TW202334213A - 可活化之抗ctla-4抗體及其用途 - Google Patents
可活化之抗ctla-4抗體及其用途 Download PDFInfo
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Abstract
本文提供可活化之抗人類CTLA-4抗體,其包含:包含VH結構域之重鏈及包含掩蔽部分(MM)、可裂解部分(CM)以及VL結構域之輕鏈。此類可活化之抗人類CTLA-4抗體在腫瘤微環境中具有CTLA-4結合活性,其中藉由腫瘤特異性蛋白酶之蛋白水解作用分裂可裂解部分,來移除該掩蔽部分,但對腫瘤外之CTLA-4則顯示顯著降低之結合性。以此方式,本發明之可活化之抗人類CTLA-4抗體不但保留抗腫瘤活性,同時減少與腫瘤外之抗CTLA-4活性相關之副作用。
Description
本文提供可活化之抗人類CTLA-4抗體。
免疫系統能夠控制腫瘤發展且調節腫瘤消退。此需要產生且活化腫瘤抗原特異性T細胞。多種T細胞共刺激受體及T細胞負調節子或共同抑制受體共同起作用以控制T細胞活化、增殖,且獲得或損失效應功能。最早及最具特徵之T細胞共刺激及共抑制分子係CD28及CTLA-4。Rudd等人(2009)
Immunol . Rev .229: 12。CD28藉由與抗原呈遞細胞上之B7-1及B7-2配位體結合向T細胞受體參與提供共刺激信號,而CTLA-4提供下調T細胞增殖及功能之負信號。CTLA-4亦結合B7-1 (CD80)及B7-2 (CD86)配位體但具有高於CD28之親和力,其經由細胞自發(或內因性)及細胞非自發(或外源性)路徑充當T細胞功能之負調節劑。CD8及CD4 T效應子(T
eff)功能之內因性控制藉由由於T細胞活化而引起之CTLA-4之可誘發表面表現調節,且T細胞增殖及細胞介素增殖之抑制藉由相對細胞上之B7配位體之多價參與調節。Peggs等人 (2008)
Immunol. Rev.224:141。
當交聯時,抗CTLA-4抗體抑制活體外T細胞功能。Krummel & Allison (1995)
J. Exp. Med.182:459;Walunas等人 (1994)
Immunity1:405。組成性表現CTLA-4之調節T細胞(T
regs)以非細胞自發方式控制效應子T細胞(T
eff)功能。缺乏CTLA-4之T
regs具有減弱之抑制能力(Wing等人 (2008)
Science322:271)且阻斷與B7之CTLA-4相互作用的抗體可抑制T
reg功能(Read等人 (2000)
J . Exp . Med .192:295;Quezada等人 (2006)
J . Clin . Invest .116:1935)。最近,T
effs亦已展示經由外源性路徑控制T細胞功能(Corse & Allison (2012)
J . Immunol .189:1123;Wang等人 (2012)
J . Immunol .189:1118)。藉由T
regs及T
effs外源性控制T細胞功能藉由CTLA-4陽性細胞移除抗原呈遞細胞上之B7配位體從而限制其共刺激潛能的能力發生。Qureshi等人 (2011)
Science332: 600;Onishi等人 (2008)
Proc. Nat'l Acad. Sci. (USA)105:10113。認為CTLA-4/B7相互作用之抗體阻斷藉由干擾由CTLA-4參與傳輸之負信號促進T
eff活化;此T細胞活化及增殖之內因性控制可促進T
eff及T
reg二者增殖(
Krummel & Allison ( 1995 ) J . Exp . Med .182
:459
;Quezada 等人 (2006)
J . Clin . Invest .116:1935)。在利用動物模型之早期研究中,展示CTLA-4之抗體阻斷加劇自體免疫。Perrin等人 (1996)
J. Immunol.157:1333;Hurwitz等人 (1997)
J. Neuroimmunol.73:57。擴展至腫瘤免疫而言,抗CTLA-4引起所建立腫瘤消退的能力提供CTLA-4阻斷之治療潛能之顯著實例。Leach等人 (1996)
Science271:1734。
選擇對人類CTLA-4之人類抗體易普利姆瑪(ipilimumab)及曲美單抗(tremelimumab)以抑制CTLA-4-B7相互作用(Keler等人 (2003)
J . Immunol .171:6251;Ribas等人 (2007)
Oncologist12:873)且其已在針對多種惡性疾病之各種臨床試驗中測試。Hoos等人 (2010)
Semin. Oncol.37:533;Ascierto等人 (2011)
J. Transl. Med.9:196。經常觀測到腫瘤消退及疾病穩定,且利用此等抗體之治療已伴隨著能夠影響各種器官系統之具有發炎性浸潤的不良事件。在2011年,基於在患有晚期黑素瘤之先前治療之患者的III期試驗中總存活率的提高,具有IgG1恆定區之易普利姆瑪在美國及歐洲經過批准以用於治療不可切除性或轉移性黑素瘤。Hodi等人 (2010)
N. Engl. J. Med.363:711。
然而,利用易普利姆瑪之治療已受劑量限制性毒性,諸如結腸炎妨礙。Di Giacomo等人
(2010)
Seminars in Oncology37:499。因此,需要具有降低之毒性但具有相當抗腫瘤功效之改良的抗CTLA-4抗體,諸如易普利姆瑪之經修飾形式。此類改良之抗CTLA-4抗體可為比當前抗體更有效之抗腫瘤劑。
本文提供可活化之抗人類CTLA-4抗體,其包含:包含VH結構域之重鏈及包含掩蔽部分(MM)、可裂解部分(CM)以及VL結構域之輕鏈。此類可活化之抗人類CTLA-4抗體在腫瘤微環境中具有CTLA-4結合活性,其中藉由腫瘤特異性蛋白酶之蛋白水解作用分裂可裂解部分來移除該掩蔽部分,但對腫瘤外之CTLA-4則顯示顯著降低之結合性。以此方式,本發明之可活化之抗人類CTLA-4抗體不但保留抗腫瘤活性,同時減少與腫瘤外之抗CTLA-4活性相關之副作用。
本文提供改良之抗CTLA-4抗體,諸如改良之易普利姆瑪,尤其在活化時結合細胞毒性T淋巴細胞抗原4 (CTLA-4)之可活化之抗體。在一些實施例中,可活化之抗人類CTLA-4抗體包含:
(i)重鏈,該重鏈包含重鏈可變結構域(VH),該重鏈可變結構域(VH)包含互補決定區(CDR):CDRH1: SYTMH (SEQ ID NO: 557);CDRH2: FISYDGNNKYYADSVKG (SEQ ID NO: 558);及CDRH3: TGWLGPFDY (SEQ ID NO: 559);及
(ii)輕鏈,其包含:
(a) 輕鏈可變結構域(VL),該輕鏈可變結構域(VL)包含CDRL1: RASQSVGSSYLA (SEQ ID NO: 560);CDRL2: GAFSRAT (SEQ ID NO: 561);及CDRL3: QQYGSSPWT (SEQ ID NO: 562);
(b) 可裂解部分(CM);及
(c) 掩蔽部分(MM),
其中該輕鏈自N端至C端具有如下結構排列:MM-CM-VL。
在一些實施例中,可活化之抗人類CTLA-4抗體包含:
(i)重鏈,該重鏈包含重鏈可變結構域(VH),該重鏈可變結構域包含:CDRH1: SYTMH (SEQ ID NO: 557);CDRH2: FISYDGNNKYYADSVKG (SEQ ID NO: 558);及CDRH3: TGWLGPFDY (SEQ ID NO: 559);及
(ii)輕鏈,該輕鏈自N端至C端包含:
(a) 掩蔽部分(MM);
(b) 可裂解部分(CM);及
(c) 輕鏈可變結構域(VL),該輕鏈可變結構域(VL)包含CDRL1: RASQSVGSSYLA (SEQ ID NO: 560);CDRL2: GAFSRAT (SEQ ID NO: 561);及CDRL3: QQYGSSPWT (SEQ ID NO: 562)。
在一些實施例中,可活化之抗體包含重鏈及輕鏈,使得輕鏈自輕鏈之N端至C端具有結構排列MM-CM-VL。如本文所用,連接至VL結構域之N端片段稱為前結構域且包含MM及CM。
在一些實施例中,可活化之抗體包含完整抗體,亦即抗體包含兩條成熟全長重鏈及兩條成熟全長輕鏈。在一些實施例中,可活化之抗體包含Fab片段、F(ab')
2片段、scFv或scAb。在一些實施例中,可活化之抗體包含單株抗體。
在一些實施例中,CM充當蛋白酶之受質。在一些實施例中,CM選自由表3中提供之CM群組。在一些實施例中,CM選自由以下組成之群:2001 (SEQ ID NO: 297)、2003 (SEQ ID NO: 298)、2005 (SEQ ID NO: 299)、2006 (SEQ ID NO: 300)、2007 (SEQ ID NO: 301)、2008 (SEQ ID NO: 302)、2009 (SEQ ID NO: 303)、2011 (SEQ ID NO: 304)、2012 (SEQ ID NO: 305)、3001 (SEQ ID NO: 306)、3006 (SEQ ID NO: 307)、3007 (SEQ ID NO: 308)、3008 (SEQ ID NO: 309)、3009 (SEQ ID NO: 310)、3011 (SEQ ID NO: 311)及3012 (SEQ ID NO: 312)。在一些實施例中,CM係2001 (SEQ ID NO: 297)。在一些實施例中,CM係2011 (SEQ ID NO: 304)。在一些實施例中,CM係2012 (SEQ ID NO: 305)。
在一些實施例中,MM選自由表4-表6中提供之MM組成之群。在一些實施例中,MM選自由以下組成之群:YV01 (SEQ ID NO: 1)、YV02 (SEQ ID NO: 2)、YV03 (SEQ ID NO: 3)、YV04 (SEQ ID NO: 4)、YV09 (SEQ ID NO: 9)、YV23 (SEQ ID NO: 23)、YV24 (SEQ ID NO: 24)、YV35 (SEQ ID NO: 35)、YV39 (SEQ ID NO: 39)、YV51 (SEQ ID NO: 51)、YV61 (SEQ ID NO: 60)、YV62 (SEQ IDNO: 61)、YV63 (SEQ ID NO: 62)、YV64 (SEQ ID NO: 63)、YV65 (SEQ ID NO: 64)及YV66 (SEQ ID NO: 65);且CM選自由以下組成之群:2001、2006、2007、2008、2009、2011及2012。在一些實施例中,MM係YV39且CM係2011。在一些實施例中,MM係YV39且CM係2012。在一些實施例中,MM係YV39且CM係2001。
在一些實施例中,可活化之抗體包含:包含胺基酸序列SEQ ID NO: 353之重鏈及包含選自由SEQ ID NO: 356至SEQ ID NO: 529組成之群之胺基酸序列的輕鏈。在一些實施例中,可活化之抗CTLA-4抗體包含具有對應於SEQ ID NO: 356至SEQ ID NO: 529之前結構域及VL之前結構域及VL的輕鏈。在一些實施例中,可活化之抗CTLA-4抗體包含具有SEQ ID NO: 564、SEQ ID NO: 565或SEQ ID NO: 563之前結構域及VL的輕鏈。在一個實施例中,可活化之抗CTLA-4抗體包含具有SEQ ID NO: 564之前結構域及VL的輕鏈。
在一些實施例中,可活化之抗CTLA-4抗體包含與SEQ ID NO: 345至少90%、91%、92%、93%、94%、95%、96%、97%、98%或99%一致之重鏈可變結構域胺基酸序列。在一些實施例中,可活化之抗CTLA-4抗體包含與選自由SEQ ID NO: 564、SEQ ID NO: 565及SEQ ID NO: 563組成之群的胺基酸序列至少90%、91%、92%、93%、94%、95%、96%、97%、98%或99%一致之輕鏈可變結構域胺基酸。
在一些實施例中,可活化之抗體包含重鏈序列SEQ ID NO: 353與輕鏈序列SEQ ID NO: 449、SEQ ID NO: 473或SEQ ID NO: 383之組合。在一些實施例中,可活化之抗體包含重鏈序列SEQ ID NO: 349與輕鏈序列SEQ ID NO: 448、SEQ ID NO: 472或SEQ ID NO: 382之組合。
本文中提供一種可活化之抗CTLA-4抗體,其在活化時特異性結合於人類CTLA-4且稱為經活化之可活化之抗CTLA-4抗體。在一些實施例中,經活化之可活化之抗CTLA-4抗體與結合親和力與易普利姆瑪相同之CTLA-4結合。本文亦提供一種可活化之抗CTLA-4抗體,其不如易普利姆瑪一樣與CTLA-4有效結合,因為該可活化之抗CTLA-4抗體包含重鏈及輕鏈,該輕鏈包含前結構域,該前結構域包含連結至易普利姆瑪輕鏈之MM及CM,使得前結構域降低易普利姆瑪與CTLA-4結合之能力。
在一些實施例中,可活化之抗體與人類CTLA-4結合,如藉由流式細胞量測術所量測,其中EC
50為1 µg/mL或更高。在一些實施例中,可活化之抗CTLA-4抗體與CTLA-4結合,其中EC
50為5 µg/mL或更高、10 µg/mL或更高、20 µg/mL或更高或40 µg/mL或更高。
在一些實施例中,MM係長度不超過40個胺基酸之多肽。在一些實施例中,MM係與任何抗體之天然結合搭配物之一致性不超過50%的多肽。在一些實施例中,MM不包含超過25%與CTLA-4之胺基酸序列一致性。在一些實施例中,MM不包含超過10%與CTLA-4之胺基酸序列一致性。
當可裂解部分藉由蛋白酶裂解時,本發明之可活化之抗CTLA-4抗體經活化。在一些實施例中,蛋白酶由接近表現CTLA-4之T細胞的腫瘤產生。在一些實施例中,蛋白酶由與表現CTLA-4之T細胞共同定位的腫瘤產生。在一些實施例中,蛋白酶選自下文提供之表1中所提供之蛋白酶的群組。在一些實施例中,蛋白酶選自由以下組成之群:基質金屬蛋白酶(MMP)、凝血酶、嗜中性白血球彈性蛋白酶、半胱胺酸蛋白酶、天冬醯胺內肽酶及絲胺酸蛋白酶,諸如間質蛋白酶或尿激酶(uPA)。在一些實施例中,蛋白酶選自由以下組成之群:MMP1、MMP2、MMP3、MMP8、MMP9、MMP11、MMP13、MMP14、MMP17、天冬醯胺內肽酶、間質蛋白酶及uPA,或此類蛋白酶中之一或多者之組合。在一些實施例中,CM藉由基質金屬蛋白酶(MMP)及絲胺酸蛋白酶裂解。在一些實施例中,CM藉由基質金屬蛋白酶(MMP)、絲胺酸蛋白酶及天冬醯胺內肽酶裂解。
表1:例示性蛋白酶及/或酶
本文提供進一步包含一或多種連接肽之可活化之抗CTLA-4抗體。在一些實施例中,連接肽在MM與CM之間。在一些實施例中,連接肽在CM與VL之間。在一些實施例中,可活化之抗體包含第一連接肽(LP1)及第二連接肽(LP2)。在一些實施例中,可活化之抗體包含重鏈及輕鏈,使得輕鏈自輕鏈之N端至C端具有結構排列MM-LP1-CM-LP2-VL。在一些實施例中,LP1與LP2彼此不同。在一些實施例中,LP1與LP2彼此相同。在一些實施例中,前結構域包含MM-LP1-CM-LP2。
在一些實施例中,LP1及/或LP2包含甘胺酸-絲胺酸聚合物。在一些實施例中,LP1及/或LP2包含選自由以下組成之群的胺基酸序列:(GS)
n(SEQ ID NO: 532)、(GGS)
n(SEQ ID NO: 533)、(GSGGS)
n(SEQ ID NO: 534)及(GGGS)
n(SEQ ID NO: 535),其中n是至少為1之整數。在一些實施例中,LP1包含胺基酸序列GGGSSGGS (SEQ ID NO: 542)。在一些實施例中,LP2包含胺基酸序列GGGS (SEQ ID NO: 543)。
本文提供亦包含間隔子之可活化之抗CTLA-4抗體。在一些實施例中,間隔子直接連接至MM且自N端至C端具有如下結構排列:間隔子-MM-CM-VL。在一些實施例中,間隔子包含選自由以下組成之群的胺基酸序列:QGQSGQG (SEQ ID NO: 544)、GQSGQG (SEQ ID NO: 545)、QGQSGS (SEQ ID NO: 546)、QGQSGQ (SEQ ID NO: 547)、QSGQG (SEQ ID NO: 548)、GQSGS (SEQ ID NO: SEQ ID NO: 549)、QGQSG (SEQ ID NO: 550)、SGQG (SEQ ID NO: 551)、QSGS (SEQ ID NO: 552)、QGQS (SEQ ID NO: 553)、GQG、SGS、QGQ、QG、GS、G、S及Q。在一些實施例中,間隔子及MM包含胺基酸序列QGQSGSCRTQLYGYNLCPY (SEQ ID NO: 556)。
本文亦提供包含毒性劑之可活化之抗體,該毒性劑諸如海兔毒素、奧瑞斯他汀(auristatin)、奧瑞斯他汀E (auristatin E)、單甲基奧瑞斯他汀E (MMAE)、類美登素、倍癌黴素、卡奇黴素、吡咯并苯并二氮呯或其衍生物。在一些實施例中,毒性劑藉助於連接子與可活化之抗體結合。在一些實施例中,連接子為可裂解連接子。在一些實施例中,連接子為不可裂解連接子。
本文提供包含可偵測部分之可活化之抗CTLA-4抗體。在一些實施例中,可偵測部分係診斷劑。
本文提供包含本文所述之可活化之抗CTLA-4抗體之醫藥組合物。在一些實施例中,醫藥組合物包含另一種治療劑。
本文亦提供編碼本文所述之可活化之抗CTLA-4抗體之重及/或輕鏈的經分離之核酸分子;包含一或多種經分離之核酸分子的載體;及藉由在引起可活化之抗體表現之條件下培養包含一或多種載體之細胞來產生可活化之抗體之方法。
本文提供製造可活化之抗體之方法,該等方法包含:(a)培養細胞,該細胞包含在引起可活化之抗體表現之條件下編碼本文所述之可活化之抗體的核酸構築體;及(b)回收可活化之抗體。
本文提供降低CTLA-4活性之方法,其包含向有需要之個體投與有效量之本文所述之可活化之抗體或包含本文所述之可活化之抗CTLA-4抗體的醫藥組合物。
本文提供阻斷天然配位體與CTLA-4結合之方法,其包含向有需要之個體投與有效量之本文所述之可活化之抗體或包含本文所述之可活化之抗CTLA-4抗體的醫藥組合物。
本文提供治療CTLA-4相關病症、緩解CTLA-4相關病症之症狀或延緩CTLA-4相關病症之演進的方法,其包含向有需要之個體投與治療有效量之本文所述之可活化之抗體或包含本文所述之可活化之抗CTLA-4抗體的醫藥組合物。在一些實施例中,CTLA-4相關病症係癌症。在一些實施例中,癌症係諸如不可切除性或轉移性黑素瘤之黑素瘤、乳癌、結腸直腸癌、胃癌、神經膠母細胞瘤、頭頸癌、肺癌、卵巢癌、子宮內膜癌、胰臟癌、前列腺癌、腎癌、肉瘤或皮膚癌。在一些實施例中,CTLA-4相關病症係已知可利用易普利姆瑪處理之病症。
當本發明之態樣或實施例根據馬庫西群組(Markush group)或其他替代群組進行描述時,本發明不僅涵蓋整體列出之全部群組,而且涵蓋獨立群組之各成員及主群組之所有可能子組,以及缺乏一或多個群組成員之主群組。本發明亦設想明確排除所主張之發明中之任何群組成員中之一或多者。
ADAMS,ADAMTS,例如 | 半胱胺酸蛋白酶,例如 | 絲胺酸蛋白酶,例如 |
ADAM8 | 克魯茲蛋白酶(Cruzipain) | 經活化蛋白C |
ADAM9 | 天冬醯胺內肽酶 | 組織蛋白酶A |
ADAM10 | Otubain-2 | 組織蛋白酶G |
ADAM12 | 凝乳酶 | |
ADAM15 | KLKs,例如 | 凝血因子蛋白酶 |
ADAM17/TACE | KLK4 | (例如,FVIIa、FIXa、FXa、FXIa、FXIIa) |
ADAMDEC1 | KLK5 | |
ADAMTS1 | KLK6 | 彈性蛋白酶 |
ADAMTS4 | KLK7 | 顆粒酶B |
ADAMTS5 | KLK8 | 胍基苯甲酸酶(Guanidinobenzoatase) |
KLK10 | HtrA1 | |
天冬胺酸蛋白酶,例如 | KLK11 | 人類嗜中性白血球彈性蛋白酶 |
BACE | KLK13 | 乳鐵傳遞蛋白 |
腎素 | KLK14 | Marapsin |
NS3/4A | ||
天冬胺酸組織蛋白酶,例如 | 金屬蛋白酶,例如 | PACE4 |
組織蛋白酶D | 甲基多巴 | 纖維蛋白溶酶 |
組織蛋白酶E | 腦啡肽酶 | PSA |
PSMA | tPA | |
半胱天冬酶,例如 | BMP-1 | 凝血酶 |
卡斯蛋白酶1 | 類胰蛋白酶 | |
卡斯蛋白酶2 | MMPs,例如 | uPA |
卡斯蛋白酶3 | MMP1 | |
卡斯蛋白酶4 | MMP2 | II型跨膜 |
卡斯蛋白酶5 | MMP3 | 絲胺酸蛋白酶(TTSP) ,例如 |
卡斯蛋白酶6 | MMP7 | DESC1 |
卡斯蛋白酶7 | MMP8 | DPP-4 |
卡斯蛋白酶8 | MMP9 | FAP |
卡斯蛋白酶9 | MMP10 | 第二型穿膜絲胺酸蛋白酶 |
卡斯蛋白酶10 | MMP11 | 間質蛋白酶-2 |
卡斯蛋白酶14 | MMP12 | MT-SP1/間質蛋白酶 |
MMP13 | TMPRSS2 | |
半胱胺酸組織蛋白酶,例如 | MMP14 | TMPRSS3 |
組織蛋白酶B | MMP15 | TMPRSS4 |
組織蛋白酶C | MMP16 | |
組織蛋白酶K | MMP17 | |
組織蛋白酶L | MMP19 | |
組織蛋白酶S | MMP20 | |
組織蛋白酶V/L2 | MMP23 | |
組織蛋白酶X/Z/P | MMP24 | |
MMP26 | ||
MMP27 |
相關申請案之交叉引用
本申請案主張2016年11月3日申請之美國臨時申請案第62/417,212號的權益,該案以全文引用的方式併入本文中。
藉助於EFS-WEB電子提交之序列表之引用
電子提交之序列表之內容(名稱:3338_059PC02_SeqListing.txt;大小:527,968位元組;及創建日期:2017年10月27日)以全文引用的方式併入本文中。
為使本發明之描述可更易於理解,首先定義某些術語。在整個實施方式中,闡述其他定義。
應注意,術語「一(a)或(an)」實體係指一或多個彼實體;例如,「一個核苷酸序列」理解為表示一或多個核苷酸序列。因此,術語「一個(a/an)」、「一或多個」及「至少一個」在本文中可互換使用。
此外,本文所用之「及/或」應視為兩種指定特徵或組分中之每一者具有或不具有另一者之特定揭示內容。因此,諸如本文中「A及/或B」之片語中所用之術語「及/或」意欲包括「A及B」、「A或B」、「A」(單獨)及「B」(單獨)。同樣,諸如「A、B及/或C」之片語中所用之術語「及/或」意欲涵蓋以下態樣中之每一者:A、B及C;A、B或C;A或C;A或B;B或C;A及C;A及B;B及C;A (單獨);B (單獨);及C (單獨)。
應瞭解每當本文中用語言「包含」描述態樣時,則亦提供用術語「由……組成」及/或「基本上由……組成」所描述之類似態樣。
除非另外定義,否則本文中所用之所有技術及科學術語均具有與本發明所屬領域之一般技術者通常所理解相同之含義。舉例而言,the Concise Dictionary of Biomedicine and Molecular Biology, Juo, Pei-Show, 第2版, 2002, CRC Press;The Dictionary of Cell and Molecular Biology, 第3版, 1999, Academic Press;及the Oxford Dictionary Of Biochemistry And Molecular Biology, Revised, 2000, Oxford University Press,向此項技術者提供本發明中所用之許多術語的通用辭典。
單位、前綴及符號以其國際單位制(Système International de Unites;SI)接受形式表示。數值範圍包括界定該範圍之數字。除非另外指示,否則核苷酸序列沿5'至3'方向從左向右書寫。胺基酸序列沿胺基至羧基方向從左向右書寫。本文提供之標題並非本發明之各種態樣的限制,其可作為整體由說明書提及。因此,下文緊接著定義之術語參考整個說明書來更完全地定義。
如本文所用之術語「細胞毒性T淋巴細胞抗原4」或「CTLA-4」係指受體,該受體為由經活化之T細胞表現且將抑制信號傳輸至T細胞之免疫球蛋白總科之成員。CTLA-4與T細胞共刺激蛋白CD28同源,且兩種分子均與抗原呈遞細胞上之亦分別稱為B7-1及B7-2之CD80及CD86結合。CTLA4亦於調節T細胞中發現且促進其抑制功能。CTLA-4亦稱為細胞毒性T淋巴細胞相關蛋白4、CD152、胰島素依賴型糖尿病12 (IDDM12)、乳糜瀉3 (CELIAC3)、GRD4及GSE。術語「CTLA-4」包括由細胞自然表現之CTLA-4之任何變體或同功異型物。
如本文所用之術語「T細胞」定義為參與各種細胞調節之免疫反應之胸腺衍生的淋巴細胞。如本文所用之術語「調節T細胞」係指具有抑制特性之CD4
+CD25
+FoxP3
+T細胞。「Treg」係調節T細胞之本文中所用之縮寫。
如本文所用之術語「輔助T細胞」係指CD4
+T細胞;輔助T細胞識別抗原與II類MHC分子結合。存在至少兩種類型之輔助T細胞Th1及Th2,其產生不同細胞介素。輔助T細胞在活化時變為CD25
+,但僅短暫變為FoxP3
+。
如本文所用之術語「細胞毒性T細胞」係指CD8
+T細胞;細胞毒性T細胞識別抗原與I類MHC分子結合。
術語「抗體」係指免疫球蛋白分子及免疫球蛋白(Ig)分子,亦即含有特異性結合抗原(與抗原免疫反應)之抗原結合位點之分子的免疫活性部分。藉由「特異性結合」或「與……免疫反應」或「免疫特異結合」意謂抗體與所需抗原之一或多個抗原決定子反應且不與其他多肽反應或以極低親和力(Kd >10
- 6)結合。抗體包括但不限於多株、單株、嵌合、域抗體、單鏈、Fab及F(ab′)2片段、scFvs及Fab表現程式庫。
已知基本抗體結構單元包含四聚體。各四聚體由兩個相同之多肽鏈對組成,各對具有一個「輕」鏈(約25 kDa)及一個「重」鏈(約50-70 kDa)。各鏈之胺基端部分包括主要負責抗原識別之具有約100至110個或超過110個胺基酸之可變區。各鏈之羧基端部分界定主要負責效應功能之恆定區。一般而言,獲自人類之抗體分子係關於類別IgG、IgM、IgA、IgE及IgD中之任一者,其根據分子中存在之重鏈之性質彼此不同。某些類別亦具有子類,諸如IgG1、IgG2及其他。此外,在人類中,輕鏈可為κ鏈或λ鏈。
如本文所用,術語「可活化之抗體」係指亦包含掩蔽部分(MM)及可裂解部分(CM)之抗體,其中MM藉助於CM連接至抗體之VL,該CM可由蛋白酶裂解。如本文所用,「前結構域」包含連接至抗人類CTLA-4可活化之抗體之VL結構域且因此包含MM及CM之N端片段。在一些實施例中,可活化之抗體之輕鏈自N端至C端具有如下結構排列:MM-CM-VL。在一些實施例中,前結構域連接至抗人類CTLA-4抗體之VH結構域。可活化之抗體經設計以由存在於大多數(若非全部)癌症中之上調蛋白分解活性裂解。此類蛋白水解分裂或活化移除前結構域且釋放活性抗體,亦即經活化之可活化之抗體。歸因於正常組織中蛋白分解活性之緊密控制,正常組織中之可活化之抗體之蛋白酶活化顯著降低。因此,可活化之抗體在循環及正常組織中很大程度上保持惰性。
鑒於其前結構域掩蔽抗原結合結構域從而抑制抗原結合結構域與其標靶結合之能力,可活化之抗體用於與標靶結合之親和力低於經活化之可活化之抗體,其中MM已由CM之蛋白水解分裂來移除從而釋放活性抗體。此類經釋放之抗體呈現用於與其標靶結合之較高親和力。在一些實施例中,MM與易普利姆瑪之抗原結合結構域特異性相互作用以降低抗體與其標靶結合之能力。當MM由可活化之抗體之蛋白水解分裂來移除時,經釋放之抗體以類似於親本序列易普利姆瑪之親和力與其標靶結合。
本發明之可活化之抗體之示意性表示,例如MM-CM-VL不意欲為排他性的。諸如連接子、間隔子及信號序列之其他序列要素可在呈此類示意性表示形式之所列出之序列要素之前、之後或之間呈現。亦應瞭解,包含MM及CM之前結構域可與抗體之VH連接代替與抗體之VL連接,使得重鏈自N端至C端具有如下結構排列:MM-CM-VH。
如本文所用之術語「單株抗體」(mAb)或「單株抗體組合物」係指抗體分子之群體,該等抗體分子僅含有由單一輕鏈基因產物及單一重鏈基因產物組成之抗體分子之一種分子物種。詳言之,單株抗體之互補決定區(CDR)在群體之所有分子中均相同。MAb含有能夠與抗原之特定抗原決定基免疫反應之抗原結合位點或結構域,其特徵在於對其具有特有結合親和力。單株抗體分子將通常包含兩個重鏈及兩個輕鏈。
術語「抗原結合結構域」係指參與抗原結合之免疫球蛋白分子之部分。抗原結合位點由重鏈(「H」)及輕鏈(「L」)之N端可變(「V」)區之胺基酸殘基形成。稱為「高變區」之重鏈及輕鏈之V區內的三個高度分叉區段插入於稱為「構架區」或「FR」之間的更加保守的側翼區段。因此,術語「FR」係指自然發現於免疫球蛋白中之高變區之間及鄰接於高變區的胺基酸序列。在抗體分子中,輕鏈之三個高變區與重鏈之三個高變區在三維空間中相對於彼此安置以形成抗原結合表面。抗原結合表面與結合抗原之三維表面互補,且重鏈及輕鏈中之每一者之三個高變區稱為「互補決定區」或「CDR」。胺基酸至各結構域之分配係根據Kabat Sequences of Proteins of Immunological Interest (美國國家衛生研究院(National Institutes of Health), Bethesda, Md. (1987及1991))或Chothia & Lesk
J . Mol . Biol. 196:901-917 (1987), Chothia等人
Nature342:878-883 (1989)之定義進行。
如本文所用,術語「抗原決定基」包括能夠特異性結合於免疫球蛋白、scFv或T細胞受體之任何蛋白質決定子。術語「抗原決定基」包括能夠特異性結合於免疫球蛋白或T細胞受體之任何蛋白質決定子。抗原決定基決定子通常由諸如胺基酸或糖側鏈之分子之化學活性表面團基團組成,且通常具有特定三維結構特徵,以及荷質比特徵。舉例而言,可針對多肽之N端或C端肽產生抗體。據稱當解離常數≦1 μM、較佳≦100 nM且最佳≦10 nM時,抗體特異性結合抗原。
如本文所使用,術語「特異性結合」、「免疫結合」及「免疫結合特性」指代類型之非共價相互作用,其發生在免疫球蛋白分子與免疫球蛋白對其具有特異性之抗原之間。免疫結合相互作用之強度或親和力可根據相互作用之解離常數(K
d)表示,其中較小的K
d表示較大的親和力。所選多肽之免疫結合特性可使用此項技術中熟知之方法定量。一種此類方法需要量測抗原結合位點/抗原複合物形成及解離之速率,其中彼等速率視複合搭配物之濃度、相互作用之親和力及同等影響兩個方向上速率之幾何參數而定。因此,「締合速率常數」(「k
on」)及「解離速率常數」(「k
off」)可藉由計算濃度及締合與解離之實際速率來確定。(參見
Nature361:186-87 (1993))。k
off/k
on之比率能夠抵消不與親和力相關之所有參數,且等於解離常數K
d。(參見,一般而言,Davies
等人(1990)
Annual Rev Biochem59:439-473)。據稱當平衡結合常數(K
d)≦1 μM、較佳≦100 nM、更佳≦10 nM且最佳≦100 pM至約1 pM時,本發明之抗體特異性結合於CTLA-4,如藉由分析,諸如放射性配位體結合分析或熟習此項技術者已知之相似分析所量測。
如本文所用之術語「分離之聚核苷酸」係指基因組、cDNA或合成來源或其某一組合之聚核苷酸,藉助於其來源,該「分離之聚核苷酸」(1)不與自然界中發現「分離之聚核苷酸」之所有或一部分聚核苷酸相關聯,(2)可操作地連接於自然界中不與其連接之聚核苷酸,或(3)在自然界中不作為較大序列之部分存在。根據本發明之聚核苷酸包括編碼本文中展示之重鏈免疫球蛋白分子之核酸分子,及編碼本文中展示之輕鏈免疫球蛋白分子之核酸分子。
本文所提及之術語「分離之蛋白質」意謂cDNA、重組RNA或合成來源或其某一組合之蛋白質,藉助於其來源或衍生源,「分離之蛋白質」(1)不與自然界中發現之蛋白質相關聯,(2)不含同一源之其他蛋白質,例如不含小鼠蛋白質,(3)由不同物種之細胞表現,或(4)不在自然界中出現。
在本文中使用術語「多肽」作為通用術語用於指代天然蛋白質、片段或多肽序列之類似物。因此,天然蛋白質片段及類似物係多肽屬之物種。根據本發明之多肽包含本文中展示之重鏈免疫球蛋白分子及本文中展示之輕鏈免疫球蛋白分子,以及由組合形成之抗體分子,該等組合包含重鏈免疫球蛋白分子以及輕鏈免疫球蛋白分子,諸如κ輕鏈免疫球蛋白分子,且反之亦然以及片段及其類似物。
如本文所用,術語「天然產生」在應用於一個對象時係指一個對象可在自然界中發現的事實。舉例而言,存在於可自自然界中之來源分離之生物體(包括病毒)中且未經人類在實驗室中或以其他方式有意修飾的多肽或聚核苷酸序列為天然存在的。
如本文所用之術語「可操作地連接」係指因此所描述之組分位置處於准許其以其預期方式作用的關係中。「可操作地連接」至編碼序列之控制序列以使得編碼序列之表現在與控制序列相容之條件下實現的方式接合。
如本文所用之術語「控制序列」係指實現所接合之編碼序列的表現及加工所需之聚核苷酸序列。此類控制序列之性質視宿主生物體而不同,在原核生物中,此類控制序列一般包括啟動子、核糖體結合位點及轉錄終止序列;在真核生物中,此類控制序列一般包括啟動子及轉錄終止序列。術語「控制序列」意欲包括在最低限度下,其存在對表現及加工而言至關重要之組分,且亦可包括其存在有利之額外組分,例如前導序列及融合搭配物序列。如本文中所提及之術語「聚核苷酸」意謂具有至少10個鹼基長度之核苷酸(核糖核苷酸或去氧核苷酸)或任一種類型之核苷酸的修飾形式。該術語包括DNA之單鏈及雙鏈形式。
本文所提及之術語「寡核苷酸」包括由天然產生及非天然產生之寡核苷酸鍵連接在一起的天然產生及經修飾之核苷酸。寡核苷酸係通常包含200個鹼基長度或更少之聚核苷酸子集。較佳地,寡核苷酸係10個至60個鹼基長且最佳12個、13個、14個、15個、16個、17個、18個、19個或20個至40個鹼基長。寡核苷酸通常為例如用於探針之單鏈,儘管寡核苷酸可為雙鏈例如用於基因突變體之構建。本發明之寡核苷酸係有義或反義寡核苷酸。
本文所提及之術語「天然產生之核苷酸」包括去氧核糖核苷酸及核糖核苷酸。本文所提及之術語「經修飾之核苷酸」包括具有經修飾或經取代之糖基團及其類似物的核苷酸。本文所提及之術語「寡核苷酸鍵」包括寡核苷酸鍵,諸如硫代磷酸酯、二硫代磷酸酯、硒代磷酸酯、二硒代磷酸酯、苯胺硫代磷酸酯、苯胺磷酸酯、胺基磷酸酯及其類似物。參見例如,LaPlanche等人
Nucl. Acids Res. 14:9081 (1986);Stec等人
J. Am. Chem. Soc. 106:6077 (1984);Stein等人
Nucl. Acids Res. 16:3209 (1988);Zon等人
Anti Cancer Drug Design6:539 (1991);Zon等人 Oligonucleotides and Analogues: A Practical Approach, 第87-108頁 (F. Eckstein, Ed., Oxford University Press, Oxford England (1991));Stec等人 美國專利第5,151,510號;Uhlmann及Peyman
Chemical Reviews90:543 (1990)。寡核苷酸視需要可包括用於偵測之標記。
如本文所用,二十種習知胺基酸及其縮寫遵循習知用法。參見Immunology-A Synthesis (第2版, E. S. Golub及D. R. Gren編, Sinauer Associates, Sunderland Mass. (1991))。二十種習知胺基酸之立體異構體(例如D-胺基酸)、非天然胺基酸(諸如α-胺基酸、α-雙取代胺基酸、N-烷基胺基酸、乳酸)及其他非習知胺基酸亦可為用於本發明之多肽之合適組分。非習知胺基酸之實例包括:4羥脯胺酸、γ-羧基麩胺酸、ε-N,N,N-三甲基離胺酸、ε-N-乙醯基離胺酸、O-磷絲胺酸、N-乙醯基絲胺酸、N-甲醯甲硫胺酸、3-甲基組胺酸、5-羥基離胺酸、σ-N-甲基精胺酸及其他類似胺基酸及亞胺基酸(例如,4-羥脯胺酸)。在本文中所用之多肽符號中,根據標準用法及慣例,左手方向為胺基端方向且右手方向為羧基端方向。
在應用於多肽時,術語「實質上一致」意謂在諸如使用默認空位權重藉由程序GAP或BESTFIT最佳對準時,兩個肽序列具有至少80序列一致性百分比、較佳至少90序列一致性百分比、更佳至少95序列一致性百分比且最佳至少99序列一致性百分比。
如本文所論述,考慮本發明涵蓋抗體或免疫球蛋白分子之胺基酸序列之少量變化,其限制條件為胺基酸序列之變化維持至少75%、更佳至少80%、90%、95%且最佳99%序列一致性。詳言之,考慮保守性胺基酸置換。保守性置換為在其側鏈中相關之胺基酸家族內進行的彼等置換。基因編碼胺基酸通常分成以下家族:(1)酸性胺基酸係天冬胺酸、麩胺酸;(2)鹼性胺基酸係離胺酸、精胺酸、組胺酸;(3)非極性胺基酸係丙胺酸、纈胺酸、白胺酸、異白胺酸、脯胺酸、苯丙胺酸、甲硫胺酸、色胺酸;且(4)不帶電極性胺基酸係甘胺酸、天冬醯胺、麩醯胺酸、半胱胺酸、絲胺酸、蘇胺酸、酪胺酸。親水性胺基酸包括精胺酸、天冬醯胺、天冬胺酸、麩醯胺酸、麩胺酸、組胺酸、離胺酸、絲胺酸及蘇胺酸。疏水性胺基酸包括丙胺酸、半胱胺酸、異白胺酸、白胺酸、甲硫胺酸、苯丙胺酸、脯胺酸、色胺酸、酪胺酸及纈胺酸。胺基酸之其他家族包括(i)絲胺酸及蘇胺酸,其為脂肪族-羥基家族;(ii)天冬醯胺及麩醯胺酸,其為含有醯胺之家族;(iii)丙胺酸、纈胺酸、白胺酸及異白胺酸,其為脂族家族;及(iv)苯丙胺酸、色胺酸及酪胺酸,其為芳族家族。就抗體而言,合理的係預期異白胺酸或纈胺酸對白胺酸、麩胺酸對天冬胺酸、絲胺酸對蘇胺酸之分離置換,或結構相關之胺基酸對胺基酸之類似置換將不對所得分子之結合或特性造成主要影響,尤其在置換不涉及CDR或構架區內之胺基酸時。藉由分析多肽衍生物之比活性可輕易確定胺基酸變化是否產生功能肽。在本文中詳細地描述分析。抗體或免疫球蛋白分子之片段或類似物可藉由一般熟習此項技術者輕易製備。片段或類似物之較佳胺基及羧基端在功能性結構域之邊界附近出現。可藉由比較核苷酸及/或胺基酸序列資料與公用或專用序列資料庫來鑑別結構及功能性結構域。較佳地,使用電腦化比較方法鑑別序列主結構或預測其他具有已知結構及/或功能之蛋白質中存在的蛋白質構形結構域。已知用於鑑別摺疊成已知三維結構之蛋白質序列的方法。Bowie等人
Science253:164 (1991)因此,前述實例表明熟習此項技術者可識別可用於界定根據本發明之結構及功能性結構域之序列主結構及結構構形。
較佳的胺基酸取代係:(1)降低除包含CM之可裂解連接子中以外之可活化之抗體之區中的蛋白分解之易感性;(2)降低對氧化之易感性;(3)改變用於形成蛋白質複合物之結合親和力;(4)改變結合親和力及(5)賦予或修改此類類似物之其他物理化學或功能性特性的彼等胺基酸取代。類似物可包括除天然產生之肽序列以外之序列的各種突變蛋白。舉例而言,單個或多個胺基酸取代(較佳地,保守胺基酸取代)可在天然產生之序列中(較佳在形成分子間接觸之結構域外之多肽部分中)進行。保守性胺基酸取代不應實質上改變親本序列之結構特徵(例如,置換胺基酸不應傾向於使在親本序列中出現之螺旋斷裂,或破壞表徵親本序列之其他類型之二級結構)。此項技術中公認的多肽二級及三級結構之實例描述於Proteins, Structures and Molecular Principles (Creighton編, W. H. Freeman and Company, New York (1984));Introduction to Protein Structure (C. Branden及J. Tooze編, Garland Publishing, New York, N.Y. (1991));及Thornton等人
Nature354:105 (1991)中。
如本文所用之術語「多肽片段」係指具有胺基端及/或羧基端缺失及/或一或多個內部缺失但其中殘餘胺基酸序列與例如自全長cDNA序列推斷之天然產生之序列中的對應位置一致的多肽。片段通常為至少5個、6個、8個或10個胺基酸長、較佳至少14個胺基酸長、更佳至少20個胺基酸長、通常至少50個胺基酸長且甚至更佳至少70個胺基酸長。如本文所用之術語「類似物」係指包含具有至少25個胺基酸之片段的多肽,該片段具有與一部分推斷之胺基酸序列大體一致性且在合適結合條件下具有與CTLA-4之特異性結合。通常,多肽類似物包含相對於天然產生之序列之保守性胺基酸取代(或添加或缺失)。類似物通常為至少20個胺基酸長、較佳至少50個胺基酸長或更長,且常常可長至全長天然產生之多肽。
術語「試劑」在本文中用以表示化合物、化合物之混合物、生物巨分子或由生物材料製成之提取物。
如本文所使用,術語「標記(label)或經標記(labeled)」係指併入可偵測標記物,例如藉由併入經放射性標記胺基酸或附著至可由標記抗生素蛋白偵測之生物素基部分的多肽(例如,可藉由光學或量熱方法偵測之含有螢光標記物或酶活性的抗生蛋白鏈菌素)。在某些情況下,標記或標記物亦可為治療性的。標記多肽及糖蛋白之各種方法為此項技術中已知且可使用。用於多肽之標記之實例包括但不限於以下:放射性同位素或放射性核素(例如
3H、
14C、
15N、
35S、
90Y、
99Tc、
111In、
125I、
131I)、螢光標記(例如FITC、若丹明(rhodamine)、鑭系元素磷光體)、酶標記(例如辣根過氧化酶、p-半乳糖酶、螢光素酶、鹼性磷酸酶)、化學發光、生物素基、由二級報告子識別之預定多肽抗原決定基(例如白胺酸拉鏈對序列、二級抗體之結合位點、金屬結合結構域、抗原決定基標籤)。在一些實施例中,標記藉由各種長度之間隔臂附著以降低潛在位阻。
本文中之其他化學術語根據此項技術中之習知用法使用,如藉由The McGraw-Hill Dictionary of Chemical Terms (Parker, S.編, McGraw-Hill, San Francisco (1985))所例示。
如本文所用,「實質上純」意謂對象物種係存在之主要物種(亦即,以莫耳計其比組合物中之任何其他單獨物種更加充足),且較佳地實質上純化部分係其中對象物種包含所存在之所有巨分子物種之至少約50%(以莫耳計)的組合物。一般而言,實質上的純組合物將包含組合物中所存在之所有巨分子物種之超過約80%、更佳超過約85%、90%、95%及99%。最佳地,將對象物種純化至基本均質性(無法藉由習知偵測方法在組合物中偵測到之污染物種),其中組合物基本上由單一巨分子物種組成。
如本文中所用,「治療」為用於獲得有益或所需臨床結果之方法。有益或所需臨床結果可包括但不限於以下中之任何一或多者:緩解一或多種症狀、減輕疾病程度、穩定(亦即不惡化)的疾病病況、預防或延緩疾病擴散(例如癌轉移)、預防或延緩疾病發生或復發、延遲或減緩疾病演進、改善疾病病況以及緩解(無論局部或總體)。「治療」亦涵蓋諸如癌症之增生性疾病之病理後果減少。本文所提供之方法涵蓋此等治療態樣中之任何一或多者。
本文中所用之術語「有效量」係指當單獨或與第二療法組合使用時之化合物或組合物之量足以治療指定病症、病狀或疾病,諸如改善、緩和、減輕及/或延遲其症狀中之一或多者。關於癌症或其他不期望之細胞增殖,有效量包括足以使腫瘤縮減及/或降低腫瘤之增長率(諸如抑制腫瘤生長)或防止或延遲其他不期望之細胞增殖之量。有效量可以投與一或多次。
如本文所用,藉由「組合療法」意謂第一試劑與另一試劑結合投與。「與……結合」係指投與一種治療模式外加另一治療模式。因此,「與……結合」係指在向個體遞送一種治療模式之前、期間或之後再投與另一種處理模式。
如本文所用之術語「醫藥試劑或藥物」係指當向個體適當投與時能夠誘發所需治療效果之化合物或組合物。
如本文所用,藉由「醫藥學上可接受」或「藥理學上相容」意謂在生物學上或在其他方面無不適宜之材料,例如,該材料可併入投與個體(individual或subject)之醫藥組合物中,不會引起任何顯著不當生物學效應或以有害方式與含有其之組合物中任何其他組分相互作用。醫藥學上可接受之載劑或賦形劑已例如滿足毒理學及製造測試之所要求標準及/或包括於美國食品藥物管理局(U.S. Food and Drug administration)制定之非活性成分指南(Inactive Ingredient Guide)中。
術語「癌症」、「癌性」或「惡性」係指或描述哺乳動物中通常以失控之細胞生長為特徵之生理病狀。癌症之實例包括例如諸如不可切除性或轉移性黑素瘤之黑素瘤、白血病、淋巴瘤、母細胞瘤、癌及肉瘤。此類癌症之更特定實例包括慢性骨髓性白血病、急性淋巴母細胞白血病、費城染色體陽性急性淋巴母細胞白血病(Ph+ ALL)、鱗狀細胞癌、小細胞肺癌、非小細胞肺癌、神經膠質瘤、胃腸癌、腎癌(renal cancer)、卵巢癌、肝癌、結腸直腸癌、子宮內膜癌、腎癌(kidney cancer)、前列腺癌、甲狀腺癌、神經母細胞瘤、胰臟癌、多形性膠質母細胞瘤、子宮頸癌、胃癌(stomach cancer)、膀胱癌、肝癌、乳癌、結腸癌及頭頸癌、胃癌(gastric cancer)、生殖細胞腫瘤、小兒肉瘤、鼻腔鼻竇自然殺手、多發性骨髓瘤、急性骨髓性白血病(AML)及慢性淋巴球性白血病(CML)。
「白血病」係指造血器官之進行性惡性疾病且其特徵通常在於血液及骨髓中之白細胞及其前驅體的變形增殖及發展。白血病通常基於以下各者臨床上分類(1)疾病之持續時間及特徵--急性或慢性;(2)所涉及之細胞類型;骨髓(骨髓性)、淋巴性(淋巴生成)或單核細胞性;及(3)血液中之異常細胞數目之增加或非增加--白血病或白血球缺乏(亞白血病)。白血病包括例如急性非淋巴球性白血病、慢性淋巴球性白血病、急性顆粒球性白血病、慢性顆粒球性白血病、急性前髓細胞性白血病、成人T細胞白血病、白血球缺乏白血病、白血球血症性白血病(leukocythemic leukemia)、嗜鹼性白血病、胚細胞白血病、牛白血病、慢性骨髓細胞性白血病、皮膚白血病、胚胎白血病、嗜酸性白血病、Gross白血病、毛細胞白血病、產血白血病、血胚細胞白血病、組織細胞白血病、幹細胞白血病、急性單核細胞性白血病、白細胞減少白血病、淋巴性白血病、淋巴母細胞白血病、淋巴球性白血病、淋巴生成白血病、淋巴球性白血病、淋巴肉瘤細胞白血病、肥大細胞白血病、巨核細胞白血病、微骨髓母細胞白血病、單核細胞性白血病、骨髓母細胞白血病、骨髓細胞性白血病、骨髓顆粒球性白血病、骨髓單核細胞性白血病、Naegeli型白血病、漿細胞白血病、漿球性白血病、前髓細胞性白血病、Rieder細胞性白血病、Schilling白血病、幹細胞白血病、亞白血病白血病及未分化細胞白血病。在某些態樣中,本發明提供用於慢性骨髓性白血病、急性淋巴母細胞白血病及/或費城染色體陽性急性淋巴母細胞白血病(Ph+ ALL)之治療。
I. 抗 CTLA - 4 可活化之抗體本發明提供與傳統抗CTLA-4抗體(例如易普利姆瑪)一樣有效但具有更好亦即改良之安全分佈的改良之抗CTLA-4抗體。具體而言,改良之抗CTLA-4抗體係在活化時特異性結合人類CTLA-4之可活化單株抗體(mAb)。此等改良之抗CTLA-4抗體在本文中亦稱為可活化之抗CTLA-4抗體或CTLA-4可活化之抗體,其用於治療疾病或病症、預防疾病或病症、延緩疾病或病症之演進、改善及/或緩解疾病或病症之症狀的方法,該疾病或病症包括但不限於與異常CTLA-4表現及/或活性相關之疾病或病症。舉例而言,可活化之抗CTLA-4抗體用於治療癌症或其他贅生性病狀、預防癌症或其他贅生性病狀、延緩癌症或其他贅生性病狀之演進、改善及/或緩解癌症或其他贅生性病狀之症狀的方法。可活化之抗體描述於例如美國專利第8,513,390號、第8,518,404號、第9,120,853號、第9,127,053號及國際公開案第WO 2016/149201號中。
在一些實施例中,本文所提供之可活化之抗CTLA-4抗體包含(i)易普利姆瑪或其抗原結合結構域(AB),諸如易普利姆瑪可變輕鏈(VL);(ii)可裂解部分(CM);及(iii)掩蔽部分(MM)。在一些實施例中,VL偶合於MM,使得MM之偶合降低易普利姆瑪與CTLA-4結合之能力。在一些實施例中,MM藉助於可裂解部分(CM)(亦稱為受質連接子)偶合於VL,該可裂解部分包括蛋白酶,例如在腫瘤微環境中過度表現之蛋白酶之受質。
抗體或其抗原結合片段
在一些實施例中,抗體或其抗原結合結構域(AB)包含抗CTLA-4抗體易普利姆瑪之互補決定區(CDR),在美國專利第6,984,720號及第7,605,238號中識別為10D1,該等專利以全文引用的方式併入。易普利姆瑪(以前亦稱為MDX-010及BMS-734016)以YERVOY®市售且已經過批准用於治療轉移性黑素瘤且處於其他癌症之臨床測試中。參見Hoos等人 (2010)
Semin. Oncol.37:533;Hodi等人 (2010)
N. Engl. J. Med.363:711;Pardoll (2012)
Nat. Immunol.13(12): 1129。
易普利姆瑪具有與大多數人類受體最佳結合之人類IgG1同型(Bruhns等人 (2009)
Blood113: 3716)且考慮相對於活化其結合之Fc受體等效於小鼠IgG2a。因為IgG1與人類NK細胞及單核球所表現之活化受體CD16 (FcγRIIIa)結合,所以易普利姆瑪可調節ADCC。IgG1同型易普利姆瑪最初直接與融合瘤分離但隨後經選殖且在中國倉鼠卵巢(CHO)細胞中表現。儘管考慮到調節ADCC及/或CDC之同型在試圖上調免疫反應之靶向T細胞上之受體的抗體中可能為不期望的,但仍部分保留抗體之IgG1同型,因為其促進食蟹獼猴中之疫苗反應且考慮為功能性的。易普利姆瑪已展示增加血液中之經活化T細胞之數量,如以下所證明:例如HLA-DR在後處理CD4
+及CD8
+細胞之表面上的表現顯著增加以及絕對淋巴細胞計數之增加(Ku等人 (2010)
Cancer116:1767;Attia等人 (2005)
J . Clin . Oncol .23:6043;Maker等人 (2005)
J . Immunol .175:7746;Berman等人 (2009)
J . Clin . Oncol .27(增刊):15s.3020;Hamid等人 (2009)
J . Clin . Oncol .27(增刊): 15s.9008),表明T細胞之耗盡並未發生在人類中之外周。易普利姆瑪表明使用IL-2活化之PBMC作為效應細胞僅中等水準之經活化T細胞之ADCC;然而,未測試T
regs作為標靶之用途。已觀測到在用易普利姆瑪治療之患者之血液中的外周T
reg頻率之少量變化(Maker等人 (2005)
J . Immunol .175:7746),但易普利姆瑪對瘤內T
regs之影響之資訊極少可用。然而,已描述高CD8
+比T
reg比值與用易普利姆瑪治療之患者中之轉移性黑素瘤病變之活檢體中的腫瘤壞死之間的正相關性。Hodi等人 (2008)
Proc. Nat'l Acad. Sci. (USA)105:3005。另外,來自易普利姆瑪治療之膀胱癌患者之腫瘤組織的CD4
+Foxp3
+T細胞之百分比低於來自未經治療之膀胱癌患者之腫瘤的CD4
+Foxp3
+T細胞之百分比。Liakou等人 (2008)
Proc. Nat'l Acad. Sci. (USA)105:14987。
在一些實施例中,可活化之抗CTLA-4抗體包含可變重鏈CDR1 (VH CDR1,在本文中亦稱為CDRH1)、CDR2 (VH CDR2,在本文中亦稱為CDRH2)及CDR3 (VH CDR3,在本文中亦稱為CDRH3)與可變輕鏈CDR1 (VL CDR1,在本文中亦稱為CDRL1)、CDR2 (VL CDR2,在本文中亦稱為CDRL2)及CDR3 (VL CDR3,在本文中亦稱為CDRL3)之組合。此等CDR序列提供於表2中。
表2:易普利姆瑪之重鏈及輕鏈之CDR序列
易普利姆瑪-VL鏈
易普利姆瑪-VH鏈
下文提供如所指示之各種其他序列。
人類κ恆定區LC
小鼠κ恆定區輕鏈
易普利姆瑪-人類κ LC
易普利姆瑪-小鼠κ LC
人類IgG1恆定區HC
小鼠IgG1恆定區HC
小鼠IgG2a恆定區HC
易普利姆瑪-VH-人類IgG1恆定區HC
易普利姆瑪-VH-小鼠IgG1恆定區HC
易普利姆瑪-VH-IgG2a恆定區HC
在一些實施例中,抗體包含VH CDR1序列、VH CDR2序列、VH CDR3序列、VL CDR1序列、VL CDR2序列及VL CDR3序列之組合,其中至少一個CDR序列相比於表2中所示之CDR序列包含1個、2個、3個、4個或更多個胺基酸序列差異,包括保守性胺基酸差異。
在一些實施例中,可活化之抗CTLA-4抗體包含與由SEQ ID NO: 345組成之群至少90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或超過99%一致之重鏈可變結構域。在一些實施例中,可活化之抗CTLA-4抗體包含輕鏈可變結構域,該輕鏈可變結構域不包括任何MM、CM、連接子、間隔子或在建立抗體之可活化形式時所添加之其他序列,其與由SEQ ID NO: 563至SEQ ID NO: 565組成之群至少90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或超過99%一致。
在一些實施例中,在可活化之抗體中結合CTLA-4之抗體或其抗原結合片段可包括修飾,尤其在抗體或其抗原結合片段之Fc區中。舉例而言,抗體與FcγRs之相互作用可藉由改性附著至N297殘基處之各Fc片段的聚糖部分來促進。詳言之,核心海藻糖殘基之缺少藉助於在不改變抗原結合或CDC之情況下IgG與活化FcγRIIIA之改良結合強烈提高ADCC。Natsume等人 (2009)
Drug Des. Devel. Ther. 3:7。存在有說服力的證據證明去海藻糖基化腫瘤特異性抗體在活體內小鼠模型中翻譯成提高之治療活性。Nimmerjahn & Ravetch (2005)
Science310:1510;Mossner等人 (2010)
Blood115:4393。
抗體糖基化之修飾可藉由例如在具有經改變之糖基化機構之宿主細胞中表現抗體來實現。具有經改變之糖基化機構之細胞已描述於此項技術中,且可用作表現本發明之重組抗體以藉此產生具有經改變之糖基化之抗體的宿主細胞。舉例而言,細胞株Ms704、Ms705及Ms709缺乏海藻糖基轉移酶基因FUT8 (α-(1,6) 海藻糖基轉移酶)(參見美國專利申請公開案第20040110704號;Yamane-Ohnuki等人 (2004)
Biotechnol . Bioeng. 87: 614),使得在此等細胞株中表現之抗體在其碳水化合物上缺乏海藻糖。作為另一實例,EP 1176195亦描述與抗體之Fc區結合之具有功能性破壞FUT8基因的細胞株以及具有極少或無用於將海藻糖添加至N-乙醯基葡糖胺的活性之細胞株,例如大鼠骨髓瘤細胞株YB2/0 (ATCC CRL 1662)。PCT公開案WO 03/035835描述一種變異CHO細胞株,Lec13細胞,其將海藻糖附著至Asn (297)連接之碳水化合物的能力降低,亦使得在彼宿主細胞中表現之抗體低海藻糖基化。亦參見Shields等人 (2002)
J. Biol. Chem. 277:26733。具有經修飾之糖基化分佈之抗體亦可產生於雞蛋中,如PCT公開案第WO 2006/089231號中所描述。可替代地,具有經修飾之糖基化分佈之抗體可產生於諸如浮萍之植物細胞中。參見例如美國公開案第2012/0276086號。PCT公開案第WO 99/54342號描述經工程改造以表現醣蛋白修飾之糖基轉移酶(例如β(1,4)-N-乙醯胺基葡萄糖轉移酶III (GnTIII))的細胞株,使得在經工程改造之細胞株中表現的抗體展現增加之二等分GlcNac結構,引起抗體之ADCC活性提高。
亦參見Umaña等人 (1999)
Nat. Biotech. 17:176。可替代地,抗體之海藻糖殘基可使用海藻糖苷酶裂解開。舉例而言,酶α-L-海藻糖苷將海藻糖基殘基自抗體移除。Tarentino 等人 (1975)
Biochem. 14:5516。核心海藻糖基化亦可藉由在諸如在EP2282773B1中所描述之彼等的小分子海藻糖類似物存在下或在如WO 08/052030中所描述之栗樹精胺存在下培養產抗體細胞來減少。
可裂解部分
在一些實施例中,CM對蛋白酶具有特異性,適用於減少針對治療及/或診斷部位處之靶向可活化之抗體活化之腫瘤細胞中的調節異常蛋白酶活性。大量研究已表明固態腫瘤中之異常蛋白酶含量,例如uPA、天冬醯胺內肽酶、MT-SP1、基質金屬蛋白酶(MMP)之相關性。(參見例如,Murthy R V等人 「Legumain expression in relation to clinicopathologic and biological variables in colorectal cancer.」
Clin Cancer Res .11 (2005): 2293-2299;Nielsen B S等人 「Urokinase plasminogen activator is localized in stromal cells in ductal breast cancer.」
Lab Invest81 (2001): 1485-1501;Look O R等人 「In situ localization of gelatinolytic activity in the extracellular matrix of metastases of colon cancer in rat liver using quenched fluorogenic DQ-gelatin.」
J Histochem Cytochem. 51 (2003): 821-829)。
此方法之總體概述論述於美國專利第7,666,817號、第8,513,390號及第9,120,853號及國際公開案第WO 2016/118629號及第WO 2016/149201號,其以全文引用之方式併入。可裂解部分選擇過程用於鑑別具有大量所需特徵之可裂解部分。舉例而言,所選擇之可裂解部分為全身性穩定的(亦即,在個體之全身循環中穩定),通常不易由循環蛋白酶,諸如纖維蛋白溶酶、凝血酶、組織纖維蛋白溶酶原活化因子(tPA)或諸如KLK-5及/或KLK-7之激肽釋放酶(KLK)裂解,為無毒的,通常不易在毒性之潛在部位裂解,諸如由蛋白酶(諸如ADAM 9、ADAM 10、ADAM 17)及/或激肽釋放酶(諸如KLK-5及KLK-7)在皮膚裂解,且在治療及/或診斷之預期部位具有活性。在一些實施例中,所鑑別之可裂解部分經選擇以用於蛋白酶,該等蛋白酶在療法及/或診斷之預期部位過度表現但通常不在正常、健康或其他非患病或非受損組織處或中表現,且隨後所選擇之受質接著針對在正常組織,例如非患病組織中表現之蛋白酶經反篩選。例示性蛋白酶及/或酶提供於如先前所指示之表1中。
在一些實施例中,可裂解部分選自由2001及3001以及其衍生物組成之群。在一些實施例中,可裂解部分選自由以下組成之群:2001 (SEQ ID NO: 297)、2006 (SEQ ID NO: 300)、2007 (SEQ ID NO: 301)、2008 (SEQ ID NO: 302)、2009 (SEQ ID NO: 303)、2012 (SEQ ID NO: 305)、2011 (SEQ ID NO: 304)、2003 (SEQ ID NO: 298)、3001 (SEQ ID NO: 306)、3006 (SEQ ID NO: 307)、3007 (SEQ ID NO: 308)、3008 (SEQ ID NO: 309)、3009 (SEQ ID NO: 310)、3012 (SEQ ID NO: 312)、3011 (SEQ ID NO: 311)及2005 (SEQ ID NO: 299)。表3提供可用於本文所揭示之可活化之抗CTLA-4抗體之其他可裂解部分。
表3.抗CTLA-4可活化可裂解部分
掩蔽部分
本文所提供之可活化之抗CTLA-4抗體包含掩蔽部分(MM)。在一些實施例中,MM係偶合或以其他方式附著至抗CTLA-4抗體且安置在可活化之抗CTLA-4抗體構築體內使得MM降低抗CTLA-4抗體特異性結合CTLA-4之能力的胺基酸序列。在一些實施例中,MM與抗原結合結構域特異性結合。使用各種已知技術中之任一者鑑別合適MM。舉例而言,肽MM使用描述於Daugherty等人之美國專利申請公開案第2009/0062142號及Daugherty等人之2012/0244154中的方法鑑別,該等案之內容以全文引用之方式併入。
在一些實施例中,MM選自由YV01至YV66組成之群且包含選自下表4之胺基酸序列。
表4:抗CTLA4掩蔽部分(MM)
在一些實施例中,針對標靶之包含本文所揭示之MM的可活化之抗CTLA-4抗體之K
d 比針對標靶之未用MM修飾之AB的K
d或親本序列AB之K
d大2、3、4、5、10、25、50、100、250、500、1,000倍或在5-10、10-100、10-200、10-500、10-1,000之間。
在一些實施例中,MM並非可活化之抗體之天然結合搭配物。在一些實施例中,MM不含或實質上不含與可活化之抗體之任何天然結合搭配物之同源性。在一些實施例中,MM與可活化之抗體之任何天然結合搭配物的一致性不超過5%、10%、15%、20%、25%、30%、35%、40%、45%、50%、55%、60%、65%、70%、75%或80%。在一些實施例中,MM與可活化之抗體之任何天然結合搭配物的一致性不超過50%、25%、20%或10%。在一些實施例中,MM與人類CTLA-4的一致性不超過5%、10%、15%、20%、25%、30%、35%、40%、45%、50%、55%、60%、65%、70%、75%或80%。在一些實施例中,MM與人類CTLA-4的一致性不超過50%、25%、20%或10%。
例示性可活化之抗CTLA-4抗體
本文所述之特定抗體係包含表2-表6中提供之掩蔽部分、可裂解部分、輕鏈可變結構域(VL)(或對應CDR)及重鏈可變結構域(VH)(或對應CDR)之任何組合的可活化之抗CTLA-4抗體。在一些實施例中,可活化之抗CTLA-4抗體包含輕鏈,該輕鏈包含易普利姆瑪之YV01 (SEQ ID NO: 1)作為掩蔽部分,LSGRSDNH (SEQ ID NO: 313)作為可裂解部分及輕鏈可變結構域(VL)(SEQ ID NO: 344)。在一些實施例中,可活化之抗CTLA-4抗體包含輕鏈,該輕鏈包含易普利姆瑪之YV01 (SEQ ID NO: 1)作為掩蔽部分,ISSGLLSGRSDNH (2001) (SEQ ID NO: 297)作為可裂解部分及輕鏈可變結構域之CDR (分別為SEQ ID NO: 560、SEQ ID NO: 561及SEQ ID NO: 562)。在一些實施例中,可活化之抗CTLA-4抗體包含易普利姆瑪之重鏈可變結構域(VH) (SEQ ID NO: 345)或僅對應CDR (SEQ ID NO: 557、SEQ ID NO: 558及SEQ ID NO: 559)。
在一些實施例中,可活化之抗CTLA-4包含易普利姆瑪之YV39 (SEQ ID NO: 39)作為掩蔽部分,及ISSGLLSGRSDNP (「2011」) (SEQ ID NO: 304)作為可裂解部分,及重鏈及輕鏈可變域(分別為SEQ ID NO: 345及SEQ ID NO: 344),其中MM及CM呈佈置MM-CM-VL連結至VL。
在一些實施例中,可活化之抗CTLA-4抗體包括信號肽。信號肽可藉由間隔子連結至可活化之抗CTLA-4抗體。在一些實施例中,間隔子在無信號肽存在下與可活化之抗體結合。在一些實施例中,間隔子直接連接至可活化之抗體之MM。在一些實施例中,間隔子具有胺基酸序列QGQSGS (SEQ ID NO: 546)。在一些實施例中,可活化之抗體包含呈「間隔子-MM-CM-VL」或「間隔子-MM-CM-AB」之自N端至C端之結構排列直接連接至MM序列CRTQLYGYNLCPY (YV39) (SEQ ID NO: 39)的序列QGQSGS (SEQ ID NO: 546)之間隔子。
在一些實施例中,可活化之抗CTLA-4抗體包含在MM與CM之間的連接肽(LP)。在一些實施例中,可活化之抗CTLA-4抗體包含在CM與抗體或其抗原結合結構域(AB)之間的連接肽。在一些實施例中,可活化之抗CTLA-4抗體包含第一連接肽(LP1)及第二連接肽(LP2),且其中可活化之抗CTLA-4抗體自N端至C端具有如下結構排列:MM-LP1-CM-LP2-AB。在一些實施例中,可活化之抗CTLA-4抗體之輕鏈自N端至C端具有如下結構排列:MM-LP1-CM-LP2-VL。在一些實施例中,兩種連接肽不必彼此相同。可用於如本文所揭示之可活化之抗CTLA-4抗體之連接肽的實例提供於美國專利公開案第2016/0193332號及國際公開案第WO 2016/149201號,同上。
本發明亦包含經修飾之抗CTLA-4抗體,該抗CTLA-4抗體包含藉助於非蛋白酶可裂解連接子連接至抗體之輕鏈的MM。在一些實施例中,非蛋白酶可裂解連接子包含以SEQ ID NO: 570闡述之胺基酸序列。在一些實施例中,此類經修飾之抗CTLA-4抗體具有包含YV39之輕鏈及非蛋白酶可裂解連接子。在一些實施例中,經修飾之抗CTLA-4抗體之輕鏈包含胺基酸序列:
適用於本文所述之組合物的連接子通常係提供可活化之抗CTLA-4抗體之可撓性以促進抑制可活化之抗體與標靶結合之連接子。此類連接子通常稱為可撓性連接子(在本文中亦稱為連接肽)。合適連接子可經輕易選擇且可為具有不同長度之合適連接子中之任一者,諸如具有1個胺基酸(例如Gly)至20個胺基酸、2個胺基酸至15個胺基酸、3個胺基酸至12個胺基酸,包括4個胺基酸至10個胺基酸、5個胺基酸至9個胺基酸、6個胺基酸至8個胺基酸或7個胺基酸至8個胺基酸,且可為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個胺基酸長。
例示性可撓性連接子包括甘胺酸聚合物(G)n、甘胺酸-絲胺酸聚合物(包括例如(GS)n、(GSGGS)n (GSGGS係SEQ ID NO: 534)及(GGGS)n (GGGS係SEQ ID NO: 535),其中n係至少為1之整數)、甘胺酸-丙胺酸聚合物、丙胺酸-絲胺酸聚合物及此項技術中已知之其他可撓性連接子。甘胺酸及甘胺酸-絲胺酸聚合物係相對非結構化的,且因此能夠充當各組分之間的中性繫鏈。甘胺酸甚至比丙胺酸存取顯著更多的φ-ψ空間,且所受限制比具有較長側鏈之殘基少得多(參見Scheraga,
Rev . Computational Chem. 11173-142 (1992))。例示性可撓性連接子包括但不限於Gly-Gly-Ser-Gly (SEQ ID NO: 536)、Gly-Gly-Ser-Gly-Gly (SEQ ID NO: 537)、Gly-Ser-Gly-Ser-Gly (SEQ ID NO: 538)、Gly-Ser-Gly-Gly-Gly (SEQ ID NO: 539)、Gly- Gly-Gly-Ser-Gly (SEQ ID NO: 540)、Gly-Ser-Ser-Ser-Gly (SEQ ID NO: 541)及其類似物。一般熟練技術人員將認識到可活化之抗體之設計可包括全部或部分為可撓的連接子,使得連接子可包括可撓性連接子以及一或多個賦予較低可撓性結構以提供所需可活化之抗體結構之部分。
在一些實施例中,可活化之抗CTLA-4抗體包含易普利姆瑪之VL及VH (或對應CDR)以及下表5中提供之MM與CM之組合,使得第2列中之任何MM可與第4列中之任何CM組合。
表5.可活化之抗CTLA-4抗體組合
在一些實施例中,可活化之抗CTLA-4抗體包含下表6中提供之MM與CM之特異性組合。
表6.例示性可活化之抗CTLA-4抗體組合
在一些實施例中,本文所述之可活化之抗CTLA-4抗體亦包括與可活化之抗體結合之試劑。在一些實施例中,結合試劑係治療劑,諸如抗腫瘤劑。在一些實施例中,試劑與可活化之抗體之碳水化合物部分結合,較佳地其中碳水化合物部分定位在可活化之抗體中之抗體或抗原結合片段的抗原結合區外部。在一些實施例中,試劑與可活化之抗體中之抗體或抗原結合片段之硫氫基結合。在一些實施例中,試劑與可活化之抗體之抗體或抗原結合片段之胺基結合。在一些實施例中,試劑與可活化之抗體之抗體或抗原結合片段之羧酸基團結合。
在一些實施例中,試劑係細胞毒性劑,諸如毒素(例如,細菌、真菌、植物或動物來源之酶活性毒素或其片段)或放射性同位素(亦即放射性結合物)。
在一些實施例中,結合之可活化之抗體可經修飾以用於藉由插入或以其他方式包括於可活化之抗體序列中之經修飾之胺基酸序列的位點特異性結合。此等經修飾之胺基酸序列經設計以允許結合之可活化之抗CTLA-4抗體內之結合試劑的受控置放及/或給藥。舉例而言,可活化之抗體可經工程改造以包括輕及重鏈上之位置處的半胱胺酸取代,該等取代提供反應性硫醇基且不會不利地影響蛋白質摺疊及組裝,亦不改變抗原結合。在一些實施例中,可活化之抗體可經工程改造以包括或以其他方式在可活化之抗體內引入一或多個非天然胺基酸殘基,從而提供用於結合之合適位點。在一些實施例中,可活化之抗體可經工程改造以包括或以其他方式在可活化之抗體序列內引入酶可活化肽序列。
在一些實施例中,試劑為可偵測部分,諸如標記或其他標記物。舉例而言,試劑為或包括放射性標記胺基酸、可由標記抗生素蛋白偵測之一或多種生物素基部分(例如,可由光學或量熱方法偵測之含有螢光標記物或酶活性的抗生蛋白鏈菌素)、一或多種放射性同位素或放射性核素、一或多種螢光標記、一或多種酶標記及/或一或多種化學發光劑。在一些實施例中,可偵測部分由連接子分子附著。
抗體與細胞毒性劑之結合物係使用多種雙官能蛋白質偶合劑來製備,該等蛋白質偶合劑諸如N-琥珀醯亞胺基-3-(2-吡啶基二硫醇)丙酸酯(SPDP)、亞胺基硫雜環戊烷(IT)、醯亞胺酯之雙官能衍生物(諸如二亞胺代己二酸二甲酯鹽酸鹽)、活性酯(諸如辛二酸二琥珀醯亞胺酯)、醛(諸如戊二醛)、雙疊氮基化合物(諸如雙(對疊氮基苯甲醯基)己二胺)、雙重氮衍生物(諸如雙-(對重氮苯甲醯基)-乙二胺)、二異氰酸酯(諸如2,6-二異氰酸甲苯酯)及雙活性氟化合物(諸如1,5-二氟-2,4-二硝基苯)。舉例而言,蓖麻毒素免疫毒素可如Vitetta等人,
Science238: 1098 (1987)中所述來製備。經碳14標記之1-異硫氰基苯甲基-3-甲基二伸乙三胺五乙酸(MX-DTPA)為使放射性核苷酸結合至抗體之例示性螯合劑(參見WO94/11026)。
一般熟習此項技術者將認識到大量多種可能部分可偶合於本發明之所得抗體(參見例如,「Conjugate Vaccines」, Contributions to Microbiology and Immunology, J. M. Cruse及R. E. Lewis, Jr (編), Carger Press, New York, (1989),其全部內容以引用之方式併入本文中)。
II. 抗 CTLA - 4 可活化之抗體之用途包括可活化之抗CTLA-4抗體之本發明之治療調配物用於預防、治療或以其他方式改善疾病或病症,該疾病或病症包括但不限於與異常CTLA-4表現及/或活性相關之疾病或病症。舉例而言,包括可活化之抗CTLA-4抗體之本發明之治療調配物用作癌症免疫療法,例如增強罹患癌症之個體之內源性免疫反應以便藉此治療個體,該方法包含向個體投與治療有效量之本文所述之可活化之抗CTLA-4抗體中的任一者。
可使用本發明之免疫治療方法治療之癌症的實例包括骨癌、胰臟癌、皮膚癌、頭頸癌、乳癌、肺癌、皮膚或眼內惡性黑素瘤、不可切除性或轉移性黑素瘤、腎癌、子宮癌、卵巢癌、結腸直腸癌、結腸癌、直腸癌、肛門區癌、胃癌、睾丸癌、子宮癌、輸卵管癌、子宮內膜癌、子子宮頸癌、陰道癌、外陰癌、食道癌、小腸癌、內分泌系統癌、甲狀腺癌、副甲狀腺癌、腎上腺癌、軟組織肉瘤、尿道癌、陰莖癌、血液惡性病、兒童固態腫瘤、淋巴球性淋巴瘤、膀胱癌、腎或輸尿管癌、腎盂癌、中樞神經系統(CNS)腫瘤、原發性CNS淋巴瘤、腫瘤血管生成、脊椎軸線腫瘤、腦幹神經膠質瘤、垂體腺瘤、卡堡氏肉瘤(Kaposi's sarcoma)、表皮樣癌、鱗狀細胞癌、環境誘發癌,包括由石棉誘發之癌症、轉移性癌及該等癌症之任何組合。在一些實施例中,癌症選自MEL、RCC、鱗狀NSCLC、非鱗狀NSCLC、CRC、CRPC、頭頸鱗狀細胞癌及食道、卵巢、胃腸道及乳房之癌瘤。本發明方法亦適用於轉移性癌症之治療。
其他癌症包括血液科惡性疾病,包括例如多發性骨髓瘤、B細胞淋巴瘤、霍奇金氏淋巴瘤(Hodgkin lymphoma)/原發性縱隔B細胞淋巴瘤、非霍奇金氏淋巴瘤、急性骨髓淋巴瘤、慢性骨髓性白血病、慢性淋巴性白血病、濾泡性淋巴瘤、彌漫性大B細胞淋巴瘤、伯基特氏淋巴瘤(Burkitt's lymphoma)、免疫胚細胞大細胞淋巴瘤、前驅體B-淋巴母細胞性淋巴瘤、套細胞淋巴瘤、急性淋巴母細胞白血病、蕈樣黴菌病、多形性大細胞淋巴瘤、T細胞淋巴瘤及前驅體T-淋巴母細胞性淋巴瘤以及該等癌症之任何組合。
已知蛋白分解增加為癌症標誌。(參見例如,Affara N I等人 「Delineating protease functions during cancer development.」
Methods Mol Biol. 539 (2009): 1-32)。腫瘤之演進、侵入及癌轉移由其中牽涉蛋白酶之若干相互依存過程引起。此過程通常描述於以全文併入之美國公開案第2016/0193332 A1號中。
在用於治療癌症個體之此等方法的一些實施例中,向個體投與本發明之可活化之抗體,例如可活化易普利姆瑪作為單藥療法。在一些實施例中,免疫調節標靶之刺激或阻斷可與標準癌症治療有效組合,該等治療包括化學治療方案、輻射、手術、激素剝奪及血管生成抑制劑。可活化之抗CTLA-4抗體可連結至抗腫瘤劑(作為免疫結合物)或可與試劑分別投與。在後者情況(分別投藥)中,抗體可在試劑之前、之後或與其同時投與或可與其他已知治療劑共同投與。化學治療藥物除其他之外包括小紅莓(ADRIAMYCIN®)、順鉑、卡鉑、博萊黴素硫酸鹽(bleomycin sulfate)、卡莫司汀(carmustine)、氯芥苯丁酸(LEUKERAN®)、環磷醯胺(CYTOXAN®;NEOSAR®)、來那度胺(lenalidomide)(REVLIMID®)、硼替佐米(bortezomib)(VELCADE®)、地塞米松(dexamethasone)、米托蒽醌(mitoxantrone)、依託泊苷(etoposide)、阿糖胞苷、苯達莫司汀(bendamustine)(TREANDA®)、利妥昔單抗(rituximab)(RITUXAN®)、異環磷醯胺、長春新鹼(ONCOVIN®)、氟達拉賓(fludarabine)(FLUDARA®)、沙立度胺(thalidomide)(THALOMID®)、阿侖單抗(alemtuzumab)(CAMPATH®)、奧伐木單抗(ofatumumab)(ARZERRA®)、依維莫司(everolimus)(AFINITOR®、ZORTRESS®)及卡非佐米(carfilzomib)(KYPROLISTM)。藉助於不同機制操作之抗癌劑之共同投藥可幫助克服對藥物抗性之出現或腫瘤細胞之抗原性的變化。
本發明之可活化之抗CTLA-4抗體,諸如可活化易普利姆瑪亦可用於與其他免疫調節劑組合,該等免疫調節劑諸如針對其他免疫調節受體或其配位體之抗體。已鑑別調節T細胞反應之若干其他共刺激及抑制受體及配位體。刺激受體之實例包括可誘發T細胞共同刺激物(ICOS)、CD137 (4-1BB)、CD134 (OX40)、CD27、糖皮質激素誘發之TNFR相關蛋白(GITR)及疱疹病毒進入介體(HVEM),而抑制受體之實例包括程式化死亡-1 (PD-1)、程式化死亡配位體-1 (PD-L1)、B及T淋巴細胞弱化子(BTLA)、T細胞免疫球蛋白及黏蛋白結構域-3 (TIM-3)、淋巴細胞活化基因-3 (LAG-3)、腺苷A2a受體(A2aR)、殺手細胞凝集素樣受體G1 (KLRG-1)、自然殺手細胞受體2B4 (CD244)、CD160、具有Ig及ITIM結構域之T細胞免疫受體(TIGIT)以及T細胞活化之V結構域Ig抑制因子(VISTA)之受體。Mellman等人 (2011)
Nature480:480;Pardoll (2012)
Nat. Rev. Cancer12: 252;Baitsch等人 (2012)
PloS One7:e30852。
抗-PD-1抗體OPDIVO®(納武單抗(nivolumab))及KEYTRUDA®(派立珠單抗(pembrolizumab))以及抗-PD-L1抗體TECENTRIQ®(阿特珠單抗(atezolizumab))已經過批准以用於治療癌症,且可與本發明之可活化之抗CLTA-4抗體,例如可活化易普利姆瑪組合。此等受體及其配位體提供用於療法之標靶,其經設計以刺激或預防免疫反應之抑制以便藉此攻擊腫瘤細胞。Weber (2010)
Semin. Oncol. 37:430;Flies等人 (2011)
Yale J. Biol. Med. 84:409;Mellman等人 (2011)
Nature480:480;Pardoll (2012) Nat. Rev. Cancer 12:252。刺激受體或受體配位體藉由促效劑靶向,而抑制受體或受體配位體藉由阻斷劑靶向。提高免疫治療抗腫瘤活性之最有前景方法係阻斷所謂的「免疫檢查點」,其指代過多抑制性信號傳遞路徑,該等信號傳遞路徑調節免疫系統且對於維持自身耐受性及調節外周組織中之生理免疫反應之持續時間及幅度以便將間接組織損壞降至最低而言至關重要。參見例如Weber (2010)
Semin. Oncol. 37:430;Pardoll (2012)
Nat. Rev. Cancer12:252。因為許多免疫檢查點藉由配位體受體相互作用啟動,所以其可藉由抗體來阻斷或藉由配位體或受體之重組形式來調節。
適用於本發明之抗-PD-1抗體
此項技術中已知之任何抗-PD-1抗體均可用於當前描述之方法。詳言之,與具有高親和力之PD-1特異性結合之各種人類單株抗體已揭示於美國專利第8,008,449號中。揭示於美國專利第8,008,449號中之抗-PD-1人類化抗體中之每一者已表明呈現以下特徵中之一或多者:(a)與具有1 × 10
- 7M或更小之K
D的人類PD-1結合,如使用Biacore生物感測器系統藉由表面電漿子共振所測定;(b)實質上並未與人類CD28、CTLA-4或ICOS結合;(c)增加混合淋巴細胞反應(MLR)分析中之T細胞增殖;(d)提高MLR分析中之干擾素-γ產量;(e)增加MLR分析中之IL-2分泌;(f)與人類PD-1及食蟹獼猴PD-1結合;(g)抑制PD-L1及/或PD-L2與PD-1之結合;(h)刺激抗原特異性記憶體反應;(i)刺激抗體反應;及(j)抑制活體內腫瘤細胞生長。可用於本發明中之抗-PD-1抗體包括與人類PD-1特異性結合且呈現至少一個、在一些實施例中至少五個前述特徵之單株抗體。
其他抗-PD-1單株抗體已描述於例如以下各者中:美國專利第6,808,710號、第7,488,802號、第8,168,757號及第8,354,509號、美國公開案第2016/0272708號及PCT公開案第WO 2012/145493號、第WO 2008/156712號、第WO 2015/112900號、第WO 2012/145493號、第WO 2015/112800號、第WO 2014/206107號、第WO 2015/35606號、第WO 2015/085847號、第WO 2014/179664號、第WO 2017/020291號、第WO 2017/020858號、第WO 2016/197367號、第WO 2017/024515號、第WO 2017/025051號、第WO 2017/123557號、第WO 2016/106159號、第WO 2014/194302號、第WO 2017/040790號、第WO 2017/133540號、第WO 2017/132827號、第WO 2017/024465號、第WO 2017/025016號、第WO 2017/106061號,其中之每一者以全文引用之方式併入本文中。
在一些實施例中,抗-PD-1抗體選自由以下組成之群:納武單抗(亦稱為「OPDIVO®」;以前表示5C4、BMS-936558、MDX-1106或ONO-4538)、派立珠單抗(Merck,亦稱為「KEYTRUDA®」、拉立珠單抗及MK-3475。參見WO2008156712A1)、PDR001 (Novartis;參見WO 2015/112900)、MEDI-0680 (AstraZeneca;AMP-514;參見WO 2012/145493)、REGN-2810 (Regeneron;參見WO 2015/112800)、JS001 (TAIZHOU JUNSHI PHARMA;參見Si-Yang Liu等人,
J . Hematol . Oncol . 10:136 (2017))、BGB-A317 (Beigene;參見WO 2015/35606及US 2015/0079109)、INCSHR1210 (SHR-1210;Jiangsu Hengrui Medicine;參見WO 2015/085847;Si-Yang Liu等人,
J . Hematol . Oncol . 10:136 (2017))、TSR-042 (ANB011;Tesaro Biopharmaceutical;參見WO2014/179664)、GLS-010 (WBP3055;Wuxi/Harbin Gloria Pharmaceuticals;參見Si-Yang Liu等人,
J . Hematol . Oncol . 10:136 (2017))、AM-0001 (Armo)、STI-1110 (Sorrento Therapeutics;參見WO 2014/194302)、AGEN2034 (Agenus;參見WO 2017/040790)及MGD013 (Macrogenics)。
在一個實施例中,抗PD-1抗體為納武單抗。納武單抗係全人類IgG4 (S228P) PD-1免疫檢查點抑制劑抗體,其選擇性防止與PD-1配位體(PD-L1及PD-L2)相互作用,藉此阻斷抗腫瘤T細胞功能之下調(美國專利第8,008,449號;Wang等人, 2014
Cancer Immunol Res . 2 ( 9 ):846-56)。
在另一實施例中,抗-PD-1抗體係派立珠單抗。派立珠單抗係針對人類細胞表面受體PD-1 (程式化死亡-1或程式化細胞死亡-1)之人類化單株IgG4抗體。派立珠單抗描述於例如美國專利第8,354,509號及第8,900,587號中;亦參見www.cancer.gov/drugdictionary?cdrid=695789 (最後訪問:2014年12月14日)。FDA已批准派立珠單抗用於治療復發性或難治癒黑素瘤。
可用於所揭示之方法的抗-PD-1抗體亦包括與人類PD-1特異性結合且與本文所揭示之任何抗-PD-1抗體交叉競爭與人類PD-1結合的分離抗體,例如納武單抗(參見例如美國專利第8,008,449號及第號8,779,105;WO 2013/173223)。在一些實施例中,抗-PD-1抗體結合與本文所述之任何抗-PD-1抗體,例如納武單抗相同之抗原決定基。抗體交叉競爭與抗原結合之能力指示此等單株抗體與抗原之相同抗原決定基區結合且空間上阻礙其他交叉競爭抗體與特定抗原決定基區之結合。預期此等交叉競爭抗體藉助於其與PD-1之相同抗原決定基區結合具有與參比抗體,例如納武單抗極其類似之功能性特性。基於交叉競爭抗體在標準PD-1結合分析(諸如Biacore分析、ELISA分析或流動式細胞量測術(參見例如WO 2013/173223))中與納武單抗交叉競爭之能力輕易易鑑別交叉競爭抗體。
在某些實施例中,與納武單抗交叉競爭與人類PD-1結合,或與人類PD-1抗體之相同抗原決定基區結合之抗體係單株抗體。為向人類個體投與,此等交叉競爭抗體為嵌合抗體、經工程改造之抗體或為人類化或人類抗體。此類嵌合、經工程改造、人類化或人類單株抗體可藉由此項技術中熟知之方法製備及分離。
可用於本發明所揭示方法中的抗PD-1抗體亦包括以上抗體之抗原結合部分。已充分證實抗體之抗原結合功能可藉由全長抗體之片段進行。
適用於所揭示之方法或組合物之抗-PD-1抗體係與具有高特異性及親和力之PD-1結合,阻斷PD-L1及或PD-L2之結合,且抑制PD-1信號傳遞路徑之免疫抑制效應的抗體。在本文揭示之任一組合物或方法中,抗PD-1「抗體」包括與PD-1受體結合且在抑制配位體結合性及上調免疫系統上具有類似全抗體之功能特性的抗原結合部分或片段。在某些實施例中,抗-PD-1抗體或其抗原結合部分與納武單抗交叉競爭與人類PD-1結合。
適用於本發明之抗PD-L1抗體
任何抗-PD-L1抗體均可用於本發明之方法。適用於本發明之方法之抗PD-L1抗體的實例包括揭示於美國專利第9,580,507號中的抗體。揭示於美國專利第9,580,507號中之每一種抗PD-L1人類單株抗體已證實呈現以下一或多項特徵:(a)與人類PD-L1結合之K
D為1 × 10
- 7M或更低,如使用Biacore生物感測器系統藉由表面電漿子共振所測定;(b)於混合淋巴細胞反應(MLR)分析中,T細胞增殖提高;(c) 於MLR分析中,干擾素-γ產量提高;(d) 於MLR分析中,IL-2分泌增加;(e)刺激抗體反應;及(f)逆轉T調節細胞對T細胞效應細胞及/或樹突狀細胞之影響。可用於本發明中之抗PD-L1抗體包括與人類PD-L1特異性結合且具有至少一項,在一些實施例中為至少五項前述特徵之單株抗體。
在某些實施例中,抗-PD-L1抗體選自由以下組成之群:BMS-936559 (過去稱為12A4或MDX-1105;參見例如美國專利第7,943,743號及WO 2013/173223)、MPDL3280A (亦稱為RG7446、阿特珠單抗及TECENTRIQ®;US 8,217,149;
亦參見,Herbst等人 (2013) J Clin Oncol 31(增刊):3000)、德瓦魯單抗(durvalumab)(IMFINZI™;MEDI-4736;AstraZeneca;參見WO 2011/066389)、巴文西亞(avelumab)(Pfizer;MSB-0010718C;BAVENCIO®;參見WO 2013/079174)、STI-1014 (Sorrento;參見WO2013/181634)、CX-072 (CytomX;參見WO2016/149201)、KN035 (3D Med/Alphamab;參見Zhang等人,
Cell Discov . 7:3 (2017年3月))、LY3300054 (Eli Lilly Co.;參見例如, WO 2017/034916)及CK-301 (核查點療法;參見Gorelik等人, AACR:Abstract 4606 (2016年4月))。
在某些實施例中,PD-L1抗體係阿特珠單抗(TECENTRIQ®)。阿特珠單抗係完全人類化IgG1單株抗-PD-L1抗體。
在某些實施例中,PD-L1抗體係德瓦魯單抗(IMFINZI™)。德瓦魯單抗係人類IgG1 κ單株抗-PD-L1抗體。
在某些實施例中,PD-L1抗體係巴文西亞(BAVENCIO®)。巴文西亞係人類IgG1 λ單株抗-PD-L1抗體。
在其他實施例中,抗PD-L1單株抗體選自由以下組成之群:28-8、28-1、28-12、29-8、5H1及其任何組合。
可用於所揭示之方法之抗PD-L1抗體亦包括與人類PD-L1特異性結合且與本文所揭示之任何抗-PD-L1抗體交叉競爭與人類PD-L1結合的分離抗體,例如阿特珠單抗及/或巴文西亞。在一些實施例中,抗-PD-L1抗體結合與本文所述之抗PD-L1抗體中之任一者,例如阿特珠單抗及/或巴文西亞相同的抗原決定基。抗體交叉競爭與抗原結合之能力指示此等抗體與抗原之相同抗原決定基區結合且空間上阻礙其他交叉競爭抗體與特定抗原決定基區之結合。預期此等交叉競爭抗體藉助於其與PD-L1之相同抗原決定基區結合具有與參比抗體,例如阿特珠單抗及/或巴文西亞極其類似之功能性特性。基於交叉競爭抗體在標準PD-L1結合分析(諸如Biacore分析、ELISA分析或流動式細胞量測術(參見例如WO 2013/173223))中與阿特珠單抗及/或巴文西亞交叉競爭之能力輕易易鑑別交叉競爭抗體。
在某些實施例中,與阿特珠單抗及/或巴文西亞交叉競爭與人類PD-L1結合或結合與阿特珠單抗及/或巴文西亞相同的人類PD-L1抗體之抗原決定基區的抗體係單株抗體。為向人類個體投與,此等交叉競爭抗體為嵌合抗體、經工程改造之抗體或為人類化或人類抗體。此類嵌合、經工程改造、人類化或人類單株抗體可藉由此項技術中熟知之方法製備及分離。
可用於本發明所揭示方法中的抗PD-L1抗體亦包括以上抗體之抗原結合部分。已充分表明抗體之抗原結合功能可藉由全長抗體之片段進行。
適用於所揭示之方法或組合物之抗PD-L1抗體係與具有高特異性及親和力之PD-L1結合,阻斷PD-1之結合,且抑制PD-1信號傳遞路徑之免疫抑制影響的抗體。在任一本文揭示之組合物或方法中,抗PD-L1「抗體」包括與PD-L1結合且展現類似於全抗體抑制受體結合及上調免疫系統之功能特性的抗原結合部分或片段。在某些實施例中,抗-PD-L1抗體或其抗原結合部分與阿特珠單抗及/或巴文西亞交叉競爭與人類PD-L1結合。
預防、改善或治療之有效性與用於診斷或治療疾病或病症之任何已知方法結合確定,該疾病或病症包括但不限於與異常CTLA-4表現及/或活性相關之疾病或病症。延長個體存活率或以其他方式延緩包括但不限於與個體之異常CTLA-4表現及/或活性相關之疾病或病症的疾病或病症的演進指示可活化之抗體賦予臨床益處。
應瞭解,根據本發明之治療性實體將與適合載劑、賦形劑及併入調配物中以提供經改良之轉移、遞送、耐受性及類似者的其他試劑一起投與。多種適當的調配物可以見於所有醫藥化學家已知之處方集中:Remington's Pharmaceutical Sciences (第15版,Mack Publishing Company, Easton, Pa. (1975)),尤其其中之Blaug、Seymour的第87章。此等調配物包括例如散劑、糊劑、軟膏、凝膠劑、蠟、油、脂質、含有脂質(陽離子或陰離子型)之微脂粒(諸如Lipofectin™)、DNA結合物、無水吸收糊劑、水包油及油包水乳液、乳液聚乙二醇(各種分子量之聚乙二醇)、半固體凝膠及含有聚乙二醇之半固體混合物。前述混合物中之任一者可以適用於根據本發明之治療及療法中,限制條件為調配物中之活性成分未因該調配物而失活且該調配物係生理上相容的且可耐受投藥途徑。
亦參見Baldrick P. 「Pharmaceutical excipient development: the need for preclinical guidance.」
Regul . Toxicol Pharmacol. 32(2):210-8 (2000),Wang W. 「Lyophilization and development of solid protein pharmaceuticals.」
Int . J . Pharm. 203(1-2):1-60 (2000),Charman W N 「Lipids, lipophilic drugs, and oral drug delivery-some emerging concepts.」
J Pharm Sci. 89(8):967-78 (2000),Powell等人 「Compendium of excipients for parenteral formulations」
PDA J Pharm Sci Technol. 52:238-311 (1998)及與醫藥化學家所熟知之調配物、賦形劑及載劑相關之額外資訊的其中引用。
可活化之抗CTLA-4抗體可呈醫藥組合物形式投與。涉及製備此類組合物之原理及考慮以及選擇組分之指導提供於例如Remington: The Science And Practice Of Pharmacy 第19版 (Alfonso R. Gennaro等人,編者) Mack Pub. Co., Easton, Pa.: 1995;Drug Absorption Enhancement: Concepts, Possibilities, Limitations, And Trends, Harwood Academic Publishers, Langhorne, Pa., 1994;及Peptide And Protein Drug Delivery (Advances In Parenteral Sciences, 第4卷), 1991, M. Dekker, New York中。
調配物亦可含有超過一種為所治療之特定適應症所必需之活性化合物,較佳為具有不會對彼此產生不利影響之互補活性的活性化合物。可替代地或另外,組合物可包含提高其功能之試劑,諸如細胞毒性劑、細胞介素、化學治療劑或生長抑制劑。此類分子適合地以對預期目的有效之量存在於組合中。
亦可例如藉由凝聚技術或藉由界面聚合將活性成分包埋於所製備之微膠囊中,例如羥基甲基纖維素或明膠微膠囊及聚-(甲基丙烯酸甲酯)微膠囊分別包埋於膠狀藥物遞送系統(例如脂質體、白蛋白微球體、微乳液、奈米粒子及奈米囊劑)中或於巨乳液中。
用於體內投藥之調配物必須為無菌的。此容易藉由無菌過濾膜過濾來完成。
可製備持續釋放製劑。持續釋放型製劑之適合實例包括含有抗體之固體疏水性聚合物之半滲透基質,該等基質呈成形物品形式,例如膜或微膠囊。持續釋放基質之實例包括聚酯、水凝膠(例如,聚(2-羥乙基-甲基丙烯酸酯)或聚(乙烯醇))、聚乳酸交酯(美國專利第3,773,919號)、L-麩胺酸與γ乙基-L-麩胺酸之共聚物、不可降解乙烯-乙酸乙烯酯、諸如LUPRON DEPOT
TM(由乳酸-乙醇酸共聚物及亮丙瑞林乙酸酯(leuprolide acetate)構成之可注射微球體)之可降解乳酸-乙醇酸共聚物及聚-D-(-)-3-羥基丁酸。雖然諸如乙烯-乙酸乙烯酯及乳酸-乙醇酸之聚合物允許持續超過100天釋放分子,但某些水凝膠持續較短時間段釋放蛋白質。
在一些實施例中,可活化之抗體含有可偵測標記。可以使用完整抗體或其片段(例如Fab、scFv或F(ab)2))。關於探針或抗體之術語「標記」意圖涵蓋藉由將可偵測物質偶合(亦即,以物理方式連接)至探針或抗體進行的探針或抗體之直接標記,以及藉由與經直接標記之另一試劑反應進行的探針或抗體之間接標記。間接標記之實例包括使用螢光標記之二次抗體偵測一次抗體,及用生物素對DNA探針末端標記以使其可用螢光標記之抗生蛋白鏈菌素偵測。術語「生物樣品」意欲包括自個體分離之組織、細胞及生物流體,以及存在於個體之組織、細胞及流體。因此,在術語「生物樣品」之用法內包括血液及血液之部分或組分,包括血清、血漿,或淋巴。舉例而言,可以用放射性標記物對抗體標記,該放射性標記物在個體體內之存在及位置可以藉由標準成像技術偵測。
III. 醫藥組合物本發明之可活化之抗CTLA-4抗體(在本文中亦稱為「活性化合物」)及其衍生物、片段類似物及同系物可併入適合於投藥之醫藥組合物中。此類組合物通常包含可活化之抗體及醫藥學上可接受之載劑。如本文所用,術語「醫藥學上可接受之載劑」意欲包括與醫藥上投藥相容之任何及所有溶劑、分散介質、包衣、抗菌及抗真菌劑、等張性及吸收延遲劑及類似物。合適載劑描述於領域中之標準參考文本-最新版之Remington's Pharmaceutical Sciences中,其以引用之方式併入本文中。此類載劑或稀釋劑之較佳實例包括但不限於水、鹽水、林格氏(Ringer's)溶液、右旋糖溶液及5%人類血清白蛋白。亦可使用脂質體及非水性媒劑,諸如不揮發性油。此類介質及試劑用於醫藥活性物質之用途為此項技術中所熟知。除非任何習知介質或試劑與活性化合物不相容,否則考慮其在組合物中之用途。補充活性化合物亦可併入至組合物中。
將本發明之醫藥組合物調配成與其預期投藥途徑相容。投藥途徑之實例包括非經腸,例如靜脈內、皮內、皮下、經口(例如吸入)、經皮(亦即,局部)、經黏膜及直腸投藥。用於非經腸、皮內或皮下施用之溶液或懸浮液可包括以下組分:無菌稀釋劑,諸如注射用水、鹽水溶液、不揮發性油、聚乙二醇、丙三醇、丙二醇或其他合成溶劑;抗菌劑,諸如苄醇或對羥基苯甲酸甲酯;抗氧化劑,諸如抗壞血酸或亞硫酸氫鈉;螯合劑,諸如乙二胺四乙酸(EDTA);緩衝劑,諸如乙酸鹽、檸檬酸鹽或磷酸鹽;及張力調節劑,諸如氯化鈉或右旋糖。可用酸或鹼,諸如鹽酸或氫氧化鈉調節pH值。非經腸製劑可封裝於由玻璃或塑膠製成的安瓿、拋棄式注射器或多劑量小瓶中。
適用於可注射用途之醫藥組合物包括無菌水溶液(其中水可溶)或分散液及用於無菌可注射溶液或分散液之即用型製劑之無菌散劑。關於靜脈內投與,適合載劑包括生理食鹽水、抑菌水、Cremophor EL™ (BASF, Parsippany, N.J.)或磷酸鹽緩衝鹽水(PBS)。在所有情況下,組合物必須為無菌的且流動性應達到存在易於注射能力之程度。其必須在製造及儲存條件下穩定,且必須保護其免遭微生物(諸如細菌及真菌)之污染作用。載劑可為含有例如水、乙醇、多元醇(例如,丙三醇、丙二醇及液體聚乙二醇及其類似物)及其合適混合物之溶劑或分散介質。可例如藉由使用諸如卵磷脂之包衣、在分散液之情況下藉由維持所需粒度及藉由使用界面活性劑來維持適當流動性。微生物作用之防止可藉由各種抗菌及抗真菌劑達成,例如對羥基苯甲酸酯、氯丁醇、酚、抗壞血酸、硫柳汞及其類似物。在許多情況下,組合物中將較佳包括等張劑,例如糖、多元醇(諸如甘露醇、山梨醇)、氯化鈉。可藉由將延遲吸收之試劑(例如單硬脂酸鋁及明膠)包括在組合物中而實現可注射組合物之延長吸收。
無菌可注射溶液可藉由如下方法製備:將所需量之活性化合物與上文所列舉之成分中之一者或組合一起併入適當溶劑中,視需要隨後進行過濾滅菌。一般而言,分散液藉由將活性化合物併入含有鹼性分散介質及來自以上所列舉之成分的所需其他成分的無菌媒劑中來製備。在用於製備無菌可注射溶液之無菌散劑之情況下,製備方法係真空乾燥及冷凍乾燥,其自其先前經無菌過濾之溶液產生活性成分加上任何其他所需成分之散劑。
對於藉由吸入之投藥,化合物可以氣溶膠噴霧之形式自含有合適推進劑(例如,諸如二氧化碳之氣體)之加壓容器或分配器或噴霧器來遞送化合物。
全身性投藥亦可藉由經黏膜或經皮方式。對於經黏膜或經皮投藥,在調配物中使用適於滲透阻障之滲透劑。此類滲透劑通常為此項技術中已知,且對於經黏膜投藥,包括例如清潔劑、膽汁鹽及梭鏈孢酸衍生物。經黏膜投藥可經由使用經鼻噴霧或栓劑實現。對於經皮投藥,如此項技術中一般已知將活性化合物調配成軟膏、油膏、凝膠或乳膏。
本發明之可活化之抗體亦可與促進單一部位處之大量體積之注射的試劑(間質藥物分散劑)結合,該等試劑諸如可溶性中性活性玻尿酸酶糖蛋白(sHASEGP),例如人類可溶性pH-20玻尿酸酶糖蛋白,諸如rHuPH20 (HYLENEX®,Baxter International, Inc.)。某些例示性sHASEGP及使用方法,包括rHuPH20,描述於美國專利公開案第2005/0260186號及第2006/0104968號中。在一個態樣中,sHASEGP與一或多種其他葡萄糖胺聚糖酶(諸如軟骨素酶)組合。
化合物亦可以用於直腸遞送之栓劑(例如,具有習知栓劑基質,諸如可可豆油及其他甘油酯)或保留灌腸劑形式製備。
在一些實施例中,活性化合物係用防止化合物自體內快速排除的載劑製備,諸如控制釋放型調配物,包括植入物及微囊封遞送系統。可使用可生物降解、生物相容性聚合物,諸如乙烯乙酸乙烯酯、聚酸酐、聚乙醇酸、膠原蛋白、聚原酸酯及聚乳酸。用於製備此類調配物之方法將為熟習此項技術者顯而易見的。材料亦可商業上獲自Alza Corporation and Nova Pharmaceuticals, Inc。脂質體懸浮液(包括靶向具有針對病毒抗原之單株抗體之經感染細胞的脂質體)亦可用作醫藥學上可接受之載劑。此等物質可根據熟習此項技術者已知之方法製備,例如如美國專利第4,522,811號中所描述。
為了易於投藥及劑量均一性而按單位劑型來調配經口或非經腸組合物為尤其有利的。如本文所用之單位劑型係指適合作為單位劑量用於待治療之個體的物理個別單元;各單元含有經計算可產生所需治療效果的預定數量之活性化合物與所需醫藥載劑結合。本發明之單位劑型之規格由以下因素規定且直接視以下因素而定:活性化合物之獨特特徵及欲達成之特定治療效果,及混配此類活性化合物用於治療個體之此項技術中固有的侷限性。
醫藥組合物可與投藥說明書一起包括於容器、包裝或分配器中。
本發明之實施例可參考以下非限制性實例來進一步定義,該等非限制性實例詳細描述本發明之某些抗體的製備及使用本發明之抗體的方法。熟習此項技術者將顯而易見,在不背離本發明之範疇情況下,可對材料與方法二者作出許多修改。
本發明將進一步描述於以下實例中,其不限制申請專利範圍中所描述之本發明的範疇。
實例
實例1:
可活化之抗CTLA-4抗體之掩蔽部分之鑑別
為鑑別減少抗CTLA-4抗體與其靶蛋白結合之掩蔽部分(MM),使用類似於PCT國際公開案第WO 2009/025846號、第WO 2010/081173號及第WO 2016/149201號中所描述之方法的方法使用抗CTLA-4抗體(亦即,易普利姆瑪)篩選肽程式庫,該等案之內容以其全文引用之方式併入。篩選由兩輪磁性活化細胞分類(MACS)純化繼之以三輪螢光活化細胞分類(FACS)組成。
初始MACS純化利用濃度為100 nM之蛋白質-A Dynabeads® (Invitrogen)及抗CTLA-4抗體進行。約10
11個細胞經篩選用於結合,且收集6×10
6個細胞。第二次MACS純化利用濃度為100 nM之抗生蛋白鏈菌素DYNABEADS® (Thermo Fisher Scientific)及生物素標記之抗CTLA-4抗體進行。擴展來自初始MACS純化之溶離液,約10
11個細胞經篩選以用於結合,且收集約10
7個細胞。利用以Alexa Fluor® 488 (Thermo Fisher Scientific)標記之降低濃度之抗CTLA-4使先前所描述之MACS純化之輸出物經受連續輪之FACS分類。分別使用濃度為10 nM、1 nM及200 PM之標記之抗CTLA4抗體用於第一次、第二次及第三次分類。藉由序列分析鑑別來自第三次分類之單獨肽純系且隨後檢驗其結合抗CTLA4抗體之能力。針對選擇兩種肽共同序列:XXCXXXMYGYNLCPY (SEQ ID NO: 554)及XXXCXHSMYNVCLDP (SEQ ID NO: 555)。
基於表7如所描述之此等共同序列構建親和力成熟程式庫。第1行及第3行表示共同序列且第2行及第4行表示編碼肽程式庫之核苷酸序列,該等核苷酸序列使用類似於PCT國際公開案第WO 2010/081173號,同上中所描述之方法的方法插入於顯示系統中。
表7:成熟程式庫
以類似於針對上文所述之未處理程式庫所描述之方式的方式篩選成熟程式庫。篩選由一輪MACS及後續輪之FACS分類組成。MACS利用濃度為100 nM之蛋白質-A DYNABEADS® (Thermo Fisher Scientific)及抗CTLA-4抗體進行。對於MACS而言,約10
11個細胞經篩選用於結合,且選擇約10
8個細胞。擴展來自MACS之溶離液,且利用降低濃度之Alexa Fluor® 488標記之抗CTLA-4使約10
11個細胞經受連續輪之FACS分類。使用濃度為100 nM、20 nM、5 nM、1 nM及1 nM之標記之抗CTLA4抗體分別用於第一次、第二次、第三次、第四次及第五次分類。藉由序列分析鑑別來自第四次及第五次分類之單獨肽純系且隨後檢驗其結合抗CTLA4抗體之能力。藉由上文所述之方法鑑別之抗CTLA-4掩蔽部分的序列提供於表4及表5中。四種共同序列可衍生自表4及表5中列出之掩蔽序列:
共同1. C(L/M/V/T)Y(S/V/I)(F/L/M/A)(Y/F)N(V/I)CLDP (SEQ ID NO: 566)
共同2. CAQMYGYSMC(P/A)(H/R/A)T (SEQ ID NO: 567)
共同3. CX(M/I/Y/L/N/F)(Y/W/F/Q/T)(M/Y)YG(Y/V/F)(N/D)LCP(Y/F) (SEQ ID NO: 568)
共同4. (N/T)(S/T/M/A)CP(N/Y)HP(M/L)C(H/F/Y)D(Y/F/W) (SEQ ID NO: 569)
實例2:
可活化之抗muCTLA-4抗體之構建及特徵
為展示可活化之抗CTLA-4抗體可用於治療腫瘤之概念驗證,使用類似於本文中之實例1及實例3中所揭示之彼等技術的技術構建六種可活化之抗小鼠CTLA-4抗體(基於純系9D9)。此等抗體包含MY11或MY03作為掩蔽部分,及可裂解部分:具有胺基酸序列TSTSGRSANPRG (SEQ ID NO: 320)之「0003」、具有胺基酸序列AVGLLAPP (SEQ ID NO: 323)之「1004」或具有胺基酸序列ISSGLLSGRSDNH (SEQ ID NO: 297)之「2001」。抗體均為小鼠IgG2a同型。作為對照,使用抗小鼠CTLA-4單株抗體(9D9)(「9D9 mg2a」)及具有mIgG2a同型之人類抗白喉毒素抗體(「mg2a」)。
在第0天,對BALB/c小鼠皮下注射1 × 10
6個CT26腫瘤細胞。在腫瘤植入後第7天開始投與不同抗體。在投藥之前,量測腫瘤大小且將小鼠隨機分組為不同治療組,以便具有可比較之平均腫瘤體積(例如,39-44 mm
3)。利用測徑規二維量測腫瘤,且腫瘤體積以L×(W
2/2)計算,L =長度(2次量測之較長者),W =寬度。隨後用指定抗體(例如25微克/劑量)腹膜內(i.p.)治療小鼠。每週兩次量測腫瘤體積。在腫瘤植入後第12天,處死各組中之一些小鼠,且收集腫瘤及脾用於免疫監測從而調查抗體對T細胞群體之影響。不同組中之剩餘小鼠中之一些或全部用於後續藥物動力學(PK)及/或藥物效應動力學(PD)分析。
如圖1A中所示,接受不相關小鼠IgG2a抗體(亦即,人類抗白喉毒素抗體)之小鼠未能控制腫瘤。相比之下,如圖1C中所示,接受可活化之抗小鼠CTLA-4抗體(包含MY11作為掩蔽部分及2001作為可裂解部分)之小鼠幾乎如同接受抗小鼠CTLA-4 mAb (9D9) 之彼等小鼠(圖1B)一樣控制腫瘤大小。此等資料表明腫瘤特異性蛋白酶可使可裂解部分裂解,從而導致移除掩蔽部分且釋放抗體與其靶蛋白結合。
為確定可活化之抗小鼠CTLA-4抗體在外周是否具有活性,測定脾中Foxp3+調節T細胞之增殖及活性,且測定腫瘤樣品中調節T細胞豐度以用於比較,如實例5中所描述,見下文。與圖1B及圖1C中之資料一致,所有可活化之抗CTLA-4抗體均表現地類似於腫瘤中之抗小鼠CTLA-4mAb (9D9)(圖2A)。相比之下,可活化之抗體類似於脾中之不相關小鼠IgG2a抗體(圖2B及圖2C)。此類資料表明,可活化之抗小鼠CTLA-4抗體之含掩蔽部分之前結構域保持完整且在脾中附著至抗體,從而阻斷抗體活性,而前結構域由腫瘤特異性蛋白酶裂解從而在腫瘤中產生完全活性抗CTLA-4抗體。
實例3:
可活化之抗人類CTLA-4抗體之構建
包含抗CTLA4掩蔽部分、可裂解部分及本發明之抗CTLA4抗體(例如易普利姆瑪)的可活化之抗CTLA4抗體根據類似於PCT公開案第WO 2009/025846號,同上及第WO 2010/081173號,同上,以及第WO 2016/118629號,同上中所描述之彼等方法的方法製造。可活化之抗CTLA4抗體在EXPI293™細胞(Thermo Fisher Scientific)中表現且根據製造商之方案藉由蛋白A層析法(MabSelect SuRe, GE Healthcare)純化。所得可活化之抗體之品質控制指示大多數包含至少95%單體。
為評估在人類環境中使用本文所揭示之可活化之抗CTLA-4抗體的可行性,抗體按人類IgG1(hIgG1)重鏈(Hc)及人類κ (hK)輕鏈(Lc)型式製造。可活化之抗體均包含易普利姆瑪之抗體或其抗原結合結構域。可裂解部分選自由以下組成之群:在本文中稱為「2001」且包含序列ISSGLLSGRSDNH (SEQ ID NO: 297)及其衍生物之可裂解部分及在本文中稱為「3001」且包含序列AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306)及其衍生物的可裂解部分。在一些實施例中,可裂解部分選自由以下組成之群:在本文中亦稱為「2001」之ISSGLLSGRSDNH (SEQ ID NO: 297);在本文中亦稱為「2006」之ISSGLLSGRSDDH (SEQ ID NO: 300);在本文中亦稱為「2007」之ISSGLLSGRSDIH (SEQ ID NO: 301);在本文中亦稱為「2008」之ISSGLLSGRSDQH (SEQ ID NO: 302);在本文中亦稱為「2009」之ISSGLLSGRSDTH (SEQ ID NO: 303);在本文中亦稱為「2012」之ISSGLLSGRSANP (SEQ ID NO: 305);在本文中亦稱為「2011」之ISSGLLSGRSDNP (SEQ ID NO: 304);在本文中亦稱為「2003」之ISSGLLSGRSANPRG (SEQ ID NO: 298);在本文中亦稱為「3001」之AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306);在本文中亦稱為「3006」之AVGLLAPPGGLSGRSDDH (SEQ ID NO: 307);在本文中亦稱為「3007」之AVGLLAPPGGLSGRSDIH (SEQ ID NO: 308);在本文中亦稱為「3008」之AVGLLAPPGGLSGRSDQH (SEQ ID NO: 309);在本文中亦稱為「3009」之AVGLLAPPGGLSGRSDTH (SEQ ID NO: 310);在本文中亦稱為「3012」之AVGLLAPPGGLSGRSANP (SEQ ID NO: 312);在本文中亦稱為「3011」之AVGLLAPPGGLSGRSDNP (SEQ ID NO: 311);及在本文中亦稱為「2005」之AVGLLAPPSGRSANPRG (SEQ ID NO: 299)。掩蔽部分選自表4及表5中提供之掩蔽部分的群組。在一些實施例中,掩蔽部分為在本文中稱為YV39之CRTQLYGYNLCPY (SEQ ID NO: 39)。一些可活化之抗CTLA-4抗體亦包括間隔子序列及/或連接肽。
實例4:
可活化之抗人類CTLA-4抗體之活體外特徵化
為評估在無蛋白酶活性存在下可活化之抗體與CTLA-4結合之能力,使用酶聯結免疫吸附分析法(ELISA)量測結合親和力。簡言之,利用100微升/孔人類CTLA-4蛋白質(Sino Biological)於PBS,pH 7.4中之1 μg/mL溶液在40℃下塗佈Nunc MaxiSorp
®板隔夜。隨後用PBST (PBS,pH 7.4,0.05% Tween-20)將板洗滌三次,且在室溫下用PBST中之200 微升/孔,10 mg/mL牛血清白蛋白(BSA)阻斷孔,持續2小時。之後,用PBST再洗滌板3次。隨後連續稀釋可活化之抗體,如下表8中所示。
表8.用於結合分析之可活化之抗CTLA-4抗體之連續稀釋
在當前實例中,用於親本序列抗體及可活化之抗體之最高濃度分別為10 nM及100 nM。然而,濃度可提高或降低以獲得具有較強或較弱掩蔽之可活化之抗體之完全飽和結合曲線。
將經稀釋之抗體添加至板中且在室溫下培育1小時。之後,用PBST洗滌板3次。隨後,將100 µL山羊-抗人類IgG (Fab特異性,Sigma目錄編號A0293;在10 mg/mL 於PBST中之BSA中以1:4,000稀釋)添加至各孔中,且在室溫下將板培育另外1小時。接著,用四甲基聯苯胺(TMB)及1 N HCl使板顯色。隨後量測450 nm處之吸光度且報導為光學密度(OD 450 nm)。
如圖3A至圖3E中所示,抗CTLA-4可活化之抗體相比於易普利姆瑪(「YV1」)通常具有與CTLA-4降低之結合。
亦參見圖4A至圖4D、圖5A至圖5F及圖6A至圖6B。此類資料表明掩蔽部分有效隱藏抗CTLA-4可活化之抗體上之抗原結合結構域。
為進一步評估結合能力,可活化人類抗CTLA-4抗體經連續稀釋(例如,60 µg/mL至0.0003 µg/mL)且添加至58 α-β- CTLA-4/CD3ζ細胞中,該等細胞穩定表現人類CTLA-4。在4℃下培育30分鐘後,添加別藻藍蛋白(APC)標記之抗人類二次抗體且使用Canto流式細胞儀評估可活化之抗人類CTLA-4抗體與人類CTLA-4之結合。使用FlowJo
®分析軟體測定幾何平均螢光強度(GMFI)。易普利姆瑪用作對照。如圖7A及圖7B中所示,可活化人類抗CTLA-4抗體未與易普利姆瑪一樣有效與人類CTLA-4結合。此等資料進一步表明在無特異性蛋白酶存在下,可活化之抗體之掩蔽部分抑制此類可活化之抗體與人類CTLA-4之結合。
為證實用可活化之抗CTLA-4抗體觀測到之降低之結合歸因於掩蔽部分,針對包含YV39作為掩蔽部分及2011作為可裂解部分之可活化之抗體之單一削減、MMP完全削減及uPA完全削減的形式進行研究。抗體之單一削減形式藉由表現產生一個完整輕鏈(包括掩蔽部分)及在同一位置如同其已由MMP14裂解一樣截斷之第二輕鏈的構築體製造。MMP或uPA完全削減之形式自具有如同其已分別由MMP或µPA裂解一樣截斷之兩個輕鏈的構築體表現。如圖7C及圖7D中所示,單一削減之可活化之抗體相比於未削減之可活化之抗體(EC50 = 22 nM)及易普利姆瑪(EC50 = 0.54 nM)具有中間結合(EC50 = 2.8 nM)。相比之下,MMP或uPA完全削減之可活化之抗體表現地類似於易普利姆瑪(MMP削減:EC50 = 0.65 nM;µPA削減:EC50 = 0.76)。此類資料證實用可活化之抗CTLA-4抗體觀測到之降低之結合歸因於掩蔽部分。
接著,為確定所觀測到之與CTLA-4降低之結合與降低之活性相關,使用葡萄球菌腸毒素B (SEB)使包含YV39作為掩蔽部分及2011作為可裂解部分之可活化人類抗CTLA-4抗體(「Ipi YV39 2011」)之活性在活體外功能性分析中表徵。SEB係強烈活化T細胞且刺激細胞介素分泌之超抗原。使用標準Ficoll-Paque分離方法將完全新鮮之外周血液單核細胞(PBMC)自健康人類供體中分離。進行抗體之連續稀釋(例如,40 µg/mL至0.01 µg/mL)且在96孔平底組織培養板中一式三份地接種。所用之抗體包括(i) Ipi YV39 2011、(ii)易普利姆瑪及(iii)不相關同型對照。接著,將分離之PBMC再懸浮於T細胞分析培養基(RPMI介質+10%加熱不活化胎牛血清(HI-FBS)+1% HEPES緩衝液+1% MEM非必需胺基酸+1%丙酮酸鈉)中且添加至每孔1×10
5個細胞之板中。用次最佳濃度(例如,85 ng/mL-藉由滴定SEB測定且觀測對T細胞增殖之刺激)之SEB刺激細胞。將細胞在37℃下培育3天。隨後,藉由均質時差式螢光(HTRF)量測上清液中之IL-2濃度。使用Softmax Pro分析HTRF資料且使用GraphPad Prism繪成圖。
如圖8中所示,易普利姆瑪以劑量依賴性方式藉由PBMC提高SEB調節之IL-2產量。相比之下,Ipi YV39 2011可活化之抗體之活性類似於同型對照之活性,表明掩蔽部分(YV39)有效阻斷易普利姆瑪之功能活性。此等資料與上文所述之結合資料一致且表明在無特異性蛋白酶存在下,可活化之抗人類CTLA-4抗體呈現降低之活性。
實例5:
可活化之抗人類CTLA-4抗體之活體內特徵
為活體內表徵本文所揭示之抗體,使用小鼠IgG2a製備四種可活化人類抗人類CTLA-4抗體(基於易普利姆瑪)。抗體包含YV04、YV23、YV24或YV39作為掩蔽部分及2001作為可裂解部分(分別為「Ipi YV04 2001」、「Ipi YV23 2001」、「Ipi YV24 2001」及「Ipi YV39 2001」)。作為對照,使用易普利姆瑪(「Ipi mg2a」)及不相關人類抗白喉毒素(「對照mg2a」)。使用如下所述之MC38腫瘤模型評估此等可活化之抗CTLA-4抗體之活性。
簡言之,在第0天,將2 × 10
6個MC38結腸腺癌細胞注入人類CTLA-4基因嵌入C57BL/6小鼠左下腹部。利用測徑規二維量測腫瘤,且腫瘤體積以L×(W
2/2)計算,L =長度(2次量測之較長者),W =寬度。接著,將小鼠隨機分組為不同組,以便具有類似平均腫瘤體積(例如,37 mm
3)。在腫瘤植入後第7天開始抗體之投藥,小鼠藉助於腹膜內(i.p.)注射接受相關抗體之單次給藥(例如200微克/小鼠)。在腫瘤植入後第12天,處死各組中之若干小鼠,且收集腫瘤及脾用於免疫監測從而調查抗體對T細胞群體之影響。不同組中之剩餘小鼠中之一些或全部用於後續藥物動力學(PK)及/或藥物效應動力學(PD)分析。
T 細胞群體之免疫監測所收集之腫瘤及脾在gentleMACS Octo Dissociator™ (Miltenyi, San Diego, CA)上處理。單細胞懸浮液用以下T細胞標記物染色:CD4、CD8、CD19、ICOS、CD45、FoxP3、CTLA-4、CD3、Ki-67、PD-1、顆粒酶B及LIVE/DEAD
®。
PK/PD 分析針對體態、整毛及呼吸變化以及嗜睡每日檢查小鼠。一週兩次記錄腫瘤及組體重直至死亡、安樂死或研究時段結束。量測隨腫瘤生長抑制(TGI)而變之治療之反應,其計算如下:% TGI = {1-[(Tt-To)/(Ct-Co)]}×100;Tt =在指定天治療組之腫瘤體積;To =初始腫瘤體積;Ct =在指定天對照組之腫瘤體積;Co =對照組之初始腫瘤體積。若腫瘤達到大於約2500 mm
3之容積或出現潰瘍,則將動物安樂死。
統計學分析
使用Microsoft Excel計算平均標準偏差(SD)以及腫瘤體積及體重之中值。當研究動物之100%及至少60%仍留在各治療組時,分別計算平均值及中值。GraphPad Prism
®v.4軟體用於曲線資料。
如所預期,接受不相關對照抗體之小鼠未能控制腫瘤生長(圖9A),而接受易普利姆瑪之所有小鼠均有效控制腫瘤生長(圖9B)。接受不同可活化人類抗CTLA-4抗體之小鼠與易普利姆瑪相當地控制腫瘤生長(圖9C至圖9F)。在可活化之抗體中,Ipi YV39 2001最接近地類似於易普利姆瑪在控制腫瘤生長方面之功效(圖9F)。
關於治療小鼠之腫瘤及脾中之調節T細胞的頻率,如先前用可活化之抗小鼠CTLA-4抗體所觀測(參見實例2),可活化之抗人類CTLA-4抗體(小鼠IgG2a同型)在腫瘤中表現地類似於(圖12A及圖12B),但在脾中,可活化之抗體更加與不相關對照抗體相當(圖12C至圖12F)。
本文中展示之資料共同表明本文所揭示之可活化人類抗CTLA-4抗體可如傳統易普利姆瑪一樣有效控制腫瘤同時呈現不期望副作用之較小風險。
實例6:
包含經修飾之可裂解部分之可活化之抗人類CTLA-4抗體的活體內特徵
為尋址某些可裂解部分序列中之可能脫醯胺位點(參見實例10),使用人類IgG1及各種CM序列製備可活化人類抗CTLA4抗體。可活化之抗體包含YV39作為掩蔽部分及2001可裂解部分之若干變體中之一者:WT (2001)、ANP (2012)、DNP (2011)或Q (2008)(分別為「Ipi YV39 2001」、「Ipi YV39 2012」、「Ipi YV39 2011」及「Ipi YV39 2008」)。易普利姆瑪及不相關人類抗白喉毒素同樣用作對照。
為量測可活化之抗CTLA-4抗體之活性,使用如上文實例5中所述之MC38腫瘤模型。為劑量滴定研究(圖11A至圖11F),用劑量為200微克/劑量、60微克/劑量及20微克/劑量之易普利姆瑪或包含YV39作為掩蔽部分及2011作為可裂解部分之可活化之抗體(「Ipi YV39 2011」)治療小鼠。
如圖10A及圖10B中所示,用對照抗體治療之小鼠未能控制腫瘤,而用易普利姆瑪治療之10隻小鼠中之6隻在實驗結束時不含腫瘤。用不同可活化之抗體治療之小鼠能夠控制腫瘤,如用傳統易普利姆瑪所觀測(圖10C至圖10F)。
亦參見圖11B-圖11G。
關於治療小鼠之腫瘤及脾中之調節T細胞的頻率,如先前所觀測,需要腫瘤特異性蛋白酶裂解2001可裂解部分變體。在腫瘤中,此等可活化之抗體在降低Foxp3+ 調節T細胞之頻率方面表現地如易普利姆瑪(圖13A、圖13B、圖14A及圖14B)。
亦參見圖15。在脾中,抗體更加接近地反映不相關對照抗體(圖13C至圖13E、圖14D至圖14G及圖16A至圖16B),表明掩蔽部分在無腫瘤特異性相關蛋白酶存在下仍偶合於可活化之抗體。
實例7:
非海藻糖基化版之可活化之抗人類CTLA-4抗體之活體內特徵
如上所述,核心海藻糖殘基之缺少藉助於在不改變抗原結合或CDC之情況下IgG與活化FcγRIIIA之改良結合可強烈提高ADCC。Natsume
等人(2009)
Drug Des. Devel. Ther. 3:7。製備易普利姆瑪(「Ipi NF」)及ipi YV39 2011 (「Ipi YV39 2011 NF」)之非海藻糖基化形式。針對各種小鼠、人類及食蟹獼猴Fc受體測定Ipi與Ipi NF之結合。在圖19中提供結果。如所預期,Ipi NF展示用於活化受體人類CD16a (FcγRIIIa)、食蟹獼猴CD16 (FcγRIII)及小鼠FcγRIV之顯著提高之親和力(亦即,較低K
d)。
在實例5中所描述之MC38腫瘤模型中,以各種劑量測試Ipi YV39 2011 NF及Ipi-NF。易普利姆瑪及不相關hIgG1用作對照。結果提供於圖17A至圖17D中。Ipi NF在限制或預防腫瘤生長方面比易普利姆瑪略微更加有效(比較圖17B及圖17C),且Ipi YV39 2011 NF等效於Ipi NF (比較圖17C及圖17D)。另外,在用Ipi NF及Ipi YV39 2011抗體治療之小鼠之腫瘤中亦類似地耗盡FoxP3+調節T細胞(參見圖18)。在兩個實驗中,Ipi YV39 2011 NF展示在腫瘤中經完全活化。
此等結果證實本發明之方法同等適用於易普利姆瑪之非海藻糖基化形式,包括非海藻糖基化可活化CTLA-4抗體,諸如YV39 2011 NF。
實例8:
食蟹獼猴中之可活化之抗人類CTLA-4抗體之活體內特徵
為評估靈長類動物中之抗CTLA-4抗體,向獼猴投與包含YV39作為掩蔽部分及2001作為可裂解部分之可活化之抗體。媒劑及易普利姆瑪用作對照。各猴接受10 mg抗體或抗CTLA-4可活化之抗體,且在抗體投藥後第0天、第4天、第8天、第15天、第22天、第36天及第43天收集血液。如圖20中所示,在接受易普利姆瑪之猴中,在CD4+ T細胞增殖中存在尖峰,如在抗體投藥後約第8天-第15天藉由Ki67染色所量測。相比之下,可活化之抗CTLA-4抗體表現地類似於媒劑對照且未在猴中誘發CD4+ T細胞增殖。此等資料表明即使在靈長類動物中,可活化之抗CTLA-4抗體亦展示極少(若存在)活化,表明缺少特異性蛋白酶。
共同地,圖1至圖20中提供之資料表明本文所述之可活化之抗CTLA-4抗體提供對易普利姆瑪之改良。可活化之抗體如同易普利姆瑪一樣有效地控制腫瘤生長,同時降低用易普利姆瑪治療常常觀測到之嚴重不良事件的風險。
實例9:
可活化CTLA-4抗體之K
app及ME值
表9提供呈IgG1型式之人類中之包含各種掩蔽部分及可裂解部分的本文所揭示之可活化之抗體之K
app及掩蔽效率(ME)值。自圖式中描繪之資料計算此表中提供之值。K
app表示在此實例中藉由ELISA結合之在量測條件下之可活化之抗體的結合親和力;然而,應瞭解結合親和力亦可藉由與在原發性或經轉染細胞上表現之CTLA-4結合或藉由諸如但不限於表面電漿子共振或平衡滲析之其他物理方法量測。掩蔽效率(ME)藉由可活化之抗體之K
app除以易普利姆瑪之K
D計算,在相同條件下量測。
表9:K
app及ME值
表10提供呈YV1小鼠Ig2a型式之包含各種掩蔽部分及可裂解部分之本文所揭示的可活化之抗體之K
app及ME值。自圖式中描繪之資料計算所提供之值。
表10:K
app及ME值
表11提供呈aYV1小鼠IgG2a型式之包含具有較高ME值之掩蔽部分及2012可裂解部分的可活化之抗體之K
app及ME值。自圖式中描繪之資料計算所提供之值。
表11:K
app及ME值
實例10:
可活化CTLA-4抗體之脫醯胺、異構化及穩定評估
如實例6中所表明,為尋址某些可活化人類抗CTLA-4抗體中之某些可裂解部分(CM)序列中之可能脫醯胺位點,使用各種CM序列(亦即,2001、2011、2012及2008)製備此類可活化之抗體。在可裂解部分2011、2012及2008中,發現於2001可裂解部分中之DNH序列分別用DNP、ANP及DQH置換。
此等可活化CTLA-4抗體藉由HEK 293細胞中之相關構築體之短暫轉染製造,且經受肽映射液相層析-質譜(LC-MS)以偵測潛在分解產物。最初經選擇以用於本發明之可活化之抗CTLA-4抗體之2001 (DNH)可裂解部分在4℃下在PBS中7天之後展示天冬醯胺(N)殘基之脫醯胺(6.4%)。強制穩定性研究展示當在25℃下儲存4週時脫醯胺自18.5%增加至32.8%,且當在40℃下儲存一週及四週時分別增加至36.5%及66.6%。
可裂解部分2008、2011及2012經選擇以嘗試克服與此等可活化CTLA-4抗體中之2001的脫醯胺問題。全部此等可裂解部分在PBS中儲存在40℃下持續一週時,相比於2001之6.4%脫醯胺具有0.1%或更少脫醯胺。然而,進一步穩定性分析(亦藉由LC-MS)展示儘管包含2008 (DQH)可裂解部分之此等可活化CTLA-4抗體展示極少脫醯胺,但其在各種條件下在天冬胺酸殘基處展示顯著的天冬胺酸異構化(參見表12)。相比之下,2011 (DNP)展示極少天冬胺酸異構化。天冬胺酸異構化對於2012 (ANP)而言為不相關的,其中天冬胺酸殘基用丙胺酸置換。
表12:異構化值
然而,小鼠、大鼠及食蟹獼猴血清中之活體外穩定性研究展示對於此等可活化CTLA-4抗體中之2012 (ANP) (參見表13)而言天冬醯胺與脯胺酸殘基之間的實質削減。2011 (DNP)仍作為具有可接受地低含量之脫醯胺、天冬胺酸異構化及輕鏈削減的可裂解部分。
表13:天冬醯胺與脯胺酸殘基之間所觀測到之削減程度
出於所有目的,在本文中所引用之全部公開案、專利、專利申請案、網際網路站點及寄存編號/資料庫序列(包括聚核苷酸及多肽序列兩者)以全文引用之方式併入本文中,至如同專門及單獨指示各單獨公開案、專利、專利申請案、網際網路站點或寄存編號/資料庫序列因此通過引用併入之程度。
鏈 | CDR1 | CDR2 | CDR3 |
輕 | RASQSVGSSYLA (SEQ ID NO: 560) | GAFSRAT (SEQ ID NO: 561) | QQYGSSPWT (SEQ ID NO: 562) |
重 | SYTMH (SEQ ID NO: 557) | FISYDGNNKYYADSVKG (SEQ ID NO: 558) | TGWLGPFDY (SEQ ID NO: 559) |
序列識別符 | CM 序列 |
313 | LSGRSDNH |
314 | LSGRSANPRG |
315 | TGRGPSWV |
316 | PLTGRSGG |
317 | TARGPSFK |
318 | NTLSGRSENHSG |
319 | NTLSGRSGNHGS |
320 | TSTSGRSANPRG |
321 | TSGRSANP |
322 | VHMPLGFLGP |
306 | AVGLLAPPGGLSGRSDNH |
307 | AVGLLAPPGGLSGRSDDH |
308 | AVGLLAPPGGLSGRSDIH |
309 | AVGLLAPPGGLSGRSDQH |
310 | AVGLLAPPGGLSGRSDTH |
338 | AVGLLAPPGGLSGRSDYH |
339 | AVGLLAPPGGLSGRSANI |
340 | AVGLLAPPGGLSGRSDNI |
312 | AVGLLAPPGGLSGRSANP |
311 | AVGLLAPPGGLSGRSDNP |
299 | AVGLLAPPSGRSANPRG |
323 | AVGLLAPP |
324 | AQNLLGMV |
325 | QNQALRMA |
326 | LAAPLGLL |
327 | STFPFGMF |
328 | ISSGLLSS |
329 | PAGLWLDP |
330 | VAGRSMRP |
331 | VVPEGRRS |
332 | ILPRSPAF |
333 | MVLGRSLL |
334 | VAGRSMRP |
335 | QGRAITFI |
336 | SPRSIMLA |
337 | SMLRSMPL |
297 | ISSGLLSGRSDNH |
300 | ISSGLLSGRSDDH |
301 | ISSGLLSGRSDIH |
302 | ISSGLLSGRSDQH |
303 | ISSGLLSGRSDTH |
341 | ISSGLLSGRSDYH |
342 | ISSGLLSGRSANI |
343 | ISSGLLSGRSDNI |
305 | ISSGLLSGRSANP |
304 | ISSGLLSGRSDNP |
298 | ISSGLLSGRSANPRG |
序列識別符 | MM 序列 | 序列識別符 | MM 序列 |
1 | DFSCLHSMYNVCLDP | 147 | EHCDVWMFGFNLCPY |
2 | QPCAQMYGYSMCPHT | 148 | EPCDYWMFGVNLCPY |
3 | LHCRTQMYGYNLCPY | 149 | EQCTMWMYGFNLCPY |
4 | LHCRTQLYGYNLCPY | 150 | ESACSLRMYEVCLQP |
5 | CTYSFFNVC | 151 | ESCASMYGYSMCPRT |
6 | CAQMYGYSMC | 152 | ESCSYWMFGYNLCPY |
7 | CPNHPMC | 153 | FSNTCPHHPMCYDYR |
8 | GTACTYSFFNVCLDP | 154 | FWNTCPHHPMCHDYK |
9 | FGTACPNHPMCHDWQ | 155 | FYQNCYPPTWCSMFS |
10 | SACAYWMFGVNLCPY | 156 | GECSYWMFGYNLCPY |
11 | CRTQLYGYNLC | 157 | GGSCMYSFFNICLDP |
12 | CRTQIYGYNLC | 158 | GGSCVYVMYNVCLDP |
13 | LHCRTQIYGYNLCPY | 159 | GHCLMHMYGYNLCPK |
14 | CPNHPMCHDWQ | 160 | GHCRMSMYEMTLCPR |
15 | GTACPNHPMCHDWQ | 161 | GISCVHIMFNFCLDP |
16 | CAYWMFGVNLCPY | 162 | GLCVMYMFGVNLCPY |
17 | QECHLYMYGVNLCPY | 163 | GSCDYWMFGYNLCPY |
18 | CHLYMYGVNLCPY | 164 | GSYCMYVMYNVCLDP |
19 | GQCQFYMFGYNLCPY | 165 | GTKCIYSFYNVCLDP |
20 | LSTCMYSFFNVCLDP | 166 | GTSTCPYHPMCHDYR |
21 | CLHSMYNVCLDP | 167 | GTTCTYSFFNVCLDP |
22 | CLHSMYNVC | 168 | GVCHFFMYGVSMCPA |
23 | CLHSLYNVCLDP | 169 | GVPCWYSMYNVCLDP |
24 | CLHSAYNVCLDP | 170 | GVSCMYSMFNICLDP |
25 | CMYSFFNVCLDP | 171 | HAKCVYSFFNVCLDP |
26 | CMYSFFNVC | 172 | HDSCMYSMYNFCLDP |
27 | QPCAQMYGYSMC | 173 | HGNTCPNHPMCHDYQ |
28 | CAQLYGYSMCPHT | 174 | HKGCLYSFYNICLDP |
29 | CAQMYGYSMCAHT | 175 | HKGCLYSFYNVCLDP |
30 | CAQMYGYSMCPAT | 176 | HLSCMYIMYNVCLDP |
31 | CAQMYGYSMCPHT | 177 | HSSCIYSMFNVCLDP |
32 | CPNHPLCHDWQ | 178 | HTNMCPYHPMCYDYK |
33 | CPNHPMCADWQ | 179 | HTPCTYSFFNVCLDP |
34 | CPNHPMCHAWQ | 180 | IMNTCPYHPMCHDYQ |
35 | CPNHPMCHDAQ | 181 | IVPCTYMMFGVCLQP |
36 | CPNHPMCHDWA | 182 | KKCDYWFYGVNLCPY |
37 | GTACPNHPMC | 183 | KNTCVYSFFNVCLDP |
38 | LHCRTQLYGYNLC | 184 | KPCAQMYGYSMCPHP |
39 | CRTQLYGYNLCPY | 185 | KPSCMYSFFNVCLDP |
40 | CRTQLYGYNLCAY | 186 | KRPCMYSFYNVCLDP |
41 | CRTQLYGYNLCPA | 187 | KTSCMYSFYNICLDP |
42 | FGTACPNHPLCHDWQ | 188 | KTTCTYSFFNVCLDP |
43 | CPNHPLCHDFQ | 189 | LDCQMYWWFGACGDM |
44 | CPNHPLCHDYQ | 190 | LHCAIYMYGYNLCPF |
45 | CPNHPLCPY | 191 | LHCPFQMYGYNLCPH |
46 | CPNHPLCPA | 192 | LHCSMYMYGFNLCPN |
47 | CMYSFFNVCYP | 193 | RECMAYMYGYNLCPY |
48 | CMYSFFNVCYA | 194 | RHCQMHMFGYDLCPY |
49 | CLYSFFNVCYP | 195 | LIHCRYVMYGMCLEP |
50 | CLYSFFNVCYA | 196 | LLPCEVMGPSRCKHD |
51 | FGAACPNHPICHDWQ | 197 | LPCHAYMYGYSLCPY |
52 | FGAACPNHPLCHDWQ | 198 | LPCLAYMYGVNLCPN |
53 | FGAACPNHPMCHDAQ | 199 | LPCMAYMFGFNLCPH |
54 | CLHSAYNACLDP | 200 | LPCNFHMFGFNLCPY |
55 | CAHSAYNVCLDP | 201 | LQCAMYMYGYNLCPY |
56 | CLHSAYNVCADP | 202 | LSSCTYSFFNVCLDP |
57 | CLHSAYNVCLAP | 203 | LTCPFQMYGYNLCPY |
58 | CLHSAYNVCLDA | 204 | LTSQCSPWYWCQIYD |
59 | KNTCTYVMYNVCLDP | 205 | LYCPYMMYGYNLCPY |
60 | YISDCPYHPMCHDYQ | 206 | LYHCTYSFYNVCLDP |
61 | FRNTCPYHPMCHDYR | 207 | LYRCIYSFYNVCLDP |
62 | RECHMWMFGVNLCPY | 208 | MGCSMRMWGMELCPE |
63 | AVCHMYMYGYNLCPF | 209 | MKCDYWLYGYNLCPY |
64 | RSCPQMYGYSMCPHT | 210 | MNHCTLHMYNICMDP |
65 | QPCAQMFGYSMCPHT | 211 | MNPECPHHPMCHNSN |
66 | TAKCTYSFFNVCLDP | 212 | MPACTYSFFNICLDP |
67 | DFSCLYSMYNVCLDP | 213 | MPQCHVIMYNLCLDP |
68 | DVSCMYMMYNFCLDP | 214 | MSTCTYSFFNVCLDP |
69 | CPNHPMC | 215 | MTCNYWFYGVNLCPY |
70 | CMYSFFNVCPY | 216 | MYCHQSMFGFRMCPD |
71 | CMYSFFNVCPA | 217 | NACAQMYGYSMCPHT |
72 | CTYSFFNVCPY | 218 | NDCDISMFDQSLCPY |
73 | CTYSFFNVCPA | 219 | NFSCVYVMFNVCLDP |
74 | GFPCMYSMFNVCLDP | 220 | NFTCALTMYEVCLDP |
75 | GLSCMYSMYGYCLDP | 221 | NLCHAFMFGFNLCPY |
76 | IPCDYWMFGVNLCPY | 222 | NLNNCPHHPMCHDYQ |
77 | QVCHAYMYGYNLCPY | 223 | NPPCMYSFFNICLDP |
78 | RMYCTYSFYNVCLDP | 224 | NSACTYSFFNVCLDP |
79 | ALSCMYIMYNVCLDP | 225 | NVCTVSMFGVMLCPS |
80 | DFSCMYVMFNVCLDP | 226 | PACATLMYSVPLCPA |
81 | DFSCVYSMFNVCLDP | 227 | PAPCMYSFYNVCLDP |
82 | DMNTCPNHPMCYDYR | 228 | PLCAEMYGYSMCPHN |
83 | DMNTCPRHPMCHDYH | 229 | PQCHLYMYGYNLCPY |
84 | DSRCMYVMYNVCLDP | 230 | PRPCMYSFYNVCLDP |
85 | EHLCTYSFYNVCLDP | 231 | QHCPFQMYGYNLCPY |
86 | ELSCVYSMFGFCLDP | 232 | QHCQMHMFGYNLCPY |
87 | FTNNCPYHPMCHDYL | 233 | QHSCMYSFFNVCLDP |
88 | GFSCTYIMYDVCLDP | 234 | QKCHSYLYGVNLCPY |
89 | GSSCMYSMYNVCLDP | 235 | QKCNMFMFGYNLCPY |
90 | HFSCMYIMYNVCLDP | 236 | QMNDCPNHPMCHDYH |
91 | LHCGMWMFGVNLCPK | 237 | QPCAQMYGYSMCPAT |
92 | LPCQMWMFGHNLCPH | 238 | QPCAQMYGYSMCPRT |
93 | LPCTMYMYGYNLCPY | 239 | RECHFFFYGVNLCPY |
94 | LTCHHWMFGVNLCPY | 240 | LNCGMFMYGYNLCPY |
95 | NFSCMYSMFNVCLDP | 241 | RLCTSYMFGYNLCPQ |
96 | NNHCMYSFFNICLDP | 242 | RLSCMYSMFNVCLDP |
97 | NRSCMYIMYNVCLDP | 243 | RNCPFVMFGVNLCPY |
98 | NSCTMFMFGVNLCPY | 244 | RNGCMYSFFNVCLDP |
99 | NTCELYMFGVNLCPY | 245 | RNGCVYSFFNVCLDP |
100 | QHCDMWMFGYNLCPY | 246 | RPCHLYMFGYNLCPD |
101 | QHCPMYMFGYNLCPF | 247 | RPCHSYMYGINLCPY |
102 | QVCHIQMYGFDLCPH | 248 | RSCDMIMFGFNLCPY |
103 | RACDYWMYGVNLCPY | 249 | RSCPMWFYGVNLCPY |
104 | RQCHMQMFGYDLCPF | 250 | RSTVCFYDFCGPWER |
105 | SGSCLYSFYNVCLDP | 251 | RTCHFYMYGVNLCPY |
106 | SNGCTYSFFNVCLDP | 252 | RTCSMVMFGVNLCPY |
107 | STCAQMYGYSMCPH | 253 | SGKCTYSFFNVCLDP |
108 | SYKCLYSFYNVCLDP | 254 | SIVCDLYWEATCLRP |
109 | VLYCTYVMYNVCLDP | 255 | SLSCTYSFFNICLDP |
110 | VNCGMWMFGYNLCPK | 256 | SMNTCPYHPMCFDYK |
111 | YGSCLYSFYNICLDP | 257 | SQCWMWMYGYNLCPK |
112 | YPCAQMYGYSMCPHT | 258 | SSSCMYSFFNVCLDP |
113 | AACDLWMFGVNLCPY | 259 | STACTYSFYNVCLDP |
114 | AFCTLAPYNQACIAN | 260 | STCAQMYGYSMCPHT |
115 | AGSCLYSMYNVCLDP | 261 | STRCVYSFYNVCLDP |
116 | ALCENTMYGYHLCPW | 262 | TACGAWMFGVNLCPY |
117 | ALSCMYIMYGVCLDP | 263 | TGACMYSFYNVCLDP |
118 | APVCDVLMFGFCMQP | 264 | TLSCMYSMYNVCLDP |
119 | AQVCSIMMYGTCLMP | 265 | TSCTVTMYQISMCPY |
120 | ASTCMYSFYNVCLDP | 266 | VGGCRHSFYNVCLDP |
121 | AVCEFWMFGFNLCPY | 267 | VHCQMYMYGYNLCPY |
122 | DANTCPNHPMCYDYH | 268 | VHNCMYSFFNVCLDP |
123 | DFSCIYIMFDVCLDP | 269 | VMCKLHMYGIPVCPK |
124 | DFSCMYVMYGFCLDP | 270 | VNFCNYSMYGICLLP |
125 | DFTCMYSMYNVCLDP | 271 | VNFCYACYCMSCVFS |
126 | DFTCTYSMYNVCLDP | 272 | VNQCTYSFFNVCLDP |
127 | DHYCTYIMYSICLDP | 273 | VPCPFHMFGYNLCPY |
128 | DICTNFMFGVNLCPY | 274 | VRCQMWMYGFNLCPH |
129 | DINTCPYHPMCHDYH | 275 | VRPCTYSFFNVCLDP |
130 | DKNTCPLHPMCHDYR | 276 | VSGCTYSFFNICLDP |
131 | DMNMCPNHPMCHDWH | 277 | YCSSWDTMTIPACNN |
132 | DMNSCPNHPMCHDYH | 278 | YDCDLSMFGIEMCPQ |
133 | DMNSCPNHPMCYDYR | 279 | YGNTCPFHPMCHDYK |
134 | DMNTCPNHPMCFDYR | 280 | YGYCMYSFFNVCLDP |
135 | DMNTCPNHPMCHDFQ | 281 | YHCTMHMFGYNLCPF |
136 | DMNTCPNHPMCHDYR | 282 | YMNTCPNHPMCFDYQ |
137 | DMNTCPNHPMCYDYH | 283 | YMNTCPYHPMCHDYL |
138 | DMNTCPNHPMCYDYK | 284 | YMNTCPYHPMCHDYR |
139 | DMSTCPNHPMCHDYM | 285 | YNNCTYSFFNVCLDP |
140 | DRNMCPYHPMCYDYR | 286 | YPGCQYSFFNVCLDP |
141 | DSCAFMMFGVNLCPY | 287 | YRSCTHIMYNVCLDP |
142 | DSCRSVFDMVWNCWN | 288 | YSFCDMLMYDVCLVP |
143 | DTPNCPHHPMCHNHM | 289 | YSIDCGLSWWCGGMT |
144 | DVSCLYVMYSVCLDP | 290 | YSTTCPYHPMCHDYH |
145 | DWCASMMFGYNLCPY | 291 | YVNTCPHHPMCHDYH |
146 | EFSCMYSMFNVCLDP | 292 | YVNTCPYHPMCHDYN |
SEQ ID NO. | 掩蔽部分 (MM ) | SEQ ID NO. | 可裂解部分 (CM ) |
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 33 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 | (YV01) DFSCLHSMYNVCLDP (YV02) QPCAQMYGYSMCPHT (YV03) LHCRTQMYGYNLCPY (YV04) LHCRTQLYGYNLCPY (YV05) CTYSFFNVC (YV06) CAQMYGYSMC (YV07) CPNHPMC (YV08) GTACTYSFFNVCLDP (YV09) FGTACPNHPMCHDWQ (YV10) SACAYWMFGVNLCPY (YV11) CRTQLYGYNLC (YV12) CRTQIYGYNLC (YV13) LHCRTQIYGYNLCPY (YV14) CPNHPMCHDWQ (YV15) GTACPNHPMCHDWQ (YV16) CAYWMFGVNLCPY (YV17) QECHLYMYGVNLCPY (YV18) CHLYMYGVNLCPY (YV19) GQCQFYMFGYNLCPY (YV20) LSTCMYSFFNVCLDP (YV21) CLHSMYNVCLDP (YV22) CLHSMYNVC (YV23) CLHSLYNVCLDP (YV24) CLHSAYNVCLDP (YV25) CMYSFFNVCLDP (YV26) CMYSFFNVC (YV27) QPCAQMYGYSMC (YV28) CAQLYGYSMCPHT (YV29) CAQMYGYSMCAHT (YV30) CAQMYGYSMCPAT (YV31) CAQMYGYSMCPHT (YV32) CPNHPLCHDWQ (YV33) CPNHPMCADWQ (YV34) CPNHPMCHAWQ (YV35) CPNHPMCHDAQ (YV36) CPNHPMCHDWA (YV37) GTACPNHPMC (YV38) LHCRTQLYGYNLC (YV39) CRTQLYGYNLCPY (YV40) CRTQLYGYNLCAY (YV41) CRTQLYGYNLCPA (YV42) FGTACPNHPLCHDWQ (YV43) CPNHPLCHDFQ (YV44) CPNHPLCHDYQ (YV45) CPNHPLCPY (YV46) CPNHPLCPA (YV47) CMYSFFNVCYP (YV48) CMYSFFNVCYA (YV49) CLYSFFNVCYP (YV50) CLYSFFNVCYA (YV51) FGAACPNHPICHDWQ (YV52) FGAACPNHPLCHDWQ (YV53) FGAACPNHPMCHDAQ (YV54) CLHSAYNACLDP (YV55) CAHSAYNVCLDP (YV56) CLHSAYNVCADP (YV57) CLHSAYNVCLAP (YV58) CLHSAYNVCLDA (YV60) KNTCTYVMYNVCLDP (YV61) YISDCPYHPMCHDYQ (YV62) FRNTCPYHPMCHDYR (YV63) RECHMWMFGVNLCPY (YV64) AVCHMYMYGYNLCPF (YV65) RSCPQMYGYSMCPHT (YV66) QPCAQMFGYSMCPHT | 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 297 300 301 302 303 341 342 343 305 304 298 306 307 308 309 310 338 339 340 312 311 299 | LSGRSDNH LSGRSANPRG TGRGPSWV PLTGRSGG TARGPSFK NTLSGRSENHSG NTLSGRSGNHGS TSTSGRSANPRG TSGRSANP VHMPLGFLGP AVGLLAPP AQNLLGMV QNQALRMA LAAPLGLL STFPFGMF ISSGLLSS PAGLWLDP VAGRSMRP VVPEGRRS ILPRSPAF MVLGRSLL VAGRSMRP QGRAITFI SPRSIMLA SMLRSMPL ISSGLLSGRSDNH ISSGLLSGRSDDH ISSGLLSGRSDIH ISSGLLSGRSDQH ISSGLLSGRSDTH ISSGLLSGRSDYH ISSGLLSGRSANI ISSGLLSGRSDNI ISSGLLSGRSANP ISSGLLSGRSDNP ISSGLLSGRSANPRG AVGLLAPPGGLSGRSDNH AVGLLAPPGGLSGRSDDH AVGLLAPPGGLSGRSDIH AVGLLAPPGGLSGRSDQH AVGLLAPPGGLSGRSDTH AVGLLAPPGGLSGRSDYH AVGLLAPPGGLSGRSANI AVGLLAPPGGLSGRSDNI AVGLLAPPGGLSGRSANP AVGLLAPPGGLSGRSDNP AVGLLAPPSGRSANPRG |
組合編號 | 掩蔽部分(MM) | 可裂解部分(CM) |
1 | CRTQLYGYNLCPY (SEQ ID NO: 39) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
2 | CRTQLYGYNLCPY (SEQ ID NO: 39) | ISSGLLSGRSDNP (SEQ ID NO: 304) |
3 | CRTQLYGYNLCPY (SEQ ID NO: 39) | ISSGLLSGRSANP (SEQ ID NO: 305) |
4 | CRTQLYGYNLCPY (SEQ ID NO: 39) | ISSGLLSGRSDQH (SEQ ID NO: 302) |
5 | CRTQLYGYNLCPY (SEQ ID NO: 39) | ISSGLLSGRSDDH (SEQ ID NO: 300) |
6 | CRTQLYGYNLCPY (SEQ ID NO: 39) | ISSGLLSGRSDTH (SEQ ID NO: 303) |
7 | LHCRTQMYGYNLCPY (SEQ ID NO: 3) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
8 | LHCRTQMYGYNLCPY (SEQ ID NO: 3) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
9 | LHCRTQMYGYNLCPY (SEQ ID NO: 3) | ISSGLLSGRSDDH (SEQ ID NO: 300) |
10 | LHCRTQMYGYNLCPY (SEQ ID NO: 3) | ISSGLLSGRSDIH (SEQ ID NO: 301) |
11 | LHCRTQMYGYNLCPY (SEQ ID NO: 3) | ISSGLLSGRSDQH (SEQ ID NO: 302) |
12 | LHCRTQMYGYNLCPY (SEQ ID NO: 3) | ISSGLLSGRSDTH (SEQ ID NO: 303) |
13 | CAQMYGYSMC (SEQ ID NO: 06) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
14 | CAQMYGYSMC (SEQ ID NO: 06) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
15 | FGTACPNHPMCHDWQ (SEQ ID NO: 09) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
16 | FGTACPNHPMCHDWQ (SEQ ID NO: 09) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
17 | CLHSLYNVCLDP (SEQ ID NO: 23) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
18 | CLHSLYNVCLDP (SEQ ID NO: 23) | ISSGLLSGRSDDH (SEQ ID NO: 300) |
19 | CLHSLYNVCLDP (SEQ ID NO: 23) | ISSGLLSGRSDIH (SEQ ID NO: 301) |
20 | CLHSLYNVCLDP (SEQ ID NO: 23) | ISSGLLSGRSDQH (SEQ ID NO: 302) |
21 | CLHSLYNVCLDP (SEQ ID NO: 23) | ISSGLLSGRSDTH (SEQ ID NO: 303) |
22 | CLHSLYNVCLDP (SEQ ID NO: 23) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
23 | CLHSAYNVCLDP (SEQ ID NO: 24) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
24 | CLHSAYNVCLDP (SEQ ID NO: 24) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
25 | QPCAQMYGYSMC (SEQ ID NO: 27) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
26 | QPCAQMYGYSMC (SEQ ID NO: 27) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
27 | CAQMYGYSMCAHT (SEQ ID NO: 29) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
28 | CAQMYGYSMCAHT (SEQ ID NO: 29) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
29 | CPNHPLCHDWQ (SEQ ID NO: 32) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
30 | CPNHPLCHDWQ (SEQ ID NO: 32) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
31 | CPNHPMCADWQ (SEQ ID NO: 33) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
32 | CPNHPMCADWQ (SEQ ID NO: 33) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
33 | CPNHPMCHDAQ (SEQ ID NO: 35) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
34 | CPNHPMCHDAQ (SEQ ID NO: 35) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
35 | CRTQLYGYNLCPY (SEQ ID NO: 39) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
36 | CRTQLYGYNLCPA (SEQ ID NO: 41) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
37 | CRTQLYGYNLCPA (SEQ ID NO: 41) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
38 | FGAACPNHPICHDWQ (SEQ ID NO: 51) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
39 | FGAACPNHPICHDWQ (SEQ ID NO: 51) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
40 | FGAACPNHPLCHDWQ (SEQ ID NO: 52) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
41 | FGAACPNHPLCHDWQ (SEQ ID NO: 52) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
42 | FGAACPNHPMCHDAQ (SEQ ID NO: 53) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
43 | FGAACPNHPMCHDAQ (SEQ ID NO: 53) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
44 | CLHSAYNACLDP (SEQ ID NO: 54) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
45 | CLHSAYNACLDP (SEQ ID NO: 54) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
46 | CAHSAYNVCLDP (SEQ ID NO: 55) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
47 | CAHSAYNVCLDP (SEQ ID NO: 55) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
48 | CLHSAYNVCADP (SEQ ID NO: 56) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
49 | CLHSAYNVCADP (SEQ ID NO: 56) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
50 | CLHSAYNVCLAP (SEQ ID NO: 57) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
51 | CLHSAYNVCLAP (SEQ ID NO: 57) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
52 | CLHSAYNVCLDA (SEQ ID NO: 58) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
53 | CLHSAYNVCLDA (SEQ ID NO: 58) | AVGLLAPPGGLSGRSDNH (SEQ ID NO: 306) |
54 | YISDCPYHPMCHDYQ (SEQ ID NO: 60) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
55 | FRNTCPYHPMCHDYR (SEQ ID NO: 61) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
56 | AVCHMYMYGYNLCPF (SEQ ID NO: 63) | ISSGLLSGRSDNH (SEQ ID NO: 297) |
57 | RSCPQMYGYSMCPHT (SEQ ID NO: 64) | ISSGLLSGRSANP (SEQ ID NO: 305) |
58 | QPCAQMFGYSMCPHT (SEQ ID NO: 65) | ISSGLLSGRSANP (SEQ ID NO: 305) |
1 | X | X | C | X | X | X | M | Y | G | Y | N | L | C | P | Y |
2 | NNK | NNK | TGC | NNK | NNK | NNK | NTT | TWT | GGG | KWT | AAT | CTG | TGC | CCG | TAT |
3 | X | X | X | C | X | H | S | M | Y | N | V | C | L | D | P |
4 | NNK | NNK | NNK | TGC | NNK | NWT | AGT | NTT | TWT | AAT | NTT | TGC | CTT | GAT | CCT |
[抗體] = nM 第1行-第3行 | [可活化之抗體1] = nM 第4行-第6行 | [可活化之抗體2] = nM 第7行-第9行 | [可活化之抗體3] = nM 第10行-第12行 | |
A | 10 | 1000 | 1000 | 1000 |
B | 3.33 | 333 | 333 | 333 |
C | 1.11 | 111 | 111 | 111 |
D | 0.37 | 37 | 37 | 37 |
E | 0.123 | 12.3 | 12.3 | 12.3 |
F | 0.041 | 4.1 | 4.1 | 4.1 |
G | 0.0137 | 1.34 | 1.34 | 1.34 |
H | .0046 | 0.45 | 0.45 | 空白 |
CM 2001 | CM 3001 | CM 2008 | CM 2011 | CM 2012 | NSUB | |||||||
K appnM | ME | K appnM | ME | K appnM | ME | K appnM | ME | K appnM | ME | K appnM | ME | |
YV04-YV1 | 17.8 | 57 | ||||||||||
YV06-YV1 | 0.6 | 2 | ||||||||||
YV09-YV1 | 33.6 | 112 | 44.4 | 126 | ||||||||
YV23-YV1 | 11.4 | 38 | 13.8 | 39 | ||||||||
YV24-YV1 | 9.0 | 29 | ||||||||||
YV27-YV1 | 0.7 | 2.3 | 0.8 | 2.3 | ||||||||
YV29-YV1 | 0.7 | 2.3 | 0.8 | 2.3 | ||||||||
YV32-YV1 | 0.9 | 3.0 | 1.2 | 3.4 | ||||||||
YV33-YV1 | 1.3 | 4.3 | 1.9 | 5 | ||||||||
YV35-YV1 | 3.7 | 12.3 | 5.3 | 15 | ||||||||
YV39-YV1 | 16.9 | 56 | 14.3 | 41 | 31.4 | 135 | 13.2 | 57 | 14.9 | 64 | 31.8 | 137 |
YV41-YV1 | 14.4 | 48 | 22.6 | 65 | ||||||||
YV51-YV1 | 4.4 | 15 | 4.9 | 14 | ||||||||
YV52-YV1 | 0.8 | 2.7 | 0.9 | 2.6 | ||||||||
YV53-YV1 | 4.1 | 14 | 5.3 | 15 | ||||||||
YV54-YV1 | 0.6 | 2 | 1.0 | 2.8 | ||||||||
YV55-YV1 | 4.8 | 16 | 6.0 | 18 | ||||||||
YV56-YV1 | 0.4 | 1.3 | 0.4 | 1 | ||||||||
YV57-YV1 | 0.4 | 1.3 | 1.6 | 4.6 | ||||||||
YV58-YV1 | 0.3 | 1 | 0.4 | 1 |
CM 2001 | CM 2006 | CM 2007 | CM 2008 | CM 2009 | ||||||
K appnM | ME | K appnM | ME | K appnM | ME | K appnM | ME | K appnM | ME | |
YV04-YV1 | 5.7 | 16.2 | 26.4 | 75 | 19.3 | 55 | 19.1 | 54 | 16.4 | 47 |
YV23-YV1 | 12.5 | 36 | 7.8 | 22 | 2.7 | 8 | 9.4 | 27 | ||
YV39-YV1 | 18.0 | 51 | 23.9 | 68 | 17.6 | 50 | 18.0 | 51 |
CM 2001 | CM 2011 | CM 2012 | NSUB | |||||
K appnM | ME | K appnM | ME | K appnM | ME | K appnM | ME | |
YV39-YV1 | 18.0 | 51 | 18.0 | 51 | 12.9 | 144 | 29.8 | 85 |
YV61-YV1 | 17.9 | 200 | ||||||
YV62-YV1 | 15.5 | 173 | ||||||
YV63-YV1 | 104 | 1170 | ||||||
YV64-YV1 | 56.5 | 631 | ||||||
YV65-YV1 | 12.3 | 156 | ||||||
YV66-YV1 | 18.9 | 242 | ||||||
YV01-YV1 | 38.6 | 493 | ||||||
YV02-YV1 | 14.8 | 189 |
溫度 | 時間 | 可裂解部分 - 異構化值 | ||
2011 (DNP) | 2012 (ANP) | 2008 (DQH) | ||
-80℃ | 0天 (T 0) | 0.1% | N/A | 1.8% |
4℃ | 0天 (T 0) | 0.1% | N/A | 2.4% |
25℃ | 3個月 | 0.2% | N/A | 8.2% |
40℃ | 3個月 | 0.2% | N/A | 34.5% |
血清 | 可裂解部分 - 天冬醯胺與脯胺酸殘基之間的削減 | |
2011 (DNP) | 2012 (ANP) | |
小鼠 | - | ++ |
食蟹獼猴 | +/- | +++ |
圖1A至圖1C展示在用(i)不相關小鼠IgG2a抗體(圖1A)、(ii)小鼠抗CTLA-4 (9D9) IgG2a抗體(圖2B)、或(iii)可活化9D9抗體(圖1C)治療之小鼠(n = 10)中隨腫瘤植入後天數而變之腫瘤體積。所有抗體及可活化之抗體均以25微克/小鼠給藥。可活化9D9抗體包含MY11 (SEQ ID NO: 294)作為掩蔽部分及2001 (SEQ ID NO: 297)作為可裂解部分。「TF」指示在各實驗結束時無腫瘤小鼠之數目。不相關小鼠IgG2a抗體及小鼠抗CTLA-4 (9D9) IgG2a抗體用作對照。
圖2A至圖2C展示用不同可活化小鼠抗CTLA-4 (9D9) IgG2a抗體治療之小鼠之腫瘤(圖2A)中的調節T細胞之頻率及脾(圖2B及圖2C)中的調節T細胞之增殖及活化。不同可活化9D9抗體包含(i)MY03 (SEQ ID NO: 293)或MY11 (SEQ ID NO: 294)作為掩蔽部分及(2)0003 (SEQ ID NO: 320)、1004 (SEQ ID NO: 323)或2001 (SEQ ID NO: 297)作為可裂解部分。不相關小鼠IgG2a抗體(「DT 1D12 mg2a」)及小鼠抗CTLA-4 (9D9) IgG2a抗體(「9D9 mg2a」)用作對照。在圖2A中,調節T細胞之頻率以在腫瘤中為Foxp3+之總CD4+ T細胞之百分比形式展示。圖2B及圖2C分別展示呈脾中Foxp3+ T細胞之百分比形式之增殖(Ki-67+)及經活化(ICOS+)調節T細胞的頻率。
圖3A至圖3E展示不同抗CTLA-4可活化之抗體(人類IgG1同型)與人類CTLA-4結合之能力,如利用ELISA結合分析活體外量測。易普利姆瑪(「YV1」)在所有實驗中均用作對照。在圖3A中,抗CTLA-4可活化之抗體包含YV04 (SEQ ID NO: 4)、YV06 (SEQ ID NO: 6)、YV09 (SEQ ID NO: 9)或YV23 (SEQ ID NO: 23)作為掩蔽部分。在圖3B中,抗CTLA-4可活化之抗體包含YV27 (SEQ ID NO: 27)、YV29 (SEQ ID NO: 29)、YV32 (SEQ ID NO: 32)或YV33 (SEQ ID NO: 33)作為掩蔽部分。在圖3C中,抗CTLA-4可活化之抗體包含YV35 (SEQ ID NO: 35)或YV41 (SEQ ID NO: 41)作為掩蔽部分。在圖3D中,抗CTLA-4可活化之抗體包含YV24 (SEQ ID NO: 24)、YV39 (SEQ ID NO: 39)、YV51 (SEQ ID NO: 51)、YV52 (SEQ ID NO: 52)或YV53 (SEQ ID NO: 53)作為掩蔽部分。在圖3E中,抗CTLA-4可活化之抗體包含YV54 (SEQ ID NO: 54)、YV55 (SEQ ID NO: 55)、YV56 (SEQ ID NO: 56)、YV57 (SEQ ID NO: 57)或YV58 (SEQ ID NO: 58)作為掩蔽部分。在圖3A至圖3E中,所有抗CTLA-4可活化之抗體均包含2001 (SEQ ID NO: 297)作為可裂解部分。
圖4A至圖4D展示其他抗CTLA-4可活化之抗體(人類IgG1同型)與人類CTLA-4結合之能力,如利用ELISA結合分析活體外量測。易普利姆瑪(「YV1」)在所有實驗中均用作對照。在圖4A中,抗CTLA-4可活化之抗體包含YV04、YV06、YV09、YV23、YV27或YV29作為掩蔽部分。在圖4B中,抗CTLA-4可活化之抗體包含YV32、YV33、YV35或YV41作為掩蔽部分。在圖4C中,抗CTLA-4可活化之抗體包含YV24、YV39、YV51、YV52或YV53作為掩蔽部分。在圖4D中,抗CTLA-4可活化之抗體包含YV54、YV55、YV56、YV57或YV58作為掩蔽部分。在圖4A至圖4D中,所有抗CTLA-4可活化之抗體均包含3001作為可裂解部分。
圖5A至圖5F展示若干抗CTLA-4可活化之抗體(小鼠IgG2a同型)與人類CTLA-4結合之能力,如利用結合分析活體外量測。易普利姆瑪(「YV1」)用作對照。在圖5A中,抗CTLA-4可活化之抗體包含YV04作為掩蔽部分及2001 (SEQ ID NO: 297)、2006 (SEQ ID NO: 300)、2007 (SEQ ID NO: 301)、2008 (SEQ ID NO: 302)或2009 (SEQ ID NO: 303)作為可裂解部分。在圖5B中,抗CTLA-4可活化之抗體包含YV04或YV23作為掩蔽部分,及2001、2006、2007、2008或2009作為可裂解部分。在圖5C中,抗CTLA-4可活化之抗體包含YV39作為掩蔽部分及2001、2006、2008或2009作為可裂解部分。在圖5D中,抗CTLA-4可活化之抗體包含YV61 (SEQ ID NO: 60)、YV62 (SEQ ID NO: 61)、YV63 (SEQ ID NO: 62)、YV64 (SEQ ID NO: 63)或YV39 (SEQ ID NO: 39)作為掩蔽部分及2001或2012作為可裂解部分。在圖5E中,抗CTLA-4可活化之抗體包含YV65 (SEQ ID NO: 64)、YV66 (SEQ ID NO: 65)、YV01 (SEQ ID NO: 1)、YV02 (SEQ ID NO: 2)或YV39 (SEQ ID NO: 39)作為掩蔽部分及2001或2012作為可裂解部分。在圖5F中,抗CTLA-4可活化之抗體包含YV39或YV03 (SEQ ID NO: 3)作為掩蔽部分及2001或2012作為可裂解部分。
圖6A及圖6B比較具有小鼠IgG2a同型(圖6A)或人類IgG1同型(圖6B)之抗CTLA-4可活化之抗體與人類CTLA-4結合之能力,如利用ELISA結合分析活體外量測。易普利姆瑪(「YV1」)用作對照。在圖6A及圖6B二者中,抗CTLA-4可活化之抗體包含YV39作為掩蔽部分及2001、2008、2011或2012作為可裂解部分。在經修飾之本發明抗體(YV39-NSUB)中,可裂解部分經包含胺基酸序列GGSGGSGGGSGGGS (SEQ ID NO: 570)之抗蛋白酶連接子(「NSUB」)置換。
圖7A至圖7D展示不同抗CTLA-4可活化之抗體與過度表現人類CTLA-4之58 α
-β
-細胞結合之能力,如藉助於流式細胞量測術所量測。結合隨所添加之抗CTLA-4抗體濃度而變以任意螢光單位(平均螢光強度、MFI或幾何平均螢光強度、gMFI)呈現。在圖7A中,抗CTLA-4可活化之抗體包含YV04、YV23、YV24或YV39作為掩蔽部分及2001作為可裂解部分。在圖7B中,抗CTLA-4可活化之抗體包含YV61、YV62、YV64或YV39作為掩蔽部分及2001或2011作為可裂解部分。在圖7C中,抗CTLA-4可活化之抗體包含YV39作為掩蔽部分及2011用於可裂解部分(「Ipi YV39 2011」)或三種Ipi YV39 2011之變體:(i)單一削減(「Ipi YV39 MMP單一削減」)、(ii)由MMP完全削減(「Ipi YV39 MMP」)、或(iii)由uPA完全削減(「Ipi YV39 2011 uPA」)。圖7D提供圖7C中所示之不同可活化之抗體之EC50值。易普利姆瑪用作圖7A至圖7D之對照。
圖8展示在不同濃度下包含YV39作為掩蔽部分及2011作為可裂解部分之抗CTLA-4可活化之抗體(「Ipi YV39 2011」)之活性(方塊),如利用葡萄球菌腸毒素B(Staphylococcal enterotoxin B,SEB)分析所活體外量測。抗體活性藉助於在SEB刺激之後由人類PBMC之IL-2產量展示。不相關人類IgG1同型(三角形)、易普利姆瑪(圓形)及僅SEB刺激(x標記)用作對照。
圖9A至圖9F展示在用以10 mg/kg給藥一次之不同抗人類CTLA-4可活化之抗體(小鼠IgG2a同型)治療之人類CTLA-4基因嵌入小鼠(n = 10)中隨腫瘤植入後天數而變之腫瘤體積。不相關小鼠IgG2a抗體(圖9A)及具有小鼠IgG2a同型(圖9B)之易普利姆瑪用作對照。在圖9C至圖9F中,可活化之抗體分別包含YV04、YV23、YV24及YV39作為掩蔽部分及2001作為可裂解部分。
圖10A至圖10F展示在用不同抗人類CTLA-4可活化之抗體(人類IgG1同型)治療之人類CTLA-4基因嵌入小鼠(n=10)中隨腫瘤植入後天數而變之腫瘤體積。在植入後第7天以200微克/小鼠給藥一次抗體。不相關人類IgG1抗體(圖10A)及具有人類IgG1同型(圖10B)之易普利姆瑪用作對照。在圖10C至圖10F中,可活化之抗體包含YV39作為掩蔽部分及2001、2012、2011或2008作為可裂解部分。可裂解部分2012、2011及2008已經修飾以克服2001中之脫醯胺位點。
圖11A至圖11G展示在用不同劑量之包含YV39作為掩蔽部分及2011作為可裂解部分 (圖11E至圖11G)之可活化之抗體(「Ipi YV39 2011」)治療的人類CTLA-4基因嵌入小鼠(n=16)中隨腫瘤植入後天數而變之腫瘤體積。在腫瘤植入後第7天以10 mg/kg(圖11E)、3 mg/kg(圖11F)或1 mg/kg(圖11G)給藥一次抗體。對照動物用易普利姆瑪(10 mg/Kg、3 mg/Kg或1 mg/kg;分別為圖11B至11D)或不相關人類IgG1抗體(圖11A)治療。
圖12A至圖12D展示在用不同具有小鼠IgG2a同型之抗人類CTLA-4可活化之抗體治療之人類CTLA-4基因嵌入小鼠(n = 10)中,腫瘤(圖12A及圖12B)或脾(圖12C及圖12D)中之調節T細胞之頻率。所有抗體均以10 mg/kg給藥一次。可活化之抗體包含YV04、YV23、YV24或YV39作為掩蔽部分及2001作為可裂解部分。圖12C及圖12D之橫座標軸上之標記亦分別適用於圖12A及圖12B。不相關人類IgG1抗體及具有小鼠IgG2a同型之易普利姆瑪用作對照。在圖12A及圖12C中,調節T細胞之頻率以為Foxp3+之總CD4+ T細胞之百分比形式展示。在圖12B及圖12D中,調節T細胞之頻率以為Foxp3+之總CD45+ T細胞之百分比形式展示。圖12E及圖12F展示經活化之(ICOS+)細胞之頻率且增殖(Ki-67+)細胞以脾中調節T細胞之百分比形式展示。
圖13A至圖13C展示在用抗CTLA-4可活化之抗體治療之人類CTLA-4基因嵌入小鼠中,腫瘤(圖13A及圖13B)或脾(圖13C)中之調節T細胞之頻率。所用之可活化之抗體包含YV39作為掩蔽部分且係小鼠IgG2a同型或人類IgG1同型。不相關人類IgG1抗體及具有人類IgG1同型之易普利姆瑪用作對照。在圖13A及圖13C中,調節T細胞之頻率以為Foxp3+之總CD4+ T細胞之百分比形式展示。在圖13B中,調節T細胞之頻率以為Foxp3+之總CD45+ T細胞之百分比形式展示。圖13D及圖13E展示呈脾中調節T細胞之百分比形式之增殖(Ki-67+)及經活化之(ICOS+)細胞的頻率。
圖14A至圖14C展示在用不同抗CTLA-4可活化之抗體治療之小鼠之腫瘤中,調節T細胞(圖14A及圖14B)或CD4+效應子T細胞(圖14C)之頻率。圖14D及圖14E展示脾中之調節T細胞。抗CTLA-4可活化之抗體包含YV39作為掩蔽部分及2012、2011、2008或2001作為可裂解部分。不相關人類IgG1抗體及具有人類IgG1同型之易普利姆瑪用作對照。在圖14A及圖14D中,調節T細胞之頻率以為Foxp3+之總CD4+ T細胞之百分比形式展示。在圖14B及圖14E中,調節T細胞之頻率以為Foxp3+之總CD45+ T細胞之百分比形式展示。圖14C展示呈腫瘤中總CD45+ T細胞之百分比形式之CD4+效應子T細胞之頻率。圖14F及圖14G展示脾中增殖(Ki-67+)及經活化之(ICOS+)調節T細胞的百分比。
圖15展示在用不同劑量之易普利姆瑪或包含YV39作為掩蔽部分及2011作為可裂解部分之抗CTLA-4可活化之抗體(「Ipi YV39 2011」)治療的人類CTLA-4基因嵌入小鼠(n = 8)之腫瘤中,調節T細胞之頻率。在腫瘤植入後第7天以10 mg/kg、3 mg/kg或1 mg/kg給藥一次抗體。不相關人類IgG1抗體用作對照。
圖16A及圖16B展示在用不同劑量之易普利姆瑪或包含YV39作為掩蔽部分及2011作為可裂解部分之抗CTLA-4可活化之抗體(「Ipi YV39 2011」)治療的人類CTLA-4基因嵌入小鼠(n = 8)之脾中,經活化之(ICOS+)及增殖(Ki-67+)調節T細胞之百分比。在腫瘤植入後第7天以10 mg/kg、3 mg/kg或1 mg/kg給藥一次抗體。不相關人類IgG1抗體用作對照。
圖17A至圖17D展示在用不同劑量之易普利姆瑪(「Ipi」)(圖17B)、未經海藻糖基化版本之易普利姆瑪(「Ipi NF」)(圖17C)或未經海藻糖基化版本之包含YV39作為掩蔽部分及2011作為可裂解部分之抗CTLA-4可活化之抗體(「Ipi YV39 2011 NF」)(圖17D)治療的人類CTLA-4基因嵌入小鼠(n = 10)中,隨腫瘤植入後天數而變之腫瘤體積。以10 mg/kg、3 mg/kg或1 mg/kg給藥一次抗體(分別為圖17B至圖17D中之左圖、中圖及右圖)。對照動物接受不相關人類IgG1抗體(圖17A)。
圖18展示在用未經海藻糖基化版本之易普利姆瑪(「Ipi NF」)或未經海藻糖基化版本之包含YV39作為掩蔽部分及2011作為可裂解部分之抗CTLA-4可活化之抗體(「NF Ipi YV39 2011」)治療的人類CTLA-4基因嵌入小鼠(n = 5)之腫瘤中,調節T細胞之頻率。在腫瘤植入後第7天以200 微克/小鼠給藥一次抗體。不相關人類IgG1抗體用作對照。
圖19展示易普利姆瑪(「Ipi」)及未經海藻糖基化版本之易普利姆瑪(「Ipi NF」)二者對各種人類、食蟹獼猴及小鼠Fc受體之結合親和力(Kd)。
圖20展示在用抗CTLA-4可活化之抗體治療後,食蟹獼猴之血液中之Ki67+ CD4+ T細胞之中值百分比。抗CTLA-4可活化之抗體包含YV39作為掩蔽部分及2001作為可裂解部分。媒劑及易普利姆瑪用作對照。
<![CDATA[<110> 美商必治妥美雅史谷比公司(BRISTOL-MYERS SQUIBB COMPANY)]]> <![CDATA[<120> 可活化之抗CTLA-4抗體及其用途]]> <![CDATA[<130> 106138139]]> <![CDATA[<150> US 62/417,212]]> <![CDATA[<151> 2016-11-03]]> <![CDATA[<160> 570 ]]> <![CDATA[<170> PatentIn version 3.5]]> <![CDATA[<210> 1]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 ]]>- YV1 <![CDATA[<400> 1]]> Asp Phe Ser Cys Leu His Ser Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 2]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV2]]> <![CDATA[<400> 2]]> Gln Pro Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro His Thr 1 5 10 15 <![CDATA[<210> 3]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV3]]> <![CDATA[<400> 3]]> Leu His Cys Arg Thr Gln Met Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 4]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV4]]> <![CDATA[<400> 4]]> Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 5]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - ]]>YV5 <![CDATA[<400> 5]]> Cys Thr Tyr Ser Phe Phe Asn Val Cys 1 5 <![CDATA[<210> 6]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV6]]> <![CDATA[<400> 6]]> Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys 1 5 10 <![CDATA[<210> 7]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV7]]> <![CDATA[<400> 7]]> Cys Pro Asn His Pro Met Cys 1 5 <![CDATA[<210> 8]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV8]]> <![CDATA[<400> 8]]> Gly Thr Ala Cys Thr Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 9]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV9]]> <![CDATA[<400> 9]]> Phe Gly Thr Ala Cys Pro Asn His Pro Met Cys His Asp Trp Gln 1 5 10 15 <![CDATA[<210> 10]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV10]]> <![CDATA[<400> 10]]> Ser Ala Cys Ala Tyr Trp Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 11]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV11]]> <![CDATA[<400> 11]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys 1 5 10 <![CDATA[<210> 12]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV12]]> <![CDATA[<400> 12]]> Cys Arg Thr Gln Ile Tyr Gly Tyr Asn Leu Cys 1 5 10 <![CDATA[<210> 13]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV13]]> <![CDATA[<400> 13]]> Leu His Cys Arg Thr Gln Ile Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 14]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV14]]> <![CDATA[<400> 14]]> Cys Pro Asn His Pro Met Cys His Asp Trp Gln 1 5 10 <![CDATA[<210> 15]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV15]]> <![CDATA[<400> 15]]> Gly Thr Ala Cys Pro Asn His Pro Met Cys His Asp Trp Gln 1 5 10 <![CDATA[<210> 16]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV16]]> <![CDATA[<400> 16]]> Cys Ala Tyr Trp Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 <![CDATA[<210> 17]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV17]]> <![CDATA[<400> 17]]> Gln Glu Cys His Leu Tyr Met Tyr Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 18]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV18]]> <![CDATA[<400> 18]]> Cys His Leu Tyr Met Tyr Gly Val Asn Leu Cys Pro Tyr 1 5 10 <![CDATA[<210> 19]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV19]]> <![CDATA[<400> 19]]> Gly Gln Cys Gln Phe Tyr Met Phe Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 20]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV20]]> <![CDATA[<400> 20]]> Leu Ser Thr Cys Met Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 21]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV21]]> <![CDATA[<400> 21]]> Cys Leu His Ser Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 <![CDATA[<210> 22]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV22]]> <![CDATA[<400> 22]]> Cys Leu His Ser Met Tyr Asn Val Cys 1 5 <![CDATA[<210> 23]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV23]]> <![CDATA[<400> 23]]> Cys Leu His Ser Leu Tyr Asn Val Cys Leu Asp Pro 1 5 10 <![CDATA[<210> 24]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV24]]> <![CDATA[<400> 24]]> Cys Leu His Ser Ala Tyr Asn Val Cys Leu Asp Pro 1 5 10 <![CDATA[<210> 25]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV25]]> <![CDATA[<400> 25]]> Cys Met Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 <![CDATA[<210> 26]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV26]]> <![CDATA[<400> 26]]> Cys Met Tyr Ser Phe Phe Asn Val Cys 1 5 <![CDATA[<210> 27]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV27]]> <![CDATA[<400> 27]]> Gln Pro Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys 1 5 10 <![CDATA[<210> 28]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV28]]> <![CDATA[<400> 28]]> Cys Ala Gln Leu Tyr Gly Tyr Ser Met Cys Pro His Thr 1 5 10 <![CDATA[<210> 29]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV29]]> <![CDATA[<400> 29]]> Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Ala His Thr 1 5 10 <![CDATA[<210> 30]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV30]]> <![CDATA[<400> 30]]> Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro Ala Thr 1 5 10 <![CDATA[<210> 31]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV31]]> <![CDATA[<400> 31]]> Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro His Thr 1 5 10 <![CDATA[<210> 32]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV32]]> <![CDATA[<400> 32]]> Cys Pro Asn His Pro Leu Cys His Asp Trp Gln 1 5 10 <![CDATA[<210> 33]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV33]]> <![CDATA[<400> 33]]> Cys Pro Asn His Pro Met Cys Ala Asp Trp Gln 1 5 10 <![CDATA[<210> 34]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV34]]> <![CDATA[<400> 34]]> Cys Pro Asn His Pro Met Cys His Ala Trp Gln 1 5 10 <![CDATA[<210> 35]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV35]]> <![CDATA[<400> 35]]> Cys Pro Asn His Pro Met Cys His Asp Ala Gln 1 5 10 <![CDATA[<210> 36]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV36]]> <![CDATA[<400> 36]]> Cys Pro Asn His Pro Met Cys His Asp Trp Ala 1 5 10 <![CDATA[<210> 37]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV37]]> <![CDATA[<400> 37]]> Gly Thr Ala Cys Pro Asn His Pro Met Cys 1 5 10 <![CDATA[<210> 38]]> <![CDATA[<211> 1]]>3 <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV38]]> <![CDATA[<400> 38]]> Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys 1 5 10 <![CDATA[<210> 39]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV39]]> <![CDATA[<400> 39]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 <![CDATA[<210> 40]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV40]]> <![CDATA[<400> 40]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Ala Tyr 1 5 10 <![CDATA[<210> 41]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV41]]> <![CDATA[<400> 41]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Ala 1 5 10 <![CDATA[<210> 42]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV42]]> <![CDATA[<400> 42]]> Phe Gly Thr Ala Cys Pro Asn His Pro Leu Cys His Asp Trp Gln 1 5 10 15 <![CDATA[<210> 43]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV43]]> <![CDATA[<400> 43]]> Cys Pro Asn His Pro Leu Cys His Asp Phe Gln 1 5 10 <![CDATA[<210> 44]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV44]]> <![CDATA[<400> 44]]> Cys Pro Asn His Pro Leu Cys His Asp Tyr Gln 1 5 10 <![CDATA[<210> 45]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV45]]> <![CDATA[<400> 45]]> Cys Pro Asn His Pro Leu Cys Pro Tyr 1 5 <![CDATA[<210> 46]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV46]]> <![CDATA[<400> 46]]> Cys Pro Asn His Pro Leu Cys Pro Ala 1 5 <![CDATA[<210> 47]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV47]]> <![CDATA[<400> 47]]> Cys Met Tyr Ser Phe Phe Asn Val Cys Tyr Pro 1 5 10 <![CDATA[<210> 48]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV48]]> <![CDATA[<400> 48]]> Cys Met Tyr Ser Phe Phe Asn Val Cys Tyr Ala 1 5 10 <![CDATA[<210> 49]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV49]]> <![CDATA[<400> 49]]> Cys Leu Tyr Ser Phe Phe Asn Val Cys Tyr Pro 1 5 10 <![CDATA[<210> 50]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV50]]> <![CDATA[<400> 50]]> Cys Leu Tyr Ser Phe Phe Asn Val Cys Tyr Ala 1 5 10 <![CDATA[<210> 51]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV51]]> <![CDATA[<400> 51]]> Phe Gly Ala Ala Cys Pro Asn His Pro Ile Cys His Asp Trp Gln 1 5 10 15 <![CDATA[<210> 52]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV52]]> <![CDATA[<400> 52]]> Phe Gly Ala Ala Cys Pro Asn His Pro Leu Cys His Asp Trp Gln 1 5 10 15 <![CDATA[<210> 53]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV53]]> <![CDATA[<400> 53]]> Phe Gly Ala Ala Cys Pro Asn His Pro Met Cys His Asp Ala Gln 1 5 10 15 <![CDATA[<210> 54]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV54]]> <![CDATA[<400> 54]]> Cys Leu His Ser Ala Tyr Asn Ala Cys Leu Asp Pro 1 5 10 <![CDATA[<210> 55]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV55]]> <![CDATA[<400> 55]]> Cys Ala His Ser Ala Tyr Asn Val Cys Leu Asp Pro 1 5 10 <![CDATA[<210> 56]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV56]]> <![CDATA[<400> 56]]> Cys Leu His Ser Ala Tyr Asn Val Cys Ala Asp Pro 1 5 10 <![CDATA[<210> 57]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV57]]> <![CDATA[<400> 57]]> Cys Leu His Ser Ala Tyr Asn Val Cys Leu Ala Pro 1 5 10 <![CDATA[<210> 58]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV58]]> <![CDATA[<400> 58]]> Cys Leu His Ser Ala Tyr Asn Val Cys Leu Asp Ala 1 5 10 <![CDATA[<210> 59]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV60]]> <![CDATA[<400> 59]]> Lys Asn Thr Cys Thr Tyr Val Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 60]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV61]]> <![CDATA[<400> 60]]> Tyr Ile Ser Asp Cys Pro Tyr His Pro Met Cys His Asp Tyr Gln 1 5 10 15 <![CDATA[<210> 61]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV62]]> <![CDATA[<400> 61]]> Phe Arg Asn Thr Cys Pro Tyr His Pro Met Cys His Asp Tyr Arg 1 5 10 15 <![CDATA[<210> 62]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV63]]> <![CDATA[<400> 62]]> Arg Glu Cys His Met Trp Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 63]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV64]]> <![CDATA[<400> 63]]> Ala Val Cys His Met Tyr Met Tyr Gly Tyr Asn Leu Cys Pro Phe 1 5 10 15 <![CDATA[<210> 64]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV65]]> <![CDATA[<400> 64]]> Arg Ser Cys Pro Gln Met Tyr Gly Tyr Ser Met Cys Pro His Thr 1 5 10 15 <![CDATA[<210> 65]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - YV66]]> <![CDATA[<400> 65]]> Gln Pro Cys Ala Gln Met Phe Gly Tyr Ser Met Cys Pro His Thr 1 5 10 15 <![CDATA[<210> 66]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 66]]> Thr Ala Lys Cys Thr Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 67]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 67]]> Asp Phe Ser Cys Leu Tyr Ser Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 68]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 68]]> Asp Val Ser Cys Met Tyr Met Met Tyr Asn Phe Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 69]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 69]]> Cys Pro Asn His Pro Met Cys 1 5 <![CDATA[<210> 70]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 70]]> Cys Met Tyr Ser Phe Phe Asn Val Cys Pro Tyr 1 5 10 <![CDATA[<210> 71]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 71]]> Cys Met Tyr Ser Phe Phe Asn Val Cys Pro Ala 1 5 10 <![CDATA[<210> 72]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 72]]> Cys Thr Tyr Ser Phe Phe Asn Val Cys Pro Tyr 1 5 10 <![CDATA[<210> 73]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 73]]> Cys Thr Tyr Ser Phe Phe Asn Val Cys Pro Ala 1 5 10 <![CDATA[<210> 74]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 74]]> Gly Phe Pro Cys Met Tyr Ser Met Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 75]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 75]]> Gly Leu Ser Cys Met Tyr Ser Met Tyr Gly Tyr Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 76]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 76]]> Ile Pro Cys Asp Tyr Trp Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 77]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 77]]> Gln Val Cys His Ala Tyr Met Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 78]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 78]]> Arg Met Tyr Cys Thr Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 79]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 79]]> Ala Leu Ser Cys Met Tyr Ile Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 80]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 80]]> Asp Phe Ser Cys Met Tyr Val Met Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 81]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 81]]> Asp Phe Ser Cys Val Tyr Ser Met Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 82]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 82]]> Asp Met Asn Thr Cys Pro Asn His Pro Met Cys Tyr Asp Tyr Arg 1 5 10 15 <![CDATA[<210> 83]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 83]]> Asp Met Asn Thr Cys Pro Arg His Pro Met Cys His Asp Tyr His 1 5 10 15 <![CDATA[<210> 84]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 84]]> Asp Ser Arg Cys Met Tyr Val Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 85]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 85]]> Glu His Leu Cys Thr Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 86]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 86]]> Glu Leu Ser Cys Val Tyr Ser Met Phe Gly Phe Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 87]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 87]]> Phe Thr Asn Asn Cys Pro Tyr His Pro Met Cys His Asp Tyr Leu 1 5 10 15 <![CDATA[<210> 88]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 88]]> Gly Phe Ser Cys Thr Tyr Ile Met Tyr Asp Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 89]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 89]]> Gly Ser Ser Cys Met Tyr Ser Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 90]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 90]]> His Phe Ser Cys Met Tyr Ile Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 91]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 91]]> Leu His Cys Gly Met Trp Met Phe Gly Val Asn Leu Cys Pro Lys 1 5 10 15 <![CDATA[<210> 92]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 92]]> Leu Pro Cys Gln Met Trp Met Phe Gly His Asn Leu Cys Pro His 1 5 10 15 <![CDATA[<210> 93]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 93]]> Leu Pro Cys Thr Met Tyr Met Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 94]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 94]]> Leu Thr Cys His His Trp Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 95]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 95]]> Asn Phe Ser Cys Met Tyr Ser Met Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 96]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 96]]> Asn Asn His Cys Met Tyr Ser Phe Phe Asn Ile Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 97]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 97]]> Asn Arg Ser Cys Met Tyr Ile Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 98]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 98]]> Asn Ser Cys Thr Met Phe Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 99]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 99]]> Asn Thr Cys Glu Leu Tyr Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 100]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 100]]> Gln His Cys Asp Met Trp Met Phe Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 101]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 101]]> Gln His Cys Pro Met Tyr Met Phe Gly Tyr Asn Leu Cys Pro Phe 1 5 10 15 <![CDATA[<210> 102]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 102]]> Gln Val Cys His Ile Gln Met Tyr Gly Phe Asp Leu Cys Pro His 1 5 10 15 <![CDATA[<210> 103]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 103]]> Arg Ala Cys Asp Tyr Trp Met Tyr Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 104]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 104]]> Arg Gln Cys His Met Gln Met Phe Gly Tyr Asp Leu Cys Pro Phe 1 5 10 15 <![CDATA[<210> 105]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 105]]> Ser Gly Ser Cys Leu Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 106]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 106]]> Ser Asn Gly Cys Thr Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 107]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 107]]> Ser Thr Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro His 1 5 10 <![CDATA[<210> 108]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 108]]> Ser Tyr Lys Cys Leu Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 109]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 109]]> Val Leu Tyr Cys Thr Tyr Val Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 110]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 110]]> Val Asn Cys Gly Met Trp Met Phe Gly Tyr Asn Leu Cys Pro Lys 1 5 10 15 <![CDATA[<210> 111]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 111]]> Tyr Gly Ser Cys Leu Tyr Ser Phe Tyr Asn Ile Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 112]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 112]]> Tyr Pro Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro His Thr 1 5 10 15 <![CDATA[<210> 113]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 113]]> Ala Ala Cys Asp Leu Trp Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 114]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> ]]>掩蔽部分 <![CDATA[<400> 114]]> Ala Phe Cys Thr Leu Ala Pro Tyr Asn Gln Ala Cys Ile Ala Asn 1 5 10 15 <![CDATA[<210> 115]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 115]]> Ala Gly Ser Cys Leu Tyr Ser Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 116]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 116]]> Ala Leu Cys Glu Asn Thr Met Tyr Gly Tyr His Leu Cys Pro Trp 1 5 10 15 <![CDATA[<210> 117]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 117]]> Ala Leu Ser Cys Met Tyr Ile Met Tyr Gly Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 118]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220]]>>]]> <br/><![CDATA[<223> 掩蔽部分]]> <br/> <br/><![CDATA[<400> 118]]> <br/> <br/><![CDATA[Ala Pro Val Cys Asp Val Leu Met Phe Gly Phe Cys Met Gln Pro 1 5 10 15 <![CDATA[<210> 119]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 119]]> Ala Gln Val Cys Ser Ile Met Met Tyr Gly Thr Cys Leu Met Pro 1 5 10 15 <![CDATA[<210> 120]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 120]]> Ala Ser Thr Cys Met Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 121]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 121]]> Ala Val Cys Glu Phe Trp Met Phe Gly Phe Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 122]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 122]]> Asp Ala Asn Thr Cys Pro Asn His Pro Met Cys Tyr Asp Tyr His 1 5 10 15 <![CDATA[<210> 123]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 123]]> Asp Phe Ser Cys Ile Tyr Ile Met Phe Asp Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 124]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 124]]> Asp Phe Ser Cys Met Tyr Val Met Tyr Gly Phe Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 125]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 125]]> Asp Phe Thr Cys Met Tyr Ser Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 126]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 126]]> Asp Phe Thr Cys Thr Tyr Ser Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 127]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 127]]> Asp His Tyr Cys Thr Tyr Ile Met Tyr Ser Ile Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 128]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 128]]> Asp Ile Cys Thr Asn Phe Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 129]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 129]]> Asp Ile Asn Thr Cys Pro Tyr His Pro Met Cys His Asp Tyr His 1 5 10 15 <![CDATA[<210> 130]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 130]]> Asp Lys Asn Thr Cys Pro Leu His Pro Met Cys His Asp Tyr Arg 1 5 10 15 <![CDATA[<210> 131]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 131]]> Asp Met Asn Met Cys Pro Asn His Pro Met Cys His Asp Trp His 1 5 10 15 <![CDATA[<210> 132]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 132]]> Asp Met Asn Ser Cys Pro Asn His Pro Met Cys His Asp Tyr His 1 5 10 15 <![CDATA[<210> 133]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 133]]> Asp Met Asn Ser Cys Pro Asn His Pro Met Cys Tyr Asp Tyr Arg 1 5 10 15 <![CDATA[<210> 134]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 134]]> Asp Met Asn Thr Cys Pro Asn His Pro Met Cys Phe Asp Tyr Arg 1 5 10 15 <![CDATA[<210> 135]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 135]]> Asp Met Asn Thr Cys Pro Asn His Pro Met Cys His Asp Phe Gln 1 5 10 15 <![CDATA[<210> 136]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 136]]> Asp Met Asn Thr Cys Pro Asn His Pro Met Cys His Asp Tyr Arg 1 5 10 15 <![CDATA[<210> 137]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 137]]> Asp Met Asn Thr Cys Pro Asn His Pro Met Cys Tyr Asp Tyr His 1 5 10 15 <![CDATA[<210> 138]]> <![CDATA[<21]]>1> 15]]> <br/><![CDATA[<212> PRT]]> <br/><![CDATA[<213> 人工序列]]> <br/> <br/><![CDATA[<220>]]> <br/><![CDATA[<223> 掩蔽部分]]> <br/> <br/><![CDATA[<400> 138]]> <br/> <br/><![CDATA[Asp Met Asn Thr Cys Pro Asn His Pro Met Cys Tyr Asp Tyr Lys 1 5 10 15 <![CDATA[<210> 139]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 139]]> Asp Met Ser Thr Cys Pro Asn His Pro Met Cys His Asp Tyr Met 1 5 10 15 <![CDATA[<210> 140]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 140]]> Asp Arg Asn Met Cys Pro Tyr His Pro Met Cys Tyr Asp Tyr Arg 1 5 10 15 <![CDATA[<210> 141]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 141]]> Asp Ser Cys Ala Phe Met Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 142]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 142]]> Asp Ser Cys Arg Ser Val Phe Asp Met Val Trp Asn Cys Trp Asn 1 5 10 15 <![CDATA[<210> 143]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 143]]> Asp Thr Pro Asn Cys Pro His His Pro Met Cys His Asn His Met 1 5 10 15 <![CDATA[<210> 144]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 144]]> Asp Val Ser Cys Leu Tyr Val Met Tyr Ser Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 145]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 145]]> Asp Trp Cys Ala Ser Met Met Phe Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 146]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 146]]> Glu Phe Ser Cys Met Tyr Ser Met Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 147]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 147]]> Glu His Cys Asp Val Trp Met Phe Gly Phe Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 148]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 148]]> Glu Pro Cys Asp Tyr Trp Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 149]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 149]]> Glu Gln Cys Thr Met Trp Met Tyr Gly Phe Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 150]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 150]]> Glu Ser Ala Cys Ser Leu Arg Met Tyr Glu Val Cys Leu Gln Pro 1 5 10 15 <![CDATA[<210> 151]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 151]]> Glu Ser Cys Ala Ser Met Tyr Gly Tyr Ser Met Cys Pro Arg Thr 1 5 10 15 <![CDATA[<210> 152]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 152]]> Glu Ser Cys Ser Tyr Trp Met Phe Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 153]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 153]]> Phe Ser Asn Thr Cys Pro His His Pro Met Cys Tyr Asp Tyr Arg 1 5 10 15 <![CDATA[<210> 154]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 154]]> Phe Trp Asn Thr Cys Pro His His Pro Met Cys His Asp Tyr Lys 1 5 10 15 <![CDATA[<210> 155]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 155]]> Phe Tyr Gln Asn Cys Tyr Pro Pro Thr Trp Cys Ser Met Phe Ser 1 5 10 15 <![CDATA[<210> 156]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 156]]> Gly Glu Cys Ser Tyr Trp Met Phe Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 157]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 157]]> Gly Gly Ser Cys Met Tyr Ser Phe Phe Asn Ile Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 158]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 158]]> Gly Gly Ser Cys Val Tyr Val Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 159]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 159]]> Gly His Cys Leu Met His Met Tyr Gly Tyr Asn Leu Cys Pro Lys 1 5 10 15 <![CDATA[<210> 160]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 160]]> Gly His Cys Arg Met Ser Met Tyr Glu Met Thr Leu Cys Pro Arg 1 5 10 15 <![CDATA[<210> 161]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 161]]> Gly Ile Ser Cys Val His Ile Met Phe Asn Phe Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 162]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 162]]> Gly Leu Cys Val Met Tyr Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 163]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 163]]> Gly Ser Cys Asp Tyr Trp Met Phe Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 164]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 164]]> Gly Ser Tyr Cys Met Tyr Val Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 165]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 165]]> Gly Thr Lys Cys Ile Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 166]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 166]]> Gly Thr Ser Thr Cys Pro Tyr His Pro Met Cys His Asp Tyr Arg 1 5 10 15 <![CDATA[<210> 167]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 167]]> Gly Thr Thr Cys Thr Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 168]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 168]]> Gly Val Cys His Phe Phe Met Tyr Gly Val Ser Met Cys Pro Ala 1 5 10 15 <![CDATA[<210> 169]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 169]]> Gly Val Pro Cys Trp Tyr Ser Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 170]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 170]]> Gly Val Ser Cys Met Tyr Ser Met Phe Asn Ile Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 171]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 171]]> His Ala Lys Cys Val Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 172]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 172]]> His Asp Ser Cys Met Tyr Ser Met Tyr Asn Phe Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 173]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> ]]> 173 His Gly Asn Thr Cys Pro Asn His Pro Met Cys His Asp Tyr Gln 1 5 10 15 <![CDATA[<210> 174]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 174]]> His Lys Gly Cys Leu Tyr Ser Phe Tyr Asn Ile Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 175]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 175]]> His Lys Gly Cys Leu Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 176]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 176]]> His Leu Ser Cys Met Tyr Ile Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 177]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 177]]> His Ser Ser Cys Ile Tyr Ser Met Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 178]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 178]]> His Thr Asn Met Cys Pro Tyr His Pro Met Cys Tyr Asp Tyr Lys 1 5 10 15 <![CDATA[<210> 179]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 179]]> His Thr Pro Cys Thr Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 180]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 180]]> Ile Met Asn Thr Cys Pro Tyr His Pro Met Cys His Asp Tyr Gln 1 5 10 15 <![CDATA[<210> ]]>181 <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 181]]> Ile Val Pro Cys Thr Tyr Met Met Phe Gly Val Cys Leu Gln Pro 1 5 10 15 <![CDATA[<210> 182]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 182]]> Lys Lys Cys Asp Tyr Trp Phe Tyr Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 183]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 183]]> Lys Asn Thr Cys Val Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 184]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 184]]> Lys Pro Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro His Pro 1 5 10 15 <![CDATA[<210> 185]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> ]]> 掩蔽部分 <![CDATA[<400> 185]]> Lys Pro Ser Cys Met Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 186]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 186]]> Lys Arg Pro Cys Met Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 187]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 187]]> Lys Thr Ser Cys Met Tyr Ser Phe Tyr Asn Ile Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 188]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 188]]> Lys Thr Thr Cys Thr Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 189]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<22]]>0>]]> <br/><![CDATA[<223> 掩蔽部分]]> <br/> <br/><![CDATA[<400> 189]]> <br/> <br/><![CDATA[Leu Asp Cys Gln Met Tyr Trp Trp Phe Gly Ala Cys Gly Asp Met 1 5 10 15 <![CDATA[<210> 190]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 190]]> Leu His Cys Ala Ile Tyr Met Tyr Gly Tyr Asn Leu Cys Pro Phe 1 5 10 15 <![CDATA[<210> 191]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213>]]> 人工序列 <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 191]]> Leu His Cys Pro Phe Gln Met Tyr Gly Tyr Asn Leu Cys Pro His 1 5 10 15 <![CDATA[<210> 192]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 192]]> Leu His Cys Ser Met Tyr Met Tyr Gly Phe Asn Leu Cys Pro Asn 1 5 10 15 <![CDATA[<210> 193]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 193]]> Arg Glu Cys Met Ala Tyr Met Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 194]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 194]]> Arg His Cys Gln Met His Met Phe Gly Tyr Asp Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 195]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 195]]> Leu Ile His Cys Arg Tyr Val Met Tyr Gly Met Cys Leu Glu Pro 1 5 10 15 <![CDATA[<210> 196]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 196]]> Leu Leu Pro Cys Glu Val Met Gly Pro Ser Arg Cys Lys His Asp 1 5 10 15 <![CDATA[<210> 197]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 197]]> Leu Pro Cys His Ala Tyr Met Tyr Gly Tyr Ser Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 198]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 198]]> Leu Pro Cys Leu Ala Tyr Met Tyr Gly Val Asn Leu Cys Pro Asn 1 5 10 15 <![CDATA[<210> 199]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 199]]> Leu Pro Cys Met Ala Tyr Met Phe Gly Phe Asn Leu Cys Pro His 1 5 10 15 <![CDATA[<210> 200]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 200]]> Leu Pro Cys Asn Phe His Met Phe Gly Phe Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 201]]> <![CDATA[<211> 15]]> <![CDATA[<212> ]]>PRT <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 201]]> Leu Gln Cys Ala Met Tyr Met Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 202]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 202]]> Leu Ser Ser Cys Thr Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 203]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 203]]> Leu Thr Cys Pro Phe Gln Met Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 204]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 204]]> Leu Thr Ser Gln Cys Ser Pro Trp Tyr Trp Cys Gln Ile Tyr Asp 1 5 10 15 <![CDATA[<210> 205]]> <![CDATA[<211> 1]]>5 <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 205]]> Leu Tyr Cys Pro Tyr Met Met Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 206]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 206]]> Leu Tyr His Cys Thr Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 207]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 207]]> Leu Tyr Arg Cys Ile Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 208]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 208]]> Met Gly Cys Ser Met Arg Met Trp Gly Met Glu Leu Cys Pro Glu 1 5 10 15 <![CDATA[<210> 209]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 209]]> Met Lys Cys Asp Tyr Trp Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 210]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 210]]> Met Asn His Cys Thr Leu His Met Tyr Asn Ile Cys Met Asp Pro 1 5 10 15 <![CDATA[<210> 211]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 211]]> Met Asn Pro Glu Cys Pro His His Pro Met Cys His Asn Ser Asn 1 5 10 15 <![CDATA[<210> 212]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 212]]> Met Pro Ala Cys Thr Tyr Ser Phe Phe Asn Ile Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 213]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 213]]> Met Pro Gln Cys His Val Ile Met Tyr Asn Leu Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 214]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 214]]> Met Ser Thr Cys Thr Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 215]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 215]]> Met Thr Cys Asn Tyr Trp Phe Tyr Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 216]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 216]]> Met Tyr Cys His Gln Ser Met Phe Gly Phe Arg Met Cys Pro Asp 1 5 10 15 <![CDATA[<210> 217]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 217]]> Asn Ala Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro His Thr 1 5 10 15 <![CDATA[<210> 218]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 218]]> Asn Asp Cys Asp Ile Ser Met Phe Asp Gln Ser Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 219]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 219]]> Asn Phe Ser Cys Val Tyr Val Met Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 220]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 220]]> Asn Phe Thr Cys Ala Leu Thr Met Tyr Glu Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 221]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 221]]> Asn Leu Cys His Ala Phe Met Phe Gly Phe Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 222]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 222]]> Asn Leu Asn Asn Cys Pro His His Pro Met Cys His Asp Tyr Gln 1 5 10 15 <![CDATA[<210> 223]]> <![CDATA[<21]]>1> 15]]> <br/><![CDATA[<212> PRT]]> <br/><![CDATA[<213> 人工序列]]> <br/> <br/><![CDATA[<220>]]> <br/><![CDATA[<223> 掩蔽部分]]> <br/> <br/><![CDATA[<400> 223]]> <br/> <br/><![CDATA[Asn Pro Pro Cys Met Tyr Ser Phe Phe Asn Ile Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 224]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 224]]> Asn Ser Ala Cys Thr Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 225]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 225]]> Asn Val Cys Thr Val Ser Met Phe Gly Val Met Leu Cys Pro Ser 1 5 10 15 <![CDATA[<210> 226]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 226]]> Pro Ala Cys Ala Thr Leu Met Tyr Ser Val Pro Leu Cys Pro Ala 1 5 10 15 <![CDATA[<210> 227]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 227]]> Pro Ala Pro Cys Met Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 228]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 228]]> Pro Leu Cys Ala Glu Met Tyr Gly Tyr Ser Met Cys Pro His Asn 1 5 10 15 <![CDATA[<210> 229]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 229]]> Pro Gln Cys His Leu Tyr Met Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 230]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 230]]> Pro Arg Pro Cys Met Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 231]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 231]]> Gln His Cys Pro Phe Gln Met Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 232]]> <![CDATA[<211> 15]]> <![CDATA[<212> ]]>PRT <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 232]]> Gln His Cys Gln Met His Met Phe Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 233]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 233]]> Gln His Ser Cys Met Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 234]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 234]]> Gln Lys Cys His Ser Tyr Leu Tyr Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 235]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 235]]> Gln Lys Cys Asn Met Phe Met Phe Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 236]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 236]]> Gln Met Asn Asp Cys Pro Asn His Pro Met Cys His Asp Tyr His 1 5 10 15 <![CDATA[<210> 237]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 237]]> Gln Pro Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro Ala Thr 1 5 10 15 <![CDATA[<210> 238]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 238]]> Gln Pro Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro Arg Thr 1 5 10 15 <![CDATA[<210> 239]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 239]]> Arg Glu Cys His Phe Phe Phe Tyr Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 240]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 240]]> Leu Asn Cys Gly Met Phe Met Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 241]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 241]]> Arg Leu Cys Thr Ser Tyr Met Phe Gly Tyr Asn Leu Cys Pro Gln 1 5 10 15 <![CDATA[<210> 242]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 242]]> Arg Leu Ser Cys Met Tyr Ser Met Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 243]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 243]]> Arg Asn Cys Pro Phe Val Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 244]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 244]]> Arg Asn Gly Cys Met Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 245]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 245]]> Arg Asn Gly Cys Val Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 246]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 246]]> Arg Pro Cys His Leu Tyr Met Phe Gly Tyr Asn Leu Cys Pro Asp 1 5 10 15 <![CDATA[<210> 247]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 247]]> Arg Pro Cys His Ser Tyr Met Tyr Gly Ile Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 248]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 248]]> Arg Ser Cys Asp Met Ile Met Phe Gly Phe Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 249]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 249]]> Arg Ser Cys Pro Met Trp Phe Tyr Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 250]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 250]]> Arg Ser Thr Val Cys Phe Tyr Asp Phe Cys Gly Pro Trp Glu Arg 1 5 10 15 <![CDATA[<210> 251]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 251]]> Arg Thr Cys His Phe Tyr Met Tyr Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 252]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 252]]> Arg Thr Cys Ser Met Val Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 253]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 253]]> Ser Gly Lys Cys Thr Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 254]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 254]]> Ser Ile Val Cys Asp Leu Tyr Trp Glu Ala Thr Cys Leu Arg Pro 1 5 10 15 <![CDATA[<210> 255]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 255]]> Ser Leu Ser Cys Thr Tyr Ser Phe Phe Asn Ile Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 256]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 256]]> Ser Met Asn Thr Cys Pro Tyr His Pro Met Cys Phe Asp Tyr Lys 1 5 10 15 <![CDATA[<210> 257]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 257]]> Ser Gln Cys Trp Met Trp Met Tyr Gly Tyr Asn Leu Cys Pro Lys 1 5 10 15 <![CDATA[<210> 258]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> ]]> 258 Ser Ser Ser Cys Met Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 259]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 259]]> Ser Thr Ala Cys Thr Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 260]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 260]]> Ser Thr Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro His Thr 1 5 10 15 <![CDATA[<210> 261]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 261]]> Ser Thr Arg Cys Val Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 262]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 262]]> Thr Ala Cys Gly Ala Trp Met Phe Gly Val Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 263]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 263]]> Thr Gly Ala Cys Met Tyr Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 264]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 264]]> Thr Leu Ser Cys Met Tyr Ser Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 265]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 265]]> Thr Ser Cys Thr Val Thr Met Tyr Gln Ile Ser Met Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 266]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 266]]> Val Gly Gly Cys Arg His Ser Phe Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 267]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 267]]> Val His Cys Gln Met Tyr Met Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 268]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 268]]> Val His Asn Cys Met Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 269]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 269]]> Val Met Cys Lys Leu His Met Tyr Gly Ile Pro Val Cys Pro Lys 1 5 10 15 <![CDATA[<210> 270]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 270]]> Val Asn Phe Cys Asn Tyr Ser Met Tyr Gly Ile Cys Leu Leu Pro 1 5 10 15 <![CDATA[<210> 271]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 271]]> Val Asn Phe Cys Tyr Ala Cys Tyr Cys Met Ser Cys Val Phe Ser 1 5 10 15 <![CDATA[<210> 272]]> <![CDATA[<211> 15]]> <![CDATA[<212> ]]>PRT <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 272]]> Val Asn Gln Cys Thr Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 273]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 273]]> Val Pro Cys Pro Phe His Met Phe Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 274]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 274]]> Val Arg Cys Gln Met Trp Met Tyr Gly Phe Asn Leu Cys Pro His 1 5 10 15 <![CDATA[<210> 275]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 275]]> Val Arg Pro Cys Thr Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 276]]> <![CDATA[<211> 1]]>5 <![CDATA[<212> PRT]]> <![CDATA[<213>]]> 人工序列 <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 276]]> Val Ser Gly Cys Thr Tyr Ser Phe Phe Asn Ile Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 277]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 277]]> Tyr Cys Ser Ser Trp Asp Thr Met Thr Ile Pro Ala Cys Asn Asn 1 5 10 15 <![CDATA[<210> 278]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 278]]> Tyr Asp Cys Asp Leu Ser Met Phe Gly Ile Glu Met Cys Pro Gln 1 5 10 15 <![CDATA[<210> 279]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 279]]> Tyr Gly Asn Thr Cys Pro Phe His Pro Met Cys His Asp Tyr Lys 1 5 10 15 <![CDATA[<210> 280]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 280]]> Tyr Gly Tyr Cys Met Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 281]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 281]]> Tyr His Cys Thr Met His Met Phe Gly Tyr Asn Leu Cys Pro Phe 1 5 10 15 <![CDATA[<210> 282]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 282]]> Tyr Met Asn Thr Cys Pro Asn His Pro Met Cys Phe Asp Tyr Gln 1 5 10 15 <![CDATA[<210> 283]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 283]]> Tyr Met Asn Thr Cys Pro Tyr His Pro Met Cys His Asp Tyr Leu 1 5 10 15 <![CDATA[<210> 284]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 284]]> Tyr Met Asn Thr Cys Pro Tyr His Pro Met Cys His Asp Tyr Arg 1 5 10 15 <![CDATA[<210> 285]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 285]]> Tyr Asn Asn Cys Thr Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 286]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 286]]> Tyr Pro Gly Cys Gln Tyr Ser Phe Phe Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 287]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 287]]> Tyr Arg Ser Cys Thr His Ile Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 288]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 288]]> Tyr Ser Phe Cys Asp Met Leu Met Tyr Asp Val Cys Leu Val Pro 1 5 10 15 <![CDATA[<210> 289]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 289]]> Tyr Ser Ile Asp Cys Gly Leu Ser Trp Trp Cys Gly Gly Met Thr 1 5 10 15 <![CDATA[<210> 290]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 290]]> Tyr Ser Thr Thr Cys Pro Tyr His Pro Met Cys His Asp Tyr His 1 5 10 15 <![CDATA[<210> 291]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 291]]> Tyr Val Asn Thr Cys Pro His His Pro Met Cys His Asp Tyr His 1 5 10 15 <![CDATA[<210> 292]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分]]> <![CDATA[<400> 292]]> Tyr Val Asn Thr Cys Pro Tyr His Pro Met Cys His Asp Tyr Asn 1 5 10 15 <![CDATA[<210> 293]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - MY03]]> <![CDATA[<400> 293]]> Met Cys Leu Pro Pro Leu Phe Glu Leu Ala Ser Thr Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 294]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - MY11]]> <![CDATA[<400> 294]]> Leu Pro Asp Cys Gly Met Trp Gly Ile Ser Cys Gly Gly Thr Val 1 5 10 15 <![CDATA[<210> 295]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - MY16]]> <![CDATA[<400> 295]]> Arg Asp His Thr Cys Asn Pro Arg Asn Cys His Pro Asn Met Phe 1 5 10 15 <![CDATA[<210> 296]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 掩蔽部分 - MY04]]> <![CDATA[<400> 296]]> Trp Arg Cys Met Pro Pro Thr Trp Glu Thr Thr Gln Cys His Thr 1 5 10 15 <![CDATA[<210> 297]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 20]]>01 <![CDATA[<400> 297]]> Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn His 1 5 10 <![CDATA[<210> 298]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 2003]]> <![CDATA[<400> 298]]> Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Ala Asn Pro Arg Gly 1 5 10 15 <![CDATA[<210> ]]> 299 <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 2005]]> <![CDATA[<400> 299]]> Ala Val Gly Leu Leu Ala Pro Pro Ser Gly Arg Ser Ala Asn Pro Arg 1 5 10 15 Gly <![CDATA[<210> 300]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 2006]]> <![CDATA[<400> 300]]> Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asp His 1 5 10 <![CDATA[<210> 301]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 2007]]> <![CDATA[<400> 301]]> Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Ile His 1 5 10 <![CDATA[<210> 302]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 2008]]> <![CDATA[<400> 302]]> Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Gln His 1 5 10 <![CDATA[<210> 303]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 2009]]> <![CDATA[<400> 303]]> Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Thr His 1 5 10 <![CDATA[<210> 304]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 2011]]> <![CDATA[<400> 304]]> Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn Pro 1 5 10 <![CDATA[<210> 305]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 2012]]> <![CDATA[<400> 305]]> Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Ala Asn Pro 1 5 10 <![CDATA[<210> 306]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 3001]]> <![CDATA[<400> 306]]> Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp 1 5 10 15 Asn His <![CDATA[<210> 307]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序]]>列 <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 3006]]> <![CDATA[<400> 307]]> Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp 1 5 10 15 Asp His <![CDATA[<210> 308]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 3007]]> <![CDATA[<400> 308]]> Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp 1 5 10 15 Ile His <![CDATA[<210> 309]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 3008]]> <![CDATA[<400> 309]]> Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp 1 5 10 15 Gln His <![CDATA[<210> 310]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 3009]]> <![CDATA[<400> 310]]> Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp 1 5 10 15 Thr His <![CDATA[<210> 311]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 3011]]> <![CDATA[<400> 311]]> Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp 1 5 10 15 Asn Pro <![CDATA[<210> 312]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分 - 3012]]> <![CDATA[<400> 312]]> Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Ala 1 5 10 15 Asn Pro <![CDATA[<210> 313]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 313]]> Leu Ser Gly Arg Ser Asp Asn His 1 5 <![CDATA[<210> 314]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 314]]> Leu Ser Gly Arg Ser Ala Asn Pro Arg Gly 1 5 10 <![CDATA[<210> 315]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 315]]> Thr Gly Arg Gly Pro Ser Trp Val 1 5 <![CDATA[<210> 316]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 316]]> Pro Leu Thr Gly Arg Ser Gly Gly 1 5 <![CDATA[<210> 317]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220]]>>]]> <br/><![CDATA[<223> 可裂解部分]]> <br/> <br/><![CDATA[<400> 317]]> <br/> <br/><![CDATA[Thr Ala Arg Gly Pro Ser Phe Lys 1 5 <![CDATA[<210> 318]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 318]]> Asn Thr Leu Ser Gly Arg Ser Glu Asn His Ser Gly 1 5 10 <![CDATA[<210> 319]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 319]]> Asn Thr Leu Ser Gly Arg Ser Gly Asn His Gly Ser 1 5 10 <![CDATA[<210> 320]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 320]]> Thr Ser Thr Ser Gly Arg Ser Ala Asn Pro Arg Gly 1 5 10 <![CDATA[<210> 321]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 321]]> Thr Ser Gly Arg Ser Ala Asn Pro 1 5 <![CDATA[<210> 322]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 322]]> Val His Met Pro Leu Gly Phe Leu Gly Pro 1 5 10 <![CDATA[<210> 323]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 323]]> Ala Val Gly Leu Leu Ala Pro Pro 1 5 <![CDATA[<210> 324]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 324]]> Ala Gln Asn Leu Leu Gly Met Val 1 5 <![CDATA[<210> 325]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 325]]> Gln Asn Gln Ala Leu Arg Met Ala 1 5 <![CDATA[<210> 326]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 326]]> Leu Ala Ala Pro Leu Gly Leu Leu 1 5 <![CDATA[<210> 327]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 327]]> Ser Thr Phe Pro Phe Gly Met Phe 1 5 <![CDATA[<210> 328]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 328]]> Ile Ser Ser Gly Leu Leu Ser Ser 1 5 <![CDATA[<210> 329]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 329]]> Pro Ala Gly Leu Trp Leu Asp Pro 1 5 <![CDATA[<210> 330]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 330]]> Val Ala Gly Arg Ser Met Arg Pro 1 5 <![CDATA[<210> 331]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 331]]> Val Val Pro Glu Gly Arg Arg Ser 1 5 <![CDATA[<210> 332]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 332]]> Ile Leu Pro Arg Ser Pro Ala Phe 1 5 <![CDATA[<210> 333]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 333]]> Met Val Leu Gly Arg Ser Leu Leu 1 5 <![CDATA[<210> 334]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 334]]> Val Ala Gly Arg Ser Met Arg Pro 1 5 <![CDATA[<210> 335]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 335]]> Gln Gly Arg Ala Ile Thr Phe Ile 1 5 <![CDATA[<210> 336]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 336]]> Ser Pro Arg Ser Ile Met Leu Ala 1 5 <![CDATA[<210> 337]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 337]]> Ser Met Leu Arg Ser Met Pro Leu 1 5 <![CDATA[<210> 338]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 338]]> Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp 1 5 10 15 Tyr His <![CDATA[<210> 339]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 339]]> Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Ala 1 5 10 15 Asn Ile <![CDATA[<210> 340]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 340]]> Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp 1 5 10 15 Asn Ile <![CDATA[<210> 341]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 341]]> Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Tyr His 1 5 10 <![CDATA[<210> 342]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 342]]> Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Ala Asn Ile 1 5 10 <![CDATA[<210> 343]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 可裂解部分]]> <![CDATA[<400> 343]]> Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn Ile 1 5 10 <![CDATA[<210> 344]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 易普利姆瑪-VL]]> <![CDATA[<400> 344]]> Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 85 90 95 Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 <![CDATA[<210> 345]]> <![CDATA[<211> 118]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 易普利姆瑪-VH]]> <![CDATA[<400> 345]]> Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Thr Phe Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile Tyr Tyr Cys 85 90 95 Ala Arg Thr Gly Trp Leu Gly Pro Phe Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 346]]> <![CDATA[<211> 107]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人類 Kappa 恆定區 LC]]> <![CDATA[<400> 346]]> Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 1 5 10 15 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 20 25 30 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 35 40 45 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 50 55 60 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 65 70 75 80 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 85 90 95 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 100 105 <![CDATA[<210> 347]]> <![CDATA[<211> 107]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 小鼠 Kappa 恆定區 LC]]> <![CDATA[<400> 347]]> Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu 1 5 10 15 Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe 20 25 30 Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg 35 40 45 Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser 50 55 60 Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu 65 70 75 80 Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser 85 90 95 Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys 100 105 <![CDATA[<210> 348]]> <![CDATA[<211> 215]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 易普利姆瑪-人類 Kappa LC]]> <![CDATA[<400> 348]]> Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 85 90 95 Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala 100 105 110 Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 115 120 125 Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 130 135 140 Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 145 150 155 160 Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 165 170 175 Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 180 185 190 Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 195 200 205 Ser Phe Asn Arg Gly Glu Cys 210 215 <![CDATA[<210> 349]]> <![CDATA[<211> 215]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 易普利姆瑪-小鼠 Kappa LC]]> <![CDATA[<400> 349]]> Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 85 90 95 Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Asp Ala 100 105 110 Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser 115 120 125 Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp 130 135 140 Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val 145 150 155 160 Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met 165 170 175 Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser 180 185 190 Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys 195 200 205 Ser Phe Asn Arg Asn Glu Cys 210 215 <![CDATA[<210> 350]]> <![CDATA[<211> 329]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人類 IgG1 恆定區 HC]]> <![CDATA[<400> 350]]> Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 1 5 10 15 Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 20 25 30 Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 35 40 45 Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 50 55 60 Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 65 70 75 80 Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 85 90 95 Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 100 105 110 Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 115 120 125 Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 130 135 140 Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 145 150 155 160 Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 165 170 175 Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 180 185 190 His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 195 200 205 Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 210 215 220 Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 225 230 235 240 Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 245 250 255 Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 260 265 270 Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 275 280 285 Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 290 295 300 Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 305 310 315 320 Gln Lys Ser Leu Ser Leu Ser Pro Gly 325 <![CDATA[<210> 351]]> <![CDATA[<211> 329]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 小鼠 IgG1 恆定區 HC]]> <![CDATA[<400> 351]]> Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 1 5 10 15 Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 20 25 30 Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 35 40 45 Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 50 55 60 Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 65 70 75 80 Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 85 90 95 Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 100 105 110 Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 115 120 125 Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 130 135 140 Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 145 150 155 160 Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 165 170 175 Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 180 185 190 His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 195 200 205 Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 210 215 220 Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu 225 230 235 240 Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 245 250 255 Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 260 265 270 Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 275 280 285 Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 290 295 300 Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 305 310 315 320 Gln Lys Ser Leu Ser Leu Ser Pro Gly 325 <![CDATA[<210> 352]]> <![CDATA[<211> 330]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 小鼠 IgG2a 恆定區 HC]]> <![CDATA[<400> 352]]> Ala Lys Thr Thr Ala Pro Ser Val Tyr Pro Leu Ala Pro Val Cys Gly 1 5 10 15 Asp Thr Thr Gly Ser Ser Val Thr Leu Gly Cys Leu Val Lys Gly Tyr 20 25 30 Phe Pro Glu Pro Val Thr Leu Thr Trp Asn Ser Gly Ser Leu Ser Ser 35 40 45 Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu 50 55 60 Ser Ser Ser Val Thr Val Thr Ser Ser Thr Trp Pro Ser Gln Ser Ile 65 70 75 80 Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys 85 90 95 Ile Glu Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys 100 105 110 Pro Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro 115 120 125 Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys 130 135 140 Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp 145 150 155 160 Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg 165 170 175 Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln 180 185 190 His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn 195 200 205 Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly 210 215 220 Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu 225 230 235 240 Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met 245 250 255 Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu 260 265 270 Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe 275 280 285 Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn 290 295 300 Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr 305 310 315 320 Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys 325 330 <![CDATA[<210> 353]]> <![CDATA[<211> 447]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 易普利姆瑪-VH-人類 IgG1 恆定區 HC]]> <![CDATA[<400> 353]]> Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Thr Phe Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile Tyr Tyr Cys 85 90 95 Ala Arg Thr Gly Trp Leu Gly Pro Phe Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 115 120 125 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 130 135 140 Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 145 150 155 160 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 165 170 175 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 180 185 190 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 195 200 205 Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr 210 215 220 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 225 230 235 240 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 245 250 255 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 260 265 270 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 275 280 285 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 290 295 300 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 305 310 315 320 Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 325 330 335 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 340 345 350 Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys 355 360 365 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 370 375 380 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 385 390 395 400 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 405 410 415 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 420 425 430 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 445 <![CDATA[<210> 354]]> <![CDATA[<211> 447]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 易普利姆瑪-VH-小鼠 IgG1 恆定區 HC]]> <![CDATA[<400> 354]]> Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Thr Phe Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile Tyr Tyr Cys 85 90 95 Ala Arg Thr Gly Trp Leu Gly Pro Phe Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 115 120 125 Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 130 135 140 Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 145 150 155 160 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 165 170 175 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 180 185 190 Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 195 200 205 Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 210 215 220 His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 225 230 235 240 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 245 250 255 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 260 265 270 Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 275 280 285 Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val 290 295 300 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 305 310 315 320 Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 325 330 335 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 340 345 350 Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 355 360 365 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 370 375 380 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 385 390 395 400 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 405 410 415 Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 420 425 430 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 435 440 445 <![CDATA[<210> 355]]> <![CDATA[<211> 448]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 易普利姆瑪-VH-小鼠 IgG2a 恆定區 HC]]> <![CDATA[<400> 355]]> Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Thr Phe Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile Tyr Tyr Cys 85 90 95 Ala Arg Thr Gly Trp Leu Gly Pro Phe Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser Ala Lys Thr Thr Ala Pro Ser Val Tyr Pro 115 120 125 Leu Ala Pro Val Cys Gly Asp Thr Thr Gly Ser Ser Val Thr Leu Gly 130 135 140 Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Leu Thr Trp Asn 145 150 155 160 Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 165 170 175 Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Thr Ser Ser Thr 180 185 190 Trp Pro Ser Gln Ser Ile Thr Cys Asn Val Ala His Pro Ala Ser Ser 195 200 205 Thr Lys Val Asp Lys Lys Ile Glu Pro Arg Gly Pro Thr Ile Lys Pro 210 215 220 Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn Leu Leu Gly Gly Pro Ser 225 230 235 240 Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu 245 250 255 Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro 260 265 270 Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala 275 280 285 Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val 290 295 300 Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe 305 310 315 320 Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr 325 330 335 Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu 340 345 350 Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys 355 360 365 Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn 370 375 380 Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp 385 390 395 400 Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys 405 410 415 Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly 420 425 430 Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys 435 440 445 <![CDATA[<210> 356]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV01-2001 LC]]> <![CDATA[<400> 356]]> Gln Gly Gln Ser Gly Gln Gly Asp Phe Ser Cys Leu His Ser Met Tyr 1 5 10 15 Asn Val Cys Leu Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 357]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV01-2001 LC]]> <![CDATA[<400> 357]]> Asp Phe Ser Cys Leu His Ser Met Tyr Asn Val Cys Leu Asp Pro Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 358]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV02-2001 LC]]> <![CDATA[<400> 358]]> Gln Gly Gln Ser Gly Gln Gly Gln Pro Cys Ala Gln Met Tyr Gly Tyr 1 5 10 15 Ser Met Cys Pro His Thr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 359]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV02-2001 LC]]> <![CDATA[<400> 359]]> Gln Pro Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro His Thr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 360]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV03-2001 LC]]> <![CDATA[<400> 360]]> Gln Gly Gln Ser Gly Gln Gly Leu His Cys Arg Thr Gln Met Tyr Gly 1 5 10 15 Tyr Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 361]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV03-2001 LC]]> <![CDATA[<400> 361]]> Leu His Cys Arg Thr Gln Met Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 362]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV04-2001 LC]]> <![CDATA[<400> 362]]> Gln Gly Gln Ser Gly Ser Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr 1 5 10 15 Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 363]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV04-2001 LC]]> <![CDATA[<400> 363]]> Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 364]]> <![CDATA[<211> 256]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV06-2001 LC]]> <![CDATA[<400> 364]]> Gln Gly Gln Ser Gly Ser Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys 1 5 10 15 Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly 20 25 30 Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser 35 40 45 Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 50 55 60 Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 65 70 75 80 Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg 85 90 95 Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 100 105 110 Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 115 120 125 Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr 130 135 140 Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 145 150 155 160 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 165 170 175 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 180 185 190 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 195 200 205 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 210 215 220 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 225 230 235 240 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 365]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV06-2001 LC]]> <![CDATA[<400> 365]]> Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Gly Gly Gly Ser Ser Gly 1 5 10 15 Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly 20 25 30 Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu 35 40 45 Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val 50 55 60 Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 65 70 75 80 Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp 85 90 95 Arg Phe Ser Gly Ser Gly Tyr Val Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 366]]> <![CDATA[<211> 263]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV09-2001 LC]]> <![CDATA[<400> 366]]> Gln Gly Gln Ser Gly Ser Phe Gly Tyr Val Thr Ala Cys Pro Asn His 1 5 10 15 Pro Met Cys His Asp Trp Gln Gly Gly Gly Ser Ser Gly Gly Ser Ile 20 25 30 Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser 35 40 45 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 50 55 60 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser 65 70 75 80 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 85 90 95 Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 100 105 110 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 115 120 125 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 130 135 140 Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala 145 150 155 160 Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 165 170 175 Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 180 185 190 Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 195 200 205 Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 210 215 220 Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 225 230 235 240 Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 245 250 255 Ser Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 367]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV09-2001 LC]]> <![CDATA[<400> 367]]> Phe Gly Thr Ala Cys Pro Asn His Pro Met Cys His Asp Trp Gln Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 368]]> <![CDATA[<211> 258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV23-20]]>01 LC <![CDATA[<400> 368]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Leu Tyr Asn Val Cys Leu 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu 20 25 30 Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr 35 40 45 Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 50 55 60 Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr 65 70 75 80 Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe 85 90 95 Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 100 105 110 Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 115 120 125 Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln 130 135 140 Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 145 150 155 160 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 165 170 175 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 180 185 190 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 195 200 205 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 210 215 220 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 225 230 235 240 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 245 250 255 Glu Cys <![CDATA[<210> 369]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV23-2001 LC]]> <![CDATA[<400> 369]]> Cys Leu His Ser Leu Tyr Asn Val Cys Leu Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn 20 25 30 His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 35 40 45 Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 50 55 60 Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 65 70 75 80 Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile 85 90 95 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 370]]> <![CDATA[<211> 258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV24-2001 LC]]> <![CDATA[<400> 370]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Ala Tyr Asn Val Cys Leu 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu 20 25 30 Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr 35 40 45 Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 50 55 60 Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr 65 70 75 80 Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe 85 90 95 Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 100 105 110 Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 115 120 125 Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln 130 135 140 Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 145 150 155 160 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 165 170 175 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 180 185 190 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 195 200 205 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 210 215 220 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 225 230 235 240 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 245 250 255 Glu Cys <![CDATA[<210> 371]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV24-2001 LC]]> <![CDATA[<400> 371]]> Cys Leu His Ser Ala Tyr Asn Val Cys Leu Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn 20 25 30 His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 35 40 45 Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 50 55 60 Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 65 70 75 80 Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile 85 90 95 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 372]]> <![CDATA[<211> 258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV27-2001 LC]]> <![CDATA[<400> 372]]> Gln Gly Gln Ser Gly Ser Gln Pro Cys Ala Gln Met Tyr Gly Tyr Ser 1 5 10 15 Met Cys Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu 20 25 30 Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr 35 40 45 Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 50 55 60 Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr 65 70 75 80 Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe 85 90 95 Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 100 105 110 Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 115 120 125 Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln 130 135 140 Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 145 150 155 160 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 165 170 175 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 180 185 190 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 195 200 205 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 210 215 220 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 225 230 235 240 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 245 250 255 Glu Cys <![CDATA[<210> 373]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV27-2001 LC]]> <![CDATA[<400> 373]]> Gln Pro Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn 20 25 30 His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 35 40 45 Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 50 55 60 Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 65 70 75 80 Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile 85 90 95 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 374]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV29-2001 LC]]> <![CDATA[<400> 374]]> Gln Gly Gln Ser Gly Ser Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys 1 5 10 15 Ala His Thr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu 20 25 30 Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 375]]> <![CDATA[<211> 253]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV29-2001 LC]]> <![CDATA[<400> 375]]> Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Ala His Thr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp 20 25 30 Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser 145 150 155 160 Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn 165 170 175 Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala 180 185 190 Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys 195 200 205 Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp 210 215 220 Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu 225 230 235 240 Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 376]]> <![CDATA[<211> 257]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV32-2001 LC]]> <![CDATA[<400> 376]]> Gln Gly Gln Ser Gly Ser Cys Pro Asn His Pro Leu Cys His Asp Trp 1 5 10 15 Gln Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser 20 25 30 Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln 35 40 45 Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser 50 55 60 Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln 65 70 75 80 Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser 85 90 95 Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr 100 105 110 Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val 115 120 125 Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly 130 135 140 Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile 145 150 155 160 Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val 165 170 175 Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys 180 185 190 Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu 195 200 205 Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu 210 215 220 Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr 225 230 235 240 His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu 245 250 255 Cys <![CDATA[<210> 377]]> <![CDATA[<211> 251]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV32-2001 LC]]> <![CDATA[<400> 377]]> Cys Pro Asn His Pro Leu Cys His Asp Trp Gln Gly Gly Gly Ser Ser 1 5 10 15 Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn His 20 25 30 Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser 35 40 45 Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser 50 55 60 Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala 65 70 75 80 Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro 85 90 95 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 100 105 110 Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr 115 120 125 Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 130 135 140 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 145 150 155 160 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 165 170 175 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 180 185 190 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 195 200 205 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 210 215 220 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 225 230 235 240 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 378]]> <![CDATA[<211> 257]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV33-2001 LC]]> <![CDATA[<400> 378]]> Gln Gly Gln Ser Gly Ser Cys Pro Asn His Pro Met Cys Ala Asp Trp 1 5 10 15 Gln Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser 20 25 30 Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln 35 40 45 Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser 50 55 60 Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln 65 70 75 80 Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser 85 90 95 Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr 100 105 110 Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val 115 120 125 Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly 130 135 140 Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile 145 150 155 160 Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val 165 170 175 Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys 180 185 190 Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu 195 200 205 Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu 210 215 220 Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr 225 230 235 240 His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu 245 250 255 Cys <![CDATA[<210> 379]]> <![CDATA[<211> 251]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV33-2001 LC]]> <![CDATA[<400> 379]]> Cys Pro Asn His Pro Met Cys Ala Asp Trp Gln Gly Gly Gly Ser Ser 1 5 10 15 Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn His 20 25 30 Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser 35 40 45 Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser 50 55 60 Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala 65 70 75 80 Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro 85 90 95 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 100 105 110 Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr 115 120 125 Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 130 135 140 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 145 150 155 160 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 165 170 175 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 180 185 190 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 195 200 205 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 210 215 220 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 225 230 235 240 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 380]]> <![CDATA[<211> 257]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV35-2001 LC]]> <![CDATA[<400> 380]]> Gln Gly Gln Ser Gly Ser Cys Pro Asn His Pro Met Cys His Asp Ala 1 5 10 15 Gln Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser 20 25 30 Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln 35 40 45 Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser 50 55 60 Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln 65 70 75 80 Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser 85 90 95 Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr 100 105 110 Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val 115 120 125 Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly 130 135 140 Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile 145 150 155 160 Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val 165 170 175 Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys 180 185 190 Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu 195 200 205 Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu 210 215 220 Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr 225 230 235 240 His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu 245 250 255 Cys <![CDATA[<210> 381]]> <![CDATA[<211> 251]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV35-2001 LC]]> <![CDATA[<400> 381]]> Cys Pro Asn His Pro Met Cys His Asp Ala Gln Gly Gly Gly Ser Ser 1 5 10 15 Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn His 20 25 30 Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser 35 40 45 Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser 50 55 60 Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala 65 70 75 80 Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro 85 90 95 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 100 105 110 Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr 115 120 125 Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 130 135 140 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 145 150 155 160 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 165 170 175 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 180 185 190 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 195 200 205 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 210 215 220 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 225 230 235 240 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210]]>> 382]]> <br/><![CDATA[<211> 259]]> <br/><![CDATA[<212> PRT]]> <br/><![CDATA[<213> 人工序列]]> <br/> <br/><![CDATA[<220>]]> <br/><![CDATA[<223> 間隔子 - YV39-2001 LC]]> <br/> <br/><![CDATA[<400> 382]]> <br/> <br/><![CDATA[Gln Gly Gln Ser Gly Ser Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu 1 5 10 15 Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu 20 25 30 Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 383]]> <![CDATA[<211> 253]]> <![CDATA[<212> ]]> PRT <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV39-2001 LC]]> <![CDATA[<400> 383]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp 20 25 30 Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser 145 150 155 160 Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn 165 170 175 Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala 180 185 190 Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys 195 200 205 Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp 210 215 220 Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu 225 230 235 240 Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 384]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV41-2001 LC]]> <![CDATA[<400> 384]]> Gln Gly Gln Ser Gly Ser Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu 1 5 10 15 Cys Pro Ala Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu 20 25 30 Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 385]]> <![CDATA[<211> 253]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV41-2001 LC]]> <![CDATA[<400> 385]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Ala Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp 20 25 30 Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser 145 150 155 160 Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn 165 170 175 Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala 180 185 190 Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys 195 200 205 Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp 210 215 220 Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu 225 230 235 240 Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 386]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV51-2001 LC]]> <![CDATA[<400> 386]]> Gln Gly Gln Ser Gly Ser Phe Gly Ala Ala Cys Pro Asn His Pro Ile 1 5 10 15 Cys His Asp Trp Gln Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 387]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV51-2001 LC]]> <![CDATA[<400> 387]]> Phe Gly Ala Ala Cys Pro Asn His Pro Ile Cys His Asp Trp Gln Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 388]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV52-2001 LC]]> <![CDATA[<400> 388]]> Gln Gly Gln Ser Gly Ser Phe Gly Ala Ala Cys Pro Asn His Pro Leu 1 5 10 15 Cys His Asp Trp Gln Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 389]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV52-2001 LC]]> <![CDATA[<400> 389]]> Phe Gly Ala Ala Cys Pro Asn His Pro Leu Cys His Asp Trp Gln Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 390]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV53-2001 LC]]> <![CDATA[<400> 390]]> Gln Gly Gln Ser Gly Ser Phe Gly Ala Ala Cys Pro Asn His Pro Met 1 5 10 15 Cys His Asp Ala Gln Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 391]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV53-2001 LC]]> <![CDATA[<400> 391]]> Phe Gly Ala Ala Cys Pro Asn His Pro Met Cys His Asp Ala Gln Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 392]]> <![CDATA[<211> 258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV54-2001 LC]]> <![CDATA[<400> 392]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Ala Tyr Asn Ala Cys Leu 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu 20 25 30 Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr 35 40 45 Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 50 55 60 Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr 65 70 75 80 Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe 85 90 95 Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 100 105 110 Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 115 120 125 Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln 130 135 140 Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 145 150 155 160 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 165 170 175 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 180 185 190 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 195 200 205 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 210 215 220 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 225 230 235 240 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 245 250 255 Glu Cys <![CDATA[<210> 393]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV54-2001 LC]]> <![CDATA[<400> 393]]> Cys Leu His Ser Ala Tyr Asn Ala Cys Leu Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn 20 25 30 His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 35 40 45 Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 50 55 60 Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 65 70 75 80 Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile 85 90 95 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 394]]> <![CDATA[<211> 258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV55-2001 LC]]> <![CDATA[<400> 394]]> Gln Gly Gln Ser Gly Ser Cys Ala His Ser Ala Tyr Asn Val Cys Leu 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu 20 25 30 Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr 35 40 45 Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 50 55 60 Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr 65 70 75 80 Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe 85 90 95 Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 100 105 110 Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 115 120 125 Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln 130 135 140 Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 145 150 155 160 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 165 170 175 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 180 185 190 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 195 200 205 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 210 215 220 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 225 230 235 240 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 245 250 255 Glu Cys <![CDATA[<210> 395]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV55-2001 LC]]> <![CDATA[<400> 395]]> Cys Ala His Ser Ala Tyr Asn Val Cys Leu Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn 20 25 30 His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 35 40 45 Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 50 55 60 Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 65 70 75 80 Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile 85 90 95 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 396]]> <![CDATA[<211> 258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV56-2001 LC]]> <![CDATA[<400> 396]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Ala Tyr Asn Val Cys Ala 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu 20 25 30 Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr 35 40 45 Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 50 55 60 Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr 65 70 75 80 Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe 85 90 95 Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 100 105 110 Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 115 120 125 Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln 130 135 140 Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 145 150 155 160 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 165 170 175 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 180 185 190 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 195 200 205 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 210 215 220 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 225 230 235 240 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 245 250 255 Glu Cys <![CDATA[<210> 397]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV56-2001 LC]]> <![CDATA[<400> 397]]> Cys Leu His Ser Ala Tyr Asn Val Cys Ala Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn 20 25 30 His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 35 40 45 Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 50 55 60 Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 65 70 75 80 Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile 85 90 95 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 398]]> <![CDATA[<211> 258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV57-2001 LC]]> <![CDATA[<400> 398]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Ala Tyr Asn Val Cys Leu 1 5 10 15 Ala Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu 20 25 30 Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr 35 40 45 Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 50 55 60 Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr 65 70 75 80 Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe 85 90 95 Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 100 105 110 Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 115 120 125 Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln 130 135 140 Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 145 150 155 160 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 165 170 175 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 180 185 190 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 195 200 205 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 210 215 220 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 225 230 235 240 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 245 250 255 Glu Cys <![CDATA[<210> 399]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV57-2001 LC]]> <![CDATA[<400> 399]]> Cys Leu His Ser Ala Tyr Asn Val Cys Leu Ala Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn 20 25 30 His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 35 40 45 Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 50 55 60 Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 65 70 75 80 Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile 85 90 95 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 400]]> <![CDATA[<211> 258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV58-2001 LC]]> <![CDATA[<400> 400]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Ala Tyr Asn Val Cys Leu 1 5 10 15 Asp Ala Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu 20 25 30 Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr 35 40 45 Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 50 55 60 Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr 65 70 75 80 Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe 85 90 95 Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 100 105 110 Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 115 120 125 Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln 130 135 140 Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 145 150 155 160 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 165 170 175 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 180 185 190 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 195 200 205 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 210 215 220 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 225 230 235 240 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 245 250 255 Glu Cys <![CDATA[<210> 401]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV58-2001 LC]]> <![CDATA[<400> 401]]> Cys Leu His Ser Ala Tyr Asn Val Cys Leu Asp Ala Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn 20 25 30 His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 35 40 45 Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 50 55 60 Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 65 70 75 80 Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile 85 90 95 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 402]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV61-2001 LC]]> <![CDATA[<400> 402]]> Gln Gly Gln Ser Gly Ser Tyr Ile Ser Asp Cys Pro Tyr His Pro Met 1 5 10 15 Cys His Asp Tyr Gln Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 403]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV61-2001 LC]]> <![CDATA[<400> 403]]> Tyr Ile Ser Asp Cys Pro Tyr His Pro Met Cys His Asp Tyr Gln Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 404]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV62-2001 LC]]> <![CDATA[<400> 404]]> Gln Gly Gln Ser Gly Ser Phe Arg Asn Thr Cys Pro Tyr His Pro Met 1 5 10 15 Cys His Asp Tyr Arg Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 405]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV62-2001 LC]]> <![CDATA[<400> 405]]> Phe Arg Asn Thr Cys Pro Tyr His Pro Met Cys His Asp Tyr Arg Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 406]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV63-2001 LC]]> <![CDATA[<400> 406]]> Gln Gly Gln Ser Gly Ser Arg Glu Cys His Met Trp Met Phe Gly Val 1 5 10 15 Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 407]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV63-2001 LC]]> <![CDATA[<400> 407]]> Arg Glu Cys His Met Trp Met Phe Gly Val Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 408]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV64-2001 LC]]> <![CDATA[<400> 408]]> Gln Gly Gln Ser Gly Ser Ala Val Cys His Met Tyr Met Tyr Gly Tyr 1 5 10 15 Asn Leu Cys Pro Phe Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 409]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV64-2001 LC]]> <![CDATA[<400> 409]]> Ala Val Cys His Met Tyr Met Tyr Gly Tyr Asn Leu Cys Pro Phe Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 410]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV65-2001 LC]]> <![CDATA[<400> 410]]> Gln Gly Gln Ser Gly Gln Gly Arg Ser Cys Pro Gln Met Tyr Gly Tyr 1 5 10 15 Ser Met Cys Pro His Thr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 411]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV65-2001 LC]]> <![CDATA[<400> 411]]> Arg Ser Cys Pro Gln Met Tyr Gly Tyr Ser Met Cys Pro His Thr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 412]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV66-2001 LC]]> <![CDATA[<400> 412]]> Gln Gly Gln Ser Gly Gln Gly Gln Pro Cys Ala Gln Met Phe Gly Tyr 1 5 10 15 Ser Met Cys Pro His Thr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 413]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV66-2001 LC]]> <![CDATA[<400> 413]]> Gln Pro Cys Ala Gln Met Phe Gly Tyr Ser Met Cys Pro His Thr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 414]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV04-2006 LC]]> <![CDATA[<400> 414]]> Gln Gly Gln Ser Gly Ser Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr 1 5 10 15 Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asp His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys Cys 260 <![CDATA[<210> 415]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV04-2006 LC]]> <![CDATA[<400> 415]]> Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asp His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 416]]> <![CDATA[<211> 258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV23-2006 LC]]> <![CDATA[<400> 416]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Leu Tyr Asn Val Cys Leu 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu 20 25 30 Ser Gly Arg Ser Asp Asp His Gly Gly Gly Ser Glu Ile Val Leu Thr 35 40 45 Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 50 55 60 Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr 65 70 75 80 Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe 85 90 95 Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 100 105 110 Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 115 120 125 Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln 130 135 140 Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 145 150 155 160 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 165 170 175 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 180 185 190 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 195 200 205 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 210 215 220 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 225 230 235 240 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 245 250 255 Glu Cys <![CDATA[<210> 417]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV23-2006 LC]]> <![CDATA[<400> 417]]> Cys Leu His Ser Leu Tyr Asn Val Cys Leu Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asp 20 25 30 His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 35 40 45 Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 50 55 60 Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 65 70 75 80 Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile 85 90 95 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 418]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV39-2006 LC]]> <![CDATA[<400> 418]]> Gln Gly Gln Ser Gly Ser Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu 1 5 10 15 Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu 20 25 30 Leu Ser Gly Arg Ser Asp Asp His Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 419]]> <![CDATA[<211> 253]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV39-2006 LC]]> <![CDATA[<400> 419]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp 20 25 30 Asp His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser 145 150 155 160 Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn 165 170 175 Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala 180 185 190 Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys 195 200 205 Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp 210 215 220 Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu 225 230 235 240 Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 420]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV04-2007 LC]]> <![CDATA[<400> 420]]> Gln Gly Gln Ser Gly Ser Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr 1 5 10 15 Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Ile His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 421]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV04-2007 LC]]> <![CDATA[<400> 421]]> Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Ile His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 422]]> <![CDATA[<211> 258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV23-2007 LC]]> <![CDATA[<400> 422]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Leu Tyr Asn Val Cys Leu 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu 20 25 30 Ser Gly Arg Ser Asp Ile His Gly Gly Gly Ser Glu Ile Val Leu Thr 35 40 45 Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 50 55 60 Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr 65 70 75 80 Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe 85 90 95 Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 100 105 110 Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 115 120 125 Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln 130 135 140 Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 145 150 155 160 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 165 170 175 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 180 185 190 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 195 200 205 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 210 215 220 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 225 230 235 240 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 245 250 255 Glu Cys <![CDATA[<210> 423]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV23-2007 LC]]> <![CDATA[<400> 423]]> Cys Leu His Ser Leu Tyr Asn Val Cys Leu Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Ile 20 25 30 His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 35 40 45 Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 50 55 60 Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 65 70 75 80 Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile 85 90 95 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 424]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV39-2007 LC]]> <![CDATA[<400> 424]]> Gln Gly Gln Ser Gly Ser Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu 1 5 10 15 Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu 20 25 30 Leu Ser Gly Arg Ser Asp Ile His Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 425]]> <![CDATA[<211> 253]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV39-2007 LC]]> <![CDATA[<400> 425]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp 20 25 30 Ile His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser 145 150 155 160 Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn 165 170 175 Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala 180 185 190 Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys 195 200 205 Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp 210 215 220 Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu 225 230 235 240 Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 426]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV04-2008 LC]]> <![CDATA[<400> 426]]> Gln Gly Gln Ser Gly Ser Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr 1 5 10 15 Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Gln His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 427]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV04-2008 LC]]> <![CDATA[<400> 427]]> Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Gln His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 428]]> <![CDATA[<211> 258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV23-2008 LC]]> <![CDATA[<400> 428]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Leu Tyr Asn Val Cys Leu 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu 20 25 30 Ser Gly Arg Ser Asp Gln His Gly Gly Gly Ser Glu Ile Val Leu Thr 35 40 45 Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 50 55 60 Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr 65 70 75 80 Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe 85 90 95 Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 100 105 110 Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 115 120 125 Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln 130 135 140 Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 145 150 155 160 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 165 170 175 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 180 185 190 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 195 200 205 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 210 215 220 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 225 230 235 240 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 245 250 255 Glu Cys <![CDATA[<210> 429]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV23-2008 LC]]> <![CDATA[<400> 429]]> Cys Leu His Ser Leu Tyr Asn Val Cys Leu Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Gln 20 25 30 His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 35 40 45 Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 50 55 60 Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 65 70 75 80 Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile 85 90 95 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 430]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV39-2008 LC]]> <![CDATA[<400> 430]]> Gln Gly Gln Ser Gly Ser Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu 1 5 10 15 Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu 20 25 30 Leu Ser Gly Arg Ser Asp Gln His Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 431]]> <![CDATA[<211> 253]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV39-20]]>08 LC <![CDATA[<400> 431]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp 20 25 30 Gln His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser 145 150 155 160 Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn 165 170 175 Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala 180 185 190 Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys 195 200 205 Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp 210 215 220 Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu 225 230 235 240 Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 432]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV04-2009 LC]]> <![CDATA[<400> 432]]> Gln Gly Gln Ser Gly Ser Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr 1 5 10 15 Asn Leu Cys Pro Tyr Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu 20 25 30 Leu Ser Gly Arg Ser Asp Thr His Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 433]]> <![CDATA[<211> 253]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV04-2009 LC]]> <![CDATA[<400> 433]]> Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly 1 5 10 15 Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp 20 25 30 Thr His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser 145 150 155 160 Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn 165 170 175 Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala 180 185 190 Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys 195 200 205 Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp 210 215 220 Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu 225 230 235 240 Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 434]]> <![CDATA[<211> 256]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV23-2009 LC]]> <![CDATA[<400> 434]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Leu Tyr Asn Val Cys Leu 1 5 10 15 Asp Pro Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly 20 25 30 Arg Ser Asp Thr His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser 35 40 45 Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 50 55 60 Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 65 70 75 80 Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg 85 90 95 Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 100 105 110 Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 115 120 125 Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr 130 135 140 Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 145 150 155 160 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 165 170 175 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 180 185 190 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 195 200 205 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 210 215 220 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 225 230 235 240 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 435]]> <![CDATA[<211> 250]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV23-2009 LC]]> <![CDATA[<400> 435]]> Cys Leu His Ser Leu Tyr Asn Val Cys Leu Asp Pro Gly Ser Ser Gly 1 5 10 15 Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Thr His Gly 20 25 30 Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu 35 40 45 Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val 50 55 60 Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 65 70 75 80 Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp 85 90 95 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 100 105 110 Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly 115 120 125 Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 130 135 140 Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 145 150 155 160 Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 165 170 175 Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 180 185 190 Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 195 200 205 Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 210 215 220 His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 225 230 235 240 Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 436]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV39-2009 LC]]> <![CDATA[<400>]]> 436 Gln Gly Gln Ser Gly Ser Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu 1 5 10 15 Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu 20 25 30 Leu Ser Gly Arg Ser Asp Thr His Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 437]]> <![CDATA[<211> 253]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV39-2009 LC]]> <![CDATA[<400> 437]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp 20 25 30 Thr His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser 145 150 155 160 Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn 165 170 175 Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala 180 185 190 Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys 195 200 205 Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp 210 215 220 Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu 225 230 235 240 Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 438]]> <![CDATA[<211> 263]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV01-2011 ]]>LC <![CDATA[<400> 438]]> Gln Gly Gln Ser Gly Gln Gly Asp Phe Ser Cys Leu His Ser Met Tyr 1 5 10 15 Asn Val Cys Leu Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn Pro Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys Cys 260 <![CDATA[<210> 439]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV01-2011 LC]]> <![CDATA[<400> 439]]> Asp Phe Ser Cys Leu His Ser Met Tyr Asn Val Cys Leu Asp Pro Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 440]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV02-2011 LC]]> <![CDATA[<400> 440]]> Gln Gly Gln Ser Gly Gln Gly Gln Pro Cys Ala Gln Met Tyr Gly Tyr 1 5 10 15 Ser Met Cys Pro His Thr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn Pro Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 441]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV02-2011 LC]]> <![CDATA[<400> 441]]> Gln Pro Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro His Thr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 442]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV03-2011 LC]]> <![CDATA[<400> 442]]> Gln Gly Gln Ser Gly Gln Gly Leu His Cys Arg Thr Gln Met Tyr Gly 1 5 10 15 Tyr Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn Pro Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 443]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV03-2011 LC]]> <![CDATA[<400> 443]]> Leu His Cys Arg Thr Gln Met Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 444]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV04-2011 LC]]> <![CDATA[<400> 444]]> Gln Gly Gln Ser Gly Ser Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr 1 5 10 15 Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 445]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV04-2011 LC]]> <![CDATA[<400> 445]]> Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 446]]> <![CDATA[<211> 258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV23-2011 LC]]> <![CDATA[<400> 446]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Leu Tyr Asn Val Cys Leu 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu 20 25 30 Ser Gly Arg Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr 35 40 45 Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 50 55 60 Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr 65 70 75 80 Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe 85 90 95 Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 100 105 110 Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 115 120 125 Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln 130 135 140 Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 145 150 155 160 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 165 170 175 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 180 185 190 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 195 200 205 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 210 215 220 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 225 230 235 240 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 245 250 255 Glu Cys <![CDATA[<210> 447]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV23-2011 LC]]> <![CDATA[<400> 447]]> Cys Leu His Ser Leu Tyr Asn Val Cys Leu Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn 20 25 30 Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 35 40 45 Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 50 55 60 Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 65 70 75 80 Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile 85 90 95 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 448]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV39-2011 LC]]> <![CDATA[<400> 448]]> Gln Gly Gln Ser Gly Ser Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu 1 5 10 15 Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu 20 25 30 Leu Ser Gly Arg Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 449]]> <![CDATA[<211> 253]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV39-2011 LC]]> <![CDATA[<400> 449]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp 20 25 30 Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser 145 150 155 160 Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn 165 170 175 Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala 180 185 190 Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys 195 200 205 Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp 210 215 220 Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu 225 230 235 240 Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 450]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV61-2011 LC]]> <![CDATA[<400> 450]]> Gln Gly Gln Ser Gly Ser Tyr Ile Ser Asp Cys Pro Tyr His Pro Met 1 5 10 15 Cys His Asp Tyr Gln Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 451]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV61-2011 LC]]> <![CDATA[<400> 451]]> Tyr Ile Ser Asp Cys Pro Tyr His Pro Met Cys His Asp Tyr Gln Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 452]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV62-2011 LC]]> <![CDATA[<400> 452]]> Gln Gly Gln Ser Gly Ser Phe Arg Asn Thr Cys Pro Tyr His Pro Met 1 5 10 15 Cys His Asp Tyr Arg Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 453]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV62-2011 LC]]> <![CDATA[<400> 453]]> Phe Arg Asn Thr Cys Pro Tyr His Pro Met Cys His Asp Tyr Arg Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 454]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV63-2011 LC]]> <![CDATA[<400> 454]]> Gln Gly Gln Ser Gly Ser Arg Glu Cys His Met Trp Met Phe Gly Val 1 5 10 15 Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 455]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> Y]]>V63-2011 LC <![CDATA[<400> 455]]> Arg Glu Cys His Met Trp Met Phe Gly Val Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 456]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV64-2011 LC]]> <![CDATA[<400> 456]]> Gln Gly Gln Ser Gly Ser Ala Val Cys His Met Tyr Met Tyr Gly Tyr 1 5 10 15 Asn Leu Cys Pro Phe Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys Cys 260 <![CDATA[<210> 457]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV64-2011 LC]]> <![CDATA[<400> 457]]> Ala Val Cys His Met Tyr Met Tyr Gly Tyr Asn Leu Cys Pro Phe Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 458]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV65-2011 LC]]> <![CDATA[<400> 458]]> Gln Gly Gln Ser Gly Gln Gly Arg Ser Cys Pro Gln Met Tyr Gly Tyr 1 5 10 15 Ser Met Cys Pro His Thr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn Pro Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 459]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV65-2011 LC]]> <![CDATA[<400> 459]]> Arg Ser Cys Pro Gln Met Tyr Gly Tyr Ser Met Cys Pro His Thr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 460]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV66-2011 LC]]> <![CDATA[<400> 460]]> Gln Gly Gln Ser Gly Gln Gly Gln Pro Cys Ala Gln Met Phe Gly Tyr 1 5 10 15 Ser Met Cys Pro His Thr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Asp Asn Pro Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 461]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV66-2011 LC]]> <![CDATA[<400> 461]]> Gln Pro Cys Ala Gln Met Phe Gly Tyr Ser Met Cys Pro His Thr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Asp Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 462]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV01-2012 LC]]> <![CDATA[<400> 462]]> Gln Gly Gln Ser Gly Gln Gly Asp Phe Ser Cys Leu His Ser Met Tyr 1 5 10 15 Asn Val Cys Leu Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Ala Asn Pro Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 463]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工]]>序列 <![CDATA[<220>]]> <![CDATA[<223> YV01-2012 LC]]> <![CDATA[<400> 463]]> Asp Phe Ser Cys Leu His Ser Met Tyr Asn Val Cys Leu Asp Pro Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 464]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV02-2012 LC]]> <![CDATA[<400> 464]]> Gln Gly Gln Ser Gly Gln Gly Gln Pro Cys Ala Gln Met Tyr Gly Tyr 1 5 10 15 Ser Met Cys Pro His Thr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Ala Asn Pro Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 465]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV02-2012 LC]]> <![CDATA[<400> 465]]> Gln Pro Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro His Thr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 466]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV03-2012 LC]]> <![CDATA[<400> 466]]> Gln Gly Gln Ser Gly Gln Gly Leu His Cys Arg Thr Gln Met Tyr Gly 1 5 10 15 Tyr Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Ala Asn Pro Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 467]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV03-2012 LC]]> <![CDATA[<400> 467]]> Leu His Cys Arg Thr Gln Met Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 468]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV04-2012 LC]]> <![CDATA[<400> 468]]> Gln Gly Gln Ser Gly Ser Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr 1 5 10 15 Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 469]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV04-2012 LC]]> <![CDATA[<400> 469]]> Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 470]]> <![CDATA[<211> 258]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV23-2012 LC]]> <![CDATA[<400> 470]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Leu Tyr Asn Val Cys Leu 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu 20 25 30 Ser Gly Arg Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr 35 40 45 Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 50 55 60 Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr 65 70 75 80 Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe 85 90 95 Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 100 105 110 Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 115 120 125 Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln 130 135 140 Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 145 150 155 160 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 165 170 175 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 180 185 190 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 195 200 205 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 210 215 220 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 225 230 235 240 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 245 250 255 Glu Cys <![CDATA[<210> 471]]> <![CDATA[<211> 252]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV23-2012 LC]]> <![CDATA[<400> 471]]> Cys Leu His Ser Leu Tyr Asn Val Cys Leu Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Ala Asn 20 25 30 Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 35 40 45 Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 50 55 60 Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 65 70 75 80 Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile 85 90 95 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 100 105 110 Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 115 120 125 Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 130 135 140 Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 145 150 155 160 Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 165 170 175 Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 180 185 190 Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 195 200 205 Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 210 215 220 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 225 230 235 240 Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 472]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV39-2012 LC]]> <![CDATA[<400> 472]]> Gln Gly Gln Ser Gly Ser Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu 1 5 10 15 Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu 20 25 30 Leu Ser Gly Arg Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 473]]> <![CDATA[<211> 253]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV39-2012 LC]]> <![CDATA[<400> 473]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Ala 20 25 30 Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser 145 150 155 160 Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn 165 170 175 Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala 180 185 190 Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys 195 200 205 Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp 210 215 220 Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu 225 230 235 240 Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 474]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV61-2012 LC]]> <![CDATA[<400> 474]]> Gln Gly Gln Ser Gly Ser Tyr Ile Ser Asp Cys Pro Tyr His Pro Met 1 5 10 15 Cys His Asp Tyr Gln Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 475]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV61-2012 LC]]> <![CDATA[<400> 475]]> Tyr Ile Ser Asp Cys Pro Tyr His Pro Met Cys His Asp Tyr Gln Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 476]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV62-2012 LC]]> <![CDATA[<400> 476]]> Gln Gly Gln Ser Gly Ser Phe Arg Asn Thr Cys Pro Tyr His Pro Met 1 5 10 15 Cys His Asp Tyr Arg Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 477]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV62-2012 LC]]> <![CDATA[<400> 477]]> Phe Arg Asn Thr Cys Pro Tyr His Pro Met Cys His Asp Tyr Arg Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 478]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV63-2012 LC]]> <![CDATA[<400> 478]]> Gln Gly Gln Ser Gly Ser Arg Glu Cys His Met Trp Met Phe Gly Val 1 5 10 15 Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 479]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV63-2012 LC]]> <![CDATA[<400> 479]]> Arg Glu Cys His Met Trp Met Phe Gly Val Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 480]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV64-2012 LC]]> <![CDATA[<400> 480]]> Gln Gly Gln Ser Gly Ser Ala Val Cys His Met Tyr Met Tyr Gly Tyr 1 5 10 15 Asn Leu Cys Pro Phe Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser 20 25 30 Gly Leu Leu Ser Gly Arg Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 481]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV64-2012 LC]]> <![CDATA[<400> 481]]> Ala Val Cys His Met Tyr Met Tyr Gly Tyr Asn Leu Cys Pro Phe Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 482]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV65-2012 LC]]> <![CDATA[<400> 482]]> Gln Gly Gln Ser Gly Gln Gly Arg Ser Cys Pro Gln Met Tyr Gly Tyr 1 5 10 15 Ser Met Cys Pro His Thr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Ala Asn Pro Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 483]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV65-2012 LC]]> <![CDATA[<400> 483]]> Arg Ser Cys Pro Gln Met Tyr Gly Tyr Ser Met Cys Pro His Thr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 484]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV66-2012 LC]]> <![CDATA[<400> 484]]> Gln Gly Gln Ser Gly Gln Gly Gln Pro Cys Ala Gln Met Phe Gly Tyr 1 5 10 15 Ser Met Cys Pro His Thr Gly Gly Gly Ser Ser Gly Gly Ser Ile Ser 20 25 30 Ser Gly Leu Leu Ser Gly Arg Ser Ala Asn Pro Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 485]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV66-2012 LC]]> <![CDATA[<400> 485]]> Gln Pro Cys Ala Gln Met Phe Gly Tyr Ser Met Cys Pro His Thr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg 20 25 30 Ser Ala Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 486]]> <![CDATA[<211> 267]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV01-3001 LC]]> <![CDATA[<400> 486]]> Gln Gly Gln Ser Gly Gln Gly Asp Phe Ser Cys Leu His Ser Met Tyr 1 5 10 15 Asn Val Cys Leu Asp Pro Gly Gly Gly Ser Ser Gly Gly Ser Ala Val 20 25 30 Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His 35 40 45 Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser 50 55 60 Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser 65 70 75 80 Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala 85 90 95 Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro 100 105 110 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 115 120 125 Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr 130 135 140 Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 145 150 155 160 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 165 170 175 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 180 185 190 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 195 200 205 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 210 215 220 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 225 230 235 240 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 245 250 255 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 260 265 <![CDATA[<210> 487]]> <![CDATA[<211> 260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV01-3001 LC]]> <![CDATA[<400> 487]]> Asp Phe Ser Cys Leu His Ser Met Tyr Asn Val Cys Leu Asp Pro Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ala Val Gly Leu Leu Ala Pro Pro Gly 20 25 30 Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val 35 40 45 Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala 50 55 60 Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala 65 70 75 80 Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly 85 90 95 Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly 100 105 110 Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp 115 120 125 Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe 130 135 140 Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser 145 150 155 160 Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala 165 170 175 Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val 180 185 190 Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser 195 200 205 Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr 210 215 220 Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys 225 230 235 240 Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn 245 250 255 Arg Gly Glu Cys 260 <![CDATA[<210> 488]]> <![CDATA[<211> 267]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV02-3001 LC]]> <![CDATA[<400> 488]]> Gln Gly Gln Ser Gly Gln Gly Gln Pro Cys Ala Gln Met Tyr Gly Tyr 1 5 10 15 Ser Met Cys Pro His Thr Gly Gly Gly Ser Ser Gly Gly Ser Ala Val 20 25 30 Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His 35 40 45 Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser 50 55 60 Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser 65 70 75 80 Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala 85 90 95 Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro 100 105 110 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 115 120 125 Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr 130 135 140 Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 145 150 155 160 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 165 170 175 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 180 185 190 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 195 200 205 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 210 215 220 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 225 230 235 240 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 245 250 255 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 260 265 <![CDATA[<210> 489]]> <![CDATA[<211> 260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> Y]]>V02-3001 LC <![CDATA[<400> 489]]> Gln Pro Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Pro His Thr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ala Val Gly Leu Leu Ala Pro Pro Gly 20 25 30 Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val 35 40 45 Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala 50 55 60 Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala 65 70 75 80 Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly 85 90 95 Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly 100 105 110 Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp 115 120 125 Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe 130 135 140 Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser 145 150 155 160 Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala 165 170 175 Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val 180 185 190 Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser 195 200 205 Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr 210 215 220 Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys 225 230 235 240 Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn 245 250 255 Arg Gly Glu Cys 260 <![CDATA[<210> 490]]> <![CDATA[<211> 267]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV03-3001 LC]]> <![CDATA[<400> 490]]> Gln Gly Gln Ser Gly Gln Gly Leu His Cys Arg Thr Gln Met Tyr Gly 1 5 10 15 Tyr Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Ala Val 20 25 30 Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His 35 40 45 Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser 50 55 60 Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser 65 70 75 80 Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala 85 90 95 Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro 100 105 110 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 115 120 125 Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr 130 135 140 Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 145 150 155 160 Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 165 170 175 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 180 185 190 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 195 200 205 Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 210 215 220 Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 225 230 235 240 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 245 250 255 Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 260 265 <![CDATA[<210> 491]]> <![CDATA[<211> 260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV03-3001 LC]]> <![CDATA[<400> 491]]> Leu His Cys Arg Thr Gln Met Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ser Ala Val Gly Leu Leu Ala Pro Pro Gly 20 25 30 Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val 35 40 45 Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala 50 55 60 Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala 65 70 75 80 Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly 85 90 95 Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly 100 105 110 Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp 115 120 125 Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe 130 135 140 Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser 145 150 155 160 Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala 165 170 175 Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val 180 185 190 Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser 195 200 205 Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr 210 215 220 Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys 225 230 235 240 Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn 245 250 255 Arg Gly Glu Cys 260 <![CDATA[<210> 492]]> <![CDATA[<211> 265]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV04-3001 LC]]> <![CDATA[<400> 492]]> Gln Gly Gln Ser Gly Ser Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr 1 5 10 15 Asn Leu Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu 20 25 30 Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly 35 40 45 Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser 50 55 60 Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly 65 70 75 80 Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg 85 90 95 Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg 100 105 110 Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg 115 120 125 Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser 130 135 140 Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr 145 150 155 160 Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 165 170 175 Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 180 185 190 Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 195 200 205 Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 210 215 220 Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 225 230 235 240 Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 245 250 255 Thr Lys Ser Phe Asn Arg Gly Glu Cys 260 265 <![CDATA[<210> 493]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV04-3001 LC]]> <![CDATA[<400> 493]]> Leu His Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly 20 25 30 Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 494]]> <![CDATA[<211> 260]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV06-3001 LC]]> <![CDATA[<400> 494]]> Gln Gly Gln Ser Gly Ser Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys 1 5 10 15 Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly 20 25 30 Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val 35 40 45 Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala 50 55 60 Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala 65 70 75 80 Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly 85 90 95 Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly 100 105 110 Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp 115 120 125 Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe 130 135 140 Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser 145 150 155 160 Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala 165 170 175 Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val 180 185 190 Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser 195 200 205 Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr 210 215 220 Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys 225 230 235 240 Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn 245 250 255 Arg Gly Glu Cys 260 <![CDATA[<210> 495]]> <![CDATA[<211> 254]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV06-3001 LC]]> <![CDATA[<400> 495]]> Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Gly Gly Gly Ser Ser Gly 1 5 10 15 Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser 20 25 30 Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly 35 40 45 Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala 50 55 60 Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro 65 70 75 80 Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr 85 90 95 Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 100 105 110 Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys 115 120 125 Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val 130 135 140 Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro 145 150 155 160 Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu 165 170 175 Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn 180 185 190 Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser 195 200 205 Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala 210 215 220 Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly 225 230 235 240 Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 496]]> <![CDATA[<211> 265]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV09-3001 LC]]> <![CDATA[<400> 496]]> Gln Gly Gln Ser Gly Ser Phe Gly Thr Ala Cys Pro Asn His Pro Met 1 5 10 15 Cys His Asp Trp Gln Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu 20 25 30 Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly 35 40 45 Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser 50 55 60 Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly 65 70 75 80 Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg 85 90 95 Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg 100 105 110 Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg 115 120 125 Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser 130 135 140 Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr 145 150 155 160 Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 165 170 175 Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 180 185 190 Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 195 200 205 Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 210 215 220 Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 225 230 235 240 Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 245 250 255 Thr Lys Ser Phe Asn Arg Gly Glu Cys 260 265 <![CDATA[<210> 497]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV09-3001 LC]]> <![CDATA[<400> 4]]>97 Phe Gly Thr Ala Cys Pro Asn His Pro Met Cys His Asp Trp Gln Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly 20 25 30 Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 498]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV23-3001 LC]]> <![CDATA[<400> 498]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Leu Tyr Asn Val Cys Leu 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro 20 25 30 Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 499]]> <![CDATA[<211> 256]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV23-3001 LC]]> <![CDATA[<400> 499]]> Cys Leu His Ser Leu Tyr Asn Val Cys Leu Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly 20 25 30 Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser 35 40 45 Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 50 55 60 Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 65 70 75 80 Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg 85 90 95 Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 100 105 110 Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 115 120 125 Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr 130 135 140 Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 145 150 155 160 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 165 170 175 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 180 185 190 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 195 200 205 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 210 215 220 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 225 230 235 240 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 500]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV27-300]]>1 LC <![CDATA[<400> 500]]> Gln Gly Gln Ser Gly Ser Gln Pro Cys Ala Gln Met Tyr Gly Tyr Ser 1 5 10 15 Met Cys Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro 20 25 30 Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 501]]> <![CDATA[<211> 256]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV27-3001 LC]]> <![CDATA[<400> 501]]> Gln Pro Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly 20 25 30 Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser 35 40 45 Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 50 55 60 Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 65 70 75 80 Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg 85 90 95 Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 100 105 110 Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 115 120 125 Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr 130 135 140 Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 145 150 155 160 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 165 170 175 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 180 185 190 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 195 200 205 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 210 215 220 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 225 230 235 240 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 502]]> <![CDATA[<211> 263]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV29-3001 LC]]> <![CDATA[<400> 502]]> Gln Gly Gln Ser Gly Ser Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys 1 5 10 15 Ala His Thr Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala 20 25 30 Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser 35 40 45 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 50 55 60 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser 65 70 75 80 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 85 90 95 Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 100 105 110 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 115 120 125 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 130 135 140 Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala 145 150 155 160 Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 165 170 175 Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 180 185 190 Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 195 200 205 Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 210 215 220 Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 225 230 235 240 Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 245 250 255 Ser Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 503]]> <![CDATA[<211> 257]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV29-3001 LC]]> <![CDATA[<400> 503]]> Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Ala His Thr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser 20 25 30 Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln 35 40 45 Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser 50 55 60 Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln 65 70 75 80 Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser 85 90 95 Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr 100 105 110 Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val 115 120 125 Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly 130 135 140 Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile 145 150 155 160 Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val 165 170 175 Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys 180 185 190 Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu 195 200 205 Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu 210 215 220 Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr 225 230 235 240 His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu 245 250 255 Cys <![CDATA[<210> 504]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV32-3001 LC]]> <![CDATA[<400> 504]]> Gln Gly Gln Ser Gly Ser Cys Pro Asn His Pro Leu Cys His Asp Trp 1 5 10 15 Gln Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro 20 25 30 Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 505]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV32-3001 LC]]> <![CDATA[<400> 505]]> Cys Pro Asn His Pro Leu Cys His Asp Trp Gln Gly Gly Gly Ser Ser 1 5 10 15 Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 506]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV33-3001 LC]]> <![CDATA[<400> 506]]> Gln Gly Gln Ser Gly Ser Cys Pro Asn His Pro Met Cys Ala Asp Trp 1 5 10 15 Gln Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro 20 25 30 Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 507]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV33-3001 LC]]> <![CDATA[<400> 507]]> Cys Pro Asn His Pro Met Cys Ala Asp Trp Gln Gly Gly Gly Ser Ser 1 5 10 15 Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 508]]> <![CDATA[<211> 261]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV35-3001 LC]]> <![CDATA[<400> 508]]> Gln Gly Gln Ser Gly Ser Cys Pro Asn His Pro Met Cys His Asp Ala 1 5 10 15 Gln Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro 20 25 30 Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile 35 40 45 Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 50 55 60 Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu 65 70 75 80 Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 85 90 95 Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 100 105 110 Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 115 120 125 Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr 130 135 140 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 145 150 155 160 Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 165 170 175 Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 180 185 190 Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 195 200 205 Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 210 215 220 Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 225 230 235 240 Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 245 250 255 Asn Arg Gly Glu Cys 260 <![CDATA[<210> 509]]> <![CDATA[<211> 255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV35-3001 LC]]> <![CDATA[<400> 509]]> Cys Pro Asn His Pro Met Cys His Asp Ala Gln Gly Gly Gly Ser Ser 1 5 10 15 Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg 20 25 30 Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro 35 40 45 Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 50 55 60 Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 65 70 75 80 Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala 85 90 95 Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 100 105 110 Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 115 120 125 Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys 130 135 140 Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 145 150 155 160 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 165 170 175 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 180 185 190 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 195 200 205 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 210 215 220 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 225 230 235 240 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 510]]> <![CDATA[<211> 263]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV39-3001 LC]]> <![CDATA[<400> 510]]> Gln Gly Gln Ser Gly Ser Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu 1 5 10 15 Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala 20 25 30 Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser 35 40 45 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 50 55 60 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser 65 70 75 80 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 85 90 95 Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 100 105 110 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 115 120 125 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 130 135 140 Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala 145 150 155 160 Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 165 170 175 Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 180 185 190 Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 195 200 205 Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 210 215 220 Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 225 230 235 240 Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 245 250 255 Ser Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 511]]> <![CDATA[<211> 257]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV39-3001 LC]]> <![CDATA[<400> 511]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser 20 25 30 Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln 35 40 45 Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser 50 55 60 Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln 65 70 75 80 Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser 85 90 95 Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr 100 105 110 Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val 115 120 125 Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly 130 135 140 Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile 145 150 155 160 Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val 165 170 175 Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys 180 185 190 Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu 195 200 205 Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu 210 215 220 Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr 225 230 235 240 His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu 245 250 255 Cys <![CDATA[<210> 512]]> <![CDATA[<211> 263]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV41-3001 LC]]> <![CDATA[<400> 512]]> Gln Gly Gln Ser Gly Ser Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu 1 5 10 15 Cys Pro Ala Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala 20 25 30 Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser 35 40 45 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 50 55 60 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser 65 70 75 80 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 85 90 95 Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 100 105 110 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 115 120 125 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 130 135 140 Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala 145 150 155 160 Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 165 170 175 Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 180 185 190 Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 195 200 205 Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 210 215 220 Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 225 230 235 240 Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 245 250 255 Ser Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 513]]> <![CDATA[<211> 257]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV41-3001 LC]]> <![CDATA[<400> 513]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Ala Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser 20 25 30 Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln 35 40 45 Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser 50 55 60 Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln 65 70 75 80 Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser 85 90 95 Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr 100 105 110 Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val 115 120 125 Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly 130 135 140 Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile 145 150 155 160 Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val 165 170 175 Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys 180 185 190 Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu 195 200 205 Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu 210 215 220 Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr 225 230 235 240 His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu 245 250 255 Cys <![CDATA[<210> 514]]> <![CDATA[<211> 265]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV51-3001 LC]]> <![CDATA[<400> 514]]> Gln Gly Gln Ser Gly Ser Phe Gly Ala Ala Cys Pro Asn His Pro Ile 1 5 10 15 Cys His Asp Trp Gln Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu 20 25 30 Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly 35 40 45 Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser 50 55 60 Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly 65 70 75 80 Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg 85 90 95 Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg 100 105 110 Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg 115 120 125 Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser 130 135 140 Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr 145 150 155 160 Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 165 170 175 Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 180 185 190 Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 195 200 205 Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 210 215 220 Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 225 230 235 240 Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 245 250 255 Thr Lys Ser Phe Asn Arg Gly Glu Cys 260 265 <![CDATA[<210> 515]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV51-3001 LC]]> <![CDATA[<400> 515]]> Phe Gly Ala Ala Cys Pro Asn His Pro Ile Cys His Asp Trp Gln Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly 20 25 30 Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 516]]> <![CDATA[<211> 265]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV52-3001 LC]]> <![CDATA[<400> 516]]> Gln Gly Gln Ser Gly Ser Phe Gly Ala Ala Cys Pro Asn His Pro Leu 1 5 10 15 Cys His Asp Trp Gln Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu 20 25 30 Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly 35 40 45 Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser 50 55 60 Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly 65 70 75 80 Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg 85 90 95 Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg 100 105 110 Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg 115 120 125 Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser 130 135 140 Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr 145 150 155 160 Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 165 170 175 Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 180 185 190 Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 195 200 205 Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 210 215 220 Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 225 230 235 240 Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 245 250 255 Thr Lys Ser Phe Asn Arg Gly Glu Cys 260 265 <![CDATA[<210> 517]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV52-3001 LC]]> <![CDATA[<400> 517]]> Phe Gly Ala Ala Cys Pro Asn His Pro Leu Cys His Asp Trp Gln Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly 20 25 30 Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 518]]> <![CDATA[<211> 265]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV53-3001 LC]]> <![CDATA[<400> 518]]> Gln Gly Gln Ser Gly Ser Phe Gly Ala Ala Cys Pro Asn His Pro Met 1 5 10 15 Cys His Asp Ala Gln Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu 20 25 30 Leu Ala Pro Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly 35 40 45 Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser 50 55 60 Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly 65 70 75 80 Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg 85 90 95 Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg 100 105 110 Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg 115 120 125 Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser 130 135 140 Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr 145 150 155 160 Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 165 170 175 Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 180 185 190 Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 195 200 205 Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 210 215 220 Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 225 230 235 240 Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 245 250 255 Thr Lys Ser Phe Asn Arg Gly Glu Cys 260 265 <![CDATA[<210> 519]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223]]>> YV53-3001 LC]]> <br/> <br/><![CDATA[<400> 519]]> <br/> <br/><![CDATA[Phe Gly Ala Ala Cys Pro Asn His Pro Met Cys His Asp Ala Gln Gly 1 5 10 15 Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly 20 25 30 Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 520]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV54-3001 LC]]> <![CDATA[<400> 520]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Ala Tyr Asn Ala Cys Leu 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro 20 25 30 Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 521]]> <![CDATA[<211> 256]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV54-3001 LC]]> <![CDATA[<400> 521]]> Cys Leu His Ser Ala Tyr Asn Ala Cys Leu Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly 20 25 30 Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser 35 40 45 Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 50 55 60 Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 65 70 75 80 Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg 85 90 95 Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 100 105 110 Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 115 120 125 Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr 130 135 140 Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 145 150 155 160 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 165 170 175 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 180 185 190 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 195 200 205 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 210 215 220 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 225 230 235 240 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 522]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV55-3001 LC]]> <![CDATA[<400> 522]]> Gln Gly Gln Ser Gly Ser Cys Ala His Ser Ala Tyr Asn Val Cys Leu 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro 20 25 30 Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 523]]> <![CDATA[<211> 256]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV55-3001 LC]]> <![CDATA[<400> 523]]> Cys Ala His Ser Ala Tyr Asn Val Cys Leu Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly 20 25 30 Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser 35 40 45 Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 50 55 60 Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 65 70 75 80 Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg 85 90 95 Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 100 105 110 Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 115 120 125 Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr 130 135 140 Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 145 150 155 160 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 165 170 175 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 180 185 190 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 195 200 205 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 210 215 220 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 225 230 235 240 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 524]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV56-3001 LC]]> <![CDATA[<400> 524]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Ala Tyr Asn Val Cys Ala 1 5 10 15 Asp Pro Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro 20 25 30 Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 525]]> <![CDATA[<211> 256]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV56-3001 LC]]> <![CDATA[<400> 525]]> Cys Leu His Ser Ala Tyr Asn Val Cys Ala Asp Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly 20 25 30 Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser 35 40 45 Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 50 55 60 Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 65 70 75 80 Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg 85 90 95 Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 100 105 110 Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 115 120 125 Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr 130 135 140 Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 145 150 155 160 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 165 170 175 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 180 185 190 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 195 200 205 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 210 215 220 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 225 230 235 240 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 526]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV57-3001 LC]]> <![CDATA[<400> 526]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Ala Tyr Asn Val Cys Leu 1 5 10 15 Ala Pro Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro 20 25 30 Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 527]]> <![CDATA[<211> 256]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV57-3001 LC]]> <![CDATA[<400> 527]]> Cys Leu His Ser Ala Tyr Asn Val Cys Leu Ala Pro Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly 20 25 30 Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser 35 40 45 Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 50 55 60 Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 65 70 75 80 Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg 85 90 95 Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 100 105 110 Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 115 120 125 Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr 130 135 140 Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 145 150 155 160 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 165 170 175 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 180 185 190 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 195 200 205 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 210 215 220 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 225 230 235 240 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 528]]> <![CDATA[<211> 262]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV58-3001 LC]]> <![CDATA[<400> 528]]> Gln Gly Gln Ser Gly Ser Cys Leu His Ser Ala Tyr Asn Val Cys Leu 1 5 10 15 Asp Ala Gly Gly Gly Ser Ser Gly Gly Ala Val Gly Leu Leu Ala Pro 20 25 30 Pro Gly Gly Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser Glu 35 40 45 Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 50 55 60 Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr 65 70 75 80 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 85 90 95 Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly 100 105 110 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 115 120 125 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp 130 135 140 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 145 150 155 160 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 165 170 175 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 180 185 190 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 195 200 205 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 210 215 220 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 225 230 235 240 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 245 250 255 Phe Asn Arg Gly Glu Cys 260 <![CDATA[<210> 529]]> <![CDATA[<211> 256]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV58-3001 LC]]> <![CDATA[<400> 529]]> Cys Leu His Ser Ala Tyr Asn Val Cys Leu Asp Ala Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Ala Val Gly Leu Leu Ala Pro Pro Gly Gly Leu Ser Gly 20 25 30 Arg Ser Asp Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser 35 40 45 Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 50 55 60 Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 65 70 75 80 Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg 85 90 95 Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 100 105 110 Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 115 120 125 Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr 130 135 140 Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 145 150 155 160 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 165 170 175 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 180 185 190 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 195 200 205 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 210 215 220 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 225 230 235 240 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 255 <![CDATA[<210> 530]]> <![CDATA[<211> 259]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子 - YV39-NSUB LC]]> <![CDATA[<400> 530]]> Gln Gly Gln Ser Gly Ser Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu 1 5 10 15 Cys Pro Tyr Gly Gly Gly Ser Ser Gly Gly Ser Gly Gly Ser Gly Gly 20 25 30 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Ser Glu Ile Val Leu 35 40 45 Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 50 55 60 Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp 65 70 75 80 Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 85 90 95 Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 100 105 110 Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 115 120 125 Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly 130 135 140 Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 145 150 155 160 Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 165 170 175 Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 180 185 190 Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 195 200 205 Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 210 215 220 Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 225 230 235 240 Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 245 250 255 Gly Glu Cys <![CDATA[<210> 531]]> <![CDATA[<211> 253]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV39-NSUB LC]]> <![CDATA[<400> 531]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Gly Ser Gly 20 25 30 Gly Gly Ser Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser 145 150 155 160 Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn 165 170 175 Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala 180 185 190 Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys 195 200 205 Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp 210 215 220 Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu 225 230 235 240 Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 245 250 <![CDATA[<210> 532]]> <![CDATA[<211> 2]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (1)..(2)]]> <![CDATA[<223> 序列可重複任何次數]]> <![CDATA[<400> 532]]> Gly Ser 1 <![CDATA[<210> 533]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (1)..(3)]]> <![CDATA[<223> 序列可重複任何次數]]> <![CDATA[<400> 533]]> Gly Gly Ser 1 <![CDATA[<210> 534]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (1)..(5)]]> <![CDATA[<223> 序列可重複任何次數]]> <![CDATA[<400> 534]]> Gly Ser Gly Gly Ser 1 5 <![CDATA[<210> 535]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (1)..(4)]]> <![CDATA[<223> 序列可重複任何次數]]> <![CDATA[<400> 535]]> Gly Gly Gly Ser 1 <![CDATA[<210> 536]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<400> 536]]> Gly Gly Ser Gly 1 <![CDATA[<210> 537]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<400> 537]]> Gly Gly Ser Gly Gly 1 5 <![CDATA[<210> 538]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<400> 538]]> Gly Ser Gly Ser Gly 1 5 <![CDATA[<210> 539]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<400> 539]]> Gly Ser Gly Gly Gly 1 5 <![CDATA[<210> 540]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<400> 540]]> Gly Gly Gly Ser Gly 1 5 <![CDATA[<210> 541]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<400> 541]]> Gly Ser Ser Ser Gly 1 5 <![CDATA[<210> 542]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<400> 542]]> Gly Gly Gly Ser Ser Gly Gly Ser 1 5 <![CDATA[<210> 543]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 連接子]]> <![CDATA[<400> 543]]> Gly Gly Gly Ser 1 <![CDATA[<210> 544]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子]]> <![CDATA[<400> 544]]> Gln Gly Gln Ser Gly Gln Gly 1 5 <![CDATA[<210> 545]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子]]> <![CDATA[<400> 545]]> Gly Gln Ser Gly Gln Gly 1 5 <![CDATA[<210> 546]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子]]> <![CDATA[<400> 546]]> Gln Gly Gln Ser Gly Ser 1 5 <![CDATA[<210> 547]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子]]> <![CDATA[<400> 547]]> Gln Gly Gln Ser Gly Gln 1 5 <![CDATA[<210> 548]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子]]> <![CDATA[<400> 548]]> Gln Ser Gly Gln Gly 1 5 <![CDATA[<210> 549]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子]]> <![CDATA[<400> 549]]> Gly Gln Ser Gly Ser 1 5 <![CDATA[<210> 550]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子]]> <![CDATA[<400> 550]]> Gln Gly Gln Ser Gly 1 5 <![CDATA[<210> 551]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子]]> <![CDATA[<400> 551]]> Ser Gly Gln Gly 1 <![CDATA[<210> 552]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子]]> <![CDATA[<400> 552]]> Gln Ser Gly Ser 1 <![CDATA[<210> 553]]> <![CDATA[<211> 4]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子]]> <![CDATA[<400> 553]]> Gln Gly Gln Ser 1 <![CDATA[<210> 554]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 共同序列]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (1)..(2)]]> <![CDATA[<223> Xaa 可為任何胺基酸]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (4)..(6)]]> <![CDATA[<223> Xaa 可為任何胺基酸]]> <![CDATA[<400> 554]]> Xaa Xaa Cys Xaa Xaa Xaa Met Tyr Gly Tyr Asn Leu Cys Pro Tyr 1 5 10 15 <![CDATA[<210> 555]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 共同序列]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (1)..(3)]]> <![CDATA[<223> Xaa 可為任何胺基酸]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (5)..(5)]]> <![CDATA[<223> Xaa 可為任何胺基酸]]> <![CDATA[<400> 555]]> Xaa Xaa Xaa Cys Xaa His Ser Met Tyr Asn Val Cys Leu Asp Pro 1 5 10 15 <![CDATA[<210> 556]]> <![CDATA[<211> 19]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 間隔子-YV39]]> <![CDATA[<400> 556]]> Gln Gly Gln Ser Gly Ser Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu 1 5 10 15 Cys Pro Tyr <![CDATA[<210> 557]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 易普利姆瑪之 CDR1 HC ]]> <![CDATA[<400> 557]]> Ser Tyr Thr Met His 1 5 <![CDATA[<210> 558]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 易普利姆瑪之 CDR2 HC]]> <![CDATA[<400> 558]]> Phe Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala Asp Ser Val Lys 1 5 10 15 Gly <![CDATA[<210> 559]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 易普利姆瑪之 CDR3 HC]]> <![CDATA[<400> 559]]> Thr Gly Trp Leu Gly Pro Phe Asp Tyr 1 5 <![CDATA[<210> 560]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 易普利姆瑪之 CDR1 LC]]> <![CDATA[<400> 560]]> Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala 1 5 10 <![CDATA[<210> 561]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 易普利姆瑪之 CDR2 LC]]> <![CDATA[<400> 561]]> Gly Ala Phe Ser Arg Ala Thr 1 5 <![CDATA[<210> 562]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 易普利姆瑪之 CDR3 LC]]> <![CDATA[<400> 562]]> Gln Gln Tyr Gly Ser Ser Pro Trp Thr 1 5 <![CDATA[<210> 563]]> <![CDATA[<211> 146]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV39-2001 VL]]> <![CDATA[<400> 563]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp 20 25 30 Asn His Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys 145 <![CDATA[<210> 564]]> <![CDATA[<211> 146]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV39-2011 VL]]> <![CDATA[<400> 564]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Asp 20 25 30 Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys 145 <![CDATA[<210> 565]]> <![CDATA[<211> 146]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> YV39-2012 VL]]> <![CDATA[<400> 565]]> Cys Arg Thr Gln Leu Tyr Gly Tyr Asn Leu Cys Pro Tyr Gly Gly Gly 1 5 10 15 Ser Ser Gly Gly Ser Ile Ser Ser Gly Leu Leu Ser Gly Arg Ser Ala 20 25 30 Asn Pro Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr 35 40 45 Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser 50 55 60 Gln Ser Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 65 70 75 80 Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly 85 90 95 Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 100 105 110 Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln 115 120 125 Gln Tyr Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu 130 135 140 Ile Lys 145 <![CDATA[<21]]>0> 566]]> <br/><![CDATA[<211> 12]]> <br/><![CDATA[<212> PRT]]> <br/><![CDATA[<213> 人工序列]]> <br/> <br/><![CDATA[<220>]]> <br/><![CDATA[<223> MM 共同序列 1]]> <br/> <br/> <br/><![CDATA[<220>]]> <br/><![CDATA[<221> MISC_FEATURE]]> <br/><![CDATA[<222> (2)..(2)]]> <br/><![CDATA[<223> Xaa 可為 L, M, V 或 T]]> <br/> <br/><![CDATA[<220>]]> <br/><![CDATA[<221> MISC_FEATURE]]> <br/><![CDATA[<222> (4)..(4)]]> <br/><![CDATA[<223> Xaa 可為 S, V 或 I]]> <br/> <br/><![CDATA[<220>]]> <br/><![CDATA[<221> MISC_FEA]]><![CDATA[TURE <![CDATA[<222> (5)..(5)]]> <![CDATA[<223> Xaa 可為 F, L, M 或 A]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (6)..(6)]]> <![CDATA[<223> Xaa 可為 Y 或 F]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (8)..(8)]]> <![CDATA[<223> Xaa 可為 V 或 I]]> <![CDATA[<400> 566]]> Cys Xaa Tyr Xaa Xaa Xaa Asn Xaa Cys Leu Asp Pro 1 5 10 <![CDATA[<210> 567]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> MM 共同序列 2]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (11)..(11)]]> <![CDATA[<223> Xaa 可為 P 或 A]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (12)..(12)]]> <![CDATA[<223> Xaa 可為 H, R 或 A]]> <![CDATA[<400> 567]]> Cys Ala Gln Met Tyr Gly Tyr Ser Met Cys Xaa Xaa Thr 1 5 10 <![CDATA[<210> 568]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> MM 共同序列 3]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (2)..(2)]]> <![CDATA[<223> Xaa 可為任何胺基酸]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (3)..(3)]]> <![CDATA[<223> Xaa 可為 M, I, Y, L, N 或 F]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (4)..(4)]]> <![CDATA[<223> Xaa 可為 Y, W, F, Q 或 T]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (5)..(5)]]> <![CDATA[<223> Xaa 可為 M 或 Y]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (8)..(8)]]> <![CDATA[<223> Xaa 可為 Y, V 或 F]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (9)..(9)]]> <![CDATA[<223> Xaa 可為 N 或 D]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (13)..(13)]]> <![CDATA[<223> Xaa 可為 Y 或 F]]> <![CDATA[<400> 568]]> Cys Xaa Xaa Xaa Xaa Tyr Gly Xaa Xaa Leu Cys Pro Xaa 1 5 10 <![CDATA[<210> 569]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> MM 共同序列 4]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (1)..(1)]]> <![CDATA[<223> Xaa 可為 N 或 T]]> <![CDATA[<220>]]> <![CDATA[<221> MISC_FEATURE]]> <![CDATA[<222> (2)..(2)]]> <![CDATA[<223]]>> Xaa 可為 S, T, M 或 A]]> <br/> <br/><![CDATA[<220>]]> <br/><![CDATA[<221> MISC_FEATURE]]> <br/><![CDATA[<222> (5)..(5)]]> <br/><![CDATA[<223> Xaa 可為 N 或 Y]]> <br/> <br/><![CDATA[<220>]]> <br/><![CDATA[<221> MISC_FEATURE]]> <br/><![CDATA[<222> (8)..(8)]]> <br/><![CDATA[<223> Xaa 可為 M 或 L]]> <br/> <br/><![CDATA[<220>]]> <br/><![CDATA[<221> MISC_FEATURE]]> <br/><![CDATA[<222> (10)..(10)]]> <br/><![CDATA[<223> Xaa 可為 H, F 或 Y]]> <br/> <br/><![CDATA[<220>]]> <br/><![CDATA[<221> MISC_FEATURE]]> <br/><![CDATA[<222> (12)..(12)]]> <br/><![CDATA[<223> Xaa 可為 Y, F 或 W]]> <br/> <br/><![CDATA[<400> 569]]> <br/> <br/><![CDATA[Xaa Xaa Cys Pro Xaa His Pro Xaa Cys Xaa Asp Xaa 1 5 10 <![CDATA[<210> 570]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 抗蛋白酶連接子]]> <![CDATA[<400> 570]]> Gly Gly Ser Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser 1 5 10
Claims (27)
- 一種可活化之抗人類CTLA-4抗體,其包含, (i) 重鏈,該重鏈包含重鏈可變結構域(VH),該重鏈可變結構域(VH)包含:CDRH1: SYTMH (SEQ ID NO: 557);CDRH2: FISYDGNNKYYADSVKG (SEQ ID NO: 558);及CDRH3: TGWLGPFDY (SEQ ID NO: 559);及 (ii) 輕鏈,其包含: (a) 輕鏈可變結構域(VL),該輕鏈可變結構域(VL)包含CDRL1: RASQSVGSSYLA (SEQ ID NO: 560);CDRL2: GAFSRAT (SEQ ID NO: 561);及CDRL3: QQYGSSPWT (SEQ ID NO: 562); (b) 可裂解部分(CM);及 (c) 掩蔽部分(MM), 其中該輕鏈自N端至C端具有如下結構排列:MM-CM-VL。
- 如請求項1之可活化之抗人類CTLA-4抗體,其中該MM選自由以下組成之群:YV01、YV02、YV03、YV04、YV09、YV23、YV24、YV35、YV39、YV51、YV61、YV62、YV63、YV64、YV65及YV66。
- 如請求項2之可活化之抗人類CTLA-4抗體,其中該CM係選自由以下組成之群之蛋白酶的受質:MMP1、MMP2、MMP3、MMP8、MMP9、MMP11、MMP13、MMP14、MMP17、天冬醯胺內肽酶(legumain)、間質蛋白酶(matriptase)及uPA。
- 如請求項3之可活化之抗人類CTLA-4抗體,其中該CM選自由以下組成之群:2001、2003、2005、2006、2007、2008、2009、2011、2012、3001、3006、3007、3008、3009、3011及3012。
- 如請求項4之可活化之抗人類CTLA-4抗體,其中該MM係YV04、YV23、YV24、YV39、YV61、YV62、YV63或YV64。
- 如請求項5之可活化之抗人類CTLA-4抗體,其中該MM係YV39。
- 如請求項6之可活化之抗人類CTLA-4抗體,其中該CM係2001、2011或2012。
- 如請求項7之可活化之抗人類CTLA-4抗體,其中該CM係2011。
- 如請求項1至8中任一項之可活化之抗人類CTLA-4抗體,其包含: (i) 包含胺基酸序列SEQ ID NO: 345之重鏈;及 (ii) 包含選自由SEQ ID NO: 563、SEQ ID NO: 564及SEQ ID NO: 565組成之群之胺基酸序列的輕鏈。
- 如請求項9之可活化之抗人類CTLA-4抗體,其包含: (i) 包含該胺基酸序列SEQ ID NO: 345之重鏈;及 (ii) 包含該胺基酸序列SEQ ID NO: 564之輕鏈。
- 如請求項10之可活化之抗人類CTLA-4抗體,其中: (i) 該重鏈進一步包含人類IgG1恆定域序列SEQ ID NO: 350;且 (ii) 該輕鏈進一步包含人類輕鏈κ恆定域序列SEQ ID NO: 346。
- 如請求項1至11中任一項之可活化之抗人類CTLA-4抗體,其進一步包含如本文所揭示之第二連接肽(LP2),且其中該可活化之抗人類CTLA-4抗體自N端至C端具有結構排列MM-LP1-CM-LP2-VL或MM-LP2-CM-LP1-VL。
- 如請求項12之可活化之抗人類CTLA-4抗體,其中該LP1與該LP2彼此不同。
- 如請求項1至13中任一項之可活化之抗人類CTLA-4抗體,其進一步包含間隔子,且自N端至C端具有結構排列為:間隔子-MM-CM-VL。
- 如請求項1至14中任一項之可活化之抗人類CTLA-4抗體,其進一步包含毒性劑。
- 如請求項15之可活化之抗人類CTLA-4抗體,其中該毒性劑藉助於可裂解連接子與該可活化之抗體結合。
- 如請求項1至14中任一項之可活化之抗人類CTLA-4抗體,其進一步包含可偵測部分。
- 如請求項17之可活化之抗人類CTLA-4抗體,其中該可偵測部分係診斷劑。
- 一種醫藥組合物,其包含如請求項1至18中任一項之可活化之抗人類CTLA-4抗體及載劑。
- 如請求項19之醫藥組合物,其包含另一種治療劑。
- 一種分離之核酸分子,其編碼如請求項1至14中任一項之可活化之抗人類CTLA-4抗體之重鏈及/或輕鏈。
- 一種載體,其包含如請求項21之分離之核酸分子。
- 一種產生可活化之抗人類CTLA-4抗體之方法,其包含: (i) 在引起該可活化之抗體表現之條件下培養包含如請求項22之載體之細胞;及 (ii) 回收該可活化之抗體。
- 一種為有需要之個體降低CTLA-4活性的方法,其包含向該個體投與有效量之如請求項19或20之醫藥組合物。
- 一種治療個體之癌症、緩解個體之癌症症狀或延緩個體之癌症演進的方法,其包含向該個體投與治療有效量之如請求項19或20之醫藥組合物。
- 如請求項25之方法,其中該癌症係膀胱癌、骨癌、乳癌、類癌、子宮頸癌、結腸癌、子宮內膜癌、神經膠質瘤、頭頸癌、肝癌、肺癌、淋巴瘤、黑素瘤、卵巢癌、胰臟癌、前列腺癌、腎癌、肉瘤、皮膚癌、胃癌、睾丸癌、甲狀腺癌、泌尿生殖器癌或尿道上皮癌。
- 如請求項26之方法,其中該癌症係黑素瘤。
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2017
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JP7472183B2 (ja) | 2024-04-22 |
TWI784983B (zh) | 2022-12-01 |
EA201990875A1 (ru) | 2019-09-30 |
AU2017355446A1 (en) | 2019-05-02 |
WO2018085555A8 (en) | 2018-05-31 |
KR20230141941A (ko) | 2023-10-10 |
BR112019008223A2 (pt) | 2019-07-16 |
CL2019001226A1 (es) | 2019-09-13 |
CA3042679A1 (en) | 2018-05-11 |
US11117968B2 (en) | 2021-09-14 |
KR20190072626A (ko) | 2019-06-25 |
KR102584340B1 (ko) | 2023-10-10 |
JP2022091800A (ja) | 2022-06-21 |
US20220089734A1 (en) | 2022-03-24 |
JP2020500016A (ja) | 2020-01-09 |
IL265625A (en) | 2019-05-30 |
PE20191131A1 (es) | 2019-09-02 |
CN110072890B (zh) | 2022-11-29 |
AR110678A1 (es) | 2019-04-24 |
WO2018085555A1 (en) | 2018-05-11 |
CO2019004469A2 (es) | 2019-05-10 |
MX2019004775A (es) | 2019-08-05 |
MY200695A (en) | 2024-01-11 |
CN110072890A (zh) | 2019-07-30 |
JP7039582B2 (ja) | 2022-03-22 |
US20190359714A1 (en) | 2019-11-28 |
SG11201902857SA (en) | 2019-05-30 |
TW201819412A (zh) | 2018-06-01 |
EP3535300A1 (en) | 2019-09-11 |
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