | 1822 | 2 | 1582 | 1942 | 122 | 1702 | 2062 | 242 | ||
1463 | 1823 | 3 | 1583 | 1943 | 123 | 1703 | 2063 | 243 | ||
1464 | 1824 | 4 | 1584 | 1944 | 124 | 1704 | 2064 | 244 | ||
1465 | 1825 | 5 | 1585 | 1945 | 125 | 1705 | 2065 | 245 | ||
1466 | 1826 | 6 | 1586 | 1946 | 126 | 1706 | 2066 | 246 | ||
1467 | 1827 | 7 | 1587 | 1947 | 127 | 1707 | 2067 | 247 | ||
1468 | 1828 | 8 | 1588 | 1948 | 128 | 1708 | 2068 | 248 | ||
1469 | 1829 | 9 | 1589 | 1949 | 129 | 1709 | 2069 | 249 | ||
1470 | 1830 | 10 | 1590 | 1950 | 130 | 1710 | 2070 | 250 | ||
1471 | 1831 | 11 | 1591 | 1951 | 131 | 1711 | 2071 | 251 | ||
1472 | 1832 | 12 | 1592 | 1952 | 132 | 1712 | 2072 | 252 | ||
1473 | 1833 | 13 | 1593 | 1953 | 133 | 1713 | 2073 | 253 | ||
1474 | 1834 | 14 | 1594 | 1954 | 134 | 1714 | 2074 | 254 | ||
1475 | 1835 | 15 | 1595 | 1955 | 135 | 1715 | 2075 | 255 | ||
1476 | 1836 | 16 | 1596 | 1956 | 136 | 1716 | 2076 | 256 | ||
1477 | 1837 | 17 | 1597 | 1957 | 137 | 1717 | 2077 | 257 | ||
1478 | 1838 | 18 | 1598 | 1958 | 138 | 1718 | 2078 | 258 | ||
1479 | 1839 | 19 | 1599 | 1959 | 139 | 1719 | 2079 | 259 | ||
1480 | 1840 | 20 | 1600 | 1960 | 140 | 1720 | 2080 | 260 | ||
1481 | 1841 | 21 | 1601 | 1961 | 141 | 1721 | 2081 | 261 | ||
1482 | 1842 | 22 | 1602 | 1962 | 142 | 1722 | 2082 | 262 | ||
1483 | 1843 | 23 | 1603 | 1963 | 143 | 1723 | 2083 | 263 | ||
1484 | 1844 | 24 | 1604 | 1964 | 144 | 1724 | 2084 | 264 | ||
1485 | 1845 | 25 | 1605 | 1965 | 145 | 1725 | 2085 | 265 | ||
1486 | 1846 | 26 | 1606 | 1966 | 146 | 1726 | 2086 | 266 | ||
1487 | 1847 | 27 | 1607 | 1967 | 147 | 1727 | 2087 | 267 | ||
1488 | 1848 | 28 | 1608 | 1968 | 148 | 1728 | 2088 | 268 | ||
1489 | 1849 | 29 | 1609 | 1969 | 149 | 1729 | 2089 | 269 | ||
1490 | 1850 | 30 | 1610 | 1970 | 150 | 1730 | 2090 | 270 | ||
1491 | 1851 | 31 | 1611 | 1971 | 151 | 1731 | 2091 | 271 | ||
1492 | 1852 | 32 | 1612 | 1972 | 152 | 1732 | 2092 | 272 | ||
1493 | 1853 | 33 | 1613 | 1973 | 153 | 1733 | 2093 | 273 | ||
1494 | 1854 | 34 | 1614 | 1974 | 154 | 1734 | 2094 | 274 | ||
1495 | 1855 | 35 | 1615 | 1975 | 155 | 1735 | 2095 | 275 | ||
1496 | 1856 | 36 | 1616 | 1976 | 156 | 1736 | 2096 | 276 | ||
1497 | 1857 | 37 | 1617 | 1977 | 157 | 1737 | 2097 | 277 | ||
1498 | 1858 | 38 | 1618 | 1978 | 158 | 1738 | 2098 | 278 | ||
1499 | 1859 | 39 | 1619 | 1979 | 159 | 1739 | 2099 | 279 | ||
1500 | 1860 | 40 | 1620 | 1980 | 160 | 1740 | 2100 | 280 | ||
1501 | 1861 | 41 | 1621 | 1981 | 161 | 1741 | 2101 | 281 | ||
1502 | 1862 | 42 | 1622 | 1982 | 162 | 1742 | 2102 | 282 | ||
1503 | 1863 | 43 | 1623 | 1983 | 163 | 1743 | 2103 | 283 | ||
1504 | 1864 | 44 | 1624 | 1984 | 164 | 1744 | 2104 | 284 | ||
1505 | 1865 | 45 | 1625 | 1985 | 165 | 1745 | 2105 | 285 | ||
1506 | 1866 | 46 | 1626 | 1986 | 166 | 1746 | 2106 | 286 | ||
1507 | 1867 | 47 | 1627 | 1987 | 167 | 1747 | 2107 | 287 | ||
1508 | 1868 | 48 | 1628 | 1988 | 168 | 1748 | 2108 | 288 | ||
1509 | 1869 | 49 | 1629 | 1989 | 169 | 1749 | 2109 | 289 | ||
1510 | 1870 | 50 | 1630 | 1990 | 170 | 1750 | 2110 | 290 | ||
1511 | 1871 | 51 | 1631 | 1991 | 171 | 1751 | 2111 | 291 | ||
1512 | 1872 | 52 | 1632 | 1992 | 172 | 1752 | 2112 | 292 | ||
1513 | 1873 | 53 | 1633 | 1993 | 173 | 1753 | 2113 | 293 | ||
1514 | 1874 | 54 | 1634 | 1994 | 174 | 1754 | 2114 | 294 | ||
1515 | 1875 | 55 | 1635 | 1995 | 175 | 1755 | 2115 | 295 | ||
1516 | 1876 | 56 | 1636 | 1996 | 176 | 1756 | 2116 | 296 | ||
1517 | 1877 | 57 | 1637 | 1997 | 177 | 1757 | 2117 | 297 | ||
1518 | 1878 | 58 | 1638 | 1998 | 178 | 1758 | 2118 | 298 | ||
1519 | 1879 | 59 | 1639 | 1999 | 179 | 1759 | 2119 | 299 | ||
1520 | 1880 | 60 | 1640 | 2000 | 180 | 1760 | 2120 | 300 | ||
1521 | 1881 | 61 | 1641 | 2001 | 181 | 1761 | 2121 | 301 | ||
1522 | 1882 | 62 | 1642 | 2002 | 182 | 1762 | 2122 | 302 | ||
1523 | 1883 | 63 | 1643 | 2003 | 183 | 1763 | 2123 | 303 | ||
1524 | 1884 | 64 | 1644 | 2004 | 184 | 1764 | 2124 | 304 | ||
1525 | 1885 | 65 | 1645 | 2005 | 185 | 1765 | 2125 | 305 | ||
1526 | 1886 | 66 | 1646 | 2006 | 186 | 1766 | 2126 | 306 | ||
1527 | 1887 | 67 | 1647 | 2007 | 187 | 1767 | 2127 | 307 | ||
1528 | 1888 | 68 | 1648 | 2008 | 188 | 1768 | 2128 | 308 | ||
1529 | 1889 | 69 | 1649 | 2009 | 189 | 1769 | 2129 | 309 | ||
1530 | 1890 | 70 | 1650 | 2010 | 190 | 1770 | 2130 | 310 | ||
1531 | 1891 | 71 | 1651 | 2011 | 191 | 1771 | 2131 | 311 | ||
1532 | 1892 | 72 | 1652 | 2012 | 192 | 1772 | 2132 | 312 | ||
1533 | 1893 | 73 | 1653 | 2013 | 193 | 1773 | 2133 | 313 | ||
1534 | 1894 | 74 | 1654 | 2014 | 194 | 1774 | 2134 | 314 | ||
1535 | 1895 | 75 | 1655 | 2015 | 195 | 1775 | 2135 | 315 | ||
1536 | 1896 | 76 | 1656 | 2016 | 196 | 1776 | 2136 | 316 | ||
1537 | 1897 | 77 | 1657 | 2017 | 197 | 1777 | 2137 | 317 | ||
1538 | 1898 | 78 | 1658 | 2018 | 198 | 1778 | 2138 | 318 | ||
1539 | 1899 | 79 | 1659 | 2019 | 199 | 1779 | 2139 | 319 | ||
1540 | 1900 | 80 | 1660 | 2020 | 200 | 1780 | 2140 | 320 | ||
1541 | 1901 | 81 | 1661 | 2021 | 201 | 1781 | 2141 | 321 | ||
1542 | 1902 | 82 | 1662 | 2022 | 202 | 1782 | 2142 | 322 | ||
1543 | 1903 | 83 | 1663 | 2023 | 203 | 1783 | 2143 | 323 | ||
1544 | 1904 | 84 | 1664 | 2024 | 204 | 1784 | 2144 | 324 | ||
1545 | 1905 | 85 | 1665 | 2025 | 205 | 1785 | 2145 | 325 | ||
1546 | 1906 | 86 | 1666 | 2026 | 206 | 1786 | 2146 | 326 | ||
1547 | 1907 | 87 | 1667 | 2027 | 207 | 1787 | 2147 | 327 | ||
1548 | 1908 | 88 | 1668 | 2028 | 208 | 1788 | 2148 | 328 | ||
1549 | 1909 | 89 | 1669 | 2029 | 209 | 1789 | 2149 | 329 | ||
1550 | 1910 | 90 | 1670 | 2030 | 210 | 1790 | 2150 | 330 | ||
1551 | 1911 | 91 | 1671 | 2031 | 211 | 1791 | 2151 | 331 | ||
1552 | 1912 | 92 | 1672 | 2032 | 212 | 1792 | 2152 | 332 | ||
1553 | 1913 | 93 | 1673 | 2033 | 213 | 1793 | 2153 | 333 | ||
1554 | 1914 | 94 | 1674 | 2034 | 214 | 1794 | 2154 | 334 | ||
1555 | 1915 | 95 | 1675 | 2035 | 215 | 1795 | 2155 | 335 | ||
1556 | 1916 | 96 | 1676 | 2036 | 216 | 1796 | 2156 | 336 | ||
1557 | 1917 | 97 | 1677 | 2037 | 217 | 1797 | 2157 | 337 | ||
1558 | 1918 | 98 | 1678 | 2038 | 218 | 1798 | 2158 | 338 | ||
1559 | 1919 | 99 | 1679 | 2039 | 219 | 1799 | 2159 | 339 | ||
1560 | 1920 | 100 | 1680 | 2040 | 220 | 1800 | 2160 | 340 | ||
1561 | 1921 | 101 | 1681 | 2041 | 221 | 1801 | 2161 | 341 | ||
1562 | 1922 | 102 | 1682 | 2042 | 222 | 1802 | 2162 | 342 | ||
1563 | 1923 | 103 | 1683 | 2043 | 223 | 1803 | 2163 | 343 | ||
1564 | 1924 | 104 | 1684 | 2044 | 224 | 1804 | 2164 | 344 | ||
1565 | 1925 | 105 | 1685 | 2045 | 225 | 1805 | 2165 | 345 | ||
1566 | 1926 | 106 | 1686 | 2046 | 226 | 1806 | 2166 | 346 | ||
1567 | 1927 | 107 | 1687 | 2047 | 227 | 1807 | 2167 | 347 | ||
1568 | 1928 | 108 | 1688 | 2048 | 228 | 1808 | 2168 | 348 | ||
1569 | 1929 | 109 | 1689 | 2049 | 229 | 1809 | 2169 | 349 | ||
1570 | 1930 | 110 | 1690 | 2050 | 230 | 1810 | 2170 | 350 | ||
1571 | 1931 | 111 | 1691 | 2051 | 231 | 1811 | 2171 | 351 | ||
1572 | 1932 | 112 | 1692 | 2052 | 232 | 1812 | 2172 | 352 | ||
1573 | 1933 | 113 | 1693 | 2053 | 233 | 1813 | 2173 | 353 | ||
1574 | 1934 | 114 | 1694 | 2054 | 234 | 1814 | 2174 | 354 | ||
1575 | 1935 | 115 | 1695 | 2055 | 235 | 1815 | 2175 | 355 | ||
1576 | 1936 | 116 | 1696 | 2056 | 236 | 1816 | 2176 | 356 | ||
1577 | 1937 | 117 | 1697 | 2057 | 237 | 1817 | 2177 | 357 | ||
1578 | 1938 | 118 | 1698 | 2058 | 238 | 1818 | 2178 | 358 | ||
1579 | 1939 | 119 | 1699 | 2059 | 239 | 1819 | 2179 | 359 | ||
1580 | 1940 | 120 | 1700 | 2060 | 240 | 1820 | 2180 | 360 | ||
2901 | 2936 | 2971 | 2913 | 2948 | 2983 | 2925 | 2960 | 2995 | ||
2902 | 2937 | 2972 | 2914 | 2949 | 2984 | 2926 | 2961 | 2996 | ||
2903 | 2938 | 2973 | 2915 | 2950 | 2985 | 2927 | 2962 | 2997 | ||
2904 | 2939 | 2974 | 2916 | 2951 | 2986 | 2928 | 2963 | 2998 | ||
2905 | 2940 | 2975 | 2917 | 2952 | 2987 | 2929 | 2964 | 2999 | ||
2906 | 2941 | 2976 | 2918 | 2953 | 2988 | 2930 | 2965 | 3000 | ||
2907 | 2942 | 2977 | 2919 | 2954 | 2989 | 2931 | 2966 | 3001 | ||
2908 | 2943 | 2978 | 2920 | 2955 | 2990 | 2932 | 2967 | 3002 | ||
2909 | 2944 | 2979 | 2921 | 2956 | 2991 | 2933 | 2968 | 3003 | ||
2910 | 2945 | 2980 | 2922 | 2957 | 2992 | 2934 | 2969 | 3004 | ||
2911 | 2946 | 2981 | 2923 | 2958 | 2993 | 2935 | 2970 | 3005 | ||
2912 | 2947 | 2982 | 2924 | 2959 | 2994 |
LCDR1 | LCDR2 | LCDR3 | LCDR1 | LCDR2 | LCDR3 | LCDR1 | LCDR2 | LCDR3 | ||
2181 | 2541 | 361 | 2301 | 2661 | 481 | 2421 | 2781 | 601 | ||
2182 | 2542 | 362 | 2302 | 2662 | 482 | 2422 | 2782 | 602 | ||
2183 | 2543 | 363 | 2303 | 2663 | 483 | 2423 | 2783 | 603 | ||
2184 | 2544 | 364 | 2304 | 2664 | 484 | 2424 | 2784 | 604 | ||
2185 | 2545 | 365 | 2305 | 2665 | 485 | 2425 | 2785 | 605 | ||
2186 | 2546 | 366 | 2306 | 2666 | 486 | 2426 | 2786 | 606 | ||
2187 | 2547 | 367 | 2307 | 2667 | 487 | 2427 | 2787 | 607 | ||
2188 | 2548 | 368 | 2308 | 2668 | 488 | 2428 | 2788 | 608 | ||
2189 | 2549 | 369 | 2309 | 2669 | 489 | 2429 | 2789 | 609 | ||
2190 | 2550 | 370 | 2310 | 2670 | 490 | 2430 | 2790 | 610 | ||
2191 | 2551 | 371 | 2311 | 2671 | 491 | 2431 | 2791 | 611 | ||
2192 | 2552 | 372 | 2312 | 2672 | 492 | 2432 | 2792 | 612 | ||
2193 | 2553 | 373 | 2313 | 2673 | 493 | 2433 | 2793 | 613 | ||
2194 | 2554 | 374 | 2314 | 2674 | 494 | 2434 | 2794 | 614 | ||
2195 | 2555 | 375 | 2315 | 2675 | 495 | 2435 | 2795 | 615 | ||
2196 | 2556 | 376 | 2316 | 2676 | 496 | 2436 | 2796 | 616 | ||
2197 | 2557 | 377 | 2317 | 2677 | 497 | 2437 | 2797 | 617 | ||
2198 | 2558 | 378 | 2318 | 2678 | 498 | 2438 | 2798 | 618 | ||
2199 | 2559 | 379 | 2319 | 2679 | 499 | 2439 | 2799 | 619 | ||
2200 | 2560 | 380 | 2320 | 2680 | 500 | 2440 | 2800 | 620 | ||
2201 | 2561 | 381 | 2321 | 2681 | 501 | 2441 | 2801 | 621 | ||
2202 | 2562 | 382 | 2322 | 2682 | 502 | 2442 | 2802 | 622 | ||
2203 | 2563 | 383 | 2323 | 2683 | 503 | 2443 | 2803 | 623 | ||
2204 | 2564 | 384 | 2324 | 2684 | 504 | 2444 | 2804 | 624 | ||
2205 | 2565 | 385 | 2325 | 2685 | 505 | 2445 | 2805 | 625 | ||
2206 | 2566 | 386 | 2326 | 2686 | 506 | 2446 | 2806 | 626 | ||
2207 | 2567 | 387 | 2327 | 2687 | 507 | 2447 | 2807 | 627 | ||
2208 | 2568 | 388 | 2328 | 2688 | 508 | 2448 | 2808 | 628 | ||
2209 | 2569 | 389 | 2329 | 2689 | 509 | 2449 | 2809 | 629 | ||
2210 | 2570 | 390 | 2330 | 2690 | 510 | 2450 | 2810 | 630 | ||
2211 | 2571 | 391 | 2331 | 2691 | 511 | 2451 | 2811 | 631 | ||
2212 | 2572 | 392 | 2332 | 2692 | 512 | 2452 | 2812 | 632 | ||
2213 | 2573 | 393 | 2333 | 2693 | 513 | 2453 | 2813 | 633 | ||
2214 | 2574 | 394 | 2334 | 2694 | 514 | 2454 | 2814 | 634 | ||
2215 | 2575 | 395 | 2335 | 2695 | 515 | 2455 | 2815 | 635 | ||
2216 | 2576 | 396 | 2336 | 2696 | 516 | 2456 | 2816 | 636 | ||
2217 | 2577 | 397 | 2337 | 2697 | 517 | 2457 | 2817 | 637 | ||
2218 | 2578 | 398 | 2338 | 2698 | 518 | 2458 | 2818 | 638 | ||
2219 | 2579 | 399 | 2339 | 2699 | 519 | 2459 | 2819 | 639 | ||
2220 | 2580 | 400 | 2340 | 2700 | 520 | 2460 | 2820 | 640 | ||
2221 | 2581 | 401 | 2341 | 2701 | 521 | 2461 | 2821 | 641 | ||
2222 | 2582 | 402 | 2342 | 2702 | 522 | 2462 | 2822 | 642 | ||
2223 | 2583 | 403 | 2343 | 2703 | 523 | 2463 | 2823 | 643 | ||
2224 | 2584 | 404 | 2344 | 2704 | 524 | 2464 | 2824 | 644 | ||
2225 | 2585 | 405 | 2345 | 2705 | 525 | 2465 | 2825 | 645 | ||
2226 | 2586 | 406 | 2346 | 2706 | 526 | 2466 | 2826 | 646 | ||
2227 | 2587 | 407 | 2347 | 2707 | 527 | 2467 | 2827 | 647 | ||
2228 | 2588 | 408 | 2348 | 2708 | 528 | 2468 | 2828 | 648 | ||
2229 | 2589 | 409 | 2349 | 2709 | 529 | 2469 | 2829 | 649 | ||
2230 | 2590 | 410 | 2350 | 2710 | 530 | 2470 | 2830 | 650 | ||
2231 | 2591 | 411 | 2351 | 2711 | 531 | 2471 | 2831 | 651 | ||
2232 | 2592 | 412 | 2352 | 2712 | 532 | 2472 | 2832 | 652 | ||
2233 | 2593 | 413 | 2353 | 2713 | 533 | 2473 | 2833 | 653 | ||
2234 | 2594 | 414 | 2354 | 2714 | 534 | 2474 | 2834 | 654 | ||
2235 | 2595 | 415 | 2355 | 2715 | 535 | 2475 | 2835 | 655 | ||
2236 | 2596 | 416 | 2356 | 2716 | 536 | 2476 | 2836 | 656 | ||
2237 | 2597 | 417 | 2357 | 2717 | 537 | 2477 | 2837 | 657 | ||
2238 | 2598 | 418 | 2358 | 2718 | 538 | 2478 | 2838 | 658 | ||
2239 | 2599 | 419 | 2359 | 2719 | 539 | 2479 | 2839 | 659 | ||
2240 | 2600 | 420 | 2360 | 2720 | 540 | 2480 | 2840 | 660 | ||
2241 | 2601 | 421 | 2361 | 2721 | 541 | 2481 | 2841 | 661 | ||
2242 | 2602 | 422 | 2362 | 2722 | 542 | 2482 | 2842 | 662 | ||
2243 | 2603 | 423 | 2363 | 2723 | 543 | 2483 | 2843 | 663 | ||
2244 | 2604 | 424 | 2364 | 2724 | 544 | 2484 | 2844 | 664 | ||
2245 | 2605 | 425 | 2365 | 2725 | 545 | 2485 | 2845 | 665 | ||
2246 | 2606 | 426 | 2366 | 2726 | 546 | 2486 | 2846 | 666 | ||
2247 | 2607 | 427 | 2367 | 2727 | 547 | 2487 | 2847 | 667 | ||
2248 | 2608 | 428 | 2368 | 2728 | 548 | 2488 | 2848 | 668 | ||
2249 | 2609 | 429 | 2369 | 2729 | 549 | 2489 | 2849 | 669 | ||
2250 | 2610 | 430 | 2370 | 2730 | 550 | 2490 | 2850 | 670 | ||
2251 | 2611 | 431 | 2371 | 2731 | 551 | 2491 | 2851 | 671 | ||
2252 | 2612 | 432 | 2372 | 2732 | 552 | 2492 | 2852 | 672 | ||
2253 | 2613 | 433 | 2373 | 2733 | 553 | 2493 | 2853 | 673 | ||
2254 | 2614 | 434 | 2374 | 2734 | 554 | 2494 | 2854 | 674 | ||
2255 | 2615 | 435 | 2375 | 2735 | 555 | 2495 | 2855 | 675 | ||
2256 | 2616 | 436 | 2376 | 2736 | 556 | 2496 | 2856 | 676 | ||
2257 | 2617 | 437 | 2377 | 2737 | 557 | 2497 | 2857 | 677 | ||
2258 | 2618 | 438 | 2378 | 2738 | 558 | 2498 | 2858 | 678 | ||
2259 | 2619 | 439 | 2379 | 2739 | 559 | 2499 | 2859 | 679 | ||
2260 | 2620 | 440 | 2380 | 2740 | 560 | 2500 | 2860 | 680 | ||
2261 | 2621 | 441 | 2381 | 2741 | 561 | 2501 | 2861 | 681 | ||
2262 | 2622 | 442 | 2382 | 2742 | 562 | 2502 | 2862 | 682 | ||
2263 | 2623 | 443 | 2383 | 2743 | 563 | 2503 | 2863 | 683 | ||
2264 | 2624 | 444 | 2384 | 2744 | 564 | 2504 | 2864 | 684 | ||
2265 | 2625 | 445 | 2385 | 2745 | 565 | 2505 | 2865 | 685 | ||
2266 | 2626 | 446 | 2386 | 2746 | 566 | 2506 | 2866 | 686 | ||
2267 | 2627 | 447 | 2387 | 2747 | 567 | 2507 | 2867 | 687 | ||
2268 | 2628 | 448 | 2388 | 2748 | 568 | 2508 | 2868 | 688 | ||
2269 | 2629 | 449 | 2389 | 2749 | 569 | 2509 | 2869 | 689 | ||
2270 | 2630 | 450 | 2390 | 2750 | 570 | 2510 | 2870 | 690 | ||
2271 | 2631 | 451 | 2391 | 2751 | 571 | 2511 | 2871 | 691 | ||
2272 | 2632 | 452 | 2392 | 2752 | 572 | 2512 | 2872 | 692 | ||
2273 | 2633 | 453 | 2393 | 2753 | 573 | 2513 | 2873 | 693 | ||
2274 | 2634 | 454 | 2394 | 2754 | 574 | 2514 | 2874 | 694 | ||
2275 | 2635 | 455 | 2395 | 2755 | 575 | 2515 | 2875 | 695 | ||
2276 | 2636 | 456 | 2396 | 2756 | 576 | 2516 | 2876 | 696 | ||
2277 | 2637 | 457 | 2397 | 2757 | 577 | 2517 | 2877 | 697 | ||
2278 | 2638 | 458 | 2398 | 2758 | 578 | 2518 | 2878 | 698 | ||
2279 | 2639 | 459 | 2399 | 2759 | 579 | 2519 | 2879 | 699 | ||
2280 | 2640 | 460 | 2400 | 2760 | 580 | 2520 | 2880 | 700 | ||
2281 | 2641 | 461 | 2401 | 2761 | 581 | 2521 | 2881 | 701 | ||
2282 | 2642 | 462 | 2402 | 2762 | 582 | 2522 | 2882 | 702 | ||
2283 | 2643 | 463 | 2403 | 2763 | 583 | 2523 | 2883 | 703 | ||
2284 | 2644 | 464 | 2404 | 2764 | 584 | 2524 | 2884 | 704 | ||
2285 | 2645 | 465 | 2405 | 2765 | 585 | 2525 | 2885 | 705 | ||
2286 | 2646 | 466 | 2406 | 2766 | 586 | 2526 | 2886 | 706 | ||
2287 | 2647 | 467 | 2407 | 2767 | 587 | 2527 | 2887 | 707 | ||
2288 | 2648 | 468 | 2408 | 2768 | 588 | 2528 | 2888 | 708 | ||
2289 | 2649 | 469 | 2409 | 2769 | 589 | 2529 | 2889 | 709 | ||
2290 | 2650 | 470 | 2410 | 2770 | 590 | 2530 | 2890 | 710 | ||
2291 | 2651 | 471 | 2411 | 2771 | 591 | 2531 | 2891 | 711 | ||
2292 | 2652 | 472 | 2412 | 2772 | 592 | 2532 | 2892 | 712 | ||
2293 | 2653 | 473 | 2413 | 2773 | 593 | 2533 | 2893 | 713 | ||
2294 | 2654 | 474 | 2414 | 2774 | 594 | 2534 | 2894 | 714 | ||
2295 | 2655 | 475 | 2415 | 2775 | 595 | 2535 | 2895 | 715 | ||
2296 | 2656 | 476 | 2416 | 2776 | 596 | 2536 | 2896 | 716 | ||
2297 | 2657 | 477 | 2417 | 2777 | 597 | 2537 | 2897 | 717 | ||
2298 | 2658 | 478 | 2418 | 2778 | 598 | 2538 | 2898 | 718 | ||
2299 | 2659 | 479 | 2419 | 2779 | 599 | 2539 | 2899 | 719 | ||
2300 | 2660 | 480 | 2420 | 2780 | 600 | 2540 | 2900 | 720 | ||
3006 | 3041 | 3076 | 3018 | 3053 | 3088 | 3030 | 3065 | 3100 | ||
3007 | 3042 | 3077 | 3019 | 3054 | 3089 | 3031 | 3066 | 3101 | ||
3008 | 3043 | 3078 | 3020 | 3055 | 3090 | 3032 | 3067 | 3102 | ||
3009 | 3044 | 3079 | 3021 | 3056 | 3091 | 3033 | 3068 | 3103 | ||
3010 | 3045 | 3080 | 3022 | 3057 | 3092 | 3034 | 3069 | 3104 | ||
3011 | 3046 | 3081 | 3023 | 3058 | 3093 | 3035 | 3070 | 3105 | ||
3012 | 3047 | 3082 | 3024 | 3059 | 3094 | 3036 | 3071 | 3106 | ||
3013 | 3048 | 3083 | 3025 | 3060 | 3095 | 3037 | 3072 | 3107 | ||
3014 | 3049 | 3084 | 3026 | 3061 | 3096 | 3038 | 3073 | 3108 | ||
3015 | 3050 | 3085 | 3027 | 3062 | 3097 | 3039 | 3074 | 3109 | ||
3016 | 3051 | 3086 | 3028 | 3063 | 3098 | 3040 | 3075 | 3110 | ||
3017 | 3052 | 3087 | 3029 | 3064 | 3099 |
此外,應該理解的是,除上述表A-表D所列示例性CDR序列外,基於本申請的抗原結合單元中VH和VL序列,通過本領域熟知的其他編號系統如Kabat、Chothia、AbM或Contact所確定的CDR區域也涵蓋在本申請的範圍內。
本文所述的抗原結合單元的所述的VH CDR1可包含與SEQ ID NO: 721-1080和3111-3145中所包含的CDR1相同的序列;本文所述的抗原結合單元的所述的VH CDR2可包含與SEQ ID NO: 721-1080和3111-3145中所包含的CDR2相同的序列;本文所述的抗原結合單元的所述的VH CDR3可包含與SEQ ID NO: 721-1080和3111-3145中所包含的CDR3相同的序列;所述抗原結合單元的所述VL CDR1可包含與SEQ ID NO: 1081-1440和3146-3180中所包含的CDR1相同的序列;所述抗原結合單元的所述VL CDR2可包含與SEQ ID NO: 1081-1440和3146-3180中所包含的CDR2相同的序列;和/或所述抗原結合單元的所述VL CDR3可包含與SEQ ID NO: 1081-1440和3146-3180中所包含的CDR3相同的序列。
在一些實施方案中,所述VH CDR1、VH CDR2、VH CDR3、VL CDR1、VL CDR2和VL CDR3區域是基於本申請的抗原結合單元中VH和VL序列由IMGT系統確定的。在一些實施方案中,所述VH CDR1、VH CDR2、VH CDR3、VL CDR1、VL CDR2和VL CDR3區域是基於本申請的抗原結合單元中VH和VL序列由Kabat系統確定的。在一些實施方案中,所述VH CDR1、VH CDR2、VH CDR3、VL CDR1、VL CDR2和VL CDR3區域是基於本申請的抗原結合單元中VH和VL序列通過Chothia系統確定的。在一些實施方案中,所述VH CDR1、VH CDR2、VH CDR3、VL CDR1、VL CDR2和VL CDR3區域是基於本申請的抗原結合單元中VH和VL序列通過AbM系統確定的。在一些實施方案中,所述VH CDR1、VH CDR2、VH CDR3、VL CDR1、VL CDR2和VL CDR3區域是基於本申請的抗原結合單元中VH和VL序列通過Contact系統確定的。
本文所述的抗原結合單元可與新型冠狀病毒(SARS-CoV-2)S蛋白結合。本文所述的抗原結合單元可與新型冠狀病毒(SARS-CoV-2)S蛋白的受體結合結構域(RBD)。抗原結合單元與RBD的結合可的結合可通過本領域已知的任何方法來表徵或表示。例如,結合可以用結合親和力來表徵,結合親和力可以是抗原結合單元與抗原之間的相互作用的強度。結合親和力可通過本領域中已知的任何方法,如體外結合試驗來確定。本文抗原結合單元的結合親和力可按照KD來表示,KD被定義為兩個動力學速率常數Ka/Kd的比率,其中“Ka”指抗體與抗原結合的速率常數,“Kd”指抗體從抗體/抗原複合物中解離的速率常數。如本文公開的抗原結合單元以約10 μM至約1 fM範圍內的KD特異性結合新型冠狀病毒(SARS-CoV-2)S蛋白的受體結合結構域(RBD)。例如,抗原結合單元可以以小於約10 µM、1 µM、0.1 µM、50 nM、20 nM、15 nM、10 nM、5 nM、4 nM、3 nM、2 nM、1 nM、0.5 nM、0.1 nM、50 pM、10 pM、1 pM、0.1 pM、10 fM、1 fM、0.1 fM或小於0.1 fM的KD特異性結合新型冠狀病毒(SARS-CoV-2)S蛋白的受體結合結構域(RBD)。本文公開的抗原結合單元可以以小於100nM、小於50nM、小於20nM、小於15nM、小於10 nM、小於5nM、小於4nM、小於3nM、小於2nM、小於1nM、小於0.5nM、小於0.1 nM、小於0.05 nM、或小於0.01 nM的平衡解離常數(KD
)結合新型冠狀病毒(SARS-CoV-2)S蛋白的受體結合結構域(RBD)。
本文所述的抗原結合單元對新型冠狀病毒(SARS-CoV-2)具有中和活性。本文所述的抗原結合單元對新型冠狀病毒(SARS-CoV-2)的中和活性可通過假病毒進行分析。假病毒具有與疹病毒相似的細胞感染特點,能夠類比真病毒感染細胞的早期過程,並且可以安全、快速地進行檢測分析。本文所述的抗原結合單元對新型冠狀病毒(SARS-CoV-2)的中和活性可通過本領域已知的方法檢測,如採用微孔細胞中和試驗,參照Temperton N J等人, Emerg Infect Dis, 2005, 11(3), 411-416的描述進行。
本文所述的抗原結合單元對新型冠狀病毒(SARS-CoV-2)的中和活性可採用實驗細胞如Huh-7細胞以及假病毒SARS-CoV-2病毒檢測。本文所述的抗原結合單元可以以例如小於100 µg/ml、小於50 µg/ml、小於20 µg/ml、小於10 µg/ml、小於9 µg/ml、小於8 µg/ml、小於7 µg/ml、小於6 µg/ml、小於5 µg/ml、小於4 µg/ml、小於3 µg/ml、小於2 µg/ml、小於1 µg/ml、小於0.5µg/ml、小於0.25 µg/ml、小於0.2 µg/ml、小於0.1 µg/ml、小於0.05 µg/ml、小於1 ng/ml、小於0.5 ng/ml、小於0.25 ng/ml、小於 0.2ng/ml、小於0.1ng/ml、小於50 pg/ml、小於25pg/ml、小於20pg/ml、小於10pg/ml、小於5pg/ml、小於2.5pg/ml、小於2pg/ml、或小於1pg/ml的IC50中和新型冠狀病毒(SARS-CoV-2)假病毒。
本文所述的抗原結合單元對新型冠狀病毒(SARS-CoV-2)的中和活性可採用SARS-CoV-2真病毒通過空斑減少中和試驗(Plaque Reduction Neutralization Test, PRNT)進行檢測,通過孵育後空斑(plaque)的減少計算本文所述中的抗原結合單元中和SARS-CoV-2真病毒的IC50。本文所述的抗原結合單元可以以例如小於100 µg/ml、小於50 µg/ml、小於20 µg/ml、小於10 µg/ml、小於9 µg/ml、小於8 µg/ml、小於7 µg/ml、小於6 µg/ml、小於5 µg/ml、小於4 µg/ml、小於3 µg/ml、小於2 µg/ml、小於1 µg/ml、小於0.5µg/ml、小於0.25 µg/ml、小於0.2 µg/ml、小於0.1 µg/ml、小於0.05 µg/ml、小於1 ng/ml、小於0.5 ng/ml、小於0.25 ng/ml、小於 0.2ng/ml、小於0.1ng/ml、小於50 pg/ml、小於25pg/ml、小於20pg/ml、小於10pg/ml、小於5pg/ml、小於2.5pg/ml、小於2pg/ml、或小於1pg/ml的IC50中和新型冠狀病毒(SARS-CoV-2)真病毒。抗原結合單元的製備
本文提供了產生任何本文公開的抗原結合單元的方法,其中該方法包括在適於表達抗原結合單元的條件下培養表達抗原結合單元的宿主細胞,以及分離由宿主細胞表達的抗原結合單元。
所表達的抗原結合單元可以使用本領域已知的多種蛋白質純化技術分離。通常,抗原結合單元作為分泌的多肽從培養基中分離,儘管它們也可在無信號肽的情況下直接產生時從宿主細胞裂解物或細菌周質中回收。如果抗原結合單元是膜結合的,它們可以通過本領域技術人員常用的適當去污劑溶液溶解。回收的抗原結合單元可以通過鹽沉澱(例如,用硫酸銨)、離子交換色譜法(例如在中性pH下在陽離子或陰離子交換柱上運行並用離子強度增加的步驟梯度洗脫)、凝膠過濾色譜法(包括凝膠過濾HPLC)以及標籤親和柱色譜法,或親和樹脂如蛋白A、蛋白G、羥基磷灰石和抗免疫球蛋白進一步純化。
在本文所述的方法和組合物中可以使用添加了以下部分的衍生免疫球蛋白:化學連接體,可檢測部分如螢光染料,酶,底物,化學發光部分,特異性結合部分如鏈黴親和素、親和素或生物素,或藥物綴合物。
本文還提供與化學功能部分綴合的抗原結合單元。通常,該部分是能夠產生可檢測信號的標記。這些綴合的抗原結合單元可用於例如檢測系統,如病毒感染嚴重程度、感染灶的成像等。此類標記是本領域已知的,並且包括但不限於放射性同位素、酶、螢光化合物、化學發光化合物、生物發光化合物底物輔因數和抑制劑。教導使用此類標籤的專利的實例參見美國專利3,817,837;3,850,752;3,939,350;3,996,345;4,277,437;4,275,149;和4,366,241。該部分可以與抗原結合單元共價連接、重組連接或通過第二試劑如第二抗體、蛋白A或生物素-親和素複合物與抗原結合單元綴合。
其它功能部分包括信號肽、增強免疫反應性的試劑、促進與固體支持物偶聯的試劑、疫苗載體、生物反應調節劑、順磁標記和藥物。信號肽是短氨基酸序列,其引導新合成的蛋白質通過細胞膜(通常是真核細胞中的內質網)以及細菌的內膜或內膜和外膜二者。信號肽可以位於多肽的N-末端部分或多肽的C-末端部分,並且信號肽可以在多肽的生物合成與分泌之間從細胞酶促除去。這類肽可以被引入抗原結合單元中,以允許合成分子的分泌。
增強免疫反應性的試劑包括但不限於細菌超抗原。促進與固體支持物偶聯的試劑包括但不限於生物素或親和素。免疫原載體包括但不限於任何生理學上可接受的緩衝液。生物反應調節劑包括細胞因數,特別是腫瘤壞死因數(TNF)、白介素-2、白介素-4、粒細胞巨噬細胞集落刺激因數和γ-干擾素。
化學功能部分可以重組製備,例如通過產生編碼抗原結合單元和功能部分的融合基因。或者,抗原結合單元可以通過各種熟知的化學程式中的任何一種化學鍵合到該部分。例如,當該部分是蛋白質時,連接可以通過異雙官能交聯劑,例如,SPDP、碳二亞胺戊二醛等。該部分可以通過第二試劑,如第二抗體、蛋白A或生物素-親和素複合物共價連接或綴合。順磁部分及其與抗體的綴合在本領域中是公知的。參見,例如,Miltenyi等人(1990)Cytometry
11:231-238。核酸
在一個方面,本文提供了編碼本文所述的抗原結合單元的分離的多核苷酸。對應于現有抗體的L或H鏈的各個區域的核苷酸序列可以使用常規技術(包括但不限於雜交、PCR和DNA測序)容易地獲得並進行測序。產生單克隆抗體的雜交瘤細胞用作抗體核苷酸序列的優選來源。可以從公共或私人儲存庫獲得產生一系列單克隆抗體的大量雜交瘤細胞。最大的儲藏機構是美國典型培養物保藏中心(American Type Culture Collection),它提供了多種不同的充分表徵的雜交瘤細胞系。或者,抗體核苷酸可以從免疫的或未免疫的齧齒動物或人,以及從諸如脾和外周血淋巴細胞的器官獲得。適用于提取和合成抗體核苷酸的具體技術描述於Orlandi等人 (1989) Proc. Natl. Acad. Sci. U.S.A 86: 3833-3837;Larrick等人 1989) biochem. Biophys. Res. Commun. 160: 1250-1255;Sastry等人 (1989) Proc. Natl. Acad. Sci., U.S.A. 86: 5728-5732;以及美國專利號5,969,108。
還可以修飾抗體核苷酸序列,例如,通過用編碼序列取代人重鏈和輕鏈恒定區從而代替同源非人序列。以這種方式,製備嵌合抗體,其保留原始抗體的結合特異性。
另外,可以對編碼抗原結合單元的重鏈和/或輕鏈的多核苷酸進行密碼子優化,以實現受試者抗原結合單元在所需宿主細胞中的優化表達。例如,在一種密碼子優化方法中,天然密碼子被來自參考基因組的最常見密碼子所取代,其中每種氨基酸的密碼子翻譯速率被設計得較高。用於生成用於表達所需蛋白質的密碼子優化的多核苷酸的另外的示例性方法描述於Kanaya等人, Gene, 238:143-155 (1999),Wang等人, Mol. Biol. Evol., 18(5):792-800 (2001),美國專利號5,795,737,美國公開號2008/0076161和WO 2008/000632中,所述方法可應用於抗原結合單元的重鏈和/或輕鏈。
本文內容的多核苷酸包括編碼示例性多肽的功能等同物及其片段的多核苷酸。
由於遺傳密碼的簡並性,L和H序列的核苷酸以及適於構建本文所述的多核苷酸和載體的異二聚化序列可以有相當大的變異。這些變異包含在本文內容中。治療方法
本文提供了使用本文所述的抗原結合單元來預防或治療受試者的新型冠狀病毒(SARS-CoV-2)感染的方法,包括向所述受試者給予本文所述的抗原結合單元。
本文提供了使用本文所述的抗原結合單元與第二藥劑聯合治療哺乳動物的疾病、病況或病症的方法。第二藥劑可以與抗體一起、在抗體之前或之後施用。所述第二藥劑可以是抗病毒劑。抗病毒劑包括但不限於特拉匹韋(telaprevir)、波普瑞韋(boceprevir)、西美瑞韋(semiprevir)、索菲布韋(sofosbuvir)、達拉他韋(daclastavir)、阿那匹韋(asunaprevir)、拉米夫定(lamivudine)、阿德福韋(adefovir)、恩替卡韋(entecavir)、替諾福韋(tenofovir)、替比夫定(telbivudine)、干擾素α和PEG化干擾素α。所述第二藥劑可以選自羥氯喹、氯喹、法維拉韋、金西單抗(Gimsilumab)、AdCOVID(University of Alabama at Birmingham)、AT-100(Airway Therapeutics)、TZLS-501(Tiziana Life Sciences)、OYA1(OyaGen)、BPI-002(BeyondSpring)、INO-4800(Inovio Pharmaceutical)、NP-120(ifenprodil)、瑞德西韋(GS-5734)、Actemra(Roche)、加利地韋(BCX4430)、SNG001(Synairgen Research)、或其組合。
所述第二藥劑可以是用於緩解受試者併發的炎性病況的症狀的藥劑。所述抗炎劑包括非甾體抗炎藥(NSAID)和皮質類固醇。NSAID包括但不限於水楊酸鹽,如乙醯水楊酸;二氟尼柳、水楊酸和雙水楊酯;丙酸衍生物,如布洛芬;萘普生;右布洛芬、右酮洛芬、氟比洛芬、奧沙普嗪、非諾洛芬、洛索洛芬和酮洛芬;乙酸衍生物,如吲哚美辛、雙氯芬酸、托美汀、醋氯芬酸、舒林酸、萘丁美酮、依託度酸和酮咯酸;烯醇酸衍生物,如吡羅昔康、氯諾昔康、美洛昔康、伊索昔康、替諾昔康、苯基丁氮酮和屈惡昔康;鄰氨基苯甲酸衍生物,如甲芬那酸、氟芬那酸、甲氯芬那酸和托芬那酸;選擇性COX-2抑制劑,如塞來昔布、羅美昔布、羅非昔布、艾托考昔、伐地考昔、非羅考昔和帕瑞考昔;磺胺尼西林,如尼美舒利;和其他非甾體抗炎藥如氯尼辛和利考非隆。皮質類固醇包括但不限於可的松、地塞米松、氫化可的松、甲潑尼龍、潑尼松和潑尼松龍。
所述第二藥劑可以是免疫抑制劑。可與抗原結合單元組合使用的免疫抑制劑包括但不限於羥氯喹、柳氮磺胺吡啶、來氟米特、依那西普、英夫利昔單抗、阿達木單抗、D-青黴胺、口服金化合物、可注射金化合物(肌內注射)、米諾環素、硫代蘋果酸金鈉、金諾芬、D-青黴胺、氯苯紮利、布西拉明、阿克他利、環磷醯胺、硫唑嘌呤、甲氨蝶呤、咪唑立賓、環孢菌素和他克莫司。
具體劑量將根據所選擇的特定抗原結合單元、要遵循的給藥方案、是否與其他藥劑組合施用、施用時間、施用的組織以及攜帶該特定抗原結合單元的物理遞送系統而變化。在一些實施方案中,在治療週期的過程中,平均每週向受試者施用約1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、60、61、62、63、64、65、66、67、68、69或70 mg範圍內的抗原結合單元。例如,每週向受試者施用約35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、51、52、53、54或55 mg範圍內的抗原結合單元。在一些實施方案中,每週向受試者施用約40、41、42、43、44、45、46、47、48、49、50、51、52、53、54或55 mg範圍內的抗原結合單元。
在治療週期的過程中,可以平均每天以大於1、1.5、2、2.5、3、3.5、4、4.5、5、5.5、6、6.5、7、7.5、8、8.5、9、9.5或10 mg的量向受試者施用抗原結合單元。例如,在治療週期的過程中,平均每天以約6至10 mg、約6.5至9.5 mg、約6.5至8.5 mg、約6.5至8 mg或約7至9 mg的量向受試者施用抗原結合單元。
抗原結合單元的劑量可以是約、至少約或至多約0.1、0.5、1、2、3、4、5、6、7、8、9、10、15、20、25、30、35、40、45、50、55、60、65、70、75、80、85、90、95、100、125、150、175、200、225、250、275、300、325、350、375、400、425、450、475、500、525、550、575、600、625、650、675、700、725、750、775、800、825、850、875、900、925、950、975、1000 mg或mg/kg,或者其中可衍生的任何範圍。預期mg/kg的劑量是指每千克受試者總體重的抗原結合單元mg量。預期當給予患者多劑量時,劑量可以在量上變化或者它們可以是相同的。藥物組合物
本文提供了藥物組合物,其包含受試者抗體或其功能片段和藥學上可接受的載體、賦形劑或穩定劑,其包括但不限於惰性固體稀釋劑和填充劑、稀釋劑、無菌水溶液和各種有機溶劑、滲透促進劑、增溶劑和佐劑。(Remington's Pharmaceutical Sciences第16版, Osol, A.編著 (1980))。
藥物組合物可以是適合於單次施用精確劑量的單位劑型。藥物組合物可進一步包含抗原結合單元作為活性成分,並且可包括常規的藥物載體或賦形劑。此外,它可包括其他藥物或藥劑、載體、佐劑等。示例性的腸胃外施用形式包括活性多肽和/或PEG修飾的多肽在無菌水溶液中的溶液或懸浮液,例如丙二醇水溶液或右旋糖溶液。如果需要,此類劑型可以適當地用鹽如組氨酸和/或磷酸鹽緩衝。
所述組合物可進一步包括一種或多種藥學上可接受的添加劑和賦形劑。這些添加劑和賦形劑包括但不限於防粘劑、消泡劑、緩衝劑、聚合物、抗氧化劑、防腐劑、螯合劑、粘度調節劑(viscomodulator)、張力調節劑、調味劑、著色劑、增味劑、遮光劑、懸浮劑、粘合劑、填充劑、增塑劑、潤滑劑及其混合物。試劑盒
本文所述的試劑盒包含本文所述的抗原結合單元或如本文所述的其綴合物。還提供了本文所述的抗原結合單元在製備試劑盒中的用途,所述試劑盒用於檢測新型冠狀病毒或其S蛋白或S蛋白的RBD在樣品中的存在或其水準,或用於診斷受試者是否感染了新型冠狀病毒。
在一些實施方案中,所述樣品包括但不限於來自受試者(例如哺乳動物,優選人)的排泄物、口腔或鼻腔分泌物、肺泡灌洗液等。
使用抗體或其抗原結合片段來檢測目標病毒或抗原(例如,新型冠狀病毒或其S蛋白或S蛋白的RBD)在樣品中的存在或其水準的一般方法是本領域技術人員所熟知的。在一些實施方案中,所述檢測方法可以使用酶聯免疫吸附(ELISA)、酶免疫檢測、化學發光免疫檢測、放射免疫檢測、螢光免疫檢測、免疫色譜法、競爭法及類似檢測方法。[ 實例 ]
現參照下列意在舉例說明本發明(而非限定本發明)的實施例來描述本發明。
除非特別指明,本文中所使用的分子生物學實驗方法和免疫檢測法,基本上參照J. Sambrook等人,分子克隆:實驗室手冊,第2版,冷泉港實驗室出版社,1989,以及F. M. Ausubel等人,精編分子生物學實驗指南,第3版,John Wiley & Sons, Inc.,1995中所述的方法進行;限制性內切酶的使用依照產品製造商推薦的條件。實施例中未注明具體條件者,按照常規條件或製造商建議的條件進行。所用試劑或儀器未注明生產廠商者,均為可以通過市購獲得的常規產品。本領域技術人員知曉,實施例以舉例方式描述本發明,且不意欲限制本發明所要求保護的範圍。實施例 1 :記憶 B 細胞的分離
採集感染SARS-CoV-2病毒且痊癒出院的人員的血液(由北京佑安醫院提供),並在P2+生物安全實驗室中,利用STEMCELL SepMate™-15 (Stemcell Technologies,產品目錄號:86415)進行PBMCs的提取。隨後,根據製造商的說明書,使用STEMCELL EasySep Human Memory B Cell Isolation Kit(Stemcell Technologies,產品目錄號:17864)對提取的PBMCs進行記憶B細胞的富集。實施例 2 :抗原結合單元序列的獲得與鑒定
根據製造商的說明書,使用Chromium Single Cell V(D)J Reagent Kits(購自10X genomics,產品目錄號:100006)對上述富集後的記憶B細胞進行單細胞轉錄組的VDJ測序。對測序結果進行分析,獲得360株抗原結合單元,分別命名為ABU 1-395。其中所獲得的抗原結合單元的序列資訊如下表1所示。
表1 本文中獲得的示例性抗原結合單元
實施例 3 :本文中抗原結合單元的製備和純化
ABU No. | VH SEQ ID No. | VL SEQ ID NO. |
ABU-1 | 721 | 1081 |
ABU-2 | 722 | 1082 |
ABU-3 | 723 | 1083 |
ABU-4 | 724 | 1084 |
ABU-5 | 725 | 1085 |
ABU-6 | 726 | 1086 |
ABU-7 | 727 | 1087 |
ABU-8 | 728 | 1088 |
ABU-9 | 729 | 1089 |
ABU-10 | 730 | 1090 |
ABU-11 | 731 | 1091 |
ABU-12 | 732 | 1092 |
ABU-13 | 733 | 1093 |
ABU-14 | 734 | 1094 |
ABU-15 | 735 | 1095 |
ABU-16 | 736 | 1096 |
ABU-17 | 737 | 1097 |
ABU-18 | 738 | 1098 |
ABU-19 | 739 | 1099 |
ABU-20 | 740 | 1100 |
ABU-21 | 741 | 1101 |
ABU-22 | 742 | 1102 |
ABU-23 | 743 | 1103 |
ABU-24 | 744 | 1104 |
ABU-25 | 745 | 1105 |
ABU-26 | 746 | 1106 |
ABU-27 | 747 | 1107 |
ABU-28 | 748 | 1108 |
ABU-29 | 749 | 1109 |
ABU-30 | 750 | 1110 |
ABU-31 | 751 | 1111 |
ABU-32 | 752 | 1112 |
ABU-33 | 753 | 1113 |
ABU-34 | 754 | 1114 |
ABU-35 | 755 | 1115 |
ABU-36 | 756 | 1116 |
ABU-37 | 757 | 1117 |
ABU-38 | 758 | 1118 |
ABU-39 | 759 | 1119 |
ABU-40 | 760 | 1120 |
ABU-41 | 761 | 1121 |
ABU-42 | 762 | 1122 |
ABU-43 | 763 | 1123 |
ABU-44 | 764 | 1124 |
ABU-45 | 765 | 1125 |
ABU-46 | 766 | 1126 |
ABU-47 | 767 | 1127 |
ABU-48 | 768 | 1128 |
ABU-49 | 769 | 1129 |
ABU-50 | 770 | 1130 |
ABU-51 | 771 | 1131 |
ABU-52 | 772 | 1132 |
ABU-53 | 773 | 1133 |
ABU-54 | 774 | 1134 |
ABU-55 | 775 | 1135 |
ABU-56 | 776 | 1136 |
ABU-57 | 777 | 1137 |
ABU-58 | 778 | 1138 |
ABU-59 | 779 | 1139 |
ABU-60 | 780 | 1140 |
ABU-61 | 781 | 1141 |
ABU-62 | 782 | 1142 |
ABU-63 | 783 | 1143 |
ABU-64 | 784 | 1144 |
ABU-65 | 785 | 1145 |
ABU-66 | 786 | 1146 |
ABU-67 | 787 | 1147 |
ABU-68 | 788 | 1148 |
ABU-69 | 789 | 1149 |
ABU-70 | 790 | 1150 |
ABU-71 | 791 | 1151 |
ABU-72 | 792 | 1152 |
ABU-73 | 793 | 1153 |
ABU-74 | 794 | 1154 |
ABU-75 | 795 | 1155 |
ABU-76 | 796 | 1156 |
ABU-77 | 797 | 1157 |
ABU-78 | 798 | 1158 |
ABU-79 | 799 | 1159 |
ABU-80 | 800 | 1160 |
ABU-81 | 801 | 1161 |
ABU-82 | 802 | 1162 |
ABU-83 | 803 | 1163 |
ABU-84 | 804 | 1164 |
ABU-85 | 805 | 1165 |
ABU-86 | 806 | 1166 |
ABU-87 | 807 | 1167 |
ABU-88 | 808 | 1168 |
ABU-89 | 809 | 1169 |
ABU-90 | 810 | 1170 |
ABU-91 | 811 | 1171 |
ABU-92 | 812 | 1172 |
ABU-93 | 813 | 1173 |
ABU-94 | 814 | 1174 |
ABU-95 | 815 | 1175 |
ABU-96 | 816 | 1176 |
ABU-97 | 817 | 1177 |
ABU-98 | 818 | 1178 |
ABU-99 | 819 | 1179 |
ABU-100 | 820 | 1180 |
ABU-101 | 821 | 1181 |
ABU-102 | 822 | 1182 |
ABU-103 | 823 | 1183 |
ABU-104 | 824 | 1184 |
ABU-105 | 825 | 1185 |
ABU-106 | 826 | 1186 |
ABU-107 | 827 | 1187 |
ABU-108 | 828 | 1188 |
ABU-109 | 829 | 1189 |
ABU-110 | 830 | 1190 |
ABU-111 | 831 | 1191 |
ABU-112 | 832 | 1192 |
ABU-113 | 833 | 1193 |
ABU-114 | 834 | 1194 |
ABU-115 | 835 | 1195 |
ABU-116 | 836 | 1196 |
ABU-117 | 837 | 1197 |
ABU-118 | 838 | 1198 |
ABU-119 | 839 | 1199 |
ABU-120 | 840 | 1200 |
ABU-121 | 841 | 1201 |
ABU-122 | 842 | 1202 |
ABU-123 | 843 | 1203 |
ABU-124 | 844 | 1204 |
ABU-125 | 845 | 1205 |
ABU-126 | 846 | 1206 |
ABU-127 | 847 | 1207 |
ABU-128 | 848 | 1208 |
ABU-129 | 849 | 1209 |
ABU-130 | 850 | 1210 |
ABU-131 | 851 | 1211 |
ABU-132 | 852 | 1212 |
ABU-133 | 853 | 1213 |
ABU-134 | 854 | 1214 |
ABU-135 | 855 | 1215 |
ABU-136 | 856 | 1216 |
ABU-137 | 857 | 1217 |
ABU-138 | 858 | 1218 |
ABU-139 | 859 | 1219 |
ABU-140 | 860 | 1220 |
ABU-141 | 861 | 1221 |
ABU-142 | 862 | 1222 |
ABU-143 | 863 | 1223 |
ABU-144 | 864 | 1224 |
ABU-145 | 865 | 1225 |
ABU-146 | 866 | 1226 |
ABU-147 | 867 | 1227 |
ABU-148 | 868 | 1228 |
ABU-149 | 869 | 1229 |
ABU-150 | 870 | 1230 |
ABU-151 | 871 | 1231 |
ABU-152 | 872 | 1232 |
ABU-153 | 873 | 1233 |
ABU-154 | 874 | 1234 |
ABU-155 | 875 | 1235 |
ABU-156 | 876 | 1236 |
ABU-157 | 877 | 1237 |
ABU-158 | 878 | 1238 |
ABU-159 | 879 | 1239 |
ABU-160 | 880 | 1240 |
ABU-161 | 881 | 1241 |
ABU-162 | 882 | 1242 |
ABU-163 | 883 | 1243 |
ABU-164 | 884 | 1244 |
ABU-165 | 885 | 1245 |
ABU-166 | 886 | 1246 |
ABU-167 | 887 | 1247 |
ABU-168 | 888 | 1248 |
ABU-169 | 889 | 1249 |
ABU-170 | 890 | 1250 |
ABU-171 | 891 | 1251 |
ABU-172 | 892 | 1252 |
ABU-173 | 893 | 1253 |
ABU-174 | 894 | 1254 |
ABU-175 | 895 | 1255 |
ABU-176 | 896 | 1256 |
ABU-177 | 897 | 1257 |
ABU-178 | 898 | 1258 |
ABU-179 | 899 | 1259 |
ABU-180 | 900 | 1260 |
ABU-181 | 901 | 1261 |
ABU-182 | 902 | 1262 |
ABU-183 | 903 | 1263 |
ABU-184 | 904 | 1264 |
ABU-185 | 905 | 1265 |
ABU-186 | 906 | 1266 |
ABU-187 | 907 | 1267 |
ABU-188 | 908 | 1268 |
ABU-189 | 909 | 1269 |
ABU-190 | 910 | 1270 |
ABU-191 | 911 | 1271 |
ABU-192 | 912 | 1272 |
ABU-193 | 913 | 1273 |
ABU-194 | 914 | 1274 |
ABU-195 | 915 | 1275 |
ABU-196 | 916 | 1276 |
ABU-197 | 917 | 1277 |
ABU-198 | 918 | 1278 |
ABU-199 | 919 | 1279 |
ABU-200 | 920 | 1280 |
ABU-201 | 921 | 1281 |
ABU-202 | 922 | 1282 |
ABU-203 | 923 | 1283 |
ABU-204 | 924 | 1284 |
ABU-205 | 925 | 1285 |
ABU-206 | 926 | 1286 |
ABU-207 | 927 | 1287 |
ABU-208 | 928 | 1288 |
ABU-209 | 929 | 1289 |
ABU-210 | 930 | 1290 |
ABU-211 | 931 | 1291 |
ABU-212 | 932 | 1292 |
ABU-213 | 933 | 1293 |
ABU-214 | 934 | 1294 |
ABU-215 | 935 | 1295 |
ABU-216 | 936 | 1296 |
ABU-217 | 937 | 1297 |
ABU-218 | 938 | 1298 |
ABU-219 | 939 | 1299 |
ABU-220 | 940 | 1300 |
ABU-221 | 941 | 1301 |
ABU-222 | 942 | 1302 |
ABU-223 | 943 | 1303 |
ABU-224 | 944 | 1304 |
ABU-225 | 945 | 1305 |
ABU-226 | 946 | 1306 |
ABU-227 | 947 | 1307 |
ABU-228 | 948 | 1308 |
ABU-229 | 949 | 1309 |
ABU-230 | 950 | 1310 |
ABU-231 | 951 | 1311 |
ABU-232 | 952 | 1312 |
ABU-233 | 953 | 1313 |
ABU-234 | 954 | 1314 |
ABU-235 | 955 | 1315 |
ABU-236 | 956 | 1316 |
ABU-237 | 957 | 1317 |
ABU-238 | 958 | 1318 |
ABU-239 | 959 | 1319 |
ABU-240 | 960 | 1320 |
ABU-241 | 961 | 1321 |
ABU-242 | 962 | 1322 |
ABU-243 | 963 | 1323 |
ABU-244 | 964 | 1324 |
ABU-245 | 965 | 1325 |
ABU-246 | 966 | 1326 |
ABU-247 | 967 | 1327 |
ABU-248 | 968 | 1328 |
ABU-249 | 969 | 1329 |
ABU-250 | 970 | 1330 |
ABU-251 | 971 | 1331 |
ABU-252 | 972 | 1332 |
ABU-253 | 973 | 1333 |
ABU-254 | 974 | 1334 |
ABU-255 | 975 | 1335 |
ABU-256 | 976 | 1336 |
ABU-257 | 977 | 1337 |
ABU-258 | 978 | 1338 |
ABU-259 | 979 | 1339 |
ABU-260 | 980 | 1340 |
ABU-261 | 981 | 1341 |
ABU-262 | 982 | 1342 |
ABU-263 | 983 | 1343 |
ABU-264 | 984 | 1344 |
ABU-265 | 985 | 1345 |
ABU-266 | 986 | 1346 |
ABU-267 | 987 | 1347 |
ABU-268 | 988 | 1348 |
ABU-269 | 989 | 1349 |
ABU-270 | 990 | 1350 |
ABU-271 | 991 | 1351 |
ABU-272 | 992 | 1352 |
ABU-273 | 993 | 1353 |
ABU-274 | 994 | 1354 |
ABU-275 | 995 | 1355 |
ABU-276 | 996 | 1356 |
ABU-277 | 997 | 1357 |
ABU-278 | 998 | 1358 |
ABU-279 | 999 | 1359 |
ABU-280 | 1000 | 1360 |
ABU-281 | 1001 | 1361 |
ABU-282 | 1002 | 1362 |
ABU-283 | 1003 | 1363 |
ABU-284 | 1004 | 1364 |
ABU-285 | 1005 | 1365 |
ABU-286 | 1006 | 1366 |
ABU-287 | 1007 | 1367 |
ABU-288 | 1008 | 1368 |
ABU-289 | 1009 | 1369 |
ABU-290 | 1010 | 1370 |
ABU-291 | 1011 | 1371 |
ABU-292 | 1012 | 1372 |
ABU-293 | 1013 | 1373 |
ABU-294 | 1014 | 1374 |
ABU-295 | 1015 | 1375 |
ABU-296 | 1016 | 1376 |
ABU-297 | 1017 | 1377 |
ABU-298 | 1018 | 1378 |
ABU-299 | 1019 | 1379 |
ABU-300 | 1020 | 1380 |
ABU-301 | 1021 | 1381 |
ABU-302 | 1022 | 1382 |
ABU-303 | 1023 | 1383 |
ABU-304 | 1024 | 1384 |
ABU-305 | 1025 | 1385 |
ABU-306 | 1026 | 1386 |
ABU-307 | 1027 | 1387 |
ABU-308 | 1028 | 1388 |
ABU-309 | 1029 | 1389 |
ABU-310 | 1030 | 1390 |
ABU-311 | 1031 | 1391 |
ABU-312 | 1032 | 1392 |
ABU-313 | 1033 | 1393 |
ABU-314 | 1034 | 1394 |
ABU-315 | 1035 | 1395 |
ABU-316 | 1036 | 1396 |
ABU-317 | 1037 | 1397 |
ABU-318 | 1038 | 1398 |
ABU-319 | 1039 | 1399 |
ABU-320 | 1040 | 1400 |
ABU-321 | 1041 | 1401 |
ABU-322 | 1042 | 1402 |
ABU-323 | 1043 | 1403 |
ABU-324 | 1044 | 1404 |
ABU-325 | 1045 | 1405 |
ABU-326 | 1046 | 1406 |
ABU-327 | 1047 | 1407 |
ABU-328 | 1048 | 1408 |
ABU-329 | 1049 | 1409 |
ABU-330 | 1050 | 1410 |
ABU-331 | 1051 | 1411 |
ABU-332 | 1052 | 1412 |
ABU-333 | 1053 | 1413 |
ABU-334 | 1054 | 1414 |
ABU-335 | 1055 | 1415 |
ABU-336 | 1056 | 1416 |
ABU-337 | 1057 | 1417 |
ABU-338 | 1058 | 1418 |
ABU-339 | 1059 | 1419 |
ABU-340 | 1060 | 1420 |
ABU-341 | 1061 | 1421 |
ABU-342 | 1062 | 1422 |
ABU-343 | 1063 | 1423 |
ABU-344 | 1064 | 1424 |
ABU-345 | 1065 | 1425 |
ABU-346 | 1066 | 1426 |
ABU-347 | 1067 | 1427 |
ABU-348 | 1068 | 1428 |
ABU-349 | 1069 | 1429 |
ABU-350 | 1070 | 1430 |
ABU-351 | 1071 | 1431 |
ABU-352 | 1072 | 1432 |
ABU-353 | 1073 | 1433 |
ABU-354 | 1074 | 1434 |
ABU-355 | 1075 | 1435 |
ABU-356 | 1076 | 1436 |
ABU-357 | 1077 | 1437 |
ABU-358 | 1078 | 1438 |
ABU-359 | 1079 | 1439 |
ABU-360 | 1080 | 1440 |
ABU-361 | 3111 | 3146 |
ABU-362 | 3112 | 3147 |
ABU-363 | 3113 | 3148 |
ABU-364 | 3114 | 3149 |
ABU-365 | 3115 | 3150 |
ABU-366 | 3116 | 3151 |
ABU-367 | 3117 | 3152 |
ABU-368 | 3118 | 3153 |
ABU-369 | 3119 | 3154 |
ABU-370 | 3120 | 3155 |
ABU-371 | 3121 | 3156 |
ABU-372 | 3122 | 3157 |
ABU-373 | 3123 | 3158 |
ABU-374 | 3124 | 3159 |
ABU-375 | 3125 | 3160 |
ABU-376 | 3126 | 3161 |
ABU-377 | 3127 | 3162 |
ABU-378 | 3128 | 3163 |
ABU-379 | 3129 | 3164 |
ABU-380 | 3130 | 3165 |
ABU-381 | 3131 | 3166 |
ABU-382 | 3132 | 3167 |
ABU-383 | 3133 | 3168 |
ABU-384 | 3134 | 3169 |
ABU-385 | 3135 | 3170 |
ABU-386 | 3136 | 3171 |
ABU-387 | 3137 | 3172 |
ABU-388 | 3138 | 3173 |
ABU-389 | 3139 | 3174 |
ABU-390 | 3140 | 3175 |
ABU-391 | 3141 | 3176 |
ABU-392 | 3142 | 3177 |
ABU-393 | 3143 | 3178 |
ABU-394 | 3144 | 3179 |
ABU-395 | 3145 | 3180 |
根據實施例2中獲得的抗原結合單元的序列資訊,委託北京義翹神州有限公司表達和純化所獲得的抗原結合單元,並檢測了它們的抗原反應性。
簡言之,在體外合成編碼抗體重鏈和輕鏈的核酸分子,然後分別克隆至表達載體中,從而得到分別編碼抗體重鏈和輕鏈的重組表達載體。將上述得到的分別編碼抗體重鏈和輕鏈的重組表達載體共轉染HEK293細胞。轉染4-6小時後,將細胞培養液更換成無血清的培養基,並且繼續在37℃下培養6天。培養結束後,通過親和純化柱從培養物中純化細胞所表達的抗體蛋白。隨後,通過還原性和非還原性SDS-PAGE檢測所純化的目的蛋白。其中,以ABU-174、ABU-175和ABU190為例,其製備後的電泳結果分別如圖1A-1C所示。結果顯示,經純化的ABU-174、ABU-175和ABU190的純度分別為95.9%、96.4%、98.2%。
隨後,使用重組表達的S蛋白RBD作為包被抗原,使用辣根過氧化物酶(HRP)標記的Goat anti-human IgG Fc作為二抗,通過ELISA實驗,檢測經純化的待測抗體的抗原反應性。簡言之,用重組表達的S蛋白RBD(其氨基酸序列如SEQ ID NO: 1459所示,濃度為0.01μg/ml或1μg/ml)包被96孔板,隨後用封閉液對96孔板進行封閉。然後,分別加入待測單抗(對照抗體、ABU-174、ABU-175和ABU190;濃度分別為0.1μg/ml),並孵育。用ELISA洗滌液進行洗滌後,加入辣根過氧化物酶(HRP)標記的Goat anti-human IgG Fc作為二抗(以1:500稀釋),並繼續孵育。然後,用PBST洗滌酶標板,並加入顯色劑顯色。隨後在酶標儀上讀取OD450 nm的吸收值。結果如表2所示。由表2可知,ABU-174、ABU-175和ABU190均能夠特異性識別並結合S蛋白RBD。
表2:通過ELISA檢測的ABU-174、ABU-175和ABU190抗原結合單元與S蛋白RBD的反應性(OD450讀數)
實施例 4 :本文中的抗原結合單元 與 S 蛋白的結合能力的評估
待測樣品 | RBD 蛋白濃度 | |
0.01 μ g/ml | 1 μ g/ml | |
無關抗體(1ug/ml) | 0.006 | 0.025 |
ABU-174(1ug/ml) | 1.261 | 2.909 |
ABU-175(1ug/ml) | 2.274 | 2.963 |
ABU190(1ug/ml) | 0.288 | 3.057 |
本實施例採用表面等離子體共振技術(SPR)檢測抗體與Spike蛋白RBD區域的親和力。使用Biacore T200進行測量,先將生物素標記的SARS-COV-2 RBD結構域偶聯到SA晶片(GE公司)上,信號共振單位RU值上升100個單位。運行緩衝液是PH 7.4的PBS加上0.005% P20,確保分析物(如抗體)中的緩衝液與運行緩衝液一致。3倍梯度稀釋純化好的抗體,使其濃度在50-0.78125 nM間。測量結果使用Biacore Evaluation軟體進行分析,1:1模型擬合所有曲線,獲得抗體與抗原結合的速率常數Ka以及抗體從抗體/抗原複合物中解離的速率常數Kd,並計算解離平衡常數KD,其中KD=Kd/Ka,結果如下表3所示。
表3列舉了本文中示例性抗原結合單元與Spike蛋白RBD區域的結合親和力,其中各抗原結合單元的KD值均小於20 nM。
表3. 本文示例性抗原結合單元與
Spike蛋白RBD區域的結合親和力的KD值
AUB No. | KD (Kd/Ka, nM) |
ABU-145 | <10 |
ABU-149 | <10 |
ABU-174 | <1 |
ABU-175 | <1 |
ABU-181 | <10 |
ABU-190 | <10 |
ABU-205 | <10 |
ABU-207 | <10 |
ABU-208 | <1 |
ABU-210 | <10 |
ABU-211 | <20 |
ABU-254 | <10 |
ABU-257 | <10 |
ABU-258 | <1 |
ABU-288 | <1 |
ABU-289 | <10 |
ABU-290 | <1 |
ABU-291 | <1 |
ABU-296 | <1 |
ABU-297 | <1 |
ABU-298 | <20 |
ABU-305 | <20 |
ABU-308 | <10 |
ABU-312 | <20 |
ABU-316 | <10 |
ABU-317 | <20 |
ABU-319 | <10 |
ABU-320 | <10 |
ABU-322 | <1 |
ABU-323 | <20 |
ABU-325 | <10 |
ABU-327 | <20 |
ABU-328 | <10 |
ABU-329 | <10 |
ABU-330 | <10 |
ABU-337 | <20 |
ABU-339 | <20 |
ABU-340 | <10 |
ABU-341 | <10 |
ABU-343 | <20 |
ABU-344 | <1 |
ABU-346 | <10 |
ABU-348 | <10 |
ABU-349 | <1 |
ABU-351 | <10 |
ABU-352 | <10 |
ABU-354 | <1 |
ABU-355 | <1 |
ABU-356 | <10 |
ABU-357 | <10 |
ABU-358 | <10 |
ABU-359 | <10 |
ABU-360 | <1 |
ABU-361 | <20 |
ABU-362 | <20 |
ABU-365 | <10 |
ABU-367 | <1 |
ABU-368 | <20 |
ABU-369 | <10 |
ABU-371 | <20 |
ABU-372 | <20 |
ABU-373 | <10 |
ABU-375 | <10 |
ABU-376 | <10 |
ABU-377 | <10 |
ABU-379 | <10 |
ABU-380 | <1 |
ABU-381 | <1 |
ABU-382 | <10 |
ABU-383 | <20 |
ABU-384 | <20 |
ABU-385 | <20 |
ABU-386 | <10 |
ABU-390 | <10 |
ABU-391 | <20 |
ABU-392 | <10 |
ABU-393 | <20 |
ABU-394 | <20 |
ABU-395 | <10 |
圖2A-2C進一步示例性地顯示了ABU-174、ABU-175和ABU190與Spike蛋白RBD區域的結合親和力。由圖2A-2C可見,ABU-174的KD值為0.29nM,ABU-175的KD值為0.039nM,ABU190的KD值為2.8nM。圖2A-2C表明,ABU-174、ABU-175和ABU190與新型冠狀病毒S蛋白均具有良好的親和力。實施例 5 :本文抗原結合單元 中和 SARS-CoV-2 假病毒的能力的評估
在本實施例中,參照Temperton N J等人, Emerg Infect Dis, 2005, 11(3), 411-416的描述,利用微孔細胞中和實驗法,檢測了本文中的抗原結合單元對SARS-CoV-2假病毒的中和活性。本實施例所應用的SARS-CoV-2假病毒由中國食品藥品檢定研究院提供,其具有與真病毒相似的細胞感染特點,能夠類比真病毒感染細胞的早期過程,並且攜帶報告基因luciferase,可以快速方便地進行檢測分析。操作假病毒的安全性高,在P2級實驗室內就可完成中和實驗,檢測抗體的中和活性(Neutralization titer)。實驗方法的具體步驟如下。
1.平衡試劑
將保存於2-8℃的試劑(0.25%胰酶-EDTA,DMEM完全培養基)取出,室溫平衡30分鐘以上。
2.試驗操作
(1) 取96孔板,按照表4所示,設置樣品的排布方式;其中,A2-H2的孔設置為細胞對照孔(CC),其僅含有實驗細胞;A3-H3的孔設置為病毒對照孔(VV),其含有實驗細胞和假病毒;A4-A11、B4-B11、C4-C11、D4-D11、E4-E11、F4-F11、G4-G11、H4-H11的孔設置為實驗孔,其含有實驗細胞、假病毒以及不同濃度的待測抗體;其餘的孔設置為空白。本實施例中所使用的實驗細胞和假病毒分別為Huh-7細胞和SARS-CoV-2病毒(均由中國食品藥品檢定研究院提供)。表 4. 96 孔板中樣品的排布方式
(2) 在細胞對照孔中加入100μl/孔的DMEM完全培養基(含有1%的抗生素,25mM HEPES,10%FBS);在病毒對照孔中加入100μl/孔的DMEM完全培養基;並且,在實驗孔中加入50μl/孔的指定濃度的、稀釋于DMEM完全培養基中的待測抗體。表4中所使用的稀釋度1-8的抗體濃度分別為1/30 μg/μl,1/90 μg/μl,1/270 μg/μl, 1/810 μg/μl, 1/2430 μg/μl, 1/7290 μg/μl,1/21870 μg/μl, 1/65610 μg/μl。
(3) 用DMEM完全培養基將SARS-CoV-2假病毒稀釋至約1.3×104
/ml (TCID50);然後向病毒對照孔和實驗孔中添加50μl/孔的SARS-CoV-2假病毒。
(4) 將96孔板置於細胞培養箱中(37℃,5% CO2
)孵育1小時。
(5) 用DMEM完全培養基將預先培養好的Huh-7細胞稀釋至2×105
個/ml。在前一步驟的孵育結束後,向細胞對照孔、病毒對照孔和實驗孔中添加100μl/孔的細胞。
(6) 將96孔板置於細胞培養箱中(37℃,5% CO2
)培養20-28小時。
(7) 從細胞培養箱中取出96孔板,從每個孔中吸棄150μl上清,然後加入100μl螢光素酶檢測試劑,室溫避光反應2min。
(8) 反應結束後,用移液器將各個孔中的液體反復吹吸6~8次,使細胞充分裂解。然後,從每孔中吸出150μl液體,轉移至對應的96孔化學發光檢測板中,用化學發光檢測儀(Perkinelmer EnSight多功能酶標儀)讀取發光值。
(9) 計算中和抑制率:
抑制率=[1-(實驗孔的發光強度均值-CC孔的發光強度均值)/(VV孔的發光強度均值-CC孔的發光強度均值)]×100%。
(10) 根據中和抑制率的結果,利用Reed-Muench法計算待測抗體的IC50。
1 | 2 | 3 | 4 | 5-10 | 11 | 12 | |
A | - | CC | VV | 稀釋度1 | 稀釋度1 | 稀釋度1 | - |
B | - | CC | VV | 稀釋度2 | 稀釋度2 | 稀釋度2 | - |
C | - | CC | VV | 稀釋度3 | 稀釋度3 | 稀釋度3 | - |
D | - | CC | VV | 稀釋度4 | 稀釋度4 | 稀釋度4 | - |
E | - | CC | VV | 稀釋度5 | 稀釋度5 | 稀釋度5 | - |
F | - | CC | VV | 稀釋度6 | 稀釋度6 | 稀釋度6 | - |
G | - | CC | VV | 稀釋度7 | 稀釋度7 | 稀釋度7 | - |
H | - | CC | VV | 稀釋度8 | 稀釋度8 | 稀釋度8 | - |
表5列舉了本文中示例性抗原結合單元中和SARS-CoV-2假病毒的IC50
,其中各抗原結合單元的IC50值均小於1µg/ml。表 5. 本文示例性抗原結合單元中和 SARS-CoV-2 假病毒的 IC50
ABU No. | IC50 (µg/ml) |
ABU-174 | <0.1 |
ABU-175 | <0.1 |
ABU-190 | <0.1 |
ABU-207 | <0.5 |
ABU-208 | <0.5 |
ABU-257 | <0.5 |
ABU-290 | <0.1 |
ABU-291 | <0.5 |
ABU-296 | <0.1 |
ABU-297 | <0.1 |
ABU-308 | <0.5 |
ABU-322 | <0.1 |
ABU-340 | <0.5 |
ABU-341 | <0.1 |
ABU-344 | <1 |
ABU-349 | <0.1 |
ABU-351 | <0.1 |
ABU-352 | <0.1 |
ABU-354 | <0.1 |
ABU-355 | <0.1 |
ABU-356 | <0.1 |
ABU-357 | <1 |
ABU-358 | <0.1 |
ABU-359 | <0.1 |
ABU-360 | <0.1 |
ABU-361 | <0.5 |
ABU-362 | <0.5 |
ABU-365 | <0.1 |
ABU-367 | <0.1 |
ABU-368 | <0.5 |
ABU-369 | <0.1 |
ABU-371 | <1 |
ABU-372 | <0.5 |
ABU-373 | <0.5 |
ABU-375 | <0.1 |
ABU-376 | <0.1 |
ABU-377 | <0.5 |
ABU-379 | <0.5 |
ABU-380 | <0.1 |
ABU-381 | <0.1 |
ABU-382 | <0.1 |
ABU-386 | <0.1 |
ABU-391 | <1 |
ABU-392 | <0.1 |
ABU-395 | <0.1 |
圖3A-3C進一步示例性地顯示了ABU-174、ABU-175和ABU190對SARS-CoV-2假病毒的中和活性。由圖3A-3C可見,ABU-174、ABU-175和ABU190均具有良好的中和活性,其IC50分別為0.026μg/ml (ABU-174)、0.0086μg/ml (ABU-175)、0.039μg/ml (ABU190)。實施例 6 :本文中的抗原結合單元 中和 SARS-CoV-2 真病毒的能力的評估
在本實施例中,分別通過細胞病變(CPE)測定和空斑減少中和試驗(PRNT)來評估待測抗體的中和活性。所使用的SARS-CoV-2病毒由軍事醫學研究院提供,其滴度(TCID50)為105
/ml,並且,所有實驗操作均在BSL-3實驗室內完成。
6.1 細胞病變(CPE)測定
(1) 以5×104
/ml的濃度,向96孔培養板的每孔中加入100µl Vero E6細胞,並在37℃,5% CO2
的條件下培養24小時。
(2) 將待測抗體稀釋成10個濃度:為1/10 μg/μl,1/30 μg/μl,1/90 μg/μl,1/270 μg/μl, 1/810 μg/μl, 1/2430 μg/μl, 1/7290 μg/μl,1/21870 μg/μl, 1/65610 μg/μl,1/196830 μg/μl。取100µl指定濃度的待測抗體,加入等體積的SARS-CoV-2真病毒(100 TCID50),並在37℃,5% CO2
的條件下孵育1h。
(3) 在步驟(1)的培養結束後,棄去96孔培養板中的細胞培養液,加入步驟(2)製備的含有待測抗體和真病毒的混合液(200µl),作為實驗組。孵育1h後,從孔中吸出上清,每孔加入200 µl DMEM培養基(含有2%抗生素和16μg/ml胰蛋白酶)。
在實驗過程中,平行設置細胞對照組和病毒對照組。在細胞對照組(4個複孔)中,棄去孔中的細胞培養液後,每孔添加200µl DMEM培養基(含有2%抗生素和16μg/ml胰蛋白酶)。在病毒對照組(3個複孔)中,棄去孔中的細胞培養液後,每孔添加100 TCID50的真病毒(100µl),並在37℃孵育1h;孵育結束後,從孔中吸出上清,每孔加入200 µl DMEM培養基(含有2%抗生素和16μg/ml胰蛋白酶)。
(4) 在37℃,5% CO2
的條件下培養細胞4-5天。
(5) 在光學顯微鏡下觀察細胞病變(CPE),並根據細胞病變情況,評估不同濃度的單抗對CPE的抑制活性。
抗原結合單元ABU-174的檢測結果如下表6所示,結果表明抗原結合單元ABU-174在細胞上對病毒有抑制效果,中和抗體滴度為1.6ng/μl。表 6. 抗原結合單元 ABU-174 對 SARS-CoV-2 的中和活性效果
“+”為細胞有CPE變化,“-”為細胞無CPE變化或正常細胞形態
待測抗體 | 稀釋度 | 結果( 3 個複孔) | ||
抗原結合單元ABU-174 | 1:10 | - | - | - |
1:30 | - | - | - | |
1:90 | - | - | - | |
1:270 | - | - | - | |
1:810 | - | + | + | |
1:2430 | + | + | + | |
1:7290 | + | + | + | |
1:21870 | + | + | + | |
1:65610 | + | + | + | |
1:196830 | + | + | + | |
細胞對照 | 200µl DMEM | - | - | - |
陰性對照 | 100TCID50 | + | + | + |
抗原結合單元ABU-175的檢測結果如下表7及圖4所示,結果表明抗原結合單元ABU-175在細胞上對病毒有抑制效果,中和抗體滴度為0.7ng/μl。表 7. 抗原結合單元 ABU-175 對 SARS-CoV-2 的中和活性效果
“+”為細胞有CPE變化,“-”為細胞無CPE變化或正常細胞形態
6.2 空斑減少中和試驗(PRNT):
(1) 以5×104
/ml的濃度,向96孔培養板的每孔中加入100µl Vero E6細胞,並在37℃,5% CO2
的條件下培養24小時。
(2) 將待測抗體稀釋成5個濃度:為50μg/ml,10 μg/ml,2 μg/ml,0.4 μg/ml, 0.08 μg/ml。
(3) 在步驟(1)的培養結束後,棄去96孔培養板中的細胞培養液,加入步驟(2)製備的含有待測抗體和真病毒的混合液(200µl),作為實驗組。孵育1h後,從孔中吸出上清,每孔加入200 µl DMEM培養基(含有2%抗生素和16μg/ml胰蛋白酶)。
待測抗體 | 稀釋度 | 結果( 3 個複孔) | ||
抗原結合單元ABU-175 | 1:10 | - | - | - |
1:30 | - | - | - | |
1:90 | - | - | - | |
1:270 | - | - | - | |
1:810 | - | - | - | |
1:2430 | + | + | + | |
1:7290 | + | + | + | |
1:21870 | + | + | + | |
1:65610 | + | + | + | |
1:196830 | + | + | + | |
細胞對照 | 200µl DMEM | - | - | - |
陰性對照 | 100TCID50 | + | + | + |
在實驗過程中,平行設置細胞對照組和病毒對照組。在細胞對照組中,棄去孔中的細胞培養液後,每孔添加200µl DMEM培養基(含有2%抗生素和16μg/ml胰蛋白酶)。在病毒對照組(4個複孔)中,棄去孔中的細胞培養液後,每孔添加100 TCID50的真病毒(100µl),並在37℃孵育1h;孵育結束後,從孔中吸出上清,每孔加入200 µl DMEM培養基(含有2%抗生素和16μg/ml胰蛋白酶)。
(4) 在37℃,5% CO2
的條件下培養細胞4天。
(5) 細胞甲醛固定後,利用兔抗SARS-COV血清(sino生物)和過氧化物酶標記的山羊抗兔IgG(Dako)標記。利用TMB(True Blue,KPL)顯色後觀測空斑,計算抑制率並繪製劑量-反應曲線。
圖5顯示了本文示例性的抗原結合單元ABU-174、ABU-175和ABU190的劑量-反應曲線。由圖5可見,抗原結合單元ABU-174、ABU-175和ABU190對SARS-CoV-2真病毒均具有良好的中和活性,能夠有效抑制病毒感染和侵入細胞,IC50分別為0.5 μg/ml(ABU-174),0.3 μg/ml(ABU-175)和0.8 μg/ml(ABU-190)。實施例 7 本申請的抗原結合單元在 hACE2 轉基因小鼠體內的效力
使用了hACE2轉基因小鼠作為動物模型,並以暴露前預防或暴露後預防2種不同模式進行了治療。具體而言,將hACE2轉基因小鼠經鼻內感染SARS-CoV-2種病毒(2019-nCoV Beta CoV/Wuhan/AMMS01/2020),劑量為105 TCID50。
在暴露前預防治療模式中,在病毒感染前24小時,將20 mg/kg劑量的本文中的抗原結合單元腹膜內注射到hACE2轉基因小鼠中,並檢測了所述抗原結合單元作為暴露前預防干預的功效。
在暴露後預防治療模式中,病毒感染後2小時,將20 mg / kg劑量的抗原結合單元注射至小鼠中。使用HG1K(抗H7N9病毒的IgG1抗體)作為陰性對照,在病毒感染後2小時以20 mg/kg 注射。連續5天每天記錄能夠反映受感染小鼠健康狀況的體重。實施例 8. 本申請的抗原結合單元在倉鼠體內的效力
使用倉鼠(Mesocricetus auratus)作為動物模型,並以暴露前預防或暴露後預防2種不同模式進行了治療。具體而言,類似於hACE2轉基因小鼠,在倉鼠鼻內感染SARS-CoV-2原病毒(SARS-COV-2/WH-09/human/020/CHN),劑量為 105 TCID50。
在倉鼠暴露前預防治療模式中,在病毒感染前1天,將20 mg/kg劑量的本文中的抗原結合單元注射到倉鼠中。對照組中, 感染後2小時向動物注射PBS。
在倉鼠暴露後預防治療模式中,感染後2小時,將本文中的抗原結合單元根據體重以不同劑量(包括20、10、5和2 mg/kg)腹膜內注射到倉鼠中。同時將注射了磷酸鹽緩衝液(PBS)的倉鼠作為對照。連續7天每天記錄受感染倉鼠的體重。 感染後7天將倉鼠處死,收集肺用於病毒載量分析。[ 序列資訊 ]
本文所涉及的部分序列的資訊如下表8所示。
表8. 序列表
SEQ ID | 序列 |
1 | ARDVTLVRGTASPRFDY |
2 | ARDVTLVRGTASPRFDY |
3 | ARSTRRWLQFVFPFDY |
4 | ARSTRRWLQFVFPFDY |
5 | ARSTRRWLQFVFPFDY |
6 | ARSTRRWLQFVFPFDY |
7 | ARSTRRWLQFVFPFDY |
8 | ARQAPGGGLLGYYHGLDV |
9 | ARQAPGGGLLGYYHGLDV |
10 | ARDRYCGGDCSGPHYYYYGMDV |
11 | ARWDCSGGSCNYYYYYNMDV |
12 | ARWDCSGGSCNYYYYYNMDV |
13 | AREDILLVPAASNFYYFGMDV |
14 | ARGDYYDPDDRYNAYYSLGA |
15 | TKGSMLLEVY |
16 | ARAPSDSSGINGAFDI |
17 | ARPKAPGYSYLSLDY |
18 | CGFGVVTTDAYGMDV |
19 | VKDKACTTTSCYEGTFFDY |
20 | VRGDDSILTPTFDH |
21 | ARAGKGFMVITHFDY |
22 | ARPHTNSWDQFDY |
23 | ARPQGGSSWYRDYYYGMDV |
24 | ATSTAVLRYFAPTGGWFDP |
25 | AKDNGHSYGYSWFDP |
26 | ATDGATIPINYYGMDV |
27 | ARSPITMIVVVNAFDI |
28 | ARARITMIVVVNHFDY |
29 | ARVQSTGYKYWYFDI |
30 | ARGFDY |
31 | ARARDYGSGSPMDV |
32 | ARDGVYYGSVIYHHYDLHV |
33 | ARGGGELLRYPFDY |
34 | AKAGLGLETSGGNYFES |
35 | AKDRVTMNYFDY |
36 | ARVREGYTSGWYADY |
37 | ARDRSYYHSSGYHYYFDY |
38 | VRDRIVGGYSYGGDY |
39 | AKGRLSPRL |
40 | ARVKVDNVVFDL |
41 | ARDRGLAARPAGWVDL |
42 | ARENFHFSGTPPLY |
43 | ARKYTYDTSGFFLSSSRNAFDV |
44 | ARLGSNGYGL |
45 | ARTYSYDSSGFFLTSSREAFDI |
46 | VRKYSFDVSGFFLSSSRHAFDV |
47 | ARKYSYDTSGFFLTSSRDAFDV |
48 | VRKFSYDISGFFLTSSRDAFDV |
49 | ATEGV |
50 | LLIEGMGATSGD |
51 | ATTNDGYYYGMDV |
52 | ATNPHNTAMVLDYYGMDV |
53 | AGAYIAAAGWGWELFQYYFDY |
54 | AHQAPFEWFGVDY |
55 | TTDGLYCSGGSCYYHSYYYYYGMDV |
56 | ARDGLGNYDILTGYTERAFDI |
57 | ARVKPILRVVVVAATPCDY |
58 | ARHARGYQLLSPRLGELSLYRSFDY |
59 | ARATTTKMIVVVINAFDI |
60 | ARHWITMIVVVIKGGWFDP |
61 | ARIRGQWLVGKYYYGMDV |
62 | AHRGWGFSSSFFDY |
63 | ARMSSSLQHYYGMDV |
64 | ARMSSSLQHYYGMDV |
65 | ARDVTLVRGTASPRFDY |
66 | ARDVTLVRGTASPRFDY |
67 | AQEGRNYDRNWFDP |
68 | ARLIPIDGRDV |
69 | TTYWDQYTSTWT |
70 | ASIVKYDSSGYNFDY |
71 | TRDPWHESEHRFDP |
72 | AKDNKVSSWYSFDI |
73 | ARGLGYYVAL |
74 | VRGGQEVSLRRLDWFVGY |
75 | AKERGGSGKMYDY |
76 | ARRGAAVAGTTGGSAFDI |
77 | TKTSDLLYYGSGSYLPY |
78 | TRDGGAWD |
79 | ARGIPREYTTRWENAFDI |
80 | ARDRGADKDSNSGDVFDI |
81 | VGPQGAY |
82 | ARDPRGSSTSCSYDY |
83 | TGQERITIFGVVIISSDY |
84 | ARRLNDGANHS |
85 | SWDATVYYDMAV |
86 | ARPSSGSYADPFDI |
87 | VASRSSSLDY |
88 | ARSRGYGGLAGVDY |
89 | ARAYFDDSSGGFDY |
90 | AGSTYGDYVPHFYF |
91 | ARGLSSFTTIVVVFVGASFYFDS |
92 | ARGTTSTTMIVIVITAVSTWFDP |
93 | ARHPLKVDTIFGVVIIDPAPFDY |
94 | ARIASYYYDSSGYYQTRPIGHAFDI |
95 | AKDRAQLLWFGQSRGMDV |
96 | TSTSDW |
97 | TRLRSGLVGFDWLPLYGMDV |
98 | ARRGVGILKDLPVYAMDV |
99 | AREARQIFITMMTTKTSWFDP |
100 | ARVSSTAVVTGLDYYYGMDV |
101 | TTISVGLLWFGLAVRDHYYFDY |
102 | ARSYYDSSTGYYPDALDL |
103 | AKSGSVWGSYHKTYYFDY |
104 | AKEILKGYSSGWKYYYYGMDV |
105 | ARATTTMVRGVIYHYYYYGMDV |
106 | ARERLGRMVRGVNWFDP |
107 | ASWTMVRGVIRWFDP |
108 | ARQFHYVGIVVVVAPHYYYGMDV |
109 | ASPRGYSYGPFDY |
110 | ARVLYYDILTGYWWYYYGMDV |
111 | ARGAPITIFGVVISTWFDP |
112 | ARAHTDSLELGI |
113 | VRKYTYDTSGFFLTSTRSAFDV |
114 | ARKHVYDTSGFFLSSSRNAFDV |
115 | ARKYSFDISGFFLSSSRYALDV |
116 | ARDEGVTFHDHWANEIRYGMDV |
117 | ARARTTMIVVVSQFDY |
118 | ARDRGGWLLGSYYYYGMDV |
119 | ARGQISHYGFGESH |
120 | AHSGIAVVGNQLFHYYAMDV |
121 | AKERSSGSQWGWTYYYYGMDV |
122 | ARDPYGGNRRFHGWVYYYYGMDV |
123 | ARESTPDVRGVMNY |
124 | AKDAVASAGSPDY |
125 | ARDKLLWFGEPVVGYYYYYYMDV |
126 | ARDGGGDYAQIYFDY |
127 | ARDRLMTTYNYYSSMDV |
128 | AREPGDCSGGSCYYYGMDV |
129 | ARATRGYSYDDAFDI |
130 | ASPSYTDLLTGYYVPVDY |
131 | AKDPRVNELLWFGSLTQFYFDD |
132 | AKSGGPFHLSLYYYMDV |
133 | ARAFYGHAFDF |
134 | AKGLTIPFDK |
135 | AKGLTIPFDK |
136 | ARRGKYCSGGRCYSWWFDP |
137 | ARVASLIGDDY |
138 | ARVASLIGDDY |
139 | AHKPSGWSLRFDS |
140 | ARESLFNWFDS |
141 | AKGLTIPFDN |
142 | ARVDYDSSRNY |
143 | ARVERWLVLGYYYYGMDV |
144 | GSIDY |
145 | AKMYSDYDDNYYGLDV |
146 | ARDRYCSSTSCGGYYYYMDV |
147 | ARAPNDFWSGYPYYFDY |
148 | TRDGSTAAIFGNIDY |
149 | ARGVVRNDYGDPGFDY |
150 | ATAPAYCSGGSCPENNWFDP |
151 | AILWFGEFYFYDLFYNAVDV |
152 | AILWFGEFYFYDLFYNAVDV |
153 | ASRREQWLGDLGYYYYGMDV |
154 | ARGGAHSEDY |
155 | ARHQDPLDIVATVDWGGLDY |
156 | ARVASLIGDDY |
157 | ATTGTDNYYYYMDV |
158 | ARKNCSGGICYFHDY |
159 | AHKPSGWSLRFDS |
160 | AKGQTIQLWLFGAL |
161 | ALTVSSWYPGIFEN |
162 | AKAFSGSYWDAFDI |
163 | AKAASGARGYYGMDV |
164 | ARSSSGHYVSDLGY |
165 | ARALNGYRYNDY |
166 | AREEGGGSSTHFDC |
167 | ARTREGSYYYGMDV |
168 | VRGGLQFVVAVGPYGVDV |
169 | VRGGLQFVVAVGPYGVDV |
170 | ARDIGGGAPDY |
171 | AIKPSIPGYFDP |
172 | ARVGGWQRSPRPN |
173 | ARVGGWQRSPRPN |
174 | ARGQGYGRVLLWFGE |
175 | ARGQGYGRVLLWFGE |
176 | ARPSSGSRFDY |
177 | ARGFDY |
178 | AKARGVVLFDY |
179 | ARHSYGSGTYLDPFDY |
180 | ARQPHLAYYYDSSGYNDAFDI |
181 | ARGAVVTPFGLDS |
182 | ASEDYYDSSGYYWY |
183 | ARLSAIAVVGYYYYAMDV |
184 | ARDFIAASPFYYYYYMDV |
185 | ATSPGGYGVRRTVLEDFRH |
186 | WTMEYDDYSFVYDY |
187 | ARGGKQQLVRNYYLDS |
188 | ATGFGGVIVRGFDY |
189 | ARVYGDYSYYMDV |
190 | ARDLGEAGGMDV |
191 | VREIESGVDFWSGHYY |
192 | ARDSAYYDTIGYYSGDY |
193 | GRSFRGSCFDYL |
194 | ALGTGSYYGVNY |
195 | AKDMGGRYSSGLYYYYYGMDV |
196 | ARELRGYFDY |
197 | ARDPNDFWSGFPRGAFDI |
198 | ASHARYEEETFDY |
199 | VRDSYTSAWTPAGYFDL |
200 | AKDHYGSIDY |
201 | ARPYTSRWFWSN |
202 | ALLPPNAYDYGDGLLDH |
203 | ARHRAAGGNYYYGMDV |
204 | ARERVGPAAGYMDV |
205 | ARAAYYYDSSGYGWFDP |
206 | ARGDYTEYSYYYMDV |
207 | ALPTGASSSYSGPNY |
208 | ARDEVIAVATGEGMDV |
209 | AKDMGYDILTGSGLGDY |
210 | AKEPLFGETYGMDV |
211 | ARDKGSGSYYSGAYYYYMDV |
212 | ATFNSGNDNAYEY |
213 | AREYPDFWSGHYYYYMDV |
214 | ARLPYGMDV |
215 | ARGLYDKSGYRSDGFDS |
216 | ARGFEGYCSGGRCYSYFDY |
217 | ARVKNWDYGLY |
218 | ARDGQSDWHFDL |
219 | ARVYGDYLDH |
220 | AHRSFLYNIFNGYSYAPFDY |
221 | AKDLFSGDRDF |
222 | AKDSGAVLLWFGADF |
223 | AREGAYDIWRGSYMRAYDH |
224 | ARYIEMFDP |
225 | ARQAYGDYGWDYYYGMDV |
226 | LKDWDWEYEDSRPTLRGSVY |
227 | ARGSVFWFGEGKNWFDP |
228 | ARGSVFWFGEGKNWFDP |
229 | AREDSSGWSRGDY |
230 | ARRFVVREVEYNWFDP |
231 | ARDGYCNSMRCYRYYHGMDV |
232 | ATGPTAKPNKQWGYWFDP |
233 | ASPVSVEQDFDI |
234 | TTPVGDF |
235 | STSHPPFFDY |
236 | ARGLWQLVSPVFDY |
237 | AKVTNRGVRGLYFDY |
238 | ASPVSVEQDFDI |
239 | AINTLLVTA |
240 | VHRSFLYDIFSGYSYAPFDY |
241 | AHRSFLYNIFDGYSYAPFDY |
242 | AGGADCRRTSCHYLVSNREEYMGV |
243 | ARGLVLSGTRYSYFYGMDV |
244 | VKDWDWEYEDNRPTLRGSVY |
245 | VKDWDWEYEESRPTLRGSVY |
246 | AKGGPIFWLGEGKNWFDA |
247 | ARDKGGILMLRGADF |
248 | ARTLIAAAGSAFDI |
249 | ARGPTSITMIVVVDDAFDI |
250 | ARVMNSSWYTRYYYNYMDV |
251 | ARRGGGCSEGVCYNFDR |
252 | ARGDPRDY |
253 | ARGSYYYDSSGYYLDY |
254 | ARAAYYYDSSGYGWFDP |
255 | TTDLGATGIYYYYYMDV |
256 | ARFPRDYYDSSGYLIQEGNFDY |
257 | ARVTRAGAAGDGGAFDI |
258 | ARSVVPVAGTDY |
259 | ARDQHPGYPALVYYYYYMDV |
260 | ARDNIQTFDY |
261 | ATSSPVAGYNSWFDP |
262 | ATGPAVIPLRWFDP |
263 | ATAPAAAGPTDWFDP |
264 | AISPSVHSLWWFDP |
265 | ARDEIHYDILTGYYNRFWFHP |
266 | ARDAETGYYDSSGYPINWFDP |
267 | ARHYYDTGAYYVPFDH |
268 | AHFQGFGESEYFQH |
269 | AHRHPLTGFDS |
270 | ATPRGYSYGPLDY |
271 | ASPRGYSYGPFDY |
272 | ARDRVDKGYDFWSSWYFDL |
273 | ASGGGSYFDAFDI |
274 | ARDRSGSYYGGFDY |
275 | AKAVYGGNSVYFDY |
276 | ARIYGGNYENYFDY |
277 | ARESEAGTTPSFDY |
278 | ARSLVRGVITYFDY |
279 | ARGLSMEV |
280 | ARGGYSSSWYGTKYYFDY |
281 | ARGPTVTTFFRRNAWFDP |
282 | ARGRYSSGWYGSRNWFDP |
283 | ARLSMGAARQSGFDP |
284 | ARDGGRDGYNELGARVYYYYGMDV |
285 | ARIGSYGI |
286 | AKLGCSGGSCYYYYGMDV |
287 | ARGDHYYDRSGPHKFDY |
288 | ARDSPLKFDSFGYPLYGMDV |
289 | ARGIVGATPGYFDY |
290 | AKAVSGWPIYFDA |
291 | AKAVSGWPIYFDA |
292 | AHTIHSGYDRTFDS |
293 | AREESYSSSSPLDY |
294 | AAGSDFWSGYYVNYYMDV |
295 | ARLTAAGVYFDY |
296 | AKTRGRGLYDYVWGSKDY |
297 | AKTRGRGLYDYVWGSKDY |
298 | ARDESGSYYGDQAFDI |
299 | ARDRRARAYEIPFGSDHYYFGMDV |
300 | ARDYYGSGSYPIGYMDV |
301 | TTSYCSTKVCFDYWFDP |
302 | ASNLYATSPYGGVKN |
303 | AKDIGSGSPDAFDI |
304 | VKDLEFRGGTGGFDL |
305 | ARDGHSAWGAFDI |
306 | ARDHPTLRRAFDY |
307 | ARDRGSSSWWGWLDP |
308 | ATRRGYSGYGAAYYFDY |
309 | AREVYVGGEDDYSYYYGLDV |
310 | TTDLGEAGPTEWLRSSLFDY |
311 | TTSYCNPKVCFDYWFDP |
312 | AKEYYYDSSGYYYREDAFDI |
313 | AKDGGLTAYLEY |
314 | ATEKWEVVDVCFDY |
315 | AKDIGWDVVVVAATHGVFDY |
316 | AKDPYYYGSGSSNFFDY |
317 | ARGPDYYDTGGYFDL |
318 | ARDGYKQIYWYLDL |
319 | AKGEGVYGSGSRYFLDY |
320 | AREWSRGAVAGTGYFDY |
321 | AKVAKLPGDYYGMDV |
322 | ARELRGAFDI |
323 | ARDWGEYYFDY |
324 | ARDYGDLYFDY |
325 | ARDRRVGSPYYYYYMDV |
326 | ARDLGDNAFDI |
327 | ARDRYSGYDF |
328 | ARLSGTGYGGDGGWFDP |
329 | AGKKIYYGSSFDP |
330 | ARGGSGSGWYGGRFDY |
331 | ARVWRETYYYDSSGDSFDY |
332 | ARGRSITGIRDVDF |
333 | ARGRGNYMFRWFDP |
334 | ARGGLWYDSINYYGMDV |
335 | ARLILRWPTTWDYFDY |
336 | ARVDGPFDY |
337 | ARCPFWNYGHCYLDN |
338 | ARPSVRWYYHAMDV |
339 | AKERRPVLRYFDWLPIEAPDY |
340 | ARGQYDILTGYQYGAFDI |
341 | AAHYYSRTDAFHI |
342 | ARDSVSGSGSYYKGLWFDP |
343 | VVGIGYCSSPSCPPLRWFDY |
344 | ARERGYSGSGSLYYFDY |
345 | AHYSSSRPPLFDY |
346 | AKGHWST |
347 | ANGAYYYGSGSYYNGAAY |
348 | AKGGYYDILTGYFPFDY |
349 | ARDLVVYGMDV |
350 | ARDPIRNGMDV |
351 | ARDLVVYGMDV |
352 | ARDAMSYGMDV |
353 | ARDRVVYGMDV |
354 | ARDAAVYGIDV |
355 | ARDLISRGMDV |
356 | ARDRVVYGMDV |
357 | ARDLVSYGMDV |
358 | ARDLVVYGMDV |
359 | ARDAQNYGMDV |
360 | ARDRGLVSDY |
361 | QQTYIIPYS |
362 | QQYYSYPYT |
363 | SSYAGSNNLV |
364 | QRYDSYRT |
365 | QQSYSTPYT |
366 | QQYDNLPLT |
367 | QQYATSPWT |
368 | AAWDDSLSSWG |
369 | QTWGTGTVV |
370 | QSADSSGTWV |
371 | QQRSDWTPT |
372 | QQFNSYPRT |
373 | CSYAGNTTF |
374 | STWDASLKEVL |
375 | MQGTHWPLT |
376 | QQYDSYPWT |
377 | QQLTTYPRT |
378 | QSADSSGTWV |
379 | QQFYSTPVT |
380 | QSYDGSNVV |
381 | QQYYSTPLT |
382 | QQYYDTPMYT |
383 | QQYNSYPYT |
384 | SSYTSSSTFV |
385 | QSADSSGTYSNWV |
386 | SSYTSSSTVV |
387 | QQYGSSPLT |
388 | QQYGSSPLT |
389 | QQYGA |
390 | QQYGSSPWT |
391 | AVWDDSLNGVV |
392 | SSFAGSNNPYV |
393 | QQYYSTPYT |
394 | HQYDSWPPT |
395 | QNRDDWPPLFT |
396 | QQYYSTPRT |
397 | QQAHSFLSLT |
398 | QSADTSGTYLWV |
399 | QQYDSLPIT |
400 | QQYYGIPT |
401 | QKCDNFPWT |
402 | AAWDDSLSVVV |
403 | QQSYSSPPT |
404 | QSYDDTLTI |
405 | QQSYGAPPT |
406 | QQSYSTPPT |
407 | QQSFSTPPT |
408 | QQSYSSPPT |
409 | YSTDSSGNHWV |
410 | LLSYSGVRI |
411 | QSYDSSLSKV |
412 | QAWDSSTFYV |
413 | GTWDSSLSAVV |
414 | QQYNNWPWT |
415 | LLSYSGARPV |
416 | QQSYSTPPYT |
417 | SSYTSSSTRVV |
418 | QQYYSTPIT |
419 | QQYGSSPLT |
420 | GTWDSSLSVVV |
421 | SSYTSSSTFAV |
422 | MQALQTPLT |
423 | MQALQTVFT |
424 | MQALQTVFT |
425 | QQTYIIPYS |
426 | QQYYSYPYT |
427 | QVWDSSSDHVV |
428 | QAWDSSTSYVV |
429 | GTWDSSLSVGV |
430 | NSYTSNSTAV |
431 | QQSYNWPRT |
432 | LQHNSYPYT |
433 | QQYNGYPHT |
434 | QQYSYYSA |
435 | QQYGT |
436 | SAWDSSLSAWV |
437 | QQYYSTPIT |
438 | QSFDDNDQV |
439 | LLYVGGGIWV |
440 | QQYNIWLT |
441 | MQGTLLLT |
442 | ETWDSSLDAVI |
443 | AAWDDSLSGRV |
444 | MQGTHWPHPT |
445 | MQGTPWPT |
446 | QQSGSSYT |
447 | MQSLPSGFT |
448 | MQSLDLPPT |
449 | QQGSSFPLT |
450 | QQYDSSPIT |
451 | NSRDSSGQLHVVV |
452 | NSRDNNDDLPL |
453 | SSYAGSNNLGV |
454 | QSYDSSLSGVV |
455 | QQYYSTPFT |
456 | MQGTHWPIT |
457 | SSYTSSSTLVV |
458 | QQSYSTPYT |
459 | CSYAGSYVV |
460 | QQSYSTLHT |
461 | NSRDSSGNHLV |
462 | QAWDTITHEEV |
463 | QQYNYYPVA |
464 | TQATQFPLT |
465 | QQSYSTPPYT |
466 | QSYDSSLSSPVV |
467 | AAWDDSLSGPV |
468 | NSRDSSGNHLV |
469 | QQYDNLPYT |
470 | GTWDSSLSAGV |
471 | QQYNNWPPWT |
472 | QAWDSSTYVV |
473 | QQSYSSPPT |
474 | QQSYSSPPT |
475 | QQSYSSPPT |
476 | HHYGTSPPFT |
477 | QQYGSSPLT |
478 | QSADSSGTYYV |
479 | QQSYSTPRT |
480 | QAWDSSTVV |
481 | MQSIQLPLT |
482 | MQSIQLPFT |
483 | MQALQTYT |
484 | YSTDSSGNHRRV |
485 | SSYTSSSTLV |
486 | YSTDSSGNHRGV |
487 | QQYNSFPYT |
488 | QQRSNWPVT |
489 | LQHNSYPLT |
490 | LQHNSYPFT |
491 | QQYGTSAGT |
492 | QQYGNLPPFT |
493 | QQYYSTPLT |
494 | MQNRHLYT |
495 | MQNRHLYT |
496 | MQTLQTSIT |
497 | QQYGSSQYS |
498 | QQYGSSQYT |
499 | QHYDTLLT |
500 | QQYFDTPWT |
501 | MQNRQLYT |
502 | QQFDNLPPFT |
503 | QQSYSARMST |
504 | MQGTQWPWT |
505 | QQFDNSPPWT |
506 | QSADSSGTYVV |
507 | CSYAGSYTLV |
508 | QQSYSTPFT |
509 | MQGTHSYT |
510 | QAWDSSTASYV |
511 | SSYTSASTVV |
512 | SSYTSASTVV |
513 | MQGTHSPWT |
514 | GTWDSSLSAWV |
515 | QSADGRGDWV |
516 | QQYGSSQYS |
517 | QQYDSYSGT |
518 | ETWDSPYVV |
519 | QHYDSLLT |
520 | SSYTSSSTVV |
521 | MQALQTLT |
522 | QQYNSYPLFT |
523 | MQGTHWPMT |
524 | QQYGSSPMYT |
525 | QQANSFPA |
526 | QAWDSHTVV |
527 | QQYNSYSWT |
528 | QQYTSWPLT |
529 | QQYTSWPLT |
530 | YSPKV |
531 | QQYNILPHT |
532 | QQYYNAPLS |
533 | QQYYNAPLS |
534 | QQRSNWIT |
535 | QQRSNWIT |
536 | AAWDDSLNGPV |
537 | QQYGSSPQT |
538 | QQYNNWPPLT |
539 | QQYYSYSLT |
540 | CSYAGSSTFYV |
541 | QSADSSGTWV |
542 | QQYGSSPEMYT |
543 | HQYGSGLGT |
544 | MQSIQLRT |
545 | QQCSSWPLSLT |
546 | QQYNNWPPIT |
547 | QQSNSFPPT |
548 | QSYDISLSAYV |
549 | QQYNTYSLT |
550 | QQLNSYPPA |
551 | QQYYRTPLT |
552 | LQHHTYPLT |
553 | MQSIQLWS |
554 | LLSYSGPWV |
555 | SSYAGSNNYV |
556 | QQYDNLPSFT |
557 | CSYAGSYTLV |
558 | CSYAGSSTVV |
559 | QQSYNVPPWT |
560 | MQGTHWPWT |
561 | QSYDINLSAV |
562 | HQYHNSPWT |
563 | MQALQTPYT |
564 | QVWDSSSDHYV |
565 | QQYGSSPRT |
566 | QQYDNWLPYT |
567 | LLSYSGAYVL |
568 | QQYSNWPLYT |
569 | AAWDDSLNGPYV |
570 | SSYTSISTVL |
571 | QVWDGGSDDRGYV |
572 | SSFTSNGAWV |
573 | QQNYIRPYT |
574 | QQYDNLPIT |
575 | ATWDDSLNGV |
576 | QQYNNWPYT |
577 | GADHGSGSNFVYV |
578 | CSYAGSSTLV |
579 | QQHDSAPYT |
580 | QQYNSYVT |
581 | MQGKHLRWT |
582 | YSTDYSGNHGV |
583 | QQCSNWPNT |
584 | QSADSNDSWV |
585 | GTWDSSLSAGV |
586 | QQGHNFPWT |
587 | QQYGSLPLT |
588 | QQYGSLPLT |
589 | QSYDSSLSGWV |
590 | QQRRNWPLT |
591 | QHRSNWPYT |
592 | AAWDDSLNGVV |
593 | MQTTQFPRT |
594 | QSQDSSATYVV |
595 | QAWDSSIEV |
596 | QQYGSSPPWT |
597 | QSGDSSGTYVV |
598 | MQTTQFPRT |
599 | LQYNTYSYS |
600 | QQYNSYIT |
601 | QQYNSYVT |
602 | YSTDSSDNQRV |
603 | QHLKSYPLT |
604 | QQGHNFPWT |
605 | QQGHNFPWT |
606 | QQYHNFP |
607 | QSYDSSLSVV |
608 | QAWDSNTGV |
609 | QSYDSSLSGSV |
610 | QSVDNTGASPHVV |
611 | QQYHTYWT |
612 | QAWDSGT |
613 | QQYGSSPRT |
614 | QQYGSSPRT |
615 | QHYGTSPYT |
616 | QQYGSSTLVT |
617 | CSYAGSSLWV |
618 | QSYDSSFWV |
619 | GTWDSSLSAVV |
620 | YSTDRSGNHRGV |
621 | NSRDSSGNHLYWV |
622 | QSYDSSLSGHVV |
623 | GTWDSSLSAGGV |
624 | CSYAGSSTFVV |
625 | GTWDSSLSAVV |
626 | QQLNSYPPT |
627 | QQSYSTLWT |
628 | QQYGDSPET |
629 | QAWDSSTVV |
630 | QQYDNLPYT |
631 | QQYDNLPYT |
632 | QQRSNWPSIT |
633 | QQANSFPLA |
634 | QQSYSTPFG |
635 | LSYDSSLSGSV |
636 | QQFNNYPLT |
637 | QQYDNLPFT |
638 | SSYTSSSAYV |
639 | NSRDSSGNHVV |
640 | CSYAGSYPVV |
641 | SSYAGSNKV |
642 | QQYGSSGGYT |
643 | QQSYSTPYT |
644 | QQYGSSSWT |
645 | QQSYSTPYT |
646 | QAWDSSTANWV |
647 | SSFTDSSTLVV |
648 | QQSYSVPHT |
649 | QQYNNWLT |
650 | QQYNNWPPIT |
651 | QQYNNWPPIT |
652 | SSYAGTNKIL |
653 | QQSYSTPLT |
654 | SSYTSSSTWV |
655 | QQSYSTPYT |
656 | MQALQTPGT |
657 | MQALQTPGT |
658 | QQYNSYSA |
659 | QAWDRTTAT |
660 | QSYDSSLSGWV |
661 | SSYTSLNTLEVV |
662 | MQALQTPYS |
663 | QVWDSSSDRTVV |
664 | ASWDDKVRGWV |
665 | QQYGSSPWT |
666 | QQYNSYSRT |
667 | QQYNTSPLT |
668 | QSYDSSLSGSL |
669 | QSADSSGTYRV |
670 | QQYGRT |
671 | SSYTNIDTLEIV |
672 | LQHNSYPRT |
673 | QVWHSSFDPWV |
674 | QQSYSTPPTT |
675 | QQYNSYFPT |
676 | QVWDSSSDHYWV |
677 | GTWDSSLSAGV |
678 | QTWGTGPQVL |
679 | QQYDNLLT |
680 | QVWDSSGDHWV |
681 | QQRSNWLT |
682 | QQHDNLPSFT |
683 | QQYGSSPRT |
684 | QQYGSSPRT |
685 | LLYYGGAPV |
686 | QQLNSYPPA |
687 | QQYDNLPQT |
688 | CSYAGSSLWV |
689 | QSYDSSNQV |
690 | QQRSNWLFT |
691 | GTWDSSLSAGV |
692 | MQASQFPLT |
693 | CSFAGSNRE |
694 | QQYGSSPWT |
695 | GTWDSSLSAWV |
696 | QHYSSSAPIT |
697 | QQRNKWPGT |
698 | QQYGDSPYT |
699 | QQLNSYPLT |
700 | CTYAGSSTWV |
701 | QQSYSSPYT |
702 | QQANSFPRT |
703 | QQFNDYPLT |
704 | QSYDSSLSGSV |
705 | QQYSTYYT |
706 | MQGSHWPWT |
707 | AAWDDSLNGPWV |
708 | CSYAGSYTWV |
709 | QQLNSYPFT |
710 | QQYDNLPRT |
711 | QQLNSYPLT |
712 | QQSYSTPPDT |
713 | QQYDNLPPT |
714 | QQSYTTPLFT |
715 | QQLNGYPHSA |
716 | HQYDNLPPT |
717 | QQLNSYPLT |
718 | QQLNSNPPIT |
719 | QQSYSTPPYT |
720 | HQYDNLPRT |
721 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREGVDTAMVGFDYWGQGTLVTVSS |
722 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREGVDTAMVGFDYWGQGTLVTVSS |
723 | EVQLVQSGAEVKKPGESLRISCKGSGYSFTSYWISWVRQMPGKGLEWMGRIDPSDSYTNYSPSFQGHVTISADKSISTAYLQWSSLKASDTAMYYCARSTRRWLQFVFPFDYWGQGTLVTVSS |
724 | EVQLVQSGAEVKKPGESLRISCKGSGYSFTSYWISWVRQMPGKGLEWMGRIDPSDSYTNYSPSFQGHVTISADKSISTAYLQWSSLKASDTAMYYCARSTRRWLQFVFPFDYWGQGTLVTVSS |
725 | EVQLVQSGAEVKKPGESLRISCKGSGYSFTSYWISWVRQMPGKGLEWMGRIDPSDSYTNYSPSFQGHVTISADKSISTAYLQWSSLKASDTAMYYCARSTRRWLQFVFPFDYWGQGTLVTVSS |
726 | EVQLVQSGAEVKKPGESLRISCKGSGYSFTSYWISWVRQMPGKGLEWMGRIDPSDSYTNYSPSFQGHVTISADKSISTAYLQWSSLKASDTAMYYCARSTRRWLQFVFPFDYWGQGTLVTVSS |
727 | EVQLVQSGAEVKKPGESLRISCKGSGYSFTSYWISWVRQMPGKGLEWMGRIDPSDSYTNYSPSFQGHVTISADKSISTAYLQWSSLKASDTAMYYCARSTRRWLQFVFPFDYWGQGTLVTVSS |
728 | QMQLQESGPGLVEPSETLALTCTVSGGSINRNHFWAWLRRPPGKGLEWIGSASYTGTTHDNPSLRSRLTISVDTSKNQFSLKMTSVTVADTAVYFCARQAPGGGLLGYYHGLDVWGQGTTVTVSP |
729 | QMQLQESGPGLVEPSETLALTCTVSGGSINRNHFWAWLRRPPGKGLEWIGSASYTGTTHDNPSLRSRLTISVDTSKNQFSLKMTSVTVADTAVYFCARQAPGGGLLGYYHGLDVWGQGTTVTVSP |
730 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDRYCGGDCSGPHYYYYGMDVWGQGTTVTVSS |
731 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSYFEMNWVRQAPGKGLEWISYISSSGTNIYYADSVKGRFTISRDNAENSLYLQMNSLRVEDTAVYYCARWDCSGGSCNYYYYYNMDVWGQGTRVTVSS |
732 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSYFEMNWVRQAPGKGLEWISYISSSGTNIYYADSVKGRFTISRDNAENSLYLQMNSLRVEDTAVYYCARWDCSGGSCNYYYYYNMDVWGQGTRVTVSS |
733 | QVQLVQSGAEVKKPGASVKVSCKASGYKFSNYYIHWVRQAPGQGLEWMGWINPYSGETNYAQKFQGRVTMTRDTSTSTAYMELSRLRADDTAVFFCAREDILLVPAASNFYYFGMDVWGQGTTVAVSS |
734 | QVQLVQSGAEVRKPGASVKISCKSSGYIFTNFYVDWVRQAPGRGLEWMGRVNPNDGSSIYAQKFRDRFSLTSDTSTSTVFLNLRGLTSEDTALYFCARGDYYDPDDRYNAYYSLGAWGQGTTVIVSS |
735 | EVQLLESGGGLQQRGGSLRLSCAASGFNFSSYAMSWVRQAPGKGLEWVSSISATGGTTFYADSEKGRFTISRDNSKNILYLQMNSLRAEDTAVYYCTKGSMLLEVYWGQGTLVTVSS |
736 | EVQLVESGGGLVQPGGSLRLSCGVSGIIVSRNEMSWVRQAPGKGLEWVSYISSSGTGVHYADSVKGRFTSSRDSAKNSVYLQMHSLRAEDTAVYYCARAPSDSSGINGAFDIWGQGTMVTVSS |
737 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSTYAISWVRQAPGQGLEWMGGIIPIFGTPTYAQRFQGRVTITADESTSTAYMELTSLRSDDTAVFYCARPKAPGYSYLSLDYWGQGTLVTVSS |
738 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCCGFGVVTTDAYGMDVWGQGTTVTVSS |
739 | EVQLVESGGGLVQPGGSLRLSCSASGFTFNNYAMHWVRQAPGKGLEHVSVISSYGDNTFYADSVKGRFTISRDNSKNTLYLQMSSLRAEDTAVYYCVKDKACTTTSCYEGTFFDYWGQGTLVTVSS |
740 | EVQLVESGGGLVQPGGSLRLSCAASGFVFSNYWMTWVRQAPGKGLEWVANIKQDESEEYYRDSLKGRFTISRDNAKNSVFLQMDSLRVEDSAVYYCVRGDDSILTPTFDHWGQGTLVTVSS |
741 | QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARAGKGFMVITHFDYWGQGTLVTVSS |
742 | EVELVQSGAEMKEPGESLKISCKGFGYNFNNYWVAWVRQTPGKGLEWMGIIYGGDSDTRYNPSMQGQVTISADKSINTIYLEWDVLRASDSGIYYCARPHTNSWDQFDYWGQGTLVTVSS |
743 | QVQLVQSGSELKKPGASVKVSCKASGYTFTSYAMNWVRQAPGQGLEWMGWINTNTGNPTYAQGFTGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCARPQGGSSWYRDYYYGMDVWGQGTTVTVSS |
744 | QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATSTAVLRYFAPTGGWFDPWGQGTLVTVSS |
745 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDNGHSYGYSWFDPWGQGTLVTVSS |
746 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYPMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCATDGATIPINYYGMDVWGQGTTVTVSS |
747 | QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSPITMIVVVNAFDIWGQGTMVTVSS |
748 | QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARARITMIVVVNHFDYWGQGTLVTVSS |
749 | EVQLVESGGRSVQPGGSLRLSCEASGFTVSSNYMNWVRQAPGKGLEWLSVLYSGGNEYYADSVRGRFTISRHSSKNTLFLQMNRLRPEDTAVYYCARVQSTGYKYWYFDIWGRGTLVIVSS |
750 | QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGFDYWGQGTLVTVSS |
751 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYFIYWVRQAPGQGLEWMGRINPSSGVANYAQKFQGRVTMTRDTSITTAYMELSRLTSDDTVVYYCARARDYGSGSPMDVWGQGTTVTVSS |
752 | EVQLVESGGGLVQPGGSLRLSCVASGFTASSNYMNWVRQAPGKGLEWVSVIYAGGGTHYADSVKGRFTISRDNFKNTVYLQMNSLRSEDTAVYYCARDGVYYGSVIYHHYDLHVWGQGTTVTVSS |
753 | QVQLVQSGPEVKKPGSSVKVSCKVSGGTFSSYGISWVRLAPGRGLEWMGRILPVLDTTTYAPKFEGRVTITADESTTTAYMELTSLKSDDTAVYYCARGGGELLRYPFDYWGQGTPVTVSS |
754 | QVHLVQSGPEVKKPGSSVKVSCKASGGRFGSFAFSWLRQAPGQGLEWMGKVTPIVGVPVYAEKFQGTVTISADESTNTAYMEVSSLRSEDTALYYCAKAGLGLETSGGNYFESWGQGTLVTVSS |
755 | QVRLVESGGGLVQPGRSLRLSCAASGFTFTDYAIHWVRQAPGKGLEWMATISYDGNDKYFAASVRGRFSISRDNSNNTLFLQMNNLRAEDTAVYYCAKDRVTMNYFDYWGQGTLVSVSS |
756 | QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARVREGYTSGWYADYWGQGTLVTVSS |
757 | QVQLVQSGAEVQKPGASVRVSCKASGYTFTDYYIHWVRQAPGQGLEWMGWVNPNRGGTNNAQKFQGRVTMTRDTSITTAYMELHSLRSDDTAVYYCARDRSYYHSSGYHYYFDYWGQGSLVTVSS |
758 | QVQLVQSGAEVKKPGASVKVSCKASGYSFTGHYIHWVRQAPGQGLEWMGWINPDSGGTNNAQKFQGRVTMARDTSISTAYMDLSTLTNDDTAVYYCVRDRIVGGYSYGGDYWGQGTLVTVSS |
759 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYGMSWVRQAPGKGLEWVSAITGSGGSTHYADSVKGRFTISRDNSNNTLSLQMNSLRAEDTAVYYCAKGRLSPRLGQGTLVTVSS |
760 | QLQLKESGSGLVKSSQTLSLTCAVSGGSISSDVYSWSWIRQAPGKGLEYIGYVFHTGSAYYNPSLKSRVIISVDRSKNQVSLNVTSVTAADTAIYYCARVKVDNVVFDLWGQGTMVTVSS |
761 | QVQLVQSGTEVKKPGSSVKVSCKASGDTFNSYAISWVRQAPGQGLEWMGRIIPILRLATYAQEFQGRVTITADKSTTTTYMEVTSLKSEDTAIYYCARDRGLAARPAGWVDLWGQGTLVTVSS |
762 | QTQLVESGGGVVQPGRSLRLSCAASGFTFSHYGMHWVRQAPGKGLEWVALIWYDGSKKYYADSVKGRFTISRDISENTLYLQMNSLRAEDTAVYYCARENFHFSGTPPLYWGQGTLVTVSS |
763 | EVQLVQSAAEQKKPGESLKLSCKGSGYSFPAHWIDWVRQMPGGGLEWVGSIFPGDSDTKYSPSFEGQVNISADRSINTAYLQWSSLKASDTAIYYCARKYTYDTSGFFLSSSRNAFDVWGQGSMVFVSS |
764 | EVQLVQSGAEVKKPGESLKISCKGSGYNFDTYWIAWVRQTPGKGLEWMGDIYPGDSDSRYSPSFQGRVTFSADKSISVAYLQWSTLKASDTAMYFCARLGSNGYGLWGQGTLITVSS |
765 | EVQLVQSGAEVKEPGESLKISCKGSGYSFSGYWIAWVRQRPGKGLEWMGTIFPSDSDTRYSPSFEGQVTISTDKSISTAYLQWSSLKASDTAMYYCARTYSYDSSGFFLTSSREAFDIWGQGTMVIVSS |
766 | EVQLVQSGAEVKKPGESLKISCKASGYYFAAHWIDWVRQMPGRGLEWMGSIFPSDSDTEYGPSFQGQVNISADKSITTAYLQLKNLKASDTALYYCVRKYSFDVSGFFLSSSRHAFDVWGQGTMVTVSS |
767 | EVHLVQSGPEQKKPGESLRISCKGSGYSFPAFWIVWVRQMPGEGLEWMGSVFPGDSDTEYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARKYSYDTSGFFLTSSRDAFDVWGQGTMIAVSS |
768 | DVQLVQSGAEEKKPGEFLKISCKGSGYSFPAYWIGWVRQMPGKGLEWMGSIFPGDSDTEYSPSFQGHVTISADKSISTAYLQWSSLKASDTAMYYCVRKFSYDISGFFLTSSRDAFDVWGQGTKVTISS |
769 | QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATEGVWGQGTTVTVSS |
770 | QVQLVQSGAEAKKPGASVKVSCKASGYTFTRYWMHWVRQGPGQGLEWMGLMKPGDGKTIYAQKFQYRVTLTRDTSTSTVYMELRSLTSADTAMYYCLLIEGMGATSGDWGQGTLVTVSS |
771 | EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCATTNDGYYYGMDVWGQGTTVTVSS |
772 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSYISSSSSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCATNPHNTAMVLDYYGMDVWGQGTTVTVSS |
773 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAGAYIAAAGWGWELFQYYFDYWGQGTLVTVSS |
774 | QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVGVGWIRQPPGKALEWLALIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHQAPFEWFGVDYWGQGTLVTVSS |
775 | EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTTDGLYCSGGSCYYHSYYYYYGMDVWGQGTTVTVSS |
776 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDGLGNYDILTGYTERAFDIWGQGTMVTVSS |
777 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVKPILRVVVVAATPCDYWGQGTLVTVSS |
778 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARHARGYQLLSPRLGELSLYRSFDYWGQGTLVTVSS |
779 | QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARATTTKMIVVVINAFDIWGQGTMVTVSS |
780 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSRSYYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARHWITMIVVVIKGGWFDPWGQGTLVTVSS |
781 | QVTLKESGPVLVKPTETLTLTCTVSGFSLSNARMGVSWIRQPPGKALEWLAHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLTMTNMDPVDTATYYCARIRGQWLVGKYYYGMDVWGQGTTVTVSS |
782 | QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVGVGWIRQPPGKALEWLALIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHRGWGFSSSFFDYWGQGTLVTVSS |
783 | QVQLVESGGGVVQPGRSLRLSCAASGFTISPYGMHWVRQAPGKGLECVAIIWYDGSNKYYADSVKGRFTISRDSSKNTLYLQMDRLRAEDTAVYYCARMSSSLQHYYGMDVWGQGTTVTVSS |
784 | QVQLVESGGGVVQPGRSLRLSCAASGFTISPYGMHWVRQAPGKGLECVAIIWYDGSNKYYADSVKGRFTISRDSSKNTLYLQMDRLRAEDTAVYFCARMSSSLQHYYGMDVWGQGTTVTVSS |
785 | QVQVVQSEGEVKKPGASVKVSCMASGYTFGDYGISWVRQAPGQGLEWMGWISGYNGDPKYAQKFQGRITLTTDAATSSAYMELRSLRSDDTAVYFCARDVTLVRGTASPRFDYWGQGTLITVSS |
786 | QVQVVQSEGEVKKPGASVKVSCMASGYTFGDYGISWVRQAPGQGLEWMGWISGYNGDPKYAQKFQGRITLTTDAATSSAYMELRSLRSDDTAVYFCARDVTLVRGTASPRFDYWGQGTLITVSS |
787 | QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVGVGWIRQPPGKALEWLALIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAQEGRNYDRNWFDPWGQGTLVTVSS |
788 | QVRLQESGPGLVKPSETLSLTCTVSGGSISTYRWSWIRQPPGKGLEWIGYIYYSGRTNYHPSLKSRVTMSVDTSKNQFSLKLTFVSAADTAVYYCARLIPIDGRDVWGRGTTVTVSS |
789 | EVQLVESGGGLVEPGGSLRLSCAASGFTFSNAWMCWVRQAPGKGLEWVGRIKRIIDGGTINYAAPVKGRFTISRDDSTNTVYLQMNSLRSEDTAVYYCTTYWDQYTSTWTWGQGTLVTVSS |
790 | QVQLVQSGSELKKPGASVKVSCKASGYIFTNYAINWVRQAPGQGLEWMGWTNTNTGNPTYAQGFTGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCASIVKYDSSGYNFDYWGQGTLVTVSS |
791 | QVQLVQSGAEVKKPGASVKLSCKTSGYAFTSYQVHWVRQAPGQGLEWMGMINPSGSATHYAQKWQGRVSMTADTSTTTVYMELSGLRSEDTAVYYCTRDPWHESEHRFDPWGQGTLVTVSS |
792 | EVQLVESGGGLVQPGRSLRLSCAASGFTFGDYAMHWVRQVPGKGLEWVSSITWNSGNIGYADSVKGRFTISRDNAKNSLYLQMNSLRIEDTALYYCAKDNKVSSWYSFDIWGQGTMVTVSS |
793 | QVQLQQWGAGLLKPSETLSLTCAVSGASFSSYYWTWIRQPPGKGLEWIGDISQSASTNYSPSLKSRVTISADASRTQFSLNLISVTAADTAVYYCARGLGYYVALGQGTLVTVSS |
794 | EVQLVQSGVEVKEPGESLKISCKSSGYSFTKYWIGWVRQMPGKGLEWLGIIYPDDSETRYSPSFRGQVTISADKSISTAYLAWDRLKASDTAIYYCVRGGQEVSLRRLDWFVGYWGQGTLVTVSS |
795 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSSISGSGDKTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTALYYCAKERGGSGKMYDYWGQGNLVTVSS |
796 | QVQLQQSGPGLLKPSQTLSLTCAISGDSVSSNTVAWSWIRQSPSRGLEWLGRTYYRSNWYNDYAVSVKGRITLNSDTSKNQLSLQLNSVTPEDTAVYYCARRGAAVAGTTGGSAFDIWGQGTMVTVSS |
797 | EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYGMNWVRQAPGKGLEWVSGISWNSNSVAYADSVNGRFTISRDNAKNSLYLQMNSLRIEDTAFYYCTKTSDLLYYGSGSYLPYWGQGTLVVVSS |
798 | AVQLVESGGGFVQPGRSLRLSCAGSGFAFDDFAMHWVRQAPGKGLEWVSGINWNSDNIAYAASVKGRFIVSRDNGKNSLYLQMNSLRPEDTALYYCTRDGGAWDWGRGTLVTVSS |
799 | EVQVVESGGGLVQPGGSLRLSCAASGFTVSSTFMSWVRQAPGKGLEWVSVIYTVGDTFYADSVKGRFTISRHTSNNALYFQMNSLRTEDTAVYYCARGIPREYTTRWENAFDIWGQGTMVTVSS |
800 | QVQLQESGSGLVKPSQTLSLTCSVSGGSIKRRGYYWSWIRQHPGKGLEWIGYIYYSGTTYYNPSLQSRVNISVDTSKNQFSLNLRSVTAADTAVYYCARDRGADKDSNSGDVFDIWGQGTMVTVSS |
801 | QVQLQQWGAGLLKPSETLSLTCAVYGGSFSAYYWSWIRQPPGKGLEWIGEINRRGNTNYNPSLKGRVTISIHTSKNQFSLNLSSMTAADTAVYYCVGPQGAYWGQGTLVTVSS |
802 | QLQLQESGPGLVKPSETLSLTCVVSGGSISSSDYYWGWIRQPPGKGLEWIGTIYYSGNTFYNPSLKSRVTMSVDPSKNQFSLKLSSVTAADTAVYYCARDPRGSSTSCSYDYWGQGTLVTVSS |
803 | EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTGQERITIFGVVIISSDYWGQGTLVTVSS |
804 | QVHLVQSGAEVKKPGSSVKVSCKASGGTFSTYAISWVRQAPGQGLEYMGGIIPSLRTANYAQRFQDRVSITADESTTTAYMELSSLRSDDTAVYYCARRLNDGANHSWGQGTRVTVSS |
805 | EVQLVQSGGGLVKPGESLRLSCAVSGLRFTDAWLNWVRQAPGKGLEWVGRIKSRGSGGTIELAAPVKGRFTISRDDSKSTLFLQMNSLRTEDTAIYYCSWDATVYYDMAVWGQGTTVTVSS |
806 | QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYALHWVRQAPGKGLEWVALISYDGRNKYYADSVKGRFTISRDNSKKTLYLQMSTLTAEDTAVFYCARPSSGSYADPFDIWGQGTMVTVSS |
807 | QTVVESGGAVVQPGKSLTLSCEASGFSFSDFAMHWVRQSPGKGLEWVAVVSYDSRQQYYADSVQGRFRISRDNSQYTVTLRMDTLSFEDTGIYFCVASRSSSLDYWGQGTRVTVSS |
808 | QIQLVESGGGVVQPGRSLRLSCAASGFTFTTYGFHWVRQAPGKGLEWVAVIWYDGSNEAYADSVKGRITISRDNSRNTVYLQMNSLRAEDTAIYHCARSRGYGGLAGVDYWGQGTLVTVSS |
809 | DVQLVESGGGLVQPGGSLRLSCLATGFTFRSYSMNWVRQAPGKGLEWISYLSNDDRTRKYADSVNGRFTISRDNDGSSLFLQMDSLRDEDTAIYYCARAYFDDSSGGFDYWGQGALVIVSS |
810 | QVQLQESGPGLVKPAETLSLTCTVSGDSITSYYWSWIRQPAGKGLEWIGRIYSSGDTNYDPSLKSRVTMSVDTSKDQFSLRLSSVTAADTAIYYCAGSTYGDYVPHFYFWGQGTLVTVSS |
811 | QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGSYWSWIRQSPGKGLEWIGEINPSGGSNYNPSLKSRVIISLDTSKNQFSLKLNSVTAADTAVYYCARGLSSFTTIVVVFVGASFYFDSWGQGTLATVAS |
812 | QVQLQQWGAGLLKPSETLSLTCAVSGGSFTDHYWTWIRQPPGKGLEWIGEINHSGRTNYSPSLKSRVTMSLDTSKNQFSLKLRSVTAADTGIYYCARGTTSTTMIVIVITAVSTWFDPWGQGTLVTVSS |
813 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARHPLKVDTIFGVVIIDPAPFDYWGQGTLVTVSS |
814 | QVTLKESGPVLVKPTETLTLTCTVSGFSLSNARMGVSWIRQPPGKALEWLAHIFSNDEKSYSTSLKSRLTISKDTSKSQVVLTMTNMDPVDTATYYCARIASYYYDSSGYYQTRPIGHAFDIWGQGTMVTVSS |
815 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDRAQLLWFGQSRGMDVWGQGTTVTVSS |
816 | EVQLVESGGGLVKPGRSLRLSCTASGFTFGDYAMSWFRQAPGKGLEWVGFIRSKAYGGTTEYAASVKGRFTISRDDSKSIAYLQMNSLKTEDTAVYYCTSTSDWWGQGTLVTVSS |
817 | EVQLVESGGGLVQPGGSLKLSCAASGFTFSGSAMHWVRQASGKGLEWVGRIRSKANSYATAYAASVKGRFTISRDDSKNTAYLQMNSLKTEDTAVYYCTRLRSGLVGFDWLPLYGMDVWGQGTTVTVSS |
818 | EVQLVQSGAEVKKPGESLRISCKGSGYSFTSYWISWVRQMPGKGLEWMGRIDPSDSYTNYSPSFQGHVTISADKTISTAYLQWSSLKASDTAMYYCARRGVGILKDLPVYAMDVWGQGTTVTVSS |
819 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREARQIFITMMTTKTSWFDPWGQGTLVTVSS |
820 | QVRLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGRIIPIFHIANSAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARVSSTAVVTGLDYYYGMDVWGQGTTVTVSS |
821 | EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTTISVGLLWFGLAVRDHYYFDYWGQGTLVTVSS |
822 | EVQLVESGGGSVRSGGSLRLSCAASGFTFRSYWMHWVRQAPGKGLVWVSRIFSDWSTTTYADSVRGRFTISRDNAKNTLYLEMNRLKVEDTAVYYCARSYYDSSTGYYPDALDLWGQGTTVTVSS |
823 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMSWVRQAPGKGLEWVAAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSGSVWGSYHKTYYFDYWGQGTLVTVSS |
824 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKNYADSVKGRFTISRENSKNTLYLQMNSLRAEDTAVYYCAKEILKGYSSGWKYYYYGMDVWGQGTTVTVSS |
825 | EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMNWVRQAPGKGLEWVSVIYSGSSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATTTMVRGVIYHYYYYGMDVWGQGTTVTVSS |
826 | QVQLQESGPGLVKPSQTLSLTCTVSGGPISSGGYYWSWIRQHPGKGLEWLGCIYYSGSTYYNPSLKSRVSISVDTSKSQFSLKLSSVTAADTAVYYCARERLGRMVRGVNWFDPWGQGILVTVSS |
827 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSYYYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCASWTMVRGVIRWFDPWGQGTLVTVSS |
828 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARQFHYVGIVVVVAPHYYYGMDVWGQGTTVTVSS |
829 | EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCASPRGYSYGPFDYWGQGTLVTVSS |
830 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARVLYYDILTGYWWYYYGMDVWGQGTTVTVSS |
831 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQAPGKGLVWVSRINSDGSSTSYADSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCARGAPITIFGVVISTWFDPWGQGTLVTVSS |
832 | QLQLQESGSGLVKPSQTLSLTCAVSGGSISSGGYSWSWIRQPPGKGLEWIGYIYHSGSTYYNPSLKSRVTISVDRSKNQFSLKLSSVTAADTAVYYCARAHTDSLELGIWGQGTMVTVSS |
833 | EVQLLQSGGEVRRPGESLKISCKASGYSFPAHWIGWVRQMPGRGLEWMGSIFPSDSDTEYSPSFEGQVKISADKSITTAYLQWSSLKASDTAFYYCVRKYTYDTSGFFLTSTRSAFDVWGQGTMVTVSS |
834 | EVQLEQSGAEEKKPGESLKISCKGSGYSFPAFYIAWMRQMPGKGLEWMGSIFPGDSETEYNPSFQGQVTISADKSITTAYLQWDNLKASDTALYYCARKHVYDTSGFFLSSSRNAFDVWGQGTKVTVFS |
835 | EVQLVQSGAEQRKPGESLRISCKGSGYSFPAHWIAWVRQMPGRGLEWMGSIFPGDSDTEYNPSFQGHVNISADRSINTAYLQWSSLKASDSAIYYCARKYSFDISGFFLSSSRYALDVWAQGTTVTVSS |
836 | DMQLVESGGGLVQPGGSLKLSCAASGFTFSASAIHWVRQASGKGLEWVGHIRTRTNRYATAFSESVNGRFTISRDDSKSTAYLQMNSLKAEDTAVYYCARDEGVTFHDHWANEIRYGMDVWGRGTTVTVSS |
837 | QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARARTTMIVVVSQFDYWGQGTLVTVSS |
838 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQAPGKGLVWVSRINSDGSSTSYADSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCARDRGGWLLGSYYYYGMDVWGQGTTVTVSS |
839 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARGQISHYGFGESHWGQGTLVTVSS |
840 | QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVSVGWIRQPPGKALEWLALIYWDDDKRYSPSLKSRLTITKDTSKKQVVLTLTNMDPVDTASYYCAHSGIAVVGNQLFHYYAMDVWGQGTTVTVSS |
841 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKERSSGSQWGWTYYYYGMDVWGQGTTVTVSS |
842 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDPYGGNRRFHGWVYYYYGMDVWGQGTTVTVSS |
843 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARESTPDVRGVMNYWGQGTLVTVSS |
844 | EVQLLESGGGLVLPGGSLRLSCAASGFTFSIYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDAVASAGSPDYWGQGTLVTVSS |
845 | QVQLVESGVGVVQPGKSLRLSCAASGFTFTSYGMHWVRQAPGKGLEWVAVISFDGSNIYYADSVKGRFTISRDNFKNTLYLQMNSLRAEDTAVYYCARDKLLWFGEPVVGYYYYYYMDVWGKGTTVTVSS |
846 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGGDYAQIYFDYWGQGTLVTVSS |
847 | QVQLVESGGGVVHPGRSLRLSCAASGFAFNKYGIHWVRQAPGKGLEWVALIWNDGNKQYYGDSVKGRFTVSRDNSKNTVSLQMDTLRDEDTAVYYCARDRLMTTYNYYSSMDVWGRGATVIVSS |
848 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREPGDCSGGSCYYYGMDVWGQGTTVTVSS |
849 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGSIFYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARATRGYSYDDAFDIWGQGTMVTVSS |
850 | QVQLQESGPGLVKPSGTLSLTCSVSGGAITTSSYFWGWIRQPPGRGLEWIGSISYSGDTFYNPSLNDRVTISVDSSKNQFFLKLRSVTAADSAVYYCASPSYTDLLTGYYVPVDYWGQGILVIVSS |
851 | QVHLVESGGGVVQPGKSLTLSCAASGFTFSAYGMHWVRQTPGKGLEWVALISFDGSNKYYRDSVKDRFTIARDNSKNTLSLQMNSLRPEDTAIYYCAKDPRVNELLWFGSLTQFYFDDWGQGTLVTVSS |
852 | QVQLVESGGGVVQPGRSLTLSCAASGFTFNNYGMHWVRQAPGKGLEWLALISYEGSIRYYGDSVKGRFTISRDSSKNTVYLQMISLRAEDTAVYYCAKSGGPFHLSLYYYMDVWGKGTTVTVSS |
853 | QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQTAGQGLEWIGRIYSGGSTNYNPSLKSRVTMSVDTSQNQFSLNLNSVTAADTAVYYCARAFYGHAFDFWGLGVLVIVSS |
854 | QVQLVESGGGVVHPGRSLRLSCAASGFTFSRFGMHWVRQAPGKGLEWVALISYEGSTEQYSDSVKGRFAISRDNSKNTLYLQMNSLRPEDTAVYYCAKGLTIPFDKWGHGTLVTVSS |
855 | QVQLVESGGGVVHPGRSLRLSCAASGFTFSRFGMHWVRQAPGKGLEWVALISYEGSTEQYSDSVKGRFAISRDNSKNTLYLQMNSLRAEDTAVYYCAKGLTIPFDKWGHGTLVTVSS |
856 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSSFWMTWFRQTPGKGLEWVANIKEDGSEKQYVDSVKGRFNISRDNAHNSLYLEMNSLRSEDAAVYYCARRGKYCSGGRCYSWWFDPWGQGTQVTVSS |
857 | QVQLVQSGGEMRKPGSSVKVSCKASGGTFSSYTISWVRQAPGQGLEWMGRIIPMLNKTYYAQKFQGRVTFAADESTSTVYMELSSLRSEDTAMYYCARVASLIGDDYWGQGSLVTVSS |
858 | QVQLVQSGGEMRKPGSSVKVSCKASGGSFSSYTISWVRQAPGHGLEWMGRIIPMLNKTYYAQKFQGRVTVAADESTSTVYMELSSLSSEDTAIYYCARVASLIGDDYWGQGSLVTVSS |
859 | QITLKESGPTLVKPTQTLTLTCTFSEFSLDSRGVGVGWIRQPPGRALEWLALIYWNDNKRYNPSLRSRLTITKDTSKNQVVLTMSNMDPVDTATYYCAHKPSGWSLRFDSWGQGTLVTVSS |
860 | QVQLQEAGPGLVKPSETLSLTCSVFGGSISSYYWSWIRQPPGKGLEWIGYIYYRGSTNYNPSLKSRVTMSVDTSKNQFSLNLTSVTAADTAVYFCARESLFNWFDSWGHGTLVTVSS |
861 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGMHWVRQAPGKGLEWVALISYEGSTEQYSDSVKGRFAISRDNSKNTLYLQMNSLRHEDTAVYYCAKGLTIPFDNWGQGTLVTVSS |
862 | EVQLVESGGGLVQTGGSLRLSCAASGFPFSGYALNWVRQAPGKGLEWVSYISSSSSTVYYADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCARVDYDSSRNYWGQGTLVTVSS |
863 | EVQLVESGGGLVQPGGSLRLSCAASGFTFINYDMTWVRQAPGKGLEWISYISSSSSTTHYSDSVKGRFTISRDNARNSLYLEMNSLRAEDTAVYYCARVERWLVLGYYYYGMDVWGQGTTVTVSS |
864 | EVQLVESGGGLVQPGESLRLSCVASGFAFDKFWMAWLRQAPGKGLEWVALLNKDESEKYYVDSVKGRFTISRDNAIDSVFLQMNSLRTEDTAVYYCGSIDYWGQGALVTVSS |
865 | QVQLQESGPGLVKPSQTLSVTCTVSGGSINRDGHYWIWIRQHPEKGLEWLGYIYSGRNTFYNPSLRSRLSISADTSKSQFSLNLHSVTAADTAVYYCAKMYSDYDDNYYGLDVWGRGTTVTVSS |
866 | QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDRYCSSTSCGGYYYYMDVWGKGTTVTVSS |
867 | QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGSYFWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLRSVTAADTAVYYCARAPNDFWSGYPYYFDYWGQGTLVTVSS |
868 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCTRDGSTAAIFGNIDYWGQGTLVTVSS |
869 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARGVVRNDYGDPGFDYWGQGTLVTVSS |
870 | QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATAPAYCSGGSCPENNWFDPWGQGTLVTVSS |
871 | QVLLVQSGAEVKKPGASVKVSCKASGYRFTSYGIHWVRQAPGQSLEWMGCINTDNEKTEYSQKFQGRVTITRDTSASTAYMELSTLRFEDTAVYYCAILWFGEFYFYDLFYNAVDVWGQGTTVTVSS |
872 | QVLLVQSEAEVKKPGASVKVSCKASGYRFTSYGIHWVRQAPGQGLEWMGSINTDNGKTEYSQKFQGRVTITRDTSAGTAYMELSTLRSEDTAVYYCAILWFGEFYFYDLFYNAVDVWGQGTTVTVSS |
873 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMHWVRQAPGQRLEWMGWINAGNGNTRYSQKFQGRVTITRDTSASTAYMELSSLRSEDTAVYYCASRREQWLGDLGYYYYGMDVWGQGTTVTVSS |
874 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPEQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGAHSEDYWGQGTLVTVSS |
875 | QVQMVQSGAEVKKPGASVKVSCKASGYTFTNYYVHWVRQAPGQGLEWMGRINPSDGSTSYTQKFQGRVTMTRDTSTSTVYMQLSSLRSEDTALYYCARHQDPLDIVATVDWGGLDYWGQATLVTVSS |
876 | QVQLVQSGGELRKPGSSVKVSCKASGGTFSSYTISWVRQAPGQGLEWMGRIIPMLNKTYYAQKFQGRVTFAADESTNTVYMELSSLRSEDTAMYYCARVASLIGDDYWGQGSLVTVSS |
877 | QVQLVQSGAEVKKPGSAVKVSCKASGGTFNSYAFNWVRQAPGQGLEWMGGIIPIFGPPNYAQNFQGRVTITADESTSTAYMELSSLTSEDTAVYYCATTGTDNYYYYMDVWGKGTTVTVSS |
878 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSSDINWVRQATGQGLEWMGWMNPNTGTTGYAQKFQDRVTMTRDTSINTAYMELSSLRSEDTAVYYCARKNCSGGICYFHDYWGQGTRVTVSS |
879 | QITLKESGPTLVKPTQTLTLTCTFSEFSLDARGVGVGWIRQPPGRALEWLALIYWNDYKRYSPSLQSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHKPSGWSLRFDSWGQGTLVTVSS |
880 | EVQLLESGGGLVQPGGSLRLSCAASGFTFISYATSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKGQTIQLWLFGALWGQGTLVTVSS |
881 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGTTYYADSVKGRFTISRDNSKNTLYLQMDSLRGDDTAVYSCALTVSSWYPGIFENWGQGTLVTVSS |
882 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKAFSGSYWDAFDIWGQGTMVTVSS |
883 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSHGMHWVRQAPGKGLEWVAVISYDGINKYYADSVKGRFTISRDNSKNTLFLQLNSLRAEDTAVYYCAKAASGARGYYGMDVWGQGTTVTVSS |
884 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSSSGHYVSDLGYWGQGTLVTVSS |
885 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARALNGYRYNDYWGQGTLVTVSS |
886 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKGLEWVAVMWFDGVDKYYADSVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCAREEGGGSSTHFDCWGQGTLVTVSS |
887 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSTFAMHWVRQAPGKGLEWVAIISYDEINKYYADSVKGRFTISRDNSKNMLYLQMNSLRAEDTAVYYCARTREGSYYYGMDVWGQGTTVTVSS |
888 | EVKLVESGGHLVQPGRSLRLSCTASGFIFGDYAMGWVRQAPGKGLEWVSFIRGRLVGATVEYAASVKGRFTMSRDDSERVAYLQMNSLKIEDTGVYYCVRGGLQFVVAVGPYGVDVWGQGTTVTVSS |
889 | EVKLVESGGHLVQPGGSLRLSCTASGFIFGDYAMGWVRQAPGKGLEWVSFIRGRLVGATVEYAASVKGRFTMSRDDSERVAYLQMSSLKIDDTGVYYCVRGGLQFVVAVGPYGVDVWGQGTTVTVSS |
890 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRVEDTAVYYCARDIGGGAPDYWGQGTLVTVSS |
891 | QVLLQESGPGLVRPSQTLSLTCSVSGASISSGDYYWTWVRQTPGKGLEWLGFIYYSGSTYYNPSLQRRVLISMDTAMNQFSLRLTSVTAADTAVYYCAIKPSIPGYFDPWGQGTLVTVSS |
892 | QVQLQQWGAGLLKPSETLSLTCALNGGVLSDYYWSWIRQPPGQGLEWIGAIHRSGSTSYTPSLKSRVTMSVDTSKNQFSLRLSSVTAADTAVYYCARVGGWQRSPRPNWGQGTRVTVSS |
893 | QVQLQQWGAGLLKPSETLSLTCALNGGVLSDYYWSWIRQPPGQGLEWIGAIHRSGSTSYTPSLKGRVTMSVDTSKNQFSLRLSSVTAADTAVYYCARVGGWQRSPRPNWGQGTRVTVSS |
894 | QVQLQQWGAGLLKPSETLSLTCAVYGGSFSDYYWNWIRRPPGKGLEWIGEITHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGQGYGRVLLWFGEWGQGTLVTVSS |
895 | QVQLQQWGAGLLKPSETLSLTCAVYGGSFSDYFWYWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVSISVDTSKNQFSLKLSSVTAADTAVYYCARGQGYGRVLLWFGEWGQGTLVTVSS |
896 | QVQLQESGPGLVKPSGTLSLTCDVSGDSISSNNWWTWVRQPPGKGLEWIGDIYHSGTTNYNPSLKSRLTMSVDKSKNHFSLKLTSVTAADTAVYYCARPSSGSRFDYWGQGTLVTVSS |
897 | QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPAGKGLEWIGHIYTSGSTNYNPSLKSRVTMSVDTSKNQFSLKLSSVTAADTAVYYCARGFDYWGQGTLVTVSS |
898 | QVQLQESGPGLVKPSETLSLTCTVSGDSISSYYWSWIRQSPGKGLEWIGYIYHSGSADYNPSLKSRVSMSLDASKNQFSLKMSSVTAADTALYYCAKARGVVLFDYWGQGTLVTVSS |
899 | QVQLRESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYLHYSGRSNSSPSLNSRVSISVDTSQNRFSLKVTSLTAADTAVYYCARHSYGSGTYLDPFDYWGQGTLVTVSS |
900 | QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGSYYWSWIRQPAGKGLEWIGRIYTSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARQPHLAYYYDSSGYNDAFDIWGQGTMVTVSS |
901 | QVQLQESGPGLVKPSQTLSLICTVSDDSISSGSYYWSWIRQPAGKGLEWIGRIYAGESTNYNPSLKSRVIISVDTSKKQFSLRLSSVTAADTAVYYCARGAVVTPFGLDSWGQGTLVTVSS |
902 | EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCASEDYYDSSGYYWYWGQGTLVTVSS |
903 | EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWGSLKASDTAMYYCARLSAIAVVGYYYYAMDVWGQGTTVTVSS |
904 | QVQLVQSGSELKKPGASVKVSCKASGYTFTSYAMNWVRQAPGQGLEWMGWINTNTGNPTYAQGFTGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCARDFIAASPFYYYYYMDVWGKGTTVTVSS |
905 | EVQLVQSGAEVKKPGESLKIFCKGSGYTFSFYWIGWVRQTPGKGLEWMGIIYPGDFDTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAMYYCATSPGGYGVRRTVLEDFRHWGQGTLVTVAS |
906 | QLQLQESGPGLVKPSETLSLTCTVSGGAFSSGRHYWGWIRQPPGKGLEWIGSIYSGVITHYNAPLKSRVTIAVDTSKNQFSLKLSSVTAADTAVYYCWTMEYDDYSFVYDYWGQGTLVTVSS |
907 | QVHLQQWGAGLLKPSQTLSLTCAVYGGSFSSYYWSWIRQTPGKGLEWIGEVTHSGSTNYKPSLKSRVTMSVDTSRNQFSLNLTSVTAADTAVYYCARGGKQQLVRNYYLDSWGQGTLVTVSS |
908 | QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMDWVRQAPGKGLEWMGGFDPEDGETIDAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATGFGGVIVRGFDYWGQGTLVTVSS |
909 | QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVYGDYSYYMDVWGKGTTVTVSS |
910 | EVQLVESGGGLIQPGGSLRLSCAASGITVSSNYMSWVRQAPGKGLEWVSVIYSGGSTDYADSVKGRFTISRDKSKNTLYLQMNSLRAEDTAVYYCARDLGEAGGMDVWGQGTTVTVSS |
911 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSRFWMTWVRQAPGKGLEWVANIKEDGSVMFYVDSVKGRFSISRDNSKNSLYLEMNSLRAEDTAVYFCVREIESGVDFWSGHYYWGQGTLVTVSS |
912 | EVQLVESGGGLVQPGGSQRLSCVASGFTFSNYWMSWVRQAPGKGLHWVANIKSDGSETYYVDSLRGRFTISRDNAKNSLYLQLTSLTVEDTAVYYCARDSAYYDTIGYYSGDYWGRGTLVTVSS |
913 | QVQLVESGGGAVQPGRSLRLSCEASAFSFHLHGMHWVRQAPGKGLEWVALIWFDGSKKFYADAVKGRFTISRDNSKNTLYLQMNSLRVEDTAIYYCGRSFRGSCFDYLGQGTLVTVSS |
914 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISSSGGGTYYADSVKGRFTISRDNSKNTLYVQMNSLRAEDTAVYYCALGTGSYYGVNYWGQGTLVTVSS |
915 | EVQLVESGGGLVQPGRSLRLSCAAFGFIFDDYGMHWVRQVPGKGLEWVSGITWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYFCAKDMGGRYSSGLYYYYYGMDVWGQGTTVTVSS |
916 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRHNSKNTLYLQMNSLRAEDTAVYYCARELRGYFDYWGQGTLVTVSS |
917 | QMRLQESGPGLVKPSETLSLTCTVSGGSIGSSSYFWGWIRQPPGKGLEWIGNIYYGGSTYYKPSLKSRVTISLDTSKNQLTLRLSSVTAADTAVYYCARDPNDFWSGFPRGAFDIWGQGTMVTVSS |
918 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCASHARYEEETFDYWGQGTLVTVSS |
919 | EVQLVESGGGLAQPGGSLRLSCAASGFTFSSYDMHWVRQAAGKGLEWVSTIGTAGDTYYPGSVKGRFTISRENDKNSLYLQMNSLRAGDTAVYYCVRDSYTSAWTPAGYFDLWGRGTLVTVSS |
920 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSRSAMHWVRQGPGKGLEWVAMMSYDGSDIQYADSVKGRFTISRGNSKNTLFLQMNSLRLADTAMYYCAKDHYGSIDYWGQGTLVTVSS |
921 | QVQLVESGGGVVQPGRSLRLSCVASGFTFSSQSMHWVRQAPGKGLEWVSIISYDGNNKQYADSVKGRFTISRDNSKSTLFLQINSLRPQDTAVYYCARPYTSRWFWSNWGQGTLVTVSS |
922 | EVQLVESGGGLVQPGRSLRLSCAASGFTFEEYSIHWVRQAPGKGLEWVSGVSWNSGTIAYADSVRGRFTISRDNAKNSLYLQMSRLRADDTALYYCALLPPNAYDYGDGLLDHWGQGTLVTVSS |
923 | EVQVVQSGAEVKKPGESLKISCKGSGYTFGRYWIAWVRQMPGKGLEWMGIINPADSDTRYSPTFQGQVTISVDQAISTAYLQWSSLKASDTAMYHCARHRAAGGNYYYGMDVWGQGTTVTVSS |
924 | QVQLVQSGAEVKKPGASVKVSCKASGYTFSTYYMHWVRQAPGQGLEWMGIINPSGDSTRYAQKFQGRVTMTRDTSTSTVYMEVSSLRFEDTAVYYCARERVGPAAGYMDVWGKGTTVTVSS |
925 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGRIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAAYYYDSSGYGWFDPWGQGTLVTVSS |
926 | QVQLVQSGAEVKNPGSSVKVSCKTSGATFTTYAINWVRQAPGQGLEWIGGIFPIFTAAVYAQKFQGRVTITADESTTTAYLELSSLRSEDTAVYYCARGDYTEYSYYYMDVWGKGTTVTVSS |
927 | EVQLLESGGGLVQPGGSLRLSCAASGFTLSSYAMSWVRQAPGRGLEWVSAVSGSGGSTYYADSVKGRFTISRDNSKNMLYLQMNSLRAEDTAIYYCALPTGASSSYSGPNYWGQGTLVTVSS |
928 | QVQLVESGGGVVQPGRSLRLSCVASGFTFSNYDMHWVRQAPGKGLEWVTVISSDGNNRRYADSVKGRFTISRDNSKNMLYLQMNSLKAEDTAVYYCARDEVIAVATGEGMDVWGQGTTVTVSP |
929 | EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKDMGYDILTGSGLGDYWGQGTLVTVSS |
930 | EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGTIGYEDSVKGRFIISRDNAKNSLYLQMNSLRAEDTALYYCAKEPLFGETYGMDVWGQGTTVTVSS |
931 | EAQLVESGGGLVQPGRSLTVSCAVSGFTFDDYAMHWVRQAPGKGLEWVSSISWNSEKIAYADSVKGRFTVSRDNAKNSLYLQMTSLRPEDTALYYCARDKGSGSYYSGAYYYYMDVWGKGTTVTVSS |
932 | EVQLVESGGGLVPPGGSLRLSCAASGFTFSSYTINWVRQAPGKGLEWVSYINSGSSIIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCATFNSGNDNAYEYWGQGTLVTVSS |
933 | EVRLVESGGGWVQPGGSLRLSCEASTFIFSNSEMNWVRQAPGKGLEWVSYISSSDNSVHYADSVKGRFTISKDSAKKTLYLQMNSLRAEDTGVYYCAREYPDFWSGHYYYYMDVWGKGTTVTVSS |
934 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLPYGMDVWGQGTTVTVSS |
935 | QVKLQQWGAGLVKPSETLSRTCAVYGGSFSGYFWSWIRQSPGKGLEWIGEINHSGKTNYSPSLKSRVSISVDTSKNQFSLKLTSVTAADTAVYYCARGLYDKSGYRSDGFDSWGQGAVVTVYS |
936 | QVQLQQWGAGLLKPSETLSRTCAVYGGSFSGYYWTWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRITMSVDTSKNQFSLELRSVSAADTAVYYCARGFEGYCSGGRCYSYFDYWGQGTLVTVSS |
937 | QVQLQESGPGLVKPSETLSLTCTVSGGSLSSYYWNWIRQPPGKGLEWIGYMYNSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARVKNWDYGLYWGQGTLVIVSS |
938 | QVQLQESGPGLVKPSETLSLTCTVSGGSISTFYWNWVRQPPGKGLEWIGFIYYSGRTNYNPSLKSRVTISVDTSKNQFSLKVSSVTAADTAVYYCARDGQSDWHFDLWGRGTLVTVSS |
939 | QVQLQESGPGLVKPSETLSLTCTVSGGSVSSYFWSWLRQPPGKGLEWIAYIFYTGTSNYNPSLKSRVTISLDTSKNQMSLNLSSVTTADTAVYYCARVYGDYLDHWGQGTVVTVSS |
940 | QITLKESGPTLVKPTQTLTLTCTFSGFSFNTPGVGVGWIRQPPGKAPECLALIYWDDEKLYNPSLKTRLTITKDPSKNQVVLTMTTMDPVDTATYYCAHRSFLYNIFNGYSYAPFDYWGQGSMVTVSS |
941 | QVQLVESGGGVVQPGRSLRLSCAASGFSFSNHGMHWVRQAPGKGLEWVAVIWYDGDNRFYADSVRGRFTISRDNSKNTLFLQMDSLRAEDTGIYYCAKDLFSGDRDFWGQGTLVTVSS |
942 | QVQLVESGGGVVQPGRSLRLSCVASGFTFSNSAMHWVRQAPGMGLEWVAVIYYDGSNEYYADSVKGRFTISRDNSKNTLYLQMNSLRADDTAVYYCAKDSGAVLLWFGADFWGQGTLVTVSS |
943 | DVQLVESGGSLVQPGGSLRLSCAASEFTFSSYEMNWVRQAPGKGLEWVSYIDSSSTTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAREGAYDIWRGSYMRAYDHWGQGTLVTVSS |
944 | QVQLVQSGSELKKPGASVKVSCKASGYTFTNFAINWVRQAPGQGLEWMGWINTKTGIPTYAQGFTGRFVFSLDTSVSTAYLQISGLKAEDTAVYYCARYIEMFDPWGQGTLVTVSS |
945 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARQAYGDYGWDYYYGMDVWGQGTTVTVSS |
946 | QVQLAEAGGGVVQPGTSLRLSCVVSGFSFSRYGMHWVRQAPGKGLEWVAVISHDDSQKYYGDSVKGRFTISRDNSKDTLYLEMTSLRLEDTAVYYCLKDWDWEYEDSRPTLRGSVYWGQGTLVIVSA |
947 | QVQLVESGGGAVQPGRSLRLSCVTSGFNFNSYTMHWIRQAPGKGLEWVAVISYEGSKKYYADSLKGRFTISKDNSKNTVYLEMNSLTTEDTAVYYCARGSVFWFGEGKNWFDPWGQGTLVTVSS |
948 | QVQLVESGGGAVQPGRSLRLSCVTSGFNFNSYTMHWIRQAPGKGLEWVAVISYEGSKKYYADSLKGRFTISKDNSKNTVYLEMNSLTTEDTAVYYCARGSVFWFGEGKNWFDPWGQGTLVIVSS |
949 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAREDSSGWSRGDYWGQGTLVTVSS |
950 | QVQLVQSGSELKKPGASVKVSCKASGYIFTSYGMNWVRQAPGQGLEWMGWINTNTGSPMYAQGFTGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCARRFVVREVEYNWFDPWGQGTLVTVSS |
951 | QAQLVQSGSEVRKPGASVKVSCKASGYSFNDYGITWVRQAPGQGLEWMGWISAYNGETNYAQKFQDTVTMTTDTSTNTAYLELRSLRFADTALYYCARDGYCNSMRCYRYYHGMDVWGQGTTVTVSS |
952 | QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATGPTAKPNKQWGYWFDPWGQGTLVTVSS |
953 | QVQLVQSGAEVKKPGASVKVSCKASGNTFSTYYIHWVRQAPGQGLEWMGIISPSGDDANYTQKFQDRVTMTRDTPTNTVYLELSSLRSEDTAVYYCASPVSVEQDFDIWGQGTMVTVSA |
954 | EVQLVESGGGSVKPGGSLRLSCAASGFTFSDVWMSWVRQAPGKGLEWVGRIRSKSDGGTTDYAAPMKERFSISRDDAKNTMYLQMNSLKTEDTGVYYCTTPVGDFWGQGTMVTVSS |
955 | EVQLMESGGGLVKPGGSLRLSCAGSGLTFDNAWMSWVRQAPGKGLEWVGRVKSKTDGGTTDYAAPVKGRFTISRDDSKNTLFLQMNSLKTEDTAVYYCSTSHPPFFDYWGQGTLVTVSS |
956 | QVQLVESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVALISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMDSLRPEDTAVYYCARGLWQLVSPVFDYWGQGTLVTVSS |
957 | EVQLVESGGVVVQPGGSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSLISWDGGSTYYADSVEGRFTISRDNSKNSLYLQMNSLRAEDSALYYCAKVTNRGVRGLYFDYWGQGTLVTVSS |
958 | QVQLVQSGAEVKKPGASVKVSCKASGNTFTTYYIHWVRQAPGQGLEWMGIISPSGDDANYTQKFQDRVTMTRDTPTNTVYLELSSLRSEDTAVYYCASPVSVEQDFDIWGQGTMVTVSA |
959 | QVQLVQSGAEVKKPGSSVNVSCKASGGTFNSYTLSWVRQAPGQGLEWMGRIVPMLGITNYAQKFQDRVTITADESTATAYMDLSSLTSEDTAVYFCAINTLLVTAWGQGTLVTVSS |
960 | QITLKESGPTLVKPTQTVTLTCTFSGFSLNTPGAGVGWIRQPPGQALECLALIYWDDDKRYSPSLRSRLSIAKDTAKNQVVLTVTNLDPVDTATYYCVHRSFLYDIFSGYSYAPFDYWGQGMLVTVSS |
961 | QITLKESGPTLVKPTQTLTLTCTFSGFSFNTPGVGVGWIRQPPGKAPECLGLIYWDDEKRYSPSLKSRLTITKDPSKNQVVLTMTTMDPVDTATYYCAHRSFLYNIFDGYSYAPFDYWGQGSMVTVSS |
962 | QVQLVESGGGLVKPGGSLRLSCAASGFTFTFSDYYMNWIRQAPGGGLEYIAYISSGGDAIYYADSVKGRFIISRDNSESSVSLQMTSLRADDTAVYYCAGGADCRRTSCHYLVSNREEYMGVWGKGTTVTVSS |
963 | EVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMNWVRQAPGKGLEWVSSMSSDSDYIFYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARGLVLSGTRYSYFYGMDVWGQGTTVTVSS |
964 | QVHLAEAGGGVVQPGRSLRLSCVVSGFSFSRYGMHWVRQAPGKGLEWVAVISHDESQKYYGESVKGRFTISRDNSKDTVYLQMDSLRVEDTAVYYCVKDWDWEYEDNRPTLRGSVYWGQGTLVIVSA |
965 | QVQLAEAGGGVVPPGRSLRLSCVVSGLSFSRYGMHWVRQAPGKGLEWVAVISHDESQKYYGESVKGRFTISRDNSKDTLYLQMDGLRVEDTAMYYCVKDWDWEYEESRPTLRGSVYWGQGALVIVSA |
966 | QVQLVESGGGVVQPGRSLRLSCATSGFSFNNFGMHWVRQAPGKGLEWLAVISYEGSKKYYADSLKGRFTISRDGSKDTLYLQLSSLGVEDTAVYHCAKGGPIFWLGEGKNWFDAWGPGTPVIVSS |
967 | QVQLVESGGGVVQPGRSLRLSCAASGFTLSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYRDSVKGRFTISRDNSKNTLYLQINSLRVDDTAVYYCARDKGGILMLRGADFWGQGTLATVSS |
968 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYITSSGNTILYADSVKGRFTISRDNAKNSLYLRMNSLRAEDTALYYCARTLIAAAGSAFDIWGQGTMVTVSS |
969 | EVQLVESGGGLGLPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWISYISSSSGTIYYADSVKGRFTISRDNAKNSLFLQMNSLRDEDTAVYYCARGPTSITMIVVVDDAFDIWGQGTMVTVSS |
970 | QVQLQESGPGLVKPSETLSLTCSVSGGSISPYSWSWIRQPPGKGLEWIGYIYYTGKTNYNSSLKTRVTISLDTSKNQFSLRLTSVTTADTAIYYCARVMNSSWYTRYYYNYMDVWGKGTSVTVSS |
971 | QLQLQESGPRLVKPSATLSLTCTVSGDSIRSSSFYWGWIRQPPEKGLEWLGSVYNSGTAYYNPSLKSRVSVSVDTSKNQFSLKVNSVTAADTAVYYCARRGGGCSEGVCYNFDRWGQGTLVTVSS |
972 | QVQLVQSGSELKKPGASVKISCKAFGYSFTTYAMNWVRQAPGRGLEWMGWIDTNTGKPTYARGFTGRFVFSLDTSVRTSYMQINTLKAEDTAVYYCARGDPRDYWGQGTLVTVSS |
973 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGRIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGSYYYDSSGYYLDYWGQGTLVTVSS |
974 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGRIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAAYYYDSSGYGWFDPWGQGTLVTVSS |
975 | EVQLVESGGGLVKPGGSLRLSCAASGFTFSHAWMCWVRQAPGKGLEWVGRIKSNTDGGTTDYAAPVKGRFTISRHDSKNTLYLQLNSLKTEDTAVYYCTTDLGATGIYYYYYMDVWGKGTTVTVSS |
976 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARFPRDYYDSSGYLIQEGNFDYWGQGTLVTVSS |
977 | EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVTRAGAAGDGGAFDIWGQGTMVTVSS |
978 | QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGSTKYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSVVPVAGTDYWGQGTLVTVSS |
979 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDQHPGYPALVYYYYYMDVWGKGTTVTVSS |
980 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGITWVRQAPGQGLEWMGWISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDNIQTFDYWGQGTLVTVSS |
981 | QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATSSPVAGYNSWFDPWGQGTLVTVSS |
982 | QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATGPAVIPLRWFDPWGQGTLVTVSS |
983 | QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATAPAAAGPTDWFDPWGQGTLVTVSS |
984 | QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAISPSVHSLWWFDPWGQGTLVTVSS |
985 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMHWVRQAPGQRLEWMGWINAGNGNTKYSQKFQGRVTITRDTSASTSYMELSSLRSGDTAVYYCARDEIHYDILTGYYNRFWFHPWGQGTLVTVSS |
986 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDAETGYYDSSGYPINWFDPWGQGTLVTVSS |
987 | QVTLKESGPVLVKPTETLTLTCTVSGFSLSNARMGVSWIRQPPGKALEWLAHIFSNDKKSYSTSLKSRLTISKDTSKSQVVLTMTNMDPVDTATYYCARHYYDTGAYYVPFDHWGQGTLVTVSS |
988 | QITLKESGPTLVKPTQTLTLTCTFSGFSLSTTGVGLAWIRQPPGKALEWLAFIYWDDDKRYSPSLQTRLTITKDTSKNQVVLTLTNMDPMDTATYYCAHFQGFGESEYFQHWGQGTLVTVSS |
989 | QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVGVGWIRQPPGKALEWLALIFWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHRHPLTGFDSWGQGTLVTVSS |
990 | EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCATPRGYSYGPLDYWGQGTLVTVSS |
991 | EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCASPRGYSYGPFDYWGQGTLVTVSS |
992 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRVDKGYDFWSSWYFDLWGRGTLVTVSS |
993 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASGGGSYFDAFDIWGQGTMVTVSS |
994 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRSGSYYGGFDYWGQGTLVTVSS |
995 | QVQLVESGGGVVQPGWSLRLSCAASGFTFGSYGMHWVRQAPGKGLEWVALIWNDGSNKYYADSVKGRFTISRDKSKNTLYLQMNSLRAEDTAVYYCAKAVYGGNSVYFDYWGQGTLVTVSS |
996 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARIYGGNYENYFDYWGQGTLVTVSS |
997 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSIYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARESEAGTTPSFDYWGQGTLVTVSS |
998 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTNYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSLVRGVITYFDYWGQGTLVTVSS |
999 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYWMNWVRQAPGKGLEWVANIKEDGSETYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARGLSMEVWGQGTTVTVSS |
1000 | QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEIDHSGSTNDNPSLKSRVTISVDTSKNQFSLKLSSVTAADAAVYYCARGGYSSSWYGTKYYFDYWGQGTLVTVSS |
1001 | QVQLQQWGAGLLKPSETLSLTCAVYDGSFSGHYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGPTVTTFFRRNAWFDPWGQGTLLTVSS |
1002 | QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGRYSSGWYGSRNWFDPWGQGTLVTVSS |
1003 | QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARLSMGAARQSGFDPWGQGTLVTVSS |
1004 | QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDGGRDGYNELGARVYYYYGMDVWGQGTTVTVSS |
1005 | EVQLVQSGAEVKKPGESLRISCKGSGYNFTSYWISWVRQMPGKGLEWMGTIDPSDSYTNYRPSFQGHVTISADKSINTAYLQWSSLKASDTAMYYCARIGSYGIWGQGTLVTVSS |
1006 | QVQLVQSGSELKKPGASVKVSCKASGYTFTSYAMNWVRQAPGQGLEWMGWINTNTGNPTYAQGFTGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCAKLGCSGGSCYYYYGMDVWGQGTTVTVSS |
1007 | EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYVSWVRQAPGTGLEWVSVVYSGGHAYYADSVKGRFTMSRDNSENAVYLQMNSLRAEDTAVYYCARGDHYYDRSGPHKFDYWGQGTLVTVSS |
1008 | QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGLYHWSWIRQPAGKGLEWIGRIFSSGSTAYSPSLKSRVIISADTSKNQFSLKLSSVTAADTAVYYCARDSPLKFDSFGYPLYGMDVWGQGTTVTVSS |
1009 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYTISWVRQAPGQGLEWMGRIIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARGIVGATPGYFDYWGQGTLVTVSS |
1010 | QVQLVQSGAEVKKPGASVKVSCKASGFTFGRHGITWVRQAPGQGLEWMGWISTYSGNTNYAQNLQGRVTMTTDTSTNTAYMELRSLFFDDTAVYYCAKAVSGWPIYFDAWGQGTLVTVSS |
1011 | QIQLVQSGAEVKKPGASVRVSCKASGFTFGRYGITWVRQVPGQGLEWMGWISTYSGNTNYAQNLQGRVTMTTDTSTNTAYMELRSLFFDDTAMYYCAKAVSGWPIYFDAWGQGTLVTVSS |
1012 | QITLEESGPTLVKPTQTLTLTCTFSGFSLTTRGEGVAWIRQPPGKALEWLALIYWDDDQRYTPSLDSRLTITKDISKNHVVLTLTDVEPVDTATYFCAHTIHSGYDRTFDSWGQGTLVIVSS |
1013 | QVQLVQSGSELKKPGASVKVSCKASGYTFTFYTIYWVRQAPGQGLEWMGWINTNTGTPTYAQGFTGRFVFSLDTSVSTAYLQISSLKAEDTAIYYCAREESYSSSSPLDYWGPGTLVAVSS |
1014 | QMQLVQSGPEVKKPGTSVKVSCKASGFTFTSSAVQWVRQARGQRLEWIGWIVVGSGNTNYAQKFQERVTITRDMSTSTAYMELSSLRSEDTAVYYCAAGSDFWSGYYVNYYMDVWGKGTTVTVSS |
1015 | QVTLRESGPALVKPTQTLTLTCTFSGFSLSTSGMCVSWIRQPPGKALEWLARIDWDDDKYYSTSLKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARLTAAGVYFDYWGQGTLVTVSS |
1016 | EVQLLESGGGVVQPGGSLRLSCAASGFTFTTYAMNWVRQAPGRGLEWVSAISDSGGSAYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKTRGRGLYDYVWGSKDYWGQGTLVTVSS |
1017 | EVQLLESGGGVVQPGGSLRLSCAASGFAFTTYAMNWVRQAPGRGLEWVSAISDGGGSAYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKTRGRGLYDYVWGSKDYWGQGTLVTVSS |
1018 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDESGSYYGDQAFDIWGQGTMVTVSS |
1019 | QAQLVQSGPEVKKPGASVKVSCEASGYTFSRYGISWVRQAPGQGLEWMGWISGYNGNTTSEQKVQGRVTMTTDTSTNKVFLELRSLRSDDTAMYYCARDRRARAYEIPFGSDHYYFGMDVWGQGTTVTVSS |
1020 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYYGSGSYPIGYMDVWGKGTTVTVSS |
1021 | EVQLVESGGGLAKPGGSLRVSCVVSGSGFTFRNAWMSWVRQAPGKGLEWVGRIKSKNDGGTTDYAASVKGRFTISRDDSKNSLDLQMQSLKTEDTAVYYCTTSYCSTKVCFDYWFDPWGQGTLVTVSS |
1022 | QVQLVESGGDVVQPGNSLRLSCAASGFTFNFYGMHWVRQAPGKGLEWVAFISYDGNKRYYVDSVRGRFTASRDNSKNTLFLQMNGLRNDDSAVYYCASNLYATSPYGGVKNWGRGTLVAVAS |
1023 | EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKDIGSGSPDAFDIWGQGTMVTVSS |
1024 | GVQLVESGGGLVQPGRSLRLSCAASGFIFDDYTMHWVRQAPTKGLEWVSGITWNYATVGYADSVRGRFTISRDNVKNSLFLQIHSLRPDDTAFYYCVKDLEFRGGTGGFDLWGQGTLVTVSS |
1025 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDGHSAWGAFDIWGQGTMVTVSS |
1026 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDHPTLRRAFDYWGQGTLVTVSS |
1027 | QVELVQSGAQVRKPGASVKVSCKASGDTFNDYHMHWVRQAPGQGLEWMGWINPNSGETRYSQRFQGTVTMTRDTSISTVYMELRSLPSDDTAVYFCARDRGSSSWWGWLDPWGQGTLVTVSS |
1028 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAHKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCATRRGYSGYGAAYYFDYWGQGTLVTVSS |
1029 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGRIIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAREVYVGGEDDYSYYYGLDVWGQGTTVTVSS |
1030 | EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTTDLGEAGPTEWLRSSLFDYWGQGTLVTVSS |
1031 | DIHMAESGGGLVKPGGSLRLSCAVSGLTFTKAWMSWVRQAPGKGPEWVGRIKSRSDGGKIDYAAPVKGRFIISRDDSKNTLYLQMHSLKTEDTALYYCTTSYCNPKVCFDYWFDPWGQGTLVTVSS |
1032 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMSWVRQAPGKGLEWVSVISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKEYYYDSSGYYYREDAFDIWGQGTMVTVSS |
1033 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMTWVRQAPGKGLEWVSGISANGRSPYYADSVKGRFTISRDNSKNTMYVQMNSLRVEDTAVYYCAKDGGLTAYLEYWGLGTLVTVSA |
1034 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCATEKWEVVDVCFDYWGQGTLVTVSS |
1035 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDIGWDVVVVAATHGVFDYWGQGTLVTVSS |
1036 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDPYYYGSGSSNFFDYWGQGTLVTVSS |
1037 | QVQLVESGGGVVQPGWSLRLSCAASGFTFSSFAMYWVRQAPGKGLEWVAVISYDGANKYYADSVKGRFTISRDNSKNTLYLQVNSLRVEDTAVYYCARGPDYYDTGGYFDLWGRGTLVTVSS |
1038 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVMWHDGSNKYHSDSVKGRFTISRDNSKNTLYLQMKTLRADDTAVYYCARDGYKQIYWYLDLWGRGTLVTVSS |
1039 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKGEGVYGSGSRYFLDYWGQGTLVTVSS |
1040 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYATHWVRQAPGKGLEWVAVISYDGSNKYHADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREWSRGAVAGTGYFDYWGQGTLVTVSS |
1041 | EVQLVESGGGLVQPGRSLRLSCAASGFTFHDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKVAKLPGDYYGMDVWGQGTTVTVSS |
1042 | EVQLVESGGGLIQPGGSLRLSCAASGVIVSRNYMNWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARELRGAFDIWGQGTMVTVSS |
1043 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGTTYYADSVKGRFTISRHNSKNTLYLQMNSLRAEDTAVYYCARDWGEYYFDYWGQGTLVTVSS |
1044 | EVQLVESGGGLIQPGGSLRLSCAASEFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDYGDLYFDYWGQGTLVTVSS |
1045 | EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRRVGSPYYYYYMDVWGKGTTVTVSS |
1046 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSILYSGGTTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLGDNAFDIWGQGTMVTVSS |
1047 | EVQLVESGGGLVQPGGSLRLSCAASGITVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRITISRDNSKNTLYLQMNSLRAEDTAVYYCARDRYSGYDFWGQGTLVTVSS |
1048 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLSGTGYGGDGGWFDPWGQGTLVTVSS |
1049 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQAPGKGLVWVSRIKSDGSSTSYADSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCAGKKIYYGSSFDPWGQGTLVTVSS |
1050 | QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGGSGSGWYGGRFDYWGQGTLVTVSS |
1051 | QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARVWRETYYYDSSGDSFDYWGQGTLVTVSS |
1052 | QVQLQQWGAGLLKPSETLSRTCAVYGGSFSGYYWTWIRQSPGKRLEWIGEISHGGKTNYNIFFEGRVTLSVDSSKSQFSLTLASVTAADTAIYYCARGRSITGIRDVDFWGQGALVTVSS |
1053 | QVQLHQWGAGLLKPSETLSLTCAVSGGSFSDDFWNWIRQPPGKGLEWIGEINHSGTTNYNPSLKSRITMSVDTSKSQFSLKLNSVTAADSAMYFCARGRGNYMFRWFDPWGQGTLVTVSS |
1054 | QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGGLWYDSINYYGMDVWGQGTTVTVSS |
1055 | EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARLILRWPTTWDYFDYWGQGTLVTVSS |
1056 | QVQLVQSGTEVKEPGSSVKVSCKASGDTFSNYPIAWVREAPGQGLEWMGRIIPIVGFANYAQKFQGRVTITADKSTSTAYMELSSLRFEDTAVYYCARVDGPFDYWGQGTLVTVSS |
1057 | QVQLVESGGGVVQPGRSLRLSCAASGFTFSTSAMHWVRQAPGKGLEWVAGISYDGSNEHLDSVKGRFTISRDNSKNTLYLQMSSLRPEDTAVYYCARCPFWNYGHCYLDNWGQGTLVTVSS |
1058 | QVQLVESGGGVVQPGGSLRLSCAASGFTFSTYAMHWLRQAPGRGLEWVAVISYDGSNKYNADSVKGRFTISRDNSKNTLSLHMNSLRPEDTAVYYCARPSVRWYYHAMDVWGQGTTVTVTS |
1059 | EMQLLESGGGLVQPGGSLRLSCAASGFTFFSYALSWVRQAPGKGLEWVSGISGISDSGGNTYYADSVKGRFTISRDNSQNMLYLQMNSLRVEDTAVYYCAKERRPVLRYFDWLPIEAPDYWGPGTLVTVSS |
1060 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMNWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTLSRDNSKNTLYLQMNSLRAEDTAVYYCARGQYDILTGYQYGAFDIWGQGTMVTVSS |
1061 | QVQLQESGPGLVKPSQTLSLTCTVSAGSISSDTYYWSWIRQPAGKGLEWIGRIYTTGSTIYNPSLNSRVLISADTSNNQFSLKLTSVTASDTAVYYCAAHYYSRTDAFHIWGQGTMVTVSS |
1062 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSVSGSGSYYKGLWFDPWGQGTLVTVSS |
1063 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWMRQAPGQGLEWMGIINPSGGSTSYAHQFQGRVTMTRDTSTSTVYMEMSSLRSEDTAVYFCVVGIGYCSSPSCPPLRWFDYWGQGTLVTVSS |
1064 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYTISWVRQAPGQGLEWMGRIIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARERGYSGSGSLYYFDYWGQGTLVTVSS |
1065 | QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVGVGWIRQPPGKALEWLALIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHYSSSRPPLFDYWGQGTLVTVSS |
1066 | EAQLLESGGGLVQPGGSLRLSCAVSGFTVSSYDMSWVRQAPGKRLEWVSFISARGSVTYYADSVRGRFTISRDNFKNTLYVEMNNLRVEDTAVYYCAKGHWSTWGQGTLVTVSS |
1067 | QVQLVESGGGVVQPGRSLRLSCAASGFTFRNYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKSTLYLQMNSLRAEDTAVYYCANGAYYYGSGSYYNGAAYWGQGTLVTVSS |
1068 | QVQLVESGGGVVQPGKSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISNYGSNKYHADSVKGRITISRDNSKNTLYLQMNSLRAEDTAVYYCAKGGYYDILTGYFPFDYWGQGTLVTVSS |
1069 | EVQLVESGGGLIQPGGSLRLSCAASGFTVSRNYMSWVRQAPGKGLEWVSLIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNTLRSEDTAVYYCARDLVVYGMDVWGQGTTVTVSS |
1070 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDPIRNGMDVWGQGTTVTVSS |
1071 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSRNYMSWVRQAPGKGLEWVSVIYSGGTTHYADSVKGRFTISRHNSKNTLYLQMNSLRAEDTAVYYCARDLVVYGMDVWGQGTTVTVSS |
1072 | EVQLVESGGGLIQPGGSLRLSCAASGLTVSSNYMTWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRHNSKNTLYLQMNSLRAEDTAVYYCARDAMSYGMDVWGQGTTVTVSS |
1073 | EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRVVYGMDVWGQGTTVTVSS |
1074 | EVQLVESGGGLIQPGGSLRLSCAASGLIVSSNYMSWVRQAPGKGLEWVSVLYAGGSTDYAGSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDAAVYGIDVWGQGTTVTVSS |
1075 | EVQLVESGGGLVQPGGSLRLSCAASGITVRSNYMSWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLISRGMDVWGQGTTVTVSS |
1076 | EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMNWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRVVYGMDVWGQGTTVTVSS |
1077 | EVQLVESGGGLVQPGGSLRLSCAASGVTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTNYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLVSYGMDVWGQGTTVTVSS |
1078 | EVQLVESGGGLIQPGGSLRLSCAASGLTVSSNYMNWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNMVYLQMNSLRAEDTAVYYCARDLVVYGMDVWGQGTTVIVSS |
1079 | EVQLVESGGGLVQPGGSLRLSCAASGFIVSSNYMTWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRHNSKNTLFLQMNSLRAEDTAVYYCARDAQNYGMDVWGQGTTVTVSS |
1080 | EVQLVESGGGLVQPGGSLRLSCAASEFIVSRNYMSWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTGVYYCARDRGLVSDYWGQGTLVTVSS |
1081 | DIEMTQSPSSLSASVGDRVTITCRASQSIASYAYWYQQKPGKAPKLLISAASILQSGVPSRFSGSGSGGHFTLTINSLQPEDVATYYCQQTYIIPYSFGQGTKLEIK |
1082 | AIRMTQSPSSFSASTGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISCLQSEDFATYYCQQYYSYPYTFGQGTKLEIK |
1083 | QSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNLVFGGGTKLTVL |
1084 | GIQMTQSPSTLSASVGDRVTITCRASQSISDWLAWYQQKPGKIPKLLIYKASTLESGVPSRFSGSGSGTEFTLTISSLQPDDFGTYYCQRYDSYRTFGQGTKVEIK |
1085 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKSPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK |
1086 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKVLIYDASNLKTGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIK |
1087 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASHRASGIPDRFSGSGSGTDFTLTISRLEPGDFAMYYCQQYATSPWTFGQGTTVEIK |
1088 | QSVLAQPPSASGTPGQSVTISCSGNNSNIGINNVYWYQQFPGTAPKLLIHRSNQRPSGVPDRFSGSRSGTSASLVISGLRSEDEAEYHCAAWDDSLSSWGFGGGTKLTVL |
1089 | QLVLTQSPSASASLGASVKLTCTLSSGHSSYAIAWHQQQPEKGPRYLMKLSSDGSHRKGDGIPDRFSGSSSGAERYLTISSLQSEDEADYYCQTWGTGTVVFGGGTKLTVL |
1090 | SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWYQQKPGQAPVLVIYKDSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYCQSADSSGTWVFGGGTKLTVL |
1091 | EIVLTQSPATLSLSPGERATLSCRASQSISSYLAWYQQKPGQAPRLLIYEAANRATGIADRFSGSGSGTDFTLTISSLEPEDFAIYYCQQRSDWTPTFGQGTKVEIK |
1092 | AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPRTFGGGTKVEIK |
1093 | QSALTQPASVSGSPGQSITISCTATSSDFGTFHLVSWYQQHPGKAPQLMIYEVNKRPSGVSDRFSASKSGNTASLTISGLQPEDEADYYCCSYAGNTTFFGGGTKLTVL |
1094 | QAVLTQPPSVSAAPGQRVSISCSGSAFNIGTNFVSWYQHLPGAAPKLLIYGDQWRISGTPDRFSGSKSGTSATLAITGLQSGDEAHYYCSTWDASLKEVLFGGGTRLDVL |
1095 | DVVMTQSPLSLPVTLGQPASISCRSSQSLVYYDGNTYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWPLTFGPGTKVDIK |
1096 | DIQMTQSPSTLSASVGDSVTITCRPSQSISRWLAWYQQKPGKAPKLLIYKASTLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYDSYPWTFGQGTKVEIK |
1097 | DIQLTQSPSFLPASVGDRVTITCRASQHISNYVAWYQQKPGKAPKLLIYAASTLESGVPSRFGGSGSGTEFTLTINSLQPEDFATYYCQQLTTYPRTFGQGTKLEIK |
1098 | SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWYQQKPGQAPVLVIYKDSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYCQSADSSGTWVFGGGTKLTVL |
1099 | DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYFCQQFYSTPVTFGPGTKVDIK |
1100 | NFMLTQPHSLSESPGKTVTISCTGSGASIASNYVQWYQQRPGSAPVTVIFEDTQRPSGVPDRFSGSIDRSSNSASLTISGLRTEDEADYYCQSYDGSNVVFGGGTKLTVL |
1101 | DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPLTFGGGTKVEIK |
1102 | DIVMIQSPDSLAVSLGERATINCKSSHSVFFSKVNKDYLAWYQQKPGLPPKLLIYWASTRQTGVPDRFSGSGSGTDFSLTISNLQAEDVAVYYCQQYYDTPMYTFGQGTKLEIK |
1103 | DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYPYTFGQGTKLEIK |
1104 | QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTFVFGTGTKVTVL |
1105 | SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWYQQKPGQAPVLVIYKDSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYCQSADSSGTYSNWVFGGGTKLTVL |
1106 | QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTVVFGGGTKLTVL |
1107 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGGGTKVEIK |
1108 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGGGTKVEIK |
1109 | DFQMTQSPSSLSASVGDRVTISCQASEDIDNHLNWYQQKPGKAPRLLIYDASNLETGVPSRFSGSGSGTDFLFTITSLQPEDFATYYCQQYGAFGQGTKVEIK |
1110 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIK |
1111 | QSVLTQPPSASGTPGQRVTISCSGSRSNIGSKNVHWYQQLPGTAPKFLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAVWDDSLNGVVFGGGTKLTVL |
1112 | QSALTQPPSASGSPGQSVTISCTGTSSDVGSYHYVSWYQQHPGKAPKLIIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQTDDEADYYCSSFAGSNNPYVFGTGTKVTVL |
1113 | DIVMTQSPDSLAVSLGERATINCRSSQSVLYSANNKYYLAWYQHKPGQPPKLLIHWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAIYYCQQYYSTPYTFGQGTKLEIK |
1114 | EIVMTQSPATLSVSPGERATLSCRASQSVKSYLAWYQQKAGQAPRLLIYGASSRATGIPARFSGSRSGTEFTLTISSLQSEDFAVYFCHQYDSWPPTFGGGTKVEIK |
1115 | DVVLTQSPATLSLSPGERATLSCRASKDINSYLAWYQQKPGQAPRLLIYDASKRATGVPVRFSGSGSGTDFTLTISSLEPEDSAIYFCQNRDDWPPLFTFGPGTKVDFK |
1116 | DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPRTFGQGTKLEIK |
1117 | DMQMTQSPSSVSASVGDRVTITCRASQDISSSLAWYQQKPGKPPKLLIYAASSLQRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAHSFLSLTFGGGTKVEIK |
1118 | SCELTQPPSVSVSPGQTARITCSGDALSNQYTYWYQQRPGQAPLLVIYKGTKRPSAIPERFSGSRSGTTVTLTISGVQAEDEADYYCQSADTSGTYLWVFGGGTKLTVL |
1119 | DIQMTQSPSSLSASVGDRVTITCQASQDISNFLNWYQQKPGKAPELLIYDASNLETGVPSRISGSGSGTDFTFTISSLQPEDIATYYCQQYDSLPITFGQGTRLEIK |
1120 | DIQMTQSPSSLSAVLGDRVTITCRASQAISNSLAWYQQKPGKAPKLLLYAASRLESGVPSRFSGSGSGTDYTLTISSLRPEDFATYYCQQYYGIPTFGQGTRLENK |
1121 | DVQMTQSPSSLSASVGDRVTITCQASRDIHNLLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTITGLQPEDVATYYCQKCDNFPWTFGQGTKVEIK |
1122 | QSVLTQSPSASGTPGQRVTISCSGSNSNIGSNYVFWYHQLPGTTPKLLIYKNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSVVVFGGGTKLTVL |
1123 | DIHMTQSPSSLSASEGDRVTISCRASQGISTNYLNWYQQKSGKAPRLLIYATSTLQSGVSSRFSGSGSGTDFTLTINSVQPEDFATYYCQQSYSSPPTFGGGTKLDIK |
1124 | QSVLTQPPSVSGAPGQRVTISCTGIGARYNVHWYQQVPGTAPKLLIYRNTNRPSGVPDRFSGSKSDTSASLAITGLQAEDEADYYCQSYDDTLTIFGGGTKLTVL |
1125 | DIQMTQSPSSLSASVGDRVTITCRASQSISNHFNWYQHRPQKAPKLLIYSASNLQSGVPSRFSGSGSGRNFTLTISSLQPEDFATYYCQQSYGAPPTFGGGTKVEIK |
1126 | DIQMTQSPSSLSASEGDRVTITCRANQSISTNYLNWYQQQSGKAPKLLIYASSTLQSGVPTRFSGSGSGTDFALTINSLQPEDFAAYYCQQSYSTPPTFGGGTRVDLR |
1127 | DIQMTQSPSSLSASEGDRVTILCRASQSISTNYLNWYQQKSGKAPKLLIYSTSNLQSGVPSRFSGSGSGTDFTLTIDSLQGEDFATYYCQQSFSTPPTFGGGTKVDIK |
1128 | DIQMTQSPSSLSASEGDRVTITCRANQSISTNYLNWYQQKSGKAPNLLIYATSSLERGVPSRFSGSGSGTEFSLTINSLQPEDFVTYYCQQSYSSPPTFGGGTKVEIKRMEIK |
1129 | SYELTQPPSVSVSPGQTARITCSGDALPKKYAYWYQQKSGQAPVLVIYEDSKRPSGIPERFSGSSSGTMATLTISGAQVEDEADYYCYSTDSSGNHWVFGGGTKLTVL |
1130 | QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGHYPYWFQQKPGQGPRTLIYDINNKYSWTPARFSGSLLGGKAALTLFGAQPEDEADYYCLLSYSGVRIFGGGTKLTVL |
1131 | QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSKVFGGGTKLTVL |
1132 | SYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTFYVFGTGTKVTVL |
1133 | QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVL |
1134 | EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPWTFGQGTKVEIK |
1135 | QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGHYPYWFQQKPGQAPRTLIYDTSNKHSWTPARFSGSLLGGKAALTLSGAQPEDEAEYYCLLSYSGARPVFGGGTKLTVL |
1136 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPYTFGQGTKLEIK |
1137 | QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTRVVFGGGTKLTVL |
1138 | DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPITFGQGTRLEIK |
1139 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGGGTKVEIK |
1140 | QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSVVVFGGGTKLTVL |
1141 | QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTFAVFGGGTQLTVL |
1142 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVEIK |
1143 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTVFTFGPGTKVDIK |
1144 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTVFTFGPGTKVDIK |
1145 | DIEMTQSPSSLSASVGDRVTITCRASQSIASYAYWYQQKPGKAPKLLISAASILQSGVPSRFSGSGSGGHFTLTINSLQPEDVATYYCQQTYIIPYSFGQGTKLEIK |
1146 | AIRMTQSPSSFSASTGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISCLQSEDFATYYCQQYYSYPYTFGQGTKLEIK |
1147 | SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHVVFGGGTKLTVL |
1148 | SYELTQPPSVSVSPGQTASITCSRDKLGDEYACWYQQKPGQSPILVIYQNNKRPAGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTSYVVFGGGTKLTVL |
1149 | QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRLSGIPDRFSGSKSGTSATLDITGLQTGDEADYYCGTWDSSLSVGVFGGGTKLTVL |
1150 | QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCNSYTSNSTAVFGGGTKLTVL |
1151 | EVVLTQSPATLSASPGERATLSCRASLSINTDLAWYQQRPGQPPRLLIYGASTRATGIPARFSGSGSGTEFTLTVSSLQSEDFALYYCQQSYNWPRTFGQGTRVEIK |
1152 | DIQMTQSPSAMSASVGDRVTITCRASQGMSNYLAWFQQKPGKVPKRLIYAASSLASGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNSYPYTFGQGTKLEIK |
1153 | DIQMTQSPSTLSAPVGDRVTITCRASQSINSWLAWYQQKPGKAPKLLIYKASNLESGVSSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNGYPHTFGQGTKLEIK |
1154 | DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASNLESGVPSRFSGSGSGTDFTLTISSLQPDDFATYYCQQYSYYSAFGQGTQVEFK |
1155 | EIVLTQSPGTLSLSPGERASLSCRASQTVSSTYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTITRLEPEDFAVYYCQQYGTFGQGTKLEIK |
1156 | QAGLTQPPSVSKGLRQTATLTCTGTSSNVGNQGAAWLQQHQGHPPKLLSYRNDNRPSGISERLSASRSGNTASLTITGLQPEDEADYYCSAWDSSLSAWVFGGGTKLTVL |
1157 | DIVMTQSPDSLAVSLGERATINCKSSQSVLYNSNNKDYLAWYQQKPGQPPKLLFSWASTRQSGVPARFSGGGSGTDFTLTISSLQAEDVAVYYCQQYYSTPITFGGGTKVEIK |
1158 | DFVLTQPHSVSESPGKTVTISCTRSSGSIASYFVHWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLIISGLKTEDEADYYCQSFDDNDQVFGGGTKLTVL |
1159 | QTVVTQEPSFSVSPGGTVTLTCGLTSGSVSTTYYPSWYQQTPGQPPRTLIYSTNIRSSGVPDRFSGSILGNKAALTITGAQADDESNYYCLLYVGGGIWVFGGGTKLTVL |
1160 | EIVMTQSPATLAVSPGERATLSCRASQSVSDNLAWYQQRPGQPPRLLIYAASTRATGIPPRFSGSGSGTEFTLTIASLQSEDFALYYCQQYNIWLTFGGGTKVEIK |
1161 | AVVMTQSPLSLPVTLGQPASISCRSSQSLVHSDGNTYLNWFQQRPGQSPRRLIYKVSDRDSGVPDRFSGSGSGTDFTLKINRVEAEDVGVYYCMQGTLLLTFGGGTKVEIK |
1162 | QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGVPDRFSGSKSGTSATLGITGLQTGDEADYYCETWDSSLDAVIFGGGTKLTVL |
1163 | QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKVLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGRVFGGGTKLTVL |
1164 | DVVVTQSPLSLSVTLGQPASISCRSSQSLVHSDGNTYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGSGSGTDFTLKISRVEADDVGVYYCMQGTHWPHPTFGQGTRVEIK |
1165 | AVVVTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGSGSGTDFTLQISKVEAEDVGVYYCMQGTPWPTFGQGTKVEIK |
1166 | EIVLTQSPGTLSLSPGERATLSCRASQSVRSNYLAWYQLKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQSGSSYTFGQGTKLEIK |
1167 | AIVMTQSPLSLPVTPGEPASISCRSSQSLRQSQRFSYLDWYVQKPGQSPQLLIYLNSRRAPGVPDRFSASGSGTDFTLKISRVEAEDVGVYYCMQSLPSGFTFGPGTNVHIK |
1168 | DIVMTQAPLSLSVTPGQPASISCKSSQSLLHSIGKTHLYWYLQKPGQPPQLLIYEVSNRFSGVPERVSGSGSGTDFTLTISRVEAEDVGVYYCMQSLDLPPTFGQGTKVDIK |
1169 | DIQMTQSPSFVSASVGDRVTITCRASHDIRTWLSWYQQKPGKAPKLLIYTAFRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYFCQQGSSFPLTFGGGTTVDIR |
1170 | DIQMTQSPSSLSASVGDSVTVTCRASQDIGNWLAWYQLKPEKAPRSLIFAASILRSGVPSRFSGSGSGTEFTLTISSLQPEDFGVFYCQQYDSSPITFGQGTRLEIK |
1171 | SSQLTQDPAVSVALGQTVRITCQGDSLETYYATWYQQKPGQAPLLVIYGKNSRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGQLHVVVFGGGTKLTVL |
1172 | SSELTQDPAVSVALGQTVRITCQGDSLRTSYASWYQQKPGQAPMLVIYEKNNRPSGVPDRFSGSTSFNTASLTITGAQAEDEAEYYCNSRDNNDDLPLFGGGTRLTVL |
1173 | QSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNLGVFGTGTKVTVL |
1174 | QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGVVFGGGTKLTVL |
1175 | DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPFTFGPGTKVDIK |
1176 | DVVMTQSPLSLPVTLGQPASISCRSSQSLVHSDGNTYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWPITFGQGTRLEIK |
1177 | QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTLVVFGGGTKLTVL |
1178 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK |
1179 | QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSYVVFGGGTKLTVL |
1180 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTLHTFGQGTKVEIK |
1181 | SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNHLVFGGGTKLTVL |
1182 | SYELTQPPSVSVSPGQTATITCSGDELGDTDIAWYQQKPGQSPVLVILQDTKRPSGIPERFSGSNSGTTATLTIGGTQAMDEAEYYCQAWDTITHEEVFGGGTKLTVL |
1183 | DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNYYPVAFGQGTKVEIK |
1184 | DIVMTQTPLSSPVTLGQPASISCRSSQSLVHSDGNTYLSWLQQRPGQPPRLLIYKISNRFSGVPDRFSGSGAGTDFTLKISRVEAEDVGVYYCTQATQFPLTFGGGTKVEIK |
1185 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDLATYYCQQSYSTPPYTFGQGTKLEIK |
1186 | QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGIAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSSPVVFGGGTKLTVL |
1187 | QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGPVFGGGTKLTVL |
1188 | SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNHLVFGGGTKLTVL |
1189 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPYTFGQGTKLEIK |
1190 | QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAGVFGGGTKLTVL |
1191 | EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPPWTFGQGTKVEIK |
1192 | SYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTYVVFGGGTKLTVL |
1193 | DIQMTQSPSSLSASEGDRVTITCRASQSISTNYLNWYQQKSGRAPTLLIYATSTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPPTFGGGTTVDVK |
1194 | DIQMTQSPSSVYASEGDRVTITCRASHSISTNYLNWYQQNSGKAPKLLIYATSSLQSGVPFRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPPTFGGGTKVEIK |
1195 | DIQMTQSPSSLSASEGDRVTISCRASQTISTNYLNWYQQKSGKAPRLLIYATSTLESGVPSRFSGSGSGTDFTLTINTLQPDDFATYYCQQSYSSPPTFGGGTKVDIK |
1196 | EIVLTQSPATLSLSPGERAALSCRASQTINSGYLAWYQQKPGQAPRLLIYAASHRATGIPNRFSGSGSATDFTLTITRLEPEDVAVYYCHHYGTSPPFTFGPGTKVDIK |
1197 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGGGTKVEIK |
1198 | SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWYQQKPGQAPVLVIYKDSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYCQSADSSGTYYVFGTGTKVTVL |
1199 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPRTFGQGTKVEIK |
1200 | SYELTQPPSVSVSPGQTASISCSGDKLGDTYASWYQQKPGQSPVLVMYQDNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVL |
1201 | DIVMTQTPLSLSVTPGQPASISCKSSQSLLHSDGKTYLYWYLQKPGQSPQLLIYEVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQSIQLPLTFGGGTKVEIK |
1202 | DIVMTQTPLSLSVTPGQPASISCKSSQSLLHSDGKTYLYWYLQKPGQSPQLLIYEVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQSIQLPFTFGQGTRLEIK |
1203 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTYTFGQGTKLEIK |
1204 | SYELTQPPSVSVSPGQTARITCSGDALPKKYAYWYQQKSGQAPVLVIYEDSKRPSGIPERFSGSSSGTMATLTISGAQVEDEADYYCYSTDSSGNHRRVFGGGTKLTVL |
1205 | QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSKWPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTLVFGGGTKLTVL |
1206 | SYELTQPPSVSVSPGQTARITCSGDALPKKYAYWYQQKSGQAPVLVIYEDSKRPSGIPERFSGSSSGTMATLTISGAQVEDEADYYCYSTDSSGNHRGVFGGGTKLTVL |
1207 | DIQMTQSPDTLSASVGDRVTITCRASESISNWLAWYQKKVGQAPNLLIDKASNLHRGVPSRFSGSGSGTEFTLTITSLQPDDSASYYCQQYNSFPYTFGQGTTLEIK |
1208 | EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPVTFGQGTKVEIK |
1209 | DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASSLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNSYPLTFGGGTKVEIK |
1210 | DIQMTQSPSSLSASVGDRVTITCRASQGIGNDLGWFQQKPGKAPKRLIYGASNLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNSYPFTFGGGTKVEIK |
1211 | ETVLTQSPGTLSLSPGERATLSCRASQSVSGSYLAWYQQKPGQAPRLLIYGASRRATGIADRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGTSAGTFGQGTKVEIK |
1212 | EIVLTQSPGTLSLSPGERGTLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASTRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGNLPPFTFGPGTKVDIK |
1213 | DIVVTQSPDSLAVSLGERATINCKSSQSLLYNFNNENYLGWYQQKPGQPPKLLIYWASTRESGVPDRFNGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPLTFGGGTKVEIK |
1214 | GIVMTQSPLSLSVTPGQPASISCKSSQSLLDSDGKTYMCWYLQKPGQPPQLLIYEVSNRFSGVPERFSGSGSGTDFTLKISRVETEDVGVYYCMQNRHLYTFGQGTKLEIK |
1215 | GIVMTQSPLSLSVTPGQPASISCKSSQSLLDSDGKTYMCWYLQKPGQPPQLLIYEVSNRFSGVPERFSGSGSGTDFTLKISRVEAEDVGVYYCMQNRHLYTFGQGTKLEIK |
1216 | NIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQTLQTSITFGQGTRLEIK |
1217 | EIVLTQSPGTLSLSPGERATLSCRASQSVSTYLAWYQQRPGQAPRLLIYGSSSRAAGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSQYSFGQGTKLEIK |
1218 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSYLAWYQQRPGQAPRLLIYGASSRAAGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSQYTFGQGTKLEIK |
1219 | DIQMTQSPSSLSASVGDRVTITCQASQDSSKYLNWYQQKPGKAPKLLIYDASTLETGVPSRFSGSGSGTDFTFTISGLQPEDVATYYCQHYDTLLTFGPGTKVEIK |
1220 | DIVMTQSPDSLAVSLGERATINCKSSQSVSFTSNNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVALYLCQQYFDTPWTFGQGTKVEIK |
1221 | GIVMTQSPLSLSVTPGQPASISCKSSQSLLDSDGKTYLCWYLQKPGQPPQLLIYEVSNRFSGVPERFSGSGSGTDFTLKISRVEAEDVGVYYCMQNRQLYTFGQGTKLEIK |
1222 | DIQMTQSPSSLSASVGDRVTITCQASQDISTYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQFDNLPPFTFGPGTRVHIT |
1223 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGRAPKVLIYGASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSARMSTFGQGTKLEIK |
1224 | DVVMTQSPLSLPVTLGQPASISCRSSQSVVHSDGKTYLNWYHQRPGQSPRRLIYEVSNRDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGTQWPWTFGQGTKVEIK |
1225 | EIVLTQSPGTLSLSPGERATLSCRASHTISSSYLAWYQQKAGQAPRLLIYAASSRATGIPARFSGSGSGTDFTLTISRLEPEDFAVYYCQQFDNSPPWTFGRGTKVEMR |
1226 | SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWYQQKPGQAPVLVIYKDSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYCQSADSSGTYVVFGGGTKLTVL |
1227 | QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSYTLVFGGGTKLTVL |
1228 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASGLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIK |
1229 | DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGTHSYTFGQGTKLEIK |
1230 | SYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTASYVFGTGTKVTVL |
1231 | QSALTQPASVSGSPGQAITISCTGTSSDVGGHDYVSWYQQHPGKVPKLVVYDVTNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSASTVVFGGGTKLTVL |
1232 | QSALTQPASVSGSPGQAITISCTGTSSDVGGHDYVSWYQQHPGKVPKLVVYDVTNRPSGISNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSASTVVFGGGTKLTVL |
1233 | DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGTHSPWTFGQGTKVEIK |
1234 | QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYHCGTWDSSLSAWVFGGGTKLTVL |
1235 | SYELTQPPSVSVSPGQTASITCSGDALPKQYGYWYQQKPGQAPVMVIYKDNERPSGIPERFSGSSSGTTVTLTISGAQAEDEADYYCQSADGRGDWVFGGGTKLTVL |
1236 | EIVLTQSPGTLSLSPGERATLSCRASQSVSTYLAWYQQRPGQAPRLLIYGSSSRAAGIPDRFSGSGSGTDFTLTISRLEPEDFAVYFCQQYGSSQYSFGQGTKLDIK |
1237 | DIQMTQSPSTLSASIGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYETSSLEPGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYDSYSGTFGQGTKVEIK |
1238 | QPVLTQSSSASASLGSSVKLTCTLSVGHDYFTIAWHQQQPGKAPRFLMKLEGSGSYYKGSGVPDRFSGSSSGADRYLIISNLQSEDEADYFCETWDSPYVVFGGGTKLTVL |
1239 | DIQMTQYPSSLSASVGDTVTITCQASQDSNTYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISGLQPEDIATYYCQHYDSLLTFGPGTKVDIK |
1240 | QSALTQPASVSGSPGQSITISCNGTNSDVGGYNYVSWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDDADYYCSSYTSSSTVVFGGGTKLTVL |
1241 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTLTFGPGTKVDIK |
1242 | DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYPLFTFGPGTKVDIK |
1243 | DVVLTQSPLSLPVTLGQPASISCRSSQSLIYSDGNTYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGSGSGTDFTLRISRVEAEDVGVYYCMQGTHWPMTFGQGTKVEIK |
1244 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPMYTFGQGTKLEIK |
1245 | DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPAFGGGTKVEIK |
1246 | SYEVTQSPSVSVSPGQTASITCSGDKLGDKYACWYQQRPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSHTVVFGGGTKLTVL |
1247 | DIQMTQSPSTLSASVGDRVTITCRASQSISTWLAWYQQRPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSWTFGQGTKVEIK |
1248 | ETMMTQSPVALSVSPGDRATLSCEASQYVGDNLAWYQQKPGQAPRLLIYGAFTRATGVPARFSASGSGAGFTLTISSLQSEDFAVYYCQQYTSWPLTFGGGTKVEIK |
1249 | ETMMTQSPVALSVSPGDRATLSCKASQYIGDNLAWYQQKPGQTPRLLIYGASTRATGVPARFSASGSGAGFTLTISSLQSEDFAVYYCQQYTSWPLTFGGGTKVEIK |
1250 | SYELTQPPSVSVSPGQTARITCSGDALPKKYAYWYQQKSGQAPVLVIYEDSKRPSGIPERFSGSSSGTMATLTISGAQVEDEADYYCYSPKVFGGGTKLTVL |
1251 | DIQMTQSPSSLSASVGDRVTVACQASQDVSIYLNWYQQKPGRAPKLLIYDAYNLQTGVPSRFSGSGSGTHFTLTISSLQPEDVATYHCQQYNILPHTFGGGTKVELT |
1252 | DIVMTQSPDSLAVSLGERATIKCKSSQSVYDSSNSKNYLAWFQQKPGQPPQLLIFWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYNAPLSFGGGTKVEIK |
1253 | DIVMTQSPDSLPVSLGERATIKCKSSQSVYDTSNSKNYLAWFQQKPGQPPQLLIFWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYNAPLSFGGGTKVEIK |
1254 | EIVLTQSPATLSLSPGERATLSCRASQSVSTYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWITFGQGTRLEIK |
1255 | EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWITFGQGTRLEIK |
1256 | QSVLTQPPSASGTPGQGVTISCSGGSSNIGAYTVSWYQQLPGTAPKLLIYSTDQRPSGVPDRFSGSKSGTSASLAVTGLQSEDEADYYCAAWDDSLNGPVFGGGTKLTVL |
1257 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSIYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPQTFGQGTKLEIK |
1258 | EIVMTQSPATLSVSPGERATLSCRASQSVTSYLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPPLTFGGGTKVEIK |
1259 | DIQMTQSPSTLSASVGDRVTITCRASQSITNWLAWYQQRPGKAPKLLLSKASSLESGVPSRFSGSGSGTDFTLTISSLQPDDFATYYCQQYYSYSLTFGGGTKVESK |
1260 | QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLVSWYQQHPGKAPKLMIYEVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSSTFYVFGTGTKVTVL |
1261 | SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWYQQKTGQAPVLVIYKDSERPSGIPERVSGSSSGTTVTLTISGVQAEDEADYYCQSADSSGTWVFGGGTKLTVL |
1262 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSRYLAWYQQKPGQAPRLLIYGASRRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPEMYTFGQGTKLEIK |
1263 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCHQYGSGLGTFGPGTKVDIK |
1264 | DIVMTQTPLSLSVTPGQPASISCKSSQSLLDSDGKTYLYWYLQKPGQTPQLLIYEVSDRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQSIQLRTFGQGTKVEIK |
1265 | EIVLTQSPATLSLSPGERATLSCRASQRVGSSLAWYQQKPGQAPRLLIYGASNRATGIPARFSGSGSGTDFTLTITRLEPEDFAVYYCQQCSSWPLSLTFGGGTKVEIR |
1266 | EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPPITFGQGTRLDIK |
1267 | DIQMTQSPSSVSASVGDRVTITCRASQGIRFWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSNSFPPTFGGGTKVEIK |
1268 | QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNTNRPSGVPDRFSGSKSGTSPSLAITGLQAEDEAGYYCQSYDISLSAYVFGGGTKLTVL |
1269 | DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTEFTLTISSLLPADFATYYCQQYNTYSLTFGQGTRLEIK |
1270 | AIQLTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLNSYPPAFGGGTKVEIK |
1271 | EIVMTQSPDSLAVSLGERATINCKSSQSVLYSASNKNYLAWYQQKQGQSPKLLIYWASTRESGVPDRFSGSGSGTDFTLTINGLQAEDVAVYYCQQYYRTPLTFGGGTKVEIK |
1272 | DIQMTQSPSAMSASVGDRVTITCRASQDISNYLAWFQQRPGKVPKRLIYAASSLQSGVPSRFSGTGSGTEFTLTISSLQPEDFATYYCLQHHTYPLTFGGGTKVEIR |
1273 | EIVLTQTPLSLSVTPGQPASISCKSSHSLLHSDGKTYVYWYLQRPGQPPQLLIYELFNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGTYYCMQSIQLWSFGQGTKVEIK |
1274 | QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGHYPYWFQQKPGQAPRTLIYDTNNKHSWTPARFSGSLLGGKAALTLSGAQPEDEAEYYCLLSYSGPWVFGGGTKLTVL |
1275 | QSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNYVFGTGTKVTVL |
1276 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPSFTFGPGTKVDIK |
1277 | QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVNKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSYTLVFGGGTKLSVL |
1278 | QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLVSWYQQHPGKAPKLMIYEVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSSTVVFGGGTKLTVL |
1279 | DIQMTQSPSSLSASVGDRVTISCRASQSIGKYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTINNLQPEDFATYYCQQSYNVPPWTFGQGTKVEIK |
1280 | DVVMTQSPVSLTVTLGQPASISCRPSQSIEHSDGNIYLNWFQQRPGQSPRRLIYKISNRDSGVPDRISGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWPWTFGQGTKVEIK |
1281 | QSVLTQPPSVSGAPGQRVIIPCTGSSSNTGAGYDVHWYQQLPGTAPKLVIYDNSHRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDINLSAVFGGGTKLTVL |
1282 | EIVLTQSPGTLSLSPGERATLSCRATQSLTSSSLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLKPEDFAVYYCHQYHNSPWTFGQGTKVEIK |
1283 | DFVMTQSPLSLPVTPGEPASISCRSSQSLLHGNGYTYLDWYLQKPGQSPQLLIYLGSTRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPYTFGQGTKLEIK |
1284 | SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHYVFGTGTKVTVL |
1285 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKVEIK |
1286 | QIVMTQSPATLSVSPGGGATLSCRASQSVSSKVAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDSAVYYCQQYDNWLPYTFGQGTKLEIK |
1287 | QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGHYPYWFQQKPGQAPRTLIYDTSNKHSWTPARFSGSLLGGKAALTLSGAQPEDEAEYYCLLSYSGAYVLFGGGTKLTVL |
1288 | EIVMTQSPAILSVSPGERATLSCRASQSVTRNLAWYQQKPGQAPRLLIYGASTRATNIPARFSGSGFGTEFTLIISSLQSEDFAVYYCQQYSNWPLYTFGQGTKLEIK |
1289 | QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGPYVFGTGTKVTVL |
1290 | QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQHHPGKAPKLMIYEVSNRPSGVSNRFSGSKSANTASLTISGLQTEDEADYYCSSYTSISTVLFGGGTKLTVL |
1291 | SDALTQPPSVSVAPGKTAAITCGGDNIGSKNVHWYQQKPGQAPLLVVFDDGDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDGGSDDRGYVFGTGTKVTVL |
1292 | QSALTQPASVSGSPGQSITISCTGTSSDVGAYNYVSWYQQHPGKAPKLMIYDVTKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSFTSNGAWVFGGGTKVTVL |
1293 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKFLIYAASTLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQNYIRPYTFGQGTKLEIK |
1294 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPITFGGGTKVEIK |
1295 | QSVLTQPPSTSGAPGQRVTISCSGSSSNVALNAVSWYQQLPRMAPKLLIYRDNQRPSGVPERFSGSRSGTSASLAITGLQSDDEADYYCATWDDSLNGVFGGGTKLTVL |
1296 | EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQSEDFGVYYCQQYNNWPYTFGQGTKLEIK |
1297 | QPVLTQPPSASASLGASVTLTCTLSSGYSNYKVDWYQQRPGKGPRFVMRVGTGGIVGSKGDGIPDRFSVLGSGLNRYLTIKNIQEEDESDYHCGADHGSGSNFVYVFGTGTKVTVL |
1298 | QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLVSWYQQHPGKAPKLMIYEVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSSTLVFGGGTKVTVL |
1299 | DIKMTQSPSTLSASVGDRVTITCRASQHINRWLAWYQQKPGKAPKLLIYEASSLKSGVPSRFSGSGSGTEFTLTITSLQLDDFATYSCQQHDSAPYTFGQGTKLEIK |
1300 | DIQMTQSPSTLSASLGDRVMITCRASQNISRWLAWYQQKPGKAPKFLIYKASALETGVPSRFSGSGSGTEFTLTITGLQPDDFATYYCQQYNSYVTFGGGTKVEMK |
1301 | DIVMTQTPLSLSVTPGQPASISCKSSQSLLHSDGKTYLYWFLLKPGQSPQFLIYEVSSRFSGVPDRFRGSGSGTDFTLKISRVEAEDVGVYYCMQGKHLRWTFGQGTKVEIK |
1302 | SYELAQPPSVSVSPGQTARITCSGDALPIKYAYWYQQKSGQAPVLVISEDSKRPSGIPERFSGSSSGTMATLTISGAQVEDEADYYCYSTDYSGNHGVFGGGTKLTVV |
1303 | EIVLTQSPATLSLSPGERATLSCRASQSVSTYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQCSNWPNTFGQGTKLEIK |
1304 | SYELTQPPSVSVSPGQTARITCSGDELPKQYSYWFQQRPGQAPVLVIYKDRERPSGIPERFSGSHSGTTVTLTISGVQAEDEADYYCQSADSNDSWVFGGGTKLTVL |
1305 | QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAGVFGGGTKLTVL |
1306 | GIQLTQSPSSVSASLGDTVTITCRASQNINVFLAWYQQRPGSAPSLLIYAASNLQSGVPSRFVGSGSGTDFTLTISGLQPEDFATYYCQQGHNFPWTFGRGTKVEVK |
1307 | EIVLTQSPGTLSLSPGDRATLSCRASQSLNNNQLAWYQQKLGQAPRLLIYGASSRATGIPDKISGSGSGTVFTLTISRLEPEDFAVYYCQQYGSLPLTFGGGTKVEIK |
1308 | EIVLTQSPGTLSLSPGDRATLSCRASQSLNNNQLAWYQQKLGQAPRLLIYGASSRATGIPDKISGSGSGTVFTLTISRLEPEDFAVYYCQQYGSLPLTFGGGTKVEIK |
1309 | QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGGTKLTVL |
1310 | EIVLTQSPATLSLSPGERATLSCRASQSISSHLGWYQQKPGQAPRLLIYDASNRAPGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFGGGTKVEIK |
1311 | EIVLTQSPATLSLSPGEGATLSCRASQSVASYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQHRSNWPYTFGQGTKLEIK |
1312 | QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGVVFGGGTKLTVL |
1313 | DIVMTQTPLSSPVILGQSASISCRSSHSLLHNNGNTYLSWLHQRPGQPPRLLIYEISNRFSGVPDRFSGSGAGTDFTLKISRVEAEDVGIYYCMQTTQFPRTFGQGTKVEIR |
1314 | SYELTQPPSVSVSPGQTAKITCSGDALPKEFAYWYQQKPGQAPVLIIYKDKERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYCQSQDSSATYVVFGGGTKLTVL |
1315 | SSDLTQPPSVSVSPGQTASIACSGDKLGDKYVSWYQQKPRQSPVLVIYQDNKRPSGIPERFAGSNSGNTATLTISGTQTMDEADYYCQAWDSSIEVFGTGTKVTVL |
1316 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPPWTFGQGTKVEIK |
1317 | SYELTQPPSVSVSPGQTARITCSADALSKQYAYWYQQKPGQAPVLVIYKDSERPSGIPERFSGSNSGTTVTLTISGVQAEDEAEYYCQSGDSSGTYVVFGGGTKLTVL |
1318 | DIVMTQTPLSSPVILGQSASISCRSSQSLLHNNGNTYLSWLHQRPGQPPRLLIYEISNRFSGVPDRFSGSGAGTDFTLKISRVEAEDVGIYYCMQTTQFPRTFGQGTKVEIR |
1319 | DIQMTQSPSAMSASVGDRVTITCRASQGIRNSLAWFQQKPGKVPKRLIYDASNLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQYNTYSYSFGQGTKLEIK |
1320 | DIQMTQSPSILSASVGDRVTITCRASQNISRWLAWYQQKPGKAPKFLIYKASGLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYITFGGGTKIEIK |
1321 | DIQMTQSPSTLSASVGDRVIITCRASQNISRWLAWYQQKPGTAPKFLIYKASALESGVPSRFSGSGSGTEFTLTITSLQPDDFATYYCQQYNSYVTFGGGTKVEMK |
1322 | SYELTQPPSVSVSPGQTARITCSGDALPQRYAYWYQQKSGQAPVLVIYEDTKRPSGIPERFSGFSLGTLATLTISGAQVEDEADYYCYSTDSSDNQRVFGGGTKLTVL |
1323 | AIQLTQSPSSLSASVGDRVTITCRASQGVASYLAWYQQKPGKAPNLLIYAASTLQGGVPSRFSGSGSGTDFTLTISNLQPEDFATYYCQHLKSYPLTFGGGTKVEIK |
1324 | DIQMTQSPPSVSASIGDTVTITCRATQNINVFLAWYQQKPGSAPTLLIYGASSLQSGVPSRFVGSGSGTDFTLTISGLQPEDFATYYCQQGHNFPWTFGRGTKVEVK |
1325 | DIQMTQSPSSVSASIGDTVTITCRATQNINVFLAWYQQKPGSAPTLLIYGASSLQSGVPSRFVGSGSGTDFTLTISGLQPEDFATYYCQQGHNFPWTFGRGTKVEVK |
1326 | EIVMTQSPATLSVSPGERATLSCRASQSLNSNLAWYQQKPGQAPRLVIYGASTRAAGFPARFSGSGSETEFTLTISSLQSEDFAIYFCQQYHNFPLTFGQGTEVEVR |
1327 | QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQLLPGTAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAIIGLQAEDEATYYCQSYDSSLSVVFGGGTKVTVL |
1328 | SYELTQPPSVSVSPGQTAIITCSGDKLGEKYASWYQQRPGQSPMLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAVDEADYFCQAWDSNTGVFGTGTKVTVL |
1329 | QSVLTQPPSLSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGDSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGSVFGGGTKLTVL |
1330 | SYELTQPPSVSVSPGQTARISCSADALPKQNAYWYQCKPGQAPILLIYKDTERPSGIPERFSGSSSGTTVTLTISGVQPEDDADYYCQSVDNTGASPHVVFGGGTKLTVL |
1331 | DIQMTQSPSTLSASVGDSVTITCRANETIASWVAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSESGTEFTLTISSLQPDDFATYYCQQYHTYWTFGQGTKVEVK |
1332 | SYELTQPPSVSVSPGQTASIACSGDKLGDKYTCWYQQKPGQSPVLVMYQDSKRPSGIPERFSGSNSGNTATLTISGTQVMDEADYYCQAWDSGTVVFGGGTKLTVL |
1333 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKVEIK |
1334 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKVEIK |
1335 | DIVLTQSPGTLSLSPGERATLSCRASQSISSSYLAWYQQKPGQAPRLVIHGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGTSPYTFGQGTKLEIK |
1336 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSTLVTFGQGTKVEIK |
1337 | QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLVSWYQQHPGKAPKLMIYEVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSSLWVFGGGTKLTVL |
1338 | NFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSFWVFGGGTKLTVL |
1339 | QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVL |
1340 | SYELTQPPSVSVSPGQTARITCSGDALPEKYAYWFQQKSGQAPVLVIYEDNKRPSGIPERFSGSSSGTMATLTISGAQVEDEADYYCYSTDRSGNHRGVFGTGTKVTVL |
1341 | SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNHLYWVFGGGTKLTVL |
1342 | QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGHVVFGGGTKLTVL |
1343 | QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAGGVFGTGTKVTVL |
1344 | QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLVSWYQQHPGKAPKLMIYEGSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSSTFVVFGGGTKLTVL |
1345 | QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQFPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVL |
1346 | AIQLTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLNSYPPTFGQGTKVEIK |
1347 | DIQMTQSPSSLSASVGDRVTITCRASQSIRFYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTLWTFGQGTKVEIK |
1348 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSTYLAWYQQKPGQAPRLLIYDASSRATGIPDRFSGGGSGTDFTLTISRLEPEDFAVYYCQQYGDSPETFGQGTKVEIK |
1349 | SYELTQPPSVSVSPGQTASITCSGDKLGDNYASWYQQKSGQSPVLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVL |
1350 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPYTFGQGTKLEIK |
1351 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPYTFGQGTKLEIK |
1352 | EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPSITFGQGTRLEIK |
1353 | DIQMTQSPSSVSASVGDRVTITCRASQGISNWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLAFGGGTKVEIK |
1354 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFGFGPGTKVDIK |
1355 | QSVLTQPPSVSGAPGQRVTISCTGSRSNIGAGFDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEAVYYCLSYDSSLSGSVFGGGTKLTVL |
1356 | AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKVLIYDASSLESGVPPRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNNYPLTFGGGTKVEIK |
1357 | DIQMTQSPSSLSASVGDRVTITCQASQDMSNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPFTFGPGTKVDIK |
1358 | QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSAYVFGTGTKVTVL |
1359 | SSELTQDPAVSVALGQTVRITCQGDSLRSYSASWYQQKPGQAPVLVIYVKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNHVVFGGGTRLTVL |
1360 | QSALTQPRSVSGSPGQSVTISCTGTSSDVGDYDYVSWYQHHPGKAPKLMIYDVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDDADYYCCSYAGSYPVVFGGGTKLTVL |
1361 | QSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNKVFGGGTKLTVL |
1362 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSGGYTFGQGTKLEIK |
1363 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK |
1364 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSSWTFGQGTKVEIK |
1365 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK |
1366 | SYELTQPPSVSVSPGQTASITCSGDKLGNKYACWYQQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTANWVFGGGTKLTVL |
1367 | QSALTQPASVSGSPGQSITISCTATSGDVGGYNYVSWYQQHPGKAPKLMIFDVYNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSFTDSSTLVVFGGGTKLTVL |
1368 | DIQMTQSPSSLSASVRDKVTITCRASQSISSCLNWYQQKPGKAPKVLIYAASSLQSGVPSRFSGSGSGTDFTLTISSVQPEDFATYYCQQSYSVPHTFGQGTKVEIK |
1369 | EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWLTFGGGTKVEIK |
1370 | EIVMTQSPATLSVSPGERVTLSCRASQSINRNLAWYQQKPGQAPRLLVYDASTRAPGIPTRVSGSGSGTDFTLTISSLQSEDFAVYYCQQYNNWPPITFGQGTRLEIQ |
1371 | EIVMTQSPATLSVSPGERVTLSCRASQSVNRNLAWYQQKPGQAPRLLVYDASTRAPGIPTRVRGSGSGTDFTLTISSLQSEDFAVYYCQQYNNWPPITFGQGTRLEIQ |
1372 | QTALTQPPSASGSPGQSVTISCTGSSGDVGGYNYVSWYQQYPGKAPKLILSEVSQRPSGVPDRFFGSKSGNTASLTVFGLQAEDEADYYCSSYAGTNKILFGGGTKLTVL |
1373 | DIQMTQSPSSLSASVGDRVTITCRASQSISSFLNWFQQKPGKAPKLLIYAASSLQGGVPSRFSGSGSGTDFTLTINSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK |
1374 | QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTWVFGGGTKLTVL |
1375 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK |
1376 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPGTFGQGTRLEIK |
1377 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPGTFGQGTRLEIK |
1378 | DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSAFGQGTKLEIK |
1379 | PYDLTQPPSVSVSPGQTATITCSGDKLGKKYACWYQQKPGQSPVLLIYQDVKRPSGIPERFSGSNSGTTATLTISETQTMDEADYYCQAWDRTTATFGGGTRLTVL |
1380 | QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGGTKLTVL |
1381 | QSALTQPASVSGSPGQSITISCTGTTFDVGVYDFVSWYQQLPGKAPKLIIHDDTHRPSGVSDRFSGSRSGTTASLTISGLQADDEADYYCSSYTSLNTLEVVFGGGTKLTVL |
1382 | DIVMTQSPLSLPVTPGEPASMSCKSTQSLLHSNGNYYVTWYLQKPGQSPHLLIYLASNRASGVPDRFSGSGSGTDFTLKISSVEAEDVGVYYCMQALQTPYSFGQGTKLEIK |
1383 | SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDRTVVFGGGTKLTVL |
1384 | QSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVYWYQHLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSENEADYYCASWDDKVRGWVFGGGTKLTVL |
1385 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIK |
1386 | DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSRTFGQGTKVEIK |
1387 | DIQMTQSPSTLSASVGDRVTITCRASQSISDWLAWYQQKPGKAPKLLIYKASTLEGGVPSRFSGSESGTEFTLTISSLQPDDFATYYCQQYNTSPLTFGGGTKVEIK |
1388 | QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGSLFGGGTKLTVL |
1389 | SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWYQQKPGQAPVLVIYKDSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYCQSADSSGTYRVFGGGTKLTVL |
1390 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGRTFGQGTKVEIK |
1391 | QSALTQPASVAGSPGQTITISCTGPNSDINSYDYVSWYQQRPGKAPKLIIHDVDHRPSGVSDRFSGFMSDNTASLTISGLQAEDEAHYYCSSYTNIDTLEIVFGAGTKLTVL |
1392 | DIQMTQSPSAMSASVGDRVTITCRASQGISNYLAWFQQKPGKVPKRLIYAASSLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNSYPRTFGQGTKVEIK |
1393 | SYELTQPPSVSVAPGKAASITCGGINIGSKSVHWYQQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTATLTISRVESGDEADYYCQVWHSSFDPWVFGGGTKLTVL |
1394 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPTTFGPGTKVDIK |
1395 | DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYFPTFGQGTKVEIK |
1396 | SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDDNDRPSGIPDRFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHYWVFGGGTKLTVL |
1397 | QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAGVFGGGTKLTVL |
1398 | QLVVTQSPSASASLGASVKLTCTLSSGHSSYVIAWHQQQPEKGPRFLMKLNSDGSHNKGDGIPDRFSGSSSGAERYLTISNLQSEDEADYYCQTWGTGPQVLFGGGTKLTVL |
1399 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGRAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLLTFGGGTKVEIK |
1400 | SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSGDHWVFGGGTKLTVL |
1401 | EIVLTQSPATLSLSPGERATLSCRASQSVSNYLAWYQQKPGQVPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWLTFGGGTKVEIK |
1402 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLISDASLLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQHDNLPSFTFGPGTKVDIK |
1403 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKVEIK |
1404 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQTPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKVEIK |
1405 | QTVVTQEPSLTVSPGGTVTLTCASSTGAVTSGYYPNWFQQKPGQAPRALIYSTSNKHSWTPARFSGSLLGGKAALTLSGVQPEDEAEYYCLLYYGGAPVFGGGTKLTVL |
1406 | DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPPAFGQGTKVEIK |
1407 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPQTFGPGTKVDIK |
1408 | QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLVSWYQQHPGKAPKLMIYEVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSSLWVFGGGTKLTVL |
1409 | NFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNQVFGGGTKLTVL |
1410 | EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWLFTFGPGTKVDIK |
1411 | QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAGVFGGGTKLTVL |
1412 | VIVLTQTPLSSPVTLGQPASISCRSRRSLVHTNGNTYLSWLHQRPGQTPRLLIHNVSNRFSGVPDRFSGSGAGTDFTLNISRVEADDVGIYYCMQASQFPLTFGGGTKLEIK |
1413 | QSALTQPASVSGSPGQSITISCTGTFSDIGNYDLVSWYQQHPGKAPKVIIYEGYKRPSGVSDRFSGSKSGNTASLTISGLQAEDEADYFCCSFAGSNREFGGGTKLTVL |
1414 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIK |
1415 | QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAWVFGGGTKLTVL |
1416 | EIVLTQSPGTLSLSPGERATLSCRASQSVSNYLAWYQHKPGQAPRLLIYGASNGATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYSSSAPITFGQGTRLEIK |
1417 | EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIFDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRNKWPGTFGQGTKVEIK |
1418 | ETVLTQSPGTLSLSPGERATLSCRASQSVNSNYLAWYQQKPGQAPRLLIYGASSRATGIPDNFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGDSPYTFGQGTNLEIK |
1419 | AIQLTQSPSSLSASVGDRVTITCRASQGISSSLAWYQQKPGKAPKLLIYSASTLQSGVPSRFSGSGSGTDFTLTITSLQPEDFATYYCQQLNSYPLTFGGGTKVEIK |
1420 | QSALTQPASVSGSPGQSITISCTGTSSDVGTYNLVSWYQQHPGKAPKLMIYEVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCCTYAGSSTWVFGGGTKLTVL |
1421 | DIQMTQSPSSLSASVGDRVTITCRASQSIAKFLNWYQKKPGKAPNLLISTASSFQSGVPSRFSGSGSGTDYTLTISGLQPEDFATYYCQQSYSSPYTFGQGTNLEIK |
1422 | DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYAASSLQSGIPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPRTFGQGTKVEIK |
1423 | AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKVLIYDASGLQSGVPSRFSGGGSGTDFTLTISSLQPEDFATYYCQQFNDYPLTFGGGTKVEIK |
1424 | QSVLTQPPSVSGAPGQRVTISCTGSNSNIGAGYDVHWYQQLPGTAPKLLIYVNTNRPSGVPDRFSGSKSGTSASLAITGLQAEDEAHYYCQSYDSSLSGSVFGGGTKLTVL |
1425 | DIQMTQSPSTLSASVGDRVTITCRASQIISSWLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYSTYYTFGQGTKLEIK |
1426 | DVVLTQSPLSLPVTLGQPASISCRSSHSLVYSDGYTHLHWIQERPGQSPRRLIYSVSHRDSGVPDRFSGSGSATDFTLQISRVEAEDVGVYYCMQGSHWPWTFGQGTKVEIK |
1427 | QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGPWVFGGGTKLTVL |
1428 | QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQYPGKAPKLMIYEVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSYTWVFGTGTKVTVL |
1429 | DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQVGVPSRFSGSGSGTEFTLTISSLQPEDFATYFCQQLNSYPFTFGPGTKVDIK |
1430 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPRTFGQGTKVEIK |
1431 | DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSSFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPLTFGGGTKVEIK |
1432 | DIQMTQSPSSLSASVGDRVTITCRASQSISNFLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTGFTLTISSLQPEDFATYYCQQSYSTPPDTFGQGTRLEIK |
1433 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPPTFGGGTKVEIK |
1434 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTTPLFTFGPGTKVDIK |
1435 | DIQLTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLNGYPHSAFGPGTKVDIK |
1436 | DIQMTQSPSSLSASVGDRVTITCQASQDIINYLNWYQQKPGKAPKLLIYGASNLETGVPSRFSGGGSGTDFTFTISSLQPEDIATYYCHQYDNLPPTFGQGTRLEIK |
1437 | DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPLTFGGGTKVEIK |
1438 | DIQLTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQQLNSNPPITFGPGTKVDIK |
1439 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIFAASSLQTGAPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPYTFGQGTKLEIK |
1440 | DIQMTQSPSSLSASVGDRVTITCQASQDINKYLNWYQQKPGKAPKLLIFDASHLETGVPSRFSASGSGTDFTFTISSLQPEDIATYYCHQYDNLPRTFGQGTRLEIK |
1441 | GGSFSDYY |
1442 | GGSFSDYF |
1443 | GITVSSNY |
1444 | GYTFTSYA |
1445 | ITHSGST |
1446 | INHSGST |
1447 | IYSGGST |
1448 | INTNTGNP |
1449 | QSVSTY |
1450 | QSVSSY |
1451 | QGISSY |
1452 | QSISSW |
1453 | DAS |
1454 | DAS |
1455 | AAS |
1456 | KAS |
1457 | ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK |
1458 | RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC |
1459 | RVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNF |
1460 | MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT |
1461 | GFTFSSYG |
1462 | GFTFSSYG |
1463 | GYSFTSYW |
1464 | GYSFTSYW |
1465 | GYSFTSYW |
1466 | GYSFTSYW |
1467 | GYSFTSYW |
1468 | GGSINRNHF |
1469 | GGSINRNHF |
1470 | GYTFTSYG |
1471 | GFTFSYFE |
1472 | GFTFSYFE |
1473 | GYKFSNYY |
1474 | GYIFTNFY |
1475 | GFNFSSYA |
1476 | GIIVSRNE |
1477 | GGTFSTYA |
1478 | GFTFSSYG |
1479 | GFTFNNYA |
1480 | GFVFSNYW |
1481 | GGSISSGGYY |
1482 | GYNFNNYW |
1483 | GYTFTSYA |
1484 | GYTLTELS |
1485 | GFTFSSYG |
1486 | GFTFSSYP |
1487 | GGSISSGGYY |
1488 | GGSISSGGYY |
1489 | GFTVSSNY |
1490 | GGSISSYY |
1491 | GYTFTGYF |
1492 | GFTASSNY |
1493 | GGTFSSYG |
1494 | GGRFGSFA |
1495 | GFTFTDYA |
1496 | GGSISSYY |
1497 | GYTFTDYY |
1498 | GYSFTGHY |
1499 | GFTFSNYG |
1500 | GGSISSDVYS |
1501 | GDTFNSYA |
1502 | GFTFSHYG |
1503 | GYSFPAHW |
1504 | GYNFDTYW |
1505 | GYSFSGYW |
1506 | GYYFAAHW |
1507 | GYSFPAFW |
1508 | GYSFPAYW |
1509 | GYTLTELS |
1510 | GYTFTRYW |
1511 | GFTFSSYS |
1512 | GFTFSSYS |
1513 | GGSISSSSYY |
1514 | GFSLSTSGVG |
1515 | GFTFSNAW |
1516 | GFTFSSYE |
1517 | GFTFSSYE |
1518 | GGSISSSSYY |
1519 | GGSISSGGYY |
1520 | GGSISSRSYY |
1521 | GFSLSNARMG |
1522 | GFSLSTSGVG |
1523 | GFTISPYG |
1524 | GFTISPYG |
1525 | GYTFGDYG |
1526 | GYTFGDYG |
1527 | GFSLSTSGVG |
1528 | GGSISTYR |
1529 | GFTFSNAW |
1530 | GYIFTNYA |
1531 | GYAFTSYQ |
1532 | GFTFGDYA |
1533 | GASFSSYY |
1534 | GYSFTKYW |
1535 | GFTFSSYA |
1536 | GDSVSSNTVA |
1537 | GFTFDDYG |
1538 | GFAFDDFA |
1539 | GFTVSSTF |
1540 | GGSIKRRGYY |
1541 | GGSFSAYY |
1542 | GGSISSSDYY |
1543 | GFTFSNAW |
1544 | GGTFSTYA |
1545 | GLRFTDAW |
1546 | GFSFSSYA |
1547 | GFSFSDFA |
1548 | GFTFTTYG |
1549 | GFTFRSYS |
1550 | GDSITSYY |
1551 | GGSFSGSY |
1552 | GGSFTDHY |
1553 | GGSISSSSYY |
1554 | GFSLSNARMG |
1555 | GFTFSSYG |
1556 | GFTFGDYA |
1557 | GFTFSGSA |
1558 | GYSFTSYW |
1559 | GYTFTSYY |
1560 | GGTFSSYA |
1561 | GFTFSNAW |
1562 | GFTFRSYW |
1563 | GFTFSTYA |
1564 | GFTFSSYG |
1565 | GFTVSSNY |
1566 | GGPISSGGYY |
1567 | GGSISSSYYY |
1568 | GGSISSSSYY |
1569 | GFTFSSYS |
1570 | GYTFTSYG |
1571 | GFTFSSYW |
1572 | GGSISSGGYS |
1573 | GYSFPAHW |
1574 | GYSFPAFY |
1575 | GYSFPAHW |
1576 | GFTFSASA |
1577 | GGSISSGGYY |
1578 | GFTFSSYW |
1579 | GYTFTSYG |
1580 | GFSLSTSGVS |
1581 | GFTFSSYG |
1582 | GFTFSSYA |
1583 | GFTFSSYE |
1584 | GFTFSIYA |
1585 | GFTFTSYG |
1586 | GFTFSSYG |
1587 | GFAFNKYG |
1588 | GFTFSSYG |
1589 | GGSISSSSYY |
1590 | GGAITTSSYF |
1591 | GFTFSAYG |
1592 | GFTFNNYG |
1593 | GGSINSYY |
1594 | GFTFSRFG |
1595 | GFTFSRFG |
1596 | GFTFSSFW |
1597 | GGTFSSYT |
1598 | GGSFSSYT |
1599 | EFSLDSRGVG |
1600 | GGSISSYY |
1601 | GFTFSRYG |
1602 | GFPFSGYA |
1603 | GFTFINYD |
1604 | GFAFDKFW |
1605 | GGSINRDGHY |
1606 | GGSISSYY |
1607 | GGSVSSGSYF |
1608 | GYTFTSYG |
1609 | GYTFTGYY |
1610 | GYTLTELS |
1611 | GYRFTSYG |
1612 | GYRFTSYG |
1613 | GYTFTSYA |
1614 | GYTFTSYY |
1615 | GYTFTNYY |
1616 | GGTFSSYT |
1617 | GGTFNSYA |
1618 | GYTFTSSD |
1619 | EFSLDARGVG |
1620 | GFTFISYA |
1621 | GFTFSSYA |
1622 | GFTFSSYG |
1623 | GFTFSSHG |
1624 | GFTFSSYA |
1625 | GFTFSSYA |
1626 | GFTFSTYG |
1627 | GFTFSTFA |
1628 | GFIFGDYA |
1629 | GFIFGDYA |
1630 | GFTFSSYW |
1631 | GASISSGDYY |
1632 | GGVLSDYY |
1633 | GGVLSDYY |
1634 | GGSFSDYY |
1635 | GGSFSDYF |
1636 | GDSISSNNW |
1637 | GGSISSYY |
1638 | GDSISSYY |
1639 | GGSISGYY |
1640 | GGSISSGSYY |
1641 | DDSISSGSYY |
1642 | GYSFTSYW |
1643 | GYSFTSYW |
1644 | GYTFTSYA |
1645 | GYTFSFYW |
1646 | GGAFSSGRHY |
1647 | GGSFSSYY |
1648 | GYTLTELS |
1649 | GFTFSDYY |
1650 | GITVSSNY |
1651 | GFTFSRFW |
1652 | GFTFSNYW |
1653 | AFSFHLHG |
1654 | GFTFSSYA |
1655 | GFIFDDYG |
1656 | GFTVSSNY |
1657 | GGSIGSSSYF |
1658 | GGSISSSSYY |
1659 | GFTFSSYD |
1660 | GFTFSRSA |
1661 | GFTFSSQS |
1662 | GFTFEEYS |
1663 | GYTFGRYW |
1664 | GYTFSTYY |
1665 | GGTFSSYA |
1666 | GATFTTYA |
1667 | GFTLSSYA |
1668 | GFTFSNYD |
1669 | GFTFDDYA |
1670 | GFTFDDYA |
1671 | GFTFDDYA |
1672 | GFTFSSYT |
1673 | TFIFSNSE |
1674 | GFTVSSNY |
1675 | GGSFSGYF |
1676 | GGSFSGYY |
1677 | GGSLSSYY |
1678 | GGSISTFY |
1679 | GGSVSSYF |
1680 | GFSFNTPGVG |
1681 | GFSFSNHG |
1682 | GFTFSNSA |
1683 | EFTFSSYE |
1684 | GYTFTNFA |
1685 | GYTFTSYG |
1686 | GFSFSRYG |
1687 | GFNFNSYT |
1688 | GFNFNSYT |
1689 | GFTFSSYE |
1690 | GYIFTSYG |
1691 | GYSFNDYG |
1692 | GYTLTELS |
1693 | GNTFSTYY |
1694 | GFTFSDVW |
1695 | GLTFDNAW |
1696 | RFTFSSYA |
1697 | GFTFDDYA |
1698 | GNTFTTYY |
1699 | GGTFNSYT |
1700 | GFSLNTPGAG |
1701 | GFSFNTPGVG |
1702 | GFTFTFSDYY |
1703 | GFTFSDYY |
1704 | GFSFSRYG |
1705 | GLSFSRYG |
1706 | GFSFNNFG |
1707 | GFTLSSYA |
1708 | GFTFSSYE |
1709 | GFTFSSYA |
1710 | GGSISPYS |
1711 | GDSIRSSSFY |
1712 | GYSFTTYA |
1713 | GGTFSSYA |
1714 | GGTFSSYA |
1715 | GFTFSHAW |
1716 | GFTFSSYE |
1717 | GFTVSSNY |
1718 | GGSISSYY |
1719 | GYTFTTYG |
1720 | GYTFTNYG |
1721 | GYTLTELS |
1722 | GYTLTELS |
1723 | GYTLTELS |
1724 | GYTLTELS |
1725 | GYTFTSYA |
1726 | GGTFSSYA |
1727 | GFSLSNARMG |
1728 | GFSLSTTGVG |
1729 | GFSLSTSGVG |
1730 | GFTFSSYS |
1731 | GFTFSSYS |
1732 | GFTFSSYA |
1733 | GFTFSSYA |
1734 | GFTFSSYA |
1735 | GFTFGSYG |
1736 | GFTFSSYA |
1737 | GFTFSIYA |
1738 | GFTVSSNY |
1739 | GFTFSNYW |
1740 | GGSFSGYY |
1741 | DGSFSGHY |
1742 | GGSFSGYY |
1743 | GGSISSYY |
1744 | GGSISSYY |
1745 | GYNFTSYW |
1746 | GYTFTSYA |
1747 | GFTVSSNY |
1748 | GGSISSGLYH |
1749 | GGTFSSYT |
1750 | GFTFGRHG |
1751 | GFTFGRYG |
1752 | GFSLTTRGEG |
1753 | GYTFTFYT |
1754 | GFTFTSSA |
1755 | GFSLSTSGMC |
1756 | GFTFTTYA |
1757 | GFAFTTYA |
1758 | GYTFTSYG |
1759 | GYTFSRYG |
1760 | GYTFTGYY |
1761 | GSGFTFRNAW |
1762 | GFTFNFYG |
1763 | GFTFDDYA |
1764 | GFIFDDYT |
1765 | GYTFTSYG |
1766 | GYTFTSYG |
1767 | GDTFNDYH |
1768 | GGTFSSYA |
1769 | GGTFSSYA |
1770 | GFTFSNAW |
1771 | GLTFTKAW |
1772 | GFTFSTYA |
1773 | GFTFSNYA |
1774 | GFTFSSYA |
1775 | GFTFSSYG |
1776 | GFTFSSYG |
1777 | GFTFSSFA |
1778 | GFTFSNYG |
1779 | GFTFSSYG |
1780 | GFTFSSYA |
1781 | GFTFHDYA |
1782 | GVIVSRNY |
1783 | GFTVSSNY |
1784 | EFTVSSNY |
1785 | GFTVSSNY |
1786 | GFTVSSNY |
1787 | GITVSSNY |
1788 | GFTVSSNY |
1789 | GFTFSSYW |
1790 | GGSISSGGYY |
1791 | GGSISSGGYY |
1792 | GGSFSGYY |
1793 | GGSFSDDF |
1794 | GGSISSYY |
1795 | GYSFTSYW |
1796 | GDTFSNYP |
1797 | GFTFSTSA |
1798 | GFTFSTYA |
1799 | GFTFFSYA |
1800 | GFTVSSNY |
1801 | AGSISSDTYY |
1802 | GYTFTSYG |
1803 | GYTFTNYY |
1804 | GGTFSSYT |
1805 | GFSLSTSGVG |
1806 | GFTVSSYD |
1807 | GFTFRNYG |
1808 | GFTFSSYG |
1809 | GFTVSRNY |
1810 | GFTVSSNY |
1811 | GFTVSRNY |
1812 | GLTVSSNY |
1813 | GFTVSSNY |
1814 | GLIVSSNY |
1815 | GITVRSNY |
1816 | GFTVSSNY |
1817 | GVTVSSNY |
1818 | GLTVSSNY |
1819 | GFIVSSNY |
1820 | EFIVSRNY |
1821 | IWYDGSNK |
1822 | IWYDGSNK |
1823 | IDPSDSYT |
1824 | IDPSDSYT |
1825 | IDPSDSYT |
1826 | IDPSDSYT |
1827 | IDPSDSYT |
1828 | ASYTGTT |
1829 | ASYTGTT |
1830 | ISAYNGNT |
1831 | ISSSGTNI |
1832 | ISSSGTNI |
1833 | INPYSGET |
1834 | VNPNDGSS |
1835 | ISATGGTT |
1836 | ISSSGTGV |
1837 | IIPIFGTP |
1838 | ISYDGSNK |
1839 | ISSYGDNT |
1840 | IKQDESEE |
1841 | IYYSGST |
1842 | IYGGDSDT |
1843 | INTNTGNP |
1844 | FDPEDGET |
1845 | ISYDGSNK |
1846 | ISYDGSNK |
1847 | IYYSGST |
1848 | IYYSGST |
1849 | LYSGGNE |
1850 | IYYSGST |
1851 | INPSSGVA |
1852 | IYAGGGT |
1853 | ILPVLDTT |
1854 | VTPIVGVP |
1855 | ISYDGNDK |
1856 | IYYSGST |
1857 | VNPNRGGT |
1858 | INPDSGGT |
1859 | ITGSGGST |
1860 | VFHTGSA |
1861 | IIPILRLA |
1862 | IWYDGSKK |
1863 | IFPGDSDT |
1864 | IYPGDSDS |
1865 | IFPSDSDT |
1866 | IFPSDSDT |
1867 | VFPGDSDT |
1868 | IFPGDSDT |
1869 | FDPEDGET |
1870 | MKPGDGKT |
1871 | ISSSSSYI |
1872 | ISSSSSTI |
1873 | IYYSGST |
1874 | IYWDDDK |
1875 | IKSKTDGGTT |
1876 | ISSSGSTI |
1877 | ISSSGSTI |
1878 | IYYSGST |
1879 | IYYSGST |
1880 | IYYSGST |
1881 | IFSNDEK |
1882 | IYWDDDK |
1883 | IWYDGSNK |
1884 | IWYDGSNK |
1885 | ISGYNGDP |
1886 | ISGYNGDP |
1887 | IYWDDDK |
1888 | IYYSGRT |
1889 | IKRIIDGGTI |
1890 | TNTNTGNP |
1891 | INPSGSAT |
1892 | ITWNSGNI |
1893 | ISQSAST |
1894 | IYPDDSET |
1895 | ISGSGDKT |
1896 | TYYRSNWYN |
1897 | ISWNSNSV |
1898 | INWNSDNI |
1899 | IYTVGDT |
1900 | IYYSGTT |
1901 | INRRGNT |
1902 | IYYSGNT |
1903 | IKSKTDGGTT |
1904 | IIPSLRTA |
1905 | IKSRGSGGTI |
1906 | ISYDGRNK |
1907 | VSYDSRQQ |
1908 | IWYDGSNE |
1909 | LSNDDRTR |
1910 | IYSSGDT |
1911 | INPSGGS |
1912 | INHSGRT |
1913 | IYYSGST |
1914 | IFSNDEK |
1915 | ISYDGSNK |
1916 | IRSKAYGGTT |
1917 | IRSKANSYAT |
1918 | IDPSDSYT |
1919 | INPSGGST |
1920 | IIPIFHIA |
1921 | IKSKTDGGTT |
1922 | IFSDWSTT |
1923 | ISGSGGST |
1924 | ISYDGSNK |
1925 | IYSGSST |
1926 | IYYSGST |
1927 | IYYSGST |
1928 | IYYSGST |
1929 | ISSSSSYI |
1930 | ISAYNGNT |
1931 | INSDGSST |
1932 | IYHSGST |
1933 | IFPSDSDT |
1934 | IFPGDSET |
1935 | IFPGDSDT |
1936 | IRTRTNRYAT |
1937 | IYYSGST |
1938 | INSDGSST |
1939 | ISAYNGNT |
1940 | IYWDDDK |
1941 | ISYDGSNK |
1942 | ISYDGSNK |
1943 | ISSSGSTI |
1944 | ISGSGGST |
1945 | ISFDGSNI |
1946 | ISYDGSNK |
1947 | IWNDGNKQ |
1948 | IWYDGSNK |
1949 | IFYSGST |
1950 | ISYSGDT |
1951 | ISFDGSNK |
1952 | ISYEGSIR |
1953 | IYSGGST |
1954 | ISYEGSTE |
1955 | ISYEGSTE |
1956 | IKEDGSEK |
1957 | IIPMLNKT |
1958 | IIPMLNKT |
1959 | IYWNDNK |
1960 | IYYRGST |
1961 | ISYEGSTE |
1962 | ISSSSSTV |
1963 | ISSSSSTT |
1964 | LNKDESEK |
1965 | IYSGRNT |
1966 | IYYSGST |
1967 | IYYSGST |
1968 | ISAYNGNT |
1969 | INPNSGGT |
1970 | FDPEDGET |
1971 | INTDNEKT |
1972 | INTDNGKT |
1973 | INAGNGNT |
1974 | INPSGGST |
1975 | INPSDGST |
1976 | IIPMLNKT |
1977 | IIPIFGPP |
1978 | MNPNTGTT |
1979 | IYWNDYK |
1980 | ISGSGGST |
1981 | ISGSGGTT |
1982 | ISYDGSNK |
1983 | ISYDGINK |
1984 | ISYDGSNK |
1985 | ISYDGSNK |
1986 | MWFDGVDK |
1987 | ISYDEINK |
1988 | IRGRLVGATV |
1989 | IRGRLVGATV |
1990 | IKQDGSEK |
1991 | IYYSGST |
1992 | IHRSGST |
1993 | IHRSGST |
1994 | ITHSGST |
1995 | INHSGST |
1996 | IYHSGTT |
1997 | IYTSGST |
1998 | IYHSGSA |
1999 | LHYSGRS |
2000 | IYTSGST |
2001 | IYAGEST |
2002 | IYPGDSDT |
2003 | IYPGDSDT |
2004 | INTNTGNP |
2005 | IYPGDFDT |
2006 | IYSGVIT |
2007 | VTHSGST |
2008 | FDPEDGET |
2009 | ISSSGSTI |
2010 | IYSGGST |
2011 | IKEDGSVM |
2012 | IKSDGSET |
2013 | IWFDGSKK |
2014 | ISSSGGGT |
2015 | ITWNSGSI |
2016 | IYSGGST |
2017 | IYYGGST |
2018 | IYYSGST |
2019 | IGTAGDT |
2020 | MSYDGSDI |
2021 | ISYDGNNK |
2022 | VSWNSGTI |
2023 | INPADSDT |
2024 | INPSGDST |
2025 | IIPIFGTA |
2026 | IFPIFTAA |
2027 | VSGSGGST |
2028 | ISSDGNNR |
2029 | ISWNSGSI |
2030 | ISWNSGTI |
2031 | ISWNSEKI |
2032 | INSGSSII |
2033 | ISSSDNSV |
2034 | IYSGGST |
2035 | INHSGKT |
2036 | INHSGST |
2037 | MYNSGST |
2038 | IYYSGRT |
2039 | IFYTGTS |
2040 | IYWDDEK |
2041 | IWYDGDNR |
2042 | IYYDGSNE |
2043 | IDSSSTTI |
2044 | INTKTGIP |
2045 | ISAYNGNT |
2046 | ISHDDSQK |
2047 | ISYEGSKK |
2048 | ISYEGSKK |
2049 | ISSSGSTI |
2050 | INTNTGSP |
2051 | ISAYNGET |
2052 | FDPEDGET |
2053 | ISPSGDDA |
2054 | IRSKSDGGTT |
2055 | VKSKTDGGTT |
2056 | ISYDGSNK |
2057 | ISWDGGST |
2058 | ISPSGDDA |
2059 | IVPMLGIT |
2060 | IYWDDDK |
2061 | IYWDDEK |
2062 | ISSGGDAI |
2063 | MSSDSDYI |
2064 | ISHDESQK |
2065 | ISHDESQK |
2066 | ISYEGSKK |
2067 | ISYDGSNK |
2068 | ITSSGNTI |
2069 | ISSSSGTI |
2070 | IYYTGKT |
2071 | VYNSGTA |
2072 | IDTNTGKP |
2073 | IIPIFGTA |
2074 | IIPIFGTA |
2075 | IKSNTDGGTT |
2076 | ISSSGSTI |
2077 | IYSGGST |
2078 | IYYSGST |
2079 | ISAYNGNT |
2080 | ISTYSGNT |
2081 | FDPEDGET |
2082 | FDPEDGET |
2083 | FDPEDGET |
2084 | FDPEDGET |
2085 | INAGNGNT |
2086 | IIPIFGTA |
2087 | IFSNDKK |
2088 | IYWDDDK |
2089 | IFWDDDK |
2090 | ISSSSSYI |
2091 | ISSSSSYI |
2092 | ISYDGSNK |
2093 | ISYDGSNK |
2094 | ISYDGSNK |
2095 | IWNDGSNK |
2096 | ISYDGSNK |
2097 | ISYDGSNK |
2098 | IYSGGST |
2099 | IKEDGSET |
2100 | IDHSGST |
2101 | INHSGST |
2102 | INHSGST |
2103 | IYYSGST |
2104 | IYYSGST |
2105 | IDPSDSYT |
2106 | INTNTGNP |
2107 | VYSGGHA |
2108 | IFSSGST |
2109 | IIPILGIA |
2110 | ISTYSGNT |
2111 | ISTYSGNT |
2112 | IYWDDDQ |
2113 | INTNTGTP |
2114 | IVVGSGNT |
2115 | IDWDDDK |
2116 | ISDSGGSA |
2117 | ISDGGGSA |
2118 | ISAYNGNT |
2119 | ISGYNGNT |
2120 | INPNSGGT |
2121 | IKSKNDGGTT |
2122 | ISYDGNKR |
2123 | ISWNSGSI |
2124 | ITWNYATV |
2125 | ISAYNGNT |
2126 | ISAYNGNT |
2127 | INPNSGET |
2128 | IIPIFGTA |
2129 | IIPILGIA |
2130 | IKSKTDGGTT |
2131 | IKSRSDGGKI |
2132 | ISGSGGST |
2133 | ISANGRSP |
2134 | ISGSGGST |
2135 | ISYDGSNK |
2136 | ISYDGSNK |
2137 | ISYDGANK |
2138 | MWHDGSNK |
2139 | IWYDGSNK |
2140 | ISYDGSNK |
2141 | ISWNSGSI |
2142 | IYSGGST |
2143 | IYSGGTT |
2144 | IYSGGST |
2145 | IYSGGST |
2146 | LYSGGTT |
2147 | IYSGGST |
2148 | IYSGGST |
2149 | IKSDGSST |
2150 | IYYSGST |
2151 | IYYSGST |
2152 | ISHGGKT |
2153 | INHSGTT |
2154 | IYYSGST |
2155 | IYPGDSDT |
2156 | IIPIVGFA |
2157 | ISYDGSN |
2158 | ISYDGSNK |
2159 | ISGISDSGGNT |
2160 | IYSGGST |
2161 | IYTTGST |
2162 | ISAYNGNT |
2163 | INPSGGST |
2164 | IIPILGIA |
2165 | IYWDDDK |
2166 | ISARGSVT |
2167 | ISYDGSNK |
2168 | ISNYGSNK |
2169 | IYSGGST |
2170 | IYSGGST |
2171 | IYSGGTT |
2172 | IYSGGST |
2173 | IYSGGST |
2174 | LYAGGST |
2175 | IYSGGST |
2176 | IYSGGST |
2177 | IYSGGST |
2178 | IYSGGST |
2179 | IYSGGST |
2180 | IYSGGST |
2181 | QSIASY |
2182 | QGISSY |
2183 | SSDVGGYNY |
2184 | QSISDW |
2185 | QSISSY |
2186 | QDISNY |
2187 | QSVSSSY |
2188 | NSNIGINN |
2189 | SGHSSYA |
2190 | ALPKQY |
2191 | QSISSY |
2192 | QGISSA |
2193 | SSDFGTFHL |
2194 | AFNIGTNF |
2195 | QSLVYYDGNTY |
2196 | QSISRW |
2197 | QHISNY |
2198 | ALPKQY |
2199 | QSVLYSSNNNKNY |
2200 | GASIASNY |
2201 | QSVLYSSNNKNY |
2202 | HSVFFSKVNKDY |
2203 | QSISSW |
2204 | SSDVGGYNY |
2205 | ALPKQY |
2206 | SSDVGGYNY |
2207 | QSVSSSY |
2208 | QSVSSSY |
2209 | EDIDNH |
2210 | QSVSSSY |
2211 | RSNIGSKN |
2212 | SSDVGSYHY |
2213 | QSVLYSANNKYY |
2214 | QSVKSY |
2215 | KDINSY |
2216 | QSVLYSSNNKNY |
2217 | QDISSS |
2218 | ALSNQY |
2219 | QDISNF |
2220 | QAISNS |
2221 | RDIHNL |
2222 | NSNIGSNY |
2223 | QGISTNY |
2224 | GARYN |
2225 | QSISNH |
2226 | QSISTNY |
2227 | QSISTNY |
2228 | QSISTNY |
2229 | ALPKKY |
2230 | TGAVTSGHY |
2231 | SSNIGAGYD |
2232 | KLGDKY |
2233 | SSNIGNNY |
2234 | QSVSSN |
2235 | TGAVTSGHY |
2236 | QSISSY |
2237 | SSDVGGYNY |
2238 | QSVLYSSNNKNY |
2239 | QSVSSSY |
2240 | SSNIGNNY |
2241 | SSDVGGYNY |
2242 | QSLLHSNGYNY |
2243 | QSLLHSNGYNY |
2244 | QSLLHSNGYNY |
2245 | QSIASY |
2246 | QGISSY |
2247 | NIGSKS |
2248 | KLGDEY |
2249 | SSNIGNNY |
2250 | SSDVGGYNY |
2251 | LSINTD |
2252 | QGMSNY |
2253 | QSINSW |
2254 | QSISSW |
2255 | QTVSSTY |
2256 | SSNVGNQG |
2257 | QSVLYNSNNKDY |
2258 | SGSIASYF |
2259 | SGSVSTTYY |
2260 | QSVSDN |
2261 | QSLVHSDGNTY |
2262 | SSNIGNNY |
2263 | SSNIGSNY |
2264 | QSLVHSDGNTY |
2265 | QSLVYSDGNTY |
2266 | QSVRSNY |
2267 | QSLRQSQRFSY |
2268 | QSLLHSIGKTH |
2269 | HDIRTW |
2270 | QDIGNW |
2271 | SLETYY |
2272 | SLRTSY |
2273 | SSDVGGYNY |
2274 | SSNIGAGYD |
2275 | QSVLYSSNNKNY |
2276 | QSLVHSDGNTY |
2277 | SSDVGGYNY |
2278 | QSISSY |
2279 | SSDVGGYNY |
2280 | QSISSY |
2281 | SLRSYY |
2282 | ELGDTD |
2283 | QSISSW |
2284 | QSLVHSDGNTY |
2285 | QSISSY |
2286 | SSNIGAGYD |
2287 | SSNIGSNY |
2288 | SLRSYY |
2289 | QDISNY |
2290 | SSNIGNNY |
2291 | QSVSSN |
2292 | KLGDKY |
2293 | QSISTNY |
2294 | HSISTNY |
2295 | QTISTNY |
2296 | QTINSGY |
2297 | QSVSSSY |
2298 | ALPKQY |
2299 | QSISSY |
2300 | KLGDTY |
2301 | QSLLHSDGKTY |
2302 | QSLLHSDGKTY |
2303 | QSLLHSNGYNY |
2304 | ALPKKY |
2305 | SSDVGGYNY |
2306 | ALPKKY |
2307 | ESISNW |
2308 | QSVSSY |
2309 | QGIRND |
2310 | QGIGND |
2311 | QSVSGSY |
2312 | QSVSSSY |
2313 | QSLLYNFNNENY |
2314 | QSLLDSDGKTY |
2315 | QSLLDSDGKTY |
2316 | QSLLHSNGYNY |
2317 | QSVSTY |
2318 | QSVSSY |
2319 | QDSSKY |
2320 | QSVSFTSNNKNY |
2321 | QSLLDSDGKTY |
2322 | QDISTY |
2323 | QSISNY |
2324 | QSVVHSDGKTY |
2325 | HTISSSY |
2326 | ALPKQY |
2327 | SSDVGGYNY |
2328 | QSISNY |
2329 | QSLVYSDGNTY |
2330 | KLGDKY |
2331 | SSDVGGHDY |
2332 | SSDVGGHDY |
2333 | QSLVYSDGNTY |
2334 | SSNIGNNY |
2335 | ALPKQY |
2336 | QSVSTY |
2337 | QSISSW |
2338 | VGHDYFT |
2339 | QDSNTY |
2340 | NSDVGGYNY |
2341 | QSLLHSNGYNY |
2342 | QSISSW |
2343 | QSLIYSDGNTY |
2344 | QSVSSSY |
2345 | QGISSW |
2346 | KLGDKY |
2347 | QSISTW |
2348 | QYVGDN |
2349 | QYIGDN |
2350 | ALPKKY |
2351 | QDVSIY |
2352 | QSVYDSSNSKNY |
2353 | QSVYDTSNSKNY |
2354 | QSVSTY |
2355 | QSVSSY |
2356 | SSNIGAYT |
2357 | QSVSSIY |
2358 | QSVTSY |
2359 | QSITNW |
2360 | SSDVGSYNL |
2361 | ALPKQY |
2362 | QSVSSRY |
2363 | QSVSSSY |
2364 | QSLLDSDGKTY |
2365 | QRVGSS |
2366 | QSVSSN |
2367 | QGIRFW |
2368 | SSNIGAGYD |
2369 | QSISSW |
2370 | QGISSY |
2371 | QSVLYSASNKNY |
2372 | QDISNY |
2373 | HSLLHSDGKTY |
2374 | TGAVTSGHY |
2375 | SSDVGGYNY |
2376 | QDISNY |
2377 | SSDVGGYNY |
2378 | SSDVGSYNL |
2379 | QSIGKY |
2380 | QSIEHSDGNIY |
2381 | SSNTGAGYD |
2382 | QSLTSSS |
2383 | QSLLHGNGYTY |
2384 | NIGSKS |
2385 | QSVSSSY |
2386 | QSVSSK |
2387 | TGAVTSGHY |
2388 | QSVTRN |
2389 | SSNIGSNT |
2390 | SSDVGGYNY |
2391 | NIGSKN |
2392 | SSDVGAYNY |
2393 | QSISNY |
2394 | QDISNY |
2395 | SSNVALNA |
2396 | QSVSSN |
2397 | SGYSNYK |
2398 | SSDVGSYNL |
2399 | QHINRW |
2400 | QNISRW |
2401 | QSLLHSDGKTY |
2402 | ALPIKY |
2403 | QSVSTY |
2404 | ELPKQY |
2405 | SSNIGNNY |
2406 | QNINVF |
2407 | QSLNNNQ |
2408 | QSLNNNQ |
2409 | SSNIGAGYD |
2410 | QSISSH |
2411 | QSVASY |
2412 | SSNIGSNT |
2413 | HSLLHNNGNTY |
2414 | ALPKEF |
2415 | KLGDKY |
2416 | QSVSSSY |
2417 | ALSKQY |
2418 | QSLLHNNGNTY |
2419 | QGIRNS |
2420 | QNISRW |
2421 | QNISRW |
2422 | ALPQRY |
2423 | QGVASY |
2424 | QNINVF |
2425 | QNINVF |
2426 | QSLNSN |
2427 | SSNIGAGYD |
2428 | KLGEKY |
2429 | SSNIGAGYD |
2430 | ALPKQN |
2431 | ETIASW |
2432 | KLGDKY |
2433 | QSVSSSY |
2434 | QSVSSSY |
2435 | QSISSSY |
2436 | QSVSSSY |
2437 | SSDVGSYNL |
2438 | SGSIASNY |
2439 | SSNIGNNY |
2440 | ALPEKY |
2441 | SLRSYY |
2442 | SSNIGAGYD |
2443 | SSNIGNNY |
2444 | SSDVGSYNL |
2445 | SSNIGNNY |
2446 | QGISSY |
2447 | QSIRFY |
2448 | QSVSSTY |
2449 | KLGDNY |
2450 | QDISNY |
2451 | QDISNY |
2452 | QSVSSY |
2453 | QGISNW |
2454 | QSISSY |
2455 | RSNIGAGFD |
2456 | QGISSA |
2457 | QDMSNY |
2458 | SSDVGGYNY |
2459 | SLRSYS |
2460 | SSDVGDYDY |
2461 | SSDVGGYNY |
2462 | QSVSSSY |
2463 | QSISSY |
2464 | QSVSSSY |
2465 | QSISSY |
2466 | KLGNKY |
2467 | SGDVGGYNY |
2468 | QSISSC |
2469 | QSVSSN |
2470 | QSINRN |
2471 | QSVNRN |
2472 | SGDVGGYNY |
2473 | QSISSF |
2474 | SSDVGGYNY |
2475 | QSISSY |
2476 | QSLLHSNGYNY |
2477 | QSLLHSNGYNY |
2478 | QSISSW |
2479 | KLGKKY |
2480 | SSNIGAGYD |
2481 | TFDVGVYDF |
2482 | QSLLHSNGNYY |
2483 | NIGSKS |
2484 | SSNIGNNY |
2485 | QSVSSSY |
2486 | QSISSW |
2487 | QSISDW |
2488 | SSNIGAGYD |
2489 | ALPKQY |
2490 | QSVSSSY |
2491 | NSDINSYDY |
2492 | QGISNY |
2493 | NIGSKS |
2494 | QSISSY |
2495 | QSISSW |
2496 | NIGSKS |
2497 | SSNIGNNY |
2498 | SGHSSYV |
2499 | QDISNY |
2500 | NIGSKS |
2501 | QSVSNY |
2502 | QDISNY |
2503 | QSVSSSY |
2504 | QSVSSSY |
2505 | TGAVTSGYY |
2506 | QGISSY |
2507 | QDISNY |
2508 | SSDVGSYNL |
2509 | SGSIASNY |
2510 | QSVSSY |
2511 | SSNIGNNY |
2512 | RSLVHTNGNTY |
2513 | FSDIGNYDL |
2514 | QSVSSSY |
2515 | SSNIGNNY |
2516 | QSVSNY |
2517 | QSVSSY |
2518 | QSVNSNY |
2519 | QGISSS |
2520 | SSDVGTYNL |
2521 | QSIAKF |
2522 | QGISSW |
2523 | QGISSA |
2524 | NSNIGAGYD |
2525 | QIISSW |
2526 | HSLVYSDGYTH |
2527 | SSNIGSNT |
2528 | SSDVGGYNY |
2529 | QGISSY |
2530 | QDISNY |
2531 | QGISSY |
2532 | QSISNF |
2533 | QDISNY |
2534 | QSISSY |
2535 | QGISSY |
2536 | QDIINY |
2537 | QGISSY |
2538 | QGISSY |
2539 | QSISSY |
2540 | QDINKY |
2541 | AAS |
2542 | AAS |
2543 | EVS |
2544 | KAS |
2545 | AAS |
2546 | DAS |
2547 | GAS |
2548 | RSN |
2549 | LSSDGSH |
2550 | KDS |
2551 | EAA |
2552 | DAS |
2553 | EVN |
2554 | GDQ |
2555 | KVS |
2556 | KAS |
2557 | AAS |
2558 | KDS |
2559 | WAS |
2560 | EDT |
2561 | WAS |
2562 | WAS |
2563 | KAS |
2564 | DVS |
2565 | KDS |
2566 | DVS |
2567 | GAS |
2568 | GAS |
2569 | DAS |
2570 | GAS |
2571 | SNN |
2572 | EVS |
2573 | WAS |
2574 | GAS |
2575 | DAS |
2576 | WAS |
2577 | AAS |
2578 | KGT |
2579 | DAS |
2580 | AAS |
2581 | DAS |
2582 | KNN |
2583 | ATS |
2584 | RNT |
2585 | SAS |
2586 | ASS |
2587 | STS |
2588 | ATS |
2589 | EDS |
2590 | DIN |
2591 | GNS |
2592 | QDS |
2593 | DNN |
2594 | GAS |
2595 | DTS |
2596 | AAS |
2597 | DVS |
2598 | WAS |
2599 | GAS |
2600 | DNN |
2601 | DVS |
2602 | LGS |
2603 | LGS |
2604 | LGS |
2605 | AAS |
2606 | AAS |
2607 | YDS |
2608 | QNN |
2609 | DNN |
2610 | DVS |
2611 | GAS |
2612 | AAS |
2613 | KAS |
2614 | KAS |
2615 | GAS |
2616 | RND |
2617 | WAS |
2618 | EDN |
2619 | STN |
2620 | AAS |
2621 | KVS |
2622 | DNN |
2623 | RNN |
2624 | KVS |
2625 | KVS |
2626 | GAS |
2627 | LNS |
2628 | EVS |
2629 | TAF |
2630 | AAS |
2631 | GKN |
2632 | EKN |
2633 | EVS |
2634 | GNS |
2635 | WAS |
2636 | KVS |
2637 | DVS |
2638 | AAS |
2639 | DVS |
2640 | AAS |
2641 | GKN |
2642 | QDT |
2643 | KAS |
2644 | KIS |
2645 | AAS |
2646 | GNN |
2647 | RNN |
2648 | GKN |
2649 | DAS |
2650 | DNN |
2651 | GAS |
2652 | QDS |
2653 | ATS |
2654 | ATS |
2655 | ATS |
2656 | AAS |
2657 | GAS |
2658 | KDS |
2659 | AAS |
2660 | QDN |
2661 | EVS |
2662 | EVS |
2663 | LGS |
2664 | EDS |
2665 | DVS |
2666 | EDS |
2667 | KAS |
2668 | DAS |
2669 | AAS |
2670 | GAS |
2671 | GAS |
2672 | GAS |
2673 | WAS |
2674 | EVS |
2675 | EVS |
2676 | LGS |
2677 | GSS |
2678 | GAS |
2679 | DAS |
2680 | WAS |
2681 | EVS |
2682 | DAS |
2683 | GAS |
2684 | EVS |
2685 | AAS |
2686 | KDS |
2687 | DVS |
2688 | AAS |
2689 | KVS |
2690 | QDS |
2691 | DVT |
2692 | DVT |
2693 | KVS |
2694 | DNN |
2695 | KDN |
2696 | GSS |
2697 | ETS |
2698 | LEGSGSY |
2699 | DAS |
2700 | DVS |
2701 | LGS |
2702 | KAS |
2703 | KVS |
2704 | GAS |
2705 | AAS |
2706 | QDS |
2707 | KAS |
2708 | GAF |
2709 | GAS |
2710 | EDS |
2711 | DAY |
2712 | WAS |
2713 | WAS |
2714 | DAS |
2715 | DAS |
2716 | STD |
2717 | GAS |
2718 | GAS |
2719 | KAS |
2720 | EVS |
2721 | KDS |
2722 | GAS |
2723 | GAS |
2724 | EVS |
2725 | GAS |
2726 | GAS |
2727 | AAS |
2728 | GNT |
2729 | DAS |
2730 | AAS |
2731 | WAS |
2732 | AAS |
2733 | ELF |
2734 | DTN |
2735 | EVS |
2736 | DAS |
2737 | DVN |
2738 | EVS |
2739 | AAS |
2740 | KIS |
2741 | DNS |
2742 | GAS |
2743 | LGS |
2744 | DDS |
2745 | GAS |
2746 | GAS |
2747 | DTS |
2748 | GAS |
2749 | SNN |
2750 | EVS |
2751 | DDG |
2752 | DVT |
2753 | AAS |
2754 | DAS |
2755 | RDN |
2756 | GAS |
2757 | VGTGGIVG |
2758 | EVS |
2759 | EAS |
2760 | KAS |
2761 | EVS |
2762 | EDS |
2763 | DAS |
2764 | KDR |
2765 | DNN |
2766 | AAS |
2767 | GAS |
2768 | GAS |
2769 | GNS |
2770 | DAS |
2771 | DAS |
2772 | SNN |
2773 | EIS |
2774 | KDK |
2775 | QDN |
2776 | GAS |
2777 | KDS |
2778 | EIS |
2779 | DAS |
2780 | KAS |
2781 | KAS |
2782 | EDT |
2783 | AAS |
2784 | GAS |
2785 | GAS |
2786 | GAS |
2787 | GNN |
2788 | QDT |
2789 | GDS |
2790 | KDT |
2791 | KAS |
2792 | QDS |
2793 | GAS |
2794 | GAS |
2795 | GAS |
2796 | GAS |
2797 | EVS |
2798 | EDN |
2799 | DNN |
2800 | EDN |
2801 | GKN |
2802 | GNS |
2803 | DNN |
2804 | EGS |
2805 | DNN |
2806 | AAS |
2807 | AAS |
2808 | DAS |
2809 | QDT |
2810 | DAS |
2811 | DAS |
2812 | DAS |
2813 | AAS |
2814 | AAS |
2815 | GNS |
2816 | DAS |
2817 | DAS |
2818 | DVS |
2819 | VKN |
2820 | DVS |
2821 | EVS |
2822 | GAS |
2823 | AAS |
2824 | GAS |
2825 | AAS |
2826 | QDS |
2827 | DVY |
2828 | AAS |
2829 | GAS |
2830 | DAS |
2831 | DAS |
2832 | EVS |
2833 | AAS |
2834 | DVS |
2835 | AAS |
2836 | LGS |
2837 | LGS |
2838 | KAS |
2839 | QDV |
2840 | GNS |
2841 | DDT |
2842 | LAS |
2843 | YDS |
2844 | RNN |
2845 | GAS |
2846 | KAS |
2847 | KAS |
2848 | GNS |
2849 | KDS |
2850 | GAS |
2851 | DVD |
2852 | AAS |
2853 | DDS |
2854 | AAS |
2855 | KAS |
2856 | DDN |
2857 | DNN |
2858 | LNSDGSH |
2859 | DAS |
2860 | DDS |
2861 | DAS |
2862 | DAS |
2863 | GAS |
2864 | GAS |
2865 | STS |
2866 | AAS |
2867 | DAS |
2868 | EVS |
2869 | EDN |
2870 | DAS |
2871 | DNN |
2872 | NVS |
2873 | EGY |
2874 | GAS |
2875 | DNN |
2876 | GAS |
2877 | DAS |
2878 | GAS |
2879 | SAS |
2880 | EVS |
2881 | TAS |
2882 | AAS |
2883 | DAS |
2884 | VNT |
2885 | KAS |
2886 | SVS |
2887 | SNN |
2888 | EVS |
2889 | AAS |
2890 | DAS |
2891 | AAS |
2892 | AAS |
2893 | DAS |
2894 | AAS |
2895 | AAS |
2896 | GAS |
2897 | AAS |
2898 | AAS |
2899 | AAS |
2900 | DAS |
2901 | GLTVSSNY |
2902 | GFTVSRNY |
2903 | GVIVSSNY |
2904 | GFTVSSNY |
2905 | GVTVSSNY |
2906 | GIIVSSNY |
2907 | GIIVSSNY |
2908 | GFTVSSNY |
2909 | GLTVSSNY |
2910 | GLTVSSNY |
2911 | GIIVSSNY |
2912 | GVTVSRNY |
2913 | GITVSSNY |
2914 | GFTVSSNY |
2915 | GLTVSSNY |
2916 | GLTVSSNY |
2917 | GLIVSSNY |
2918 | GFTVSSNY |
2919 | GFIVSSNY |
2920 | GFTVSSNY |
2921 | GFIVSRNY |
2922 | GITVSSNY |
2923 | GFTVSSNY |
2924 | GFTVSSNY |
2925 | GFTVSSNY |
2926 | GVTVSSNY |
2927 | GFTVSSNY |
2928 | GYTFSSYG |
2929 | GYSFTYYG |
2930 | GFTFSSYD |
2931 | GFIVSSNY |
2932 | EFIVSRNY |
2933 | GFTVSSNY |
2934 | GFTVSSNY |
2935 | GFTVSFNY |
2936 | IYSGGST |
2937 | IYSGGTT |
2938 | IYSGGTT |
2939 | IYSGGST |
2940 | IYSGGST |
2941 | IYSGGST |
2942 | IYSGGST |
2943 | IYSGGST |
2944 | IYSGGST |
2945 | IYSGGST |
2946 | IYSGGST |
2947 | IYSGGST |
2948 | IYSGGST |
2949 | IYSGGST |
2950 | IYSGGST |
2951 | IYSGGST |
2952 | IYSGGST |
2953 | IYRGGST |
2954 | IYSGGST |
2955 | IYPGGST |
2956 | IYSGGST |
2957 | IYSGGST |
2958 | IYSGGST |
2959 | IYSGGST |
2960 | IYSGGST |
2961 | VYSGGST |
2962 | IYSGGST |
2963 | ISGYNGHT |
2964 | ISPYNGDT |
2965 | IGTAGDT |
2966 | IYSGGST |
2967 | IYSGGST |
2968 | IYSGGST |
2969 | IYSGGST |
2970 | IYPGGST |
2971 | ARDLDYYGMDV |
2972 | ARDLVVYGMDV |
2973 | ARDLDYYGMDV |
2974 | ARDLDYGGGMDV |
2975 | ARPIVGARSGMDV |
2976 | ARDLGTYGMDV |
2977 | ARDLGPYGMDV |
2978 | ARDLGAYGMDV |
2979 | ARDLYYYGMDV |
2980 | ARDLDYYGMDV |
2981 | ARDLDYYGMDV |
2982 | ARDGYGMDV |
2983 | ARGGAYYYGMDV |
2984 | ARDLDYMDV |
2985 | ARLPYGMDV |
2986 | ARLPYGMDV |
2987 | ARARIYTYGPDY |
2988 | ARVGDSRSWPFEY |
2989 | ARAPYSSRSET |
2990 | AREIRVITPVEV |
2991 | ARGPYPRFDY |
2992 | ARERGGRFDY |
2993 | ARDRPAAAIRF |
2994 | ARDYAGRV |
2995 | ARELSYSSSSGVGPKY |
2996 | ARLINHYYDSSGDGGAFDI |
2997 | ARIGGVAAAGTADGAFDI |
2998 | ARERFGISHDY |
2999 | AKGVVALTGTLLRLDP |
3000 | ARDRDNGSGSYLGWAFDI |
3001 | ARDYGDYYFDY |
3002 | ARDYGDYYFDY |
3003 | ARDYGDYWFDP |
3004 | ARSYGDYYFDY |
3005 | ARDYGDFYFDY |
3006 | QGISSY |
3007 | QGISSY |
3008 | QGISSY |
3009 | QGISSY |
3010 | QDINNY |
3011 | QGISSY |
3012 | QGISSD |
3013 | QGISSY |
3014 | QGISSY |
3015 | QGISSY |
3016 | QGISSY |
3017 | QGISSY |
3018 | QGISSY |
3019 | QGISSY |
3020 | QDVSKY |
3021 | QDIRNY |
3022 | QDINNY |
3023 | QDISNY |
3024 | QDIRNY |
3025 | QDINKY |
3026 | QDIRNY |
3027 | QDISNY |
3028 | QDISNY |
3029 | QDIRSY |
3030 | QDISNY |
3031 | SSDVGSYNL |
3032 | SSDVGSYNL |
3033 | QSVGSN |
3034 | QSVRTN |
3035 | QSISSY |
3036 | QSVSSSY |
3037 | QGVSSF |
3038 | QSVSSSY |
3039 | QGISSY |
3040 | QSVSSSY |
3041 | AAS |
3042 | AAS |
3043 | AAS |
3044 | AAS |
3045 | DAS |
3046 | AAS |
3047 | AAS |
3048 | AAS |
3049 | AAS |
3050 | AAS |
3051 | AAS |
3052 | AAS |
3053 | AAS |
3054 | AAS |
3055 | DAS |
3056 | DAS |
3057 | DAS |
3058 | DAS |
3059 | DAS |
3060 | DAS |
3061 | DAS |
3062 | DAS |
3063 | DAS |
3064 | DAS |
3065 | DAS |
3066 | EVT |
3067 | EGS |
3068 | GAF |
3069 | EAS |
3070 | AAS |
3071 | GAS |
3072 | GAS |
3073 | GTS |
3074 | AAS |
3075 | GAS |
3076 | QHLNSYPPIT |
3077 | QQLNSYPLT |
3078 | QQLNSYGLT |
3079 | QQLNSYPHRFT |
3080 | QQHDNLPVT |
3081 | QQLNSYLYT |
3082 | QQLNSDLYT |
3083 | QQLNSDLYT |
3084 | QQLDSYPL |
3085 | QQLNSYLAIT |
3086 | QQLNSYPPFT |
3087 | QQLNSYPPA |
3088 | QQLNTYPPFG |
3089 | QQLNSYPPMYT |
3090 | QQYDNLPVT |
3091 | QQYDNLPIT |
3092 | QQYDNLPPV |
3093 | QQYDNLPLFT |
3094 | QQYDNLPIT |
3095 | HQYDNLPRT |
3096 | QQYDNLPVT |
3097 | QQHDNLPSFT |
3098 | QQYDNLPPA |
3099 | QQYDNLPQT |
3100 | QQYDNLPPT |
3101 | CSYAGSSTWV |
3102 | CSYAGSSTWV |
3103 | QQYNNWYT |
3104 | QQYNNWPPIT |
3105 | QQSYSMPPVT |
3106 | QQYGSTPRT |
3107 | QQYGSSPRT |
3108 | QQYGSSPRT |
3109 | QQLNS |
3110 | QQYDSSPRT |
3111 | EVQLVESGGGLIQPGGSLRLSCAASGLTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSTNTLYLQMNSLRAEDTAVYYCARDLDYYGMDVWGQGTTVTVSS |
3112 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSRNYMSWVRQAPGKGLEWVSVIYSGGTTHYADSVKGRFTISRHNSKNTLYLQMNSLRAEDTAVYYCARDLVVYGMDVWGQGTTVTVSS |
3113 | EVQLVESGGGLVQPGGSLRLSCAASGVIVSSNYMRWVRQAPGKGLEWVSVIYSGGTTYYADSVKGRFTISRHNSKNTLYLQMNSLRTEDTAVYYCARDLDYYGMDVWGQGTTVTVSS |
3114 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRHNSKNTLYLQMNSLRAEDTAVYYCARDLDYGGGMDVWGQGTTVTVSS |
3115 | EVQLVESGGGLIQPGGSLRLSCAASGVTVSSNYMSWVRQAPGKGLEWVSLIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARPIVGARSGMDVWGQGTTVTVSS |
3116 | EVQLVESGGGLIQPGGSLRLSCAASGIIVSSNYMSWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNTMRAEDTAVYYCARDLGTYGMDVWGQGTTVTVS |
3117 | EVQLVESGGGLIQPGGSLRLSCAASGIIVSSNYMTWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMSSLRAEDTAVYYCARDLGPYGMDVWGQGTTVTVSS |
3118 | EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLGAYGMDVWGQGTTVTVSS |
3119 | EVQLVESGGGLIQPGGSLRLSCAASGLTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLYYYGMDVWGQGTTVTVSS |
3120 | EVQLVESGGGLIQPGGSLRLSCAASGLTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLDYYGMDVWGQGTTVTVSS |
3121 | EVQLVESGGGLVQPGGSLRLSCAASGIIVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLDYYGMDVWGQGTTVTVSS |
3122 | EVQLVESGGGLVQPGGSLRLSCAASGVTVSRNYMSWVRQAPGKGLEWVSVIYSGGSTDYADSVKGRFTISRHNSKNTLYLQMNSLRVEDTAVYYCARDGYGMDVWGQGTTVTVSS |
3123 | EVQLVESGGGLIQPGGSLRLSCAASGITVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGGAYYYGMDVWGQGTTVTVSS |
3124 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLDYMDVWGKGTTVTVSS |
3125 | EVQLVESGGGLVQPGGSLRLSCAASGLTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSVRAEDTAVYYCARLPYGMDVWGQGTTVTVSS |
3126 | EVQLVESGGGLVQPGGSLRLSCAASGLTVSSNYMSWVRQAPGKGLNWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLEMNSLKPEDTAVYYCARLPYGMDVWGQGTTVTVSS |
3127 | QVQLVESGGGLVQPGGSLRLSCAASGLIVSSNYMSWVRQAPGEGLEWVSVIYSGGSTYYADSVKGRFTISRDTSKNTLYLQMNSLRAEDTAVYYCARARIYTYGPDYWGQGTLVTVSS |
3128 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGRGLEWVSVIYRGGSTYYADSVKGRFSISRDNSKNTLYLQMNSLRVEDTAVYYCARVGDSRSWPFEYWGQGTLVTVSS |
3129 | EVQLVESGGGLVQPGGSLRLSCAASGFIVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLRMNSLRAEDTAVYYCARAPYCSSRSCETWGQGTLVTVSS |
3130 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSLIYPGGSTYYADSVEGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREIRVITPVEVWGQGTLVTVSS |
3131 | EVQLVESGGGLVQPGGSLRLSCAVSGFIVSRNYMTWVRQAPGKGLEWVSLIYSGGSTFYTNSVKGRFTISRDNSKNTLYLQMDSLRAEDTAVYYCARGPYPRFDYWGQGTLVTVSS |
3132 | EVQLVESGGGLIQPGGSLRLSCAASGITVSSNYMSWVRQAPGKGLEWVSVIYSGGSTFYSDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARERGGRFDYWGQGTLVTVSS |
3133 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSLIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRPAAAIRFGQGTLVTVSS |
3134 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSIIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDYAGRVWGQGTLVTVSS |
3135 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARELSYSSSSGVGPKYWGQGTLVTVSS |
3136 | EVQLVESGGGLVQPGGSLRLSCAASGVTVSSNYMSWVRQAPGKGLEWVSAVYSGGSTYYADSVKGRFTISRHNSKNTLYLQMKSLRPEDTAIYYCARLINHYYDSSGDGGAFDIWGQGTMVTVSS |
3137 | EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARIGGVAAAGTADGAFDIWGQGTMVTVSS |
3138 | QVQLVQSGAEVKKPGASVKVSCKTSGYTFSSYGLSWVRQAPGQGLEWMGWISGYNGHTVNAQNFQDRVTMTTDTSTDTAYMELRSLRSDDTALYFCARERFGISHDYWGQGTLVIVSS |
3139 | QIQLVQSGPEVKRPGASVKVSCKASGYSFTYYGISWVRQAPGQGLEWMGWISPYNGDTKFAQKFQDRVILTTDTSTSTAYMELKSLRSDDTAVYYCAKGVVALTGTLLRLDPWGQGTLVTVSS |
3140 | EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYDMHWVRQATGKGLEWVSVIGTAGDTYYPGSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARDRDNGSGSYLGWAFDIWGQGTMVTVSS |
3141 | EVQLVESGGGLIQPGGSLRLSCAASGFIVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDYGDYYFDYWGQGTLVTVSS |
3142 | EVQLVESGGGLIQPGGSLRLSCAASEFIVSRNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLNLQMNSLRAEDTAVYYCARDYGDYYFDYWGQGTLVTVSS |
3143 | EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDYGDYWFDPWGQGTLVTVSS |
3144 | EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSYGDYYFDYWGQGTLVTVSS |
3145 | EVQVVESGGGLVQPGGSLRLSCAASGFTVSFNYMSWVRQAPGKGLEWVSVIYPGGSTYYADSVKGRFTISRHNSKNTVYLQMNSLRAEDTAVYYCARDYGDFYFDYWGQGTLVTVSS |
3146 | DIQLTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPNLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQHLNSYPPITFGQGTRLEIK |
3147 | DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSSFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPLTFGGGTKVEIK |
3148 | DIQLTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQRGVPSRFSGSGSGTDFNLTISSLQPEDFGTYYCQQLNSYGLTFGGGTKVEIK |
3149 | DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPHRFTFGPGTKVDIK |
3150 | DIQMTQSPSSLSASVGDRVTITCQASQDINNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFIISSLQPEDIATYYCQQHDNLPVTFGGGTKVEIK |
3151 | DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYEQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTEFTLTISTLQPGDFATYYCQQLNSYLYTFGQGTKLEIK |
3152 | DIQLTQSPSFLSASVGDRVTITCRASQGISSDLAWYQQKPGKAPNLLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSDLYTFGQGTKLEIK |
3153 | DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSDLYTFGQGTKLEIK |
3154 | AIQLTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIFAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLDSYPLFGGGTKVEIK |
3155 | AIQLTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLNSYLAITFGQGTRLEIK |
3156 | DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPPFTFGPGTKVDIK |
3157 | DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPNLLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPPAFGPGTKVDIK |
3158 | DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNTYPPFGFGPGTKVDIK |
3159 | DIQLTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLNSYPPMYTFGQGTKLEIK |
3160 | DIQMTQSPSSLSASVGDRVTITCQASQDVSKYLNWYQQKPGKAPKLLIHDASNLQTGVPSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPVTFGGGTKVEIK |
3161 | DIQMTQSPSSLSASVGDRVTITCQASQDIRNYLNWYQQKPGKAPKLLIHDASNLETGVPSRFIGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPITFGQGTRLEIK |
3162 | DIQMTQSPSSLSASVGDRVTITCQASQDINNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPPVFGPGTKVDIK |
3163 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLFTFGPGTKVDIK |
3164 | DIQMTQSPSSLSASVGDRVTITCQASQDIRNYLNWYQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTINSLQPEDIATYYCQQYDNLPITFGQGTRLEIK |
3165 | DIQMTQSPSSLSASVGDRVTITCQASQDINKYLNWYQLKPGKAPNLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDNLPRTFGQGTKVEIK |
3166 | DIQMTQSPSSLSASLGDRVTITCQASQDIRNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPVTFGGGTKVEIK |
3167 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASTLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQHDNLPSFTFGPGTKVDIK |
3168 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPPAFGGGTKVEIK |
3169 | DIQMTQSPSSLSASVGDRVTITCQASQDIRSYLNWYQQKPGKAPKLLIYDASNLETGVASRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPQTFGQGTKLEIK |
3170 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPPTFGGGTKVEIK |
3171 | QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLVSWYQQRPGKAPKLILYEVTKRPSGVSNRFSGSKSGNTASLAISGLQAEDEADYYCCSYAGSSTWVFGGGTKLTVL |
3172 | QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLVSWYQQHPGKAPKLMIYEGSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCCSYAGSSTWVFGGGTKLTVL |
3173 | EIVMTQFPATLSVSPGERATLFCRASQSVGSNLAWYQQKPGQAPRLLIYGAFTRATGVPARFSGSGSGSEFSLTISSLQSEDFAVYYCQQYNNWYTFGQGTKLEIK |
3174 | EIVMTQSPATLSVSPGERATLSCRASQSVRTNLAWYQQKRGQAPRLLIYEASTRATGVPDRFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPPITFGQGTRLDIK |
3175 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSASGSGTDFTLTISSLQPEDFATYYCQQSYSMPPVTFGQGTKVEIK |
3176 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPERFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSTPRTFGQGTKVEIK |
3177 | EIVLTQSPGTLSLSPGERATLSCRASQGVSSFLAWYQQKPGQAPRLLIHGASSRATGIPDRFSGSGSGTDFTLTITRLEPEDFAVYYCQQYGSSPRTFGQGTKVEIK |
3178 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGTSSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKVEIK |
3179 | DIQLTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLNSFGPGTKVDIK |
3180 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAMYYCQQYDSSPRTFGQGTKVEIK |
儘管本文所述的具體實施方式已經得到詳細的描述,但本領域技術人員將理解:根據已經公佈的所有教導,可以對細節進行各種修改和變動,並且這些改變均在本文所述的保護範圍之內。本文所述的全部分為由所附請求項及其任何等同物給出。
圖 1A-1C
示例性地顯示了抗原結合單元ABU-174、ABU-175和ABU190的SDS-PAGE檢測結果。圖 2A-2C
示例性地顯示了使用SPR技術檢測抗原結合單元ABU-174 (A)、ABU-175 (B)、ABU190 (C)與S蛋白的親和力的測定結果。圖 3A-3C
示例性地顯示了抗原結合單元ABU-174 (A)、ABU-175 (B)、ABU190 (C)對SARS-CoV-2假病毒的中和抑制活性的測定結果。圖 4
示例性地顯示了ABU-175 抗體對SARS-CoV-2真病毒的中和抑制活性的CPE測定結果。圖 5
示例性地顯示了抗原結合單元ABU-174、ABU-175和ABU190對SARS-CoV-2真病毒的中和抑制活性的PRNT測定結果。
Claims (52)
- 一種抗原結合單元,其包含重鏈可變區(VH)和輕鏈可變區(VL),所述重鏈可變區包含VH CDR1、VH CDR2和VH CDR3,所述輕鏈可變區包含VL CDR1、VL CDR2和VL CDR3;其中所述VH CDR3包含選自SEQ ID NO: 1-360和2971-3005的序列或者與SEQ ID NO: 1-360和2971-3005相比包含一個或多個氨基酸添加、刪除、或取代的序列,和/或其中所述VL CDR3包含選自SEQ ID NO: 361-720和3076-3110的序列或者與SEQ ID NO: 361-720和3076-3110相比包含一個或多個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其以小於100nM、小於50nM、小於20nM、小於15nM、小於10 nM、小於5nM、小於4nM、小於3nM、小於2nM、小於1nM、小於0.5nM、小於0.1 nM、小於0.05 nM、或小於0.01 nM的平衡解離常數(KD )結合新型冠狀病毒(SARS-CoV-2)S蛋白的受體結合結構域(RBD)。
- 如前述請求項之一所述的抗原結合單元,其以小於20 µg/ml、小於10 µg/ml、小於9 µg/ml、小於8 µg/ml、小於7 µg/ml、小於6 µg/ml、小於5 µg/ml、小於4 µg/ml、小於3 µg/ml、小於2 µg/ml、小於1 µg/ml、小於0.5µg/ml、小於0.25 µg/ml、小於0.2 µg/ml、小於0.1 µg/ml、小於0.05 µg/ml、或小於0.001 µg/ml的IC50 中和新型冠狀病毒(SARS-CoV-2)。
- 如前述請求項之一所述的抗原結合單元,其中所述VH CDR1包含選自SEQ ID NO: 1461-1820和2901-2935的序列或者與SEQ ID NO: 1461-1820和2901-2935相比包含一個或多個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH CDR1包含選自SEQ ID NO: 1461-1820和2901-2935的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH CDR1包含與SEQ ID NO: 1461-1820和2901-2935相比包含5、4、3、2或1個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH CDR1包含與SEQ ID NO: 721-1080和3111-3145中所包含的CDR1相同的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH CDR2包含選自SEQ ID NO: 1821-2180和2936-2970的序列或者與SEQ ID NO: 1821-2180和2936-2970相比包含一個或多個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH CDR2包含選自SEQ ID NO: 1821-2180和2936-2970的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH CDR2包含與SEQ ID NO: 1821-2180和2936-2970相比包含5、4、3、2或1個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH CDR2包含與SEQ ID NO: 721-1080和3111-3145中所包含的CDR2相同的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL CDR1包含選自SEQ ID NO: 2181-2540和3006-3040的序列或者與SEQ ID NO: 2181-2540和3006-3040相比包含一個或多個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL CDR1包含選自SEQ ID NO: 2181-2540和3006-3040的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL CDR1包含與SEQ ID NO: 2181-2540和3006-3040相比包含5、4、3、2或1個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL CDR1包含與SEQ ID NO: 1081-1440和3146-3180中所包含的CDR1相同的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL CDR2包含選自SEQ ID NO: 2541-2900和3041-3075的序列或者與SEQ ID NO: 2541-2900和3041-3075相比包含一個或多個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL CDR2包含選自SEQ ID NO: 2541-2900和3041-3075的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL CDR2包含與SEQ ID NO: 2541-2900和3041-3075相比包含5、4、3、2或1個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL CDR2包含與SEQ ID NO: 1081-1440和3146-3180中所包含的CDR2相同的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH包含選自SEQ ID NO: 721-1080和3111-3145的序列或者與SEQ ID NO: 721-1080和3111-3145相比包含一個或多個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH包含選自SEQ ID NO: 721-1080和3111-3145的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH包含與SEQ ID NO: 721-1080和3111-3145相比包含10、9、8、7、6、5、4、3、2或1個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH包含與選自SEQ ID NO: 721-1080和3111-3145的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL包含選自SEQ ID NO: 1081-1440和3146-3180的序列或者與SEQ ID NO: 1081-1440和3146-3180相比包含一個或多個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL包含選自SEQ ID NO: 1081-1440和3146-3180的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL包含與SEQ ID NO: 1081-1440和3146-3180相比包含10、9、8、7、6、5、4、3、2或1個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL包含與選自SEQ ID NO: 1081-1440和3146-3180的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
- 一種抗原結合單元,其包含重鏈可變區(VH)和輕鏈可變區(VL),所述重鏈可變區包含VH CDR1、VH CDR2和VH CDR3,所述輕鏈可變區包含VL CDR1、VL CDR2和VL CDR3;其中所述VH CDR1包含選自SEQ ID NO: 1461-1820和2901-2935的序列、與SEQ ID NO: 1461-1820和2901-2935相比包含一個或多個氨基酸添加、刪除、或取代的序列、或者與SEQ ID NO: 721-1080和3111-3145中所包含的CDR1相同的序列,其中所述VH CDR2包含選自SEQ ID NO: 1821-2180和2936-2970的序列、與SEQ ID NO: 1821-2180和2936-2970相比包含一個或多個氨基酸添加、刪除、或取代的序列、或者與SEQ ID NO: 721-1080和3111-3145中所包含的CDR2相同的序列,其中所述VH CDR3包含選自SEQ ID NO: 1-360和2971-3005的序列、與SEQ ID NO: 1-360和2971-3005相比包含一個或多個氨基酸添加、刪除、或取代的序列、或者與SEQ ID NO: 721-1080和3111-3145中所包含的CDR3相同的序列;和/或其中所述VL CDR1包含選自SEQ ID NO: 2181-2540和3006-3040的序列、與SEQ ID NO: 2181-2540和3006-3040相比包含一個或多個氨基酸添加、刪除、或取代的序列、或者與SEQ ID NO: 1081-1440和3146-3180中所包含的CDR1相同的序列,所述VL CDR2包含選自SEQ ID NO: 2541-2900和3041-3075的序列、與SEQ ID NO: 2541-2900和3041-3075相比包含一個或多個氨基酸添加、刪除、或取代的序列、或者與SEQ ID NO: 1081-1440和3146-3180中所包含的CDR2相同的序列,所述VL CDR3包含選自SEQ ID NO: 361-720和3076-3110的序列、與SEQ ID NO: 361-720和3076-3110相比包含一個或多個氨基酸添加、刪除、或取代的序列、或者與SEQ ID NO: 1081-1440和3146-3180中所包含的CDR3相同的序列。
- 一種抗原結合單元,其包含重鏈可變區(VH)和輕鏈可變區(VL),所述重鏈可變區包含VH CDR1、VH CDR2和VH CDR3,所述輕鏈可變區包含VL CDR1、VL CDR2和VL CDR3;其中所述VH CDR1包含選自SEQ ID NO: 1461-1820和2901-2935的序列或者與SEQ ID NO: 1461-1820和2901-2935相比包含一個或多個氨基酸添加、刪除、或取代的序列,其中所述VH CDR2包含選自SEQ ID NO: 1821-2180和2936-2970的序列或者與SEQ ID NO: 1821-2180和2936-2970相比包含一個或多個氨基酸添加、刪除、或取代的序列,其中所述VH CDR3包含選自SEQ ID NO: 1-360和2971-3005的序列或者與SEQ ID NO: 1-360和2971-3005相比包含一個或多個氨基酸添加、刪除、或取代的序列;和/或其中所述VL CDR1包含選自SEQ ID NO: 2181-2540和3006-3040的序列或者與SEQ ID NO: 2181-2540和3006-3040相比包含一個或多個氨基酸添加、刪除、或取代的序列,所述VL CDR2包含選自SEQ ID NO: 2541-2900和3041-3075的序列或者與SEQ ID NO: 2541-2900和3041-3075相比包含一個或多個氨基酸添加、刪除、或取代的序列,所述VL CDR3包含選自SEQ ID NO: 361-720和3076-3110的序列或者與SEQ ID NO: 361-720和3076-3110相比包含一個或多個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH包含選自SEQ ID NO: 721-1080和3111-3145的序列或者與SEQ ID NO: 721-1080和3111-3145相比包含一個或多個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH包含選自SEQ ID NO: 721-1080和3111-3145的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH包含與SEQ ID NO: 721-1080和3111-3145相比包含10、9、8、7、6、5、4、3、2或1個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VH包含與選自SEQ ID NO: 721-1080和3111-3145的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL包含選自SEQ ID NO: 1081-1440和3146-3180的序列或者與SEQ ID NO: 1081-1440和3146-3180相比包含一個或多個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL包含選自SEQ ID NO: 1081-1440和3146-3180的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL包含與SEQ ID NO: 1081-1440和3146-3180相比包含10、9、8、7、6、5、4、3、2或1個氨基酸添加、刪除、或取代的序列。
- 如前述請求項之一所述的抗原結合單元,其中所述VL包含與選自SEQ ID NO: 1081-1440和3146-3180的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
- 如前述請求項之一所述的抗原結合單元,其以小於100nM、小於50nM、小於20nM、小於15nM、小於10 nM、小於5nM、小於4nM、小於3nM、小於2nM、小於1nM、小於0.5nM、小於0.1 nM、小於0.05 nM、或小於0.01 nM的平衡解離常數(KD )結合新型冠狀病毒(SARS-CoV-2)S蛋白的受體結合結構域(RBD)。
- 如前述請求項之一所述的抗原結合單元,其以小於20 µg/ml、小於10 µg/ml、小於9 µg/ml、小於8 µg/ml、小於7 µg/ml、小於6 µg/ml、小於5 µg/ml、小於4 µg/ml、小於3 µg/ml、小於2 µg/ml、小於1 µg/ml、小於0.5µg/ml、小於0.25 µg/ml、小於0.2 µg/ml、小於0.1 µg/ml、小於0.05 µg/ml、或小於0.001 µg/ml的IC50 中和新型冠狀病毒(SARS-CoV-2)。
- 一種抗原結合單元,其包含重鏈可變區(VH)和輕鏈可變區(VL),其中所述VH包含與選自SEQ ID NO: 721-1080和3111-3145的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列,和/或其中所述VL包含與選自SEQ ID NO: 1081-1440和3146-3180的序列具有至少80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或99%的同一性的序列。
- 如前述請求項之一所述的抗原結合單元,其以小於100nM、小於50nM、小於20nM、小於15nM、小於10 nM、小於5nM、小於4nM、小於3nM、小於2nM、小於1nM、小於0.5nM、小於0.1 nM、小於0.05 nM、或小於0.01 nM的平衡解離常數(KD )結合新型冠狀病毒(SARS-CoV-2)S蛋白的受體結合結構域(RBD)。
- 如前述請求項之一所述的抗原結合單元,其以小於20 µg/ml、小於10 µg/ml、小於9 µg/ml、小於8 µg/ml、小於7 µg/ml、小於6 µg/ml、小於5 µg/ml、小於4 µg/ml、小於3 µg/ml、小於2 µg/ml、小於1 µg/ml、小於0.5µg/ml、小於0.25 µg/ml、小於0.2 µg/ml、小於0.1 µg/ml、小於0.05 µg/ml、或小於0.001 µg/ml的IC50 中和新型冠狀病毒(SARS-CoV-2)。
- 一種藥物組合物,其包含如請求項1至42之一所述的抗原結合單元和藥學上可接受的賦形劑。
- 一種分離的核酸,其編碼如請求項1至42之一所述的抗原結合單元。
- 一種載體,其包含編碼如請求項1至42之一所述的抗原結合單元的核酸序列。
- 一種宿主細胞,其表達如請求項1至42之一所述的抗原結合單元。
- 一種宿主細胞,其包含編碼如請求項1至42之一所述的抗原結合單元的核酸。
- 一種產生如請求項1至42之一所述的抗原結合單元的方法,其包括:在適合表達所述抗原結合單元的條件下培養請求項46或47的宿主細胞;以及分離由所述宿主細胞表達的所述抗原結合單元。
- 一種綴合物,其包含如請求項1至42之一所述的抗原結合單元,其中所述抗原結合單元與化學功能部分綴合。
- 如請求項49所述的綴合物,其中所述化學功能部分選自射性同位素、酶、螢光化合物、化學發光化合物、生物發光化合物底物輔因數和抑制劑。
- 一種預防和/或治療有需要的患者的SARS-CoV-2感染的方法,包括向所述患者給予如請求項1至42之一所述的抗原結合單元的方法或者編碼所述抗原結合單元的核酸。
- 一種用於檢測SARS-CoV-2的試劑盒,其包含如請求項1至42之一所述的抗原結合單元。
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