TW202229547A - 包含磺基葡萄糖胺磺基水解酶之融合蛋白及其方法 - Google Patents

包含磺基葡萄糖胺磺基水解酶之融合蛋白及其方法 Download PDF

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TW202229547A
TW202229547A TW110138229A TW110138229A TW202229547A TW 202229547 A TW202229547 A TW 202229547A TW 110138229 A TW110138229 A TW 110138229A TW 110138229 A TW110138229 A TW 110138229A TW 202229547 A TW202229547 A TW 202229547A
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蒂娜 吉斯
古納斯卡蘭 卡南
米漢利斯 卡里歐立斯
凱瑟 馬翁
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Abstract

本文提供能夠轉運跨過血腦障壁(BBB)且包含磺基葡萄糖胺磺基水解酶(SGSH)酶-Fc融合多肽之蛋白質。某些實施例亦提供使用此類蛋白質治療聖菲利浦症候群A (Sanfilippo syndrome A)之方法。

Description

包含磺基葡萄糖胺磺基水解酶之融合蛋白及其方法
聖菲利浦症候群或MPS III係一種罕見的神經退化性病症，由溶酶體功能之某些缺陷引起。聖菲利浦症候群最常見之類型為A型，係由 SGSH基因之基因突變引起。N-磺基葡萄糖胺磺基水解酶(SGSH)活性不足會導致硫酸乙醯肝素衍生之寡醣積聚，且導致多個器官及組織，尤其是腦及脊髓中之溶酶體功能障礙。聖菲利浦症候群之治療仍然主要為支持性的；雖然缺乏之酶可經靜脈內注射，但由於重組酶難以穿過血腦障壁(BBB)，因此其對大腦之影響很小。因此，需要更有效的療法來治療聖菲利浦症候群A之周圍及中樞神經系統(CNS)症狀。
因此，本文提供一種特定酶替代療法，該療法能夠跨過BBB且治療聖菲利浦症候群A之周圍與CNS表現。詳言之，某些實施例提供一種蛋白質，其包含：(a)第一Fc多肽，其連接於第一N-磺基葡萄糖胺磺基水解酶(SGSH)胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段；及(b)第二Fc多肽，其連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段，其中該第二Fc多肽包含與SEQ ID NO: 37具有至少80%一致性且具有根據EU編號在位置389處之Ala的序列。在一些實施例中，根據EU編號，第二Fc多肽在以下位置處包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，根據EU編號，第二Fc多肽在以下位置處包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe。在某些實施例中，第二Fc多肽特異性結合於運鐵蛋白受體(TfR)或能夠特異性結合於TfR。在某些實施例中，第二Fc多肽結合於TfR之頂端結構域。在某些實施例中，蛋白質與TfR之結合實質上不抑制運鐵蛋白與TfR之結合。在某些實施例中，蛋白質以約100 nM至約500 nM或視情況約150 nM至約400 nM之親和力結合於TfR。在某些實施例中，蛋白質能夠轉運跨過個體之血腦障壁。
在某些實施例中，第一SGSH胺基酸序列包含與SEQ ID NO:58-60中之任一者具有至少80%、85%、90%或95%一致性之胺基酸序列。在某些實施例中，第一SGSH胺基酸序列包含SEQ ID NO:58-60中之任一者之胺基酸序列。
在某些實施例中，第二SGSH胺基酸序列包含與SEQ ID NO:58-60中之任一者具有至少80%、85%、90%或95%一致性之胺基酸序列。在某些實施例中，第二SGSH胺基酸序列包含SEQ ID NO:58-60中之任一者之胺基酸序列。
在某些實施例中，第一Fc多肽藉由肽鍵或藉由多肽連接子連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。在某些實施例中，第二Fc多肽藉由肽鍵或藉由多肽連接子連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。在某些實施例中，多肽連接子為可撓性多肽連接子。在某些實施例中，可撓性多肽連接子為富甘胺酸連接子。在某些實施例中，多肽連接子為GS (SEQ ID NO:7)、G 4S (SEQ ID NO:8)或(G 4S) 2(SEQ ID NO:9)。
在某些實施例中，第一Fc多肽之N端連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。在某些實施例中，第一Fc多肽之C端連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。在某些實施例中，第二Fc多肽之N端連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。在某些實施例中，第二Fc多肽之C端連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。在某些實施例中，第一Fc多肽之N端連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段；且第二Fc多肽之N端連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。在某些實施例中，第一Fc多肽之C端連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段；且第二Fc多肽之C端連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。
在某些實施例中，第一Fc多肽及第二Fc多肽各自含有促進異二聚合之修飾。在某些實施例中，根據EU編號，Fc多肽中之一者具有T366W取代且其他Fc多肽具有T366S、L368A及Y407V取代。
在某些實施例中，第一Fc多肽含有T366S、L368A及Y407V取代且第二Fc多肽含有T366W取代。在某些實施例中，第一Fc多肽包含與SEQ ID NO: 12-19及28-31中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列；且第二Fc多肽包含與SEQ ID NO: 34-41及54-57中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
在某些實施例中，第一Fc多肽含有T366W取代且第二Fc多肽含有T366S、L368A及Y407V取代。在某些實施例中，第一Fc多肽包含與SEQ ID NO: 24-27中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列；且第二Fc多肽包含與SEQ ID NO: 48-53中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
在某些實施例中，第一Fc多肽及/或第二Fc多肽包含天然FcRn結合位點。
在某些實施例中，第一Fc多肽及第二Fc多肽不具有效應功能。在某些實施例中，第一Fc多肽及/或第二Fc多肽包括降低效應功能之修飾。在某些實施例中，降低效應功能之修飾為根據EU編號，在位置234處之Ala及在位置235處之Ala的取代。
在某些實施例中，第一Fc多肽包含與SEQ ID NO: 14-19及26-31中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。在某些實施例中，第一Fc多肽包含與SEQ ID NO: 14、15、28及29中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。在某些實施例中，第一Fc多肽包含與SEQ ID NO: 18、19、30及31中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。在某些實施例中，連接於第一SGSH胺基酸序列之第一Fc多肽包含與SEQ ID NO: 61-88及117-118中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。在某些實施例中，連接於第一SGSH胺基酸序列之第一Fc多肽包含與SEQ ID NO: 61-68、73-76、81-84及117-118中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
在某些實施例中，第二Fc多肽包含與SEQ ID NO: 36-41及50-57中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。在某些實施例中，第二Fc多肽包含與SEQ ID NO: 36、37、54及55中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。在某些實施例中，第二Fc多肽包含與SEQ ID NO: 40、41、56及57中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。在某些實施例中，連接於第二SGSH胺基酸序列之第二Fc多肽包含與SEQ ID NO: 89-116及119-120中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。在某些實施例中，連接於第二SGSH胺基酸序列之第二Fc多肽包含與SEQ ID NO: 89-96、101-104、109-112及119-120中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
在某些實施例中，相對於天然Fc序列，第一Fc多肽及/或第二Fc多肽包含延長血清半衰期之胺基酸變化。在某些實施例中，胺基酸變化包含根據EU編號在位置252處之Tyr、在位置254處之Thr及在位置256處之Glu的取代。在某些實施例中，胺基酸變化包含根據EU編號在位置428處之Leu及在位置434處之Ser的取代。在某些實施例中，胺基酸變化包含根據EU編號在位置434處之Ser或Ala的取代。
在某些實施例中，連接於第一SGSH胺基酸序列之第一Fc多肽包含SEQ ID NO: 61-68、73-76及81-84中之任一者之胺基酸序列；且連接於第二SGSH胺基酸序列之第二Fc多肽包含SEQ ID NO: 89-96、101-104及109-112中之任一者之胺基酸序列。
在某些實施例中，連接於第一SGSH胺基酸序列之第一Fc多肽包含SEQ ID NO: 61-64中之任一者之胺基酸序列；且連接於第二SGSH胺基酸序列之第二Fc多肽包含SEQ ID NO: 89-92中之任一者之胺基酸序列。在某些實施例中，連接於第一SGSH胺基酸序列之第一Fc多肽包含SEQ ID NO: 63或64之胺基酸序列；且連接於第二SGSH胺基酸序列之第二Fc多肽包含SEQ ID NO: 91或92之胺基酸序列。
在某些實施例中，連接於第一SGSH胺基酸序列之第一Fc多肽包含SEQ ID NO: 75或76之胺基酸序列；且連接於第二SGSH胺基酸序列之第二Fc多肽包含SEQ ID NO: 103或104之胺基酸序列。
在某些實施例中，連接於第一SGSH胺基酸序列之第一Fc多肽包含SEQ ID NO: 83或84之胺基酸序列；且連接於第二SGSH胺基酸序列之第二Fc多肽包含SEQ ID NO: 111或112之胺基酸序列。
在某些實施例中，連接於第一SGSH胺基酸序列之第一Fc多肽包含SEQ ID NO: 65-68中之任一者之胺基酸序列；且連接於第二SGSH胺基酸序列之第二Fc多肽包含SEQ ID NO: 93-96中之任一者之胺基酸序列。在某些實施例中，連接於第一SGSH胺基酸序列之第一Fc多肽包含SEQ ID NO: 67或68之胺基酸序列；且連接於第二SGSH胺基酸序列之第二Fc多肽包含SEQ ID NO: 95或96之胺基酸序列。
在某些實施例中，連接於第一SGSH胺基酸序列之第一Fc多肽包含SEQ ID NO: 118之胺基酸序列；且連接於第二SGSH胺基酸序列之第二Fc多肽包含SEQ ID NO: 120之胺基酸序列。
在某些實施例中，與在缺乏第一Fc多肽及第二Fc多肽之情況下SGSH胺基酸序列之吸收相比或與未對第二Fc多肽進行促成TfR結合之修飾的情況下SGSH酶之吸收相比，SGSH胺基酸序列在腦中之吸收大至少十倍。
在某些實施例中，第一Fc多肽未經修飾以結合於血腦障壁(BBB)受體且第二Fc多肽經修飾以特異性結合於TfR。
在某些實施例中，蛋白質不包括免疫球蛋白重鏈及/或輕鏈可變區序列或其抗原結合部分。
某些實施例亦提供一種多肽，其包含連接於SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段之Fc多肽，其中該Fc多肽：i)包含與SEQ ID NO: 37具有至少90%一致性之序列；ii)具有一或多個促進其與另一種Fc多肽進行異二聚合之修飾；且iii)具有根據EU編號在位置389處之Ala。在一些實施例中，根據EU編號，Fc多肽在以下位置處進一步包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，根據EU編號，Fc多肽在以下位置處進一步包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe。在某些實施例中，Fc多肽特異性結合於運鐵蛋白受體(TfR)或能夠特異性結合於TfR。在某些實施例中，Fc多肽藉由肽鍵或藉由多肽連接子連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。在某些實施例中，多肽為自N端至C端包含以下之融合多肽：SGSH胺基酸序列、SGSH變異體胺基酸序列或催化活性片段；多肽連接子；及Fc多肽。在某些實施例中，多肽為自N端至C端包含以下之融合多肽：Fc多肽；多肽連接子；及SGSH胺基酸序列、SGSH變異體胺基酸序列或催化活性片段。
在某些實施例中，根據EU編號，Fc多肽含有T366S、L368A及Y407V取代。在某些實施例中，多肽包含與SEQ ID NO: 97-100、105-108及113-116中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
在某些實施例中，Fc多肽含有T366W取代。在某些實施例中，多肽包含與SEQ ID NO: 89-96、101-104、109-112及119-120中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
在某些實施例中，蛋白質包含Fc多肽，其中該Fc多肽與另一Fc多肽二聚。因此，某些實施例提供一種蛋白質，其包含如本文所述之Fc多肽及另一Fc多肽。
某些實施例提供一種多核苷酸，其包含編碼如本文所述之多肽之核酸序列。某些實施例亦提供一種載體，其包含如本文所述之多核苷酸。某些實施例提供一種宿主細胞，其包含如本文所述之多核苷酸或如本文所述之載體。在某些實施例中，此類宿主細胞進一步包括包含編碼另一Fc多肽之核酸序列的多核苷酸。
本文提供一種製造如本文所述之蛋白質或多肽之方法。
某些實施例提供一種用於產生多肽之方法，該多肽包含連接於SGSH胺基酸序列、SGSH變異體胺基酸序列或催化活性片段之Fc多肽，該方法包括在表現由如本文所述之多核苷酸編碼之多肽的條件下培養宿主細胞。
某些實施例提供一種多核苷酸對，該多核苷酸對包含編碼連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段之第一Fc多肽的第一核酸序列；及編碼連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段之第二Fc多肽的第二核酸序列。某些實施例亦提供一或多種載體，其包含如本文所述之多核苷酸對。某些實施例提供一種宿主細胞，其包含如本文所述之多核苷酸對或一或多種如本文所述之載體。
某些實施例亦提供一種用於產生蛋白質之方法，該蛋白質包含連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段之第一Fc多肽及連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段之第二Fc多肽，該方法包括在表現如本文所述之多核苷酸對的條件下培養宿主細胞。
某些實施例提供一種醫藥組合物，該醫藥組合物包含如本文所述之蛋白質或多肽及醫藥學上可接受之載劑及/或賦形劑。
某些實施例提供一種治療聖菲利浦症候群A之方法，該方法包括向有需要之患者投與如本文所述之蛋白質或如本文所述之多肽。
某些實施例提供如本文所述之蛋白質或如本文所述之多肽，其用於治療有需要之患者之聖菲利浦症候群A。
某些實施例提供如本文所述之蛋白質或如本文所述之多肽的用途，其用於製備供治療有需要之患者之聖菲利浦症候群A用的藥劑。
某些實施例提供一種減少患有聖菲利浦症候群A之患者中之毒性代謝產物積聚的方法，該方法包括向該患者投與如本文所述之蛋白質或如本文所述之多肽。
某些實施例提供如本文所述之蛋白質或如本文所述之多肽，其用於減少患有聖菲利浦症候群A之患者中之毒性代謝產物積聚。
某些實施例提供如本文所述之蛋白質或如本文所述之多肽的用途，其用於製備供減少患有聖菲利浦症候群A之患者中之毒性代謝產物積聚的藥劑。
在某些實施例中，毒性代謝產物包含硫酸乙醯肝素衍生之寡醣。
相關申請案之交叉引用
本申請案主張2020年10月14日申請之美國臨時申請案序列號63/091,800之優先權。以上提及之申請案的全部內含以引用的方式併入本文中。
當前需要治療聖菲利浦症候群A之新治療劑，特別是治療神經認知表型之治療劑。本文描述一種特定酶替代療法，稱為ETV:SGSH，該療法能夠跨過BBB且治療聖菲利浦症候群A之周圍與CNS表現。如本文所用，術語「ETV:SGSH」係指能夠轉運跨過BBB且包含各自連接(例如稠合)至SGSH酶、SGSH酶變異體或其催化活性片段之第一Fc多肽及第二Fc多肽的二聚蛋白。如實例中所論述，聖菲利浦症候群A之鼠類小鼠模型展示在單一靜脈內ETV:SGSH劑量之後腦糖胺聚糖(GAG)減少超過50%且CSF GAG減少超過80%。 包含 SGSH 酶 -FC 融合多肽之蛋白質分子
如本文所述，某些實施例提供一種蛋白質分子，其包含SGSH酶-Fc融合多肽。摻入蛋白質中之SGSH酶為催化活性的，亦即其保持酶活性。在一些態樣中，本文所述之蛋白質包含：(i)Fc多肽，其可含有修飾(例如一或多個促進異二聚合之修飾)或可為野生型Fc多肽；及SGSH酶；以及(ii) Fc多肽，其含有引起結合於血腦障壁(BBB)受體、例如運鐵蛋白受體(TfR)之修飾，及視情況一或多個額外修飾(例如一或多個促進異二聚合之修飾)；及SGSH酶。
在一些實施例中，如本文所述之蛋白質包含野生型SGSH之催化活性片段或變異體。在一些實施例中，SGSH酶為包含SEQ ID NO:58、59及60中之任一者之胺基酸序列的SGSH蛋白之變異體或催化活性片段。在一些實施例中，SGSH酶之催化活性變異體或片段具有野生型SGSH酶之活性的至少50%、至少55%、至少60%、至少65%、至少70%、至少75%、至少80%、至少85%、至少90%、至少95%或更大。
在一些實施例中，存在於本文所述之蛋白質中的SGSH酶或其催化活性變異體或片段與其在未接合於Fc多肽或結合TfR之Fc多肽時的活性相比保持其活性之至少25%。在一些實施例中，SGSH酶或其催化活性變異體或片段與其在未接合於Fc多肽或結合TfR之Fc多肽時的活性相比保持其活性之至少10%或至少15%、20%、25%、30%、35%、40%、45%、50%、55%、60%、65%、70%、75%、80%、85%、90%或95%。在一些實施例中，SGSH酶或其催化活性變異體或片段與其在未接合於Fc多肽或結合TfR之Fc多肽時的活性相比保持其活性之至少80%、85%、90%或95%。在一些實施例中，與Fc多肽融合不會降低SGSH酶或其催化活性變異體或片段的活性。在一些實施例中，與結合TfR之Fc多肽融合不會降低SGSH酶之活性。 Fc 多肽修飾
併入本文所述之融合蛋白中之Fc多肽可包含某些修飾。舉例而言，Fc多肽可包含引起結合於血腦屏障(BBB)受體、例如運鐵蛋白受體(TfR)之修飾。另外，Fc多肽可包含其他修飾，例如促進異二聚合、增加血清穩定性或血清半衰期、調節效應功能、影響糖基化及/或降低在人類中之免疫原性的修飾。因此，在某些實施例中，本文所述之融合蛋白包含兩種Fc多肽，其中一種Fc為野生型Fc多肽，例如人類IgG1 Fc多肽；且另一種Fc經修飾以結合於血腦障壁(BBB)受體、例如運鐵蛋白受體(TfR)，且視情況進一步包含一或多個額外修飾。在某些其他實施例中，兩種Fc多肽各包含獨立選擇之修飾(例如本文所述之修飾)。
本文中使用EU索引編號對多種Fc修飾，包括在結合於BBB受體、例如TfR之經修飾之Fc多肽中引入的修飾中所指定的胺基酸殘基進行編號。任何Fc多肽，例如IgG1、IgG2、IgG3或IgG4 Fc多肽，可在如本文所述之一或多個位置處具有修飾，例如胺基酸取代。
本文所述之融合蛋白中存在的經修飾(例如增強異二聚合及/或BBB受體結合)之Fc多肽可與天然Fc區序列或其片段，例如至少50個胺基酸或至少100個胺基酸或長度更長之片段具有至少70%一致性、至少75%一致性、至少80%一致性、至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性。在一些實施例中，天然Fc胺基酸序列為SEQ ID NO:1之Fc區序列。在一些實施例中，經修飾之Fc多肽與SEQ ID NO:1之胺基酸1-110、或SEQ ID NO:1之胺基酸111-217或其片段，例如至少50個胺基酸或至少100個胺基酸或長度更長之片段具有至少70%一致性、至少75%一致性、至少80%一致性、至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性。
在一些實施例中，經修飾(例如增強異二聚合及/或BBB受體結合)之Fc多肽包含與天然Fc區胺基酸序列對應的至少50個胺基酸，或至少60個、65個、70個、75個、80個、85個、90個或95個或更多個、或至少100個胺基酸或更多個。在一些實施例中，經修飾之Fc多肽包含與例如SEQ ID NO:1之天然Fc區胺基酸序列對應的至少25個相連胺基酸，或至少30個、35個、40個或45個相連胺基酸，或50個相連胺基酸，或至少60個、65個、70個、75個、80個、85個、90個或95個或更多個相連胺基酸，或100個或更多個相連胺基酸。 用於血腦障壁 (BBB) 受體結合之修飾
在一些態樣中，本文提供能夠轉運跨過血腦障壁(BBB)之融合蛋白。此類蛋白質包含結合於BBB受體之經修飾之Fc多肽。BBB受體在BBB內皮以及其他細胞及組織類型上表現。在一些實施例中，BBB受體為運鐵蛋白受體(TfR)。
在一些實施方案中，本文所述之融合蛋白特異性結合於TfR。在一些實施例中，本文所述之融合蛋白以約50 nM至約500 nM之親和力特異性結合於TfR。在一些實施例中，蛋白質以約50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490或500 nM之親和力結合(例如特異性結合)於TfR。在一些實施例中，蛋白質以約100 nM至約500 nM之親和力結合於TfR。在一些實施例中，蛋白質以約100 nM至約300 nM、或約150 nM至約250 nM、或約200 nM至約250 nM之親和力結合於TfR。在一些實施例中，蛋白質以約230 nM之親和力結合於TfR。在一些實施例中，蛋白質以約150 nM至約400 nM、或約200 nM至約400 nM、或約250 nM至約350 nM、或約300 nM至約350 nM之親和力結合於TfR。
在一些實施例中，特異性結合於TfR之經修飾之Fc多肽在CH3結構域中包含取代。在一些實施例中，經修飾之Fc多肽包含針對TfR結合活性進行修飾之人類Ig CH3結構域，諸如IgG CH3結構域。CH3結構域可能屬於任何IgG亞型，亦即來自IgG1、IgG2、IgG3或IgG4。在IgG抗體之上下文中，CH3結構域係指如根據EU編號方案編號，自約位置341至約位置447之胺基酸區段。
在一些實施例中，特異性結合於TfR之經修飾之Fc多肽結合於TfR之頂端結構域且可在不阻斷或以其他方式抑制運鐵蛋白與TfR之結合的情況下結合於TfR。在一些實施例中，運鐵蛋白與TfR之結合實質上不受抑制。在一些實施例中，運鐵蛋白與TfR之結合被抑制不到約50% (例如不到約45%、40%、35%、30%、25%、20%、15%、10%或5%)。在一些實施例中，運鐵蛋白與TfR之結合被抑制不到約20% (例如不到約15%、10%、9%、8%、7%、6%、5%、4%、3%、2%或1%)。
在一些實施例中，本文所述之融合蛋白中存在的經修飾(例如結合BBB受體)之Fc多肽包含根據EU編號方案在胺基酸位置384、386、387、388、389、413、415、416及421處之取代。
在一些實施例中，特異性結合於TfR之經修飾之Fc多肽包含根據EU編號在位置389處之Ala。在一些實施例中，根據EU編號，特異性結合於TfR之經修飾之Fc多肽在以下位置處包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，根據EU編號，特異性結合於TfR之經修飾之Fc多肽在以下位置處包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe。
在額外實施例中，經修飾之Fc多肽進一步在根據EU編號方案包含414、424及426之位置處包含一個、兩個或三個取代。在一些實施例中，位置414為Lys、Arg、Gly或Pro；位置424為Ser、Thr、Glu或Lys；及/或位置426為Ser、Trp或Gly。
在一些實施例中，經修飾之Fc多肽與SEQ ID NO:32之胺基酸111-217具有至少70%一致性、至少75%一致性、至少80%一致性、至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性；且在SEQ ID NO:32之EU索引位置380、384-390及/或413-421處包含該等胺基酸。在一些實施例中，經修飾之Fc多肽與SEQ ID NO: 33之胺基酸111-216具有至少70%一致性、至少75%一致性、至少80%一致性、至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性；且在SEQ ID NO:32或33之EU索引位置380、384-390及/或413-421處包含該等胺基酸。在一些實施例中，經修飾之Fc多肽與SEQ ID NO: 32或33具有至少70%一致性、至少75%一致性、至少80%一致性、至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性；且在SEQ ID NO:32或33之EU索引位置380、384-390及/或413-421處包含該等胺基酸。
在一些實施例中，經修飾之Fc多肽與SEQ ID NO:32或33具有至少75%一致性、至少80%一致性、至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且具有根據EU編號在位置389處之Ala。在一些實施例中，經修飾之Fc多肽與SEQ ID NO:32或33具有至少75%一致性、至少80%一致性、至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置處包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，經修飾之Fc多肽與SEQ ID NO:32或33具有至少75%一致性、至少80%一致性、至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置處包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe。
在一些實施例中，經修飾之Fc多肽包含SEQ ID NO:32或33之胺基酸序列。 額外 Fc 多肽突變
在一些態樣中，本文所述之融合蛋白包含兩種Fc多肽，其中一種或兩種Fc多肽各自包含獨立選擇之修飾(例如本文所述之修飾)。可引入一種或兩種Fc多肽中之其他突變的非限制性實例包括例如增加血清穩定性或血清半衰期、調節效應功能、影響糖基化、降低在人類中之免疫原性及/或提供Fc多肽之杵臼異二聚合的突變。
在一些實施例中，融合蛋白中存在之Fc多肽獨立地與相應野生型Fc多肽(例如人類IgG1、IgG2、IgG3或IgG4 Fc多肽)具有至少約75%、80%、85%、90%、95%、96%、97%、98%或99%之胺基酸序列一致性。
在一些實施例中，融合蛋白中存在之Fc多肽包括杵及臼突變以促進異二聚體形成且阻礙同二聚體形成。一般地，修飾在第一多肽之界面處引入突起(「杵」)且在第二多肽之界面中引入相應腔(「臼」)，使得突起可位於腔中以便促進異二聚體形成且因此阻礙同二聚體形成。突起係藉由用較大側鏈(例如酪胺酸或色胺酸)替換來自第一多肽之界面的小胺基酸側鏈來構築。藉由用較小胺基酸側鏈(例如丙胺酸或蘇胺酸)替換大胺基酸側鏈，在第二多肽之界面中產生與突起相同或類似尺寸之補償腔。在一些實施例中，此類額外突變處於Fc多肽中對多肽與BBB受體、例如TfR之結合無負面影響之位置處。
在用於二聚之杵臼方法的一個示意性實施例中，融合蛋白中存在之Fc多肽中之一者的位置366 (根據EU編號方案編號)包含色胺酸，代替天然蘇胺酸。二聚體中之另一種Fc多肽在位置407處(根據EU編號方案編號)具有纈胺酸，代替天然酪胺酸。另一種Fc多肽可進一步包含取代，其中在位置366處(根據EU編號方案編號)之天然蘇胺酸經絲胺酸取代且在位置368處(根據EU編號方案編號)之天然白胺酸經丙胺酸取代。因此，本文所述之融合蛋白之一種Fc多肽具有T366W杵突變且另一種Fc多肽具有Y407V突變，其通常伴有T366S及L368A臼突變。在某些實施例中，第一Fc多肽含有T366S、L368A及Y407V取代且第二Fc多肽含有T366W取代。在某些其他實施例中，第一Fc多肽含有T366W取代且第二Fc多肽含有T366S、L368A及Y407V取代。
在一些實施例中，可引入增強血清半衰期之修飾。舉例而言，在一些實施例中，如根據EU編號方案編號，本文所述之融合蛋白中存在之一種或兩種Fc多肽可包含在位置252處之酪胺酸、在位置254處之蘇胺酸及在位置256處之麩胺酸。因此，一種或兩種Fc多肽可具有M252Y、S254T及T256E取代。可替代地，如根據EU編號方案編號，一種或兩種Fc多肽可具有M428L及N434S取代。可替代地，一種或兩種Fc多肽可具有N434S或N434A取代。
在一些實施例中，本文所述之融合蛋白中存在之一種或兩種Fc多肽可包含降低效應功能，亦即在結合於在介導效應功能之效應細胞上表現的Fc受體後誘導某些生物功能之能力降低的修飾。抗體效應功能之實例包括(但不限於) C1q結合及補體依賴性細胞毒性(CDC)、Fc受體結合、抗體依賴性細胞介導之細胞毒性(ADCC)、抗體依賴性細胞介導之吞噬作用(ADCP)、下調細胞表面受體(例如B細胞受體)及B細胞活化。效應功能可隨抗體類別而變。舉例而言，在結合於在免疫系統細胞上存在之適當Fc受體後，天然人類IgG1及IgG3抗體可引起ADCC和CDC活性，且在結合於在免疫細胞上存在之適當Fc受體後，天然人類IgG1、IgG2、IgG3及IgG4可引起ADCP功能。
在一些實施例中，本文所述之融合蛋白中存在之一種或兩種Fc多肽亦可經工程改造以含有用於異二聚合之其他修飾，例如CH3-CH3界面內接觸殘基之靜電工程改造，該等修飾為天然帶電的或疏水性補丁修飾。
在一些實施例中，本文所述之融合蛋白中存在之一種或兩種Fc多肽可包括調節效應功能之額外修飾。
在一些實施例中，本文所述之融合蛋白中存在之一種或兩種Fc多肽可包含降低或消除效應功能之修飾。降低效應功能之例示性Fc多肽突變包括(但不限於) CH2結構域中例如在根據EU編號方案之位置234及235處的取代。舉例而言，在一些實施例中，一種或兩種Fc多肽可在位置234及235處包含丙胺酸殘基。因此，一種或兩種Fc多肽可具有L234A和L235A (LALA)取代。
調節效應功能之額外Fc多肽突變包括(但不限於)以下：位置329可具有如下突變，其中脯胺酸經甘胺酸或精胺酸或足夠大以破壞在Fc之脯胺酸329與FcγRIII之色胺酸殘基Trp 87及Trp 110之間形成的Fc/Fcγ受體界面的胺基酸殘基取代。額外例示性取代包括根據EU編號方案之S228P、E233P、L235E、N297A、N297D及P331S。亦可存在多個取代，例如根據EU編號方案，人類IgG1 Fc區之L234A及L235A；人類IgG1 Fc區之L234A、L235A及P329G；人類IgG1 Fc區之L234A、L235A及P329S；人類IgG4 Fc區之S228P及L235E；人類IgG1 Fc區之L234A及G237A；人類IgG1 Fc區之L234A、L235A及G237A；人類IgG2 Fc區之V234A及G237A；人類IgG4 Fc區之L235A、G237A及E318A；以及人類IgG4 Fc區之S228P及L236E。在一些實施例中，一種或兩種Fc多肽可具有一或多個調節ADCC之胺基酸取代，例如在根據EU編號方案之位置298、333及/或334處的取代。
在一些實施例中，在本文所述之Fc多肽中移除C端Lys殘基(亦即，根據EU編號方案，在位置447處之Lys殘基)。 包含額外突變之例示性 Fc 多肽
如本文所述，且藉助於非限制性實例，本文所述之融合蛋白中存在之一種或兩種Fc多肽可包含額外突變，包括杵突變(例如，如根據EU編號方案編號之T366W)、臼突變(例如，如根據EU編號方案編號之T366S、L368A及Y407V)、調節效應功能之突變(例如，如根據EU編號方案編號之L234A、L235A及/或P329G或P329S (例如L234A及L235A；L234A、L235A及P329G；或L234A、L235A及P329S))及/或增加血清穩定性或血清半衰期之突變(例如，(i)如參考EU編號進行編號之M252Y、S254T及T256E，或(ii)如根據EU編號方案編號之N434S，有或無M428L)。作為例證，SEQ ID NO:12-19、24-31、34-41及48-57提供包含此等額外突變中之一或多者的經修飾之Fc多肽的非限制性實例。
在一些實施例中，Fc多肽可具有杵突變(例如，如根據EU編號方案編號之T366W)且與SEQ ID NO:1、2、32及33中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性。在一些實施例中，具有SEQ ID NO: 1、2、32及33中之任一者之序列的Fc多肽可經修飾以具有杵突變。
在一些實施例中，經修飾之Fc多肽包含杵突變(例如，如參考EU編號進行編號之T366W)，且與SEQ ID NO: 24及25中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性。在一些實施例中，經修飾之Fc多肽包含SEQ ID NO: 24及25中之任一者之序列。
在一些實施例中，經修飾之Fc多肽包含杵突變(例如，如參考EU編號進行編號之T366W)，且與SEQ ID NO: 34及35中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且包含根據EU編號在位置389處之Ala。在一些實施例中，經修飾之Fc多肽與SEQ ID NO:34或35具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置處包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，經修飾之Fc多肽與SEQ ID NO:34或35具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置處包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe。在一些實施例中，經修飾之Fc多肽包含SEQ ID NO: 34及35中之任一者之序列。
在一些實施例中，Fc多肽可具有杵突變(例如，如根據EU編號方案編號之T366W)、調節效應功能之突變(例如，如根據EU編號方案編號之L234A、L235A及/或P329G或P329S (例如L234A及L235A；L234A、L235A及P329G；或L234A、L235A及P329S))，且與SEQ ID NO: 1、2、32及33中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性。在一些實施例中，具有SEQ ID NO: 1、2、32及33中之任一者之序列的Fc多肽可經修飾以具有杵突變及調節效應功能之突變。
在一些實施例中，經修飾之Fc多肽包含杵突變(例如，如參考EU編號進行編號之T366W)及調節效應功能之突變(例如，如參考EU編號進行編號之L234A、L235A及/或P329G或P329S (例如L234A及L235A；L234A、L235A及P329G；或L234A、L235A及P329S))，且與SEQ ID NO: 26及27中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性。在一些實施例中，經修飾之Fc多肽包含SEQ ID NO: 26及27中之任一者之序列。
在一些實施例中，經修飾之Fc多肽包含杵突變(例如，如參考EU編號進行編號之T366W)及調節效應功能之突變(例如，如參考EU編號進行編號之L234A、L235A及/或P329G或P329S (例如L234A及L235A；L234A、L235A及P329G；或L234A、L235A及P329S))，與SEQ ID NO: 36-41及54-57中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且包含根據EU編號在位置389處之Ala。在一些實施例中，經修飾之Fc多肽與SEQ ID NO: 36-41及54-57中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，經修飾之Fc多肽與SEQ ID NO: 36-41及54-57中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe。在一些實施例中，經修飾之Fc多肽包含SEQ ID NO: 36-41及54-57中之任一者之序列。
在一些實施例中，Fc多肽可具有臼突變(例如，如根據EU編號方案編號之T366S、L368A及Y407V)，且與SEQ ID NO: 1、2、32及33具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性。在一些實施例中，具有SEQ ID NO: 1、2、32及33中之任一者之序列的Fc多肽可經修飾以具有臼突變。
在一些實施例中，經修飾之Fc多肽包含臼突變(例如，如參考EU編號進行編號之T366S、L368A及Y407V)，且與SEQ ID NO: 12及13具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性。在一些實施例中，經修飾之Fc多肽包含SEQ ID NO: 12及13中之任一者之序列。
在一些實施例中，經修飾之Fc多肽包含臼突變(例如，如參考EU編號進行編號之T366S、L368A及Y407V)，且與SEQ ID NO: 48及49具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且包含根據EU編號在位置389處之Ala。在一些實施例中，經修飾之Fc多肽與SEQ ID NO: 48及49中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，經修飾之Fc多肽與SEQ ID NO: 48及49中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe。在一些實施例中，經修飾之Fc多肽包含SEQ ID NO: 48及49中之任一者之序列。
在一些實施例中，Fc多肽可具有臼突變(例如，如根據EU編號方案編號之T366S、L368A及Y407V)、調節效應功能之突變(例如L234A、L235A及/或P329G或P329S (例如，如根據EU編號方案編號之L234A及L235A；L234A、L235A及P329G；或L234A、L235A及P329S))，且與SEQ ID NO: 1、2、32及33中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性。在一些實施例中，具有SEQ ID NO: 1、2、32及33中之任一者之序列的Fc多肽可經修飾以具有臼突變及調節效應功能之突變。
在一些實施例中，經修飾之Fc多肽包含臼突變(例如，如參考EU編號進行編號之T366S、L368A及Y407V)及調節效應功能之突變(例如，如參考EU編號進行編號之L234A、L235A及/或P329G或P329S (例如，L234A及L235A；L234A、L235A及P329G；或L234A、L235A及P329S))，且與SEQ ID NO: 14-19及28-31中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性。在一些實施例中，經修飾之Fc多肽包含SEQ ID NO: 14-19及28-31中之任一者之序列。
在一些實施例中，經修飾之Fc多肽包含臼突變(例如，如參考EU編號進行編號之T366S、L368A及Y407V)及調節效應功能之突變(例如，如參考EU編號進行編號之L234A、L235A及/或P329G或P329S (例如L234A及L235A；L234A、L235A及P329G；或L234A、L235A及P329S))，且與SEQ ID NO: 50-53中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且包含根據EU編號在位置389處之Ala。在一些實施例中，經修飾之Fc多肽與SEQ ID NO: 50-53中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，經修飾之Fc多肽與SEQ ID NO: 50-53中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe。在一些實施例中，經修飾之Fc多肽包含SEQ ID NO: 50-53中之任一者之序列。 FcRn 結合位點
在某些態樣中，經修飾(例如結合BBB受體)之Fc多肽或本文所述之融合蛋白中存在的不特異性結合於BBB受體之Fc多肽可包含FcRn結合位點。在一些實施例中，FcRn結合位點在Fc多肽或其片段內。
在一些實施例中，FcRn結合位點包含天然FcRn結合位點。在一些實施例中，FcRn結合位點不包含相對於天然FcRn結合位點之胺基酸序列的胺基酸變化。在一些實施例中，天然FcRn結合位點為IgG結合位點，例如人類IgG結合位點。在一些實施例中，FcRn結合位點包含改變FcRn結合之修飾。
在一些實施例中，FcRn結合位點具有一或多個發生突變，例如經取代之胺基酸殘基，其中該(等)突變增加血清半衰期或實質上不減少血清半衰期(亦即，當在相同條件下分析時，與在突變位置處具有野生型殘基之對應經修飾之Fc多肽相比血清半衰期減少至多25%)。在一些實施例中，FcRn結合位點具有一或多個在根據EU編號方案之位置250-256、307、380、428及433-436處經取代之胺基酸殘基。
在一些實施例中，在FcRn結合位點上或其附近之一或多個殘基相對於天然人類IgG序列發生突變，以延長經修飾之多肽的血清半衰期。在一些實施例中，突變引入位置252、254及256中之一個、兩個或三個中。在一些實施例中，突變為M252Y、S254T及T256E。在一些實施例中，經修飾之Fc多肽進一步包含突變M252Y、S254T及T256E。在一些實施例中，經修飾之Fc多肽在根據EU編號方案之位置T307、E380及N434中之一個、兩個或全部三個處包含取代。在一些實施例中，突變為T307Q及N434A。在一些實施例中，經修飾之Fc多肽包含突變T307A、E380A及N434A。在一些實施例中，經修飾之Fc多肽在根據EU編號方案之位置T250及M428處包含取代。在一些實施例中，經修飾之Fc多肽包含突變T250Q及/或M428L。在一些實施例中，經修飾之Fc多肽在根據EU編號方案之位置M428及N434處包含取代。在一些實施例中，經修飾之Fc多肽包含突變M428L及N434S。在一些實施例中，經修飾之Fc多肽包含N434S或N434A突變。 連接於 Fc 多肽之 SGSH 酶
在一些實施例中，本文所述之融合蛋白包含兩種如本文所述之Fc多肽且該等Fc多肽中之一種或兩種可進一步包含部分或完全鉸鏈區。鉸鏈區可來自於任何免疫球蛋白亞類或同型。例示性免疫球蛋白鉸鏈為IgG鉸鏈區，諸如IgG1鉸鏈區，例如人類IgG1鉸鏈胺基酸序列EPKSCDKTHTCPPCP (SEQ ID NO:5)或其一部分(例如DKTHTCPPCP；SEQ ID NO:6)。在一些實施例中，鉸鏈區在Fc多肽之N端區。
在某些實施例中，第一Fc多肽之N端連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。在某些實施例中，第一Fc多肽之C端連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。在某些實施例中，第二Fc多肽之N端連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。在某些實施例中，第二Fc多肽之C端連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。
在某些實施例中，第一Fc多肽之N端連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段；且第二Fc多肽之N端連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。
在某些實施例中，第一Fc多肽之C端連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段；且第二Fc多肽之C端連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。
在一些實施例中，Fc多肽藉由連接子，例如肽連接子接合於SGSH酶。在一些實施例中，Fc多肽藉由肽鍵或藉由肽連接子接合於SGSH酶，例如為融合多肽。肽連接子可經組態，使得其允許SGSH酶相對於其所接合之Fc多肽旋轉；及/或抵抗蛋白酶消化。肽連接子可含有天然胺基酸、非天然胺基酸或其組合。在一些實施例中，肽連接子可為可撓性連接子，例如含有胺基酸，例如Gly、Asn、Ser、Thr、Ala及其類似物(例如富甘胺酸連接子)。此類連接子使用已知參數設計，且可為任何長度，且含有任何長度之任何數目之重複單元(例如Gly及Ser殘基之重複單元)。舉例而言，連接子可具有重複單元，例如兩個、三個、四個、五個或更多個Gly 4-Ser (SEQ ID NO:8)重複單元或單一Gly 4-Ser (SEQ ID NO:8)。在其他態樣中，連接子可為Gly-Ser (SEQ ID NO:7)。在一些實施例中，肽連接子可包括蛋白酶裂解位點，例如可由中樞神經系統中存在之酶裂解。
在一些實施例中，SGSH酶例如藉由Gly-Ser連接子(SEQ ID NO:7)、Gly 4-Ser連接子(SEQ ID NO:8)或(Gly 4-Ser) 2連接子(SEQ ID NO:9)接合於Fc多肽之N端。在一些實施例中，Fc多肽可在N端包含接合於連接子或直接接合於SGSH酶的鉸鏈序列或部分鉸鏈序列。
在一些實施例中，SGSH酶例如藉由Gly-Ser連接子(SEQ ID NO:7)、Gly 4-Ser連接子(SEQ ID NO:8)或(Gly 4-Ser) 2連接子(SEQ ID NO:9)接合於Fc多肽之C端。在一些實施例中，Fc多肽之C端直接接合於SGSH酶。
在一些實施例中，SGSH酶藉由化學交聯劑接合於Fc多肽。此類結合物可使用熟知之化學交聯試劑及方案產生。舉例而言，存在所屬領域之技術人員已知且可用於使多肽與所關注試劑交聯之大量化學交聯劑。舉例而言，交聯劑為異雙官能交聯劑，其可用於以逐步方式連接分子。異雙官能交聯劑能夠針對結合蛋白質設計更特定之偶合方法，從而減少諸如同型蛋白質聚合物之不必要副反應的發生。所屬領域中已知多種異雙官能交聯劑，包括N-羥基丁二醯亞胺(NHS) 或其水溶性類似物N-羥基磺基丁二醯亞胺(磺基-NHS)、丁二醯亞胺基4-(N-順丁烯二醯亞胺基甲基)環己烷-1-甲酸酯(SMCC)、間順丁烯二醯亞胺基苯甲醯基-N-羥基丁二醯亞胺酯(MBS)；N-丁二醯亞胺基(4-碘乙醯基) 胺基苯甲酸酯(SIAB)、丁二醯亞胺基4-(對順丁烯二醯亞胺基苯基)丁酸酯(SMPB)、1-乙基-3-(3-二甲基胺基丙基)碳化二亞胺鹽酸鹽(EDC)；4-丁二醯亞胺基氧基羰基-a-甲基-a-(2-吡啶基二硫基)-甲苯(SMPT)、N-丁二醯亞胺基3-(2-吡啶基二硫基)丙酸酯(SPDP)及丁二醯亞胺基6-[3-(2-吡啶基二硫基)丙酸酯]己酸酯(LC-SPDP)。彼等具有N-羥基丁二醯亞胺部分之交聯劑可作為N-羥基磺基丁二醯亞胺類似物獲得，其通常具有更大水溶性。另外，彼等在連接鏈內具有二硫鍵之交聯劑可代之以合成為烷基衍生物，以便降低活體內連接子裂解之量。除異雙官能交聯劑外，存在許多其他交聯劑，包括同雙官能及光反應性交聯劑。二丁二醯亞胺基辛二酸酯(DSS)、雙順丁烯二醯亞胺己烷(BMH)及庚二亞胺酸二甲酯2HCl (DMP)為有用同雙官能交聯劑之實例，且雙-[B-(4-疊氮基水楊醯胺)乙基]二硫化物(BASED)及N-丁二醯亞胺基-6(4'-疊氮基-2'-硝基苯基胺基)己酸酯(SANPAH)為有用光反應性交聯劑之實例。 包含 SGSH 酶 -Fc 融合多肽之例示性蛋白質分子
在一些態樣中，本文所述之融合蛋白包含：第一Fc多肽，其連接於第一SGSH酶、SGSH酶變異體或其催化活性片段；及第二Fc多肽，其連接於第二SGSH酶、SGSH酶變異體或其催化活性片段，其中該第二Fc多肽包含根據EU編號在位置389處之Ala；且其中該第二Fc多肽與該第一Fc多肽形成Fc二聚體。在一些實施例中，根據EU編號，第二Fc多肽在以下位置處包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，根據EU編號，第二Fc多肽在以下位置處包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe。在某些實施例中，第二Fc多肽特異性結合於TfR。在一些實施例中，第一Fc多肽及/或第二Fc多肽不包括免疫球蛋白重鏈及/或輕鏈可變區序列或其抗原結合部分。在一些實施例中，第一Fc多肽為經修飾之Fc多肽。在某些實施例中，第二Fc多肽(亦即經修飾之Fc多肽)包含一或多個額外修飾。在一些實施例中，如本文所述之經修飾之Fc多肽含有一或多個促進其與另一Fc多肽之異二聚合的修飾。在一些實施例中，如本文所述之經修飾之Fc多肽含有一或多個降低效應功能之修飾。在一些實施例中，如本文所述之經修飾之Fc多肽含有一或多個延長血清半衰期之修飾。
在一些實施例中，本文所述之融合蛋白包含第一多肽鏈，該第一多肽鏈包括包含T366S、L368A及Y407V (臼)取代之第一Fc多肽；及第二多肽鏈，該第二多肽鏈包含結合於TfR且包含T366W (杵)取代之第二Fc多肽。在一些實施例中，第一Fc多肽及/或第二Fc多肽進一步包含L234A及L235A (LALA)取代。在一些實施例中，第一Fc多肽及/或第二Fc多肽進一步包含L234A、L235A及P329G (LALAPG)取代或包含L234A、L235A及P329S (LALAPS)取代。在一些實施例中，第一Fc多肽及/或第二Fc多肽進一步包含M252Y、S254T及T256E (YTE)取代。在一些實施例中，第一Fc多肽及/或第二Fc多肽進一步包含：1) L234A及L235A (LALA)取代；L234A、L235A及P329G (LALAPG)取代；或L234A、L235A及P329S (LALAPS)取代；及2) M252Y、S254T及T256E (YTE)取代。在一些實施例中，第一Fc多肽及/或第二Fc多肽在位置234、235、252、254、256及366處包含人類IgG1野生型殘基。
在一些實施例中，第二Fc多肽包含杵、LALA/LALAPG/LALAPS及/或YTE突變，與SEQ ID NO:34-41中之任一者具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且包含根據EU編號在位置389處之Ala。在一些實施例中，第二Fc多肽與SEQ ID NO: 34-41中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，第二Fc多肽與SEQ ID NO: 34-41中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe；或包含SEQ ID NO: 34-41中之任一者之序列。在一些實施例中，第一Fc多肽包含臼、LALA/LALAPG/LALAPS及/或YTE突變，且與SEQ ID NO:12-19中之任一者具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性；或包含SEQ ID NO: 12-19中之任一者之序列。在一些實施例中，第二Fc多肽包含SEQ ID NO:34-41中之任一者，且第一Fc多肽包含SEQ ID NO:12-19中之任一者。在一些實施例中，第一Fc多肽及/或第二Fc多肽之N端包括IgG1鉸鏈區之一部分(例如DKTHTCPPCP；SEQ ID NO:6)。在一些實施例中，第二Fc多肽與SEQ ID NO: 54-57中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且包含根據EU編號在位置389處之Ala。在一些實施例中，第二Fc多肽與SEQ ID NO: 54-57中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，第二Fc多肽與SEQ ID NO: 54-57中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe，或包含SEQ ID NO: 54-57中之任一者之序列。在一些實施例中，第一Fc多肽與SEQ ID NO: 28-31中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，或包含SEQ ID NO:28-31中之任一者之序列。
在一些實施例中，本文所述之融合蛋白包含第一多肽鏈，該第一多肽鏈包括包含T366W (杵)取代之第一Fc多肽；及第二多肽鏈，該第二多肽鏈包含結合於TfR且包含T366S、L368A及Y407V (臼)取代之第二Fc多肽。在一些實施例中，第一Fc多肽及/或第二Fc多肽進一步包含L234A及L235A (LALA)取代。在一些實施例中，第一Fc多肽及/或第二Fc多肽進一步包含L234A、L235A及P329G (LALAPG)取代或包含L234A、L235A及P329S (LALAPS)取代。在一些實施例中，第一Fc多肽及/或第二Fc多肽進一步包含M252Y、S254T及T256E (YTE)取代。在一些實施例中，第一Fc多肽及/或第二Fc多肽進一步包含：1) L234A及L235A (LALA)取代；L234A、L235A及P329G (LALAPG)取代；或L234A、L235A及P329S (LALAPS)取代；及2) M252Y、S254T及T256E (YTE)取代。在一些實施例中，第一Fc多肽及/或第二Fc多肽在位置234、235、252、254、256及366處包含人類IgG1野生型殘基。
在一些實施例中，第二Fc多肽包含臼、LALA/LALAPG/LALAPS及/或YTE突變，與SEQ ID NO:48-53中之任一者具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且包含根據EU編號在位置389處之Ala。在一些實施例中，第二Fc多肽與SEQ ID NO: 48-53中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，第二Fc多肽與SEQ ID NO: 48-53中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe；或包含SEQ ID NO:48-53中之任一者的序列。在一些實施例中，第一Fc多肽包含杵、LALA/LALAPG/LALAPS及/或YTE突變，且與SEQ ID NO:24-27中之任一者具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性；或包含SEQ ID NO: 24-27中之任一者之序列。在一些實施例中，第二Fc多肽包含SEQ ID NO: 48-53中之任一者，且第一Fc多肽包含SEQ ID NO:24-27中之任一者。在一些實施例中，經修飾之Fc多肽及/或Fc多肽之N端包括IgG1鉸鏈區之一部分(例如DKTHTCPPCP；SEQ ID NO:6)。
在一些實施例中，本文所述之融合蛋白中存在之第一SGSH酶連接於第一多肽鏈(例如呈融合多肽)，該第一多肽鏈包含與SEQ ID NO: 12-19中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性或包含SEQ ID NO: 12-19中之任一者之序列的第一Fc多肽。在一些實施例中，第一SGSH酶藉由連接子，諸如可撓性連接子，及/或鉸鏈區或其一部分(例如DKTHTCPPCP；SEQ ID NO:6)連接於第一Fc多肽。在一些實施例中，第一Fc多肽之N端包括IgG1鉸鏈區之一部分(例如DKTHTCPPCP；SEQ ID NO:6)。在一些實施例中，第一Fc多肽與SEQ ID NO:28-31中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，或包含SEQ ID NO:28-31中之任一者之序列。在一些實施例中，第一SGSH酶包含與SEQ ID NO:58-60中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性的SGSH序列，或包含SEQ ID NO:58-60中之任一者之序列。在一些實施例中，連接於Fc多肽之第一SGSH序列與SEQ ID NO:61-68、73-76、81-84及117-118中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，或包含SEQ ID NO:61-68、73-76、81-84及117-118中之任一者之序列。在一些實施例中，融合蛋白包含與SEQ ID NO: 34-41中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性且包含根據EU編號在位置389處之Ala的第二Fc多肽。在一些實施例中，第二Fc多肽與SEQ ID NO: 34-41中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，第二多肽與SEQ ID NO: 34-41中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe，或包含SEQ ID NO: 34-41中之任一者之序列。在一些實施例中，第二SGSH酶藉由連接子，諸如可撓性連接子，及/或鉸鏈區或其一部分(例如DKTHTCPPCP；SEQ ID NO:6)連接於第二Fc多肽。在一些實施例中，第二Fc多肽之N端包括IgG1鉸鏈區之一部分(例如DKTHTCPPCP；SEQ ID NO:6)。在一些實施例中，第二Fc多肽與SEQ ID NO:54-57中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且包含根據EU編號在位置389處之Ala。在一些實施例中，第二Fc多肽與SEQ ID NO: 54-57中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，第二Fc多肽與SEQ ID NO: 54-57中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe，或包含SEQ ID NO: 54-57中之任一者之序列。在一些實施例中，第二SGSH酶包含與SEQ ID NO:58-60中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性的SGSH序列，或包含SEQ ID NO:58-60中之任一者之序列。在一些實施例中，連接於第二Fc多肽之第二SGSH序列與SEQ ID NO: 89-96、101-104、109-112及119-120中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且包含根據EU編號在位置389處之Ala。在一些實施例中，第二Fc多肽與SEQ ID NO: 89-96、101-104、109-112及119-120中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，第二Fc多肽與SEQ ID NO: 89-96、101-104、109-112及119-120中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe，或包含SEQ ID NO: 89-96、101-104、109-112及119-120中之任一者之序列。
在一些實施例中，融合蛋白包括包含SEQ ID NO:61-64中之任一者之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:89-92中之任一者之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:65-68中之任一者之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:93-96中之任一者之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:73-76中之任一者之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:101-104中之任一者之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:81-84中之任一者之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:109-112中之任一者之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:117-118中之任一者之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:119-120中之任一者之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:61或62之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:89或90之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:65或66之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:93或94之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:63或64之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:91或92之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:64之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:92之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:67或68之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:95或96之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:68之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:96之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:73或74之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:101或102之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:75或76之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:103或104之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:76之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:104之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:81或82之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:109或110之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:83或84之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:111或112之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:84之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:112之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:117之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:119之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:118之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:120之序列的第二SGSH-Fc多肽。
在一些實施例中，本文所述之融合蛋白中存在之第一SGSH酶連接於第一多肽鏈(例如呈融合多肽)，該第一多肽鏈包含與SEQ ID NO: 24-27中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性或包含SEQ ID NO: 24-27中之任一者之序列的第一Fc多肽。在一些實施例中，第一SGSH酶藉由連接子，諸如可撓性連接子，及/或鉸鏈區或其一部分(例如DKTHTCPPCP；SEQ ID NO:6)連接於第一Fc多肽。在一些實施例中，第一Fc多肽之N端包括IgG1鉸鏈區之一部分(例如DKTHTCPPCP；SEQ ID NO:6)。在一些實施例中，第一SGSH酶包含與SEQ ID NO:58-60中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性的SGSH序列，或包含SEQ ID NO:58-60中之任一者之序列。在一些實施例中，連接於Fc多肽之第一SGSH序列與SEQ ID NO:69-72、77-80及85-88中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，或包含SEQ ID NO: 69-72、77-80及85-88中之任一者之序列。在一些實施例中，融合蛋白包含與SEQ ID NO: 48-53中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性且包含根據EU編號在位置389處之Ala的第二Fc多肽。在一些實施例中，第二多肽與SEQ ID NO: 48-53中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，第二Fc多肽與SEQ ID NO: 48-53中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe，或包含SEQ ID NO:48-53中之任一者的序列。在一些實施例中，第二SGSH酶藉由連接子，諸如可撓性連接子，及/或鉸鏈區或其一部分(例如DKTHTCPPCP；SEQ ID NO:6)連接於第二Fc多肽。在一些實施例中，第二Fc多肽之N端包括IgG1鉸鏈區之一部分(例如DKTHTCPPCP；SEQ ID NO:6)。在一些實施例中，第二SGSH酶包含與SEQ ID NO:58-60中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性的SGSH序列，或包含SEQ ID NO:58-60中之任一者之序列。在一些實施例中，連接於第二Fc多肽之第二SGSH序列與SEQ ID NO:97-100、105-108及113-116中之任一者具有至少85%、至少90%、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且包含根據EU編號在位置389處之Ala。在一些實施例中，第二Fc多肽與SEQ ID NO:97-100、105-108及113-116中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置389處之Ala；及在位置390處之Asn。在一些實施例中，第二Fc多肽與SEQ ID NO: 97-100、105-108及113-116中之任一者之序列具有至少85%一致性、至少90%一致性、至少95%一致性、至少96%%一致性、至少97%一致性、至少98%一致性或至少99%一致性，且根據EU編號，在以下位置包含：在位置380處之Glu；在位置384處之Tyr；在位置386處之Thr；在位置387處之Glu；在位置388處之Trp；在位置389處之Ala；在位置390處之Asn；在位置413處之Thr；在位置415處之Glu；在位置416處之Glu；及在位置421處之Phe，或包含SEQ ID NO: 97-100、105-108及113-116中之任一者之序列。
在一些實施例中，融合蛋白包括包含SEQ ID NO:69或70之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:97或98之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:71或72之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:99或100之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:77或78之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:105或106之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:79或80之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:107或108之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:85或86之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:113-114之序列的第二SGSH-Fc多肽。
在一些實施例中，融合蛋白包括包含SEQ ID NO:87或88之序列的第一SGSH-Fc融合多肽，及包含SEQ ID NO:115-116之序列的第二SGSH-Fc多肽。
本文所述之融合蛋白及其他組合物可具有一系列結合親和力。舉例而言，在一些實施例中，蛋白質對運鐵蛋白受體(TfR)具有親和力，在1 pM至10 μM之範圍內的任何數值。在一些實施例中，對TfR之親和力在1 nM至5 μM或10 nM至1 μM範圍內。在一些實施例中，對TfR之親和力在約50 nM至約500 nM或約100 nM至約500 nM範圍內。在一些實施例中，對TfR之親和力在約50 nM至約300 nM範圍內。在一些實施例中，對TfR之親和力在約100 nM至約350 nM範圍內。在一些實施例中，對TfR之親和力在約150 nM至約400 nM範圍內。在一些實施例中，對TfR之親和力在約200 nM至約450 nM範圍內。在一些實施例中，對TfR之親和力為單價親和力。 評估蛋白質活性
可使用各種分析，包括使用人工受質量測活體外活性之分析，諸如實例部分中所述之彼等分析，評定包含SGSH酶之本文所述之融合蛋白的活性。用於量測活體外SGSH活性之其他例示性方案提供於例如WO2019/070577中。
在一些實施例中，評估組織樣品。可使用如上所述之分析評估組織樣品，除了在音波處理步驟之前通常包括多次凍融循環，例如2次、3次、4次、5次或更多次，以保證微泡破開。
可藉由本文所述之分析評估的樣品包括腦、肝臟、腎、肺、脾、血漿、血清、腦脊髓液(CSF)及尿液。在一些實施例中，可評估來自接受本文所述之酶-Fc融合蛋白(例如SGSH-Fc融合蛋白)之患者的CSF樣品。 核酸、載體及宿主細胞
通常使用重組方法製備如本文所述之融合蛋白中所含的多肽鏈。因此，在一些態樣中，本揭示案提供經分離之核酸，其包含編碼包含如本文所述之Fc多肽之任一多肽鏈的核酸序列；及宿主細胞，其中引入核酸，用於複製編碼多肽之核酸及/或表現該等多肽。在一些實施例中，宿主細胞為真核的，例如人類細胞。
在另一個態樣中，提供多核苷酸，其包含編碼本文所述之多肽鏈中之一或多者的核苷酸序列。在一些實施例中，多核苷酸編碼本文所述之多肽序列中之一者。在一些實施例中，多核苷酸編碼本文所述之多肽序列中之兩者。多核苷酸可為單股或雙股的。在一些實施例中，多核苷酸為DNA。在特定實施例中，多核苷酸為cDNA。在一些實施例中，多核苷酸為RNA。
一些實施例亦提供一種核酸序列對，其中各核酸序列編碼本文所述之多肽。舉例而言，某些實施例提供一種核酸序列對，其中該對中之第一核酸序列編碼連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段之第一Fc多肽；且該對中之第二核酸序列編碼連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段之第二Fc多肽。
在一些實施例中，多核苷酸包括在核酸構築體內或多核苷酸對包括在一或多個核酸構築體內。在一些實施例中，構築體為可複製載體。在一些實施例中，載體係選自質體、病毒載體、噬粒、酵母染色體載體及非游離型哺乳動物載體。
在一些實施例中，在表現構築體中多核苷酸可操作地連接於一或多個調控核苷酸序列。在一系列實施例中，核酸表現構築體適宜用作表面表現文庫。在一些實施例中，文庫適宜在酵母中進行表面表現。在一些實施例中，文庫適宜在噬菌體中進行表面表現。在另一系列實施例中，核酸表現構築體適宜在允許以毫克或公克之量分離多肽之系統中表現多肽。在一些實施例中，系統為哺乳動物細胞表現系統。在一些實施例中，系統為酵母細胞表現系統。
用於產生重組多肽之表現媒劑包括質體及其他載體。舉例而言，合適載體包括以下類型之質體：pBR322衍生之質體、pEMBL衍生之質體、pEX衍生之質體、pBTac衍生之質體及pUC衍生之質體，用於在諸如大腸桿菌之原核細胞中表現。pcDNAI/amp、pcDNAI/neo、pRc/CMV、pSV2gpt、pSV2neo、pSV2-dhfr、pTk2、pRSVneo、pMSG、pSVT7、pko-neo及pHyg衍生之載體為適合於轉染真核細胞之哺乳動物表現載體之實例。可替代地，諸如牛乳頭狀瘤病毒(BPV-1)或艾司坦-巴爾病毒(Epstein-Barr virus) (pHEBo、pREP衍生及p205)之病毒衍生物可用於在真核細胞中短暫表現多肽。在一些實施例中，可能需要藉由使用桿狀病毒表現系統表現重組多肽。此類桿狀病毒表現系統之實例包括pVL衍生之載體(諸如pVL1392、pVL1393及pVL941)、pAcUW衍生之載體(諸如pAcUW1)及pBlueBac衍生之載體。額外表現系統包括腺病毒、腺相關病毒及其他病毒表現系統。
載體可轉型至任何合適宿主細胞中。在一些實施例中，例如細菌或酵母細胞之宿主細胞可適合用作表面表現文庫。在一些細胞中，載體在宿主細胞中表現以表現相對大量之多肽。此類宿主細胞包括哺乳動物細胞、酵母細胞、昆蟲細胞及原核細胞。在一些實施例中，細胞為哺乳動物細胞，諸如中國倉鼠卵巢(CHO)細胞、幼倉鼠腎(BHK)細胞、NS0細胞、Y0細胞、HEK293細胞、COS細胞、Vero細胞或HeLa細胞。
可在允許表現一或多種多肽之適當條件下培養經編碼如本文所述之一或多個Fc多肽鏈之表現載體轉染的宿主細胞。多肽可分泌且自細胞與含有多肽之培養基的混合物中分離。可替代地，多肽可保持在細胞質中或保持在膜部分中，且使用期望方法收穫細胞，溶解，且分離多肽。 治療方法
如本文所述之融合蛋白可在治療上用於治療聖菲利浦症候群A。
因此，某些實施例提供一種減少患有聖菲利浦症候群A之個體中毒性代謝產物(例如硫酸乙醯肝素衍生之寡醣)積聚的方法，該方法包括向該個體投與如本文所述之蛋白質。
某些實施例提供如本文所述之蛋白質，其用於減少患有聖菲利浦症候群A之個體中之毒性代謝產物(例如硫酸乙醯肝素衍生之寡醣)積聚。
某些實施例提供如本文所述之蛋白質的用途，其用於製備供減少患有聖菲利浦症候群A之個體中之毒性代謝產物(例如硫酸乙醯肝素衍生之寡醣)積聚的藥劑。
某些實施例亦提供一種治療聖菲利浦症候群A之方法，該方法包括向有需要之個體投與如本文所述之蛋白質。
某些實施例提供如本文所述之蛋白質，其用於治療有需要之個體之聖菲利浦症候群A。
某些實施例提供如本文所述之蛋白質的用途，其用於製備供治療有需要之個體之聖菲利浦症候群A用的藥劑。
在一些實施例中，與在缺乏與本文所述之融合蛋白連接之情況下SGSH的吸收相比或與連接於參考蛋白(例如，未對第二Fc多肽進行促成TfR結合之修飾的如本文所述之融合蛋白)之SGSH之吸收相比，投與蛋白質(例如連接於SGSH酶)提高(例如增加)腦中SGSH之C max。
在一些實施例中，與在缺乏與本文所述之融合蛋白連接之情況下SGSH的吸收相比或與連接於參考蛋白(例如，未對第二Fc多肽進行促成TfR結合之修飾的如本文所述之融合蛋白)之SGSH之吸收相比，腦中SGSH之C max提高(例如增加)至少約1.1倍、1.2倍、1.3倍、1.4倍、1.5倍、1.6倍、1.7倍、1.8倍、1.9倍、2倍、2.2倍、2.4倍、2.6倍、2.8倍、3倍、4倍、5倍、6倍或更多。
本文所述之融合蛋白以治療有效量或劑量投與個體。
在多個實施例中，本文所述之融合蛋白亦可非經腸投與。在一些實施例中，蛋白質經靜脈內投與。
在一些非經腸實施例中，如本文所述之融合蛋白經腹膜內、皮下、皮內或肌肉內投與。在一些實施例中，如本文所述之融合蛋白經皮內或肌肉內投與。在一些實施例中，如本文所述之融合蛋白經鞘內投與，諸如藉由硬膜外投與，或經腦室內投與。
在其他實施例中，如本文所述之融合蛋白可經口投與，藉由肺部投與，鼻內投與，眼內投與，或藉由局部投與。亦可採用肺部投與，例如藉由使用吸入器或霧化器，以及與霧化劑一起調配。 醫藥組合物及套組
在其他態樣中，提供包含本文所述之融合蛋白之醫藥組合物及套組。 醫藥組合物
關於製備用於本揭示案中之調配物的指導可見於所屬領域之技術人員已知之許多醫藥製備與調配手冊中。
在一些實施例中，醫藥組合物包含如本文所述之融合蛋白且進一步包含一或多種醫藥學上可接受之載劑及/或賦形劑。醫藥學上可接受之載劑包括生理學上相容且不干擾或以其他方式抑制活性劑活性之任何溶劑、分散介質或包衣。
本文所述之醫藥組合物之劑量及期望藥物濃度可視所設想之具體用途而變化。本文描述示例性劑量。 套組
在一些實施例中，提供一種用於治療聖菲利浦症候群A之套組，其包含如本文所述之融合蛋白。
在一些實施例中，套組進一步包含一或多種額外治療劑。舉例而言，在一些實施例中，套組包含如本文所述之融合蛋白且進一步包含一或多種用於治療聖菲利浦症候群A之神經症狀的額外治療劑。在一些實施例中，套組進一步包含含有關於實行本文所述之方法之指導(亦即方案)的說明材料(例如使用套組投與包含跨過血腦障壁之SGSH酶之融合蛋白的說明書)。雖然說明材料通常包含書面或打印材料，但其不侷限於此。本揭示案涵蓋能夠儲存此類說明書及將其傳遞至最終使用者之任何媒體。此類媒體包括(但不限於)電子儲存媒體(例如磁碟、磁帶、盒式磁盤、晶片)、光學媒體(例如CD-ROM)及其類似物。此類媒體可包括提供此類說明材料之網際網路網站之地址。 某些定義
如本文所用，除非內容另外清楚規定，否則單數形式「一種(a/an)」及「該」包括複數個指示物。因此，舉例而言，提及「多肽」可包括兩種或更多種此類分子及其類似物。
如本文所用，術語「約」及「大約」在用於修飾以數值或範圍指定之量時，指示數值以及所屬領域之技術人員已知之與該數值之合理偏差，例如±20%、±10%或±5%，在所列舉數值之所欲含義內。
如本文中可互換使用之術語「個體(subject)」、「個體(individual)」及「患者」是指哺乳動物，包括但不限於人類、非人類靈長類動物、囓齒動物(例如大鼠、小鼠及豚鼠)、兔、母牛、馬及其他哺乳動物物種。在一個實施例中，患者為人類。在一些實施例中，人類為需要治療聖菲利浦症候群A之患者。在一些實施例中，患者具有聖菲利浦症候群A之一或多種徵象或症狀。
術語「醫藥學上可接受之賦形劑」係指生物學上或藥理學上適合用於人類或動物之非活性醫藥成分，諸如(但不限於)緩衝劑、載劑或防腐劑。
術語「投與」係指遞送藥劑(例如聖菲利浦症候群A治療劑，諸如本文所述之ETV:SGSH療法)、化合物或組合物(例如醫藥組合物)至期望之生物作用部位的方法。此等方法包括(但不限於)口服、局部遞送、非經腸遞送、靜脈內遞送、皮內遞送、肌肉內遞送、鞘內遞送或腹膜內遞送。在一個實施例中，本文所述之多肽經靜脈內投與。
如本文所用，「治療(treatment)」(及其語法變體，諸如「治療(treat或treating)」)係指改變所治療之個體之天然病程的臨床介入，且可為預防臨床病理而進行或在臨床病理之過程中進行。所需治療作用包括(但不限於)預防疾病發生或復發、緩和症狀、減少疾病之任何直接或間接病理性結果、降低疾病進展速率、改善或緩解疾病病況及症狀緩解或改善預後。
短語「有效量」意謂本文所述之化合物實現以下之量：(i)治療或預防本文所述之具體疾病、疾患或病症，(ii)減弱、改善或消除具體疾病、疾患或病症之一或多種症狀，或(iii)預防或延遲具體疾病、疾患或病症之一種或多種症狀的發作。
本文揭示之物質/分子之「治療有效量」可根據諸如個體之疾病病況、年齡、性別及體重以及物質/分子在個體中引起所需反應之能力的因素而變化。治療有效量涵蓋使物質/分子之治療有益作用勝過任何有毒或不利影響之量。「預防有效量」係指在必需劑量及時段下有效實現所需預防結果之量。通常但不一定，因為預防劑量在發病前或在疾病早期用於個體，所以預防有效量將小於治療有效量。
如本文所用，「磺基葡萄糖胺磺基水解酶」、「N-磺基葡萄糖胺磺基水解酶」或「SGSH」係指N-磺基葡萄糖胺磺基水解酶(EC 3.10.1.1)，其為與硫酸乙醯肝素之溶酶體降解相關之酶。此基因之突變引起聖菲利浦症候群A，一種類型溶酶體貯積症，III型黏多糖貯積症，係由硫酸乙醯肝素之降解削弱引起。如本文所用，術語「SGSH」作為包含Fc多肽之蛋白質之組分，具有催化活性，且涵蓋野生型SGSH或其片段之功能變異體，包括對偶基因及剪接變異體。人類SGSH之序列在UniProt登錄號P51688下可獲得，且由17q25.3之人類SGSH基因編碼。全長序列提供為SEQ ID NO:58。如本文所用，「成熟」SGSH序列係指缺乏天然存在之全長多肽鏈之信號序列的一種形式多肽鏈。成熟人類SGSH多肽之胺基酸序列提供為SEQ ID NO:59，其與全長人類序列之胺基酸21-502對應。如本文所用，「截短」SGSH序列係指天然存在之全長多肽鏈之催化活性片段。已充分表徵人類SGSH之結構。一種例示性結構在PDB寄存碼4MHX下可獲得。亦已描述非人類靈長類動物SGSH序列，包括黑猩猩(UniProt登錄號K7C218)。小鼠SGSH序列在Uniprot登錄號Q9EQ08下可獲得。例如當在相同條件下分析時，SGSH變異體具有相應野生型SGSH或其片段之活性的至少50%、至少55%、至少60%、至少65%、至少70%、至少75%、至少80%、至少85%、至少90%或至少95%。例如當在相同條件下分析時，催化活性SGSH片段具有相應全長SGSH或其變異體之活性的至少50%、至少55%、至少60%、至少65%、至少70%、至少75%、至少80%、至少85%、至少90%或至少95%。
如本文所用，「運鐵蛋白受體」或「TfR」係指運鐵蛋白受體蛋白1。人類運鐵蛋白受體1多肽序列闡述於SEQ ID NO:10中。亦已知來自其他物種之運鐵蛋白受體蛋白1序列(例如黑猩猩，寄存號XP_003310238.1；恆河猴，NP_001244232.1；犬，NP_001003111.1；牛，NP_001193506.1；小鼠，NP_035768.1；大鼠，NP_073203.1；及雞，NP_990587.1)。術語「運鐵蛋白受體」亦涵蓋由運鐵蛋白受體蛋白1染色體基因座之基因編碼的示例性參考序列，例如人類序列之對偶基因變異體。全長運鐵蛋白受體蛋白包括短N端細胞內區、跨膜區及大胞外結構域。胞外結構域藉由三個結構域表徵：蛋白酶樣結構域、螺旋狀結構域及頂端結構域。人類運鐵蛋白受體1之頂端結構域序列闡述於SEQ ID NO:11中。
如本文所用，「融合蛋白」或「[SGSH酶]-Fc融合蛋白」係指一種二聚蛋白質，其包含第一Fc多肽，該第一Fc多肽與SGSH酶、SGSH酶變異體或其催化活性片段連接(例如融合)(亦即「[SGSH]-Fc融合多肽」)；及第二Fc多肽，該第二Fc多肽與第一Fc多肽形成Fc二聚體。第二Fc多肽亦可與SGSH酶、SGSH酶變異體或其催化活性片段連接(例如融合)。第一Fc多肽及/或第二Fc多肽可藉由肽鍵或藉由多肽連接子連接於SGSH酶、SGSH酶變異體或其催化活性片段。第一Fc多肽及/或第二Fc多肽可為經修飾之Fc多肽，其含有一或多個促進其與另一Fc多肽之異二聚合的修飾。第一Fc多肽及/或第二Fc多肽可為經修飾之Fc多肽，其含有一或多個賦予與運鐵蛋白受體之結合能力的修飾。第一Fc多肽及/或第二Fc多肽可為經修飾之Fc多肽，其含有一或多個降低效應功能之修飾。在某些實施例中，第一Fc多肽及第二Fc多肽不具有效應功能。第一Fc多肽及/或第二Fc多肽可為經修飾之Fc多肽，其含有一或多個延長血清半衰期之修飾。在某些實施例中，第一Fc多肽及/或第二Fc多肽不包括免疫球蛋白重鏈及/或輕鏈可變區序列或其抗原結合部分。在某些實施例中，第一Fc多肽及第二Fc多肽不包括免疫球蛋白重鏈及/或輕鏈可變區序列或其抗原結合部分。
如本文所用，「融合多肽」或「[SGSH酶]-Fc融合多肽」係指與SGSH酶、SGSH酶變異體或其催化活性片段連接(例如融合)之Fc多肽。Fc多肽可藉由肽鍵或藉由多肽連接子連接於SGSH酶、SGSH酶變異體或其催化活性片段。Fc多肽可為經修飾之Fc多肽，其含有一或多個促進其與另一Fc多肽之異二聚合的修飾。Fc多肽可為經修飾之Fc多肽，其含有一或多個賦予與運鐵蛋白受體之結合能力的修飾。Fc多肽可為經修飾之Fc多肽，其含有一或多個降低效應功能之修飾。Fc多肽可為經修飾之Fc多肽，其含有一或多個延長血清半衰期之修飾。
如本文所用，術語「Fc多肽」係指天然存在之免疫球蛋白重鏈多肽之C端區，其特徵在於Ig摺疊作為結構域。Fc多肽含有至少包括CH2結構域及/或CH3結構域之恆定區序列且可含有鉸鏈區之至少一部分。一般而言，Fc多肽不含可變區。
「經修飾之Fc多肽」係指與野生型免疫球蛋白重鏈Fc多肽序列相比，具有至少一個突變，例如取代、缺失或插入，但保持天然Fc多肽之總體Ig摺疊或結構的Fc多肽。
術語「FcRn」係指新生兒Fc受體。Fc多肽與FcRn之結合降低Fc多肽之清除率且增加其血清半衰期。人類FcRn蛋白為一種異二聚體，其由類似於主要組織相容性(MHC) I類蛋白之尺寸約50 kDa之蛋白質及尺寸約15 kDa之β2-微球蛋白構成。
如本文所用，「FcRn結合位點」係指結合於FcRn之Fc多肽之區域。在人類IgG中，如使用EU索引編號之FcRn結合位點包括T250、L251、M252、I253、S254、R255、T256、T307、E380、M428、H433、N434、H435及Y436。此等位置對應於SEQ ID NO:1之位置20至26、77、150、198及203至206。
如本文所用，「天然FcRn結合位點」係指結合於FcRn且具有與結合於FcRn之天然存在之Fc多肽之區域相同的胺基酸序列的Fc多肽之區域。
如本文所用，術語「CH3結構域」及「CH2結構域」係指免疫球蛋白恆定區結構域多肽。出於本申請案之目的，CH3結構域多肽係指如根據EU編號自約位置341至約位置447之胺基酸區段，且CH2結構域多肽係指如根據EU編號方案編號自約位置231至約位置340之胺基酸區段且不包括鉸鏈區序列。CH2及CH3結構域多肽亦可藉由IMGT (ImMunoGeneTics)編號方案編號，其中根據IMGT Scientific chart編號(IMGT網址)，CH2結構域編號為1-110且CH3結構域編號為1-107。CH2及CH3結構域為免疫球蛋白之Fc區的一部分。Fc區係指如根據EU編號方案編號自約位置231至約位置447之胺基酸區段，但如本文所用，可包括抗體鉸鏈區之至少一部分。例示性鉸鏈區序列為人類IgG1鉸鏈序列EPKSCDKTHTCPPCP (SEQ ID NO:5)。
「天然存在」、「天然」或「野生型」用於描述可發現性質不同於人工所產生之物體的物體。例如，存在於生物體(包括病毒)中的可自天然來源分離且未經實驗室有意修飾的核苷酸序列係天然存在的。此外，「野生型」係指在自然界中發現且無任何已知之突變的正常基因或生物體。
例如，關於CH3或CH2結構域之術語「野生型」、「天然」及「天然存在」在本文中用以指具有在自然界中存在之序列的結構域。
如本文所用，關於突變多肽或突變多核苷酸之術語「突變體」與「變異」可互換使用。關於給定之野生型CH3或CH2結構域參考序列的變異體可包括天然存在之對偶基因變異體。「非天然」存在之CH3或CH2結構域係指在自然界中不存在於細胞中且藉由例如使用基因工程改造技術或誘變技術對天然CH3結構域或CH2結構域多核苷酸或多肽進行遺傳修飾所產生的變異或突變結構域。「變異」包括相對於野生型包含至少一個胺基酸突變之任何結構域。突變可包括取代、插入及缺失。
術語「胺基酸」係指天然存在及合成之胺基酸，以及以類似於天然存在之胺基酸的方式起作用之胺基酸類似物及胺基酸模擬物。
天然存在之胺基酸為由遺傳密碼編碼之胺基酸，以及隨後經修飾之彼等胺基酸，例如羥基脯胺酸、γ-羧基麩胺酸及O-磷酸絲胺酸。「胺基酸類似物」係指具有與天然存在之胺基酸相同之基礎化學結構，亦即α碳結合於氫、羧基、胺基及R基團的化合物，例如高絲胺酸、正白胺酸、甲硫胺酸亞碸、甲硫胺酸甲基鋶。此類類似物具有經修飾之R基團(例如正白胺酸)或經修飾之肽主鏈，但保持與天然存在之胺基酸相同的基礎化學結構。「胺基酸模擬物」係指具有與胺基酸之通用化學結構不同之結構，但以類似於天然存在之胺基酸的方式起作用的化合物。
天然存在之α-胺基酸包括不限於丙胺酸(Ala)、半胱胺酸(Cys)、天冬胺酸(Asp)、麩胺酸(Glu)、苯丙胺酸(Phe)、甘胺酸(Gly)、組胺酸(His)、異白胺酸(Ile)、精胺酸(Arg)、離胺酸(Lys)、白胺酸(Leu)、甲硫胺酸(Met)、天冬醯胺酸(Asn)、脯胺酸(Pro)、麩醯胺酸(Gln)、絲胺酸(Ser)、蘇胺酸(Thr)、纈胺酸(Val)、色胺酸(Trp)、酪胺酸(Tyr)及其組合。天然存在之α-胺基酸之立體異構體包括不限於D-丙胺酸(D-Ala)、D-半胱胺酸(D-Cys)、D-天冬胺酸(D-Asp)、D-麩胺酸(D-Glu)、D-苯丙胺酸(D-Phe)、D-組胺酸(D-His)、D-異白胺酸(D-Ile)、D-精胺酸(D-Arg)、D-離胺酸(D-Lys)、D-白胺酸(D-Leu)、D-甲硫胺酸(D-Met)、D-天冬醯胺酸(D-Asn)、D-脯胺酸(D-Pro)、D-麩醯胺酸(D-Gln)、D-絲胺酸(D-Ser)、D-蘇胺酸(D-Thr)、D-纈胺酸(D-Val)、D-色胺酸(D-Trp)、D-酪胺酸(D-Tyr)及其組合。
在本文中胺基酸可藉由其通常已知之三字母符號提及，或藉由IUPAC-IUB生物化學命名委員會推薦之單字母符號提及。
在本文中術語「多肽」及「肽」可互換使用以指呈單鏈之胺基酸殘基之聚合物。該等術語適用於一或多個胺基酸殘基為相應天然存在之胺基酸之人工化學模擬物的胺基酸聚合物，以及天然存在之胺基酸聚合物及非天然存在之胺基酸聚合物。胺基酸聚合物可包含完全L-胺基酸、完全D-胺基酸或L-胺基酸與D-胺基酸之混合物。
如本文所用，術語「蛋白質」係指多肽，或單鏈多肽之二聚體(亦即，兩種)或多聚體(亦即三種或更多種)。蛋白質之單鏈多肽可藉由共價鍵，例如二硫鍵，或非共價相互作用接合。
術語「保守取代」、「保守突變」或「經保守修飾之變異體」係指引起胺基酸經可分類為具有類似特徵之另一胺基酸取代的改變。以此方式定義之保守胺基酸組之類別的實例可包括：「帶電/極性組」，包括Glu (麩胺酸或E)、Asp (天冬胺酸或D)、Asn (天冬醯胺酸或N)、Gln (麩醯胺酸或Q)、Lys (離胺酸或K)、Arg (精胺酸或R)及His (組胺酸或H)；「芳族組」，包括Phe (苯丙胺酸或F)、Tyr (酪胺酸或Y)、Trp (色胺酸或W)及(組胺酸或H)；及「脂族組」，包括Gly (甘胺酸或G)、Ala (丙胺酸或A)、Val (纈胺酸或V)、Leu (白胺酸或L)、Ile (異白胺酸或I)、Met (甲硫胺酸或M)、Ser (絲胺酸或S)、Thr (蘇胺酸或T)及Cys (半胱胺酸或C)。在各組內，亦可鑑定子組。例如，帶電或極性胺基酸組可再分成子組，包括：「帶正電荷之子組」，包含Lys、Arg及His；「帶負電荷之子組」，包含Glu及Asp；及「極性子組」，包含Asn及Gln。在另一個實例中，芳族或環狀組可再分成子組，包括：「氮環子組」，包含Pro、His及Trp；及「苯基子組」，包含Phe及Tyr。在另一進一步實例中，脂族組可再分成子組，例如「脂族非極性子組」，包含Val、Leu、Gly及Ala；及「脂族微極性子組」，包含Met、Ser、Thr及Cys。保守突變之類別之實例包括以上子組內之胺基酸的胺基酸取代，諸如但不限於：Lys取代Arg或反之亦然，以便可維持正電荷；Glu取代Asp或反之亦然，以便可維持負電荷；Ser取代Thr或反之亦然，以便可維持游離-OH；及Gln取代Asn或反之亦然，以便可維持游離-NH 2。在一些實施例中，疏水性胺基酸取代例如活性位點中之天然存在之疏水性胺基酸，以維持疏水性。
在兩種或更多種多肽序列之情況下，術語「一致」或「一致性」百分比係指當在比較窗或指定區域上為求最大對應進行比較及比對時，如使用序列比較演算法或藉由手動比對及目測檢查所量測，相同或在指定區域上具有指定百分比，例如至少60%一致性、至少65%、至少70%、至少75%、至少80%、至少85%、至少90%或至少95%或更大百分比之胺基酸殘基一致的兩種或更多種序列或子序列。在一些實施例中，相對於參考序列具有指定一致性百分比之序列與參考序列的不同之處在於一或多個保守取代。
為進行多肽序列比較，通常一個胺基酸序列用作候選序列進行比較之參考序列。可使用所屬領域之技術人員可利用之各種方法進行，例如目視比對或使用公眾可獲得之軟體使用已知演算法實現最大比對。此類程式包括BLAST程式、ALIGN、ALIGN-2 (Genentech, South San Francisco, Calif.)或Megalign (DNASTAR)。用於進行比對以實現最大比對之參數可由所屬領域之技術人員測定。為出於本申請案之目的對多肽序列進行序列比較，使用用於利用預設參數比對兩種蛋白質序列之BLASTP演算法標準蛋白質BLAST。
當鑑定多肽序列中所給定胺基酸殘基之情況下使用時術語「對應於……」、「參考……確定」或「參考……編號」係指當所給定胺基酸序列最大限度地與參考序列進行比對及比較時指定參考序列之殘基之位置。因此，舉例而言，當殘基與SEQ ID NO:1中之胺基酸比對時，當最佳地與SEQ ID NO:1進行比對時，經修飾之Fc多肽中之胺基酸殘基「對應於」SEQ ID NO:1中之胺基酸。與參考序列進行比對之多肽不需要長度與參考序列相同。
術語「多核苷酸」及「核酸」可互換地指具有任何長度之核苷酸之聚合物，且包括DNA及RNA。核苷酸可為去氧核糖核苷酸、核糖核苷酸、經修飾之核苷酸或鹼基及/或其類似物，或可藉由DNA或RNA聚合酶併入鏈中之任何受質。多核苷酸可包含經修飾之核苷酸，諸如甲基化核苷酸及其類似物。本文中涵蓋之多核苷酸之實例包括單股及雙股DNA、單股及雙股RNA及具有單股及雙股DNA與RNA之混合物的雜合分子。
如本文所用，「結合親和力」係指兩種分子，例如多肽上之單個結合位點與其結合之標靶(例如運鐵蛋白受體)之間的非共價相互作用之強度。因此，舉例而言，除非另外指示或上下文清楚可見，否則該術語可指多肽與其標靶之間的1:1相互作用。結合親和力可藉由量測平衡解離常數(K D)來定量，平衡解離常數係指解離速率常數(k d，時間 -1)除以締合速率常數(k a，時間 -1M -1)。K D可藉由例如使用以下量測複合物形成及解離之動力學來確定：表面電漿子共振(SPR)法，例如Biacore™系統；動力學排除分析，諸如KinExA ®：及BioLayer干涉測量法(例如使用ForteBio ®Octet ®平台)。如本文所用，「結合親和力」不僅包括形式結合親和力，諸如反映多肽與其標靶之間的1:1相互作用之結合親和力，且亦包括計算K D之可反映親合結合之表觀親和力。
如本文所用，當提及如本文所述的經工程改造之結合TfR之多肽、結合TfR之肽或結合TfR之抗體時術語「特異性結合」或「選擇性結合」於標靶，例如TfR係指經工程改造之結合TfR之多肽、結合TfR之肽或結合TfR之抗體以比其結合於結構上不同之標靶更大的親和力、更大的親合力及/或更長的持續時間結合於標靶的結合反應。在典型實施例中，當在相同親和力分析條件下分析時，經工程改造之結合TfR之多肽、結合TfR之肽或結合TfR之抗體對例如TfR之特定標靶的親和力與無關標靶相比大至少5倍、10倍、50倍、100倍、1,000倍、10,000倍或更大。如本文所用，術語「特異性結合」、「特異性結合於」具體標靶(例如TfR)或對具體標靶(例如TfR)「具有特異性」可展現在例如分子對其結合之標靶的平衡解離常數K D為例如10 -4M或更小，例如10 -5M、10 -6M、10 -7M、10 -8M、10 -9M、10 -10M、10 -11M或10 -12M。在一些實施例中，經工程改造之結合TfR之多肽、結合TfR之肽或結合TfR之抗體特異性結合於TfR上在物種當中保守(例如在物種當中在結構上保守)，例如在非人類靈長類動物與人類物種之間保守(在非人類靈長類動物與人類物種之間在結構上保守)之抗原決定基。在一些實施例中，經工程改造之結合TfR之多肽、結合TfR之肽或結合TfR之抗體可僅結合於人類TfR。
術語「可變區」或「可變結構域」係指抗體重鏈或輕鏈中源自於生殖系可變(V)基因、多樣性(D)基因或接合(J)基因(且不源自於恆定(Cμ及Cδ)基因區段)且賦予抗體對結合於抗原之特異性的結構域。通常，抗體可變區包含四個保守「構架」區，中間散佈有三個高變「互補決定區」。
術語「抗原結合部分」及「抗原結合片段」在本文中可互換使用且係指保留經由可變區特異性結合於抗原之能力的抗體之一或多個片段。抗原結合片段之實例包括(但不限於) Fab片段(單價片段，由VL、VH、CL及CH1結構域組成)、F(ab’) 2片段(二價片段，包含兩個由鉸鏈區之二硫鍵連接之Fab片段)、單鏈Fv (scFv)、二硫化物連接之Fv (dsFv)、互補決定區(CDR)、VL (輕鏈可變區)及VH (重鏈可變區)。
以下實例意欲為非限制性的。 實例1： 包含 N- 磺基葡萄糖胺磺基水解酶 (SGSH) 之融合蛋白的構築 設計及選殖
設計含有以下之SGSH-Fc融合蛋白：(i)第一融合多肽，其中成熟人類SGSH酶與包括Fc區之人類IgG1片段融合(「SGSH-Fc融合多肽」)；及(ii)第二融合多肽，其中成熟人類SGSH酶與在Fc區中含有賦予運鐵蛋白受體(TfR)結合能力之突變的經修飾之人類IgG1片段融合(「經修飾之Fc多肽」)。詳言之，產生SGSH-Fc融合多肽，其中SGSH片段與人類IgG1 Fc區之N端融合。在一些情況下，連接子置於SGSH與IgG1片段之間以減輕兩個片段之間的任何位阻。在所有構築體中，信號肽MGWSCIILFLVATATGAYA (SEQ ID NO: 121)插入融合物上游以促進分泌，且對SGSH進行截短以由胺基酸R21-L502組成(UniProtKB ID-P51688)。所用之人類IgG1 Fc區之片段對應於UniProtKB ID P01857中之序列之胺基酸D104-K330 (EU編號之位置221-447，其包括鉸鏈之10個胺基酸(位置221-230))。將含有與經修飾之Fc多肽融合之SGSH的第二融合多肽與SGSH-Fc融合多肽共轉染以產生具有兩個SGSH酶(「雙酶」)之異二聚體融合蛋白。在一些構築體中，IgG1片段含有促進兩個Fc區之異二聚合的額外突變。因此，實例中所用之包含TfR結合之SGSH-Fc融合蛋白為由以下形成之二聚體：i) SGSH-Fc融合多肽；及ii)包含與第二SGSH分子融合之經修飾之Fc多肽的結合於TfR之SGSH-Fc融合多肽(「雙酶」)。
類似地設計且構築缺乏賦予TfR結合能力之突變的對照SGSH-Fc融合蛋白。產生一種示例性對照SGSH-Fc融合蛋白，其包含具有SEQ ID NO:61及63中之任一者之序列的第一SGSH-Fc融合多肽及具有SEQ ID NO: 69及71中之任一者之序列的第二SGSH-Fc融合多肽。在細胞培養物產生期間亦可進一步加工SGSH-Fc融合蛋白，使得第一SGSH-Fc融合多肽具有SEQ ID NO:62或64之序列及/或第二SGSH-Fc融合多肽具有SEQ ID NO:70或72之序列。因此，如本文所用，術語SGSH-Fc融合蛋白可用於指具有未加工之序列(亦即SEQ ID NO:61、63、69及71)的蛋白質分子；包含一或多個經加工序列(亦即選自SEQ ID NO: 62、64、70及72)之蛋白質分子；或包含經加工及未加工蛋白質分子之混合物。
包含與具有臼及LALA突變之IgG1 Fc多肽序列之N端融合的成熟人類SGSH序列的SGSH-Fc融合多肽具有SEQ ID NO:61-64中之任一者之序列。SGSH酶藉由GGGGS連接子(SEQ ID NO:8)接合於Fc多肽，且Fc多肽之N端包括IgG1鉸鏈區之一部分(DKTHTCPPCP；SEQ ID NO:6)。
包含與具有臼及LALA突變之IgG1 Fc多肽序列之N端融合的成熟人類SGSH序列的SGSH-Fc融合多肽具有SEQ ID NO:73-76中之任一者之序列。SGSH酶藉由GS連接子(SEQ ID NO:7)接合於Fc多肽，且Fc多肽之N端包括IgG1鉸鏈區之一部分(DKTHTCPPCP；SEQ ID NO:6)。
包含與具有臼及LALA突變之IgG1 Fc多肽序列之N端融合的成熟人類SGSH序列的SGSH-Fc融合多肽具有SEQ ID NO:81-84中之任一者之序列。SGSH酶藉由(GGGGSGGGGS)連接子(SEQ ID NO:9)接合於Fc多肽，且Fc多肽之N端包括IgG1鉸鏈區之一部分(DKTHTCPPCP；SEQ ID NO:6)。
包含與具有臼及LALAPS突變之IgG1 Fc多肽序列之N端融合的成熟人類SGSH序列的SGSH-Fc融合多肽具有SEQ ID NO:65-68中之任一者之序列。SGSH酶藉由GGGGS連接子(SEQ ID NO:8)接合於Fc多肽，且Fc多肽之N端包括IgG1鉸鏈區之一部分(DKTHTCPPCP；SEQ ID NO:6)。
包含與具有臼及LALA突變之IgG1 Fc多肽序列之 C端融合的成熟人類SGSH序列的 Fc-SGSH融合多肽具有SEQ ID NO:117-118中之任一者之序列。SGSH酶藉由GGGGS連接子(SEQ ID NO:8)接合於Fc多肽，且Fc多肽之N端包括IgG1鉸鏈區之一部分(DKTHTCPPCP；SEQ ID NO:6)。
包含與具有杵及LALA突變的結合TfR之經修飾之Fc多肽之序列的N端融合的成熟人類SGSH序列的結合TfR之SGSH-Fc融合多肽具有SEQ ID NO:89-92中之任一者之序列。SGSH酶藉由GGGGS連接子(SEQ ID NO:8)接合於經修飾之Fc多肽，且經修飾之Fc多肽之N端包括IgG1鉸鏈區之一部分(DKTHTCPPCP；SEQ ID NO:6)。
包含與具有杵及LALA突變的結合TfR之經修飾之Fc多肽之序列的N端融合的成熟人類SGSH序列的結合TfR之SGSH-Fc融合多肽具有SEQ ID NO:101-104中之任一者之序列。SGSH酶藉由GS連接子(SEQ ID NO:7)接合於經修飾之Fc多肽，且經修飾之Fc多肽之N端包括IgG1鉸鏈區之一部分(DKTHTCPPCP；SEQ ID NO:6)。
包含與具有杵及LALA突變的結合TfR之經修飾之Fc多肽之序列的N端融合的成熟人類SGSH序列的結合TfR之SGSH-Fc融合多肽具有SEQ ID NO:109-112中之任一者之序列。SGSH酶藉由GGGGSGGGGS連接子(SEQ ID NO:9)接合於經修飾之Fc多肽，且經修飾之Fc多肽之N端包括IgG1鉸鏈區之一部分(DKTHTCPPCP；SEQ ID NO:6)。
包含與具有杵及LALAPS突變的結合TfR之經修飾之Fc多肽之序列的N端融合的成熟人類SGSH序列的結合TfR之SGSH-Fc融合多肽具有SEQ ID NO:93-96中之任一者之序列。SGSH酶藉由GGGGS連接子(SEQ ID NO:8)接合於經修飾之Fc多肽，且經修飾之Fc多肽之N端包括IgG1鉸鏈區之一部分(DKTHTCPPCP；SEQ ID NO:6)。
包含與具有杵及LALA突變的結合TfR之經修飾之Fc多肽之序列的C端融合的成熟人類SGSH序列的結合TfR之SGSH-Fc融合多肽具有SEQ ID NO:119-120中之任一者之序列。SGSH酶藉由GGGGS連接子(SEQ ID NO:8)接合於經修飾之Fc多肽，且經修飾之Fc多肽之N端包括IgG1鉸鏈區之一部分(DKTHTCPPCP；SEQ ID NO:6)。
產生第一「N端雙酶」SGSH-Fc融合多肽(「ETV:SGSH雙酶結構1」)，其包含具有SEQ ID NO:61及63中之任一者之序列的第一SGSH-Fc融合多肽，及具有SEQ ID NO: 89及91中之任一者之序列的結合TfR之第二SGSH-Fc融合多肽。在細胞培養物產生期間亦可進一步加工SGSH-Fc融合蛋白，使得第一SGSH-Fc融合多肽具有SEQ ID NO:62或64之序列及/或結合TfR之第二SGSH-Fc融合多肽具有SEQ ID NO:90或92之序列。因此，如本文所用，術語ETV:SGSH雙酶結構1可用於指具有未加工之序列(亦即SEQ ID NO:61、63、89及91)的蛋白質分子；包含一或多個經加工序列(亦即選自SEQ ID NO: 62、64、90及92)之蛋白質分子；或包含經加工及未加工蛋白質分子之混合物。
產生第二「N端雙酶」SGSH-Fc融合多肽(「ETV:SGSH雙酶結構2」)，其包含具有SEQ ID NO:73及75中之任一者之序列的第一SGSH-Fc融合多肽，及具有SEQ ID NO:101及103中之任一者之序列的結合TfR之第二SGSH-Fc融合多肽。在細胞培養物產生期間亦可進一步加工SGSH-Fc融合蛋白，使得第一SGSH-Fc融合多肽具有SEQ ID NO:74或76之序列及/或結合TfR之第二SGSH-Fc融合多肽具有SEQ ID NO:102或104之序列。因此，如本文所用，術語ETV:SGSH雙酶結構2可用於指具有未加工之序列(亦即SEQ ID NO:73、75、101及103)的蛋白質分子；包含一或多個經加工序列(亦即選自SEQ ID NO: 74、76、102及104)之蛋白質分子；或包含經加工及未加工蛋白質分子之混合物。
產生第三「N端雙酶」SGSH-Fc融合多肽(「ETV:SGSH雙酶結構3」)，其包含具有SEQ ID NO:81及83中之任一者之序列的第一SGSH-Fc融合多肽，及具有SEQ ID NO:109及111中之任一者之序列的結合TfR之第二SGSH-Fc融合多肽。在細胞培養物產生期間亦可進一步加工SGSH-Fc融合蛋白，使得第一SGSH-Fc融合多肽具有SEQ ID NO:82或84之序列及/或結合TfR之第二SGSH-Fc融合多肽具有SEQ ID NO:110或112之序列。因此，如本文所用，術語ETV:SGSH雙酶結構3可用於指具有未加工之序列(亦即SEQ ID NO:81、83、109及111)的蛋白質分子；包含一或多個經加工序列(亦即選自SEQ ID NO: 82、84、110及112)之蛋白質分子；或包含經加工及未加工蛋白質分子之混合物。
產生第四「N端雙酶」SGSH-Fc融合多肽(「ETV:SGSH雙酶結構4」)，其包含具有SEQ ID NO:65及67中之任一者之序列的第一SGSH-Fc融合多肽，及具有SEQ ID NO:93及95中之任一者之序列的結合TfR之第二SGSH-Fc融合多肽。在細胞培養物產生期間亦可進一步加工SGSH-Fc融合蛋白，使得第一SGSH-Fc融合多肽具有SEQ ID NO:66或68之序列及/或結合TfR之第二SGSH-Fc融合多肽具有SEQ ID NO:94或96之序列。因此，如本文所用，術語ETV:SGSH雙酶結構4可用於指具有未加工之序列(亦即SEQ ID NO:65、67、93及95)的蛋白質分子；包含一或多個經加工序列(亦即選自SEQ ID NO: 66、68、94及96)之蛋白質分子；或包含經加工及未加工蛋白質分子之混合物。
產生「C端雙酶」SGSH-Fc融合多肽(「ETV:SGSH雙酶結構5」)，其包含具有SEQ ID NO:117及118中之任一者之序列的第一SGSH-Fc融合多肽，及具有SEQ ID NO:119及120中之任一者之序列的結合TfR之第二經修飾之SGSH-Fc多肽。因此，如本文所用，術語ETV:SGSH雙酶結構5可用於指包含SEQ ID NO:117及119之蛋白質分子；包含SEQ ID NO: 118及120之蛋白質分子；或包含SEQ ID NO:117及/或118與SEQ ID NO:119及/或120組合之混合物。
包含ETV:SGSH (例如上述結構)之組合物可用於指包含以下之組合物：具有未加工之序列之蛋白質分子；包含一或多個經加工序列之蛋白質分子；或包含未加工與經加工蛋白質分子之混合物。 重組蛋白表現及純化
為表現與Fc區融合之重組SGSH酶，使用Expifectamine™ CHO轉染套組，根據製造商說明書(Thermo Fisher Scientific)，將ExpiCHO細胞(Thermo Fisher Scientific)用相關DNA構築體轉染。在迴轉式震盪器(Infors HT Multitron)中，細胞在補充有如製造商之方案所描述之饋料的ExpiCHO™表現培養基中在37℃、5% CO 2及125 rpm下生長。簡言之，將對數生長之ExpiCHO™細胞以6×10 6個細胞/毫升之密度用每毫升培養物體積0.8 μg總DNA質體進行轉染。將表現SGSH融合物之培養物與表現輔因子SUMF1之質體以5:1之質體比率(SGSH:SUMF1)共轉染。所編碼之SUMF1序列描述於Genbank NM_182760中。在轉染之後，使細胞恢復至37℃且在轉染後18-22小時，經轉染之培養物補充如所指示之饋料。在轉染後120小時，通過在3,500 rpm下離心20分鐘，收穫所轉染之細胞培養物上清液。過濾(0.22 μM膜)澄清上清液且儲存在4℃下。
使用蛋白A親和層析法自細胞培養物上清液純化具有(或不具有)賦予TfR結合能力之經工程改造之Fc區的SGSH-Fc融合蛋白。將上清液負載至HiTrap MabSelect SuRe蛋白A親和管柱(GE Healthcare Life Sciences，使用Akta Pure系統)上。接著用10管柱體積(CV) PBS洗滌管柱。使用含有150 mM NaCl之50 mM檸檬酸鹽/NaOH緩衝液pH 3.6溶析結合之蛋白。在溶析之後立即使用1 M Tris pH8 (以1:7稀釋)中和溶析份。藉由多種技術，包括還原及非還原SDS-PAGE及HPLC-SEC評定溶析份中SGSH-Fc融合物之均質性。 實例2： SGSH 融合蛋白之表徵 融合蛋白之甲醯甘胺酸及 M6P 含量
為表徵影響SGSH之酶活性及融合蛋白之運輸的SGSH-Fc融合蛋白之某些特性，評估SGSH-Fc融合蛋白之甲醯甘胺酸(fGly)含量及甘露糖-6-磷酸(M6P)含量。如實例1中所述之ETV:SGSH N端雙酶(雙酶結構1)及對照SGSH-Fc融合蛋白(缺乏TfR結合)用於該分析。
fGly 含量之量測 .藉由LC-MS/MS同時評定含Cys及FGly之肽的身分及量。簡言之，用Tris(2-羧乙基)瞵鹽酸鹽(TCEP·HCl)還原約20 μg SGSH融合蛋白且用碘乙醯胺烷基化，接著用胰蛋白酶以蛋白水解方式消化(70℃下2小時)。藉由LC-MS/MS分析甲酸淬火反應。藉由UHPLC Vanquish (Thermo Scientific, CA, USA)上液相層析法聯合UV/Vis及Q Exactive Orbitrap電噴霧電離質譜儀(Thermo Scientific, CA, USA)，進行肽定量分析。對於分析，將樣品注射在CSH C18管柱(Waters公司, Milford, Massachusetts, USA)上於40℃下，其中具有0.1%甲酸之水為移動相。接著樣品分別經受自含有1% B至70% B的具有0.1%甲酸之水(A)及具有0.1%甲酸之乙腈(B)的線性45分鐘梯度。質譜儀在全掃描下以正離子模式操作。Thermo Scientific Freestyle軟體用於整合峰面積或所謂的曲線下面積(AUC)。整合如下在位置70 (CXPXR基元(SEQ ID NO:126))處含有SGSH半胱胺酸之三種主要胰蛋白酶肽：(1)游離Cys，NAFTSVSSCSPSR (SEQ ID NO:127) (2+，m/z 671.806)；(2)烷基化脲基甲基Cys：NAFTSVSSC(CAM)SPSR (SEQ ID NO:128) (2+，m/z 700.317)及(3) FGly肽：NAFTSVSS (Fgly) SPSR (SEQ ID NO:129) (2+，m/z 663.810)。計算之FGly %係基於三種FGly肽之AUC除以FGly與游離及烷基化Cys肽之AUC和且乘以100。發現SGSH-Fc及ETV:SGSH之fGly含量彼此類似(圖2)。
甘露糖 -6- 磷酸 ( M6P ) 含量之量測 .藉由液相層析-質譜分析量測SGSH-Fc融合蛋白中之M6P含量。重組純化蛋白(20 μg)經緩衝液交換成50 mM乙酸銨pH 7.0。取五(5) μg蛋白質且外加穩定同位素標記(SIL)之 13C 6甘露糖-6-磷酸(M6P-IS，Omicronbio公司，目錄號MAN-05，每個樣品125 ng)作為內標。向蛋白質樣品添加120 μL 6.6M三氟乙酸溶液且在震盪的同時在95℃下使用加熱塊水解105分鐘。接著用乙腈(ACN)洗滌藉由氮氣流乾燥之樣品且再次乾燥。藉由LC-MS/MS分析再懸浮於50 μL ACN:水(20:80，v:v)中之最終糰粒。藉由UHPLC Vanquish (Thermo Scientific, CA, USA)上液相層析法聯合UV/Vis及Q Exactive Orbitrap電噴霧電離質譜儀(Thermo Scientific, CA, USA)，進行M6P分析。將樣品注射在1.9 μm 2.1×150 mm之BEH Amide管柱(Waters)上，在60℃下在負離子電離模式下於具有0.1%甲酸之水之移動相中，且用具有0.1%甲酸之乙腈之梯度溶析。使用平行反應監視(PRM)採集，在負離子模式下收集資料，包括M6P及M6P內標(IS)，包括時間1.6至2.2分鐘，前驅物為259.0224 (M6P)及265.0426 (M6P-IS)。M6P/M6P-IS之AUC比率用於計算自蛋白質釋放之M6P之分子量且獲得每莫耳蛋白質之M6P莫耳數。表1中提供SGSH-Fc及ETV:SGSH之M6P含量。 表 1.融合蛋白之甘露糖-6-磷酸含量
分子 M6P (Mol/Mol)
ETV:SGSH 1.4
SGSH-Fc 1.2
具有經工程改造之 TfR 結合位點之 SGSH-Fc 融合蛋白結合於人類 TfR
為確定具有經工程改造之TfR結合的SGSH-Fc融合蛋白是否影響經修飾之Fc結構域與人類TfR相互作用之能力，使用Biacore ™表面電漿子共振分析評定ETV:SGSH雙酶結構1 (實例1)對人類TfR之親和力。用抗人類Fab (來自GE Healthcare之人類Fab捕獲套組)固定Biacore ™系列S CM5感測器晶片。在各流動池上捕獲5 μg/mL SGSH-Fc融合蛋白1分鐘且將連續3倍稀釋之人類頂端結構域TfR以30 μL/min之流速注射。利用3分鐘締合及3分鐘解離來分析各樣品。在每次注射之後，使用10 mM甘胺酸-HCl (pH 2.1)使晶片再生。藉由自捕獲類似密度之不相關IgG的流動池減去RU來校正結合反應。藉由使用Biacore ™T200評估軟體3.1版針對濃度擬合平衡下之反應來獲得穩態親和力。Biacore ™分析確定，具有工程改造至Fc區中之TfR結合位點之SGSH-Fc融合蛋白結合於人類TfR。詳言之，測得ETV:SGSH雙酶結構1對人類TfR之結合親和力為約230 nM。 具有經工程改造之 TfR 結合位點的 SGSH-Fc 融合蛋白在活體外及細胞中具有活性
評定經工程改造之結合TfR之SGSH-Fc融合蛋白的活體外及細胞活性以證明SGSH在與人類IgG片段融合時維持其酶活性。使用兩步螢光酶分析，使用人工受質量測重組SGSH之活體外活性。具體而言，將在分析緩衝液(0.03 M乙酸鈉、0.12 M NaCl，pH 6.5)中稀釋之20 mL 1 mM 4-甲基傘形酮基2-去氧-2-磺胺基-a-D-吡喃葡萄糖苷鈉鹽受質(Carbosynth Limited，#EM06602)與10-20 μL 140 nM SGSH混合。將第一反應在37℃培育17小時，且接著用10 μL 0.2 M磷酸鹽-檸檬酸鹽緩衝液pH 6.7終止。然後，藉由添加10 μL (0.5 U)酵母α-葡糖苷酶(Sigma，#G0660-750UN)起始第二反應，在37℃下培育24小時，且藉由添加100 μL 0.5 M碳酸鈉緩衝液pH 10.3而停止。接著量測反應溶液之螢光(在365 nm下激發及在450 nm下發射)。藉由線性回歸擬合4-甲基傘形酮標準曲線以計算產物之量且證實總受質少於10%裂解。藉由產物之量除以反應時間及SGSH莫耳量計算比活性(fmol產物/min/pmol SGSH)。
活體外酶活性分析證明，SGSH-Fc融合蛋白具有活性且在Fc-SGSH (對照；實例1)與ETV:SGSH (雙酶結構1；實例1)之間相似(圖3)。
亦在來自MPS IIIA患者及健康對照之纖維母細胞中，使用 35S脈衝追蹤分析，檢驗SGSH-Fc融合蛋白之細胞活性，在該分析中 35S整合至新合成之GAG中，如前所述(Boado et al., Mol. Pharm. 11(8): 2928-2934 [2014])。MPS IIIA患者纖維母細胞缺乏SGSH活性，引起 35S信號之積聚增加。包括ETV:SGSH (雙酶結構1)之SGSH-Fc融合蛋白在MPS IIIA患者來源之細胞中高度有效，其顯示減少S 35標記物質之積聚的低皮莫耳細胞EC 50(圖4)。 經工程改造之 TfR 結合位點的 SGSH-Fc 融合蛋白在 MPSIII 小鼠模型中展示改善之腦遞送
為確定結合TfR之SGSH-Fc融合蛋白與對照SGSH-Fc融合蛋白相比是否顯示改善之腦遞送，向人類TfR敲入(TfR mu/huKI)小鼠給與40 mg/kg結合TfR之SGSH-Fc融合蛋白ETV:SGSH (雙酶結構1)或缺乏賦予TfR結合之突變的對照SGSH-Fc融合蛋白(「SGSH:Fc」) (參見實例1)，且在給藥後2小時及8小時，使用基於夾心式ELISA之分析量測肝臟及腦中SGSH-Fc融合蛋白之濃度。用於分析中之SGSH-Fc融合蛋白在上文描述且根據實例1製備(本文中稱為ETV:SGSH (雙酶結構1)及對照SGSH-Fc)。對Fc片段具有特異性之多株驢抗人類IgG捕獲抗體(Jackson ImmunoResearch，#709-006-098)塗佈至384孔MaxiSorp™盤(Thermo Scientific #464718)上隔夜。將盤用5% BSA阻斷，且接著與經稀釋之血清、腦及肝臟溶解產物一起培育。然後，添加對Fc片段具有特異性之結合HRP之多株山羊抗人類IgG (Jackson ImmunoResearch，#109-036-098)，用於偵測。使用TMB受質使盤顯影，用硫酸停止，且在BioTek盤式讀數器上量測450 nm吸光度。標準曲線為進行3倍連續稀釋之2000-2.74 pM的個別構築體，且使用五參數邏輯曲線擬合而成。如國際專利公開案第WO 2018/152285號中所述，使用CRISPR/Cas9技術表現鼠類 Tfrc基因內之人類 Tfrc頂端結構域，產生TfR mu/huKI小鼠；在內源啟動子控制下表現所得到之嵌合TfR。結果在圖5-7中示出。
投與結合TfR之SGSH-Fc融合蛋白引起在給藥後2小時腦吸收相對於對照SGSH-Fc融合蛋白增加大約6倍，且在給藥後8小時腦濃度增加大約4倍(圖7)。在給藥後2小時，對於ETV:SGSH與SGSH:Fc而言，肝臟中融合蛋白之積聚為同等的，但在給藥後8小時顯著降低(大約30倍)，其中ETV:SGSH展現與SGSH:Fc相比較低之水準(圖6)。如上所述使用基於夾心式ELISA之分析，在給藥後0.5、1、2、4及8小時量測血清中融合蛋白之濃度。在給藥後2小時ETV:SGSH與SGSH:Fc之血清PK為同等的，但在給藥後2小時與8小時之間ETV:SGSH展現與SGSH:Fc相比較低之水準(圖5)。雖然與對照SGSH:Fc融合蛋白相比，結合TfR之SGSH-Fc融合蛋白之腦水準保持升高8小時，但更快的周圍清除可解釋在給藥後2小時至8小時腦及肝臟濃度之下降。總體而言，此等資料證明，結合TfR之SGSH-Fc融合蛋白與TfR的相互作用一般維持周圍分佈，同時顯著改善腦暴露。 ETV:SGSH 之靜脈內投與減少腦中之 GAG
為檢驗在上文所述且根據實例1製備之結合TfR之SGSH-Fc融合蛋白(本文中稱為ETV:SGSH)下觀測到的提高之腦暴露是否引起腦中積聚之受質相應減少，產生含有具有敲入鼠類TfR之人類TfR頂端結構域之磺醯胺酶突變的小鼠模型(本文中稱為 Sgsh mps3a × TfR mu/huKI小鼠或可替代地稱為SGSH D31N; TfR mu/huKI小鼠)。自The Jackson Laboratories (JAX原料號003780)獲得含有新穎磺醯胺酶突變D31N之 Sgsh mps3a 小鼠。簡言之，使TfR mu/huKI雄性小鼠與雌性 Sgsh mps3a 異型接合小鼠交配，產生在TfR mu/huKI同型接合背景下對 Sgsh mps3a 突變為同型接合的小鼠。將用於此研究之小鼠性別混合且圈養在12小時光-暗循環下，隨意取用食物(LabDiet JL輻照6F)及水。
經由靜脈內注射向 Sgsh mps3a ×TfR mu/huKI小鼠投與單劑量40 mg/kg體重之ETV:SGSH (雙酶結構1)或SGSH-Fc且評定藥效反應(融合蛋白參見實例1)。詳言之，使用靜脈內(i.v.)注射鹽水、SGSH-Fc (40 mg/kg體重)或ETV:SGSH (40 mg/kg體重)之3月齡 Sgsh mps3a ×TfR mu/huKI小鼠(n = 8/組)測定 Sgsh mps3a ×TfR mu/huKI小鼠中ETV:SGSH之周圍投與對肝臟、腦及CSF HS水準之作用。3月齡同窩出生之i.v.注射鹽水之TfR mu/huKI小鼠用作對照。除注射ETV:SGSH之 Sgsh mps3a ×TfR mu/huKI小鼠子集(n = 4)在單劑量後3天處死外，在單劑量後7天處死所有動物。收集血清、CSF、肝臟及腦且速凍在乾冰上。
如下所述使用基於LC-MS/MS方法在活體內量測硫酸乙醯肝素衍生之二醣。簡言之，收集所有組織及流體且接著立即冷凍及儲存在-80℃下。使用Qiagen TissueLyzer II在30 Hz下將組織等分試樣(50 mg)在水(750μL)中均質化3分鐘。將組織勻漿轉移至96孔深盤且使用96尖端超音波儀(Q Sonica)進行音波處理10×1秒脈衝。將進行音波處理之組織勻漿在4℃下在2,500×g下旋轉30分鐘以使細胞碎片形成糰粒。將所得到之溶解產物轉移至乾淨96孔深盤，且進行BCA以定量總蛋白。在LC-MS/MS分析之前將樣品中之硫酸乙醯肝素(HS)消化成其相應之二醣。在PCR盤中在震盪下在30℃下將10 μg總蛋白溶解產物或3 μl CSF與肝素酶I、II及III在消化緩衝液[111 mM NH4OAc、0.11 mM CaOAc、2mM DTT，pH 7.0]中培育3小時。在3小時之後，將EDTA及20 ng內標D4UA-2S-GlcNCOEt-6S (HD009，Iduron有限公司, Manchester, UK)添加至各樣品中且使混合物在95℃下沸騰10分鐘以使酶失活。將消化之樣品在3,364× g下旋轉5分鐘且將上清液轉移至乙酸纖維素濾板(Millipore，MSUN03010)且在3,364× g下旋轉5分鐘。在玻璃小瓶中將所得到之溶析液與同等份之乙腈混合且藉由質譜法如下分析。
藉由液相層析(Shimadzu Nexera X2系統, Shimadzu Scientific Instrument, Columbia, MD, USA)聯合電噴霧質譜法(Sciex 6500+ QTRAP, Sciex, Framingham, MA, USA)對流體及組織中之HS衍生之二醣進行定量。對於每次分析，使用0.4毫升/分鐘之流速將樣品注射在ACQUITY UPLC BEH Amide 1.7 mm，2.1×150 mm管柱(Waters公司, Milford, MA, USA)上，管柱溫度為50℃。移動相A由具有10 mM甲酸銨及0.1%甲酸之水組成，且移動相B由具有0.1%甲酸之乙腈組成。梯度程式如下：85% B下0.0-1.0分鐘，85% B至50% B 1.0-5.0分鐘，50% B至85% B 5.0-6.0分鐘，6-8.0分鐘保持在85% B下。應用以下設定，以負離子電離模式進行電噴霧電離：氣簾氣為30；碰撞氣中等；離子噴霧電壓在-4500下；溫度在450℃下；離子源氣體1為50；及離子源氣體2為60。使用Analyst 1.6.3 (Sciex)，以多反應監測模式(MRM)，利用以下設定來進行資料獲取：停留時間為30毫秒；碰撞能量為-30；去簇電位為-80；入口電位為-10；碰撞出口電壓為-10。使用市售參考標準(Iduron公司)，個別二醣物種基於其滯留時間及MRM轉變來鑑定。監測以下二醣轉變：D0A0 (HS)，m/z 378.1 ＞ 87.0；D0S0 (HS)，m/z 416.1 ＞ 138.0；D4UA-2S-GlcNCOEt-6S (內標) m/z 472.0 ＞ 97.0。二醣量相對於如藉由BCA分析量測之總蛋白水準正規化，或相對於每個樣品使用之體液體積正規化。
為確定ETV:SGSH是否減少腦中之受質水準，評定在單劑量酶之後 Sgsh mps3a× TfR mu/huKI小鼠中之HS水準。在單劑量之後，SGSH-Fc無法降低腦HS水準(圖9)。然而，在單劑量之後3天及7天ETV:SGSH使腦HS水準分別減少大約50%及57% (圖9)。此引起CSF HS水準伴隨著減少，在單劑量之後3天及7天分別減少大約70%及80% (圖10)。在一週之後兩種分子有效降低肝臟中之HS水準(圖8)，此證明TfR結合不負面影響此等組織中之藥效反應。圖8-10中之資料由平均值+/-平均值標準誤差表示(*p＜0.05，**p＜0.01，***p＜0.001，****p＜0.0001，ns = 不顯著)。總體而言，此等資料證明ETV:SGSH顯著地增加酶之腦暴露且是周圍及CNS中之受質積聚大大減少。 實例3： ETV:SGSH 雙酶結構之產品品質屬性
根據產品品質評估ETV:SGSH融合蛋白之不同雙酶結構。對於此研究，將ETV:SGSH雙酶結構1 (實例1)與具有不同的結合TfR之Fc區之結構(ETV:SGSH雙酶結構6，以下描述)進行比較。兩種結構如實例1中所述製備，額外純化步驟如下所述。 結果
所量測之對雙酶結構1及雙酶結構6之人類TfR親和力為可比較的(分別約290 nM對比約245 nM之K D)。
測得雙酶結構1之表現效價為約30-40 mg/L，而測得雙酶結構6之表現效價稍微較少(約12-23 mg/L)。
評估雙酶結構1與雙酶結構6之蛋白A後層析純化回收率。對雙酶結構1與雙酶結構6之蛋白A後池之分析說明約50-60%純度(如藉由HPLC-SEC量測)，完整ETV結構(維持包含杵及臼對之經修飾之Fc二聚體)為至少約80%。雙酶結構之蛋白A後池進行疏水性相互作用層析法(HIC)以進一步精製(以下描述)。雙酶結構1之HIC後池實現純度水準＞ 95% (藉由HPLC-SEC量測)，完整ETV結構＞ 90%，而雙酶結構6之HIC後池實現純度水準為約85% (藉由HPLC-SEC量測)，完整ETV結構＞ 90%。為實現雙酶結構6較高之純度水準(＞ 90%)，需要額外純化步驟，此會降低純化後蛋白質之產率及回收率。
因此，鑒定出雙酶結構1及其P329S變異體(雙酶結構4)為移至大規模生產之較佳結構。 實驗方法
產生第六「N端雙酶」SGSH-Fc融合多肽(「ETV:SGSH雙酶結構6」)，其包含具有SEQ ID NO:61及63中之任一者之序列的第一SGSH-Fc融合多肽，及具有SEQ ID NO:122及124中之任一者之序列的結合TfR之第二SGSH-Fc融合多肽。在細胞培養物產生期間亦可進一步加工SGSH-Fc融合蛋白，使得第一SGSH-Fc融合多肽具有SEQ ID NO:62或64之序列及/或結合TfR之第二SGSH-Fc融合多肽具有SEQ ID NO:123或125之序列。因此，如本文所用，術語ETV:SGSH雙酶結構6可用於指具有未加工之序列(亦即SEQ ID NO:61、63、122及124)的蛋白質分子；包含一或多個經加工序列(亦即選自SEQ ID NO: 62、64、123及125)之蛋白質分子；或包含經加工及未加工蛋白質分子之混合物。
ETV:SGSH雙酶結構1及ETV:SGSH雙酶結構6如實例1中所述表現及純化，修改如下：用1M Tris pH 8.0中和自蛋白A親和管柱溶析之所彙集之蛋白質溶析份至目標pH 6.0。接著將中和之蛋白質A池用1 M檸檬酸鈉調節至0.6 M檸檬酸鈉之最終濃度。將所彙集之溶析份裝載至ButylHP疏水性相互作用層析(HIC)管柱上，用0.6 M檸檬酸鈉(pH 6.0)洗滌，且經由(i)經10CV，0.6 M檸檬酸鈉(pH 6.0)至WFI之50%步驟梯度，接著(ii)經5CV，0.6 M檸檬酸鈉(pH 6.0)至WFI之100%步驟梯度。
藉由多種技術，包括還原及非還原SDS-PAGE及HPLC-SEC評定溶析份中ETV:SGSH融合蛋白之均質性。人類TfR之親和力如實例2中所述量測。 實例4： 靜脈內投與 ETV:SGSH 之不同雙酶結構實現可比的腦中之 GAG 之減少
根據對MPS III之小鼠模型中之腦GAG水準的作用評估ETV:SGSH融合蛋白之不同雙酶結構。對於此研究，將ETV:SGSH雙酶結構1與在Fc區中含有P329S突變之相應結構(ETV:SGSH雙酶結構4)進行比較。 結果
使用實例2中所述之方法分析雙酶結構之甲醯甘胺酸(fGly)含量、甘露糖-6-磷酸(M6P)含量及人類TfR親和力。表2提供各雙酶結構之分析結果。雙酶結構1及雙酶結構4之HIC後彙集溶析份實現純度水準＞ 95% (如藉由HPLC-SEC量測)，完整ETV結構＞ 90%。 表 2.ETV:SGSH蛋白特徵
分子 fGly M6P (mol/mol) TfR親和力(K D)
雙酶結構1 98% 4.05 290 nM
雙酶結構4 99% 2.93 340 nM
為確定ETV:SGSH結構是否減少腦中之受質水準，評定在單劑量ETV:SGSH蛋白質之後 Sgsh mps3a× TfR mu/huKI小鼠中之HS水準。在單劑量之後7天，ETV:SGSH雙酶結構1與ETV:SGSH雙酶結構4分別減少腦HS水準大約63%及59% (圖11)。圖11中之資料由平均值+/-平均標準誤差表示。此資料證明ETV:SGSH之兩種雙酶結構大大地減少腦中之受質積聚。在來自各隊列之腦組織樣品中，給藥後7天之兩種雙酶結構的腦吸收可偵測，且定量為超過0.5 nM。 實驗方法
ETV:SGSH雙酶結構1如實例3中所述表現及純化。
自經相關DNA構築體轉染之穩定CHO細胞株表現ETV:SGSH雙酶結構4且藉由評估所表現及純化之蛋白質的表現效價、穩定性及活性進行選擇。簡言之，CHO-K1 GS敲除細胞株(Horizon Discovery)經相關DNA構築體轉染(編碼融合蛋白及SUMF1之質體共轉染)，接著進行選擇，以產生表現所關注基因之穩定細胞株。接著細胞株經受饋料分批生產商業CHO細胞培養基(例如BalanCD CHO培養基(Irvine Scientific)，視情況補充有BalanCD CHO饋料4 (Irvine Scientific))。將培養物維持在37℃下5天，接著溫度變至32℃。在第12天收穫時，將細胞培養物離心，且經商業(0.8 μm/0.2 μm膜式過濾器)無菌過濾上清液且儲存在4℃下。使用蛋白A親和力及疏水性相互作用層析法自細胞培養物上清液純化融合蛋白。將上清液負載至製備規模之MabSelect SuRe LX蛋白A親和管柱(GE Healthcare Life Sciences，使用Akta Pure系統)上。接著將管柱用2管柱體積(CV) PBS洗滌，接著4 CV 0.4 M磷酸鉀pH 7.0，接著3 CV PBS洗滌。使用50 mM檸檬酸鹽/NaOH緩衝液pH 3.7溶析結合之蛋白質。在溶析之後立即使用1.5 M Tris pH11中和溶析份至目標pH 6.0。在疏水性相互作用層析法之前，將經中和之蛋白A以1:1.3之比率用1 M檸檬酸鈉pH 6.0調整。將經調整之蛋白A池裝載至ButylHP疏水性相互作用層析法(HIC)管柱上，用0.6 M檸檬酸鈉pH 6.0洗滌，且接著經由經25CV 0.6 M檸檬酸鈉至WFI之20-55%梯度溶析。藉由多種技術，包括還原及非還原SDS-PAGE及HPLC-SEC評定溶析份中融合蛋白之均質性。
使用實例2中所述之方法分析融合蛋白之甲醯甘胺酸(fGly)含量、M6P含量及TfR親和力。
經由靜脈內注射向 Sgsh mps3a× TfR mu/huKI小鼠(實例2)投與單劑量ETV:SGSH雙酶結構1或ETV:SGSH雙酶結構4，且評定腦暴露及藥效反應。使用靜脈內(i.v.)注射鹽水、ETV:SGSH雙酶結構1 (15 mg/kg體重)或ETV:SGSH雙酶結構4 (15 mg/kg體重)之9月齡 Sgsh mps3a× TfR mu/huKI小鼠(n = 4-5/組)測定 Sgsh mps3a× TfR mu/huKI小鼠中ETV:SGSH雙酶結構之周圍投與對腦HS水準之作用。九月齡同窩出生之i.v.注射鹽水之TfR mu/huKI小鼠(非MPS III小鼠)用作對照。單劑量後7天處死所有動物。收集腦組織且在乾冰上速凍。ETV:SGSH及硫酸乙醯肝素衍生之二醣之腦吸收如實例2中所述量測。 非正式序列表
SEQ ID NO: 序列 描述
1 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 野生型人類Fc序列位置231-447 EU索引編號
2 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 野生型人類Fc序列位置231-446 EU索引編號
3 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK CH2結構域序列 位置231-340 EU索引編號
4 GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK CH3結構域序列 位置341-447 EU索引編號
5 EPKSCDKTHTCPPCP 人類IgG1鉸鏈胺基酸序列
6 DKTHTCPPCP 人類IgG1鉸鏈序列之一部分
7 GS GS連接子
8 GGGGS 富甘胺酸連接子
9 GGGGSGGGGS 富甘胺酸連接子
10 MMDQARSAFSNLFGGEPLSYTRFSLARQVDGDNSHVEMKLAVDEEENADNNTKANVTKPKRCSGSICYGTIAVIVFFLIGFMIGYLGYCKGVEPKTECERLAGTESPVREEPGEDFPAARRLYWDDLKRKLSEKLDSTDFTGTIKLLNENSYVPREAGSQKDENLALYVENQFREFKLSKVWRDQHFVKIQVKDSAQNSVIIVDKNGRLVYLVENPGGYVAYSKAATVTGKLVHANFGTKKDFEDLYTPVNGSIVIVRAGKITFAEKVANAESLNAIGVLIYMDQTKFPIVNAELSFFGHAHLGTGDPYTPGFPSFNHTQFPPSRSSGLPNIPVQTISRAAAEKLFGNMEGDCPSDWKTDSTCRMVTSESKNVKLTVSNVLKEIKILNIFGVIKGFVEPDHYVVVGAQRDAWGPGAAKSGVGTALLLKLAQMFSDMVLKDGFQPSRSIIFASWSAGDFGSVGATEWLEGYLSSLHLKAFTYINLDKAVLGTSNFKVSASPLLYTLIEKTMQNVKHPVTGQFLYQDSNWASKVEKLTLDNAAFPFLAYSGIPAVSFCFCEDTDYPYLGTTMDTYKELIERIPELNKVARAAAEVAGQFVIKLTHDVELNLDYERYNSQLLSFVRDLNQYRADIKEMGLSLQWLYSARGDFFRATSRLTTDFGNAEKTDRFVMKKLNDRVMRVEYHFLSPYVSPKESPFRHVFWGSGSHTLPALLENLKLRKQNNGAFNETLFRNQLALATWTIQGAANALSGDVWDIDNEF 人類運鐵蛋白受體蛋白1 (TFR1)
11 NSVIIVDKNGRLVYLVENPGGYVAYSKAATVTGKLVHANFGTKKDFEDLYTPVNGSIVIVRAGKITFAEKVANAESLNAIGVLIYMDQTKFPIVNAELSFFGHAHLGTGDPYTPGFPSFNHTQFPPSRSSGLPNIPVQTISRAAAEKLFGNMEGDCPSDWKTDSTCRMVTSESKNVKLTVS 人類TfR頂端結構域
12 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有臼突變之Fc序列
13 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有臼突變之Fc序列
14 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有臼及LALA突變之Fc序列
15 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有臼及LALA突變之Fc序列
16 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有臼及LALAPG突變之Fc序列
17 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有臼及LALAPG突變之Fc序列
18 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有臼及LALAPS突變之Fc序列
19 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有臼及LALAPS突變之Fc序列
24 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有杵突變之Fc序列
25 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有杵突變之Fc序列
26 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有杵及LALA突變之Fc序列
27 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有杵及LALA突變之Fc序列
28 DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有臼及LALA突變之Fc序列及人類IgG1鉸鏈序列之一部分
29 DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有臼及LALA突變之Fc序列及人類IgG1鉸鏈序列之一部分
30 DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有臼及LALAPS突變之Fc序列及人類IgG1鉸鏈序列之一部分
31 DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有臼及LALAPS突變之Fc序列及人類IgG1鉸鏈序列之一部分
32 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 純系CH3C.35.23.2
33 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 純系CH3C.35.23.2
34 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有杵突變之純系CH3C.35.23.2
35 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有杵突變之純系CH3C.35.23.2
36 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有杵及LALA突變之純系CH3C.35.23.2
37 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有杵及LALA突變之純系CH3C.35.23.2
38 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有杵及LALAPG突變之純系CH3C.35.23.2
39 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有杵及LALAPG突變之純系CH3C.35.23.2
40 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有杵及LALAPS突變之純系CH3C.35.23.2
41 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有杵及LALAPS突變之純系CH3C.35.23.2
48 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有臼突變之純系CH3C.35.23.2
49 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有臼突變之純系CH3C.35.23.2
50 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有臼及LALA突變之純系CH3C.35.23.2
51 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有臼及LALA突變之純系CH3C.35.23.2
52 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有臼及LALAPG突變之純系CH3C.35.23.2
53 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有臼及LALAPG突變之純系CH3C.35.23.2
54 DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有杵及LALA突變之純系CH3C.35.23.2及人類IgG1鉸鏈序列之一部分
55 DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有杵及LALA突變之純系CH3C.35.23.2及人類IgG1鉸鏈序列之一部分
56 DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有杵及LALAPS突變之純系CH3C.35.23.2及人類IgG1鉸鏈序列之一部分
57 DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有杵及LALAPS突變之純系CH3C.35.23.2及人類IgG1鉸鏈序列之一部分
58 MSCPVPACCALLLVLGLCRARPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNEL 全長人類磺基葡萄糖胺磺基水解酶多肽序列
59 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNEL 成熟人類磺基葡萄糖胺磺基水解酶多肽序列
60 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fGSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNEL 成熟人類磺基葡萄糖胺磺基水解酶多肽序列(甲醯甘胺酸殘基「fG」加雙底線)
61 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALA突變之Fc序列之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
62 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALA突變之Fc序列之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
63 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSfGSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALA突變之Fc序列之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
64 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALA突變之Fc序列之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
65 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALAPS突變之Fc序列之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
66 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALAPS突變之Fc序列之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
67 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALAPS突變之Fc序列之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
68 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALAPS突變之Fc序列之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
69 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之Fc序列之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
70 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之Fc序列之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
71 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之Fc序列之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
72 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之Fc序列之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
73 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALA突變之Fc序列之N端融合的具有GS連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
74 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALA突變之Fc序列之N端融合的具有GS連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
75 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALA突變之Fc序列之N端融合的具有GS連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
76 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALA突變之Fc序列之N端融合的具有GS連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
77 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之Fc序列之N端融合的具有GS連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
78 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之Fc序列之N端融合的具有GS連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
79 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之Fc序列之N端融合的具有GS連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
80 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之Fc序列之N端融合的具有GS連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
81 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALA突變之Fc序列之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
82 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALA突變之Fc序列之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
83 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALA突變之Fc序列之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
84 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALA突變之Fc序列之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
85 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之Fc序列之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
86 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之Fc序列之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
87 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之Fc序列之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
88 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之Fc序列之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
89 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之純系CH3C.35.23.2之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
90 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之純系CH3C.35.23.2之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
91 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之純系CH3C.35.23.2之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
92 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之純系CH3C.35.23.2之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
93 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALAPS突變之純系CH3C.35.23.2之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
94 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALAPS突變之純系CH3C.35.23.2之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
95 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALAPS突變之純系CH3C.35.23.2之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
96 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALSAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALAPS突變之純系CH3C.35.23.2之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
97 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALA突變之純系CH3C.35.23.2之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
98 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALA突變之純系CH3C.35.23.2之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
99 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALA突變之純系CH3C.35.23.2之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
100 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALA突變之純系CH3C.35.23.2之N端融合的具有G4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
101 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之純系CH3C.35.23.2之N端融合的具有GS連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
102 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之純系CH3C.35.23.2之N端融合的具有GS連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
103 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之純系CH3C.35.23.2之N端融合的具有GS連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
104 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之純系CH3C.35.23.2之N端融合的具有GS連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
105 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALA突變之純系CH3C.35.23.2之N端融合的具有GS連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
106 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALA突變之純系CH3C.35.23.2之N端融合的具有GS連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
107 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALA突變之純系CH3C.35.23.2之N端融合的具有GS連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
108 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALA突變之純系CH3C.35.23.2之N端融合的具有GS連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
109 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGsDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之純系CH3C.35.23.2之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
110 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGsDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之純系CH3C.35.23.2之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
111 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGsDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之純系CH3C.35.23.2之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
112 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGsDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之純系CH3C.35.23.2之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
113 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGsDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALA突變之純系CH3C.35.23.2之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
114 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGsDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALA突變之純系CH3C.35.23.2之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
115 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGsDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有臼及LALA突變之純系CH3C.35.23.2之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
116 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSGGGGsDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLVSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有臼及LALA突變之純系CH3C.35.23.2之N端融合的具有(G 4S) 2連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
117 DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGS RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNEL 具有與具有臼及LALA突變之Fc序列之C端融合的成熟人類SGSH序列(加底線)的Fc-SGSH融合多肽
118 DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGS RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNEL 具有與具有臼及LALA突變之Fc序列之C端融合的成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的Fc-SGSH融合多肽
119 DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGGGGGS RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNEL 具有與具有杵及LALA突變之純系CH3C.35.23.2之C端融合的成熟人類SGSH序列(加底線)的Fc-SGSH融合多肽
120 DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESYGTEWANYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGGGGGS RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNEL 具有與具有杵及LALA突變之純系CH3C.35.23.2之C端融合的成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的Fc-SGSH融合多肽
121 MGWSCIILFLVATATGAYA 分泌信號肽
122 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVLWESYGTEWSSYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之純系CH3C.35.21.17之N端融合的具有G 4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
123 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVLWESYGTEWSSYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之純系CH3C.35.21.17之N端融合的具有G 4S連接子之成熟人類SGSH序列(加底線)的SGSH-Fc融合多肽
124 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVLWESYGTEWSSYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPGK 具有與具有杵及LALA突變之純系CH3C.35.21.17之N端融合的具有G 4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
125 RPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLFRNAFTSVSS fG SPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWVCAPDGVLEEKLSPQCQPLHNELGGGGSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVLWESYGTEWSSYKTTPPVLDSDGSFFLYSKLTVTKEEWQQGFVFSCSVMHEALHNHYTQKSLSLSPG 具有與具有杵及LALA突變之純系CH3C.35.21.17之N端融合的具有G 4S連接子之成熟人類SGSH序列(加底線；甲醯甘胺酸殘基「fG」加雙底線)的SGSH-Fc融合多肽
126 CXPXR CXPXR基元，其中「X」為任何胺基酸
127 NAFTSVSSCSPSR 胰蛋白酶肽實施例
128 NAFTSVSSC(CAM)SPSR 胰蛋白酶肽實施例；C(CAM)為烷基化脲基甲基Cys
129 NAFTSVSS(Fgly)SPSR 胰蛋白酶肽實施例；Fgly為甲醯甘胺酸
所有公開案、專利及專利檔均以引用的方式併入本文中，如同以引用的方式個別地併入一般。本發明已經參考各種特定及較佳實施例及技術來描述。但是，應瞭解在保持在本發明之精神及範疇內的同時可進行許多變化及修改。
圖 1A-1C.示出在SGSH酶與Fc多肽鉸鏈區之間具有變化連接子長度的示例性ETV:SGSH融合蛋白。 圖 2.如藉由LCMS確定之SGSH-Fc及ETV:SGSH融合蛋白之fGly含量。 圖 3.對SGSH-Fc及ETV:SGSH融合蛋白之酶活性的活體外評估。 圖 4.使用 35S脈衝追蹤分析評估SGSH-Fc融合蛋白在來自MPSIIIA患者及健康對照之纖維母細胞中的細胞活性。 圖 5.SGSH-Fc及ETV:SGSH融合蛋白之血清濃度。 圖 6A-6B.在2小時(圖6A)及8小時(圖6B) SGSH-Fc及ETV:SGSH融合蛋白之肝臟濃度。 圖 7.SGSH-Fc及ETV:SGSH融合蛋白之腦濃度。 圖 8.肝臟中之總硫酸乙醯肝素水準。 圖 9.腦中之總硫酸乙醯肝素水準。 圖 10.CSF中之總硫酸乙醯肝素水準。 圖 11.在投與兩種不同ETV:SGSH融合蛋白之後腦中之總硫酸乙醯肝素水準。 

          <![CDATA[<110> 美商戴納立製藥公司(DENALI THERAPEUTICS INC.)]]>
          <![CDATA[<120> 包含磺基葡萄糖胺磺基水解酶之融合蛋白及其方法]]>
          <![CDATA[<130> 02900.027TW1]]>
          <![CDATA[<140> TW 110138229]]>
          <![CDATA[<141> 2021-10-14]]>
          <![CDATA[<150> 63/091,800]]>
          <![CDATA[<151> 2020-10-14]]>
          <![CDATA[<160> 129   ]]>
          <![CDATA[<170> PatentIn version 3.5]]>
          <![CDATA[<210> 1]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 智人(Homo sapiens)]]>
          <![CDATA[<400> 1]]>
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 2]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 智人(Homo sapiens)]]>
          <![CDATA[<400> 2]]>
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 3]]>
          <![CDATA[<211> 110]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 智人(Homo sapiens)]]>
          <![CDATA[<400> 3]]>
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
                      100                 105                 110 
          <![CDATA[<210> 4]]>
          <![CDATA[<211> 107]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 智人(Homo sapiens)]]>
          <![CDATA[<400> 4]]>
          Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp 
          1               5                   10                  15      
          Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
                      20                  25                  30          
          Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
                  35                  40                  45              
          Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
              50                  55                  60                  
          Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
          65                  70                  75                  80  
          Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
                          85                  90                  95      
          Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                      100                 105         
          <![CDATA[<210> 5]]>
          <![CDATA[<211> 15]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 智人(Homo sapiens)]]>
          <![CDATA[<400> 5]]>
          Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
          1               5                   10                  15  
          <![CDATA[<210> 6]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 智人(Homo sapiens)]]>
          <![CDATA[<400> 6]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
          1               5                   10  
          <![CDATA[<210> 7]]>
          <![CDATA[<211> 2]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成肽]]>
          <![CDATA[<400> 7]]>
          Gly Ser 
          1       
          <![CDATA[<210> 8]]>
          <![CDATA[<211> 5]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成肽]]>
          <![CDATA[<400> 8]]>
          Gly Gly Gly Gly Ser 
          1               5   
          <![CDATA[<210> 9]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成肽]]>
          <![CDATA[<400> 9]]>
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          1               5                   10  
          <![CDATA[<210> 10]]>
          <![CDATA[<211> 760]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 智人(Homo sapiens)]]>
          <![CDATA[<400> 10]]>
          Met Met Asp Gln Ala Arg Ser Ala Phe Ser Asn Leu Phe Gly Gly Glu 
          1               5                   10                  15      
          Pro Leu Ser Tyr Thr Arg Phe Ser Leu Ala Arg Gln Val Asp Gly Asp 
                      20                  25                  30          
          Asn Ser His Val Glu Met Lys Leu Ala Val Asp Glu Glu Glu Asn Ala 
                  35                  40                  45              
          Asp Asn Asn Thr Lys Ala Asn Val Thr Lys Pro Lys Arg Cys Ser Gly 
              50                  55                  60                  
          Ser Ile Cys Tyr Gly Thr Ile Ala Val Ile Val Phe Phe Leu Ile Gly 
          65                  70                  75                  80  
          Phe Met Ile Gly Tyr Leu Gly Tyr Cys Lys Gly Val Glu Pro Lys Thr 
                          85                  90                  95      
          Glu Cys Glu Arg Leu Ala Gly Thr Glu Ser Pro Val Arg Glu Glu Pro 
                      100                 105                 110         
          Gly Glu Asp Phe Pro Ala Ala Arg Arg Leu Tyr Trp Asp Asp Leu Lys 
                  115                 120                 125             
          Arg Lys Leu Ser Glu Lys Leu Asp Ser Thr Asp Phe Thr Gly Thr Ile 
              130                 135                 140                 
          Lys Leu Leu Asn Glu Asn Ser Tyr Val Pro Arg Glu Ala Gly Ser Gln 
          145                 150                 155                 160 
          Lys Asp Glu Asn Leu Ala Leu Tyr Val Glu Asn Gln Phe Arg Glu Phe 
                          165                 170                 175     
          Lys Leu Ser Lys Val Trp Arg Asp Gln His Phe Val Lys Ile Gln Val 
                      180                 185                 190         
          Lys Asp Ser Ala Gln Asn Ser Val Ile Ile Val Asp Lys Asn Gly Arg 
                  195                 200                 205             
          Leu Val Tyr Leu Val Glu Asn Pro Gly Gly Tyr Val Ala Tyr Ser Lys 
              210                 215                 220                 
          Ala Ala Thr Val Thr Gly Lys Leu Val His Ala Asn Phe Gly Thr Lys 
          225                 230                 235                 240 
          Lys Asp Phe Glu Asp Leu Tyr Thr Pro Val Asn Gly Ser Ile Val Ile 
                          245                 250                 255     
          Val Arg Ala Gly Lys Ile Thr Phe Ala Glu Lys Val Ala Asn Ala Glu 
                      260                 265                 270         
          Ser Leu Asn Ala Ile Gly Val Leu Ile Tyr Met Asp Gln Thr Lys Phe 
                  275                 280                 285             
          Pro Ile Val Asn Ala Glu Leu Ser Phe Phe Gly His Ala His Leu Gly 
              290                 295                 300                 
          Thr Gly Asp Pro Tyr Thr Pro Gly Phe Pro Ser Phe Asn His Thr Gln 
          305                 310                 315                 320 
          Phe Pro Pro Ser Arg Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr 
                          325                 330                 335     
          Ile Ser Arg Ala Ala Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp 
                      340                 345                 350         
          Cys Pro Ser Asp Trp Lys Thr Asp Ser Thr Cys Arg Met Val Thr Ser 
                  355                 360                 365             
          Glu Ser Lys Asn Val Lys Leu Thr Val Ser Asn Val Leu Lys Glu Ile 
              370                 375                 380                 
          Lys Ile Leu Asn Ile Phe Gly Val Ile Lys Gly Phe Val Glu Pro Asp 
          385                 390                 395                 400 
          His Tyr Val Val Val Gly Ala Gln Arg Asp Ala Trp Gly Pro Gly Ala 
                          405                 410                 415     
          Ala Lys Ser Gly Val Gly Thr Ala Leu Leu Leu Lys Leu Ala Gln Met 
                      420                 425                 430         
          Phe Ser Asp Met Val Leu Lys Asp Gly Phe Gln Pro Ser Arg Ser Ile 
                  435                 440                 445             
          Ile Phe Ala Ser Trp Ser Ala Gly Asp Phe Gly Ser Val Gly Ala Thr 
              450                 455                 460                 
          Glu Trp Leu Glu Gly Tyr Leu Ser Ser Leu His Leu Lys Ala Phe Thr 
          465                 470                 475                 480 
          Tyr Ile Asn Leu Asp Lys Ala Val Leu Gly Thr Ser Asn Phe Lys Val 
                          485                 490                 495     
          Ser Ala Ser Pro Leu Leu Tyr Thr Leu Ile Glu Lys Thr Met Gln Asn 
                      500                 505                 510         
          Val Lys His Pro Val Thr Gly Gln Phe Leu Tyr Gln Asp Ser Asn Trp 
                  515                 520                 525             
          Ala Ser Lys Val Glu Lys Leu Thr Leu Asp Asn Ala Ala Phe Pro Phe 
              530                 535                 540                 
          Leu Ala Tyr Ser Gly Ile Pro Ala Val Ser Phe Cys Phe Cys Glu Asp 
          545                 550                 555                 560 
          Thr Asp Tyr Pro Tyr Leu Gly Thr Thr Met Asp Thr Tyr Lys Glu Leu 
                          565                 570                 575     
          Ile Glu Arg Ile Pro Glu Leu Asn Lys Val Ala Arg Ala Ala Ala Glu 
                      580                 585                 590         
          Val Ala Gly Gln Phe Val Ile Lys Leu Thr His Asp Val Glu Leu Asn 
                  595                 600                 605             
          Leu Asp Tyr Glu Arg Tyr Asn Ser Gln Leu Leu Ser Phe Val Arg Asp 
              610                 615                 620                 
          Leu Asn Gln Tyr Arg Ala Asp Ile Lys Glu Met Gly Leu Ser Leu Gln 
          625                 630                 635                 640 
          Trp Leu Tyr Ser Ala Arg Gly Asp Phe Phe Arg Ala Thr Ser Arg Leu 
                          645                 650                 655     
          Thr Thr Asp Phe Gly Asn Ala Glu Lys Thr Asp Arg Phe Val Met Lys 
                      660                 665                 670         
          Lys Leu Asn Asp Arg Val Met Arg Val Glu Tyr His Phe Leu Ser Pro 
                  675                 680                 685             
          Tyr Val Ser Pro Lys Glu Ser Pro Phe Arg His Val Phe Trp Gly Ser 
              690                 695                 700                 
          Gly Ser His Thr Leu Pro Ala Leu Leu Glu Asn Leu Lys Leu Arg Lys 
          705                 710                 715                 720 
          Gln Asn Asn Gly Ala Phe Asn Glu Thr Leu Phe Arg Asn Gln Leu Ala 
                          725                 730                 735     
          Leu Ala Thr Trp Thr Ile Gln Gly Ala Ala Asn Ala Leu Ser Gly Asp 
                      740                 745                 750         
          Val Trp Asp Ile Asp Asn Glu Phe 
                  755                 760 
          <![CDATA[<210> 11]]>
          <![CDATA[<211> 181]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 智人(Homo sapiens)]]>
          <![CDATA[<400> 11]]>
          Asn Ser Val Ile Ile Val Asp Lys Asn Gly Arg Leu Val Tyr Leu Val 
          1               5                   10                  15      
          Glu Asn Pro Gly Gly Tyr Val Ala Tyr Ser Lys Ala Ala Thr Val Thr 
                      20                  25                  30          
          Gly Lys Leu Val His Ala Asn Phe Gly Thr Lys Lys Asp Phe Glu Asp 
                  35                  40                  45              
          Leu Tyr Thr Pro Val Asn Gly Ser Ile Val Ile Val Arg Ala Gly Lys 
              50                  55                  60                  
          Ile Thr Phe Ala Glu Lys Val Ala Asn Ala Glu Ser Leu Asn Ala Ile 
          65                  70                  75                  80  
          Gly Val Leu Ile Tyr Met Asp Gln Thr Lys Phe Pro Ile Val Asn Ala 
                          85                  90                  95      
          Glu Leu Ser Phe Phe Gly His Ala His Leu Gly Thr Gly Asp Pro Tyr 
                      100                 105                 110         
          Thr Pro Gly Phe Pro Ser Phe Asn His Thr Gln Phe Pro Pro Ser Arg 
                  115                 120                 125             
          Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr Ile Ser Arg Ala Ala 
              130                 135                 140                 
          Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp Cys Pro Ser Asp Trp 
          145                 150                 155                 160 
          Lys Thr Asp Ser Thr Cys Arg Met Val Thr Ser Glu Ser Lys Asn Val 
                          165                 170                 175     
          Lys Leu Thr Val Ser 
                      180     
          <![CDATA[<210> 12]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 12]]>
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 13]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 13]]>
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 14]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 14]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 15]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 15]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 16]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 16]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 17]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 17]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 18]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 18]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Ser Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 19]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 19]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Ser Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 20]]>
          <![CDATA[<400> 20]]>
          000
          <![CDATA[<210> 21]]>
          <![CDATA[<400> 21]]>
          000
          <![CDATA[<210> 22]]>
          <![CDATA[<400> 22]]>
          000
          <![CDATA[<210> 23]]>
          <![CDATA[<400> 23]]>
          000
          <![CDATA[<210> 24]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 24]]>
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 25]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 25]]>
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 26]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 26]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 27]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 27]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 28]]>
          <![CDATA[<211> 227]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 28]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Lys 
          225         
          <![CDATA[<210> 29]]>
          <![CDATA[<211> 226]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 29]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly 
          225     
          <![CDATA[<210> 30]]>
          <![CDATA[<211> 227]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 30]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Ser Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Lys 
          225         
          <![CDATA[<210> 31]]>
          <![CDATA[<211> 226]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 31]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Ser Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly 
          225     
          <![CDATA[<210> 32]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 32]]>
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 33]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 33]]>
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 34]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 34]]>
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 35]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 35]]>
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 36]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 36]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 37]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 37]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 38]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 38]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 39]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 39]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 40]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 40]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Ser Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 41]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 41]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Ser Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 42]]>
          <![CDATA[<400> 42]]>
          000
          <![CDATA[<210> 43]]>
          <![CDATA[<400> 43]]>
          000
          <![CDATA[<210> 44]]>
          <![CDATA[<400> 44]]>
          000
          <![CDATA[<210> 45]]>
          <![CDATA[<400> 45]]>
          000
          <![CDATA[<210> 46]]>
          <![CDATA[<400> 46]]>
          000
          <![CDATA[<210> 47]]>
          <![CDATA[<400> 47]]>
          000
          <![CDATA[<210> 48]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 48]]>
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 49]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 49]]>
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 50]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 50]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 51]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 51]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 52]]>
          <![CDATA[<211> 217]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 52]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              210                 215         
          <![CDATA[<210> 53]]>
          <![CDATA[<211> 216]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 53]]>
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          1               5                   10                  15      
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      20                  25                  30          
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  35                  40                  45              
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              50                  55                  60                  
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          65                  70                  75                  80  
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          85                  90                  95      
          Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      100                 105                 110         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
                  115                 120                 125             
          Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
              130                 135                 140                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn 
          145                 150                 155                 160 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          165                 170                 175     
          Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val 
                      180                 185                 190         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  195                 200                 205             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              210                 215     
          <![CDATA[<210> 54]]>
          <![CDATA[<211> 227]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 54]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Lys 
          225         
          <![CDATA[<210> 55]]>
          <![CDATA[<211> 226]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 55]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly 
          225     
          <![CDATA[<210> 56]]>
          <![CDATA[<211> 227]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 56]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Ser Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Lys 
          225         
          <![CDATA[<210> 57]]>
          <![CDATA[<211> 226]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 57]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Ser Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly 
          225     
          <![CDATA[<210> 58]]>
          <![CDATA[<211> 502]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 智人(Homo sapiens)]]>
          <![CDATA[<400> 58]]>
          Met Ser Cys Pro Val Pro Ala Cys Cys Ala Leu Leu Leu Val Leu Gly 
          1               5                   10                  15      
          Leu Cys Arg Ala Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp 
                      20                  25                  30          
          Gly Gly Phe Glu Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro 
                  35                  40                  45              
          His Leu Asp Ala Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe 
              50                  55                  60                  
          Thr Ser Val Ser Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly 
          65                  70                  75                  80  
          Leu Pro Gln His Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His 
                          85                  90                  95      
          His Phe Asn Ser Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser 
                      100                 105                 110         
          Gln Ala Gly Val Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro 
                  115                 120                 125             
          Glu Thr Val Tyr Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser 
              130                 135                 140                 
          Val Leu Gln Val Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg 
          145                 150                 155                 160 
          Lys Phe Leu Gln Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala 
                          165                 170                 175     
          Phe His Asp Pro His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr 
                      180                 185                 190         
          Phe Cys Glu Lys Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro 
                  195                 200                 205             
          Asp Trp Thr Pro Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr 
              210                 215                 220                 
          Phe Val Pro Asn Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr 
          225                 230                 235                 240 
          Thr Thr Val Gly Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu 
                          245                 250                 255     
          Leu Arg Asp Ala Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser 
                      260                 265                 270         
          Asp Asn Gly Ile Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro 
                  275                 280                 285             
          Gly Thr Ala Glu Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg 
              290                 295                 300                 
          Trp Gly Gln Val Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro 
          305                 310                 315                 320 
          Thr Ile Leu Asp Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe 
                          325                 330                 335     
          Gly Ser Lys Thr Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu 
                      340                 345                 350         
          Glu Ala Glu Pro Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His 
                  355                 360                 365             
          Glu Val Thr Met Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe 
              370                 375                 380                 
          Arg Leu Val His Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln 
          385                 390                 395                 400 
          Asp Phe Tyr Val Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr 
                          405                 410                 415     
          Ala Gly Gln Pro Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr 
                      420                 425                 430         
          Arg Ala Arg Trp Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr 
                  435                 440                 445             
          Gln Asn Leu Ala Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu 
              450                 455                 460                 
          Arg Asp Gln Leu Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val 
          465                 470                 475                 480 
          Cys Ala Pro Asp Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln 
                          485                 490                 495     
          Pro Leu His Asn Glu Leu 
                      500         
          <![CDATA[<210> 59]]>
          <![CDATA[<211> 482]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 智人(Homo sapiens)]]>
          <![CDATA[<400> 59]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu 
          <![CDATA[<210> 60]]>
          <![CDATA[<211> 482]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 智人(Homo sapiens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 60]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu 
          <![CDATA[<210> 61]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 61]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 62]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 62]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 63]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 63]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 64]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 64]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 65]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 65]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Ser Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 66]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 66]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Ser Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 67]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 67]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Ser Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 68]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 68]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Ser Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 69]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 69]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 70]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 70]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 71]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 71]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 72]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 72]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 73]]>
          <![CDATA[<211> 711]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 73]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Lys 
          705                 710     
          <![CDATA[<210> 74]]>
          <![CDATA[<211> 710]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 74]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly 
          705                 710 
          <![CDATA[<210> 75]]>
          <![CDATA[<211> 711]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 75]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Lys 
          705                 710     
          <![CDATA[<210> 76]]>
          <![CDATA[<211> 710]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 76]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly 
          705                 710 
          <![CDATA[<210> 77]]>
          <![CDATA[<211> 711]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 77]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Lys 
          705                 710     
          <![CDATA[<210> 78]]>
          <![CDATA[<211> 710]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 78]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly 
          705                 710 
          <![CDATA[<210> 79]]>
          <![CDATA[<211> 711]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 79]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Lys 
          705                 710     
          <![CDATA[<210> 80]]>
          <![CDATA[<211> 710]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 80]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly 
          705                 710 
          <![CDATA[<210> 81]]>
          <![CDATA[<211> 719]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 81]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
                          645                 650                 655     
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg 
                  675                 680                 685             
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 715                 
          <![CDATA[<210> 82]]>
          <![CDATA[<211> 718]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 82]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
                          645                 650                 655     
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg 
                  675                 680                 685             
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710                 715             
          <![CDATA[<210> 83]]>
          <![CDATA[<211> 719]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 83]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
                          645                 650                 655     
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg 
                  675                 680                 685             
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 715                 
          <![CDATA[<210> 84]]>
          <![CDATA[<211> 718]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 84]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
                          645                 650                 655     
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg 
                  675                 680                 685             
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710                 715             
          <![CDATA[<210> 85]]>
          <![CDATA[<211> 719]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 85]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
                          645                 650                 655     
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                  675                 680                 685             
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 715                 
          <![CDATA[<210> 86]]>
          <![CDATA[<211> 718]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 86]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
                          645                 650                 655     
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                  675                 680                 685             
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710                 715             
          <![CDATA[<210> 87]]>
          <![CDATA[<211> 719]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 87]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
                          645                 650                 655     
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                  675                 680                 685             
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 715                 
          <![CDATA[<210> 88]]>
          <![CDATA[<211> 718]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 88]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
                          645                 650                 655     
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                  675                 680                 685             
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710                 715             
          <![CDATA[<210> 89]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 89]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 90]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 90]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 91]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 91]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 92]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 92]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 93]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 93]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Ser Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 94]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 94]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Ser Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 95]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 95]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Ser Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 96]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 96]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Ser Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 97]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 97]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 98]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 98]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 99]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 99]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 100]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 100]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala 
                          645                 650                 655     
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 101]]>
          <![CDATA[<211> 711]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 101]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Lys 
          705                 710     
          <![CDATA[<210> 102]]>
          <![CDATA[<211> 710]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 102]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly 
          705                 710 
          <![CDATA[<210> 103]]>
          <![CDATA[<211> 711]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 103]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Lys 
          705                 710     
          <![CDATA[<210> 104]]>
          <![CDATA[<211> 710]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 104]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly 
          705                 710 
          <![CDATA[<210> 105]]>
          <![CDATA[<211> 711]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 105]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Lys 
          705                 710     
          <![CDATA[<210> 106]]>
          <![CDATA[<211> 710]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 106]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly 
          705                 710 
          <![CDATA[<210> 107]]>
          <![CDATA[<211> 711]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 107]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Lys 
          705                 710     
          <![CDATA[<210> 108]]>
          <![CDATA[<211> 710]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 108]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly 
          705                 710 
          <![CDATA[<210> 109]]>
          <![CDATA[<211> 719]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 109]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr 
                          645                 650                 655     
          Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu 
                  675                 680                 685             
          Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 715                 
          <![CDATA[<210> 110]]>
          <![CDATA[<211> 718]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 110]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr 
                          645                 650                 655     
          Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu 
                  675                 680                 685             
          Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710                 715             
          <![CDATA[<210> 111]]>
          <![CDATA[<211> 719]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 111]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr 
                          645                 650                 655     
          Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu 
                  675                 680                 685             
          Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 715                 
          <![CDATA[<210> 112]]>
          <![CDATA[<211> 718]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 112]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr 
                          645                 650                 655     
          Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu 
                  675                 680                 685             
          Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710                 715             
          <![CDATA[<210> 113]]>
          <![CDATA[<211> 719]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 113]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr 
                          645                 650                 655     
          Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Thr Lys Glu Glu 
                  675                 680                 685             
          Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 715                 
          <![CDATA[<210> 114]]>
          <![CDATA[<211> 718]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 114]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr 
                          645                 650                 655     
          Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Thr Lys Glu Glu 
                  675                 680                 685             
          Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710                 715             
          <![CDATA[<210> 115]]>
          <![CDATA[<211> 719]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 115]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr 
                          645                 650                 655     
          Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Thr Lys Glu Glu 
                  675                 680                 685             
          Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 715                 
          <![CDATA[<210> 116]]>
          <![CDATA[<211> 718]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 116]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
                          485                 490                 495     
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                      500                 505                 510         
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                  515                 520                 525             
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
              530                 535                 540                 
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
          545                 550                 555                 560 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                          565                 570                 575     
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                      580                 585                 590         
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                  595                 600                 605             
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
              610                 615                 620                 
          Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
          625                 630                 635                 640 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr 
                          645                 650                 655     
          Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                      660                 665                 670         
          Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Thr Lys Glu Glu 
                  675                 680                 685             
          Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
              690                 695                 700                 
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710                 715             
          <![CDATA[<210> 117]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 117]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Gly Gly Gly Gly Ser Arg Pro Arg Asn Ala Leu Leu Leu Leu 
          225                 230                 235                 240 
          Ala Asp Asp Gly Gly Phe Glu Ser Gly Ala Tyr Asn Asn Ser Ala Ile 
                          245                 250                 255     
          Ala Thr Pro His Leu Asp Ala Leu Ala Arg Arg Ser Leu Leu Phe Arg 
                      260                 265                 270         
          Asn Ala Phe Thr Ser Val Ser Ser Cys Ser Pro Ser Arg Ala Ser Leu 
                  275                 280                 285             
          Leu Thr Gly Leu Pro Gln His Gln Asn Gly Met Tyr Gly Leu His Gln 
              290                 295                 300                 
          Asp Val His His Phe Asn Ser Phe Asp Lys Val Arg Ser Leu Pro Leu 
          305                 310                 315                 320 
          Leu Leu Ser Gln Ala Gly Val Arg Thr Gly Ile Ile Gly Lys Lys His 
                          325                 330                 335     
          Val Gly Pro Glu Thr Val Tyr Pro Phe Asp Phe Ala Tyr Thr Glu Glu 
                      340                 345                 350         
          Asn Gly Ser Val Leu Gln Val Gly Arg Asn Ile Thr Arg Ile Lys Leu 
                  355                 360                 365             
          Leu Val Arg Lys Phe Leu Gln Thr Gln Asp Asp Arg Pro Phe Phe Leu 
              370                 375                 380                 
          Tyr Val Ala Phe His Asp Pro His Arg Cys Gly His Ser Gln Pro Gln 
          385                 390                 395                 400 
          Tyr Gly Thr Phe Cys Glu Lys Phe Gly Asn Gly Glu Ser Gly Met Gly 
                          405                 410                 415     
          Arg Ile Pro Asp Trp Thr Pro Gln Ala Tyr Asp Pro Leu Asp Val Leu 
                      420                 425                 430         
          Val Pro Tyr Phe Val Pro Asn Thr Pro Ala Ala Arg Ala Asp Leu Ala 
                  435                 440                 445             
          Ala Gln Tyr Thr Thr Val Gly Arg Met Asp Gln Gly Val Gly Leu Val 
              450                 455                 460                 
          Leu Gln Glu Leu Arg Asp Ala Gly Val Leu Asn Asp Thr Leu Val Ile 
          465                 470                 475                 480 
          Phe Thr Ser Asp Asn Gly Ile Pro Phe Pro Ser Gly Arg Thr Asn Leu 
                          485                 490                 495     
          Tyr Trp Pro Gly Thr Ala Glu Pro Leu Leu Val Ser Ser Pro Glu His 
                      500                 505                 510         
          Pro Lys Arg Trp Gly Gln Val Ser Glu Ala Tyr Val Ser Leu Leu Asp 
                  515                 520                 525             
          Leu Thr Pro Thr Ile Leu Asp Trp Phe Ser Ile Pro Tyr Pro Ser Tyr 
              530                 535                 540                 
          Ala Ile Phe Gly Ser Lys Thr Ile His Leu Thr Gly Arg Ser Leu Leu 
          545                 550                 555                 560 
          Pro Ala Leu Glu Ala Glu Pro Leu Trp Ala Thr Val Phe Gly Ser Gln 
                          565                 570                 575     
          Ser His His Glu Val Thr Met Ser Tyr Pro Met Arg Ser Val Gln His 
                      580                 585                 590         
          Arg His Phe Arg Leu Val His Asn Leu Asn Phe Lys Met Pro Phe Pro 
                  595                 600                 605             
          Ile Asp Gln Asp Phe Tyr Val Ser Pro Thr Phe Gln Asp Leu Leu Asn 
              610                 615                 620                 
          Arg Thr Thr Ala Gly Gln Pro Thr Gly Trp Tyr Lys Asp Leu Arg His 
          625                 630                 635                 640 
          Tyr Tyr Tyr Arg Ala Arg Trp Glu Leu Tyr Asp Arg Ser Arg Asp Pro 
                          645                 650                 655     
          His Glu Thr Gln Asn Leu Ala Thr Asp Pro Arg Phe Ala Gln Leu Leu 
                      660                 665                 670         
          Glu Met Leu Arg Asp Gln Leu Ala Lys Trp Gln Trp Glu Thr His Asp 
                  675                 680                 685             
          Pro Trp Val Cys Ala Pro Asp Gly Val Leu Glu Glu Lys Leu Ser Pro 
              690                 695                 700                 
          Gln Cys Gln Pro Leu His Asn Glu Leu 
          705                 710             
          <![CDATA[<210> 118]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (281)..(281)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 118]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Gly Gly Gly Gly Ser Arg Pro Arg Asn Ala Leu Leu Leu Leu 
          225                 230                 235                 240 
          Ala Asp Asp Gly Gly Phe Glu Ser Gly Ala Tyr Asn Asn Ser Ala Ile 
                          245                 250                 255     
          Ala Thr Pro His Leu Asp Ala Leu Ala Arg Arg Ser Leu Leu Phe Arg 
                      260                 265                 270         
          Asn Ala Phe Thr Ser Val Ser Ser Gly Ser Pro Ser Arg Ala Ser Leu 
                  275                 280                 285             
          Leu Thr Gly Leu Pro Gln His Gln Asn Gly Met Tyr Gly Leu His Gln 
              290                 295                 300                 
          Asp Val His His Phe Asn Ser Phe Asp Lys Val Arg Ser Leu Pro Leu 
          305                 310                 315                 320 
          Leu Leu Ser Gln Ala Gly Val Arg Thr Gly Ile Ile Gly Lys Lys His 
                          325                 330                 335     
          Val Gly Pro Glu Thr Val Tyr Pro Phe Asp Phe Ala Tyr Thr Glu Glu 
                      340                 345                 350         
          Asn Gly Ser Val Leu Gln Val Gly Arg Asn Ile Thr Arg Ile Lys Leu 
                  355                 360                 365             
          Leu Val Arg Lys Phe Leu Gln Thr Gln Asp Asp Arg Pro Phe Phe Leu 
              370                 375                 380                 
          Tyr Val Ala Phe His Asp Pro His Arg Cys Gly His Ser Gln Pro Gln 
          385                 390                 395                 400 
          Tyr Gly Thr Phe Cys Glu Lys Phe Gly Asn Gly Glu Ser Gly Met Gly 
                          405                 410                 415     
          Arg Ile Pro Asp Trp Thr Pro Gln Ala Tyr Asp Pro Leu Asp Val Leu 
                      420                 425                 430         
          Val Pro Tyr Phe Val Pro Asn Thr Pro Ala Ala Arg Ala Asp Leu Ala 
                  435                 440                 445             
          Ala Gln Tyr Thr Thr Val Gly Arg Met Asp Gln Gly Val Gly Leu Val 
              450                 455                 460                 
          Leu Gln Glu Leu Arg Asp Ala Gly Val Leu Asn Asp Thr Leu Val Ile 
          465                 470                 475                 480 
          Phe Thr Ser Asp Asn Gly Ile Pro Phe Pro Ser Gly Arg Thr Asn Leu 
                          485                 490                 495     
          Tyr Trp Pro Gly Thr Ala Glu Pro Leu Leu Val Ser Ser Pro Glu His 
                      500                 505                 510         
          Pro Lys Arg Trp Gly Gln Val Ser Glu Ala Tyr Val Ser Leu Leu Asp 
                  515                 520                 525             
          Leu Thr Pro Thr Ile Leu Asp Trp Phe Ser Ile Pro Tyr Pro Ser Tyr 
              530                 535                 540                 
          Ala Ile Phe Gly Ser Lys Thr Ile His Leu Thr Gly Arg Ser Leu Leu 
          545                 550                 555                 560 
          Pro Ala Leu Glu Ala Glu Pro Leu Trp Ala Thr Val Phe Gly Ser Gln 
                          565                 570                 575     
          Ser His His Glu Val Thr Met Ser Tyr Pro Met Arg Ser Val Gln His 
                      580                 585                 590         
          Arg His Phe Arg Leu Val His Asn Leu Asn Phe Lys Met Pro Phe Pro 
                  595                 600                 605             
          Ile Asp Gln Asp Phe Tyr Val Ser Pro Thr Phe Gln Asp Leu Leu Asn 
              610                 615                 620                 
          Arg Thr Thr Ala Gly Gln Pro Thr Gly Trp Tyr Lys Asp Leu Arg His 
          625                 630                 635                 640 
          Tyr Tyr Tyr Arg Ala Arg Trp Glu Leu Tyr Asp Arg Ser Arg Asp Pro 
                          645                 650                 655     
          His Glu Thr Gln Asn Leu Ala Thr Asp Pro Arg Phe Ala Gln Leu Leu 
                      660                 665                 670         
          Glu Met Leu Arg Asp Gln Leu Ala Lys Trp Gln Trp Glu Thr His Asp 
                  675                 680                 685             
          Pro Trp Val Cys Ala Pro Asp Gly Val Leu Glu Glu Lys Leu Ser Pro 
              690                 695                 700                 
          Gln Cys Gln Pro Leu His Asn Glu Leu 
          705                 710             
          <![CDATA[<210> 119]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 119]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Gly Gly Gly Gly Ser Arg Pro Arg Asn Ala Leu Leu Leu Leu 
          225                 230                 235                 240 
          Ala Asp Asp Gly Gly Phe Glu Ser Gly Ala Tyr Asn Asn Ser Ala Ile 
                          245                 250                 255     
          Ala Thr Pro His Leu Asp Ala Leu Ala Arg Arg Ser Leu Leu Phe Arg 
                      260                 265                 270         
          Asn Ala Phe Thr Ser Val Ser Ser Cys Ser Pro Ser Arg Ala Ser Leu 
                  275                 280                 285             
          Leu Thr Gly Leu Pro Gln His Gln Asn Gly Met Tyr Gly Leu His Gln 
              290                 295                 300                 
          Asp Val His His Phe Asn Ser Phe Asp Lys Val Arg Ser Leu Pro Leu 
          305                 310                 315                 320 
          Leu Leu Ser Gln Ala Gly Val Arg Thr Gly Ile Ile Gly Lys Lys His 
                          325                 330                 335     
          Val Gly Pro Glu Thr Val Tyr Pro Phe Asp Phe Ala Tyr Thr Glu Glu 
                      340                 345                 350         
          Asn Gly Ser Val Leu Gln Val Gly Arg Asn Ile Thr Arg Ile Lys Leu 
                  355                 360                 365             
          Leu Val Arg Lys Phe Leu Gln Thr Gln Asp Asp Arg Pro Phe Phe Leu 
              370                 375                 380                 
          Tyr Val Ala Phe His Asp Pro His Arg Cys Gly His Ser Gln Pro Gln 
          385                 390                 395                 400 
          Tyr Gly Thr Phe Cys Glu Lys Phe Gly Asn Gly Glu Ser Gly Met Gly 
                          405                 410                 415     
          Arg Ile Pro Asp Trp Thr Pro Gln Ala Tyr Asp Pro Leu Asp Val Leu 
                      420                 425                 430         
          Val Pro Tyr Phe Val Pro Asn Thr Pro Ala Ala Arg Ala Asp Leu Ala 
                  435                 440                 445             
          Ala Gln Tyr Thr Thr Val Gly Arg Met Asp Gln Gly Val Gly Leu Val 
              450                 455                 460                 
          Leu Gln Glu Leu Arg Asp Ala Gly Val Leu Asn Asp Thr Leu Val Ile 
          465                 470                 475                 480 
          Phe Thr Ser Asp Asn Gly Ile Pro Phe Pro Ser Gly Arg Thr Asn Leu 
                          485                 490                 495     
          Tyr Trp Pro Gly Thr Ala Glu Pro Leu Leu Val Ser Ser Pro Glu His 
                      500                 505                 510         
          Pro Lys Arg Trp Gly Gln Val Ser Glu Ala Tyr Val Ser Leu Leu Asp 
                  515                 520                 525             
          Leu Thr Pro Thr Ile Leu Asp Trp Phe Ser Ile Pro Tyr Pro Ser Tyr 
              530                 535                 540                 
          Ala Ile Phe Gly Ser Lys Thr Ile His Leu Thr Gly Arg Ser Leu Leu 
          545                 550                 555                 560 
          Pro Ala Leu Glu Ala Glu Pro Leu Trp Ala Thr Val Phe Gly Ser Gln 
                          565                 570                 575     
          Ser His His Glu Val Thr Met Ser Tyr Pro Met Arg Ser Val Gln His 
                      580                 585                 590         
          Arg His Phe Arg Leu Val His Asn Leu Asn Phe Lys Met Pro Phe Pro 
                  595                 600                 605             
          Ile Asp Gln Asp Phe Tyr Val Ser Pro Thr Phe Gln Asp Leu Leu Asn 
              610                 615                 620                 
          Arg Thr Thr Ala Gly Gln Pro Thr Gly Trp Tyr Lys Asp Leu Arg His 
          625                 630                 635                 640 
          Tyr Tyr Tyr Arg Ala Arg Trp Glu Leu Tyr Asp Arg Ser Arg Asp Pro 
                          645                 650                 655     
          His Glu Thr Gln Asn Leu Ala Thr Asp Pro Arg Phe Ala Gln Leu Leu 
                      660                 665                 670         
          Glu Met Leu Arg Asp Gln Leu Ala Lys Trp Gln Trp Glu Thr His Asp 
                  675                 680                 685             
          Pro Trp Val Cys Ala Pro Asp Gly Val Leu Glu Glu Lys Leu Ser Pro 
              690                 695                 700                 
          Gln Cys Gln Pro Leu His Asn Glu Leu 
          705                 710             
          <![CDATA[<210> 120]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (281)..(281)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 120]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Gly Gly Gly Gly Ser Arg Pro Arg Asn Ala Leu Leu Leu Leu 
          225                 230                 235                 240 
          Ala Asp Asp Gly Gly Phe Glu Ser Gly Ala Tyr Asn Asn Ser Ala Ile 
                          245                 250                 255     
          Ala Thr Pro His Leu Asp Ala Leu Ala Arg Arg Ser Leu Leu Phe Arg 
                      260                 265                 270         
          Asn Ala Phe Thr Ser Val Ser Ser Gly Ser Pro Ser Arg Ala Ser Leu 
                  275                 280                 285             
          Leu Thr Gly Leu Pro Gln His Gln Asn Gly Met Tyr Gly Leu His Gln 
              290                 295                 300                 
          Asp Val His His Phe Asn Ser Phe Asp Lys Val Arg Ser Leu Pro Leu 
          305                 310                 315                 320 
          Leu Leu Ser Gln Ala Gly Val Arg Thr Gly Ile Ile Gly Lys Lys His 
                          325                 330                 335     
          Val Gly Pro Glu Thr Val Tyr Pro Phe Asp Phe Ala Tyr Thr Glu Glu 
                      340                 345                 350         
          Asn Gly Ser Val Leu Gln Val Gly Arg Asn Ile Thr Arg Ile Lys Leu 
                  355                 360                 365             
          Leu Val Arg Lys Phe Leu Gln Thr Gln Asp Asp Arg Pro Phe Phe Leu 
              370                 375                 380                 
          Tyr Val Ala Phe His Asp Pro His Arg Cys Gly His Ser Gln Pro Gln 
          385                 390                 395                 400 
          Tyr Gly Thr Phe Cys Glu Lys Phe Gly Asn Gly Glu Ser Gly Met Gly 
                          405                 410                 415     
          Arg Ile Pro Asp Trp Thr Pro Gln Ala Tyr Asp Pro Leu Asp Val Leu 
                      420                 425                 430         
          Val Pro Tyr Phe Val Pro Asn Thr Pro Ala Ala Arg Ala Asp Leu Ala 
                  435                 440                 445             
          Ala Gln Tyr Thr Thr Val Gly Arg Met Asp Gln Gly Val Gly Leu Val 
              450                 455                 460                 
          Leu Gln Glu Leu Arg Asp Ala Gly Val Leu Asn Asp Thr Leu Val Ile 
          465                 470                 475                 480 
          Phe Thr Ser Asp Asn Gly Ile Pro Phe Pro Ser Gly Arg Thr Asn Leu 
                          485                 490                 495     
          Tyr Trp Pro Gly Thr Ala Glu Pro Leu Leu Val Ser Ser Pro Glu His 
                      500                 505                 510         
          Pro Lys Arg Trp Gly Gln Val Ser Glu Ala Tyr Val Ser Leu Leu Asp 
                  515                 520                 525             
          Leu Thr Pro Thr Ile Leu Asp Trp Phe Ser Ile Pro Tyr Pro Ser Tyr 
              530                 535                 540                 
          Ala Ile Phe Gly Ser Lys Thr Ile His Leu Thr Gly Arg Ser Leu Leu 
          545                 550                 555                 560 
          Pro Ala Leu Glu Ala Glu Pro Leu Trp Ala Thr Val Phe Gly Ser Gln 
                          565                 570                 575     
          Ser His His Glu Val Thr Met Ser Tyr Pro Met Arg Ser Val Gln His 
                      580                 585                 590         
          Arg His Phe Arg Leu Val His Asn Leu Asn Phe Lys Met Pro Phe Pro 
                  595                 600                 605             
          Ile Asp Gln Asp Phe Tyr Val Ser Pro Thr Phe Gln Asp Leu Leu Asn 
              610                 615                 620                 
          Arg Thr Thr Ala Gly Gln Pro Thr Gly Trp Tyr Lys Asp Leu Arg His 
          625                 630                 635                 640 
          Tyr Tyr Tyr Arg Ala Arg Trp Glu Leu Tyr Asp Arg Ser Arg Asp Pro 
                          645                 650                 655     
          His Glu Thr Gln Asn Leu Ala Thr Asp Pro Arg Phe Ala Gln Leu Leu 
                      660                 665                 670         
          Glu Met Leu Arg Asp Gln Leu Ala Lys Trp Gln Trp Glu Thr His Asp 
                  675                 680                 685             
          Pro Trp Val Cys Ala Pro Asp Gly Val Leu Glu Glu Lys Leu Ser Pro 
              690                 695                 700                 
          Gln Cys Gln Pro Leu His Asn Glu Leu 
          705                 710             
          <![CDATA[<210> 121]]>
          <![CDATA[<211> 19]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成肽]]>
          <![CDATA[<400> 121]]>
          Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 
          1               5                   10                  15      
          Ala Tyr Ala 
          <![CDATA[<210> 122]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 122]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser 
                          645                 650                 655     
          Ser Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 123]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<400> 123]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser 
                          645                 650                 655     
          Ser Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 124]]>
          <![CDATA[<211> 714]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 124]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser 
                          645                 650                 655     
          Ser Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
          705                 710                 
          <![CDATA[<210> 125]]>
          <![CDATA[<211> 713]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成多肽]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (50)..(50)]]>
          <![CDATA[<223> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 125]]>
          Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp Gly Gly Phe Glu 
          1               5                   10                  15      
          Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro His Leu Asp Ala 
                      20                  25                  30          
          Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe Thr Ser Val Ser 
                  35                  40                  45              
          Ser Gly Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly Leu Pro Gln His 
              50                  55                  60                  
          Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His His Phe Asn Ser 
          65                  70                  75                  80  
          Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser Gln Ala Gly Val 
                          85                  90                  95      
          Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro Glu Thr Val Tyr 
                      100                 105                 110         
          Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser Val Leu Gln Val 
                  115                 120                 125             
          Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg Lys Phe Leu Gln 
              130                 135                 140                 
          Thr Gln Asp Asp Arg Pro Phe Phe Leu Tyr Val Ala Phe His Asp Pro 
          145                 150                 155                 160 
          His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr Phe Cys Glu Lys 
                          165                 170                 175     
          Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro Asp Trp Thr Pro 
                      180                 185                 190         
          Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr Phe Val Pro Asn 
                  195                 200                 205             
          Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr Thr Thr Val Gly 
              210                 215                 220                 
          Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu Leu Arg Asp Ala 
          225                 230                 235                 240 
          Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser Asp Asn Gly Ile 
                          245                 250                 255     
          Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro Gly Thr Ala Glu 
                      260                 265                 270         
          Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg Trp Gly Gln Val 
                  275                 280                 285             
          Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro Thr Ile Leu Asp 
              290                 295                 300                 
          Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe Gly Ser Lys Thr 
          305                 310                 315                 320 
          Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu Glu Ala Glu Pro 
                          325                 330                 335     
          Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His Glu Val Thr Met 
                      340                 345                 350         
          Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe Arg Leu Val His 
                  355                 360                 365             
          Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln Asp Phe Tyr Val 
              370                 375                 380                 
          Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr Ala Gly Gln Pro 
          385                 390                 395                 400 
          Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr Arg Ala Arg Trp 
                          405                 410                 415     
          Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr Gln Asn Leu Ala 
                      420                 425                 430         
          Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu Arg Asp Gln Leu 
                  435                 440                 445             
          Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val Cys Ala Pro Asp 
              450                 455                 460                 
          Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln Pro Leu His Asn 
          465                 470                 475                 480 
          Glu Leu Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
                          485                 490                 495     
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                      500                 505                 510         
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                  515                 520                 525             
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
              530                 535                 540                 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
          545                 550                 555                 560 
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                          565                 570                 575     
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                      580                 585                 590         
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                  595                 600                 605             
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
              610                 615                 620                 
          Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
          625                 630                 635                 640 
          Pro Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser 
                          645                 650                 655     
          Ser Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                      660                 665                 670         
          Leu Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe 
                  675                 680                 685             
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
              690                 695                 700                 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
          705                 710             
          <![CDATA[<210> 126]]>
          <![CDATA[<211> 5]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![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> 任何胺基酸]]>
          <![CDATA[<220>]]>
          <![CDATA[<221> MOD_RES]]>
          <![CDATA[<222> (4)..(4)]]>
          <![CDATA[<223> 任何胺基酸]]>
          <![CDATA[<400> 126]]>
          Cys Xaa Pro Xaa Arg 
          1               5   
          <![CDATA[<210> 127]]>
          <![CDATA[<211> 13]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> 人工序列之描述：合成肽]]>
          <![CDATA[<400> 127]]>
          Asn Ala Phe Thr Ser Val Ser Ser Cys Ser Pro Ser Arg 
          1               5                   10              
          <![CDATA[<210> 128]]>
          <![CDATA[<211> 13]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![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> 烷基化脲甲基Cys]]>
          <![CDATA[<400> 128]]>
          Asn Ala Phe Thr Ser Val Ser Ser Cys Ser Pro Ser Arg 
          1               5                   10              
          <![CDATA[<210> 129]]>
          <![CDATA[<211> 13]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列(Artificial Sequence)]]>
          <![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> 甲酰甘胺酸殘基]]>
          <![CDATA[<400> 129]]>
          Asn Ala Phe Thr Ser Val Ser Ser Gly Ser Pro Ser Arg 
          1               5                   10
Figure 12_A0101_SEQ_0001
Figure 12_A0101_SEQ_0002
Figure 12_A0101_SEQ_0003
Figure 12_A0101_SEQ_0004
Figure 12_A0101_SEQ_0005
Figure 12_A0101_SEQ_0006
Figure 12_A0101_SEQ_0007
Figure 12_A0101_SEQ_0008
Figure 12_A0101_SEQ_0009
Figure 12_A0101_SEQ_0010
Figure 12_A0101_SEQ_0011
Figure 12_A0101_SEQ_0012
Figure 12_A0101_SEQ_0013
Figure 12_A0101_SEQ_0014
Figure 12_A0101_SEQ_0015
Figure 12_A0101_SEQ_0016
Figure 12_A0101_SEQ_0017
Figure 12_A0101_SEQ_0018
Figure 12_A0101_SEQ_0019
Figure 12_A0101_SEQ_0020
Figure 12_A0101_SEQ_0021
Figure 12_A0101_SEQ_0022
Figure 12_A0101_SEQ_0023
Figure 12_A0101_SEQ_0024
Figure 12_A0101_SEQ_0025
Figure 12_A0101_SEQ_0026
Figure 12_A0101_SEQ_0027
Figure 12_A0101_SEQ_0028
Figure 12_A0101_SEQ_0029
Figure 12_A0101_SEQ_0030
Figure 12_A0101_SEQ_0031
Figure 12_A0101_SEQ_0032
Figure 12_A0101_SEQ_0033
Figure 12_A0101_SEQ_0034
Figure 12_A0101_SEQ_0035
Figure 12_A0101_SEQ_0036
Figure 12_A0101_SEQ_0037
Figure 12_A0101_SEQ_0038
Figure 12_A0101_SEQ_0039
Figure 12_A0101_SEQ_0040
Figure 12_A0101_SEQ_0041
Figure 12_A0101_SEQ_0042
Figure 12_A0101_SEQ_0043
Figure 12_A0101_SEQ_0044
Figure 12_A0101_SEQ_0045
Figure 12_A0101_SEQ_0046
Figure 12_A0101_SEQ_0047
Figure 12_A0101_SEQ_0048
Figure 12_A0101_SEQ_0049
Figure 12_A0101_SEQ_0050
Figure 12_A0101_SEQ_0051
Figure 12_A0101_SEQ_0052
Figure 12_A0101_SEQ_0053
Figure 12_A0101_SEQ_0054
Figure 12_A0101_SEQ_0055
Figure 12_A0101_SEQ_0056
Figure 12_A0101_SEQ_0057
Figure 12_A0101_SEQ_0058
Figure 12_A0101_SEQ_0059
Figure 12_A0101_SEQ_0060
Figure 12_A0101_SEQ_0061
Figure 12_A0101_SEQ_0062
Figure 12_A0101_SEQ_0063
Figure 12_A0101_SEQ_0064
Figure 12_A0101_SEQ_0065
Figure 12_A0101_SEQ_0066
Figure 12_A0101_SEQ_0067
Figure 12_A0101_SEQ_0068
Figure 12_A0101_SEQ_0069
Figure 12_A0101_SEQ_0070
Figure 12_A0101_SEQ_0071
Figure 12_A0101_SEQ_0072
Figure 12_A0101_SEQ_0073
Figure 12_A0101_SEQ_0074
Figure 12_A0101_SEQ_0075
Figure 12_A0101_SEQ_0076
Figure 12_A0101_SEQ_0077
Figure 12_A0101_SEQ_0078
Figure 12_A0101_SEQ_0079
Figure 12_A0101_SEQ_0080
Figure 12_A0101_SEQ_0081
Figure 12_A0101_SEQ_0082
Figure 12_A0101_SEQ_0083
Figure 12_A0101_SEQ_0084
Figure 12_A0101_SEQ_0085
Figure 12_A0101_SEQ_0086
Figure 12_A0101_SEQ_0087
Figure 12_A0101_SEQ_0088
Figure 12_A0101_SEQ_0089
Figure 12_A0101_SEQ_0090
Figure 12_A0101_SEQ_0091
Figure 12_A0101_SEQ_0092
Figure 12_A0101_SEQ_0093
Figure 12_A0101_SEQ_0094
Figure 12_A0101_SEQ_0095
Figure 12_A0101_SEQ_0096
Figure 12_A0101_SEQ_0097
Figure 12_A0101_SEQ_0098
Figure 12_A0101_SEQ_0099
Figure 12_A0101_SEQ_0100
Figure 12_A0101_SEQ_0101
Figure 12_A0101_SEQ_0102
Figure 12_A0101_SEQ_0103
Figure 12_A0101_SEQ_0104
Figure 12_A0101_SEQ_0105
Figure 12_A0101_SEQ_0106
Figure 12_A0101_SEQ_0107
Figure 12_A0101_SEQ_0108
Figure 12_A0101_SEQ_0109
Figure 12_A0101_SEQ_0110
Figure 12_A0101_SEQ_0111
Figure 12_A0101_SEQ_0112
Figure 12_A0101_SEQ_0113
Figure 12_A0101_SEQ_0114
Figure 12_A0101_SEQ_0115
Figure 12_A0101_SEQ_0116
Figure 12_A0101_SEQ_0117
Figure 12_A0101_SEQ_0118
Figure 12_A0101_SEQ_0119
Figure 12_A0101_SEQ_0120
Figure 12_A0101_SEQ_0121
Figure 12_A0101_SEQ_0122
Figure 12_A0101_SEQ_0123
Figure 12_A0101_SEQ_0124
Figure 12_A0101_SEQ_0125
Figure 12_A0101_SEQ_0126
Figure 12_A0101_SEQ_0127
Figure 12_A0101_SEQ_0128
Figure 12_A0101_SEQ_0129
Figure 12_A0101_SEQ_0130
Figure 12_A0101_SEQ_0131
Figure 12_A0101_SEQ_0132
Figure 12_A0101_SEQ_0133
Figure 12_A0101_SEQ_0134
Figure 12_A0101_SEQ_0135
Figure 12_A0101_SEQ_0136
Figure 12_A0101_SEQ_0137
Figure 12_A0101_SEQ_0138
Figure 12_A0101_SEQ_0139
Figure 12_A0101_SEQ_0140
Figure 12_A0101_SEQ_0141
Figure 12_A0101_SEQ_0142
Figure 12_A0101_SEQ_0143
Figure 12_A0101_SEQ_0144
Figure 12_A0101_SEQ_0145
Figure 12_A0101_SEQ_0146
Figure 12_A0101_SEQ_0147
Figure 12_A0101_SEQ_0148
Figure 12_A0101_SEQ_0149
Figure 12_A0101_SEQ_0150
Figure 12_A0101_SEQ_0151
Figure 12_A0101_SEQ_0152
Figure 12_A0101_SEQ_0153
Figure 12_A0101_SEQ_0154
Figure 12_A0101_SEQ_0155
Figure 12_A0101_SEQ_0156
Figure 12_A0101_SEQ_0157
Figure 12_A0101_SEQ_0158
Figure 12_A0101_SEQ_0159
Figure 12_A0101_SEQ_0160
Figure 12_A0101_SEQ_0161
Figure 12_A0101_SEQ_0162
Figure 12_A0101_SEQ_0163
Figure 12_A0101_SEQ_0164
Figure 12_A0101_SEQ_0165
Figure 12_A0101_SEQ_0166
Figure 12_A0101_SEQ_0167
Figure 12_A0101_SEQ_0168
Figure 12_A0101_SEQ_0169
Figure 12_A0101_SEQ_0170
Figure 12_A0101_SEQ_0171
Figure 12_A0101_SEQ_0172
Figure 12_A0101_SEQ_0173
Figure 12_A0101_SEQ_0174
Figure 12_A0101_SEQ_0175
Figure 12_A0101_SEQ_0176
Figure 12_A0101_SEQ_0177
Figure 12_A0101_SEQ_0178
Figure 12_A0101_SEQ_0179
Figure 12_A0101_SEQ_0180
Figure 12_A0101_SEQ_0181
Figure 12_A0101_SEQ_0182
Figure 12_A0101_SEQ_0183
Figure 12_A0101_SEQ_0184
Figure 12_A0101_SEQ_0185
Figure 12_A0101_SEQ_0186
Figure 12_A0101_SEQ_0187
Figure 12_A0101_SEQ_0188
Figure 12_A0101_SEQ_0189
Figure 12_A0101_SEQ_0190
Figure 12_A0101_SEQ_0191
Figure 12_A0101_SEQ_0192
Figure 12_A0101_SEQ_0193
Figure 12_A0101_SEQ_0194
Figure 12_A0101_SEQ_0195
Figure 12_A0101_SEQ_0196
Figure 12_A0101_SEQ_0197
Figure 12_A0101_SEQ_0198
Figure 12_A0101_SEQ_0199
Figure 12_A0101_SEQ_0200
Figure 12_A0101_SEQ_0201
Figure 12_A0101_SEQ_0202
Figure 12_A0101_SEQ_0203
Figure 12_A0101_SEQ_0204
Figure 12_A0101_SEQ_0205
Figure 12_A0101_SEQ_0206
Figure 12_A0101_SEQ_0207
Figure 12_A0101_SEQ_0208
Figure 12_A0101_SEQ_0209
Figure 12_A0101_SEQ_0210
Figure 12_A0101_SEQ_0211
Figure 12_A0101_SEQ_0212
Figure 12_A0101_SEQ_0213
Figure 12_A0101_SEQ_0214
Figure 12_A0101_SEQ_0215
Figure 12_A0101_SEQ_0216
Figure 12_A0101_SEQ_0217
Figure 12_A0101_SEQ_0218
Figure 12_A0101_SEQ_0219
Figure 12_A0101_SEQ_0220
Figure 12_A0101_SEQ_0221
Figure 12_A0101_SEQ_0222
Figure 12_A0101_SEQ_0223
Figure 12_A0101_SEQ_0224
Figure 12_A0101_SEQ_0225
Figure 12_A0101_SEQ_0226
Figure 12_A0101_SEQ_0227
Figure 12_A0101_SEQ_0228
Figure 12_A0101_SEQ_0229
Figure 12_A0101_SEQ_0230
Figure 12_A0101_SEQ_0231
Figure 12_A0101_SEQ_0232
Figure 12_A0101_SEQ_0233
Figure 12_A0101_SEQ_0234
Figure 12_A0101_SEQ_0235
Figure 12_A0101_SEQ_0236
Figure 12_A0101_SEQ_0237
Figure 12_A0101_SEQ_0238
Figure 12_A0101_SEQ_0239
Figure 12_A0101_SEQ_0240
Figure 12_A0101_SEQ_0241
Figure 12_A0101_SEQ_0242
Figure 12_A0101_SEQ_0243
Figure 12_A0101_SEQ_0244
Figure 12_A0101_SEQ_0245
Figure 12_A0101_SEQ_0246
Figure 12_A0101_SEQ_0247
Figure 12_A0101_SEQ_0248
Figure 12_A0101_SEQ_0249
Figure 12_A0101_SEQ_0250
Figure 12_A0101_SEQ_0251
Figure 12_A0101_SEQ_0252
Figure 12_A0101_SEQ_0253
Figure 12_A0101_SEQ_0254
Figure 12_A0101_SEQ_0255
Figure 12_A0101_SEQ_0256
Figure 12_A0101_SEQ_0257
Figure 12_A0101_SEQ_0258
Figure 12_A0101_SEQ_0259
Figure 12_A0101_SEQ_0260
Figure 12_A0101_SEQ_0261
Figure 12_A0101_SEQ_0262
Figure 12_A0101_SEQ_0263
Figure 12_A0101_SEQ_0264
Figure 12_A0101_SEQ_0265
Figure 12_A0101_SEQ_0266
Figure 12_A0101_SEQ_0267
Figure 12_A0101_SEQ_0268
Figure 12_A0101_SEQ_0269
Figure 12_A0101_SEQ_0270
Figure 12_A0101_SEQ_0271
Figure 12_A0101_SEQ_0272
Figure 12_A0101_SEQ_0273
Figure 12_A0101_SEQ_0274
Figure 12_A0101_SEQ_0275
Figure 12_A0101_SEQ_0276
Figure 12_A0101_SEQ_0277
Figure 12_A0101_SEQ_0278
Figure 12_A0101_SEQ_0279
Figure 12_A0101_SEQ_0280
Figure 12_A0101_SEQ_0281
Figure 12_A0101_SEQ_0282
Figure 12_A0101_SEQ_0283
Figure 12_A0101_SEQ_0284
Figure 12_A0101_SEQ_0285
Figure 12_A0101_SEQ_0286
Figure 12_A0101_SEQ_0287
Figure 12_A0101_SEQ_0288
Figure 12_A0101_SEQ_0289
Figure 12_A0101_SEQ_0290
Figure 12_A0101_SEQ_0291
Figure 12_A0101_SEQ_0292
Figure 12_A0101_SEQ_0293
Figure 12_A0101_SEQ_0294
Figure 12_A0101_SEQ_0295
Figure 12_A0101_SEQ_0296
Figure 12_A0101_SEQ_0297
Figure 12_A0101_SEQ_0298
Figure 12_A0101_SEQ_0299
Figure 12_A0101_SEQ_0300
Figure 12_A0101_SEQ_0301
Figure 12_A0101_SEQ_0302
Figure 12_A0101_SEQ_0303
Figure 12_A0101_SEQ_0304
Figure 12_A0101_SEQ_0305
Figure 12_A0101_SEQ_0306
Figure 12_A0101_SEQ_0307
Figure 12_A0101_SEQ_0308
Figure 12_A0101_SEQ_0309
Figure 12_A0101_SEQ_0310
Figure 12_A0101_SEQ_0311
Figure 12_A0101_SEQ_0312
Figure 12_A0101_SEQ_0313
Figure 12_A0101_SEQ_0314
Figure 12_A0101_SEQ_0315

Claims (85)

  1. 一種蛋白質，該蛋白質包含： a.     第一Fc多肽，該第一Fc多肽連接於第一N-磺基葡萄糖胺磺基水解酶(SGSH)胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段；及 b.    第二Fc多肽，該第二Fc多肽連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段，其中該第二Fc多肽能夠特異性結合於運鐵蛋白受體(TfR)；且其中該第二Fc多肽包含與SEQ ID NO: 37具有至少80%一致性之序列且具有根據EU編號在位置389處之Ala。
  2. 如請求項1之蛋白質，其中根據EU編號，該第二Fc多肽進一步包含：在位置380處之Glu；及在位置390處之Asn。
  3. 如請求項2之蛋白質，其中根據EU編號，該第二Fc多肽在以下位置處進一步包含： i.     在位置384處之Tyr； ii.    在位置386處之Thr； iii.   在位置387處之Glu； iv.    在位置388處之Trp； v.     在位置413處之Thr； vi.   在位置415處之Glu； vii.  在位置416處之Glu；及 viii. 在位置421處之Phe。
  4. 如請求項1至3中任一項之蛋白質，其中該蛋白質能夠轉運跨過個體之血腦障壁。
  5. 如請求項1至4中任一項之蛋白質，其中該蛋白質以約100 nM至約500 nM或視情況約150 nM至約400 nM之親和力結合於TfR。
  6. 如請求項1至5中任一項之蛋白質，其中該第二Fc多肽結合於該TfR之頂端結構域。
  7. 如請求項1至6中任一項之蛋白質，其中該蛋白質與該TfR之結合實質上不抑制運鐵蛋白與該TfR之結合。
  8. 如請求項1至7中任一項之蛋白質，其中該第一SGSH胺基酸序列包含與SEQ ID NO:58-60中之任一者具有至少80%、85%、90%或95%一致性之胺基酸序列。
  9. 如請求項8之蛋白質，其中該第一SGSH胺基酸序列包含SEQ ID NO:58-60中之任一者之胺基酸序列。
  10. 如請求項1至9中任一項之蛋白質，其中該第二SGSH胺基酸序列包含與SEQ ID NO:58-60中之任一者具有至少80%、85%、90%或95%一致性之胺基酸序列。
  11. 如請求項10之蛋白質，其中該第二SGSH胺基酸序列包含SEQ ID NO:58-60中之任一者之胺基酸序列。
  12. 如請求項1至11中任一項之蛋白質，其中該第一Fc多肽藉由肽鍵或藉由多肽連接子連接於該第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。
  13. 如請求項1至12中任一項之蛋白質，其中該第二Fc多肽藉由肽鍵或藉由多肽連接子連接於該第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。
  14. 如請求項12或13之蛋白質，其中該多肽連接子為可撓性多肽連接子。
  15. 如請求項14之蛋白質，其中該可撓性多肽連接子為富甘胺酸連接子。
  16. 如請求項12至15中任一項之蛋白質，其中該多肽連接子為GS (SEQ ID NO:7)、G 4S (SEQ ID NO:8)或(G 4S) 2(SEQ ID NO:9)。
  17. 如請求項1至16中任一項之蛋白質，其中該第一Fc多肽之N端連接於該第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。
  18. 如請求項1至16中任一項之蛋白質，其中該第一Fc多肽之C端連接於該第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。
  19. 如請求項1至18中任一項之蛋白質，其中該第二Fc多肽之N端連接於該第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。
  20. 如請求項1至18中任一項之蛋白質，其中該第二Fc多肽之C端連接於該第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。
  21. 如請求項1至16中任一項之蛋白質，其中該第一Fc多肽之N端連接於該第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段；且其中該第二Fc多肽之N端連接於該第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。
  22. 如請求項1至16中任一項之蛋白質，其中該第一Fc多肽之C端連接於該第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段；且其中該第二Fc多肽之C端連接於該第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。
  23. 如請求項1至22中任一項之蛋白質，其中該第一Fc多肽及該第二Fc多肽各自含有促進異二聚合之修飾。
  24. 如請求項23之蛋白質，其中根據EU編號，該等Fc多肽中之一者具有T366W取代且另一Fc多肽具有T366S、L368A及Y407V取代。
  25. 如請求項24之蛋白質，其中該第一Fc多肽含有T366S、L368A及Y407V取代且該第二Fc多肽含有T366W取代。
  26. 如請求項25之蛋白質，其中該第一Fc多肽包含與SEQ ID NO: 12-19及28-31中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列；且該第二Fc多肽包含與SEQ ID NO: 34-41及54-57中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  27. 如請求項24之蛋白質，其中該第一Fc多肽含有T366W取代且該第二Fc多肽含有T366S、L368A及Y407V取代。
  28. 如請求項27之蛋白質，其中該第一Fc多肽包含與SEQ ID NO: 24-27中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列；且該第二Fc多肽包含與SEQ ID NO: 48-53中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  29. 如請求項1至28中任一項之蛋白質，其中該第一Fc多肽及/或該第二Fc多肽包含天然FcRn結合位點。
  30. 如請求項1至28中任一項之蛋白質，其中該第一Fc多肽及該第二Fc多肽不具有效應功能。
  31. 如請求項1至28中任一項之蛋白質，其中該第一Fc多肽及/或該第二Fc多肽包括降低效應功能之修飾。
  32. 如請求項31之蛋白質，其中該降低效應功能之修飾為根據EU編號在位置234處之Ala及在位置235處之Ala的取代。
  33. 如請求項32之蛋白質，其中該第一Fc多肽包含與SEQ ID NO: 14-19及26-31中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  34. 如請求項33之蛋白質，其中該第一Fc多肽包含與SEQ ID NO: 14、15、28及29中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  35. 如請求項33之蛋白質，其中該第一Fc多肽包含與SEQ ID NO:18、19、30及31中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  36. 如請求項32之蛋白質，其中連接於該第一SGSH胺基酸序列之該第一Fc多肽包含與SEQ ID NO: 61-88及117-118中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  37. 如請求項36之蛋白質，其中連接於該第一SGSH胺基酸序列之該第一Fc多肽包含與SEQ ID NO: 61-68、73-76、81-84及117-118中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  38. 如請求項32至37中任一項之蛋白質，其中該第二Fc多肽包含與SEQ ID NO: 36-41及50-57中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  39. 如請求項38之蛋白質，其中該第二Fc多肽包含與SEQ ID NO: 36、37、54及55中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  40. 如請求項38之蛋白質，其中該第二Fc多肽包含與SEQ ID NO:40、41、56及57中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  41. 如請求項32至37中任一項之蛋白質，其中連接於該第二SGSH胺基酸序列之該第二Fc多肽包含與SEQ ID NO: 89-116及119-120中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  42. 如請求項41之蛋白質，其中連接於該第二SGSH胺基酸序列之該第二Fc多肽包含與SEQ ID NO: 89-96、101-104、109-112及119-120中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  43. 如請求項1至42中任一項之蛋白質，其中相對於天然Fc序列，該第一Fc多肽及/或該第二Fc多肽包含延長血清半衰期之胺基酸變化。
  44. 如請求項43之蛋白質，其中該等胺基酸變化包含根據EU編號在位置252處之Tyr、在位置254處之Thr及在位置256處之Glu的取代。
  45. 如請求項43之蛋白質，其中該等胺基酸變化包含根據EU編號在位置428處之Leu及在位置434處之Ser的取代。
  46. 如請求項43之蛋白質，其中該等胺基酸變化包含根據EU編號在位置434處之Ser或Ala的取代。
  47. 如請求項23之蛋白質，其中連接於該第一SGSH胺基酸序列之該第一Fc多肽包含SEQ ID NO: 61-68、73-76及81-84中之任一者之胺基酸序列；且其中連接於該第二SGSH胺基酸序列之該第二Fc多肽包含SEQ ID NO: 89-96、101-104及109-112中之任一者之胺基酸序列。
  48. 如請求項47之蛋白質，其中連接於該第一SGSH胺基酸序列之該第一Fc多肽包含SEQ ID NO: 61-64中之任一者之胺基酸序列；且其中連接於該第二SGSH胺基酸序列之該第二Fc多肽包含SEQ ID NO: 89-92中之任一者之胺基酸序列。
  49. 如請求項48之蛋白質，其中連接於該第一SGSH胺基酸序列之該第一Fc多肽包含SEQ ID NO: 63或64之胺基酸序列；且其中連接於該第二SGSH胺基酸序列之該第二Fc多肽包含SEQ ID NO: 91或92之胺基酸序列。
  50. 如請求項47之蛋白質，其中連接於該第一SGSH胺基酸序列之該第一Fc多肽包含SEQ ID NO: 75或76之胺基酸序列；且其中連接於該第二SGSH胺基酸序列之該第二Fc多肽包含SEQ ID NO: 103或104之胺基酸序列。
  51. 如請求項47之蛋白質，其中連接於該第一SGSH胺基酸序列之該第一Fc多肽包含SEQ ID NO: 83或84之胺基酸序列；且其中連接於該第二SGSH胺基酸序列之該第二Fc多肽包含SEQ ID NO: 111或112之胺基酸序列。
  52. 如請求項47之蛋白質，其中連接於該第一SGSH胺基酸序列之該第一Fc多肽包含SEQ ID NO: 65-68中之任一者之胺基酸序列；且其中連接於該第二SGSH胺基酸序列之該第二Fc多肽包含SEQ ID NO: 93-96中之任一者之胺基酸序列。
  53. 如請求項52之蛋白質，其中連接於該第一SGSH胺基酸序列之該第一Fc多肽包含SEQ ID NO: 67或68之胺基酸序列；且其中連接於該第二SGSH胺基酸序列之該第二Fc多肽包含SEQ ID NO: 95或96之胺基酸序列。
  54. 如請求項23之蛋白質，其中連接於該第一SGSH胺基酸序列之該第一Fc多肽包含SEQ ID NO: 118之胺基酸序列；且其中連接於該第二SGSH胺基酸序列之該第二Fc多肽包含SEQ ID NO: 120之胺基酸序列。
  55. 如請求項1至54中任一項之蛋白質，其中與在缺乏該第一Fc多肽及該第二Fc多肽之情況下該SGSH胺基酸序列之吸收相比或與未對該第二Fc多肽進行促成TfR結合之修飾的情況下該SGSH酶之吸收相比，該SGSH胺基酸序列在腦中之吸收大至少十倍。
  56. 如請求項1至55中任一項之蛋白質，其中該第一Fc多肽未經修飾以結合於血腦障壁(BBB)受體且該第二Fc多肽經修飾以特異性結合於TfR。
  57. 如請求項1至56中任一項之蛋白質，其中該蛋白質不包括免疫球蛋白重鏈及/或輕鏈可變區序列或其抗原結合部分。
  58. 一種多肽，該多肽包含連接於SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段之Fc多肽，其中該Fc多肽i)能夠特異性結合於運鐵蛋白受體(TfR)；ii)包含與SEQ ID NO: 37具有至少90%一致性之序列；iii)具有一或多個促進其與另一Fc多肽進行異二聚合之修飾；且iv)具有根據EU編號在位置389處之Ala。
  59. 如請求項58之多肽，其中根據EU編號，該Fc多肽進一步包含：在位置380處之Glu；及在位置390處之Asn。
  60. 如請求項59之多肽，其中根據EU編號，該Fc多肽在以下位置處進一步包含： i.     在位置384處之Tyr； ii.    在位置386處之Thr； iii.   在位置387處之Glu； iv.    在位置388處之Trp； v.     在位置413處之Thr； vi.   在位置415處之Glu； vii.  在位置416處之Glu；及 viii. 在位置421處之Phe。
  61. 如請求項58至60中任一項之多肽，其中該Fc多肽藉由肽鍵或藉由多肽連接子連接於該SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段。
  62. 如請求項61之多肽，該多肽為自N端至C端包含以下之融合多肽：該SGSH胺基酸序列、SGSH變異體胺基酸序列或催化活性片段；該多肽連接子；及該Fc多肽。
  63. 如請求項61之多肽，該多肽為自N端至C端包含以下之融合多肽：該Fc多肽；該多肽連接子；及該SGSH胺基酸序列、SGSH變異體胺基酸序列或催化活性片段。
  64. 如請求項58至63中任一項之多肽，其中根據EU編號，該Fc多肽含有T366S、L368A及Y407V取代。
  65. 如請求項64之多肽，其中該多肽包含與SEQ ID NO:97-100、105-108及113-116中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  66. 如請求項58至63中任一項之多肽，其中該Fc多肽含有T366W取代。
  67. 如請求項66之多肽，其中該多肽包含與SEQ ID NO:89-96、101-104、109-112及119-120中之任一者具有至少80%、85%、90%、95%或100%一致性之胺基酸序列。
  68. 一種蛋白質，其包含如請求項58至67中任一項之多肽及另一Fc多肽。
  69. 一種醫藥組合物，該醫藥組合物包含如請求項1至57及68中任一項之蛋白質或如請求項58至67中任一項之多肽及醫藥學上可接受之賦形劑。
  70. 一種多核苷酸，該多核苷酸包含編碼如請求項58至67中任一項之多肽的核酸序列。
  71. 一種載體，該載體包含如請求項70之多核苷酸。
  72. 一種宿主細胞，該宿主細胞包含如請求項70之多核苷酸或如請求項71之載體。
  73. 如請求項72之宿主細胞，該宿主細胞進一步包括包含編碼該另一Fc多肽之核酸序列的多核苷酸。
  74. 一種用於產生包含連接於SGSH胺基酸序列、SGSH變異體胺基酸序列或催化活性片段之Fc多肽之多肽的方法，該方法包括在表現由如請求項70之多核苷酸編碼之該多肽的條件下培養宿主細胞。
  75. 一種多核苷酸對，該多核苷酸對包含編碼如請求項1至57中之任一項中所述的連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段之第一Fc多肽的第一核酸序列；及編碼如請求項1至57中之任一項中所述的連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段之第二Fc多肽的第二核酸序列。
  76. 一或多種載體，其包含如請求項75之多核苷酸對。
  77. 一種宿主細胞，其包含如請求項75之多核苷酸雙或如請求項76之一或多種載體。
  78. 一種用於產生蛋白質之方法，該蛋白質包含連接於第一SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段之第一Fc多肽及連接於第二SGSH胺基酸序列、SGSH變異體胺基酸序列或其催化活性片段之第二Fc多肽，該方法包括在表現如請求項75之多核苷酸對的條件下培養宿主細胞。
  79. 一種治療聖菲利浦症候群A (Sanfilippo syndrome A)之方法，該方法包括向有需要之患者投與如請求項1至57及68中任一項之蛋白質或如請求項58至67中任一項之多肽。
  80. 如請求項1至57及68中任一項之蛋白質或如請求項58至67中任一項之多肽，其用於治療有需要之患者之聖菲利浦症候群A。
  81. 一種如請求項1至57及68中任一項之蛋白質或如請求項58至67中任一項之多肽的用途，其用於製備供治療有需要之患者之聖菲利浦症候群A用的藥劑。
  82. 一種減少患有聖菲利浦症候群A之患者中之毒性代謝產物積聚的方法，該方法包括向該患者投與如請求項1至57及68中任一項之蛋白質或如請求項58至67中任一項之多肽。
  83. 如請求項1至57及68中任一項之蛋白質或如請求項58至67中任一項之多肽，其用於減少患有聖菲利浦症候群A之患者中之毒性代謝產物積聚。
  84. 一種如請求項1至57及68中任一項之蛋白質或如請求項58至67中任一項之多肽的用途，其用於製備供減少患有聖菲利浦症候群A之患者中之毒性代謝產物積聚用的藥劑。
  85. 如請求項82至84中任一項之方法、蛋白質或用途，其中該毒性代謝產物包含硫酸乙醯肝素衍生之寡醣。
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Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK3583120T5 (da) 2017-02-17 2024-09-02 Denali Therapeutics Inc Modificerede transferrinreceptorbindende polypeptider
CA3076369A1 (en) 2017-10-02 2019-04-11 Denali Therapeutics Inc. Fusion proteins comprising enzyme replacement therapy enzymes
EP4081536A1 (en) 2019-12-23 2022-11-02 Denali Therapeutics Inc. Progranulin variants

Family Cites Families (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5863782A (en) 1995-04-19 1999-01-26 Women's And Children's Hospital Synthetic mammalian sulphamidase and genetic sequences encoding same
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
EP1463512B1 (en) 2002-01-11 2014-05-28 biOasis Technologies Inc. Use of p97 as an enzyme delivery system for the delivery of therapeutic lysosomal enzymes
US20050142141A1 (en) 2002-11-27 2005-06-30 Pardridge William M. Delivery of enzymes to the brain
AU2003286870A1 (en) 2003-06-05 2005-01-04 Salk Institute For Biological Studies Targeting polypeptides to the central nervous system
CN105274072A (zh) 2008-01-18 2016-01-27 生物马林药物股份有限公司 制备活性高度磷酸化人溶酶体硫酸酯酶及其应用
EP2394667A1 (en) 2010-06-10 2011-12-14 Laboratorios Del Dr. Esteve, S.A. Vectors and sequences for the treatment of diseases
PT3626257T (pt) 2010-06-25 2021-11-12 Shire Human Genetic Therapies Métodos e composições de arilsulfatase a para a administração no snc
MX2013000320A (es) 2010-06-25 2013-06-05 Shire Human Genetic Therapies Composiciones y metodos para suministro al sistema nervioso central de heparan n-sulfatasa.
HUE041335T2 (hu) 2011-03-29 2019-05-28 Roche Glycart Ag Antitest FC-variánsok
US8722019B2 (en) 2011-08-05 2014-05-13 Bioasis Technologies, Inc. P97 fragments with transfer activity
AU2013296557B2 (en) 2012-07-31 2019-04-18 Bioasis Technologies Inc. Dephosphorylated lysosomal storage disease proteins and methods of use thereof
TR201909156T4 (tr) 2012-08-29 2019-07-22 Hoffmann La Roche Kan beyin bariyeri mekiği.
EP2970433B1 (en) 2013-03-13 2019-09-18 Bioasis Technologies Inc. Fragments of p97 and uses thereof
US20160184458A1 (en) 2013-03-14 2016-06-30 Shire Human Genetic Therapies, Inc. Mrna therapeutic compositions and use to treat diseases and disorders
EP3730516A1 (en) 2013-07-22 2020-10-28 Armagen, Inc. Methods and compositions for increasing enzyme activity in the cns
MX368947B (es) 2014-04-01 2019-10-22 Swedish Orphan Biovitrum Ab Publ Sulfamidasa modificada y su producción.
ES2749383T3 (es) 2014-11-06 2020-03-20 Hoffmann La Roche Variantes de la región Fc con unión al FcRn modificada y procedimientos de uso
EP3221361B1 (en) 2014-11-19 2021-04-21 Genentech, Inc. Anti-transferrin receptor / anti-bace1 multispecific antibodies and methods of use
KR20180020277A (ko) 2015-06-24 2018-02-27 제이씨알 파마 가부시키가이샤 혈액뇌관문을 통과하는 항인간 트랜스페린 수용체 항체
HUE057952T2 (hu) 2015-06-24 2022-06-28 Hoffmann La Roche Anti-transzferrin receptor antitestek testreszabott affinitással
DK3386534T3 (da) 2015-12-08 2020-11-30 Regeneron Pharma Sammensætninger og fremgangsmåder til internalisering af enzymer
AR107483A1 (es) 2016-01-29 2018-05-02 Hanmi Pharm Ind Co Ltd Conjugado de enzimas terapéuticas
AU2017222620B2 (en) 2016-02-24 2022-06-16 Biomarin Pharmaceutical Inc. Targeted therapeutic lysosomal enzyme fusion proteins, associated formulations and uses thereof
AU2017311040B2 (en) 2016-08-06 2023-08-31 Ossianix, Inc. In vivo methods for selecting peptides that cross the blood brain barrier, related compositions and methods of use
MX2019002252A (es) 2016-08-25 2019-07-04 Japan Chem Res Metodo para producir una proteina de fusion de anticuerpo.
EP3556399A1 (en) 2016-12-19 2019-10-23 Hanmi Pharm. Co., Ltd. Brain targeting long-acting protein conjugate
BR112019009316A2 (pt) 2016-12-26 2019-08-06 Japan Chem Res anticorpo antirreceptor de transferrina humana, proteína de fusão, fragmento de dna, vetor de expressão, célula de mamífero, complexo de composto farmacologicamente ativo e de anticorpo antirreceptor de transferrina humana, usos do anticorpo antirreceptor de transferrina humana e da proteína de fusão, e, métodos para tratamento de um distúrbio do sistema nervoso central e de uma doença do sistema nervoso central que acompanha a doença de pompe, a síndrome de hurler ou a síndrome de hurler-scheie.
KR102471458B1 (ko) 2016-12-28 2022-11-25 제이씨알 파마 가부시키가이샤 동결건조 제제
MX2019009817A (es) 2017-02-17 2019-11-21 Denali Therapeutics Inc Anticuerpos anti-tau y metodos de uso de los mismos.
DK3583120T5 (da) 2017-02-17 2024-09-02 Denali Therapeutics Inc Modificerede transferrinreceptorbindende polypeptider
SG11201907419PA (en) 2017-02-17 2019-09-27 Denali Therapeutics Inc Transferrin receptor transgenic models
GB201702863D0 (en) 2017-02-22 2017-04-05 Evox Therapeutics Ltd Improved loading of EVs with therapeutic proteins
CN111094559A (zh) 2017-07-07 2020-05-01 韩美药品株式会社 新型治疗酶融合蛋白及其用途
HUE063021T2 (hu) 2017-08-10 2023-12-28 Denali Therapeutics Inc Mesterségesen elõállított transzferrin receptor-kötõ polipeptidek
CA3076369A1 (en) 2017-10-02 2019-04-11 Denali Therapeutics Inc. Fusion proteins comprising enzyme replacement therapy enzymes
WO2019094608A1 (en) 2017-11-08 2019-05-16 Denali Therapeutics Inc. Anti-bace1 antibodies and methods of use thereof
BR112020012346A2 (pt) 2017-12-22 2020-11-24 Hanmi Pharm. Co., Ltd. proteína de fusão enzimática terapêutica tendo uma nova estrutura e uso da mesma
CN111741977A (zh) 2018-01-10 2020-10-02 戴纳立制药公司 转铁蛋白受体结合性多肽和其用途
WO2019145500A1 (en) 2018-01-26 2019-08-01 Swedish Orphan Biovitrum Ab (Publ) Method of treatment
MX2020012518A (es) 2018-06-18 2021-02-16 Denali Therapeutics Inc Proteinas de fusion que comprenden progranulina.
EP3850007A4 (en) 2018-08-16 2022-08-10 Denali Therapeutics Inc. MODIFIED B-SPECIFIC PROTEINS
JP2021534220A (ja) 2018-08-22 2021-12-09 デナリ セラピューティクス インコーポレイテッドDenali Therapeutics Inc. 抗ｈｅｒ２ポリペプチド及びそれらの使用の方法
MX2021011612A (es) 2019-04-03 2021-12-10 Denali Therapeutics Inc Formulaciones de moleculas proteicas que comprenden iduronato 2-sulfatasa.
TW202138384A (zh) 2019-12-23 2021-10-16 美商戴納立製藥公司 顆粒蛋白前體變異體
EP4081536A1 (en) 2019-12-23 2022-11-02 Denali Therapeutics Inc. Progranulin variants
WO2021146256A1 (en) 2020-01-13 2021-07-22 Denali Therapeutics Inc. Anti-trem2 antibodies and methods of use thereof
EP4090682A1 (en) 2020-01-13 2022-11-23 Denali Therapeutics Inc. Anti-trem2 antibodies and methods of use thereof
EP4100419A4 (en) 2020-02-07 2024-05-29 Denali Therapeutics Inc. METHODS OF TREATING HUNTER SYNDROME
BR112022016232A2 (pt) 2020-02-19 2022-11-16 Denali Therapeutics Inc Proteínas biespecíficas anti-her2 manipuladas

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