TW202315890A - 結合cd80及/或cd86及ox40l之蛋白質 - Google Patents
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Abstract
本發明大體上係關於抑制T細胞協同刺激信號傳導之蛋白質，其包含：特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物，及特異性結合OX40L之多肽或兩種或更多種多肽之複合物。在一些實施例中，本申請案提供特異性結合OX40L之抗體。在一些實施例中，本申請案亦提供在治療自體免疫疾病中使用此類蛋白質之治療方法。
Description
本發明大體上係關於能夠調節T細胞協同刺激信號傳導之蛋白質及其在治療自體免疫疾病/病症中之用途。
治療自體免疫疾病之主要治療目標為藉由特異性靶向協同刺激路徑調節T細胞刺激。T細胞在其接受兩種來自以下之信號時變得完全活化：1) T細胞受體(TCR)活化，其由與抗原呈遞細胞(APC)之表面上之肽/MHC複合體的相互作用引起；及2) T細胞協同刺激受體活化，其由與其同源配位體之相互作用引起。在不存在第二協同刺激信號下的T細胞刺激引起產生無變應性或耐受性T細胞反應。
存在兩個主要協同刺激分子組：1) B7-CD28超家族，及2)腫瘤壞死因子受體(TNFR)超家族。B7-CD28超家族中之協同刺激分子包括T細胞上之CD28及ICOS及其分別位於APC之表面上的同源配位體CD80/CD86 (亦稱為B7.1/B7.2)及ICOS-L。TNFR超家族中之協同刺激分子分別包括T細胞上之4-1BB、CD40L、OX40、CD27、GITR及CD30及其各自的同源配位體4-1BBL、CD40、OX40L、CD70、GITRL及CD30L。
諸如B細胞、單核球、巨噬細胞及樹突狀細胞之APC在被抗原性、發炎性或病原體相關分子模式受體活化後上調CD80及CD86之表現。此等配位體接合T細胞上之CD28且提供必要的第二協同刺激信號以活化初始T細胞且促進T細胞增殖。
由於CD80及CD86對CTLA4之親和力高於CD28，因此T細胞上之CTLA4表現藉由隔離協同刺激配位體且減弱T細胞活化抑制CD80/CD86結合於CD28。阿巴西普(Abatacept)為包含人類CTLA4之細胞外域及經修飾之人類免疫球蛋白1 (IgG1) Fc域的可溶性重組CTLA4-Ig融合蛋白。阿巴西普選擇性地結合APC上之CD80/CD86且防止T細胞上之CD28協同刺激活化，從而引起T細胞活化、信號傳導及增殖減少。阿巴西普被證明在治療包括成人類風濕性關節炎、牛皮癬性關節炎及幼年特發性關節炎之多種自體免疫疾病方面有臨床功效。然而，在全身性紅斑狼瘡(SLE)、狼瘡性腎炎(LN)及原發性休格倫氏症候群(primary Sjogren's Syndrome；pSS)之臨床試驗中，阿巴西普未能實現其臨床指標。
OX40配位體(OX40L，亦稱為CD252、gp34及TNFSF4)為TNF超家族之34kDa II型跨膜蛋白。OX40L表現在APC及慢性活化T細胞活化後誘導。OX40L亦在非淋巴細胞(如人類扁桃體肥大細胞、支氣管平滑肌細胞及發炎或患病組織之血管內皮細胞)中上調。OX40L由於蛋白水解酶裂解而以可溶性形式存在，其為大部分TNF家族配位體之典型特點。已報導相較於健康個體，可溶性OX40L血清水準在自體免疫疾病患者中升高。
APC上之OX40L結合於表現於活化CD4及CD8 T細胞上之OX40 (CD134，TNFRSF4)。OX40不表現於休眠初始或休眠記憶T細胞上。OX40L係以均三聚複合物形式結合於T細胞上之三個OX40單體。OX40L與OX40結合刺激T細胞膨脹、分化及T效應細胞亞群(包括T輔助細胞1 (Th1)、T輔助細胞2 (Th2)、T濾泡輔助細胞(Tfh)及T輔助細胞17 (Th17))之存活。OX40信號傳導對於記憶CD4+ T細胞之產生、維持及最佳再活化亦為關鍵的。
OX40L-OX40路徑之調節異常已牽涉到廣泛多種發炎性疾病，諸如多發性硬化症、關節炎、移植物抗宿主疾病(GVHD)、狼瘡性腎炎及類風濕性關節炎。TNFSF4 (編碼OX40L之基因)為全身性紅斑狼瘡(SLE)及全身性硬化症(SSc)之易感性基因座。表現OX40L之骨髓細胞及B細胞已被證明可支持Tfh細胞發展，促成SLE疾病致病機制。OX40L-OX40信號傳導亦藉由使T調節細胞(Treg或T
reg)失調而促成自體免疫疾病之致病機制。Foxp3+ Treg藉由抑制過度活化T效應細胞(Teff、T
eff或T
效應)而在建立免疫耐受性方面起重要作用。在人類SLE中，OX40L-OX40信號傳導抑制Treg中之Foxp3表現且不利地影響其抑制功能。
本發明大體上係關於能夠調節T細胞協同刺激信號傳導之蛋白質及其在治療自體免疫疾病/病症中之用途。
在一個態樣中，本發明提供一種蛋白質，其包含特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物，及特異性結合OX40L之多肽或兩種或更多種多肽之複合物。在一些實施例中，特異性結合CD80及/或CD86之多肽兩種或更多種多肽之複合物為包含CTLA4細胞外域或其功能片段的多肽；包含CD28細胞外域或其功能片段的多肽；抗體；Fab；Fab'；F(ab')
2；單鏈可變片段(scFv)；微型抗體或奈米抗體(VHH)。在一些實施例中，特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物包含CTLA4之細胞外域或其功能片段，該CTLA4之細胞外域或其功能片段由與SEQ ID NO: 29、SEQ ID NO: 173或SEQ ID NO: 174具有至少90%序列一致性之序列組成或包含該序列。在一些實施例中，特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物抑制T細胞中之CD28協同刺激信號傳導。
在本發明之另一態樣中，特異性結合OX40L之多肽或兩種或更多種多肽之複合物抑制內源性OX40L與內源性OX40之結合。在一些實施例中，特異性結合OX40L之多肽或兩種或更多種多肽之複合物包含抗原結合位點。在一些實施例中，抗原結合位點為抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)。在一些實施例中，抗原結合位點為Fab，其包含連接於Fab重鏈CH1域之C端的包含序列SEQ ID NO: 336之多肽。在其他實施例中，特異性結合OX40L之多肽或兩種或更多種多肽之複合物為OX40之細胞外域或其功能片段。
在一些實施例中，本發明之蛋白質進一步包含橋接部分。在一些實施例中，橋接部分為功能性或非功能性。在一些實施例中，橋接部分包含免疫球蛋白Fc域之多肽或其功能片段、人類血清白蛋白(HSA)多肽或其功能片段、多肽連接子或多肽鉸鏈。在一些實施例中，橋接部分包含人類IgG1、IgG2、IgG3或IgG4 Fc域之多肽。在一些實施例中，人類IgG1 Fc域之多肽包含與選自由以下組成之群的胺基酸序列具有至少90%或100%序列一致性之序列：SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 238、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240。在一些實施例中，人類IgG1 Fc域之多肽包含一種或多於一種效應功能靜默突變。在某些實施例中，鉸鏈多肽包含位置234及235處由白胺酸成為丙胺酸之突變。
在一些實施例中，橋接部分進一步包含鉸鏈多肽，其包含與選自由以下組成之群的胺基酸序列具有至少90%序列一致性之胺基酸序列：SEQ ID NO: 175、SEQ ID NO: 242、SEQ ID NO: 176、SEQ ID NO: 249、SEQ ID NO: 177、SEQ ID NO: 243、SEQ ID NO: 212、SEQ ID NO: 244、SEQ ID NO: 213、SEQ ID NO: 245、SEQ ID NO: 247及SEQ ID NO: 248。
在本發明蛋白質之一些實施例中，橋接部分連接於特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物的N端或C端。在一些實施例中，特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物連接於橋接部分之N端。在一些實施例中，橋接部分連接於特異性結合OX40L之多肽或兩種或更多種多肽之複合物的N端或C端。在一些實施例中，特異性結合OX40L之多肽或兩種或更多種多肽之複合物連接於橋接部分之C端。在一些實施例中，包含(GGGGS)
n(SEQ ID NO: 181)序列之連接子多肽將特異性結合OX40L之多肽或兩種或更多種多肽之複合物連接於橋接部分，其中n為1至12。
在一些實施例中，本發明之蛋白質包含特異性結合OX40L之第二多肽或兩個或更多個多肽之複合物。在一些實施例中，橋接部分為人類IgG1 Fc域之多肽，且特異性結合OX40L之多肽或兩種或更多種多肽之複合物連接於人類IgG1 Fc域之多肽之C端，且特異性結合OX40L之第二多肽或兩種或更多種多肽之複合物連接於人類IgG1 Fc域之第二多肽之C端。在一些實施例中，特異性結合OX40L之第一及/或第二多肽或兩種或更多種多肽之複合物包含抗原結合位點，例如Fab或OX40之細胞外域或其功能片段。在一些實施例中，特異性結合OX40L之第二多肽或兩種或更多種多肽之複合物係藉由包含(GGGGS)
n(SEQ ID NO: 181)序列之連接子多肽連接於橋接部分，其中n為1至12。
在一些實施例中，本發明之蛋白質包括包含以下之胺基酸序列的抗原結合位點：(a) ARHRGX
1YX
2FDX
3(SEQ ID NO: 220)，其中X
1為S或I，X
2為F或H且X
3為I或Y；或(b) ARERSX
1X
2WYPX
3DY (SEQ ID NO: 221)，其中X
1為N或S，X
2為N、D、G或S且X
3為I或F。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：(a)包含胺基酸序列GX
1SX
2X
3X
4SX
5YY (SEQ ID NO: 222)之重鏈可變互補決定區1 (VHCDR1)，其中X
1為A、G或V，X
2為V或I，X
3為S或R，X
4為S或T，及X
5為S或G；(b)包含以下之胺基酸序列之重鏈可變互補決定區2 (VHCDR2)：(1) IX
1YX
2GST (SEQ ID NO: 223)，其中X
1為Y或N且X
2為S或G，(2) X
1DYSGT (SEQ ID NO: 224)，其中X
1為I或M或(3) IGSVDYSGX
1T (SEQ ID NO: 225)，其中X
1為N、A或S；及(c)包含以下之胺基酸序列之重鏈可變互補決定區3 (VHCDR3)：(1) ARHRGX
1YX
2FDX
3(SEQ ID NO: 220)，其中X
1為S或I，X
2為F或H且X
3為I或Y；或(2) ARERSX
1X
2WYPX
3DY (SEQ ID NO: 221)，其中X
1為N或S，X
2為N、D、G或S且X
3為I或F。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：(a)包含以下之胺基酸序列之輕鏈可變互補決定區1 (VLCDR1)：(1) X
1IENKN
(SEQ ID NO: 226)，其中X
1為N或D，或(2) SX
1RX
2X
3X
4(SEQ ID NO: 227)，其中X
1為V或L，X
2為R或N，X
3為F或Y且X
4為F或Y；(b)包含以下之胺基酸序列之輕鏈可變互補決定區2 (VLCDR2)：RDN (SEQ ID NO: 82)、GKD (SEQ ID NO: 228)或RDS (SEQ ID NO: 90)；及(c)包含以下之胺基酸序列之輕鏈可變互補決定區3 (VLCDR3)：(1) QVX
1DSX
2X
3VV (SEQ ID NO: 231)，其中X
1為R或W，X
2為N、T或A且X
3為I、T或A，或(2) NSRDSSGYX
1VX
2(SEQ ID NO: 232)，其中X
1為L或H且X
2為L或V。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：(i) (a)包含胺基酸序列GX
1SX
2X
3X
4SX
5YY (SEQ ID NO: 222)之重鏈可變互補決定區1 (VHCDR1)，其中X
1為A、G或V，X
2為V或I，X
3為S或R，X
4為S或T，且X
5為S或G；及(b)包含胺基酸序列IX
1YX
2GST (SEQ ID NO: 223)之重鏈可變互補決定區2 (VHCDR2)，其中X
1為Y或N且X
2為S或G；及(c)包含胺基酸序列ARHRGX
1YX
2FDX
3(SEQ ID NO: 220)之重鏈可變互補決定區3 (VHCDR3)，其中X
1為S或I，X
2為F或H且X
3為I或Y；及(ii) (a)包含胺基酸序列X
1IENKN
(SEQ ID NO: 226)之輕鏈可變互補決定區1 (VLCDR1)，其中X
1為N或D；(b)包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及(c)包含胺基酸序列QVX
1DSX
2X
3VV (SEQ ID NO: 231)之輕鏈可變互補決定區3 (VLCDR3)，其中X
1為R或W，X
2為N、T或A且X
3為I、T或A。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：(i) (a)包含胺基酸序列GX
1SX
2X
3X
4SX
5YY (SEQ ID NO: 222)之重鏈可變互補決定區1 (VHCDR1)，其中X
1為A、G或V，X
2為V或I，X
3為S或R，X
4為S或T，且X
5為S或G；及(b)包含胺基酸序列X
1DYSGT (SEQ ID NO: 224)之重鏈可變互補決定區2 (VHCDR2)，其中X
1為I或M；及(c)包含胺基酸序列ARERSX
1X
2WYPX
3DY (SEQ ID NO: 221)之重鏈可變互補決定區3 (VHCDR3)，其中X
1為N或S，X
2為N、D、G或S且X
3為I或F；及(ii) (a)包含胺基酸序列SX
1R X
2X
3X
4(SEQ ID NO: 227)之輕鏈可變互補決定區1 (VLCDR1)，其中X
1為V或L，X
2為R或N, X
3為F或Y且X
4為F或Y；(b)包含胺基酸序列GKD (SEQ ID NO: 229)之輕鏈可變互補決定區2 (VLCDR2)；及(c)包含胺基酸序列NSRDSSGYX
1VX
2(SEQ ID NO: 232)之輕鏈可變互補決定區3 (VLCDR3)，其中X
1為L或H且X
2為L或V。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈互補決定區1 (VHCDR1)、包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈互補決定區2 (VHCDR2)、包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈互補決定區3 (VHCDR3)、包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈互補決定區1 (VLCDR1)、包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈互補決定區2 (VLCDR2)及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈互補決定區3 (VLCDR3)。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：包含胺基酸序列GVSIRSNGYY (SEQ ID NO: 93)之重鏈互補決定區1 (VHCDR1)、包含胺基酸序列MDYSGT (SEQ ID NO: 94)之重鏈互補決定區2 (VHCDR2)、包含胺基酸序列ARERSNNWYPIDY (SEQ ID NO: 95)之重鏈互補決定區3 (VHCDR3)、包含胺基酸序列SVRRFF (SEQ ID NO: 97)之輕鏈互補決定區1 (VLCDR1)、包含胺基酸序列GKD (SEQ ID NO: 98)之輕鏈互補決定區2 (VLCDR2)及包含胺基酸序列NSRDSSGYLVL (SEQ ID NO: 99)之輕鏈互補決定區3 (VLCDR3)。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：包含胺基酸序列GASVSSSSYY (SEQ ID NO: 85)之重鏈互補決定區1 (VHCDR1)、包含胺基酸序列INYGGST (SEQ ID NO: 86)之重鏈互補決定區2 (VHCDR2)、包含胺基酸序列ARHRGIYHFDY (SEQ ID NO: 87)之重鏈互補決定區3 (VHCDR3)、包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈互補決定區1 (VLCDR1)、包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈互補決定區2 (VLCDR2)及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈互補決定區3 (VLCDR3)。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：包含胺基酸序列GGSISSSSYY (SEQ ID NO: 101)之重鏈互補決定區1 (VHCDR1)、包含胺基酸序列IGSVDYSGNT (SEQ ID NO: 102)之重鏈互補決定區2 (VHCDR2)、包含胺基酸序列ARHRGIYFFDY (SEQ ID NO: 103)之重鏈互補決定區3 (VHCDR3)、包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈互補決定區1 (VLCDR1)、包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈互補決定區2 (VLCDR2)及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈互補決定區3 (VLCDR3)。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：與SEQ ID NO: 76、SEQ ID NO: 92、SEQ ID NO: 84或SEQ ID NO: 100具有至少90%序列一致性之胺基酸序列，及與SEQ ID NO: 80、SEQ ID NO: 96、SEQ ID NO: 88或SEQ ID NO: 104具有至少90%序列一致性之胺基酸序列。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：與SEQ ID NO: 76具有至少90%序列一致性之胺基酸序列，及與SEQ ID NO: 80具有至少90%序列一致性之胺基酸序列。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：與SEQ ID NO: 92具有至少90%序列一致性之胺基酸序列，及與SEQ ID NO: 96具有至少90%序列一致性之胺基酸序列。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：與SEQ ID NO: 8、SEQ ID NO: 16、SEQ ID NO: 14或SEQ ID NO: 18具有至少90%序列一致性之胺基酸序列，及與SEQ ID NO: 7、SEQ ID NO: 15、SEQ ID NO: 13或SEQ ID NO: 17具有至少90%序列一致性之胺基酸序列。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：與SEQ ID NO: 8具有至少90%序列一致性之胺基酸序列，及與SEQ ID NO: 7具有至少90%序列一致性之胺基酸序列。
在一些實施例中，本發明之蛋白質包括包含以下之抗原結合位點：與SEQ ID NO: 16具有至少90%序列一致性之胺基酸序列，及與SEQ ID NO: 15具有至少90%序列一致性之胺基酸序列。
在一些實施例中，本發明之蛋白質包含在人類OX40L之細胞外域之位置60及/或83處結合的抗原結合位點。在一些實施例中，抗原結合位點在人類OX40L之細胞外域之位置17、18、19、20、21、23、26、28、60、83、110、111、112、113及114處結合。在一些實施例中，抗原結合位點在人類OX40L之細胞外域之位置58、59、60、61、62、63、81、82及83處結合。
在一些實施例中，本發明之蛋白質包含(i)包含CTLA4之細胞外域的多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之橋接部分：包含SEQ ID NO: 177之序列及包含SEQ ID NO: 179之序列；及(iii)包含以下之抗原結合位點：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)。
在一些實施例中，本發明之蛋白質包含第一臂及第二臂，該第一臂包含(i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之第一橋接部分：包含SEQ ID NO: 177之序列及包含SEQ ID NO: 179之序列；及(iii)包含以下之第一抗原結合位點：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)，且該第二臂包含：(i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之第二橋接部分：包含SEQ ID NO: 177之序列及包含SEQ ID NO: 179之序列；及(iii)包含以下之第二抗原結合位點：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)，其中該第一臂與該第二臂彼此二聚合。
在一些實施例中，本發明之蛋白質包含(i)包含CTLA4之細胞外域的多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及(iii)包含以下之抗原結合位點：包含胺基酸序列GVSIRSNGYY (SEQ ID NO: 93)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列MDYSGT (SEQ ID NO: 94)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARERSNNWYPIDY (SEQ ID NO: 95)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列SVRRFF (SEQ ID NO: 97)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列GKD (SEQ ID NO: 98)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列NSRDSSGYLVL (SEQ ID NO: 99)之輕鏈可變互補決定區3 (VLCDR3)。
在一些實施例中，本發明之蛋白質包含第一臂及第二臂，該第一臂包含(i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之第一橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及(iii)包含以下之第一抗原結合位點：包含胺基酸序列GVSIRSNGYY (SEQ ID NO: 93)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列MDYSGT (SEQ ID NO: 94)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARERSNNWYPIDY (SEQ ID NO: 95)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列SVRRFF (SEQ ID NO: 97)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列GKD (SEQ ID NO: 98)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列NSRDSSGYLVL (SEQ ID NO: 99)之輕鏈可變互補決定區3 (VLCDR3)，且該第二臂包含：(i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之第二橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及(iii)包含以下之第二抗原結合位點：包含胺基酸序列GVSIRSNGYY (SEQ ID NO: 93)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列MDYSGT (SEQ ID NO: 94)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARERSNNWYPIDY (SEQ ID NO: 95)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列SVRRFF (SEQ ID NO: 97)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列GKD (SEQ ID NO: 98)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列NSRDSSGYLVL (SEQ ID NO: 99)之輕鏈可變互補決定區3 (VLCDR3)，其中該第一臂與該第二臂彼此二聚合。
在一些實施例中，本發明之蛋白質包含(i)包含CTLA4之細胞外域的多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 214之序列；及(iii)包含以下之抗原結合位點：包含胺基酸序列GASVSSSSYY (SEQ ID NO: 85)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列INYGGST (SEQ ID NO: 86)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYHFDY (SEQ ID NO: 87)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)。
在一些實施例中，本發明之蛋白質包含第一臂及第二臂，該第一臂包含(i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之第一橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 214之序列；及(iii)包含以下之第一抗原結合位點：包含胺基酸序列GASVSSSSYY (SEQ ID NO: 85)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列INYGGST (SEQ ID NO: 86)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYHFDY (SEQ ID NO: 87)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)，且該第二臂包含：(i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之第二橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 214之序列；及(iii)包含以下之第二抗原結合位點：包含胺基酸序列GASVSSSSYY (SEQ ID NO: 85)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列INYGGST (SEQ ID NO: 86)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYHFDY (SEQ ID NO: 87)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)，其中該第一臂與該第二臂彼此二聚合。
在一些實施例中，本發明之蛋白質包含(i)包含CTLA4之細胞外域的多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及(iii)包含以下之抗原結合位點：包含胺基酸序列GGSISSSSYY (SEQ ID NO: 101)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IGSVDYSGNT (SEQ ID NO: 102)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYFFDY (SEQ ID NO: 103)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)。
在一些實施例中，本發明之蛋白質包含第一臂及第二臂，該第一臂包含(i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之第一橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及(iii)包含以下之第一抗原結合位點：包含胺基酸序列GGSISSSSYY (SEQ ID NO: 101)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IGSVDYSGNT (SEQ ID NO: 102)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYFFDY (SEQ ID NO: 103)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)，且該第二臂包含：(i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之第二橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及(iii)包含以下之第二抗原結合位點：包含胺基酸序列GGSISSSSYY (SEQ ID NO: 101)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IGSVDYSGNT (SEQ ID NO: 102)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYFFDY (SEQ ID NO: 103)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)，其中該第一臂與該第二臂彼此二聚合。
在一些實施例中，本發明之蛋白質包含(i)包含CTLA4之細胞外域的多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及(iii)包含以下之抗原結合位點：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)。
在一些實施例中，本發明之蛋白質包含第一臂及第二臂，該第一臂包含(i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之第一橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及(iii)包含以下之第一抗原結合位點：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)，且該第二臂包含：(i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含SEQ ID NO: 174；(ii)包含以下之第二橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及(iii)包含以下之第二抗原結合位點：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)，其中該第一臂與該第二臂彼此二聚合。
在一些實施例中，本發明之蛋白質包含(i)包含CTLA4之細胞外域的多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列；(ii)包含以下之橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及(iii)包含以下之抗原結合位點：包含胺基酸序列GFTFSNYA (SEQ ID NO: 133)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列ISGSGGAT (SEQ ID NO: 113)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列TKDRLIMATVRGPYYYGMDV (SEQ ID NO: 114)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列QSISSY (SEQ ID NO: 121)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列AAS (SEQ ID NO: 146)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QQSHSVSFT (SEQ ID NO: 154)之輕鏈可變互補決定區3 (VLCDR3)。
在一些實施例中，本發明之蛋白質包含第一臂及第二臂，該第一臂包含(i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列；(ii)包含以下之第一橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及(iii)包含以下之第一抗原結合位點：包含胺基酸序列GFTFSNYA (SEQ ID NO: 133)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列ISGSGGAT (SEQ ID NO: 113)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列TKDRLIMATVRGPYYYGMDV (SEQ ID NO: 114)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列QSISSY (SEQ ID NO: 121)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列AAS (SEQ ID NO: 146)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QQSHSVSFT (SEQ ID NO: 154)之輕鏈可變互補決定區3 (VLCDR3)，且該第二臂包含：(i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列；(ii)包含以下之第二橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及(iii)包含以下之第二抗原結合位點：包含胺基酸序列GFTFSNYA (SEQ ID NO: 133)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列ISGSGGAT (SEQ ID NO: 113)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列TKDRLIMATVRGPYYYGMDV (SEQ ID NO: 114)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列QSISSY (SEQ ID NO: 121)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列AAS (SEQ ID NO: 146)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QQSHSVSFT (SEQ ID NO: 154)之輕鏈可變互補決定區3 (VLCDR3)，其中該第一臂與該第二臂彼此二聚合。
在一些實施例中，本發明之蛋白質包含(i)包含CTLA4之細胞外域的多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列；(ii)包含以下之橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及(iii)包含以下之抗原結合位點：包含胺基酸序列SYAMS (SEQ ID NO: 105)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IISGSGGFTYYADSVK (SEQ ID NO: 106)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列DRLVAPGTFDY (SEQ ID NO: 107)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列RASQGISSWLA (SEQ ID NO: 169)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列AASSLQS (SEQ ID NO: 170)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QQYNSYPYT (SEQ ID NO: 171)之輕鏈可變互補決定區3 (VLCDR3)。
在一些實施例中，本發明之蛋白質包含第一臂及第二臂，該第一臂包含(i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列；(ii)包含以下之第一橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及(iii)包含以下之第一抗原結合位點：包含胺基酸序列SYAMS (SEQ ID NO: 105)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IISGSGGFTYYADSVK (SEQ ID NO: 106)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列DRLVAPGTFDY (SEQ ID NO: 107)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列RASQGISSWLA (SEQ ID NO: 169)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列AASSLQS (SEQ ID NO: 170)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QQYNSYPYT (SEQ ID NO: 171)之輕鏈可變互補決定區3 (VLCDR3)，且該第二臂包含：(i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列；(ii)包含以下之第二橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及(iii)包含以下之第二抗原結合位點：包含胺基酸序列SYAMS (SEQ ID NO: 105)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IISGSGGFTYYADSVK (SEQ ID NO: 106)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列DRLVAPGTFDY (SEQ ID NO: 107)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列RASQGISSWLA (SEQ ID NO: 169)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列AASSLQS (SEQ ID NO: 170)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QQYNSYPYT (SEQ ID NO: 171)之輕鏈可變互補決定區3 (VLCDR3)，其中該第一臂與該第二臂彼此二聚合。
在一些實施例中，本發明之蛋白質包含(i)包含CTLA4之細胞外域的多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列；(ii)包含以下之橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及(iii)根據IMGT獨特編號方案，包含以下之抗原結合位點：VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3，其各自包含分別對應於表3中所列之重鏈可變域及輕鏈可變域之VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3序列的胺基酸序列。
在一些實施例中，本發明之蛋白質包含第一臂及第二臂，該第一臂包含(i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列；(ii)包含以下之第一橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及(iii)根據IMGT獨特編號方案，包含以下之第一抗原結合位點：VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3，其各自包含分別對應於表3中所列之重鏈可變域及輕鏈可變域之VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3序列的胺基酸序列；且該第二臂包含：(i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列；(ii)包含以下之第二橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及(iii)根據IMGT獨特編號方案，包含以下之第二抗原結合位點：VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3，其各自包含分別對應於表3中所列之重鏈可變域及輕鏈可變域之VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3序列的胺基酸序列，其中該第一臂與該第二臂彼此二聚合。
在一些實施例中，本發明之蛋白質包含(i)包含CTLA4之細胞外域的多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列；(ii)包含以下之橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及(iii)包含特異性結合於OX40L之多肽的抗原結合位點。
在一些實施例中，本發明之蛋白質包含第一臂及第二臂，該第一臂包含(i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列；(ii)包含以下之第一橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及(iii)包含特異性結合於OX40L之多肽的第一抗原結合位點；且該第二臂包含：(i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列；(ii)包含以下之第二橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及(iii)包含特異性結合於OX40L之多肽的第二抗原結合位點，其中該第一臂與該第二臂彼此二聚合。
在一些實施例中，本發明之蛋白質包含與以下胺基酸序列具有至少90%一致性之胺基酸序列：SEQ ID NO: 40、SEQ ID NO: 62、SEQ ID NO: 64、SEQ ID NO: 182、SEQ ID NO: 183、SEQ ID NO: 184、SEQ ID NO: 185、SEQ ID NO: 186、SEQ ID NO: 48、SEQ ID NO: 68、SEQ ID NO: 187、SEQ ID NO: 188、SEQ ID NO: 189、SEQ ID NO: 190、SEQ ID NO: 191、SEQ ID NO: 46、SEQ ID NO: 66、SEQ ID NO: 192、SEQ ID NO: 193、SEQ ID NO: 194、SEQ ID NO: 195、SEQ ID NO: 196、SEQ ID NO: 50、SEQ ID NO: 70、SEQ ID NO: 197、SEQ ID NO: 198、SEQ ID NO: 199、SEQ ID NO: 200、SEQ ID NO: 201、SEQ ID NO: 38、SEQ ID NO: 73、SEQ ID NO: 42、SEQ ID NO: 44、SEQ ID NO: 52、SEQ ID NO: 54、SEQ ID NO: 56、SEQ ID NO: 58、SEQ ID NO: 60、SEQ ID NO: 37、SEQ ID NO: 256、SEQ ID NO: 257、SEQ ID NO: 258、SEQ ID NO: 259、SEQ ID NO: 260、SEQ ID NO: 261、SEQ ID NO: 262、SEQ ID NO: 263、SEQ ID NO: 264、SEQ ID NO: 265、SEQ ID NO: 266、SEQ ID NO: 267、SEQ ID NO: 268、SEQ ID NO: 269、SEQ ID NO: 270、SEQ ID NO: 271、SEQ ID NO: 272、SEQ ID NO: 273、SEQ ID NO: 274、SEQ ID NO: 275、SEQ ID NO: 276、SEQ ID NO: 277、SEQ ID NO: 278、SEQ ID NO: 279、SEQ ID NO: 280、SEQ ID NO: 281、SEQ ID NO: 282、SEQ ID NO: 283、SEQ ID NO: 284、SEQ ID NO: 285、SEQ ID NO: 286、SEQ ID NO: 287、SEQ ID NO: 288、SEQ ID NO: 289、SEQ ID NO: 290、SEQ ID NO: 291、SEQ ID NO: 292、SEQ ID NO: 293、SEQ ID NO: 294、SEQ ID NO: 295、SEQ ID NO: 296、SEQ ID NO: 297、SEQ ID NO: 298、SEQ ID NO: 299、SEQ ID NO: 300、SEQ ID NO: 301、SEQ ID NO: 302、SEQ ID NO: 303、SEQ ID NO: 304、SEQ ID NO: 305、SEQ ID NO: 306、SEQ ID NO: 307、SEQ ID NO: 308、SEQ ID NO: 309、SEQ ID NO: 310、SEQ ID NO: 311、SEQ ID NO: 312、SEQ ID NO: 313、SEQ ID NO: 314、SEQ ID NO: 315、SEQ ID NO: 316、SEQ ID NO: 317、SEQ ID NO: 318、SEQ ID NO: 319、SEQ ID NO: 320、SEQ ID NO: 321、SEQ ID NO: 322、SEQ ID NO: 323、SEQ ID NO: 324、SEQ ID NO: 325、SEQ ID NO: 326、SEQ ID NO: 327、SEQ ID NO: 328、SEQ ID NO: 329、SEQ ID NO: 330、SEQ ID NO: 331、SEQ ID NO: 332、SEQ ID NO: 333、SEQ ID NO: 334或SEQ ID NO: 335。
在一些實施例中，本發明之蛋白質包括包含與以下胺基酸序列具有至少90%一致性之胺基酸序列的多肽：SEQ ID NO: 40及SEQ ID NO: 39；SEQ ID NO: 62及SEQ ID NO: 61；SEQ ID NO: 64及SEQ ID NO: 63；SEQ ID NO: 182及SEQ ID NO: 63；SEQ ID NO: 183及SEQ ID NO: 63；SEQ ID NO: 184及SEQ ID NO: 63；SEQ ID NO: 185及SEQ ID NO: 63；SEQ ID NO: 186及SEQ ID NO: 63；SEQ ID NO: 48及SEQ ID NO: 47；SEQ ID NO: 68及SEQ ID NO: 67；SEQ ID NO: 187及SEQ ID NO: 67；SEQ ID NO: 188及SEQ ID NO: 67；SEQ ID NO: 189及SEQ ID NO: 67；SEQ ID NO: 190及SEQ ID NO: 67；SEQ ID NO: 191及SEQ ID NO: 67；SEQ ID NO: 46及SEQ ID NO: 45；SEQ ID NO: 66及SEQ ID NO: 65；SEQ ID NO: 192及SEQ ID NO: 65；SEQ ID NO: 193及SEQ ID NO: 65；SEQ ID NO: 194及SEQ ID NO: 65；SEQ ID NO: 195及SEQ ID NO: 65；SEQ ID NO: 196及SEQ ID NO: 65；SEQ ID NO: 50及SEQ ID NO: 49；SEQ ID NO: 70及SEQ ID NO: 69；SEQ ID NO: 197及SEQ ID NO: 69；SEQ ID NO: 198及SEQ ID NO: 69；SEQ ID NO: 199及SEQ ID NO: 69；SEQ ID NO: 200及SEQ ID NO: 69；SEQ ID NO: 201及SEQ ID NO: 69；SEQ ID NO: 38及SEQ ID NO: 5；SEQ ID NO: 73及SEQ ID NO: 5；SEQ ID NO: 42及SEQ ID NO: 41；SEQ ID NO: 44及SEQ ID NO: 43；SEQ ID NO: 52及SEQ ID NO: 51；SEQ ID NO: 54及SEQ ID NO: 53；SEQ ID NO: 56及SEQ ID NO: 55；SEQ ID NO: 58及SEQ ID NO: 57；SEQ ID NO: 60及SEQ ID NO: 59；SEQ ID NO: 37及SEQ ID NO: 35；SEQ ID NO: 256及SEQ ID NO: 63；SEQ ID NO: 257及SEQ ID NO: 63；SEQ ID NO: 258及SEQ ID NO: 63；SEQ ID NO: 259及SEQ ID NO: 63；SEQ ID NO: 260及SEQ ID NO: 63；SEQ ID NO: 261及SEQ ID NO: 63；SEQ ID NO: 262及SEQ ID NO: 63；SEQ ID NO: 263及SEQ ID NO: 63；SEQ ID NO: 264及SEQ ID NO: 63；SEQ ID NO: 265及SEQ ID NO: 63；SEQ ID NO: 266及SEQ ID NO: 63；SEQ ID NO: 267及SEQ ID NO: 63；SEQ ID NO: 268及SEQ ID NO: 63；SEQ ID NO: 269及SEQ ID NO: 63；SEQ ID NO: 270及SEQ ID NO: 63；SEQ ID NO: 271及SEQ ID NO: 63；SEQ ID NO: 272及SEQ ID NO: 63；SEQ ID NO: 273及SEQ ID NO: 63；SEQ ID NO: 274及SEQ ID NO: 63；SEQ ID NO: 275及SEQ ID NO: 63；SEQ ID NO: 276及SEQ ID NO: 63；SEQ ID NO: 277及SEQ ID NO: 63；SEQ ID NO: 278及SEQ ID NO: 63；SEQ ID NO: 279及SEQ ID NO: 63；SEQ ID NO: 280及SEQ ID NO: 63；SEQ ID NO: 281及SEQ ID NO: 63；SEQ ID NO: 282及SEQ ID NO: 63；SEQ ID NO: 283及SEQ ID NO: 63；SEQ ID NO: 284及SEQ ID NO: 63；SEQ ID NO: 285及SEQ ID NO: 63；SEQ ID NO: 286及SEQ ID NO: 63；SEQ ID NO: 287及SEQ ID NO: 63；SEQ ID NO: 288及SEQ ID NO: 63；SEQ ID NO: 289及SEQ ID NO: 63；SEQ ID NO: 290及SEQ ID NO: 63；SEQ ID NO: 291及SEQ ID NO: 63；SEQ ID NO: 292及SEQ ID NO: 63；SEQ ID NO: 293及SEQ ID NO: 63；SEQ ID NO: 294及SEQ ID NO: 67；SEQ ID NO: 295及SEQ ID NO: 67；SEQ ID NO: 296及SEQ ID NO: 67；SEQ ID NO: 297及SEQ ID NO: 67；SEQ ID NO: 298及SEQ ID NO: 67；SEQ ID NO: 299及SEQ ID NO: 67；SEQ ID NO: 300及SEQ ID NO: 67；SEQ ID NO: 301及SEQ ID NO: 67；SEQ ID NO: 302及SEQ ID NO: 67；SEQ ID NO: 303及SEQ ID NO: 67；SEQ ID NO: 304及SEQ ID NO: 67；SEQ ID NO: 305及SEQ ID NO: 67；SEQ ID NO: 306及SEQ ID NO: 67；SEQ ID NO: 307及SEQ ID NO: 67；SEQ ID NO: 308及SEQ ID NO: 67；SEQ ID NO: 309及SEQ ID NO: 67；SEQ ID NO: 310及SEQ ID NO: 67；SEQ ID NO: 311及SEQ ID NO: 67；SEQ ID NO: 312及SEQ ID NO: 67；SEQ ID NO: 313及SEQ ID NO: 67；SEQ ID NO: 314及SEQ ID NO: 67；SEQ ID NO: 315及SEQ ID NO: 67；SEQ ID NO: 316及SEQ ID NO: 67；SEQ ID NO: 317及SEQ ID NO: 67；SEQ ID NO: 318及SEQ ID NO: 67；SEQ ID NO: 319及SEQ ID NO: 67；SEQ ID NO: 320及SEQ ID NO: 67；SEQ ID NO: 321及SEQ ID NO: 67；SEQ ID NO: 322及SEQ ID NO: 67；SEQ ID NO: 323及SEQ ID NO: 67；SEQ ID NO: 324及SEQ ID NO: 67；SEQ ID NO: 325及SEQ ID NO: 67；SEQ ID NO: 326及SEQ ID NO: 67；SEQ ID NO: 327及SEQ ID NO: 67；SEQ ID NO: 328及SEQ ID NO: 67；SEQ ID NO: 329及SEQ ID NO: 67；SEQ ID NO: 330及SEQ ID NO: 67；SEQ ID NO: 331及SEQ ID NO: 67；SEQ ID NO: 332及SEQ ID NO: 253；SEQ ID NO: 333及SEQ ID NO: 255；SEQ ID NO: 334及SEQ ID NO: 253；或SEQ ID NO: 335及SEQ ID NO: 255。
在一些實施例中，本發明之蛋白質包括包含胺基酸序列SEQ ID NO: 63之兩種多肽及包含胺基酸序列SEQ ID NO: 64之兩種多肽；或包含胺基酸序列SEQ ID NO: 68之兩種多肽及包含胺基酸序列SEQ ID NO: 67之兩種多肽。
在一些實施例中，依OX40L中和/OX40-HEK報導子分析中所量測，本發明之蛋白質之IC
50小於12 nM，例如5 nM至12 nM或5 nM至9 nM。
在一些實施例中，依初級T細胞活化分析中所量測，本發明之蛋白質之IC
50為2 nM至12 nM，例如2 nM至9.5 nM。
在一些實施例中，依Biacore分析中所量測，本發明之蛋白質針對OX40L結合之K
D 小於75 nM，例如20 nM至75 nM。
在一些實施例中，相較於在相同條件下但不存在蛋白質下，或在存在於人類IgG1 Fc域之N端處融合的人類CTLA4細胞外域(CTLA4-Ig)及抗OX40L抗體(獨立存在或以分開存在的兩種蛋白質之組合形式存在)下處理的細胞，本發明之蛋白質在活體外混合淋巴球反應分析中顯著抑制細胞產生IL-2、IFNγ、IL-6及TNFα中之至少一者。
在一些實施例中，相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig及/或抗OX40L抗體下處理的同種異體反應性CD4
+及CD8
+T細胞，本發明之蛋白質在活體外混合淋巴球反應分析中顯著抑制同種異體反應性CD4
+及CD8
+T細胞增殖。
在一些實施例中，相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig及/或抗OX40L抗體下處理的同種異體反應性CD4
+及CD8
+T細胞，本發明之蛋白質在活體外混合淋巴球反應分析中相比於調節T細胞(T
reg)增殖優先抑制同種異體反應性CD4
+及CD8
+T細胞增殖。
在一些實施例中，相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig及/或抗OX40L抗體下處理的T
reg細胞，本發明之蛋白質在活體外混合淋巴球反應分析中顯著增強T
reg抑制功能。
在一些實施例中，相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig及/或抗OX40L抗體下處理的小鼠中之同種異體反應性CD4
+及CD8
+T細胞，本發明之蛋白質在授受性轉移分析中顯著抑制人類化小鼠中之同種異體反應性CD4
+及CD8
+T細胞增殖。
在一些實施例中，相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig及/或抗OX40L抗體下處理之小鼠，本發明之蛋白質在授受性轉移分析中顯著抑制人類化小鼠中之血清IFNγ水準。
在一些實施例中，本發明之蛋白質未顯著內化於源於骨髓之樹突狀細胞(MDDC)中。
在一些實施例中，本發明之蛋白質與食蟹獼猴OX40L具有交叉反應性及/或與小鼠、兔或大鼠OX40L不具有交叉反應性。在一些實施例中，本發明之蛋白質與食蟹獼猴CD80及CD86具有交叉反應性。
在另一態樣中，本發明提供如本文所揭示之重鏈多肽的用途，其用於製備如本文所揭示之包含重鏈多肽及輕鏈多肽的蛋白質。
在另一態樣中，本發明提供一種調配物，其包含如本文所揭示之蛋白質及醫藥學上可接受之載劑。
在另一態樣中，本發明提供一種編碼如本文所揭示之蛋白質的核酸。
在另一態樣中，本發明提供一種細胞，其包含一或多種編碼如本文所揭示之蛋白質的核酸。
在另一態樣中，本發明提供一種治療患者之自體免疫疾病之方法，其包含向該患者投與如本文所揭示之蛋白質或調配物。舉例而言，可藉由本發明之蛋白質治療之自體免疫疾病包括類風濕性關節炎、幼年特發性關節炎、牛皮癬性關節炎、異位性皮膚炎、弛緩不能、阿狄森氏病(Addison's disease)、成人斯蒂爾氏病(Adult Still's disease)、無γ球蛋白血症、斑禿、澱粉樣變性病、僵直性脊椎炎、抗GBM/抗TBM腎炎、抗磷脂症候群、自體免疫血管性水腫、自體免疫自主神經障礙、自體免疫腦脊髓炎、自體免疫肝炎、自體免疫內耳疾病(AIED)、自體免疫心肌炎、自體免疫卵巢炎、自體免疫睪丸炎、自體免疫胰臟炎、自體免疫視網膜病變、自體免疫蕁麻疹、軸突與神經元神經病變(AMAN)、貝羅氏病(Baló disease)、白塞氏病(Behcet's disease)、良性黏膜類天疱瘡、大皰性類天疱瘡、卡斯特曼氏病(Castleman disease；CD)、乳糜瀉、卻格司氏病(Chagas disease)、慢性發炎性脫髓鞘型多發性神經病變(CIDP)、慢性復發性多灶性骨髓炎(CRMO)、徹奇-斯全司症候群(Churg-Strauss Syndrome；CSS)或嗜酸性肉芽腫(EGPA)、瘢痕性類天疱瘡、科根氏症候群(Cogan's syndrome)、冷凝集素病、先天性心臟阻滯、柯薩奇心肌炎(Coxsackie myocarditis)、CREST症候群、克羅恩氏病(Crohn's disease)、皮膚狼瘡、疱疹樣皮炎、皮肌炎、德維奇氏病(Devic's disease) (視神經脊髓炎)、盤狀狼瘡、戴斯勒氏症候群(Dressler's syndrome)、子宮內膜異位、嗜酸性食道炎(EoE)、嗜酸性筋膜炎、結節性紅斑、原發性混合型冷凝球蛋白血症、伊凡氏症候群(Evans syndrome)、肌肉纖維疼痛、纖維化肺泡炎、巨大細胞動脈炎(顳動脈炎)、巨大細胞心肌炎、絲球體腎炎、古巴士德氏症候群(Goodpasture's syndrome)、伴有多血管炎之肉芽腫、格雷夫氏病(Graves' disease)、格-巴二氏症候群(Guillain-Barre syndrome)、橋本氏甲狀腺炎(Hashimoto's thyroiditis)、溶血性貧血、亨偌-絲奇恩賴紫癜(Henoch-Schonlein purpura；HSP)、妊娠性疱疹或妊娠性類天疱瘡(PG)、化膿性汗腺炎(HS) (反常性痤瘡)、低γ球蛋白血症、IgA腎病、IgG4相關之硬化性疾病、免疫性血小板減少性紫癜(ITP)、包涵體肌炎(IBM)、間質性膀胱炎(IC)、青少年關節炎、青少年糖尿病(第1型糖尿病)、青少年肌炎(JM)、川崎病(Kawasaki disease)、蘭伯特-伊頓症候群(Lambert-Eaton syndrome)、白血球破裂性脈管炎、扁平苔癬、硬化性苔癬、木質性結膜炎、線性IgA疾病(LAD)、狼瘡、慢性萊姆病(Lyme disease)、梅尼爾氏病(Meniere's disease)、顯微多血管炎(MPA)、混合型結締組織疾病(MCTD)、穆倫氏潰瘍(Mooren's ulcer)、穆哈-哈伯曼疾病(Mucha-Habermann disease)、多灶性運動神經病(MMN)或MMNCB、多發性硬化、重症肌無力、肌炎、發作性睡病、新生兒狼瘡、視神經脊髓炎、嗜中性白血球減少症、眼部瘢痕性類天疱瘡、視神經炎、陣發性風濕症(PR)、PANDAS、腫瘤伴生性小腦變性(PCD)、陣發性夜間血紅素尿症(PNH)、帕瑞隆伯格症候群(Parry Romberg syndrome)、睫狀體扁平部炎(周邊葡萄膜炎)、帕森吉-特納症候群(Parsonage-Turner syndrome)、天疱瘡、周邊神經病變、靜脈周邊腦脊髓炎、惡性貧血(PA)、POEMS症候群、結節性多動脈炎、第I、II、III型多腺症候群、風濕性多肌痛、多發性肌炎、心肌後梗塞症候群、心包切開術後症候群、原發性膽汁性肝硬化、原發性硬化性膽管炎、孕酮皮膚炎、牛皮癬、牛皮癬性關節炎、純紅血球發育不全(PRCA)、壞疽性膿皮病、雷諾氏現象(Raynaud's phenomenon)、反應性關節炎、反射性交感神經失養症、復發性多軟骨炎、不寧腿症候群(RLS)、腹膜後纖維化、風濕熱、類風濕性關節炎、類肉瘤病、斯密特症候群(Schmidt syndrome)、鞏膜炎、硬皮病、休格倫氏症候群、精子及睪丸自體免疫、僵硬人症候群(SPS)、亞急性細菌性心內膜炎(SBE)、蘇薩克氏症候群(Susac's syndrome)、交感眼炎(SO)、高安氏動脈炎(Takayasu's arteritis)、顳動脈炎/巨大細胞動脈炎、血小板減少性紫癲(TTP)、甲狀腺眼病(TED)、托洛薩-亨特症候群(Tolosa-Hunt syndrome；THS)、橫貫性脊髓炎、第1型糖尿病、潰瘍性結腸炎(UC)、未分化結締組織疾病(UCTD)、葡萄膜炎、血管炎、白斑病及沃格特-小柳-原田病(Vogt-Koyanagi-Harada Disease)。在另一態樣中，本發明提供一種治療患者之移植物抗宿主疾病(GVHD)之方法，其包含向患者投與如本文所揭示之蛋白質或調配物。
在另一態樣中，本發明提供一種抗體或其功能片段，根據IMGT獨特編號方案，其包含包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)。
在一些實施例中，本發明之抗體包括包含與SEQ ID NO: 76具有至少90%一致性之胺基酸序列的重鏈可變域及包含與SEQ ID NO: 80具有至少90%一致性之胺基酸序列的輕鏈可變域。
在一些實施例中，根據IMGT獨特編號方案，本發明之抗體或其功能片段包含：包含胺基酸序列GVSIRSNGYY (SEQ ID NO: 93)之VHCDR1、包含胺基酸序列MDYSGT (SEQ ID NO: 94)之VHCDR2、包含胺基酸序列ARERSNNWYPIDY (SEQ ID NO: 95)之VHCDR3、包含胺基酸序列SVRRFF (SEQ ID NO: 97)之VLCDR1、包含胺基酸序列GKD (SEQ ID NO: 98)之VLCDR2及包含胺基酸序列NSRDSSGYLVL (SEQ ID NO: 99)之VLCDR3。
在一些實施例中，本發明之抗體包括包含與SEQ ID NO: 92具有至少90%一致性之胺基酸序列的重鏈可變域及包含與SEQ ID NO: 96具有至少90%一致性之胺基酸序列的輕鏈可變域。
在一些實施例中，根據IMGT獨特編號方案，本發明之抗體或其功能片段包含：包含胺基酸序列GASVSSSSYY (SEQ ID NO: 85)之VHCDR1、包含胺基酸序列INYGGST (SEQ ID NO: 86)之VHCDR2、包含胺基酸序列ARHRGIYHFDY (SEQ ID NO: 87)之VHCDR3、包含胺基酸序列NIENKN (SEQ ID NO: 89)之VLCDR1、包含胺基酸序列RDS (SEQ ID NO: 90)之VLCDR2及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之VLCDR3。
在一些實施例中，本發明之抗體包括包含與SEQ ID NO: 84具有至少90%一致性之胺基酸序列的重鏈可變域及包含與SEQ ID NO: 88具有至少90%一致性之胺基酸序列的輕鏈可變域(VL)。
在一些實施例中，根據IMGT獨特編號方案，本發明之抗體或其功能片段包含：包含胺基酸序列GGSISSSSYY (SEQ ID NO: 101)之VHCDR1、包含胺基酸序列IGSVDYSGNT (SEQ ID NO: 102)之VHCDR2、包含胺基酸序列ARHRGIYFFDY (SEQ ID NO: 103)之VHCDR3、包含胺基酸序列NIENKN (SEQ ID NO: 89)之VLCDR1、包含胺基酸序列RDS (SEQ ID NO: 90)之VLCDR2及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之VLCDR3。
在一些實施例中，本發明之抗體包括包含與SEQ ID NO: 100具有至少90%一致性之胺基酸序列的重鏈可變域(VH)及包含與SEQ ID NO: 104具有至少90%一致性之胺基酸序列的輕鏈可變域(VL)。
在一些實施例中，本發明之抗體或其功能片段為人類IgG1抗體。
在另一態樣中，本發明提供如本文中所揭示之抗體或其功能片段在製備如本文中所揭示之蛋白質中之用途。
本發明之其他實施例及細節呈現於下文。
相關申請案之交叉引用
本申請案主張2021年6月8日申請的美國臨時專利申請案第63/208,478號；及2022年5月18日申請的美國臨時專利申請案第63/343,268號之權益及優先權，其中之每一者之全部揭示內容係出於所有目的以引用之方式併入本文中。
序列表
本申請案含有序列表，該序列表已以ASCII格式以電子方式提交且以全文引用之方式併入本文中。2022年5月25日創建的該ASCII複本命名為EMD-015WO_SL.txt且位元組大小為872,058。
本申請案提供抑制T細胞協同刺激信號傳導之蛋白質，其包含：特異性結合CD80及/或CD86之多肽及特異性結合OX40L之多肽。在一些實施例中，本申請案提供特異性結合OX40L之抗體。在一些實施例中，本申請案亦提供在治療自體免疫疾病中使用此類蛋白質之治療方法。本申請案中所述之蛋白質之各種態樣如下闡述於各章節中；然而，一個特定章節中所述之蛋白質之態樣不限於任何特定章節。
定義
為促進對本申請案之理解，下文定義多個術語及片語。
除非上下文不適當，否則如本文所用，術語「一(a及an)」意謂「一或多個(種)」且包括複數個(種)。
如本文所用，術語「抗原結合位點」係指參與抗原結合之免疫球蛋白(Ig)分子的一部分。在人類抗體中，抗原結合位點係藉由重(「H」)鏈及輕(「L」)鏈之N端可變(「V」)域之胺基酸殘基形成。重鏈及輕鏈之V區內的三個高度分叉區段稱為「高變區」，其插入於稱為「構架區」或「FR」之更保守側接區段之間。因此，術語「FR」係指天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。在人類抗體分子中，輕鏈之三個高變區及重鏈之三個高變區相對於彼此安置於三維空間中以形成抗原結合表面。抗原結合表面與抗原結合位點特異性所結合之抗原之三維表面互補，且重鏈及輕鏈中之每一者的三個高變區稱為「互補決定區」或「CDR」。在某些動物(諸如駱駝及軟骨魚)中，抗原結合位點係由提供「單域抗體」之單一抗體鏈形成。抗原結合位點可存在於完整抗體中、保留抗原結合表面之抗體之抗原結合片段(例如，Fab、Fab'、F(ab')
2)中或重組多肽(諸如scFv)中，以使用肽連接子將單一多肽、微型抗體或奈米抗體(VHH)中之重鏈可變域連接於輕鏈可變域。
如本文所用，術語「其功能性片段」涉及蛋白質或多肽的維持執行完整蛋白或多肽之生物功能之能力的一部分。舉例而言，本申請案之多肽或蛋白質之功能片段維持其結合其同源結合搭配物或配位體之能力。
如本文所用，術語「個體」及「患者」係指藉由本文所述之方法及組合物治療的生物體。此類生物體較佳包括(但不限於)哺乳動物(例如鼠類、猿猴、馬、牛、豬、犬、貓及其類似者)，且最佳包括人類。
如本文所用，術語「有效量」係指足以實現有益或所需結果之化合物(例如本申請案之蛋白質)的量。有效量可以一或多次投藥、施藥或給藥來投與且不欲限於特定調配物或投藥途徑。如本文所用，術語「治療」包括引起病況、疾病、病症及其類似者改善或緩解其症狀的任何作用，例如減輕、減少、調節、緩解或消除。
如本文所用，CTLA4 (亦稱為CD152)係指SEQ ID NO: 172之蛋白質及相關同功異型物及直系同源物。
如本文所用，OX40L (亦稱為TNFSF4或CD252)係指SEQ ID NO: 2之蛋白質及相關同功異型物及直系同源物。
如本文所用，OX40 (亦稱為TNFRSF4或CD134)係指SEQ ID NO: 1之蛋白質及相關同功異型物及直系同源物。
OX40 人類胺基酸序列： 
如本文所用，CD28 (又稱為TP44)係指SEQ ID NO: 230之蛋白質及相關同功異型物及直系同源物。
CD28 胺基酸序列(加下劃線之胺基酸表示信號肽)：
如本文所用，CD80 (亦稱為B7.1)係指SEQ ID NO: 3之蛋白質及相關同功異型物及直系同源物。
CD80 人類胺基酸序列 
如本文所用，CD86 (亦稱為B7.2)係指SEQ ID NO: 4之蛋白質及相關同功異型物及直系同源物。
CD86 人類胺基酸序列 
在通篇說明書中，在蛋白質描述為具有、包括或包含特定組分的情況下，或在製程及方法描述為具有、包括或包含特定步驟的情況下，另外經審慎考慮，本申請案中所述之蛋白質基本上由所述組分組成或由所述組分組成，且根據本申請案之製程及方法基本上由所述加工步驟組成或由所述加工步驟組成。
I. 蛋白質
本申請案提供特異性結合於表現於抗原呈遞細胞(APC)上之CD80及CD86以及OX40L的蛋白質。蛋白質與CD80/CD86及OX40L之結合分別藉由阻斷CD28及OX40下游之協同刺激信號傳導來抑制T細胞活化。本發明之蛋白質包括兩個臂，各臂包括兩種組分(例如多肽或兩種或更多種多肽之複合物)，即一種特異性結合於CD80及/或CD86之組分及另一種特異性結合於OX40L之組分。在一些實施例中，結合於CD80及/或CD86或OX40L之組分可包含單一多肽。在一些實施例中，結合於CD80及/或CD86或OX40L之組分可包含兩種或更多種多肽之複合物。在一些實施例中，多肽複合物之兩種或更多種多肽之複合可藉由一個或多於一個共價鍵(例如二硫鍵)及/或一種或多於一種非共價相互作用(例如離子或疏水相互作用)連接。下文提供例示性蛋白質之進一步描述。
本發明之蛋白質包括第一組分，其為特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物，其可包括(但不限於) CTLA4之細胞外域或其功能片段。在一些實施例中，第一組分可為(但不限於) CD28之細胞外域或其功能片段。在一些實施例中，第一組分可為(但不限於)一或多個抗原結合位點，例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)。
本發明之蛋白質包括第二組分，其為特異性結合OX40L之多肽或兩種或更多種多肽之複合物。在一些實施例中，第二組分可包括(但不限於)抗原結合位點，例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)。在一些實施例中，第二組分可為(但不限於) OX40之細胞外域或其功能片段。
在一些實施例中，本發明之蛋白質另外包含橋接部分，其可包括(但不限於)：免疫球蛋白Fc域之多肽或其功能片段、人類血清白蛋白(HSA)多肽或其功能片段或多肽連接子。在一些實施例中，橋接部分為免疫球蛋白Fc域之多肽。在一些實施例中，本發明之蛋白質進一步包含緊靠免疫球蛋白Fc域之多肽或其功能片段之N端的多肽鉸鏈。
在一些實施例中，本發明之蛋白質進一步包含連接子多肽，其將特異性結合OX40L之多肽或兩種或更多種多肽之複合物連接於橋接部分。在一些實施例中，本發明之蛋白質進一步包含連接子多肽，其將特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物連接於橋接部分。
本文所述之蛋白質可呈多種形式。例如，一種蛋白質形式包含：(i)第一臂，其自N端至C端包含：特異性結合CD80及/或CD86之第一多肽或兩種或更多種多肽之複合物、免疫球蛋白Fc域之第一多肽及特異性結合OX40L之第一多肽或兩種或更多種多肽之複合物；及(ii)第二臂，其自N端至C端包含：特異性結合CD80及/或CD86之第二多肽或兩種或更多種多肽之複合物、免疫球蛋白Fc域之第二多肽及特異性結合OX40L之第二多肽或兩種或更多種多肽之複合物，其中該免疫球蛋白Fc域之第一及第二多肽二聚合。在此形式中，特異性結合CD80及/或CD86之第一及第二多肽或兩種或更多種多肽之複合物包括：CD28之細胞外域或其功能片段(
圖 1A及
圖 1J)；CTLA4之細胞外域或其功能片段(
圖 1C、
圖 1K及
圖 1W)；或其中特異性結合CD80及/或CD86之第一多肽或兩種或更多種多肽之複合物為特異性結合CD80之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH))，且特異性結合CD80及/或CD86之第二多肽或兩種或更多種多肽之複合物為特異性結合CD86之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1N)。
在此形式中，特異性結合OX40L之第一及第二多肽或兩種或更多種多肽之複合物包括：OX40之細胞外域或其功能片段(
圖 1A及
圖 1C)；或抗原結合位點(例如，抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1J、
圖 1K及
圖 1N)。在一些實施例中，特異性結合OX40L之兩種或更多種多肽之第一及第二複合物包含Fab，其中部分鉸鏈(例如具有序列SEQ ID NO: 336之多肽)連接於Fab重鏈(HC) CH1域之C端且與Fab輕鏈(LC)形成二硫鍵。
此形式之蛋白質可視情況在第一臂及第二臂中之每一者中包含多肽鉸鏈，其將特異性結合CD80及/或CD86之第一或第二多肽或兩種或更多種多肽之複合物之C端分別連接於免疫球蛋白Fc域之第一或第二多肽之N端。此形式之蛋白質亦可視情況在第一臂及/或第二臂中之一者或兩者中包含連接子多肽，其將免疫球蛋白Fc域之第一及/或第二多肽之C端分別連接於特異性結合OX40L之第一及/或第二多肽或兩個或更多個多肽之複合物之N端。
另一蛋白質形式包含：(i)第一臂，其自N端至C端包含：特異性結合OX40L之第一多肽或兩種或更多種多肽之複合物、免疫球蛋白Fc域之第一多肽及特異性結合CD80及/或CD86之第一多肽或兩種或更多種多肽之複合物；及(ii)第二臂，其自N端至C端包含：特異性結合OX40L之第二多肽或兩種或更多種多肽之複合物、免疫球蛋白Fc域之第二多肽及特異性結合CD80及/或CD86之第二多肽或兩種或更多種多肽之複合物，其中該免疫球蛋白Fc域之第一及第二多肽二聚合。在此形式中，特異性結合OX40L之第一及第二多肽或兩種或更多種多肽之複合物包括：OX40之細胞外域或其功能片段(
圖 1B、
圖 1D及
圖 1L) ；或抗原結合位點(例如，抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1M、
圖 1U及
圖 1V)。在一些實施例中，特異性結合OX40L之兩種或更多種多肽之第一及第二複合物包含Fab，其中部分鉸鏈(例如具有序列SEQ ID NO: 336之多肽)連接於Fab重鏈(HC) CH1域之C端且與Fab輕鏈(LC)形成二硫鍵。在此形式中，特異性結合CD80及/或CD86之第一及第二多肽或兩種或更多種多肽之複合物包括：CD28之細胞外域或其功能片段(
圖 1B及
圖 1U) ；CTLA4之細胞外域或其功能片段(
圖 1D及
圖 1V)；或其中特異性結合CD80及/或CD86之第一多肽或兩種或更多種多肽之複合物為特異性結合CD80之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH))，且特異性結合CD80及/或CD86之第二多肽或兩種或更多種多肽之複合物為特異性結合CD86之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1L及
圖 1M)。此形式之蛋白質可視情況在第一臂及第二臂中之每一者中包含多肽鉸鏈，其將特異性結合OX40L之第一或第二多肽或兩種或更多種多肽之複合物之C端分別連接於免疫球蛋白Fc域之第一或第二多肽之N端。此形式之蛋白質亦可視情況在第一臂及/或第二臂中之一者或兩者中包含連接子多肽，其將免疫球蛋白Fc域之第一及/或第二多肽之C端分別連接於特異性結合CD80及/或CD86之第一及/或第二多肽或兩種或更多種多肽之複合物之N端。
在另一實例中，蛋白質形式包含：(i)第一臂，其自N端至C端包含：特異性結合CD80及/或CD86之第一多肽或兩種或更多種多肽之複合物、特異性結合OX40L之第一多肽或兩種或更多種多肽之複合物及免疫球蛋白Fc域之第一多肽；及(ii)第二臂，其自N端至C端包含：特異性結合CD80及/或CD86之第二多肽或兩種或更多種多肽之複合物、特異性結合OX40L之第二多肽或兩種或更多種多肽之複合物及免疫球蛋白Fc域之第二多肽，其中該免疫球蛋白Fc域之第一及第二多肽二聚合。在此形式中，特異性結合CD80及/或CD86之第一及第二多肽或兩種或更多種多肽之複合物包括：CD28之細胞外域或其功能片段(
圖 1E)；CTLA4之細胞外域或其功能片段(
圖 1F)；或其中特異性結合CD80及/或CD86之第一多肽或兩種或更多種多肽之複合物為特異性結合CD80之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH))，且特異性結合CD80及/或CD86之第二多肽或兩種或更多種多肽之複合物為特異性結合CD86之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1O)。在此形式中，特異性結合OX40L之第一及第二多肽或兩種或更多種多肽之複合物包括：OX40之細胞外域或其功能片段(
圖 1E及
圖 1F)；或抗原結合位點(例如，抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1O)。在一些實施例中，特異性結合OX40L之兩種或更多種多肽之第一及第二複合物包含Fab，其中部分鉸鏈(例如具有序列SEQ ID NO: 336之多肽)連接於Fab重鏈(HC) CH1域之C端且與Fab輕鏈(LC)形成二硫鍵。此形式之蛋白質可視情況在第一臂及第二臂中之每一者中包含多肽鉸鏈，其將特異性結合OX40L之第一或第二多肽或兩種或更多種多肽之複合物之C端分別連接於免疫球蛋白Fc域之第一或第二多肽之N端。此形式之蛋白質亦可視情況在第一臂及/或第二臂中之一者或兩者中包含連接子多肽，其將特異性結合CD80及/或CD86之第一及/或第二多肽或兩種或更多種多肽之複合物之C端分別連接於特異性結合OX40L之第一及/或第二多肽或兩種或更多種多肽之複合物之N端。
另一蛋白質形式包含：(i)第一臂，其自N端至C端包含：特異性結合OX40L之第一多肽或兩種或更多種多肽之複合物、特異性結合CD80及/或CD86之第一多肽或兩種或更多種多肽之複合物及免疫球蛋白Fc域之第一多肽；及(ii)第二臂，其自N端至C端包含：特異性結合OX40L之兩種或更多種多肽之第二複合物、特異性結合CD80及/或CD86之第二多肽或兩種或更多種多肽之複合物及免疫球蛋白Fc域之第二多肽，其中該免疫球蛋白Fc域之第一及第二多肽二聚合。在此形式中，特異性結合OX40L之第一及第二多肽或兩種或更多種多肽之複合物包括：OX40之細胞外域或其功能片段(
圖 1G及
圖 1H)；或抗原結合位點(例如，抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1P)。在一些實施例中，特異性結合OX40L之兩種或更多種多肽之第一及第二複合物包含Fab，其中部分鉸鏈(例如具有序列SEQ ID NO: 336之多肽)連接於Fab重鏈(HC) CH1域之C端且與Fab輕鏈(LC)形成二硫鍵。在此形式中，特異性結合CD80及/或CD86之第一及第二多肽或兩種或更多種多肽之複合物包括：CD28之細胞外域或其功能片段(
圖 1G)；CTLA4之細胞外域或其功能片段(
圖 1H)；或其中特異性結合CD80及/或CD86之第一多肽或兩種或更多種多肽之複合物為特異性結合CD80之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH))，且特異性結合CD80及/或CD86之第二多肽或兩種或更多種多肽之複合物為特異性結合CD86之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1P)。此形式之蛋白質可視情況在第一臂及第二臂中之每一者中包含多肽鉸鏈，其將特異性結合CD80及/或CD86之第一或第二多肽或兩種或更多種多肽之複合物之C端分別連接於免疫球蛋白Fc域之第一或第二多肽之N端。此形式之蛋白質亦可視情況在第一臂及/或第二臂中之一者或兩者中包含連接子多肽，其將特異性結合OX40L之第一及/或第二多肽或兩種或更多種多肽之複合物之C端分別連接於特異性結合CD80及/或CD86之第一及/或第二多肽或兩種或更多種多肽之複合物之N端。
在另一實例中，蛋白質形式包含：(i)第一臂，其自N端至C端包含：免疫球蛋白Fc域之第一多肽、特異性結合CD80及/或CD86之第一多肽或兩種或更多種多肽之複合物及特異性結合OX40L之第一多肽或兩種或更多種多肽之複合物；及(ii)第二臂，其自N端至C端包含：免疫球蛋白Fc域之第二多肽、特異性結合CD80及/或CD86之第二多肽或兩種或更多種多肽之複合物及特異性結合OX40L之第二多肽或兩種或更多種多肽之複合物，其中該免疫球蛋白Fc域之第一及第二多肽二聚合。在此形式中，特異性結合CD80及/或CD86之第一及第二多肽或兩種或更多種多肽之複合物包括：CD28之細胞外域或其功能片段(
圖 1I)；CTLA4之細胞外域或其功能片段；或其中特異性結合CD80及/或CD86之第一多肽或兩種或更多種多肽之複合物為特異性結合CD80之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH))，且特異性結合CD80及/或CD86之第二多肽或兩種或更多種多肽之複合物為特異性結合CD86之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1Q)。在此形式中，特異性結合OX40L之第一及第二多肽或兩種或更多種多肽之複合物包括：OX40之細胞外域或其功能片段(
圖 1I) ；或抗原結合位點(例如，抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1Q)。在一些實施例中，特異性結合OX40L之兩種或更多種多肽之第一及第二複合物包含Fab，其中部分鉸鏈(例如具有序列SEQ ID NO: 336之多肽)連接於Fab重鏈(HC) CH1域之C端且與Fab輕鏈(LC)形成二硫鍵。此形式之蛋白質可視情況在第一臂及第二臂中之每一者中包含多肽鉸鏈，分別連接免疫球蛋白Fc域之第一或第二多肽之N端。此形式之蛋白質亦可視情況在第一臂及/或第二臂中之一者或兩者中包含連接子多肽，其將免疫球蛋白Fc域之第一及/或第二多肽之C端分別連接於特異性結合CD80及/或CD86之第一及/或第二多肽或兩種或更多種多肽之複合物之N端。此形式之蛋白質亦可視情況在第一臂及/或第二臂中之一者或兩者中包含連接子多肽，其將特異性結合CD80及/或CD86之第一及/或第二多肽或兩種或更多種多肽之複合物之C端分別連接於特異性結合OX40L之第一及/或第二多肽或兩種或更多種多肽之複合物之N端。
另一蛋白質形式包含：(i)第一臂，其自N端至C端包含：免疫球蛋白Fc域之第一多肽、特異性結合OX40L之第一多肽或兩種或更多種多肽之複合物及特異性結合CD80及/或CD86之第一多肽或兩種或更多種多肽之複合物；及(ii)第二臂，其自N端至C端包含：免疫球蛋白Fc域之第二多肽、特異性結合OX40L之第二多肽或兩種或更多種多肽之複合物及特異性結合CD80及/或CD86之第二多肽或兩種或更多種多肽之複合物，其中該免疫球蛋白Fc域之第一及第二多肽二聚合。在此形式中，特異性結合OX40L之第一及第二多肽或兩種或更多種多肽之複合物包括：OX40之細胞外域或其功能片段(
圖 1I) ；或抗原結合位點(例如，抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1R)。在一些實施例中，特異性結合OX40L之兩種或更多種多肽之第一及第二複合物包含Fab，其中部分鉸鏈(例如具有序列SEQ ID NO: 336之多肽)連接於Fab重鏈(HC) CH1域之C端且與Fab輕鏈(LC)形成二硫鍵。在此形式中，特異性結合CD80及/或CD86之第一及第二多肽或兩種或更多種多肽之複合物包括：CD28之細胞外域或其功能片段(
圖 1I)；CTLA4之細胞外域或其功能片段；或其中特異性結合CD80及/或CD86之第一多肽或兩種或更多種多肽之複合物為特異性結合CD80之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH))，且特異性結合CD80及/或CD86之第二多肽或兩種或更多種多肽之複合物為特異性結合CD86之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1R)。此形式之蛋白質可視情況在第一臂及第二臂中之每一者中包含多肽鉸鏈，分別連接免疫球蛋白Fc域之第一或第二多肽之N端。此形式之蛋白質亦可視情況在第一臂及/或第二臂中之一者或兩者中包含連接子多肽，其將免疫球蛋白Fc域之第一及/或第二多肽之C端分別連接於特異性結合OX40L之第一及/或第二多肽或兩種或更多種多肽之複合物之N端。此形式之蛋白質亦可視情況在第一臂及/或第二臂中之一者或兩者中包含連接子多肽，其將特異性結合OX40L之第一及/或第二多肽或兩種或更多種多肽之複合物之C端分別連接於特異性結合CD80及/或CD86之第一及/或第二多肽或兩種或更多種多肽之複合物之N端。
另一蛋白質形式包含：(i)第一臂，其自N端至C端包含：特異性結合OX40L之第一多肽或兩種或更多種多肽之複合物、免疫球蛋白Fc域之第一多肽及特異性結合CD80及CD86之第一多肽或兩種或更多種多肽之複合物；及(ii)第二臂，其自N端至C端包含：特異性結合OX40L之第二多肽或兩種或更多種多肽之複合物、免疫球蛋白Fc域之第二多肽及特異性結合CD80及CD86之第二多肽或兩種或更多種多肽之複合物，其中該免疫球蛋白Fc域之第一及第二多肽二聚合。在此形式中，特異性結合OX40L之第一及第二多肽或兩種或更多種多肽之複合物包括：OX40之細胞外域或其功能片段；或抗原結合位點(例如，抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1S)。在一些實施例中，特異性結合OX40L之兩種或更多種多肽之第一及第二複合物包含Fab，其中部分鉸鏈(例如具有序列SEQ ID NO: 336之多肽)連接於Fab重鏈(HC) CH1域之C端且與Fab輕鏈(LC)形成二硫鍵。在此形式中，特異性結合CD80及/或CD86之第一及第二多肽或兩種或更多種多肽之複合物包括：特異性結合CD80之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFV)、微型抗體或奈米抗體(VHH))，其在存在或不存在連接子多肽下連接於特異性結合CD86之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFV)、微型抗體或奈米抗體(VHH)) (
圖 1S)，或特異性結合CD86之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFV)、微型抗體或奈米抗體(VHH))，其在存在或不存在連接子多肽下連接於特異性結合CD80之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFV)、微型抗體或奈米抗體(VHH))。此形式之蛋白質可視情況在第一臂及第二臂中之每一者中包含多肽鉸鏈，其將特異性結合OX40L之第一或第二多肽或兩種或更多種多肽之複合物之C端分別連接於免疫球蛋白Fc域之第一或第二多肽之N端。此形式之蛋白質亦可視情況在第一臂及/或第二臂中之一者或兩者中包含連接子多肽，其將免疫球蛋白Fc域之第一及/或第二多肽之C端分別連接於特異性結合CD80及/或CD86之第一及/或第二多肽或兩種或更多種多肽之複合物之N端。
另一蛋白質形式包含：(i)第一臂，其自N端至C端包含：特異性結合CD80及CD86之第一多肽或兩種或更多種多肽之複合物、免疫球蛋白Fc域之第一多肽及特異性結合OX40L之第一多肽或兩種或更多種多肽之複合物；及(ii)第二臂，其自N端至C端包含：特異性結合CD80及CD86之第二多肽或兩種或更多種多肽之複合物、免疫球蛋白Fc域之第二多肽及特異性結合OX40L之第二多肽或兩種或更多種多肽之複合物，其中該免疫球蛋白Fc域之第一及第二多肽二聚合。在此形式中，特異性結合OX40L之第一及第二多肽或兩種或更多種多肽之複合物包括：OX40之細胞外域或其功能片段；或抗原結合位點(例如，抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)) (
圖 1T)。在一些實施例中，特異性結合OX40L之兩種或更多種多肽之第一及第二複合物包含Fab，其中部分鉸鏈(例如具有序列SEQ ID NO: 336之多肽)連接於Fab重鏈(HC) CH1域之C端且與Fab輕鏈(LC)形成二硫鍵。在此形式中，特異性結合CD80及/或CD86之第一及第二多肽或多肽複合物包括：特異性結合CD80之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFV)、微型抗體或奈米抗體(VHH))，其在存在或不存在連接子多肽下連接於特異性結合CD86之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFV)、微型抗體或奈米抗體(VHH)) (
圖 1T)，或特異性結合CD86之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFV)、微型抗體或奈米抗體(VHH))，其在存在或不存在連接子多肽下連接於特異性結合CD80之抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFV)、微型抗體或奈米抗體(VHH))。此形式之蛋白質可視情況在第一臂及第二臂中之每一者中包含多肽鉸鏈，其將特異性結合CD80及/或CD86之第一或第二多肽或兩種或更多種多肽之複合物之C端分別連接於免疫球蛋白Fc域之第一或第二多肽之N端。此形式之蛋白質亦可視情況在第一臂及/或第二臂中之一者或兩者中包含連接子多肽，其將免疫球蛋白Fc域之第一及/或第二多肽之C端分別連接於特異性結合OX40L之第一及/或第二多肽或兩個或更多個多肽之複合物之N端。在一些實施例中，第一及/或第二多肽可為單一多肽鏈。在一些實施例中，第一及/或第二多肽可為兩條或更多條多肽鏈之複合物。
蛋白質之個別組分更詳細地描述於下文中。
I.A 特異性結合 CD80 及 / 或 CD86 之多肽或兩種或更多種多肽之複合物
抗原呈遞細胞(APC) (諸如B細胞、單核球、巨噬細胞及樹突狀細胞)之表面上特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物阻斷內源性CD80及/或CD86結合於T細胞表面上之CD28。藉由防止CD80/CD86與CD28之間發生相互作用，特異性結合CD80及/或CD86之多肽可抑制T細胞協同刺激受體信號傳導，引起T細胞活化、增殖及誘導無變應性、免疫抑制性、耐受性T細胞反應減少。
如本文所用，特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物為結合於具有序列SEQ ID NO: 3之蛋白質及相關同功異型物及直系同源物及/或具有序列SEQ ID NO: 4之蛋白質及相關同功異型物及直系同源物的多肽或兩種或更多種多肽之複合物。
在一些實施例中，特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物包括(但不限於) CTLA4細胞外域或其功能片段、抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)。
舉例而言，在一些實施例中，特異性結合CD80及/或CD86之多肽為CTLA4之細胞外域或其功能片段。在一些實施例中，CTLA4之細胞外域可包含源自人類CTLA4之野生型序列(例如GenBank寄存編號NP_005205)之序列。替代地，CTLA4多肽序列可為如以下中所述之變異CTLA4序列：Larsen等人
Am J Transplant. 2005年3月;5(3):443-53.；Xu等人
J Immunol. 2012年11月1日;189(9):4470-7.；Bernett等人,
MAbs. 2013年5月-6月;5(3):384-96.；Oshima等人
Protein Eng Des Sel.2016年5月;29(5):159-67.；Douthwaite等人
J Immunol.2017年1月1日;198(1):528-537. 勘誤表:
J Immunol.2017年9月1日;199(5):1943。舉例而言，CTLA4序列可包含選自位置16、24、25、27、28、29、30、32、49、50、51、53、54、55、56、58、61、64、65、70、80、85、93、96及104 (相對於SEQ ID NO: 174編號)處之突變的一或多種突變。
本發明之特異性結合CD80及/或CD86之多肽可包含選自
表 1中所列之任何野生型或變異序列或其功能性片段的胺基酸序列。
表
1
：野生型及變異
CTLA4
序列
| 描述 | 序列 |
| 完整未加工人類CTLA4(Genbank寄存編號NP_005205) (加下劃線之胺基酸表示信號肽，根據RefSeq註釋) | MACLGFQRHKAQLNLATRTWPCTLLFFLLFIPVFCKAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDFLLWILAAVSSGLFFYSFLLTAVSLSKMLKKRSPLTTGVYVKMPPTEPECEKQFQPYFIPIN (SEQ ID NO: 172) |
| 人類CTLA4 (細胞外域胺基酸殘基36-161) | KAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSD (SEQ ID NO: 29) |
| 人類CTLA4 (細胞外域胺基酸殘基37-161) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSD (SEQ ID NO: 173) |
| 人類CTLA4 (細胞外域胺基酸殘基38-161) | MHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSD (SEQ ID NO: 174) |
| CTLA4變異體1 Larsen等人 Am J Transplant.2005年3月;5(3):443-53. [A29Y、L104E] | MHVAQPAVVLASSRGIASFVCEYASPGK Y TEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYY E GIGNGTQIYVIDPEPCPDSD (SEQ ID NO: 119) |
| CTLA4變異體2 Xu等人 J Immunol.2012年11月1日;189(9):4470-7. [K28H、A29H、A29K、A29T、A29W、A29Y、T51N、T51Y、L58G、K93M、K93Q、L96K] | MHVAQPAVVLASSRGIASFVCEYASPG KX 1 TEVRVTVLRQADSQVTEVCAA X 2 YMMGNE G TFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYIC X 3 VE K MYPPPYYLGIGNGTQIYVIDPEPCPDSD 其中X 1為H、K、T、W或Y； X 2為N或Y；及 X 3為M或Q (SEQ ID NO: 215) |
| CTLA4變異體3 Bernett等人 , MAbs.2013年5月-6月;5(3):384-96. [A29H、A29K、A29W、A29Y、A49F、T51N、M53Y、L61D、L61E、K93Q、L104E] | MHVAQPAVVLASSRGIASFVCEYASPGK X 1 TEVRVTVLRQADSQVTEVC F A N Y Y MGNELTF X 2 DDSICTGTSSGNQVNLTIQGLRAMDTGLYIC Q VELMYPPPYY E GIGNGTQIYVIDPEPCPDSD 其中X 1為H、K、W或Y；及 X 2為D或E (SEQ ID NO: 233) |
| CTLA4變異體4 Oshima等人 Protein Eng Des Sel.2016年5月;29(5):159-67. [A24E、T30N、V32I、A50M、M54K、G55E、N56D、S64P、I65S、S70F、L104E] | MHVAQPAVVLASSRGIASFVCEY E SPGKA N E I RVTVLRQADSQVTEVCA M TYM KED ELTFLDD PS CTGT F SGNQVNLTIQGLRAMDTGLYICKVELMYPPPYY E GIGNGTQIYVIDPEPCPDSD (SEQ ID NO: 234) |
| CTLA4變異體5 Douthwaite等人 J Immunol.2017年1月1日;198(1):528-537. [I16R、I16V、I16S、A24T、S25N、G27S、M54K、L58A、L58G、S70A、Q80R、M85Q、M85S、K93Q] | MHVAQPAVVLASSRG X 1 ASFVCEY TN P S KATEVRVTVLRQADSQVTEVCAATYM K GNE X 2 TFLDDSICTGT A SGNQVNLTI R GLRA X 3 DTGLYIC Q VELMYPPPYYLGIGNGTQIYVIDPEPCPDSD 其中X 1為R或V； X 2為A或G；及 X 3為Q或S (SEQ ID NO: 235) |
在一些實施例中，特異性結合CD80及/或CD86之多肽為CTLA4之細胞外域或其功能片段，其包含與
表 1中所列之序列具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性的胺基酸序列。
在一些實施例中，特異性結合CD80及/或CD86之多肽包含CD28 (SEQ ID NO: 236)之細胞外域或其功能片段。
CD28(加下劃線表示信號肽序列)
在一些實施例中，特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物包含抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體及奈米抗體(VHH)。
在本發明之蛋白質之一些實施例中，特異性結合CD80及/或CD86之兩種或更多種多肽之複合物的多肽或重鏈可連接於特異性結合OX40L之兩種或更多種多肽之複合物的多肽或重鏈(例如包含
表 3中所列之胺基酸序列的多肽)以形成連續多肽鏈。在本發明之蛋白質之一些實施例中，特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物係經由橋接部分(例如包含
表 4中所列之胺基酸序列的多肽)連接於特異性結合OX40L之多肽或兩種或更多種多肽之複合物，其中該橋接部分將特異性結合CD80及/或CD86之兩種或更多種多肽之複合物的多肽或重鏈之C端連接於特異性結合OX40L之兩種或更多種多肽之複合物的多肽或重鏈之N端以形成連續多肽鏈。在一些實施例中，特異性結合CD80及/或CD86之兩種或更多種多肽之複合物的多肽或重鏈係經由鉸鏈多肽(例如包含
表 5中所列之胺基酸序列的多肽)連接於橋接部分，其中該等鉸鏈多肽將特異性結合CD80及/或CD86之兩種或更多種多肽之複合物的多肽或重鏈之C端連接於橋接部分之N端以形成連續多肽鏈。
I. B 特異性結合 OX40L 之多肽或兩種或更多種多肽之複合物
抗原呈遞細胞(APC) (諸如B細胞、單核球、巨噬細胞及樹突狀細胞)之表面上特異性結合OX40L之多肽或兩種或更多種多肽之複合物阻斷結合於T細胞表面上之內源性OX40。藉由防止OX40L與OX40之間發生相互作用，特異性結合OX40L之多肽可抑制T細胞協同刺激受體信號傳導，引起T細胞活化、增殖及誘導無變應性、免疫抑制性、耐受性T細胞反應減少。
如本文所用，特異性結合OX40L之多肽或兩種或更多種多肽之複合物為結合於GenBank寄存編號NP_003317 (SEQ ID NO: 2)之蛋白質及相關同功異型物及直系同源物的多肽。
OX40L(加下劃線表示跨膜區，粗體表示細胞外域之位置1)
在一些實施例中，依本文中所述之特異性結合OX40L之多肽或兩種或更多種多肽之複合物結合於人類OX40L之細胞外域之位置17、18、19、20、21、23、26、28、60、83、110、111、112、113及114。在其他實施例中，依本文中所述之特異性結合OX40L之多肽或兩種或更多種多肽之複合物結合於人類OX40L之細胞外域之位置58、59、60、61、62、63、81、82及83。在一些實施例中，特異性結合OX40L之多肽或兩種或更多種多肽之複合物結合人類OX40L之細胞外域之位置60及/或83。
在一些實施例中，特異性結合OX40L之多肽或兩種或更多種多肽之複合物包括(但不限於)：抗原結合位點，例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)；或OX40之胞外域或其功能性片段。
在一些實施例中，特異性結合OX40L之多肽或兩種或更多種多肽之複合物包含抗原結合位點。在某些實施例中，抗原結合位點為Fab。
表 2列出可特異性結合於OX40L的呈組合形式之共同重鏈可變域(VH)及輕鏈可變域(VL)互補決定區(CDR)。在一些實施例中，重鏈可變域及輕鏈可變域係以具有選自
表 2中之共同VH及VL序列的VH及VL CDR序列的Fab形式排列。在一些實施例中，部分鉸鏈(例如具有序列SEQ ID NO: 336之多肽)連接於Fab重鏈(HC) CH1域之C端且與Fab輕鏈(LC)形成二硫鍵。
除非另外指明，否則
表 2中所提供之CDR序列係根據IMGT獨特編號方案確定。
表
2
：
特異性結合
OX40L
之抗原結合位點之
VHCDR
及
VLCDR
序列
| 共同序列 | |
| 重鏈 | 輕鏈 |
| CDR1 | |
| GX 1SX 2X 3X 4SX 5YY 其中X 1為A、G或V， X 2為V或I， X 3為S或R， X 4為S或T，及 X 5為S或G； (SEQ ID NO: 222) | X 1IENKN 其中X 1為N或D (SEQ ID NO: 226) |
| SX 1RX 2X 3X 4其中X 1為V或L， X 2為R或N， X 3為F或Y，及 X 4為F或Y (SEQ ID NO: 227) | |
| CDR2 | |
| IX 1YX 2GST 其中X 1為Y或N，及 X 2為S或G， (SEQ ID NO: 223) | RDN (SEQ ID NO: 82) |
| X 1DYSGT 其中X 1為I或M，及 (SEQ ID NO: 224) | GKD (SEQ ID NO: 228) |
| IGSVDYSGX 1T 其中X 1為N、A或S (SEQ ID NO: 225) | RDS (SEQ ID NO: 90) |
| CDR3 | |
| ARHRGX 1YX 2FDX 3其中X 1為S或I， X 2為F或H，及 X 3為I或Y (SEQ ID NO: 220) | QVX 1DSX 2X 3VV 其中X 1為R或W， X 2為N、T或A，及 X 3為I、T或A，及 (SEQ ID NO: 231) |
| ARERSX 1X 2WYPX 3DY 其中X 1為N或S， X 2為N、D、G或S，及 X 3為I或F (SEQ ID NO: 221) | NSRDSSGYX 1VX 2其中X 1為L或H，及 X 2為L或V (SEQ ID NO: 232) |
在某些實施例中，特異性結合於OX40L之抗原結合位點包含選自SEQ ID NO: 220或SEQ ID NO: 221之共同序列的胺基酸序列。
在一些實施例中，特異性結合於OX40L之抗原結合位點包含：包含胺基酸序列SEQ ID NO: 222之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列SEQ ID NO: 223、SEQ ID NO: 224或SEQ ID NO: 225之重鏈可變互補決定區2 (VHCDR2)；及包含以下之胺基酸序列之重鏈可變互補決定區3 (VHCDR3)：SEQ ID NO: 220或SEQ ID NO: 221。
在一些實施例中，特異性結合於OX40L之抗原結合位點包含：包含胺基酸序列SEQ ID NO: 226或SEQ ID NO: 227之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列SEQ ID NO: 82、SEQ ID NO: 228或SEQ ID NO: 90之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列SEQ ID NO: 231或SEQ ID NO: 232之輕鏈可變互補決定區3 (VLCDR3)。
在一些實施例中，特異性結合於OX40L之抗原結合位點包含：包含胺基酸序列SEQ ID NO: 222之VHCDR1；包含胺基酸序列SEQ ID NO: 223之VHCDR2；包含胺基酸序列SEQ ID NO: 220之VHCDR3；包含胺基酸序列SEQ ID NO: 226之VLCDR1；包含胺基酸序列SEQ ID NO: 82之VLCDR2；及包含胺基酸序列SEQ ID NO: 231之VLCDR3。
在一些實施例中，特異性結合於OX40L之抗原結合位點包含：包含胺基酸序列SEQ ID NO: 222之VHCDR1；包含胺基酸序列SEQ ID NO: 224之VHCDR2；包含胺基酸序列SEQ ID NO: 221之VHCDR3；包含胺基酸序列SEQ ID NO: 227之VLCDR1；包含胺基酸序列SEQ ID NO: 228之VLCDR2；及包含胺基酸序列SEQ ID NO: 232之VLCDR3。
在一些實施例中，根據IMGT獨特編號方案，特異性結合於OX40L之抗原結合位點包含VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3，其各自包含分別對應於
表 2之VHCDR及VLCDR共同序列的VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3序列的胺基酸序列。
在一些實施例中，特異性結合OX40L之多肽或兩種或更多種多肽之複合物包含抗原結合位點。在某些實施例中，抗原結合位點為Fab。
表 3列出可特異性結合於OX40L的呈組合形式之重鏈可變域(VH)及輕鏈可變域(VL)之多肽序列。在一些實施例中，重鏈可變域及輕鏈可變域係以具有選自
表 3中之VH及VL序列的VH及VL序列的Fab形式排列。表3另外列出可特異性結合於OX40L的呈組合形式之重鏈(HC)及輕鏈(LC)之多肽序列。在一些實施例中，重鏈及輕鏈係以具有選自
表 3中之HC及LC序列的HC及LC序列的Fab形式排列。
除非另外指明，否則
表 3中所提供之CDR序列係根據IMGT獨特編號方案確定。
表
3
：
特異性結合
OX40L
之抗原結合位點的
VH/VL
及
HC/LC
序列
| 純系 | 胺基酸序列 |
| 67B06 | 重鏈QLQLQESGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 8) 輕鏈SYELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 7) |
| 重鏈可變域(VH) QLQLQESGPGLVKPSETLSLTCSVS GGSISTSSYYWGWIRQPPGKGLEWSGS IYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYC ARHRGSYFFDIWGLGTLVTVSS (SEQ ID NO: 76) CDR1 - GGSISTSSYY (SEQ ID NO: 77) CDR2 - IYYSGST (SEQ ID NO: 78) CDR3 - ARHRGSYFFDI (SEQ ID NO: 79) | 輕鏈可變域(VL) SYELTQPLSVSVALGQTARMTCGGS DIENKNVHWYQQKPGQAPVLVIH RDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYC QVRDSNIVVFGGGTKLTVL (SEQ ID NO: 80) CDR1 - DIENKN (SEQ ID NO: 81) CDR2 - RDN (SEQ ID NO: 82) CDR3 - QVRDSNIVV (SEQ ID NO: 83) |
| 98E10 | 重鏈QLQLQESGPGLVKPSETLSLTCTVAGASVSSSSYYWGWIRQSPGKGLEWIGTINYGGSTYHNPSLKRRVTVSVDTSKNQFSLKLTSVTAADTAVYYCARHRGIYHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 14) 輕鏈SYELTQPLSVSVALGQTARITCGGNNIENKNVHWYQQMPGQAPVLVIYRDSNRPSGIPERFSGSNSGNTATLTINRAQAGDEADYYCQVWDSNTVVFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 13) |
| 重鏈可變域(VH) QLQLQESGPGLVKPSETLSLTCTVA GASVSSSSYYWGWIRQSPGKGLEWIGT INYGGSTYHNPSLKRRVTVSVDTSKNQFSLKLTSVTAADTAVYYC ARHRGIYHFDYWGQGTLVTVSS (SEQ ID NO: 84) CDR1 - GASVSSSSYY (SEQ ID NO: 85) CDR2 - INYGGST (SEQ ID NO: 86) CDR3 - ARHRGIYHFDY (SEQ ID NO: 87) | 輕鏈可變域(VL) SYELTQPLSVSVALGQTARITCGGN NIENKNVHWYQQMPGQAPVLVIY RDSNRPSGIPERFSGSNSGNTATLTINRAQAGDEADYYC QVWDSNTVVFGGGTKVTVL (SEQ ID NO: 88) CDR1 - NIENKN (SEQ ID NO: 89) CDR2 - RDS (SEQ ID NO: 90) CDR3 - QVWDSNTVV (SEQ ID NO: 91) |
| 89B09 | 重鏈EVQLVESGPGLVKPSETLSLTCTVSGVSIRSNGYYWGWIRQSPGKGLEWIGNMDYSGTYQNPSLTSRVTISGDASKNQFSLKLRSVTAADTAVYFCARERSNNWYPIDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 16) 輕鏈SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPILVISGKDTRPSGIPDRFSGSISGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 15) |
| 重鏈可變域(VH) EVQLVESGPGLVKPSETLSLTCTVS GVSIRSNGYYWGWIRQSPGKGLEWIGN MDYSGTYQNPSLTSRVTISGDASKNQFSLKLRSVTAADTAVYFC ARERSNNWYPIDYWGQGTLVTVSS (SEQ ID NO: 92) CDR1 - GVSIRSNGYY (SEQ ID NO: 93) CDR2 - MDYSGT (SEQ ID NO: 94) CDR3 - ARERSNNWYPIDY (SEQ ID NO: 95) | 輕鏈可變域(VL) SSELTQDPAVSVALGQTVRITCQGD SVRRFFAHWYQQKPGQAPILVIS GKDTRPSGIPDRFSGSISGNTASLTITGAQAEDEADYYC NSRDSSGYLVLFGGGTKLTVL (SEQ ID NO: 96) CDR1 - SVRRFF (SEQ ID NO: 97) CDR2 - GKD (SEQ ID NO: 98) CDR3 - NSRDSSGYLVL (SEQ ID NO: 99) |
| 98C01 | 重鏈QVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGGIGSVDYSGNTYYKPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYHCARHRGIYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 18) 輕鏈SYELTQPPSVSVALGQTARITCGGNNIENKNVHWYQQKPGQAPVLVIYRDSNRPSGIPERFSGSNSGNTATLSINRAQAGDEADYYCQVWDSNTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 17) |
| 重鏈可變域(VH) QVQLQESGPGLVKPSETLSLTCTVS GGSISSSSYYWGWIRQPPGKGLEWIGG IGSVDYSGNTYYKPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYHC ARHRGIYFFDYWGQGTLVTVSS (SEQ ID NO: 100) CDR1 - GGSISSSSYY (SEQ ID NO: 101) CDR2 - IGSVDYSGNT (SEQ ID NO: 102) CDR3 - ARHRGIYFFDY (SEQ ID NO: 103) | 輕鏈可變域(VL) SYELTQPPSVSVALGQTARITCGGN NIENKNVHWYQQKPGQAPVLVIY RDSNRPSGIPERFSGSNSGNTATLSINRAQAGDEADYYC QVWDSN TVVFGGGTKLTVL (SEQ ID NO: 104) CDR1 - NIENKN (SEQ ID NO: 89) CDR2 - RDS (SEQ ID NO: 90) CDR3 - QVWDSNTVV (SEQ ID NO: 91) |
| 97G07 | 重鏈QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGGIGSVDYSGNTYYKPSLKSRVTISVDTSKNQFSLKLSTVTAADTAVYHCARHRGIYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 6) 輕鏈YYELTQPLSVSVALGQTARIPCGGNNIENKNVHWYQQKPGQAPVLVIYRDSNRPSGIPERFSGSNSGNTATLSINRAQAGDEADYYCQVWDSNTVIFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 5) |
| 重鏈可變域(VH) QLQLQESGPGLVKPSETLSLTCTVS GGSISSSSYYWGWIRQPPGKGLEWIGG IGSVDYSGNTYYKPSLKSRVTISVDTSKNQFSLKLSTVTAADTAVYHC ARHRGIYFFDYWGQGTLVTVSS (SEQ ID NO: 108) CDR1 - GGSISSSSYY (SEQ ID NO: 109) CDR2 - IGSVDYSGNT (SEQ ID NO: 110) CDR3 - ARHRGIYFFDY (SEQ ID NO: 103) | 輕鏈可變域(VL) YYELTQPLSVSVALGQTARIPCGGN NIENKNVHWYQQKPGQAPVLVIY RDSNRPSGIPERFSGSNSGNTATLSINRAQAGDEADYYC QVWDSN TVIFGGGTKVTVL (SEQ ID NO: 112) CDR1 - NIENKN (SEQ ID NO: 89) CDR2 - RDS (SEQ ID NO: 90) CDR3 - QVWDSNTVI (SEQ ID NO: 115) |
| 68F03 | 重鏈QLQLQESGPGLVKPSETLSLTCTVSGGSIDTSSQYWAWIRQPPGKGLEWIGGIYFSGSTYQNPSLKSRVTTSVDTSKNQFSLRLSSMTAADTAVYYCARHRGIYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 10) 輕鏈SFELTQPLSVSVALGQTARITCGGINIENKNVHYYQQKPGQAPVLVIYRDTNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVWDSNTVIFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 9) |
| 重鏈可變域(VH) QLQLQESGPGLVKPSETLSLTCTVS GGSIDTSSQYWAWIRQPPGKGLEWIGG IYFSGSTYQNPSLKSRVTTSVDTSKNQFSLRLSSMTAADTAVYYC ARHRGIYFFDYWGQGTLVTVSS (SEQ ID NO: 116) CDR1 - GGSIDTSSQY (SEQ ID NO: 117) CDR2 - IYFSGST (SEQ ID NO: 118) CDR3 - ARHRGIYFFDY (SEQ ID NO: 103) | 輕鏈可變域(VL) SFELTQPLSVSVALGQTARITCGGI NIENKNVHYYQQKPGQAPVLVIY RDTNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYC QVWDSNT VIFGGGTKVTVL (SEQ ID NO: 120) CDR1 - NIENKN (SEQ ID NO: 89) CDR2 - RDT (SEQ ID NO: 122) CDR3 - QVWDSNTVI (SEQ ID NO: 123) |
| 84E11 | 重鏈QLQLQESGPGLVKPSETLSLTCTVSGGSISSGSFYWGWIRQPPGKGLEWIGTIYYSGSTYYNPSLKSRVAISVDTSKNQFYLNLNFVTAADTAVYHCARERSSSWYPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 12) 輕鏈SSELTQDPAVSVALGQTVRITCQGDSLRNYFANWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYHVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 11) |
| 重鏈可變域(VH) QLQLQESGPGLVKPSETLSLTCTVS GGSISSGSFYWGWIRQPPGKGLEWIGT IYYSGSTYYNPSLKSRVAISVDTSKNQFYLNLNFVTAADTAVYHC ARERSSSWYPFDYWGQGTLVTVSS (SEQ ID NO: 124) CDR1 - GGSISSGSFY (SEQ ID NO: 125) CDR2 - IYYSGST (SEQ ID NO: 126) CDR3 - ARERSSSWYPFDY (SEQ ID NO: 127) | 輕鏈可變域(VL) SSELTQDPAVSVALGQTVRITCQGD SLRNYFANWYQQKPGQAPVLVIY GKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYC NSRDSSGYHVVFGGGTKLTVL (SEQ ID NO: 128) CDR1 - SLRNYF (SEQ ID NO: 129) CDR2 - GKN (SEQ ID NO: 130) CDR3 - NSRDSSGYHVV (SEQ ID NO: 131) |
| 88B06 | 重鏈EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMSWVRQAPGKGLEWVSVISGSGDSTYYAESVKGRFTISRDNSKNTLYLQMTSLRAEDTAEYYCAKDRTPVYGLDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 20) 輕鏈SYELTQPLSVSVALGQTARISCGGNNIGRKNVHWYQQKPGQAPVLVIYGDSNRPSGIPERFSGSNSGNTATLTIGRAQAGDEADYYCQVWDSSTVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 19) |
| 重鏈可變域(VH) EVQLLESGGGLVQPGGSLRLSCAAS GFTFSNYAMSWVRQAPGKGLEWVSV ISGSGDSTYYAESVKGRFTISRDNSKNTLYLQMTSLRAEDTAEYYC AKDRTPVYGLDVWGQGTTVTVSS (SEQ ID NO: 132) CDR1 - GFTFSNYA (SEQ ID NO: 133) CDR2 - ISGSGDST (SEQ ID NO: 134) CDR3 - AKDRTPVYGLDV (SEQ ID NO: 135) | 輕鏈可變域(VL) SYELTQPLSVSVALGQTARISCGGN NIGRKNVHWYQQKPGQAPVLVIY GDSNRPSGIPERFSGSNSGNTATLTIGRAQAGDEADYYC QVWDSSTVFGGGTKLTVL (SEQ ID NO: 136) CDR1 - NIGRKN (SEQ ID NO: 137) CDR2 - GDS (SEQ ID NO: 138) CDR3 - QVWDSSTV (SEQ ID NO: 139) |
| 95B06 | 重鏈EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMTWVRQAPGKGLEWVSDISGSGGSTKYADSVKGRFTISRDNPKNTLYLQMNSLRAEDTAVYYCAKDLGFYSTWDTDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 22) 輕鏈DMQMTQSPSSLSASVGDRVTITCRASQGIRNDLDWYQQKPGKVPKRLIHAASSLQSGVPSRFSGSGSGTEFTLTISSLQPEDFVTYYCLQHNTYPWTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 21) |
| 重鏈可變域(VH) EVQLLESGGGLVQPGGSLRLSCAAS GFTFSSYAMTWVRQAPGKGLEWVSD ISGSGGSTKYADSVKGRFTISRDNPKNTLYLQMNSLRAEDTAVYYC AKDLGFYSTWDTDYWGQGTLVTVSS (SEQ ID NO: 140) CDR1 -GFTFSSYA (SEQ ID NO: 141) CDR2 - ISGSGGST (SEQ ID NO: 142) CDR3 - AKDLGFYSTWDTDY (SEQ ID NO: 143) | 輕鏈可變域(VL) DMQMTQSPSSLSASVGDRVTITCRAS QGIRNDLDWYQQKPGKVPKRLIH AASSLQSGVPSRFSGSGSGTEFTLTISSLQPEDFVTYYC LQHNTYPWTFGQGTKLEIK (SEQ ID NO: 144) CDR1 - QGIRND (SEQ ID NO: 145) CDR2 - AAS (SEQ ID NO: 146) CDR3 - LQHNTYPWT (SEQ ID NO: 147) |
| 30F02 | 重鏈QLQLQESGPGLVKPSETLSLTCTVSGASISSSNHYWGWGWIRQPPGKGLEWIGSIYYSGNTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARHRGSYFFDHWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 24) 輕鏈SYVLTQPLSVSVALGQTARITCGGNNIGDKNVHWYQQKPGQAPVLVISRDSNRPSGIPERFSGSNSGNTATLTISRAQAGDESDYYCQVWDSSTVVFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 23) |
| 重鏈可變域(VH) QLQLQESGPGLVKPSETLSLTCTVS GASISSSNHYWGWGWIRQPPGKGLEWIGS IYYSGNTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYC ARHRGSYFFDHWGQGTLVTVSS (SEQ ID NO: 148) CDR1 - GASISSSNHYWG (SEQ ID NO: 149) CDR2 - IYYSGNT (SEQ ID NO: 150) CDR3 - ARHRGSYFFDH (SEQ ID NO: 151) | 輕鏈可變域(VL) SYVLTQPLSVSVALGQTARITCGGN NIGDKNVHWYQQKPGQAPVLVIS RDSNRPSGIPERFSGSNSGNTATLTISRAQAGDESDYYC QVWDSSTVVFGGGTKVTVL (SEQ ID NO: 152) CDR1 - NIGDKN (SEQ ID NO: 153) CDR2 - RDS (SEQ ID NO: 90) CDR3 - QVWDSSTVV (SEQ ID NO: 155) |
| 85F12 | 重鏈QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAVWNWIRQSPSRGLEWLGRTDYRSKWNNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCARGDAGMASFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 26) 輕鏈SSELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKAGQSPVVVIYQDRKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQTWDRRTAVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 25) |
| 重鏈可變域(VH) QVQLQQSGPGLVKPSQTLSLTCAIS GDSVSSNSAVWNWIRQSPSRGLEWLGR TDYRSKWNNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYC ARGDAGMASFDYWGQGTLVTVSS (SEQ ID NO: 156) CDR1 - GDSVSSNSAV (SEQ ID NO: 157) CDR2 - TDYRSKWNN (SEQ ID NO: 158) CDR3 - ARGDAGMASFDY (SEQ ID NO: 159) | 輕鏈可變域(VL) SSELTQPPSVSVSPGQTASITCSGD KLGDKYACWYQQKAGQSPVVVIY QDRKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QTWDRR TAVFGGGTKLTVL (SEQ ID NO: 160) CDR1 - KLGDKY (SEQ ID NO: 161) CDR2 - QDR (SEQ ID NO: 162) CDR3 - QTWDRRTAV (SEQ ID NO: 163) |
| 85F10 | 重鏈EVQLLESGAGLLKPSETLSLTCAVYGGSFSDYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARKRGANFFDDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 28) 輕鏈SYELTQPLSVSVALGQTARITCGGNNIENKNVHWYQQKPGQAPVLVIKRDSNRPSGIPERLSGSNSGNTATLTISRAQAGDEADYYCQVWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 27) |
| 重鏈可變域(VH) EVQLLESGAGLLKPSETLSLTCAVY GGSFSDYYWSWIRQPPGKGLEWIGE INHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYC ARKRGANFFDDWGQGTLVTVSS (SEQ ID NO: 164) CDR1 - GGSFSDYY (SEQ ID NO: 165) CDR2 - INHSGST (SEQ ID NO: 166) CDR3 - ARKRGANFFDD (SEQ ID NO: 167) | 輕鏈可變域(VL) SYELTQPLSVSVALGQTARITCGGN NIENKNVHWYQQKPGQAPVLVIK RDSNRPSGIPERLSGSNSGNTATLTISRAQAGDEADYYC QVWDSSTVVFGGGTKLTVL (SEQ ID NO: 168) CDR1 - NIENKN (SEQ ID NO: 89) CDR2 - RDS (SEQ ID NO: 90) CDR3 - QVWDSSTVV (SEQ ID NO: 155) |
| 抗OX40L (美國專利9,139,653) | 重鏈EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYAMNWVRQAPGKGLEWVSTISGSGGATRYADSVKGRFTISRDNSRNTVYLQMNSLRVEDTAVFYCTKDRLIMATVRGPYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 252) 輕鏈DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPNLLIYAASSLQSGVPSRFSGSGSETDFTLTISSLQPEDFATYYCQQSHSVSFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 253) |
| 重鏈可變域(VH) EVQLVESGGGLVQPGGSLRLSCAAS GFTFSNYAMNWVRQAPGKGLEWVST ISGSGGATRYADSVKGRFTISRDNSRNTVYLQMNSLRVEDTAVFYC TKDRLIMATVRGPYYYGMDVWGQGTTVTVSS (SEQ ID NO: 31) CDR1 - GFTFSNYA (SEQ ID NO: 133) CDR2 - ISGSGGAT (SEQ ID NO: 113) CDR3 - TKDRLIMATVRGPYYYGMDV (SEQ ID NO: 114) | 輕鏈可變域(VL) DIQMTQSPSSLSASVGDRVTITCRAS QSISSYLNWYQQKPGKAPNLLIY AASSLQSGVPSRFSGSGSETDFTLTISSLQPEDFATYYC QQSHSVSFTFGPGTKVDIK (SEQ ID NO: 30) CDR1 - QSISSY (SEQ ID NO: 121) CDR2 - AAS (SEQ ID NO: 146) CDR3 - QQSHSVSFT (SEQ ID NO: 154) |
| 抗OX40L (美國專利7,501,496) *基於Kabat編號 | 重鏈EVQLLESGGGLVQPGGSLRLSCAASGFTFNSYAMSWVRQAPGKGLEWVSIISGSGGFTYYADSVKGRFTISRDNSRTTLYLQMNSLRAEDTAVYYCAKDRLVAPGTFDYWGQGALVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 254) 輕鏈DIQMTQSPSSLSASVGDRVTITCRASQGISSWLAWYQQKPEKAPKSLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYNSYPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 255) |
| 重鏈可變域(VH) EVQLLESGGGLVQPGGSLRLSCAASGFTFN SYAMSWVRQAPGKGLEWVS IISGSGGFTYYADSVKGRFTISRDNSRTTLYLQMNSLRAEDTAVYYCAK DRLVAPGTFDYWGQGALVTVSS (SEQ ID NO: 33) CDR1 - SYAMS (SEQ ID NO: 105) CDR2 - IISGSGGFTYYADSVK (SEQ ID NO: 106) CDR3 - DRLVAPGTFDY (SEQ ID NO: 107) | 輕鏈可變域(VL) DIQMTQSPSSLSASVGDRVTITC RASQGISSWLAWYQQKPEKAPKSLIY AASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYNSYPYTFGQGTKLEIK (SEQ ID NO: 32) CDR1 - RASQGISSWLA (SEQ ID NO: 169) CDR2 - AASSLQS (SEQ ID NO: 170) CDR3 - QQYNSYPYT (SEQ ID NO: 171) |
在某些實施例中，特異性結合OX40L之抗原結合位點包含抗體重鏈(HC)，其包含與
表 3中所揭示之抗體之HC具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及抗體輕鏈(LC)，其包含與
表 3中所揭示之同一抗體之LC具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。在某些實施例中，特異性結合OX40L之抗原結合位點包含抗體重鏈可變域(VH)，其包含與
表 3中所揭示之抗體之VH具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及抗體輕鏈可變域(VL)，其包含與
表 3中所揭示之同一抗體之VL具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。在某些實施例中，抗原結合位點包含
表 3中所揭示之VH及VL序列的重鏈CDR1、CDR2及CDR3以及輕鏈CDR1、CDR2及CDR3，其根據IMGT獨特編號方案，Kabat (參見Kabat等人, (1991) Sequences of Proteins of Immunological Interest, NIH公開案第91-3242號, Bethesda)、Chothia (參見例如Chothia C及Lesk A M, (1987), J. Mol. Biol. 196: 901-917)、MacCallum (參見MacCallum R M等人, (1996) J. Mol. Biol. 262: 732-745)，或此項技術中已知的任何其他CDR確定方法確定。
在某些實施例中，特異性結合於OX40L之抗原結合位點包含包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈互補決定區1 (VHCDR1)、包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈互補決定區2 (VHCDR2)、包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈互補決定區3 (VHCDR3)、包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈互補決定區1 (VLCDR1)、包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈互補決定區2 (VLCDR2)及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈互補決定區3 (VLCDR3)。
在一些實施例中，特異性結合於OX40L之抗原結合位點包括包含胺基酸序列GVSIRSNGYY (SEQ ID NO: 93)之VHCDR1、包含胺基酸序列MDYSGT (SEQ ID NO: 94)之VHCDR2、包含胺基酸序列ARERSNNWYPIDY (SEQ ID NO: 95)之VHCDR3、包含胺基酸序列SVRRFF (SEQ ID NO: 97)之VLCDR1、包含胺基酸序列GKD (SEQ ID NO: 98)之VLCDR2及包含胺基酸序列NSRDSSGYLVL (SEQ ID NO: 99)之VLCDR3。
在一些實施例中，特異性結合於OX40L之抗原結合位點包括包含胺基酸序列GASVSSSSYY (SEQ ID NO: 85)之VHCDR1、包含胺基酸序列INYGGST (SEQ ID NO: 86)之VHCDR2、包含胺基酸序列ARHRGIYHFDY (SEQ ID NO: 87)之VHCDR3、包含胺基酸序列NIENKN (SEQ ID NO: 89)之VLCDR1、包含胺基酸序列RDS (SEQ ID NO: 90)之VLCDR2及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之VLCDR3。
在一些實施例中，特異性結合於OX40L之抗原結合位點包括包含胺基酸序列GGSISSSSYY (SEQ ID NO: 101)之VHCDR1、包含胺基酸序列IGSVDYSGNT (SEQ ID NO: 102)之VHCDR2、包含胺基酸序列ARHRGIYFFDY (SEQ ID NO: 103)之VHCDR3、包含胺基酸序列NIENKN (SEQ ID NO: 89)之VLCDR1、包含胺基酸序列RDS (SEQ ID NO: 90)之VLCDR2及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之VLCDR3。
在一些實施例中，特異性結合於OX40L之抗原結合位點包括包含胺基酸序列GFTFSNYA (SEQ ID NO: 133)之VHCDR1、包含胺基酸序列ISGSGGAT (SEQ ID NO: 113)之VHCDR2、包含胺基酸序列TKDRLIMATVRGPYYYGMDV (SEQ ID NO: 114)之VHCDR3、包含胺基酸序列QSISSY (SEQ ID NO: 121)之VLCDR1、包含胺基酸序列AAS (SEQ ID NO: 146)之VLCDR2及包含胺基酸序列QQSHSVSFT (SEQ ID NO: 154)之VLCDR3。
在一些實施例中，特異性結合於OX40L之抗原結合位點包括包含胺基酸序列SYAMS (SEQ ID NO: 105)之VHCDR1、包含胺基酸序列IISGSGGFTYYADSVK (SEQ ID NO: 106)之VHCDR2、包含胺基酸序列DRLVAPGTFDY (SEQ ID NO: 107)之VHCDR3、包含胺基酸序列RASQGISSWLA (SEQ ID NO: 169)之VLCDR1、包含胺基酸序列AASSLQS (SEQ ID NO: 170)之VLCDR2及包含胺基酸序列QQYNSYPYT (SEQ ID NO: 171)之VLCDR3。
在某些實施例中，特異性結合OX40L之抗原結合位點包含VH，其包含與SEQ ID NO:76具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及VL，其包含與SEQ ID NO: 80具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗原結合位點包含VH，其包含與SEQ ID NO: 92具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及VL，其包含與SEQ ID NO: 96具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗原結合位點包含VH，其包含與SEQ ID NO: 84具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及VL，其包含與SEQ ID NO: 88具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗原結合位點包含VH，其包含與SEQ ID NO: 100具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及VL，其包含與SEQ ID NO: 104具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗原結合位點包含VH，其包含與SEQ ID NO: 31具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及VL，其包含與SEQ ID NO: 30具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗原結合位點包含VH，其包含與SEQ ID NO: 33具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及VL，其包含與SEQ ID NO: 32具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗原結合位點包含HC，其包含與SEQ ID NO: 8具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及LC，其包含與SEQ ID NO: 7具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗原結合位點包含HC，其包含與SEQ ID NO: 16具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及LC，其包含與SEQ ID NO: 15具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗原結合位點包含HC，其包含與SEQ ID NO: 14具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及LC，其包含與SEQ ID NO: 13具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗原結合位點包含HC，其包含與SEQ ID NO: 18具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及LC，其包含與SEQ ID NO: 17具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗原結合位點包含HC，其包含與SEQ ID NO: 252具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及LC，其包含與SEQ ID NO: 253具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗原結合位點包含VH，其包含與SEQ ID NO: 254具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及VL，其包含與SEQ ID NO: 255具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
I.C 橋接部分
在一些實施例中，本發明之蛋白質進一步包含橋接部分。在某些實施例中，橋接部分可為非功能性的，亦即僅充當結構連接及/或附屬物且不執行生物功能或具有生物目的。在其他實施例中，橋接部分為功能性的且在蛋白質之情況下具有生物功能。
在一些實施例中，橋接部分之N端連接於特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物之C端，且橋接部分之C端連接於特異性結合OX40L之多肽或兩種或更多種多肽之複合物的N端。在一些實施例中，橋接部分連接特異性結合CD80及/或CD86之兩種或更多種多肽之複合物的多肽或重鏈及特異性結合OX40L之兩種或更多種多肽之複合物的多肽或重鏈以形成相鄰多肽鏈。
在一些實施例中，橋接部分連接於特異性結合OX40L之多肽或兩種或更多種多肽之複合物的C端。在其他實施例中，橋接部分連接於特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物的C端。在一些實施例中，橋接部分連接於特異性結合OX40L之多肽或兩種或更多種多肽之複合物的N端。在其他實施例中，橋接部分連接於特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物的N端。
在一些實施例中，橋接部分包括但不限於免疫球蛋白Fc域之多肽或其功能片段、人類血清白蛋白(HSA)多肽或其功能片段、多肽連接子或多肽鉸鏈。在某些實施例中，橋接部分包含免疫球蛋白Fc域之多肽。舉例而言，在一些實施例中，橋接部分為IgG、IgM、IgA、IgD或IgE Fc域之多肽。在某些實施例中，橋接部分為IgG1、IgG2、IgG3或IgG4 Fc域之多肽。在某些實施例中，橋接部分為IgG1 Fc域之多肽。在某些實施例中，橋接部分為人類IgG1 Fc域之多肽。在某些實施例中，本發明之蛋白質包含免疫球蛋白Fc域之第一多肽及免疫球蛋白Fc域之第二多肽，其彼此二聚合。
人類 IgG Fc
在Fc域之多肽內，CD16結合係由鉸鏈區及CH2域介導。例如，在人類IgG1內，根據如Kabat中之EU索引編號，與CD16之相互作用主要集中於胺基酸殘基Asp 265 - Glu 269、Asn 297 - Thr 299、Ala 327 - Ile 332、Leu 234 - Ser 239及CH2域中之碳水化合物殘基N-乙醯基-D-葡糖胺(參見Sondermann等人,
Nature, 406 (6793):267-273)。基於已知域，可以選擇增強或減小針對CD16之結合親和力的突變，諸如藉由使用噬菌體呈現文庫或酵母表面呈現cDNA文庫來選擇，或可基於相互作用之已知三維結構來設計。因此，在某些實施例中，免疫球蛋白Fc域之多肽或其部分包含鉸鏈多肽及CH2域。
在某些實施例中，橋接部分為人類IgG1 Fc域之多肽，其包含一或多個突變以減少結合於人類IgG1 Fc域之第一及/或第二多肽中的Fcγ受體(例如FcγRI、FcγRIIA、FcγRIIB、FcγRIIIA或FcγRIIIB)或補體組分(例如C1q)。此類突變適用於降低效應功能。舉例而言，本發明之蛋白質包括LALA (L234A及L235A)突變、LALAPA (L234A、L235A及P329A)突變、LALAPG (L234A、L235A及P329G)突變或LALEGAASPS (L234A、L235E、G237A、A330S及P331S)突變。在一些實施例中，人類IgG1 Fc域之末端離胺酸殘基發生突變(K447A)或缺失(K447Δ)。在一些實施例中，位置322、330、331、355及358中之任何一或多者處之胺基酸可突變。除非另外說明，否則胺基酸取代之位置均根據如Kabat中之EU索引編號。
表 4列出人類免疫球蛋白Fc域之例示性野生型及突變多肽。在一些實施例中，橋接部分包含選自
表 4中所列之人類免疫球蛋白Fc序列中之任一者的胺基酸序列。
表
4
：例示性人類
IgG Fc
域序列
| Fc 域 | 胺基酸序列 |
| IgG1Fc野生型 | PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 178) |
| IgG1 Fc PA | PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALAAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:237) |
| IgG1 Fc PG | PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:238) |
| IgG1.4 Fc | PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGA (SEQ ID NO: 214) |
| IgG1.6 Fc | PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGA (SEQ ID NO: 216) |
| IgG1 Fc K447A | PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGA (SEQ ID NO: 179) |
| IgG1 Fc K447Δ | PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 180) |
| Orencia IgG | PSPAPELLGGSSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 239) |
| CTLA4Ig變異體Fc | PSPAPELLGGSSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 240) |
| IgG2 Fc野生型 | PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDISVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 217) |
| IgG3 Fc野生型 | PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVDGVEVHNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSDGSFFLYSKLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSLSLSPG (SEQ ID NO: 241) |
| IgG4 Fc野生型 | PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 205) |
在某些實施例中，本發明之蛋白質包含人類IgG Fc域橋接部分之多肽，其包含與根據如Kabat中之EU索引編號，
表 4中所列之野生型或變異人類IgG Fc域序列具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，本發明之蛋白質包含人類IgG1 Fc域橋接部分之多肽，其包含與SEQ ID NO: 178具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之蛋白質包含人類IgG1 Fc域橋接部分之多肽，其包含與SEQ ID NO: 237具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之蛋白質包含人類IgG1 Fc域橋接部分之多肽，其包含與SEQ ID NO: 238具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之蛋白質包含人類IgG1 Fc域橋接部分之多肽，其包含與SEQ ID NO: 214具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之蛋白質包含人類IgG1 Fc域橋接部分之多肽，其包含與SEQ ID NO: 216具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之蛋白質包含人類IgG1 Fc域橋接部分之多肽，其包含與SEQ ID NO: 179具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之蛋白質包含人類IgG1 Fc域橋接部分之多肽，其包含與SEQ ID NO: 180具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之蛋白質包含人類IgG1 Fc域橋接部分之多肽，其包含與SEQ ID NO: 239具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之蛋白質包含人類IgG1 Fc域橋接部分之多肽，其包含與SEQ ID NO: 240具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
鉸鏈多肽
在一些實施例中，橋接部分包含鉸鏈多肽之至少一部分。鉸鏈多肽可來源於免疫球蛋白重鏈，例如IgG1、IgG2、IgG3、IgG4或其他類別。較佳地，鉸鏈區來源於人類IgG1、IgG2、IgG3或IgG4。更佳地，鉸鏈區來源於人類IgG1重鏈。
在一些實施例中，鉸鏈多肽之至少一部分連接於人類免疫球蛋白Fc域之多肽之重鏈恆定域2 (CH2)的N端。在一些實施例中，鉸鏈多肽將特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物的C端連接於人類免疫球蛋白Fc域之多肽之CH2域的N端。在其他實施例中，鉸鏈多肽將特異性結合OX40L之多肽或兩種或更多種多肽之複合物的C端連接於人類免疫球蛋白Fc域之多肽之CH2域的N端。在一些實施例中，部分鉸鏈(例如具有序列SEQ ID NO: 336之多肽)連接於特異性結合OX40L之Fab重鏈(HC)之CH1域的C端且與特異性結合OX40L之Fab輕鏈(LC)形成二硫鍵。在一些實施例中，部分鉸鏈(例如具有序列SEQ ID NO: 336之多肽)連接於特異性結合CD80或CD86之Fab重鏈(HC)之CH1域的C端且與分別特異性結合CD80或CD86之Fab輕鏈(LC)形成二硫鍵。
在一些實施例中，位置C220、E233、L234或L235中之任何一或多者處的胺基酸可在人類IgG1之鉸鏈區中突變。除非另外說明，否則胺基酸取代之位置均根據如Kabat中之EU索引編號。
表 5列出例示性野生型及突變人類免疫球蛋白鉸鏈多肽。在一些實施例中，橋接部分包含選自
表 5中所列之人類免疫球蛋白Fc鉸鏈多肽序列中之任一者的胺基酸序列。
表
5
：人類免疫球蛋白之鉸鏈多肽
| 鉸鏈 | 胺基酸序列 |
| IgG1野生型鉸鏈 | EPKSCDKTHTCPPCPAPELLGG (SEQ ID NO: 175) |
| IgG1野生型Q鉸鏈 | QEPKSCDKTHTCPPCPAPELLGG (SEQ ID NO: 242) |
| IgG1鉸鏈C220S | EPKS SDKTHTCPPCPAPELLGG (SEQ ID NO: 176) |
| IgG1鉸鏈C220S Q | QEPKS SDKTHTCPPCPAPELLGG (SEQ ID NO: 249) |
| IgG1鉸鏈C220S/ L234A/ L235A | EPKS SDKTHTCPPCPAPE AAGG (SEQ ID NO: 177) |
| IgG1鉸鏈Q C220S/ L234A/ L235A | QEPKS SDKTHTCPPCPAPE AAGG (SEQ ID NO: 243) |
| IgG1鉸鏈L234A/ L235A (及LALAPA) | EPKSCDKTHTCPPCPAPE AAGG (SEQ ID NO: 212) |
| IgG1鉸鏈Q L234A/ L235A (及LALAPA) | QEPKSCDKTHTCPPCPAPE AAGG (SEQ ID NO: 244) |
| IgG1.4鉸鏈 | EPKSSDKTHTCPPCPAP PVAG (SEQ ID NO: 213) |
| IgG1.4鉸鏈Q | QEPKSSDKTHTCPPCPAP PVAG (SEQ ID NO: 245) |
| IgG2野生型鉸鏈 | ERKCCVECPPCPAPPVAG (SEQ ID NO: 246) |
| IgG4野生型鉸鏈 | ESKYGPPCPSCPAPEFLGG (SEQ ID NO: 218) |
| IgG4共同鉸鏈 | RVESKYGPPCPPCPAPEF XGG 其中X為L或E (SEQ ID NO: 202) |
| IgG4鉸鏈S228P | RVESKYGPPCP PCPAPEFLGG (SEQ ID NO: 203) |
| IgG4鉸鏈S228P/ L235E | RVESKYGPPCP PCPAPEF EGG (SEQ ID NO: 204) |
| Orencia IgG鉸鏈 | QEPKSSDKTHTSP (SEQ ID NO: 247) |
| Orencia鉸鏈變異體 | EPKSSDKTHTSP (SEQ ID NO: 248) |
| IgG1部分鉸鏈 | EPKSC (SEQ ID NO: 336) |
在一些實施例中，本發明之橋接部分包含鉸鏈多肽，其包含與根據如Kabat中之EU索引編號，
表 5中所列之野生型或變異人類免疫球蛋白Fc鉸鏈序列具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，本發明之橋接部分包含鉸鏈多肽，其包含與SEQ ID NO: 175具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之橋接部分包含鉸鏈多肽，其包含與SEQ ID NO: 242具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之橋接部分包含鉸鏈多肽，其包含與SEQ ID NO: 176具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之橋接部分包含鉸鏈多肽，其包含與SEQ ID NO: 249具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之橋接部分包含鉸鏈多肽，其包含與SEQ ID NO: 177具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之橋接部分包含鉸鏈多肽，其包含與SEQ ID NO: 243具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之橋接部分包含鉸鏈多肽，其包含與SEQ ID NO: 212具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之橋接部分包含鉸鏈多肽，其包含與SEQ ID NO: 244具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之橋接部分包含鉸鏈多肽，其包含與SEQ ID NO: 213具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之橋接部分包含鉸鏈多肽，其包含與SEQ ID NO: 245具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之橋接部分包含鉸鏈多肽，其包含與SEQ ID NO: 247具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
在某些實施例中，本發明之橋接部分包含鉸鏈多肽，其包含與SEQ ID NO: 248具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸。
人血清白蛋白
在一些實施例中，本發明之橋接部分包含其功能性片段之人類血清白蛋白(HSA)多肽。舉例而言，本發明之橋接部分可包含與SEQ ID NO: 219具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
I.D 連接子
在一些實施例中，特異性結合OX40L之多肽或兩種或更多種多肽之複合物的N端經由連接子多肽連接於橋接部分之C端。在其他實施例中，特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物的N端經由連接子多肽連接於橋接部分之C端。在一些實施例中，特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物的N端經由連接子多肽連接於特異性結合OX40L之多肽或兩種或更多種多肽之複合物的C端。在其他實施例中，特異性結合OX40L之多肽或兩種或更多種多肽之複合物的N端經由連接子多肽連接於特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物的C端。
關於連接子多肽之胺基酸組成，連接子多肽序列經選擇具有賦予可撓性之特性，且對於本申請案中所述之蛋白質之其他域及/或多肽之結構及功能的干擾最小。亦選擇對蛋白水解分裂具有抗性之連接子多肽序列。舉例而言，甘胺酸及絲胺酸殘基通常提供蛋白酶抗性。
在某些實施例中，本文所述之蛋白質包含(GlyGlyGlyGlySer)
4((G
4S)
4)連接子(SEQ ID NO: 111)。連接子(例如可撓性連接子)之長度可為「短的」，例如0、1、2、3、4、5、6、7、8、9、10、11或12個胺基酸殘基，或「長的」，例如至少13個胺基酸殘基。在某些實施例中，連接子之長度為10-50、10-40、10-30、10-25、10-20、15-50、15-40、15-30、15-25、15-20、20-50、20-40、20-30或20-25個胺基酸殘基。
在某些實施例中，本發明之蛋白質包含一或多個多肽連接子，其包含
表 6中所列之胺基酸序列或由其組成。
表
6 -
例示性連接子多肽
I.E
例示性蛋白質
| SEQ ID | 胺基酸序列 |
| SEQ ID NO: 181 | (GGGGS) n，其中n為1至12 |
| SEQ ID NO: 206 | GSGSGSGSGSGSGSGSGSGS |
| SEQ ID NO: 207 | GGSGGSGGSGGSGGSGGSGGSGGSGGSGGS |
| SEQ ID NO: 208 | GGGSGGGSGGGSGGGSGGGSGGGSGGGSGGGSGGGSGGGS |
| SEQ ID NO: 209 | GGSGGGSGGGSGGGSGGGSGGGSGGGSGGGSGGGSGGGSG |
| SEQ ID NO: 210 | GGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGG |
| SEQ ID NO: 211 | GGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGG |
下文列舉包含特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物，及特異性結合OX40L之多肽或兩種或更多種多肽之複合物的本發明蛋白質之實例。
舉例而言，特異性結合CD80及/或CD86之多肽可包含選自
表 1中所列之序列中之任一者的CTLA4之野生型或變異細胞外域。替代地，特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物可包含CD28之野生型或變異細胞外域或其功能片段，或抗原結合位點(例如抗體、Fab、Fab'、F(ab')
2、單鏈可變片段(scFv)；微型抗體或奈米抗體(VHH))。
在一些實施例中，特異性結合OX40L之多肽或兩種或更多種多肽之複合物為抗原結合位點(例如抗體、Fab、Fab'、F(ab')2、單鏈可變片段(scFv)；微型抗體或奈米抗體(VHH))。舉例而言，特異性結合OX40L之抗原結合位點可包含Fab，其包含VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3序列，該等序列選自
表 2中所列之VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3序列；
表 3中所列之VH及VL序列；及/或
表 3中所列之HC及LC序列。在其他實施例中，結合OX40L之多肽可包含OX40之細胞外域或其功能片段。
如上所述，本發明之蛋白質可包含橋接部分。在一些實施例中，特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物在其C端處連接於橋接部分之N端，且特異性結合OX40L之多肽或兩種或更多種多肽之複合物在其N端處連接於橋接部分之C端。如上文所述，橋接部分可為野生型人類IgG1 Fc域之多肽，其視情況包含一或多種突變且包含選自
表 4中所列之序列中之任一者的序列。橋接部分亦可在其N端處包含鉸鏈多肽，其視情況包含一或多個突變，諸如選自表5中所列之序列中之任一者的序列。
亦如上文所述，特異性結合OX40L之多肽或兩種或更多種多肽之複合物可經由連接子多肽連接於橋接部分之C端。舉例而言，連接子多肽可包括包含選自
表 6中所列之序列中之任一者的序列的多肽。
本發明之蛋白質可包含重鏈及輕鏈。舉例而言，本發明之重鏈可自N端至C端包含：CTLA4之細胞外域或其功能性片段；橋接部分，其在N端處包含鉸鏈多肽之至少一部分及人類IgG1 Fc之多肽之CH2及CH3域；連接子多肽；及包含VH域及CH1域的抗OX40L Fab之重鏈。重鏈可在CH1域之C端處另外包含部分IgG1鉸鏈序列(例如包含胺基酸序列SEQ ID NO: 336之多肽)，其包含能夠與輕鏈恆定域(CL)中之半胱胺酸殘基形成二硫鍵的半胱胺酸殘基。
表 7列出本發明之例示性重鏈序列。
本發明之輕鏈自N端至C端可包含：抗OX40L Fab之VL域及CL域。
表 7列出本發明之例示性輕鏈序列。
在組合中，依表7中所列之重鏈及輕鏈例如藉由二硫鍵締合，且可特異性結合於CD80及CD86以及OX40L。如本發明之蛋白質中所涵蓋，鉸鏈多肽及人類IgG1 Fc之多肽之CH3域可促成兩條重鏈發生二聚合，從而產生包含兩條重鏈及兩條輕鏈之蛋白質。
表
7
：例示性重鏈及輕鏈序列
| 重鏈 | 輕鏈 | |
| 67B06(1) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 40) | SYELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 39) |
| 67B06(2) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 62) | SYELTQPLSVSVALGQTARITCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 61) |
| 67B06(3) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 64) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| 67B06(4) | KAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 182) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| 67B06(5) | MHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 183) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| 67B06(6) | KAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 184) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| 67B06(7) | MHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 185) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| 67B06(8) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 186) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| 89B09(1) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLVESGPGLVKPSETLSLTCTVSGVSIRSNGYYWGWIRQSPGKGLEWIGNMDYSGTYQNPSLTSRVTISGDASKNQFSLKLRSVTAADTAVYFCARERSNNWYPIDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 48) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPILVISGKDTRPSGIPDRFSGSISGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 47) |
| 89B09(2) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCTVSGVSIRSSGYYWGWIRQPPGKGLEWIGNIDYSGTYQNPSLTSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARERSNNWYPIDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 68) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67) |
| 89B09(3) | KAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLVESGPGLVKPSETLSLTCTVSGVSIRSNGYYWGWIRQSPGKGLEWIGNMDYSGTYQNPSLTSRVTISGDASKNQFSLKLRSVTAADTAVYFCARERSNNWYPIDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 187) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67) |
| 89B09(4) | MHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLVESGPGLVKPSETLSLTCTVSGVSIRSNGYYWGWIRQSPGKGLEWIGNMDYSGTYQNPSLTSRVTISGDASKNQFSLKLRSVTAADTAVYFCARERSNNWYPIDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 188) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67) |
| 89B09(5) | KAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLVESGPGLVKPSETLSLTCTVSGVSIRSNGYYWGWIRQSPGKGLEWIGNMDYSGTYQNPSLTSRVTISGDASKNQFSLKLRSVTAADTAVYFCARERSNNWYPIDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 189) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67) |
| 89B09(6) | MHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLVESGPGLVKPSETLSLTCTVSGVSIRSNGYYWGWIRQSPGKGLEWIGNMDYSGTYQNPSLTSRVTISGDASKNQFSLKLRSVTAADTAVYFCARERSNNWYPIDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 190) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67) |
| 89B09(7) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLVESGPGLVKPSETLSLTCTVSGVSIRSNGYYWGWIRQSPGKGLEWIGNMDYSGTYQNPSLTSRVTISGDASKNQFSLKLRSVTAADTAVYFCARERSNNWYPIDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 191) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67) |
| 98E10(1) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCTVAGASVSSSSYYWGWIRQSPGKGLEWIGTINYGGSTYHNPSLKRRVTVSVDTSKNQFSLKLTSVTAADTAVYYCARHRGIYHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 46) | SYELTQPLSVSVALGQTARITCGGNNIENKNVHWYQQMPGQAPVLVIYRDSNRPSGIPERFSGSNSGNTATLTINRAQAGDEADYYCQVWDSNTVVFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 45) |
| 98E10(2) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCTVSGASVSSSSYYWGWIRQPPGKGLEWIGTINYGGSTYHNPSLKRRVTISVDTSKNQFSLKLSSVTAADTAVYYCARHRGIYHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 66) | SYELTQPLSVSVALGQTARITCGGNNIENKNVHWYQQKPGQAPVLVIYRDSNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVWDSTTVVFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 65) |
| 98E10(3) | KAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCTVAGASVSSSSYYWGWIRQSPGKGLEWIGTINYGGSTYHNPSLKRRVTVSVDTSKNQFSLKLTSVTAADTAVYYCARHRGIYHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 192) | SYELTQPLSVSVALGQTARITCGGNNIENKNVHWYQQKPGQAPVLVIYRDSNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVWDSTTVVFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 65) |
| 98E10(4) | MHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCTVAGASVSSSSYYWGWIRQSPGKGLEWIGTINYGGSTYHNPSLKRRVTVSVDTSKNQFSLKLTSVTAADTAVYYCARHRGIYHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 193) | SYELTQPLSVSVALGQTARITCGGNNIENKNVHWYQQKPGQAPVLVIYRDSNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVWDSTTVVFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 65) |
| 98E10(5) | KAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCTVAGASVSSSSYYWGWIRQSPGKGLEWIGTINYGGSTYHNPSLKRRVTVSVDTSKNQFSLKLTSVTAADTAVYYCARHRGIYHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 194) | SYELTQPLSVSVALGQTARITCGGNNIENKNVHWYQQKPGQAPVLVIYRDSNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVWDSTTVVFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 65) |
| 98E10(6) | MHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCTVAGASVSSSSYYWGWIRQSPGKGLEWIGTINYGGSTYHNPSLKRRVTVSVDTSKNQFSLKLTSVTAADTAVYYCARHRGIYHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 195) | SYELTQPLSVSVALGQTARITCGGNNIENKNVHWYQQKPGQAPVLVIYRDSNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVWDSTTVVFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 65) |
| 98E10(7) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCTVAGASVSSSSYYWGWIRQSPGKGLEWIGTINYGGSTYHNPSLKRRVTVSVDTSKNQFSLKLTSVTAADTAVYYCARHRGIYHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 196) | SYELTQPLSVSVALGQTARITCGGNNIENKNVHWYQQKPGQAPVLVIYRDSNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVWDSTTVVFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 65) |
| 98C01(1) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGGIGSVDYSGNTYYKPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYHCARHRGIYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 50) | SYELTQPPSVSVALGQTARITCGGNNIENKNVHWYQQKPGQAPVLVIYRDSNRPSGIPERFSGSNSGNTATLSINRAQAGDEADYYCQVWDSNTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 49) |
| 98C01(2) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGGIGSVDYSGNTYYKPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYHCARHRGIYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 70) | SYELTQPPSMSVAPGQTARITCGGSNIEDKNVHWYQQKPGQAPVLVIKRDSDRPSGIPERFSGSNSGNTATLTISRAQAGDEAEYYCQVWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 69) |
| 98C01(3) | KAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGGIGSVDYSGNTYYKPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYHCARHRGIYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 197) | SYELTQPPSMSVAPGQTARITCGGSNIEDKNVHWYQQKPGQAPVLVIKRDSDRPSGIPERFSGSNSGNTATLTISRAQAGDEAEYYCQVWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 69) |
| 98C01(4) | MHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGGIGSVDYSGNTYYKPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYHCARHRGIYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 198) | SYELTQPPSMSVAPGQTARITCGGSNIEDKNVHWYQQKPGQAPVLVIKRDSDRPSGIPERFSGSNSGNTATLTISRAQAGDEAEYYCQVWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 69) |
| 98C01(5) | KAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGGIGSVDYSGNTYYKPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYHCARHRGIYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 199) | SYELTQPPSMSVAPGQTARITCGGSNIEDKNVHWYQQKPGQAPVLVIKRDSDRPSGIPERFSGSNSGNTATLTISRAQAGDEAEYYCQVWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 69) |
| 98C01(6) | MHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGGIGSVDYSGNTYYKPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYHCARHRGIYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 200) | SYELTQPPSMSVAPGQTARITCGGSNIEDKNVHWYQQKPGQAPVLVIKRDSDRPSGIPERFSGSNSGNTATLTISRAQAGDEAEYYCQVWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 69) |
| 98C01(7) | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGGIGSVDYSGNTYYKPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYHCARHRGIYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 201) | SYELTQPPSMSVAPGQTARITCGGSNIEDKNVHWYQQKPGQAPVLVIKRDSDRPSGIPERFSGSNSGNTATLTISRAQAGDEAEYYCQVWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 69) |
| 97G07 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGGIGSVDYSGNTYYKPSLKSRVTISVDTSKNQFSLKLSTVTAADTAVYHCARHRGIYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 38) | YYELTQPLSVSVALGQTARIPCGGNNIENKNVHWYQQKPGQAPVLVIYRDSNRPSGIPERFSGSNSGNTATLSINRAQAGDEADYYCQVWDSNTVIFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 5) |
| 97G07(2) | EPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGGIGSVDYSGNTYYKPSLKSRVTISVDTSKNQFSLKLSTVTAADTAVYHCARHRGIYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 73) | YYELTQPLSVSVALGQTARIPCGGNNIENKNVHWYQQKPGQAPVLVIYRDSNRPSGIPERFSGSNSGNTATLSINRAQAGDEADYYCQVWDSNTVIFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 5) |
| 68F03 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCTVSGGSIDTSSQYWAWIRQPPGKGLEWIGGIYFSGSTYQNPSLKSRVTTSVDTSKNQFSLRLSSMTAADTAVYYCARHRGIYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 42) | SFELTQPLSVSVALGQTARITCGGINIENKNVHYYQQKPGQAPVLVIYRDTNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVWDSNTVIFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 41) |
| 84E11 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCTVSGGSISSGSFYWGWIRQPPGKGLEWIGTIYYSGSTYYNPSLKSRVAISVDTSKNQFYLNLNFVTAADTAVYHCARERSSSWYPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 44) | SSELTQDPAVSVALGQTVRITCQGDSLRNYFANWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYHVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 43) |
| 88B06 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMSWVRQAPGKGLEWVSVISGSGDSTYYAESVKGRFTISRDNSKNTLYLQMTSLRAEDTAEYYCAKDRTPVYGLDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 52) | SYELTQPLSVSVALGQTARISCGGNNIGRKNVHWYQQKPGQAPVLVIYGDSNRPSGIPERFSGSNSGNTATLTIGRAQAGDEADYYCQVWDSSTVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 51) |
| 95B06 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMTWVRQAPGKGLEWVSDISGSGGSTKYADSVKGRFTISRDNPKNTLYLQMNSLRAEDTAVYYCAKDLGFYSTWDTDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 54) | DMQMTQSPSSLSASVGDRVTITCRASQGIRNDLDWYQQKPGKVPKRLIHAASSLQSGVPSRFSGSGSGTEFTLTISSLQPEDFVTYYCLQHNTYPWTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 53) |
| 30F02 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGPGLVKPSETLSLTCTVSGASISSSNHYWGWGWIRQPPGKGLEWIGSIYYSGNTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARHRGSYFFDHWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 56) | SYVLTQPLSVSVALGQTARITCGGNNIGDKNVHWYQQKPGQAPVLVISRDSNRPSGIPERFSGSNSGNTATLTISRAQAGDESDYYCQVWDSSTVVFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 55) |
| 85F12 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAVWNWIRQSPSRGLEWLGRTDYRSKWNNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCARGDAGMASFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 58) | SSELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKAGQSPVVVIYQDRKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQTWDRRTAVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 57) |
| 85F10 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPSSIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLLESGAGLLKPSETLSLTCAVYGGSFSDYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARKRGANFFDDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 60) | SYELTQPLSVSVALGQTARITCGGNNIENKNVHWYQQKPGQAPVLVIKRDSNRPSGIPERLSGSNSGNTATLTISRAQAGDEADYYCQVWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 59) |
| CTLA4_anti OX40L融合4 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTSPPSPAPELLGGSSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFNSYAMSWVRQAPGKGLEWVSIISGSGGFTYYADSVKGRFTISRDNSRTTLYLQMNSLRAEDTAVYYCAKDRLVAPGTFDYWGQGALVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 37) | DIQMTQSPSSLSASVGDRVTITCRASQGISSWLAWYQQKPEKAPKSLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYNSYPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 35) |
| Larsen 變異體_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYEGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 256) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體1_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKHTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICMVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 257) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體2_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKKTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICMVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 258) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體3_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKTTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICMVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 259) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體4_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKWTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICMVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 260) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體5_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICMVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 261) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體6_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKHTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 262) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體7_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKKTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 263) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體8_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKTTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 264) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體9_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKWTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 265) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體10_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 266) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體11_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKHTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 267) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體12_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKKTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 268) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體13_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKTTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 269) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體14_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKWTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 270) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體15_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 271) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體16_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKHTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 272) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體17_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKKTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 273) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體18_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKTTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 274) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體19_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKWTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 275) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Xu變異體20_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 276) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Bernett變異體1_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKHTEVRVTVLRQADSQVTEVCFANYYMGNELTFDDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSD QEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 277) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Bernett變異體2_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKKTEVRVTVLRQADSQVTEVCFANYYMGNELTFDDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSD QEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 278) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Bernett變異體3_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKWTEVRVTVLRQADSQVTEVCFANYYMGNELTFDDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSD QEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 279) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Bernett變異體4_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCFANYYMGNELTFDDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSD QEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 280) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Bernett變異體5_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKHTEVRVTVLRQADSQVTEVCFANYYMGNELTFEDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 281) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Bernett變異體6_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKKTEVRVTVLRQADSQVTEVCFANYYMGNELTFEDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 282) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Bernett變異體7_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKWTEVRVTVLRQADSQVTEVCFANYYMGNELTFEDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 283) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Bernett變異體8_67B06 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCFANYYMGNELTFEDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 284) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Oshima 變異體_67B06 | MHVAQPAVVLASSRGIASFVCEYESPGKANEIRVTVLRQADSQVTEVCAMTYMKEDELTFLDDPSCTGTFSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYEGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 285) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Douthwaite變異體1_67B06 | MHVAQPAVVLASSRGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEATFLDDSICTGTASGNQVNLTIRGLRAQDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 286) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Douthwaite變異體2_67B06 | MHVAQPAVVLASSVGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEATFLDDSICTGTASGNQVNLTIRGLRAQDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 287) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Douthwaite變異體3_67B06 | MHVAQPAVVLASSRGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEGTFLDDSICTGTASGNQVNLTIRGLRAQDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 288) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Douthwaite變異體4_67B06 | MHVAQPAVVLASSVGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEGTFLDDSICTGTASGNQVNLTIRGLRAQDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 289) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Douthwaite變異體5_67B06 | MHVAQPAVVLASSRGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEATFLDDSICTGTASGNQVNLTIRGLRASDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 290) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Douthwaite變異體6_67B06 | MHVAQPAVVLASSVGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEATFLDDSICTGTASGNQVNLTIRGLRASDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 291) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Douthwaite變異體7_67B06 | MHVAQPAVVLASSRGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEGTFLDDSICTGTASGNQVNLTIRGLRASDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 292) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Douthwaite變異體8_67B06 | MHVAQPAVVLASSVGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEGTFLDDSICTGTASGNQVNLTIRGLRASDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSQLQLQESGGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 293) | SSELTQPLSVSVALGQTARMTCGGSDIENKNVHWYQQKPGQAPVLVIHRDNNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVRDSNIVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 63) |
| Larsen 變異體_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYEGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 294) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體1_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKHTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICMVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 295) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體2_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKKTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICMVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 296) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體3_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKTTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICMVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 297) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體4_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKWTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICMVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 298) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體5_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICMVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 299) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體6_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKHTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 300) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體7_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKKTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 301) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體8_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKTTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 302) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體9_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKWTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 303) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體10_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 304) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體11_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKHTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 305) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體12_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKKTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 306) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體13_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKTTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 307) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體14_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKWTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 308) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體15_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCAAYYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 309) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體16_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKHTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 310) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體17_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKKTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 311) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體18_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKTTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 312) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體19_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKWTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 313) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Xu變異體20_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCAANYMMGNEGTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVEKMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 314) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Bernett變異體1_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKHTEVRVTVLRQADSQVTEVCFANYYMGNELTFDDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSD AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 315) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Bernett變異體2_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKKTEVRVTVLRQADSQVTEVCFANYYMGNELTFDDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSD AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 316) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Bernett變異體3_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKWTEVRVTVLRQADSQVTEVCFANYYMGNELTFDDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSD AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 317) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Bernett變異體4_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCFANYYMGNELTFDDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSD AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 318) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Bernett變異體5_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKHTEVRVTVLRQADSQVTEVCFANYYMGNELTFEDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 319) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Bernett變異體6_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKKTEVRVTVLRQADSQVTEVCFANYYMGNELTFEDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 320) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Bernett變異體7_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKWTEVRVTVLRQADSQVTEVCFANYYMGNELTFEDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 321) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Bernett變異體8_89B09 | MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCFANYYMGNELTFEDDSICTGTSSGNQVNLTIQGLRAMDTGLYICQVELMYPPPYYEGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 322) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Oshima 變異體_89B09 | MHVAQPAVVLASSRGIASFVCEYESPGKANEIRVTVLRQADSQVTEVCAMTYMKEDELTFLDDPSCTGTFSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYEGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 323) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Douthwaite變異體1_89B09 | MHVAQPAVVLASSRGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEATFLDDSICTGTASGNQVNLTIRGLRAQDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 324) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Douthwaite變異體2_89B09 | MHVAQPAVVLASSVGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEATFLDDSICTGTASGNQVNLTIRGLRAQDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 325) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Douthwaite變異體3_89B09 | MHVAQPAVVLASSRGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEGTFLDDSICTGTASGNQVNLTIRGLRAQDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 326) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Douthwaite變異體4_89B09 | MHVAQPAVVLASSVGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEGTFLDDSICTGTASGNQVNLTIRGLRAQDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 327) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Douthwaite變異體5_89B09 | MHVAQPAVVLASSRGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEATFLDDSICTGTASGNQVNLTIRGLRASDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 328) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Douthwaite變異體6_89B09 | MHVAQPAVVLASSVGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEATFLDDSICTGTASGNQVNLTIRGLRASDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 329) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Douthwaite變異體7_89B09 | MHVAQPAVVLASSRGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEGTFLDDSICTGTASGNQVNLTIRGLRASDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 330) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| Douthwaite變異體8_89B09 | MHVAQPAVVLASSVGRASFVCEYTNPSKATEVRVTVLRQADSQVTEVCAATYMKGNEGTFLDDSICTGTASGNQVNLTIRGLRASDTGLYICQVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREGPGLVKPSETLSLTCSVSGGSISTSSYYWGWIRQPPGKGLEWSGSIYYSGSTYYRPSLQGRATISVDTSKNQFSLKLTSVTAADTAVYYCARHRGSYFFDIWGLGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC (SEQ ID NO: 331) | SSELTQDPAVSVALGQTVRITCQGDSVRRFFAHWYQQKPGQAPVLVISGKDTRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGYLVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 67)) |
| US 9139653變異體1 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSNYAMNWVRQAPGKGLEWVSTISGSGGATRYADSVKGRFTISRDNSRNTVYLQMNSLRVEDTAVFYCTKDRLIMATVRGPYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRV (SEQ ID NO: 332) | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPNLLIYAASSLQSGVPSRFSGSGSETDFTLTISSLQPEDFATYYCQQSHSVSFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 253) |
| US 7501496變異體1 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFNSYAMSWVRQAPGKGLEWVSIISGSGGFTYYADSVKGRFTISRDNSRTTLYLQMNSLRAEDTAVYYCAKDRLVAPGTFDYWGQGALVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV (SEQ ID NO: 333) | DIQMTQSPSSLSASVGDRVTITCRASQGISSWLAWYQQKPEKAPKSLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYNSYPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 255) |
| US 9139653變異體2 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSNYAMNWVRQAPGKGLEWVSTISGSGGATRYADSVKGRFTISRDNSRNTVYLQMNSLRVEDTAVFYCTKDRLIMATVRGPYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRV (SEQ ID NO: 334) | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPNLLIYAASSLQSGVPSRFSGSGSETDFTLTISSLQPEDFATYYCQQSHSVSFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 253) |
| US 7501496變異體2 | AMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDQEPKSSDKTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALAAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFNSYAMSWVRQAPGKGLEWVSIISGSGGFTYYADSVKGRFTISRDNSRTTLYLQMNSLRAEDTAVYYCAKDRLVAPGTFDYWGQGALVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV (SEQ ID NO: 335) | DIQMTQSPSSLSASVGDRVTITCRASQGISSWLAWYQQKPEKAPKSLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYNSYPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 255) |
本文中亦提供選自
表 7中所列之胺基酸序列中之任一者的重鏈在製備蛋白質中之用途，其中該重鏈與選自
表 7中所列之胺基酸序列中之任一者的輕鏈締合(例如經由二硫鍵)。
本發明中亦考慮編碼本發明蛋白質之核酸。編碼本文所揭示之蛋白質的核酸可使用標準生物資訊學方法進行密碼子優化以用於最佳表現。亦考慮包含一或多種編碼本發明之蛋白質之核酸的細胞且其可藉由標準轉染或轉導方法(例如電穿孔、氯化鈣轉染、脂質體轉染、慢病毒遞送或腺相關病毒遞送)產生。
I.E 蛋白質之特徵
本發明之蛋白質能夠特異性結合CD80及/或CD86及OX40L。在一些實施例中，依藉由本領域中已知之多種分析中之任一者所量測，本發明之蛋白質係以高親和力結合於CD80及/或CD86及OX40L。本發明之蛋白質的結合及免疫抑制活性可與CTLA4-Ig及/或抗OX40L參考分子進行比較。
CTLA4-Ig (Ref3_CTLA4Ig) 
CTLA4-IgG_ 變異體 
IgG1_Fc_ 變異體 -CTLA4 
Ref2_ 抗 _OX40L重鏈序列
輕鏈序列
美國專利 9,139,653 (Ref1_ 抗 OX40L)重鏈可變域(VH)
輕鏈可變域(VL)
舉例而言，本文所述之蛋白質可特異性結合且中和APC表面上之OX40L，由此抑制T細胞協同刺激信號傳導及活化。在一些實施例中，依以下實例3中所述的OX40L中和/OX40-HEK報導子分析中所量測，本發明之蛋白質之IC
50小於12 nM。在一些實施例中，依OX40L中和/OX40-HEK報導子分析中所量測，本發明之蛋白質之IC
50為5 nM至12 nM、5 nM至11.5 nM、5 nM至11 nM、5 nM至11.5 nM、5 nM至10 nM、5 nM至10.5 nM或5 nM至9 nM。
T細胞活化之抑制亦可使用依以下實例3中所述之初級T細胞活化分析量測。舉例而言，在一些實施例中，依初級T細胞活化分析中所量測，本發明之蛋白質之IC
50為2 nM至12 nM、2 nM至11.5 nM、2 nM至11 nM、2 nM至10.5 nM、2 nM至10 nM或2 nM至9.5 nM。
在一些實施例中，依Biacore分析(描述於下文實例3中)中所量測，本發明之蛋白質以小於75 nM之K
D結合於OX40L。舉例而言，在一些實施例中，依Biacore分析中所量測，OX40L結合之K
D為20 nM至75 nM、20 nM至70 nM、20 nM至65 nM、20 nM至60 nM、25 nM至75 nM、25 nM至70 nM、25 nM至65 nM、25 nM至60 nM、30 nM至75 nM、30 nM至70 nM、30 nM至65 nM及30 nM至60 nM。
阻斷T細胞協同刺激信號傳導會抑制T細胞活化及促炎性介體產生。在一些實施例中，本文所述之蛋白質顯著抑制至少一或多種促炎性細胞介素之產生，包括(但不限於) IL-2、IFNγ、IL-6或TNFα。抑制促炎性細胞介素產生可使用活體外混合淋巴球反應分析，且由使用本文所述之蛋白質處理之細胞與在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig (在人類IgG1 Fc域之N端處融合的人類CTLA4之細胞外域；SEQ ID NO: 34)及抗OX40L抗體(SEQ ID NO: 35及SEQ ID NO: 36；SEQ ID NO: 30及SEQ ID NO: 31)(獨立存在或以分開存在的兩種蛋白質之組合形式存在)下處理的細胞進行比較來量測。舉例而言，在一些實施例中，相較於在相同條件下但不存在蛋白質下處理之細胞，本文所述之蛋白質在混合淋巴球反應分析中抑制細胞產生至少一種促炎性細胞介素至少10%、至少20%、至少30%、至少40%、至少50%或至少60%。
T細胞協同刺激阻斷亦引起對T細胞增殖之抑制。在一些實施例中，相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig (在人類IgG1 Fc域之N端處融合的人類CTLA4之細胞外域；SEQ ID NO: 34)及抗OX40L抗體(SEQ ID NO: 35及SEQ ID NO: 36；SEQ ID NO: 30及SEQ ID NO: 31)(獨立存在或以分開存在的兩種蛋白質之組合形式存在)下處理的同種異體反應性CD4
+及CD8
+T細胞，本文所述之蛋白質在活體外混合淋巴球反應分析中顯著抑制同種異體反應性CD4
+及CD8
+T細胞增殖。舉例而言，在一些實施例中，相較於在相同條件下但不存在蛋白質下處理之細胞，本文所述之蛋白質在混合淋巴球反應分析中抑制CD4
+及CD8
+T細胞增殖至少10%、至少20%、至少30%、至少40%或至少50%。
在某些實施例中，相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig (在人類IgG1 Fc域之N端處融合的人類CTLA4之細胞外域；SEQ ID NO: 34)及抗OX40L抗體(SEQ ID NO: 35及SEQ ID NO: 36；SEQ ID NO: 30及SEQ ID NO: 31)(獨立存在或以分開存在的兩種蛋白質之組合形式存在)下處理的同種異體反應性CD4
+及CD8
+T細胞，本文所述之蛋白質在活體外混合淋巴球反應分析中相比於調節T細胞(T
reg或Treg)增殖，優先抑制同種異體反應性CD4
+及CD8
+T細胞增殖。舉例而言，在一些實施例中，相較於在相同條件下但不存在蛋白質下處理之細胞，用本文所述之蛋白質處理的混合淋巴球反應分析使T
reg:T
效應細胞比率增加至少10%、至少20%、至少30%、至少40%、至少50%或至少60%。
協同刺激CD28及OX40活化之抑制可促成T
reg細胞分化。在一些實施例中，相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig (在人類IgG1 Fc域之N端處融合的人類CTLA4之細胞外域；SEQ ID NO: 34)及抗OX40L抗體(SEQ ID NO: 35及SEQ ID NO: 36；SEQ ID NO: 30及SEQ ID NO: 31)(獨立存在或以分開存在的兩種蛋白質之組合形式存在)下處理的T
reg細胞，本文中所述之蛋白質在活體外混合淋巴球反應分析中顯著增強T
reg抑制功能。舉例而言，在一些實施例中，相較於在相同條件下但不存在蛋白質下處理之細胞，用本文所述之蛋白質處理的混合淋巴球反應分析使與T
reg之共培養物中之增殖T
效應(Teff或T
eff)細胞之數目減少至少10%、至少20%、至少30%、至少40%、至少50%或至少60%。
在一些實施例中，相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig (在人類IgG1 Fc域之N端處融合的人類CTLA4之細胞外域；SEQ ID NO: 34)及抗OX40L抗體(SEQ ID NO: 35及SEQ ID NO: 36；SEQ ID NO: 30及SEQ ID NO: 31)(獨立存在或以分開存在的兩種蛋白質之組合形式存在)下處理的小鼠中之同種異體反應性CD4
+及CD8
+T細胞，本發明之蛋白質在授受性轉移分析中顯著抑制人類化小鼠中的同種異體反應性CD4
+及CD8
+T細胞增殖。舉例而言，在一些實施例中，相較於在相同條件下但不存在蛋白質下處理之小鼠，用本文所述之蛋白質處理之小鼠在授受性轉移分析中使增殖同種異體反應性CD4
+及CD8
+T細胞之數目減少至少10%、至少20%、至少30%、至少40%、至少50%或至少60%。
在一些實施例中，相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig (在人類IgG1 Fc域之N端處融合的人類CTLA4之細胞外域；SEQ ID NO: 34)及抗OX40L抗體(SEQ ID NO: 35及SEQ ID NO: 36；SEQ ID NO: 30及SEQ ID NO: 31)(獨立存在或以分開存在的兩種蛋白質之組合形式存在)下處理的小鼠，本文所述之蛋白質在授受性轉移分析中顯著抑制人類化小鼠中之血清IFNγ水準。舉例而言，在一些實施例中，相較於在相同條件下但不存在蛋白質下處理之小鼠，用本文所述之蛋白質處理之小鼠在授受性轉移分析中使血清IFNγ水準減少至少10%、至少20%、至少30%、至少40%、至少50%或至少60%。
在本發明之一些實施例中，本文所述之蛋白質未顯著內化於源於骨髓之樹突狀細胞(MDDC)中。
在一些實施例中，本文所述之蛋白質與食蟹獼猴OX40L具有交叉反應性。舉例而言，依藉由表面電漿子共振(SPR)所量測，本發明之蛋白質可以20 nM至120 nM、40 nM至120 nM、60 nM至120 nM、80 nM至120 nM、20 nM至100 nM、40 nM至100 nM、60 nM至100 nM、80 nM至100 nM、20 nM至80 nM、40 nM至80 nM或60 nM至80 nM之K
D結合食蟹獼猴OX40L。在某些實施例中，本發明之蛋白質與小鼠、兔或大鼠OX40L不具有交叉反應性。舉例而言，當利用表面電漿子共振(SPR)藉由穩態親和力分析量測時，本發明之蛋白質係以大於200 nM、大於250 nM或大於500 nM之K
D結合於小鼠、兔或大鼠OX40L。在一些實施例中，本發明之蛋白質與食蟹獼猴CD80及CD86具有交叉反應性。舉例而言，依利用表面電漿子共振(SPR)藉由穩態親和力分析所量測，本發明之蛋白質可以20 nM至120 nM、40 nM至120 nM、60 nM至120 nM、80 nM至120 nM、20 nM至100 nM、40 nM至100 nM、60 nM至100 nM、80 nM至100 nM、20 nM至80 nM、40 nM至80 nM或60 nM至80 nM之K
D結合食蟹獼猴CD80及CD86。
II 抗體
本發明亦提供特異性結合OX40L之抗體。在一些實施例中，特異性結合OX40L之抗體包含選自
表 2中所列之序列的重鏈可變域(VH)及輕鏈可變域(VL)。
在一些實施例中，本文所述之抗體的重鏈可變域及輕鏈可變域包含選自
表 2中所列之共同VH及VL序列的VH及VL CDR序列。
除非另外指明，否則
表 2中所提供之CDR序列係根據IMGT獨特編號方案確定。
在一些實施例中，本發明抗體可為IgG、IgM、IgA、IgD或IgE。在某些實施例中，本文所述之抗體為IgG1、IgG1、IgG3或IgG4。在某些實施例中，本發明之抗體為人類IgG1抗體。
在某些實施例中，特異性結合於OX40L之抗體包含選自SEQ ID NO: 220或SEQ ID NO: 221之共同序列的VHCDR3序列。
在一些實施例中，特異性結合於OX40L之抗體包含：包含胺基酸序列SEQ ID NO: 222之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列SEQ ID NO: 223、SEQ ID NO: 224或SEQ ID NO: 225之重鏈可變互補決定區2 (VHCDR2)；及包含以下之胺基酸序列之重鏈可變互補決定區3 (VHCDR3)：SEQ ID NO: 220或SEQ ID NO: 221。
在一些實施例中，特異性結合於OX40L之抗體包含：包含胺基酸序列SEQ ID NO: 226或SEQ ID NO: 227之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列SEQ ID NO: 82、SEQ ID NO: 228或SEQ ID NO: 90之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列SEQ ID NO: 231或SEQ ID NO: 232之輕鏈可變互補決定區3 (VLCDR3)。
在一些實施例中，特異性結合於OX40L之抗體包含：包含胺基酸序列SEQ ID NO: 222之VHCDR1；包含胺基酸序列SEQ ID NO: 223之VHCDR2；包含胺基酸序列SEQ ID NO: 220之VHCDR3；包含胺基酸序列SEQ ID NO: 226之VLCDR1；包含胺基酸序列SEQ ID NO: 82之VLCDR2；及包含胺基酸序列SEQ ID NO: 231之VLCDR3。
在一些實施例中，特異性結合OX40L之抗體包含：包含胺基酸序列SEQ ID NO: 222之VHCDR1；包含胺基酸序列SEQ ID NO: 224之VHCDR2；包含胺基酸序列SEQ ID NO: 221之VHCDR3；包含胺基酸序列SEQ ID NO: 227之VLCDR1；包含胺基酸序列SEQ ID NO: 228之VLCDR2；及包含胺基酸序列SEQ ID NO: 232之VLCDR3。
在一些實施例中，根據IMGT獨特編號方案，特異性結合於OX40L之抗體包含VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3，其各自包含分別對應於
表 2之VHCDR及VLCDR共同序列的VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3序列的胺基酸序列。
在某些實施例中，特異性結合OX40L之抗體包含抗體重鏈(HC)，其包含與
表 3中所揭示之抗體之HC具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及抗體輕鏈(LC)，其包含與
表 3中所揭示之同一抗體之LC具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。在某些實施例中，特異性結合OX40L之抗體包含抗體重鏈可變域(VH)，其包含與
表 3中所揭示之抗體之VH具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及抗體輕鏈可變域(VL)，其包含與
表 3中所揭示之同一抗體之VL具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。在某些實施例中，抗體包含
表 3中所揭示之VH及VL序列的重鏈CDR1、CDR2及CDR3以及輕鏈CDR1、CDR2及CDR3，其根據IMGT獨特編號方案，Kabat (參見Kabat等人, (1991) Sequences of Proteins of Immunological Interest, NIH公開案第91-3242號, Bethesda)、Chothia (參見例如Chothia C及Lesk A M, (1987), J. Mol. Biol. 196: 901-917)、MacCallum (參見MacCallum R M等人, (1996) J. Mol. Biol. 262: 732-745)，或此項技術中已知的任何其他CDR確定方法確定。
在某些實施例中，特異性結合於OX40L之抗體包括包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈互補決定區1 (VHCDR1)、包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈互補決定區2 (VHCDR2)、包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈互補決定區3 (VHCDR3)、包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈互補決定區1 (VLCDR1)、包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈互補決定區2 (VLCDR2)及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈互補決定區3 (VLCDR3)。
在一些實施例中，特異性結合於OX40L之抗體包括包含胺基酸序列GVSIRSNGYY (SEQ ID NO: 93)之VHCDR1、包含胺基酸序列MDYSGT (SEQ ID NO: 94)之VHCDR2、包含胺基酸序列ARERSNNWYPIDY (SEQ ID NO: 95)之VHCDR3、包含胺基酸序列SVRRFF (SEQ ID NO: 97)之VLCDR1、包含胺基酸序列GKD (SEQ ID NO: 98)之VLCDR2及包含胺基酸序列NSRDSSGYLVL (SEQ ID NO: 99)之VLCDR3。
在一些實施例中，特異性結合於OX40L之抗體包括包含胺基酸序列GASVSSSSYY (SEQ ID NO: 85)之VHCDR1、包含胺基酸序列INYGGST (SEQ ID NO: 86)之VHCDR2、包含胺基酸序列ARHRGIYHFDY (SEQ ID NO: 87)之VHCDR3、包含胺基酸序列NIENKN (SEQ ID NO: 89)之VLCDR1、包含胺基酸序列RDS (SEQ ID NO: 90)之VLCDR2及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之VLCDR3。
在一些實施例中，特異性結合於OX40L之抗體包括包含胺基酸序列GGSISSSSYY (SEQ ID NO: 101)之VHCDR1、包含胺基酸序列IGSVDYSGNT (SEQ ID NO: 102)之VHCDR2、包含胺基酸序列ARHRGIYFFDY (SEQ ID NO: 103)之VHCDR3、包含胺基酸序列NIENKN (SEQ ID NO: 89)之VLCDR1、包含胺基酸序列RDS (SEQ ID NO: 90)之VLCDR2及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之VLCDR3。
在一些實施例中，特異性結合於OX40L之抗體包括包含胺基酸序列GFTFSNYA (SEQ ID NO: 133)之VHCDR1、包含胺基酸序列ISGSGGAT (SEQ ID NO: 113)之VHCDR2、包含胺基酸序列TKDRLIMATVRGPYYYGMDV (SEQ ID NO: 114)之VHCDR3、包含胺基酸序列QSISSY (SEQ ID NO: 121)之VLCDR1、包含胺基酸序列AAS (SEQ ID NO: 146)之VLCDR2及包含胺基酸序列QQSHSVSFT (SEQ ID NO: 154)之VLCDR3。
在一些實施例中，特異性結合於OX40L之抗體包括包含胺基酸序列SYAMS (SEQ ID NO: 105)之VHCDR1、包含胺基酸序列IISGSGGFTYYADSVK (SEQ ID NO: 106)之VHCDR2、包含胺基酸序列DRLVAPGTFDY (SEQ ID NO: 107)之VHCDR3、包含胺基酸序列RASQGISSWLA (SEQ ID NO: 169)之VLCDR1、包含胺基酸序列AASSLQS (SEQ ID NO: 170)之VLCDR2及包含胺基酸序列QQYNSYPYT (SEQ ID NO: 171)之VLCDR3。
在某些實施例中，特異性結合OX40L之抗體包含 VH，其包含與SEQ ID NO: 76具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及VL，其包含與SEQ ID NO: 80具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗體包含VH，其包含與SEQ ID NO: 92具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及VL，其包含與SEQ ID NO: 96具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗體包含VH，其包含與SEQ ID NO: 84具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及VL，其包含與SEQ ID NO: 88具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗體包含VH，其包含與SEQ ID NO: 100具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及VL，其包含與SEQ ID NO: 104具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗體包含VH，其包含與SEQ ID NO: 31具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及VL，其包含與SEQ ID NO: 30具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗體包含VH，其包含與SEQ ID NO: 33具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及VL，其包含與SEQ ID NO: 32具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗體包含HC，其包含與SEQ ID NO: 8具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及LC，其包含與SEQ ID NO: 7具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗體包含HC，其包含與SEQ ID NO: 16具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及LC，其包含與SEQ ID NO: 15具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗體包含HC，其包含與SEQ ID NO: 14具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及LC，其包含與SEQ ID NO: 13具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
在某些實施例中，特異性結合OX40L之抗體包含HC，其包含與SEQ ID NO: 18具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列；及LC，其包含與SEQ ID NO: 17具有至少90% (例如至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%或100%)一致性之胺基酸序列。
III 治療性應用
本發明亦提供含有治療有效量之本文所揭示之蛋白質的醫藥調配物。醫藥調配物包含一或多種賦形劑且維持在一定pH下。如本文所用，術語「賦形劑」意謂添加至調配物中以提供所需物理或化學特性，例如pH、容積滲透濃度、黏度、清晰度、顏色、等張性、氣味、無菌性、穩定性、溶解或釋放速率、吸收或滲透的任何非治療劑。
本申請案提供使用本文所述之蛋白質及/或本文所述之醫藥調配物治療自體免疫疾病之方法。該等方法可用於治療多種自體免疫疾病，其包括(但不限於)類風濕性關節炎、幼年特發性關節炎、牛皮癬性關節炎、異位性皮膚炎、弛緩不能、阿狄森氏病、成人斯蒂爾氏病、無γ球蛋白血症、斑禿、澱粉樣變性病、僵直性脊椎炎、抗GBM/抗TBM腎炎、抗磷脂症候群、自體免疫血管性水腫、自體免疫自主神經障礙、自體免疫腦脊髓炎、自體免疫肝炎、自體免疫內耳疾病(AIED)、自體免疫心肌炎、自體免疫卵巢炎、自體免疫睪丸炎、自體免疫胰臟炎、自體免疫視網膜病變、自體免疫蕁麻疹、軸突與神經元神經病變(AMAN)、貝羅氏病、白塞氏病、良性黏膜類天疱瘡、大皰性類天疱瘡、卡斯特曼氏病(CD)、乳糜瀉、卻格司氏病、慢性發炎性脫髓鞘型多發性神經病變(CIDP)、慢性復發性多灶性骨髓炎(CRMO)、徹奇-斯全司症候群(CSS)或嗜酸性肉芽腫(EGPA)、瘢痕性類天疱瘡、科根氏症候群、冷凝集素病、先天性心臟阻滯、柯薩奇心肌炎、CREST症候群、克羅恩氏病、皮膚狼瘡、疱疹樣皮炎、皮肌炎、德維奇氏病(視神經脊髓炎)、盤狀狼瘡、戴斯勒氏症候群、子宮內膜異位、嗜酸性食道炎(EoE)、嗜酸性筋膜炎、結節性紅斑、原發性混合型冷凝球蛋白血症、伊凡氏症候群、肌肉纖維疼痛、纖維化肺泡炎、巨大細胞動脈炎(顳動脈炎)、巨大細胞心肌炎、絲球體腎炎、古巴士德氏症候群、伴有多血管炎之肉芽腫、格雷夫氏病、格-巴二氏症候群、橋本氏甲狀腺炎、溶血性貧血、亨偌-絲奇恩賴紫癜(HSP)、妊娠性疱疹或妊娠性類天疱瘡(PG)、化膿性汗腺炎(HS) (反常性痤瘡)、低γ球蛋白血症、IgA腎病、IgG4相關之硬化性疾病、免疫性血小板減少性紫癜(ITP)、包涵體肌炎(IBM)、間質性膀胱炎(IC)、青少年關節炎、青少年糖尿病(第1型糖尿病)、青少年肌炎(JM)、川崎病、蘭伯特-伊頓症候群、白血球破裂性脈管炎、扁平苔癬、硬化性苔癬、木質性結膜炎、線性IgA疾病(LAD)、狼瘡、慢性萊姆病、梅尼爾氏病、顯微多血管炎(MPA)、混合型結締組織疾病(MCTD)、穆倫氏潰瘍、穆哈-哈伯曼疾病、多灶性運動神經病(MMN)或MMNCB、多發性硬化、重症肌無力、肌炎、發作性睡病、新生兒狼瘡、視神經脊髓炎、嗜中性白血球減少症、眼部瘢痕性類天疱瘡、視神經炎、陣發性風濕症(PR)、PANDAS、腫瘤伴生性小腦變性(PCD)、陣發性夜間血紅素尿症(PNH)、帕瑞隆伯格症候群、睫狀體扁平部炎(周邊葡萄膜炎)、帕森吉-特納症候群、天疱瘡、周邊神經病變、靜脈周邊腦脊髓炎、惡性貧血(PA)、POEMS症候群、結節性多動脈炎、第I、II、III型多腺症候群、風濕性多肌痛、多發性肌炎、心肌後梗塞症候群、心包切開術後症候群、原發性膽汁性肝硬化、原發性硬化性膽管炎、孕酮皮膚炎、牛皮癬、牛皮癬性關節炎、純紅血球發育不全(PRCA)、壞疽性膿皮病、雷諾氏現象、反應性關節炎、反射性交感神經失養症、復發性多軟骨炎、不寧腿症候群(RLS)、腹膜後纖維化、風濕熱、類風濕性關節炎、類肉瘤病、斯密特症候群、鞏膜炎、硬皮病、休格倫氏症候群、精子及睪丸自體免疫、僵硬人症候群(SPS)、亞急性細菌性心內膜炎(SBE)、蘇薩克氏症候群、交感眼炎(SO)、高安氏動脈炎、顳動脈炎/巨大細胞動脈炎、血小板減少性紫癲(TTP)、甲狀腺眼病(TED)、托洛薩-亨特症候群(THS)、橫貫性脊髓炎、第1型糖尿病、潰瘍性結腸炎(UC)、未分化結締組織疾病(UCTD)、葡萄膜炎、血管炎、白斑病及沃格特-小柳-原田病。
本申請案另外提供用於治療患者之移植物抗宿主疾病(GVHD)之方法，其包含投與如本文所述之蛋白質或醫藥調配物。
實例
參照以下實例將更容易地理解現大體上描述的本發明，該等實例僅出於說明本發明某些態樣及實施例之目的而包括在內，且不意欲以任何方式限制本發明之範疇。
實例1：試劑製備、免疫接種方法及篩選分析
此實例描述用於產生本文所提供之資料的試劑、免疫接種方法及篩選分析。
1.1 試劑製備及篩選分析
1.1.1 OX40-HEK 報導細胞之產生
用質體載體轉染HEK293 EBNA-NFkb-Luc細胞株以穩定表現全長人類OX40 (SEQ ID NO: 250)。使用潮黴素選擇穩定微型池且在細胞與重組His標籤人類OX40L蛋白質(R&D systems)一起培育之後針對螢光素酶活性之誘導進行篩選。
人類 OX40(加下劃線表示信號肽)
1.1.2 多價人類 OX40L 重組蛋白之產生
使人類OX40L細胞外域(ECD) (SEQ ID NO: 2之胺基酸51-183)與Avi-GST-6His-標籤域(「6His」揭示為SEQ ID NO: 338)融合表現，經由GST域純化且藉由尺寸排阻層析進一步純化。所得OX40L ECD融合蛋白「AVI-GST-His6-hOX40L」(「His6」揭示為SEQ ID NO: 338)為對OX40L ECD呈多價之可溶性蛋白質試劑。
1.1.3 表現人類、食蟹獼猴或小鼠 OX40L 之 CHO-S 細胞之產生
用質體載體轉染CHO-S細胞以穩定表現全長人類OX40L (SEQ ID NO: 2)、全長食蟹獼猴OX40L (SEQ ID NO: 337)或全長小鼠OX40L (SEQ ID NO: 251)。使用潮黴素選擇穩定微型池且藉由流式細胞術針對OX40L蛋白質之表面表現對細胞進行進一步篩選及選擇。
食蟹獼猴 OX40L 胺基酸序列 
小鼠 OX40L 胺基酸序列 
1.1.4 進行流式細胞術分析以針對人類、食蟹獼猴或小鼠 OX40L 結合進行篩選
用由經免疫接種之大鼠血清製備之稀釋系列或用重組抗OX40L抗體對1.1.2中所產生的表現表面OX40L (人類、食蟹獼猴或小鼠)之CHO-S細胞進行染色。視需要用螢光標記之抗大鼠-IgG或抗人類IgG Fc二級抗體偵測結合於CHO-S-OX40L細胞之抗體且藉由流式細胞術量測。
1.1.5 針對結合於重組人類、食蟹獼猴或小鼠 OX40L 之 ELISA 篩選
使ELISA分析盤塗有重組人類(Novoprotein目錄號CJ45)、食蟹獼猴(Novoprotein目錄號CP72)或小鼠OX40L (R&D systems目錄號1236-OX)蛋白質，之後與由經免疫接種之大鼠血清製備之稀釋系列或與重組抗OX40L抗體一起培育。視需要用過氧化酶共軛之抗大鼠-IgG或IgM或抗人類IgG Fc二級抗體偵測結合於含有重組OX40L之經塗佈ELISA盤的抗體。
1.1.6 針對阻斷 OX40L:OX40 蛋白質結合相互作用之抗 OX40L 抗體之 ELISA 篩選
將重組OX40-Fc融合蛋白(R&D Systems)塗佈於384孔ELISA分析盤上且隨後用BSA封閉。將可溶性重組OX40L-His蛋白質(R&D Systems或內部製備)添加至經OX40-Fc塗佈之分析盤中，且在培育及洗滌之後，用過氧化酶共軛之抗His抗體偵測可溶性OX40L-His與經塗佈OX40-Fc之結合。此條件產生在無抑制之情況下OX40L結合於OX40之最大信號。為了測試抗OX40L抗體對OX40L:OX40結合之抑制，使可溶性OX40L-His蛋白質與抗OX40L抗體混合，培育，添加至經OX40-Fc塗佈之分析盤中且如上偵測OX40L與OX40之結合。
1.1.7 藉由表面電漿子共振 (SPR) 進行人類及食蟹獼猴 OX40L 穩態親和力分析
將重組OX40L蛋白質(人類OX40L蛋白質，R&D systems，目錄號1054-OX；食蟹獼猴OX40L，Novoprotein目錄號CP72)固定於Biacore CM5感測器晶片上，且以一系列濃度使抗OX40L抗體結合於此表面。用Biacore T200儀器(GE Healthcare)量測穩態下之反應且相對於抗體濃度繪圖且擬合成1:1結合模型。穩態K
D確定為反應等於最大反應(R
max)一半時的抗體濃度。
1.1.8 藉由表面電漿子共振 (SPR) 或生物膜層干涉術 (BLI) 進行 人類及食蟹獼猴 CD80 及 CD86 穩態親和力分析
固定於Biacore CM5感測器晶片上的山羊抗人類IgG Fc (Jackson ImmunoResearch山羊抗人類IgG Fc抗體，目錄號109-005-098)用於經由其Fc區捕獲實驗CTLA4_抗OX40L融合蛋白或CTLA4-Ig參考蛋白質。以一系列濃度使重組CD80蛋白質(人類CD80，Novoprotein目錄號CK61；食蟹獼猴CD80，Novoprotein目錄號CP54)及CD86蛋白質(人類CD86，Novoprotein目錄號C404)結合於此表面。用Biacore T200儀器(GE Healthcare)量測穩態下之反應且相對於抗體濃度繪圖且擬合成1:1結合模型。穩態K
D確定為反應等於最大反應(R
max)一半時的抗體濃度。
在BLI分析中用Octet RED96儀器(ForteBio)量測食蟹獼猴CD86(Novoprotein目錄號CP41)穩態親和力。使用抗人類IgG Fc捕獲(AHC)生物感測器(ForteBio，目錄號18-5060)捕獲實驗CTLA4_抗OX40L融合蛋白或CTLA4-Ig參考蛋白質之Fc區。以一系列濃度使重組食蟹獼猴CD86結合於此表面。相對於重組蛋白之濃度對穩態下之反應進行繪圖且擬合成1:1結合模型。穩態K
D確定為反應等於最大反應(R
max)一半時的重組蛋白濃度。
1.1.9 OX40L 中和分析篩選
將HEK293 NFkB-Luc hOX40報導細胞(如1.1.1中所述)以0.5×10
6個細胞/毫升塗鋪於無血清培養基(Life Technologies：DMEM、潮黴素B、殺稻瘟菌素(Blasticidin)及L-麩醯胺酸)中，以50,000個細胞/60微升/孔塗鋪於組織培養物處理之透明底96孔培養盤(Falcon)中，且在37℃，5% CO
2下培育隔夜。在96孔培養盤(NUNC)中之培養基中製備利用經免疫接種之大鼠血清之稀釋系列或抗OX40L抗體。將30 µl滴定系列轉移至各孔中含有30 µL之10 µg/mL重組人類OX40L (1.1.2中所述)的96孔培養盤(NUNC)。將抗體及重組OX40L混合物培育30分鐘。在室溫下，以20 µL混合物/孔添加至報導細胞，且在37℃，5% CO
2下培育隔夜。各條件一式兩份地進行。將100 µL SteadyGlo受質(Promega，# E2520)添加至各孔，蓋住各盤，避光且在室溫下培育30分鐘。在Envision盤讀取器(Perkin Elmer)上利用超靈敏螢光程序(Luminescence 0.1sec)讀取各盤。
1.1.10 初級 T 細胞活化分析中之人類 OX40L 誘導之 IL-2
使用RosetteSep人類T細胞富集套組(StemCell Technologies，15062)分離CD4
+T細胞。在室溫下用5 µg/mL抗CD3 (BD Biosciences，555338)及5 µg/mL抗CD28 (BD Biosciences，555725)塗佈96孔盤1小時。用200 µL 1×PBS洗滌各盤兩次。以1:3.5連續滴定由100 nM製備抗體，且隨後在37℃，5% CO
2下與10 µg/mL重組人類OX40L (R&D Systems，1054-OX)一起培育30分鐘。使細胞以1×10
6個細胞/毫升再懸浮，且將600 µL細胞添加至具有120 µL抗體/rhOX40L混合物之0.5 mL 96孔深孔盤中。將200 µL細胞/抗體/rhOX40L混合物添加至抗CD3/抗CD28塗佈之盤之各孔中。將培養盤在37℃，5% CO
2下培育48小時。在培育之後，收集50 µL上清液且用人類IL-2 AlphaLISA (Perkin Elmer，AL221C)測試。在Envision盤讀取器(Perkin Elmer )上利用AlphaScreen方案讀取各盤。
實例2：抗OX40L抗體之鑑別、產生及表徵
此實例描述抗OX40L抗體之鑑別、產生及表徵。為了產生抗OX40L抗體，首先用人類OX40L DNA表現載體對OmniRat®嚙齒動物(一種轉殖基因動物，購自Open Monoclonal Technology公司(Palo Alto, CA，Ligand Pharmaceuticals公司(San Diego, CA)之子公司)，其表現具有完全人類可變區之免疫球蛋白)進行免疫接種，接著his標記之重組人類OX40L細胞外域(ECD)蛋白質進行多輪免疫接種。使用如實例1之1.1.4中所述之流式細胞術，針對與表現細胞表面OX40L蛋白質之CHO-S細胞之結合篩選來自經免疫接種之OmniRats®之血清。亦使用如實例1之1.1.5中所述之ELISA，針對與重組OX40L蛋白質之結合篩選經免疫接種之OmniRats®之血清。在多輪經由DNA表現載體與人類OX40L抗原進行免疫接種及重組蛋白免疫接種之後，用血清免疫反應鑑別OmniRats®以供結合於人類及食蟹獼猴OX40L。隨後在實例1之1.1.6中所述之封閉ELISA分析及實例1之1.1.9中所述之人類OX40L中和分析中針對相對於可溶性重組OX40L之中和活性篩選血清。選擇血清展現良好中和活性及高效價以結合細胞表面OX40L及可溶性重組OX40L之大鼠。自所選大鼠之脾臟及淋巴結收集細胞以用於後續直接B細胞選殖及B細胞培養及篩選，隨後再進行選殖。
2.1 B 細胞分選、 B 細胞培養及抗 OX40L 抗體之選殖
利用自經免疫接種之所選大鼠收集之淋巴球進行單一B細胞分選，該等大鼠具有展現OX40L中和活性及與OX40L目標之結合的高血清免疫反應。簡言之，將自所選大鼠之脾臟及/或淋巴結收集之細胞首先與抗大鼠CD32 (純系D34-485，BD Biosciences)一起在4℃下培育以阻斷此等細胞上之Fc受體，隨後與多價人類OX40L重組蛋白(如實例1之1.1.2中所述產生)一起培育。隨後洗滌細胞且與FITC共軛之山羊抗大鼠IgM (SouthernBiotech目錄號3020-02)、PE-Cy7共軛之小鼠抗大鼠CD45R (純系HIS 24，eBioscience)、APC共軛之小鼠抗His (純系AD1.1.10R，R&D)，及視所選OmniRat®之遺傳背景及分選策略而定的PE共軛之小鼠抗人類Igλ (純系1-155 -2，BD Biosciences)或V450共軛之小鼠抗人類Igκ (純系G20-193，BD Biosciences)之混合物一起培育。用FACS Aria III (BD Biosciences)將單一OX40L結合B細胞分選於96孔盤之各孔中。對於直接B細胞選殖，將單一OX40L結合B細胞直接分選於含有裂解緩衝液(0.1M DTT，40 U/ml RNAse抑制劑，Invitrogen，Cat# 10777-019)之孔中，且密封各盤且立即在乾冰上冷凍，之後儲存在-80℃下。對於B細胞培養及篩選，將OX40L結合B細胞分選於具有含細胞介素及受輻射之內部產生之飼養細胞的B細胞培養基的孔中。此等B細胞培養盤在5% CO
2培育箱中在37℃下培育7天且隨後如實例1之1.1.5中所述藉由ELISA針對與人類及食蟹獼猴OX40L之結合篩選來自各孔之上清液。自各孔回收所選OX40L結合B細胞培養物純系且將其置放於裂解緩衝液中。
使用根據Tiller等人, J Immunol Methods, 2008, 1; 329 (1-2)調整之方案自各單一分選之B細胞進行Ig V基因選殖。簡言之，遵循製造商之方案，使用最終量/濃度之150 ng隨機六聚體引子(pd(N)6，Applied Biosystems，P/N N808-0127)及50U Superscript IV逆轉錄酶(Invitrogen，目錄號18090050)，將來自單一分選之B細胞之總RNA以14微升/孔之最終體積在具有無核酸酶之水(Invitrogen，目錄號AM9935)之原始96孔分選盤中逆轉錄。引子係基於先前出版物(Wardemann等人, Science, 2003, 301:1374-1377)進行修飾及/或藉由檢查來自IMGT
®，國際免疫遺傳學資訊系統(http://www.imgt.org；(Lefranc等人, 2009)及NCBI (http://www.ncbi.nlm.nih.gov/igblast/)資料庫的已公佈之Ig基因區段核苷酸序列而設計。以5 μl cDNA作為模板為起始，藉由兩輪嵌套(IgH、IgK及IgL) PCR獨立擴增人類Igh、IgK及IgL V基因轉錄物。所有PCR反應均在96孔盤中以每孔50微升之總體積，藉由使用針對第一輪PCR之Platinum多重PCR反應(Invitrogen，目錄號4464269)，隨後藉由針對嵌套PCR之AccuPrime Taq DNA聚合酶高保真套組(Invitrogen，目錄號12346-094)，遵循製造商之方案進行。第一輪PCR係在95℃下進行2分鐘，之後進行94℃下30秒，50℃下30秒，72℃下40秒之30次循環，且最後在72℃下培育5分鐘。
在95℃下用5 μl未純化之第一輪PCR產物進行第二輪嵌套PCR 2分鐘，之後進行94℃下30秒，42℃下30秒，72℃下45秒之5次循環，且隨後進行94℃下30秒，55℃下30秒，72℃下45秒之35次循環，且最後在72℃下培育5分鐘。
由來自直接B細胞分選及選殖之360個OX40L結合B細胞獲得配對V
H及V
L抗體序列，且由B細胞培養、篩選及選殖獲得54個配對V
H及V
L抗體序列。將此等配對V
H及V
L序列選殖於IgG表現載體中以作為標準形式IgG1抗體進行重組抗體表現，用於進一步篩選、表徵及DNA序列確認及分析。在所選B細胞純系中，捕獲抗體基因序列之多樣性，該等序列屬於多種純系序列集群。
2.2 抗 OX40L 抗體純系篩選及選擇
IgG 形式：用Ig表現載體產生重組抗OX40L抗體，該等表現載體用經由如本實例之章節2.1中所述的直接B細胞選殖及B細胞培養方法獲得之配對V
H及V
L序列構築。將源於B細胞純系之恰當配對的重鏈及輕鏈載體用於Expi293F細胞之小規模短暫性轉染，且隨後在7天培育之後收集細胞培養物上清液。藉由如實例1之1.1.4中所述之流式細胞術針對與表現細胞表面OX40L蛋白質之CHO-S細胞的結合篩選含重組抗OX40L抗體純系之細胞培養物上清液；藉由如實例1之1.1.5中所述之ELISA針對與重組OX40L蛋白質之結合進行篩選；藉由如實例1之1.1.6中所述之ELISA競爭分析針對阻斷OX40L蛋白質結合於OX40進行篩選；且藉由如實例1之1.1.9中所述之OX40報導細胞分析針對OX40L之中和進行篩選。
基於細胞培養物上清液中之重組抗OX40L純系的篩選資料及抗OX40L純系序列之分析，選擇出總共85種抗OX40L抗體，其自ExpiCHO細胞之短暫性轉染以15 ml規模產生且使用蛋白質A珠粒進行親和純化，以允許在純系與等效產生之參考蛋白質之間進行更詳細表徵及比較。藉由如實例1之1.1.4中所述之流式細胞術基於與表現細胞表面OX40L蛋白質之CHO-S細胞的結合比較此等純化抗OX40L抗體；藉由如實例1之1.1.5中所述之ELISA針對與重組OX40L蛋白質之結合進行比較；藉由如實例1之1.1.6中所述之ELISA競爭分析基於阻斷OX40L蛋白質結合於OX40進行比較；藉由如實例1之1.1.9中所述之OX40報導細胞分析基於OX40L之中和進行比較；且基於如實例1之1.1.10中所述之初級T細胞活化分析基於OX40L誘導之IL-2之中和進行比較，隨後藉由如實例1之1.1.7中所述之表面電漿子共振(SPR)使用結合於OX40L蛋白質之穩態K
D量測比較24個候選物。
如上文所述比較純化候選抗OX40L抗體且以包括純系序列分析、中和分析IC
50＜20 nM(報導細胞及初級細胞分析)及穩態SPR結合K
D＜60 nM之標準進一步選擇。結合於人類及食蟹獼猴OX40L之所有所選候選物中無一者對結合於小鼠OX40L具有交叉反應性。85個候選物中有22個符合以上標準。分析此等22個候選物之抗體序列且選擇呈現抗體純系序列多樣性之12個候選純系用於進一步研究。在此等12個抗OX40L抗體中，純系97G07 (IgG)、67B06 (IgG)、68F03 (IgG)、98E10 (IgG)、89B09 (IgG)、98C01 (IgG)、88B06 (IgG)及85F10 (IgG)以15-31.9 nM之間的K
D結合於人類OX40L，其類似於參考抗OX40L抗體之結合K
D。其餘純系以穩態K
D＞32 nM結合於人類OX40L。此等12個抗OX40L抗體純系之所選資料概述於
表 8中。
2.3 所選抗 OX40L 抗體純系之表徵 2.3.1 OX40L 中和分析
使用OX40L中和分析，測試抗OX40L抗體純系之OX40L阻斷功能。簡言之，在培養基中連續滴定測試抗體、同型對照組及已知抗OX40L參考抗體(陽性對照組)，與重組人類OX40L一起培育，且添加於表現HEK-螢光素酶報導細胞之OX40受體中，依實例1之1.1.9中所述。用Graphpad Prism 8軟體標繪資料。使用未刺激之細胞作為0%及在不存在抗體下使用OX40L之刺激作為100%螢光素酶活性對各實驗培養盤進行標準化。利用GraphPad Prism，藉由曲線擬合使用log(抑制劑)對比標準化之反應-可變斜率方程式確定抗OX40L抗體之IC
50值。十一個抗OX40L IgG抗體純系在HEK報導子分析上以不同效能中和OX40L。純系97G07 (IgG)、67B06 (IgG)、68F03 (IgG)、98E10 (IgG)、89B09 (IgG)、98C01 (IgG)及95B06 (IgG)展現3.6-7.5 nM之IC
50值，其與參考抗OX40L抗體相當。純系30F02 (IgG)、88B06 (IgG)、85F10 (IgG)及84E11 (IgG)之IC
50值為17.7至72.7nM。
表 8概述根據此報導子分析之資料。
2.3.2 初級 T 細胞 活化分析
用1.1.10中所述之初級T細胞活化分析另外測試抗OX40L抗體純系中之10個(在此分析中未測試純系85F12及85F10)。簡言之，用抗CD3、抗CD28及重組人類OX40L刺激CD4
+T細胞，且在此分析中在連續稀釋中測試抗OX40L抗體純系。OX40L介導之T細胞活化產生高水準之IL-2細胞介素，其可隨著抗OX40L IgG抗體之濃度增加而減少，表明中和活性。用Graphpad Prism 8軟體標繪資料。使用未刺激之細胞作為0%及在不存在抗體下使用OX40L刺激作為100% IL-2反應對各實驗培養盤進行標準化。利用GraphPad Prism，藉由曲線擬合使用log(抑制劑)對比標準化之反應-可變斜率方程式來確定IC
50值。
表 8概述根據2次實驗之IC
50(以nM+/-SEM計)。大部分所測試之抗OX40L抗體純系證實OX40L中和活性，其中IC
50＜20 nM。
2.3.3 穩態親和力分析
如實例1之章節1.1.7中所述進行穩態親和力分析。
表 8概述根據此分析之資料。
表 8：根據十二種抗OX40L (IgG)之資料
| 試劑 (IgG) | OX40L 中和 /OX40-HEK 報導子 IC 50nM (+/-SEM) | 初級 T 細胞活化分析 IC 50nM (+/- SEM) | 穩態親和力人類 OX40L K D(nM) |
| 97G07 | 7.5 ± 5.32 | 16.7± 11.77 | 16.6 |
| 67B06 | 5.2 ± 3.66 | 20.9± 14.78 | 12.7 |
| 68F03 | 5.7 ± 3.99 | 18.8± 13.29 | 25.8 |
| 84E11 | 17.7 ± 12.50 | 8.8 ± 6.22 | 39.5 |
| 98E10 | 5.4 ± 3.85 | 8.8 ± 6.19 | 32.8 |
| 89B09 | 4.4 ± 3.13 | 10.7± 7.57 | 31.6 |
| 98C01 | 3.6 ± 2.57 | 12.9± 9.12 | 17.7 |
| 88B06 | 18.9 | 28.5 | 23.2 |
| 95B06 | 3.7 ± 2.66 | 7.4 ± 5.20 | 42.4 |
| 30F02 | 72.7 | 12.4± 8.77 | 53.9 |
| 85F12 | 未測試 | 未測試 | 75.6 |
| 85F10 | 54.6 ± 38.59 | 未測試 | 28.2 |
圖 2A為提供抗OX40L抗體之抗體篩選級聯之流程圖。該流程圖顯示用於篩選抗OX40L抗體純系且列入候選名單以獲得十二個候選物之分析。
圖 2B為提供候選物表徵級聯之流程圖。
實例 3 ： 抗 OX40L FcFab 抗體及 CTLA4_ 抗 OX40L 融合蛋白之產生及表徵
FcFab形式及CTLA4_抗OX40L融合蛋白形式：此實例描述FcFab中如何產生十二個抗OX40L純系及與CTLA4形式之融合，隨後係表徵分析。
3.1 抗 OX40L FcFAb 及 CTLA4_ 抗 OX40L ( 「 CTLA4-Fc- 抗 OX40L 」 ) 融合蛋白之產生
在兩種經工程改造之蛋白質形式中產生十二個抗OX40L純系(如實例2之章節2.2中所述)之Fab域：「FcFab」抗體及「CTLA4-Fc-抗OX40L」。在兩種蛋白質形式中，抗體Fab域連接在變異IgG1 Fc域蛋白質之C端。簡言之，使由VH-CH1-及部分IgG1鉸鏈(EPKSC)序列組成之抗體純系之重鏈之N端融合於與Fc多肽之C端融合的16個胺基酸連接子序列之C端。此等蛋白質形式之重鏈多肽與抗體純系輕鏈多肽共表現，該等抗體純系輕鏈多肽與Fab之重鏈多肽締合，且在輕鏈與重鏈之C端部分IgG1鉸鏈之間形成二硫鍵。
抗OX40L FcFab抗體重鏈N端係以IgG1鉸鏈元件E216(Kabat EU索引編號)之第一胺基酸開始，依SEQ ID NO: 73之序列中所示。十二個CTLA4_抗OX40L融合蛋白之重鏈及輕鏈胺基酸序列示於SEQ ID NO: 37-60中。
抗OX40L FcFab抗體中之每一者的重鏈DNA表現載體係藉由抗OX40L抗體VH序列之PCR擴增產生，且PCR產物係使用5' BamHI及3'NheI限制酶位點選殖於FcFab重鏈表現載體中，該等限制酶位點側接VH序列且分別為16-胺基酸連接子及CH1域之密碼子序列的一部分。FcFab重鏈表現載體係藉由基因合成(Quintara Biosciences)產生且隨後將基因合成產物選殖於短暫性表現載體pTT5中(Durocher等人, Nucleic Acids Res. 2002年1月15日;30(2):E9.)。CTLA4_抗OX40L重鏈表現載體係藉由基因合成(Genewiz)產生，且隨後將基因合成產物選殖於短暫性表現載體pTT5中。對於12個CTLA4_抗OX40L重鏈載體中之每一者，純系特異性VH序列經選殖以位於5' BamHI與3'NheI限制酶位點之間，該等限制酶位點側接VH序列且分別為16-胺基酸連接子及CH1域之密碼子序列之一部分。在此等CTLA4_抗OX40L表現載體中構築之例示性DNA序列示於SEQ ID NO: 74 (輕鏈序列)及SEQ ID NO: 75 (重鏈序列)中。
97G07 重鏈 DNA 序列 
97G07 輕鏈 DNA 序列 
抗OX40L FcFab抗體及CTLA4_抗OX40L蛋白質係藉由短暫性轉染上文詳述之恰當配對之輕鏈及重鏈DNA表現載體產生。抗OX40L FcFab抗體係在ExpiCHO細胞之15 ml規模短暫性轉染中產生且使用蛋白質A珠粒進行親和純化且表徵。CTLA4_抗OX40L蛋白質係在ExpiCHO細胞之1000 ml規模短暫性轉染中產生且在Akta Avant 25層析系統(GE Healthcare)上用蛋白A管柱(Hi-Trap MAbSelect SuRe，GE Healthcare)進行親和純化。量測最終蛋白質濃度且藉由分析型尺寸排阻層析(SEC)、SDS-PAGE凝膠表徵蛋白質且在用於計劃研究之前測試內毒素。
由於未保證任何抗OX40L IgG在針對抗OX40L Fab或CTLA4_抗OX40L融合蛋白再格式化時將保持與原始抗Ox40L IgG之OX40L之結合及中和特徵，因此根據與針對IgG格式所用相同之篩選分析級聯(
圖 2A)測試FcFab形式及融合蛋白形式。在所有分析中使用陽性參考對照組抗OX40L IgG。
3.2 抗 OX40L FcFab 抗體之表徵 3.2.1 OX40L 中和分析
使用OX40L中和分析，測試抗OX40L FcFAb抗體純系之OX40L阻斷功能。簡言之，在培養基中連續滴定測試抗體、同型對照組及已知抗OX40L參考抗體(陽性對照組)，與重組人類OX40L一起培育，且添加於表現HEK-螢光素酶報導細胞之OX40受體中，依實例1之1.1.9中所述。用Graphpad Prism 8軟體標繪資料。使用未刺激之細胞作為0%及在不存在抗體下使用OX40L之刺激作為100%螢光素酶活性對各實驗培養盤進行標準化。
如藉由其IC
50值可見，FcFab抗體純系97G07 (FcFab)、67B06 (FcFab)、68F03 (FcFab)、98E10 (FcFab)、89B09 (FcFab)、98C01 (FcFab)之OX40L阻斷活性與其IgG對應物類似，表明再格式化為FcFab不影響其中和效能。然而，FcFab抗體純系84E11 (FcFab)、88B06 (FcFab)、95B06 (FcFab)、30F02 (FcFab)、85F12 (FcFab)及85F10 (FcFab)展示出效能顯著降低，與其IgG對應物相比，其IC
50增加至少兩倍。利用GraphPad Prism，藉由曲線擬合使用log(抑制劑)對比標準化反應-可變斜率方程式來確定抗OX40L FcFab抗體之IC
50值。表9概述根據1次實驗之重複的資料。
3.2.2 初級 T 細胞活化分析
另外用1.1.10中所述之初級T細胞活化分析測試抗OX40L FcFab抗體純系中之十一個(在此分析中未測試純系98C01)。簡言之，用抗CD3、抗CD28及重組人類OX40L刺激CD4
+T細胞，且在此分析中在連續稀釋中測試抗OX40L FcFAb抗體純系。用Graphpad Prism 8軟體標繪資料。使用未刺激之細胞作為0%及在不存在抗體下使用OX40L刺激作為100% IL-2反應對各實驗培養盤進行標準化。利用GraphPad Prism，藉由曲線擬合使用log(抑制劑)對比標準化之反應-可變斜率方程式來確定IC
50值。表
9概述根據2次實驗之IC
50(以nM+/-SEM計)。儘管再格式化，97G07 (FcFab)、67B06 (FcFab)、98E10 (FcFab)、89B09 (FcFab)、30F02 (FcFab)及85F10 (FcFab)仍保持其效能類似於參考對照組抗OX40L (IC
50=5.7-9.3 nM)。
3.2.3 穩態親和力分析
如同IgG純系，使用如實例1之章節1.1.7中所述之穩態親和力分析確定所有十二個FcFab與人類OX40L之結合親和力。大部分FcFab保持與目標結合，顯示K
D=20.3-64.1nM之親和力範圍，但84E11 (FcFab)除外，其完全失去結合活性。
表 9概述根據此分析之資料。
表 9：根據12個抗OX40L (FcFab)之資料
3.3 CTLA4_ 抗 OX40L 融合蛋白之表徵 3.3.1 OX40L 中和分析
| 試劑 (FcFAb) | OX40L 中和 /OX40-HEK 報導子 IC 50nM (+/-SEM) | 初級 T 細胞活化分析 IC 50nM (+/- SEM) | 穩態親和力人類 OX40L K D(nM) |
| 97G07 (FcFab) | 6.2 | 4.6 ± 3.22 | 27.9 |
| 67B06 (FcFab) | 5.5 | 7.2 ± 5.10 | 20.3 |
| 68F03 (FcFab) | 5.5 | 15.6 ± 11.00 | 33.1 |
| 84E11 (FcFab) | 57.2 | 15.2 ± 10.76 | 無結合 |
| 98E10 (FcFab) | 5.7 | 5.3 ± 3.75 | 33.0 |
| 89B09 (FcFab) | 4.7 | 6.1 ± 4.28 | 44.8 |
| 98C01 (FcFab) | 5.4 | 未測試 | 27.8 |
| 88B06 (FcFab) | 101.9 | ＞161 | 35.5 |
| 95B06 (FcFab) | 30.79 | 38.0 ± 26.87 | 64.1 |
| 30F02 (FcFab) | 52.8 | 2.9 ± 2.02 | 56.0 |
| 85F12 (FcFab) | ＞161 | ＞161 | 34.1 |
| 85F10 (FcFab) | ＞161 | 6.3 ± 4.42 | 50.1 |
使用OX40L中和分析測試CTLA4_抗OX40L融合蛋白之OX40L阻斷功能。簡言之，在培養基中連續滴定測試融合蛋白、同型對照組及已知抗OX40L參考抗體(陽性對照組)，與重組人類OX40L一起培育，且添加於表現HEK-螢光素酶報導細胞之OX40受體中，依實例1之1.1.9中所述。用Graphpad Prism 8軟體標繪資料。使用未刺激之細胞作為0%及在不存在融合蛋白下使用OX40L之刺激作為100%螢光素酶活性對各實驗培養盤進行標準化。根據兩個實驗之資料概述於
表 10中。
圖 4為顯示使用OX40螢光素酶報導子分析，CTLA4_抗OX40L融合蛋白95B06、98C01、98E10、84E11、68F03、67B06、97G07、89B09及Ref4_CTLA4_O13、參考抗OX40L單株抗體Ref1_抗_OX40L及Ref2_抗OX40L或同型對照組OX40L中和的圖式。如
圖 4中所示，七種CTLA4_抗OX40L融合蛋白(97G07、68F03、67B06、98E10、89B09、98C01、95B06)保留與參考抗OX40L單株抗體類似之效能。與其IgG對應物相比，五種融合蛋白顯示效能顯著下降或其中和能力損失：84E11 (IgG) IC
50=17nM→ CTLA4_抗OX40L IC
50=50.2nM；88B06 (IgG)、30F02 (IgG)、85F12 (IgG)、85F10 (IgG) IC
50=19-72.7nM → CTLA4_抗OX40L IC
50= ＞100nM，資料示於
表 8中。
3.3.2 初級 T 細胞活化分析
因為88B06、30F02、85F12及85F10顯示較弱甚至無阻斷，因此在初級人類T細胞活化分析(描述於實例1之1.1.10中)中僅評估八種融合蛋白之人類OX04L中和。用Graphpad Prism 8軟體標繪資料。使用未刺激之細胞作為0%及在不存在融合蛋白下使用OX40L刺激作為100% IL-2反應對各實驗培養盤進行標準化。利用GraphPad Prism，藉由曲線擬合使用log(抑制劑)對比標準化之反應-可變斜率方程式來確定IC
50值。
表 10概述IC
50(以nM+/-SEM計)。
如
表 10中所示，儘管再格式化，但融合蛋白97G07、67B06、68F03、84E11、98E10、89B09及98C01仍保持效能類似於其IgG對應物及參考對照組抗OX40L(IC
50=5.7-9.3 nM)。
3.3.3 對 OX40L 、 CD80 及 CD86 之穩態親和力
使用如實例1之章節1.1.7中所述之穩態親和力分析確定所有12種CTLA4_抗OX40L融合蛋白對人類OX40L之結合親和力。如同FcFab形式，大部分CTLA4_抗OX40L融合蛋白保持與目標結合，顯示出K
D=27.6-106.1 nM之結合親和力範圍。如所預期，融合蛋白84E11(類似於其FcFab對應物)喪失對人類OX40L之結合親和力。
表 10概述此分析之資料。
此外，藉由如實例1之章節1.1.4中所述之流式細胞術評估CTLA4_抗OX40L融合蛋白89B09、67B06及98C01及參考抗OX40L抗體與表現於CHO-S細胞上之人類及食蟹獼猴OX40L之結合。89B09 (CHO-S-huOX40L EC
50= 4.62且CHO-S-cynoOX40L EC
50= 4.37nM)、67B06 (CHO-S-huOX40L EC
50= 1.85且CHO-S-cynoOX40L EC
50= 2.77nM)及98C01 (CHO-S-huOX40L EC
50= 2.79且CHO-S-cynoOX40L EC
50= 3.45nM)之結合EC
50與參考抗OX40L (CHO-S-huOX40L EC
50= 1.14且CHO-S-cynoOX40L EC
50= 0.95nM)之結合EC
50相當，其表明人類及食蟹獼猴OX40L之間有極佳交叉反應性。確定融合蛋白67B06及89B09與食蟹獼猴OX40L之結合親和力且與參考抗Ox40L抗體進行比較。發現融合蛋白之K
D(85nM)類似於參考抗OX40L抗體之K
D(57nM)。
使用如實例1之章節1.1.8中所述之穩態親和力分析確定CTLA4_抗OX40L融合蛋白及參考CTLA4-Ig蛋白質對人類及食蟹獼猴CD80及CD86之結合親和力。67B06 (人類CD80/人類CD86 = 538 nM/670 nM；食蟹獼猴CD80/食蟹獼猴CD86 = 486 nM/770 nM)及89B09 (人類CD80/人類CD86 = 540 nM/654 nM；食蟹獼猴CD80/食蟹獼猴CD86 = 474 nM/750 nM)之穩態結合KD與針對CTLA4-Ig參考蛋白質(人類CD80/人類CD86 = 450 nM/663 nM；食蟹獼猴CD80/食蟹獼猴CD86 = 433 nM/910 nM)確定之穩態結合KD相當。因此，抗OX40L Fab域與CTLA4-Ig蛋白質之C端融合以產生CTLA4_抗OX40L融合蛋白未明顯改變N端CTLA4域對CD80或CD86之結合親和力。總之，CTLA4_抗OX40L融合蛋白保持與人類及食蟹獼猴OX40L、CD80與CD86的結合且在其之間展現出極佳交叉反應性。
對七種CTLA4_抗OX40L融合蛋白進行排序且基於最接近單株抗OX40L IgG參考抗體之高效中和活性及親和力選擇四個純系不同之序列。
表 10：根據十二個CTLA4_抗OX40L候選物之資料
*
包含不同橋接部分之 67B06 之變異體均展現類似之與人類 OX40L 之穩態結合 ( 資料未示出 ) 。**
包含不同橋接部分之 89B09 之變異體均展現出類似之與人類 OX40L 之穩態結合 ( 資料未示出 ) 。 三種形式之比較
| 試劑 ( 融合蛋白 ) | OX40L 中和 /OX40-HEK 報導子 IC 50nM (+/-SEM) | 初級 T 細胞活化分析 IC 50nM (+/- SEM) | 穩態親和力人類 OX40L K D(nM) |
| 97G07 | 7.7 ± 0.95 | 7.1 | 57.4 |
| 67B06* | 7.3 ± 1.10 | 6.4 ± 3.71 | 27.6 |
| 68F03 | 10.1 ± 1.12 | 2.2 | 38.2 |
| 84E11 | 50.2 ± 0.86 | 8.1 | NB |
| 98E10 | 8.3 ± 0.86 | 3.5 ± 2.05 | 57.9 |
| 89B09** | 6.4 ± 0.88 | 5.4 ± 3.12 | 71.4 |
| 98C01 | 7.5 ± 1.22 | 5.1 ± 2.93 | 72.3 |
| 88B06 | ＞161 | 未測試 | 63.8 |
| 95B06 | 12.7 ± 3.09 | 20.8 | 106.1 |
| 30F02 | ＞161 | 未測試 | 68.5 |
| 85F12 | ＞161 | 未測試 | 65.8 |
| 85F10 | 119.6 | 未測試 | 51.1 |
| Ref1_抗OX40L | 7.3 ± 0.66 | 5.7 ± 3.28 | 31.9 |
| Ref2_抗OX40L | 6.6 ± 1.04 | 9.3 ± 5.39 | 15.0 |
| CTLA4_抗OX40L_O13 | 8.8 | 未測試 | 未測試 |
為了直接比較根據三種不同形式(抗OX40L (IgG)、抗OX40L (FcFab)及CTLA4_抗OX40L融合蛋白)之資料，根據中和分析標繪資料。
圖 3A 至圖 3C為顯示使用OX40螢光素酶報導子分析在IgG (
圖 3A)、FcFab (
圖 3B)及融合蛋白(
圖 3C)形式中藉由抗OX40L (97G07及67B06)中和OX40L的圖式。單株抗OX40L抗體(Ref1_抗OX40L及/或Ref2_抗OX40L)用作參考對照組。抗HEL IgG1用作同型對照組(同型-IgG1)。
實例 4 ： 使用活體外分析之 CTLA4_ 抗 OX40L 融合蛋白之作用機制
此實例闡明利用活體外分析之CTLA4_抗OX40L融合蛋白之作用機制。
4.1 同種異體 MDDC:T 混合淋巴球反應 (MLR) 分析
測試保持良好人類OX40L中和及結合之CTLA4_抗OX40L融合蛋白之雙功能活性。為查詢融合蛋白是否可阻斷由經由CD80/CD86-CD28路徑及OX40L-OX40路徑接收協同刺激信號之T細胞產生之發炎性細胞介素，建立人類同種異體MDDC:T混合淋巴球反應(MLR)。此分析利用活化初始源於單核球之樹突狀細胞(MDDC)作為表現全部三種目標CD80、CD86及OX40L之抗原呈遞細胞，以允許評定促成T細胞促炎性細胞介素釋放及T增殖的CD28及OX40路徑。
簡言之，在GMCSF及IL-4 (在具有5%人類AB血清、50 U/ml青黴素、50 µg/ml鏈黴素之AIM-V培養基中)存在下培養新鮮分離之單核球5天以變為不成熟之源自單核球之樹突狀細胞(iMDDC)。接著用1 µg/ml前列腺素E2 (PGE2)及20 ng/ml TNFα、10 ng/mL IL-1b、20 ng/mL IL-6處理iMMDC持續2天以產生成熟MDDC。藉由流式細胞術確認CD86、CD80及OX40L在成熟MDDC上之細胞表面表現。為建立混合淋巴球反應，使用菲科爾(Ficoll)梯度自白血球層分離新製PBMC。使用泛T細胞分離套組(Miltenyi Biotec，130-096-535)自PBMC分離總T細胞。在平底96孔組織培養盤中，將20,000個MDDC及80,000個泛T細胞塗鋪於各孔中，充分混合，且用各種濃度之培養基對照組、同型對照組或測試劑處理。與等莫耳濃度之單一參考試劑(Ref2_抗OX40L、Ref3_CTLA4Ig)及單株抗OX40L抗體與CTLA4 -Ig之組合(組合)相比較，在三種濃度(0.8 nM、6.25 nM及50 nM)下測試CTLA4_抗OX40L融合蛋白89B09、67B06、98E10及98C01。隨後將細胞在37℃，5% CO
2下培養4天，接著在上清液中進行細胞介素分析。藉由AlphaLISA分析(Perkin Elmer)評估IL-2、IFNγ、TNFα及IL-6之水準。
如
圖 5A 至圖 5B中所示，單獨的CTLA4-Ig (Ref3-CTLA4Ig)或單獨的抗OX40L (Ref2_抗OX40L)顯示細胞介素之濃度依賴性降低，表明該分析可量測任一路徑阻斷之影響，儘管在較低濃度下不太強效。相比之下，相較於單一參考試劑，融合蛋白(67B06、98E10及98C01)在所有測試濃度下均顯示IL-2 (
圖 5A)及TNFα (
圖 5B)細胞介素之優異抑制。出人意料地，優於靶向CTLA4-Ig與抗OX40L之組合，融合蛋白強效抑制細胞介素，其表明雙功能融合蛋白相較於組合形式之單一試劑之協同作用。所示資料係自4個供體MLR對標準化。藉由曲線擬合使用log(抑制劑)對比標準化反應-可變斜率方程式來確定所有測試融合蛋白之IC
50值。
表 11概述4至6個供體對之以nM±SEM計的IC
50。包含不同橋接部分之67B06之變異體均展現出類似之對IL-2及TNFα之抑制(資料未示出)。
在後續分析中連續滴定67B06、89B09融合蛋白以確定IL-2 (
圖 10A)、TNFα (
圖 10B)及IL6 (
圖 10C)抑制之IC
50值。相較於單一試劑對照組或組合，
圖 10A 至圖 10C顯示89B09及67B06在抑制發炎性細胞介素IL-2、TNFα及IL-6方面一致地為最強效試劑，其中各試劑之IC
50nM標繪為各細胞介素之平均值±SEM。所示資料為4個不同MDDC:T MLR對之概述，使用單因子變異數分析執行統計顯著性，*p = ＜0.05，**p= ＜0.005，***p=＜ 0.0005，****p=＜0.00005。
單獨的抗OX40L處理證實四個MLR實驗中之兩者之可量測IC
50，其表明融合蛋白在多個實驗及多個供體中具有較穩固且恆定的作用。
為了測試CTLA4_抗OX40L融合蛋白是否調節同種異體反應性增殖，在MDDC:T MLR分析中測試同型對照組融合蛋白、單一試劑及組合。對於增殖讀數，T細胞用Cell Trace Violet染料(Invitrogen)標記且與如上文所述之成熟MDDC一起培養，伴隨添加0.35 µL/mL抗CD3珠粒(StemCell，10309)。以6.25 nM或50 nM之等莫耳濃度測試融合蛋白(89B09、67B06、98E10及98C01)、CTLA4-Ig (Ref3_CTLA4Ig)、抗OX40L (Ref2_抗OX40L)或CTLA4-Ig與抗OX40L之組合(組合)。細胞隨後在37℃及5% CO
2下培養4天，用針對以下標記物CD3、CD4及OX40的螢光標記之抗體染色以在BD LSR Fortessa X-20上進行FACS分析，且藉由FlowJo分析CD4
+OX40
+及增殖CD4
-OX40
+或CD8
+OX40
+細胞之百分比。
如
圖 6A 至圖 6B中所示，優於CTLA4-Ig及抗OX40L之組合(組合)，融合蛋白(89B09、67B06、98E10及98C01)以統計學上顯著之方式強效降低同種異體反應性CD4
+OX40
+及CD8
+OX40
+細胞之增殖。在GraphPad PRISM8上以百分比標繪兩個實驗之結果且使用單因子變異數分析執行統計顯著性，*p= ＜0.05。此為顯著的，因為僅使用融合蛋白之處理，而非單一試劑參考對照組或組合能夠減弱通常與記憶T細胞及疾病病理學相關之CD8
+OX40
+T細胞，其表明需要CD28及OX40路徑兩者之同時雙重阻斷來達成此作用。
4.2 Treg 誘導分析
可溶性OX40L已顯示活體外抑制Treg誘導。相較於參考抗OX40L(Ref1_抗OX40L及Ref2_抗OX40L)及CTLA4-Ig (Ref3_CTLA4Ig)對照組，評定融合蛋白(89B09、67B06及98C01)之OX40L中和功能及其在Treg誘導分析中恢復Treg產生之能力。
使用人類初始CD4 T細胞分離套組(Miltenyi)自人類血液新鮮分離初始T細胞。完全RPMI1640培養基(補充有10%加熱不活化FBS、2 mM L-麩醯胺酸、50 IU青黴素/50 μg/ml鏈黴素、1 mM丙酮酸鈉、55 µM β-巰基乙醇及0.01 M HEPES)用於活體外T細胞培養。100,000 將初始T細胞置放於96孔組織培養盤之各孔中且用培養盤結合之抗CD3 (5 μg/ml)及可溶性抗CD28 (1 μg/ml)外加5 ng/ml TGF-β及50 U/ml IL-2刺激。在37℃下在CO
2培育箱中培養細胞5天。
重組可溶性OX40L (1 µg/ml，R&D Systems)添加至大多數條件，對照組除外。在第0天將同型對照組IgG、融合蛋白或參考對照組處理(50 nM)添加至各別孔中。在實驗結束時，收集細胞，且使用製造商(eBioscience)之「染色細胞內FoxP3(Staining Intracellular FoxP3)」說明書進行細胞內FoxP3染色。使用BD LSR Fortessa X-20進行FACS分析。使用FlowJo軟體進行資料分析。將Treg之出現率標準化至同型處理條件之出現率，且使用單因子變異數分析執行統計顯著性，*p = ＜0.05。如
圖 7中所示，在含有可溶OX40L之誘導條件下，iTreg產生顯著下降3倍。然而，等莫耳CTLA4_抗OX40L融合蛋白(89B09、67B06及98C01)或參考抗OX40L抗體(Ref1_抗OX40L及Ref2_抗OX40L)之存在中和可溶性OX40L之影響且充分恢復活體外Treg誘導。如所預期，未結合OX40L之CTLA4-Ig(Ref3_CTLA4Ig)未影響Treg恢復。
4.3 三因子 MDDC:Treg:Teff MLR 分析
為了證明融合CTLA4_抗OX40L融合蛋白是否與Treg協同以進一步抑制Teff增殖，利用3因子MDDC:Treg:Teff MLR分析。
在50 ng/ml GM-CSF及50 ng/ml IL-4(在具有5%人類AB血清、50 U/ml青黴素，50 µg/ml鏈黴素之AIM-V培養基中)存在下培養新鮮分離之單核球5天以變為不成熟之源自單核球之樹突狀細胞，且用1 µg /ml PGE2、20 ng/ml TNFα、20 ng/ml IL-6及10 ng/mlIL-1β處理2天以變為成熟MDDC (MDDC)。藉由FACS確認CD86、CD80及OX40L之細胞表面表現。
為建立混合淋巴球反應，使用菲科爾梯度自白血球層分離新製PBMC。使用人類CD4
+T細胞分離套組(Miltenyi)自PBMC分離CD4
+T細胞。隨後藉由流式細胞術將新鮮分離之CD4
+T細胞分選為CD4
+CD25
hiCD127
lowTreg及非Treg CD4
+T (或Teff、T
eff或T
效應)細胞。經分選之Treg用2 µM CellTrace Violet標記，且Teff CD4
+T細胞用2 µM CellTrace CFSE標記。在平底96孔組織培養盤中，將25,000個MDDC及50,000個Teff CD4
+T細胞塗鋪於各孔中，且在完全AIM-V培養基(補充有5%人類AB血清、可溶抗CD3 (0.6 µl/ml) (StemCell)、50 IU青黴素/50 µg/ml鏈黴素)中培養。在Treg之條件下，添加12,500個Treg。亦用10 nM之培養基對照組、同型對照組Ab、CTLA4-Ig、抗OX40L參考抗體、CTLA4_抗OX40L融合蛋白(89B09、67B06及98C01)任一者處理經培養細胞。
在單獨實驗中，在各種Treg:Teff比率條件存在下以10 nM測試融合蛋白89B09及相關對照組。隨後在37℃，5% CO
2下培養細胞4至5天，隨後用BD LSR Fortessa X-20分析細胞。藉由CFSE稀釋確定效應T細胞增殖。藉由FlowJo分析直方圖，使用Graphpad PRISM8標繪Treg與Teff之比率及增殖Teff細胞之絕對細胞計數。
如
圖 8中所示，相較於對照試劑，在Treg(1:4 Treg:Teff條件)存在下，融合蛋白(89B09、67B06、98C01)顯示甚至更顯著之Teff增殖抑制。此結果表明融合蛋白可更有效地削減Teff且可與Treg一起起作用以影響進一步Teff抑制。
雷帕黴素為mTOR抑制劑及移植中所用之一般T細胞免疫抑制劑，以有效抑制Teff，同時增加Treg，從而增加Treg:Teff比率。作為第二代環孢素之伏環孢素為一種鈣調神經磷酸酶抑制劑及已知T細胞免疫抑制劑，其最近獲得FDA批准用於治療狼瘡性腎炎。如上文所述之相同MLR分析係在不同濃度之融合蛋白、單一試劑、組合及100 nM雷帕黴素或伏環孢素存在下進行。如
圖 9A中所示，相較於單一試劑或組合，CTLA4_抗OX40L融合蛋白(89B09、67B06、98C01)以濃度依賴性方式增加Treg:Teff比率。在此活體外分析中，儘管測試出臨床有效濃度，但雷帕黴素或伏環孢素未增加Treg:Teff比率。
因為Treg亦需要CD28信號傳導以進行活化及增殖，所以必需解決融合蛋白是否可抑制Treg且不利地影響其對Teff之抑制功能。藉由調節上文所論述之3因子MLR培養物中之Treg:Teff比率，亦測試融合蛋白處理在增加Treg存在下對抑制T效應增殖之影響。如
圖 9B中所示，依所預期，經同型對照組處理之培養物，增加之Treg:Teff比率使Teff增殖減少。CTLA4-Ig處理未在Treg之上提供對Teff抑制之額外調節，而抗OX40L及組合提供Teff增殖之適度調節。印象深刻地，融合蛋白89B09在增加Treg存在下比其他處理更好地抑制Teff增殖，其表明融合蛋白不會不利地影響Treg功能，且與Treg協同作用以更有效地減弱Teff增殖。觀測到，融合蛋白而非單一試劑之組合與Treg協同作用以優先減少Teff增殖為出人意料之發現，且揭示具有雙重協同刺激阻斷特性的CTLA4_抗OX40L融合蛋白處理相較於用單一試劑之組合處理之間的潛在受關注之機制差異。
表 11 ：
實例 5 ： CTLA4_ 抗 OX40L 融合蛋白之效能之表徵
| 試劑 | 活體外MLR IL-2 IC 50nM (+/- SEM) | 活體外MLR TNFα IC 50nM (+/- SEM) | 與人類 OX40L 之細胞結合 EC 50(nM) | 穩態親和力人類 OX40L K D(nM) | 穩態親和力人類 CD80/CD86 K D(nM) |
| 67B06 (1) | 0.02 ± 0.004 | 0.06 ± 0.018 | 1.5 | 27.6/ 35.2 | 538/670 |
| 89B09 (1) | 0.03 ± 0.01 | 0.12 + 0.05 | 4.1 | 71.4/ 53.1 | 654/654 |
| 98C01 (1) | 0.04 | NT | 4.2 | 72.3/ 54.7 | |
| 98E10 (1) | NA | NT | 1.7 | 57.9/ 63.9 | |
| 30F02 (1) | NT | NT | 68.5 | ||
| Ref1抗OX40L IgG mAb | 0.69 ± 0.26 | 1.47 ± 0.52 | 31.9 | ||
| Ref2抗OX40L IgG mAb | NT | NT | 15.0 | ||
| Ref 3 CTLA4-Ig | 12.4 ± 2.7 | 9.72 ± 1.4 | NB | NB | 450/663 |
此實例描述促成CTLA4_抗OX40L融合蛋白之優良效能之事實。67B06融合蛋白之出人意料的態樣顯示相比於組合處理(數量級)大得多的效能，其表明相較於兩種獨立分子之組合，優良效能為單一雙功能蛋白之獨特特性。為了研究何種因子可促成融合蛋白中所見到之抑制細胞介素方面之優良效能，將融合蛋白、單一試劑及組合之受體佔有率與目標配位體(CD80及OX40L)進行比較，且在MDDC:T MLR分析中量測IL-2產生。
5.1 CD80 及 OX40L 受體佔有率分析
在第4天藉由流式細胞術評定同種異體MDDC:T MLR分析中根據CTLA4_抗OX40L融合蛋白或單一活性參考對照組的CD80及OX40L之受體佔有率百分比。簡言之，將細胞用PBS洗滌且用抗CD11c (純系3.9，Biolegend)、抗CD80(純系2D10，Biolegend)、抗CD86(純系FUN-1，BD)及抗OX40L(純系ik-1，BD)染色且藉由FACS在BD Fortessa上評定以測定MDDC上之CD80、CD86及OX40L表現。確定CD80、CD86及OX40L之平均螢光強度，使用GraphPad PRISM 8擬合劑量反應曲線。使用以下等式進行資料至佔有率百分比之轉變，其中MFI
NS設定為100%抑制且在不存在抗體之情況下MDDC:T共培養物在圖11圖例中表示為「僅M+T」，(0CPDΔMFI)作為最低抑制：
樣品A之抑制%= 100 - (AΔMFI / 0CPDΔMFI) * 100
MFI
T=相關群之PE通道之總中值螢光強度
MFI
NS=在所培育之重複樣品中PE之非特定中值螢光強度
ΔMFI = MFI
T- MFI
NS=背景校正之MFI
0CPDΔMFI =投加有0 mg/mL化合物之樣品之ΔMFI
如
圖 11A 至圖 11C中所示，CTLA4_抗OX40L融合蛋白之效能增加係由CD80而非OX40L之受體佔有率增加引起。與單一參考試劑或其組合相比，67B06融合蛋白在此分析中強效地抑制IL-2產生(
圖 11A)。此作用藉由目標CD80之67B06佔有率表明，其中相較於CTLA4-Ig (RO
50=3.5nM)或組合(RO
50= 1.03nM)，存在0.019 nM之50%受體佔有率(RO
50)。此結果顯示，67B06之CD80結合效能相較於CTLA4-Ig增加184倍，且相較於組合增加54倍(
圖 11B)。相較於抗OX40L (RO
50=0.02nM)或組合處理(RO
50=0.01nM)，67B06係以RO
50=0.003nM之效能佔有OX40L，其表示對OX40L之效能分別增加6倍及3倍(
圖 11C)。因此，67B06抑制細胞介素之強力作用很可能歸因於更強效CD80佔有率，其由錨定於其另一目標OX40L之蛋白質之親合力所致。
5.2 內化分析
為測試其他機制(諸如測試劑之物理內化或清除)是否可影響其在MDDC:T MLR分析中之效能，使用活細胞成像技術即時進行內化分析。
在活細胞成像儀Celldiscoverer7 (Zeiss)上歷經20小時在MDDC上比較CTLA4-Ig、抗OX40L及CTLA4_抗OX40L 67B06融合蛋白之即時內化。簡言之，將活化之MDDC與100 nM pHrodo標記之抗體一起培育。藉由利用pH rodo染料來追蹤67B06、CTLA4-Ig及抗OX40L試劑之內化，該等染料在低pH下在內化於細胞之胞吞隔室中會發螢光。在同一分析中測試內化之陰性對照組，諸如pHrodo標記之同型對照組及抗CD20抗體利妥昔單抗(Rituxumab)。隨時間推移追蹤測試劑之內化及所偵測之pHrodo信號且進行記錄。據報導，CTLA4-Ig在結合於其目標後內化，而其可為藉由自細胞表面移除其而阻斷目標CD80及CD86之有效方式，目標介導之藥物清除可影響其效能。如
圖 12中所示，在6小時內快速內化CTLA4-Ig (Ref3_CTLA4Ig)且歷經20小時持續內化，依藉由MDDC中增加之pHrodo信號所指示(
圖 12)。另一方面，抗CD20抗體利妥昔單抗(抗CD20-IgG1)、同型對照組(同型Ctl及同型-IgG1)或抗OX40L參考對照組(Ref1_抗OX40L)未內化。儘管CTLA4_抗OX40L融合蛋白(67B06)與CTLA4-Ig結合相同CD80及CD86目標，但其驚人地未共有相同內化概況，且實際上在20小時時段內顯示在MDDC中之有限內化(
圖 12)。此可允許融合在較長時段內阻斷目標CD80、CD86及OX40L，而不被內化或清除，此可解釋其在MDDC:T MLR分析中相較於單一試劑比較物增強之效能。
5.3 MDDC: SLE PBMC MLR 分析
為了評估CTLA4_抗OX40L融合蛋白在抑制額外促炎性細胞介素方面之增強之效能，進行MDDC:SLE PBMC分析。進行與章節3.1中之同種異體MDDC:T MLR分析類似之分析設定，以評定融合蛋白在源於全身性紅斑狼瘡(SLE)患者之PBMC中之作用。除利用患者PBMC代替來自健康志願者之T細胞以外，分析條件類似於3.1。在第4天，收集來自共培養物之上清液且使用MSD Immuno-Oncology Group 1及Biomarker Group 1套組分析促炎性細胞介素(GM-CSF、顆粒酶B、IFNγ、IL-2、IL-4、IL-10、IL-13、IL-17A、TNFα、IL-9、IL-17/IL-25、IL-17F、IL-21、IL-22、MIP-3α)。使用GraphPad PRISM 8標繪3個供體對之資料。對於ELISPOT讀數，MDDC:SLE PBMC分析需要添加抗CD3。將細胞培養物直接接種於IFNγ ELISPOT盤上且在第4天根據製造商說明書(人類IFNγ，R&D Systems)分析。在CTL ImmunoSpot S6分析儀上對斑點進行計數且使用GraphPad PRISM 8進行資料分析。
如
圖 13A 至圖 13C中所示，當與MDDC共培養時，狼瘡PBMC誘導培養上清液中之IL-2 (資料未示出)、TNFα (資料未示出)、GMCSF(
圖 13A)、IL-13 (
圖 13B)及GZMB (
圖 13C)水準升高，且相較於單一試劑或組合，此等細胞介素可被1 nM融合蛋白(67B06)強效抑制。在50 nM下，融合及組合處理同等地有效抑制此等細胞介素。相較於單一試劑，藉由融合蛋白及組合處理以50 nM顯著減少產生同種異體反應性IFNγ之細胞。
圖 13A 至圖 13C顯示根據3個供體之標準化資料。
實例 6 ： CTLA4_ 抗 OX40L 融合蛋白之活體內藥效學作用
此實例描述使用人類化MLR PD模型之CTLA4_抗OX40L融合蛋白之活體內藥效學作用。
6.1 活體內人類化 MLR PD 模型
由於CTLA4_抗OX40L融合蛋白中無一者與小鼠OX40L交叉反應，因此開發用於評估融合蛋白之人類化活體內藥效學(PD)模型。簡言之，依先前在章節3.1中之活體外MDDC:T MLR分析中所述來活化源於單核球之樹突狀細胞。在第-1天，用各種濃度之融合蛋白(67B06、89B09)、單臂對照組或同型對照組靜脈內處理NOD.Cg-
Prkdc
scidIl2rg
tm1Wjl/
SzJ或NSG小鼠(Jackson Labs)，接著在第0天經由腹膜內轉移混合活化MDDC (1×10
6個細胞)及新鮮分離之同種異體T細胞(1×10
7個細胞)。6天後，收集血清用於使用MSD套組(人類u-Plex促炎性組合套組，目錄號K15049K-2)進行人類細胞介素量測。使用GraphPad PRISM 8進行IFNγ水準及統計分析(單因子變異數分析)。
如
圖 14A中所示，相較於同型對照組，67B06與89B09劑量依賴性地減少人類IFNγ產生，其表明在小鼠中之活體內功效。在一單獨研究中，相較於同型對照組，用單一等莫耳(2.88 nmol/kg或0.58 nmol/kg)劑量之67B06融合蛋白、各單一試劑對照組CTLA4-Ig或抗OX40L 67B06 (IgG)處理小鼠以評估活體外觀測到之融合蛋白之增強效能是否反映於活體內。如
圖 14B中所示，相較於在相同等莫耳濃度測試下之比較物，2.88 nmol/kg (等效於0.5 mg/kg)之融合蛋白67B06提供對人類IFNγ產生之優異抑制。
實例 7：CTLA4_抗OX40L融合蛋白之活體內功效
此實例描述使用異種移植、急性及慢性移植物抗宿主病(xeno-GVHD)模型之CTLA4_抗OX40L融合蛋白之活體內功效。
xeno-GVHD模型為良好表徵之模型，其視所輸注之人類PBMC而定，對缺乏鼠類免疫系統之宿主小鼠產生強異種反應性反應。xeno-GVHD模型在填入動物且誘發疾病之免疫亞群方面具有熟知侷限性。舉例而言，人類B細胞及骨髓細胞在小鼠中由於缺乏存活因子而存活不超過7至10天。然而，人類T細胞在小鼠中存活且良好擴增，使得在第7天，小鼠中之大部分移植細胞為T細胞。擴增T細胞為異種反應性浸潤性靶器官，諸如肝臟、肺臟及腸道，伴隨增加之發炎性細胞介素(如IFNγ)引起組織損傷，導致體重下降。若未經處理，則小鼠死於GVHD。因此，此模型適用於評估多種T細胞靶向生物製劑，其可藉由評定其對減少GVHD介導之體重減輕及IFNγ產生之影響來抑制T細胞且緩解GVHD。
在第一實驗中，評估CTLA4_抗OX40L融合蛋白(67B06)及抗OX40L(Ref1_抗OX40L)。簡言之，使雌性NSG小鼠(每組n=8)受輻射(200 rad)且在第-1天開始，每隻小鼠腹膜內投與200 µg (等效於10 mg/kg)融合蛋白、單一試劑參考比較物或同型對照組IgG，一週3次(Q3W)。在第0天，小鼠接受1千萬個人類外周血液單核細胞(PBMC)。在第7天，藉由流式細胞術對移植之人類CD45
+細胞進行表現型分析。研究在第25天終止，且量測存活率、體重減輕、血清IFNγ之指標量測結果。執行Prism GraphPad 8進行統計分析(單因子變異數分析)。
圖 15A為顯示在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(67B06)、參考單株抗OX40L抗體(Ref1_抗_OX40L)或同型對照組對體重減輕之影響的圖式。
圖 15B為顯示在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(67B06)、參考單株抗OX40L抗體(Ref1_抗_OX40L)或同型對照組對IFNγ產生之影響的圖式。如
圖 15A 至 圖 15B中所示，儘管兩種試劑均使小鼠免於體重減輕，但相較於單獨的抗OX40L處理，僅67B06融合蛋白顯示出優異的IFNγ減少(
圖 15BANOVA：**** p= ＜0.0001，*p= 0.0175，***p= 0.0002)。
在基本上如上文所述進行及評估之第二實驗中，比較CTLA4_抗OX40L融合蛋白(67B06)及CTLA4-Ig。以20 µg/小鼠或1 µg/小鼠(分別等效於1mg/kg或0.05mg/kg)之劑量腹膜內投與CTLA4_抗OX40L融合蛋白(67B06)、CTLA4-Ig(Ref3_CTLA4Ig)或同型對照組，一週一次(Q1W)。
圖 16A為顯示在xeno-GVHD鼠類模型中，1mg/kg或0.05mg/kg Q1W腹膜內投與之CTLA4_抗OX40L融合蛋白(67B06)、參考CTLA4Ig (Ref3_CTLA4Ig)或同型對照組對體重減輕之影響的圖式。
圖 16B為顯示在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(67B06)、參考CTLA4Ig (Ref3_CTLA4Ig)或同型對照組對IFNγ產生之影響的圖式。如
圖 16A 至 圖 16B中所示，儘管兩種試劑均使小鼠免於體重減輕，但相較於單獨的CTLA4Ig處理，僅67B06融合蛋白顯示出優異的IFNγ減少(
圖 16BANOVA：* p= 0.0455，**p= 0.0086)。
在使用此模型之另一實驗中，將CTLA4_抗OX40L融合蛋白(67B06)之影響與組合使用的CTLA4Ig及抗Ox40L之影響進行比較。以20 µg/小鼠(1mg/kg)之劑量腹膜內投與CTLA4_抗OX40L融合蛋白(67B06)、Ref3_CTLA4Ig、Ref1_抗Ox40L及Ref3_CTLA4Ig及Ref1_抗OX40L之組合，每週一次(Q1W)。在第41天終止研究。
圖 17A為顯示在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(67B06)、參考CTLA4Ig (Ref3_CTLA4Ig)、抗OX40L (Ref1_抗OX40L)、組合(Ref3及Ref1)或同型對照組對體重減輕之影響的圖式。
圖 17B為顯示在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(67B06)、參考CTLA4Ig (Ref3_CTLA4Ig)、抗OX40L (Ref1_抗OX40L)、組合(Ref3及Ref1)或同型對照組對IFNγ產生之影響的圖式。如
圖 17A 至圖 17B中所示，儘管融合蛋白(67B06)、參考CTLA4Ig (Ref3_CTLA4Ig)及組合(Ref3_CTLA4Ig及Ref1_抗OX40L)均使小鼠免於體重減輕，但相較於單獨的CTLA4Ig或抗OX40L處理，僅融合蛋白67B06或組合顯示優異的IFNγ減少(
圖 17BANOVA：* p= 0.0110，**p= 0.0084)。
在單獨實驗中，測試不同CTLA4_抗OX40L融合蛋白(89B09)且與同型對照組進行比較。簡言之，在第-1天開始，以20 µg/小鼠(1mg/kg)之劑量腹膜內投與融合蛋白(89B09)或同型對照組，每週一次(Q1W)。類似於融合蛋白67B06之實驗，在處理之第41天監測小鼠體重減輕且相較於單獨的同型處理比較IFNγ產生。
圖 17C為顯示在第12天，在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(89B09)或同型對照組對IFNγ產生之影響的圖式。該圖顯示融合蛋白顯著減少IFNγ產生(ANOVA：** p= 0.0036)。
在另一急性GVHD模型中，用20 µg大鼠抗小鼠IL-2Rβ抗體注射嚴重組合免疫缺乏(SCID)小鼠(5至10週齡)使內源性NK細胞耗竭。次日，使用銫源使小鼠接受2.5 Gy輻射。四小時後，藉由腹膜內(IP)注射使各小鼠接受一千萬個總人類PBMC，之後立即靜脈內(IV)注射各種劑量之CTLA4_抗OX40L融合蛋白、參考單株抗OX40L抗體或同型對照組。替代地，可延遲各種劑量之CTLA4_抗OX40L融合蛋白、參考單株抗OX40L抗體或同型對照組之IV注射直至PBMC之IP注射後第3天或第6天。每3至4天對小鼠進行稱重且每週接受抗IL-2Rβ抗體一次。在第12天，處死小鼠以供評定總體病理學、脾細胞之流式細胞術分析、肝臟及腸組織學及血清收集以用於細胞介素及抗體分析。
參考文獻併入
本文所提及之專利文獻及科學論文中之每一者的全部揭示內容以引用之方式併入以達成所有目的。
等效方案
在不偏離本發明之精神或基本特徵之情況下，本發明可以其他特定形式體現。因此，前述實施例在所有方面中應視為說明性的，而非限制本文所描述之揭示內容。不同實施例及多種所揭示方法步驟之多種結構要素可以多種組合及排列形式加以利用，且所有此類變化形式均被視為本發明之形式。因此，本發明之範圍係由所附申請專利範圍而非前述描述指示，且在與申請專利範圍等效之含義及範圍內的所有變化均意欲包括在本文中。
圖 1A 至圖 1W提供結合CD80及/或CD86及OX40L之具有Ig Fc恆定域的融合蛋白之各種蛋白質設計的圖解說明。
圖 1A為例示性融合蛋白之圖解說明，其中CD28之細胞外域(ECD)融合於Fc域之N端且OX40之ECD融合於同一Fc域之C端。
圖 1B為例示性融合蛋白之圖解說明，其中OX40之ECD融合於Fc域之N端且CD28之ECD融合於同一Fc域之C端。
圖 1C為例示性融合蛋白之圖解說明，其中CTLA4之ECD融合於Fc域之N端且OX40之ECD融合於同一Fc域之C端。
圖 1D為例示性融合蛋白之圖解說明，其中OX40之ECD融合於Fc域之N端且CTLA4之ECD融合於同一Fc域之C端。
圖 1E為例示性融合蛋白之圖解說明，其中CD28之ECD各自串聯融合於OX40之ECD之N端，其隨後融合於Fc域之N端。
圖 1F為例示性融合蛋白之圖解說明，其中CTLA4之ECD各自串聯融合於OX40之ECD之N端，其隨後融合於Fc域之N端。
圖 1G為例示性融合蛋白之圖解說明，其中OX40之ECD各自串聯融合於CD28之ECD之N端，其隨後融合於Fc域之N端。
圖 1H為例示性融合蛋白之圖解說明，其中OX40之ECD串聯融合於CTLA4之ECD之N端，其隨後融合於Fc域之N端。
圖 1I為例示性融合蛋白之圖解說明，其中圖1E至圖1H之任何串聯ECD組合(本文標記為X及Y)融合於Fc域之C端。
圖 1J為例示性融合蛋白之圖解說明，其中CD28之ECD融合於Fc域之N端且抗OX40L抗體結合域融合於同一Fc域之C端。
圖 1K為例示性融合蛋白之圖解說明，其中CTLA4之ECD融合於Fc域之N端且抗OX40L抗體結合域融合於同一Fc域之C端。
圖 1L為例示性融合蛋白之圖解說明，其中OX40之ECD融合於Fc域之N端，且抗CD80及抗CD86抗體結合域融合於Fc域之C端。
圖 1M為例示性融合蛋白之圖解說明，其中抗OX40L抗體結合域融合於Fc域之N端且抗CD80及抗CD86抗體結合域融合於Fc域之C端。
圖 1N為例示性融合蛋白之圖解說明，其中抗CD80及抗CD86抗體結合域融合於Fc域之N端且抗OX40L抗體結合域融合於Fc域之C端。
圖 1O為例示性融合蛋白之圖解說明，其中抗CD80及抗CD86抗體結合域串聯融合於抗OX40L抗體結合域之N端，其隨後融合於Fc域之N端。
圖 1P為例示性融合蛋白之圖解說明，其中抗OX40L抗體結合域串聯融合於抗CD80及抗CD86抗體結合域之N端，其隨後融合於Fc域之N端。
圖 1Q為例示性融合蛋白之圖解說明，其中抗CD80及抗CD86抗體結合域融合於Fc域之C端且串聯融合於抗OX40L抗體結合域之N端。
圖 1R為例示性融合蛋白之圖解說明，其中抗OX40L抗體結合域融合於Fc域之C端且串聯融合於抗CD80及抗CD86抗體結合域之N端。
圖 1S為例示性融合蛋白之圖解說明，其中抗OX40L抗體結合域融合於Fc域之N端且抗CD80及抗CD86抗體結合域彼此串聯融合且融合於Fc域之C端。
圖 1T為例示性融合蛋白之圖解說明，其中抗CD80及抗CD86抗體結合域彼此串聯融合且融合於Fc域之N端且抗OX40L抗體結合域融合於Fc域之C端。
圖 1U為例示性融合蛋白之圖解說明，其中抗OX40L抗體結合域融合於Fc域之N端且CD28之ECD融合於同一Fc域之C端。
圖 1V為例示性融合蛋白之圖解說明，其中抗OX40L抗體結合域融合於Fc域之N端且CTLA4之ECD融合於同一Fc域之C端。
圖 1W為例示性融合蛋白之圖解說明，其中CTLA4之ECD融合於具有降低Fc效應功能之突變的變異IgG1 Fc域之N端且抗OX40L Fab融合於變異IgG1 Fc域之C端。
圖 2A為顯示抗體篩選級聯之流程圖。
圖 2B為顯示候選物表徵級聯之流程圖。
圖 3A 至圖 3C為顯示使用OX40螢光素酶報導子分析在IgG (
圖 3A)、FcFab (
圖 3B)及融合蛋白(
圖 3C)形式中藉由抗OX40L中和OX40L的圖式。
圖 4為顯示使用OX40螢光素酶報導子分析，使用CTLA4_抗OX40L融合蛋白(95B06、98C01、98E10、84E11、68F03、67B06、97G07、89B09及Ref4_CTLA4_O13)、參考單株抗OX40L抗體(Ref1_抗_OX40L，Ref2_抗OX40L)或同型對照組進行的OX40L之中和的圖式。
圖 5A 至圖 5B為顯示使用活體外混合淋巴球反應(MLR)分析，在不同濃度的CTLA4_抗OX40L融合蛋白(89B09、67B06、98E10及98C01)、參考單一試劑(Ref2_抗OX40L、Ref3_CTLA4Ig)、單株抗OX40L抗體及CTLA4-Ig之組合(組合)或同型對照組存在下的促炎性細胞介素IL-2 (
圖 5A)及TNFα (
圖 5B)之表現的圖式。
圖 6A 至圖 6B為顯示使用源自單核球之樹突狀細胞:T細胞(MDDC:T) MLR分析，在CTLA4_抗OX40L融合蛋白(89B09、67B06、98E10及98C01)、參考單一試劑(Ref2_抗OX40L、Ref3_CTLA4Ig)、單株抗OX40L抗體及CTLA4-Ig之組合(組合)或同型對照組存在下，同種異體反應性CD4
+OX40
+(
圖 6A)及CD8
+OX40
+(
圖 6B)T細胞增殖的圖式。
圖 7為顯示使用Treg誘導分析，在存在或不存在CTLA4_抗OX40L融合蛋白(89B09、67B06及98C01)、參考單一試劑(Ref1_抗OX40L、Ref2_抗OX40L、Ref3_CTLA4Ig)或同型IgG1對照組(Iso)下的活體外Treg誘導水準的圖式。
圖 8為顯示使用MLR分析，在CTLA4_抗OX40L融合蛋白(89B09、67B06及98C01)、參考單一試劑(Ref2_抗OX40L、Ref3_CTLA4Ig)或同型對照組存在下的Treg:Teff比率的直方圖。
圖 9A為顯示使用MLR分析，在不同濃度之CTLA4_抗OX40L融合蛋白(89B09、67B06及98C01)、參考單一試劑(Ref2_抗OX40L、Ref3_CTLA4Ig)、單株抗OX40L抗體及CTLA4-Ig之組合(組合)、雷帕黴素(rapamycin)、伏環孢素(voclosporin)或同型對照組存在下的Treg:Teff比率的圖式。
圖 9B為顯示使用MLR分析，在CTLA4_抗OX40L融合蛋白(89B09)、參考單一試劑(Ref2_抗OX40L、Ref3_CTLA4Ig)、單株抗OX40L抗體及CTLA4-Ig之組合(組合)或同型對照組存在下的效應T細胞增殖的圖式。
圖 10A 至圖 10C為顯示使用MLR分析，在CTLA4_抗OX40L融合蛋白(67B06及89B09)、參考單一試劑(Ref1_抗OX40L、Ref3_CTLA4Ig)或單株抗OX40L抗體及CTLA4-Ig之組合(組合)存在下的IL-2 (
圖 10A)、TNFα (
圖 10B)及IL-6 (
圖 10C)之IC
50值的圖式。
圖 11A為顯示根據CD80及OX40L受體佔有率分析的IL-2濃度水準的圖式。
圖 11B為顯示根據CD80及OX40L受體佔有率分析的人類OX40L佔有率百分比的圖式。
圖 11C為顯示根據CD80及OX40L受體佔有率分析的人類CD80佔有率百分比的圖式。
圖 12為顯示利用源於骨髓之樹突狀細胞(MDDC)的CTLA4-Ig (Ref3_CTLA4Ig)、抗OX40L (Ref1_抗OX40L)、CTLA4_抗OX40L融合蛋白(67B06)、IgG同型對照組(同型Ctl、同型IgG1)及非內化抗CD20抗體的即時內化的圖式。
圖 13A 至圖 13D為顯示CTLA4_抗OX40L融合蛋白(67B06)、參考單一試劑(Ref1_抗OX40L、Ref3_CTLA4Ig)或單株抗OX40L抗體及CTLA4-Ig之組合(組合)對源自全身性紅斑狼瘡(SLE)患者之PBMC中的粒細胞-巨噬細胞群落刺激因子(GM-CSF)(
圖 13A)、IL13 (
圖 13B)、顆粒酶B(GZMB) (
圖 13C)及IFNγ (
圖 13D)之表現量的影響的圖式。
圖 14A為顯示在異種移植物抗宿主病(xeno-GVHD)鼠類模型中，CTLA4_抗OX40L融合蛋白(67B06及89B09)或同型對照組對抑制IFNγ反應之影響的圖式。
圖 14B為顯示在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(67B06)、參考單一試劑67B06(IgG形式)、Ref3_CTLA4Ig或同型對照組對抑制IFNγ反應之影響的圖式。
圖 15A為顯示在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(67B06)、參考單株抗OX40L抗體(Ref1_抗_OX40L)或同型對照組對體重減輕之影響的圖式。
圖 15B為顯示在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(67B06)、參考單株抗OX40L抗體(Ref1_抗_OX40L)或同型對照組對IFNγ產生之影響的圖式。統計分析(單因子變異數分析)係在Prism Graphpad 8上進行(**** p= ＜0.0001，*p= 0.0175，***p= 0.0002)。
圖 16A為顯示在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(67B06)、參考CTLA4Ig (Ref3_CTLA4Ig)或同型對照組對體重減輕之影響的圖式。
圖 16B為顯示在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(67B06)、參考CTLA4Ig (Ref3_CTLA4Ig)或同型對照組對IFNγ產生之影響的圖式。統計分析(單因子變異數分析)係在Prism Graphpad 8上進行(* p= 0.0455, **p= 0.0086)。
圖 17A為顯示在第41天，在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(67B06)、參考CTLA4Ig (Ref3_CTLA4Ig)、抗OX40L (Ref1_抗OX40L)、組合(Ref3及Ref1)或同型對照組對體重減輕之影響的圖式。
圖 17B為顯示在第41天，在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(67B06)、參考CTLA4Ig (Ref3_CTLA4Ig)、抗OX40L (Ref1_抗OX40L)、組合(Ref3及Ref1)或同型對照組對IFNγ產生之影響的圖式。統計分析(單因子變異數分析)係在Prism Graphpad 8上進行(* p= 0.0110，**p= 0.0084)。
圖 17C為顯示在第12天，在xeno-GVHD鼠類模型中，CTLA4_抗OX40L融合蛋白(89B09)或同型對照組對IFNγ產生之影響的圖式。統計分析(非成對t-測試)係在Prism Graphpad 8上進行(** p= 0.0036)。
<![CDATA[<110> 德商馬克專利公司(MERCK PATENT GMBH)]]>
<![CDATA[<120> 結合CD80及/或CD86及OX40L之蛋白質]]>
<![CDATA[<130> EMD-015WO]]>
<![CDATA[<140> 111121114]]>
<![CDATA[<141> 2022-06-07]]>
<![CDATA[<150> US 63/343,268]]>
<![CDATA[<151> 2022-05-18]]>
<![CDATA[<150> US 63/208,478]]>
<![CDATA[<151> 2021-06-08]]>
<![CDATA[<160> 338 ]]>
<![CDATA[<170> PatentIn version 3.5]]>
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Leu His Cys Val Gly Asp Thr Tyr Pro Ser Asn Asp Arg Cys Cys His
1 5 10 15
Glu Cys Arg Pro Gly Asn Gly Met Val Ser Arg Cys Ser Arg Ser Gln
20 25 30
Asn Thr Val Cys Arg Pro Cys Gly Pro Gly Phe Tyr Asn Asp Val Val
35 40 45
Ser Ser Lys Pro Cys Lys Pro Cys Thr Trp Cys Asn Leu Arg Ser Gly
50 55 60
Ser Glu Arg Lys Gln Leu Cys Thr Ala Thr Gln Asp Thr Val Cys Arg
65 70 75 80
Cys Arg Ala Gly Thr Gln Pro Leu Asp Ser Tyr Lys Pro Gly Val Asp
85 90 95
Cys Ala Pro Cys Pro Pro Gly His Phe Ser Pro Gly Asp Asn Gln Ala
100 105 110
Cys Lys Pro Trp Thr Asn Cys Thr Leu Ala Gly Lys His Thr Leu Gln
115 120 125
Pro Ala Ser Asn Ser Ser Asp Ala Ile Cys Glu Asp Arg Asp Pro Pro
130 135 140
Ala Thr Gln Pro Gln Glu Thr Gln Gly Pro Pro Ala Arg Pro Ile Thr
145 150 155 160
Val Gln Pro Thr Glu Ala Trp Pro Arg Thr Ser Gln Gly Pro Ser Thr
165 170 175
Arg Pro Val Glu Val Pro Gly Gly Arg Ala Val Ala Ala Ile Leu Gly
180 185 190
Leu Gly Leu Val Leu Gly Leu Leu Gly Pro Leu Ala Ile Leu Leu Ala
195 200 205
Leu Tyr Leu Leu Arg Arg Asp Gln Arg Leu Pro Pro Asp Ala His Lys
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Pro Pro Gly Gly Gly Ser Phe Arg Thr Pro Ile Gln Glu Glu Gln Ala
225 230 235 240
Asp Ala His Ser Thr Leu Ala Lys Ile
245
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Met Glu Arg Val Gln Pro Leu Glu Glu Asn Val Gly Asn Ala Ala Arg
1 5 10 15
Pro Arg Phe Glu Arg Asn Lys Leu Leu Leu Val Ala Ser Val Ile Gln
20 25 30
Gly Leu Gly Leu Leu Leu Cys Phe Thr Tyr Ile Cys Leu His Phe Ser
35 40 45
Ala Leu Gln Val Ser His Arg Tyr Pro Arg Ile Gln Ser Ile Lys Val
50 55 60
Gln Phe Thr Glu Tyr Lys Lys Glu Lys Gly Phe Ile Leu Thr Ser Gln
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Lys Glu Asp Glu Ile Met Lys Val Gln Asn Asn Ser Val Ile Ile Asn
85 90 95
Cys Asp Gly Phe Tyr Leu Ile Ser Leu Lys Gly Tyr Phe Ser Gln Glu
100 105 110
Val Asn Ile Ser Leu His Tyr Gln Lys Asp Glu Glu Pro Leu Phe Gln
115 120 125
Leu Lys Lys Val Arg Ser Val Asn Ser Leu Met Val Ala Ser Leu Thr
130 135 140
Tyr Lys Asp Lys Val Tyr Leu Asn Val Thr Thr Asp Asn Thr Ser Leu
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Asp Asp Phe His Val Asn Gly Gly Glu Leu Ile Leu Ile His Gln Asn
165 170 175
Pro Gly Glu Phe Cys Val Leu
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Val Ile His Val Thr Lys Glu Val Lys Glu Val Ala Thr Leu Ser Cys
1 5 10 15
Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile Tyr Trp
20 25 30
Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn
35 40 45
Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn
50 55 60
Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr
65 70 75 80
Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His
85 90 95
Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro Ser
100 105 110
Ile Ser Asp Phe Glu Ile Pro Thr Ser Asn Ile Arg Arg Ile Ile Cys
115 120 125
Ser Thr Ser Gly Gly Phe Pro Glu Pro His Leu Ser Trp Leu Glu Asn
130 135 140
Gly Glu Glu Leu Asn Ala Ile Asn Thr Thr Val Ser Gln Asp Pro Glu
145 150 155 160
Thr Glu Leu Tyr Ala Val Ser Ser Lys Leu Asp Phe Asn Met Thr Thr
165 170 175
Asn His Ser Phe Met Cys Leu Ile Lys Tyr Gly His Leu Arg Val Asn
180 185 190
Gln Thr Phe Asn Trp Asn Thr Thr Lys Gln Glu His Phe Pro Asp Asn
195 200 205
Leu Leu Pro Ser Trp Ala Ile Thr Leu Ile Ser Val Asn Gly Ile Phe
210 215 220
Val Ile Cys Cys Leu Thr Tyr Cys Phe Ala Pro Arg Cys Arg Glu Arg
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Arg Arg Asn Glu Arg Leu Arg Arg Glu Ser Val Arg Pro Val
245 250
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Ala Pro Leu Lys Ile Gln Ala Tyr Phe Asn Glu Thr Ala Asp Leu Pro
1 5 10 15
Cys Gln Phe Ala Asn Ser Gln Asn Gln Ser Leu Ser Glu Leu Val Val
20 25 30
Phe Trp Gln Asp Gln Glu Asn Leu Val Leu Asn Glu Val Tyr Leu Gly
35 40 45
Lys Glu Lys Phe Asp Ser Val His Ser Lys Tyr Met Gly Arg Thr Ser
50 55 60
Phe Asp Ser Asp Ser Trp Thr Leu Arg Leu His Asn Leu Gln Ile Lys
65 70 75 80
Asp Lys Gly Leu Tyr Gln Cys Ile Ile His His Lys Lys Pro Thr Gly
85 90 95
Met Ile Arg Ile His Gln Met Asn Ser Glu Leu Ser Val Leu Ala Asn
100 105 110
Phe Ser Gln Pro Glu Ile Val Pro Ile Ser Asn Ile Thr Glu Asn Val
115 120 125
Tyr Ile Asn Leu Thr Cys Ser Ser Ile His Gly Tyr Pro Glu Pro Lys
130 135 140
Lys Met Ser Val Leu Leu Arg Thr Lys Asn Ser Thr Ile Glu Tyr Asp
145 150 155 160
Gly Val Met Gln Lys Ser Gln Asp Asn Val Thr Glu Leu Tyr Asp Val
165 170 175
Ser Ile Ser Leu Ser Val Ser Phe Pro Asp Val Thr Ser Asn Met Thr
180 185 190
Ile Phe Cys Ile Leu Glu Thr Asp Lys Thr Arg Leu Leu Ser Ser Pro
195 200 205
Phe Ser Ile Glu Leu Glu Asp Pro Gln Pro Pro Pro Asp His Ile Pro
210 215 220
Trp Ile Thr Ala Val Leu Pro Thr Val Ile Ile Cys Val Met Val Phe
225 230 235 240
Cys Leu Ile Leu Trp Lys Trp Lys Lys Lys Lys Arg Pro Arg Asn Ser
245 250 255
Tyr Lys Cys Gly Thr Asn Thr Met Glu Arg Glu Glu Ser Glu Gln Thr
260 265 270
Lys Lys Arg Glu Lys Ile His Ile Pro Glu Arg Ser Asp Glu Ala Gln
275 280 285
Arg Val Phe Lys Ser Ser Lys Thr Ser Ser Cys Asp Lys Ser Asp Thr
290 295 300
Cys Phe
305
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Tyr Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Pro Cys Gly Gly Asn Asn Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Ser Ile Asn Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Asn Thr Val Ile
85 90 95
Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
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Thr Glu Cys Ser
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<br/><![CDATA[Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Gly Ile Gly Ser Val Asp Tyr Ser Gly Asn Thr Tyr Tyr
50 55 60
Lys Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys
65 70 75 80
Asn Gln Phe Ser Leu Lys Leu Ser Thr Val Thr Ala Ala Asp Thr Ala
85 90 95
Val Tyr His Cys Ala Arg His Arg Gly Ile Tyr Phe Phe Asp Tyr Trp
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Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
115 120 125
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
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Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
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Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
165 170 175
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
180 185 190
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
195 200 205
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser
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Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
225 230 235 240
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
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Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
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His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
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Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
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Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
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Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
325 330 335
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
340 345 350
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
355 360 365
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
370 375 380
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
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Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
405 410 415
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
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Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
435 440 445
Ser Pro Gly Lys
450
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Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Met Thr Cys Gly Gly Ser Asp Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile His
35 40 45
Arg Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Arg Asp Ser Asn Ile Val Val
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Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 8]]>
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Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser Ile Ser Thr Ser
20 25 30
Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Arg Pro Ser
50 55 60
Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
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Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile Trp Gly Leu Gly
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Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys
<![CDATA[<210> 9]]>
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Ser Phe Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Ile Asn Ile Glu Asn Lys Asn Val
20 25 30
His Tyr Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Arg Asp Thr Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Asn Thr Val Ile
85 90 95
Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 10]]>
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Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Asp Thr Ser
20 25 30
Ser Gln Tyr Trp Ala Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Gly Ile Tyr Phe Ser Gly Ser Thr Tyr Gln Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Thr Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Arg Leu Ser Ser Met Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg His Arg Gly Ile Tyr Phe Phe Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys
<![CDATA[<210> 11]]>
<![CDATA[<211> 214]]>
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<![CDATA[<213> 人工序列]]>
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<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 1]]>1
Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Asn Tyr Phe Ala
20 25 30
Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser
50 55 60
Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Tyr His
85 90 95
Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys
100 105 110
Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln
115 120 125
Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly
130 135 140
Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly
145 150 155 160
Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala
165 170 175
Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser
180 185 190
Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val
195 200 205
Ala Pro Thr Glu Cys Ser
210
<![CDATA[<210> 12]]>
<![CDATA[<211> 451]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
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<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 12]]>
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Ser Phe Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Thr Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Ala Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Tyr Leu Asn Leu Asn Phe Val Thr Ala Ala Asp Thr Ala Val Tyr His
85 90 95
Cys Ala Arg Glu Arg Ser Ser Ser Trp Tyr Pro Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
355 360 365
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<![CDATA[<210> 13]]>
<![CDATA[<211> 212]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
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<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 13]]>
Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Met Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Asn Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Asn Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 14]]>
<![CDATA[<211> 449]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
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<![CDATA[<223> ]]>人工序列之描述：合成多肽
<![CDATA[<400> 14]]>
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ala Gly Ala Ser Val Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Thr Ile Asn Tyr Gly Gly Ser Thr Tyr His Asn Pro Ser
50 55 60
Leu Lys Arg Arg Val Thr Val Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg His Arg Gly Ile Tyr His Phe Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys
<![CDATA[<210> 15]]>
<![CDATA[<211> 214]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
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<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 15]]>
Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Val Arg Arg Phe Phe Ala
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Ile Leu Val Ile Ser
35 40 45
Gly Lys Asp Thr Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser
50 55 60
Ile Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Tyr Leu
85 90 95
Val Leu Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys
100 105 110
Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln
115 120 125
Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly
130 135 140
Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly
145 150 155 160
Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala
165 170 175
Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser
180 185 190
Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val
195 200 205
Ala Pro Thr Glu Cys Ser
210
<![CDATA[<210> 16]]>
<![CDATA[<211> 450]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 16]]>
Glu Val Gln Leu Val Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Ile Arg Ser Asn
20 25 30
Gly Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Asn Met Asp Tyr Ser Gly Thr Tyr Gln Asn Pro Ser Leu
50 55 60
Thr Ser Arg Val Thr Ile Ser Gly Asp Ala Ser Lys Asn Gln Phe Ser
65 70 75 80
Leu Lys Leu Arg Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Phe Cys
85 90 95
Ala Arg Glu Arg Ser Asn Asn Trp Tyr Pro Ile Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Lys
450
<![CDATA[<210> 17]]>
<![CDATA[<211> 212]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 17]]>
Ser Tyr Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Ser Ile Asn Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Asn Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 18]]>
<![CDATA[<211> 452]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 18]]>
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Gly Ile Gly Ser Val Asp Tyr Ser Gly Asn Thr Tyr Tyr
50 55 60
Lys Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys
65 70 75 80
Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala
85 90 95
Val Tyr His Cys Ala Arg His Arg Gly Ile Tyr Phe Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
115 120 125
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
130 135 140
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
145 150 155 160
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
165 170 175
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
180 185 190
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
195 200 205
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser
210 215 220
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
225 230 235 240
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
245 250 255
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
260 265 270
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
275 280 285
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
290 295 300
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
305 310 315 320
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
325 330 335
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
340 345 350
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
355 360 365
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
370 375 380
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
385 390 395 400
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
405 410 415
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
435 440 445
Ser Pro Gly Lys
450
<![CDATA[<210> 19]]>
<![CDATA[<211> 211]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 19]]>
Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Ser Cys Gly Gly Asn Asn Ile Gly Arg Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Gly Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Gly Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Thr Val Phe
85 90 95
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala Pro
100 105 110
Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys
115 120 125
Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr
130 135 140
Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu Thr
145 150 155 160
Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr
165 170 175
Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser Cys
180 185 190
Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro Thr
195 200 205
Glu Cys Ser
210
<![CDATA[<210> 20]]>
<![CDATA[<211> 449]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 20]]>
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Ser Gly Ser Gly Asp Ser Thr Tyr Tyr Ala Glu 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 Thr Ser Leu Arg Ala Glu Asp Thr Ala Glu Tyr Tyr Cys
85 90 95
Ala Lys Asp Arg Thr Pro Val Tyr Gly Leu Asp Val Trp Gly Gln Gly
100 105 110
Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys
<![CDATA[<210> 21]]>
<![CDATA[<211> 214]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 21]]>
Asp Met Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Asp
20 25 30
Leu Asp Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Arg Leu Ile
35 40 45
His Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Val Thr Tyr Tyr Cys Leu Gln His Asn Thr Tyr Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<![CDATA[<210> 22]]>
<![CDATA[<211> 45]]>1
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 22]]>
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Asp Ile Ser Gly Ser Gly Gly Ser Thr Lys Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Pro Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Lys Asp Leu Gly Phe Tyr Ser Thr Trp Asp Thr Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
355 360 365
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<![CDATA[<210> 23]]>
<![CDATA[<211> 212]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
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<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 23]]>
Ser Tyr Val Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Asp Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Ser
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ser Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 24]]>
<![CDATA[<211> 451]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 24]]>
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Ala Ser Ile Ser Ser Ser
20 25 30
Asn His Tyr Trp Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly
35 40 45
Leu Glu Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Asn Thr Tyr Tyr Asn
50 55 60
Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn
65 70 75 80
Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val
85 90 95
Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp His Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
355 360 365
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<![CDATA[<210> 25]]>
<![CDATA[<211> 212]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 25]]>
Ser Ser Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ser Pro Gly Gln
1 5 10 15
Thr Ala Ser Ile Thr Cys Ser Gly Asp Lys Leu Gly Asp Lys Tyr Ala
20 25 30
Cys Trp Tyr Gln Gln Lys Ala Gly Gln Ser Pro Val Val Val Ile Tyr
35 40 45
Gln Asp Arg Lys Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Met
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Thr Trp Asp Arg Arg Thr Ala Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 26]]>
<![CDATA[<211> 452]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 26]]>
Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asn
20 25 30
Ser Ala Val Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu
35 40 45
Trp Leu Gly Arg Thr Asp Tyr Arg Ser Lys Trp Asn Asn Asp Tyr Ala
50 55 60
Val Ser Val Lys Ser Arg Ile Thr Ile Asn Pro Asp Thr Ser Lys Asn
65 70 75 80
Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Val
85 90 95
Tyr Tyr Cys Ala Arg Gly Asp Ala Gly Met Ala Ser Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
115 120 125
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
130 135 140
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
145 150 155 160
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
165 170 175
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
180 185 190
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
195 200 205
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser
210 215 220
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
225 230 235 240
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
245 250 255
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
260 265 270
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
275 280 285
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
290 295 300
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
305 310 315 320
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
325 330 335
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
340 345 350
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
355 360 365
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
370 375 380
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
385 390 395 400
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
405 410 415
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
435 440 445
Ser Pro Gly Lys
450
<![CDATA[<210> 27]]>
<![CDATA[<211> 212]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 27]]>
Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Lys
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Leu Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 28]]>
<![CDATA[<211> 447]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 28]]>
Glu Val Gln Leu Leu Glu Ser Gly Ala Gly Leu Leu Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Ala Val Tyr Gly Gly Ser Phe Ser Asp Tyr
20 25 30
Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn His Ser Gly Ser Thr Asn Tyr Asn Pro Ser Leu Lys
50 55 60
Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu
65 70 75 80
Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Lys Arg Gly Ala Asn Phe Phe Asp Asp Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu
115 120 125
Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys
130 135 140
Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
145 150 155 160
Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser
165 170 175
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser
180 185 190
Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn
195 200 205
Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His
210 215 220
Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu
260 265 270
Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440 445
<![CDATA[<210> 29]]>
<![CDATA[<211> 126]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 29]]>
Lys Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg
1 5 10 15
Gly Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr
20 25 30
Glu Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu
35 40 45
Val Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp
50 55 60
Asp Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr
65 70 75 80
Ile Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val
85 90 95
Glu Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr
100 105 110
Gln Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp
115 120 125
<![CDATA[<210> 30]]>
<![CDATA[<211> 107]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 30]]>
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Glu Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser His Ser Val Ser Phe
85 90 95
Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys
100 105
<![CDATA[<210> 31]]>
<![CDATA[<211> 127]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 31]]>
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Thr Ile Ser Gly Ser Gly Gly Ala Thr Arg Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Val Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Val Glu Asp Thr Ala Val Phe Tyr Cys
85 90 95
Thr Lys Asp Arg Leu Ile Met Ala Thr Val Arg Gly Pro Tyr Tyr Tyr
100 105 110
Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<![CDATA[<210> 32]]>
<![CDATA[<211> 107]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 32]]>
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<![CDATA[<210> 33]]>
<![CDATA[<211> 120]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 33]]>
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Ser Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ile Ile Ser Gly Ser Gly Gly Phe Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Thr Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Lys Asp Arg Leu Val Ala Pro Gly Thr Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Ala Leu Val Thr Val Ser Ser
115 120
<![CDATA[<210> 34]]>
<![CDATA[<211> 358]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 34]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Pro Glu
130 135 140
Leu Leu Gly Gly Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
180 185 190
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
195 200 205
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
210 215 220
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
225 230 235 240
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
245 250 255
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn
260 265 270
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
275 280 285
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
290 295 300
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
305 310 315 320
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
325 330 335
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
340 345 350
Ser Leu Ser Pro Gly Lys
355
<![CDATA[<210> 35]]>
<![CDATA[<211> 214]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 35]]>
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<![CDATA[<210> 36]]>
<![CDATA[<211> 449]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 36]]>
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Ser Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ile Ile Ser Gly Ser Gly Gly Phe Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Thr Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Lys Asp Arg Leu Val Ala Pro Gly Thr Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Ala Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly
<![CDATA[<210> 37]]>
<![CDATA[<211> 596]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 37]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Pro Glu
130 135 140
Leu Leu Gly Gly Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
180 185 190
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
195 200 205
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
210 215 220
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
225 230 235 240
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
245 250 255
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
260 265 270
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
275 280 285
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
290 295 300
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
305 310 315 320
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
325 330 335
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
340 345 350
Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
355 360 365
Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
370 375 380
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
385 390 395 400
Thr Phe Asn Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys
405 410 415
Gly Leu Glu Trp Val Ser Ile Ile Ser Gly Ser Gly Gly Phe Thr Tyr
420 425 430
Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser
435 440 445
Arg Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Lys Asp Arg Leu Val Ala Pro Gly Thr Phe
465 470 475 480
Asp Tyr Trp Gly Gln Gly Ala Leu Val Thr Val Ser Ser Ala Ser Thr
485 490 495
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
500 505 510
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
515 520 525
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
530 535 540
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
545 550 555 560
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
565 570 575
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
580 585 590
Pro Lys Ser Cys
595
<![CDATA[<210> 38]]>
<![CDATA[<211> 597]]>
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<![CDATA[<213> 人工序列]]>
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<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 38]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ser
225 230 235 240
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Gly Ile Gly Ser Val Asp Tyr Ser Gly
420 425 430
Asn Thr Tyr Tyr Lys Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val
435 440 445
Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Thr Val Thr Ala
450 455 460
Ala Asp Thr Ala Val Tyr His Cys Ala Arg His Arg Gly Ile Tyr Phe
465 470 475 480
Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser
485 490 495
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr
500 505 510
Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro
515 520 525
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val
530 535 540
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser
545 550 555 560
Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile
565 570 575
Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val
580 585 590
Glu Pro Lys Ser Cys
595
<![CDATA[<210> 39]]>
<![CDATA[<211> 212]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
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<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 39]]>
Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Met Thr Cys Gly Gly Ser Asp Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile His
35 40 45
Arg Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Arg Asp Ser Asn Ile Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 40]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 40]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ser
225 230 235 240
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 41]]>
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<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 41]]>
Ser Phe Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Ile Asn Ile Glu Asn Lys Asn Val
20 25 30
His Tyr Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Arg Asp Thr Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Asn Thr Val Ile
85 90 95
Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 42]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 42]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ser
225 230 235 240
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser
385 390 395 400
Ile Asp Thr Ser Ser Gln Tyr Trp Ala Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Gly Ile Tyr Phe Ser Gly Ser Thr Tyr
420 425 430
Gln Asn Pro Ser Leu Lys Ser Arg Val Thr Thr Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Met Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ile Tyr Phe Phe Asp Tyr
465 470 475 480
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 43]]>
<![CDATA[<211> 214]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 43]]>
Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Asn Tyr Phe Ala
20 25 30
Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser
50 55 60
Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Tyr His
85 90 95
Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys
100 105 110
Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln
115 120 125
Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly
130 135 140
Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly
145 150 155 160
Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala
165 170 175
Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser
180 185 190
Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val
195 200 205
Ala Pro Thr Glu Cys Ser
210
<![CDATA[<210> 44]]>
<![CDATA[<211> 596]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 44]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ser
225 230 235 240
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Ser Gly Ser Phe Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Thr Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Asn Pro Ser Leu Lys Ser Arg Val Ala Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Tyr Leu Asn Leu Asn Phe Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr His Cys Ala Arg Glu Arg Ser Ser Ser Trp Tyr Pro Phe
465 470 475 480
Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
485 490 495
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
500 505 510
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
515 520 525
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
530 535 540
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
545 550 555 560
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
565 570 575
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
580 585 590
Pro Lys Ser Cys
595
<![CDATA[<210> 45]]>
<![CDATA[<211> 212]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 45]]>
Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Met Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Asn Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Asn Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 46]]>
<![CDATA[<211> 59]]>4
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 46]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ser
225 230 235 240
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ala Gly Ala Ser
385 390 395 400
Val Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Thr Ile Asn Tyr Gly Gly Ser Thr Tyr
420 425 430
His Asn Pro Ser Leu Lys Arg Arg Val Thr Val Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ile Tyr His Phe Asp Tyr
465 470 475 480
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 47]]>
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Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Val Arg Arg Phe Phe Ala
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Ile Leu Val Ile Ser
35 40 45
Gly Lys Asp Thr Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser
50 55 60
Ile Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Tyr Leu
85 90 95
Val Leu Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys
100 105 110
Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln
115 120 125
Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly
130 135 140
Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly
145 150 155 160
Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala
165 170 175
Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser
180 185 190
Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val
195 200 205
Ala Pro Thr Glu Cys Ser
210
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Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ser
225 230 235 240
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser
385 390 395 400
Ile Arg Ser Asn Gly Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Asn Met Asp Tyr Ser Gly Thr Tyr Gln
420 425 430
Asn Pro Ser Leu Thr Ser Arg Val Thr Ile Ser Gly Asp Ala Ser Lys
435 440 445
Asn Gln Phe Ser Leu Lys Leu Arg Ser Val Thr Ala Ala Asp Thr Ala
450 455 460
Val Tyr Phe Cys Ala Arg Glu Arg Ser Asn Asn Trp Tyr Pro Ile Asp
465 470 475 480
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys
485 490 495
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
500 505 510
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
515 520 525
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
530 535 540
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
545 550 555 560
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
565 570 575
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro
580 585 590
Lys Ser Cys
595
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Ser Tyr Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Ser Ile Asn Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Asn Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
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Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ser
225 230 235 240
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Gly Ile Gly Ser Val Asp Tyr Ser Gly
420 425 430
Asn Thr Tyr Tyr Lys Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val
435 440 445
Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala
450 455 460
Ala Asp Thr Ala Val Tyr His Cys Ala Arg His Arg Gly Ile Tyr Phe
465 470 475 480
Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser
485 490 495
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr
500 505 510
Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro
515 520 525
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val
530 535 540
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser
545 550 555 560
Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile
565 570 575
Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val
580 585 590
Glu Pro Lys Ser Cys
595
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Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Ser Cys Gly Gly Asn Asn Ile Gly Arg Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Gly Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Gly Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Thr Val Phe
85 90 95
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala Pro
100 105 110
Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys
115 120 125
Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr
130 135 140
Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu Thr
145 150 155 160
Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr
165 170 175
Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser Cys
180 185 190
Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro Thr
195 200 205
Glu Cys Ser
210
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<br/><![CDATA[Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ser
225 230 235 240
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val
370 375 380
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
385 390 395 400
Phe Ser Asn Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
405 410 415
Leu Glu Trp Val Ser Val Ile Ser Gly Ser Gly Asp Ser Thr Tyr Tyr
420 425 430
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys
435 440 445
Asn Thr Leu Tyr Leu Gln Met Thr Ser Leu Arg Ala Glu Asp Thr Ala
450 455 460
Glu Tyr Tyr Cys Ala Lys Asp Arg Thr Pro Val Tyr Gly Leu Asp Val
465 470 475 480
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Asp Met Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Asp
20 25 30
Leu Asp Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Arg Leu Ile
35 40 45
His Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Val Thr Tyr Tyr Cys Leu Gln His Asn Thr Tyr Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
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Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ser
225 230 235 240
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val
370 375 380
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
385 390 395 400
Phe Ser Ser Tyr Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly
405 410 415
Leu Glu Trp Val Ser Asp Ile Ser Gly Ser Gly Gly Ser Thr Lys Tyr
420 425 430
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Pro Lys
435 440 445
Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala
450 455 460
Val Tyr Tyr Cys Ala Lys Asp Leu Gly Phe Tyr Ser Thr Trp Asp Thr
465 470 475 480
Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
485 490 495
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
500 505 510
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
515 520 525
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
530 535 540
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
545 550 555 560
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
565 570 575
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
580 585 590
Pro Lys Ser Cys
595
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Ser Tyr Val Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Asp Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Ser
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ser Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
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Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ser
225 230 235 240
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Ala Ser
385 390 395 400
Ile Ser Ser Ser Asn His Tyr Trp Gly Trp Gly Trp Ile Arg Gln Pro
405 410 415
Pro Gly Lys Gly Leu Glu Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Asn
420 425 430
Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp
435 440 445
Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala
450 455 460
Asp Thr Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe
465 470 475 480
Asp His Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
485 490 495
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
500 505 510
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
515 520 525
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
530 535 540
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
545 550 555 560
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
565 570 575
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
580 585 590
Pro Lys Ser Cys
595
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Ser Ser Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ser Pro Gly Gln
1 5 10 15
Thr Ala Ser Ile Thr Cys Ser Gly Asp Lys Leu Gly Asp Lys Tyr Ala
20 25 30
Cys Trp Tyr Gln Gln Lys Ala Gly Gln Ser Pro Val Val Val Ile Tyr
35 40 45
Gln Asp Arg Lys Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Met
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Thr Trp Asp Arg Arg Thr Ala Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 58]]>
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<![CDATA[<400> 58]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ser
225 230 235 240
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser
385 390 395 400
Val Ser Ser Asn Ser Ala Val Trp Asn Trp Ile Arg Gln Ser Pro Ser
405 410 415
Arg Gly Leu Glu Trp Leu Gly Arg Thr Asp Tyr Arg Ser Lys Trp Asn
420 425 430
Asn Asp Tyr Ala Val Ser Val Lys Ser Arg Ile Thr Ile Asn Pro Asp
435 440 445
Thr Ser Lys Asn Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu
450 455 460
Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Asp Ala Gly Met Ala Ser
465 470 475 480
Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser
485 490 495
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr
500 505 510
Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro
515 520 525
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val
530 535 540
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser
545 550 555 560
Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile
565 570 575
Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val
580 585 590
Glu Pro Lys Ser Cys
595
<![CDATA[<210> 59]]>
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<![CDATA[<400> 59]]>
Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Lys
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Leu Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 60]]>
<![CDATA[<211> 592]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
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<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 60]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ser
225 230 235 240
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Ala Gly Leu Leu
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ala Val Tyr Gly Gly Ser
385 390 395 400
Phe Ser Asp Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly
405 410 415
Leu Glu Trp Ile Gly Glu Ile Asn His Ser Gly Ser Thr Asn Tyr Asn
420 425 430
Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn
435 440 445
Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val
450 455 460
Tyr Tyr Cys Ala Arg Lys Arg Gly Ala Asn Phe Phe Asp Asp Trp Gly
465 470 475 480
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
485 490 495
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
500 505 510
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
515 520 525
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
530 535 540
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
545 550 555 560
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
565 570 575
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys
580 585 590
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Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Ser Asp Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile His
35 40 45
Arg Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Arg Asp Ser Asn Ile Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 62]]>
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<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
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<![CDATA[<223> 人工序列之描述：合成多肽]]>
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Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 63]]>
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Ser Ser Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Met Thr Cys Gly Gly Ser Asp Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile His
35 40 45
Arg Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Arg Asp Ser Asn Ile Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 64]]>
<![CDATA[<211> 595]]>
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<![CDATA[<213> 人工序列]]>
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Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
130 135 140
Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
180 185 190
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
195 200 205
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
210 215 220
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
225 230 235 240
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
245 250 255
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
260 265 270
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
275 280 285
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
290 295 300
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
305 310 315 320
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
325 330 335
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
340 345 350
Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
355 360 365
Gly Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu
370 375 380
Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly
385 390 395 400
Ser Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro
405 410 415
Gly Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr
420 425 430
Tyr Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr
435 440 445
Ser Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp
450 455 460
Thr Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp
465 470 475 480
Ile Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys
485 490 495
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
500 505 510
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
515 520 525
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
530 535 540
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
545 550 555 560
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
565 570 575
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro
580 585 590
Lys Ser Cys
595
<![CDATA[<210> 65]]>
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Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Thr Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 66]]>
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Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Ala Ser
385 390 395 400
Val Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Thr Ile Asn Tyr Gly Gly Ser Thr Tyr
420 425 430
His Asn Pro Ser Leu Lys Arg Arg Val Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ile Tyr His Phe Asp Tyr
465 470 475 480
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 67]]>
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Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Val Arg Arg Phe Phe Ala
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Ser
35 40 45
Gly Lys Asp Thr Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser
50 55 60
Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Tyr Leu
85 90 95
Val Leu Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys
100 105 110
Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln
115 120 125
Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly
130 135 140
Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly
145 150 155 160
Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala
165 170 175
Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser
180 185 190
Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val
195 200 205
Ala Pro Thr Glu Cys Ser
210
<![CDATA[<210> 68]]>
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Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser
385 390 395 400
Ile Arg Ser Ser Gly Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Asn Ile Asp Tyr Ser Gly Thr Tyr Gln
420 425 430
Asn Pro Ser Leu Thr Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys
435 440 445
Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala
450 455 460
Val Tyr Tyr Cys Ala Arg Glu Arg Ser Asn Asn Trp Tyr Pro Ile Asp
465 470 475 480
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys
485 490 495
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
500 505 510
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
515 520 525
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
530 535 540
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
545 550 555 560
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
565 570 575
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro
580 585 590
Lys Ser Cys
595
<![CDATA[<210> 69]]>
<![CDATA[<211> 212]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 69]]>
Ser Tyr Glu Leu Thr Gln Pro Pro Ser Met Ser Val Ala Pro Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Ser Asn Ile Glu Asp Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Lys
35 40 45
Arg Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Glu Tyr Tyr Cys Gln Val Trp Asp Ser Ser Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala
100 105 110
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn
115 120 125
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val
130 135 140
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu
145 150 155 160
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser
165 170 175
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Lys Ser Tyr Ser
180 185 190
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro
195 200 205
Thr Glu Cys Ser
210
<![CDATA[<210> 70]]>
<![CDATA[<211> 597]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 70]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Gly Ile Gly Ser Val Asp Tyr Ser Gly
420 425 430
Asn Thr Tyr Tyr Lys Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val
435 440 445
Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala
450 455 460
Ala Asp Thr Ala Val Tyr His Cys Ala Arg His Arg Gly Ile Tyr Phe
465 470 475 480
Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser
485 490 495
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr
500 505 510
Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro
515 520 525
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val
530 535 540
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser
545 550 555 560
Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile
565 570 575
Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val
580 585 590
Glu Pro Lys Ser Cys
595
<![CDATA[<210> 71]]>
<![CDATA[<211> 357]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 71]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Pro Glu
130 135 140
Leu Leu Gly Gly Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
180 185 190
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
195 200 205
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
210 215 220
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
225 230 235 240
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
245 250 255
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
260 265 270
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
275 280 285
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
290 295 300
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
305 310 315 320
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
325 330 335
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
340 345 350
Ser Leu Ser Pro Gly
355
<![CDATA[<210> 72]]>
<![CDATA[<211> 371]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223]]>> 人工序列之描述：合成多肽]]>
<br/>
<br/><![CDATA[<400> 72]]>
<br/><![CDATA[Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Glu Ala Glu Gly Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
20 25 30
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
35 40 45
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
50 55 60
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
65 70 75 80
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
85 90 95
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
100 105 110
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
115 120 125
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr
130 135 140
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
145 150 155 160
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
165 170 175
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
180 185 190
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
195 200 205
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
210 215 220
Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly
225 230 235 240
Gly Ser Gly Gly Gly Gly Ser Ala Met His Val Ala Gln Pro Ala Val
245 250 255
Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe Val Cys Glu Tyr Ala
260 265 270
Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr Val Leu Arg Gln Ala
275 280 285
Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr Tyr Met Met Gly Asn
290 295 300
Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr Gly Thr Ser Ser Gly
305 310 315 320
Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg Ala Met Asp Thr Gly
325 330 335
Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro Pro Pro Tyr Tyr Leu
340 345 350
Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile Asp Pro Glu Pro Cys
355 360 365
Pro Asp Ser
370
<![CDATA[<210> 73]]>
<![CDATA[<211> 471]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 73]]>
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
20 25 30
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
35 40 45
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
50 55 60
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
65 70 75 80
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
85 90 95
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu
100 105 110
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
115 120 125
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys
130 135 140
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
145 150 155 160
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
165 170 175
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
180 185 190
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
195 200 205
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
210 215 220
Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly
225 230 235 240
Ser Gly Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly
245 250 255
Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly
260 265 270
Gly Ser Ile Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro
275 280 285
Pro Gly Lys Gly Leu Glu Trp Ile Gly Gly Ile Gly Ser Val Asp Tyr
290 295 300
Ser Gly Asn Thr Tyr Tyr Lys Pro Ser Leu Lys Ser Arg Val Thr Ile
305 310 315 320
Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Thr Val
325 330 335
Thr Ala Ala Asp Thr Ala Val Tyr His Cys Ala Arg His Arg Gly Ile
340 345 350
Tyr Phe Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
355 360 365
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
370 375 380
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
385 390 395 400
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
405 410 415
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
420 425 430
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
435 440 445
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
450 455 460
Arg Val Glu Pro Lys Ser Cys
465 470
<![CDATA[<210> 74]]>
<![CDATA[<211> 636]]>
<![CDATA[<212> DNA]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成聚核苷酸]]>
<![CDATA[<400> 74]]>
tactatgagc tgactcagcc actctcagtg tcagtggccc tgggacagac ggccaggatt 60
ccctgtgggg gaaacaacat tgaaaataaa aatgtgcact ggtaccaaca gaagccaggc 120
caggcccctg tactggtcat ctatagggat agcaaccggc cctctgggat ccctgagcga 180
ttctctggct ccaactcggg gaacacggcc accctgtcca tcaacagagc ccaagccggg 240
gatgaggctg actattactg tcaggtgtgg gacagcaaca ctgtgatatt cggcggaggg 300
accaaggtca ccgtcctagg acagcccaag gctgccccct cggtcactct gttcccgccc 360
tcctctgagg agcttcaagc caacaaggcc acactggtgt gtctcataag tgacttctac 420
ccgggagccg tgacagtggc ctggaaggca gatagcagcc ccgtcaaggc gggagtggag 480
accaccacac cctccaaaca aagcaacaac aagtacgcgg ccagcagcta cctgagcctg 540
acgcctgagc agtggaagtc ccacaaaagc tacagctgcc aggtcacgca tgaagggagc 600
accgtggaga agacagtggc ccctacagaa tgttca 636
<![CDATA[<210> 75]]>
<![CDATA[<211> 1791]]>
<![CDATA[<212> DNA]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成聚核苷酸]]>
<![CDATA[<400> 75]]>
gcaatgcacg tggcccagcc tgctgtggta ctggccagca gccgaggcat cgccagcttt 60
gtgtgtgagt acgcatctcc aggcaaagcc actgaggtcc gggtgacagt gcttcggcag 120
gctgacagcc aggtgactga agtctgtgcg gcaacctaca tgatggggaa tgagttgacc 180
ttcctagatg attccatctg cacgggcacc tccagtggaa atcaagtgaa cctcactatc 240
caaggactga gggctatgga cacgggactc tacatctgca aggtggagct catgtaccca 300
ccgccatact acctgggcat aggcaacgga acccagattt atgtaattga tccagaaccg 360
tgcccagatt ctgaccagga acccaagagc tccgacaaga cccatacctg tcctccctgt 420
cctgctccac cggtcgctgg gccctccgtg ttcctgttcc cccccaagcc caaggacacc 480
ctgatgatca gcaggacccc cgaggtgacc tgcgtggtgg tggacgtgag ccacgaggac 540
ccagaggtga agttcaattg gtatgtggac ggcgtggagg tgcacaacgc caagaccaag 600
cccagagagg aacagtacaa cagcacctac agggtggtgt ccgtgctgac cgtgctgcac 660
caggactggc tgaacggcaa ggaatacaag tgcgccgtat ccaacaaggc cctgccctcc 720
agcatcgaga aaaccatcag caaggccaag ggccagccac gggagcccca ggtgtacaca 780
ctgcccccat ctcgggaaga aatgaccaag aaccaggtgt ccctgacctg tctggtgaag 840
ggcttttacc ccagcgacat cgccgtggag tgggagagca acggccagcc cgagaacaac 900
tacaagacca ccccccctgt gctggacagc gacggcagct tcttcctgta cagcaagctg 960
accgtggaca agtccaggtg gcagcagggc aacgtgttca gctgcagcgt gatgcacgag 1020
gccctgcaca accactacac acagaagagc ctgagcctgt ccccgggtgc cggaggtggc 1080
ggaagtggtg gcggtggctc aggtggcggt ggatcccagc tgcagctgca ggagtctgga 1140
ccaggactgg tgaagccctc ggagaccctg tccctcacct gcactgtctc tggtggctcc 1200
atcagcagta gtagttacta ctggggctgg atccgccagc ccccagggaa ggggctggag 1260
tggattgggg gtattgggag tgtcgattat agtgggaaca cctactacaa accgtccctc 1320
aagagtcgag tcaccatatc cgtagacacg tccaagaacc agttttccct gaagctgagc 1380
actgtgaccg ccgcagacac ggctgtgtat cactgtgcga gacatcgtgg gatatacttc 1440
tttgactact ggggccaggg aaccctggtc accgtctctt cagctagcac caagggtcca 1500
tcggtcttcc ccctggcacc ctcctccaag agcacctctg ggggcacagc ggccctgggc 1560
tgcctggtca aggactactt ccccgaacca gtgacggtgt cgtggaactc aggcgccctg 1620
accagcggcg tgcacacctt cccggctgtc ctacagtcct caggactcta ctccctcagc 1680
agcgtggtga ccgtgccctc cagcagcttg ggcacccaga cctacatctg caacgtgaat 1740
cacaagccca gcaacaccaa ggtggacaag agagttgagc ccaaatcttg t 1791
<![CDATA[<210> 76]]>
<![CDATA[<211> 119]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 76]]>
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser Ile Ser Thr Ser
20 25 30
Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Arg Pro Ser
50 55 60
Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile Trp Gly Leu Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<![CDATA[<210> 77]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 77]]>
Gly Gly Ser Ile Ser Thr Ser Ser Tyr Tyr
1 5 10
<![CDATA[<210> 78]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 78]]>
Ile Tyr Tyr Ser Gly Ser Thr
1 5
<![CDATA[<210> 79]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 79]]>
Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
1 5 10
<![CDATA[<210> 80]]>
<![CDATA[<211> 106]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 80]]>
Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Met Thr Cys Gly Gly Ser Asp Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile His
35 40 45
Arg Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Arg Asp Ser Asn Ile Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 81]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 81]]>
Asp Ile Glu Asn Lys Asn
1 5
<![CDATA[<210> 82]]>
<![CDATA[<211> 3]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 82]]>
Arg Asp Asn
1
<![CDATA[<210> 83]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 83]]>
Gln Val Arg Asp Ser Asn Ile Val Val
1 5
<![CDATA[<210> 84]]>
<![CDATA[<211> 119]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 84]]>
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ala Gly Ala Ser Val Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Thr Ile Asn Tyr Gly Gly Ser Thr Tyr His Asn Pro Ser
50 55 60
Leu Lys Arg Arg Val Thr Val Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg His Arg Gly Ile Tyr His Phe Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<![CDATA[<210> 85]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 85]]>
Gly Ala Ser Val Ser Ser Ser Ser Tyr Tyr
1 5 10
<![CDATA[<210> 86]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 86]]>
Ile Asn Tyr Gly Gly Ser Thr
1 5
<![CDATA[<210> 87]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 87]]>
Ala Arg His Arg Gly Ile Tyr His Phe Asp Tyr
1 5 10
<![CDATA[<210> 88]]>
<![CDATA[<211> 106]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 88]]>
Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Met Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Asn Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Asn Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Val Thr Val Leu
100 105
<![CDATA[<210> 89]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 89]]>
Asn Ile Glu Asn Lys Asn
1 5
<![CDATA[<210> 90]]>
<![CDATA[<211> 3]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 90]]>
Arg Asp Ser
1
<![CDATA[<210> 91]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 91]]>
Gln Val Trp Asp Ser Asn Thr Val Val
1 5
<![CDATA[<210> 92]]>
<![CDATA[<211> 120]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 92]]>
Glu Val Gln Leu Val Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Ile Arg Ser Asn
20 25 30
Gly Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Asn Met Asp Tyr Ser Gly Thr Tyr Gln Asn Pro Ser Leu
50 55 60
Thr Ser Arg Val Thr Ile Ser Gly Asp Ala Ser Lys Asn Gln Phe Ser
65 70 75 80
Leu Lys Leu Arg Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Phe Cys
85 90 95
Ala Arg Glu Arg Ser Asn Asn Trp Tyr Pro Ile Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<![CDATA[<210> 93]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 93]]>
Gly Val Ser Ile Arg Ser Asn Gly Tyr Tyr
1 5 10
<![CDATA[<210> 94]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 94]]>
Met Asp Tyr Ser Gly Thr
1 5
<![CDATA[<210> 95]]>
<![CDATA[<211> 13]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 95]]>
Ala Arg Glu Arg Ser Asn Asn Trp Tyr Pro Ile Asp Tyr
1 5 10
<![CDATA[<210> 96]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 96]]>
Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Val Arg Arg Phe Phe Ala
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Ile Leu Val Ile Ser
35 40 45
Gly Lys Asp Thr Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser
50 55 60
Ile Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Tyr Leu
85 90 95
Val Leu Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 97]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 97]]>
Ser Val Arg Arg Phe Phe
1 5
<![CDATA[<210> 98]]>
<![CDATA[<211> 3]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 98]]>
Gly Lys Asp
1
<![CDATA[<210> 99]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 99]]>
Asn Ser Arg Asp Ser Ser Gly Tyr Leu Val Leu
1 5 10
<![CDATA[<210> 100]]>
<![CDATA[<211> 122]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 100]]>
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Gly Ile Gly Ser Val Asp Tyr Ser Gly Asn Thr Tyr Tyr
50 55 60
Lys Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys
65 70 75 80
Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala
85 90 95
Val Tyr His Cys Ala Arg His Arg Gly Ile Tyr Phe Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<![CDATA[<210> 101]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 101]]>
Gly Gly Ser Ile Ser Ser Ser Ser Tyr Tyr
1 5 10
<![CDATA[<210> 102]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 102]]>
Ile Gly Ser Val Asp Tyr Ser Gly Asn Thr
1 5 10
<![CDATA[<210> 103]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 103]]>
Ala Arg His Arg Gly Ile Tyr Phe Phe Asp Tyr
1 5 10
<![CDATA[<210> 104]]>
<![CDATA[<211> 106]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 104]]>
Ser Tyr Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Ser Ile Asn Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Asn Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 105]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 105]]>
Ser Tyr Ala Met Ser
1 5
<![CDATA[<210> 106]]>
<![CDATA[<211> 16]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 106]]>
Ile Ile Ser Gly Ser Gly Gly Phe Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
<![CDATA[<210> 107]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 107]]>
Asp Arg Leu Val Ala Pro Gly Thr Phe Asp Tyr
1 5 10
<![CDATA[<210> 108]]>
<![CDATA[<211> 122]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 108]]>
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Gly Ile Gly Ser Val Asp Tyr Ser Gly Asn Thr Tyr Tyr
50 55 60
Lys Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys
65 70 75 80
Asn Gln Phe Ser Leu Lys Leu Ser Thr Val Thr Ala Ala Asp Thr Ala
85 90 95
Val Tyr His Cys Ala Arg His Arg Gly Ile Tyr Phe Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<![CDATA[<210> 109]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 109]]>
Gly Gly Ser Ile Ser Ser Ser Ser Tyr Tyr
1 5 10
<![CDATA[<210> 110]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 110]]>
Ile Gly Ser Val Asp Tyr Ser Gly Asn Thr
1 5 10
<![CDATA[<210> 111]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 111]]>
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser
20
<![CDATA[<210> 112]]>
<![CDATA[<211> 106]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 112]]>
Tyr Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Pro Cys Gly Gly Asn Asn Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Ser Ile Asn Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Asn Thr Val Ile
85 90 95
Phe Gly Gly Gly Thr Lys Val Thr Val Leu
100 105
<![CDATA[<210> 113]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 113]]>
Ile Ser Gly Ser Gly Gly Ala Thr
1 5
<![CDATA[<210> 114]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 114]]>
Thr Lys Asp Arg Leu Ile Met Ala Thr Val Arg Gly Pro Tyr Tyr Tyr
1 5 10 15
Gly Met Asp Val
20
<![CDATA[<210> 115]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 115]]>
Gln Val Trp Asp Ser Asn Thr Val Ile
1 5
<![CDATA[<210> 116]]>
<![CDATA[<211> 119]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 116]]>
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Asp Thr Ser
20 25 30
Ser Gln Tyr Trp Ala Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Gly Ile Tyr Phe Ser Gly Ser Thr Tyr Gln Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Thr Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Arg Leu Ser Ser Met Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg His Arg Gly Ile Tyr Phe Phe Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<![CDATA[<210> 117]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之]]>描述：合成肽
<![CDATA[<400> 117]]>
Gly Gly Ser Ile Asp Thr Ser Ser Gln Tyr
1 5 10
<![CDATA[<210> 118]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 118]]>
Ile Tyr Phe Ser Gly Ser Thr
1 5
<![CDATA[<210> 119]]>
<![CDATA[<211> 124]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 119]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp
115 120
<![CDATA[<210> 120]]>
<![CDATA[<211> 106]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 120]]>
Ser Phe Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Ile Asn Ile Glu Asn Lys Asn Val
20 25 30
His Tyr Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Arg Asp Thr Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Asn Thr Val Ile
85 90 95
Phe Gly Gly Gly Thr Lys Val Thr Val Leu
100 105
<![CDATA[<210> 121]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 121]]>
Gln Ser Ile Ser Ser Tyr
1 5
<![CDATA[<210> 122]]>
<![CDATA[<211> 3]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 122]]>
Arg Asp Thr
1
<![CDATA[<210> 123]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 123]]>
Gln Val Trp Asp Ser Asn Thr Val Ile
1 5
<![CDATA[<210> 124]]>
<![CDATA[<211> 121]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 124]]>
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Ser Phe Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Thr Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Ala Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Tyr Leu Asn Leu Asn Phe Val Thr Ala Ala Asp Thr Ala Val Tyr His
85 90 95
Cys Ala Arg Glu Arg Ser Ser Ser Trp Tyr Pro Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<![CDATA[<210> 125]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 125]]>
Gly Gly Ser Ile Ser Ser Gly Ser Phe Tyr
1 5 10
<![CDATA[<210> 126]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 126]]>
Ile Tyr Tyr Ser Gly Ser Thr
1 5
<![CDATA[<210> 127]]>
<![CDATA[<211> 13]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 127]]>
Ala Arg Glu Arg Ser Ser Ser Trp Tyr Pro Phe Asp Tyr
1 5 10
<![CDATA[<210> 128]]>
<![CDATA[<211> 108]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 128]]>
Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Asn Tyr Phe Ala
20 25 30
Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser
50 55 60
Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Tyr His
85 90 95
Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 129]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 129]]>
Ser Leu Arg Asn Tyr Phe
1 5
<![CDATA[<210> 130]]>
<![CDATA[<211> 3]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 130]]>
Gly Lys Asn
1
<![CDATA[<210> 131]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 131]]>
Asn Ser Arg Asp Ser Ser Gly Tyr His Val Val
1 5 10
<![CDATA[<210> 132]]>
<![CDATA[<211> 119]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 132]]>
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Ser Gly Ser Gly Asp Ser Thr Tyr Tyr Ala Glu 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 Thr Ser Leu Arg Ala Glu Asp Thr Ala Glu Tyr Tyr Cys
85 90 95
Ala Lys Asp Arg Thr Pro Val Tyr Gly Leu Asp Val Trp Gly Gln Gly
100 105 110
Thr Thr Val Thr Val Ser Ser
115
<![CDATA[<210> 133]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工]]>序列
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 133]]>
Gly Phe Thr Phe Ser Asn Tyr Ala
1 5
<![CDATA[<210> 134]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 134]]>
Ile Ser Gly Ser Gly Asp Ser Thr
1 5
<![CDATA[<210> 135]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 135]]>
Ala Lys Asp Arg Thr Pro Val Tyr Gly Leu Asp Val
1 5 10
<![CDATA[<210> 136]]>
<![CDATA[<211> 105]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 136]]>
Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Ser Cys Gly Gly Asn Asn Ile Gly Arg Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Gly Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Gly Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Thr Val Phe
85 90 95
Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 137]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 137]]>
Asn Ile Gly Arg Lys Asn
1 5
<![CDATA[<210> 138]]>
<![CDATA[<211> 3]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 138]]>
Gly Asp Ser
1
<![CDATA[<210> 139]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 139]]>
Gln Val Trp Asp Ser Ser Thr Val
1 5
<![CDATA[<210> 140]]>
<![CDATA[<211> 121]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 140]]>
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Asp Ile Ser Gly Ser Gly Gly Ser Thr Lys Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Pro Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Lys Asp Leu Gly Phe Tyr Ser Thr Trp Asp Thr Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<![CDATA[<210> 141]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 141]]>
Gly Phe Thr Phe Ser Ser Tyr Ala
1 5
<![CDATA[<210> 142]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 142]]>
Ile Ser Gly Ser Gly Gly Ser Thr
1 5
<![CDATA[<210> 143]]>
<![CDATA[<211> 14]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 143]]>
Ala Lys Asp Leu Gly Phe Tyr Ser Thr Trp Asp Thr Asp Tyr
1 5 10
<![CDATA[<210> 144]]>
<![CDATA[<211> 107]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 144]]>
Asp Met Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Asp
20 25 30
Leu Asp Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Arg Leu Ile
35 40 45
His Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Val Thr Tyr Tyr Cys Leu Gln His Asn Thr Tyr Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<![CDATA[<210> 145]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 145]]>
Gln Gly Ile Arg Asn Asp
1 5
<![CDATA[<210> 146]]>
<![CDATA[<211> 3]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 146]]>
Ala Ala Ser
1
<![CDATA[<210> 147]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 147]]>
Leu Gln His Asn Thr Tyr Pro Trp Thr
1 5
<![CDATA[<210> 148]]>
<![CDATA[<211> 121]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 148]]>
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Ala Ser Ile Ser Ser Ser
20 25 30
Asn His Tyr Trp Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly
35 40 45
Leu Glu Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Asn Thr Tyr Tyr Asn
50 55 60
Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn
65 70 75 80
Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val
85 90 95
Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp His Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<![CDATA[<210> 149]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 149]]>
Gly Ala Ser Ile Ser Ser Ser Asn His Tyr Trp Gly
1 5 10
<![CDATA[<210> 150]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 150]]>
Ile Tyr Tyr Ser Gly Asn Thr
1 5
<![CDATA[<210> 151]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 151]]>
Ala Arg His Arg Gly Ser Tyr Phe Phe Asp His
1 5 10
<![CDATA[<210> 152]]>
<![CDATA[<211> 106]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描]]>述：合成多肽
<![CDATA[<400> 152]]>
Ser Tyr Val Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Asp Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Ser
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ser Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Val Thr Val Leu
100 105
<![CDATA[<210> 153]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 153]]>
Asn Ile Gly Asp Lys Asn
1 5
<![CDATA[<210> 154]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 154]]>
Gln Gln Ser His Ser Val Ser Phe Thr
1 5
<![CDATA[<210> 155]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 155]]>
Gln Val Trp Asp Ser Ser Thr Val Val
1 5
<![CDATA[<210> 156]]>
<![CDATA[<211> 122]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 156]]>
Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asn
20 25 30
Ser Ala Val Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu
35 40 45
Trp Leu Gly Arg Thr Asp Tyr Arg Ser Lys Trp Asn Asn Asp Tyr Ala
50 55 60
Val Ser Val Lys Ser Arg Ile Thr Ile Asn Pro Asp Thr Ser Lys Asn
65 70 75 80
Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Val
85 90 95
Tyr Tyr Cys Ala Arg Gly Asp Ala Gly Met Ala Ser Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<![CDATA[<210> 157]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 157]]>
Gly Asp Ser Val Ser Ser Asn Ser Ala Val
1 5 10
<![CDATA[<210> 158]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 158]]>
Thr Asp Tyr Arg Ser Lys Trp Asn Asn
1 5
<![CDATA[<210> 159]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 159]]>
Ala Arg Gly Asp Ala Gly Met Ala Ser Phe Asp Tyr
1 5 10
<![CDATA[<210> 160]]>
<![CDATA[<211> 106]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 160]]>
Ser Ser Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ser Pro Gly Gln
1 5 10 15
Thr Ala Ser Ile Thr Cys Ser Gly Asp Lys Leu Gly Asp Lys Tyr Ala
20 25 30
Cys Trp Tyr Gln Gln Lys Ala Gly Gln Ser Pro Val Val Val Ile Tyr
35 40 45
Gln Asp Arg Lys Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Met
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Thr Trp Asp Arg Arg Thr Ala Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 161]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 161]]>
Lys Leu Gly Asp Lys Tyr
1 5
<![CDATA[<210> 162]]>
<![CDATA[<211> 3]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 162]]>
Gln Asp Arg
1
<![CDATA[<210> 163]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 163]]>
Gln Thr Trp Asp Arg Arg Thr Ala Val
1 5
<![CDATA[<210> 164]]>
<![CDATA[<211> 117]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 164]]>
Glu Val Gln Leu Leu Glu Ser Gly Ala Gly Leu Leu Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Ala Val Tyr Gly Gly Ser Phe Ser Asp Tyr
20 25 30
Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn His Ser Gly Ser Thr Asn Tyr Asn Pro Ser Leu Lys
50 55 60
Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu
65 70 75 80
Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Lys Arg Gly Ala Asn Phe Phe Asp Asp Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<![CDATA[<210> 165]]>
<![CDATA[<211> 8]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 165]]>
Gly Gly Ser Phe Ser Asp Tyr Tyr
1 5
<![CDATA[<210> 166]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 166]]>
Ile Asn His Ser Gly Ser Thr
1 5
<![CDATA[<210> 167]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 167]]>
Ala Arg Lys Arg Gly Ala Asn Phe Phe Asp Asp
1 5 10
<![CDATA[<210> 168]]>
<![CDATA[<211> 106]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 168]]>
Ser Tyr Glu Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Glu Asn Lys Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Lys
35 40 45
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Leu Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Thr Val Val
85 90 95
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<![CDATA[<210> 169]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 169]]>
Arg Ala Ser Gln Gly Ile Ser Ser Trp Leu Ala
1 5 10
<![CDATA[<210> 170]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 170]]>
Ala Ala Ser Ser Leu Gln Ser
1 5
<![CDATA[<210> 171]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之]]>描述：合成肽
<![CDATA[<400> 171]]>
Gln Gln Tyr Asn Ser Tyr Pro Tyr Thr
1 5
<![CDATA[<210> 172]]>
<![CDATA[<211> 223]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 172]]>
Met Ala Cys Leu Gly Phe Gln Arg His Lys Ala Gln Leu Asn Leu Ala
1 5 10 15
Thr Arg Thr Trp Pro Cys Thr Leu Leu Phe Phe Leu Leu Phe Ile Pro
20 25 30
Val Phe Cys Lys Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala
35 40 45
Ser Ser Arg Gly Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly
50 55 60
Lys Ala Thr Glu Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln
65 70 75 80
Val Thr Glu Val Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr
85 90 95
Phe Leu Asp Asp Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val
100 105 110
Asn Leu Thr Ile Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile
115 120 125
Cys Lys Val Glu Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly
130 135 140
Asn Gly Thr Gln Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser
145 150 155 160
Asp Phe Leu Leu Trp Ile Leu Ala Ala Val Ser Ser Gly Leu Phe Phe
165 170 175
Tyr Ser Phe Leu Leu Thr Ala Val Ser Leu Ser Lys Met Leu Lys Lys
180 185 190
Arg Ser Pro Leu Thr Thr Gly Val Tyr Val Lys Met Pro Pro Thr Glu
195 200 205
Pro Glu Cys Glu Lys Gln Phe Gln Pro Tyr Phe Ile Pro Ile Asn
210 215 220
<![CDATA[<210> 173]]>
<![CDATA[<211> 125]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 173]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp
115 120 125
<![CDATA[<210> 174]]>
<![CDATA[<211> 124]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 174]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp
115 120
<![CDATA[<210> 175]]>
<![CDATA[<211> 22]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 175]]>
Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Glu Leu Leu Gly Gly
20
<![CDATA[<210> 176]]>
<![CDATA[<211> 22]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 176]]>
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Glu Leu Leu Gly Gly
20
<![CDATA[<210> 177]]>
<![CDATA[<211> 22]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 177]]>
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Glu Ala Ala Gly Gly
20
<![CDATA[<210> 178]]>
<![CDATA[<211> 210]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 178]]>
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
1 5 10 15
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
20 25 30
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
35 40 45
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
50 55 60
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
65 70 75 80
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
85 90 95
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
100 105 110
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
115 120 125
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
130 135 140
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
145 150 155 160
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
165 170 175
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
180 185 190
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
195 200 205
Gly Lys
210
<![CDATA[<210> 179]]>
<![CDATA[<211> 210]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 179]]>
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
1 5 10 15
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
20 25 30
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
35 40 45
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
50 55 60
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
65 70 75 80
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
85 90 95
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
100 105 110
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
115 120 125
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
130 135 140
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
145 150 155 160
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
165 170 175
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
180 185 190
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
195 200 205
Gly Ala
210
<![CDATA[<210> 180]]>
<![CDATA[<211> 209]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 180]]>
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
1 5 10 15
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
20 25 30
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
35 40 45
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
50 55 60
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
65 70 75 80
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
85 90 95
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
100 105 110
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
115 120 125
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
130 135 140
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
145 150 155 160
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
165 170 175
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
180 185 190
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
195 200 205
Gly
<![CDATA[<210> 181]]>
<![CDATA[<211> 60]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> SITE]]>
<![CDATA[<222> (1)..(60)]]>
<![CDATA[<223> 此序列可涵蓋1-12個「Gly Gly Gly Gly Ser」重複單元]]>
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Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
20 25 30
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
35 40 45
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
50 55 60
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Lys Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg
1 5 10 15
Gly Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr
20 25 30
Glu Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu
35 40 45
Val Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp
50 55 60
Asp Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr
65 70 75 80
Ile Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val
85 90 95
Glu Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr
100 105 110
Gln Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu
115 120 125
Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
130 135 140
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
145 150 155 160
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
165 170 175
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
180 185 190
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
195 200 205
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
210 215 220
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
225 230 235 240
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
245 250 255
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys
260 265 270
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
275 280 285
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
290 295 300
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
305 310 315 320
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
325 330 335
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
340 345 350
Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly
355 360 365
Ser Gly Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly
370 375 380
Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly
385 390 395 400
Gly Ser Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro
405 410 415
Pro Gly Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser
420 425 430
Thr Tyr Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp
435 440 445
Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala
450 455 460
Asp Thr Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe
465 470 475 480
Asp Ile Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
485 490 495
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
500 505 510
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
515 520 525
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
530 535 540
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
545 550 555 560
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
565 570 575
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
580 585 590
Pro Lys Ser Cys
595
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala
130 135 140
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Lys Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg
1 5 10 15
Gly Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr
20 25 30
Glu Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu
35 40 45
Val Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp
50 55 60
Asp Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr
65 70 75 80
Ile Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val
85 90 95
Glu Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr
100 105 110
Gln Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
130 135 140
Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
180 185 190
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
195 200 205
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
210 215 220
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
225 230 235 240
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
245 250 255
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
260 265 270
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
275 280 285
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
290 295 300
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
305 310 315 320
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
325 330 335
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
340 345 350
Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
355 360 365
Gly Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu
370 375 380
Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly
385 390 395 400
Ser Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro
405 410 415
Gly Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr
420 425 430
Tyr Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr
435 440 445
Ser Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp
450 455 460
Thr Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp
465 470 475 480
Ile Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys
485 490 495
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
500 505 510
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
515 520 525
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
530 535 540
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
545 550 555 560
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
565 570 575
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro
580 585 590
Lys Ser Cys
595
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Glu Pro Lys Ser
115 120 125
Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala
130 135 140
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys
370 375 380
Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser Ile
385 390 395 400
Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys
405 410 415
Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr
420 425 430
Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser Lys
435 440 445
Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr Ala
450 455 460
Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile Trp
465 470 475 480
Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
485 490 495
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
500 505 510
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
515 520 525
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
530 535 540
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
545 550 555 560
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
565 570 575
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser
580 585 590
Cys
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Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala
130 135 140
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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<br/><![CDATA[Lys Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg
1 5 10 15
Gly Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr
20 25 30
Glu Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu
35 40 45
Val Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp
50 55 60
Asp Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr
65 70 75 80
Ile Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val
85 90 95
Glu Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr
100 105 110
Gln Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu
115 120 125
Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
130 135 140
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
145 150 155 160
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
165 170 175
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
180 185 190
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
195 200 205
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
210 215 220
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
225 230 235 240
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
245 250 255
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys
260 265 270
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
275 280 285
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
290 295 300
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
305 310 315 320
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
325 330 335
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
340 345 350
Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly
355 360 365
Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Pro Gly
370 375 380
Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly
385 390 395 400
Val Ser Ile Arg Ser Asn Gly Tyr Tyr Trp Gly Trp Ile Arg Gln Ser
405 410 415
Pro Gly Lys Gly Leu Glu Trp Ile Gly Asn Met Asp Tyr Ser Gly Thr
420 425 430
Tyr Gln Asn Pro Ser Leu Thr Ser Arg Val Thr Ile Ser Gly Asp Ala
435 440 445
Ser Lys Asn Gln Phe Ser Leu Lys Leu Arg Ser Val Thr Ala Ala Asp
450 455 460
Thr Ala Val Tyr Phe Cys Ala Arg Glu Arg Ser Asn Asn Trp Tyr Pro
465 470 475 480
Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser
485 490 495
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr
500 505 510
Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro
515 520 525
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val
530 535 540
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser
545 550 555 560
Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile
565 570 575
Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val
580 585 590
Glu Pro Lys Ser Cys
595
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala
130 135 140
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser
385 390 395 400
Ile Arg Ser Asn Gly Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Asn Met Asp Tyr Ser Gly Thr Tyr Gln
420 425 430
Asn Pro Ser Leu Thr Ser Arg Val Thr Ile Ser Gly Asp Ala Ser Lys
435 440 445
Asn Gln Phe Ser Leu Lys Leu Arg Ser Val Thr Ala Ala Asp Thr Ala
450 455 460
Val Tyr Phe Cys Ala Arg Glu Arg Ser Asn Asn Trp Tyr Pro Ile Asp
465 470 475 480
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys
485 490 495
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
500 505 510
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
515 520 525
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
530 535 540
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
545 550 555 560
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
565 570 575
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro
580 585 590
Lys Ser Cys
595
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Lys Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg
1 5 10 15
Gly Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr
20 25 30
Glu Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu
35 40 45
Val Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp
50 55 60
Asp Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr
65 70 75 80
Ile Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val
85 90 95
Glu Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr
100 105 110
Gln Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
130 135 140
Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
180 185 190
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
195 200 205
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
210 215 220
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
225 230 235 240
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
245 250 255
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
260 265 270
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
275 280 285
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
290 295 300
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
305 310 315 320
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
325 330 335
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
340 345 350
Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
355 360 365
Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Pro Gly Leu
370 375 380
Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val
385 390 395 400
Ser Ile Arg Ser Asn Gly Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro
405 410 415
Gly Lys Gly Leu Glu Trp Ile Gly Asn Met Asp Tyr Ser Gly Thr Tyr
420 425 430
Gln Asn Pro Ser Leu Thr Ser Arg Val Thr Ile Ser Gly Asp Ala Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Arg Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Phe Cys Ala Arg Glu Arg Ser Asn Asn Trp Tyr Pro Ile
465 470 475 480
Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
485 490 495
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
500 505 510
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
515 520 525
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
530 535 540
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
545 550 555 560
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
565 570 575
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
580 585 590
Pro Lys Ser Cys
595
<![CDATA[<210> 190]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 190]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Glu Pro Lys Ser
115 120 125
Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala
130 135 140
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Pro Gly Leu Val Lys
370 375 380
Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Ile
385 390 395 400
Arg Ser Asn Gly Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro Gly Lys
405 410 415
Gly Leu Glu Trp Ile Gly Asn Met Asp Tyr Ser Gly Thr Tyr Gln Asn
420 425 430
Pro Ser Leu Thr Ser Arg Val Thr Ile Ser Gly Asp Ala Ser Lys Asn
435 440 445
Gln Phe Ser Leu Lys Leu Arg Ser Val Thr Ala Ala Asp Thr Ala Val
450 455 460
Tyr Phe Cys Ala Arg Glu Arg Ser Asn Asn Trp Tyr Pro Ile Asp Tyr
465 470 475 480
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 191]]>
<![CDATA[<211> 595]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 191]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala
130 135 140
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser
385 390 395 400
Ile Arg Ser Asn Gly Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Asn Met Asp Tyr Ser Gly Thr Tyr Gln
420 425 430
Asn Pro Ser Leu Thr Ser Arg Val Thr Ile Ser Gly Asp Ala Ser Lys
435 440 445
Asn Gln Phe Ser Leu Lys Leu Arg Ser Val Thr Ala Ala Asp Thr Ala
450 455 460
Val Tyr Phe Cys Ala Arg Glu Arg Ser Asn Asn Trp Tyr Pro Ile Asp
465 470 475 480
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys
485 490 495
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
500 505 510
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
515 520 525
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
530 535 540
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
545 550 555 560
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
565 570 575
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro
580 585 590
Lys Ser Cys
595
<![CDATA[<210> 192]]>
<![CDATA[<211> 596]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 192]]>
Lys Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg
1 5 10 15
Gly Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr
20 25 30
Glu Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu
35 40 45
Val Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp
50 55 60
Asp Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr
65 70 75 80
Ile Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val
85 90 95
Glu Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr
100 105 110
Gln Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu
115 120 125
Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
130 135 140
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
145 150 155 160
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
165 170 175
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
180 185 190
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
195 200 205
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
210 215 220
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
225 230 235 240
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
245 250 255
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys
260 265 270
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
275 280 285
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
290 295 300
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
305 310 315 320
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
325 330 335
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
340 345 350
Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly
355 360 365
Ser Gly Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly
370 375 380
Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ala Gly
385 390 395 400
Ala Ser Val Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Ser
405 410 415
Pro Gly Lys Gly Leu Glu Trp Ile Gly Thr Ile Asn Tyr Gly Gly Ser
420 425 430
Thr Tyr His Asn Pro Ser Leu Lys Arg Arg Val Thr Val Ser Val Asp
435 440 445
Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala
450 455 460
Asp Thr Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ile Tyr His Phe
465 470 475 480
Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
485 490 495
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
500 505 510
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
515 520 525
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
530 535 540
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
545 550 555 560
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
565 570 575
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
580 585 590
Pro Lys Ser Cys
595
<![CDATA[<210> 193]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 193]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala
130 135 140
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ala Gly Ala Ser
385 390 395 400
Val Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Thr Ile Asn Tyr Gly Gly Ser Thr Tyr
420 425 430
His Asn Pro Ser Leu Lys Arg Arg Val Thr Val Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ile Tyr His Phe Asp Tyr
465 470 475 480
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 194]]>
<![CDATA[<211> 595]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 194]]>
Lys Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg
1 5 10 15
Gly Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr
20 25 30
Glu Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu
35 40 45
Val Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp
50 55 60
Asp Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr
65 70 75 80
Ile Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val
85 90 95
Glu Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr
100 105 110
Gln Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
130 135 140
Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
180 185 190
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
195 200 205
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
210 215 220
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
225 230 235 240
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
245 250 255
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
260 265 270
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
275 280 285
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
290 295 300
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
305 310 315 320
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
325 330 335
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
340 345 350
Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
355 360 365
Gly Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu
370 375 380
Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ala Gly Ala
385 390 395 400
Ser Val Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro
405 410 415
Gly Lys Gly Leu Glu Trp Ile Gly Thr Ile Asn Tyr Gly Gly Ser Thr
420 425 430
Tyr His Asn Pro Ser Leu Lys Arg Arg Val Thr Val Ser Val Asp Thr
435 440 445
Ser Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp
450 455 460
Thr Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ile Tyr His Phe Asp
465 470 475 480
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys
485 490 495
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
500 505 510
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
515 520 525
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
530 535 540
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
545 550 555 560
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
565 570 575
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro
580 585 590
Lys Ser Cys
595
<![CDATA[<210> 195]]>
<![CDATA[<211> 593]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 195]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Glu Pro Lys Ser
115 120 125
Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala
130 135 140
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys
370 375 380
Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ala Gly Ala Ser Val
385 390 395 400
Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro Gly Lys
405 410 415
Gly Leu Glu Trp Ile Gly Thr Ile Asn Tyr Gly Gly Ser Thr Tyr His
420 425 430
Asn Pro Ser Leu Lys Arg Arg Val Thr Val Ser Val Asp Thr Ser Lys
435 440 445
Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr Ala
450 455 460
Val Tyr Tyr Cys Ala Arg His Arg Gly Ile Tyr His Phe Asp Tyr Trp
465 470 475 480
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
485 490 495
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
500 505 510
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
515 520 525
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
530 535 540
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
545 550 555 560
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
565 570 575
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser
580 585 590
Cys
<![CDATA[<210> 196]]>
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<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 196]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala
130 135 140
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ala Gly Ala Ser
385 390 395 400
Val Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Ser Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Thr Ile Asn Tyr Gly Gly Ser Thr Tyr
420 425 430
His Asn Pro Ser Leu Lys Arg Arg Val Thr Val Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ile Tyr His Phe Asp Tyr
465 470 475 480
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 197]]>
<![CDATA[<211> 599]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 197]]>
Lys Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg
1 5 10 15
Gly Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr
20 25 30
Glu Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu
35 40 45
Val Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp
50 55 60
Asp Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr
65 70 75 80
Ile Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val
85 90 95
Glu Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr
100 105 110
Gln Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu
115 120 125
Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
130 135 140
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
145 150 155 160
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
165 170 175
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
180 185 190
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
195 200 205
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
210 215 220
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
225 230 235 240
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
245 250 255
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys
260 265 270
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
275 280 285
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
290 295 300
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
305 310 315 320
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
325 330 335
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
340 345 350
Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly
355 360 365
Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly
370 375 380
Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly
385 390 395 400
Gly Ser Ile Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro
405 410 415
Pro Gly Lys Gly Leu Glu Trp Ile Gly Gly Ile Gly Ser Val Asp Tyr
420 425 430
Ser Gly Asn Thr Tyr Tyr Lys Pro Ser Leu Lys Ser Arg Val Thr Ile
435 440 445
Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val
450 455 460
Thr Ala Ala Asp Thr Ala Val Tyr His Cys Ala Arg His Arg Gly Ile
465 470 475 480
Tyr Phe Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
485 490 495
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
500 505 510
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
515 520 525
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
530 535 540
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
545 550 555 560
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
565 570 575
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
580 585 590
Arg Val Glu Pro Lys Ser Cys
595
<![CDATA[<210> 198]]>
<![CDATA[<211> 597]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 198]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala
130 135 140
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Gly Ile Gly Ser Val Asp Tyr Ser Gly
420 425 430
Asn Thr Tyr Tyr Lys Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val
435 440 445
Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala
450 455 460
Ala Asp Thr Ala Val Tyr His Cys Ala Arg His Arg Gly Ile Tyr Phe
465 470 475 480
Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser
485 490 495
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr
500 505 510
Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro
515 520 525
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val
530 535 540
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser
545 550 555 560
Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile
565 570 575
Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val
580 585 590
Glu Pro Lys Ser Cys
595
<![CDATA[<210> 199]]>
<![CDATA[<211> 598]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 199]]>
Lys Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg
1 5 10 15
Gly Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr
20 25 30
Glu Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu
35 40 45
Val Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp
50 55 60
Asp Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr
65 70 75 80
Ile Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val
85 90 95
Glu Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr
100 105 110
Gln Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
130 135 140
Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
180 185 190
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
195 200 205
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
210 215 220
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
225 230 235 240
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
245 250 255
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
260 265 270
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
275 280 285
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
290 295 300
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
305 310 315 320
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
325 330 335
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
340 345 350
Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
355 360 365
Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu
370 375 380
Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly
385 390 395 400
Ser Ile Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro
405 410 415
Gly Lys Gly Leu Glu Trp Ile Gly Gly Ile Gly Ser Val Asp Tyr Ser
420 425 430
Gly Asn Thr Tyr Tyr Lys Pro Ser Leu Lys Ser Arg Val Thr Ile Ser
435 440 445
Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr
450 455 460
Ala Ala Asp Thr Ala Val Tyr His Cys Ala Arg His Arg Gly Ile Tyr
465 470 475 480
Phe Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala
485 490 495
Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser
500 505 510
Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe
515 520 525
Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly
530 535 540
Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu
545 550 555 560
Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr
565 570 575
Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg
580 585 590
Val Glu Pro Lys Ser Cys
595
<![CDATA[<210> 200]]>
<![CDATA[<211> 596]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 200]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Glu Pro Lys Ser
115 120 125
Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala
130 135 140
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys
370 375 380
Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile
385 390 395 400
Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys
405 410 415
Gly Leu Glu Trp Ile Gly Gly Ile Gly Ser Val Asp Tyr Ser Gly Asn
420 425 430
Thr Tyr Tyr Lys Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp
435 440 445
Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala
450 455 460
Asp Thr Ala Val Tyr His Cys Ala Arg His Arg Gly Ile Tyr Phe Phe
465 470 475 480
Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
485 490 495
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
500 505 510
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
515 520 525
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
530 535 540
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
545 550 555 560
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
565 570 575
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
580 585 590
Pro Lys Ser Cys
595
<![CDATA[<210> 201]]>
<![CDATA[<211> 597]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 201]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala
130 135 140
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ile Gly Gly Ile Gly Ser Val Asp Tyr Ser Gly
420 425 430
Asn Thr Tyr Tyr Lys Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val
435 440 445
Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala
450 455 460
Ala Asp Thr Ala Val Tyr His Cys Ala Arg His Arg Gly Ile Tyr Phe
465 470 475 480
Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser
485 490 495
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr
500 505 510
Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro
515 520 525
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val
530 535 540
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser
545 550 555 560
Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile
565 570 575
Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val
580 585 590
Glu Pro Lys Ser Cys
595
<![CDATA[<210> 202]]>
<![CDATA[<211> 21]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (19)..(19)]]>
<![CDATA[<223> Leu或Glu]]>
<![CDATA[<400> 202]]>
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
1 5 10 15
Glu Phe Xaa Gly Gly
20
<![CDATA[<210> 203]]>
<![CDATA[<211> 21]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 203]]>
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
1 5 10 15
Glu Phe Leu Gly Gly
20
<![CDATA[<210> 204]]>
<![CDATA[<211> 21]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 204]]>
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
1 5 10 15
Glu Phe Glu Gly Gly
20
<![CDATA[<210> 205]]>
<![CDATA[<211> 208]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 205]]>
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
1 5 10 15
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu
20 25 30
Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
35 40 45
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg
50 55 60
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
65 70 75 80
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu
85 90 95
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
100 105 110
Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu
115 120 125
Thr Cys Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
130 135 140
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
145 150 155 160
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
165 170 175
Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu
180 185 190
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
195 200 205
<![CDATA[<210> 206]]>
<![CDATA[<211> 20]]>
<![CDATA[<212> PRT]]>
<![CDATA[<21]]>3> 人工序列]]>
<br/>
<br/><![CDATA[<220>]]>
<br/><![CDATA[<223> 人工序列之描述：合成肽]]>
<br/>
<br/><![CDATA[<400> 206]]>
<br/><![CDATA[Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser
1 5 10 15
Gly Ser Gly Ser
20
<![CDATA[<210> 207]]>
<![CDATA[<211> 30]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 207]]>
Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly
1 5 10 15
Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser
20 25 30
<![CDATA[<210> 208]]>
<![CDATA[<211> 40]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 208]]>
Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser
1 5 10 15
Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser
20 25 30
Gly Gly Gly Ser Gly Gly Gly Ser
35 40
<![CDATA[<210> 209]]>
<![CDATA[<211> 40]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 209]]>
Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly
20 25 30
Gly Gly Ser Gly Gly Gly Ser Gly
35 40
<![CDATA[<210> 210]]>
<![CDATA[<211> 50]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 210]]>
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
1 5 10 15
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
20 25 30
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
35 40 45
Gly Gly
50
<![CDATA[<210> 211]]>
<![CDATA[<211> 100]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 211]]>
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
1 5 10 15
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
20 25 30
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
35 40 45
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
50 55 60
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
65 70 75 80
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
85 90 95
Gly Ser Gly Gly
100
<![CDATA[<210> 212]]>
<![CDATA[<211> 22]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 212]]>
Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Glu Ala Ala Gly Gly
20
<![CDATA[<210> 213]]>
<![CDATA[<211> 21]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 213]]>
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
1 5 10 15
Pro Pro Val Ala Gly
20
<![CDATA[<210> 214]]>
<![CDATA[<211> 210]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 214]]>
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
1 5 10 15
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
20 25 30
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
35 40 45
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
50 55 60
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
65 70 75 80
Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ser Ser Ile Glu
85 90 95
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
100 105 110
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
115 120 125
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
130 135 140
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
145 150 155 160
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
165 170 175
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
180 185 190
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
195 200 205
Gly Ala
210
<![CDATA[<210> 215]]>
<![CDATA[<211> 124]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (29)..(29)]]>
<![CDATA[<223> His、Lys、Thr、Trp或Tyr]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (51)..(51)]]>
<![CDATA[<223> Asn或Tyr]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (93)..(93)]]>
<![CDATA[<223> Met或Gln]]>
<![CDATA[<400> 215]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Xaa Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Xaa Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Xaa Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp
115 120
<![CDATA[<210> 216]]>
<![CDATA[<211> 210]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 216]]>
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
1 5 10 15
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
20 25 30
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
35 40 45
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
50 55 60
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
65 70 75 80
Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu
85 90 95
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
100 105 110
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
115 120 125
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
130 135 140
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
145 150 155 160
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
165 170 175
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
180 185 190
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
195 200 205
Gly Ala
210
<![CDATA[<210> 217]]>
<![CDATA[<211> 210]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 217]]>
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
1 5 10 15
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
20 25 30
Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
35 40 45
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
50 55 60
Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys
65 70 75 80
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu
85 90 95
Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
100 105 110
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
115 120 125
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp
130 135 140
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met
145 150 155 160
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
165 170 175
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
180 185 190
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
195 200 205
Gly Lys
210
<![CDATA[<210> 218]]>
<![CDATA[<211> 19]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 218]]>
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro Ala Pro Glu Phe
1 5 10 15
Leu Gly Gly
<![CDATA[<210> 219]]>
<![CDATA[<211> 585]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 219]]>
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser
180 185 190
Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu
195 200 205
Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro
210 215 220
Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys
225 230 235 240
Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp
245 250 255
Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser
260 265 270
Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His
275 280 285
Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser
290 295 300
Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala
305 310 315 320
Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg
325 330 335
Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr
340 345 350
Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu
355 360 365
Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro
370 375 380
Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu
385 390 395 400
Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro
405 410 415
Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys
420 425 430
Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys
435 440 445
Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His
450 455 460
Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser
465 470 475 480
Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr
485 490 495
Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp
500 505 510
Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala
515 520 525
Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu
530 535 540
Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys
545 550 555 560
Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Lys Lys Leu Val
565 570 575
Ala Ala Ser Gln Ala Ala Leu Gly Leu
580 585
<![CDATA[<210> 220]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (6)..(6)]]>
<![CDATA[<223> Ser或Ile]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (8)..(8)]]>
<![CDATA[<223> Phe或His]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (11)..(11)]]>
<![CDATA[<223> Ile或Tyr]]>
<![CDATA[<400> 220]]>
Ala Arg His Arg Gly Xaa Tyr Xaa Phe Asp Xaa
1 5 10
<![CDATA[<210> 221]]>
<![CDATA[<211> 13]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (6)..(6)]]>
<![CDATA[<223> Asn或Ser]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (7)..(7)]]>
<![CDATA[<223> Asn、Asp、Gly或Ser]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (11)..(11)]]>
<![CDATA[<223> Ile或Phe]]>
<![CDATA[<400> 221]]>
Ala Arg Glu Arg Ser Xaa Xaa Trp Tyr Pro Xaa Asp Tyr
1 5 10
<![CDATA[<210> 222]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (2)..(2)]]>
<![CDATA[<223> Ala、Gly或Val]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (4)..(4)]]>
<![CDATA[<223> Val或Ile]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (5)..(5)]]>
<![CDATA[<223> Ser或Arg]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (6)..(6)]]>
<![CDATA[<223> Ser或Thr]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (8)..(8)]]>
<![CDATA[<223> Ser或Gly]]>
<![CDATA[<400> 222]]>
Gly Xaa Ser Xaa Xaa Xaa Ser Xaa Tyr Tyr
1 5 10
<![CDATA[<210> 223]]>
<![CDATA[<211> 7]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (2)..(2)]]>
<![CDATA[<223> Tyr或Asn]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (4)..(4)]]>
<![CDATA[<223> Ser或Gly]]>
<![CDATA[<400> 223]]>
Ile Xaa Tyr Xaa Gly Ser Thr
1 5
<![CDATA[<210> 224]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (1)..(1)]]>
<![CDATA[<223> Ile或Met]]>
<![CDATA[<400> 224]]>
Xaa Asp Tyr Ser Gly Thr
1 5
<![CDATA[<210> 225]]>
<![CDATA[<211> 10]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (9)..(9)]]>
<![CDATA[<223> Asn、Ala或Ser]]>
<![CDATA[<400> 225]]>
Ile Gly Ser Val Asp Tyr Ser Gly Xaa Thr
1 5 10
<![CDATA[<210> 226]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (1)..(1)]]>
<![CDATA[<223> Asn或Asp]]>
<![CDATA[<400> 226]]>
Xaa Ile Glu Asn Lys Asn
1 5
<![CDATA[<210> 227]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (2)..(2)]]>
<![CDATA[<223> Val或Leu]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (4)..(4)]]>
<![CDATA[<223> Arg或Asn]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (5)..(5)]]>
<![CDATA[<223> Phe或Tyr]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (6)..(6)]]>
<![CDATA[<223> Phe或Tyr]]>
<![CDATA[<400> 227]]>
Ser Xaa Arg Xaa Xaa Xaa
1 5
<![CDATA[<210> 228]]>
<![CDATA[<211> 3]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 228]]>
Gly Lys Asp
1
<![CDATA[<210> 229]]>
<![CDATA[<211> 3]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<40]]>0> 229]]>
<br/><![CDATA[Gly Lys Asp
1
<![CDATA[<210> 230]]>
<![CDATA[<211> 220]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 230]]>
Met Leu Arg Leu Leu Leu Ala Leu Asn Leu Phe Pro Ser Ile Gln Val
1 5 10 15
Thr Gly Asn Lys Ile Leu Val Lys Gln Ser Pro Met Leu Val Ala Tyr
20 25 30
Asp Asn Ala Val Asn Leu Ser Cys Lys Tyr Ser Tyr Asn Leu Phe Ser
35 40 45
Arg Glu Phe Arg Ala Ser Leu His Lys Gly Leu Asp Ser Ala Val Glu
50 55 60
Val Cys Val Val Tyr Gly Asn Tyr Ser Gln Gln Leu Gln Val Tyr Ser
65 70 75 80
Lys Thr Gly Phe Asn Cys Asp Gly Lys Leu Gly Asn Glu Ser Val Thr
85 90 95
Phe Tyr Leu Gln Asn Leu Tyr Val Asn Gln Thr Asp Ile Tyr Phe Cys
100 105 110
Lys Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser
115 120 125
Asn Gly Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro
130 135 140
Leu Phe Pro Gly Pro Ser Lys Pro Phe Trp Val Leu Val Val Val Gly
145 150 155 160
Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile
165 170 175
Phe Trp Val Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met
180 185 190
Asn Met Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro
195 200 205
Tyr Ala Pro Pro Arg Asp Phe Ala Ala Tyr Arg Ser
210 215 220
<![CDATA[<210> 231]]>
<![CDATA[<211> 9]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (3)..(3)]]>
<![CDATA[<223> Arg或Trp]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (6)..(6)]]>
<![CDATA[<223> Asn、Thr或Ala]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (7)..(7)]]>
<![CDATA[<223> I]]>le、Thr或Ala
<![CDATA[<400> 231]]>
Gln Val Xaa Asp Ser Xaa Xaa Val Val
1 5
<![CDATA[<210> 232]]>
<![CDATA[<211> 11]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (9)..(9)]]>
<![CDATA[<223> Leu或His]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (11)..(11)]]>
<![CDATA[<223> Leu或Val]]>
<![CDATA[<400> 232]]>
Asn Ser Arg Asp Ser Ser Gly Tyr Xaa Val Xaa
1 5 10
<![CDATA[<210> 233]]>
<![CDATA[<211> 124]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (29)..(29)]]>
<![CDATA[<223> His、Lys、Trp或Tyr]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (61)..(61)]]>
<![CDATA[<223> Asp或Glu]]>
<![CDATA[<400> 233]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Xaa Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Xaa Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp
115 120
<![CDATA[<210> 234]]>
<![CDATA[<211> 124]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 234]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Glu Ser Pro Gly Lys Ala Asn Glu Ile
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Met Thr Tyr Met Lys Glu Asp Glu Leu Thr Phe Leu Asp Asp Pro
50 55 60
Ser Cys Thr Gly Thr Phe Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp
115 120
<![CDATA[<210> 235]]>
<![CDATA[<211> 124]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (16)..(16)]]>
<![CDATA[<223> Arg或Val]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (58)..(58)]]>
<![CDATA[<223> Ala或Gly]]>
<![CDATA[<220>]]>
<![CDATA[<221> MOD_RES]]>
<![CDATA[<222> (85)..(85)]]>
<![CDATA[<223> Gln或Ser]]>
<![CDATA[<400> 235]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Xaa
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Xaa Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Xaa Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp
115 120
<![CDATA[<210> 236]]>
<![CDATA[<211> 123]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 236]]>
Met Leu Arg Leu Leu Leu Ala Leu Asn Leu Phe Pro Ser Ile Gln Val
1 5 10 15
Thr Gly Asn Lys Ile Leu Val Lys Gln Ser Pro Met Leu Val Ala Tyr
20 25 30
Asp Asn Ala Val Asn Leu Ser Trp Lys His Leu Cys Pro Ser Pro Leu
35 40 45
Phe Pro Gly Pro Ser Lys Pro Phe Trp Val Leu Val Val Val Gly Gly
50 55 60
Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe
65 70 75 80
Trp Val Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn
85 90 95
Met Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr
100 105 110
Ala Pro Pro Arg Asp Phe Ala Ala Tyr Arg Ser
115 120
<![CDATA[<210> 237]]>
<![CDATA[<211> 210]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 237]]>
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
1 5 10 15
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
20 25 30
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
35 40 45
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
50 55 60
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
65 70 75 80
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu
85 90 95
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
100 105 110
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
115 120 125
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
130 135 140
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
145 150 155 160
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
165 170 175
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
180 185 190
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
195 200 205
Gly Lys
210
<![CDATA[<210> 238]]>
<![CDATA[<211> 210]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 238]]>
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
1 5 10 15
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
20 25 30
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
35 40 45
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
50 55 60
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
65 70 75 80
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu
85 90 95
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
100 105 110
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
115 120 125
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
130 135 140
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
145 150 155 160
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
165 170 175
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
180 185 190
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
195 200 205
Gly Lys
210
<![CDATA[<210> 239]]>
<![CDATA[<211> 220]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> ]]>239
Pro Ser Pro Ala Pro Glu Leu Leu Gly Gly Ser Ser Val Phe Leu Phe
1 5 10 15
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
20 25 30
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
35 40 45
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
50 55 60
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
65 70 75 80
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
85 90 95
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
100 105 110
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
115 120 125
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
130 135 140
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
145 150 155 160
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
165 170 175
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
180 185 190
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215 220
<![CDATA[<210> 240]]>
<![CDATA[<211> 219]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400>]]> 240
Pro Ser Pro Ala Pro Glu Leu Leu Gly Gly Ser Ser Val Phe Leu Phe
1 5 10 15
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
20 25 30
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
35 40 45
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
50 55 60
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
65 70 75 80
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
85 90 95
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
100 105 110
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
115 120 125
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
130 135 140
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
145 150 155 160
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
165 170 175
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
180 185 190
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
210 215
<![CDATA[<210> 241]]>
<![CDATA[<211> 209]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 241]]>
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
1 5 10 15
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
20 25 30
Asp Pro Glu Val Gln Phe Lys Trp Tyr Val Asp Gly Val Glu Val His
35 40 45
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Phe Arg
50 55 60
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
65 70 75 80
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
85 90 95
Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
100 105 110
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
115 120 125
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
130 135 140
Glu Ser Ser Gly Gln Pro Glu Asn Asn Tyr Asn Thr Thr Pro Pro Met
145 150 155 160
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
165 170 175
Lys Ser Arg Trp Gln Gln Gly Asn Ile Phe Ser Cys Ser Val Met His
180 185 190
Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser Leu Ser Leu Ser Pro
195 200 205
Gly
<![CDATA[<210> 242]]>
<![CDATA[<211> 23]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 242]]>
Gln Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro
1 5 10 15
Ala Pro Glu Leu Leu Gly Gly
20
<![CDATA[<210> 243]]>
<![CDATA[<211> 23]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 243]]>
Gln Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro
1 5 10 15
Ala Pro Glu Ala Ala Gly Gly
20
<![CDATA[<210> 244]]>
<![CDATA[<211> 23]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 244]]>
Gln Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro
1 5 10 15
Ala Pro Glu Ala Ala Gly Gly
20
<![CDATA[<210> 245]]>
<![CDATA[<211> 22]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 245]]>
Gln Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro
1 5 10 15
Ala Pro Pro Val Ala Gly
20
<![CDATA[<210> 246]]>
<![CDATA[<211> 18]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 246]]>
Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val
1 5 10 15
Ala Gly
<![CDATA[<210> 247]]>
<![CDATA[<211> 13]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 247]]>
Gln Glu Pro Lys Ser Ser Asp Lys Thr His Thr Ser Pro
1 5 10
<![CDATA[<210> 248]]>
<![CDATA[<211> 12]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 248]]>
Glu Pro Lys Ser Ser Asp Lys Thr His Thr Ser Pro
1 5 10
<![CDATA[<210> 249]]>
<![CDATA[<211> 23]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 249]]>
Gln Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro
1 5 10 15
Ala Pro Glu Leu Leu Gly Gly
20
<![CDATA[<210> 250]]>
<![CDATA[<211> 277]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 250]]>
Met Cys Val Gly Ala Arg Arg Leu Gly Arg Gly Pro Cys Ala Ala Leu
1 5 10 15
Leu Leu Leu Gly Leu Gly Leu Ser Thr Val Thr Gly Leu His Cys Val
20 25 30
Gly Asp Thr Tyr Pro Ser Asn Asp Arg Cys Cys His Glu Cys Arg Pro
35 40 45
Gly Asn Gly Met Val Ser Arg Cys Ser Arg Ser Gln Asn Thr Val Cys
50 55 60
Arg Pro Cys Gly Pro Gly Phe Tyr Asn Asp Val Val Ser Ser Lys Pro
65 70 75 80
Cys Lys Pro Cys Thr Trp Cys Asn Leu Arg Ser Gly Ser Glu Arg Lys
85 90 95
Gln Leu Cys Thr Ala Thr Gln Asp Thr Val Cys Arg Cys Arg Ala Gly
100 105 110
Thr Gln Pro Leu Asp Ser Tyr Lys Pro Gly Val Asp Cys Ala Pro Cys
115 120 125
Pro Pro Gly His Phe Ser Pro Gly Asp Asn Gln Ala Cys Lys Pro Trp
130 135 140
Thr Asn Cys Thr Leu Ala Gly Lys His Thr Leu Gln Pro Ala Ser Asn
145 150 155 160
Ser Ser Asp Ala Ile Cys Glu Asp Arg Asp Pro Pro Ala Thr Gln Pro
165 170 175
Gln Glu Thr Gln Gly Pro Pro Ala Arg Pro Ile Thr Val Gln Pro Thr
180 185 190
Glu Ala Trp Pro Arg Thr Ser Gln Gly Pro Ser Thr Arg Pro Val Glu
195 200 205
Val Pro Gly Gly Arg Ala Val Ala Ala Ile Leu Gly Leu Gly Leu Val
210 215 220
Leu Gly Leu Leu Gly Pro Leu Ala Ile Leu Leu Ala Leu Tyr Leu Leu
225 230 235 240
Arg Arg Asp Gln Arg Leu Pro Pro Asp Ala His Lys Pro Pro Gly Gly
245 250 255
Gly Ser Phe Arg Thr Pro Ile Gln Glu Glu Gln Ala Asp Ala His Ser
260 265 270
Thr Leu Ala Lys Ile
275
<![CDATA[<210> 251]]>
<![CDATA[<211> 198]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 小家鼠]]>
<![CDATA[<400> 251]]>
Met Glu Gly Glu Gly Val Gln Pro Leu Asp Glu Asn Leu Glu Asn Gly
1 5 10 15
Ser Arg Pro Arg Phe Lys Trp Lys Lys Thr Leu Arg Leu Val Val Ser
20 25 30
Gly Ile Lys Gly Ala Gly Met Leu Leu Cys Phe Ile Tyr Val Cys Leu
35 40 45
Gln Leu Ser Ser Ser Pro Ala Lys Asp Pro Pro Ile Gln Arg Leu Arg
50 55 60
Gly Ala Val Thr Arg Cys Glu Asp Gly Gln Leu Phe Ile Ser Ser Tyr
65 70 75 80
Lys Asn Glu Tyr Gln Thr Met Glu Val Gln Asn Asn Ser Val Val Ile
85 90 95
Lys Cys Asp Gly Leu Tyr Ile Ile Tyr Leu Lys Gly Ser Phe Phe Gln
100 105 110
Glu Val Lys Ile Asp Leu His Phe Arg Glu Asp His Asn Pro Ile Ser
115 120 125
Ile Pro Met Leu Asn Asp Gly Arg Arg Ile Val Phe Thr Val Val Ala
130 135 140
Ser Leu Ala Phe Lys Asp Lys Val Tyr Leu Thr Val Asn Ala Pro Asp
145 150 155 160
Thr Leu Cys Glu His Leu Gln Ile Asn Asp Gly Glu Leu Ile Val Val
165 170 175
Gln Leu Thr Pro Gly Tyr Cys Ala Pro Glu Gly Ser Tyr His Ser Thr
180 185 190
Val Asn Gln Val Pro Leu
195
<![CDATA[<210> 252]]>
<![CDATA[<211> 454]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 252]]>
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Thr Ile Ser Gly Ser Gly Gly Ala Thr Arg Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Val Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Val Glu Asp Thr Ala Val Phe Tyr Cys
85 90 95
Thr Lys Asp Arg Leu Ile Met Ala Thr Val Arg Gly Pro Tyr Tyr Tyr
100 105 110
Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala
115 120 125
Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser
130 135 140
Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe
145 150 155 160
Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly
165 170 175
Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu
180 185 190
Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr
195 200 205
Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg
210 215 220
Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu
225 230 235 240
Phe Glu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
245 250 255
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
260 265 270
Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly
275 280 285
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn
290 295 300
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
305 310 315 320
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro
325 330 335
Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
340 345 350
Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn
355 360 365
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
370 375 380
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
385 390 395 400
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg
405 410 415
Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys
420 425 430
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
435 440 445
Ser Leu Ser Leu Gly Lys
450
<![CDATA[<210> 253]]>
<![CDATA[<211> 214]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 253]]>
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Glu Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser His Ser Val Ser Phe
85 90 95
Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<![CDATA[<210> 254]]>
<![CDATA[<211> 449]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 254]]>
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Ser Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ile Ile Ser Gly Ser Gly Gly Phe Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Thr Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Lys Asp Arg Leu Val Ala Pro Gly Thr Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Ala Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly
<![CDATA[<210> 255]]>
<![CDATA[<211> 214]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 255]]>
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<![CDATA[<210> 256]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 256]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 257]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：]]>合成多肽
<![CDATA[<400> 257]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys His Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Met Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 258]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 258]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Lys Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Met Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Thr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Met Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 260]]>
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<![CDATA[<400> 260]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Trp Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Met Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 261]]>
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<![CDATA[<400> 261]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Met Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 262]]>
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<![CDATA[<400> 262]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys His Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 263]]>
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<![CDATA[<400> 263]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Lys Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 264]]>
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Thr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 265]]>
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<![CDATA[<400> 265]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Trp Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys His Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Lys Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Thr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Trp Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys His Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Lys Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Thr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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<![CDATA[<400> 275]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Trp Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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<![CDATA[<400> 276]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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<![CDATA[<400> 277]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys His Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Asp Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 278]]>
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<![CDATA[<400> 278]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Lys Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Asp Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 279]]>
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<![CDATA[<400> 279]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Trp Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Asp Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 280]]>
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<![CDATA[<400> 280]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Asp Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys His Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Glu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Lys Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Glu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Trp Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Glu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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<br/><![CDATA[Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Glu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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<br/>
<br/><![CDATA[<400> 285]]>
<br/><![CDATA[Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Glu Ser Pro Gly Lys Ala Asn Glu Ile
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Met Thr Tyr Met Lys Glu Asp Glu Leu Thr Phe Leu Asp Asp Pro
50 55 60
Ser Cys Thr Gly Thr Phe Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Ala Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Gln Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Val Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Ala Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Gln Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 288]]>
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<![CDATA[<213> 人工序列]]>
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<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 288]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Gln Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 289]]>
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<![CDATA[<400> 289]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Val Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Gln Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 290]]>
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<![CDATA[<400> 290]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Ala Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Ser Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 291]]>
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<![CDATA[<400> 291]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Val Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Ala Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Ser Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 292]]>
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<![CDATA[<400> 292]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Ser Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 293]]>
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Val Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Ser Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys
115 120 125
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
130 135 140
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
165 170 175
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
180 185 190
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
210 215 220
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro
225 230 235 240
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
245 250 255
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
260 265 270
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
275 280 285
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
290 295 300
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
305 310 315 320
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
325 330 335
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
340 345 350
Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gln Leu Gln Leu Gln Glu Ser Gly Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 294]]>
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 295]]>
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Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys His Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Met Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 296]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 296]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Lys Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Met Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 297]]>
<![CDATA[<211> 594]]>
<![CDATA[<212>]]> PRT
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 297]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Thr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Met Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 298]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 298]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Trp Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Met Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 299]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 299]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Met Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 300]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 300]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys His Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 301]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 301]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Lys Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 302]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之]]>描述：合成多肽
<![CDATA[<400> 302]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Thr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 303]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 303]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Trp Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 304]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 304]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 305]]>
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<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 30]]>5
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys His Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 306]]>
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<![CDATA[<213> 人工序列]]>
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<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 306]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Lys Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 307]]>
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<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 307]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Thr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 308]]>
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<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 308]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Trp Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 309]]>
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<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 309]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Tyr Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 310]]>
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<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 310]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys His Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 311]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 311]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Lys Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 312]]>
<![CDATA[<211> 594]]>
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<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 312]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Thr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 313]]>
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<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 313]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Trp Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 314]]>
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<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 314]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Asn Tyr Met Met Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Lys
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 315]]>
<![CDATA[<211> ]]>594
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 315]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys His Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Asp Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 316]]>
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<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 316]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Lys Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Asp Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 317]]>
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<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 317]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Trp Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Asp Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 318]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 318]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Asp Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 319]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 319]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys His Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Glu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 320]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 320]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Lys Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Glu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 321]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 321]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Trp Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Glu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 322]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 322]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Tyr Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Phe Ala Asn Tyr Tyr Met Gly Asn Glu Leu Thr Phe Glu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 323]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 323]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Glu Ser Pro Gly Lys Ala Asn Glu Ile
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Met Thr Tyr Met Lys Glu Asp Glu Leu Thr Phe Leu Asp Asp Pro
50 55 60
Ser Cys Thr Gly Thr Phe Ser Gly Asn Gln Val Asn Leu Thr Ile Gln
65 70 75 80
Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Glu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 324]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 324]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Ala Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Gln Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 325]]>
<![CDATA[<211> 594]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 325]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Val Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Ala Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Gln Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 326]]>
<![CDATA[<211> 594]]>
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<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 326]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Gln Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 327]]>
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<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 327]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Val Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Gln Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 328]]>
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<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 328]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Ala Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Ser Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 329]]>
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<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 329]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Val Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Ala Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Ser Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 330]]>
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<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 330]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Ser Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 331]]>
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<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 331]]>
Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Val Gly Arg
1 5 10 15
Ala Ser Phe Val Cys Glu Tyr Thr Asn Pro Ser Lys Ala Thr Glu Val
20 25 30
Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys
35 40 45
Ala Ala Thr Tyr Met Lys Gly Asn Glu Gly Thr Phe Leu Asp Asp Ser
50 55 60
Ile Cys Thr Gly Thr Ala Ser Gly Asn Gln Val Asn Leu Thr Ile Arg
65 70 75 80
Gly Leu Arg Ala Ser Asp Thr Gly Leu Tyr Ile Cys Gln Val Glu Leu
85 90 95
Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile
100 105 110
Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Ala Met His Val
115 120 125
Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly Ile Ala Ser Phe
130 135 140
Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu Val Arg Val Thr
145 150 155 160
Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val Cys Ala Ala Thr
165 170 175
Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp Ser Ile Cys Thr
180 185 190
Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile Gln Gly Leu Arg
195 200 205
Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu Leu Met Tyr Pro
210 215 220
Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln Ile Tyr Val Ile
225 230 235 240
Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro Lys Ser Ser Asp
245 250 255
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
260 265 270
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
275 280 285
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
290 295 300
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
305 310 315 320
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
325 330 335
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
340 345 350
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys
355 360 365
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Gly Pro Gly Leu Val
370 375 380
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser
385 390 395 400
Ile Ser Thr Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly
405 410 415
Lys Gly Leu Glu Trp Ser Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr
420 425 430
Tyr Arg Pro Ser Leu Gln Gly Arg Ala Thr Ile Ser Val Asp Thr Ser
435 440 445
Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Arg His Arg Gly Ser Tyr Phe Phe Asp Ile
465 470 475 480
Trp Gly Leu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
485 490 495
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
500 505 510
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
515 520 525
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
530 535 540
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
545 550 555 560
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
565 570 575
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys
580 585 590
Ser Cys
<![CDATA[<210> 332]]>
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<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 332]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
130 135 140
Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
180 185 190
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
195 200 205
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
210 215 220
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
225 230 235 240
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
245 250 255
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
260 265 270
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
275 280 285
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
290 295 300
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
305 310 315 320
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
325 330 335
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
340 345 350
Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
355 360 365
Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
370 375 380
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
385 390 395 400
Thr Phe Ser Asn Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
405 410 415
Gly Leu Glu Trp Val Ser Thr Ile Ser Gly Ser Gly Gly Ala Thr Arg
420 425 430
Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser
435 440 445
Arg Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Arg Val Glu Asp Thr
450 455 460
Ala Val Phe Tyr Cys Thr Lys Asp Arg Leu Ile Met Ala Thr Val Arg
465 470 475 480
Gly Pro Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val
485 490 495
Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
500 505 510
Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu
515 520 525
Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
530 535 540
Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser
545 550 555 560
Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu
565 570 575
Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr
580 585 590
Lys Val Asp Lys Arg Val
595
<![CDATA[<210> 333]]>
<![CDATA[<211> 591]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 333]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
130 135 140
Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
180 185 190
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
195 200 205
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
210 215 220
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
225 230 235 240
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
245 250 255
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
260 265 270
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
275 280 285
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
290 295 300
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
305 310 315 320
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
325 330 335
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
340 345 350
Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
355 360 365
Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
370 375 380
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
385 390 395 400
Thr Phe Asn Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys
405 410 415
Gly Leu Glu Trp Val Ser Ile Ile Ser Gly Ser Gly Gly Phe Thr Tyr
420 425 430
Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser
435 440 445
Arg Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr
450 455 460
Ala Val Tyr Tyr Cys Ala Lys Asp Arg Leu Val Ala Pro Gly Thr Phe
465 470 475 480
Asp Tyr Trp Gly Gln Gly Ala Leu Val Thr Val Ser Ser Ala Ser Thr
485 490 495
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
500 505 510
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
515 520 525
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
530 535 540
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
545 550 555 560
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
565 570 575
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val
580 585 590
<![CDATA[<210> 334]]>
<![CDATA[<211> 597]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 334]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
370 375 380
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
385 390 395 400
Phe Ser Asn Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
405 410 415
Leu Glu Trp Val Ser Thr Ile Ser Gly Ser Gly Gly Ala Thr Arg Tyr
420 425 430
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg
435 440 445
Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Arg Val Glu Asp Thr Ala
450 455 460
Val Phe Tyr Cys Thr Lys Asp Arg Leu Ile Met Ala Thr Val Arg Gly
465 470 475 480
Pro Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr
485 490 495
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
500 505 510
Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val
515 520 525
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
530 535 540
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
545 550 555 560
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
565 570 575
Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys
580 585 590
Val Asp Lys Arg Val
595
<![CDATA[<210> 335]]>
<![CDATA[<211> 590]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成多肽]]>
<![CDATA[<400> 335]]>
Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly
1 5 10 15
Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu
20 25 30
Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val
35 40 45
Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp
50 55 60
Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile
65 70 75 80
Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu
85 90 95
Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln
100 105 110
Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gln Glu Pro
115 120 125
Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro
130 135 140
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Ala Ala
225 230 235 240
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
355 360 365
Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val
370 375 380
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
385 390 395 400
Phe Asn Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
405 410 415
Leu Glu Trp Val Ser Ile Ile Ser Gly Ser Gly Gly Phe Thr Tyr Tyr
420 425 430
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg
435 440 445
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala
450 455 460
Val Tyr Tyr Cys Ala Lys Asp Arg Leu Val Ala Pro Gly Thr Phe Asp
465 470 475 480
Tyr Trp Gly Gln Gly Ala Leu Val Thr Val Ser Ser Ala Ser Thr Lys
485 490 495
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
500 505 510
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
515 520 525
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
530 535 540
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
545 550 555 560
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
565 570 575
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val
580 585 590
<![CDATA[<210> 336]]>
<![CDATA[<211> 5]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 智人]]>
<![CDATA[<400> 336]]>
Glu Pro Lys Ser Cys
1 5
<![CDATA[<210> 337]]>
<![CDATA[<211> 183]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 食蟹獼猴]]>
<![CDATA[<400> 337]]>
Met Glu Arg Val Gln Pro Leu Glu Glu Asn Val Gly Asn Ala Ala Arg
1 5 10 15
Pro Arg Phe Glu Arg Asn Lys Leu Leu Leu Val Ala Ser Val Ile Gln
20 25 30
Gly Leu Gly Leu Leu Leu Cys Phe Thr Tyr Ile Cys Leu His Phe Ser
35 40 45
Ala Leu Gln Val Ser His Gln Tyr Pro Arg Ile Gln Ser Ile Lys Val
50 55 60
Gln Phe Thr Glu Tyr Lys Lys Glu Glu Gly Phe Ile Leu Thr Ser Gln
65 70 75 80
Lys Glu Asp Glu Ile Met Lys Val Gln Asn Asn Ser Val Ile Ile Asn
85 90 95
Cys Asp Gly Phe Tyr Leu Ile Ser Leu Lys Gly Tyr Phe Ser Gln Glu
100 105 110
Val Asn Ile Ser Leu His Tyr Gln Lys Asp Glu Glu Pro Leu Phe Gln
115 120 125
Leu Lys Lys Val Arg Ser Val Asn Ser Leu Met Val Ala Ser Leu Thr
130 135 140
Tyr Lys Asp Lys Val Tyr Leu Asn Val Thr Thr Asp Asn Thr Ser Leu
145 150 155 160
Asp Asp Phe His Val Asn Gly Gly Glu Leu Ile Leu Ile His Gln Asn
165 170 175
Pro Gly Glu Phe Cys Val Leu
180
<![CDATA[<210> 338]]>
<![CDATA[<211> 6]]>
<![CDATA[<212> PRT]]>
<![CDATA[<213> 人工序列]]>
<![CDATA[<220>]]>
<![CDATA[<223> 人工序列之描述：合成肽]]>
<![CDATA[<400> 338]]>
His His His His His His
1 5
Claims (118)
- 一種蛋白質，其包含： 特異性結合CD80及/或CD86之多肽或兩種或更多種多肽之複合物，及 特異性結合OX40L之多肽或兩種或更多種多肽之複合物。
- 如請求項1之蛋白質，其中特異性結合CD80及/或CD86之該多肽或兩種或更多種多肽之複合物係選自由以下組成之群：包含CTLA4之細胞外域或其功能性片段之多肽；包含CD28細胞外域或其功能性片段之多肽；抗體；Fab；Fab'；F(ab') 2；單鏈可變片段(scFv)；微型抗體；及奈米抗體(VHH)。
- 如請求項1或2之蛋白質，其中特異性結合CD80及/或CD86之該多肽或兩種或更多種多肽之複合物包含CTLA4之細胞外域或其功能片段。
- 如請求項2或3之蛋白質，其中該CTLA4細胞外域或其功能片段包含與SEQ ID NO: 29、SEQ ID NO: 173或SEQ ID NO: 174具有至少90%序列一致性之序列。
- 如請求項2至4中任一項之蛋白質，其中該CTLA4細胞外域或其功能片段包含或由SEQ ID NO: 173或SEQ ID NO: 174組成。
- 如請求項1至5中任一項之蛋白質，其中特異性結合CD80及/或CD86之該多肽或兩種或更多種多肽之複合物抑制T細胞中之CD28協同刺激信號傳導。
- 如請求項1至6中任一項之蛋白質，其中特異性結合OX40L之該多肽或兩種或更多種多肽之複合物抑制內源性OX40L與內源性OX40之結合。
- 如請求項1至7中任一項之蛋白質，其中特異性結合OX40L之該多肽或兩種或更多種多肽之複合物包含抗原結合位點。
- 如請求項8之蛋白質，其中該抗原結合位點為抗體、Fab、Fab'、F(ab') 2、單鏈可變片段(scFv)、微型抗體或奈米抗體(VHH)。
- 如請求項8或9之蛋白質，其中該抗原結合位點為Fab。
- 如請求項10之蛋白質，其中該Fab包含連接於Fab重鏈CH1域之C端的包含序列SEQ ID NO: 336之多肽。
- 如請求項7之蛋白質，其中特異性結合OX40L之該多肽或兩種或更多種多肽之複合物為OX40之細胞外域或其功能片段。
- 如請求項1至12中任一項之蛋白質，其進一步包含橋接部分。
- 如請求項13之蛋白質，其中該橋接部分為功能性或非功能性。
- 如請求項13或14之蛋白質，其中該橋接部分包含免疫球蛋白Fc域之多肽或其功能片段、人類血清白蛋白(HSA)多肽或其功能片段、多肽連接子、或多肽鉸鏈。
- 如請求項12至15中任一項之蛋白質，其中該橋接部分包含免疫球蛋白Fc域之多肽。
- 如請求項12至16中任一項之蛋白質，其中該橋接部分包含人類IgG1、IgG2、IgG3或IgG4 Fc域之多肽。
- 如請求項15至17中任一項之蛋白質，其中該橋接部分包含人類IgG1 Fc域之多肽。
- 如請求項17或18之蛋白質，其中人類IgG1 Fc域之該多肽包含與選自由以下組成之群的胺基酸序列具有至少90%序列一致性之序列：SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 238、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240。
- 如請求項17至19中任一項之蛋白質，其中人類IgG1 Fc域之該多肽包含與選自由以下組成之群的胺基酸序列具有100%序列一致性之序列：SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 238、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240。
- 如請求項17至20中任一項之蛋白質，其中該橋接部分進一步包含鉸鏈多肽。
- 如請求項21之蛋白質，其中該鉸鏈多肽包含多肽，其包含與選自由以下組成之群的胺基酸序列具有至少90%序列一致性之胺基酸序列：SEQ ID NO: 175、SEQ ID NO: 242、SEQ ID NO: 176、SEQ ID NO: 249、SEQ ID NO: 177、SEQ ID NO: 243、SEQ ID NO: 212、SEQ ID NO: 244、SEQ ID NO: 213、SEQ ID NO: 245、SEQ ID NO: 247及SEQ ID NO: 248。
- 如請求項17至22中任一項之蛋白質，其中人類IgG1 Fc域之該多肽包含一種或多於一種效應功能靜默突變。
- 如請求項17至23中任一項之蛋白質，其中該鉸鏈多肽包含位置234及235處由白胺酸成為丙胺酸之突變。
- 如請求項13至24中任一項之蛋白質，其中該橋接部分連接於特異性結合CD80及/或CD86之該多肽或兩種或更多種多肽之複合物的N端或C端。
- 如請求項25之蛋白質，其中特異性結合CD80及/或CD86之該多肽或兩種或更多種多肽之複合物連接於該橋接部分之N端。
- 如請求項13至24中任一項之蛋白質，其中該橋接部分連接於特異性結合OX40L之該多肽或兩種或更多種多肽之複合物的N端或C端。
- 如請求項27之蛋白質，其中特異性結合OX40L之該多肽或兩種或更多種多肽之複合物連接於該橋接部分之C端。
- 如請求項28之蛋白質，其中連接子多肽將特異性結合OX40L之該多肽或兩種或更多種多肽之複合物連接於該橋接部分。
- 如請求項28或29之蛋白質，其進一步包含特異性結合OX40L之第二多肽或兩種或更多種多肽之複合物。
- 如請求項30之蛋白質，其中該橋接部分為人類IgG1 Fc域之多肽，且特異性結合OX40L之該多肽或兩種或更多種多肽之複合物連接於該人類IgG1 Fc域之多肽之C端，且特異性結合OX40L之該第二多肽或兩種或更多種多肽之複合物連接於該人類IgG1 Fc域之第二多肽之C端。
- 如請求項30或31之蛋白質，其中特異性結合OX40L之該第一及/或該第二多肽或兩種或更多種多肽之複合物包含抗原結合位點或OX40之細胞外域或其功能片段。
- 如請求項32之蛋白質，其中特異性結合OX40L之該第一及/或該第二多肽或兩種或更多種多肽之複合物包含Fab。
- 如請求項30至33中任一項之蛋白質，其中特異性結合OX40L之該第二多肽或兩種或更多種多肽之複合物係藉由連接子多肽連接於該橋接部分。
- 如請求項29至34中任一項之蛋白質，其中該連接子多肽包含(GGGGS) n(SEQ ID NO: 181)序列，其中n為1至12。
- 如請求項8至11及13至35中任一項之蛋白質，其中該抗原結合位點包含選自由以下組成之群的胺基酸序列： (a) ARHRGX 1YX 2FDX 3(SEQ ID NO: 220) 其中X 1為S或I， X 2為F或H，及 X 3為I或Y；及 (b) ARERSX 1X 2WYPX 3DY (SEQ ID NO: 221) 其中X 1為N或S， X 2為N、D、G或S，及 X 3為I或F。
- 如請求項8至11及13至36中任一項之蛋白質，其中該抗原結合位點包含： (a)包含以下胺基酸序列之重鏈可變互補決定區1 (VHCDR1)： GX 1SX 2X 3X 4SX 5YY (SEQ ID NO: 222) 其中X 1為A、G或V， X 2為V或I， X 3為S或R， X 4為S或T，及 X 5為S或G； (b)包含選自由以下組成之群的胺基酸序列之重鏈可變互補決定區2 (VHCDR2)： (1) IX 1YX 2GST (SEQ ID NO: 223) 其中X 1為Y或N，及 X 2為S或G， (2) X 1DYSGT (SEQ ID NO: 224) 其中X 1為I或M，及 (3) IGSVDYSGX 1T (SEQ ID NO: 225) 其中X 1為N、A或S；及 (c)包含選自由以下組成之群的胺基酸序列之重鏈可變互補決定區3 (VHCDR3)： (1) ARHRGX 1YX 2FDX 3(SEQ ID NO: 220) 其中X 1為S或I， X 2為F或H，及 X 3為I或Y；及 (2) ARERSX 1X 2WYPX 3DY (SEQ ID NO: 221) 其中X 1為N或S， X 2為N、D、G或S，及 X 3為I或F。
- 如請求項8至11及13至37中任一項之蛋白質，其中該抗原結合位點包含： (a)包含選自由以下組成之群的胺基酸序列之輕鏈可變互補決定區1 (VLCDR1)： (1) X 1IENKN (SEQ ID NO: 226) 其中X 1為N或D，及 (2) SX 1RX 2X 3X 4(SEQ ID NO: 227) 其中X 1為V或L， X 2為R或N， X 3為F或Y，及 X 4為F或Y； (b)包含選自由以下組成之群的胺基酸序列之輕鏈可變互補決定區2 (VLCDR2)： RDN (SEQ ID NO: 82)、GKD (SEQ ID NO: 228)及RDS (SEQ ID NO: 90)； 及 (c)包含選自由以下組成之群的胺基酸序列之輕鏈可變互補決定區3 (VLCDR3)： (1) QVX 1DSX 2X 3VV (SEQ ID NO: 231) 其中X 1為R或W， X 2為N、T或A，及 X 3為I、T或A，及 (2) NSRDSSGYX 1VX 2(SEQ ID NO: 232) 其中X 1為L或H，及 X 2為L或V。
- 如請求項8至11及13至38中任一項之蛋白質，其中該抗原結合位點包含： (i) (a)包含胺基酸序列GX 1SX 2X 3X 4SX 5YY (SEQ ID NO: 222)之重鏈可變互補決定區1 (VHCDR1) 其中X 1為A、G或V， X 2為V或I， X 3為S或R， X 4為S或T，及 X 5為S或G；及 (b)包含胺基酸序列IX 1YX 2GST (SEQ ID NO: 223)之重鏈可變互補決定區2 (VHCDR2) 其中X 1為Y或N，及 X 2為S或G；及 (c)包含胺基酸序列ARHRGX 1YX 2FDX 3(SEQ ID NO: 220)之重鏈可變互補決定區3 (VHCDR3) 其中X 1為S或I， X 2為F或H，及 X 3為I或Y；及 (ii) (a)包含胺基酸序列X 1IENKN (SEQ ID NO: 226)之輕鏈可變互補決定區1 (VLCDR1) 其中X 1為N或D； (b)包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及 (c)包含胺基酸序列QVX 1DSX 2X 3VV (SEQ ID NO: 231)之輕鏈可變互補決定區3 (VLCDR3) 其中X 1為R或W， X 2為N、T或A，及 X 3為I、T或A。
- 如請求項8至11及13至38中任一項之蛋白質，其中該抗原結合位點包含： (i) (a)包含胺基酸序列GX 1SX 2X 3X 4SX 5YY (SEQ ID NO: 222)之重鏈可變互補決定區1 (VHCDR1) 其中X 1為A、G或V， X 2為V或I， X 3為S或R， X 4為S或T，及 X 5為S或G；及 (b)包含胺基酸序列X 1DYSGT (SEQ ID NO: 224)之重鏈可變互補決定區2 (VHCDR2) 其中X 1為I或M；及 (c)包含胺基酸序列ARERSX 1X 2WYPX 3DY (SEQ ID NO: 221)之重鏈可變互補決定區3 (VHCDR3) 其中X 1為N或S， X 2為N、D、G或S，及 X 3為I或F；及 (ii) (a)包含胺基酸序列SX 1R X 2X 3X 4(SEQ ID NO: 227)之輕鏈可變互補決定區1 (VLCDR1) 其中X 1為V或L， X 2為R或N， X 3為F或Y，及 X 4為F或Y； (b)包含胺基酸序列GKD (SEQ ID NO: 229)之輕鏈可變互補決定區2 (VLCDR2)；及 (c)包含胺基酸序列NSRDSSGYX 1VX 2(SEQ ID NO: 232)之輕鏈可變互補決定區3 (VLCDR3) 其中X 1為L或H，及 X 2為L或V。
- 如請求項8至11及13至38中任一項之蛋白質，其中該抗原結合位點包含：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈互補決定區1 (VHCDR1)、包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈互補決定區2 (VHCDR2)、包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈互補決定區3 (VHCDR3)、包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈互補決定區1 (VLCDR1)、包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈互補決定區2 (VLCDR2)及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈互補決定區3 (VLCDR3)。
- 如請求項8至11及13至38中任一項之蛋白質，其中該抗原結合位點包含：包含胺基酸序列GVSIRSNGYY (SEQ ID NO: 93)之重鏈互補決定區1 (VHCDR1)、包含胺基酸序列MDYSGT (SEQ ID NO: 94)之重鏈互補決定區2 (VHCDR2)、包含胺基酸序列ARERSNNWYPIDY (SEQ ID NO: 95)之重鏈互補決定區3 (VHCDR3)、包含胺基酸序列SVRRFF (SEQ ID NO: 97)之輕鏈互補決定區1 (VLCDR1)、包含胺基酸序列GKD (SEQ ID NO: 98)之輕鏈互補決定區2 (VLCDR2)及包含胺基酸序列NSRDSSGYLVL (SEQ ID NO: 99)之輕鏈互補決定區3 (VLCDR3)。
- 如請求項8至11及13至38中任一項之蛋白質，其中該抗原結合位點包含：包含胺基酸序列GASVSSSSYY (SEQ ID NO: 85)之重鏈互補決定區1 (VHCDR1)、包含胺基酸序列INYGGST (SEQ ID NO: 86)之重鏈互補決定區2 (VHCDR2)、包含胺基酸序列ARHRGIYHFDY (SEQ ID NO: 87)之重鏈互補決定區3 (VHCDR3)、包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈互補決定區1 (VLCDR1)、包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈互補決定區2 (VLCDR2)及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈互補決定區3 (VLCDR3)。
- 如請求項8至11及13至38中任一項之蛋白質，其中該抗原結合位點包含：包含胺基酸序列GGSISSSSYY (SEQ ID NO: 101)之重鏈互補決定區1 (VHCDR1)、包含胺基酸序列IGSVDYSGNT (SEQ ID NO: 102)之重鏈互補決定區2 (VHCDR2)、包含胺基酸序列ARHRGIYFFDY (SEQ ID NO: 103)之重鏈互補決定區3 (VHCDR3)、包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈互補決定區1 (VLCDR1)、包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈互補決定區2 (VLCDR2)及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈互補決定區3 (VLCDR3)。
- 如請求項8至11及13至44中任一項之蛋白質，其中根據IMGT獨特編號方案，該抗原結合位點包含VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3，其各自包含分別對應於表3中所列之重鏈可變域及輕鏈可變域之VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3序列的胺基酸序列。
- 如請求項8至11及13至38中任一項之蛋白質，其中該抗原結合位點包含與SEQ ID NO: 76、SEQ ID NO: 92、SEQ ID NO: 84或SEQ ID NO: 100具有至少90%序列一致性之胺基酸序列，及與SEQ ID NO: 80、SEQ ID NO: 96、SEQ ID NO: 88或SEQ ID NO: 104具有至少90%序列一致性之胺基酸序列。
- 如請求項46之蛋白質，其中該抗原結合位點包含與SEQ ID NO: 76具有至少90%序列一致性之胺基酸序列，及與SEQ ID NO: 80具有至少90%序列一致性之胺基酸序列。
- 如請求項46之蛋白質，其中該抗原結合位點包含與SEQ ID NO: 92具有至少90%序列一致性之胺基酸序列，及與SEQ ID NO: 96具有至少90%序列一致性之胺基酸序列。
- 如請求項8至11及13至38中任一項之蛋白質，其中根據IMGT獨特編號方案，該抗原結合位點包含重鏈可變域及輕鏈可變域，其各自包含分別對應於表3中所列之重鏈可變域及輕鏈可變域之重鏈可變域序列及輕鏈可變域序列的胺基酸序列。
- 如請求項8至11及13至38中任一項之蛋白質，其中該抗原結合位點包含與SEQ ID NO: 8、SEQ ID NO: 16、SEQ ID NO: 14或SEQ ID NO: 18具有至少90%序列一致性之胺基酸序列，及與SEQ ID NO: 7、SEQ ID NO: 15、SEQ ID NO: 13或SEQ ID NO: 17具有至少90%序列一致性之胺基酸序列。
- 如請求項50之蛋白質，其中該抗原結合位點包含與SEQ ID NO: 8具有至少90%序列一致性之胺基酸序列，及與SEQ ID NO: 7具有至少90%序列一致性之胺基酸序列。
- 如請求項50之蛋白質，其中該抗原結合位點包含與SEQ ID NO: 16具有至少90%序列一致性之胺基酸序列，及與SEQ ID NO: 15具有至少90%序列一致性之胺基酸序列。
- 如請求項8至11及13至38中任一項之蛋白質，其中根據IMGT獨特編號方案，該抗原結合位點包含重鏈及輕鏈，其各自包含分別對應於表3中所列之重鏈及輕鏈之重鏈序列及輕鏈序列的胺基酸序列。
- 如請求項8至11及13至53中任一項之蛋白質，其中該抗原結合位點在人類OX40L之細胞外域之位置60及/或83處結合。
- 如請求項54之蛋白質，其中該抗原結合位點在人類OX40L之細胞外域之位置17、18、19、20、21、23、26、28、60、83、110、111、112、113及114處結合。
- 如請求項54之蛋白質，其中該抗原結合位點在人類OX40L之細胞外域之位置58、59、60、61、62、63、81、82及83處結合。
- 一種蛋白質，其包含： (i)包含CTLA4之細胞外域的多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之橋接部分：包含SEQ ID NO: 177之序列及包含SEQ ID NO: 179之序列；及 (iii)包含以下之抗原結合位點：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)。
- 一種蛋白質，其包含第一臂及第二臂，該第一臂包含： (i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之第一橋接部分：包含SEQ ID NO: 177之序列及包含SEQ ID NO: 179之序列；及 (iii)包含以下之第一抗原結合位點：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)，及 該第二臂包含： (i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之第二橋接部分：包含SEQ ID NO: 177之序列及包含SEQ ID NO: 179之序列；及 (iii)包含以下之第二抗原結合位點：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)， 其中該第一臂與該第二臂彼此二聚合。
- 一種蛋白質，其包含： (i)包含CTLA4之細胞外域的多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及 (iii)包含以下之抗原結合位點：包含胺基酸序列GVSIRSNGYY (SEQ ID NO: 93)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列MDYSGT (SEQ ID NO: 94)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARERSNNWYPIDY (SEQ ID NO: 95)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列SVRRFF (SEQ ID NO: 97)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列GKD (SEQ ID NO: 98)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列NSRDSSGYLVL (SEQ ID NO: 99)之輕鏈可變互補決定區3 (VLCDR3)。
- 一種蛋白質，其包含第一臂及第二臂，該第一臂包含： (i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之第一橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及 (iii)包含以下之第一抗原結合位點：包含胺基酸序列GVSIRSNGYY (SEQ ID NO: 93)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列MDYSGT (SEQ ID NO: 94)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARERSNNWYPIDY (SEQ ID NO: 95)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列SVRRFF (SEQ ID NO: 97)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列GKD (SEQ ID NO: 98)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列NSRDSSGYLVL (SEQ ID NO: 99)之輕鏈可變互補決定區3 (VLCDR3)，及 該第二臂包含： (i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之第二橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及 (iii)包含以下之第二抗原結合位點：包含胺基酸序列GVSIRSNGYY (SEQ ID NO: 93)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列MDYSGT (SEQ ID NO: 94)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARERSNNWYPIDY (SEQ ID NO: 95)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列SVRRFF (SEQ ID NO: 97)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列GKD (SEQ ID NO: 98)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列NSRDSSGYLVL (SEQ ID NO: 99)之輕鏈可變互補決定區3 (VLCDR3)， 其中該第一臂與該第二臂彼此二聚合。
- 一種蛋白質，其包含： (i)包含CTLA4之細胞外域的多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 214之序列；及 (iii)包含以下之抗原結合位點：包含胺基酸序列GASVSSSSYY (SEQ ID NO: 85)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列INYGGST (SEQ ID NO: 86)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYHFDY (SEQ ID NO: 87)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)。
- 一種蛋白質，其包含第一臂及第二臂，該第一臂包含： (i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之第一橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 214之序列；及 (iii)包含以下之第一抗原結合位點：包含胺基酸序列GASVSSSSYY (SEQ ID NO: 85)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列INYGGST (SEQ ID NO: 86)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYHFDY (SEQ ID NO: 87)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)，及 該第二臂包含： (i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之第二橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 214之序列；及 (iii)包含以下之第二抗原結合位點：包含胺基酸序列GASVSSSSYY (SEQ ID NO: 85)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列INYGGST (SEQ ID NO: 86)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYHFDY (SEQ ID NO: 87)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)， 其中該第一臂與該第二臂彼此二聚合。
- 一種蛋白質，其包含： (i)包含CTLA4之細胞外域的多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及 (iii)包含以下之抗原結合位點：包含胺基酸序列GGSISSSSYY (SEQ ID NO: 101)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IGSVDYSGNT (SEQ ID NO: 102)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYFFDY (SEQ ID NO: 103)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)。
- 一種蛋白質，其包含第一臂及第二臂，該第一臂包含： (i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之第一橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及 (iii)包含以下之第一抗原結合位點：包含胺基酸序列GGSISSSSYY (SEQ ID NO: 101)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IGSVDYSGNT (SEQ ID NO: 102)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYFFDY (SEQ ID NO: 103)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)，及 該第二臂包含： (i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之第二橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及 (iii)包含以下之第二抗原結合位點：包含胺基酸序列GGSISSSSYY (SEQ ID NO: 101)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IGSVDYSGNT (SEQ ID NO: 102)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYFFDY (SEQ ID NO: 103)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)， 其中該第一臂與該第二臂彼此二聚合。
- 一種蛋白質，其包含： (i)包含CTLA4之細胞外域的多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及 (iii)包含以下之抗原結合位點：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)。
- 一種蛋白質，其包含第一臂及第二臂，該第一臂包含： (i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之第一橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及 (iii)包含以下之第一抗原結合位點：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)，及 該第二臂包含： (i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含SEQ ID NO: 174； (ii)包含以下之第二橋接部分：包含SEQ ID NO: 213之序列及包含SEQ ID NO: 216之序列；及 (iii)包含以下之第二抗原結合位點：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)， 其中該第一臂與該第二臂彼此二聚合。
- 一種蛋白質，其包含： (i)包含CTLA4之細胞外域的多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列； (ii)包含以下之橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及 (iii)包含以下之抗原結合位點：包含胺基酸序列GFTFSNYA (SEQ ID NO: 133)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列ISGSGGAT (SEQ ID NO: 113)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列TKDRLIMATVRGPYYYGMDV (SEQ ID NO: 114)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列QSISSY (SEQ ID NO: 121)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列AAS (SEQ ID NO: 146)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QQSHSVSFT (SEQ ID NO: 154)之輕鏈可變互補決定區3 (VLCDR3)。
- 一種蛋白質，其包含第一臂及第二臂，該第一臂包含： (i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列； (ii)包含以下之第一橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及 (iii)包含以下之第一抗原結合位點：包含胺基酸序列GFTFSNYA (SEQ ID NO: 133)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列ISGSGGAT (SEQ ID NO: 113)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列TKDRLIMATVRGPYYYGMDV (SEQ ID NO: 114)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列QSISSY (SEQ ID NO: 121)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列AAS (SEQ ID NO: 146)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QQSHSVSFT (SEQ ID NO: 154)之輕鏈可變互補決定區3 (VLCDR3)，及 該第二臂包含： (i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列； (ii)包含以下之第二橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及 (iii)包含以下之第二抗原結合位點：包含胺基酸序列GFTFSNYA (SEQ ID NO: 133)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列ISGSGGAT (SEQ ID NO: 113)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列TKDRLIMATVRGPYYYGMDV (SEQ ID NO: 114)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列QSISSY (SEQ ID NO: 121)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列AAS (SEQ ID NO: 146)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QQSHSVSFT (SEQ ID NO: 154)之輕鏈可變互補決定區3 (VLCDR3)， 其中該第一臂與該第二臂彼此二聚合。
- 一種蛋白質，其包含： (i)包含CTLA4之細胞外域的多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列； (ii)包含以下之橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及 (iii)包含以下之抗原結合位點：包含胺基酸序列SYAMS (SEQ ID NO: 105)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IISGSGGFTYYADSVK (SEQ ID NO: 106)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列DRLVAPGTFDY (SEQ ID NO: 107)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列RASQGISSWLA (SEQ ID NO: 169)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列AASSLQS (SEQ ID NO: 170)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QQYNSYPYT (SEQ ID NO: 171)之輕鏈可變互補決定區3 (VLCDR3)。
- 一種蛋白質，其包含第一臂及第二臂，該第一臂包含： (i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列； (ii)包含以下之第一橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及 (iii)包含以下之第一抗原結合位點：包含胺基酸序列SYAMS (SEQ ID NO: 105)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IISGSGGFTYYADSVK (SEQ ID NO: 106)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列DRLVAPGTFDY (SEQ ID NO: 107)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列RASQGISSWLA (SEQ ID NO: 169)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列AASSLQS (SEQ ID NO: 170)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QQYNSYPYT (SEQ ID NO: 171)之輕鏈可變互補決定區3 (VLCDR3)，及 該第二臂包含： (i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列； (ii)包含以下之第二橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及 (iii)包含以下之第二抗原結合位點：包含胺基酸序列SYAMS (SEQ ID NO: 105)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IISGSGGFTYYADSVK (SEQ ID NO: 106)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列DRLVAPGTFDY (SEQ ID NO: 107)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列RASQGISSWLA (SEQ ID NO: 169)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列AASSLQS (SEQ ID NO: 170)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QQYNSYPYT (SEQ ID NO: 171)之輕鏈可變互補決定區3 (VLCDR3)， 其中該第一臂與該第二臂彼此二聚合。
- 一種蛋白質，其包含： (i)包含CTLA4之細胞外域的多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列； (ii)包含以下之橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及 (iii)根據IMGT獨特編號方案，包含以下之抗原結合位點：VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3，其各自包含分別對應於表3中所列之重鏈可變域及輕鏈可變域之VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3序列的胺基酸序列。
- 一種蛋白質，其包含第一臂及第二臂，該第一臂包含： (i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列； (ii)包含以下之第一橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及 (iii)根據IMGT獨特編號方案，包含以下之第一抗原結合位點：VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3，其各自包含分別對應於表3中所列之重鏈可變域及輕鏈可變域之VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3序列的胺基酸序列，及 該第二臂包含： (i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列； (ii)包含以下之第二橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及 (iii)根據IMGT獨特編號方案，包含以下之第二抗原結合位點：VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3，其各自包含分別對應於表3中所列之重鏈可變域及輕鏈可變域之VHCDR1、VHCDR2、VHCDR3、VLCDR1、VLCDR2及VLCDR3序列的胺基酸序列， 其中該第一臂與該第二臂彼此二聚合。
- 一種蛋白質，其包含： (i)包含CTLA4之細胞外域的多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列； (ii)包含以下之橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及 (iii)包含特異性結合於OX40L之多肽的抗原結合位點。
- 一種蛋白質，其包含第一臂及第二臂，該第一臂包含： (i)包含CTLA4之細胞外域的第一多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列； (ii)包含以下之第一橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及 (iii)包含特異性結合於OX40L之多肽的第一抗原結合位點，及 該第二臂包含： (i)包含CTLA4之細胞外域的第二多肽，該細胞外域包含選自由SEQ ID NO: 174、SEQ ID NO: 119、SEQ ID NO: 215、SEQ ID NO: 233、SEQ ID NO: 234及SEQ ID NO: 235組成之群的序列； (ii)包含以下之第二橋接部分：選自由SEQ ID NO: 175、SEQ ID NO: 176、SEQ ID NO: 177、SEQ ID NO: 212、SEQ ID NO: 213及SEQ ID NO: 248組成之群的序列，及選自由SEQ ID NO: 178、SEQ ID NO: 237、SEQ ID NO: 214、SEQ ID NO: 216、SEQ ID NO: 179、SEQ ID NO: 180、SEQ ID NO: 239及SEQ ID NO: 240組成之群的序列；及 (iii)包含特異性結合於OX40L之多肽的第二抗原結合位點， 其中該第一臂與該第二臂彼此二聚合。
- 如請求項57、59、61、63、65、67、69及71中任一項之蛋白質，其中該抗原結合位點進一步包括包含序列SEQ ID NO: 336之部分鉸鏈多肽。
- 如請求項58、60、62、64、68、70及72中任一項之蛋白質，其中該第一抗原結合位點及該第二抗原結合位點兩者進一步包括包含序列SEQ ID NO: 336之部分鉸鏈多肽。
- 一種蛋白質，其包含與選自由以下組成之群的胺基酸序列具有至少90%一致性之胺基酸序列：SEQ ID NO: 40、SEQ ID NO: 62、SEQ ID NO: 64、SEQ ID NO: 182、SEQ ID NO: 183、SEQ ID NO: 184、SEQ ID NO: 185、SEQ ID NO: 186、SEQ ID NO: 48、SEQ ID NO: 68、SEQ ID NO: 187、SEQ ID NO: 188、SEQ ID NO: 189、SEQ ID NO: 190、SEQ ID NO: 191、SEQ ID NO: 46、SEQ ID NO: 66、SEQ ID NO: 192、SEQ ID NO: 193、SEQ ID NO: 194、SEQ ID NO: 195、SEQ ID NO: 196、SEQ ID NO: 50、SEQ ID NO: 70、SEQ ID NO: 197、SEQ ID NO: 198、SEQ ID NO: 199、SEQ ID NO: 200、SEQ ID NO: 201、SEQ ID NO: 38、SEQ ID NO: 73、SEQ ID NO: 42、SEQ ID NO: 44、SEQ ID NO: 52、SEQ ID NO: 54、SEQ ID NO: 56、SEQ ID NO: 58、SEQ ID NO: 60、SEQ ID NO: 37、SEQ ID NO: 256、SEQ ID NO: 257、SEQ ID NO: 258、SEQ ID NO: 259、SEQ ID NO: 260、SEQ ID NO: 261、SEQ ID NO: 262、SEQ ID NO: 263、SEQ ID NO: 264、SEQ ID NO: 265、SEQ ID NO: 266、SEQ ID NO: 267、SEQ ID NO: 268、SEQ ID NO: 269、SEQ ID NO: 270、SEQ ID NO: 271、SEQ ID NO: 272、SEQ ID NO: 273、SEQ ID NO: 274、SEQ ID NO: 275、SEQ ID NO: 276、SEQ ID NO: 277、SEQ ID NO: 278、SEQ ID NO: 279、SEQ ID NO: 280、SEQ ID NO: 281、SEQ ID NO: 282、SEQ ID NO: 283、SEQ ID NO: 284、SEQ ID NO: 285、SEQ ID NO: 286、SEQ ID NO: 287、SEQ ID NO: 288、SEQ ID NO: 289、SEQ ID NO: 290、SEQ ID NO: 291、SEQ ID NO: 292、SEQ ID NO: 293、SEQ ID NO: 294、SEQ ID NO: 295、SEQ ID NO: 296、SEQ ID NO: 297、SEQ ID NO: 298、SEQ ID NO: 299、SEQ ID NO: 300、SEQ ID NO: 301、SEQ ID NO: 302、SEQ ID NO: 303、SEQ ID NO: 304、SEQ ID NO: 305、SEQ ID NO: 306、SEQ ID NO: 307、SEQ ID NO: 308、SEQ ID NO: 309、SEQ ID NO: 310、SEQ ID NO: 311、SEQ ID NO: 312、SEQ ID NO: 313、SEQ ID NO: 314、SEQ ID NO: 315、SEQ ID NO: 316、SEQ ID NO: 317、SEQ ID NO: 318、SEQ ID NO: 319、SEQ ID NO: 320、SEQ ID NO: 321、SEQ ID NO: 322、SEQ ID NO: 323、SEQ ID NO: 324、SEQ ID NO: 325、SEQ ID NO: 326、SEQ ID NO: 327、SEQ ID NO: 328、SEQ ID NO: 329、SEQ ID NO: 330、SEQ ID NO: 331、SEQ ID NO: 332、SEQ ID NO: 333、SEQ ID NO: 334及SEQ ID NO: 335。
- 一種蛋白質，其包括包含與以下胺基酸序列具有至少90%一致性之胺基酸序列的多肽： SEQ ID NO: 40及SEQ ID NO: 39； SEQ ID NO: 62及SEQ ID NO: 61； SEQ ID NO: 64及SEQ ID NO: 63； SEQ ID NO: 182及SEQ ID NO: 63； SEQ ID NO: 183及SEQ ID NO: 63； SEQ ID NO: 184及SEQ ID NO: 63； SEQ ID NO: 185及SEQ ID NO: 63； SEQ ID NO: 186及SEQ ID NO: 63； SEQ ID NO: 48及SEQ ID NO: 47； SEQ ID NO: 68及SEQ ID NO: 67； SEQ ID NO: 187及SEQ ID NO: 67； SEQ ID NO: 188及SEQ ID NO: 67； SEQ ID NO: 189及SEQ ID NO: 67； SEQ ID NO: 190及SEQ ID NO: 67； SEQ ID NO: 191及SEQ ID NO: 67； SEQ ID NO: 46及SEQ ID NO: 45； SEQ ID NO: 66及SEQ ID NO: 65； SEQ ID NO: 192及SEQ ID NO: 65； SEQ ID NO: 193及SEQ ID NO: 65； SEQ ID NO: 194及SEQ ID NO: 65； SEQ ID NO: 195及SEQ ID NO: 65； SEQ ID NO: 196及SEQ ID NO: 65； SEQ ID NO: 50及SEQ ID NO: 49； SEQ ID NO: 70及SEQ ID NO: 69； SEQ ID NO: 197及SEQ ID NO: 69； SEQ ID NO: 198及SEQ ID NO: 69； SEQ ID NO: 199及SEQ ID NO: 69； SEQ ID NO: 200及SEQ ID NO: 69； SEQ ID NO: 201及SEQ ID NO: 69； SEQ ID NO: 38及SEQ ID NO: 5； SEQ ID NO: 73及SEQ ID NO: 5； SEQ ID NO: 42及SEQ ID NO: 41； SEQ ID NO: 44及SEQ ID NO: 43； SEQ ID NO: 52及SEQ ID NO: 51； SEQ ID NO: 54及SEQ ID NO: 53； SEQ ID NO: 56及SEQ ID NO: 55； SEQ ID NO: 58及SEQ ID NO: 57； SEQ ID NO: 60及SEQ ID NO: 59； SEQ ID NO: 37及SEQ ID NO: 35； SEQ ID NO: 256及SEQ ID NO: 63； SEQ ID NO: 257及SEQ ID NO: 63； SEQ ID NO: 258及SEQ ID NO: 63； SEQ ID NO: 259及SEQ ID NO: 63； SEQ ID NO: 260及SEQ ID NO: 63； SEQ ID NO: 261及SEQ ID NO: 63； SEQ ID NO: 262及SEQ ID NO: 63； SEQ ID NO: 263及SEQ ID NO: 63； SEQ ID NO: 264及SEQ ID NO: 63； SEQ ID NO: 265及SEQ ID NO: 63； SEQ ID NO: 266及SEQ ID NO: 63； SEQ ID NO: 267及SEQ ID NO: 63； SEQ ID NO: 268及SEQ ID NO: 63； SEQ ID NO: 269及SEQ ID NO: 63； SEQ ID NO: 270及SEQ ID NO: 63； SEQ ID NO: 271及SEQ ID NO: 63； SEQ ID NO: 272及SEQ ID NO: 63； SEQ ID NO: 273及SEQ ID NO: 63； SEQ ID NO: 274及SEQ ID NO: 63； SEQ ID NO: 275及SEQ ID NO: 63； SEQ ID NO: 276及SEQ ID NO: 63； SEQ ID NO: 277及SEQ ID NO: 63； SEQ ID NO: 278及SEQ ID NO: 63； SEQ ID NO: 279及SEQ ID NO: 63； SEQ ID NO: 280及SEQ ID NO: 63； SEQ ID NO: 281及SEQ ID NO: 63； SEQ ID NO: 282及SEQ ID NO: 63； SEQ ID NO: 283及SEQ ID NO: 63； SEQ ID NO: 284及SEQ ID NO: 63； SEQ ID NO: 285及SEQ ID NO: 63； SEQ ID NO: 286及SEQ ID NO: 63； SEQ ID NO: 287及SEQ ID NO: 63； SEQ ID NO: 288及SEQ ID NO: 63； SEQ ID NO: 289及SEQ ID NO: 63； SEQ ID NO: 290及SEQ ID NO: 63； SEQ ID NO: 291及SEQ ID NO: 63； SEQ ID NO: 292及SEQ ID NO: 63； SEQ ID NO: 293及SEQ ID NO: 63； SEQ ID NO: 294及SEQ ID NO: 67； SEQ ID NO: 295及SEQ ID NO: 67； SEQ ID NO: 296及SEQ ID NO: 67； SEQ ID NO: 297及SEQ ID NO: 67； SEQ ID NO: 298及SEQ ID NO: 67； SEQ ID NO: 299及SEQ ID NO: 67； SEQ ID NO: 300及SEQ ID NO: 67； SEQ ID NO: 301及SEQ ID NO: 67； SEQ ID NO: 302及SEQ ID NO: 67； SEQ ID NO: 303及SEQ ID NO: 67； SEQ ID NO: 304及SEQ ID NO: 67； SEQ ID NO: 305及SEQ ID NO: 67； SEQ ID NO: 306及SEQ ID NO: 67； SEQ ID NO: 307及SEQ ID NO: 67； SEQ ID NO: 308及SEQ ID NO: 67； SEQ ID NO: 309及SEQ ID NO: 67； SEQ ID NO: 310及SEQ ID NO: 67； SEQ ID NO: 311及SEQ ID NO: 67； SEQ ID NO: 312及SEQ ID NO: 67； SEQ ID NO: 313及SEQ ID NO: 67； SEQ ID NO: 314及SEQ ID NO: 67； SEQ ID NO: 315及SEQ ID NO: 67； SEQ ID NO: 316及SEQ ID NO: 67； SEQ ID NO: 317及SEQ ID NO: 67； SEQ ID NO: 318及SEQ ID NO: 67； SEQ ID NO: 319及SEQ ID NO: 67； SEQ ID NO: 320及SEQ ID NO: 67； SEQ ID NO: 321及SEQ ID NO: 67； SEQ ID NO: 322及SEQ ID NO: 67； SEQ ID NO: 323及SEQ ID NO: 67； SEQ ID NO: 324及SEQ ID NO: 67； SEQ ID NO: 325及SEQ ID NO: 67； SEQ ID NO: 326及SEQ ID NO: 67； SEQ ID NO: 327及SEQ ID NO: 67； SEQ ID NO: 328及SEQ ID NO: 67； SEQ ID NO: 329及SEQ ID NO: 67； SEQ ID NO: 330及SEQ ID NO: 67； SEQ ID NO: 331及SEQ ID NO: 67； SEQ ID NO: 332及SEQ ID NO: 253； SEQ ID NO: 333及SEQ ID NO: 255； SEQ ID NO: 334及SEQ ID NO: 253；或 SEQ ID NO: 335及SEQ ID NO: 255。
- 一種蛋白質，其包括包含胺基酸序列SEQ ID NO: 62及SEQ ID NO: 61之多肽。
- 如請求項79之蛋白質，其包括包含胺基酸序列SEQ ID NO: 62之兩種多肽及包含胺基酸序列SEQ ID NO: 61之兩種多肽。
- 一種蛋白質，其包括包含胺基酸序列SEQ ID NO: 63及SEQ ID NO: 64之多肽。
- 如請求項81之蛋白質，其包括包含胺基酸序列SEQ ID NO: 63之兩種多肽及包含胺基酸序列SEQ ID NO: 64之兩種多肽。
- 一種蛋白質，其包括包含胺基酸序列SEQ ID NO: 68及SEQ ID NO: 67之多肽。
- 如請求項83之蛋白質，其包括包含胺基酸序列SEQ ID NO: 68之兩種多肽及包含胺基酸序列SEQ ID NO: 67之兩種多肽。
- 如請求項8至11及13至84中任一項之蛋白質，其中依OX40L中和/OX40-HEK報導子分析中所量測，該蛋白質之IC 50小於12 nM。
- 如請求項8至11及13至85中任一項之蛋白質，其中依OX40L中和/OX40-HEK報導子分析中所量測，該蛋白質之IC 50為5 nM至12 nM。
- 如請求項8至11及13至86中任一項之蛋白質，其中依OX40L中和/OX40-HEK報導子分析中所量測，該蛋白質之IC 50為5 nM至9 nM。
- 如請求項8至11及13至87中任一項之蛋白質，其中依初級T細胞活化分析中所量測，該蛋白質之IC 50為2 nM至12 nM。
- 如請求項8至11及13至88中任一項之蛋白質，其中依初級T細胞活化分析中所量測，該蛋白質之IC 50為2 nM至9.5 nM。
- 如請求項8至11及13至89中任一項之蛋白質，其中依Biacore分析中所量測，該蛋白質之針對OX40L結合之K D 小於75 nM。
- 如請求項8至11及13至90中任一項之蛋白質，其中依Biacore分析中所量測，該蛋白質之針對OX40L結合之K D 為20 nM至75 nM。
- 如請求項8至11及13至91中任一項之蛋白質，其中相較於在相同條件下但不存在蛋白質下，或在存在於人類IgG1 Fc域之該N端處融合的人類CTLA4細胞外域(CTLA4-Ig)及抗OX40L抗體(獨立存在或以分開存在的該等兩種蛋白質之組合形式存在)下處理的細胞，該蛋白質在活體外混合淋巴球反應分析中顯著抑制細胞產生IL-2、IFNγ、IL-6及TNFα中之至少一者。
- 如請求項8至11及13至92中任一項之蛋白質，其中相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig及/或抗OX40L抗體下處理的同種異體反應性CD4 +及CD8 +T細胞，該蛋白質在活體外混合淋巴球反應分析中顯著抑制同種異體反應性CD4 +及CD8 +T細胞增殖。
- 如請求項8至11及13至93中任一項之蛋白質，其中相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig及/或抗OX40L抗體下處理的同種異體反應性CD4 +及CD8 +T細胞，該蛋白質在活體外混合淋巴球反應分析中相比於調節T細胞(T reg)增殖優先抑制同種異體反應性CD4 +及CD8 +T細胞增殖。
- 如請求項8至11及13至94中任一項之蛋白質，其中相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig及/或抗OX40L抗體下處理的T reg細胞，該蛋白質在活體外混合淋巴球反應分析中顯著增強T reg抑制功能。
- 如請求項8至11及13至95中任一項之蛋白質，其中相較於在相同條件下但不存在蛋白質下，或在存在CTLA4-Ig及/或抗OX40L抗體下處理的小鼠中之同種異體反應性CD4 +及CD8 +T細胞，該蛋白質在授受性轉移分析中顯著抑制人類化小鼠中之同種異體反應性CD4 +及CD8 +T細胞增殖。
- 如請求項8至11及13至96中任一項之蛋白質，其中相較於在相同條件下但在不存在蛋白質下，或在存在CTLA4-Ig及/或抗OX40L抗體下處理之小鼠，該蛋白質在授受性轉移分析中顯著抑制人類化小鼠中之血清IFNγ水準。
- 如請求項8至11及13至97中任一項之蛋白質，其中該蛋白質未顯著內化於源於骨髓之樹突狀細胞(MDDC)中。
- 如請求項8至11及13至98中任一項之蛋白質，其中該蛋白質與食蟹獼猴OX40L具有交叉反應性。
- 如請求項8至11及13至99中任一項之蛋白質，其中該蛋白質與小鼠、兔或大鼠OX40L不具有交叉反應性。
- 如請求項8至11及13至100中任一項之蛋白質，其中該蛋白質與食蟹獼猴CD80及CD86具有交叉反應性。
- 一種如請求項77之蛋白質之用途，其用於製備如請求項78之蛋白質。
- 一種調配物，其包含如請求項1至101中任一項之蛋白質及醫藥學上可接受之載劑。
- 一種核酸，其編碼如請求項1至101中任一項之蛋白質。
- 一種細胞，其包含一或多種編碼如請求項1至101中任一項之蛋白質的核酸。
- 一種治療患者之自體免疫疾病之方法，該方法包含向該患者投與如請求項1至101中任一項之蛋白質或如請求項103之調配物。
- 如請求項106之方法，其中該自體免疫疾病係選自由以下組成之群：類風濕性關節炎、幼年特發性關節炎、牛皮癬性關節炎、異位性皮膚炎、弛緩不能、阿狄森氏病(Addison's disease)、成人斯蒂爾氏病(Adult Still's disease)、無γ球蛋白血症、斑禿、澱粉樣變性病、僵直性脊椎炎、抗GBM/抗TBM腎炎、抗磷脂症候群、自體免疫血管性水腫、自體免疫自主神經障礙、自體免疫腦脊髓炎、自體免疫肝炎、自體免疫內耳疾病(AIED)、自體免疫心肌炎、自體免疫卵巢炎、自體免疫睪丸炎、自體免疫胰臟炎、自體免疫視網膜病變、自體免疫蕁麻疹、軸突與神經元神經病變(AMAN)、貝羅氏病(Baló disease)、白塞氏病(Behcet's disease)、良性黏膜類天疱瘡、大皰性類天疱瘡、卡斯特曼氏病(Castleman disease；CD)、乳糜瀉、卻格司氏病(Chagas disease)、慢性發炎性脫髓鞘型多發性神經病變(CIDP)、慢性復發性多灶性骨髓炎(CRMO)、徹奇-斯全司症候群(Churg-Strauss Syndrome；CSS)或嗜酸性肉芽腫(EGPA)、瘢痕性類天疱瘡、科根氏症候群(Cogan's syndrome)、冷凝集素病、先天性心臟阻滯、柯薩奇心肌炎(Coxsackie myocarditis)、CREST症候群、克羅恩氏病(Crohn's disease)、皮膚狼瘡、疱疹樣皮炎、皮肌炎、德維奇氏病(Devic's disease) (視神經脊髓炎)、盤狀狼瘡、戴斯勒氏症候群(Dressler's syndrome)、子宮內膜異位、嗜酸性食道炎(EoE)、嗜酸性筋膜炎、結節性紅斑、原發性混合型冷凝球蛋白血症、伊凡氏症候群(Evans syndrome)、肌肉纖維疼痛、纖維化肺泡炎、巨大細胞動脈炎(顳動脈炎)、巨大細胞心肌炎、絲球體腎炎、古巴士德氏症候群(Goodpasture's syndrome)、伴有多血管炎之肉芽腫、格雷夫氏病(Graves' disease)、格-巴二氏症候群(Guillain-Barre syndrome)、橋本氏甲狀腺炎(Hashimoto's thyroiditis)、溶血性貧血、亨偌-絲奇恩賴紫癜(Henoch-Schonlein purpura；HSP)、妊娠性疱疹或妊娠性類天疱瘡(PG)、化膿性汗腺炎(HS) (反常性痤瘡)、低γ球蛋白血症、IgA腎病、IgG4相關之硬化性疾病、免疫性血小板減少性紫癜(ITP)、包涵體肌炎(IBM)、間質性膀胱炎(IC)、青少年關節炎、青少年糖尿病(第1型糖尿病)、青少年肌炎(JM)、川崎病(Kawasaki disease)、蘭伯特-伊頓症候群(Lambert-Eaton syndrome)、白血球破裂性脈管炎、扁平苔癬、硬化性苔癬、木質性結膜炎、線性IgA疾病(LAD)、狼瘡、慢性萊姆病(Lyme disease)、梅尼爾氏病(Meniere's disease)、顯微多血管炎(MPA)、混合型結締組織疾病(MCTD)、穆倫氏潰瘍(Mooren's ulcer)、穆哈-哈伯曼疾病(Mucha-Habermann disease)、多灶性運動神經病(MMN)或MMNCB、多發性硬化、重症肌無力、肌炎、發作性睡病、新生兒狼瘡、視神經脊髓炎、嗜中性白血球減少症、眼部瘢痕性類天疱瘡、視神經炎、陣發性風濕症(PR)、PANDAS、腫瘤伴生性小腦變性(PCD)、陣發性夜間血紅素尿症(PNH)、帕瑞隆伯格症候群(Parry Romberg syndrome)、睫狀體扁平部炎(周邊葡萄膜炎)、帕森吉-特納症候群(Parsonage-Turner syndrome)、天疱瘡、周邊神經病變、靜脈周邊腦脊髓炎、惡性貧血(PA)、POEMS症候群、結節性多動脈炎、第I、II、III型多腺症候群、風濕性多肌痛、多發性肌炎、心肌後梗塞症候群、心包切開術後症候群、原發性膽汁性肝硬化、原發性硬化性膽管炎、孕酮皮膚炎、牛皮癬、牛皮癬性關節炎、純紅血球發育不全(PRCA)、壞疽性膿皮病、雷諾氏現象(Raynaud's phenomenon)、反應性關節炎、反射性交感神經失養症、復發性多軟骨炎、不寧腿症候群(RLS)、腹膜後纖維化、風濕熱、類風濕性關節炎、類肉瘤病、斯密特症候群(Schmidt syndrome)、鞏膜炎、硬皮病、休格倫氏症候群(Sjögren's syndrome)、精子及睪丸自體免疫、僵硬人症候群(SPS)、亞急性細菌性心內膜炎(SBE)、蘇薩克氏症候群(Susac's syndrome)、交感眼炎(SO)、高安氏動脈炎(Takayasu's arteritis)、顳動脈炎/巨大細胞動脈炎、血小板減少性紫癲(TTP)、甲狀腺眼病(TED)、托洛薩-亨特症候群(Tolosa-Hunt syndrome；THS)、橫貫性脊髓炎、第1型糖尿病、潰瘍性結腸炎(UC)、未分化結締組織疾病(UCTD)、葡萄膜炎、血管炎、白斑病及沃格特-小柳-原田病(Vogt-Koyanagi-Harada Disease)。
- 一種治療患者之移植物抗宿主疾病(GVHD)之方法，該方法包含向該患者投與如請求項1至101中任一項之蛋白質或如請求項103之調配物。
- 一種抗體或其功能片段，根據IMGT獨特編號方案，其包含：包含胺基酸序列GGSISTSSYY (SEQ ID NO: 77)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IYYSGST (SEQ ID NO: 78)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGSYFFDI (SEQ ID NO: 79)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列DIENKN (SEQ ID NO: 81)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDN (SEQ ID NO: 82)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVRDSNIVV (SEQ ID NO: 83)之輕鏈可變互補決定區3 (VLCDR3)。
- 如請求項109之抗體，其中該重鏈可變域包含與SEQ ID NO: 76具有至少90%一致性之胺基酸序列，且該輕鏈包含與SEQ ID NO: 80具有至少90%一致性之胺基酸序列。
- 一種抗體或其功能片段，根據IMGT獨特編號方案，其包含：包含胺基酸序列GVSIRSNGYY (SEQ ID NO: 93)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列MDYSGT (SEQ ID NO: 94)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARERSNNWYPIDY (SEQ ID NO: 95)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列SVRRFF (SEQ ID NO: 97)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列GKD (SEQ ID NO: 98)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列NSRDSSGYLVL (SEQ ID NO: 99)之輕鏈可變互補決定區3 (VLCDR3)。
- 如請求項111之抗體，其中該重鏈可變域包含與SEQ ID NO: 92具有至少90%一致性之胺基酸序列，且該輕鏈可變域包含與SEQ ID NO: 96具有至少90%一致性之胺基酸序列。
- 一種抗體或其功能片段，根據IMGT獨特編號方案，其包含：包含胺基酸序列GASVSSSSYY (SEQ ID NO: 85)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列INYGGST (SEQ ID NO: 86)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYHFDY (SEQ ID NO: 87)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)。
- 如請求項113之抗體，其中該重鏈可變域(VH)包含與SEQ ID NO: 84具有至少90%一致性之胺基酸序列，且該輕鏈可變域(VL)包含與SEQ ID NO: 88具有至少90%一致性之胺基酸序列。
- 一種抗體或其功能片段，根據IMGT獨特編號方案，其包含：包含胺基酸序列GGSISSSSYY (SEQ ID NO: 101)之重鏈可變互補決定區1 (VHCDR1)；包含胺基酸序列IGSVDYSGNT (SEQ ID NO: 102)之重鏈可變互補決定區2 (VHCDR2)；包含胺基酸序列ARHRGIYFFDY (SEQ ID NO: 103)之重鏈可變互補決定區3 (VHCDR3)；包含胺基酸序列NIENKN (SEQ ID NO: 89)之輕鏈可變互補決定區1 (VLCDR1)；包含胺基酸序列RDS (SEQ ID NO: 90)之輕鏈可變互補決定區2 (VLCDR2)；及包含胺基酸序列QVWDSNTVV (SEQ ID NO: 91)之輕鏈可變互補決定區3 (VLCDR3)。
- 如請求項115之抗體，其中該重鏈可變域(VH)包含與SEQ ID NO: 100具有至少90%一致性之胺基酸序列，且該輕鏈可變域(VL)包含與SEQ ID NO: 104具有至少90%一致性之胺基酸序列。
- 如請求項109至115中任一項之抗體或其功能片段，其中該抗體為人類IgG1抗體。
- 一種如請求項109至117中任一項之抗體或其功能片段之用途，其用於製備如請求項1至9、13至38或46中任一項之蛋白質。
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| US11673957B2 (en) * | 2015-03-10 | 2023-06-13 | Eureka Therapeutics, Inc. | Anti-ROR2 antibodies |
| WO2017058944A1 (en) * | 2015-09-29 | 2017-04-06 | Amgen Inc. | Asgr inhibitors |
| WO2020192709A1 (en) * | 2019-03-27 | 2020-10-01 | Wuxi Biologics (Shanghai) Co., Ltd. | Novel bispecific polypeptide complexes |
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