TW202305138A - Cd8特異性抗體構築體及其組合物 - Google Patents
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Abstract
本文揭示了特異性結合人類CD8之抗體或其抗原結合片段。亦揭示了包含用於靶向及轉導表現CD8之細胞之亨尼帕病毒糖蛋白G及CD8抗體之融合蛋白。亦揭示了含有該等融合蛋白之病毒載體及其他組合物,以及使用該等融合蛋白之方法。
Description
本揭示係關於特異性結合人類CD8之抗體或其抗原結合片段。亦揭示了包含用於靶向及轉導表現CD8之細胞之亨尼帕病毒糖蛋白G及CD8抗體或其抗原結合片段之融合蛋白。亦揭示了含有融合蛋白、抗體或其抗原結合片段之病毒載體及其他組合物,以及使用融合蛋白、抗體或其抗原結合片段之方法。
CD8 (分化簇8)係用作T細胞受體(TCR)之共受體之跨膜糖蛋白。CD8在針對外部及內部挑戰兩者之免疫反應中發揮多種功能。在T細胞中,CD8共受體主要用於結合主要組織相容性複合體(MHC)分子以促進T細胞信號傳導並輔助細胞毒性T細胞抗原相互作用。雖然其主要在細胞毒性T細胞之表面表現,但CD8共受體亦可在自然殺手細胞、皮質胸腺細胞及樹突狀細胞上發現。CD8分子亦用作細胞毒性T細胞群之標記物。
CD8糖蛋白存在兩種亞型,即α及β,並且每種均由不同之基因編碼。為了發揮作用,CD8形成二聚體,由一對CD8鏈組成。CD8之最常見形式由CD8-α及CD8-β鏈構成。CD8-α鏈之同源二聚體亦在一些細胞上表現。各CD8鏈之分子量為約34kDa。
T淋巴細胞係基因療法中的主要目標之一,自從嵌合抗原受體(CAR)T細胞進入臨床以來更是如此。目前用於T細胞工程改造之方法主要依賴於離體基因轉移方法。在自健康供體或患者分離出淋巴細胞後,淋巴細胞被活化並且隨後藉由慢病毒載體轉導。然後將修飾之淋巴細胞擴增並用於功能性活體內測定或用於活體內應用。然而,T淋巴細胞之離體修飾亦具有其缺點。整個程序之複雜性、製造過程之成本以及長時間之離體培養會對最終產品之品質產生負面影響。需要使用活體內遞送平台來改良T淋巴細胞工程之方法。
使用病毒載體之融合糖蛋白之活體內遞送平台已被證明有利於靶向、結合及轉導感興趣之細胞。然而,某些融合糖蛋白可能不夠穩定或在病毒載體表面表現不够。因此,需要改良之融合糖蛋白及含有此等糖蛋白之病毒載體。所提供之揭示內容解决了此需求。
本揭示提供了特異性結合CD8α或CD8β之抗體或其抗原結合片段,該抗體或其抗原結合片段包含某些重鏈互補決定區(HCDR1、HCDR2及HCDR3)及/或輕鏈互補決定區(LCDR1、LCDR2及LCDR3)。另一個實施例係特異性結合CD8α或CD8β之抗體或抗原結合片段,該抗體或其抗原結合片段包含某些重(VH)鏈及/或輕(VL)鏈可變區。本揭示同樣提供了包含抗CD8α或CD8β抗體或其抗原結合片段之分離的聚核苷酸、載體及宿主細胞。
本揭示亦提供了融合蛋白,該融合蛋白包含亨尼帕病毒糖蛋白G (G蛋白)或其生物活性部分以及至少一種揭示之CD8抗體或抗原結合片段,其中抗體或抗原結合片段與G蛋白或其生物活性部分之C末端融合。
本揭示亦提供了病毒載體,該病毒載體包含亨尼帕病毒F蛋白分子或其生物活性部分、亨尼帕病毒包膜糖蛋白G (G蛋白)或其生物活性部分以及至少一種揭示之CD8抗體或其抗原結合片段,其中該抗體或其抗原結合片段連接至G蛋白或其生物活性部分之C末端。
本揭示同樣係關於使用所揭示之病毒載體選擇性調節及轉導CD8+ T細胞之方法。亦揭示了向個體遞送外源藥劑之方法,其包含向該個體投與所揭示之病毒載體,其中該病毒載體進一步包含外源藥劑。本揭示亦係關於治療個體之癌症之方法,其包含向該個體投與所揭示之病毒載體。
序列表
本申請含有以ASCII格式以電子方式提交的序列表,並據此全文以引用方式併入。該ASCII副本創建於2022年4月6日,命名為15147_0005-00304_SL.txt,並且大小為760,000位元組。
除非另有定義,否則本文所用之所有專業術語、符號及其他技術及科學術語或術語旨在具有與要求保護之主題所屬領域之一般技術人員通常理解之相同的含義。在一些情況下,為了清楚及/或為了便於參考,本文定義了具有普遍理解含義之術語,並且本文中包括之此類定義不一定被解釋為表示與此項技術中通常所理解之內容的實質性差異。
除非另有定義,否則本文所用之所有技術及科學術語、首字母縮略詞及縮寫具有與本揭示所屬領域之一般技術人員通常所理解之相同的含義。除非另有說明,否則化學及生物化學名稱之縮寫及符號係根據IUPAC-IUB命名法。除非另有說明,否則所有數值範圍均包括限定範圍之值以及其間的所有整數值。
如本文所用,冠詞「一(a/an)」係指冠詞之語法對象之一個或多於一個(亦即至少一個)。舉例而言,「元件」意指一個元件或多於一個元件。
如本文所用,術語「約」將被一般熟習此項技術者理解並且將在一定程度上隨其使用的上下文而變化。在一些實施例中,當提及可量測值(諸如量、時間持續時間等)時,術語「約」意指涵蓋基於進行此類量測之標準誤差之領域公認之變化。在一些實施例中,當提及此類值時,術語「約」意指涵蓋從指定值有±20%或±10%、更較佳±5%、甚至更較佳±1%、並且仍更較佳±0.1%之變化,因為此類變化適合於執行所揭示之方法。
如本文所用,「CD8」或「分化簇8」係指跨膜糖蛋白,其係T細胞之子類(其包括細胞毒性T細胞)之特定標記物。CD8組裝為CD8α (「CD8α」或「CD8A」)及CD8β(「CD8β」或「CD8B」)次單元之異源二聚體(「CD8αβ」或「CD8AB」)或CD8α同源二聚體(「CD8αα」或「CD8AA」)。組裝之二聚體CD8複合體與T細胞受體(TCR)一起充當共受體,以識別MHC I類細胞之抗原呈現。CD8在T細胞發展及成熟T細胞之活化中起作用。
如本文所用,「親和力」係指分子(例如,抗體)之單個結合位點及其結合搭配物(例如,抗原)之間的非共價相互作用總和之強度。分子對其搭配物之親和力通常可由平衡解離常數(K
D)(或其逆平衡締合常數K
A)表示。親和力可藉由此項技術已知之常見方法進行量測,包括本文所描述之方法。參見例如Pope M.E.、Soste M.V.、Eyford B.A.、Anderson N.L.、Pearson T.W.,(2009)
J. Immunol. Methods,341(1-2):86-96,以及其中描述之方法。
如本文所用,「抗體」廣義上意指並包括免疫球蛋白分子,此等免疫球蛋白分子包括單株抗體(包括鼠類抗體、人類抗體、人源化抗體及嵌合抗體)、抗體片段、由至少兩種完整抗體或抗體片段形成之雙特異性或多特異性抗體,二聚、四聚或多聚抗體,單鏈抗體,以及包含所需特異性之抗原識別位點之免疫球蛋白分子之任何其他修飾構型。
根據重鏈恆定域胺基酸序列,可將免疫球蛋白指定為五大類,亦即IgA、IgD、IgE、IgG及IgM。IgA及IgG進一步細分為IgA1、IgA2、IgG1、IgG2、IgG3及IgG4。基於恆定域之胺基酸序列,可將任何脊椎物種之抗體輕鏈指定為兩種完全不同之類型即(K)及(A)中的一種。
如本文所用,「抗原結合片段」或「抗體片段」係指保持重鏈及/或輕鏈抗原結合位點之免疫球蛋白分子之一部分,諸如重鏈互補決定區(HCDR) 1 (HCDR1)、2 (HCDR2)及3 (HCDR3)、輕鏈互補決定區(LCDR) 1 (LCDR1)、2 (LCDR2)及3 (LCDR3)、重鏈可變區(VH)或輕鏈可變區(VL)。抗體片段包括Fab片段(由VL或VH組成之單價片段);F(ab) 2片段(包含藉由鉸鏈區處之二硫鍵連接之兩個Fab片段之二價片段);Fd片段,其由VH及CH1域組成;Fv片段,其由單臂抗體之VL及VH域組成;dAb片段,其由VH域組成;及可變域(VHH),其來自例如人類或駱駝科來源。VH域及VL域可被改造並經由合成接頭連接在一起以形成各種類型之單鏈抗體設計,其中在VH域及VL域由單獨的單鏈抗體構築體表現之情況下,VH/VL域在分子內或分子間配對,以形成單價抗原結合位點,諸如單鏈Fv (scFv)或雙價抗體。此等抗體片段使用熟知技術獲得,並且片段以與完整抗體相同之方式表徵。
抗體可變區由間雜三個「抗原結合位點」之「構架」區組成。使用各種術語來定義抗原結合位點,包括例如(i)三個在VH (HCDR1、HCDR2、HCDR3)中並且三個在VL(LCDR1、LCDR2、LCDR3)中的互補決定區(CDR) (Wu及Kabat,
J Exp Med,132:211-50, 1970;Kabat等人,Sequences of Proteins of Immunological Interest,第5版,Public Health Service,National Institutes of Health,Bethesda,Md.,1991)以及(ii)三個在VH (H1、H2、H3)中並且三個在VL (L1、L2、L3)中之「高變區」「HVR」或「HV」(Chothia及Lesk,
Mol Biol,196:901-17, 1987)。其他術語包括「IMGT-CDR」(Lefranc等人,
Dev Comparat Immunol27:55-77, 2003)及「特異性決定殘基使用」(SDRU) (
Almagro Mol Recognit, 17:132-43, 2004)。國際免疫遺傳學(IMGT)數據庫(http://www_imgt org)提供了抗原結合位點之標準化編號及定義。CDR、HV及IMGT描述之間的對應關係在Lefranc等人,
Dev Comparat Immunol27:55-77, 2003.中有所描述。
術語「構架」或「FR」或「構架序列」係指除定義為抗原結合位點之彼等序列之外的可變區之其餘序列。因為抗原結合位點可由如上所述之各種術語定義,因此構架之確切胺基酸序列取決於如何定義抗原結合位點。
術語「CDR」表示如由熟習此項技術者之至少一種鑑定方式所定義之互補決定區。給定CDR或FR之精確胺基酸序列邊界可容易地使用許多熟知方案中的任一種來確定,包括如下所描述之方案:Kabat等人,(1991)「Sequences of Proteins of Immunological Interest」,第5版,Public Health Service,National Institutes of Health,Bethesda,MD (「Kabat」編號方案);Al-Lazikani等人,(1997) JMB 15 273,927-948 (「Chothia」編號方案);MacCallum等人,J. Mol. Biol. 262:732-745 (1996),「Antibody-antigen interactions: Contact analysis and binding site topography」,J. Mol. Biol. 262, 732-745」(「Contact」編號方案);Lefranc MP等人,「IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains」,Dev Comp Immunol,2003年1月,27(1):55-77 (「IMGT」編號方案);Honegger A及Plückthun A,「Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool」,J Mol Biol,2001年6月8日,309(3):657-70 (「Aho」編號方案);以及Martin等人,「Modeling antibody hypervariable loops: a combined algorithm」,PNAS, 1989, 86(23):9268-9272 (「AbM」編號方案)。
給定CDR或FR之邊界可根據用於鑑定之方案而變化。例如,Kabat方案基於結構比對,而Chothia方案基於結構資訊。Kabat及Chothia方案兩者之編號基於最常見之抗體區域序列長度,其中插入藉由插入字母例如「30a」表示,並且在一些抗體中出現缺失。此兩種方案將某些插入及缺失(「indels」)放置在不同之位置,從而導致編號不同。Contact方案基於對複雜晶體結構之分析,並且在許多方面與Chothia編號方案相似。AbM方案係基於Oxford Molecular之AbM抗體建模軟體使用之Kabat及Chothia定義之間的折衷方案。
在一些實施例中,CDR可根據Chothia編號方案,Kabat編號方案,IMGT編號方案,Kabat、IMGT及Chothia之組合,AbM定義及/或contact定義中的任一種來定義。sdAb可變域包含三個CDR,指定為CDR1、CDR2及CDR3。下
表 1列出了分別藉由Kabat、Chothia、AbM及Contact方案鑑定之CDR-H1、CDR-H2、CDR-H3之例示性位置邊界。對於CDR-H1,使用Kabat及Chothia編號方案兩者列出殘基編號。FR位於CDR之間,例如FR-H1位於CDR-H1之前,FR-H2位於CDR-H1及CDR-H2之間,FR-H3位於CDR-H2及CDR-H3之間,以此類推。需注意,因為所示之Kabat編號方案在H35A及H35B處放置插入,因此當使用所示Kabat編號慣例編號時,Chothia CDR-H1環之末端在H32及H34之間變化,其取決於環之長度。
1- Kabat等人,(1991),「Sequences of Proteins of Immunological Interest」,第5版,Public Health Service,National Institutes of Health,Bethesda,MD
2- Al-Lazikani等人,(1997) JMB 273,927-948。
表 1.根據各種編號方案之CDR之邊界。 | ||||
CDR | Kabat | Chothia | AbM | Contact |
CDR-H1(Kabat編號 1) | H31--H35B | H26--H32..34 | H26--H35B | H30--H35B |
CDR-H1(Chothia編號 2) | H31--H35 | H26--H32 | H26--H35 | H30--H35 |
CDR-H2 | H50--H65 | H52--H56 | H50--H58 | H47--H58 |
CDR-H3 | H95--H102 | H95--H102 | H95--H102 | H93--H101 |
因此,除非另有指明,否則給定抗體或其區域(諸如其可變區)之「CDR」或「互補決定區」或單獨指定之CDR (例如CDR-H1、CDR-H2、CDR-H3)應理解為涵蓋如由前述方案中任一者所定義的(或特定的)互補決定區。例如,在說明特定CDR (例如CDR-H3)含有給定sdAb胺基酸序列中對應CDR之胺基酸序列之情況下,應當理解,此類CDR在sdAb內具有對應CDR (例如CDR-H3)之序列,如任何前述方案所定義。應當理解,任何抗體,諸如sdAb,包括CDR,並且可根據任何其他前述編號方案或技術人員已知之其他編號方案來鑑定。
如本文所用,「Fv」係指含有完整抗原識別及抗原結合位點之最小抗體片段。該區域由一個重鏈及一個輕鏈可變域之二聚體以緊密、非共價締合之方式組成。正是在此構型中,每個可變域之三個高變區相互作用,以在VH-VL二聚體之表面定義了抗原結合位點。總之,六個高變區賦予抗體抗原結合特異性。然而,即使係單個可變域(或僅包含對抗原具有特異性之三個高變區之Fv的一半)亦可能具有識別並結合抗原之能力,儘管親和力低於整個結合位點。
如本文所用,「單鏈Fv」或「scFv」抗體片段包含抗體之VH及VL域,其中此等域存在於單個多肽鏈中。較佳地,Fv多肽進一步包含VH及VL域之間的多肽接頭,該多肽接頭使得scFv能夠形成用於抗原結合之期望結構。關於scFv之綜述參見Pluckthun,The Pharmacology of Monoclonal Antibodies,第113卷,Rosenburg及Moore編輯,Springer-Verlag,New York,第269-315頁(1994)。
如本文所用,「VHH」或「VHH抗體」係指由IgG抗體之重鏈之可變區組成之單域抗體。例如,術語「VHH」及「VHH抗體」可指由駱駝科哺乳動物(例如美洲鴕、駱駝及羊駝)產生之重鏈IgG (hcIgG)分子之抗原結合域。
如本文所用,術語「特異性結合」目標分子(諸如抗原)意指結合分子(諸如單域抗體)與特定目標分子之反應或締合比其與替代分子之反應或締合更頻繁、更迅速、持續時間更長及/或親和力更大。若結合分子(諸如sdAb或scFv)與目標分子結合比其與其他分子結合具有更大之親和力、親合力、更容易及/或持續時間更長,則結合分子與目標分子「特異性結合」。應當理解,與第一目標特異性結合之結合分子(諸如sdAb或scFv)可以或可以不與第二目標特異性結合。因此,「特異性結合」不一定需要(儘管其可包括)排他性結合。
如本文所用,關於肽、多肽或抗體序列之「胺基酸序列同一性百分比(%)」及「同源性」可互換使用,並且定義為候選序列中與另一個肽或多肽序列中之胺基酸殘基相同之胺基酸殘基之百分比,在比對序列並引入缺口(若需要)以實現最大之序列同一性百分比之後,不考慮任何保守置換作為序列同一性之一部分。出於確定胺基酸序列同一性百分比的目的進行的比對可以本領域技術範圍內的多種方式實現,例如使用可公開獲得之電腦軟體,諸如BLAST、BLAST-2、ALIGN或MEGALIGN (DNASTAR)軟體。熟習此項技術者可確定用於量測比對之合適參數,包括在所比較序列之全長上實現最大比對所需之任何演算法。
胺基酸取代可包括但不限於用另一個胺基酸置換多肽中的一個胺基酸。例示性取代示於
表 2中。可以將胺基酸取代引入感興趣之抗體,並篩選產物以獲得期望活性,例如,保持/改良之結合。
表 2
原始殘基 | 例示性取代 |
Ala(A) | Val;Leu;Ile |
Arg(R) | Lys;Gln;Asn |
Asn(N) | Gln;His;Asp,Lys;Arg |
Asp(D) | Glu;Asn |
Cys(C) | Ser;Ala |
Gln(Q) | Asn;Glu |
Glu(E) | Asp;Gln |
Gly(G) | Ala |
His(H) | Asn;Gln;Lys;Arg |
Ile(I) | Leu;Val;Met;Ala;Phe;正白胺酸 |
Leu(L) | 正白胺酸;Ile;Val;Met;Ala;Phe |
Lys(K) | Arg;Gln;Asn |
Met(M) | Leu;Phe;Ile |
Phe(F) | Trp;Leu;Val;Ile;Ala;Tyr |
Pro(P) | Ala |
Ser(S) | Thr |
Thr(T) | Val;Ser |
Trp(W) | Tyr;Phe |
Tyr(Y) | Trp;Phe;Thr;Ser |
Val(V) | Ile;Leu;Met;Phe;Ala;正白胺酸 |
可根據共同側鏈特性對胺基酸進行分組:
(1) 疏水性:正白胺酸、Met、Ala、Val、Leu、Ile;
(2) 中性親水:Cys、Ser、Thr、Asn、Gln;
(3) 酸性:Asp、Glu;
(4) 鹼性:His、Lys、Arg;
(5) 影響鏈取向之殘基:Gly、Pro;
(6) 芳族:Trp、Tyr、Phe。
非保守置換將需要將此等類別中的一個成員置換為另一個類別。參考序列之核苷酸或胺基酸位置,如序列表中所闡述,術語「對應於」係指基於結構序列比對或使用標準比對演算法(諸如GAP演算法)在與目標序列比對後鑑定之核苷酸或胺基酸位置。例如,相似序列(例如片段或物種變體)之對應殘基可藉由結構比對方法與參考序列進行比對來確定。藉由比對序列,熟習此項技術者可例如使用保守且相同的胺基酸殘基作為指導來鑑定對應的殘基。
如本文所用,術語「經分離」係指已與其通常在自然界中發現或產生之組分中的至少一些組分分離之分子。例如,當多肽與產生其之細胞之組分的至少一些組分分離時,多肽被稱為「經分離」。當多肽在表現之後由細胞分泌時,將含有多肽的上清液與產生其之細胞物理分離被認為係「經分離」多肽。類似地,當聚核苷酸不是通常在自然界中發現的較大的聚核苷酸的一部分(諸如,基因組DNA或線粒體DNA,在DNA聚核苷酸的情況下)或者與產生其之細胞之組分的至少一些組分分離時,聚核苷酸被稱為「經分離」。因此,宿主細胞內部之載體中含有的DNA聚核苷酸可被稱為「經分離」。
如本文所用,「脂質顆粒」係指含有包封內腔或腔體之兩親性脂質雙層之任何生物或合成顆粒。通常,脂質顆粒不含細胞核。脂質顆粒之實例包括奈米顆粒、病毒衍生之顆粒或細胞衍生之顆粒。此類脂質顆粒包括但不限於病毒顆粒(例如慢病毒顆粒)、病毒樣顆粒、病毒載體(例如,慢病毒載體)、外泌體、去核細胞、囊泡(例如,微囊泡、膜囊泡、細胞外膜囊泡、質膜囊泡及巨型質膜囊泡)、凋亡小體、線粒體顆粒(mitoparticle)、核紅細胞(pyrenocyte)或溶酶體。在一些實施例中,脂質顆粒可為融合體。在一些實施例中,脂質顆粒不是血小板。
如本文所用,諸如參考蛋白諸如G蛋白或F蛋白之「生物活性部分」係指蛋白之表現或保持蛋白全長之活性或性質之部分。例如,當各自嵌入脂質雙層中時,F蛋白的生物活性部分與G蛋白一起保持了融合活性。當各自嵌入脂質雙層中時,G蛋白之生物活性部分與F蛋白一起保持了融合活性。保持之活性可包括10%至150%或更多之全長或野生型F蛋白或G蛋白之活性。F蛋白及G蛋白之生物活性部分之實例包括胞質域之截短,例如多達1個、2個、3個、4個、5個、6個、7個、8個、9個、10個、11個、12個、13個、14個、15個、20個、22個、25個、30個、33個、34個、35個或更多個連續胺基酸之截短,參見例如:Khetawat及Broder,2010 Virology Journal,7:312;Witting等人,2013 Gene Therapy 20:997-1005,國際出版;專利申請第WO/2013/148327號。
如本文所用,「G蛋白」係指亨尼帕病毒包膜附著糖蛋白G或其生物活性部分。「F蛋白」係指亨尼帕病毒融合蛋白F或其生物活性部分。F蛋白及G蛋白可來自亨德拉(HeV)或尼帕(NiV)病毒,並且可為野生型蛋白,或者可為其表現出對天然結合搭配物之結合降低之變體。F (融合)及G (附著)糖蛋白介導尼帕病毒之細胞進入。G蛋白藉由結合細胞表面受體肝配蛋白B2(EphB2)或EphB3而引發感染。隨後病毒基因組釋放至細胞質中係由F蛋白之作用介導的,其誘導了病毒包膜劑與細胞膜之融合。可藉由在F蛋白(諸如NiV-F)及G蛋白(諸如NiV-G)中的一者或兩者中進行超融合突變工程改造來改良靶向脂質顆粒之轉導效率。
如本文所用,「融合體」係指含有包封內腔或腔體之兩親性脂質雙層及與該兩親性脂質雙層相互作用之融合劑之顆粒。在一些實施例中,融合體包含核酸。在一些實施例中,融合體係膜包封之製劑。在一些實施例中,融合體衍生自源細胞。如本文所用,「融合體組合物」係指包含一種或多種融合體之組合物。
如本文所用,「融合劑」係指在兩個膜包封的內腔之間產生相互作用之藥劑或分子。在實施例中,融合劑促進膜之融合。在其他實施例中,融合劑使兩個內腔(例如逆轉錄病毒載體的內腔及目標細胞之細胞質)之間產生連接,例如孔。在一些實施例中,融合劑包含兩種或更多種蛋白的複合物,例如其中兩種蛋白質均不具有單獨的融合活性。在一些實施例中,融合劑包含靶向域。
如本文所用,「再靶向融合劑」係指包含靶向部分之融合劑,該靶向部分的序列不是融合劑的天然存在形式的一部分。在實施例中,融合劑包含相對於融合劑的天然存在形式中的靶向部分不同之靶向部分。在實施例中,融合劑之天然存在形式缺乏靶向域,並且再靶向融合劑包含融合劑之天然存在形式不存在之靶向部分。在實施例中,融合劑經修飾而包含靶向部分。在實施例中,融合劑包含位於靶向部分外部(例如在跨膜域、融合活性域或細胞質域中)之相對於融合劑之天然存在形式之一個或多個序列改變。
如本文所用,「靶向包膜蛋白」係指含有與單域抗體(sdAb)可變域(諸如VL或VH sdAb、scFv、奈米抗體、駱駝科VHH域、鯊魚IgNAR或其片段)附著之亨尼帕病毒G蛋白(G蛋白)的多肽,其靶向期望細胞類型上的分子。在一些此類實施例中,附著可經由接頭(諸如肽接頭)直接或間接進行。「靶向包膜蛋白」亦可被稱為包含G蛋白及本揭示之抗體或抗原結合片段之「融合蛋白」,其中抗體或抗原結合片段融合至G蛋白或其生物活性部分之C末端。
如本文所用,「靶向脂質顆粒」係指含有嵌入脂質雙層中的靶向包膜蛋白(例如靶向CD8)之脂質顆粒。此類靶向脂質顆粒可為病毒顆粒、病毒樣顆粒、奈米顆粒、囊泡、外泌體、樹枝狀體、慢病毒、病毒載體、去核細胞、微囊泡、膜囊泡、細胞外膜囊泡、質膜囊泡、巨型質膜囊泡、雕亡小體、線粒體顆粒、核紅細胞、溶酶體、另一種膜包封之囊泡或慢病毒載體、基於病毒之顆粒、病毒樣顆粒(VLP)或細胞衍生之顆粒。
如本文所用,「逆轉錄病毒核酸」係指單獨或與輔助細胞、輔助病毒或輔助質體組合之核酸,該核酸至少含有用於封裝於逆轉錄病毒或逆轉錄病毒載體中所需之最小序列。在一些實施例中,逆轉錄病毒核酸進一步包含或編碼外源藥劑、陽性目標細胞特異性調控元件、非目標細胞特異性調控元件或陰性TCSRE。在一些實施例中,逆轉錄病毒核酸包含5' LTR (例如,以促進整合)、U3 (例如,以活化病毒基因組RNA轉錄)、R (例如,Tat結合區)、U5、3' LTR (例如,以促進整合)、封裝位點(例如,psi (ψ))及RRE (例如,以與Rev結合並促進核輸出)中之一者或多者(例如全部)。逆轉錄病毒核酸可包含RNA (例如,當成為病毒粒子之一部分時)或DNA (例如,當引入源細胞中時或在受體細胞中逆轉錄之後)。在一些實施例中,使用包含gag、pol及env中之一者或多者(例如全部)之輔助細胞、輔助病毒或輔助質體封裝逆轉錄病毒核酸。
如本文所用,「目標細胞」係指期望靶向脂質顆粒向其遞送外源藥劑之類型之細胞。在實施例中,目標細胞係特定組織類型或類別之細胞,例如免疫效應細胞,例如T細胞。在一些實施例中,目標細胞」係病變細胞,例如癌細胞。在一些實施例中,與非目標細胞相比,融合劑(例如再靶向融合劑)導致外源藥劑優先遞送至目標細胞。
如本文所用,「非目標細胞」係指不期望靶向脂質顆粒向其遞送外源藥劑之類型之細胞。在一些實施例中,非目標細胞係特定組織類型或類別之細胞。在一些實施例中,非目標細胞係非病變細胞,例如非癌細胞。在一些實施例中,與目標細胞相比,融合劑(例如再靶向融合劑)導致外源藥劑較慢遞送至非目標細胞。
如本文所用,術語「有效量」意指足以顯著及積極地改變待治療之症狀及/或病狀(例如,提供陽性臨床反應)之醫藥組合物的量。用於醫藥組合物之本揭示之靶向脂質顆粒的有效量將隨所治療的特定病狀、病狀之嚴重程度、治療持續時間、協同療法之性質、所採用之特定脂質顆粒、所利用的特定醫藥學上可接受之賦形劑及/或載體,以及主治醫師之知識及專長等因素而變化。
如本文所用,參考靶向脂質顆粒之「外源藥劑」係指既不被對應野生型病毒或由對應野生型源細胞製成之融合劑所包含亦不由其編碼之藥劑。在一些實施例中,外源藥劑並非天然存在,諸如序列相對於天然存在之蛋白改變(例如藉由插入、缺失或取代)之蛋白或核酸。在一些實施例中,外源藥劑並非天然地存在於源細胞中。在一些實施例中,外源藥劑天然存在於源細胞中,但對於病毒而言係外源的。在一些實施例中,外源藥劑並非天然地存在於受體細胞中。在一些實施例中,外源藥劑天然地存在於受體細胞中,但不以所期望之水準或所期望之時間存在。在一些實施例中,外源藥劑包含DNA、RNA或蛋白質。
如本文所用,「啟動子」係指當可操作地連接至基因編碼序列時驅動基因轉錄之順式調控DNA序列。啟動子可包含一個或多個轉錄因子結合位點。在一些實施例中,啟動子與在基因遠側之一種或多種增強子協同作用。
如本文所用,組合物係指兩種或更多種產物、物質或化合物之任何混合物,包括細胞。其可為溶液、懸浮液、液體、粉末、糊劑、水性的、非水性的或其任何組合。
如本文所用,術語「醫藥學上可接受」係指材料,諸如載體或稀釋劑,其不消除治療化合物之生物活性或特性,並且係相對無毒的,亦即,該材料可向個體投與而不會引起不期望的生物效應或以有害方式與含有該材料之組合物之組分中的任一種相互作用。
如本文所用,術語「醫藥組合物」係指本揭示之至少一種靶向脂質顆粒與其他化學組分(諸如載體、穩定劑、稀釋劑、分散劑、懸浮劑、增稠劑及/或賦形劑)之混合物。醫藥組合物有助於向生物體投與靶向脂質顆粒。此項技術中存在投與本揭示之靶向脂質顆粒之多種技術,包括但不限於靜脈內、口服、氣霧劑、非經腸、眼部、肺部及局部投與。
如本文所用,「疾病」或「病症」係指需要及/或期望治療之病狀。
如本文所用,術語「治療」(「treat」、「treating」或「treatment」)係指改善疾病或病症,例如減緩或阻止或減少疾病或病症之發展或減少其臨床症狀中的至少一種。出於本揭示之目的,改善疾病或病症可包括獲得有益或期望之臨床結果,包括但不限於以下中的任一種或多種:減輕一種或多種症狀、減少疾病的程度、預防或延遲疾病之擴散(例如轉移,例如轉移至肺或淋巴結)、預防或延遲疾病之復發、延遲或減緩疾病進展、改善疾病狀態、抑制疾病或疾病進展、抑制或減緩疾病或其進展、阻止其進展及緩解(無論係部分抑或全部的)。
術語「個人(individual)」及「個體(subject)」在本文中可互換使用以指代動物;例如哺乳動物。此等術語包括人類及獸用動物。在一些實施例中,提供治療動物之方法,包括但不限於人類、嚙齒動物、猿猴、貓科動物、犬科動物、馬科動物、牛科動物、豬科動物、綿羊科動物、山羊科動物、哺乳動物實驗室動物、哺乳動物農場動物、哺乳動物運動動物及哺乳動物寵物。動物可為雄性或雌性,並且可為任何合適的年齡,包括嬰兒、幼年、青年、成人和及老年。在一些實例中,「個人」或「個體」係指需要治療疾病或病症之動物。在一些實施例中,接受治療之動物可為「患者(patient)」,表明該動物已被鑑定為患有與治療相關之病症,或處於患上該病症之足夠風險中。在特定實施例中,動物為人類,諸如人類患者。
CD8 特異性抗體
本文描述了特異性靶向及結合CD8α或CD8β之新穎抗體及其抗原結合片段。在一些實施例中,抗體或其抗原結合片段可與食蟹猴(或「cyno」)或南平頂猴CD8交叉反應。在一些實施例中,抗體或其抗原結合片段係由衍生自IgG分子的重(VH)鏈及輕(VL)鏈的抗原結合域構成並經由接頭域連接之單鏈可變片段(scFv)。在一些實施例中,抗體或其抗原結合片段係對應於IgG分子之VH的VHH。本揭示亦提供了編碼抗體及其片段、載體及宿主細胞的聚核苷酸,以及使用抗體或其抗原結合片段之方法。在一些實施例中,例如,抗體或其抗原結合片段可融合至亨尼帕病毒糖蛋白G以用於靶向結合及轉導至細胞。
使用Kabat編號方案之本揭示之例示性抗體及抗原結合片段之序列示於下
表 3 至表 4中。本揭示之例示性HCDR之序列示於
表3中。本揭示之例示性LCDR之序列示於
表 4中。
所揭示之VH及VL域之序列提供於
表 5 至表 6中。本文提供之
表 8 至表 11示出了使用Chothia及IMGT編號方案兩者之所揭示之抗體及其抗原結合片段之CDR序列。本揭示之變體CD8 scFv及VHH之全CD8結合劑序列示於
表 12中。
表 3. Kabat 編號方案 中的 HCDR
表 4. Kabat 編號方案 中的 LCDR
表 5. VH 序列
表 6. VL 序列
表 7.
表 8. 使用 Chothia 編號方案 之 HCDR
表 9. 使用 Chothia 編號方案 之 LCDR
表 10. 使用 IMGT 編號方案之 HCDR
表 11. 使用 IMGT 編號方案之 LCDR
表 12
表 13
CD8結合劑 | H-CDR1 | H-CDR2 | H-CDR3 | |||
序列 | SEQ ID NO: | 序列 | SEQ ID NO: | 序列 | SEQ ID NO: | |
1 | SYAIS | 1 | IIDPSDGNTNYAQNFQG | 70 | ERAAAGYYYYMDV | 148 |
2 | TYAIN | 2 | RIDPSSGGTKYAQNFQG | 71 | EHAAGTYYYYMDV | 149 |
3 | SYAIN | 3 | IIDPSGGNTNYAQNFQG | 72 | ERAAAGYYYYMDV | 148 |
4 | GYYMH | 4 | HINPNNGDTNYAQNFQG | 73 | EGYYYYGMDV | 649 |
5 | DYYIQ | 5 | WINPNSGGTSYAQKFQG | 74 | EGDYYYGMDA | 150 |
6 | RYDIH | 6 | VINPNDGSTRYAQNFQG | 75 | ERGGMPDY | 151 |
7 | SYAMN | 7 | RINPNSGGTNYAQKFQG | 76 | GHGIPKY | 152 |
8 | SYYIH | 8 | WMNPNSGNTGYAQKFQG | 77 | VRSGSPQH | 153 |
9 | RHYIH | 9 | WMNPNSGNTGYAQKFQG | 77 | GGPWIVDAFDI | 154 |
10 | SYGIS | 10 | WISAHNGVTQYAQKFQG | 78 | GIAVAGTDY | 650 |
11 | NTDIN | 11 | IINPSGGSTSYAQKFQG | 79 | EATWGPYYYYMDV | 155 |
12 | RSYVH | 12 | WISPYNGNTKYAQKFQG | 80 | NKDGLQH | 156 |
13 | GYYMH | 13 | IINPNSGDTKYAHQFQG | 81 | DAKRVGYYYYMDV | 157 |
14 | RYYMH | 14 | RINPNSGGTNYAQKFQG | 76 | LVGGSPDY | 158 |
15 | NYDIN | 15 | RINPNSGGTNYAENFQG | 1057 | GAMVDY | 159 |
16 | NTDIN | 11 | IINPSDGDTKYAQEFQG | 82 | GNYVGSYYYGMDV | 160 |
17 | NYYLH | 16 | WINPNSGDTKYAQKFQG | 83 | DSRGDWYFDL | 161 |
18 | RYSIH | 17 | VIDPSGGSTSYAQKFQG | 84 | HGGRGLADY | 162 |
19 | SRDIS | 18 | WIDPKSGDTTYAQKFQG | 85 | LKELSSILDAFDI | 163 |
20 | SYDIN | 19 | MINPGAGSSTYAQKFQG | 86 | ERFGTGYYYYMDV | 164 |
21 | NSDMN | 20 | LISGDGGTTYYADSVKG | 87 | VIGEMVDDAFDL | 165 |
22 | GYYMH | 4 | SINPNSGDTGYAQKFQG | 88 | ERLFGTYYYYMDV | 166 |
23 | TYDIN | 21 | RIIPIFGTANYAQKFQG | 89 | ADGELTDY | 167 |
24 | SYTMD | 22 | AIGTGGGIYYADSVKG | 90 | HHLPAHYYYYMDV | 168 |
25 | RYDIN | 23 | RINPNSGDTNYAQKFQG | 91 | DVPAGRYYYYMDV | 169 |
26 | SYYMH | 24 | MINPSDGSTRYAQKFQG | 92 | DRGVGRYYYYMDV | 170 |
27 | RYAVS | 25 | IINPSDGSTTYAQKFQG | 93 | DSRYGRYYYYMDV | 171 |
28 | NYAIS | 26 | IINPNGGSPSYAQKFQG | 94 | EIVVGPYYYYMDV | 172 |
29 | RYAIS | 617 | RINPNSGDTNYAQKFQG | 91 | GMVRGPYYYYMDV | 173 |
30 | SYAIS | 1 | IINPSGGSTSYAQTFQG | 1058 | EGVTGPYYYYMDV | 174 |
31 | RFDIN | 28 | IINPSDGSTDYAQNFQG | 95 | DAAAGTRYYYYYGMDV | 175 |
32 | SHAIS | 29 | IINPSGGSTSYAQKFQG | 79 | ELYSSTYYYYMDV | 176 |
33 | SYAIS | 1 | RINPNTGGTNHAQKFQG | 96 | ALYSGPYYYYMDV | 177 |
34 | NSDMN | 20 | AISGSGGSTYYADSVKG | 97 | EHAAGTYYYYMDV | 149 |
35 | SYGIN | 30 | WISGYNGDTDYARKLQG | 98 | DSLVGRYYYYMDV | 178 |
36 | DYDIY | 31 | WISADNGNTNYEQKVQG | 99 | RSELDY | 179 |
37 | SYHMH | 32 | WISPNSGATHYAQKFQG | 100 | GDDNDY | 180 |
38 | SYDIN | 19 | WINPNSGNTGYAKKFQG | 101 | GEEVDY | 181 |
39 | SYPMN | 33 | IINPSGGSTRYAQKFQG | 102 | GRRVPDY | 182 |
40 | DYYIH | 34 | WINPKSGATNYAQKFQG | 103 | GKVTTDY | 183 |
41 | SFEMN | 35 | RISESGDSSFYADSVKG | 104 | GRELIEY | 184 |
42 | DYAMH | 36 | AIGTGGGTYYADSVKG | 105 | VYDFPDV | 185 |
43 | DSYMH | 37 | WMNPSNGDTGYARKFQG | 106 | STYSHIDY | 186 |
44 | NYYMH | 38 | TISPSDGSTTYAQRFQG | 107 | EDSSGFDY | 187 |
45 | NYYIH | 39 | IINPSGGSTTYAQKFQG | 108 | DQGGGFDY | 188 |
46 | SYYMH | 40 | GFDPEDGETIYAQKFQG | 109 | DQGWGMDV | 189 |
47 | SYYIH | 8 | RINPKSGRTYYAQNFQG | 110 | LTEGIPDY | 190 |
48 | DYYIH | 41 | VINPGGGSTTYAQTFQG | 111 | DRYGPFDY | 191 |
49 | SYDIN | 19 | LMNPKTGDTNYAEKFQG | 112 | LVAGGAPDY | 192 |
50 | GYYMH | 4 | IIDPSDGYTSYAQKFQG | 113 | DGFTGDIAY | 193 |
51 | GYYMH | 4 | WINPNSGGTNYAQKFQG | 114 | VDDSSSPDY | 194 |
52 | GYYLH | 42 | GIMPISGTTIYAQKFQG | 115 | GPDGTEVDY | 195 |
52 | NHYMH | 43 | WMNPNSGNTGYAQKFQG | 77 | SESGSDLDY | 196 |
54 | NYYIH | 44 | WMSPTSGDTGYAQKFQG | 116 | EVEIEGYMDV | 197 |
55 | SYYMH | 40 | WINPNSGDTSYAQKFQG | 117 | DLDDDWYMDV | 198 |
56 | SYYMH | 40 | IIDPSGDITSYAQKFQG | 118 | DSTTWDAFDI | 199 |
57 | DYYMH | 45 | WINPNSGGTNYAQKFQG | 114 | VLVGSGSPDY | 200 |
58 | ENEMH | 46 | IIETSGGSTDYAQKFQG | 119 | EAAAGLDFQH | 201 |
59 | SYDMH | 47 | IINPNSGGTNYAQKLQG | 120 | ANSWDADY | 202 |
60 | NSDMH | 48 | VISGSGVTTYYADSVKG | 121 | EHSSSWYTFDY | 203 |
61 | AYYMH | 49 | WINPNSGGTDYAQKFQG | 122 | DDDSSGYYLDY | 204 |
62 | NYYIH | 44 | MINPSGGSTTYAQKFQG | 123 | ASGDYMDLIDYMDY | 205 |
63 | DYHMH | 50 | WINPDSGGTNYEQKFQG | 124 | VGSSGYLAPTH | 206 |
64 | DYYMH | 51 | WMNPNSGNTGYAQKFQG | 77 | VRGDGYNLGDY | 207 |
65 | DYYMH | 52 | WINPNSGGTNSAQKFQG | 125 | DVDTAMGAGDY | 208 |
66 | DYYIH | 34 | IINPSGGSASYAQKFQG | 126 | VARWGYGDYPDY | 209 |
67 | THDIN | 53 | IISPSDGSTSYAQKLQG | 127 | DRNGDYYYGMDV | 210 |
68 | NYYIH | 54 | WINPISGGTHYAQKFQG | 128 | EGLGSSWYVLDY | 211 |
69 | SYDIN | 19 | WISADNGDTSFAQKFQG | 129 | DGSHYGYYGMDV | 212 |
70 | SYDIN | 19 | GISPIYGTPAYAQKFQG | 130 | PGPEGYYYGMDV | 213 |
71 | DNYMH | 55 | WMNPNSGNTGYAQKFQG | 77 | YHWDYGDYRFDY | 214 |
72 | SYYIH | 8 | WMNPNSGNTGYAQKFQG | 77 | VEIDYGDSPPDY | 215 |
73 | SYAIS | 56 | IINPSDGDTSYAQKFQG | 131 | GAEWELRYAFDI | 216 |
74 | TYDIS | 57 | TINPSGGTTTYAQKFQG | 132 | ETYYGLYYYGMDV | 217 |
75 | SYDIN | 19 | WMNPKSGNTGYAQKFQG | 133 | APSLRGYSYGPDY | 218 |
76 | SYDIN | 58 | IINPSGGSTSYAQKFQG | 79 | DRQERYYYYYMDV | 219 |
77 | SYDIN | 19 | IINPSDGSTDYAQKFQG | 1059 | DRSYGDYYYGMDV | 220 |
78 | SYDIN | 58 | IINPGGGNARHTQKFQG | 134 | EVFSENYYYYMDV | 221 |
79 | SYYMH | 40 | IINPSDGSTTYAQKFQG | 93 | EWDYTHYYYGMDV | 222 |
80 | SHWIH | 59 | GFDPEDGETVYAQNFQG | 135 | GDSSGYYQYYFDY | 223 |
81 | SYDIN | 19 | GITPVFGIANYAQKFQG | 136 | GSWDSSSWYIPEY | 224 |
82 | DYDIV | 60 | IINPRGGSTNYAQKFQG | 137 | LVWGGAYYYYMDV | 225 |
83 | SYGIS | 10 | WMNPNNGDTDYAQKFQG | 138 | PVFSGSYYWYFDP | 226 |
84 | SYDIN | 19 | IINPSGGGTSYAQKFQG | 139 | DQAVAGPYYYGMDV | 227 |
85 | SYAIS | 1 | LINPGSGNTNYAQKFQG | 140 | DRWLAGPYYYGMDV | 228 |
86 | GHDMH | 61 | GIIPIFGTPNYAQKFQG | 141 | VMGPVDYYYYGMDV | 229 |
87 | NYDMH | 62 | IINPSDGSTTYAQKFQG | 93 | DLGPFGSYYYYMDV | 230 |
88 | SYAMT | 63 | TINGDGDDTDYADSVKG | 142 | EGVVVPPYYYYMDV | 231 |
89 | TYYMH | 64 | QIDPNSGDTIYPQKFQG | 143 | SSGWSRYYYYYMDV | 232 |
90 | NYQIH | 65 | IINPSGGSTSYAQKFQG | 79 | DNGMTTGYYYYMDV | 233 |
91 | SYDIV | 66 | IINPSGGSTSYAQKFQG | 79 | DRAMVTGYYYGMDV | 234 |
92 | SYDIN | 19 | IVNPSDGNTNYAQKFQG | 144 | DRGYGDRGYYYGMDV | 235 |
93 | SYDIN | 67 | WINTYNGNTYYAQKLQG | 145 | SPKATADYYYYYMDV | 236 |
94 | SYDIN | 19 | IINPSDGITDYAQRFQG | 146 | STVTPSYYYYYGMDV | 237 |
95 | SHAIH | 68 | IINPRDGDTVYAQKFQG | 147 | EPVAGTGYYYYYGMDV | 238 |
96 | SYGIN | 69 | WMNPNSGNTGYAQKFQG | 77 | DNLAGFWSDYYYYGMDV | 239 |
97 | GYVMG | 1061 | AISRGGLSTSYADSVKG | 1062 | DRSDLYEITAASNIDS | 1063 |
CD8結合劑 | L-CDR1 | L-CDR2 | L-CDR3 | |||
序列 | SEQ ID NO: | 序列 | SEQ ID NO: | 序列 | SEQ ID NO: | |
1 | RASQSISSYLN | 240 | AASSLQS | 294 | QQSYSTPLT | 333 |
2 | QASQDISNYLN | 241 | AASSLQS | 294 | QQSYSNLVS | 334 |
3 | RASQSISSYLN | 240 | AASSLQS | 294 | QQSYSTPLT | 333 |
4 | RSSQSLLHSNGYNYLD | 242 | LGSNRAS | 295 | MQALQTPFT | 335 |
5 | RSSQSLLHSNGYNYLD | 242 | LGSNRAS | 295 | MQGLQTPHT | 336 |
6 | RASQSISRNLN | 243 | KASNLKG | 296 | QQTYSAPL | 337 |
7 | RSSQSLLHSNGYNYLD | 242 | LGSNRAS | 295 | MQTLQTPLT | 338 |
8 | RASQSVSASDLA | 244 | GASTRAT | 297 | QQYGDSPGS | 339 |
9 | QASQDIGNYLN | 245 | AASTLQR | 298 | QQANSFPPT | 340 |
10 | RASQSISTHLA | 246 | GASTRAT | 297 | QQYGNSRT | 341 |
11 | RASQTISNYLN | 247 | AASTLQS | 299 | QQSYSTPPT | 342 |
12 | RASQGIRNDLG | 248 | DASTLQS | 300 | QQSYSSPYT | 343 |
13 | RASQSISNYLN | 249 | AASSLQS | 294 | QQSYSTPYT | 344 |
14 | RSSQSLLHSNGYNYLD | 242 | LGSNRAS | 295 | MQGAHWPPT | 345 |
15 | RASQGISDSLA | 250 | GASSLRS | 301 | QQSYRTPYT | 346 |
16 | RASQSISNYLN | 249 | AASSLQS | 294 | QESFTTQWT | 347 |
17 | QASQDIHNYLN | 251 | DASNLET | 302 | QQANSFPPT | 340 |
18 | QASQDISNYLN | 241 | SASSLQS | 303 | QQRSNWPLYT | 348 |
19 | RASQSISDWLA | 252 | AASSLQT | 304 | QQAISFPIT | 349 |
20 | QASQDISNYLN | 241 | SASTLQS | 305 | QQSYSSPFT | 350 |
21 | RASQSISTWLA | 253 | AASTLQS | 299 | QQAISFPLT | 351 |
22 | RASQSISNYLN | 249 | AASTLQS | 299 | QQSYTFPIT | 352 |
23 | RSSQSLLHSNGYNYLD | 242 | DASHLET | 306 | QQYYSYPPT | 353 |
24 | QASQDISNYLN | 241 | AASTLHS | 307 | QQSYSAPLT | 354 |
25 | QASQDISNYLN | 241 | AASTLQS | 299 | QQSFSTFYT | 355 |
26 | QASQDISNYLN | 241 | AASTLQS | 299 | QQSYSIPFT | 356 |
27 | RASQSINRFLN | 254 | AASSLQN | 308 | QQSYSTPYT | 344 |
28 | RASQSISSYLN | 240 | AASSLQS | 294 | QQSYSTPLT | 333 |
29 | QASQDISNYLN | 241 | AASTLQS | 299 | QQSYSTPIT | 357 |
30 | RASQSVSTYLN | 255 | AASSLQS | 294 | QQSYTIPST | 358 |
31 | QASQDIAKYLN | 256 | AASSLQS | 294 | QQSYSAPPT | 359 |
32 | QASQGITNYLN | 257 | GASSLQS | 309 | QQSYSTPWT | 360 |
33 | RASQSISSYLN | 240 | AASSLQS | 294 | QQSYSTPLT | 333 |
34 | QASQDIHNYLN | 251 | AASTLQS | 299 | QQSYTTPLT | 361 |
35 | QASQDISNYLN | 241 | SAFSLQS | 310 | QQSYSAPIT | 362 |
36 | RASQSISSYLN | 240 | SASNLQS | 311 | QQRSNWPPVT | 363 |
37 | QANQDISNFLE | 258 | DASSLES | 312 | QQSYSIPIT | 364 |
38 | RASQGISNNLN | 259 | EASTLES | 313 | QQSYSTPLT | 333 |
39 | RSSQSLLHSNGYNYLD | 242 | GASTLET | 314 | MQGLQPPGT | 365 |
40 | RASQSISRSLV | 260 | AASTLQT | 315 | QQSYNHFRT | 366 |
41 | QASQDISNYLN | 241 | DASNLET | 302 | QRSDSTPLT | 367 |
42 | QASHDISKSLN | 261 | GASTLQS | 316 | QQLNSYPRT | 368 |
43 | RASQDIGAYLA | 262 | AASSLQS | 294 | QQSYSIPYT | 369 |
44 | RASQSISSYLA | 263 | AASSLQS | 294 | QQSYSTPYT | 344 |
45 | RASQGIRSYLA | 264 | GASNLET | 317 | QQSYSTPYT | 344 |
46 | RASQSISSYLN | 240 | AASSLQS | 294 | QQTYSTPYT | 370 |
47 | RASQNIGTWLA | 265 | AASTLQS | 299 | QQSYSTPQT | 371 |
48 | RASQTISYYLN | 266 | AASTLQS | 299 | QQSYRTPYT | 346 |
49 | RSSQSLLHSNGYNYLD | 242 | MGSNRAS | 318 | MQGTHWPT | 372 |
50 | RASQNINNYLN | 267 | GASSLQS | 309 | QQTFSLPYT | 373 |
51 | RASQTISTYLN | 268 | DASNLET | 302 | QQSYSTPYT | 344 |
52 | RASRGIGNDLA | 269 | DASTLET | 319 | QQGYNMPLT | 374 |
52 | RASQTIGNYVN | 270 | GASNLHT | 320 | QQTYSAPLT | 375 |
54 | RASQFIGSWLA | 271 | AASTLQS | 299 | QQSYSFPWT | 376 |
55 | RASQSISSWMA | 272 | DASNLET | 302 | QQTYSTPYI | 377 |
56 | RASQGISNNLN | 259 | DASNLET | 302 | QQSYSSPWT | 378 |
57 | KSSQSVLYSSNNKNYLA | 273 | WASTRES | 321 | QQYASAPRT | 379 |
58 | RASQSISSYLN | 240 | KTSSLES | 322 | QQSFTIPYT | 380 |
59 | RVSQGISSYLN | 274 | GASSLQS | 309 | QQSYSTPLT | 333 |
60 | RASQSISDWLA | 252 | DASNLET | 302 | QQSYSTPLT | 333 |
61 | RASQGISNYLA | 275 | SASNLQS | 311 | QQTYRTPPT | 381 |
62 | RASQSIRNYLT | 276 | SASNLQS | 311 | QQSYSTPLT | 333 |
63 | RASQNIRLYLN | 277 | AASTLQS | 299 | QQSLTTPFT | 382 |
64 | QASQDIRKFLN | 278 | AASSLQS | 294 | QQLNGYPGT | 383 |
65 | RASQSISSYLN | 240 | TASNLQS | 323 | QQSYSLPLT | 384 |
66 | QASQDISNYLS | 279 | DASNLQS | 324 | QQTYTTPRT | 385 |
67 | RASQNVRSWLA | 280 | AASSLQS | 294 | QQSYNTPYT | 386 |
68 | RASQGIGNDLG | 281 | AASSLQS | 294 | QQSYAPPPT | 387 |
69 | RASQSISNWLA | 282 | GASNLET | 317 | QQSYSTPPT | 342 |
70 | RSSQSLLHSNGYNYLD | 242 | LGSNRAS | 295 | MQGLQTPLT | 388 |
71 | RASQSISSYLN | 240 | LASSLQS | 325 | QQSDSIPVT | 389 |
72 | QASQDISNYLN | 241 | STSSLQS | 326 | QQSYSTPYN | 390 |
73 | RASESIGSWLA | 283 | AASSLQS | 294 | QQSYSTPYT | 344 |
74 | RASQSISNYLN | 249 | AASSLQR | 327 | QQSYSTPLT | 333 |
75 | RASQSVTSNYLA | 284 | GASTRAT | 297 | QHYGSSPA | 391 |
76 | RASQSISSYLN | 240 | AASSLQS | 294 | QQSYSTPLT | 333 |
77 | RASQGISSYLA | 285 | AASTLQS | 299 | QQSYSTPPT | 342 |
78 | RASQDIGNYLN | 286 | AASSLQS | 294 | QQAYTYPYT | 392 |
79 | QASQDISNYLN | 241 | GASSLQS | 309 | QQSYTTPNT | 393 |
80 | RASQGISNYLA | 275 | AASTLQS | 299 | QQSYSTPYT | 344 |
81 | RASQGISNGLS | 287 | DASNLET | 302 | QQSYSTPFT | 394 |
82 | RASQNIRNYLN | 288 | GASSLQS | 309 | QQSYSTPLT | 333 |
83 | QASLDINNYLN | 289 | KASSLES | 328 | QQSYSMPLT | 395 |
84 | QASQDISNYLN | 241 | AASSLQG | 329 | QQSYTTPWT | 396 |
85 | QASQDISNYLN | 241 | AASSLQS | 294 | QQSYSSPLT | 397 |
86 | QASQDISNYLN | 241 | KASSLES | 328 | QQSYSDPLT | 398 |
87 | QASQDISNYLN | 241 | GASTLQS | 316 | QQSYSAPIT | 362 |
88 | RASQSISNYLN | 249 | AASNLQS | 330 | QQSYTTPLT | 361 |
89 | RASQNIGNYLN | 290 | AASTLQS | 299 | QQSYSTPPWT | 399 |
90 | QASQDISNYLN | 241 | AASTLRS | 331 | QQSYQTPLT | 400 |
91 | QASQDISNYLN | 241 | AASTLQS | 299 | QQSYTTPPT | 401 |
92 | QASQDISNYLN | 241 | AASSLHS | 332 | QQSYSTPQT | 371 |
93 | RASQGIRNDLN | 291 | AASNLQS | 330 | QQANSFPIT | 402 |
94 | RASQGINTWLA | 292 | AASSLQS | 294 | QQSYSTPYT | 344 |
95 | QASQDISNYLN | 241 | AASTLQS | 299 | QQSYTVPPT | 403 |
96 | RASQFIGSWLA | 293 | AASTLQS | 299 | QQDDSFPLT | 404 |
CD8結合劑 | VH序列 | SEQ ID NO: |
1 | QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIIDPSDGNTNYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKERAAAGYYYYMDVWGQGTTVTVSS | 405 |
2 | QVQLVQSGAEVKKPGASVKVSCKASGGTFNTYAINWVRQAPGQGLEWMGRIDPSSGGTKYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKEHAAGTYYYYMDVWGKGTTVTVSS | 406 |
3 | QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAINWVRQAPGQGLEWMGIIDPSGGNTNYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKERAAAGYYYYMDVWGQGTTVTVSS | 407 |
4 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGHINPNNGDTNYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKEGYYYYGMDVWGQGTTVTVSS | 651 |
5 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIQWVRQAPGQGLEWMGWINPNSGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKEGDYYYGMDAWGQGTMVTVSS | 408 |
6 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYDIHWVRQAPGQGLEWMGVINPNDGSTRYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARERGGMPDYWGQGTLVTVSS | 409 |
7 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMNWVRQAPGQGLEWMGRINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGHGIPKYWGQGTLVTVSS | 410 |
8 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARVRSGSPQHWGQGTLVTVSS | 411 |
9 | QVQLVQSGAEVKKPGASVKVSCKASGHTFSRHYIHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGPWIVDAFDIWGQGTMVTVSS | 412 |
10 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAHNGVTQYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGIAVAGTDYWGQGTLVTVSS | 652 |
11 | QVQLVQSGAEVKKPGASVKVSCKASGGTFSNTDINWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREATWGPYYYYMDVWGKGTTVTVSS | 413 |
12 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTRSYVHWVRQAPGQGLEWMGWISPYNGNTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCVRNKDGLQHWGQGTLVTVSS | 414 |
13 | QVQLVQSGAEVKKPGASVKVSCKASGDTFTGYYMHWVRQAPGQGLEWMGIINPNSGDTKYAHQFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDAKRVGYYYYMDVWGKGTTVTVSS | 415 |
14 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYYMHWVRQAPGQGLEWMGRINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARLVGGSPDYWGQGTLVTVSS | 416 |
15 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYDINWVRQAPGQGLEWMGRINPNSGGTNYAENFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGAMVDYWGQGTLVTVSS | 417 |
16 | QVQLVQSGAEVKKPGASVKVSCKASGGTFSNTDINWVRQAPGQGLEWMGIINPSDGDTKYAQEFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGNYVGSYYYGMDVWGQGTTVTVSS | 418 |
17 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYLHWVRQAPGQGLEWMGWINPNSGDTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSRGDWYFDLWGRGTLVTVSS | 419 |
18 | QVQLVQSGAEVKKPGASVKVSCKASGYGFTRYSIHWVRQAPGQGLEWMGVIDPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTRHGGRGLADYWGQGTLVTVSS | 420 |
19 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSRDISWVRQAPGQGLEWMGWIDPKSGDTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARLKELSSILDAFDIWGQGTMVTVSS | 421 |
20 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGMINPGAGSSTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARERFGTGYYYYMDVWGQGTMVTVSS | 422 |
21 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSNSDMNWVRQAPGKGLEWVSLISGDGGTTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVIGEMVDDAFDLWGQGTTVTVSS | 423 |
22 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGSINPNSGDTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARERLFGTYYYYMDVWGKGTTVTVSS | 424 |
23 | QVQLVQSGAEVKKPGSSVKVSCKASGYTFTTYDINWVRQAPGQGLEWMGRIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARADGELTDYWGQGTLVTVSS | 425 |
24 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMDWVRQAPGKGLEWVSAIGTGGGIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHHLPAHYYYYMDVWGKGTTVTVSS | 426 |
25 | QVQLVQSGAEVKKPGASVKVSCKASGGTFSRYDINWVRQAPGQGLEWMGRINPNSGDTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDVPAGRYYYYMDVWGKGTLVTVSS | 427 |
26 | QVQLVQSGAEVKKPGASVKVSCKASGNTFTSYYMHWVRQAPGQGLEWMGMINPSDGSTRYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDRGVGRYYYYMDVWGKGTTVTVSS | 428 |
27 | QVQLVQSGAEVKKPGASVKVSCKASGGTFSRYAVSWVRQAPGQGLEWMGIINPSDGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDSRYGRYYYYMDVWGKGTTVTVSS | 429 |
28 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSNYAISWVRQAPGQGLEWMGIINPNGGSPSYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAKEIVVGPYYYYMDVWGKGTTVTVSS | 430 |
29 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFTRYAISWVRQAPGQGLEWMGRINPNSGDTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGMVRGPYYYYMDVWGKGTTVTVSS | 431 |
30 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIINPSGGSTSYAQTFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGVTGPYYYYMDVWGQGTTVTVSS | 432 |
31 | QVQLVQSGAEVKKPGASVKVSCKASGGTFSRFDINWVRQAPGQGLEWMGIINPSDGSTDYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDAAAGTRYYYYYGMDVWGQGTTVTVSS | 433 |
32 | QVQLVQSGAEVKKPGASVKVSCKASGGTFSSHAISWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARELYSSTYYYYMDVWGKGTTVTVSS | 434 |
33 | QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGRINPNTGGTNHAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARALYSGPYYYYMDVWGKGTTVTVSS | 435 |
34 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSNSDMNWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKEHAAGTYYYYMDVWGKGTTVTVSS | 436 |
35 | QVQLVQSGAEVKKPGASVKVSCKASGGTFGSYGINWVRQAPGQGLEWMGWISGYNGDTDYARKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSLVGRYYYYMDVWGKGTTVTVSS | 437 |
36 | QVQLVQSGAEVKKPGASVKVSCKASGYIFTDYDIYWVRQAPGQGLEWLGWISADNGNTNYEQKVQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARRSELDYWGQGTLVTVSS | 438 |
37 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYHMHWVRQAPGQGLEWMGWISPNSGATHYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDDNDYWGQGTLVTVSS | 439 |
38 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGWINPNSGNTGYAKKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGEEVDYWGQGTLVTVSS | 440 |
39 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYPMNWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGRRVPDYWGQGTLVTVSS | 441 |
40 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIHWVRQAPGQGLEWMGWINPKSGATNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGKVTTDYWGQGTLVTVSS | 442 |
41 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFEMNWVRQAPGKGLEWVSRISESGDSSFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASGRELIEYWGQGTLVTVSS | 443 |
42 | EVQLLESGGGLVQPGGSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSAIGTGGGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVYDFPDVWGQGTTVTVSS | 444 |
43 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDSYMHWVRQAPGQGLEWMGWMNPSNGDTGYARKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSTYSHIDYWGQGTLVTVSS | 445 |
44 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQGLEWMGTISPSDGSTTYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREDSSGFDYWGQGTLVTVSS | 446 |
45 | QVQLVQSGAEVKKPGASVKVSCKASGYTFMNYYIHWVRQAPGQGLEWMGIINPSGGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQGGGFDYWGQGTLVTVSS | 447 |
46 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGGFDPEDGETIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQGWGMDVWGQGTTVTVSS | 448 |
47 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGRINPKSGRTYYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARLTEGIPDYWGQGTLVTVSS | 449 |
48 | QVQLVQSGAEVKKPGASVKVSCKASGYTLNDYYIHWVRQAPGQGLEWMGVINPGGGSTTYAQTFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRYGPFDYWGQGTLVTVSS | 450 |
49 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGLMNPKTGDTNYAEKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTRLVAGGAPDYWGQGTLVTVSS | 451 |
50 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGIIDPSDGYTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGFTGDIAYWGQGTLVTVSS | 452 |
51 | QVQLVQSGAEVKKPGSSVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARVDDSSSPDYWGQGTLVTVSS | 453 |
52 | QVQLVQSGAEVKKPGSSVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGGIMPISGTTIYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCTTGPDGTEVDYWGQGTLVTVSS | 454 |
52 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSS | 455 |
54 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYIHWVRQAPGQGLEWMGWMSPTSGDTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREVEIEGYMDVWGQGTTVTVSS | 456 |
55 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGWINPNSGDTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDLDDDWYMDVWGKGTTVTVSS | 457 |
56 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIIDPSGDITSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTDSTTWDAFDIWGQGTMVTVSS | 458 |
57 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARVLVGSGSPDYWGQGTLVTVSS | 459 |
58 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTENEMHWVRQAPGQGLEWMGIIETSGGSTDYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREAAAGLDFQHWGQGTLVTVSS | 460 |
59 | QVQLVQSGAEVKKPGASVKVSCKASGYTFASYDMHWVRQAPGQGLEWMGIINPNSGGTNYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARANSWDAMVIDYWGQGTLVTVSS | 461 |
60 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSNSDMHWVRQAPGKGLEWVSVISGSGVTTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREHSSSWYTFDYWGQGTLVTVSS | 462 |
61 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTAYYMHWVRQAPGQGLEWLGWINPNSGGTDYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDDDSSGYYLDYWGQGTLVTVSS | 463 |
62 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYIHWVRQAPGQGLEWMGMINPSGGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARASGDYMDLIDYWGQGTLVTVSS | 464 |
63 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQGLEWLGWINPDSGGTNYEQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCALVGSSGYLAPTHWGQGTLVTVSS | 465 |
64 | QVQLVQSGAEVKKPGSSVKVSCKASGYPFTDYYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARVRGDGYNLGDYWGQGTLVTVSS | 466 |
65 | QVQLVQSGAEVKKPGASVKVSCKASGYTFSDYYMHWVRQAPGQGLEWMGWINPNSGGTNSAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDVDTAMGAGDYWGQGTLVTVSS | 467 |
66 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIHWVRQAPGQGLEWIGIINPSGGSASYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARVARWGYGDYPDYWGQGTLVTVSS | 468 |
67 | QVQLVQSGAEVKKPGASVKVSCKASGDTFTTHDINWVRQAPGQGLEWMGIISPSDGSTSYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRNGDYYYGMDVWGQGTTVTVSS | 469 |
68 | QVQLVQSGAEVKKPGASVKVSCKASGDTFTNYYIHWVRQAPGQGLEWMGWINPISGGTHYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGLGSSWYVLDYWGQGTLVTVSS | 470 |
69 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGWISADNGDTSFAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGSHYGYYGMDVWGQGTTVTVSS | 471 |
70 | QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGGISPIYGTPAYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCASPGPEGYYYGMDVWGQGTTVTVSS | 472 |
71 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDNYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASYHWDYGDYRFDYWGQGTLVTVSS | 473 |
72 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARVEIDYGDSPPDYWGQGTLVTVSS | 474 |
73 | QVQLVQSGAEVKKPGASVKVSCKASGGTSSSYAISWVRQAPGQGLEWMGIINPSDGDTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGAEWELRYAFDIWGQGTMVTVSS | 475 |
74 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYDISWVRQAPGQGLEWMGTINPSGGTTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARETYYGLYYYGMDVWGKGTTVTVSS | 476 |
75 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGWMNPKSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARAPSLRGYSYGPDYWGQGTLVTVSS | 477 |
76 | QVQLVQSGAEVKKPGASVKVSCKASGGTFTSYDINWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDRQERYYYYYMDVWGKGTLVTVSS | 478 |
77 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGIINPSDGSTDYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDRSYGDYYYGMDVWGQGTTVTVSS | 479 |
78 | QVQLVQSGAEVKKPGASVKVSCKASGGTFTSYDINWVRQAPGQGLEWMGIINPGGGNARHTQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREVFSENYYYYMDVWGKGTTVTVSS | 480 |
79 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSDGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREWDYTHYYYGMDVWGQGTTVTVSS | 481 |
80 | QVQLVQSGAEVKKPGASVKVSCKASGNTFTSHWIHWVRQAPGQGLEWMGGFDPEDGETVYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDSSGYYQYYFDYWGQGTLVTVSS | 482 |
81 | QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGGITPVFGIANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGSWDSSSWYIPEYWGQGTLVTVSS | 483 |
82 | QVQLVQSGAEVKKPGASVKVSCKASGFTFSDYDIVWVRQAPGQGLEWMGIINPRGGSTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASLVWGGAYYYYMDVWGQGTTVTVSS | 484 |
83 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWMNPNNGDTDYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTPVFSGSYYWYFDPWGQGTLVTVSS | 485 |
84 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGIINPSGGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTDQAVAGPYYYGMDVWGQGTLVTVSS | 486 |
85 | QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGLINPGSGNTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRWLAGPYYYGMDVWGQGTTVTVSS | 487 |
86 | QVQLVQSGAEVKKPGSSVKVSCKASGYMFTGHDMHWVRQAPGQGLEWMGGIIPIFGTPNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARVMGPVDYYYYGMDVWGQGTTVTVSS | 488 |
87 | QVQLVQSGAEVKKPGASVKVSCKASGYIFSNYDMHWVRQAPGQGLEWMGIINPSDGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLGPFGSYYYYMDVWGKGTTVTVSS | 489 |
88 | EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYAMTWVRQAPGKGLEWVSTINGDGDDTDYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCAREGVVVPPYYYYMDVWGKGTTVTVSS | 490 |
89 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYYMHWVRQAPGQGLEWMGQIDPNSGDTIYPQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSSGWSRYYYYYMDVWGKGTTVTVSS | 491 |
90 | QVQLVQSGAEVKKPGASVKVSCKASGSTFTNYQIHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDNGMTTGYYYYMDVWGKGTTVTVSS | 492 |
91 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIVWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRAMVTGYYYGMDVWGQGTTVTVSS | 493 |
92 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGIVNPSDGNTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRGYGDRGYYYGMDVWGQGTTVTVSS | 494 |
93 | QVQLVQSGAEVKKPGASVKVSCKASGGTLSSYDINWVRQAPGQGLEWMGWINTYNGNTYYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCATSPKATADYYYYYMDVWGKGTTVTVSS | 495 |
94 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGIINPSDGITDYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTSTVTPSYYYYYGMDVWGQGTTVTVSS | 496 |
95 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSHAIHWVRQAPGQGLEWMGIINPRDGDTVYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREPVAGTGYYYYYGMDVWGQGTLVTVSS | 497 |
96 | QVQLVQSGAEVKKPGASVKVSCKASGGTFNSYGINWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDNLAGFWSDYYYYGMDVWGQGTTVTVSS | 498 |
97 |
CD8結合劑 | VL序列 | SEQ ID NO: |
1 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR | 499 |
2 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSNLVSFGQGTKVEIKR | 500 |
3 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGQGTKVEIKR | 501 |
4 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPFTFGPGTKVDIKR | 502 |
5 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPHTFGQGTKVEIKR | 503 |
6 | DIQMTQSPSSLSASVGDRVTITCRASQSISRNLNWYQQKPGKAPKLLIYKASNLKGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLFGQGTKLEIKR | 504 |
7 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQTLQTPLTFGQGTKVEIKR | 505 |
8 | EIVMTQSPATLSVSPGERATLSCRASQSVSASDLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYGDSPGSFGQGTKLEIKR | 506 |
9 | DIQMTQSPSSLSASVGDRVTITCQASQDIGNYLNWYQQKPGKAPKLLIYAASTLQRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGGGTKVEIKR | 507 |
10 | EIVMTQSPATLSVSPGERATLSCRASQSISTHLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYGNSRTFGQGTKVEIKR | 508 |
11 | DIQMTQSPSSLSASVGDRVTITCRASQTISNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPTFGQGTKLEIKR | 509 |
12 | DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYDASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPYTFGQGTKLEIKR | 510 |
13 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIKR | 511 |
14 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGAHWPPTFGQGTKLEIKR | 512 |
15 | DIQMTQSPSSLSASVGDRVTITCRASQGISDSLAWYQQKPGKAPKLLIYGASSLRSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYRTPYTFGQGTKLEIKR | 513 |
16 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQESFTTQWTFGQGTKVEIKR | 514 |
17 | DIQMTQSPSSLSASVGDRVTITCQASQDIHNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGPGTKVDIKR | 515 |
18 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYSASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQRSNWPLYTFGQGTKVEIKR | 516 |
19 | DIQMTQSPSSLSASVGDRVTITCRASQSISDWLAWYQQKPGKAPKLLIYAASSLQTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAISFPITFGQGTKVEIKR | 517 |
20 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYSASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPFTFGPGTKVDIKR | 518 |
21 | DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAISFPLTFGGGTKVEIKR | 519 |
22 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTFPITFGQGTRLEIKR | 520 |
23 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYDASHLETGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCQQYYSYPPTFGQGTKVEIKR | 521 |
24 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASTLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPLTFGPGTKVDIKR | 522 |
25 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSFSTFYTFGQGTKVEIKR | 523 |
26 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPFTFGPGTKVDIKR | 524 |
27 | DIQMTQSPSSLSASVGDRVTITCRASQSINRFLNWYQQKPGKAPKLLIYAASSLQNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKR | 525 |
28 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR | 499 |
29 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPITFGQGTRLEIKR | 526 |
30 | DIQMTQSPSSLSASVGDRVTITCRASQSVSTYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTIPSTFGQGTKVEIKR | 527 |
31 | DIQMTQSPSSLSASVGDRVTITCQASQDIAKYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPPTFGGGTKVEIKR | 528 |
32 | DIQMTQSPSSLSASVGDRVTITCQASQGITNYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPWTFGPGTKVDIKR | 529 |
33 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR | 499 |
34 | DIQMTQSPSSLSASVGDRVTITCQASQDIHNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTTPLTFGQGTKVEIKR | 530 |
35 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYSAFSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPITFGQGTRLEIKR | 531 |
36 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYSASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQRSNWPPVTFGQGTKVEIKR | 532 |
37 | DIQMTQSPSSLSASVGDRVTITCQANQDISNFLEWYQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPITFGQGTRLEIKR | 533 |
38 | DIQMTQSPSSLSASVGDRVTITCRASQGISNNLNWYQQKPGKAPKLLIYEASTLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR | 534 |
39 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYGASTLETGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQPPGTFGQGTKVEIKR | 535 |
40 | DIQMTQSPSSLSASVGDRVTITCRASQSISRSLVWYQQKPGKAPKLLIYAASTLQTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNHFRTFGPGTKVDIKR | 536 |
41 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQRSDSTPLTFGGGTKVEIKR | 537 |
42 | DIQMTQSPSSLSASVGDRVTITCQASHDISKSLNWYQQKPGKAPKLLIYGASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLNSYPRTFGGGTKVEIKR | 538 |
43 | DIQMTQSPSSLSASVGDRVTITCRASQDIGAYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPYTFGQGTKLEIKR | 539 |
44 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIKR | 540 |
45 | DIQMTQSPSSLSASVGDRVTITCRASQGIRSYLAWYQQKPGKAPKLLIYGASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIKR | 541 |
46 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPYTFGQGTKLEIKR | 542 |
47 | DIQMTQSPSSLSASVGDRVTITCRASQNIGTWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPQTFGPGTKVDIKR | 543 |
48 | DIQMTQSPSSLSASVGDRVTITCRASQTISYYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYRTPYTFGQGTKLEIKR | 544 |
49 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYMGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWPTFGQGTRLEIKR | 545 |
50 | DIQMTQSPSSLSASVGDRVTITCRASQNINNYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTFSLPYTFGQGTKVEIKR | 546 |
51 | DIQMTQSPSSLSASVGDRVTITCRASQTISTYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIKR | 547 |
52 | DIQMTQSPSSLSASVGDRVTITCRASRGIGNDLAWYQQKPGKAPKLLIYDASTLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYNMPLTFGGGTKVEIKR | 548 |
52 | DIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGGGTKVEIKR | 549 |
54 | DIQMTQSPSSLSASVGDRVTITCRASQFIGSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIKR | 550 |
55 | DIQMTQSPSSLSASVGDRVTITCRASQSISSWMAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPYIFGQGTKVEIKR | 551 |
56 | DIQMTQSPSSLSASVGDRVTITCRASQGISNNLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPWTFGQGTKVEIKR | 552 |
57 | DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYASAPRTFGQGTKLEIKR | 553 |
58 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYKTSSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSFTIPYTFGQGTKVEIKR | 554 |
59 | DIQMTQSPSSLSASVGDRVTITCRVSQGISSYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR | 555 |
60 | DIQMTQSPSSLSASVGDRVTITCRASQSISDWLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR | 556 |
61 | DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYSASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYRTPPTFGPGTKVDIKR | 557 |
62 | DIQMTQSPSSLSASVGDRVTITCRASQSIRNYLTWYQQKPGKAPKLLIYSASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGQGTKVEIKR | 558 |
63 | DIQMTQSPSSLSASVGDRVTITCRASQNIRLYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSLTTPFTFGPGTKVDIKR | 559 |
64 | DIQMTQSPSSLSASVGDRVTITCQASQDIRKFLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLNGYPGTFGQGTRLEIKR | 560 |
65 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYTASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSLPLTFGGGTKVEIKR | 561 |
66 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLSWYQQKPGKAPKLLIYDASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYTTPRTFGPGTKVDIKR | 562 |
67 | DIQMTQSPSSLSASVGDRVTITCRASQNVRSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPYTFGQGTKLEIKR | 563 |
68 | DIQMTQSPSSLSASVGDRVTITCRASQGIGNDLGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYAPPPTFGQGTKVEIKR | 564 |
69 | DIQMTQSPSSLSASVGDRVTITCRASQSISNWLAWYQQKPGKAPKLLIYGASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPTFGQGTKLEIKR | 565 |
70 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPLTFGQGTKVEIKR | 566 |
71 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYLASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSDSIPVTFGQGTKVEIKR | 567 |
72 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYSTSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYNFGQGTKLEIKR | 568 |
73 | DIQMTQSPSSLSASVGDRVTITCRASESIGSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIKR | 569 |
74 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASSLQRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGQGTKVEIKR | 570 |
75 | EIVMTQSPATLSVSPGERATLSCRASQSVTSNYLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQHYGSSPAFGQGTRLEIKR | 571 |
76 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR | 499 |
77 | DIQMTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPTFGPGTKVDIKR | 572 |
78 | DIQMTQSPSSLSASVGDRVTITCRASQDIGNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYTYPYTFGQGTKLEIKR | 573 |
79 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTTPNTFGPGTKVDIKR | 574 |
80 | DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKR | 575 |
81 | DIQMTQSPSSLSASVGDRVTITCRASQGISNGLSWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIKR | 576 |
82 | DIQMTQSPSSLSASVGDRVTITCRASQNIRNYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR | 577 |
83 | DIQMTQSPSSLSASVGDRVTITCQASLDINNYLNWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSMPLTFGPGTKVDIKR | 578 |
84 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTTPWTFGQGTKLEIKR | 579 |
85 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGTKVEIKR | 580 |
86 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSDPLTFGQGTKVEIKR | 581 |
87 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYGASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPITFGQGTRLEIKR | 582 |
88 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTTPLTFGPGTKVDIKR | 583 |
89 | DIQMTQSPSSLSASVGDRVTITCRASQNIGNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPWTFGQGTKVEIKR | 584 |
90 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASTLRSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYQTPLTFGGGTKVEIKR | 585 |
91 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTTPPTFGQGTKVEIKR | 586 |
92 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPQTFGQGTKVEIKR | 587 |
93 | DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLNWYQQKPGKAPKLLIYAASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPITFGQGTKLEIKR | 588 |
94 | DIQMTQSPSSLSASVGDRVTITCRASQGINTWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTRLEIKR | 589 |
95 | DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTVPPTFGQGTKVEIKR | 590 |
96 | DIQMTQSPSSLSASVGDRVTITCQASQDIRYFLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQDDSFPLTFGGGTKVEIKR | 591 |
SEQ ID NO: | 序列 | 註釋 |
592 | MVVILDKRCY CNLLILILMI SECSVGILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTPI KGALEIYKNN THDLVGDVRL AGVIMAGVAI GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDKI SCKQTELSLD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE TLLRTLGYAT EDFDDLLESD SITGQIIYVD LSSYYIIVRV YFPILTEIQQ AYIQELLPVS FNNDNSEWIS IVPNFILVRN TLISNIEIGF CLITKRSVIC NQDYATPMTN NMRECLTGST EKCPRELVVS SHVPRFALSN GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA VLGNVIISLG KYLGSVNYNS EGIAIGPPVF TDKVDISSQI SSMNQSLQQS KDYIKEAQRL LDTVNPSLIS MLSMIILYVL SIASLCIGLI TFISFIIVEK KRNTYSRLED RRVRPTSSGD LYYIGT | 具有信號序列之尼帕病毒NiV-F(aa 1-546) Uniprot Q9IH63 |
593 | ILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTPI KGALEIYKNN THDLVGDVRL AGVIMAGVAI GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDKI SCKQTELSLD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE TLLRTLGYAT EDFDDLLESD SITGQIIYVD LSSYYIIVRV YFPILTEIQQ AYIQELLPVS FNNDNSEWIS IVPNFILVRN TLISNIEIGF CLITKRSVIC NQDYATPMTN NMRECLTGST EKCPRELVVS SHVPRFALSN GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA VLGNVIISLG KYLGSVNYNS EGIAIGPPVF TDKVDISSQI SSMNQSLQQS KDYIKEAQRL LDTVNPSLIS MLSMIILYVL SIASLCIGLI TFISFIIVEK KRNTYSRLED RRVRPTSSGD LYYIGT | 尼帕病毒NiV-F F0(aa 27-546) |
594 | ILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVR | 尼帕病毒NiV-F F2(aa 27-109) |
595 | LAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLISMLSMIILYVLSIASLCIGLITFISFIIVEKKRNTYSRLEDRRVRPTSSGDLYYIGT | 尼帕病毒NiV F F1(aa 110-546) |
596 | ILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTPI KGALEIYKNN THDLVGDVRL AGVIMAGVAI GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDKI SCKQTELSLD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE TLLRTLGYAT EDFDDLLESD SITGQIIYVD LSSYYIIVRV YFPILTEIQQ AYIQELLPVS FNNDNSEWIS IVPNFILVRN TLISNIEIGF CLITKRSVIC NQDYATPMTN NMRECLTGST EKCPRELVVS SHVPRFALSN GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA VLGNVIISLG KYLGSVNYNS EGIAIGPPVF TDKVDISSQI SSMNQSLQQS KDYIKEAQRL LDTVNPSLIS MLSMIILYVL SIASLCIGLI TFISFIIVEK KRNTGT | 尼帕病毒NiV-F F0截短(aa 525-544) |
597 | LAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRLLDTVNPSLISMLSMIILYVLSIASLCIGLITFISFIIVEKKRNTGT | 尼帕病毒NiV F F1(aa 110-546)截短(aa 525-544) |
598 | ILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTPI KGALEIYKNQ THDLVGDVRL AGVIMAGVAI GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDKI SCKQTELSLD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE TLLRTLGYAT EDFDDLLESD SITGQIIYVD LSSYYIIVRV YFPILTEIQQ AYIQELLPVS FNNDNSEWIS IVPNFILVRN TLISNIEIGF CLITKRSVIC NQDYATPMTN NMRECLTGST EKCPRELVVS SHVPRFALSN GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA VLGNVIISLG KYLGSVNYNS EGIAIGPPVF TDKVDISSQI SSMNQSLQQS KDYIKEAQRL LDTVNPSLIS MLSMIILYVL SIASLCIGLI TFISFIIVEK KRNTGT | 尼帕病毒NiV-F F0截短(aa 525-544)及N-連接糖基化位點突變 |
599 | MVVILDKRCY CNLLILILMI SECSVGILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTPI KGALEIYKNN THDLVGDVRL AGVIMAGVAI GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDKI SCKQTELSLD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE TLLRTLGYAT EDFDDLLESD SITGQIIYVD LSSYYIIVRV YFPILTEIQQ AYIQELLPVS FNNDNSEWIS IVPNFILVRN TLISNIEIGF CLITKRSVIC NQDYATPMTN NMRECLTGST EKCPRELVVS SHVPRFALSN GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA VLGNVIISLG KYLGSVNYNS EGIAIGPPVF TDKVDISSQI SSMNQSLQQS KDYIKEAQRL LDTVNPSLIS MLSMIILYVL SIASLCIGLI TFISFIIVEK KRNT | 胞質尾部截短之NiV融合糖蛋白(FcDelta22)(具有信號序列) |
1092 | ILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTPI KGALEIYKNN THDLVGDVRL AGVIMAGVAI GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDKI SCKQTELSLD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE TLLRTLGYAT EDFDDLLESD SITGQIIYVD LSSYYIIVRV YFPILTEIQQ AYIQELLPVS FNNDNSEWIS IVPNFILVRN TLISNIEIGF CLITKRSVIC NQDYATPMTN NMRECLTGST EKCPRELVVS SHVPRFALSN GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA VLGNVIISLG KYLGSVNYNS EGIAIGPPVF TDKVDISSQI SSMNQSLQQS KDYIKEAQRL LDTVNPSLIS MLSMIILYVL SIASLCIGLI TFISFIIVEK KRNT | 截短之NiV融合糖蛋白(FcDelta22) F0 |
1093 | LAGVIMAGVAI GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDKI SCKQTELSLD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE TLLRTLGYAT EDFDDLLESD SITGQIIYVD LSSYYIIVRV YFPILTEIQQ AYIQELLPVS FNNDNSEWIS IVPNFILVRN TLISNIEIGF CLITKRSVIC NQDYATPMTN NMRECLTGST EKCPRELVVS SHVPRFALSN GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA VLGNVIISLG KYLGSVNYNS EGIAIGPPVF TDKVDISSQI SSMNQSLQQS KDYIKEAQRL LDTVNPSLIS MLSMIILYVL SIASLCIGLI TFISFIIVEK KRNT | 截短之NiV融合糖蛋白(FcDelta22) F1 |
600 | MGPAENKKVR FENTTSDKGK IPSKVIKSYY GTMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白(602aa) |
601 | MGKVR FENTTSDKGK IPSKVIKSYY GTMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白截短Δ5 |
602 | MGNTTSDKGK IPSKVIKSYY GTMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白截短Δ10 |
603 | MGKGK IPSKVIKSYY GTMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白截短Δ15 |
604 | MGSKVIKSYY GTMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白截短Δ20 |
605 | MGSYY GTMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白截短Δ25 |
606 | MGTMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白截短Δ30 |
607 | MKKINEGLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PAICAEGVYN DAFLIDRINW ISAGVFLDSN ATAANPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QCT | NiVG蛋白附著糖蛋白截短及突變(E501A、W504A、Q530A、E533A)NiV G蛋白(Gc Δ34) |
608 | MATQEVRLKC LLCGIIVLVL SLEGLGILHY EKLSKIGLVK GITRKYKIKS NPLTKDIVIK MIPNVSNVSK CTGTVMENYK SRLTGILSPI KGAIELYNNN THDLVGDVKL AGVVMAGIAI GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDQI SCKQTELALD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE TLLRTLGYAT EDFDDLLESD SIAGQIVYVD LSSYYIIVRV YFPILTEIQQ AYVQELLPVS FNNDNSEWIS IVPNFVLIRN TLISNIEVKY CLITKKSVIC NQDYATPMTA SVRECLTGST DKCPRELVVS SHVPRFALSG GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCTTV VLGNIIISLG KYLGSINYNS ESIAVGPPVY TDKVDISSQI SSMNQSLQQS KDYIKEAQKI LDTVNPSLIS MLSMIILYVL SIAALCIGLI TFISFVIVEK KRGNYSRLDD RQVRPVSNGD LYYIGT | 亨德拉病毒F蛋白 Uniprot O89342(具有信號序列) |
609 | MMADSKLVSL NNNLSGKIKD QGKVIKNYYG TMDIKKINDG LLDSKILGAF NTVIALLGSI IIIVMNIMII QNYTRTTDNQ ALIKESLQSV QQQIKALTDK IGTEIGPKVS LIDTSSTITI PANIGLLGSK ISQSTSSINE NVNDKCKFTL PPLKIHECNI SCPNPLPFRE YRPISQGVSD LVGLPNQICL QKTTSTILKP RLISYTLPIN TREGVCITDP LLAVDNGFFA YSHLEKIGSC TRGIAKQRII GVGEVLDRGD KVPSMFMTNV WTPPNPSTIH HCSSTYHEDF YYTLCAVSHV GDPILNSTSW TESLSLIRLA VRPKSDSGDY NQKYIAITKV ERGKYDKVMP YGPSGIKQGD TLYFPAVGFL PRTEFQYNDS NCPIIHCKYS KAENCRLSMG VNSKSHYILR SGLLKYNLSL GGDIILQFIE IADNRLTIGS PSKIYNSLGQ PVFYQASYSW DTMIKLGDVD TVDPLRVQWR NNSVISRPGQ SQCPRFNVCP EVCWEGTYND AFLIDRLNWV SAGVYLNSNQ TAENPVFAVF KDNEILYQVP LAEDDTNAQK TITDCFLLEN VIWCISLVEI YDTGDSVIRP KLFAVKIPAQ CSES | 亨德拉病毒G蛋白Uniprot O89343 |
610 | MVVILDKRCY CNLLILILMI SECSVGILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTPI KGALEIYKNN THDLVGDVRL AGVIMAGVAI GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDKI SCKQTELSLD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE TLLRTLGYAT EDFDDLLESD SITGQIIYVD LSSYYIIVRV YFPILTEIQQ AYIQELLPVS FNNDNSEWIS IVPNFILVRN TLISNIEIGF CLITKRSVIC NQDYATPMTN NMRECLTGST EKCPRELVVS SHVPRFALSN GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA VLGNVIISLG KYLGSVNYNS EGIAIGPPVF TDKVDISSQI SSMNQSLQQS KDYIKEAQRL LDTVNPSLIS MLSMIILYVL SIASLCIGLI TFISFIIVEK KRNTGT | 尼帕病毒NiV-F F0截短(aa 525-544)(具有信號序列) |
611 | MVVILDKRCY CNLLILILMI SECSVGILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTPI KGALEIYKNQ THDLVGDVRL AGVIMAGVAI GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDKI SCKQTELSLD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE TLLRTLGYAT EDFDDLLESD SITGQIIYVD LSSYYIIVRV YFPILTEIQQ AYIQELLPVS FNNDNSEWIS IVPNFILVRN TLISNIEIGF CLITKRSVIC NQDYATPMTN NMRECLTGST EKCPRELVVS SHVPRFALSN GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA VLGNVIISLG KYLGSVNYNS EGIAIGPPVF TDKVDISSQI SSMNQSLQQS KDYIKEAQRL LDTVNPSLIS MLSMIILYVL SIASLCIGLI TFISFIIVEK KRNTGT | 尼帕病毒NiV-F F0截短(aa 525-544)及N-連接糖基化位點突變(具有信號序列) |
599 | MVVILDKRCY CNLLILILMI SECSVGILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTPI KGALEIYKNN THDLVGDVRL AGVIMAGVAI GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDKI SCKQTELSLD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE TLLRTLGYAT EDFDDLLESD SITGQIIYVD LSSYYIIVRV YFPILTEIQQ AYIQELLPVS FNNDNSEWIS IVPNFILVRN TLISNIEIGF CLITKRSVIC NQDYATPMTN NMRECLTGST EKCPRELVVS SHVPRFALSN GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA VLGNVIISLG KYLGSVNYNS EGIAIGPPVF TDKVDISSQI SSMNQSLQQS KDYIKEAQRL LDTVNPSLIS MLSMIILYVL SIASLCIGLI TFISFIIVEK KRNT | 胞質尾部截短之NiV融合糖蛋白(FcDelta22)(具有信號序列) |
612 | MKKINEGLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QCT | NiVG蛋白附著糖蛋白截短(Gc Δ34) |
613 | ILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK MIPNVSNMSQ CTGSVMENYK TRLNGILTPI KGALEIYKNN THDLVGDVRL AGVIMAGVAI GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDKI SCKQTELSLD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE TLLRTLGYAT EDFDDLLESD SITGQIIYVD LSSYYIIVRV YFPILTEIQQ AYIQELLPVS FNNDNSEWIS IVPNFILVRN TLISNIEIGF CLITKRSVIC NQDYATPMTN NMRECLTGST EKCPRELVVS SHVPRFALSN GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA VLGNVIISLG KYLGSVNYNS EGIAIGPPVF TDKVDISSQI SSMNQSLQQS KDYIKEAQRL LDTVNPSLIS MLSMIILYVL SIASLCIGLI TFISFIIVEK KRNT | 胞質尾部截短之成熟NiV融合糖蛋白(FcDelta22) |
614 | MSNKRTTVLIIISYTLFYLNNAAIVGFDFDKLNKIGVVQGRVLNYKIKGDPMTKDLVLKFIPNIVNITECVREPLSRYNETVRRLLLPIHNMLGLYLNNTNAKMTGLMIAGVIMGGIAIGIATAAQITAGFALYEAKKNTENIQKLTDSIMKTQDSIDKLTDSVGTSILILNKLQTYINNQLVPNLELLSCRQNKIEFDLMLTKYLVDLMTVIGPNINNPVNKDMTIQSLSLLFDGNYDIMMSELGYTPQDFLDLIESKSITGQIIYVDMENLYVVIRTYLPTLIEVPDAQIYEFNKITMSSNGGEYLSTIPNFILIRGNYMSNIDVATCYMTKASVICNQDYSLPMSQNLRSCYQGETEYCPVEAVIASHSPRFALTNGVIFANCINTICRCQDNGKTITQNINQFVSMIDNSTCNDVMVDKFTIKVGKYMGRKDINNINIQIGPQIIIDKVDLSNEINKMNQSLKDSIFYLREAKRILDSVNISLISPSVQLFLIIISVLSFIILLIIIVYLYCKSKHSYKYNKFIDDPDYYNDYKRERINGKASKSNNIYYVGD | gb:JQ001776:6129-8166|生物體:松灣病毒|毒株名稱:CG1a|蛋白名稱:融合糖蛋白|基因符號:F (具有信號序列) |
615 | MALNKNMFSSLFLGYLLVYATTVQSSIHYDSLSKVGVIKGLTYNYKIKGSPSTKLMVVKLIPNIDSVKNCTQKQYDEYKNLVRKALEPVKMAIDTMLNNVKSGNNKYRFAGAIMAGVALGVATAATVTAGIALHRSNENAQAIANMKSAIQNTNEAVKQLQLANKQTLAVIDTIRGEINNNIIPVINQLSCDTIGLSVGIRLTQYYSEIITAFGPALQNPVNTRITIQAISSVFNGNFDELLKIMGYTSGDLYEILHSELIRGNIIDVDVDAGYIALEIEFPNLTLVPNAVVQELMPISYNIDGDEWVTLVPRFVLTRTTLLSNIDTSRCTITDSSVICDNDYALPMSHELIGCLQGDTSKCAREKVVSSYVPKFALSDGLVYANCLNTICRCMDTDTPISQSLGATVSLLDNKRCSVYQVGDVLISVGSYLGDGEYNADNVELGPPIVIDKIDIGNQLAGINQTLQEAEDYIEKSEEFLKGVNPSIITLGSMVVLYIFMILIAIVSVIALVLSIKLTVKGNVVRQQFTYTQHVPSMENINYVSH | gb:NC_025352:5950-8712|生物體:墨江病毒|毒株名稱:Tongguan1|蛋白名稱:融合蛋白|基因符號:F (具有信號序列) |
616 | MKKKTDNPTISKRGHNHSRGIKSRALLRETDNYSNGLIVENLVRNCHHPSKNNLNYTKTQKRDSTIPYRVEERKGHYPKIKHLIDKSYKHIKRGKRRNGHNGNIITIILLLILILKTQMSEGAIHYETLSKIGLIKGITREYKVKGTPSSKDIVIKLIPNVTGLNKCTNISMENYKEQLDKILIPINNIIELYANSTKSAPGNARFAGVIIAGVALGVAAAAQITAGIALHEARQNAERINLLKDSISATNNAVAELQEATGGIVNVITGMQDYINTNLVPQIDKLQCSQIKTALDISLSQYYSEILTVFGPNLQNPVTTSMSIQAISQSFGGNIDLLLNLLGYTANDLLDLLESKSITGQITYINLEHYFMVIRVYYPIMTTISNAYVQELIKISFNVDGSEWVSLVPSYILIRNSYLSNIDISECLITKNSVICRHDFAMPMSYTLKECLTGDTEKCPREAVVTSYVPRFAISGGVIYANCLSTTCQCYQTGKVIAQDGSQTLMMIDNQTCSIVRIEEILISTGKYLGSQEYNTMHVSVGNPVFTDKLDITSQISNINQSIEQSKFYLDKSKAILDKINLNLIGSVPISILFIIAILSLILSIITFVIVMIIVRRYNKYTPLINSDPSSRRSTIQDVYIIPNPGEHSIRSAARSIDRDRD | gb:NC_025256:6865-8853|菌種:蝙蝠副黏病毒Eid_hel/GH-M74a/GHA/2009|菌株名稱:BatPV/Eid_hel/GH-M74a/GHA/2009|蛋白名稱:融合蛋白|基因符號:F(具有信號序列) |
27 | (GGGGGS)n,其中n為1至6 | 肽接頭 |
618 | MPAENKKVRFENTTSDKGKIPSKVIKSYYGTMDIKKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQIKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPEICWEGVYNDAFLIDRINWISAGVFLDSNQTAENPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCT | gb:AF212302|生物體:尼帕病毒|毒株名稱:UNKNOWN-AF212302|蛋白名稱:附著糖蛋白|基因符號:G (Uniprot Q9IH62) |
619 | MLSQLQKNYLDNSNQQGDKMNNPDKKLSVNFNPLELDKGQKDLNKSYYVKNKNYNVSNLLNESLHDIKFCIYCIFSLLIIITIINIITISIVITRLKVHEENNGMESPNLQSIQDSLSSLTNMINTEITPRIGILVTATSVTLSSSINYVGTKTNQLVNELKDYITKSCGFKVPELKLHECNISCADPKISKSAMYSTNAYAELAGPPKIFCKSVSKDPDFRLKQIDYVIPVQQDRSICMNNPLLDISDGFFTYIHYEGINSCKKSDSFKVLLSHGEIVDRGDYRPSLYLLSSHYHPYSMQVINCVPVTCNQSSFVFCHISNNTKTLDNSDYSSDEYYITYFNGIDRPKTKKIPINNMTADNRYIHFTFSGGGGVCLGEEFIIPVTTVINTDVFTHDYCESFNCSVQTGKSLKEICSESLRSPTNSSRYNLNGIMIISQNNMTDFKIQLNGITYNKLSFGSPGRLSKTLGQVLYYQSSMSWDTYLKAGFVEKWKPFTPNWMNNTVISRPNQGNCPRYHKCPEICYGGTYNDIAPLDLGKDMYVSVILDSDQLAENPEITVFNSTTILYKERVSKDELNTRSTTTSCFLFLDEPWCISVLETNRFNGKSIRPEIYSYKIPKYC | gb:JQ001776:8170-10275|生物體:松灣病毒|毒株名稱:CG1a|蛋白名稱:附著糖蛋白|基因符號:G |
620 | MPQKTVEFINMNSPLERGVSTLSDKKTLNQSKITKQGYFGLGSHSERNWKKQKNQNDHYMTVSTMILEILVVLGIMFNLIVLTMVYYQNDNINQRMAELTSNITVLNLNLNQLTNKIQREIIPRITLIDTATTITIPSAITYILATLTTRISELLPSINQKCEFKTPTLVLNDCRINCTPPLNPSDGVKMSSLATNLVAHGPSPCRNFSSVPTIYYYRIPGLYNRTALDERCILNPRLTISSTKFAYVHSEYDKNCTRGFKYYELMTFGEILEGPEKEPRMFSRSFYSPTNAVNYHSCTPIVTVNEGYFLCLECTSSDPLYKANLSNSTFHLVILRHNKDEKIVSMPSFNLSTDQEYVQIIPAEGGGTAESGNLYFPCIGRLLHKRVTHPLCKKSNCSRTDDESCLKSYYNQGSPQHQVVNCLIRIRNAQRDNPTWDVITVDLTNTYPGSRSRIFGSFSKPMLYQSSVSWHTLLQVAEITDLDKYQLDWLDTPYISRPGGSECPFGNYCPTVCWEGTYNDVYSLTPNNDLFVTVYLKSEQVAENPYFAIFSRDQILKEFPLDAWISSARTTTISCFMFNNEIWCIAALEITRLNDDIIRPIYYSFWLPTDCRTPYPHTGKMTRVPLRSTYNY | gb:NC_025256:9117-11015|菌種:蝙蝠副黏病毒Eid_hel/GH-M74a/GHA/2009|菌株名稱:BatPV/Eid_hel/GH-M74a/GHA/2009|蛋白名稱:糖蛋白|基因符號:G |
621 | MATNRDNTITSAEVSQEDKVKKYYGVETAEKVADSISGNKVFILMNTLLILTGAIITITLNITNLTAAKSQQNMLKIIQDDVNAKLEMFVNLDQLVKGEIKPKVSLINTAVSVSIPGQISNLQTKFLQKYVYLEESITKQCTCNPLSGIFPTSGPTYPPTDKPDDDTTDDDKVDTTIKPIEYPKPDGCNRTGDHFTMEPGANFYTVPNLGPASSNSDECYTNPSFSIGSSIYMFSQEIRKTDCTAGEILSIQIVLGRIVDKGQQGPQASPLLVWAVPNPKIINSCAVAAGDEMGWVLCSVTLTAASGEPIPHMFDGFWLYKLEPDTEVVSYRITGYAYLLDKQYDSVFIGKGGGIQKGNDLYFQMYGLSRNRQSFKALCEHGSCLGTGGGGYQVLCDRAVMSFGSEESLITNAYLKVNDLASGKPVIIGQTFPPSDSYKGSNGRMYTIGDKYGLYLAPSSWNRYLRFGITPDISVRSTTWLKSQDPIMKILSTCTNTDRDMCPEICNTRGYQDIFPLSEDSEYYTYIGITPNNGGTKNFVAVRDSDGHIASIDILQNYYSITSATISCFMYKDEIWCIAITEGKKQKDNPQRIYAHSYKIRQMCYNMKSATVTVGNAKNITIRRY | gb:NC_025352:8716-11257|生物體:墨江病毒|毒株名稱:Tongguan1|蛋白名稱:附著糖蛋白|基因符號:G |
622 | FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NivG蛋白附著糖蛋白 不具有胞質尾部 Uniprot Q9IH62 |
623 | FNTVIALLGSI IIIVMNIMII QNYTRTTDNQ ALIKESLQSV QQQIKALTDK IGTEIGPKVS LIDTSSTITI PANIGLLGSK ISQSTSSINE NVNDKCKFTL PPLKIHECNI SCPNPLPFRE YRPISQGVSD LVGLPNQICL QKTTSTILKP RLISYTLPIN TREGVCITDP LLAVDNGFFA YSHLEKIGSC TRGIAKQRII GVGEVLDRGD KVPSMFMTNV WTPPNPSTIH HCSSTYHEDF YYTLCAVSHV GDPILNSTSW TESLSLIRLA VRPKSDSGDY NQKYIAITKV ERGKYDKVMP YGPSGIKQGD TLYFPAVGFL PRTEFQYNDS NCPIIHCKYS KAENCRLSMG VNSKSHYILR SGLLKYNLSL GGDIILQFIE IADNRLTIGS PSKIYNSLGQ PVFYQASYSW DTMIKLGDVD TVDPLRVQWR NNSVISRPGQ SQCPRFNVCP EVCWEGTYND AFLIDRLNWV SAGVYLNSNQ TAENPVFAVF KDNEILYQVP LAEDDTNAQK TITDCFLLEN VIWCISLVEI YDTGDSVIRP KLFAVKIPAQ CSES | 亨德拉病毒G蛋白Uniprot O89343 不具有胞質尾部 |
624 | MVVILDKRCY CNLLILILMI SECSVG | 信號序列 |
625 | GGGGGS | 肽接頭 |
626 | (GGGGS)n,其中n為1至10 | 肽接頭 |
627 | GGGGS | 肽接頭 |
628 | PAENKKVR FENTTSDKGK IPSKVIKSYY GTMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白(602aa) 不具有N末端甲硫胺酸 |
629 | KVR FENTTSDKGK IPSKVIKSYY GTMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白截短Δ5不具有N末端甲硫胺酸 |
630 | NTTSDKGK IPSKVIKSYY GTMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白截短Δ10不具有N末端甲硫胺酸 |
631 | KGK IPSKVIKSYY GTMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白截短Δ15不具有N末端甲硫胺酸 |
632 | SKVIKSYY GTMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白截短Δ20不具有N末端甲硫胺酸 |
633 | SYY GTMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白截短Δ25不具有N末端甲硫胺酸 |
634 | TMDIKKINE GLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC | NiVG蛋白附著糖蛋白截短Δ30不具有N末端甲硫胺酸 |
635 | KKINEGLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PAICAEGVYN DAFLIDRINW ISAGVFLDSN ATAANPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QCT | NiVG蛋白附著糖蛋白截短及突變(E501A、W504A、Q530A、E533A) NiV G蛋白(Gc Δ34)不具有N末端甲硫胺酸 |
636 | MADSKLVSL NNNLSGKIKD QGKVIKNYYG TMDIKKINDG LLDSKILGAF NTVIALLGSI IIIVMNIMII QNYTRTTDNQ ALIKESLQSV QQQIKALTDK IGTEIGPKVS LIDTSSTITI PANIGLLGSK ISQSTSSINE NVNDKCKFTL PPLKIHECNI SCPNPLPFRE YRPISQGVSD LVGLPNQICL QKTTSTILKP RLISYTLPIN TREGVCITDP LLAVDNGFFA YSHLEKIGSC TRGIAKQRII GVGEVLDRGD KVPSMFMTNV WTPPNPSTIH HCSSTYHEDF YYTLCAVSHV GDPILNSTSW TESLSLIRLA VRPKSDSGDY NQKYIAITKV ERGKYDKVMP YGPSGIKQGD TLYFPAVGFL PRTEFQYNDS NCPIIHCKYS KAENCRLSMG VNSKSHYILR SGLLKYNLSL GGDIILQFIE IADNRLTIGS PSKIYNSLGQ PVFYQASYSW DTMIKLGDVD TVDPLRVQWR NNSVISRPGQ SQCPRFNVCP EVCWEGTYND AFLIDRLNWV SAGVYLNSNQ TAENPVFAVF KDNEILYQVP LAEDDTNAQK TITDCFLLEN VIWCISLVEI YDTGDSVIRP KLFAVKIPAQ CSES | 亨德拉病毒G蛋白Uniprot O89343不具有N末端甲硫胺酸 |
637 | KKINEGLLDSKILSA FNTVIALLGS IVIIVMNIMI IQNYTRSTDN QAVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC LQKTSNQILK PKLISYTLPV VGQSGTCITD PLLAMDEGYF AYSHLERIGS CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE FYYVLCAVST VGDPILNSTY WSGSLMMTRL AVKPKSNGGG YNQHQLALRS IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF LVRTEFKYND SNCPITKCQY SKPENCRLSM GIRPNSHYIL RSGLLKYNLS DGENPKVVFI EISDQRLSIG SPSKIYDSLG QPVFYQASFS WDTMIKFGDV LTVNPLVVNW RNNTVISRPG QSQCPRFNTC PEICWEGVYN DAFLIDRINW ISAGVFLDSN QTAENPVFTV FKDNEILYRA QLASEDTNAQ KTITNCFLLK NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QCT | NiVG蛋白附著糖蛋白截短(Gc Δ34)不具有N末端甲硫胺酸 |
638 | LSQLQKNYLDNSNQQGDKMNNPDKKLSVNFNPLELDKGQKDLNKSYYVKNKNYNVSNLLNESLHDIKFCIYCIFSLLIIITIINIITISIVITRLKVHEENNGMESPNLQSIQDSLSSLTNMINTEITPRIGILVTATSVTLSSSINYVGTKTNQLVNELKDYITKSCGFKVPELKLHECNISCADPKISKSAMYSTNAYAELAGPPKIFCKSVSKDPDFRLKQIDYVIPVQQDRSICMNNPLLDISDGFFTYIHYEGINSCKKSDSFKVLLSHGEIVDRGDYRPSLYLLSSHYHPYSMQVINCVPVTCNQSSFVFCHISNNTKTLDNSDYSSDEYYITYFNGIDRPKTKKIPINNMTADNRYIHFTFSGGGGVCLGEEFIIPVTTVINTDVFTHDYCESFNCSVQTGKSLKEICSESLRSPTNSSRYNLNGIMIISQNNMTDFKIQLNGITYNKLSFGSPGRLSKTLGQVLYYQSSMSWDTYLKAGFVEKWKPFTPNWMNNTVISRPNQGNCPRYHKCPEICYGGTYNDIAPLDLGKDMYVSVILDSDQLAENPEITVFNSTTILYKERVSKDELNTRSTTTSCFLFLDEPWCISVLETNRFNGKSIRPEIYSYKIPKYC | gb:JQ001776:8170-10275|生物體:松灣病毒|毒株名稱:CG1a|蛋白名稱:附著糖蛋白|基因符號:G不具有N末端甲硫胺酸 |
639 | PQKTVEFINMNSPLERGVSTLSDKKTLNQSKITKQGYFGLGSHSERNWKKQKNQNDHYMTVSTMILEILVVLGIMFNLIVLTMVYYQNDNINQRMAELTSNITVLNLNLNQLTNKIQREIIPRITLIDTATTITIPSAITYILATLTTRISELLPSINQKCEFKTPTLVLNDCRINCTPPLNPSDGVKMSSLATNLVAHGPSPCRNFSSVPTIYYYRIPGLYNRTALDERCILNPRLTISSTKFAYVHSEYDKNCTRGFKYYELMTFGEILEGPEKEPRMFSRSFYSPTNAVNYHSCTPIVTVNEGYFLCLECTSSDPLYKANLSNSTFHLVILRHNKDEKIVSMPSFNLSTDQEYVQIIPAEGGGTAESGNLYFPCIGRLLHKRVTHPLCKKSNCSRTDDESCLKSYYNQGSPQHQVVNCLIRIRNAQRDNPTWDVITVDLTNTYPGSRSRIFGSFSKPMLYQSSVSWHTLLQVAEITDLDKYQLDWLDTPYISRPGGSECPFGNYCPTVCWEGTYNDVYSLTPNNDLFVTVYLKSEQVAENPYFAIFSRDQILKEFPLDAWISSARTTTISCFMFNNEIWCIAALEITRLNDDIIRPIYYSFWLPTDCRTPYPHTGKMTRVPLRSTYNY | gb:NC_025256:9117-11015|菌種:蝙蝠副黏病毒Eid_hel/GH-M74a/GHA/2009|菌株名稱:BatPV/Eid_hel/GH-M74a/GHA/2009|蛋白名稱:糖蛋白|基因符號:G不具有N末端甲硫胺酸 |
640 | ATNRDNTITSAEVSQEDKVKKYYGVETAEKVADSISGNKVFILMNTLLILTGAIITITLNITNLTAAKSQQNMLKIIQDDVNAKLEMFVNLDQLVKGEIKPKVSLINTAVSVSIPGQISNLQTKFLQKYVYLEESITKQCTCNPLSGIFPTSGPTYPPTDKPDDDTTDDDKVDTTIKPIEYPKPDGCNRTGDHFTMEPGANFYTVPNLGPASSNSDECYTNPSFSIGSSIYMFSQEIRKTDCTAGEILSIQIVLGRIVDKGQQGPQASPLLVWAVPNPKIINSCAVAAGDEMGWVLCSVTLTAASGEPIPHMFDGFWLYKLEPDTEVVSYRITGYAYLLDKQYDSVFIGKGGGIQKGNDLYFQMYGLSRNRQSFKALCEHGSCLGTGGGGYQVLCDRAVMSFGSEESLITNAYLKVNDLASGKPVIIGQTFPPSDSYKGSNGRMYTIGDKYGLYLAPSSWNRYLRFGITPDISVRSTTWLKSQDPIMKILSTCTNTDRDMCPEICNTRGYQDIFPLSEDSEYYTYIGITPNNGGTKNFVAVRDSDGHIASIDILQNYYSITSATISCFMYKDEIWCIAITEGKKQKDNPQRIYAHSYKIRQMCYNMKSATVTVGNAKNITIRRY | gb:NC_025352:8716-11257|生物體:墨江病毒|毒株名稱:Tongguan1|蛋白名稱:附著糖蛋白|基因符號:G不具有N末端甲硫胺酸 |
641 | DFDKLNKIGVVQGRVLNYKIKGDPMTKDLVLKFIPNIVNITECVREPLSRYNETVRRLLLPIHNMLGLYLNNTNAKMTGLMIAGVIMGGIAIGIATAAQITAGFALYEAKKNTENIQKLTDSIMKTQDSIDKLTDSVGTSILILNKLQTYINNQLVPNLELLSCRQNKIEFDLMLTKYLVDLMTVIGPNINNPVNKDMTIQSLSLLFDGNYDIMMSELGYTPQDFLDLIESKSITGQIIYVDMENLYVVIRTYLPTLIEVPDAQIYEFNKITMSSNGGEYLSTIPNFILIRGNYMSNIDVATCYMTKASVICNQDYSLPMSQNLRSCYQGETEYCPVEAVIASHSPRFALTNGVIFANCINTICRCQDNGKTITQNINQFVSMIDNSTCNDVMVDKFTIKVGKYMGRKDINNINIQIGPQIIIDKVDLSNEINKMNQSLKDSIFYLREAKRILDSVNISLISPSVQLFLIIISVLSFIILLIIIVYLYCKSKHSYKYNKFIDDPDYYNDYKRERINGKASKSNNIYYVGD | gb:JQ001776:6129-8166|生物體:松灣病毒|毒株名稱:CG1a|蛋白名稱:融合糖蛋白|基因符號:F(不具有信號序列) |
642 | SRALLRETDNYSNGLIVENLVRNCHHPSKNNLNYTKTQKRDSTIPYRVEERKGHYPKIKHLIDKSYKHIKRGKRRNGHNGNIITIILLLILILKTQMSEGAIHYETLSKIGLIKGITREYKVKGTPSSKDIVIKLIPNVTGLNKCTNISMENYKEQLDKILIPINNIIELYANSTKSAPGNARFAGVIIAGVALGVAAAAQITAGIALHEARQNAERINLLKDSISATNNAVAELQEATGGIVNVITGMQDYINTNLVPQIDKLQCSQIKTALDISLSQYYSEILTVFGPNLQNPVTTSMSIQAISQSFGGNIDLLLNLLGYTANDLLDLLESKSITGQITYINLEHYFMVIRVYYPIMTTISNAYVQELIKISFNVDGSEWVSLVPSYILIRNSYLSNIDISECLITKNSVICRHDFAMPMSYTLKECLTGDTEKCPREAVVTSYVPRFAISGGVIYANCLSTTCQCYQTGKVIAQDGSQTLMMIDNQTCSIVRIEEILISTGKYLGSQEYNTMHVSVGNPVFTDKLDITSQISNINQSIEQSKFYLDKSKAILDKINLNLIGSVPISILFIIAILSLILSIITFVIVMIIVRRYNKYTPLINSDPSSRRSTIQDVYIIPNPGEHSIRSAARSIDRDRD | gb:NC_025256:6865-8853|菌種:蝙蝠副黏病毒Eid_hel/GH-M74a/GHA/2009|菌株名稱:BatPV/Eid_hel/GH-M74a/GHA/2009|蛋白名稱:融合蛋白|基因符號:F(不具有信號序列) |
643 | ILHY EKLSKIGLVK GITRKYKIKS NPLTKDIVIK MIPNVSNVSK CTGTVMENYK SRLTGILSPI KGAIELYNNN THDLVGDVKL AGVVMAGIAI GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN TNLVPTIDQI SCKQTELALD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE TLLRTLGYAT EDFDDLLESD SIAGQIVYVD LSSYYIIVRV YFPILTEIQQ AYVQELLPVS FNNDNSEWIS IVPNFVLIRN TLISNIEVKY CLITKKSVIC NQDYATPMTA SVRECLTGST DKCPRELVVS SHVPRFALSG GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCTTV VLGNIIISLG KYLGSINYNS ESIAVGPPVY TDKVDISSQI SSMNQSLQQS KDYIKEAQKI LDTVNPSLIS MLSMIILYVL SIAALCIGLI TFISFVIVEK KRGNYSRLDD RQVRPVSNGD LYYIGT | 亨德拉病毒F蛋白 Uniprot O89342 (不具有信號序列) |
644 | IHYDSLSKVGVIKGLTYNYKIKGSPSTKLMVVKLIPNIDSVKNCTQKQYDEYKNLVRKALEPVKMAIDTMLNNVKSGNNKYRFAGAIMAGVALGVATAATVTAGIALHRSNENAQAIANMKSAIQNTNEAVKQLQLANKQTLAVIDTIRGEINNNIIPVINQLSCDTIGLSVGIRLTQYYSEIITAFGPALQNPVNTRITIQAISSVFNGNFDELLKIMGYTSGDLYEILHSELIRGNIIDVDVDAGYIALEIEFPNLTLVPNAVVQELMPISYNIDGDEWVTLVPRFVLTRTTLLSNIDTSRCTITDSSVICDNDYALPMSHELIGCLQGDTSKCAREKVVSSYVPKFALSDGLVYANCLNTICRCMDTDTPISQSLGATVSLLDNKRCSVYQVGDVLISVGSYLGDGEYNADNVELGPPIVIDKIDIGNQLAGINQTLQEAEDYIEKSEEFLKGVNPSIITLGSMVVLYIFMILIAIVSVIALVLSIKLTVKGNVVRQQFTYTQHVPSMENINYVSH | gb:NC_025352:5950-8712|生物體:墨江病毒|毒株名稱:Tongguan1|蛋白名稱:融合蛋白|基因符號:F (不具有信號序列) |
645 | (GGGS)n,其中n為1至10 | 肽接頭 |
646 | GGGGSGGGGSGGGGS | 肽接頭 |
647 | TTAASGSSGGSSSGA | 肽接頭 |
648 | GSTSGSGKPGSGEGSTKG | 肽接頭 |
CD8結合劑 | H-CDR1 | H-CDR2 | H-CDR3 | |||
序列 | SEQ ID NO: | 序列 | SEQ ID NO: | 序列 | SEQ ID NO: | |
1 | GGTFSSY | 653 | DPSDGN | 701 | ERAAAGYYYYMDV | 148 |
2 | GGTFNTY | 654 | DPSSGG | 702 | EHAAGTYYYYMDV | 149 |
3 | GGTFSSY | 653 | DPSGGN | 703 | ERAAAGYYYYMDV | 148 |
4 | GYTFTGY | 655 | NPNNGD | 704 | EGYYYYGMDV | 649 |
5 | GYTFTDY | 656 | NPNSGG | 705 | EGDYYYGMDA | 150 |
6 | GYTFTRY | 657 | NPNDGS | 706 | ERGGMPDY | 151 |
7 | GYTFTSY | 658 | NPNSGG | 705 | GHGIPKY | 152 |
8 | GYTFTSY | 658 | NPNSGN | 707 | VRSGSPQH | 153 |
9 | GHTFSRH | 659 | NPNSGN | 707 | GGPWIVDAFDI | 154 |
10 | GYTFTSY | 658 | SAHNGV | 708 | GIAVAGTDY | 650 |
11 | GGTFSNT | 660 | NPSGGS | 709 | EATWGPYYYYMDV | 155 |
12 | GYTFTRS | 661 | SPYNGN | 710 | NKDGLQH | 156 |
13 | GDTFTGY | 662 | NPNSGD | 711 | DAKRVGYYYYMDV | 157 |
14 | GYTFTRY | 657 | NPNSGG | 705 | LVGGSPDY | 158 |
15 | GYTFTNY | 663 | NPNSGG | 705 | GAMVDY | 159 |
16 | GGTFSNT | 660 | NPSDGD | 712 | GNYVGSYYYGMDV | 160 |
17 | GYTFTNY | 663 | NPNSGD | 711 | DSRGDWYFDL | 161 |
18 | GYGFTRY | 664 | DPSGGS | 713 | HGGRGLADY | 162 |
19 | GYTFTSR | 665 | DPKSGD | 714 | LKELSSILDAFDI | 163 |
20 | GYTFTSY | 658 | NPGAGS | 715 | ERFGTGYYYYMDV | 164 |
21 | GFTFSNS | 666 | SGDGGT | 716 | VIGEMVDDAFDL | 165 |
22 | GYTFTGY | 655 | NPNSGD | 711 | ERLFGTYYYYMDV | 166 |
23 | GYTFTTY | 667 | IPIFGT | 717 | ADGELTDY | 167 |
24 | GFTFSSY | 668 | -GTGGG | 718 | HHLPAHYYYYMDV | 168 |
25 | GGTFSRY | 669 | NPNSGD | 711 | DVPAGRYYYYMDV | 169 |
26 | GNTFTSY | 670 | NPSDGS | 719 | DRGVGRYYYYMDV | 170 |
27 | GGTFSRY | 669 | NPSDGS | 719 | DSRYGRYYYYMDV | 171 |
28 | GGTFSNY | 671 | NPNGGS | 720 | EIVVGPYYYYMDV | 172 |
29 | GGTFTRY | 672 | NPNSGD | 711 | GMVRGPYYYYMDV | 173 |
30 | GGTFSSY | 653 | NPSGGS | 709 | EGVTGPYYYYMDV | 174 |
31 | GGTFSRF | 673 | NPSDGS | 719 | DAAAGTRYYYYYGMDV | 175 |
32 | GGTFSSH | 674 | NPSGGS | 709 | ELYSSTYYYYMDV | 176 |
33 | GGTFSSY | 653 | NPNTGG | 721 | ALYSGPYYYYMDV | 177 |
34 | GFTFSNS | 666 | SGSGGS | 722 | EHAAGTYYYYMDV | 149 |
35 | GGTFGSY | 675 | SGYNGD | 723 | DSLVGRYYYYMDV | 178 |
36 | GYIFTDY | 676 | SADNGN | 724 | RSELDY | 179 |
37 | GYTFTSY | 658 | SPNSGA | 725 | GDDNDY | 180 |
38 | GYTFTSY | 658 | NPNSGN | 707 | GEEVDY | 181 |
39 | GYTFTSY | 658 | NPSGGS | 709 | GRRVPDY | 182 |
40 | GYTFTDY | 656 | NPKSGA | 726 | GKVTTDY | 183 |
41 | GFTFSSF | 677 | SESGDS | 727 | GRELIEY | 184 |
42 | GFTFDDY | 678 | -GTGGG | 718 | VYDFPDV | 185 |
43 | GYTFTDS | 679 | NPSNGD | 728 | STYSHIDY | 186 |
44 | GYTFTNY | 663 | SPSDGS | 729 | EDSSGFDY | 187 |
45 | GYTFMNY | 680 | NPSGGS | 709 | DQGGGFDY | 188 |
46 | GYTFTSY | 658 | DPEDGE | 730 | DQGWGMDV | 189 |
47 | GYTFTSY | 658 | NPKSGR | 731 | LTEGIPDY | 190 |
48 | GYTLNDY | 681 | NPGGGS | 732 | DRYGPFDY | 191 |
49 | GYTFTSY | 658 | NPKTGD | 733 | LVAGGAPDY | 192 |
50 | GYTFTGY | 655 | DPSDGY | 734 | DGFTGDIAY | 193 |
51 | GYTFTGY | 655 | NPNSGG | 705 | VDDSSSPDY | 194 |
52 | GYTFTGY | 655 | MPISGT | 735 | GPDGTEVDY | 195 |
52 | GYTFTNH | 682 | NPNSGN | 707 | SESGSDLDY | 196 |
54 | GYTFTNY | 663 | SPTSGD | 736 | EVEIEGYMDV | 197 |
55 | GYTFTSY | 658 | NPNSGD | 711 | DLDDDWYMDV | 198 |
56 | GYTFTSY | 658 | DPSGDI | 737 | DSTTWDAFDI | 199 |
57 | GYTFTDY | 656 | NPNSGG | 705 | VLVGSGSPDY | 200 |
58 | GYTFTEN | 683 | ETSGGS | 738 | EAAAGLDFQH | 201 |
59 | GYTFASY | 684 | NPNSGG | 705 | ANSWDADY | 202 |
60 | GFTFSNS | 666 | SGSGVT | 739 | EHSSSWYTFDY | 203 |
61 | GYTFTAY | 685 | NPNSGG | 705 | DDDSSGYYLDY | 204 |
62 | GYTFTNY | 663 | NPSGGS | 709 | ASGDYMDLIDYMDY | 205 |
63 | GYTFTDY | 656 | NPDSGG | 740 | VGSSGYLAPTH | 206 |
64 | GYPFTDY | 686 | NPNSGN | 707 | VRGDGYNLGDY | 207 |
65 | GYTFSDY | 687 | NPNSGG | 705 | DVDTAMGAGDY | 208 |
66 | GYTFTDY | 656 | NPSGGS | 709 | VARWGYGDYPDY | 209 |
67 | GDTFTTH | 688 | SPSDGS | 729 | DRNGDYYYGMDV | 210 |
68 | GDTFTNY | 689 | NPISGG | 741 | EGLGSSWYVLDY | 211 |
69 | GYTFTSY | 658 | SADNGD | 742 | DGSHYGYYGMDV | 212 |
70 | GYTFTSY | 658 | SPIYGT | 743 | PGPEGYYYGMDV | 213 |
71 | GYTFTDN | 690 | NPNSGN | 707 | YHWDYGDYRFDY | 214 |
72 | GYTFTSY | 658 | NPNSGN | 707 | VEIDYGDSPPDY | 215 |
73 | GGTSSSY | 691 | NPSDGD | 712 | GAEWELRYAFDI | 216 |
74 | GYTFTTY | 667 | NPSGGT | 744 | ETYYGLYYYGMDV | 217 |
75 | GYTFTSY | 658 | NPKSGN | 745 | APSLRGYSYGPDY | 218 |
76 | GGTFTSY | 692 | NPSGGS | 709 | DRQERYYYYYMDV | 219 |
77 | GYTFTSY | 658 | NPSDGS | 719 | DRSYGDYYYGMDV | 220 |
78 | GGTFTSY | 692 | NPGGGN | 746 | EVFSENYYYYMDV | 221 |
79 | GYTFTSY | 658 | NPSDGS | 719 | EWDYTHYYYGMDV | 222 |
80 | GNTFTSH | 693 | DPEDGE | 730 | GDSSGYYQYYFDY | 223 |
81 | GYTFTSY | 658 | TPVFGI | 747 | GSWDSSSWYIPEY | 224 |
82 | GFTFSDY | 694 | NPRGGS | 748 | LVWGGAYYYYMDV | 225 |
83 | GYTFTSY | 658 | NPNNGD | 704 | PVFSGSYYWYFDP | 226 |
84 | GYTFTSY | 658 | NPSGGG | 749 | DQAVAGPYYYGMDV | 227 |
85 | GGTFSSY | 653 | NPGSGN | 750 | DRWLAGPYYYGMDV | 228 |
86 | GYMFTGH | 695 | IPIFGT | 717 | VMGPVDYYYYGMDV | 229 |
87 | GYIFSNY | 696 | NPSDGS | 719 | DLGPFGSYYYYMDV | 230 |
88 | GFTFSSY | 668 | NGDGDD | 751 | EGVVVPPYYYYMDV | 231 |
89 | GYTFTTY | 667 | DPNSGD | 752 | SSGWSRYYYYYMDV | 232 |
90 | GSTFTNY | 697 | NPSGGS | 709 | DNGMTTGYYYYMDV | 233 |
91 | GYTFTSY | 658 | NPSGGS | 709 | DRAMVTGYYYGMDV | 234 |
92 | GYTFTSY | 658 | NPSDGN | 753 | DRGYGDRGYYYGMDV | 235 |
93 | GGTLSSY | 698 | NTYNGN | 754 | SPKATADYYYYYMDV | 236 |
94 | GYTFTSY | 658 | NPSDGI | 755 | STVTPSYYYYYGMDV | 237 |
95 | GYTFTSH | 699 | NPRDGD | 756 | EPVAGTGYYYYYGMDV | 238 |
96 | GGTFNSY | 700 | NPNSGN | 707 | DNLAGFWSDYYYYGMDV | 239 |
97 | GRTFSGY | 1064 | SRGGLS | 1065 | DRSDLYEITAASNIDS | 1063 |
CD8結合劑 | L-CDR1 | L-CDR2 | L-CDR3 | ||||
序列 | SEQ ID NO: | 序列 | SEQ ID NO: | 序列 | SEQ ID NO: | ||
1 | RASQSISSYLN | 240 | AASSLQS | 294 | QQSYSTPLT | 333 | |
2 | QASQDISNYLN | 241 | AASSLQS | 294 | QQSYSNLVS | 334 | |
3 | RASQSISSYLN | 240 | AASSLQS | 294 | QQSYSTPLT | 333 | |
4 | RSSQSLLHSNGYNYLD | 242 | LGSNRAS | 295 | MQALQTPFT | 335 | |
5 | RSSQSLLHSNGYNYLD | 242 | LGSNRAS | 295 | MQGLQTPHT | 336 | |
6 | RASQSISRNLN | 243 | KASNLKG | 296 | QQTYSAPL | 337 | |
7 | RSSQSLLHSNGYNYLD | 242 | LGSNRAS | 295 | MQTLQTPLT | 338 | |
8 | RASQSVSASDLA | 244 | GASTRAT | 297 | QQYGDSPGS | 339 | |
9 | QASQDIGNYLN | 245 | AASTLQR | 298 | QQANSFPPT | 340 | |
10 | RASQSISTHLA | 246 | GASTRAT | 297 | QQYGNSRT | 341 | |
11 | RASQTISNYLN | 247 | AASTLQS | 299 | QQSYSTPPT | 342 | |
12 | RASQGIRNDLG | 248 | DASTLQS | 300 | QQSYSSPYT | 343 | |
13 | RASQSISNYLN | 249 | AASSLQS | 294 | QQSYSTPYT | 344 | |
14 | RSSQSLLHSNGYNYLD | 242 | LGSNRAS | 295 | MQGAHWPPT | 345 | |
15 | RASQGISDSLA | 250 | GASSLRS | 301 | QQSYRTPYT | 346 | |
16 | RASQSISNYLN | 249 | AASSLQS | 294 | QESFTTQWT | 347 | |
17 | QASQDIHNYLN | 251 | DASNLET | 302 | QQANSFPPT | 340 | |
18 | QASQDISNYLN | 241 | SASSLQS | 303 | QQRSNWPLYT | 348 | |
19 | RASQSISDWLA | 252 | AASSLQT | 304 | QQAISFPIT | 349 | |
20 | QASQDISNYLN | 241 | SASTLQS | 305 | QQSYSSPFT | 350 | |
21 | RASQSISTWLA | 253 | AASTLQS | 299 | QQAISFPLT | 351 | |
22 | RASQSISNYLN | 249 | AASTLQS | 299 | QQSYTFPIT | 352 | |
23 | RSSQSLLHSNGYNYLD | 242 | DASHLET | 306 | QQYYSYPPT | 353 | |
24 | QASQDISNYLN | 241 | AASTLHS | 307 | QQSYSAPLT | 354 | |
25 | QASQDISNYLN | 241 | AASTLQS | 299 | QQSFSTFYT | 355 | |
26 | QASQDISNYLN | 241 | AASTLQS | 299 | QQSYSIPFT | 356 | |
27 | RASQSINRFLN | 254 | AASSLQN | 308 | QQSYSTPYT | 344 | |
28 | RASQSISSYLN | 240 | AASSLQS | 294 | QQSYSTPLT | 333 | |
29 | QASQDISNYLN | 241 | AASTLQS | 299 | QQSYSTPIT | 357 | |
30 | RASQSVSTYLN | 255 | AASSLQS | 294 | QQSYTIPST | 358 | |
31 | QASQDIAKYLN | 256 | AASSLQS | 294 | QQSYSAPPT | 359 | |
32 | QASQGITNYLN | 257 | GASSLQS | 309 | QQSYSTPWT | 360 | |
33 | RASQSISSYLN | 240 | AASSLQS | 294 | QQSYSTPLT | 333 | |
34 | QASQDIHNYLN | 251 | AASTLQS | 299 | QQSYTTPLT | 361 | |
35 | QASQDISNYLN | 241 | SAFSLQS | 310 | QQSYSAPIT | 362 | |
36 | RASQSISSYLN | 240 | SASNLQS | 311 | QQRSNWPPVT | 363 | |
37 | QANQDISNFLE | 258 | DASSLES | 312 | QQSYSIPIT | 364 | |
38 | RASQGISNNLN | 259 | EASTLES | 313 | QQSYSTPLT | 333 | |
39 | RSSQSLLHSNGYNYLD | 242 | GASTLET | 314 | MQGLQPPGT | 365 | |
40 | RASQSISRSLV | 260 | AASTLQT | 315 | QQSYNHFRT | 366 | |
41 | QASQDISNYLN | 241 | DASNLET | 302 | QRSDSTPLT | 367 | |
42 | QASHDISKSLN | 261 | GASTLQS | 316 | QQLNSYPRT | 368 | |
43 | RASQDIGAYLA | 262 | AASSLQS | 294 | QQSYSIPYT | 369 | |
44 | RASQSISSYLA | 263 | AASSLQS | 294 | QQSYSTPYT | 344 | |
45 | RASQGIRSYLA | 264 | GASNLET | 317 | QQSYSTPYT | 344 | |
46 | RASQSISSYLN | 240 | AASSLQS | 294 | QQTYSTPYT | 370 | |
47 | RASQNIGTWLA | 265 | AASTLQS | 299 | QQSYSTPQT | 371 | |
48 | RASQTISYYLN | 266 | AASTLQS | 299 | QQSYRTPYT | 346 | |
49 | RSSQSLLHSNGYNYLD | 242 | MGSNRAS | 318 | MQGTHWPT | 372 | |
50 | RASQNINNYLN | 267 | GASSLQS | 309 | QQTFSLPYT | 373 | |
51 | RASQTISTYLN | 268 | DASNLET | 302 | QQSYSTPYT | 344 | |
52 | RASRGIGNDLA | 269 | DASTLET | 319 | QQGYNMPLT | 374 | |
52 | RASQTIGNYVN | 270 | GASNLHT | 320 | QQTYSAPLT | 375 | |
54 | RASQFIGSWLA | 271 | AASTLQS | 299 | QQSYSFPWT | 376 | |
55 | RASQSISSWMA | 272 | DASNLET | 302 | QQTYSTPYI | 377 | |
56 | RASQGISNNLN | 259 | DASNLET | 302 | QQSYSSPWT | 378 | |
57 | KSSQSVLYSSNNKNYLA | 273 | WASTRES | 321 | QQYASAPRT | 379 | |
58 | RASQSISSYLN | 240 | KTSSLES | 322 | QQSFTIPYT | 380 | |
59 | RVSQGISSYLN | 274 | GASSLQS | 309 | QQSYSTPLT | 333 | |
60 | RASQSISDWLA | 252 | DASNLET | 302 | QQSYSTPLT | 333 | |
61 | RASQGISNYLA | 275 | SASNLQS | 311 | QQTYRTPPT | 381 | |
62 | RASQSIRNYLT | 276 | SASNLQS | 311 | QQSYSTPLT | 333 | |
63 | RASQNIRLYLN | 277 | AASTLQS | 299 | QQSLTTPFT | 382 | |
64 | QASQDIRKFLN | 278 | AASSLQS | 294 | QQLNGYPGT | 383 | |
65 | RASQSISSYLN | 240 | TASNLQS | 323 | QQSYSLPLT | 384 | |
66 | QASQDISNYLS | 279 | DASNLQS | 324 | QQTYTTPRT | 385 | |
67 | RASQNVRSWLA | 280 | AASSLQS | 294 | QQSYNTPYT | 386 | |
68 | RASQGIGNDLG | 281 | AASSLQS | 294 | QQSYAPPPT | 387 | |
69 | RASQSISNWLA | 282 | GASNLET | 317 | QQSYSTPPT | 342 | |
70 | RSSQSLLHSNGYNYLD | 242 | LGSNRAS | 295 | MQGLQTPLT | 388 | |
71 | RASQSISSYLN | 240 | LASSLQS | 325 | QQSDSIPVT | 389 | |
72 | QASQDISNYLN | 241 | STSSLQS | 326 | QQSYSTPYN | 390 | |
73 | RASESIGSWLA | 283 | AASSLQS | 294 | QQSYSTPYT | 344 | |
74 | RASQSISNYLN | 249 | AASSLQR | 327 | QQSYSTPLT | 333 | |
75 | RASQSVTSNYLA | 284 | GASTRAT | 297 | QHYGSSPA | 391 | |
76 | RASQSISSYLN | 240 | AASSLQS | 294 | QQSYSTPLT | 333 | |
77 | RASQGISSYLA | 285 | AASTLQS | 299 | QQSYSTPPT | 342 | |
78 | RASQDIGNYLN | 286 | AASSLQS | 294 | QQAYTYPYT | 392 | |
79 | QASQDISNYLN | 241 | GASSLQS | 309 | QQSYTTPNT | 393 | |
80 | RASQGISNYLA | 275 | AASTLQS | 299 | QQSYSTPYT | 344 | |
81 | RASQGISNGLS | 287 | DASNLET | 302 | QQSYSTPFT | 394 | |
82 | RASQNIRNYLN | 288 | GASSLQS | 309 | QQSYSTPLT | 333 | |
83 | QASLDINNYLN | 289 | KASSLES | 328 | QQSYSMPLT | 395 | |
84 | QASQDISNYLN | 241 | AASSLQG | 329 | QQSYTTPWT | 396 | |
85 | QASQDISNYLN | 241 | AASSLQS | 294 | QQSYSSPLT | 397 | |
86 | QASQDISNYLN | 241 | KASSLES | 328 | QQSYSDPLT | 398 | |
87 | QASQDISNYLN | 241 | GASTLQS | 316 | QQSYSAPIT | 362 | |
88 | RASQSISNYLN | 249 | AASNLQS | 330 | QQSYTTPLT | 361 | |
89 | RASQNIGNYLN | 290 | AASTLQS | 299 | QQSYSTPPWT | 399 | |
90 | QASQDISNYLN | 241 | AASTLRS | 331 | QQSYQTPLT | 400 | |
91 | QASQDISNYLN | 241 | AASTLQS | 299 | QQSYTTPPT | 401 | |
92 | QASQDISNYLN | 241 | AASSLHS | 332 | QQSYSTPQT | 371 | |
93 | RASQGIRNDLN | 291 | AASNLQS | 330 | QQANSFPIT | 402 | |
94 | RASQGINTWLA | 292 | AASSLQS | 294 | QQSYSTPYT | 344 | |
95 | QASQDISNYLN | 241 | AASTLQS | 299 | QQSYTVPPT | 403 | |
96 | QASQDIRYFLN | 757 | AASTLQS | 299 | QQDDSFPLT | 404 | |
CD8結合劑 | H-CDR1 | H-CDR2 | H-CDR3 | ||||
序列 | SEQ ID NO: | 序列 | SEQ ID NO: | 序列 | SEQ ID NO: | ||
1 | GGTFSSYA | 758 | IDPSDGNT | 817 | AKERAAAGYYYYMDV | 878 | |
2 | GGTFNTYA | 759 | IDPSSGGT | 818 | AKEHAAGTYYYYMDV | 879 | |
3 | GGTFSSYA | 758 | IDPSGGNT | 819 | AKERAAAGYYYYMDV | 878 | |
4 | GYTFTGYY | 760 | INPNNGDT | 820 | AKEGYYYYGMDV | 880 | |
5 | GYTFTDYY | 761 | INPNSGGT | 821 | AKEGDYYYGMDA | 881 | |
6 | GYTFTRYD | 762 | INPNDGST | 822 | ARERGGMPDY | 882 | |
7 | GYTFTSYA | 763 | INPNSGGT | 821 | ARGHGIPKY | 883 | |
8 | GYTFTSYY | 764 | MNPNSGNT | 823 | ARVRSGSPQH | 884 | |
9 | GHTFSRHY | 765 | MNPNSGNT | 823 | ARGGPWIVDAFDI | 885 | |
10 | GYTFTSYG | 766 | ISAHNGVT | 824 | ARGIAVAGTDY | 886 | |
11 | GGTFSNTD | 767 | INPSGGST | 825 | AREATWGPYYYYMDV | 887 | |
12 | GYTFTRSY | 768 | ISPYNGNT | 826 | VRNKDGLQH | 888 | |
13 | GDTFTGYY | 769 | INPNSGDT | 827 | AKDAKRVGYYYYMDV | 889 | |
14 | GYTFTRYY | 770 | INPNSGGT | 821 | ARLVGGSPDY | 890 | |
15 | GYTFTNYD | 771 | INPNSGGT | 821 | ARGAMVDY | 891 | |
16 | GGTFSNTD | 767 | INPSDGDT | 828 | ARGNYVGSYYYGMDV | 892 | |
17 | GYTFTNYY | 772 | INPNSGDT | 827 | ARDSRGDWYFDL | 893 | |
18 | GYGFTRYS | 773 | IDPSGGST | 829 | TRHGGRGLADY | 894 | |
19 | GYTFTSRD | 774 | IDPKSGDT | 830 | ARLKELSSILDAFDI | 895 | |
20 | GYTFTSYD | 775 | INPGAGSS | 831 | ARERFGTGYYYYMDV | 896 | |
21 | GFTFSNSD | 776 | ISGDGGTT | 832 | ARVIGEMVDDAFDL | 897 | |
22 | GYTFTGYY | 760 | INPNSGDT | 827 | ARERLFGTYYYYMDV | 898 | |
23 | GYTFTTYD | 777 | IIPIFGTA | 833 | ARADGELTDY | 899 | |
24 | GFTFSSYT | 778 | I-GTGGGI | 834 | ARHHLPAHYYYYMDV | 900 | |
25 | GGTFSRYD | 779 | INPNSGDT | 827 | ARDVPAGRYYYYMDV | 901 | |
26 | GNTFTSYY | 780 | INPSDGST | 835 | AKDRGVGRYYYYMDV | 902 | |
27 | GGTFSRYA | 781 | INPSDGST | 835 | AKDSRYGRYYYYMDV | 903 | |
28 | GGTFSNYA | 782 | INPNGGSP | 836 | AKEIVVGPYYYYMDV | 904 | |
29 | GGTFTRYA | 783 | INPNSGDT | 827 | ARGMVRGPYYYYMDV | 905 | |
30 | GGTFSSYA | 758 | INPSGGST | 825 | AREGVTGPYYYYMDV | 906 | |
31 | GGTFSRFD | 784 | INPSDGST | 835 | ARDAAAGTRYYYYYGMDV | 907 | |
32 | GGTFSSHA | 785 | INPSGGST | 825 | ARELYSSTYYYYMDV | 908 | |
33 | GGTFSSYA | 758 | INPNTGGT | 837 | ARALYSGPYYYYMDV | 909 | |
34 | GFTFSNSD | 776 | ISGSGGST | 838 | AKEHAAGTYYYYMDV | 879 | |
35 | GGTFGSYG | 786 | ISGYNGDT | 839 | ARDSLVGRYYYYMDV | 910 | |
36 | GYIFTDYD | 787 | ISADNGNT | 840 | ARRSELDY | 911 | |
37 | GYTFTSYH | 788 | ISPNSGAT | 841 | ARGDDNDY | 912 | |
38 | GYTFTSYD | 775 | INPNSGNT | 842 | ARGEEVDY | 913 | |
39 | GYTFTSYP | 789 | INPSGGST | 825 | ARGRRVPDY | 914 | |
40 | GYTFTDYY | 761 | INPKSGAT | 843 | ARGKVTTDY | 915 | |
41 | GFTFSSFE | 790 | ISESGDSS | 844 | ASGRELIEY | 916 | |
42 | GFTFDDYA | 791 | I-GTGGGT | 845 | ARVYDFPDV | 917 | |
43 | GYTFTDSY | 792 | MNPSNGDT | 846 | ARSTYSHIDY | 918 | |
44 | GYTFTNYY | 772 | ISPSDGST | 847 | AREDSSGFDY | 919 | |
45 | GYTFMNYY | 793 | INPSGGST | 825 | ARDQGGGFDY | 920 | |
46 | GYTFTSYY | 764 | FDPEDGET | 848 | ARDQGWGMDV | 921 | |
47 | GYTFTSYY | 764 | INPKSGRT | 849 | ARLTEGIPDY | 922 | |
48 | GYTLNDYY | 794 | INPGGGST | 850 | ARDRYGPFDY | 923 | |
49 | GYTFTSYD | 775 | MNPKTGDT | 851 | TRLVAGGAPDY | 924 | |
50 | GYTFTGYY | 760 | IDPSDGYT | 852 | ARDGFTGDIAY | 925 | |
51 | GYTFTGYY | 760 | INPNSGGT | 821 | ARVDDSSSPDY | 926 | |
52 | GYTFTGYY | 760 | IMPISGTT | 853 | TTGPDGTEVDY | 927 | |
52 | GYTFTNHY | 795 | MNPNSGNT | 823 | ASSESGSDLDY | 928 | |
54 | GYTFTNYY | 772 | MSPTSGDT | 854 | AREVEIEGYMDV | 929 | |
55 | GYTFTSYY | 764 | INPNSGDT | 827 | AKDLDDDWYMDV | 930 | |
56 | GYTFTSYY | 764 | IDPSGDIT | 855 | TTDSTTWDAFDI | 931 | |
57 | GYTFTDYY | 761 | INPNSGGT | 821 | ARVLVGSGSPDY | 932 | |
58 | GYTFTENE | 796 | IETSGGST | 856 | AREAAAGLDFQH | 933 | |
59 | GYTFASYD | 797 | INPNSGGT | 821 | ARANSWDAMVIDY | 934 | |
60 | GFTFSNSD | 776 | ISGSGVTT | 857 | AREHSSSWYTFDY | 935 | |
61 | GYTFTAYY | 798 | INPNSGGT | 821 | ARDDDSSGYYLDY | 936 | |
62 | GYTFTNYY | 772 | INPSGGST | 825 | ARASGDYMDLIDY | 937 | |
63 | GYTFTDYH | 799 | INPDSGGT | 858 | ALVGSSGYLAPTH | 938 | |
64 | GYPFTDYY | 800 | MNPNSGNT | 823 | ARVRGDGYNLGDY | 939 | |
65 | GYTFSDYY | 801 | INPNSGGT | 821 | ARDVDTAMGAGDY | 940 | |
66 | GYTFTDYY | 761 | INPSGGSA | 859 | ARVARWGYGDYPDY | 941 | |
67 | GDTFTTHD | 802 | ISPSDGST | 847 | ARDRNGDYYYGMDV | 942 | |
68 | GDTFTNYY | 803 | INPISGGT | 860 | AREGLGSSWYVLDY | 943 | |
69 | GYTFTSYD | 775 | ISADNGDT | 861 | ARDGSHYGYYGMDV | 944 | |
70 | GYTFTSYD | 775 | ISPIYGTP | 862 | ASPGPEGYYYGMDV | 945 | |
71 | GYTFTDNY | 804 | MNPNSGNT | 823 | ASYHWDYGDYRFDY | 946 | |
72 | GYTFTSYY | 764 | MNPNSGNT | 823 | ARVEIDYGDSPPDY | 947 | |
73 | GGTSSSYA | 805 | INPSDGDT | 828 | ARGAEWELRYAFDI | 948 | |
74 | GYTFTTYD | 777 | INPSGGTT | 863 | ARETYYGLYYYGMDV | 949 | |
75 | GYTFTSYD | 775 | MNPKSGNT | 864 | ARAPSLRGYSYGPDY | 950 | |
76 | GGTFTSYD | 806 | INPSGGST | 825 | AKDRQERYYYYYMDV | 951 | |
77 | GYTFTSYD | 775 | INPSDGST | 835 | AKDRSYGDYYYGMDV | 952 | |
78 | GGTFTSYD | 806 | INPGGGNA | 865 | AREVFSENYYYYMDV | 953 | |
79 | GYTFTSYY | 764 | INPSDGST | 835 | AREWDYTHYYYGMDV | 954 | |
80 | GNTFTSHW | 807 | FDPEDGET | 848 | ARGDSSGYYQYYFDY | 955 | |
81 | GYTFTSYD | 775 | ITPVFGIA | 866 | ARGSWDSSSWYIPEY | 956 | |
82 | GFTFSDYD | 808 | INPRGGST | 867 | ASLVWGGAYYYYMDV | 957 | |
83 | GYTFTSYG | 766 | MNPNNGDT | 868 | TTPVFSGSYYWYFDP | 958 | |
84 | GYTFTSYD | 775 | INPSGGGT | 869 | TTDQAVAGPYYYGMDV | 959 | |
85 | GGTFSSYA | 758 | INPGSGNT | 870 | ARDRWLAGPYYYGMDV | 960 | |
86 | GYMFTGHD | 809 | IIPIFGTP | 871 | ARVMGPVDYYYYGMDV | 961 | |
87 | GYIFSNYD | 810 | INPSDGST | 835 | ARDLGPFGSYYYYMDV | 962 | |
88 | GFTFSSYA | 811 | INGDGDDT | 872 | AREGVVVPPYYYYMDV | 963 | |
89 | GYTFTTYY | 812 | IDPNSGDT | 873 | ARSSGWSRYYYYYMDV | 964 | |
90 | GSTFTNYQ | 813 | INPSGGST | 825 | ARDNGMTTGYYYYMDV | 965 | |
91 | GYTFTSYD | 775 | INPSGGST | 825 | ARDRAMVTGYYYGMDV | 966 | |
92 | GYTFTSYD | 775 | VNPSDGNT | 874 | ARDRGYGDRGYYYGMDV | 967 | |
93 | GGTLSSYD | 814 | INTYNGNT | 875 | ATSPKATADYYYYYMDV | 968 | |
94 | GYTFTSYD | 775 | INPSDGIT | 876 | TTSTVTPSYYYYYGMDV | 969 | |
95 | GYTFTSHA | 815 | INPRDGDT | 877 | AREPVAGTGYYYYYGMDV | 970 | |
96 | GGTFNSYG | 816 | MNPNSGNT | 823 | ARDNLAGFWSDYYYYGMDV | 971 | |
97 | GRTFSGYV | 1066 | ISRGGLST | 1067 | AADRSDLYEITAASNIDS | 1068 |
CD8結合劑 | L-CDR1 | L-CDR2 | L-CDR3 | |||
序列 | SEQ ID NO: | 序列 | SEQ ID NO: | 序列 | SEQ ID NO: | |
1 | QSISSY | 972 | AAS | 1021 | QQSYSTPLT | 333 |
2 | QDISNY | 973 | AAS | 1021 | QQSYSNLVS | 334 |
3 | QSISSY | 972 | AAS | 1021 | QQSYSTPLT | 333 |
4 | QSLLHSNGYNY | 974 | LGS | 1022 | MQALQTPFT | 335 |
5 | QSLLHSNGYNY | 974 | LGS | 1022 | MQGLQTPHT | 336 |
6 | QSISRN | 975 | KAS | 1023 | QQTYSAPL | 337 |
7 | QSLLHSNGYNY | 974 | LGS | 1022 | MQTLQTPLT | 338 |
8 | QSVSASD | 976 | GAS | 1024 | QQYGDSPGS | 339 |
9 | QDIGNY | 977 | AAS | 1021 | QQANSFPPT | 340 |
10 | QSISTH | 978 | GAS | 1024 | QQYGNSRT | 341 |
11 | QTISNY | 979 | AAS | 1021 | QQSYSTPPT | 342 |
12 | QGIRND | 980 | DAS | 1025 | QQSYSSPYT | 343 |
13 | QSISNY | 981 | AAS | 1021 | QQSYSTPYT | 344 |
14 | QSLLHSNGYNY | 974 | LGS | 1022 | MQGAHWPPT | 345 |
15 | QGISDS | 982 | GAS | 1024 | QQSYRTPYT | 346 |
16 | QSISNY | 981 | AAS | 1021 | QESFTTQWT | 347 |
17 | QDIHNY | 983 | DAS | 1025 | QQANSFPPT | 340 |
18 | QDISNY | 973 | SAS | 1026 | QQRSNWPLYT | 348 |
19 | QSISDW | 984 | AAS | 1021 | QQAISFPIT | 349 |
20 | QDISNY | 973 | SAS | 1026 | QQSYSSPFT | 350 |
21 | QSISTW | 985 | AAS | 1021 | QQAISFPLT | 351 |
22 | QSISNY | 981 | AAS | 1021 | QQSYTFPIT | 352 |
23 | QSLLHSNGYNY | 974 | DAS | 1025 | QQYYSYPPT | 353 |
24 | QDISNY | 973 | AAS | 1021 | QQSYSAPLT | 354 |
25 | QDISNY | 973 | AAS | 1021 | QQSFSTFYT | 355 |
26 | QDISNY | 973 | AAS | 1021 | QQSYSIPFT | 356 |
27 | QSINRF | 986 | AAS | 1021 | QQSYSTPYT | 344 |
28 | QSISSY | 972 | AAS | 1021 | QQSYSTPLT | 333 |
29 | QDISNY | 973 | AAS | 1021 | QQSYSTPIT | 357 |
30 | QSVSTY | 987 | AAS | 1021 | QQSYTIPST | 358 |
31 | QDIAKY | 988 | AAS | 1021 | QQSYSAPPT | 359 |
32 | QGITNY | 989 | GAS | 1024 | QQSYSTPWT | 360 |
33 | QSISSY | 972 | AAS | 1021 | QQSYSTPLT | 333 |
34 | QDIHNY | 983 | AAS | 1021 | QQSYTTPLT | 361 |
35 | QDISNY | 973 | SAF | 1027 | QQSYSAPIT | 362 |
36 | QSISSY | 972 | SAS | 1026 | QQRSNWPPVT | 363 |
37 | QDISNF | 990 | DAS | 1025 | QQSYSIPIT | 364 |
38 | QGISNN | 991 | EAS | 1028 | QQSYSTPLT | 333 |
39 | QSLLHSNGYNY | 974 | GAS | 1024 | MQGLQPPGT | 365 |
40 | QSISRS | 992 | AAS | 1021 | QQSYNHFRT | 366 |
41 | QDISNY | 973 | DAS | 1025 | QRSDSTPLT | 367 |
42 | HDISKS | 993 | GAS | 1024 | QQLNSYPRT | 368 |
43 | QDIGAY | 994 | AAS | 1021 | QQSYSIPYT | 369 |
44 | QSISSY | 972 | AAS | 1021 | QQSYSTPYT | 344 |
45 | QGIRSY | 995 | GAS | 1024 | QQSYSTPYT | 344 |
46 | QSISSY | 972 | AAS | 1021 | QQTYSTPYT | 370 |
47 | QNIGTW | 996 | AAS | 1021 | QQSYSTPQT | 371 |
48 | QTISYY | 997 | AAS | 1021 | QQSYRTPYT | 346 |
49 | QSLLHSNGYNY | 974 | MGS | 1029 | MQGTHWPT | 372 |
50 | QNINNY | 998 | GAS | 1024 | QQTFSLPYT | 373 |
51 | QTISTY | 999 | DAS | 1025 | QQSYSTPYT | 344 |
52 | RGIGND | 1000 | DAS | 1025 | QQGYNMPLT | 374 |
52 | QTIGNY | 1001 | GAS | 1024 | QQTYSAPLT | 375 |
54 | QFIGSW | 1002 | AAS | 1021 | QQSYSFPWT | 376 |
55 | QSISSW | 1003 | DAS | 1025 | QQTYSTPYI | 377 |
56 | QGISNN | 991 | DAS | 1025 | QQSYSSPWT | 378 |
57 | QSVLYSSNNKNY | 1004 | WAS | 1030 | QQYASAPRT | 379 |
58 | QSISSY | 972 | KTS | 1031 | QQSFTIPYT | 380 |
59 | QGISSY | 1005 | GAS | 1024 | QQSYSTPLT | 333 |
60 | QSISDW | 984 | DAS | 1025 | QQSYSTPLT | 333 |
61 | QGISNY | 1006 | SAS | 1026 | QQTYRTPPT | 381 |
62 | QSIRNY | 1007 | SAS | 1026 | QQSYSTPLT | 333 |
63 | QNIRLY | 1008 | AAS | 1021 | QQSLTTPFT | 382 |
64 | QDIRKF | 1009 | AAS | 1021 | QQLNGYPGT | 383 |
65 | QSISSY | 972 | TAS | 1032 | QQSYSLPLT | 384 |
66 | QDISNY | 973 | DAS | 1025 | QQTYTTPRT | 385 |
67 | QNVRSW | 1010 | AAS | 1021 | QQSYNTPYT | 386 |
68 | QGIGND | 1011 | AAS | 1021 | QQSYAPPPT | 387 |
69 | QSISNW | 1012 | GAS | 1024 | QQSYSTPPT | 342 |
70 | QSLLHSNGYNY | 974 | LGS | 1022 | MQGLQTPLT | 388 |
71 | QSISSY | 972 | LAS | 1033 | QQSDSIPVT | 389 |
72 | QDISNY | 973 | STS | 1034 | QQSYSTPYN | 390 |
73 | ESIGSW | 1013 | AAS | 1021 | QQSYSTPYT | 344 |
74 | QSISNY | 981 | AAS | 1021 | QQSYSTPLT | 333 |
75 | QSVTSNY | 1014 | GAS | 1024 | QHYGSSPA | 391 |
76 | QSISSY | 972 | AAS | 1021 | QQSYSTPLT | 333 |
77 | QGISSY | 1005 | AAS | 1021 | QQSYSTPPT | 342 |
78 | QDIGNY | 977 | AAS | 1021 | QQAYTYPYT | 392 |
79 | QDISNY | 973 | GAS | 1024 | QQSYTTPNT | 393 |
80 | QGISNY | 1006 | AAS | 1021 | QQSYSTPYT | 344 |
81 | QGISNG | 1015 | DAS | 1025 | QQSYSTPFT | 394 |
82 | QNIRNY | 1016 | GAS | 1024 | QQSYSTPLT | 333 |
83 | LDINNY | 1017 | KAS | 1023 | QQSYSMPLT | 395 |
84 | QDISNY | 973 | AAS | 1021 | QQSYTTPWT | 396 |
85 | QDISNY | 973 | AAS | 1021 | QQSYSSPLT | 397 |
86 | QDISNY | 973 | KAS | 1023 | QQSYSDPLT | 398 |
87 | QDISNY | 973 | GAS | 1024 | QQSYSAPIT | 362 |
88 | QSISNY | 981 | AAS | 1021 | QQSYTTPLT | 361 |
89 | QNIGNY | 1018 | AAS | 1021 | QQSYSTPPWT | 399 |
90 | QDISNY | 973 | AAS | 1021 | QQSYQTPLT | 400 |
91 | QDISNY | 973 | AAS | 1021 | QQSYTTPPT | 401 |
92 | QDISNY | 973 | AAS | 1021 | QQSYSTPQT | 371 |
93 | QGIRND | 980 | AAS | 1021 | QQANSFPIT | 402 |
94 | QGINTW | 1019 | AAS | 1021 | QQSYSTPYT | 344 |
95 | QDISNY | 973 | AAS | 1021 | QQSYTVPPT | 403 |
96 | QDIRYF | 1020 | AAS | 1021 | QQDDSFPLT | 404 |
CD8結合劑變體 | 全結合劑序列 | SEQ ID NO: |
98 | QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIIDPSDGNTNYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKERAAAGYYYYMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR | 1035 |
99 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIIDPSDGNTNYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKERAAAGYYYYMDVWGQGTTVTVSS | 1036 |
100 | QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQCLEWMGIIDPSDGNTNYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKERAAAGYYYYMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGCGTKVEIKR | 1037 |
101 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGCGTKVEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQCLEWMGIIDPSDGNTNYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKERAAAGYYYYMDVWGQGTTVTVSS | 1038 |
102 | QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQCLEWMGIIDPSDGNTNYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKERAAAGYYYYMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGCGTKVEIKR | 1037 |
103 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGCGTKVEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQCLEWMGIIDPSDGNTNYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKERAAAGYYYYMDVWGQGTTVTVSS | 1038 |
104 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPHTFGQGTKVEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIQWVRQAPGQGLEWMGWINPNSGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKEGDYYYGMDAWGQGTMVTVSS | 1039 |
105 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIQWVRQAPGQGLEWMGWINPNSGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKEGDYYYGMDAWGQGTMVTVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPHTFGQGTKVEIKR | 1040 |
106 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPHTFGQGTKVEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIQWVRQAPGQGLEWMGWINPNSGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKEGDYYYGMDAWGQGTMVTVSS | 1039 |
107 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIQWVRQAPGQCLEWMGWINPNSGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKEGDYYYGMDAWGQGTMVTVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPHTFGCGTKVEIKR | 1041 |
108 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPHTFGCGTKVEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIQWVRQAPGQCLEWMGWINPNSGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKEGDYYYGMDAWGQGTMVTVSS | 1042 |
109 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIQWVRQAPGQCLEWMGWINPNSGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKEGDYYYGMDAWGQGTMVTVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPHTFGCGTKVEIKR | 1041 |
110 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPHTFGCGTKVEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIQWVRQAPGQCLEWMGWINPNSGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKEGDYYYGMDAWGQGTMVTVSS | 1042 |
111 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQCLEWMGGFDPEDGETIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQGWGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPYTFGCGTKLEIKR | 1043 |
112 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQCLEWMGGFDPEDGETIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQGWGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPYTFGCGTKLEIKR | 1043 |
113 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGGFDPEDGETIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQGWGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPYTFGQGTKLEIKR | 1044 |
114 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPYTFGCGTKLEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQCLEWMGGFDPEDGETIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQGWGMDVWGQGTTVTVSS | 1045 |
115 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPYTFGCGTKLEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQCLEWMGGFDPEDGETIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQGWGMDVWGQGTTVTVSS | 1045 |
116 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPYTFGQGTKLEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGGFDPEDGETIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQGWGMDVWGQGTTVTVSS | 1046 |
117 | DIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGGGTKVEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSS | 1047 |
118 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGGGTKVEIKR | 1048 |
119 | DIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGGGTKVEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSS | 1047 |
120 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQCLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGCGTKVEIKR | 1049 |
121 | DIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGCGTKVEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQCLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSS | 1050 |
122 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQCLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGCGTKVEIKR | 1049 |
123 | DIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGCGTKVEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQCLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSS | 1050 |
124 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGGGTKVEIKR | 1051 |
125 | DIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGGGTKVEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSS | 1052 |
126 | QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGGGTKVEIKR | 1051 |
127 | DIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGGGTKVEIKRGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSS | 1052 |
128 | QVQLVESGGGLVQAGGSLRLSCAASGRTFSGYVMGWFRQAPGKQRKFVAAISRGGLSTSYADSVKGRFTISRDNAKNTVFLQMNTLKPEDTAVYYCAADRSDLYEITAASNIDSWGQGTLVTVSS | 1060 |
CD8融合蛋白 | 全融合蛋白序列 | SEQ ID NO: |
NivG.002_1 | MKKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQIKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPAICAEGVYNDAFLIDRINWISAGVFLDSNATAANPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCTGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIIDPSDGNTNYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKERAAAGYYYYMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR | 1053 |
NivG.002_5 | MKKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQIKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPAICAEGVYNDAFLIDRINWISAGVFLDSNATAANPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCTGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIQWVRQAPGQGLEWMGWINPNSGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKEGDYYYGMDAWGQGTMVTVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPHTFGQGTKVEIKR | 1054 |
NivG.002_46 | MKKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQIKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPAICAEGVYNDAFLIDRINWISAGVFLDSNATAANPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCTGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGGFDPEDGETIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQGWGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPYTFGQGTKLEIKR | 1055 |
NivG.002_52 | MKKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQIKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPAICAEGVYNDAFLIDRINWISAGVFLDSNATAANPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCTGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGGGTKVEIKR | 1056 |
NIvG.002_97 | MKKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQIKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPAICAEGVYNDAFLIDRINWISAGVFLDSNATAANPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCTGGGGSGGGGSGGGGSQVQLVESGGGLVQAGGSLRLSCAASGRTFSGYVMGWFRQAPGKQRKFVAAISRGGLSTSYADSVKGRFTISRDNAKNTVFLQMNTLKPEDTAVYYCAADRSDLYEITAASNIDSWGQGTLVTVSS | 1069 |
NivG.002_1_2 | KKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQIKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPAICAEGVYNDAFLIDRINWISAGVFLDSNATAANPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCTGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIIDPSDGNTNYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKERAAAGYYYYMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR | 1070 |
NivG.002_5_2 | KKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQIKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPAICAEGVYNDAFLIDRINWISAGVFLDSNATAANPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCTGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIQWVRQAPGQGLEWMGWINPNSGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKEGDYYYGMDAWGQGTMVTVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPHTFGQGTKVEIKR | 1071 |
NivG.002_46_2 | KKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQIKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPAICAEGVYNDAFLIDRINWISAGVFLDSNATAANPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCTGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGGFDPEDGETIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQGWGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPYTFGQGTKLEIKR | 1072 |
NivG.002_52_2 | KKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQIKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPAICAEGVYNDAFLIDRINWISAGVFLDSNATAANPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCTGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSESGSDLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQTIGNYVNWYQQKPGKAPKLLIYGASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPLTFGGGTKVEIKR | 1073 |
NIvG.002_97_2 | KKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQIKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPAICAEGVYNDAFLIDRINWISAGVFLDSNATAANPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQCTGGGGSGGGGSGGGGSQVQLVESGGGLVQAGGSLRLSCAASGRTFSGYVMGWFRQAPGKQRKFVAAISRGGLSTSYADSVKGRFTISRDNAKNTVFLQMNTLKPEDTAVYYCAADRSDLYEITAASNIDSWGQGTLVTVSS | 1074 |
在一些實施例中,揭示了能夠結合CD8α或CD8β之抗體或其抗原結合片段,該抗體或其抗原結合片段包含重鏈可變區及輕鏈可變區,其中重鏈可變區包含三個重鏈互補決定區(HCDR1、HCDR2及HCDR3),並且輕鏈可變區包含三個輕鏈互補決定區(LCDR1、LCDR2及LCDR3)。在一些實施例中,HCDR1、HCDR2及HCDR3包含
表 3 、表 8及
表 10中所述之SEQ ID NO中的任一者之胺基酸序列,並且LCDR1、LCDR2及LCDR3包含
表 3 、表 9及
表 11中所述之SEQ ID NO中的任一者之胺基酸序列。在一些實施例中,重鏈可變區(VH)包含SEQ ID NO: 405-498 (表5)中的任一者之胺基酸序列,並且輕鏈可變區(VL) 包含SEQ ID NO: 499-591 (
表 6)中之任一者之胺基酸序列。
在另一個實施例中,抗體或其抗原結合片段包含具有與選自SEQ ID NO: 405-498之序列有至少90%、95%、96%、97%、98%、99%或100%同一性之胺基酸序列之VH。
在另一個實施例中,抗體或其抗原結合片段包包含具有與選自SEQ ID NO: 499-591之序列有至少90%、95%、96%、97%、98%、99%或100%同一性之胺基酸序列之VL。
在另一個實施例中,抗體或抗原結合片段包含具有與選自SEQ ID NO: 405-498之序列有至少90%、95%、96%、97%、98%、99%或100%同一性之胺基酸序列之VH以及具有與選自SEQ ID NO: 499-591之序列有至少90%、95%、96%、97%、98%、99%或100%同一性之胺基酸序列之VL。
在另一個實施例中,抗體或其抗原結合片段包含具有與SEQ ID NO: 1060有至少90%、95%、96%、97%、98%、99%或100%同一性之胺基酸序列之VH。
在另一個實施例中,抗體或其抗原結合片段包含為SEQ ID NO: 405之VH及為SEQ ID NO: 499之VL。
在另一個實施例中,抗體或其抗原結合片段包含為SEQ ID NO: 408之VH及為SEQ ID NO: 503之VL。
在另一個實施例中,抗體或其抗原結合片段包含為SEQ ID NO: 448之VH及為SEQ ID NO: 542之VL。
在另一個實施例中,抗體或其抗原結合片段包含為SEQ ID NO: 455之VH及為SEQ ID NO: 549之VL。
在另一個實施例中,抗體或其抗原結合片段包含為SEQ ID NO: 1060之VH。
在另一個實施例中,抗體或其抗原結合片段包含分別為SEQ ID NO: 1、70、148、240、294及333之HCDR1、HCDR2、HCDR3、LCDR1、LCDR2及LCDR3。
在另一個實施例中,抗體或其抗原結合片段包含分別為SEQ ID NO: 5、74、150、242、295及336之HCDR1、HCDR2、HCDR3、LCDR1、LCDR2及LCDR3。
在另一個實施例中,抗體或其抗原結合片段包含分別為SEQ ID NO: 40、109、189、240、294及370之HCDR1、HCDR2、HCDR3、LCDR1、LCDR2及LCDR3。
在另一個實施例中,抗體或其抗原結合片段包含分別為SEQ ID NO: 43、77、196、270、320及375之HCDR1、HCDR2、HCDR3、LCDR1、LCDR2及LCDR3。
在另一個實施例中,抗體或其抗原結合片段包含分別為SEQ ID NO: 1061、1062及1063之HCDR1、HCDR2及HCDR3。
在一些實施例中,單域抗體可為人類或人源化的。在一些實施例中,單域抗體或其部分係天然存在的。在一些實施例中,單域抗體或其部分係合成的。
在一些實施例中,單域抗體係其互補決定區係單域多肽之一部分之抗體。在一些實施例中,單域抗體係僅重鏈抗體可變域。在一些實施例中,單域抗體不包括輕鏈。
在各種實施例中,本文所述之抗體或抗原結合片段中之任一者可包含重鏈恆定區及輕鏈恆定區。重鏈恆定區可為保持完整重鏈的至少一個效應子功能之IgG、IgM、IgA、IgD或IgE同型或者其衍生物或片段。重鏈恆定區可為人類IgG同型。重鏈恆定區可為人類IgG1或人類IgG4同型。重鏈恆定區可為人類IgG1同型。輕鏈恆定區可為保持完整輕鏈的至少一個效應子功能之人類κ輕鏈或λ輕鏈或其衍生物或片段。輕鏈恆定區可為人類κ輕鏈。
在各種實施例中,所揭示之抗體或抗原結合片段中之任一者可為嚙齒動物抗體或其抗原結合片段、嵌合抗體或其抗原結合片段、CDR移植抗體或其抗原結合片段或者人源化抗體或其抗原結合片段。在另一個實施例中,所揭示之抗體或抗原結合片段中之任一者包含人類或人類衍生之重鏈可變區及輕鏈可變區,包括人類構架或具有一個或多個回復突變之人類構架。在各種實施例中,所揭示之抗體或抗原結合片段中的任一者可為Fab、Fab'、F(ab')2、Fd、scFv、(scFv)2、scFv-Fc、VHH或Fv片段。
其重鏈CDR、輕鏈CDR、VH或VL胺基酸序列在很大程度上不同於
表 3 至表 6中所示的抗體的抗體涵蓋在本揭示之範圍內。通常,其涉及在抗原結合位點或構架中用具有相似電荷、疏水或立體化學特徵之胺基酸進行一個或多個保守胺基酸取代,而不會不利地改變抗體之性質。亦可進行保守取代以改良抗體之性質,例如穩定性或親和力。可對VH或VL序列進行1個、2個、3個、4個、5個、6個、7個、8個、9個、10個、11個、12個、13個、14個或15個胺基酸取代。例如,「保守胺基酸取代」可涉及用非天然殘基取代天然胺基酸殘基,使得對該位置處胺基酸殘基之極性或電荷幾乎沒有影響或沒有影響。期望之胺基酸置換可由熟習此項技術者在期望此類取代時確定。例如,胺基酸取代可用於鑑定分子序列之重要殘基,或增加或降低本文所述分子之親和力。以下八個基團含有作為彼此之保守胺基酸取代之胺基酸:1)丙胺酸(A)、甘胺酸(G);2)天冬胺酸(D)、麩胺酸(E);3)天冬醯胺(N)、麩醯胺酸(Q);4)精胺酸(R)、離胺酸(K);5)異白胺酸(I)、白胺酸(L)、甲硫胺酸(M)、纈胺酸(V);6)苯丙胺酸(F)、酪胺酸(Y)、色胺酸(W);7)絲胺酸(S)、蘇胺酸(T);及8)半胱胺酸(C)、甲硫胺酸(M)。
在一些實施例中,抗體或其抗原結合片段與人類CD8α或CD8β結合。在一些實施例中,抗體或其抗原結合片段與由兩條α鏈構成之人類CD8α同源二聚體結合。在一些實施例中,抗體或其抗原結合片段與由一個α鏈及一個β鏈構成之人類CD8異源二聚體結合。
在一些實施例中,結合CD8之抗體或抗原結合片段係單鏈可變片段。在涉及含有重鏈可變區及輕鏈可變區兩者之單一多肽之實施例中,設想了此等可變區之兩個取向。在一些情況下,重鏈可變區位於輕鏈可變區之N末端側,意謂重鏈可變區更靠近多肽之N末端。在其他情況下,輕鏈可變區位於重鏈可變區之N末端側,意謂輕鏈可變區比重鏈可變區更靠近多肽之N末端。
在一些實施例中,scFv結合蛋白包含接頭。在一些實施例中,接頭在重鏈可變區(VH)及輕鏈可變區(VL)之間(或反之亦然)。在一些實施例中,接頭包含GS、GGS、GGGS(SEQ ID NO: 645)、GGGGS (SEQ ID NO: 627)、GGGGGS (SEQ ID NO: 625)、SEQ ID NO: 645-648中的任一者或其組合之胺基酸序列。引入新的二硫鍵之取代亦在本揭示之範疇內,例如藉由在VH FR 2中進行G44C取代以及在VL FR4中進行G100C取代。
在一些實施例中,抗CD8抗體或抗原結合片段以介於約1nM及約900nM之間的親和常數(K
D)與人類CD8結合。在一些實施例中,對於人類CD8,K
D介於約5nM至約500nM、約6nM至約10nM、約11nM至約20nM、約25nM至約40nM、約40nM至約60nM、約70nM至約90nM、約100nM至約120nM、約125nM至約140nM、約145nM至約160nM、約170nM至約200nM、約210nM至約250nM、約260nM至約300nM、約310nM至約350nM、約360nM至約400nM、約410nM至約450nM以及約460nM至約500nM之間。在一些實施例中,抗CD8抗體或抗原結合片段以500nM、400nM、300nM、200nM、100nM、50nM、20nM或10nM或更低之親和常數(K
D)與人類CD8結合。在一些實施例中,抗CD8抗體或抗原結合片段以相當之結合親和力(K
D)與人類CD8及食蟹猴、獼猴(M. mulatta)或南平頂猴CD8結合。
在一些實施例中,抗CD8抗體或抗原結合片段與食蟹猴、獼猴或南平頂猴CD8結合。在一些實施例中,抗CD8抗體或抗原結合與小鼠、狗、豬等CD8結合。在一些實施例中,對於食蟹猴或南平頂猴CD8,K
D介於約5nM至約500nM、約6nM至約10nM、約11nM至約20nM、約25nM至約40nM、約40nM至約60nM、約70nM至約90nM、約100nM至約120nM、約125nM至約140nM、約145nM至約160nM、約170nM至約200nM、約210nM至約250nM、約260nM至約300nM、約310nM至約350nM、約360nM至約400nM、約410nM至約450nM以及約460nM至約500nM之間。在一些實施例中,抗CD8抗體或抗原結合片段以500nM、400nM、300nM、200nM、100nM、50nM、20nM或10nM或更低之親和常數(K
D)與食蟹猴或南平頂猴CD8結合。
特異性結合CD8α或CD8β之抗體或其抗原結合片段係指相對於其他抗原靶分別優先結合CD8α或CD8β之抗體或其結合片段。如本文所用,該術語可與「抗CD8」抗體或「結合CD8之抗體」互換。在一些實施例中,能夠與CD8α或CD8β結合之抗體或結合片段可以比其他抗原更高之親和力來進行結合。在一些實施例中,能夠結合CD8α或CD8β之抗體或結合片段可以至少約10
-1、10
-2、10
-3、10
-4、10
-5、10
-6、10
-7、10
-8、10
- 9、10
-10、10
-11、10
-12或更大(或介於兩者之間的任何值)之K
D結合該抗原,例如,如藉由表面電漿子共振或熟習此項技術者已知之其他方法量測。
本揭示之另一個實施例係分離的聚核苷酸,其編碼本揭示之任一個抗體重鏈可變區或抗體輕鏈可變區。本文揭示了某些例示性聚核苷酸,但考慮到給定表現系統中的遺傳密碼之簡併性或密碼子偏好性,對本揭示之抗體或其抗原結合片段進行編碼之其他聚核苷酸亦在本揭示之範疇內。編碼本揭示之抗體或其抗原結合片段之VH或VL或其片段的聚核苷酸序列可以可操作地連接至一個或多個調控元件,諸如啟動子及增強子,此等調控元件允許核苷酸序列在預期宿主細胞中表現。聚核苷酸可為cDNA。
本揭示之另一個實施例係包含本揭示的聚核苷酸之載體。此類載體可為質體載體、病毒載體、用於桿狀病毒表現之載體、基於轉座子之載體或任何其他適於藉由任何方式將本揭示的聚核苷酸引入給定生物體或遺傳背景之載體。例如,將視情况連接至恆定區並且編碼本揭示之抗體之輕鏈可變區及重鏈可變區的聚核苷酸可插入表現載體中。可將輕鏈及重鏈選殖至相同或不同之表現載體中。可將編碼免疫球蛋白鏈之DNA片段有效連接至表現載體中確保免疫球蛋白多肽表現之對照序列。此類對照序列包括信號序列、啟動子(例如天然相關或異源啟動子)、增強子元件及轉錄終止序列,並且被選擇為與選擇以表現抗體之宿主細胞相容。載體被結合至適當之宿主後,將宿主保持在適於蛋白質之高水準表現之條件下,該蛋白質由結合的聚核苷酸編碼。
合適的表現載體通常可作為附加體或作為宿主染色體DNA之組成部分在宿主生物體中複製。通常,表現載體含有選擇標記物,諸如氨苄青黴素抗性、潮黴素抗性、四環素抗性、卡那黴素抗性或新黴素抗性,以允許偵測用期望DNA序列轉化之細胞。合適的載體、啟動子及增強子元件係此項技術中已知的;許多可商購獲得以生成個體重組構築體。
本揭示之另一個實施例係包含本揭示的載體的宿主細胞。術語「宿主細胞」係指其中已引入載體之細胞。應當理解,術語「宿主細胞」不僅旨在指特定個體細胞,亦指此細胞之子代。因為由於突變或者由於環境影響,在後代中可發生某些修飾,因此此類子代可與母體細胞不同,但仍包括在本文所用之術語「宿主細胞」之範疇內。此類宿主細胞可為真核細胞、原核細胞、植物細胞或古菌細胞。大腸桿菌(Escherichia coli)、桿菌屬(bacilli)(諸如枯草芽孢桿菌(Bacillus subtilis))及其他腸桿菌科(enterobacteriaceae)(諸如沙門氏菌(Salmonella)、沙雷氏菌(Serratia))以及各種假單胞菌屬(Pseudomonas)物種係原核宿主細胞之實例。其他微生物(諸如酵母)亦可用於表現。酵母屬(Saccharomyces)(例如,釀酒酵母(S. cerevisiae))及畢赤酵母(Pichia)係合適的酵母宿主細胞之實例。例示性真核細胞可為哺乳動物、昆蟲、禽類或其他動物來源。
靶向 CD8 之融合蛋白
本文亦提供了靶向CD8之融合蛋白,此等融合蛋白可暴露於脂質顆粒或病毒載體上之表面上。在一些實施例中,本文揭示之CD8結合劑可融合至副黏病毒科家族之包膜糖蛋白G、H及/或F蛋白。在一些實施例中,融合劑含有尼帕病毒(Nipah virus)蛋白F、麻疹病毒(measles virus) F蛋白、樹鼩副黏病毒(tupaia paramyxovirus) F蛋白、副黏病毒(paramyxovirus) F蛋白、亨德拉病毒(Hendra virus F) F蛋白、亨尼帕病毒(Henipavirus) F蛋白、麻疹病毒(Morbilivirus) F蛋白、呼吸病毒(respirovirus) F蛋白、仙台病毒(Sendai virus F) F蛋白、腮腺炎病毒(rubulavirus)F蛋白或禽腮腺炎病毒(avulavirus) F蛋白。在一些實施例中,脂質顆粒含有亨尼帕病毒包膜附著糖蛋白G (G蛋白)或其生物活性部分及/或亨尼帕病毒包膜融合糖蛋白F (F蛋白)或其生物活性部分。
在特定實施例中,融合劑係桿狀病毒之糖蛋白GP 64或糖蛋白GP 64變體E45K/T259A。
在一些實施例中,融合劑係來自呼吸道副黏病毒之血球凝集素-神經胺酸酶(HN)及/或融合(F)蛋白(F/HN)。在一些實施例中,呼吸道副黏病毒係仙台病毒。仙台病毒之HN及F糖蛋白用於經由HN蛋白連接至唾液酸,並且介導細胞融合以經由F蛋白進入細胞。在一些實施例中,融合劑係來自小鼠副流感病毒1型之F及/或HN蛋白(參見例如美國專利第10704061號)。
在一些實施例中,脂質顆粒(例如病毒載體)用如本文所述之病毒糖蛋白(諸如NiV-F及/或NiV-G蛋白)假型化。
在一些實施例中,病毒載體進一步包含與目標配體特異性結合之載體表面靶向部分。在一些實施例中,載體表面靶向部分係多肽。在一些實施例中,用靶向部分修飾對副黏病毒包膜蛋白(例如G蛋白)進行編碼之核酸,以特異性結合目標細胞上之目標分子。在一些實施例中,靶向部分可為任何靶向蛋白,包括但不一定限於抗體及其抗原結合片段。
據報導,來自不同物種之亨尼帕病毒F蛋白表現出與來自其他物種之G蛋白之相容性以觸發融合(Brandel-Tretheway等人,Journal of Virology,2019. 93(13):e00577-19)。在所提供的脂質顆粒(例如,慢病毒載體)之一些態樣中,F蛋白對G蛋白係異源的,亦即,F蛋白及G蛋白或其生物活性部分來自不同之亨尼帕病毒物種。例如,在一些實施例中,G蛋白來自亨德拉病毒,並且F蛋白係如所描述之NiV-F。在其他態樣中,F及/或G蛋白係含有來自不同物種亨尼帕病毒之F及/或G蛋白區之嵌合之F及/或G蛋白。在一些實施例中,用來自亨尼帕病毒異源序列之胺基酸置換F蛋白之一部分導致與具有異源序列之G蛋白融合。(Brandel-Tretheway等人,2019)。在一些情況下,嵌合F及/或G蛋白含有來自一個亨尼帕病毒物種之細胞外域及來自不同之亨尼帕病毒物種之跨膜及/或細胞質域。例如,在一些實施例中,F蛋白含有亨德拉病毒之細胞外域及尼帕病毒之跨膜/細胞質域。
在一些實施例中,融合蛋白含有亨尼帕病毒包膜附著糖蛋白G(G蛋白)或其生物活性部分及單域抗體(sdAb)可變域或單鏈可變片段(scFv)。sdAb可變域或scFv可直接或間接連接至G蛋白。在特定實施例中,sdAb可變域或scFv與G蛋白或其生物活性部分之C末端(C末端胺基酸)連接。該連接可經由肽接頭,諸如靈活肽接頭。
表 7提供了G蛋白之非限制性實例之清單。本揭示之例示性全長融合蛋白序列揭示於
表 13中。
在一些實施例中,G蛋白係亨尼帕病毒G蛋白或其生物活性部分。在一些實施例中,亨尼帕病毒G蛋白係亨德拉(HeV)病毒G蛋白、尼帕(NiV)病毒G蛋白(NiV-G)、松灣(Cedar) (CedPV)病毒G蛋白、墨江病毒G蛋白、蝙蝠副黏病毒G蛋白或其生物活性部分。G蛋白之非限制性實例包括對應於SEQ ID NO: 609、618、619、620及621之彼等者。
在一些實施例中,附著G蛋白係II型跨膜糖蛋白,其含有N末端胞質尾部(例如,對應於SEQ ID NO: 600之胺基酸1-49)、跨膜域(例如,對應於SEQ ID NO: 600之胺基酸50-70)以及含有細胞外莖(例如,對應於SEQ ID NO: 600之胺基酸71-187)及球狀頭部(對應於SEQ ID NO: 600之胺基酸188-602)的細胞外域。在此類實施例中,N末端細胞質域在脂質雙層的內腔內,並且C末端部分係暴露於脂質雙層外部的細胞外域。C末端區中的莖區(例如,對應於NiV-G之胺基酸159-167)已經示出參與與F蛋白的相互作用及觸發F蛋白融合(Liu等人,2015 J of Virology,89:1838)。在野生型G蛋白中,球狀頭部介導受體與亨尼帕病毒進入受體肝配蛋白B2及肝配蛋白B3之結合,但對於膜融合係可有可無的(Brandel-Tretheway等人,Journal of Virology,2019. 93(13)e00577-19)。在本文之特定實施例中,藉由將G蛋白或其生物活性片段(例如細胞質截短)連接至sdAb可變域來改變G蛋白之向性。G蛋白與結合搭配物之結合可觸發由相容F蛋白或其生物活性部分介導之融合。本文揭示之G蛋白序列主要揭示為包括轉譯開始所需之N末端甲硫胺酸之表現序列。由於此類N末端甲硫胺酸通常在轉譯時或轉譯後被裂解,因此本文揭示之所有G蛋白序列之成熟蛋白序列亦被認為缺乏N-末端甲硫胺酸。
G糖蛋白在亨尼帕病毒物種之間係高度保守的。例如,NiV及HeV病毒之G蛋白共用79%胺基酸同一性。研究已經示出,不同物種之G蛋白與F蛋白之間的高度相容性,如藉由異型融合活化所證明的(Brandel-Tretheway等人,Journal of Virology,2019年)。如下文進一步描述,靶向脂質顆粒可含有來自不同物種之異源G蛋白及F蛋白。
在一些實施例中,G蛋白具有SEQ ID NO: 600、609、618、619、620、621、628、636或638-640中任一者所示之序列,或者係其功能性活性變體或生物活性部分,該功能性活性變體或生物活性部分具有與SEQ ID NO: 600、609、618、619、620、621、628、636或638-640中任一者有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或至少為或約為99%同一性之序列。在特定實施例中,G蛋白或功能性活性變體或生物活性部分係與亨尼帕病毒F蛋白(諸如F蛋白(例如,NiV-F或HeV-F))一起保持了融合活性之蛋白。融合活性包括G蛋白與亨尼帕病毒F蛋白一起促進或便於兩個膜內腔融合之活性,諸如在其脂質雙層中嵌入了亨尼帕病毒F蛋白及G蛋白之靶向脂質顆粒的內腔及目標細胞(例如含有被靶向包膜蛋白識別或結合之表面受體或分子的細胞)的細胞質的融合。在一些實施例中,F蛋白及G蛋白來自相同之亨尼帕病毒物種(例如NiV-G及NiV-F)。在一些實施例中,F蛋白及G蛋白來自不同之亨尼帕病毒物種(例如NiV-G及HeV-F)。
在特定實施例中,G蛋白具有SEQ ID NO: 600、609、618、619、620、621、628、636或638-640所示之胺基酸序列,或者係保持融合活性之其功能性活性變體或其生物活性部分。在一些實施例中,功能性活性變體包含與SEQ ID NO: 600、609、618、619、620、621、628、636或638-640中的任一者有至少為或約為80%、至少為或約為85%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列,並且與亨尼帕病毒F蛋白(例如,NiV-F或HeV-F)一起保持了融合活性。在一些實施例中,生物活性部分具有與SEQ ID NO: 600、609、618、619、620、621、628、636或638-640中的任一者有至少為或約為80%、至少為或約為85%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列,並且與亨尼帕病毒F蛋白(例如,NiV-F或HeV-F)一起保持了融合活性。
提及保持融合活性包括為對應野生型G蛋白(諸如SEQ ID NO: 600、609、618、619、620、621、628、636或638-640中任一者所示)結合水準或程度的為或約為10%至為或約150%或更多之活性(與亨尼帕病毒F蛋白一起),諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為10%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為15%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為20%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為25%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為30%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為35%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為40%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為45%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為50%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為55%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為60%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為65%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為70%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為75%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為80%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為85%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為90%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為95%,諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為100%或者諸如為對應野生型G蛋白融合活性水準或程度的至少為或至少約為120%。
在一些實施例中,G蛋白係突變G蛋白,其係含有一個或多個胺基酸突變(諸如一個或多個胺基酸插入、缺失、取代或截短)之功能性活性變體或生物活性部分。在一些實施例中,本文所述之突變係關於與參考G蛋白序列相比胺基酸之胺基酸插入、缺失、取代或截短。在一些實施例中,參考G蛋白序列係G蛋白或其生物活性部分之野生型序列。在一些實施例中,其功能性活性變體或生物活性部分係野生型亨德拉(HeV)病毒G蛋白、野生型尼帕(NiV)病毒G蛋白(NiV-G)、野生型松灣(CedPV)病毒G蛋白、野生型墨江病毒G-蛋白、野生型蝙蝠副黏病毒G蛋白或其生物活性部分之突變體。在一些實施例中,野生型G蛋白具有SEQ ID NO: 600、609、618、619、620、621、628、636或638-640中任一者所示之序列。
在一些實施例中,G蛋白係突變G蛋白,係生物活性部分,係野生型亨德拉(HeV)病毒G蛋白、野生型尼帕(NiV)病毒G蛋白(NiV-G)、野生型松灣(CedPV)病毒G蛋白、野生型墨江病毒G-蛋白或野生型蝙蝠副黏病毒G蛋白之N末端及/或C末端截短片段。在特定實施例中,截短係所有或一部分胞質域之N末端截短。在一些實施例中,突變G蛋白係生物活性部分,該生物活性部分在野生型G蛋白之N末端處或附近被截短並且缺乏至多49個連續胺基酸殘基,諸如SEQ ID NO: 600、609、618、619、620、621、628、636或638-640中任一者所示之野生型G蛋白。在一些實施例中,突變G蛋白在野生型G蛋白之N末端被截短並且缺乏至多49個連續胺基酸,諸如缺乏至多49個、48個、47個、46個、45個、44個、43個、42個、41個、40個、30個、38個、37個、36個、35個、34個、33個、32個、31個、30個、29個、28個、27個、26個、25個、24個、23個、22個、21個、20個、19個、18個、17個、16個、15個、14個、13個、12個、11個、10個、9個、8個、7個、6個、5個、4個、3個、2個或1個連續胺基酸。
在一些實施例中,G蛋白係野生型尼帕病毒G(NiV-G)蛋白或亨德拉病毒G蛋白或者係其功能性活性變體或生物活性部分。在一些實施例中,G蛋白係NiV-G蛋白,該NiV-G蛋白具有SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628中所示之序列,或者係其功能性變體或生物活性部分,該功能性變體或生物活性部分具有與SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列。
在一些實施例中,G蛋白係突變NiV-G蛋白,其係野生型NiV-G之生物活性部分。在一些實施例中,生物活性部分係N末端截短之片段。在一些實施例中,突變NiV-G蛋白在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近被截短並且缺乏多達5個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達6個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達7個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達8個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達9個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達10個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達11個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達12個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達13個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達14個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達15個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達16個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達17個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達18個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達19個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達20個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達21個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達22個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達23個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達24個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達25個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達26個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達27個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達28個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達29個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達30個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達31個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達32個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達33個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達34個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達35個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達36個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達37個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達38個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達39個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達40個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達41個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達42個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達43個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達44個連續胺基酸殘基,或者在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近缺乏多達45個連續胺基酸殘基。
在一些實施例中,NiV-G蛋白係不含細胞質域之生物活性部分。在一些實施例中,沒有細胞質域之NiV-G蛋白由SEQ ID NO: 622編碼。
在一些實施例中,突變NiV-G蛋白包含SEQ ID NO: 601-606、629-634、612、622或637中任一者所示之序列,或者係其功能性變體,該功能性變體具有與SEQ ID NO: 601-606、629-634、612、622或637有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%或者至少為或約為87%、至少為或約為88%或者至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列。
在一些實施例中,突變NiV-G蛋白在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有5個胺基酸截短,諸如SEQ ID NO: 601或與SEQ ID NO: 601有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示,或者諸如SEQ ID NO: 629或與SEQ ID NO: 629有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能變體或者與SEQ ID NO: 629有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能變體所示。
在一些實施例中,突變NiV-G蛋白在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有10個胺基酸截短,諸如SEQ ID NO: 602或與SEQ ID NO: 602有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示,或者諸如SEQ ID NO: 630或與SEQ ID NO: 630有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能變體所示。
在一些實施例中,突變NiV-G蛋白在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有15個胺基酸截短,諸如SEQ ID NO: 603或具有與SEQ ID NO: 603有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列之其功能性變體所示,或者諸如SEQ ID NO: 631或與SEQ ID NO: 631有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示。
在一些實施例中,突變NiV-G蛋白在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有20個胺基酸截短,諸如SEQ ID NO: 604或與SEQ ID NO: 604有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示,或者諸如SEQ ID NO: 632或與SEQ ID NO: 632有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示。
在一些實施例中,突變NiV-G蛋白在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有25個胺基酸截短,諸如SEQ ID NO: 605或與SEQ ID NO: 605有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示,或者諸如SEQ ID NO: 633或與SEQ ID NO: 633有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示。
在一些實施例中,突變NiV-G蛋白在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有30個胺基酸截短,諸如SEQ ID NO: 606或與SEQ ID NO: 606有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示,或者諸如SEQ ID NO: 634或與SEQ ID NO: 634有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示。
在一些實施例中,突變NiV-G蛋白在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有33個胺基酸截短,或與SEQ ID NO: 612有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示,或者諸如SEQ ID NO: 635或與SEQ ID NO: 635有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示。
在一些實施例中,突變NiV-G蛋白在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有34個胺基酸截短,諸如SEQ ID NO: 612或與SEQ ID NO: 612有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示,或者諸如SEQ ID NO: 635或與SEQ ID NO: 635有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示。
在較佳實施例中,NiV-G蛋白具有在野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近的34個胺基酸截短以及對應於選自參考SEQ ID NO: 618所示的編號的E501A、W504A、Q530A及E533A之胺基酸取代的一個或多個胺基酸取代。
在一些實施例中,突變NiV-G蛋白缺乏野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端胞質域,諸如SEQ ID NO: 622或與SEQ ID NO: 622有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示。
在一些實施例中,突變G蛋白係突變HeV-G蛋白,該突變HeV-G蛋白具有SEQ ID NO: 609或SEQ ID NO: 636中所示之序列,或者係其功能性變體或生物活性部分,該功能性變體或生物活性部分具有與SEQ ID NO: 609或SEQ ID NO: 636有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列。
在一些實施例中,G蛋白係突變HeV-G蛋白,其係野生型HeV-G之生物活性部分。在一些實施例中,生物活性部分係N末端截短之片段。在一些實施例中,突變HeV-G蛋白在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近被截短並且缺乏多達5個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達6個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達7個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達8個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達9個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達10個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達11個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達12個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達13個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達14個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達15個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達16個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達17個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達18個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達19個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達20個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達21個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達22個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達23個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達24個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達25個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達26個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達27個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達28個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達29個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達30個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達31個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達32個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達33個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達34個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達35個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達36個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達37個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達38個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達39個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達40個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達41個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達42個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達43個連續胺基酸殘基,在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達44個連續胺基酸殘基,或者在野生型HeV-G蛋白(SEQ ID NO: 609或636)之N末端處或附近缺乏多達45個連續胺基酸殘基。
在一些實施例中,HeV-G蛋白係不含細胞質域之生物活性部分。在一些實施例中,突變HeV-G蛋白缺乏野生型HeV-G蛋白(SEQ ID NO: 609或SEQ ID NO: 636)之N末端胞質域,諸如SEQ ID NO: 623或與SEQ ID NO: 623有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之其功能性變體所示。
在一些實施例中,G蛋白或其功能性活性變體或生物活性部分與肝配蛋白B2或肝配蛋白B3結合。在一些態樣中,G蛋白具有SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621中任一者所示之胺基酸序列,或者係能够結合肝配蛋白B2或肝配蛋白B3之其功能性活性變體或其生物活性部分。在一些實施例中,功能性活性變體或生物活性部分具有與SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621或其功能性變體或生物活性部分有至少為或約為80%、至少為或約為85%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列,並且保持與肝配蛋白B2或B3之結合。
提及保持與肝配蛋白B2或B3的結合包括對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的至少為或至少約為5%的結合;為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的10%的結合;為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的15%的結合;為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的20%的結合;為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的25%的結合;為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的30%的結合;為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的35%的結合;為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的40%的結合;為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的45%的結合;為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的50%的結合;為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的55%的結合;為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的60%的結合;為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的65%的結合;為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的70%的結合;諸如為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621)或其功能性活性變體或生物活性部分結合水準或程度的至少為或至少約為75%的結合;諸如為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的至少為或至少約為80%的結合;諸如為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的至少為或至少約為85%的結合;諸如為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的至少為或至少約為90%的結合;或者諸如為對應野生型G蛋白(諸如SEQ ID NO: 600、SEQ ID NO: 609、SEQ ID NO: 618、SEQ ID NO: 619、SEQ ID NO: 628、SEQ ID NO: 620或SEQ ID NO: 621所示)或其功能性活性變體或生物活性部分結合水準或程度的至少為或至少約為95%的結合。在一些實施例中,G蛋白係NiV-G或其功能性活性變體或生物活性部分並且與肝配蛋白B2或肝配蛋白B3結合。
在一些態樣中,NiV-G具有SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示的胺基酸序列,或者係能夠結合肝配蛋白B2或肝配蛋白B3的其功能性活性變體或其生物活性部分。在一些實施例中,功能性活性變體或生物活性部分具有與SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628有至少為或約為80%、至少為或約為85%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列,並且保持與肝配蛋白B2或B3的結合。例示性生物活性部分包括N-末端截短變體,其缺乏細胞質域的全部或部分,例如1個或多個,諸如1至49個連續N末端胺基酸殘基,例如SEQ ID NO: 601-606、622及629-634中任一者所示。
提及保持與肝配蛋白B2或B3的結合包括為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的至少為或至少約為5%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的10%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的15%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 6284所示)結合水準或程度的20%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的25%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的30%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的35%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的40%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的45%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的50%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的55%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的60%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的65%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的70%的結合,諸如為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的至少為或至少約為75%的結合,諸如為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的至少為或至少約為80%的結合,為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的至少為或至少約為85%的結合,諸如為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的至少為或至少約為90%的結合,或者諸如為對應野生型NiV-G (諸如SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628所示)結合水準或程度的至少為或至少約為95%的結合。
在一些實施例中,G蛋白係HeV-G或其功能性活性變體或生物活性部分並且與肝配蛋白B2或肝配蛋白B3結合。在一些態樣中,HeV-G具有SEQ ID NO: 609或636所示之胺基酸序列,或者係能夠結合肝配蛋白B2或肝配蛋白B3的其功能性活性變體或其生物活性部分。在一些實施例中,功能性活性變體或生物活性部分具有與SEQ ID NO: 609或SEQ ID NO: 636有至少為或約為80%、至少為或約為85%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列,並且保持與肝配蛋白B2或B3的結合。例示性生物活性部分包括N-末端截短變體,其缺乏細胞質域的全部或部分,例如1個或多個,諸如1至49個連續N末端胺基酸殘基,例如SEQ ID NO: 623中任一者所示。
提及保持與肝配蛋白B2或B3的結合包括為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的至少為或至少約為5%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的10%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的15%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的20%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的25%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的30%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準程度的35%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的40%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的45%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的50%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的55%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的60%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的65%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的70%的結合,諸如為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的至少為或至少約為75%的結合,諸如為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的至少為或至少約為80%的結合,為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的至少為或至少約為85%的結合,諸如為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的至少為或至少約為90%的結合,或者諸如為對應野生型HeV-G (諸如SEQ ID NO: 609或SEQ ID NO: 636所示)結合水準或程度的至少為或至少約為95%的結合。
在一些實施例中,G蛋白或其生物學上係突變G蛋白,其表現出野生型G蛋白之天然結合搭配物之結合降低。在一些實施例中,突變G蛋白或其生物活性部分係野生型Niv-G之突變體並且表現出與天然結合搭配物肝配蛋白B2或肝配蛋白B3中的一者或兩者之結合降低。在一些實施例中,突變G蛋白或生物活性部分,諸如突變NiV-G蛋白,表現出與天然結合搭配物之結合降低。在一些實施例中,與肝配蛋白B2或肝配蛋白B3之結合降低降低了大於為或約為5%、為或約為10%、為或約為15%、為或約為20%、為或約為25%、為或約為30%、為或約為40%、為或約為50%、為或約為60%、為或約為70%、為或約為80%、為或約為90%或者為或約為100%。
在一些實施例中,本文所述之突變可改良轉導效率。在一些實施例中,本文所述之突變允許特異性靶向不是肝配蛋白B2或肝配蛋白B3之其他期望細胞類型。在一些實施例中,本文所述之突變至少導致部分無法結合至少一種天然受體,諸如以降低與肝配蛋白B2或肝配蛋白B3中的至少一者之結合。在一些實施例中,本文所述的突變干擾天然受體識別。
在一些實施例中,突變NiV-G蛋白或其生物活性部分在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近被截短並且缺乏多達5個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達6個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達7個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達8個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達9個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達10個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達11個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達12個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達13個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達14個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達15個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達16個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達17個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達18個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達19個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達20個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達21個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達22個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達23個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達24個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達25個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達26個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達27個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達28個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達29個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達30個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達31個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達32個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達33個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達34個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達35個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達36個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達37個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達38個連續胺基酸殘基,在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達39個連續胺基酸殘基,或者在野生型NiV-G蛋白(SEQ ID NO: 618)之N末端處或附近缺乏多達40個連續胺基酸殘基。
在一些實施例中,G蛋白在參與與肝配蛋白B2或肝配蛋白B3中的一者或兩者相互作用之殘基中包含一個或多個胺基酸取代。在一些實施例中,胺基酸取代對應於參考SEQ ID NO: 618所示的編號的突變E501A、W504A、Q530A及E533A。
在一些實施例中,G蛋白係突變G蛋白,其包含選自參考SEQ ID NO: 618所示的編號的E501A、W504A、Q530A及E533A之一個或多個胺基酸取代。在一些實施例中,G蛋白係突變G蛋白,其包含選自參考SEQ ID NO: 618或者其含有N末端截短之生物活性部分之E501A、W504A、Q530A及E533A一個或多個胺基酸取代。在一些實施例中,G蛋白係突變G蛋白,其包含選自E501A、W504A、Q530A及E533A之一個或多個胺基酸取代以及上述參考SEQ ID NO: 618或其生物活性部分揭示之N末端截短中的任一者。在一些實施例中,上述突變G蛋白中的任一者包含選自參考SEQ ID NO: 618所示之編號之E501A、W504A、Q530A及E533A的一個、兩個、三個或全部四個胺基酸,及其所有成對及三重組合。
在一些實施例中,突變NiV-G蛋白具有SEQ ID NO: 607或635所示之胺基酸序列或與SEQ ID NO: 607或635有至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列。在特定實施例中,G蛋白具有SEQ ID NO: 607或635所示之胺基酸序列。
在一些實施例中,靶向包膜蛋白含有G蛋白或其功能性活性變體或生物活性部分以及sdAb可變域,其中靶向包膜蛋白表現出與野生型G蛋白之天然結合搭配物不同之另一個分子之結合增加。在一些實施例中,其他分子可為在期望目標細胞之表面上表現之蛋白質。在一些實施例中,與另一個分子之結合增加增加了大於為或約為25%,為或約為30%、為或約為40%、為或約為50%、為或約為60%、為或約為70%、為或約為80%、為或約為90%或者為或約為100%。在特定實施例中,與賦予新之或不同之結合活性之野生型G蛋白結合相比,該結合賦予再靶向結合。
在一些實施例中,單域抗體之C末端與G蛋白或其生物活性部分之C末端附接。在一些實施例中,單域抗體之N末端暴露於脂質雙層的外表面上。在一些實施例中,單域抗體之N末端與目標細胞的細胞表面分子結合。在一些實施例中,單域抗體與存在於目標細胞上之細胞表面分子特異性結合。在一些實施例中,細胞表面分子係蛋白質、聚糖、脂質或低分子量分子。
在一些實施例中,目標細胞之細胞表面分子係抗原或其部分。在一些實施例中,單域抗體或其部分係具有能夠選擇性結合特定抗原之單個單體域抗原結合/識別域之抗體。在一些實施例中,單域抗體結合存在於目標細胞上之抗原。
例示性細胞包括免疫效應細胞、諸如淋巴細胞(T細胞、B細胞、天然殺傷細胞)及單核細胞之周邊血液單核細胞(PBMC)、粒細胞(中性粒細胞、嗜鹼性粒細胞、嗜酸性粒細胞)、巨噬細胞、樹突狀細胞、細胞毒性T淋巴細胞、多形核細胞(亦稱為PMN、PML、或PMNL)、幹細胞、胚胎幹細胞、神經幹細胞、間質幹細胞(MSC)、造血幹細胞(HSC)、人類肌源性幹細胞、肌肉衍生之幹細胞(MuStem)、胚胎幹細胞(ES或ESC)、角膜緣上皮幹細胞、心肌源性幹細胞、心肌細胞、祖細胞、同種異體細胞、常駐心臟細胞、誘導多能幹細胞(iPS)、脂肪衍生或表型修飾之幹細胞或祖細胞、CD133+細胞、醛脫氫酶陽性細胞(ALDH+)、臍帶血(UCB)細胞、周邊血幹細胞(PBSC)、神經元、神經祖細胞、胰腺β細胞、神經膠質細胞或肝細胞。
在一些實施例中,目標細胞係目標組織之細胞。目標組織可包括肝、肺、心臟、脾、胰腺、胃腸道、腎臟、睾丸、卵巢、腦、生殖器官、中樞神經系統、周圍神經系統、骨骼肌、內皮、內耳或眼睛。
在一些實施例中,目標細胞係肌細胞(例如骨骼肌細胞)、腎臟細胞、肝臟細胞(例如肝細胞)或心臟細胞(例如心肌細胞)。在一些實施例中,目標細胞係心臟細胞,例如心肌細胞(例如靜止心肌細胞)、成肝細胞(例如膽管成肝細胞)、上皮細胞、T細胞(例如幼稚T細胞)、巨噬細胞(例如腫瘤浸潤性巨噬細胞)或纖維母細胞(例如心臟纖維母細胞)。
在一些實施例中,目標細胞係腫瘤浸潤性淋巴細胞、T細胞、贅生性或腫瘤細胞、病毒感染細胞、幹細胞、中樞神經系統(CNS)細胞、造血幹細胞(HSC)、肝臟細胞或完全分化之細胞。在一些實施例中,目標細胞係CD3+ T細胞、CD4+ T細胞、CD8+ T細胞、肝細胞、造血幹細胞、CD34+造血幹細胞、CD105+造血幹細胞、CD117+造血幹細胞、CD105+內皮細胞、B細胞、CD20+ B細胞、CD19+ B細胞、癌細胞、CD133+癌細胞、EpCAM+癌細胞、CD19+癌細胞、Her2/Neu+癌細胞、GluA2+神經元、GluA4+神經元、NKG2D+自然殺手細胞、SLC1A3+星形膠質細胞、SLC7A10+脂肪細胞或CD30+肺上皮細胞。
在一些實施例中,目標細胞係抗原呈現細胞、MHC II+類細胞、專職抗原呈現細胞、非典型抗原呈現細胞、巨噬細胞、樹突狀細胞、骨髓樹突狀細胞、漿細胞樣樹突狀細胞、CD11c+細胞、CD11b+細胞、脾細胞、B細胞、肝細胞、內皮細胞或非癌細胞。在一些實施例中,細胞表面分子係CD8中的任一者。
在一些實施例中,G蛋白或其功能性活性變體或生物活性部分直接連接至sdAb可變域(例如,VHH)或scFv。在一些實施例中,靶向包膜蛋白係具有以下結構之融合蛋白:(N'-單域抗體-C')-(C'-G蛋白-N')。在一些實施例中,靶向包膜蛋白係具有以下結構的融合蛋白:(N'-scFv-C')-(C'-G蛋白-N')。
在一些實施例中,G蛋白或其功能性活性變體或生物活性部分經由接頭間接連接至sdAb可變域或scFv。在一些實施例中,接頭係肽接頭。在一些實施例中,接頭係化學接頭。
在一些實施例中,接頭係肽接頭,並且靶向包膜蛋白係含有經由肽接頭連接至sdAb可變域或svFv之G蛋白或其功能性活性變體或生物活性部分之融合蛋白。在一些實施例中,靶向包膜蛋白係具有以下結構之融合蛋白:(N'-單域抗體-C')-接頭-(C'-G蛋白-N')。在一些實施例中,靶向包膜蛋白係具有以下結構之融合蛋白:(N'-scFv-C')-接頭-(C'-G蛋白-N')。在一些實施例中,肽接頭之長度為多達65個胺基酸。在一些實施例中,肽接頭包含為或約為2至65個胺基酸、2至60個胺基酸、2至56個胺基酸、2至52個胺基酸、2至48個胺基酸、2至44個胺基酸、2至40個胺基酸、2至36個胺基酸、2至32個胺基酸、2至28個胺基酸、2至24個胺基酸、2至20個胺基酸、2至18個胺基酸、2至14個胺基酸、2至12個胺基酸、2至10個胺基酸、2至8個胺基酸、2至6個胺基酸、6至65個胺基酸、6至60個胺基酸、6至56個胺基酸、6至52個胺基酸、6至48個胺基酸、6至44個胺基酸、6至40個胺基酸、6至36個胺基酸、6至32個胺基酸、6至28個胺基酸、6至24個胺基酸、6至20個胺基酸、6至18個胺基酸、6至14個胺基酸、6至12個胺基酸、6至10個胺基酸、6至8個胺基酸、8至65個胺基酸、8至60個胺基酸、8至56個胺基酸、8至52個胺基酸、8至48個胺基酸、8至44個胺基酸、8至40個胺基酸、8至36個胺基酸、8至32個胺基酸、8至28個胺基酸、8至24個胺基酸、8至20個胺基酸、8至18個胺基酸、8至14個胺基酸、8至12個胺基酸、8至10個胺基酸、10至65個胺基酸、10至60個胺基酸、10至56個胺基酸、10至52個胺基酸、10至48個胺基酸、10至44個胺基酸、10至40個胺基酸、10至36個胺基酸、10至32個胺基酸、10至28個胺基酸、10至24個胺基酸、10至20個胺基酸、10至18個胺基酸、10至14個胺基酸、10至12個胺基酸、12至65個胺基酸、12至60個胺基酸、12至56個胺基酸、12至52個胺基酸、12至48個胺基酸、12至44個胺基酸、12至40個胺基酸、12至36個胺基酸、12至32個胺基酸、12至28個胺基酸、12至24個胺基酸、12至20個胺基酸、12至18個胺基酸、12至14個胺基酸、14至65個胺基酸、14至60個胺基酸、14至56個胺基酸、14至52個胺基酸、14至48個胺基酸、14至44個胺基酸、14至40個胺基酸、14至36個胺基酸、14至32個胺基酸、14至28個胺基酸、14至24個胺基酸、14至20個胺基酸、14至18個胺基酸、18至65個胺基酸、18至60個胺基酸、18至56個胺基酸、18至52個胺基酸、18至48個胺基酸、18至44個胺基酸、18至40個胺基酸、18至36個胺基酸、18至32個胺基酸、18至28個胺基酸、18至24個胺基酸、18至20個胺基酸、20至65個胺基酸、20至60個胺基酸、20至56個胺基酸、20至52個胺基酸、20至48個胺基酸、20至44個胺基酸、20至40個胺基酸、20至36個胺基酸、20至32個胺基酸、20至28個胺基酸、20至26個胺基酸、20至24個胺基酸、24至65個胺基酸、24至60個胺基酸、24至56個胺基酸、24至52個胺基酸、24至48個胺基酸、24至44個胺基酸、24至40個胺基酸、24至36個胺基酸、24至32個胺基酸、24至30個胺基酸、24至28個胺基酸、28至65個胺基酸、28至60個胺基酸、28至56個胺基酸、28至52個胺基酸、28至48個胺基酸、28至44個胺基酸、28至40個胺基酸、28至36個胺基酸、28至34個胺基酸、28至32個胺基酸、32至65個胺基酸、32至60個胺基酸、32至56個胺基酸、32至52個胺基酸、32至48個胺基酸、32至44個胺基酸、32至40個胺基酸、32至38個胺基酸、32至36個胺基酸、36至65個胺基酸、36至60個胺基酸、36至56個胺基酸、36至52個胺基酸、36至48個胺基酸、36至44個胺基酸、36至40個胺基酸、40至65個胺基酸、40至60個胺基酸、40至56個胺基酸、40至52個胺基酸、40至48個胺基酸、40至44個胺基酸、44至65個胺基酸、44至60個胺基酸、44至56個胺基酸、44至52個胺基酸、44至48個胺基酸、48至65個胺基酸、48至60個胺基酸、48至56個胺基酸、48至52個胺基酸、50至65個胺基酸、50至60個胺基酸、50至56個胺基酸、50至52個胺基酸、54至65個胺基酸、54至60個胺基酸、54至56個胺基酸、58至65個胺基酸、58至60個胺基酸或60至65個胺基酸。在一些實施例中,肽接頭為長度為3個、4個、5個、6個、7個、8個、9個、10個、11個、12個、13個、14個、15個、16個、17個、18個、19個、20個、21個、22個、23個、24個、25個、26個、27個、28個、29個、30個、31個、32個、33個、34個、35個、36個、37個、38個、39個、40個、41個、42個、43個、44個、45個、46個、47個、48個、49個、50個、51個、52個、53個、54個、55個、56個、57個、58個、59個、60個、61個、62個、63個、64個或65個胺基酸之多肽。
在特定實施例中,接頭係靈活肽接頭。在一些此類實施例中,接頭係1至20個胺基酸,諸如主要由甘胺酸構成之1至20個胺基酸。在一些實施例中,接頭係1至20個胺基酸,諸如主要由甘胺酸及絲胺酸構成之1至20個胺基酸。在一些實施例中,接頭係含有胺基酸甘胺酸及絲胺酸之靈活肽接頭,稱為GS接頭。在一些實施例中,肽接頭包括序列GS、GGS、GGGGS(SEQ ID NO: 627)、GGGGGS(SEQ ID NO: 625)或其組合。在一些實施例中,多肽接頭具有序列(GGS)n,其中n為1至10。在一些實施例中,多肽接頭具有序列(GGGGS)n,(SEQ ID NO: 626),其中n為1至10。在一些實施例中,多肽接頭具有序列(GGGGGS)n,(SEQ ID NO: 27),其中n為1至6。
本文亦提供了包含編碼靶向包膜蛋白之核酸序列的聚核苷酸。在一些實施例中,聚核苷酸包含編碼G蛋白或其生物活性部分之核酸序列。在一些實施例中,聚核苷酸進一步包含編碼單域抗體(sdAb)可變域或scFv或其生物活性部分之核酸序列。聚核苷酸可包括編碼上述靶向包膜蛋白中之任一者之核苷酸序列。聚核苷酸可為合成核酸。亦提供了含有所提供的聚核苷酸中的任一者之表現載體。
在一些實施例中,天然核酸或合成核酸之表現通常藉由將編碼感興趣基因之核酸可操作地連接至啟動子並且將構築體摻入至表現體中來實現。在一些實施例中,載體可適合於在真核生物中複製及整合。在一些實施例中,選殖載體含有可用於表現期望核酸序列之轉錄及轉譯終止子、起始序列及啟動子。在任何實施例中之一些實施例中,質體包含適合於在細胞中表現之啟動子。
在一些實施例中,聚核苷酸含有至少一個啟動子,該至少一個啟動子可操作地連接以控制含有G蛋白及單域抗體(sdAb)可變域或scFv的靶向包膜蛋白的表現。對於靶向包膜蛋白的表現,每個啟動子中的之至少一個模組用於定位RNA合成之起始位點。其最著名之實例係TATA框,但在一些缺乏TATA框的啟動子(諸如哺乳動物末端脫氧核苷酸轉移酶基因之啟動子及SV40基因之啟動子)中,覆蓋在起始位點本身上的離散元件有助於固定起始位點。
在一些實施例中,另外的啟動子元件,例如增強子,調控轉錄起始頻率。在一些實施例中,另外的啟動子元件位於起始位點上游30bp至110bp之區域中,儘管已經示出許多啟動子亦含有起始位點下游之功能性元件。在一些實施例中,啟動子元件之間的間距經常係靈活的,因此當元件相對於彼此倒置或移動時,啟動子功能得以保留。在一些實施例中,諸如用胸苷激酶(tk)啟動子,在活性開始下降之前,啟動子元件之間的間距可增加至50bp。在一些實施例中,取決於啟動子,個別元件可協作地或獨立地起作用以活化轉錄。
啟動子可為與基因或聚核苷酸序列天然相關之啟動子,如可藉由分離位於編碼區段及/或外顯子上游之5'非編碼序列來獲得。此類啟動子可被稱為「內源性的」。類似地,增強子可為與位於該序列下游或上游的聚核苷酸序列天然相關之增強子。替代地,藉由將編碼聚核苷酸區段置於重組或異源啟動子之控制下來獲得某些優勢,該重組或異源啟動子係指通常不與其天然環境中的聚核苷酸序列相關之啟動子。重組或異源增強子亦係指在其天然環境中通常不與聚核苷酸序列相關之增強子。此類啟動子或增強子可包括其他基因的啟動子或增強子,以及自任何其他原核、病毒或真核細胞分離之啟動子或增強子,並且不是「天然存在的」啟動子或增強子,亦即含有不同轉錄調控區之不同元件及/或改變表現之突變。除了合成產生啟動子及增強子之核酸序列之外,亦可以使用重組選殖及/或核酸擴增技術(包括PCR)結合本文揭示之組合物來產生序列。
在一些實施例中,合適的啟動子係即刻早期細胞巨化病毒(CMV)啟動子序列。在一些實施例中,啟動子序列係能夠驅動與其有效連接之任何聚核苷酸序列之高水準表現之強組成型啟動子序列。在一些實施例中,合適的啟動子係延伸生長因子-la(EF-la)。在一些實施例中,亦可使用其他組成型啟動子序列,包括但不限於猿猴病毒40 (SV40)早期啟動子、小鼠乳腺腫瘤病毒(MMTV)、人類免疫缺陷病毒(HIV)長末端重複序列(LTR)啟動子、MoMuLV啟動子、禽白血病病毒啟動子、愛潑斯坦-巴爾病毒即刻早期啟動子、勞斯肉瘤病毒啟動子,以及人類基因啟動子,諸如但不限於肌動蛋白啟動子、肌球蛋白啟動子、血紅蛋白啟動子及肌酸激酶啟動子。
在一些實施例中,啟動子係誘導型啟動子。在一些實施例中,誘導型啟動子提供了分子開關,當期望此表現時,該分子開關能夠打開與其有效連接的聚核苷酸序列之表現,或者在不期望表現時關閉該表現。在一些實施例中,誘導型啟動子包含金屬硫蛋白啟動子、糖皮質激素啟動子、孕酮啟動子及四環素啟動子。
在一些實施例中,外源控制之誘導型啟動子可用於調控G蛋白及單域抗體(sdAb)可變域或scFv之表現。例如,輻射誘導型啟動子、熱誘導型啟動子及/或藥物誘導型啟動子可用於選擇性地驅動例如靶區域中的轉基因表現。在此類實施例中,可藉由投與外源誘導源來調控轉基因表現之位置、持續時間及水準。
在一些實施例中,使用藥物誘導型啟動子調控含有G蛋白及單域抗體(sdAb)可變域或scFv的靶向包膜蛋白之表現。例如,在一些情況下,啟動子、增強子或反式活化因子包含Lac操縱子序列、四環素操縱子序列、半乳糖操縱子序列、強力黴素操縱子序列、雷帕黴素操縱子序列、他莫昔芬操縱子序列或激素響應性操縱子序列或其類似物。在一些情況下,誘導型啟動子包含四環素反應元件(TRE)。在一些實施例中,誘導型啟動子包含雌激素反應元件(ERE),其可在他莫昔芬之存在下活化基因表現。在一些情況下,藥物誘導型元件(諸如TRE)可與選擇的啟動子組合以增強在藥物(諸如多西環素)之存在下的轉錄。在一些實施例中,藥物誘導型啟動子係小分子誘導型啟動子。
所提供的聚核苷酸中的任一者可被修飾以去除CpG模體並且/或者最佳化用於在特定物種(諸如人類、犬、貓、馬、綿羊、牛等物種)中轉譯之密碼子。在一些實施例中,針對人類密碼子使用(亦即,人類密碼子最佳化)最佳化聚核苷酸。在一些實施例中,聚核苷酸被修飾以去除CpG模體。在其他實施例中,所提供的聚核苷酸被修飾以去除CpG模體並且係密碼子最佳化的,諸如人類密碼子最佳化的。密碼子最佳化及CpG模體偵測及修飾的方法係熟知的。通常,聚核苷酸最佳化增強了轉基因表現,增加了轉基因穩定性並保留了編碼的多肽之胺基酸序列。
為了評估靶向包膜蛋白之表現,待引入細胞之表現載體亦可含有選擇性標記基因或報告基因或兩者,以便於表現顆粒(例如病毒顆粒)的鑑定及選擇。在其他實施例中,選擇性標記可攜帶在單獨的DNA片段上並在共轉染程序中使用。選擇性標記及報告基因兩者均可側接有適當之調控序列,以使得能夠在宿主細胞中表現。有用的選擇性標記係此項技術中已知的,並且包括例如抗生素抗性基因,諸如neo等。
報告基因用於鑑定潛在轉染之細胞及評估調控序列之功能。編碼易於測定之蛋白質之報告基因係此項技術中所熟知的。一般而言,報告基因係不存在的或由受體生物體或組織表現並且其編碼之蛋白質的表現藉由一些易於偵測之特性(例如酶活性)表現之基因。在DNA已引入到受體細胞之後的合適時間測定報告基因之表現。
合適的報告基因可包括編碼螢光素酶、β-半乳糖苷酶、氯黴素乙醯基轉移酶、分泌之鹼性磷酸酶或綠色螢光蛋白基因之基因(參見例如Ui-Tei等人,2000, FEBS Lett. 479:79-82)。合適的表現系統係熟知的並且可使用熟知技術製備或商業獲得。可使用獨特的內部限制性位點或藉由部分消化非獨特限制性位點來產生內部缺失構築體。然後可將構築體轉染至顯示高水準之期望聚核苷酸及/或多肽表現之細胞中。一般而言,將具有顯示最高水準之報告基因表現之最小5'側翼區之構築體鑑定為啟動子。此類啟動子區可連接至報告基因並用於評價藥劑調節啟動子驅動的轉錄的能力。
靶向 CD8 之脂質顆粒
本文亦提供了靶向脂質顆粒(例如靶向CD8),諸如靶向病毒載體,此等靶向病毒載體包含亨尼帕病毒F蛋白分子或其生物活性部分,以及提供了融合蛋白,該融合蛋白包含(i)亨尼帕病毒包膜附著糖蛋白G(G蛋白)或其生物活性部分,以及(ii)單域抗體(sdAb)可變域或scFv,其中單域抗體可變域或scFv連接至G蛋白或生物活性部分之C末端,其中各自暴露於靶向病毒載體的外表面上。在特定實施例中,所提供的靶向脂質顆粒表現出融合活性,該融合活性由靶向包膜蛋白介導,該靶向包膜蛋白便於與目標細胞之結合,並含有參與便於脂質顆粒及目標細胞膜之兩個內腔的合併或融合之G蛋白或其生物活性部分以及F蛋白或其生物活性部分。
表 7提供了用於本揭示之靶向脂質顆粒之G蛋白及F蛋白之非限制性實例。
在一些實施例中,本文提供之靶向脂質顆粒(例如靶向慢病毒載體)與結合類似包膜蛋白但融合至除sdAb可變域之外之替代靶向部分(諸如單鏈可變片段(scFv)的參考脂質顆粒(例如參考慢病毒載體)相比具有增加或更高之靶向包膜蛋白表現。在一些實施例中,在用轉移質體、包膜質體及gag-pol質體共轉染包裝細胞後,藉由假型化病毒載體(例如慢病毒顆粒)產生靶向病毒載體。
在一些實施例中,與參考脂質顆粒(例如參考慢病毒載體)相比,例如含有類似包膜蛋白但融合至scFv之參考脂質顆粒,該表現增加了或大於5%、10%、20%、30%、40%、50%、60%、70%、80%、90%、100%、125%、150%、200%、300%、400%、500%或更多。在一些實例中,與參考脂質顆粒(例如參考慢病毒載體)相比,例如含有類似包膜蛋白但融合至scFv之參考脂質顆粒,該表現增加了或大於1.5倍、2倍、3倍、4倍、5倍、6倍、7倍、8倍、9倍、10倍、15倍、20倍、30倍或更多。在一些實施例中,可使用流動式細胞測量術(例如FAC)在活體外測定表現。在一些實施例中,表現可描繪為靶向病毒載體(例如靶向慢病毒載體)表面上的靶向包膜蛋白的數目或密度。在一些實施例中,表現可描繪為靶向病毒載體(例如靶向慢病毒載體)表面上的靶向包膜蛋白的表面表現之平均螢光強度(MFI)。在一些實施例中,表現可描繪為對靶向包膜蛋白呈表面陽性之群體中脂質顆粒(例如慢病毒載體)之百分比。
在一些實施例中,在靶向脂質顆粒(例如靶向慢病毒載體)之群體中,大於為或約為50%的脂質顆粒對靶向包膜蛋白呈表面陽性。例如,在所提供的靶向病毒載體(例如,靶向慢病毒載體)之群體中,該群體中大於為或約為55%、大於為或約為60%、大於為或約為65%、大於為或約為70%或者大於為或約為75%之病毒載體對靶向包膜蛋白呈表面陽性。
在一些實施例中,與引入至參考脂質顆粒(例如參考慢病毒載體)的相同目標細胞中的力價相比,此等參考脂質顆粒併入有類似包膜蛋白但融合至除sdAb可變域之外的替代靶向部分(諸如單鏈可變片段(scFv)),諸如藉由轉導(例如轉導細胞)引入到目標細胞之後靶向脂質顆粒之力價增加。通常,替代之靶向部分識別或結合相同之目標分子,作為靶向脂質顆粒之靶向包膜蛋白之sdAb可變域。在一些實施例中,與參考脂質顆粒(例如參考慢病毒載體)之力價相比,例如含有類似包膜蛋白但融合至scFv之參考脂質顆粒,該力價增加了或大於5%、10%、20%、30%、40%、50%、60%、70%、80%、90%、100%、125%、150%、200%、300%、400%、500%或更多。在一些實例中,與參考脂質顆粒(例如參考慢病毒載體)之力價相比,例如含有類似包膜蛋白但融合至scFv之參考病毒載體,該力價增加了或大於1.5倍、2倍、3倍、4倍、5倍、6倍、7倍、8倍、9倍、10倍、15倍、20倍、30倍或更多。在一些實施例中,目標細胞(例如轉導細胞)中靶向病毒載體的力價大於為或約為1×10
6轉導單位(TU)/mL。例如,目標細胞(例如轉導細胞)中靶向病毒載體之力價大於為或約為2×10
6TU/mL、大於為或約為3×10
6TU/mL、大於為或約為4×10
6TU/mL、大於為或約為5×10
6TU/mL、大於為或約為6×10
6TU/mL、大於為或約為7×10
6TU/mL、大於為或約為8×10
6TU/mL、大於為或約為9×10
6TU/mL或者、大於為或約為1×10
7TU/mL。
A.
F 蛋白
在一些實施例中,靶向脂質顆粒包含一種或多種融合劑,例如亨尼帕病毒F蛋白。在一些實施例中,靶向脂質顆粒含有外源或過表現之融合劑。在一些實施例中,融合劑安置於脂質雙層中。在一些實施例中,融合劑便於靶向顆粒之脂質雙層與膜之融合。在一些實施例中,膜係漿細胞膜。
在一些實施例中,融合劑包含基於蛋白質之融合劑、基於脂質之融合劑及基於化學之融合劑。在一些實施例中,靶向脂質顆粒包含具有蛋白質融合劑之第一融合劑及具有脂質融合劑或化學融合劑之第二融合劑。在一些實施例中,該融合劑結合目標細胞表面上之融合劑結合搭配物。
在一些實施例中,該融合劑包含具有疏水融合肽域之蛋白質。在一些實施例中,該融合劑包含亨尼帕病毒F蛋白分子或其生物活性部分。在一些實施例中,亨尼帕病毒F蛋白係亨德拉(Hev)病毒F蛋白、尼帕(NiV)病毒F蛋白、松灣(CedPV)病毒F蛋白、墨江病毒F蛋白、蝙蝠副黏病毒F蛋白或其生物活性部分。
在一些實施例中,F蛋白分子或其生物活性部分之N末端疏水融合肽域暴露於脂質雙層之外部。
亨尼帕病毒之F蛋白被編碼為含有信號肽之F
0前體(例如,對應於SEQ ID NO: 592之胺基酸殘基1-26)。在信號肽裂解後,成熟F
0(例如,SEQ ID NO: 593)被轉運到細胞表面,然後藉由組織蛋白酶L (例如,在SEQ ID NO: 592之胺基酸109-110之間)內吞且裂解成成熟融合次單元F1 (例如,對應於SEQ ID NO: 592之胺基酸110-546;如SEQ ID NO: 595所示)及F2 (例如,對應於SEQ ID NO: 1之胺基酸殘基27-109;如SEQ ID NO: 594所示)。F1次單元及F2次單元與二硫鍵相關並且再循環回細胞表面。F1次單元含有位於F1次單元之N末端之融合肽域(例如,對應於SEQ ID NO: 592之胺基酸110-129),其中其夠插入至細胞膜中以驅動融合。在一些情況下,藉由使F蛋白與G蛋白締合來阻斷融合活性,直至G與目標分子接合,從而導致其與F之解離以及融合肽之暴露以介導膜融合。
在不同的亨尼帕病毒物種中,F蛋白之序列及活性係高度保守的。例如,NiV及HeV病毒之F蛋白共用89%胺基酸序列同一性。此外,在一些情況下,亨尼帕病毒F蛋白表現出與來自其他物種之G蛋白之相容性以觸發融合(Brandel-Tretheway等人,Journal of Virology. 2019. 93(13):e00577-19)。在所提供的靶向脂質顆粒之一些態樣中,F蛋白對G蛋白係異源的,亦即,F蛋白及G蛋白或其生物活性部分來自不同之亨尼帕病毒物種。例如,F蛋白來自亨德拉病毒,並且G蛋白來自尼帕病毒。在其他態樣中,F蛋白可為含有來自不同亨尼帕病毒物種之F蛋白區之嵌合F蛋白。在一些實施例中,將F蛋白之胺基酸殘基區自一個亨尼帕病毒物種切換至另一種可導致與包含胺基酸插入之物種之G蛋白融合。(Brandel-Tretheway等人,2019年)。在一些情況下,嵌合F蛋白含有來自一個亨尼帕病毒物種之細胞外域及來自不同的亨尼帕病毒物種之跨膜及/或細胞質域。例如,F蛋白可含有亨德拉病毒之細胞外域及尼帕病毒之跨膜/細胞質域。本文揭示之F蛋白序列主要揭示為包括N末端信號序列之表現序列。此類N末端信號序列通常在轉譯時或轉譯後被裂解,因此本文揭示之所有F蛋白序列之成熟蛋白序列亦被認為缺乏N-末端信號序列。
在一些實施例中,F蛋白由編碼SEQ ID NO: 592、593、608、614-616或641-644中任一者所示之序列之核苷酸序列編碼,或者係其功能性活性變體或生物活性部分,該功能性活性變體或生物活性部分具有與SEQ ID NO :592、593、608、614-616或641-644有至少為或約為80%、至少為或約為85%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%同一性之序列。在特定實施例中,F蛋白或其功能性活性變體或生物活性部分與亨尼帕病毒G蛋白(諸如本文所示之G蛋白)一起保持了融合活性。融合活性包括F蛋白與亨尼帕病毒G蛋白一起促進或便於兩個膜內腔融合之活性,諸如在其脂質雙層中嵌入了亨尼帕病毒F蛋白及G蛋白之靶向脂質顆粒的內腔及目標細胞(例如含有被靶向包膜蛋白識別或結合之表面受體或分子之細胞)之細胞質的融合。在一些實施例中,F蛋白及G蛋白來自相同之亨尼帕病毒物種(例如NiV-G及NiV-F)。在一些實施例中,F蛋白及G蛋白來自不同之亨尼帕病毒物種(例如NiV-G及HeV-F)。在特定實施例中,功能性活性變體或生物活性部分之F蛋白保持被組織蛋白酶L裂解之裂解位點(例如,對應於SEQ ID NO: 592之胺基酸109-110之間的裂解位點)。
在特定實施例中,F蛋白具有SEQ ID NO: 592、SEQ ID NO: 593、SEQ ID NO: 608、SEQ ID NO: 614、SEQ ID NO: 615、SEQ ID NO: 616、SEQ ID NO: 641、SEQ ID NO: 642、SEQ ID NO: 643或SEQ ID NO: 644所示之胺基酸序列,或者係保持融合活性之其功能性活性變體或其生物活性部分。在一些實施例中,功能性活性變體包含與SEQ ID NO: 592、SEQ ID NO: 593、SEQ ID NO: 608、SEQ ID NO: 614、SEQ ID NO: 615、SEQ ID NO: 616、SEQ ID NO: 641、SEQ ID NO: 642、SEQ ID NO: 643或SEQ ID NO: 644有至少為或約為80%、至少為或約為85%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列,並且與亨尼帕病毒G蛋白(例如,NiV-G或HeV-G)一起保持了融合活性。在一些實施例中,生物活性部分具有與SEQ ID NO: 592、SEQ ID NO: 593、SEQ ID NO: 608、SEQ ID NO: 614、SEQ ID NO: 615、SEQ ID NO: 616、SEQ ID NO: 641、SEQ ID NO: 642、SEQ ID NO: 643或SEQ ID NO: 644有至少為或約為80%、至少為或約為85%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列,並且與亨尼帕病毒G蛋白(例如,NiV-G或HeV-G)一起保持了融合活性。
提及保持融合活性包括為對應野生型F蛋白(諸如SEQ ID NO: 592、SEQ ID NO: 593、SEQ ID NO: 608、SEQ ID NO: 614、SEQ ID NO: 615、SEQ ID NO: 616、SEQ ID NO: 641、SEQ ID NO: 642、SEQ ID NO: 643或SEQ ID NO: 644所示)結合水準或程度的為或約為10%至為或約150%或更多的活性(與亨尼帕病毒G蛋白一起),諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約10%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為15%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為20%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為25%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為30%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為35%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為40%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為45%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為50%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為55%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為60%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為65%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為70%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為75%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為80%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為85%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為90%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為95%,諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為100%或者諸如為對應野生型F蛋白融合活性水準或程度的至少為或至少約為120%。
在一些實施例中,F蛋白係突變F蛋白,其為含有一個或多個胺基酸突變(諸如一個或多個胺基酸插入、缺失、取代或截短)之功能活性片段或生物活性部分。在一些實施例中,本文所述之突變係關於與參考F蛋白序列相比胺基酸之胺基酸插入、缺失、取代或截短。在一些實施例中,參考F蛋白序列係F蛋白或其生物活性部分之野生型序列。在一些實施例中,突變F蛋白或其生物活性部分係野生型亨德拉(Hev)病毒F蛋白、尼帕(NiV)病毒F蛋白、松灣(CedPV)病毒F蛋白、墨江病毒F蛋白或蝙蝠副黏病毒F蛋白之突變體。在一些實施例中,野生型F蛋白由編碼SEQ ID NO: 592、593、608、614-616或641-644中任一者之核苷酸序列編碼。
在一些實施例中,突變F蛋白係野生型F蛋白之生物活性部分,其係N末端及/或C末端截短之片段。在一些實施例中,突變F蛋白或其野生型F蛋白之生物活性部分包含一個或多個胺基酸取代。在一些實施例中,本文所述之突變可改良轉導效率。在一些實施例中,本文所述之突變可增加融合能力。例示性突變包括所述之任何突變,參見例如Khetawat及Broder,2010 Virology Journal 7:312;Witting等人,2013 Gene Therapy 20:997-1005;國際出版;專利申請第WO/2013/148327號。
在一些實施例中,突變F蛋白係生物活性部分,該生物活性部分在野生型F蛋白之C末端處或附近被截短並且缺乏多達20個連續胺基酸殘基,諸如由編碼如SEQ ID NO: 592、593、608或614-616中任一者所示之F蛋白之核苷酸序列編碼之野生型F蛋白。在一些實施例中,突變F蛋白在野生型G蛋白之C末端處被截短並且缺乏至多19個連續胺基酸,諸如缺乏至多18個、17個、16個、15個、14個、13個、12個、11個、10個、9個、8個、7個、6個、5個、4個、3個、2個或1個連續胺基酸。
在一些實施例中,F蛋白或其功能性活性變體或生物活性部分包含F1次單元或其融合部分。在一些實施例中,F1次單元係F0前體之蛋白水解裂解部分。在一些實施例中,F0前體係非活性的。在一些實施例中,F0前體之裂解形成了二硫鍵連接之F1+F2異源二聚體。在一些實施例中,裂解暴露融合肽並產生成熟F蛋白。在一些實施例中,裂解發生在單個鹼性殘基處或周圍。在一些實施例中,裂解發生在NiV-F蛋白之精胺酸109處。在一些實施例中,裂解發生在亨德拉病毒F蛋白之離胺酸109處。
在一些實施例中,F蛋白係野生型尼帕病毒F (NiV-F)蛋白或其係功能性活性變體或生物活性部分。在一些實施例中,F
0前體由編碼SEQ ID NO: 592所示的序列的核苷酸序列編碼。編碼核酸可編碼具有序列MVVILDKRCY CNLLILILMI SECSVG (SEQ ID NO: 624)之信號肽序列或另一個信號肽序列。在一些實施例中,F蛋白具有SEQ ID NO: 593所示之序列。在一些實例中,F蛋白被裂解成包含SEQ ID NO: 595所示的序列的F1次單元及包含SEQ ID NO: 594所示的序列的F2次單元。
在一些實施例中,F蛋白係由編碼SEQ ID NO: 592所示之序列之核苷酸序列編碼之NiV-F蛋白,或者係其功能性活性變體或生物活性部分,該功能性活性變體或生物活性部分具有與SEQ ID NO: 592有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列。在一些實施例中,NiV-F蛋白具有SEQ ID NO: 593所示之序列,或者係其功能性活性變體或生物活性部分,該功能性活性變體或生物活性部分具有與SEQ ID NO: 593有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列。在特定實施例中,F蛋白或其功能性活性變體或生物活性部分保持被組織蛋白酶L裂解之裂解位點(例如,對應於SEQ ID NO: 592之胺基酸109-110之間的裂解位點)。
在一些實施例中,F蛋白或其功能性活性變體或生物活性部分包括具有SEQ ID NO: 595所示之序列或者與SEQ ID NO: 595有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列之F1次單元。
在一些實施例中,F蛋白或其功能性活性變體或生物活性部分包括具有SEQ ID NO: 594所示之序列或者與SEQ ID NO: 594有至少為或約為80%、至少為或約為81%、至少為或約為82%、至少為或約為83%、至少為或約為84%、至少為或約為85%、至少為或約為86%、至少為或約為87%、至少為或約為88%、至少為或約為89%、至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之胺基酸序列之F2次單元。
在一些實施例中,F蛋白係突變NiV-F蛋白,該突變NiV-F蛋白係在野生型NiV-F蛋白(例如,如SEQ ID NO: 593所示)之C末端處或附近被截短並且缺乏多達20個連續胺基酸殘基之其生物活性部分。在一些實施例中,突變NiV-F蛋白包含SEQ ID NO: 596所示之胺基酸序列。在一些實施例中,突變NiV-F蛋白具有與SEQ ID NO: 596有至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之序列。在一些實施例中,突變F蛋白包含具有SEQ ID NO: 597所示之序列之F1蛋白。在一些實施例中,突變F蛋白具有與SEQ ID NO: 597有至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之序列。
在一些實施例中,F蛋白係突變NiV-F蛋白,該突變NiV-F蛋白為其生物活性部分,該生物活性部分在野生型NiV-F蛋白(SEQ ID NO: 593)之C末端處或附近包含20個胺基酸截短;以及N-連接糖基化位點上之點突變。在一些實施例中,突變NiV-F蛋白包含SEQ ID NO: 598所示之胺基酸序列。在一些實施例中,突變NiV-F蛋白具有與SEQ ID NO: 598有至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之序列。
在一些實施例中,F蛋白係突變NiV-F蛋白,該突變NiV-F蛋白為其生物活性部分,該生物活性部分在野生型NiV-F蛋白(SEQ ID NO: 593)之C末端處或附近包含22個胺基酸截短。在一些實施例中,NiV-F蛋白包含SEQ ID NO: 599所示之胺基酸序列。在一些實施例中,NiV-F蛋白具有與SEQ ID NO: 599有至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之序列。在一些實施例中,NiV-F蛋白包含SEQ ID NO: 1092所示之胺基酸序列。在一些實施例中,NiV-F蛋白具有與SEQ ID NO: 1092有至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之序列。在一些實施例中,NiV-F蛋白包含SEQ ID NO: 1093所示之胺基酸序列。在一些實施例中,NiV-F蛋白具有與SEQ ID NO: 1093有至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之序列。在特定實施例中,變體F蛋白係具有SEQ ID NO: 613所示之胺基酸序列之突變Niv-F蛋白。在一些實施例中,NiV-F蛋白具有與SEQ ID NO: 613有至少為或約為90%、至少為或約為91%、至少為或約為92%、至少為或約為93%、至少為或約為94%、至少為或約為95%、至少為或約為96%、至少為或約為97%、至少為或約為98%或者至少為或約為99%序列同一性之序列。
B.
脂質雙層
在一些實施例中,靶向脂質顆粒包括包封內腔或腔體之天然衍生之兩親性脂質雙層。在一些實施例中,靶向脂質顆粒包含脂質雙層作為最外表面。在一些實施例中,脂質雙層包封內腔。在一些實施例中,內腔係水性的。在一些實施例中,內腔與脂質雙層之內部上的親水頭部基團接觸。在一些實施例中,內腔係細胞溶質。在一些實施例中,細胞溶質含有存在於源細胞中的細胞組分。在一些實施例中,細胞溶質不含存在於源細胞中的細胞組分。在一些實施例中,內腔係腔體。在一些實施例中,腔體含有水性環境。在一些實施例中,腔體不含水性環境。
在一些態樣中,脂質雙層衍生自在產生含脂質顆粒之過程期間之源細胞。在一些實施例中,脂質雙層包括在其中產生脂質雙層之細胞之膜組分,例如磷脂、膜蛋白等。在一些實施例中,脂質雙層包括細胞溶質,該細胞溶質包括在其中產生脂質雙層之細胞中發現之組分,例如溶質、蛋白質、核酸等,但不是細胞之所有組分,例如,其缺乏細胞核。在一些實施例中,脂質雙層被認為係外泌體樣。脂質顆粒之大小可變化,並且在一些情況下具有範圍為30nm及300nm之直徑,諸如30nm及150nm,並且包括40nm至100nm。
在一些實施例中,脂質雙層係病毒包膜劑。在一些實施例中,病毒包膜劑係自源細胞獲得的。在一些實施例中,病毒包膜劑係藉由來自源細胞質膜之病毒衣殼獲得的。在一些實施例中,脂質雙層係自除宿主細胞之質膜之外的膜獲得的。在一些實施例中,病毒包膜脂質雙層包埋有病毒蛋白,包括病毒糖蛋白。
在其他態樣中,脂質雙層包括合成脂質複合體。在一些實施例中,合成脂質複合體係脂質體。在一些實施例中,脂質顆粒係藉由磷脂雙層膜及內部水性介質表徵之囊泡結構。在一些實施例中,脂質雙層具有由水性介質分離的多個脂質層。在一些實施例中,當磷脂懸浮於過量之水溶液中時,脂質雙層自發形成。在一些實例中,脂質組分在形成閉合結構之前經歷自重排並且在脂質雙層之間截留水及溶解之溶質。
在一些實施例中,靶向包膜蛋白及融合劑,諸如上文所述之任一者包括相對於源細胞為外源性或過表現之任一者,安置於脂質雙層中。
在一些實施例中,靶向脂質顆粒包含幾種不同類型之脂質。在一些實施例中,脂質係兩親性脂質。在一些實施例中,兩親性脂質係磷脂。在一些實施例中,磷脂包含磷脂醯膽鹼、磷脂醯乙醇胺、磷脂醯肌醇及磷脂醯絲胺酸。在一些實施例中,脂質包含磷脂,諸如磷酸膽鹼及磷酸肌醇。在一些實施例中,脂質包含DMPC、DOPC及DSPC。
在一些實施例中,雙層可由相同或不同類型之一種或多種脂質構成。在一些實施例中,源細胞包含選自以下之細胞:CHO細胞、BHK細胞、MDCK細胞、C3H 10T1/2細胞、FLY細胞、Psi-2細胞、BOSC 23細胞、PA317細胞、WEHI細胞、COS細胞、BSC 1細胞、BSC 40細胞、BMT 10細胞、VERO細胞、W138細胞、MRC5細胞、A549細胞、HT1080細胞、293細胞、293T細胞、B-50細胞、3T3細胞、NIH3T3細胞、HepG2細胞、Saos-2細胞、Huh7細胞、HeLa細胞、W163細胞、211細胞及211A細胞。
C.
外源藥劑
在一些實施例中,靶向脂質顆粒進一步包含相對於源細胞為外源之藥劑(在本文中亦稱為「轉運劑」或「有效載荷」)。在一些實施例中,外源藥劑係小分子、蛋白質或核酸(例如,DNA、染色體(例如人類人工染色體)、RNA,例如mRNA或miRNA)。在一些實施例中,外源藥劑或轉運劑編碼細胞溶質蛋白。在一些實施例中,外源藥劑或轉運劑包含或編碼膜蛋白。在一些實施例中,外源藥劑或轉運劑包含治療劑。在一些實施例中,治療劑選自蛋白質中的一者或多者,例如酶、跨膜蛋白、受體、抗體;核酸,例如DNA、染色體(例如人類人工染色體)、RNA、mRNA、siRNA、miRNA;或小分子。
在一些實施例中,外源藥劑以至少或不超過10個、20個、50個、100個、200個、500個、1,000個、2,000個、5,000個、10,000個、20,000個、50,000個、100,000個、200,000個、500,000個、1,000,000個、5,000,000個、10,000,000個、50,000,000個、100,000,000個、500,000,000個或1,000,000,000個拷貝存在。在一些實施例中,靶向脂質顆粒具有改變的(例如增加或減少的)一種或多種內源分子(例如,蛋白質或核酸)水準(例如,在一些實施例中,相對於源細胞係內源的,並且在一些實施例中,相對於目標細胞係內源的),例如,由於用siRNA或基因編輯酶處理源細胞,例如哺乳動物源細胞。在一些實施例中,內源分子以至少或不超過10個、20個、50個、100個、200個、500個、1,000個、2,000個、5,000個、10,000個、20,000個、50,000個、100,000個、200,000個、500,000個、1,000,000個、5,000,000個、10,000,000個、50,000,000個、100,000,000個、500,000,000個或1,000,000,000個拷貝存在。在一些實施例中,內源分子(例如,RNA或蛋白質)以比其在源細胞中的濃度高至少1、2、3、4、5、10、20、50、100、500、10
3、5.0×10
3、10
4、5.0×10
4、10
5、5.0×10
5、10
6、5.0×10
6、1.0×10
7、5.0×10
7或1.0×10
8之濃度存在。在一些實施例中,內源分子(例如,RNA或蛋白質)以比其在源細胞中的濃度低至少1、2、3、4、5、10、20、50、100、500、10
3、5.0×10
3、10
4、5.0×10
4、10
5、5.0×10
5、10
6、5.0×10
6、1.0×10
7、5.0×10
7或1.0×10
8之濃度存在。
在一些實施例中,靶向脂質顆粒(例如,靶向病毒載體)將靶向脂質顆粒所包含的轉運劑(例如,治療劑,例如外源治療劑)的至少10%、20%、30%、40%、50%、60%、70%、80%、90%、95%、96%、97%、98%或99%遞送至目標細胞。在一些實施例中,與目標細胞融合之靶向脂質顆粒將與目標細胞融合之靶向脂質顆粒所包含的轉運劑(例如,治療劑,例如外源治療劑)之平均至少10%、20%、30%、40%、50%、60%、70%、80%、90%、95%、96%、97%、98%或99%遞送至目標細胞。在一些實施例中,靶向脂質顆粒組合物將靶向脂質顆粒組合物包含的轉運劑(例如,治療劑,例如外源治療劑)的至少10%、20%、30%、40%、50%、60%、70%、80%、90%、95%、96%、97%、98%或99%遞送至目標組織。
在一些實施例中,外源藥劑或轉運劑不在衍生自靶向脂質顆粒之細胞中天然表現。在一些實施例中,外源藥劑或轉運劑在衍生自病毒載體之細胞中天然表現。在一些實施例中,經由在衍生自病毒載體之細胞中表現(例如,自經由轉染、轉導或電穿孔引入之DNA或mRNA表現)將外源藥劑或轉運劑裝載至靶向脂質顆粒中。在一些實施例中,外源藥劑或轉運劑由整合至基因組中的DNA表現或維持游離狀態。在一些實施例中,外源藥劑或轉運劑之表現係組成型的。在一些實施例中,誘導外源藥劑或轉運劑之表現。在一些實施例中,在產生靶向脂質顆粒之前立即誘導外源藥劑或轉運劑之表現。在一些實施例中,外源藥劑或轉運劑之表現在與融合劑之表現同時誘導。
在一些實施例中,經由電穿孔將外源藥劑或轉運劑裝載至病毒載體中進入病毒載體本身或進入衍生自病毒載體之細胞中。在一些實施例中,經由轉染(例如,編碼轉運劑之DNA或mRNA)將外源藥劑或轉運劑裝載至病毒載體中進入病毒載體本身或進入衍生自病毒載體之細胞中。
在一些實施例中,外源藥劑或轉運劑可包括一個或多個核酸序列、一個或多個多肽、核酸序列及/或多肽之組合、一個或多個細胞器以及其任何組合。在一些實施例中,外源藥劑或轉運劑可包括一種或多種細胞組分。在一些實施例中,外源藥劑或轉運劑包括一種或多種細胞溶質及/或細胞核組分。
在一些實施例中,外源藥劑或轉運劑包括核酸,例如DNA、nDNA (核DNA)、mtDNA (線粒體DNA)、蛋白質編碼DNA、基因、操縱子、染色體、基因組、轉座子、反轉錄轉座子、病毒基因組、內含子、外顯子、修飾之DNA、mRNA (信使RNA)、tRNA (轉移RNA)、修飾之RNA、微RNA、siRNA (小干擾RNA)、tmRNA (轉移信使RNA)、rRNA (核糖體RNA)、mtRNA (線粒體RNA)、snRNA (小核RNA)、小核仁RNA(snoRNA)、SmY RNA (mRNA反式剪接RNA)、gRNA (引導RNA)、TERC (端粒酶RNA組分)、aRNA (反義RNA)、cis-NAT (順式天然反義轉錄)、CRISPR RNA(crRNA)、IncRNA (長鏈非編碼RNA)、piRNA(piwi相互作用RNA)、shRNA (短髮夾RNA)、tasiRNA (反式作用siRNA)、eRNA (增強子RNA)、衛星RNA、pcRNA (蛋白質編碼RNA)、dsRNA (雙鏈RNA)、RNAi (干擾RNA)、circRNA (環狀RNA)、重編程RNA、適體以及其任何組合。在一些實施例中,核酸係野生型核酸。在一些實施例中,核酸係突變核酸。在一些實施例中,核酸係多個核酸序列之融合物或嵌合體。
在一些實施例中,外源藥劑或轉運劑可包括核酸。例如,外源藥劑或轉運劑可包含增強內源性蛋白質之表現的RNA或者抑制內源性蛋白之蛋白質表現的siRNA或miRNA。舉例而言,內源性蛋白可調控目標細胞中的結構或功能。在一些實施例中,轉運劑可包括編碼工程蛋白之核酸,該工程蛋白調控目標細胞中的結構或功能。在一些實施例中,外源藥劑或轉運劑係靶向調節目標細胞中的結構或功能之轉錄活化劑的核酸。
在一些實施例中,外源藥劑或轉運劑包括多肽,例如酶、結構多肽、信號傳導多肽、調控性多肽、轉運多肽、感測器多肽、運動多肽、防禦多肽、儲存多肽、轉錄因子、抗體、細胞介素、激素、分解代謝多肽、合成代謝多肽、蛋白水解多肽、代謝多肽、激酶、轉移酶、水解酶、裂解酶、異構體酶、激酶、酶調節劑多肽、蛋白結合多肽、脂質結合多肽、膜融合多肽、細胞分化多肽、表觀遺傳多肽、細胞死亡多肽、核轉運多肽、核酸結合多肽、重編程多肽、DNA編輯多肽、DNA修復多肽、DNA重組多肽、轉座酶多肽、DNA整合多肽、靶向核酸內切酶(例如鋅指核酸酶、轉錄活化劑樣核酸酶(TALEN)、cas9及其同源物)、重組酶以及其任何組合。在一些實施例中,蛋白質靶向細胞中的蛋白質以進行降解。在一些實施例中,蛋白質藉由將蛋白質定位於蛋白酶體而靶向細胞中的蛋白質以進行降解。在一些實施例中,蛋白質係野生型蛋白質。在一些實施例中,蛋白質係突變蛋白質。在一些實施例中,蛋白質係融合體或嵌合蛋白。
在一些實施例中,外源藥劑或轉運劑包括小分子,例如離子(例如Ca
2+、C1-、Fe
2+)、碳水化合物、脂質、活性氧、活性氮、類異戊二烯、信號傳導分子、血紅素、多肽輔因子、電子接受化合物、給電子化合物、代謝物、配體以及其任何組合。在一些實施例中,小分子係與細胞中之目標相互作用之藥物。在一些實施例中,小分子靶向細胞中的蛋白質以進行降解。在一些實施例中,小分子藉由將蛋白質定位於蛋白酶體而靶向細胞中的蛋白質以進行降解。在一些實施例中,小分子係蛋白水解靶向嵌合分子(PROTAC)。
在一些實施例中,外源藥劑或轉運劑包括蛋白質、核酸或代謝物之混合物,例如多個多肽、多個核酸、多個小分子;核酸、多肽及小分子之組合;核糖核蛋白複合體(例如Cas9-gRNA複合體);多個轉錄因子、多個表觀遺傳因子、重編程因子(例如Oct4、Sox2、cMyc及Klf4);多種調控RNA;以及其任何組合。
在一些實施例中,外源藥劑或轉運劑包括一個或多個細胞器,例如軟骨體、線粒體、溶酶體、細胞核、細胞膜、細胞質、內質網、核糖體、液泡、核內體、剪接體、聚合酶、衣殼、頂體、自噬體、中心粒、糖酵解酶體、乙醛酸循環體、氫化酶體、黑素體、紡錘剩體、肌原纖維、刺絲囊、過氧化物酶體、蛋白酶體、囊泡、應激顆粒、細胞器網路以及其任何組合。
在一些實施例中,外源藥劑編碼治療劑或診斷劑。在一些實施例中,治療劑係嵌合抗原受體(CAR)或T細胞受體(TCR)。在一些實施例中,CAR靶向選自CD19、CD20、CD22或BCMA之腫瘤抗原。在另一個實施例中,CAR經工程改造以包含T細胞抗原受體複合體ζ鏈(例如,CD3ζ)之細胞內信號傳導域。在較佳實施例中,細胞內域選自CD137 (4-1BB)信號傳導域、CD28信號傳導域及CD3ζ信號傳導域。
D.
產生衍生自病毒之靶向脂質顆粒之方法
本文提供了衍生自病毒之靶向脂質顆粒,諸如病毒顆粒或病毒樣顆粒,包括衍生自逆轉錄病毒或慢病毒之彼等顆粒。在一些實施例中,靶向脂質顆粒之兩親性脂質雙層係或包含病毒包膜劑。在一些實施例中,靶向脂質顆粒之兩親性脂質雙層係或包含衍生自生產細胞之脂質。在一些實施例中,病毒包膜劑可包含融合劑,例如對病毒係內源性之融合劑或假型化融合劑。在一些實施例中,靶向脂質顆粒的內腔或腔體包含病毒核酸,例如逆轉錄病毒核酸,例如慢病毒核酸。在一些實施例中,病毒核酸可為病毒基因組。在一些實施例中,靶向脂質顆粒進一步包含一種或多種病毒非結構蛋白,例如在其腔體或內腔中。在一些實施例中,靶向脂質顆粒係或包含病毒樣顆粒(VLP)。在一些實施例中,VLP不包含包膜。在一些實施例中,VLP包含包膜。
在一些實施例中,病毒顆粒或病毒樣顆粒,諸如逆轉錄病毒或逆轉錄病毒樣顆粒,包含Gag多蛋白、聚合酶(例如,Pol)、整合酶(IN,例如功能性或非功能性變體)、蛋白酶(PR)及融合劑中的一者或多者。在一些實施例中,靶向脂質顆粒進一步包含Rev。在一些實施例中,上述蛋白質中的一者或多者在逆轉錄病毒基因組中編碼,並且在一些實施例中,上述蛋白質中的一者或多者例如藉由輔助細胞、輔助病毒或輔助質體以反式提供。在一些實施例中,靶向脂質顆粒核酸(例如,逆轉錄病毒核酸)包含以下核酸序列中的一者或多者:5' LTR(例如,包含U5並且缺乏功能性U3域)、Psi包裝元件(Psi)、有效連接至有效載荷基因之中央聚嘌呤束(cPPT)啟動子、有效載荷基因(視情况包含開放閱讀框之前的內含子)、Poly A尾部序列、WPRE及3' LTR (例如,包含U5並且缺乏功能性U3)。在一些實施例中,靶向脂質顆粒核酸進一步包含一個或多個絕緣體元件。在一些實施例中,識別位點位於聚poly A尾部序列及WPRE之間。
在一些實施例中,靶向脂質顆粒包含由自組裝至衣殼中的病毒蛋白形成之超分子複合體。在一些實施例中,靶向脂質顆粒係衍生自病毒衣殼之病毒顆粒或病毒樣顆粒。在一些實施例中,靶向脂質顆粒係衍生自病毒核衣殼之病毒顆粒或病毒樣顆粒。在一些實施例中,靶向脂質顆粒包含保持包裝核酸之特性之核衣殼衍生之蛋白質。在一些實施例中,病毒顆粒或病毒樣顆粒僅包含病毒結構糖蛋白。在一些實施例中,靶向脂質顆粒不含病毒基因組。
在一些實施例中,在表現過程期間,靶向脂質顆粒包裝來自宿主細胞之核酸。在一些實施例中,核酸不編碼涉及病毒複製之任何基因。在特定實施例中,靶向脂質顆粒係複製缺陷型病毒樣顆粒,例如逆轉錄病毒樣顆粒,諸如慢病毒樣顆粒。
在一些情況下,靶向脂質顆粒係在形態學上不可與野生型感染性病毒區分之病毒顆粒。在一些實施例中,病毒顆粒呈現整個病毒蛋白質組作為抗原。在一些實施例中,病毒顆粒僅呈現蛋白質組之一部分作為抗原。
在一些實施例中,病毒顆粒或病毒樣顆粒係利用來自副黏病毒科家族內之病毒之蛋白質(例如,包膜蛋白)產生的。在一些實施例中,副黏病毒科家族包含亨尼帕病毒屬內之成員。在一些實施例中,亨尼帕病毒係或包含亨德拉(HeV)或尼帕(NiV)病毒。在特定實施例中,病毒顆粒或病毒樣顆粒摻入了靶向包膜蛋白及融合劑。
在一些實施例中,病毒顆粒或病毒樣顆粒可在多個細胞培養系統(包含細菌、哺乳動物細胞株、昆蟲細胞株、酵母及植物細胞)中產生。
可使用之合適的細胞株包括例如CHO細胞、BHK細胞、MDCK細胞、C3H 10T1/2細胞、FLY細胞、Psi-2細胞、BOSC 23細胞、PA317細胞、WEHI細胞、COS細胞、BSC 1細胞、BSC 40細胞、BMT 10細胞、VERO細胞、W138細胞、MRC5細胞、A549細胞、HT1080細胞、293細胞、293T細胞、B-50細胞、3T3細胞、NIH3T3細胞、HepG2細胞、Saos-2細胞、Huh7細胞、HeLa細胞、W163細胞、211細胞、211A細胞以及cyno及南平頂猴(Macaca nemestrina)細胞株。在實施例中,包裝細胞係293細胞、293T細胞或A549細胞。
在一些實施例中,源細胞株包括能夠產生重組逆轉錄病毒顆粒之細胞株,該細胞株包含生產細胞株及包含包裝信號之轉移載體構築體。製備病毒儲備溶液之方法如下所示:例如Y. Soneoka等人,1995年,
Nucl. Acids Res.,第23卷:第628-633頁;以及N. R. Landau等人,1992年,
J. Virol.,第66卷,第5110-5113頁,此等方法係以引用之方式併入本文。
在一些實施例中,藉由將核心蛋白與病毒基因組(例如,具有莖-環結構之UTR)內獨特之衣殼化序列結合來引發病毒顆粒或病毒樣顆粒之組裝。在一些實施例中,核心與衣殼化序列之相互作用便於寡聚化。
在一些實施例中,靶向脂質顆粒係病毒樣顆粒,其包含不含或缺乏病毒RNA之序列。在一些實施例中,此類顆粒可為自序列去除或消除病毒RNA之結果。在一些實施例中,其可以藉由使用Gag上的內源性包裝信號結合位點來實現。在一些實施例中,內源性包裝信號結合位點位於Pol上。在一些實施例中,待遞送之RNA將含有同源包裝信號。在一些實施例中,位於待遞送之RNA上的異源結合域(與Gag異源)及位於Gag或Pol上之同源結合位點可用於確保待遞送之RNA之包裝。在一些實施例中,異源序列可係非病毒性的,或者其可係病毒性的,在此情況下,其可衍生自相同病毒或不同病毒。在一些實施例中,載體顆粒可用於遞送治療性RNA,在此情况下,不需要功能性整合酶及/或逆轉錄酶。在一些實施例中,載體顆粒亦可用於遞送感興趣之治療性基因,在此情況下,通常包括Pol。在一些實施例中,逆轉錄病毒核酸包含以下中的一者或多者(例如,全部):5'啟動子(例如,用於控制整個包裝之RNA之表現)、5'LTR (例如,包括R (多腺苷酸化尾部信號)及/或包括引子活化信號之U5)、引子結合位點、Psi包裝信號、用於核導出之RRE元件、轉基因之直接上游的用於控制轉基因表現之啟動子、轉基因(或其他外源藥劑元件)、聚嘌呤束及3'LTR (例如,包括突變之U3、R及U5)。在一些實施例中,逆轉錄病毒核酸進一步包含cPPT、WPRE及/或隔離元件中的一者或多者。
逆轉錄病毒典型地藉由將其基因組RNA逆轉錄成線性雙鏈DNA拷貝進行複製並且隨後將其基因組DNA共價整合至宿主基因組中。適用於特定實施例之例示性逆轉錄病毒包括但不限於:莫洛尼鼠白血病病毒(M-MuLV)、莫洛尼鼠肉瘤病毒(MoMSV)、哈維鼠肉瘤病毒(HaMuSV)、鼠乳腺腫瘤病毒(MuMTV)、長臂猿白血病病毒(GaLV)、貓白血病病毒(FLV)、泡沫病毒屬、弗雲德鼠白血病病毒、鼠幹細胞病毒(MSCV)、勞斯肉瘤病毒(RSV)及其他慢病毒。
在一些實施例中,逆轉錄病毒係γ逆轉錄病毒。在一些實施例中,逆轉錄病毒係ε逆轉錄病毒。在一些實施例中,逆轉錄病毒係α逆轉錄病毒。在一些實施例中,逆轉錄病毒係β逆轉錄病毒。在一些實施例中,逆轉錄病毒係δ逆轉錄病毒。在一些實施例中,逆轉錄病毒係慢病毒。在一些實施例中,逆轉錄病毒係唾液逆轉錄病毒。在一些實施例中,逆轉錄病毒係內源性逆轉錄病毒。
例示性慢病毒包括但不限於:HIV (人類免疫缺陷病毒;包括HIV型1及HIV型2);羊進行性間質肺炎病毒(visna-maedi virus,VMV)病毒;山羊關節炎腦炎病毒(caprine arthritis-encephalitis virus,CAEV);馬感染性貧血病毒(equine infectious anemia virus,EIAV);貓免疫缺陷病毒(feline immunodeficiency virus,FIV);牛免疫缺陷病毒(bovine immune deficiency virus,BIV);及猴免疫缺陷病毒(simian immunodeficiency virus,SIV)。在一些實施例中,使用基於HIV之載體主鏈(亦即,HIV順式作用序列元件)。
在一些實施例中,本文中的載體係能夠轉移或輸送另一種核酸分子之核酸分子。所轉移之核酸通常連接至載體核酸分子,例如插入到載體核酸分子中。載體可包括在細胞中引導自主複製之序列,或者可包括足以允許整合至宿主細胞DNA中的序列。有用的載體包括例如質體(例如,DNA質體或RNA質體)、轉座子、黏質體、細菌人工染色體及病毒載體。有用的病毒載體包括例如複製缺陷型逆轉錄病毒及慢病毒。
在一些實施例中,病毒載體包含核酸分子(例如,轉移質體),該核酸分子包括病毒衍生之核酸元件,此等病毒衍生之核酸元件通常便於核酸分子轉移或整合至細胞之基因組中或整合至介導核酸轉移之病毒顆粒中。除了核酸之外,病毒顆粒亦將典型地包括各種病毒組分並且有時亦包括宿主細胞組分。在一些實施例中,病毒載體包含例如能夠將核酸轉移至細胞中的病毒或病毒顆粒,或者轉移之核酸(例如,作為裸DNA)。在一些實施例中,病毒載體及轉移質體包含主要衍生自病毒之結構及/或功能性遺傳元件。逆轉錄病毒載體可包含含有主要衍生自逆轉錄病毒的結構及功能性基因元件或其一部分的病毒載體或質體。慢病毒載體可包含含有結構及功能性基因元件或其一部分(包括主要衍生自慢病毒之LTR)之病毒載體或質體。
在實施例中,慢病毒載體(例如,慢病毒表現載體)可包含慢病毒轉移質體(例如,作為裸DNA)或感染性慢病毒顆粒。關於元件諸如選殖位點、啟動子、調控元件、異源核酸等,應當理解,此等元件之序列可以RNA形式存在於慢病毒顆粒中並且可以DNA形式存在於DNA質體中。
在一些實施例中,在本文所述之載體中,與對應野生型病毒相比,可不存在有助於複製或對複製至關重要之一個或多個蛋白編碼區的至少一部分。在一些實施例中,病毒載體係複製缺陷型。在一些實施例中,載體能夠轉導目標非分裂宿主細胞及/或將其基因組整合至宿主基因組中。
在一些實施例中,不同的細胞在其使用特定密碼子方面不同。在一些實施例中,該密碼子偏差對應於細胞類型中特定tRNA之相對豐度之偏差。在一些實施例中,藉由改變序列中的密碼子,使得其被定製成與對應tRNA之相對豐度匹配,可增加表現。在一些實施例中,可藉由有意選擇已知對應之tRNA在特定細胞類型中罕見之密碼子來降低表現。在一些實施例中,可提供另外程度之轉譯控制。密碼子最佳化之另外描述見於例如WO 99/41397中,該文獻全文以引用方式併入本文。
使用或不使用包裝/輔助載體來產生逆轉錄病毒載體(並且特別係慢病毒載體)之習知技術係熟習此項技術者已知的,並且可用於產生根據本揭示之靶向脂質顆粒。(參見例如,Derse及Newbold 1993 Virology 194:530-6;Maury等人1994 Virology 200:632-42;Wanisch等人2009. Mol Ther. 1798:1316-1332;Martarano等人1994 J. Virol. 68:3102-11;Naldini等人,(1996a、1996b及1998);Zufferey等人,1999, J. Virol., 73:2886;Huang等人,Mol. Cell. Biol., 5:3864;Liu等人,1995, Genes Dev., 9:1766;Cullen等人,1991. J. Virol. 65: 1053;及Cullen等人,1991. Cell 58: 423;Dull等人,1998,美國專利第6,013,516號及第5,994,136號;PCT專利申請WO 99/15683、WO 98/17815、WO 99/32646及WO 01/79518)。根據本揭示,亦可使用與此項技術已知之包裝載體及生產細胞有關之習知技術。(參見例如,Yao等人,1998;Jones等人,2005)。
本文提供了包含天然衍生之膜之靶向脂質顆粒。在一些實施例中,天然衍生之膜包含由細胞或組織製備之膜囊泡。在一些實施例中,靶向脂質顆粒包含可自細胞獲得之囊泡。在一些實施例中,靶向脂質顆粒包含微囊泡、外泌體、膜包封體、凋亡小體(來自凋亡細胞)、顆粒(其可衍生自例如血小板)、核外顆粒體(源自例如血清中的嗜中性粒細胞及單核細胞)、前列腺體(可從前列腺癌細胞獲得)或心臟體(可自心臟細胞獲得)。
在一些實施例中,源細胞係內皮細胞、纖維母細胞、血細胞(例如,巨噬細胞、中性粒細胞、粒細胞、白細胞)、幹細胞(例如,間質幹細胞、臍帶幹細胞、骨髓幹細胞、造血幹細胞、誘導性多能幹細胞,例如衍生自個體細胞之誘導性多能幹細胞)、胚胎幹細胞(例如,來自胚胎卵黃囊、胎盤、臍帶、胎兒皮膚、青少年皮膚、血液、骨髓、脂肪組織、胸腺細胞、造紅細胞組織之幹細胞)、肌母細胞、實質細胞(例如,肝細胞)、肺泡細胞、神經元(例如,視網膜神經元細胞)、前體細胞(例如,視網膜前體細胞、骨髓母細胞、髓樣前體細胞、胸腺細胞、母細胞、巨核母細胞、幼巨核細胞、黑素細胞、淋巴母細胞、骨髓前體細胞、正母紅血球或血管母細胞)、祖細胞(例如,心臟祖細胞、衛星細胞、放射狀膠質細胞、骨髓基質細胞、胰腺祖細胞、內皮祖細胞、胚細胞)或永生化細胞(例如,HeEa、HEK293、HFF-l、MRC-5、WI-38、IMR 90、IMR 91、PER.C6、HT-1080或BJ細胞)。在一些實施例中,源細胞不是293細胞、HEK細胞、人類內皮細胞或人類上皮細胞、單核細胞、巨噬細胞、樹突狀細胞或幹細胞。
在一些實施例中,靶向脂質顆粒之密度為<1g/mL、1g/mL至1.1g/mL、1.05g/mL至1.15g/mL、1.1g/mL至1.2g/mL、1.15g/mL至1.25g/mL、1.2g/mL至1.3g/mL、1.25g/mL至1.35g/mL或>1.35g/mL。在一些實施例中,靶向脂質顆粒組合物包含小於0.01%、0.05%、0.1%、0.5%、1%、1.5%、2%、2.5%、3%、4%、5%或10%蛋白質質量之源細胞或者小於0.01%、0.05%、0.1%、0.5%、1%、1.5%、2%、2.5%、3%、4%、5%或10%具有功能性細胞核之細胞。
在實施例中,靶向脂質顆粒之大小或者靶向脂質顆粒群體之平均大小小於源細胞之約0.01%、0.05%、0.1%、0.5%、1%、2%、3%、4%、5%、10%、20%、30%、40%、50%、60%、70%、80%、90%。
在一些實施例中,靶向脂質顆粒包含細胞外囊泡,例如細胞衍生之囊泡,其包含包圍內部空間並具有比其衍生之細胞更小之直徑的膜。在實施例中,細胞外囊泡之直徑為20nm至1000nm。在實施例中,靶向脂質顆粒包含凋亡小體、細胞之片段、藉由直接或間接操縱衍生自細胞之囊泡、泡狀細胞器及由活細胞產生之囊泡(例如,藉由直接質膜出芽或晚期核內體與質膜融合)。在實施例中,細胞外囊泡衍生自活的或死的生物體、外植的組織或器官或經培養的細胞。
在實施例中,靶向脂質顆粒包含奈米囊泡,例如細胞衍生之小(例如,直徑介於20nm至250nm之間,或者直徑為30nm至150nm)囊泡,該囊泡包含包圍內部空間並且藉由直接或間接操縱自該細胞產生的膜。在一些情況下,奈米囊泡的產生可導致源細胞之破壞。奈米囊泡可包含脂質或脂肪酸及多肽。
在實施例中,靶向脂質顆粒包含外泌體。在實施例中,外泌體係細胞衍生的小(例如,直徑介於20nm至300nm之間,或者直徑為40nm至200nm)囊泡,該囊泡包含包圍內部空間並且藉由直接質膜出芽或藉由晚期核內體與質膜融合自該細胞生的膜。在實施例中,外泌體的產生不會導致源細胞之破壞。在實施例中,外泌體包含脂質或脂肪酸及多肽。
在一些實施例中,靶向脂質顆粒衍生自具有基因修飾之源細胞,該基因修飾導致免疫調節劑之表現增加。在一些實施例中,免疫抑制劑位於細胞的外表面上。在一些實施例中,將免疫抑制劑摻入至靶向脂質顆粒的外表面中。在一些實施例中,靶向脂質顆粒包含藉由共價或非共價鍵連接至固體顆粒表面之免疫調節劑。
a.
細胞衍生之顆粒的產生
在一些實施例中,藉由誘導外泌體、微囊泡、膜囊泡、細胞外膜囊泡、質膜囊泡、巨型質膜囊泡、雕亡小體、線粒體顆粒、核紅細胞、溶酶體或其他膜包封之囊泡來產生靶向脂質顆粒。
在一些實施例中,藉由誘導細胞去核產生靶向脂質顆粒。可使用測定(諸如遺傳、化學(例如使用放線菌素D (Actinomycin D),參見Bayona-Bafaluy等人,「A chemical enucleation method for the transfer of mitochondrial DNA to ρ° cells」,Nucleic Acids Res.,2003年8月15日,31(16): e98)或機械方法(例如擠壓或抽吸,參見Lee等人,「A comparative study on the efficiency of two enucleation methods in pig somatic cell nuclear transfer: effects of the squeezing and the aspiration methods」,Anim Biotechnol. 2008;19(2):71-9)或其組合來進行去核。
在一些實施例中,藉由誘導細胞碎裂產生靶向脂質顆粒。在一些實施例中,可使用以下方法進行細胞碎裂,包括但不限於:化學方法、機械方法(例如,離心(例如,超速離心或密度離心)、凍融或音波處理)或其組合。
在一些實施例中,靶向脂質顆粒係微囊泡。在一些實施例中,微囊泡之直徑為約100nm至約2000nm。在一些實施例中,靶向脂質顆粒包含細胞鬼影。在一些實施例中,囊泡係質膜囊泡,例如巨型質膜囊泡。
在一些實施例中,藉由與參考細胞進行比較來描述靶向脂質顆粒之特徵。在實施例中,參考細胞係源細胞。在實施例中,參考細胞係HeLa、HEK293、HFF-1、MRC-5、WI-38、IMR 90、IMR 91、PER. C6、HT-1080或BJ細胞。在一些實施例中,例如,當用於製備目標脂質顆粒之源細胞在目標脂質顆粒製備之後無法用於測試時,藉由與參考細胞群體(例如源細胞群體,或者HeLa、HEK293、HFF-1、MRC-5、WI-38、IMR 90、IMR 91、PER.C6、HT-1080或BJ細胞群體)進行比較來描述靶向脂質顆粒群體之特徵。
醫藥組合物
在一些態樣中,本揭示亦提供了醫藥組合物,其包含本文所述之靶向脂質顆粒(例如靶向病毒載體)組合物及醫藥學上可接受之載體。醫藥組合物可包括所述靶向病毒載體中的任一者。
在一些實施例中,靶向病毒載體符合醫藥或良好製造規範(GMP)標準。在一些實施例中,靶向病毒載體根據良好製造規範(GMP)製備。在一些實施例中,靶向病毒載體具有低於預定之參考值之病原體水準,例如實質上不含病原體。在一些實施例中,靶向病毒載體具有低於預定之參考值之污染物水準,例如實質上不含污染物。在一些實施例中,靶向病毒載體具有低免疫原性。
在一些實施例中,本文提供了使用醫藥組合物來實踐本揭示之方法。此醫藥組合物可由適合於向個體投與之形式之本揭示之至少一種靶向脂質顆粒組成,或者醫藥組合物可包含本揭示之至少一種靶向脂質顆粒及一種或多種醫藥學上可接受之載體、一種或多種另外的成分或此等之一些組合。
在一些實施例中,醫藥組合物中的靶向脂質顆粒、醫藥學上可接受之載體及任何另外的成分的相對量將變化,其取決於所治療之個體之身分、大小及病狀,並且進一步取決於組合物之待投與途徑。在一些實施例中,組合物可包含介於0.1%及100% (w/w)之間的本揭示之靶向脂質顆粒。
在一些實施例中,可用於本揭示之方法之醫藥組合物可適當地開發用於靜脈內、瘤內、口服、直腸、陰道、非經腸、局部、肺部、鼻內、頰、眼科或另一種投與途徑。在一些實施例中,可將用於本揭示之方法之組合物直接投與至哺乳動物之皮膚、陰道或任何其他組織。在一些實施例中,調配物包括脂質體製劑、含有本揭示之靶向脂質顆粒之再密封紅細胞及基於免疫學之調配物。在一些實施例中,投與途徑對於熟練技術人員將係顯而易見的,並且將取決於任何數目之因素,包括所治療疾病之類型及嚴重程度、所治療獸類個體或人類個體之類型及年齡等。
在一些實施例中,本文所述之醫藥組合物之調配物可藉由在藥理學領域中已知或以後開發之任何方法來製備。在一些實施例中,製備方法包括使本揭示之靶向脂質顆粒與載體或者一種或多種其他輔助成分締合之步驟,並且然後如有必要或期望,使產物成形或包裝成期望之單劑量單元或多劑量單元。
在一些實施例中,「單位劑量」係包含預定量之本揭示之靶向脂質顆粒之醫藥組合物之離散量。在一些實施例中,該量通常等於將投與至個體之劑量或此劑量之方便部分,諸如此劑量之一半或三分之一。在一些實施例中,單位劑型可為單次日劑量或多次日劑量中的一者(例如每天約1次至4次或更多次)。在一些實施例中,當使用多次日劑量時,對於每個劑量,單位劑型可相同或不同。
在一些實施例中,儘管本文提供之醫藥組合物之描述主要係關於適合於進行倫理地投與至人類之醫藥組合物,但熟習此項技術者將理解,此類組合物通常適合於投與至所有種類之動物。在一些實施例中,對適合於投與至人類之醫藥組合物之修飾以便使組合物適合於投與至各種動物係熟知的,並且普通技術之獸醫藥理學家可僅藉由普通之實驗(若存在)來設計及進行此修飾。在一些實施例中,設想投與本揭示之醫藥組合物之個體包括人類及其他靈長類動物、哺乳動物,包括商業相關哺乳動物,諸如牛、豬、馬、綿羊、貓及狗。
在一些實施例中,本揭示之組合物使用一種或多種醫藥學上可接受之賦形劑或載體來調配。在一個實施例中,本揭示之醫藥組合物包含治療有效量之本揭示之靶向脂質顆粒及醫藥學上可接受之載體。在一些實施例中,可用的醫藥學上可接受之載體包括但不限於甘油、水、鹽水、乙醇及其他醫藥學上可接受之鹽溶液,諸如磷酸鹽及有機酸之鹽。此等以及其他醫藥學上可接受之載體之實例在「Remington's Pharmaceutical Sciences」(1991,Mack Publication Co.,New Jersey)中進行了描述。
在一些實施例中,載體可為溶劑或分散介質,其含有例如水、乙醇、多元醇(例如,甘油、丙二醇及液體聚乙二醇等)、其合適的混合物及植物油。在一些實施例中,可例如藉由使用塗層(諸如卵磷脂),藉由在分散之情况下維持所需粒度並且藉由使用界面活性剂來維持適當之流動性。在一些實施例中,預防微生物之作用可藉由各種抗菌劑及抗真菌劑(例如對羥基苯甲酸酯、氯丁醇、苯酚、抗壞血酸、乙基汞硫代水楊酸鈉等)來實現。在一些實施例中,較佳的係在組合物中包括等滲劑,例如糖、氯化鈉或多元醇,諸如甘露糖醇及山梨糖醇。在一些實施例中,可藉由在組合物中包括延遲吸收之藥劑(例如單硬脂酸鋁或明膠)來獲得可注射組合物之延長吸收。在一個實施例中,醫藥學上可接受之載體不是單獨的DMSO。
在一些實施例中,調配物可與習知賦形劑混合使用,亦即適用於口服、經陰道、非經腸、鼻腔、靜脈內、皮下、腸內或此項技術已知之任何其他合適的投與方式之醫藥學上可接受之有機或無機載體物質。在一些實施例中,藥物製劑可被滅菌並且若期望,與輔助劑(例如潤滑劑、防腐劑、穩定劑、潤濕劑、乳化劑、用於影響滲透壓緩衝劑之鹽、著色劑、調味劑及/或芳香物質等)混合。在一些實施例中,藥物製劑亦可與其他活性劑(例如,其他鎮痛劑)組合。
在一些實施例中,「另外的成分」包括但不限於以下中的一者或多者:賦形劑;界面活性剂;分散劑;惰性稀釋劑;製粒劑及崩解劑;結合劑;潤滑劑;甜味劑;調味劑;著色劑;防腐劑;生理上可降解之組分,諸如明膠;水性媒劑及溶劑;油性媒劑及溶劑;懸浮劑;分散劑或潤濕劑;乳化劑、緩和劑;緩衝劑;鹽;増稠劑;填充劑;乳化劑;抗氧化劑;抗生素;抗真菌劑;穩定劑;及醫藥學上可接受之聚合或疏水材料。在一些實施例中,可包括在本揭示之醫藥組合物中之「另外的成分」係此項技術中已知的並且例如在以下中描述:Genaro編,(1985, Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa.),該文獻以引用之方式併入本文中。
在一些實施例中,本揭示之組合物可包含按組合物之總重量計約0.005%至2.0%之防腐劑。在一些實施例中,防腐劑用於在暴露於環境中的污染物之情況下防止腐敗。在一些實施例中,根據本揭示可用之防腐劑之實例包括但不限於選自苯甲醇、山梨酸、對羥基苯甲酸酯、咪脲以及其組合之防腐劑。在一些實施例中,特別較佳之防腐劑係約0.5%至2.0%苯甲醇及0.05%至0.5%山梨酸之組合。
在一些實施例中,可使用習知方法製備液體懸浮液以實現本揭示之靶向脂質顆粒在水性或油性媒劑中之懸浮液。在一些實施例中,水性媒劑包括例如水及等滲鹽水。在一些實施例中,油性媒劑包括例如杏仁油、油性酯、乙醇、植物油(諸如花生油、橄欖油、芝麻油或椰子油)、分餾植物油及礦物油(諸如液體石蠟)。在一些實施例中,液體懸浮液可進一步包含一種或多種另外的成分,包括但不限於懸浮劑、分散劑或潤濕劑、乳化劑、緩和劑、防腐劑、緩衝劑、鹽、調味劑、著色劑及甜味劑。在一些實施例中,油性懸浮液可進一步包含增稠劑。在一些實施例中,懸浮劑包括但不限於山梨糖醇糖漿、氫化可食用脂肪、海藻酸鈉、聚乙烯吡咯啶酮、黃蓍膠、阿拉伯膠及纖維素衍生物,諸如羧甲基纖維素鈉、甲基纖維素、羥丙基甲基纖維素。在一些實施例中,分散劑或潤濕劑包括但不限於:天然存在之磷脂,諸如卵磷脂;環氧烷與脂肪酸、與長鏈脂肪醇、與衍生自脂肪酸及己糖醇的偏酯、或與衍生自脂肪酸及己糖醇酐的偏酯的縮合產物(例如,分別為聚氧乙烯硬脂酸酯、十七乙烯氧十六烷醇、聚氧乙烯山梨糖醇單油酸酯及聚氧乙烯脫水山梨糖醇單油酸酯)。已知之乳化劑包括但不限於卵磷脂及阿拉伯樹膠。已知的防腐劑包括但不限於甲基、乙基或正丙基對羥基苯甲酸酯、抗壞血酸及山梨酸。已知的甜味劑包括例如甘油、丙二醇、山梨糖醇、蔗糖及糖精。油性懸浮液的已知增稠劑包括例如蜂蠟、硬石蠟及鯨蠟醇。
在一些實施例中,本揭示之靶向脂質顆粒之液體溶液水性或油性溶劑可以與液體懸浮液實質上相同之方式製備,主要差異係本揭示之靶向脂質顆粒溶解,而不是懸浮在溶劑中。如本文所用,「油性」液體係包含含碳液體分子並且表現出比水更小之極性特性之液體。在一些實施例中,本揭示之醫藥組合物之液體溶液可包含關於液體懸浮液描述之組分中的每一種,應當理解,懸浮劑將不一定有助於將本揭示之靶向脂質顆粒溶解在溶劑中。在一些實施例中,水性溶劑包括例如水及等滲鹽水。在一些實施例中,油性溶劑包括例如杏仁油、油性酯、乙醇、植物油(諸如花生油)、橄欖油、芝麻油或椰子油、分餾植物油及礦物油(諸如液體石蠟)。
在一些實施例中,可使用已知方法製備本揭示之藥物製劑之粉末及顆粒調配物。在一些實施例中,調配物可直接投與至個體,用於例如形成錠劑、填充膠囊或藉由向其添加水性或油性媒劑來製備水性或油性懸浮液或溶液。在一些實施例中,調配物可進一步包含分散劑或潤濕劑、懸浮劑及防腐劑中的一者或多者。此等調配物中亦可包括另外的賦形劑,諸如填充劑及甜味劑、調味劑或著色劑。
在一些實施例中,本揭示之醫藥組合物亦可以水包油乳液或油包水乳液之形式製備、包裝或銷售。在一些實施例中,油相可為植物油,諸如橄欖油或花生油、礦物油諸如液體石蠟或此等之組合。在一些實施例中,組合物進一步包含一種或多種乳化劑,諸如天然存在之樹膠(諸如阿拉伯膠或黃蓍膠)、天然存在之磷脂(諸如大豆或卵磷脂磷脂)、衍生自脂肪酸及六糖醇酐之組合之酯或偏酯(諸如脫水山梨糖醇單油酸酯),以及此類偏酯與亞乙基氧的縮合產物(諸如聚氧乙烯脫水山梨糖醇單油酸酯)。在一些實施例中,乳液亦可含有另外的成分,包括例如甜味劑或調味劑。
治療方法
本文提供了向個體投與包含CD8結合劑之慢病毒載體之方法。在一些實施例中,該方法包含a)自個體獲得全血;b)收集含有包括CD8+ T細胞之白細胞組分的血液部分;c)使包含CD8+ T細胞的白細胞組分與包含慢病毒載體的組合物接觸以產生轉染混合物;以及d)將包括CD8+ T細胞之所接觸之白細胞組分及/或轉染混合物再輸注至個體,從而向個體投與脂質顆粒及/或有效載荷基因。在一些實施例中,T細胞(例如CD8+ T細胞)在該方法期間未活化。在一些實施例中,該方法之步驟(c)進行不超過24小時,例如不超過20小時、16小時、12小時、8小時、6小時、5小時、4小時、3小時、2小時或1小時。
在一些實施例中,根據本揭示之方法能夠將慢病毒顆粒遞送至離體系統。該方法包括使用各種單采分析機器硬體組件、軟體控制模組及感測器模組之組合來在線量測檸檬酸或其他溶質水準以確保治療處方之最大準確性及安全性,以及使用旨在充分利用根據本方法設計之系統之置換液。應當理解,針對根據本發明之一個系統描述之組件亦可在根據本發明之其他系統內實施。
在一些實施例中,用於向個體投與慢病毒載體之方法包含使用血液處理集來獲得來自個體之全血、用於收集含有包括CD8+ T細胞之白細胞組分的血液部分之分離室、用於使CD8+ T細胞與包含慢病毒載體之組合物接觸之接觸容器及用於將CD8+ T細胞再輸注至患者之另一流體迴路。在一些實施例中,該方法進一步包含以下中的任一者:i)用於濃縮T細胞之洗滌組分,及ii)用於監測細胞密度及/或濃度之感測器及/或模組。在一些實施例中,此等方法允許直接從患者處理血液、用慢病毒載體轉導以及直接再輸注至患者,而無需對T細胞或CD8+ T細胞進行任何選擇步驟。此外,在一些實施例中,在任一個或多個步驟之前或之間沒有低溫保存或冷凍任何細胞之情況下進行此等方法,使得不存在用冷凍保護劑(例如DMSO)配製細胞之步驟。在一些實施例中,所提供的方法不包括淋巴清除方案。在一些實施例中,包括步驟(a)至(d)之方法進行不超過24小時之時間,諸如在2小時及12小時之間,例如3小時至6小時。
在一些實施例中,該方法在線(或原位)進行。在一些實施例中,該方法在閉合流體迴路或功能上閉合之流體迴路中進行。在一些實施例中,步驟(a)至(d)中的每一者在閉合流體迴路中在缐進行,其中該系統之所有部分諸如經由至少一個管缐可操作地連接。在一些實施例中,該系統係無菌的。在一些實施例中,該閉合流體迴路係無菌的。
本文亦提供了用於向個體投與包含CD8結合劑之慢病毒載體之系統。用於投與之例示性系統示出於
圖 14中。
在一些實施例中,本文提供之靶向脂質顆粒(例如,靶向病毒載體)或如本文所述之其醫藥組合物可投與至個體,例如哺乳動物,例如人類。在此類實施例中,個體可處於患有特定疾病或病狀之症狀之風險,或者可被診斷為或鑑定為患有該特定疾病或病狀。在一個實施例中,個體患有癌症。在一個實施例中,個體患有感染性疾病。在一些實施例中,靶向病毒載體含有編碼用於治療個體之疾病或病狀之外源藥劑之核酸序列。例如,外源藥劑係靶向或對贅生性細胞之蛋白質具有特異性的外源藥劑,並且向個體投與靶向脂質顆粒以治療個體之腫瘤或癌症。在另一個實例中,外源藥劑係炎性介體或免疫分子,諸如細胞介素,並且將靶向脂質顆粒投與至個體以治療期望調節(例如,增加)免疫反應(諸如,癌症或感染性疾病)之任何病狀。在一些實施例中,以有效量或劑量投與靶向病毒載體以實現疾病、病狀或病症之治療。本文提供了所提供的靶向病毒載體中的任一者在此類方法及治療中的用途,以及在製備藥物以便進行此類治療方法中的用途。在一些實施例中,藉由向患有、曾經患有或疑似患有該疾病或病狀或病症之個體投與靶向病毒載體或包含其之組合物來進行此等方法。在一些實施例中,此等方法借此治療個體之該疾病或病狀或病症。本文亦提供了組合物中的任一者諸如本文提供之醫藥組合物之用途,用於治療與外源藥劑靶向或由外源藥劑提供之特定基因或蛋白質相關之疾病、病病狀或病症。
在一些實施例中,所提供的方法或用途涉及投與醫藥組合物,該醫藥組合物包含口服、吸入、經皮或非經腸(包括靜脈內、腫瘤內、腹膜內、肌內、顱內及皮下)投與。在一些實施例中,靶向病毒載體可單獨投與或配製為醫藥組合物投與。在一些實施例中,本文所述之靶向病毒載體或組合物可投與至個體,例如哺乳動物,例如人類。在任何實施例中之一些實施例中,個體可處於患有特定疾病或病狀(例如,本文所述之疾病或病狀)之症狀之風險,或者可被診斷為或鑑定為患有該特定疾病或病狀。在一些實施例中,疾病係疾病或病症。在一些實施例中,疾病係B細胞惡性腫瘤。
在一些實施例中,靶向病毒載體可以單位劑量組合物(諸如單位劑量口服、非經腸、透皮或吸入組合物)之形式投與。在一些實施例中,組合物藉由摻加物製備並且適於口服、吸入、透皮或非經腸投與,並且因此可以呈錠劑、膠囊、口服液體製劑、粉末、顆粒、口含錠、可重構之粉末、可注射及可輸注之溶液或懸浮液或栓劑或氣溶膠之形式。
在一些實施例中,投與方案可能影響有效量之構成。在一些實施例中,治療性調配物可在疾病診斷之前或之後投與至個體。在一些實施例中,可每天或依次投與幾種分開之劑量以及交錯之劑量,或者可以連續輸注該劑量,或者可為彈丸式注射。在一些實施例中,治療性調配物之劑量可根據治療或預防情況之緊急情況按比例增加或減少。
在一些實施例中,可使用已知程序、劑量及有效預防或治療疾病之時間週期,將本揭示之組合物投與至個體,較佳哺乳動物,更較佳人類。在一些實施例中,實現治療效果所必需之本揭示之靶向脂質顆粒之有效量可根據以下因素而變化:諸如所採用之特定脂質顆粒之活性;投與時間;排泄速率;治療持續時間;其他藥物、化合物或材料與本揭示之靶向脂質顆粒組合使用;疾病或病症之狀態、所治療個體之年齡、性別、體重、病症、一般健康及先前病史,以及醫學領域中熟知類似因素。在一些實施例中,可調整劑量方案以提供最佳治療反應。在一些實施例中,可每天投與幾種分開之劑量,或者根據治療情況之經濟情況,劑量可按比例減少。一般熟習此項技術者將能夠研究相關因素並進行關於本揭示之治療性靶向脂質顆粒之有效量之確定,而無需過度實驗。
在一些實施例中,可改變本揭示之醫藥組合物中的靶向脂質顆粒之劑量水準,以便獲得有效實現特定個體、組合物及投與模式的期望治療反應的量,而對個體沒有毒性。
本領域具有普通技能的醫師,例如內科醫生或獸醫,可容易地確定及開出所需醫藥組合物之有效量。在一些實施例中,內科醫生或獸醫可開始在醫藥組合物中使用之本揭示之靶向脂質顆粒之劑量之水準可低於為了達到期望之治療效果所需之水準,然後逐漸增加劑量直至達到期望效果。
在一些實施例中,術語「容器」包括用於保持醫藥組合物之任何盛器。在一些實施例中,容器係含有醫藥組合物之包裝。在其他實施例中,容器不是含有醫藥組合物之包裝,亦即容器係盛器,諸如含有包裝之醫藥組合物或未包裝之醫藥組合物以及醫藥組合物之使用說明書之盒或小瓶。應當理解,醫藥組合物之使用說明可包含在含有醫藥組合物之包裝上,並且因此說明書與包裝產品形成了增强之功能性關係。在一些實施例中,說明書可包含與醫藥組合物執行其預期功能之能力有關之資訊,例如治療或預防個體之疾病,或將成像劑或診斷劑遞送至個體。
在一些實施例中,本文揭示之組合物中的任一者之投與途徑包括口服、鼻腔、直腸、非經腸、舌下、透皮、經黏膜(例如舌下、舌面、(經)頰、(經)尿道、陰道(例如,經引道及陰道周圍)、(內)鼻腔及(經)直腸)、膀胱內、肺內、十二指腸內、灌胃、鞘內、皮下、肌肉內、真皮內、動脉內、靜脉內、支氣管內、吸入及局部投與。
在一些實施例中,合適的組合物及劑型包括例如錠劑、膠囊、囊片、丸劑、軟膠囊、糖錠、分散體、懸浮液、溶液、糖漿、顆粒、珠粒、透皮貼劑、凝膠、粉末、丸粒、乳漿劑、口含锭、霜劑、糊劑、膏藥、洗劑、圓片、栓劑、用於經鼻或口服投與之液體噴霧、用於吸入之乾粉或氣溶膠調配物、用於膀胱內投與之組合物及調配物等。
在一些實施例中,包含外源藥劑或轉運劑之靶向脂質顆粒組合物可用於將此類外源藥劑或轉運劑遞送至細胞組織或個體。在一些實施例中,藉由投與本文所述之靶向脂質顆粒組合物來遞送轉運劑可修飾細胞蛋白表現水準。在某些實施例中,所投與之組合物引導提供在其中遞送多肽之細胞中實質上不存在或降低之功能活性之一種或多種轉運劑(例如,多肽或mRNA)之上調(經由在細胞中表現、在細胞中遞送或在細胞內誘導)。在一些實施例中,缺失功能活性可為酶促、結構或調控性質。在一些實施例中,所投與之組合物引導一種或多種多肽之上調,該上調增加了(例如協同地)在多肽被上調之細胞中存在但實質上缺乏之功能活性。在任何實施例中之一些實施例中,所投與之組合物引導抑制在其中遞送多肽、siRNA或miRNA之細胞中存在或上調之功能活性之一種或多種轉運劑(例如,多肽、siRNA或miRNA)的下調(經由在細胞中之表現、在細胞中的遞送或在細胞內之誘導)。在一些實施例中,上調功能活性可為酶促、結構或調控性質。在一些實施例中,所投與之組合物引導一種或多種多肽的下調,該下調減少了(例如協同地)在多肽被下調之細胞中存在或上調之功能活性。在一些實施例中,所投與之組合物引導某些功能性活性的上調及其他功能性活性的下調。
在一些實施例中,靶向脂質顆粒組合物(例如,包含線粒體或DNA之組合物)介導對目標細胞之影響,並且效果持續至少1天、2天、3天、4天、5天、6天或7天、2週、3週或4週或1個月、2個月、3個月、6個月或12個月。在一些實施例中(例如,其中靶向病毒載體組合物包含外源蛋白),該效果持續小於1天、2天、3天、4天、5天、6天或7天、2週、3週或4週或1個月、2個月、3個月、6個月或12個月。
在一些實施例中,將本文所述之靶向脂質顆粒組合物離體遞送至細胞或組織,例如人類細胞或組織。在實施例中,組合物改良離體細胞或組織之功能,例如改良細胞活力、呼吸或其他功能(例如,本文所述之另一個功能)。
在一些實施例中,將組合物遞送至處於受傷狀態(例如由於創傷、疾病、缺氧、缺血或其他損傷)之離體組織。
在一些實施例中,將組合物遞送至離體移植物(例如,用於移植之組織外植體或組織,例如人類靜脈、肌骨骼移植物諸如骨或肌腱、角膜、皮膚、心臟瓣膜、神經;或者分離或培養之器官,例如待移植到人類中之器官,例如人類心臟、肝、肺、腎、胰腺、腸、胸腺、眼睛)。在一些實施例中,在移植之前、期間及/或之後,將組合物遞送至組織或器官。
在一些實施例中,將組合物遞送、投與或與細胞(例如細胞製劑)接觸。在一些實施例中,細胞製劑可為細胞療法製劑(旨在用於向人類個體投與之細胞製劑)。在實施例中,細胞製劑包含表現T細胞受體(TCR)或嵌合抗原受體(CAR) (例如表現重組CAR)之細胞。表現CAR之細胞可為例如T細胞、自然殺手(NK)細胞、細胞毒性T淋巴細胞(CTL)、調控T細胞。在實施例中,細胞製劑係神經幹細胞製劑。在實施例中,細胞製劑係間質幹細胞(MSC)製劑。在實施例中,細胞製劑係造血幹細胞(HSC)製劑。在實施例中,細胞製劑係胰島細胞製劑。
在一些實施例中,包含本文所述之抗CD8 sdAb或scFv組合物之病毒載體用於遞送CAR或TCR。在一些實施例中,病毒載體轉導表現CD8之細胞(例如,CD8+ T細胞)並且表現及擴增CAR或TCR。然後擴增之CAR或TCR T細胞介導靶向細胞殺傷。因此,本揭示包括使用包含抗CD8 scFv融合劑構築體之病毒載體來引發對CAR或TCR之抗原結合部分具有特異性的免疫反應。在一些實施例中,CAR用於靶向選自CD19、CD20、CD22或BCMA之腫瘤抗原。在另一個實施例中,CAR經工程改造以包含T細胞抗原受體複合體ζ鏈(例如,CD3ζ)之細胞內信號傳導域。在較佳實施例中,細胞內域選自CD137 (4-1BB)信號傳導域、CD28信號傳導域及CD3ζ信號傳導域。
工程改造之受體有效載荷
在一些實施例中,本文揭示之靶向脂質顆粒(例如,靶向病毒載體)編碼經工程改造之受體。在一些實施例中,用於所提供的方法或與所提供的方法結合投與之細胞含有或經工程改造為含有經工程改造之受體,例如經工程改造之抗原受體,諸如嵌合抗原受體(CAR)。亦提供了此類細胞之群體、含有此類細胞及/或富集此類細胞之組合物,諸如其中富集或選擇某種類型之細胞,諸如T細胞或CD8+細胞。此等組合物係醫藥組合物及用於投與之調配物,諸如用於過繼細胞療法。亦提供了根據所提供的方法及/或所提供的製品或組合物將細胞及組合物投與至個體(例如患者)之治療方法。
在一些實施例中,在不首先刺激細胞之情況下完成基因轉移,諸如藉由將其與誘導反應(諸如增殖、存活及/或活化)之刺激組合,例如藉由細胞介素或活化標記物之表現量測,然後引入核酸,例如藉由轉導至刺激細胞中,並且視情况在培養物中培育或擴增至足以用於臨床應用之數目。
病毒載體可表現重組受體,諸如包括嵌合抗原受體(CAR)之抗原受體及其他抗原結合受體,諸如轉基因T細胞受體(TCR)。在此等受體中亦有其他嵌合受體。
a.
嵌合抗原受體 (CAR)
在所提供的方法及用途之一些實施例中,嵌合受體(諸如CAR)包含一個或多個域,該一個或多個域將為期望抗原(例如腫瘤抗原)提供特異性之抗原或配體結合域(例如抗體或抗體片段)與細胞內信號傳導域組合。在一些實施例中,細胞內信號傳導域係刺激或活化細胞內域部分,諸如T細胞刺激或活化域,提供初級活化信號或初級信號。在一些實施例中,細胞內信號傳導域包含或另外包含共刺激信號傳導域以便於效應子功能。在一些實施例中,當經基因工程改造成免疫細胞時,嵌合受體可調節T細胞活性,並且在一些情況下,可調節T細胞分化或穩態,從而導致在活體內具有改良之壽命、存活及/或持久性之基因工程改造細胞,諸如用於過繼細胞療法方法。
包括CAR之例示性抗原受體以及用於將此類受體工程改造及引入到細胞中的方法包括例如以下中所述:W0200014257,WO2013126726,WO2012/129514,WO2014031687,WO2013/166321,WO2013/071154,W02013/123061,美國專利申請公開案第US2002131960號、第US2013287748號、第US20130149337號、美國專利號6,451,995、7,446,190、8,252,592、8,339,645、8,398,282、7,446,179、6,410,319、7,070,995、7,265,209、7,354,762、7,446,191、8,324,353及8,479,118,以及歐洲專利申請第EP2537416號;以及/或者以下中所述:Sadelain等人,Cancer Discov.,2013年4月,3(4): 388-398;Davila等人,(2013) PLoS ONE 8(4): e61338;Turtle等人,Curr. Opin. Immunol.,2012年10月,24(5): 633-39;Wu等人,Cancer,2012年3月,18(2): 160-75。在一些態樣中,抗原受體包括如美國專利號7,446,190以及WO/2014055668中所述之CAR。CAR之實例包括如前述揭示中之任一者所揭示之CAR,諸如WO2014031687,US 8,339,645,US 7,446,179,US 2013/0149337,US 7,446,190,US 8,389,282;Kochenderfer等人,(2013) Nature Reviews Clinical Oncology, 10, 267-276;Wang等人,(2012) J. Immunother,35(9): 689-701;以及Brentjens等人,Sci Transl Med.,2013 5(177)。亦參見WO2014031687、US 8,339,645、US 7,446,179、US 2013/0149337、US 7,446,190及US 8,389,282。重組受體(諸如CAR)通常包括細胞外抗原結合域,諸如抗體分子之一部分,通常係抗體之可變重(VH)鏈區及/或可變輕(VL)鏈區,例如scFv抗體片段。在一些實施例中,CAR分子之抗原結合域包含抗體、抗體片段、scFv、Fv、Fab、(Fab')2、單域抗體(SdAb)、VH或VL域或者駱駝科VHH域。
在一些實施例中,受體靶向之抗原係多肽。在一些實施例中,其係碳水化合物或其他分子。在一些實施例中,與正常或非靶向細胞或組織相比,抗原在疾病或病狀之細胞(例如腫瘤或致病性細胞)上選擇性表現或過表現。在其他實施例中,抗原在正常細胞上表現及/或在工程改造細胞上表現。
在一些實施例中,受體靶向之抗原包括與B細胞惡性腫瘤相關之抗原,諸如許多已知B細胞標記物中的任一者。在一些實施例中,受體靶向之抗原係CD20、CD19、CD22、ROR1、CD45、CD47、CD21、CD5、CD33、Igκ、Igλ、CD79a、CD79b或CD30。
在一些實施例中,嵌合抗原受體包括含有抗體或抗體片段之細胞外部分。在一些態樣中,嵌合抗原受體包括含有抗體或片段之細胞外部分及細胞內信號傳導域。在一些實施例中,抗體或片段包括scFv。
在一些實施例中,由抗原結合域靶向之抗原係CD19。在一些態樣中,重組受體(例如CAR)之抗原結合域,及抗原結合域結合,例如特異性結合或特異性識別CD19,諸如人類CD19。在一些實施例中,scFv含有衍生自對CD19具有特異性之抗體或抗體片段之VH及VL。在一些實施例中,結合CD19之抗體或抗體片段係小鼠衍生抗體,諸如FMC63及SJ25C1。在一些實施例中,抗體或抗體片段係人類抗體,例如,如美國專利公開案第US 2016/0152723號中所述。
在一些實施例中,抗原係CD19。在一些實施例中,scFv含有衍生自對CD19具有特異性之抗體或抗體片段之VH及VL。在一些實施例中,結合CD19之抗體或抗體片段係小鼠衍生抗體,諸如FMC63及SJ25C1。在一些實施例中,抗體或抗體片段係人類抗體,例如,如美國專利公開案第US 2016/0152723號中所述。
在一些實施例中,scFv衍生自FMC63。FMC63通常係指針對表現人類源CD19之Nalm-1及-16細胞產生之小鼠單株IgG1抗體(Fing, N. R.等人,(1987). Leucocyte typing III. 302)。
在一些實施例中,由抗原結合域靶向之抗原係BCMA。在一些態樣中,重組受體(例如CAR)之抗原結合域,及抗原結合域結合,例如特異性結合或特異性識別BCMA,諸如人類BCMA。在一些實施例中,抗原結合域係US2020/0138865 (本文以引用方式整體揭示)中揭示之完全人類VH sdAb,例如FHVH74、FHVH32、FHVH33或FHVH93。
在一些實施例中,CD19特異性CAR包括抗CD19單鏈抗體片段(scFv)、跨膜域,諸如衍生自人類CD8α、4-1BB(CD137)共刺激信號傳導域及CD3ζ信號傳導域之跨膜域。在一些實施例中,CD22特異性CAR包括抗CD22 scFv、跨膜域,諸如衍生自人類CD8α、4-1BB(CD137)共刺激信號傳導域及CD3ζ信號傳導域之跨膜域。在一些實施例中,CD19/CD22雙特異性CAR包括抗CD19 scFv、抗CD22 scFv、跨膜域,諸如衍生自人類CD8α、4-1BB(CD137)共刺激信號傳導域及CD3ζ信號傳導域之跨膜域。
在一些實施例中,CAR包括由T細胞攜帶之商業CAR構築體。基於商業CAR-T細胞之療法之非限制性實例包括brexucabtagene autoleucel (TECARTUS
®)、axicabtagene ciloleucel (YESCARTA
®)、idecabtagene vicleucel (ABECMA
®)、lisocabtagene maraleucel (BREYANZI
®)、tisagenlecleucel (KYMRIAH
®)、來自Cartesian Therapeutics的Descartes-08及Descartes-11、來自Novartis的CTL110、來自Poseida Therapeutics的P-BMCA-101、來自Autolus Limited的AUTO4、來自Cellectis的UCARTCS、來自Precision Biosciences的PBCAR19B及PBCAR269A、來自Fate Therapeutics的FT819以及來自Clyad Oncology的CYAD-211。
在一些實施例中,嵌合抗原受體(CAR)包含抗原結合域。在一些實施例中,CAR係或包含第一代CAR,該第一代CAR包含抗原結合域、跨膜域及至少一個信號傳導域(例如一個、兩個或三個信號傳導域)。在一些實施例中,CAR包含第二代CAR,該第二代CAR包含抗原結合域、跨膜域及至少兩個信號傳導域。在一些實施例中,CAR包含第三代CAR,該第三代CAR包含抗原結合域、跨膜域及至少三個信號傳導域。在一些實施例中,第四代CAR包含抗原結合域、跨膜域、三個或四個信號傳導域,以及CAR成功信號傳導後誘導細胞介素基因表現之域。在一些實施例中,抗原結合域係或包含抗體、抗體片段、scFv或Fab。
1. 抗原結合域 (ABD) 靶向贅生性或癌細胞的抗原特徵
在一些實施例中,抗原結合域(ABD)靶向贅生性細胞之抗原特徵。換言之,抗原結合域靶向由贅生性或癌細胞表現之抗原。在一些實施例中,ABD結合腫瘤相關抗原。在一些實施例中,贅生性細胞(例如,與贅生性或癌細胞相關之抗原)或腫瘤相關抗原之抗原特徵選自:細胞表面受體、離子通道連接受體、酶聯受體、G蛋白偶聯受體、受體酪胺酸激酶、酪胺酸激酶相關受體、受體樣酪胺酸磷酸酶、受體絲胺酸/蘇胺酸激酶、受體鳥苷酸環化酶、組胺酸激酶相關受體、表皮生長因子受體(EGFR) (包括ErbB1/EGFR、ErbB2/HER2、ErbB3/HER3及ErbB4/HER4)、纖維母細胞生長因子受體(FGFR) (包括FGF1、FGF2、FGF3、FGF4、FGF5、FGF6、FGF7、FGF18及FGF21)、血管內皮生長因子受體(VEGFR) (包括VEGF-A、VEGF-B、VEGF-C、VEGF-D及PIGF)、RET受體及Eph受體家族(包括EphA1、EphA2、EphA3、EphA4、EphA5、EphA6、EphA7、EphA8、EphA9、EphA10、EphB1、EphB2、EphB3、EphB4及EphB6)、CXCR1、CXCR2、CXCR3、CXCR4、CXCR6、CCR1、CCR2、CCR3、CCR4、CCR5、CCR6、CCR8、CFTR、CIC-1、CIC-2、CIC-4、CIC-5、CIC-7、CIC-Ka、CIC-Kb、Bestrophins、TMEM16A、GABA受體、甘胺酸受體、ABC轉運蛋白、NAV1.1、NAV1.2、NAV1.3、NAV1.4、NAV1.5、NAV1.6、NAV1.7、NAV1.8、NAV1.9、神經鞘胺醇-1-磷酸受體(S1P1R)、NMDA通道、跨膜蛋白、多跨跨膜蛋白、T細胞受體模體、T細胞α鏈、T細胞β鏈、T細胞γ鏈、T細胞δ鏈、CCR7、CD3、CD4、CD5、CD7、CD8、CD11b、CD11c、CD16、CD19、CD20、CD21、CD22、CD25、CD28、CD34、CD35、CD40、CD45RA、CD45RO、CD52、CD56、CD62L、CD68、CD80、CD95、CD117、CD127、CD133、CD137(4-1BB)、CD163、F4/80、IL-4Ra、Sca-1、CTLA-4、GITR、GARP、LAP、顆粒酶B、LFA-1、轉鐵蛋白受體、NKp46、穿孔素、CD4+、Th1、Th2、Th17、Th40、Th22、Th9、Tfh、典型Treg、FoxP3+、Tr1、Th3、Treg17、T
REG;CDCP、NT5E、EpCAM、CEA、gpA33、黏蛋白、TAG-72、碳酸酐酶IX、PSMA、葉酸結合蛋白、神經節苷脂(例如、CD2、CD3、GM2)、Lewis-γ
2、VEGF、VEGFR 1/2/3、αVβ3、α5β1、ErbB1/EGFR、ErbB1/HER2、ErB3、c-MET、IGF1R、EphA3、TRAIL-R1、TRAIL-R2、RANKL、FAP、腱生蛋白、PDL-1、BAFF、HDAC、ABL、FLT3、KIT、MET、RET、IL-1β、ALK、RANKL、mTOR、CTLA-4、IL-6、IL-6R、JAK3、BRAF、PTCH、平滑受體(Smoothened)、PIGF、ANPEP、TIMP1、PLAUR、PTPRJ、LTBR、ANTXR1、葉酸受體a(FRa)、ERBB2(Her2/neu)、EphA2、IL-13Ra2、表皮生長因子受體(EGFR)、間皮素、TSHR、CD19、CD123、CD22、CD30、CD171、CS-1、CLL-1、CD33、EGFRvIII、GD2、GD3、BCMA、MUC16(CA125)、L1CAM、LeY、MSLN、IL13Rα1、L1-CAM、Tn Ag、前列腺特異性膜抗原(PSMA)、ROR1、FLT3、FAP、TAG72、CD38、CD44v6、CEA、EPCAM、B7H3、KIT、白介素-11受體a(IL-11Ra)、PSCA、PRSS21、VEGFR2、LewisY、CD24、血小板衍生生長因子受體-β (PDGFR-β)、SSEA-4、CD20、MUC1、NCAM、Prostase、PAP、ELF2M、肝配蛋白B2、IGF-1受體、CAIX、LMP2、gpl00、bcr-abl、酪胺酸酶、岩藻糖GM1、sLe、GM3、TGS5、HMWMAA、鄰乙醯-GD2、葉酸受體β、TEM1/CD248、TEM7R、CLDN6、GPRC5D、CXORF61、CD97、CD179a、ALK、聚唾液酸、PLACl、GloboH、NY-BR-1、UPK2、HAVCR1、ADRB3、PANX3、GPR20、LY6K、OR51E2、TARP、WT1、NY-ESO-1、LAGE-la、MAGE-A1、天冬醯胺內肽酶、HPV E6、E7、ETV6-AML、精子蛋白17、XAGE1、Tie 2、MAD-CT-1、MAD-CT-2、主要組織相容性複合體I類相關基因蛋白(MR1)、尿激酶型纖溶酶原活化劑受體(uPAR)、Fos相關抗原1、p53、p53突變體、prostein、生存素、端粒酶、PCTA-1/半乳凝素8、MelanA/MART1、Ras突變體、hTERT、肉瘤易位斷點、ML-IAP、ERG (TMPRSS2 ETS融合基因)、NA17、PAX3、雄激素受體、細胞週期蛋白B1、MYCN、RhoC、TRP-2、CYPIB I、BORIS、SART3、PAX5、OY-TES1、LCK、AKAP-4、SSX2、RAGE-1、人類端粒酶逆轉錄酶、RU1、RU2、腸羧基酯酶、mut hsp70-2、CD79a、CD79b、CD72、LAIR1、FCAR、LILRA2、CD300LF、CLEC12A、BST2、EMR2、LY75、GPC3、FCRL5、IGLL1、新抗元、CD133、CD15、CD184、CD24、CD56、CD26、CD29、CD44、HLA-A、HLA-B、HLA-C(HLA-A,B,C)、CD49f、CD151、CD340、CD200、tkrA、trkB或trkC或者其抗原片段或抗原部分。
2. ABD 靶向 T 細胞的抗原特徵
在一些實施例中,抗原結合域靶向T細胞之抗原特徵。在一些實施例中,ABD結合與T細胞相關之抗原。在一些情況下,此抗原由T細胞表現或位於T細胞之表面上。在一些實施例中,T細胞或T細胞相關抗原之抗原特徵選自細胞表面受體、膜轉運蛋白(例如,主動或被動轉運蛋白,諸如離子通道蛋白、成孔蛋白等)、跨膜受體、膜酶及/或T細胞之細胞黏附蛋白特性。在一些實施例中,T細胞之抗原特徵可以係G蛋白偶聯受體、受體酪胺酸激酶、酪胺酸激酶相關受體、受體樣酪胺酸磷酸酶、受體絲胺酸/蘇胺酸激酶、受體鳥苷酸環化酶、組胺酸激酶相關受體、AKT1;AKT2;AKT3;ATF2;BCL10;CALM1;CD3D (CD3δ);CD3E (CD3ε);CD3G(CD3γ);CD4;CD8;CD28;CD45;CD80 (B7-1);CD86 (B7-2);CD247 (CD3ζ);CTLA-4 (CD152);ELK1;ERK1 (MAPK3);ERK2;FOS;FYN;GRAP2(GADS);GRB2;HLA-DRA;HLA-DRB1;HLA-DRB3;HLA-DRB4;HLA-DRB5;HRAS;IKBKA (CHUK);IKBKB;IKBKE;IKBKG (NEMO);IL2;ITPR1;ITK;JUN;KRAS2;LAT;LCK;MAP2K1 (MEK1);MAP2K2 (MEK2);MAP2K3 (MKK3);MAP2K4 (MKK4);MAP2K6 (MKK6);MAP2K7 (MKK7);MAP3K1 (MEKK1);MAP3K3;MAP3K4;MAP3K5;MAP3K8;MAP3K14 (NIK);MAPK8 (JNK1);MAPK9 (JNK2);MAPK10 (JNK3);MAPK11 (p38β);MAPK12 (p38γ);MAPK13 (p38δ);MAPK14 (p38α);NCK;NFAT1;NFAT2;NFKB1;NFKB2;NFKBIA;NRAS;PAK1;PAK2;PAK3;PAK4;PIK3C2B;PIK3C3 (VPS34);PIK3CA;PIK3CB;PIK3CD;PIK3R1;PKCA;PKCB;PKCM;PKCQ;PLCY1;PRF1 (穿孔素);PTEN;RAC1;RAF1;RELA;SDF1;SHP2;SLP76;SOS;SRC;TBK1;TCRA;TEC;TRAF6;VAV1;VAV2;或ZAP70。
3. ABD 靶向自身免疫性或炎性 病症 的 抗原特徵
在一些實施例中,抗原結合域靶向自身免疫性或炎性病症的抗原特徵。在一些實施例中,ABD結合與自身免疫性或炎性病症相關之抗原。在一些情況下,抗原由與自身免疫性或炎性病症相關之細胞表現。在一些實施例中,自身免疫性或炎性病症選自慢性移植物抗宿主病(GVHD)、狼瘡、關節炎、免疫複合體腎小球性腎炎、肺出血腎炎綜合症、葡萄膜炎、肝炎、系統性硬化症或硬皮病、I型糖尿病、多發性硬化症、冷凝集素病、尋常型天疱瘡、格雷夫氏病(Grave's disease)、自身免疫性溶血性貧血、甲型血友病、原發性乾燥綜合症、血栓性血小板減少性紫癜、視神經脊髓炎、埃文氏綜合症、IgM介導之神經病症、冷沈球蛋白血症、皮肌炎、特發性血小板減少症、強直性脊柱炎、大皰性類天疱瘡、獲得性血管炎、慢性蕁麻疹、抗磷脂脫髓鞘性多發性神經病及自身免疫性血小板減少症或中性粒細胞減少症或純紅細胞再生障礙,而同種免疫疾病之例示性非限制性實例包括來自造血或實體器官移植、輸血、胎兒同種異體致敏妊娠、新生兒同種免疫性血小板減少症、新生兒溶血性疾病、對外來抗原致敏之同種異體致敏(參見,例如,Blazar等人,2015,Am. J. Transplant,15(4):931-41)或異種致敏,諸如可在用酶或蛋白質替代療法、血液製品及基因療法的遺傳性或獲得性缺陷病之替代中發生。在一些實施例中,自身免疫性或炎性病症之抗原特徵選自細胞表面受體、離子通道連接受體、酶連接受體、G蛋白偶聯受體、受體酪胺酸激酶、酪胺酸激酶相關受體、受體樣酪胺酸磷酸酶、受體絲胺酸/蘇胺酸激酶、受體鳥苷酸環化酶或組胺酸激酶相關受體。
在一些實施例中,CAR之抗原結合域與在B細胞、漿細胞或漿母細胞上表現之配體結合。在一些實施例中,CAR之抗原結合域與CD10、CD19、CD20、CD22、CD24、CD27、CD38、CD45R、CD138、CD319、BAFFR、BCMA、CD28、TNF、干擾素受體、GM-CSF、ZAP-70、LFA-1、CD3γ、CD5或CD2結合。參見例如,US 2003/0077249、WO 2017/058753、WO 2017/058850,此等專利之內容係以引用之方式併入本文中。
4. ABD 靶向衰老細胞的抗原特徵
在一些實施例中,抗原結合域靶向衰老細胞之抗原特徵,例如尿激酶型纖溶酶原活化劑受體(uPAR)。在一些實施例中,ABD結合與衰老細胞相關之抗原。在一些情況下,抗原由衰老細胞表現。在一些實施例中,CAR可用於治療或預防由衰老細胞的異常積累表徵之病症,例如肝及肺纖維化、動脈粥樣硬化、糖尿病及骨關節炎。
5. ABD 靶向感染性疾病 之 抗原特徵
在一些實施例中,抗原結合域靶向感染性疾病之抗原特徵。在一些實施例中,ABD結合與感染性疾病相關之抗原。在一些情況下,抗原由受感染性疾病影響之細胞表現。在一些實施例中,其中感染性疾病選自HIV、乙型肝炎病毒、丙型肝炎病毒、人類疱疹病毒、人類疱疹病毒8 (HHV-8、卡波西肉瘤相關疱疹病毒(Kaposi sarcoma-associated herpes virus,KSHV))、人類T淋巴細胞病毒-1 (HTLV-1)、默克爾細胞多瘤病毒(Merkel cell polyomavirus,MCV)、猿猴病毒40 (SV40)、愛潑斯坦-巴爾病毒(Epstein-Barr virus)、CMV、人類乳頭瘤病毒。在一些實施例中,感染性疾病之抗原特徵選自細胞表面受體、離子通道連接受體、酶連接受體、G蛋白偶聯受體、受體酪胺酸激酶、酪胺酸激酶相關受體、受體樣酪胺酸磷酸酶、受體絲胺酸/蘇胺酸激酶、受體鳥苷酸環化酶、組胺酸激酶相關受體、HIV Env、gpl20或CD4誘導之HIV-1 Env抗原决定基。
6. ABD 與細胞的細胞表面抗原結合
在一些實施例中,抗原結合域與細胞之細胞表面抗原結合。在一些實施例中,細胞表面抗原係特定或具體細胞類型之特徵(例如,由其表現)。在一些實施例中,細胞表面抗原係超過一種類型之細胞之特徵。
在一些實施例中,CAR抗原結合域結合T細胞之細胞表面抗原特徵,諸如T細胞上之細胞表面抗原。在一些實施例中,T細胞之抗原特徵可以係細胞表面受體、膜轉運蛋白(例如,主動或被動轉運蛋白,諸如離子通道蛋白、成孔蛋白等)、跨膜受體、膜酶及/或T細胞之細胞黏附蛋白特性。在一些實施例中,T細胞之抗原特徵可以係G蛋白偶聯受體、受體酪胺酸激酶、酪胺酸激酶相關受體、受體樣酪胺酸磷酸酶、受體絲胺酸/蘇胺酸激酶、受體鳥苷酸環化酶或組胺酸激酶相關受體。
在一些實施例中,CAR之抗原結合域結合T細胞受體。在一些實施例中,T細胞受體可以係AKT1;AKT2;AKT3;ATF2;BCL10;CALM1;CD3D (CD3δ);CD3E (CD3ε);CD3G (CD3γ);CD4;CD8;CD28;CD45;CD80 (B7-1);CD86 (B7-2);CD247 (CD3ζ);CTLA-4 (CD152);ELK1;ERK1 (MAPK3);ERK2;FOS;FYN;GRAP2 (GADS);GRB2;HLA-DRA;HLA-DRB1;HLA-DRB3;HLA-DRB4;HLA-DRB5;HRAS;IKBKA (CHUK);IKBKB;IKBKE;IKBKG (NEMO);IL2;ITPR1;ITK;JUN;KRAS2;LAT;LCK;MAP2K1 (MEK1);MAP2K2 (MEK2);MAP2K3 (MKK3);MAP2K4(MKK4);MAP2K6 (MKK6);MAP2K7 (MKK7);MAP3K1 (MEKK1);MAP3K3;MAP3K4;MAP3K5;MAP3K8;MAP3K14 (NIK);MAPK8 (JNK1);MAPK9 (JNK2);MAPK10 (JNK3);MAPK11 (p38β);MAPK12 (p38γ);MAPK13 (p38δ);MAPK14 (p38α);NCK;NFAT1;NFAT2;NFKB1;NFKB2;NFKBIA;NRAS;PAK1;PAK2;PAK3;PAK4;PIK3C2B;PIK3C3 (VPS34);PIK3CA;PIK3CB;PIK3CD;PIK3R1;PKCA;PKCB;PKCM;PKCQ;PLCY1;PRF1 (穿孔素);PTEN;RAC1;RAF1;RELA;SDF1;SHP2;SLP76;SOS;SRC;TBK1;TCRA;TEC;TRAF6;VAV1;VAV2;或ZAP70。
7. 跨膜域
在一些實施例中,CAR跨膜域至少包含T細胞受體、CD28、CD3ε、CD45、CD4、CD5、CD8、CD9、CD16、CD22、CD33、CD37、CD64、CD80、CD86、CD134、CD137、CD154或其功能性變體之α、β或ζ鏈之跨膜區。在一些實施例中,跨膜域至少包含CD8α、CD8β、4-1BB/CD137、CD28、CD34、CD4、FcεRIγ、CD16、OX40/CD134、CD3ζ、CD3ε、CD3γ、CD3δ、TCRα、TCRβ、TCRζ、CD32、CD64、CD64、CD45、CD5、CD9、CD22、CD37、CD80、CD86、CD40、CD40L/CD154、VEGFR2、FAS及FGFR2B或其功能性變體之跨膜區。抗原結合域結合
8. 信號傳導域或複數個信號傳導域
在一些實施例中,本文所述之CAR包含選自以下中的一者或多者之一個或至少一個信號傳導域:B7-1/CD80;B7-2/CD86;B7-H1/PD-L1;B7-H2;B7-H3;B7-H4;B7-H6;B7-H7;BTLA/CD272;CD28;CTLA-4;Gi24/VISTA/B7-H5;ICOS/CD278;PD-1;PD-L2/B7-DC;PDCD6;4-1BB/TNFSF9/CD137;4-1BB配體/TNFSF9;BAFF/BLyS/TNFSF13B;BAFF R/TNFRSF13C;CD27/TNFRSF7;CD27配體/TNFSF7;CD30/TNFRSF8;CD30配體/TNFSF8;CD40/TNFRSF5;CD40/TNFSF5;CD40配體/TNFSF5;DR3/TNFRSF25;GITR/TNFRSF18;GITR配體/TNFSF18;HVEM/TNFRSF14;LIGHT/TNFSF14;淋巴毒素-α/TNF-β;OX40/TNFRSF4;OX40配體/TNFSF4;RELT/TNFRSF19L;TACI/TNFRSF13B;TL1A/TNFSF15;TNF-α;TNF RII/TNFRSF1B;2B4/CD244/SLAMF4;BLAME/SLAMF8;CD2;CD2F-10/SLAMF9;CD48/SLAMF2;CD58/LFA-3;CD84/SLAMF5;CD229/SLAMF3;CRACC/SLAMF7;NTB-A/SLAMF6;SLAM/CD150;CD2;CD7;CD53;CD82/Kai-1;CD90/Thy1;CD96;CD160;CD200;CD300a/LMIR1;I類HLA;HLA-DR;Ikaros;整合素α 4/CD49d;整合素α 4 β 1;整合素α 4 β 7/LPAM-1;LAG-3;TCL1A;TCL1B;CRTAM;DAP12;Dectin-1/CLEC7A;DPPIV/CD26;EphB6;TIM-1/KIM-1/HAVCR;TIM-4;TSLP;TSLP R;淋巴細胞功能相關抗原-1(LFA-1);NKG2C、CD3ζ域、基於免疫受體酪胺酸之活化模體(ITAM)、CD27、CD28、4-1BB、CD134/OX40、CD30、CD40、PD-1、ICOS、淋巴細胞功能相關抗原-1 (LFA-1)、CD2、CD7、LIGHT、NKG2C、B7-H3、與CD83特異性結合之配體或其功能性片段。
在一些實施例中,該至少一個信號傳導域包含CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體。在其他實施例中,該至少一個信號傳導域包含(i) CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體;及(ii) CD28域或4-1BB域或其功能性變體。在另外實施例中,該至少一個信號傳導域包含(i) CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體;(ii) CD28域或其功能性變體;及(iii) 4-1BB域或CD134域或其功能性變體。在一些實施例中,該至少一個信號傳導域包含(i) CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體;(ii) CD28域或其功能性變體;(iii) 4-1BB域或CD134域或其功能性變體;及(iv)細胞介素或共刺激配體轉基因。
在一些實施例中,該至少兩個信號傳導域包含CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體。在其他實施例中,該至少兩個信號傳導域包含(i) CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體;及(ii) CD28域或4-1BB域或其功能性變體。在另外實施例中,該至少一個信號傳導域包含(i) CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體;(ii) CD28域或其功能性變體;及(iii) 4-1BB域或CD134域或其功能性變體。在一些實施例中,該至少兩個信號傳導域包含(i) CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體;(ii) CD28域或其功能性變體;(iii) 4-1BB域或CD134域或其功能性變體;及(iv)細胞介素或共刺激配體轉基因。
在一些實施例中,該至少三個信號傳導域包含CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體。在其他實施例中,該至少三個信號傳導域包含(i) CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體;及(ii) CD28域或4-1BB域或其功能性變體。在另外實施例中,該至少三個信號傳導域包含(i) CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體;(ii) CD28域或其功能性變體;及(iii) 4-1BB域或CD134域或其功能性變體。在一些實施例中,該至少三個信號傳導域包含(i) CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體;(ii) CD28域或其功能性變體;(iii) 4-1BB域或CD134域或其功能性變體;及(iv)細胞介素或共刺激配體轉基因。
在一些實施例中,CAR包含CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體。在一些實施例中,CAR包含(i) CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體;及(ii) CD28域或4-1BB域或其功能性變體。
在一些實施例中,CAR包含(i) CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體;(ii) CD28域或其功能性變體;及(iii) 4-1BB域或CD134域或其功能性變體。
在一些實施例中,CAR包含(i) CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體;(ii) CD28域或4-1BB域或其功能性變體,及/或(iii) 4-1BB域或CD134域或者其功能性變體。
在一些實施例中,CAR包含(i) CD3ζ域或基於免疫受體酪胺酸之活化模體(ITAM)或其功能性變體;(ii) CD28域或其功能性變體;(iii) 4-1BB域或CD134域或其功能性變體;及(iv)細胞介素或共刺激配體轉基因。
9. 在 CAR 成功信號傳導後誘導細胞 介素 基因 表現 的域
在一些實施例中,第一代、第二代、第三代或第四代CAR進一步包含在CAR成功信號傳導後誘導細胞介素基因表現之域。在一些實施例中,細胞介素基因對於包含CAR之目標細胞為內源性或外源性之,該CAR包含在CAR成功信號傳導後誘導細胞介素基因表現之域。在一些實施例中,細胞介素基因對促炎性細胞介素進行編碼。在一些實施例中,細胞介素基因對IL-1、IL-2、IL-9、IL-12、IL-18、TNF或IFN-γ或其功能片段進行編碼。在一些實施例中,在CAR成功信號傳導後之誘導細胞介素基因表現之域係或包含轉錄因子或其功能域或片段。在一些實施例中,在CAR成功信號傳導後之誘導細胞介素基因表現之域係或包含轉錄因子或其功能域或片段。在一些實施例中,轉錄因子或其功能域或片段係或包含活化之T細胞(NFAT)、NF-kB或其功能域或片段之核因子。參見例如,Zhang. C.等人,Engineering CAR-T cells. Biomarker Research. 5:22 (2017);WO 2016126608;Sha, H.等人,Chimaeric antigen receptor T-cell therapy for tumour immunotherapy,Bioscience Reports,2017年1月27日,37(1)。
在一些實施例中,CAR進一步包含一個或多個間隔子,例如,其中間隔子係抗原結合域及跨膜域之間的第一間隔子。在一些實施例中,第一間隔子包括免疫球蛋白恆定區或其變體或修飾形式的至少一部分。在一些實施例中,間隔子係跨膜域及信號傳導域之間的第二間隔子。在一些實施例中,第二間隔子係寡肽,例如,其中寡肽包含甘胺酸及絲胺酸殘基,諸如但不限於甘胺酸-絲胺酸雙聯體。在一些實施例中,CAR包含兩個或更多個間隔子,例如,抗原結合域及跨膜域之間的間隔子以及跨膜域及信號轉到域之間的間隔子。
在一些實施例中,本文所述之細胞中的任一者包含編碼CAR或第一代CAR之核酸。在一些實施例中,第一代CAR包含抗原結合域、跨膜域及信號傳導域。在一些實施例中,信號傳導域在T細胞活化期間介導下游信號傳導。
在一些實施例中,本文揭示之方法及組合物包含編碼CAR或第二代CAR之核酸。在一些實施例中,第二代CAR包含抗原結合域、跨膜域及兩個信號傳導域。在一些實施例中,信號傳導域在T細胞活化期間介導下游信號傳導。在一些實施例中,信號傳導域係共刺激域。在一些實施例中,共刺激域在T細胞活化期間增強細胞介素產生、CAR-T細胞增殖及/或CAR-T細胞持久性。
在一些實施例中,本文所述之組合物及方法中的任一者包含編碼CAR或第三代CAR之核酸。在一些實施例中,第三代CAR包含抗原結合域、跨膜域及至少三個信號傳導域。在一些實施例中,信號傳導域在T細胞活化期間介導下游信號傳導。在一些實施例中,信號傳導域係共刺激域。在一些實施例中,共刺激域在T細胞活化期間增強細胞介素產生、CAR-T細胞增殖及/或CAR-T細胞持久性。在一些實施例中,第三代CAR包含至少兩個共刺激域。在一些實施例中,該至少兩個共刺激域係不同的。
在一些實施例中,本文所述之組合物及方法中的任一者包含編碼CAR或第四代CAR之核酸。在一些實施例中,第四代CAR包含抗原結合域、跨膜域及至少兩個、三個或四個信號傳導域。在一些實施例中,信號傳導域在T細胞活化期間介導下游信號傳導。在一些實施例中,信號傳導域係共刺激域。在一些實施例中,共刺激域在T細胞活化期間增強細胞介素產生、CAR-T細胞增殖及/或CAR-T細胞持久性。
10. 包含抗體或其抗原結合部分的 ABD
在一些實施例中,CAR抗原結合域係或包含抗體或其抗原結合部分。在一些實施例中,CAR抗原結合域係或包含scFv或Fab。在一些實施例中,CAR抗原結合域包含CD19抗體之scFv或Fab片段;CD22抗體;T細胞α鏈抗體;T細胞β鏈抗體;T細胞γ鏈抗體;T細胞δ鏈抗體;CCR7抗體;CD3抗體;CD4抗體;CD5抗體;CD7抗體;CD8抗體;CD11b抗體;CD11c抗體;CD16抗體;CD20抗體;CD21抗體;CD25抗體;CD28抗體;CD34抗體;CD35抗體;CD40抗體;CD45RA抗體;CD45RO抗體;CD52抗體;CD56抗體;CD62L抗體;CD68抗體;CD80抗體;CD95抗體;CD117抗體;CD127抗體;CD133抗體;CD137 (4-1BB)抗體;CD163抗體;F4/80抗體;IL-4RA抗體;Sca-1抗體;CTLA-4抗體;GITR抗體GARP抗體;LAP抗體;顆粒酶B抗體;LFA-1抗體;MR1抗體;uPAR抗體;或轉鐵蛋白受體抗體。
在一些實施例中,CAR包含信號傳導域,該信號傳導域係共刺激域。在一些實施例中,CAR包含第二共刺激域。在一些實施例中,CAR包含至少兩個共刺激域。在一些實施例中,CAR包含至少三個共刺激域。在一些實施例中,CAR包含選自以下中的一者或多者之共刺激域:CD27、CD28、4-1BB、CD134/OX40、CD30、CD40、PD-1、ICOS、淋巴細胞功能相關抗原-1 (LFA-1)、CD2、CD7、LIGHT、NKG2C、B7-H3、與CD83特異性結合之配體。在一些實施例中,若CAR包含兩個或更多個共刺激域,則兩個共刺激域係不同的。在一些實施例中,若CAR包含兩個或更多個共刺激域,則兩個共刺激域係相同的。
除了本文所述的CAR之外,各種嵌合抗原受體及編碼其之核苷酸序列係此項技術中已知的,並且將適用於如本文所述之活體內及活體外目標細胞之融合體遞送及重編程。參見例如,WO2013040557、WO2012079000、WO2016030414,Smith T等人,Nature Nanotechnology,2017年,DOI: 10.1038/NNANO.2017.57,其揭示內容以引用方式併入本文。
11. CAR 的 另外描述
在某些實施例中,此等組合物及方法可包含編碼CAR的聚核苷酸。CAR (亦稱為嵌合免疫受體、嵌合T細胞受體或人工T細胞受體)係已經工程改造以賦予宿主細胞(例如T細胞)靶向特定蛋白質的新能力。此等受體係嵌合的,因為其將抗原結合及T細胞活化功能兩者組合至單個受體中。本揭示的多順反子載體可用於表現宿主細胞中的一種或多種CAR (例如T細胞)用於針對各種靶抗原之治療。由該一個或多個表現卡匣表現之CAR可相同或不同。在此等實施例中,CAR可包含特異性結合靶抗原、跨膜域及細胞內信號傳導域之細胞外結合域(亦稱為「結合劑」)。在某些實施例中,CAR可進一步包含一種或多種另外的元件,包括一種或多種信號肽、一種或多種細胞外鉸鏈域及/或一個或多個細胞內共刺激域。域可彼此直接相鄰,或者可存在連接此等域之一個或多個胺基酸。編碼CAR之核苷酸序列可衍生自哺乳動物序列,例如小鼠序列、靈長類動物序列、人類序列或其組合。在編碼CAR之核苷酸序列係非人類之情況下,CAR之序列可以係人源化的。編碼CAR之核苷酸序列亦可經密碼子最佳化以用於在哺乳動物細胞(例如人類細胞)中表現。在此等實施例中之任一者中,編碼CAR之核苷酸序列可與本文揭示之核苷酸序列中的任一者有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)。序列變異可以係由於密碼子最佳化、人源化、基於限制性酶之選殖疤痕及/或連接功能域之另外的胺基酸殘基等。
在某些實施例中,CAR可在N末端包含信號肽。信號肽之非限制性實例包括CD8α信號肽、IgK信號肽及粒細胞-巨噬細胞集落刺激因子受體次單元α (GMCSFR-α,亦稱為集落刺激因子2受體次單元α(CSF2RA))信號肽以及其變體,其胺基酸序列提供於下
表 A中。
表A.信號肽的例示性序列
SEQ ID NO: | 序列 | 描述 |
1106 | MALPVTALLLPLALLLHAARP | CD8α信號肽 |
1107 | METDTLLLWVLLLWVPGSTG | IgK信號肽 |
1108 | MLLLVTSLLLCELPHPAFLLIP | GMCSFR-α(CSF2RA)信號肽 |
1090 | MEFGLSWLFLVAILKGVQCSR | 免疫球蛋白重鏈信號肽 |
在某些實施例中,CAR之細胞外結合域可包含對一個靶抗原或多個靶抗原具有特異性之一種或多種抗體。該抗體可以係抗體片段,例如scFv,或單域抗體片段,例如VHH。在某些實施例中,scFv可包含藉由接頭連接之抗體之重鏈可變區(V
H)及輕鏈可變區(V
L)。V
H及V
L可以任一順序連接,亦即V
H-接頭-V
L或V
L-接頭-V
H。接頭之非限制性實例包括Whitlow接頭、(G
4S)
n(n可為正整數,例如1、2、3、4、5、6等)接頭以及其變體。在某些實施例中,抗原可以係在腫瘤細胞上排他性或優先表現之抗原,或者係自身免疫性疾病或炎性疾病特徵性之抗原。例示性靶抗原包括但不限於CD5、CD19、CD20、CD22、CD23、CD30、CD70、κ、λ及B細胞成熟劑(BCMA)、G蛋白偶聯受體家族C組5成員D (GPRC5D) (與白血病相關);CS1/SLAMF7、CD38、CD138、GPRC5D、TACI及BCMA (與骨髓瘤相關);GD2、HER2、EGFR、EGFRvIII、B7H3、PSMA、PSCA、CAIX、CD171、CEA、CSPG4、EPHA2、FAP、FRα、IL-13Rα、間皮素、MUC1、MUC16及ROR1 (與實體瘤相關)。在此等實施例中之任一者中,CAR之細胞外結合域可經密碼子最佳化以用於在宿主細胞中表現或具有變體序列以增加細胞外結合域之功能。
在某些實施例中,CAR可包含鉸鏈域,亦稱為間隔子。術語「鉸鏈」及「間隔子」在本揭示中可互換使用。鉸鏈域之非限制性實例包括CD8α鉸鏈域、CD28鉸鏈域、IgG4鉸鏈域、IgG4鉸鏈-CH2-CH3域以及其變體,其胺基酸序列提供於下表B中。
表 B.鉸鏈域之例示性序列
SEQ ID NO: | 序列 | 描述 |
1109 | TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD | CD8α鉸鏈域 |
1110 | IEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP | CD28鉸鏈域 |
1091 | AAAIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP | CD28鉸鏈域 |
1111 | ESKYGPPCPPCP | IgG4鉸鏈域 |
1112 | ESKYGPPCPSCP | IgG4鉸鏈域 |
1113 | ESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK | IgG4鉸鏈-CH2-CH3域 |
在某些實施例中,CAR之跨膜域可包含T細胞受體、CD28、CD3ε、CD45、CD4、CD5、CD8、CD9、CD16、CD22、CD33、CD37、CD64、CD80、CD86、CD134、CD137、CD154或其功能性變體之α、β或ζ鏈之跨膜區,包括此等序列中的每一者之人類版本。在其他實施例中,跨膜域可包含CD8α、CD8β、4-1BB/CD137、CD28、CD34、CD4、FcεRIγ、CD16、OX40/CD134、CD3ζ、CD3ε、CD3γ、CD3δ、TCRα、TCRβ、TCRζ、CD32、CD64、CD64、CD45、CD5、CD9、CD22、CD37、CD80、CD86、CD40、CD40L/CD154、VEGFR2、FAS及FGFR2B或其功能性變體之跨膜區,包括此等序列中的每一者之人類版本。
表 C提供了幾個例示性跨膜域之胺基酸序列。
表 C.跨膜域之例示性序列
SEQ ID NO: | 序列 | 描述 |
1114 | IYIWAPLAGTCGVLLLSLVITLYC | CD8α跨膜域 |
1115 | FWVLVVVGGVLACYSLLVTVAFIIFWV | CD28跨膜域 |
1214 | MFWVLVVVGGVLACYSLLVTVAFIIFWV | CD28跨膜域 |
在某些實施例中,CAR之細胞內信號傳導域及/或細胞內共刺激域可包含選自以下之一個或多個信號傳導域:B7-1/CD80、B7-2/CD86、B7-H1/PD-L1、B7-H2、B7-H3、B7-H4、B7-H6、B7-H7、BTLA/CD272、CD28、CTLA-4、Gi24/VISTA/B7-H5、COS/CD278、PD-1、PD-L2/B7-DC、PDCD6、4-1BB/TNFSF9/CD137、4-1BB配體/TNFSF9、BAFF/BLyS/TNFSF13B、BAFF R/TNFRSF13C、CD27/TNFRSF7、CD27配體/TNFSF7、CD30/TNFRSF8、CD30配體/TNFSF8、CD40/TNFRSF5、CD40/TNFSF5、CD40配體/TNFSF5、DR3/TNFRSF25、GITR/TNFRSF18、GITR配體/TNFSF18、HVEM/TNFRSF14、LIGHT/TNFSF14、淋巴毒素-α/TNFβ、OX40/TNFRSF4、OX40配體/TNFSF4、RELT/TNFRSF19L、TACI/TNFRSF13B、TL1A/TNFSF15、TNFα、TNF RII/TNFRSF1B、2B4/CD244/SLAMF4、BLAME/SLAMF8、CD2、CD2F-10/SLAMF9、CD48/SLAMF2、CD58/LFA-3、CD84/SLAMF5、CD229/SLAMF3、CRACC/SLAMF7、NTB-A/SLAMF6、SLAM/CD150、CD2、CD7、CD53、CD82/Kai-1、CD90/Thy1、CD96、CD160、CD200、CD300a/LMIR1、HLA I類、HLA-DR、Ikaros、整合素α 4/CD49d、整合素α 4 β 1、整合素α 4 β 7/LPAM-1、LAG-3、TCL1A、TCL1B、CRTAM、DAP12、Dectin-1/CLEC7A、DPPIV/CD26、EphB6、TIM-1/KIM-1/HAVCR、TIM-4、TSLP、TSLP R、淋巴細胞功能相關抗原-1(LFA-1)、NKG2C、CD3ζ、基於免疫受體酪胺酸之活化模體(ITAM)、CD27、CD28、4-1BB、CD134/OX40、CD30、CD40、PD-1、ICOS、淋巴細胞功能相關抗原-1 (LFA-1)、CD2、CD7、LIGHT、NKG2C、B7-H3、與CD83特異性結合之配體以及其功能性變體,包括此等序列中的每一者之人類版本。在一些實施例中,細胞內信號傳導域及/或細胞內共刺激域包含選自CD3ζ域、ITAM、CD28域、4-1BB域或其功能性變體之一個或多個信號傳導域。
表 D提供了幾個例示性細胞內共刺激及/或信號傳導域之胺基酸序列。在某些實施例中,如在如下所述之tisagenlecleucel之情況下,SEQ ID NO: 1118之CD3ζ信號傳導域可具有突變,例如,在胺基酸位置14處之麩醯胺酸(Q)至離胺酸(K)突變(參見SEQ ID NO: 1215)。
表 D.細胞內共刺激及/或信號傳導域之例示性序列
SEQ ID NO: | 序列 | 描述 |
1116 | KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL | 4-1BB共刺激域 |
1117 | RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS | CD28共刺激域 |
1091 | RSKRSRGGHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS | CD28共刺激域(LL>GG突變體) |
1118 | RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR | CD3ζ信號傳導域 |
1215 | RVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR | CD3ζ信號傳導域(在位置14處具有Q至K突變) |
在多順反子載體編碼兩個或更多個CAR之某些實施例中,該兩個或更多個CAR可包含相同之功能域或一個或多個不同之功能域,如所描述。例如,該兩個或更多個CAR可包含不同之信號肽、細胞外結合域、鉸鏈域、跨膜域、共刺激域及/或細胞內信號傳導域,以便降低由於序列相似性引起之重組風險。或者,替代地,該兩個或更多個CAR可包含相同之域。在使用相同域及/或主鏈之情況下,視情况在核苷酸序列水準下引入密碼子分歧度以最小化重組風險。
CD19 CAR
在一些實施例中,CAR係CD19 CAR (「CD19-CAR」),並且在此等實施例中,多順反子載體包含含有編碼CD19 CAR之核苷酸序列之表現卡匣。在一些實施例中,CD19 CAR可包含串聯之信號肽、特異性結合CD19之細胞外結合域、鉸鏈域、跨膜域、細胞內共刺激域及/或細胞內信號傳導域。
在一些實施例中,CD19 CAR之信號肽包含CD8α信號肽。在一些實施例中,CD8α信號肽包含SEQ ID NO: 1106所示之胺基酸序列或與SEQ ID NO: 1106所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,信號肽包含IgK信號肽。在一些實施例中,IgK信號肽包含SEQ ID NO: 1107所示之胺基酸序列或與SEQ ID NO: 1107所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,信號肽包含GMCSFR-α或CSF2RA信號肽。在一些實施例中,GMCSFR-α或CSF2RA信號肽包含SEQ ID NO: 1108所示之胺基酸序列或與SEQ ID NO: 1108所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,CD19 CAR之細胞外結合域對CD19(例如人類CD19)具有特異性。CD19 CAR之細胞外結合域可經密碼子最佳化以用於在宿主細胞中表現或具有變體序列以增加細胞外結合域之功能。在一些實施例中,細胞外結合域包含免疫球蛋白分子之免疫基因活性部分,例如scFv。
在一些實施例中,CD19 CAR之細胞外結合域包含衍生自FMC63單株抗體(FMC63)之scFv,該scFv包含藉由接頭連接之FMC63之重鏈可變區(V
H)及輕鏈可變區(V
L)。FMC63及衍生之scFv已在以下中描述:Nicholson等人,Mol. Immun. 34(16-17):1157-1165 (1997);以及PCT申請公開案第WO2018/213337號,其中每一者之全部內容係以引用之方式併入本文中。在一些實施例中,整個FMC63衍生之scFv之胺基酸序列(亦稱為FMC63 scFv)以及其不同部分提供於下
表 E中。在一些實施例中,CD19特異性scFv包含SEQ ID NO: 1075、1119、1120或1125所示之胺基酸序列或與SEQ ID NO: 1075、1119、1120或1125所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,CD19特異性scFv可包含具有SEQ ID NO: 1121-1123及1126-1128所示之胺基酸序列之一個或多個CDR。在一些實施例中,CD19特異性scFv可包含具有一個或多個CDR之輕鏈,該一個或多個CDR具有SEQ ID NO: 1121-1123所示之胺基酸序列。在一些實施例中,CD19特異性scFv可包含具有一個或多個CDR之重鏈,該一個或多個CDR具有SEQ ID NO: 1126-1128所示之胺基酸序列。在此等實施例中之任一者中,CD19特異性scFv可包含一個或多個CDR,該一個或多個CDR包含一個或多個胺基酸取代或者包含與鑑別之序列中的任一者有至少80%同一性(例如至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之序列。在一些實施例中,CD19 CAR之細胞外結合域包含如本文所述的該一個或多個CDR或由其組成。
在一些實施例中,連接scFv之V
H及V
L部分之接頭係Whitlow接頭,其具有SEQ ID NO: 1124所示之胺基酸序列。在一些實施例中,Whitlow接頭可被不同之接頭置換,例如,具有SEQ ID NO: 1130所示胺基酸序列之3×G
4S接頭,如此產生了具有SEQ ID NO: 1129所示之胺基酸序列之不同的FMC63衍生之scFv。在此等實施例中之某些實施例中,CD19特異性scFv包含SEQ ID NO: 1129所示之胺基酸序列或與SEQ ID NO: 1129所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
表 E.抗CD19 scFv和組分的例示性序列
SEQ ID NO: | 胺基酸序列 | 描述 |
1119 | DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSG VSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS | 抗CD19 FMC63 scFv整個序列,具有Whitlow接頭 |
1120 | DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT | 抗CD19 FMC63 scFv輕鏈可變區 |
1121 | QDISKY | 抗CD19 FMC63 scFv輕鏈CDR1 |
1122 | HTS | 抗CD19 FMC63 scFv輕鏈CDR2 |
1123 | QQGNTLPYT | 抗CD19 FMC63 scFv輕鏈CDR3 |
1124 | GSTSGSGKPGSGEGSTKG | Whitlow接頭 |
1125 | EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS | 抗CD19 FMC63 scFv重鏈可變區 |
1126 | GVSLPDYG | 抗CD19 FMC63 scFv重鏈CDR1 |
1127 | IWGSETT | 抗CD19 FMC63 scFv重鏈CDR2 |
1128 | AKHYYYGGSYAMDY | 抗CD19 FMC63 scFv重鏈CDR3 |
1129 | DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTCTVSG VSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS | 抗CD19 FMC63 scFv整個序列,具有3×G 4S接頭 |
1130 | GGGGSGGGGSGGGGS | 3×G 4S接頭 |
在一些實施例中,CD19 CAR之細胞外結合域衍生自對CD19特異之抗體,包括例如:SJ25C1(Bejcek等人,Cancer Res. 55:2346-2351 (1995))、HD37 (Pezutto等人,J. Immunol. 138(9):2793-2799 (1987))、4G7 (Meeker等人,Hybridoma 3:305-320 (1984))、B43 (Bejcek (1995))、BLY3 (Bejcek (1995))、B4 (Freedman等人,70:418-427 (1987))、B4 HB12b (Kansas及Tedder, J. Immunol. 147:4094-4102 (1991);Yazawa等人,Proc. Natl. Acad. Sci. USA 102:15178-15183 (2005);Herbst等人,J. Pharmacol. Exp. Ther. 335:213-222 (2010))、BU12 (Callard等人,J. Immunology, 148(10): 2983-2987 (1992))及CLB-CD19 (De Rie Cell. Immunol. 118:368-381(1989))。在此等實施例中之任一者中,CD19 CAR之細胞外結合域可包含抗體中的任一者之V
H、V
L及/或一個或多個CDR或者由其組成。
在一些實施例中,CD19 CAR之鉸鏈域包含CD8α鉸鏈域,例如人類CD8α鉸鏈域。在一些實施例中,CD8α鉸鏈域包含SEQ ID NO: 1109所示之胺基酸序列或與SEQ ID NO: 1109所示的胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,鉸鏈域包含CD28鉸鏈域,例如人類CD28鉸鏈域。在一些實施例中,CD28鉸鏈域包含SEQ ID NO: 1110所示之胺基酸序列或與SEQ ID NO: 1110所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,鉸鏈域包含IgG4鉸鏈域,例如人類IgG4鉸鏈域。在一些實施例中,IgG4鉸鏈域包含SEQ ID NO: 1111或SEQ ID NO: 1112所示之胺基酸序列或與SEQ ID NO: 1111或SEQ ID NO: 1112所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,鉸鏈域包含IgG4鉸鏈-Ch2-Ch3域,例如人類IgG4鉸鏈-Ch2-Ch3域。在一些實施例中,IgG4鉸鏈-Ch2-Ch3域包含SEQ ID NO: 1113所示之胺基酸序列或與SEQ ID NO: 1113所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,CD19 CAR之跨膜域包含CD8α跨膜域,例如人類CD8α跨膜域。在一些實施例中,CD8α跨膜域包含SEQ ID NO: 1114所示之胺基酸序列或與SEQ ID NO: 1114所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,跨膜域包含CD28跨膜域,例如人類CD28跨膜域。在一些實施例中,CD28跨膜域包含SEQ ID NO: 1115所示之胺基酸序列或與SEQ ID NO: 1115所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,CD19 CAR之細胞內共刺激域包含4-1BB共刺激域。4-1BB,亦稱為CD137,將有效之共刺激信號傳輸到T細胞,促進分化並增強T淋巴細胞之長期存活。在一些實施例中,4-1BB共刺激域係人類。在一些實施例中,4-1BB共刺激域包含SEQ ID NO: 1116所示之胺基酸序列或與SEQ ID NO: 1116所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,細胞內共刺激域包含CD28共刺激域。CD28係T細胞上之另一種共刺激分子。在一些實施例中,CD28共刺激域係人類。在一些實施例中,CD28共刺激域包含SEQ ID NO: 1117所示之胺基酸序列或與SEQ ID NO: 1117所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,CD19 CAR之細胞內共刺激域包含如所描述之4-1BB共刺激域及CD28共刺激域。
在一些實施例中,CD19 CAR之細胞內信號傳導域包含CD3 zeta(ζ)信號傳導域。CD3ζ與T細胞受體(TCR)締合以產生信號並且包含基於免疫受體酪胺酸之活化模體(ITAM)。CD3ζ信號傳導域係指來自ζ鏈之細胞質域之胺基酸殘基,此等胺基酸殘基足以功能性地傳輸T細胞活化所必需之初始信號。在一些實施例中,CD3ζ信號傳導域係人類。在一些實施例中,CD3ζ信號傳導域包含SEQ ID NO: 1118所示之胺基酸序列或與SEQ ID NO: 1118所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD19 CAR之核苷酸序列,包括例如CD19 CAR,其包含具有SEQ ID NO: 1119或SEQ ID NO: 1129所示之序列之CD19特異性scFv、SEQ ID NO:1109之CD8α鉸鏈域、SEQ ID NO: 1114之CD8α跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)。在此等實施例中之任一者中,CD19 CAR可另外包含如所描述之信號肽(例如,CD8α信號肽)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD19 CAR之核苷酸序列,包括例如CD19 CAR,其包含具有SEQ ID NO: 1119或SEQ ID NO: 1129所示之序列之CD19特異性scFv、SEQ ID NO:1111或SEQ ID NO:1112之IgG4鉸鏈域、SEQ ID NO: 1115之CD28跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性的序列)。在此等實施例中之任一者中,CD19 CAR可另外包含如所描述之信號肽(例如,CD8α信號肽)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD19 CAR之核苷酸序列,包括例如CD19 CAR,其包含具有SEQ ID NO: 1075、SEQ ID NO: 1119或SEQ ID NO: 1129所示之序列之CD19特異性scFv、SEQ ID NO:1110之CD28鉸鏈域、SEQ ID NO: 1115之CD28跨膜域、SEQ ID NO: 1117之CD28共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)。在此等實施例中之任一者中,CD19 CAR可另外包含如所描述的信號肽(例如,CD8α信號肽)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD19 CAR之核苷酸序列,該CD19 CAR包含具有SEQ ID NO: 1075所示之序列之CD19特異性scFv (參見
表 14)、SEQ ID NO: 1109之CD8鉸鏈域、SEQ ID NO: 1114之CD8跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)。在此等實施例中之任一者中,CD19 CAR可另外包含如所描述的信號肽(例如,CD8α信號肽)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼SEQ ID NO: 1216所示之CD19 CAR之核苷酸序列或者與SEQ ID NO: 1216所示之核苷酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)(參見
表 F)。所編碼之CD19 CAR具有SEQ ID NO: 1217所示之對應胺基酸序列或者與SEQ ID NO: 1217所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性),具有以下組分:CD8α信號肽、FMC63 scFv (V
L-Whitlow接頭-V
H)、CD8α鉸鏈域、CD8α跨膜域、4-1BB共刺激域及CD3ζ信號域。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD19 CAR之市售實施例之核苷酸序列。由T細胞表現及/或編碼之CD19 CAR之市售實施例之非限制性實例包括lisocabtagene maraleucel、axicabtagene ciloleucel及brexucabtagene autoleuce。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼tisagenlecleucel或其部分之核苷酸序列。tisagenlecleucel包含具有以下組分的CD19 CAR:CD8α信號肽、FMC63 scFv (V
L-3×G
4S接頭-V
H)、CD8α鉸鏈域、CD8α跨膜域、4-1BB共刺激域及CD3ζ信號傳導域。tisagenlecleucel中的CD19 CAR之核苷酸及胺基酸序列提供於
表 F中,其中序列註釋提供於
表 G中。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼lisocabtagene maraleucel或其部分之核苷酸序列。lisocabtagene maraleucel包含具有以下組分的CD19 CAR:GMCSFR-α或CSF2RA信號肽、FMC63 scFv (V
L-Whitlow接頭-V
H)、IgG4鉸鏈域、CD28跨膜域、4-1BB共刺激域及CD3ζ信號傳導域。lisocabtagene maraleucel中的CD19 CAR之核苷酸及胺基酸序列提供於
表 F中,其中序列註釋提供於
表 H中。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼axicabtagene ciloleucel或其部分之核苷酸序列。axicabtagene ciloleucel包含具有以下組分的CD19 CAR:GMCSFR-α或CSF2RA信號肽、FMC63 scFv (V
L-Whitlow接頭-V
H)、CD28鉸鏈域、CD28跨膜域、CD28共刺激域及CD3ζ信號傳導域。axicabtagene ciloleucel中的CD19 CAR之核苷酸及胺基酸序列提供於
表 F中,其中序列註釋提供於
表 I中。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼brexucabtagene autoleucel或其部分之核苷酸序列。brexucabtagene autoleucel包含具有以下組分的CD19 CAR:GMCSFR-α信號肽、FMC63 scFv、CD28鉸鏈域、CD28跨膜域、CD28共刺激域及CD3ζ信號傳導域。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼SEQ ID NO: 1131、1133或1135所示之CD19 CAR之核苷酸序列或者與SEQ ID NO: 1131、1133或1135所示之核苷酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)。所編碼之CD19 CAR分別具有SEQ ID NO: 1132、1134或1136所示之對應胺基酸序列或分別與SEQ ID NO: 1132、1134或1136所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)或者由其組成。
表 F. CD19 CAR的例示性序列
表 G. tisagenlecleucel CD19 CAR序列的註釋
表 H. lisocabtagene maraleucel CD19 CAR序列的註釋
表 I. axicabtagene ciloleucel CD19 CAR序列的註釋
SEQ ID NO: | 序列 | 描述 |
1216 | atggccttaccagtgaccgccttgctcctgccgctggccttgctgctccacgccgccaggccggacatccagatgacacagactacatcctccctgtctgcctctctgggagacagagtcaccatcagttgcagggcaagtcaggacattagtaaatatttaaattggtatcagcagaaaccagatggaactgttaaactcctgatctaccatacatcaagattacactcaggagtcccatcaaggttcagtggcagtgggtctggaacagattattctctcaccattagcaacctggagcaagaagatattgccacttacttttgccaacagggtaatacgcttccgtacacgttcggaggggggaccaagctggagatcacaggctccacctctggatccggcaagcccggatctggcgagggatccaccaagggcgaggtgaaactgcaggagtcaggacctggcctggtggcgccctcacagagcctgtccgtcacatgcactgtctcaggggtctcattacccgactatggtgtaagctggattcgccagcctccacgaaagggtctggagtggctgggagt aatatggggtagtgaaaccacatactataattcagctctcaaatccagactgaccatcatcaaggacaactccaagagccaagttttcttaaaaatgaacagtctgcaaactgatgacacagccatttactactgtgccaaacattattactacggtggtagctatgctatggactactggggccaaggaacctcagtcaccgtctcctcaaccacgacgccagcgccgcgaccaccaacaccggcgcccaccatcgcgtcgcagcccctgtccctgcgcccagaggcgtgccggccagcggcggggggcgcagtgcacacgagggggctggacttcgcctgtgatatctacatctgggcgcccttggccgggacttgtggggtccttctcctgtcactggttatcaccctttactgcaaacggggcagaaagaaactcctgtatatattcaaacaaccatttatgagaccagtacaaactactcaagaggaagatggctgtagctgccgatttccagaagaagaagaaggaggatgtgaactgagagtgaagttcagcaggagcgcagacgcccccgcgtaccagcagggccagaaccagctctataacgagctcaatctaggacgaagagaggagtacgatgttttggacaagagacgtggccgggaccctgagatggggggaaagccgagaaggaagaaccctcaggaaggcctgtacaatgaactgcagaaagataagatggcggaggcctacagtgagattgggatgaaaggcgagcgccggaggggcaaggggcacgatggcctttaccagggtctcagtacagccaccaaggacacctacgacgcccttcacatgcaggccctgccccctcgc | 例示性CD19 CAR核苷酸序列 |
1217 | MALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFM RPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR | 例示性CD19 CAR胺基酸序列 |
1231 | DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR | 例示性CD19 CAR胺基酸序列(無信號序列) |
1131 | atggccttaccagtgaccgccttgctcctgccgctggccttgctgctccacgccgccaggccggacatccagatgacacagactacatcctccctgtctgcctctctgggagacagagtcaccatcagttgcagggcaagtcaggacattagtaaatatttaaattggtatcagcagaaaccagatggaactgttaaactcctgatctaccatacatcaagattacactcaggagtcccatcaaggttcagtggcagtgggtctggaacagattattctctcaccattagcaacctggagcaagaagatattgccacttacttttgccaacagggtaatacgcttccgtacacgttcggaggggggaccaagctggagatcacaggtggcggtggctcgggcggtggtgggtcgggtggcggcggatctgaggtgaaactgcaggagtcaggacctggcctggtggcgccctcacagagcctgtccgtcacatgcactgtctcaggggtctcattacccgactatggtgtaagctggattcgccagcctccacgaaagggtctggagtggctgggagtaatatggggtagtgaaaccacatactataattcagctctcaaatccagactgaccatcatcaaggacaactccaagagccaagttttcttaaaaatgaacagtctgcaaactgatgacacagccatttactactgtgccaaacattattactacggtggtagctatgctatggactactggggccaaggaacctcagtcaccgtctcctcaaccacgacgccagcgccgcgaccaccaacaccggcgcccaccatcgcgtcgcagcccctgtccctgcgcccagaggcgtgccggccagcggcggggggcgcagtgcacacgagggggctggacttcgcctgtgatatctacatctgggcgcccttggccgggacttgtggggtccttctcctgtcactggttatcaccctttactgcaaacggggcagaaagaaactcctgtatatattcaaacaaccatttatgagaccagtacaaactactcaagaggaagatggctgtagctgccgatttccagaagaagaagaaggaggatgtgaactgagagtgaagttcagcaggagcgcagacgcccccgcgtacaag cagggccagaaccagctctataacgagctcaatctaggacgaagagaggagtacgatgttttggacaagagacgtggccgggaccctgagatggggggaaagccgagaaggaagaaccctcaggaaggcctgtacaatgaactgcagaaagataagatggcggaggcctacagtgagattgggatgaaaggcgagcgccggaggggcaaggggcacgatggcctttaccagggtctcagtacagccaccaaggacacctacgacgcccttcacatgcaggccctgccccctcgc | Tisagenlecleucel CD19 CAR核苷酸序列 |
1132 | MALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR | Tisagenlecleucel CD19 CAR胺基酸序列 |
1133 | atgctgctgctggtgaccagcctgctgctgtgcgagctgccccaccccgcctttctgctgatccccgacatccagatgacccagaccacctccagcctgagcgccagcctgggcgaccgggtgaccatcagctgccgggccagccaggacatcagcaagtacctgaactggtatcagcagaagcccgacggcaccgtcaagctgctgatctaccacaccagccggctgcacagcggcgtgcccagccggtttagcggcagcggctccggcaccgactacagcctgaccatctccaacctggaacaggaagatatcgccacctacttttgccagcagggcaacacactgccct acacctttggcggcggaacaaagctggaaatcaccggcagcacctccggcagcggcaagcctggcagcggcgagggcagcaccaagggcgaggtgaagctgcaggaaagcggccctggcctggtggcccccagccagagcctgagcgtgacctgcaccgtgagcggcgtgagcctgcccgactacggcgtgagctggatccggcagccccccaggaagggcctggaatggctgggcgtgatctggggcagcgagaccacctactacaacagcgccctgaagagccggctgaccatcatcaaggacaacagcaagagccaggtgttcctgaagatgaacagcctgcagaccgacgacaccgccatctactactgcgccaagcactactactacggcggcagctacgccatggactactggggccagggcaccagcgtgaccgtgagcagcgaatctaagtacggaccgccctgccccccttgccctatgttctgggtgctggtggtggtcggaggcgtgctggcctgctacagcctgctggtcaccgtggccttcatcatcttttgggtgaaacggggcagaaagaaactcctgtatatattcaaacaaccatttatgagaccagtacaaactactcaagaggaagatggctgtagctgccgatttccagaagaagaagaaggaggatgtgaactgcgggtgaagttcagcagaagcgccgacgcccctgcctaccagcagggccagaatcagctgtacaacgagctgaacctgggcagaagggaagagtacgacgtcctggataagcggagaggccgggaccctgagatgggcggcaagcctcggcggaagaacccccaggaaggcctgtataacgaactgcagaaagacaagatggccgaggcctacagcgagatcggcatgaagggcgagcggaggcggggcaagggccacgacggcctgtatcagggcctgtccaccgccaccaaggatacctacgacgccctgcacatgcaggccctgcccccaagg | Lisocabtagene maraleucel CD19 CAR核苷酸序列 |
1134 | MLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSESKYGPP CPPCPMFWVLVVVGGVLACYSLLVTVAFIIFWVKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR | Lisocabtagene maraleucel CD19 CAR胺基酸序列 |
1135 | atgcttctcctggtgacaagccttctgctctgtgagttaccacacccagcattcctcctgatcccagacatccagatgacacagactacatcctccctgtctgcctctctgggagacagagtcaccatcagttgcagggcaagtcaggacattagtaaatatttaaattggtatcagcagaaaccagatggaactgttaaactcctgatctaccatacatcaagattacactcaggagtcccatcaaggttcagtggcagtgggtctggaacagattattctctcaccattagcaacctggagcaagaagatattgccacttacttttgccaacagggtaatacgcttccgtacacgttcggaggggggactaagttggaaataacaggctccacctctggatccggcaagcccggatctggcgagggatccaccaagggcgaggtgaaactgcaggagtcaggacctggcctggtggcgccctcacagagcctgtccgtcacatgcactgtctcaggggtctcattacccgactatggtgtaagctggattcgccagcctccacgaaagggtctggagtggctgggagtaatatggggtagtgaaaccacatactataattcagctctcaaatccagactgaccatcatcaaggacaactccaagagccaagttttcttaaaaatgaacagtctgcaaactgatgacacagccatttactactgtgccaaacattattactacggtggtagctatgctatggactactggggtcaaggaacctcagtcaccgtctcctcagcggccgcaattgaagttatgtatcctcctccttacctagacaatgagaagagcaatggaaccattatccatgtgaaagggaaacacctttgtccaagtcccctatttcccggaccttctaagcccttttgggtgctggtggtggttgggggagtcctggcttgctatagcttgctagtaacagtggcctttattattttctgggtgaggagtaagaggagcaggctcctgcacagtgactacatgaacatgactccccgccgccccgggcccacccgcaagcattaccagccctatgccccaccacgcgacttcgcagcctatcgct ccagagtgaagttcagcaggagcgcagacgcccccgcgtaccagcagggccagaaccagctctataacgagctcaatctaggacgaagagaggagtacgatgttttggacaagagacgtggccgggaccctgagatggggggaaagccgagaaggaagaaccctcaggaaggcctgtacaatgaactgcagaaagataagatggcggaggcctacagtgagattgggatgaaaggcgagcgccggaggggcaaggggcacgatggcctttaccagggtctcagtacagccaccaaggacacctacgacgcccttcacatgcaggccctgccccctcgc | Axicabtagene ciloleucel CD19 CAR核苷酸序列 |
1136 | MLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSAAAIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR | Axicabtagene ciloleucel CD19 CAR胺基酸序列 |
特徵 | 核苷酸序列位置 | 胺基酸序列位置 |
CD8α信號肽 | 1-63 | 1-21 |
FMC63 scFv (V L-3×G 4S接頭-V H) | 64-789 | 22-263 |
CD8α鉸鏈域 | 790-924 | 264-308 |
CD8α跨膜域 | 925-996 | 309-332 |
4-1BB共刺激域 | 997-1122 | 333-374 |
CD3ζ信號傳導域 | 1123-1458 | 375-486 |
特徵 | 核苷酸序列位置 | 胺基酸序列位置 |
GMCSFR-α信號肽 | 1-66 | 1-22 |
FMC63 scFv (V L-Whitlow接頭-V H) | 67-801 | 23-267 |
IgG4鉸鏈域 | 802-837 | 268-279 |
CD28跨膜域 | 838-921 | 280-307 |
4-1BB共刺激域 | 922-1047 | 308-349 |
CD3ζ信號傳導域 | 1048-1383 | 350-461 |
特徵 | 核苷酸序列位置 | 胺基酸序列位置 |
CSF2RA信號肽 | 1-66 | 1-22 |
FMC63 scFv (V L-Whitlow接頭-V H) | 67-801 | 23-267 |
CD28鉸鏈域 | 802-927 | 268-309 |
CD28跨膜域 | 928-1008 | 310-336 |
CD28共刺激域 | 1009-1131 | 337-377 |
CD3ζ信號傳導域 | 1132-1467 | 378-489 |
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼SEQ ID NO: 1131、1133或1135所示之CD19 CAR之核苷酸序列或者與SEQ ID NO: 1131、1133或1135所示之核苷酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)。所編碼之CD19 CAR分別具有SEQ ID NO: 1132、1134或1136所示之對應胺基酸序列,分別與SEQ ID NO: 1132、1134或1136所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)或者由其組成。
CD20 CAR
在一些實施例中,CAR係CD20 CAR (「CD20-CAR」),並且在此等實施例中,多順反子載體包含含有編碼CD20 CAR之核苷酸序列之表現卡匣。CD20係一種抗原,早在原B期就存在於B細胞表面,並且水準逐漸增加,直至B細胞成熟,以及存在於大多數B細胞腫瘤之細胞中。CD20陽性細胞有時亦在霍奇金病、骨髓瘤及胸腺瘤之情況下發現。在一些實施例中,CD20 CAR可包含串聯之信號肽、特異性結合CD20之細胞外結合域、鉸鏈域、跨膜域、細胞內共刺激域及/或細胞內信號傳導域。
在一些實施例中,CD20 CAR之信號肽包含CD8α信號肽。在一些實施例中,CD8α信號肽包含SEQ ID NO: 1106所示之胺基酸序列或與SEQ ID NO: 1106所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,信號肽包含IgK信號肽。在一些實施例中,IgK信號肽包含SEQ ID NO: 1107所示之胺基酸序列或與SEQ ID NO: 1107所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,信號肽包含GMCSFR-α或CSF2RA信號肽。在一些實施例中,GMCSFR-α或CSF2RA信號肽包含SEQ ID NO: 1108所示之胺基酸序列或與SEQ ID NO: 1108所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,CD20 CAR之細胞外結合域對CD20(例如人類CD20)具有特異性。CD20 CAR之細胞外結合域可經密碼子最佳化以用於在宿主細胞中表現或具有變體序列以增加細胞外結合域之功能。在一些實施例中,細胞外結合域包含免疫球蛋白分子之免疫基因活性部分,例如scFv。
在一些實施例中,CD20 CAR之細胞外結合域衍生自對CD20具有特異性之抗體,包括例如Leu16、IF5、1.5.3、利妥昔單抗(rituximab)、奧濱尤妥珠單抗(obinutuzumab)、替伊莫單抗(ibritumomab)、奧法木單抗(ofatumumab)、托西莫單抗(tositumumab)、奧尼妥單抗(odronextamab)、維妥珠單抗(veltuzumab)、烏妥昔單抗(ublituximab)及奧瑞組單抗(ocrelizumab)。在此等實施例中之任一者中,CD20 CAR之細胞外結合域可包含抗體中的任一者之V
H、V
L及/或一個或多個CDR或者由其組成。
在一些實施例中,CD20 CAR之細胞外結合域包含衍生自Leu16單株抗體之scFv,該scFv包含通過接頭連接之Leu16之重鏈可變區(V
H)及輕鏈可變區(V
L)。參見Wu等人,Protein Engineering,14(12):1025-1033 (2001).。在一些實施例中,接頭係3×G
4S接頭。在其他實施例中,接頭係如本文所述之Whitlow接頭。在一些實施例中,整個Leu16衍生之scFv (亦稱為Leu16 scFv)之不同部分之胺基酸序列以及其不同部分提供於
表 J中。在一些實施例中,CD20特異性scFv包含SEQ ID NO: 1137、1138或1142所示的胺基酸序列或與SEQ ID NO: 1137、1138或1142所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,CD20特異性scFv可包含具有SEQ ID NO: 1139-1141、1143及1144所示之胺基酸序列之一個或多個CDR。在一些實施例中,CD20特異性scFv可包含具有一個或多個CDR之輕鏈,該一個或多個CDR具有SEQ ID NO: 1139-1141所示之胺基酸序列。在一些實施例中,CD20特異性scFv可包含具有一個或多個CDR之重鏈,該一個或多個CDR具有SEQ ID NO: 1143-1144所示之胺基酸序列。在此等實施例中之任一者中,CD20特異性scFv可包含一個或多個CDR,該一個或多個CDR包含一個或多個胺基酸取代或者包含與鑑別之序列中的任一者有至少80%同一性(例如至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之序列。在一些實施例中,CD20 CAR之細胞外結合域包含如本文所述的該一個或多個CDR或由其組成。
表 J.抗CD20 scFv和組分的例示性序列
SEQ ID NO: | 胺基酸 序列 | 描述 |
1137 | DIVLTQSPAILSASPGEKVTMTCRASSSVNYMDWYQKKPGSSPKPWIYATSNLASGVPARFSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGGGTKLEIKGSTSGSGKPGSGEGSTKGEVQLQQSGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSADYYCARSNYYGSSYWFFDVWGAGTTVTVSS | 抗CD20 Leu16 scFv整個序列,具有Whitlow接頭 |
1138 | DIVLTQSPAILSASPGEKVTMTCRASSSVNYMDWYQKKPGSSPKPWIYATSNLASGVPARFSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGGGTKLEIK | 抗CD20 Leu16 scFv輕鏈可變區 |
1139 | RASSSVNYMD | 抗CD20 Leu16 scFv輕鏈CDR1 |
1140 | ATSNLAS | 抗CD20 Leu16 scFv輕鏈CDR2 |
1141 | QQWSFNPPT | 抗CD20 Leu16 scFv輕鏈CDR3 |
1142 | EVQLQQSGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSADYYCARSNYYGSSYWFFDVWGAGTTVTVSS | 抗CD20 Leu16 scFv重鏈 |
1143 | SYNMH | 抗CD20 Leu16 scFv重鏈CDR1 |
1144 | AIYPGNGDTSYNQKFKG | 抗CD20 Leu16 scFv重鏈CDR2 |
在一些實施例中,CD20 CAR之鉸鏈域包含CD8α鉸鏈域,例如人類CD8α鉸鏈域。在一些實施例中,CD8α鉸鏈域包含SEQ ID NO: 1109所示之胺基酸序列或與SEQ ID NO: 1109所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,鉸鏈域包含CD28鉸鏈域,例如人類CD28鉸鏈域。在一些實施例中,CD28鉸鏈域包含SEQ ID NO: 1110所示之胺基酸序列或與SEQ ID NO: 1110所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,鉸鏈域包含IgG4鉸鏈域,例如人類IgG4鉸鏈域。在一些實施例中,IgG4鉸鏈域包含SEQ ID NO: 1111或SEQ ID NO: 1112所示之胺基酸序列或與SEQ ID NO: 1111或SEQ ID NO: 1112所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,鉸鏈域包含IgG4鉸鏈-Ch2-Ch3域,例如人類IgG4鉸鏈-Ch2-Ch3域。在一些實施例中,IgG4鉸鏈-Ch2-Ch3域包含SEQ ID NO: 1113所示之胺基酸序列或與SEQ ID NO: 1113所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,CD20 CAR之跨膜域包含CD8α跨膜域,例如人類CD8α跨膜域。在一些實施例中,CD8α跨膜域包含SEQ ID NO: 1114所示之胺基酸序列或與SEQ ID NO: 1114所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,跨膜域包含CD28跨膜域,例如人類CD28跨膜域。在一些實施例中,CD28跨膜域包含SEQ ID NO: 1115所示之胺基酸序列或與SEQ ID NO: 1115所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,CD20 CAR之細胞內共刺激域包含4-1BB共刺激域,例如人類4-1BB共刺激域。在一些實施例中,4-1BB共刺激域包含SEQ ID NO: 1116所示之胺基酸序列或與SEQ ID NO: 1116所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,細胞內共刺激域包含CD28共刺激域,例如人類CD28共刺激域。在一些實施例中,CD28共刺激域包含SEQ ID NO: 1117所示之胺基酸序列或與SEQ ID NO: 1117所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,CD20 CAR之細胞內信號傳導域包含CD3 zeta(ζ)信號傳導域,例如人類CD3ζ信號傳導域。在一些實施例中,CD3ζ信號傳導域包含SEQ ID NO: 1118所示之胺基酸序列或與SEQ ID NO: 1118所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD20 CAR之核苷酸序列,包括例如CD20 CAR,其包含具有SEQ ID NO: 1137所示之序列之CD20特異性scFv、SEQ ID NO:1109之CD8α鉸鏈域、SEQ ID NO: 1114之CD8α跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD20 CAR之核苷酸序列,包括例如CD20 CAR,其包含具有SEQ ID NO: 1137所示之序列之CD20特異性scFv、SEQ ID NO:1110之CD28鉸鏈域、SEQ ID NO: 1114之CD8α跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD20 CAR之核苷酸序列,包括例如CD20 CAR,其包含具有SEQ ID NO: 1137所示之序列之CD20特異性scFv、SEQ ID NO: 1111或SEQ ID NO:1112之IgG4鉸鏈域、SEQ ID NO: 1114之CD8α跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD20 CAR之核苷酸序列,包括例如CD20 CAR,其包含具有SEQ ID NO: 1137所示之序列之CD20特異性scFv、SEQ ID NO:1109之CD8α鉸鏈域、SEQ ID NO: 1115之CD28跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD20 CAR之核苷酸序列,包括例如CD20 CAR,其包含具有SEQ ID NO: 1137所示之序列之CD20特異性scFv、SEQ ID NO:1110之CD28鉸鏈域、SEQ ID NO: 1115之CD28跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD20 CAR之核苷酸序列,包括例如CD20 CAR,其包含具有SEQ ID NO: 1137所示之序列之CD20特異性scFv、SEQ ID NO: 1111或SEQ ID NO:1112之IgG4鉸鏈域、SEQ ID NO: 1115之CD28跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)。
CD22 CAR
在一些實施例中,CAR係CD22 CAR (「CD22-CAR」),並且在此等實施例中,多順反子載體包含含有編碼CD22 CAR之核苷酸序列之表現卡匣。CD22係一種跨膜蛋白,主要存在於成熟B細胞表面,可作為B細胞受體(BCR)信號傳導之抑制受體。CD22在60%至70%之B細胞淋巴瘤及白血病(例如,B-慢性淋巴細胞白血病、毛細胞白血病、急性淋巴細胞白血病(ALL)及伯基特氏淋巴瘤)中表現,並且在B細胞發育之早期階段不存在於細胞表面或幹細胞上。在一些實施例中,CD22 CAR可包含串聯之信號肽、特異性結合CD22之細胞外結合域、鉸鏈域、跨膜域、細胞內共刺激域及/或細胞內信號傳導域。
在一些實施例中,CD22 CAR之信號肽包含CD8α信號肽。在一些實施例中,CD8α信號肽包含SEQ ID NO: 1106所示之胺基酸序列或與SEQ ID NO: 1106所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,信號肽包含IgK信號肽。在一些實施例中,IgK信號肽包含SEQ ID NO: 1107所示之胺基酸序列或與SEQ ID NO: 1107所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,信號肽包含GMCSFR-α或CSF2RA信號肽。在一些實施例中,GMCSFR-α或CSF2RA信號肽包含SEQ ID NO: 1108所示之胺基酸序列或與SEQ ID NO: 1108所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,CD22 CAR之細胞外結合域對CD22(例如人類CD22)具有特異性。CD22 CAR之細胞外結合域可經密碼子最佳化以用於在宿主細胞中表現或具有變體序列以增加細胞外結合域之功能。在一些實施例中,細胞外結合域包含免疫球蛋白分子之免疫基因活性部分,例如scFv。
在一些實施例中,CD22 CAR之細胞外結合域衍生自對CD22具有特異性之抗體,包括例如SM03、奧英妥珠單抗、伊帕珠單抗、莫塞妥莫單抗及匹那妥珠單抗。在此等實施例中之任一者中,CD22 CAR之細胞外結合域可包含抗體中的任一者之V
H、V
L及/或一個或多個CDR或者由其組成。
在一些實施例中,CD22 CAR之細胞外結合域包含衍生自m971單株抗體(m971)之scFv,該scFv包含通過接頭連接之m971之重鏈可變區(V
H)及輕鏈可變區(V
L)。在一些實施例中,接頭係3×G
4S接頭。在其他實施例中,可替代地使用Whitlow接頭。在一些實施例中,整個m971衍生之scFv之胺基酸序列(亦稱為m971 scFv)以及其不同部分提供於下表K中。在一些實施例中,CD22特異性scFv包含SEQ ID NO: 1145、1146或1150所示之胺基酸序列或與SEQ ID NO: 1145、1146或1150所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,CD22特異性scFv可包含具有SEQ ID NO: 1147-1149及1151-1153所示之胺基酸序列之一個或多個CDR。在一些實施例中,CD22特異性scFv可包含具有一個或多個CDR之重鏈,該一個或多個CDR具有SEQ ID NO: 1147-1149所示之胺基酸序列。在一些實施例中,CD22特異性scFv可包含具有一個或多個CDR之輕鏈,該一個或多個CDR具有SEQ ID NO: 1151-1153所示之胺基酸序列。在此等實施例中之任一者中,CD22特異性scFv可包含一個或多個CDR,該一個或多個CDR包含一個或多個胺基酸取代或者包含與鑑別之序列中的任一者有至少80%同一性(例如至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之序列。在一些實施例中,CD22 CAR之細胞外結合域包含如本文所述的該一個或多個CDR或由其組成。
在一些實施例中,CD22 CAR的細胞外結合域包含衍生自m971-L7之scFv,該scFv係與親本抗體m971相比具有顯著改良之CD22結合親和力(改良約2 nM至小於50 pM)的m971的親和力成熟的變體。在一些實施例中,衍生自m971-L7之scFv包含藉由3×G
4S接頭連接的m971-L7的V
H及V
L。在其他實施例中,可替代地使用Whitlow接頭。在一些實施例中,整個m971-L7衍生之scFv之胺基酸序列(亦稱為m971-L7 scFv)以及其不同部分提供於下
表 K中。在一些實施例中,CD22特異性scFv包含SEQ ID NO: 1154、1155或1159所示之胺基酸序列或與SEQ ID NO: 1154、1155或1159所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,CD22特異性scFv可包含具有SEQ ID NO: 1156-1158及1160-1162所示之胺基酸序列之一個或多個CDR。在一些實施例中,CD22特異性scFv可包含具有一個或多個CDR之重鏈,該一個或多個CDR具有SEQ ID NO: 1156-1158所示之胺基酸序列。在一些實施例中,CD22特異性scFv可包含具有一個或多個CDR之輕鏈,該一個或多個CDR具有SEQ ID NO: 1160-1162所示之胺基酸序列。在此等實施例中之任一者中,CD22特異性scFv可包含一個或多個CDR,該一個或多個CDR包含一個或多個胺基酸取代或者包含與鑑別之序列中的任一者有至少80%同一性(例如至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之序列。在一些實施例中,CD22 CAR之細胞外結合域包含如本文所述的該一個或多個CDR或由其組成。
表 K.抗CD22 scFv和組分的例示性序列
SEQ ID NO: | 胺 基酸序列 | 描述 |
1145 | QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIK | 抗CD22 m971 scFv整個序列,具有3×G 4S接頭 |
1146 | QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSS | 抗CD22 m971 scFv重鏈可變區 |
1147 | GDSVSSNSAA | 抗CD22 m971 scFv重鏈CDR1 |
1148 | TYYRSKWYN | 抗CD22 m971 scFv重鏈CDR2 |
1149 | AREVTGDLEDAFDI | 抗CD22 m971 scFv重鏈CDR3 |
1150 | DIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIK | 抗CD22 m971 scFv輕鏈 |
1151 | QTIWSY | 抗CD22 m971 scFv輕鏈CDR1 |
1152 | AAS | 抗CD22 m971 scFv輕鏈CDR2 |
1153 | QQSYSIPQT | 抗CD22 m971 scFv輕鏈CDR3 |
1154 | QVQLQQSGPGMVKPSQTLSLTCAISGDSVSSNSVAWNWIRQSPSRGLEWLGRTYYRSTWYNDYAVSMKSRITINPDTNKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMIQSPSSLSASVGDRVTITCRASQTIWSYLNWYRQRPGEAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIK | 抗CD22 m971-L7 scFv整個序列,具有3×G 4S接頭 |
1155 | QVQLQQSGPGMVKPSQTLSLTCAISGDSVSSNSVAWNWIRQSPSRGLEWLGRTYYRSTWYNDYAVSMKSRITINPDTNKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSS | 抗CD22 m971-L7 scFv重鏈可變區 |
1156 | GDSVSSNSVA | 抗CD22 m971-L7 scFv重鏈CDR1 |
1157 | TYYRSTWYN | 抗CD22 m971-L7 scFv重鏈CDR2 |
1158 | AREVTGDLEDAFDI | 抗CD22 m971-L7 scFv重鏈CDR3 |
1159 | DIQMIQSPSSLSASVGDRVTITCRASQTIWSYLNWYRQRPGEAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIK | 抗CD22 m971-L7 scFv輕鏈可變區 |
1160 | QTIWSY | 抗CD22 m971-L7 scFv輕鏈CDR1 |
1161 | AAS | 抗CD22 m971-L7 scFv輕鏈CDR2 |
1162 | QQSYSIPQT | 抗CD22 m971-L7 scFv輕鏈CDR3 |
在一些實施例中,CD22 CAR之細胞外結合域包含免疫毒素HA22或BL22。免疫毒素BL22及HA22係包含對與細菌毒素融合之CD22具有特異性之scFv之治療劑,並且因此可結合表現CD22之癌細胞表面並殺死癌細胞。BL22包含與38-kDa截短形式之假單胞菌(
Pseudomonas)外毒素A融合之抗CD22抗體RFB4的dsFv (Bang等人,Clin. Cancer Res., 11:1545-50 (2005))。HA22 (CAT8015,帕舒托-莫塞妥莫單抗(moxetumomab pasudotox))係BL22之突變之更高親和力形式(Ho等人,J. Biol.
Chem.,280(1): 607-17 (2005))。對CD22具有特異性之HA22及BL22之抗原結合域之合適序列揭示於以下中,例如:美國專利號7,541,034、7,355,012及7,982,011,此等專利據此全文以引用方式併入本文。
在一些實施例中,CD22 CAR之鉸鏈域包含CD8α鉸鏈域,例如人類CD8α鉸鏈域。在一些實施例中,CD8α鉸鏈域包含SEQ ID NO: 1109所示之胺基酸序列或與SEQ ID NO: 1109所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,鉸鏈域包含CD28鉸鏈域,例如人類CD28鉸鏈域。在一些實施例中,CD28鉸鏈域包含SEQ ID NO: 1110所示之胺基酸序列或與SEQ ID NO: 1110所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,鉸鏈域包含IgG4鉸鏈域,例如人類IgG4鉸鏈域。在一些實施例中,IgG4鉸鏈域包含SEQ ID NO: 1111或SEQ ID NO: 1112所示之胺基酸序列或與SEQ ID NO: 1111或SEQ ID NO: 1112所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,鉸鏈域包含IgG4鉸鏈-Ch2-Ch3域,例如人類IgG4鉸鏈-Ch2-Ch3域。在一些實施例中,IgG4鉸鏈-Ch2-Ch3域包含SEQ ID NO: 1113所示之胺基酸序列或與SEQ ID NO: 1113所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,CD22 CAR之跨膜域包含CD8α跨膜域,例如人類CD8α跨膜域。在一些實施例中,CD8α跨膜域包含SEQ ID NO: 1114所示之胺基酸序列或與SEQ ID NO: 1114所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,跨膜域包含CD28跨膜域,例如人類CD28跨膜域。在一些實施例中,CD28跨膜域包含SEQ ID NO: 1115所示之胺基酸序列或與SEQ ID NO: 1115所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,CD22 CAR之細胞內共刺激域包含4-1BB共刺激域,例如人類4-1BB共刺激域。在一些實施例中,4-1BB共刺激域包含SEQ ID NO: 1116所示之胺基酸序列或與SEQ ID NO: 1116所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,細胞內共刺激域包含CD28共刺激域,例如人類CD28共刺激域。在一些實施例中,CD28共刺激域包含SEQ ID NO: 1117所示之胺基酸序列或與SEQ ID NO: 1117所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,CD22 CAR之細胞內信號傳導域包含CD3 zeta(ζ)信號傳導域,例如人類CD3ζ信號傳導域。在一些實施例中,CD3ζ信號傳導域包含SEQ ID NO: 1118所示之胺基酸序列或與SEQ ID NO: 1118所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD22 CAR之核苷酸序列,包括例如CD22 CAR,其包含具有SEQ ID NO: 1145或SEQ ID NO: 1154所示之序列之CD22特異性scFv、SEQ ID NO:9之CD8α鉸鏈域、SEQ ID NO: 1114之CD8α跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD22 CAR之核苷酸序列,包括例如CD22 CAR,其包含具有SEQ ID NO: 1145或SEQ ID NO: 1154所示之序列之CD22特異性scFv、SEQ ID NO:1110之CD28鉸鏈域、SEQ ID NO: 1114之CD8α跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD22 CAR之核苷酸序列,包括例如CD22 CAR,其包含具有SEQ ID NO: 1145或SEQ ID NO: 1154所示之序列之CD22特異性scFv、SEQ ID NO:1111或SEQ ID NO:1112之IgG4鉸鏈域、SEQ ID NO: 1114之CD8α跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性的序列)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD22 CAR之核苷酸序列,包括例如CD22 CAR,其包含具有SEQ ID NO: 1145或SEQ ID NO: 1154所示之序列之CD22特異性scFv、SEQ ID NO:9之CD8α鉸鏈域、SEQ ID NO: 1115之CD28跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD22 CAR之核苷酸序列,包括例如CD22 CAR,其包含具有SEQ ID NO: 1145或SEQ ID NO: 1154所示之序列之CD22特異性scFv、SEQ ID NO:1110之CD28鉸鏈域、SEQ ID NO: 1115之CD28跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼CD22 CAR之核苷酸序列,包括例如CD22 CAR,其包含具有SEQ ID NO: 1145或SEQ ID NO: 1154所示之序列之CD22特異性scFv、SEQ ID NO:1111或SEQ ID NO:1112之IgG4鉸鏈域、SEQ ID NO: 1115之CD28跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性的序列)。
BCMA CAR
在一些實施例中,CAR係BCMA CAR (「BCMA-CAR」),並且在此等實施例中,多順反子載體包含含有編碼BCMA CAR之核苷酸序列之表現卡匣。BCMA係在B細胞譜系的細胞上表現的腫瘤壞死家族受體(TNFR)成員,在末端分化之B細胞或成熟B淋巴細胞上具有最高表現。BCMA涉及介導漿細胞之存活率以維持長期體液免疫。BCMA之表現最近與許多癌症相關,諸如多發性骨髓瘤、霍奇金淋巴瘤及非霍奇金淋巴瘤、各種白血病及膠質母細胞瘤。在一些實施例中,BCMA CAR可包含串聯之信號肽、特異性結合BCMA之細胞外結合域、鉸鏈域、跨膜域、細胞內共刺激域及/或細胞內信號傳導域。
在一些實施例中,BCMA CAR之信號肽包含CD8α信號肽。在一些實施例中,CD8α信號肽包含SEQ ID NO: 1106所示之胺基酸序列或與SEQ ID NO: 1106所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,信號肽包含IgK信號肽。在一些實施例中,IgK信號肽包含SEQ ID NO: 1107所示之胺基酸序列或與SEQ ID NO: 1107所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,信號肽包含GMCSFR-α或CSF2RA信號肽。在一些實施例中,GMCSFR-α或CSF2RA信號肽包含SEQ ID NO: 1108所示之胺基酸序列或與SEQ ID NO: 1108所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,BCMA CAR之細胞外結合域對BCMA (例如人類BCMA)具有特異性。BCMA CAR之細胞外結合域可經密碼子最佳化以用於在宿主細胞中表現或具有變體序列以增加細胞外結合域之功能。
在一些實施例中,細胞外結合域包含免疫球蛋白分子之免疫基因活性部分,例如scFv。在一些實施例中,BCMA CAR之細胞外結合域衍生自對BCMA具有特異性之抗體,包括例如貝蘭他單抗、埃拉納塔單抗(erlanatamab)、特立妥單抗、LCAR-B38M及ciltacabtagene。在此等實施例中之任一者中,BCMA CAR之細胞外結合域可包含抗體中的任一者之V
H、V
L及/或一個或多個CDR或者由其組成。
在一些實施例中,BCMA CAR之細胞外結合域包含衍生自C11D5.3 (鼠類單株抗體)之scFv,如Carpenter等人,Clin. Cancer Res.,19(8):2048-2060 (2013)中所述。亦參見PCT申請公開案第WO2010/104949號。C11D5.3衍生之scFv可包含藉由Whitlow接頭連接之C11D5.3之重鏈可變區(V
H)及輕鏈可變區(V
L),其胺基酸序列提供於下
表 L中。在一些實施例中,BCMA特異性細胞外結合域包含SEQ ID NO: 1163、1164或1168所示之胺基酸序列或與SEQ ID NO: 1163、1164或1168所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,BCMA特異性細胞外結合域可包含具有SEQ ID NO: 1165-1167及1169-1171所示之胺基酸序列之一個或多個CDR。在一些實施例中,BCMA特異性細胞外結合域可包含具有一個或多個CDR之輕鏈,該一個或多個CDR具有SEQ ID NO: 1165-1167所示之胺基酸序列。在一些實施例中,BCMA特異性細胞外結合域可包含具有一個或多個CDR之重鏈,該一個或多個CDR具有SEQ ID NO: 1169-1171所示之胺基酸序列。在此等實施例中之任一者中,BCMA特異性scFv可包含一個或多個CDR,該一個或多個CDR包含一個或多個胺基酸取代或者包含與鑑別之序列中的任一者有至少80%同一性(例如至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之序列。在一些實施例中,BCMA CAR之細胞外結合域包含如本文所述的該一個或多個CDR或由其組成。
在一些實施例中,BCMA CAR之細胞外結合域包含衍生自另一種鼠類單株抗體C12A3.2之scFv,如Carpenter等人,Clin. Cancer Res.,19(8):2048-2060 (2013),以及PCT申請公開案第WO2010/104949號中所述,其胺基酸序列亦提供於下
表L。在一些實施例中,BCMA特異性細胞外結合域包含SEQ ID NO: 1172、1173或1177所示之胺基酸序列或與SEQ ID NO: 1172、1173或1177所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,BCMA特異性細胞外結合域可包含具有SEQ ID NO: 1174-1176及1178-1180所示之胺基酸序列之一個或多個CDR。在一些實施例中,BCMA特異性細胞外結合域可包含具有一個或多個CDR之輕鏈,該一個或多個CDR具有SEQ ID NO: 1174-1176所示之胺基酸序列。在一些實施例中,BCMA特異性細胞外結合域可包含具有一個或多個CDR之重鏈,該一個或多個CDR具有SEQ ID NO: 1178-1180所示之胺基酸序列。在此等實施例中之任一者中,BCMA特異性scFv可包含一個或多個CDR,該一個或多個CDR包含一個或多個胺基酸取代或者包含與鑑別之序列中的任一者有至少80%同一性(例如至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之序列。在一些實施例中,BCMA CAR之細胞外結合域包含如本文所述的該一個或多個CDR或由其組成。
在一些實施例中,BCMA CAR之細胞外結合域包含對人類BCMA具有高特異性之鼠類單株抗體,在Friedman等人,Hum. Gene Ther.,29(5):585-601 (2018)中稱為BB2121。亦參見PCT申請公開案第WO2012163805號。
在一些實施例中,BCMA CAR之細胞外結合域包含兩個重鏈(VHH)之單個可變片段,此等單個可變片段可結合如Zhao等人,J. Hematol. Oncol.,11(1):141 (2018)中所述之BCMA之兩個抗原决定基,亦稱為LCAR-B38M。亦參見PCT申請公開案第WO2018/028647號。
在一些實施例中,BCMA CAR之細胞外結合域包含完全人類重鏈可變域(FHVH),如Lam等人,Nat. Commun.,11(1):283 (2020),亦稱為FHVH33。亦參見PCT申請公開案第WO2019/006072號。FHVH33之胺基酸序列及其CDR提供於下
表 L。在一些實施例中,BCMA特異性細胞外結合域包含SEQ ID NO: 1181所示之胺基酸序列或與SEQ ID NO: 1181所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,BCMA特異性細胞外結合域可包含具有SEQ ID NO: 1182-1184所示之胺基酸序列之一個或多個CDR。在此等實施例中之任一者中,BCMA特異性細胞外結合域可包含一個或多個CDR,該一個或多個CDR包含一個或多個胺基酸取代或者包含與鑑別之序列中的任一者有至少80%同一性(例如至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之序列。在一些實施例中,BCMA CAR之細胞外結合域包含如本文所述之該一個或多個CDR或由其組成。
在一些實施例中,BCMA CAR之細胞外結合域包含衍生自CT103A (或CAR0085)的scFv,如美國專利號11,026,975 B2所述,其胺基酸序列提供於下
表 L中。在一些實施例中,BCMA特異性細胞外結合域包含SEQ ID NO: 1218、1219或1223所示之胺基酸序列或與SEQ ID NO: 1218、1219或1223所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,BCMA特異性細胞外結合域可包含具有SEQ ID NO: 1220-1222及1224-1226所示之胺基酸序列之一個或多個CDR。在一些實施例中,BCMA特異性細胞外結合域可包含具有一個或多個CDR之輕鏈,該一個或多個CDR具有SEQ ID NO: 1220-1222所示之胺基酸序列。在一些實施例中,BCMA特異性細胞外結合域可包含具有一個或多個CDR之重鏈,該一個或多個CDR具有SEQ ID NO: 1224-1226所示之胺基酸序列。在此等實施例中之任一者中,BCMA特異性scFv可包含一個或多個CDR,該一個或多個CDR包含一個或多個胺基酸取代或者包含與鑑別之序列中的任一者有至少80%同一性(例如至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之序列。在一些實施例中,BCMA CAR之細胞外結合域包含如本文所述之該一個或多個CDR或由其組成。
另外,針對BCMA之CAR及結合劑已在美國申請公開案第2020/0246381 A1號及第2020/0339699 A1號進行描述,此等申請各自的全部內容以引用方式併入本文。
表 L.抗BCMA結合劑及組分的例示性序列
SEQ ID NO: | 胺基酸 序列 | 描述 |
1163 | DIVLTQSPASLAMSLGKRATISCRASESVSVIGAHLIHWYQQKPGQPPKLLIYLASNLETGVPARFSGSGSGTDFTLTIDPVEEDDVAIYSCLQSRIFPRTFGGGTKLEIKGSTSGSGKPGSGEGSTKGQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS | 抗BCMA C11D5.3 scFv整個序列,具有Whitlow接頭 |
1164 | DIVLTQSPASLAMSLGKRATISCRASESVSVIGAHLIHWYQQKPGQPPKLLIYLASNLETGVPARFSGSGSGTDFTLTIDPVEEDDVAIYSCLQSRIFPRTFGGGTKLEIK | 抗BCMA C11D5.3 scFv輕鏈可變區 |
1165 | RASESVSVIGAHLIH | 抗BCMA C11D5.3 scFv輕鏈CDR1 |
1166 | LASNLET | 抗BCMA C11D5.3 scFv輕鏈CDR2 |
1167 | LQSRIFPRT | 抗BCMA C11D5.3 scFv輕鏈CDR3 |
1168 | QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS | 抗BCMA C11D5.3 scFv重鏈可變區 |
1169 | DYSIN | 抗BCMA C11D5.3 scFv重鏈CDR1 |
1170 | WINTETREPAYAYDFRG | 抗BCMA C11D5.3 scFv重鏈CDR2 |
1171 | DYSYAMDY | 抗BCMA C11D5.3 scFv重鏈CDR3 |
1172 | DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIYWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGSTSGSGKPGSGEGSTKGQIQLVQSGPELKKPGETVKISCKASGYTFRHYSMNWVKQAPGKGLKWMGRINTESGVPIYADDFKGRFAFSVETSASTAYLVINNLKDEDTASYFCSNDYLYSLDFWGQGTALTVSS | 抗BCMA C12A3.2 scFv整個序列,具有Whitlow接頭 |
1173 | DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIYWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK | 抗BCMA C12A3.2 scFv輕鏈可變區 |
1174 | RASESVTILGSHLIY | 抗BCMA C12A3.2 scFv輕鏈CDR1 |
1175 | LASNVQT | 抗BCMA C12A3.2 scFv輕鏈CDR2 |
1176 | LQSRTIPRT | 抗BCMA C12A3.2 scFv輕鏈CDR3 |
1177 | QIQLVQSGPELKKPGETVKISCKASGYTFRHYSMNWVKQAPGKGLKWMGRINTESGVPIYADDFKGRFAFSVETSASTAYLVINNLKDEDTASYFCSNDYLYSLDFWGQGTALTVSS | 抗BCMA C12A3.2 scFv重鏈可變區 |
1178 | HYSMN | 抗BCMA C12A3.2 scFv重鏈CDR1 |
1179 | RINTESGVPIYADDFKG | 抗BCMA C12A3.2 scFv重鏈CDR2 |
1180 | DYLYSLDF | 抗BCMA C12A3.2 scFv重鏈CDR3 |
1181 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSSISGSGDYIYYADSVKGRFTISRDISKNTLYLQMNSLRAEDTAVYYCAKEGTGANSSLADYRGQGTLVTVSS | 抗BCMA FHVH33整個序列 |
1182 | GFTFSSYA | 抗BCMA FHVH33 CDR1 |
1183 | ISGSGDYI | 抗BCMA FHVH33 CDR2 |
1184 | AKEGTGANSSLADY | 抗BCMA FHVH33 CDR3 |
1218 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQKYDLLTFGGGTKVEIKGSTSGSGKPGSGEGSTKGQLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGSISYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDRGDTILDVWGQGTMVTVSS | 抗BCMA CT103A scFv整個序列,具有Whitlow接頭 |
1219 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQKYDLLTFGGGTKVEIK | 抗BCMA CT103A scFv輕鏈可變區 |
1220 | QSISSY | 抗BCMA CT103A scFv輕鏈CDR1 |
1221 | AAS | 抗BCMA CT103A scFv輕鏈CDR2 |
1222 | QQKYDLLT | 抗BCMA CT103A scFv輕鏈CDR3 |
1223 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGSISYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDRGDTILDVWGQGTMVTVSS | 抗BCMA CT103A scFv重鏈可變區 |
1224 | GGSISSSSYY | 抗BCMA CT103A scFv重鏈CDR1 |
1225 | ISYSGST | 抗BCMA CT103A scFv重鏈CDR2 |
1226 | ARDRGDTILDV | 抗BCMA CT103A scFv重鏈CDR3 |
在一些實施例中,BCMA CAR之鉸鏈域包含CD8α鉸鏈域,例如人類CD8α鉸鏈域。在一些實施例中,CD8α鉸鏈域包含SEQ ID NO: 1109所示之胺基酸序列或與SEQ ID NO: 1109所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,鉸鏈域包含CD28鉸鏈域,例如人類CD28鉸鏈域。在一些實施例中,CD28鉸鏈域包含SEQ ID NO: 1110所示之胺基酸序列或與SEQ ID NO: 1110所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,鉸鏈域包含IgG4鉸鏈域,例如人類IgG4鉸鏈域。在一些實施例中,IgG4鉸鏈域包含SEQ ID NO: 1111或SEQ ID NO: 1112所示之胺基酸序列或與SEQ ID NO: 1111或SEQ ID NO: 1112所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,鉸鏈域包含IgG4鉸鏈-Ch2-Ch3域,例如人類IgG4鉸鏈-Ch2-Ch3域。在一些實施例中,IgG4鉸鏈-Ch2-Ch3域包含SEQ ID NO: 1113所示之胺基酸序列或與SEQ ID NO: 1113所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,BCMA CAR之跨膜域包含CD8α跨膜域,例如人類CD8α跨膜域。在一些實施例中,CD8α跨膜域包含SEQ ID NO: 1114所示之胺基酸序列或與SEQ ID NO: 1114所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,跨膜域包含CD28跨膜域,例如人類CD28跨膜域。在一些實施例中,CD28跨膜域包含SEQ ID NO: 1115所示之胺基酸序列或與SEQ ID NO: 1115所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,BCMA CAR之細胞內共刺激域包含4-1BB共刺激域,例如人類4-1BB共刺激域。在一些實施例中,4-1BB共刺激域包含SEQ ID NO: 1116所示之胺基酸序列或與SEQ ID NO: 1116所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。在一些實施例中,細胞內共刺激域包含CD28共刺激域,例如人類CD28共刺激域。在一些實施例中,CD28共刺激域包含SEQ ID NO: 1117所示之胺基酸序列或與SEQ ID NO: 1117所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,BCMA CAR之細胞內信號傳導域包含CD3 zeta(ζ)信號傳導域,例如人類CD3ζ信號傳導域。在一些實施例中,CD3ζ信號傳導域包含SEQ ID NO: 1118所示之胺基酸序列或與SEQ ID NO: 1118所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)之胺基酸序列或者由其組成。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼BCMA CAR之核苷酸序列,包括例如BCMA CAR,其包含如所描述之BCMA特異性細胞外結合域、SEQ ID NO: 1109之CD8α鉸鏈域、SEQ ID NO: 1114之CD8α跨膜域、SEQ ID NO: 1116之4-1BB共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)中的任一者。在此等實施例中之任一者中,BCMA CAR可另外地包含如所描述之信號肽(例如,CD8α信號肽)。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼BCMA CAR之核苷酸序列,包括例如BCMA CAR,其包含如所描述之BCMA特異性細胞外結合域、SEQ ID NO: 1109之CD8α鉸鏈域、SEQ ID NO: 1114之CD8α跨膜域、SEQ ID NO: 1117之CD28共刺激域、SEQ ID NO: 1118之CD3ζ信號域及/或其變體(亦即,具有與其所揭示之序列有至少80%,例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%或至少99同一性之序列)中的任一者。在此等實施例中之任一者中,BCMA CAR可另外地包含如所描述之信號肽。
在一些實施例中,多順反子載體包括表現卡匣,該表現卡匣包含編碼SEQ ID NO: 1227所示之BCMA CAR之核苷酸序列或者與SEQ ID NO: 1227所示之核苷酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性)(參見
表 M)。所編碼之BCMA CAR具有SEQ ID NO: 1228所示之對應胺基酸序列或者與SEQ ID NO: 1228所示之胺基酸序列有至少80%同一性(例如,至少80%、至少85%、至少90%、至少95%、至少96%、至少97%、至少98%、至少99%或100%同一性),具有以下組分:CD8α信號肽、CT103A scFv(V
L-Whitlow接頭-V
H)、CD8α鉸鏈域、CD8α跨膜域、4-1BB共刺激域及CD3ζ信號域。
在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼BCMA CAR之市售實施例之核苷酸序列,包括例如idecabtagene vicleucel (ide-cel,亦稱為bb 2121)。在一些實施例中,多順反子載體包含表現卡匣,該表現卡匣包含編碼idecabtagene vicleucel或其部分之核苷酸序列。idecabtagene vicleucel包含具有以下組分的BCMA CAR:BB2121結合劑、CD8α鉸鏈域、CD8α跨膜域、4-1BB共刺激域及CD3ζ信號傳導域。
表 M. BCMA CAR的例示性序列
SEQ ID NO: | 序列 | 描述 |
1227 | atggccttaccagtgaccgccttgctcctgccgctggccttgctgctccacgccgccaggccggacatccagatgacccagtctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccgggcaagtcagagcattagcagctatttaaattggtatcagcagaaaccagggaaagcccctaagctcctgatctatgctgcatccagtttgcaaagtggggtcccatcaaggttcagtggcagtggatctgggacagatttcactctcaccatcagcagtctgcaacctgaagattttgcaacttactactgtcagcaaaaatacgacctcctcacttttggcggagggaccaaggttgagatcaaaggcagcaccagcggctccggcaagcctggctctggcgagggcagcacaaagggacagctgcagctgcaggagtcgggcccaggactggtgaagccttcggagaccctgtccctcacctgcactgtctctggtggctccatcagcagtagtagttactactggggctggatccgccagcccccagggaaggggctggagtggattg ggagtatctcctatagtgggagcacctactacaacccgtccctcaagagtcgagtcaccatatccgtagacacgtccaagaaccagttctccctgaagctgagttctgtgaccgccgcagacacggcggtgtactactgcgccagagatcgtggagacaccatactagacgtatggggtcagggtacaatggtcaccgtcagctcattcgtgcccgtgttcctgcccgccaaacctaccaccacccctgcccctagacctcccaccccagccccaacaatcgccagccagcctctgtctctgcggcccgaagcctgtagacctgctgccggcggagccgtgcacaccagaggcctggacttcgcctgcgacatctacatctgggcccctctggccggcacctgtggcgtgctgctgctgagcctggtgatcaccctgtactgcaaccaccggaacaaacggggcagaaagaaactcctgtatatattcaaacaaccatttatgagaccagtacaaactactcaagaggaagatggctgtagctgccgatttccagaagaagaagaaggaggatgtgaactgagagtgaagttcagcagatccgccgacgcccctgcctaccagcagggacagaaccagctgtacaacgagctgaacctgggcagacgggaagagtacgacgtgctggacaagcggagaggccgggaccccgagatgggcggaaagcccagacggaagaacccccaggaaggcctgtataacgaactgcagaaagacaagatggccgaggcctacagcgagatcggcatgaagggcgagcggaggcgcggcaagggccacgatggcctgtaccagggcctgagcaccgccaccaaggacacctacgacgccctgcacatgcaggccctgccccccaga | 例示性BCMA CAR核苷酸序列 |
1228 | MALPVTALLLPLALLLHAARPDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQKYDLLTFGGGTKVEIKGSTSGSGKPGSGEGSTKGQLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGSISYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDRGDTILDVWGQGTMVTVSSFVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDF ACDIYIWAPLAGTCGVLLLSLVITLYCNHRNKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR | 例示性BCMA CAR胺基酸序列 |
在一些實施例中,重組受體(例如CAR)的抗體部分進一步包括跨膜域及細胞外抗原結合域之間的間隔子。在一些實施例中,間隔子包括免疫球蛋白恆定區的至少一部分,諸如鉸鏈區,例如IgG4鉸鏈區及/或CH1/CL及/或Fc區。在一些實施例中,恆定區或部分係人類IgG,諸如IgG4或IgG1。在一些態樣中,恆定區之一部分用作抗原識別組分(例如,scFv)及跨膜域之間的間隔區。與不存在間隔子之情況相比,間隔子之長度可在抗原結合後提供增加之細胞反應性。例示性間隔子包括但不限於以下所述之彼等者:Hudecek等人,(2013) Clin. Cancer Res., 19:3153、WO2014031687,美國專利第8,822,647號或公開的申請第US 2014/0271635號。在一些實施例中,恆定區或部分係人類IgG,諸如IgG4或IgG1。
在一些實施例中,抗原受體包含直接或間接連接至細胞外域之細胞內域。在一些實施例中,嵌合抗原受體包括連接胞外域及胞內信號傳導域之跨膜域。在一些實施例中,細胞內信號傳導域包含ITAM。例如,在一些態樣中,抗原識別域(例如細胞外域)通常與一個或多個細胞內信號傳導組分(諸如模擬經由抗原受體複合體(諸如在CAR之情況下之TCR複合體)之活化之信號傳導組分)連接,以及/或者經由另一個細胞表面受體發出信號。在一些實施例中,嵌合受體包含在細胞外域(例如scFv)及細胞內信號傳導域之間連接或融合之跨膜域。因此,在一些實施例中,抗原結合組分(例如抗體)與一個或多個跨膜及細胞內信號傳導域連接。
在一個實施例中,使用了與受體(例如,CAR)中之域中之一者天然相關之跨膜域。在一些情況下,藉由胺基酸取代來選擇或修飾跨膜域,以避免此類域與相同或不同表面膜蛋白之跨膜域結合,從而使與受體複合物之其他成員之相互作用最小化。
在一些實施例中,跨膜域衍生自天然來源或合成來源。在來源係天然的情況下,域在一些態樣中係衍生自任何膜結合或跨膜蛋白。跨膜區包括衍生自T細胞受體、CD28、CD3ε、CD45、CD4、CD5、CD8、CD9、CD16、CD22、CD33、CD37、CD64、CD80、CD86、CD134、CD137、CD154之α、β或ζ鏈(亦即包含至少其跨膜區)之彼等者。替代地,在一些實施例中,跨膜域係合成的。在一些態樣中,合成之跨膜域主要包含疏水性殘基,諸如白胺酸及纈胺酸。在一些態樣中,在合成跨膜域之每個末端均有三聯體苯丙胺酸、色胺酸及纈胺酸。在一些實施例中,藉由接頭、間隔子及/或跨膜域進行連接。在一些態樣中,跨膜域包含CD28之跨膜部分。
在一些實施例中,細胞外域及跨膜域可直接或間接連接。在一些實施例中,細胞外域及跨膜域藉由間隔子連接,諸如本文所述之任何間隔子。在一些實施例中,受體包含衍生自跨膜域之分子之細胞外部分,諸如CD28細胞外部分。
細胞內信號傳導域係模擬或近似通過天然抗原受體之信號、通過此受體與共刺激受體組合之信號及/或單獨通過共刺激受體之信號之彼等者。在一些實施例中,存在短寡核苷酸或多肽接頭,例如,長度介於2個及10個胺基酸之間的接頭,諸如含有甘胺酸及絲胺酸之接頭,例如甘胺酸-絲胺酸雙聯體,並且在CAR之跨膜域及細胞質信號傳導域之間形成連接。
T細胞活化在一些態樣中被描述為由兩類細胞質信號傳導序列介導:经由TCR (初級細胞質信號傳導序列)引發抗原依賴性初級活化之彼等者,以及以抗原依賴性方式起作用以提供二級或共刺激信號(二級細胞質信號傳導序列)之彼等者。在一些態樣中,CAR包括此類信號傳導組分中的一者或兩者。
受體,例如CAR,通常包括至少一個或多個細胞內信號傳導組分。在一些態樣中,CAR包括調控TCR複合體之初級活化之初級細胞質信號傳導序列。以刺激方式起作用之初級細胞質信號傳導序列可能含有信號傳導模體,此等信號傳導模體稱為基於免疫受體酪胺酸之活化模體或ITAM。含有初級細胞質信號傳導序列之ITAM之實例包括衍生自CD3ζ鏈、FcRγ、CD3γ、CD3δ及CD3ε之彼等者。在一些實施例中,CAR中的細胞質信號傳導分子含有細胞質信號傳導域、其部分或衍生自CD3ζ的序列。
在一些實施例中,受體包括TCR複合體之細胞內組分,諸如介導T細胞活化及細胞毒性之TCR CD3鏈,例如CD3ζ鏈。因此,在一些態樣中,抗原結合部分與一個或多個細胞信號傳導模組連接。在一些實施例中,細胞信號傳導模組包括CD3跨膜域、CD3細胞內信號傳導域及/或其他CD跨膜域。在一些實施例中,細胞內組分係或包括CD3-ζ細胞內信號傳導域。在一些實施例中,細胞內組分係或包括來自Fc受體γ鏈之信號傳導域。在一些實施例中,受體(例如,CAR)包括細胞內信號傳導域並且進一步包括一個或多個另外的分子(諸如CD8、CD4、CD25或CD16)之部分,諸如跨膜域及/或鉸鏈部分。例如,在一些態樣中,CAR或其他嵌合受體係CD3-ζ (CD3-z)或Fc受體g以及CD8、CD4、CD25或CD16中的一者之一部分之嵌合分子。
在一些實施例中,在連接CAR或其他嵌合受體時,受體之細胞質域或細胞內信號傳導域活化免疫細胞(例如經工程改造以表現CAR之T細胞)之正常效應子功能或反應中之至少一者。例如,在一些情況下,CAR誘導T細胞之功能,諸如細胞溶解活性或T輔助活性,諸如細胞介素其他因子之分泌。在一些實施例中,使用抗原受體組分或共刺激分子之細胞內信號域之截短部分代替完整之免疫刺激鏈,例如,若其轉導效應子功能信號。在一些實施例中,一個或多個細胞內信號傳導域包括T細胞受體(TCR)之細胞質序列,並且在一些態樣中亦包括在天然上下文中與此類受體協同作用以引發抗原受體接合後信號轉導之共同受體之彼等者。
在天然TCR的上下文中,完全活化通常不僅需要經由TCR進行信號傳導,而且需要共刺激信號。因此,在一些實施例中,為了促進完全活化,用於產生二級信號或共刺激信號之組分亦包括在CAR中。在其他實施例中,CAR不包括用於產生共刺激信號之組分。在一些態樣中,另外的CAR在同一細胞中表現並且提供用於產生二級或共刺激信號之組分。
在一些實施例中,嵌合抗原受體含有T細胞共刺激分子之細胞內域。在一些實施例中,CAR包括共刺激受體之信號傳導域及/或跨膜部分,諸如CD28、4-1BB、0X40、DAP10及ICOS。在一些態樣中,相同之CAR包括活化及共刺激組分兩者。在一些實施例中,嵌合抗原受體含有衍生自T細胞共刺激分子之細胞內域或其功能性變體,諸如在跨膜域及細胞內信號傳導域之間。在一些態樣中,T細胞共刺激分子係CD28或41BB。
在一些實施例中,活化域包括在一個CAR內,而共刺激組分由識別另一個抗原之另一個CAR提供。在一些實施例中,CAR包括活化或刺激CAR、共刺激CAR,兩者均在同一細胞上表現(參見WO2014/055668)。在一些態樣中,細胞包括一種或多種刺激性或活化CAR及/或共刺激CAR。在一些實施例中,細胞進一步包括抑制性CAR (iCAR,參見Fedorov等人,Sci. Transl. Medicine,5(215),2013年12月),諸如識別與疾病或病狀相關及/或對其具有特異性之抗原以外之抗原之CAR,由此通過抑制性CAR與其配體之結合來減少或抑制通過疾病靶向CAR遞送之活化信號,例如,以降低脫靶效應。
在某些實施例中,細胞內信號傳導域包含連接至CD3 (例如,CD3-ζ)細胞內域之CD28跨膜及信號傳導域。在一些實施例中,細胞內信號傳導域包含與CD3ζ細胞內域連接之嵌合CD28及CD137 (4-1BB、TNFRSF9)共刺激域。
在一些實施例中,CAR涵蓋細胞質部分中的一個或多個,例如兩個或更多個共刺激域及活化域,例如主要活化域。例示性CAR包括CD3-ζ、CD28及4-1BB之細胞內組分。
在一些實施例中,細胞內信號傳導域包括4-1BB信號傳導域及CD3-ζ信號傳導域之細胞內組分。在一些實施例中,細胞內信號傳導域包括CD28信號傳導域及CD3ζ信號傳導域之細胞內組分。
在一些實施例中,CAR包含與抗原(例如,腫瘤抗原)結合之細胞外抗原結合域(例如,抗體或抗體片段,諸如scFv)、間隔子(例如含有如本文所述之諸如任一個鉸鏈域)、跨膜域(例如,如本文所述之任一個)、以及細胞內信號傳導域(例如任何細胞內信號傳導域,諸如本文所述之初級信號傳導域或共刺激信號傳導域)。在一些實施例中,細胞內信號傳導域係或包括初級細胞質信號傳導域。在一些實施例中,細胞內信號傳導域另外包括共刺激分子(例如共刺激域)之細胞內信號傳導域。CAR之例示性組分的實例描述於
表 14中。在所提供的各態樣中,CAR中的每種組分的序列可包括在
表 14中列出之任何組合。
表 14
組分 | 序列 | SEQ ID NO: |
細胞外結合域 | ||
抗CD19 scFv(FMC63) | DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS | 1075 |
抗CD19 scFv(FMC63) | DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS | 1076 |
抗BCMA sdAb(FHVH74) | QVQLVESGGGLVQPGGSLRLSCAASGFTFTNHAMSWVRQAPGKGLELVSSISGNGRTTYYADSVKGRFTISRDISKNTLDLQMNSLRAEDTAVYYCAKDGGETLVDSRGQGTLVTVSS | 1077 |
抗BCMA sdAb(FHVH32) | QVQLVESGGGLVQPGGSLRLSCAASGFTFSSHAMTWVRQAPGKGLEWVAAISGSGDFTHYADSVKGRFTISRDNSKNTVSLQMNNLRAEDTAVYYCAKDEDGGSLLGYRGQGTLVTVSS | 1078 |
抗BCMA sdAb(FHVH33) | EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSSISGSGDYIYYADSVKGRFTISRDISKNTLYLQMNSLRAEDTAVYYCAKEGTGANSSLADYRGQGTLVTVSS | 1079 |
抗BCMA sdAb(FHVH93) | EVQLLESGGGLIQPGGSLRLSCAASGFTFSSHAMTWVRQAPGKGLEWVSAISGSGDYTHYADSVKGRFTISRDNSKNTVYLQMNSLRAEDSAVYYCAKDEDGGSLLGHRGQGTLVTVSS | 1080 |
間隔子(例如鉸鏈) | ||
IgG4鉸鏈 | ESKYGPPCPPCP | 1081 |
CD8鉸鏈 | TTTPAPRPPTPAPTIASQPLSLRPE | 1082 |
CD28 | IEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP | 1083 |
跨膜 | ||
CD8 | ACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYC | 1084 |
CD28 | FWVLVVVGGVLACYSLLVTVAFIIFWV | 1085 |
CD28 | MFWVLVVVGGVLACYSLLVTVAFIIFWV | 1214 |
共刺激域 | ||
CD28 | RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS | 1086 |
4-1BB | KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL | 1087 |
主信號傳導域 | ||
CD3ζ | RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR | 1088 |
CD3ζ(Q>K) | RVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR | 1089 |
在一些實施例中,抗原受體進一步包括標記物並且/或者表現CAR或其他抗原受體之細胞進一步包括替代標記物,諸如細胞表面標記物,該標記物可用於確認細胞表現受體之轉導或工程改造。在一些態樣中,標記物包括CD34、NGFR或表皮生長因子受體之全部或部分(例如截短形式),諸如此細胞表面受體(例如,tEGFR)之截短形式。在一些實施例中,編碼標記物之核酸可操作地連接至編碼接頭序列的聚核苷酸,諸如可裂解接頭序列,例如T2A。例如,標記物及視情况接頭序列可以係公開之專利申請第WO2014031687號中揭示之任一者。例如,標記物可以係截短之EGFR (tEGFR),其視情况與接頭序列(諸如T2A可裂解接頭序列)連接。
在一些實施例中,標記物係分子,例如細胞表面蛋白,不天然存在於T細胞上或不天然存在於T細胞之表面上,或其一部分。在一些實施例中,分子係非自分子,例如非自蛋白,亦即,不被細胞過繼轉移到其中的宿主之免疫系統被識別為「自身」之分子。
在一些實施例中,標記物不提供治療功能及/或不產生作用,除了用作基因工程之標記物,例如,用於選擇成功工程改造之細胞。在其他實施例中,標記物可以係治療分子或以其他方式施加一些期望效果之分子,諸如在活體內遇到之細胞之配體,諸如共刺激或免疫檢查點分子,以增強及/或抑制細胞在過繼轉移及與配體遇到時的反應。
在一些情況下,CAR被稱為第一代、第二代及/或第三代CAR。在一些態樣中,第一代CAR係抗原結合後僅提供CD3鏈誘導信號之CAR;在一些態樣中,第二代CAR係提供此類信號及共刺激信號之CAR,諸如包括來自共刺激受體諸如CD28或CD137之細胞內信號傳導域之CAR;在一些態樣中,第三代CAR係包括不同共刺激受體的多個共刺激域之CAR。
例如,在一些實施例中,CAR包含抗體,例如抗體片段、係或包含CD28之跨膜部分或其功能性變體之跨膜域,以及含有CD28或其功能性變體之信號傳導部分及CD3ζ或其功能性變體之信號傳導部分之細胞內信號傳導域。在一些實施例中,CAR包含抗體,例如抗體片段、係或含有CD28之跨膜部分或其功能性變體之跨膜域,以及含有4-IBB或其功能性變體之信號傳導部分及CD3ζ或其功能性變體之信號傳導部分之細胞內信號傳導域。在一些此類實施例中,受體進一步包括間隔子,其含有Ig分子(諸如人類Ig分子)之一部分,諸如Ig鉸鏈,例如IgG4鉸鏈,諸如僅鉸鏈間隔子。
在一些態樣中,間隔子僅含有IgG之鉸鏈區,諸如僅IgG4或IgG之鉸鏈。在其他實施例中,間隔子係或含有Ig鉸鏈,例如,IgG4衍生之鉸鏈,視情况連接至CH2及/或CH3域。在一些實施例中,間隔子係連接至CH2及CH3域之Ig鉸鏈,例如IgG4鉸鏈。在一些實施例中,間隔子係僅連接至CH3域之Ig鉸鏈,例如IgG4鉸鏈。在一些實施例中,間隔子係或包含富含甘胺酸-絲胺酸之序列或其他靈活接頭,諸如已知之靈活接頭。
例如,在一些實施例中,CAR包括:抗體,諸如抗體片段,包括scfv;間隔子,諸如含有免疫球蛋白分子之一部分,諸如鉸鏈區及/或重鏈分子之一個或多個恆定區之間隔子,諸如含有Ig鉸鏈之間隔子;含有全部或一部分CD28衍生之跨膜域之跨膜域;CD28衍生之細胞內信號傳導域及CD3ζ信號傳導域之跨膜域。在一些實施例中,CAR包括抗體或片段諸如scFv、間隔子(諸如含有Ig鉸鏈之間隔子中的任一者)、CD28衍生之跨膜域、4-lBB衍生之細胞內信號傳導域及CD3ζ衍生之信號傳導域。
由投與至個體之細胞表現之重組受體(諸如CAR)通常識別或特異性結合在所治療之疾病或病狀或其細胞中表現、與其相關及/或對其具有特異性之分子。在特異性結合分子例如抗原時,受體通常將免疫刺激性信號(諸如ITAM轉導之信號)遞送至細胞中,從而促進靶向疾病或病狀之免疫反應。例如,在一些實施例中,細胞表現與由疾病或病狀之細胞或組織表現之抗原或與疾病或病狀相關之抗原特異性結合之CAR。
b.
T 細胞受體抗原受體 (TCR)
在一些實施例中,與所提供的方法、用途、製品或組合物結合使用之工程改造細胞(諸如T細胞)係表現T細胞受體(TCR)或其抗原結合部分之細胞,該TCR或其抗原結合部分識別靶多肽之肽抗原决定基或T細胞抗原决定基,諸如腫瘤、病毒或自身免疫蛋白之抗原。
在一些實施例中,「T細胞受體」或「TCR」係含有可變a鏈及b鏈(分別為TCRα及TCRβ)或可變g鏈及d鏈(分別為TCRα及TCRβ)或其抗原結合部分並且能夠與結合至MHC分子之肽特異性結合之分子。在一些實施例中,TCR呈ab形式。通常,以ab及gd形式存在之TCR通常結構類似,但表現其T細胞可具有不同之解剖位置或功能。TCR可在細胞之表面上發現或呈可溶形式。通常,TCR在T細胞(或T淋巴細胞)之表面上發現,其中其通常負責識別與主要組織相容性複合體(MHC)分子結合之抗原。
除非另有說明,否則術語「TCR」應理解為涵蓋完全TCR以及抗原結合部分或其抗原結合片段。在一些實施例中,TCR係完整或全長TCR,包括呈ab形式或gd形式之TCR。在一些實施例中,TCR係小於全長TCR但與在MHC分子中結合之特定肽結合之抗原結合部分,諸如與MHC肽複合體結合。在一些情況下,TCR之抗原結合部分或片段可僅含有全長或完整TCR之結構域之一部分,但亦能夠結合與完全TCR結合之肽抗原决定基,諸如MHC肽複合體。在一些情況下,抗原結合部分包含TCR之可變域,諸如TCR之可變a鏈及可變b鏈,足以形成與特定MHC肽複合體結合之結合位點。通常,TCR之可變鏈含有涉及識別肽、MHC及/或MHC肽複合體之互補決定區。
c.
多靶向
在一些實施例中,與所提供的方法、用途、製品及組合物結合使用之細胞包括採用多靶向策略之細胞,諸如細胞上兩種或更多種基因工程改造受體之表現,每個識別不同抗原中的相同抗原並且通常各自包括不同之細胞內信號傳導組分。例如,在WO 2014055668(描述了活化及共刺激CAR之組合,例如,靶向單獨存在於脫靶上之兩種不同抗原,例如正常細胞,但僅一起存在於待治療之疾病或病狀之細胞上)及Fedorov等人,Sci. Transl. Medicine,5(215) (2013) (描述了表現活化及抑制性CAR之細胞,諸如其中活化之CAR與在正常或非患病細胞及待治療疾病或病狀之細胞上表現之一種抗原結合之那些,並且抑制性CAR與僅在正常細胞或不期望治療之細胞上表現之另一種抗原結合)中描述了此類多靶向策略。
例如,在一些實施例中,細胞包括表現第一基因工程改造抗原受體(例如,CAR)之受體,該受體通常在特異性結合第一受體識別之抗原(例如,第一抗原)後能夠向細胞誘導活化或刺激信號。在一些實施例中,細胞進一步包括第二基因工程改造抗原受體(例如,CAR),例如嵌合共刺激受體,該受體通常在特異性結合第二受體識別之第二抗原後能夠向免疫細胞誘導共刺激信號。在一些實施例中,第一抗原及第二抗原係相同的。在一些實施例中,第一抗原及第二抗原係不同的。
在一些實施例中,第一及/或第二基因工程改造抗原受體(例如CAR)能夠將活化信號誘導到細胞。在一些實施例中,受體包括含有ITAM或ITAM樣模體之細胞內信號傳導組分。在一些實施例中,由第一受體誘導之活化涉及信號轉導或細胞中蛋白質表現之變化,從而導致免疫反應之開始,諸如ITAM磷酸化及/或ITAM介導之信號轉導級聯之啟動、免疫突觸之形成及/或結合受體(例如CD4或CD8等)附近之分子之聚類、一種或多種轉錄因子之活化,諸如NF-KB及/或AP-1,及/或誘導因子諸如細胞介素之基因表現、增殖及/或存活。
在一些實施例中,第一及/或第二受體包括共刺激受體諸如CD28、CD137 (4-1BB)、OX40及/或ICOS之細胞內信號傳導域或區。在一些實施例中,第一及第二受體包括不同之共刺激受體之細胞內信號傳導域。在一個實施例中,第一受體含有CD28共刺激信號傳導區,並且第二受體含有4-IBB共刺激信號傳導區,或反之亦然。
在一些實施例中,第一及/或第二受體包括含有ITAM或ITAM樣模體之細胞內信號傳導域及共刺激受體之細胞內信號傳導域兩者。
在一些實施例中,第一受體包含含有ITAM或ITAM樣模體之細胞內信號傳導域,並且第二受體包含共刺激受體之細胞內信號傳導域。共刺激信號與在同一細胞中誘導之活化信號組合係產生免疫反應之一種,諸如穩健及持續免疫反應,諸如增加之基因表現、細胞介素之分泌及其他因素,以及T細胞介導之效應子功能,諸如細胞殺傷。
在一些實施例中,單獨的第一受體之連接或單獨的第二受體之連接均不誘導穩健之免疫反應。在一些態樣中,若僅連接一個受體,則細胞變得耐受或對抗原不反應,或抑制及/或不誘導增殖或分泌因子或執行效應子功能。然而,在一些此類實施例中,當該複數個受體連接時,諸如在遇到表現第一抗原及第二抗原之細胞時,實現期望之反應,諸如完全免疫活化或刺激,例如,如藉由一種或多種細胞介素之分泌、增殖、持久性及/或進行免疫效應功能諸如目標細胞之細胞毒性殺傷所指示的。
在一些實施例中,該兩種受體分別向細胞誘導活化及抑制信號,使得受體中的一者與其抗原之結合活化細胞或誘導反應,但第二抑制性受體與其抗原結合會誘導抑制或減弱該反應之信號。實例係活化CAR及抑制性CAR或iCAR之組合。例如,可使用此類策略,其中活化CAR結合在疾病或病狀中表現但亦在正常細胞上表現之抗原,並且抑制性受體與在正常細胞上表現但不在疾病或病狀之細胞上表現之單獨抗原結合。
在一些實施例中,在與特定疾病或病狀相關之抗原在非患病細胞上表現及/或在工程改造細胞本身上表現之情況下採用多靶向策略,無論係瞬時的(例如,在與基因工程相關之刺激時)抑或永久的。在此類情況下,藉由需要連接兩個單獨及單個特異性抗原受體,可改良特異性、選擇性及/或功效。
在一些實施例中,該複數個抗原(例如,第一抗原及第二抗原)在所靶向之細胞、組織或疾病或病狀上(諸如癌細胞上)表現。在一些態樣中,細胞、組織、疾病或病狀係多發性骨髓瘤或多發性骨髓瘤細胞。在一些實施例中,該複數個抗原中的一者或多者通常亦在不期望用細胞療法靶向之細胞上表現,諸如正常或非患病細胞或組織,及/或工程改造細胞本身。在此類實施例中,藉由需要連接多個受體來實現細胞之反應,實現了特異性及/或功效。
d.
嵌合自動抗體受體 (CAAR)
在一些實施例中,重組受體係嵌合自身抗體受體(CAAR)。在一些實施例中,CAAR結合,例如特異性結合或識別自身抗體。在一些實施例中,表現CAAR之細胞(諸如經工程改造以表現CAAR之T細胞)可用於結合及殺死表現自身抗體之細胞,但不能殺死表現正常抗體之細胞。在一些實施例中,表現CAAR之細胞可用於治療與自身抗原之表現相關之自身免疫疾病,諸如自身免疫疾病。在一些實施例中,表現CAAR之細胞可靶向最終產生自身抗體並在細胞表面上顯示自身抗體之B細胞,將此等B細胞標記為疾病特異性目標以進行治療干預。在一些實施例中,表現CAAR之細胞可藉由使用抗原特異性嵌合自身抗體受體靶向引起疾病之B細胞來有效地靶向及殺死自身免疫疾病中的病原性B細胞。在一些實施例中,重組受體係CAAR,諸如美國專利申請公開案第US 2017/0051035號中描述之任一者。
在一些實施例中,CAAR包含自身抗體結合域、跨膜域及一個或多個細胞內信號傳導區或域(亦可互換地稱為細胞質信號傳導域或區)。在一些實施例中,細胞內信號傳導區包含細胞內信號傳導域。在一些實施例中,細胞內信號傳導域係或包含初級信號傳導域、能夠刺激及/或誘導T細胞中的主要活化信號之信號傳導域、T細胞受體(TCR)組分的信號傳導域(例如CD3-ζ鏈或其功能性變體或信號傳導部分之細胞內信號傳導域或區)及/或包含基於免疫受體酪胺酸之活化模體(ITAM)之信號傳導域。
在一些實施例中,自身抗體結合域包含自身抗原或其片段。自身抗原之選擇可取決於所靶向之自身抗體之類型。例如,可選擇自身抗原,因為其識別與特定疾病狀態(例如自身免疫疾病,諸如自身抗體介導之自身免疫疾病)相關之目標細胞(諸如B細胞)上之自身抗體。在一些實施例中,自身免疫疾病包括尋常型天疱瘡(PV)。例示性自身抗原包括橋粒芯糖蛋白1(Dsgl)及Dsg3。
在一些實施例中,所編碼之核酸有效連接至「陽性目標細胞特異性調控元件」(或陽性TCSRE)。在一些實施例中,陽性TCSRE係功能性核酸序列。在一些實施例中,陽性TCSRE包含啟動子或增強子。在一些實施例中,TCSRE係增加目標細胞中外源藥劑水準之核酸序列。在一些實施例中,陽性目標細胞特異性調控元件包括T細胞特異性啟動子、T細胞特異性增強子、T細胞特異性剪接位點、延長RNA或蛋白質之半衰期之T細胞特異性位點、T細胞特異性mRNA核導出促進位點、T細胞特異性轉譯增強位點或T細胞特異性轉譯後修飾位點。在一些實施例中,T細胞特異性啟動子係Immgen consortium中描述之啟動子,其全文以引用方式併入本文,例如,T細胞特異性啟動子係IL2RA (CD25)、LRRC32、FOXP3或IKZF2啟動子。在一些實施例中,T細胞特異性啟動子或增強子係Schmidl等人,Blood,2014年4月24日,123(17):e68-78中描述之啟動子或增強子,其全文以引用方式併入本文。在一些實施例中,T細胞特異性啟動子係前述中的任一者之轉錄活性片段。在一些實施例中,T細胞特異性啟動子係與前述中的任一者有至少70%、75%、80%、85%、90%、95%、96%、97%、98%或99%同一性之變體。
在一些實施例中,所編碼之核酸有效連接至「陰性目標細胞特異性調控元件」(或陰性TCSRE)。在一些實施例中,陰性TCSRE係功能性核酸序列。在一些實施例中,陰性TCSRE係引起非目標細胞中病毒載體抑制之降解之miRNA識別位點。在一些實施例中,外源藥劑有效連接至「非目標細胞特異性調控元件」(或NTCSRE)。在一些實施例中,NTCSRE包含與目標細胞相比在非目標細胞中降低外源藥劑水準之核酸序列。在一些實施例中,NTCSRE包含非目標細胞特異性miRNA識別序列、非目標細胞特異性蛋白酶識別位點、非目標細胞特異性泛素連接酶位點、非目標細胞特異性轉錄阻遏位點或非目標細胞特異性表觀遺傳阻遏位點。在一些實施例中,NTCSRE包含組織特異性miRNA識別序列、組織特異性蛋白酶識別位點、組織特異性泛素連接酶位點、組織特異性轉錄阻遏位點或組織特異性表觀遺傳阻遏位點。在一些實施例中,NTCSRE包含非目標細胞特異性miRNA識別序列、非目標細胞特異性蛋白酶識別位點、非目標細胞特異性泛素連接酶位點、非目標細胞特異性轉錄阻遏位點或非目標細胞特異性表觀遺傳阻遏位點。在一些實施例中,NTCSRE包含非目標細胞特異性miRNA識別序列,並且miRNA識別序列能夠由miR3 1、miR363或miR29c中的一者或多者結合。在一些實施例中,NTCSRE被定位或編碼在編碼外源藥劑之轉錄區內,視情况其中由轉錄區產生之RNA包含UTR或編碼區內之miRNA識別序列。
在一些實施例中,可將包含本文所述之抗CD8 scFv或sdAb組合物之病毒載體投與至個體,例如哺乳動物,例如人類。在此類實施例中,個體可處於患有特定疾病或病狀(例如,本文所述之疾病或病狀)之症狀之風險,或者可被診斷為或鑑定為患有該特定疾病或病狀。
在一些態樣中,使靜息或未活化之T細胞與包括CD8結合劑之本揭示之病毒載體(例如逆轉錄病毒載體或慢病毒載體)接觸。接觸可在活體外進行(例如,用衍生自健康供體或需要細胞療法之供體之T細胞)或藉由向個體投與病毒載體活體內進行。
在一些實施例中,不用一種或多種T細胞刺激分子(例如抗CD-3抗體)、一種或多種T細胞共刺激分子及/或一種或多種T細胞活化細胞介素治療靜息或未活化之T細胞。在一些實施例中,不用一種或多種T細胞刺激分子(例如抗CD-3抗體)、一種或多種T細胞共刺激分子及/或一種或多種T細胞活化細胞介素中之任一者治療靜息或未活化之T細胞。
在另外的態樣中,該應用包括向包括抗CD8結合劑之病毒載體之個體投與之方法,其中未向該個體投與或尚未投與T細胞活化治療。在一些實施例中,T細胞活化治療包括一種或多種T細胞刺激分子(例如,抗CD-3抗體)、一種或多種T細胞共刺激分子及/或一種或多種T細胞活化細胞介素。在一些實施例中,未向個體投與或尚未投與一種或多種T細胞刺激分子(例如,抗CD-3抗體)、一種或多種T細胞共刺激分子及/或一種或多種T細胞活化細胞介素之任一者。在一些實施例中,T細胞活化治療係淋巴清除。在某些實施例中,在投與病毒載體之前或之後1個月內,未向個體投與或尚未投與T細胞活化治療。在一些實施例中,在投與病毒載體之前1個月內,諸如在投與病毒載體之前4週內或為或約為4週、3週內或為或約為3週、2週內或為或約為2週、1週內或為或約為1週,諸如為或約為1天、2天、3天、4天、5天、6天或7天,未向個體投與或尚未投與T細胞活化治療。在一些實施例中,在投與病毒載體之後1個月內,諸如在投與病毒載體之後4週內或為或約為4週、3週內或為或約為3週、2週內或為或約為2週、1週內或為或約為1週,諸如為或約為1天、2天、3天、4天、5天、6天或7天,未向個體投與T細胞活化治療。
在一些態樣中,本揭示之病毒載體不包括一種或多種T細胞刺激分子(例如,抗CD-3抗體)、一種或多種T細胞共刺激分子及/或一種或多種T細胞活化細胞介素。
眾所周知,使用抗CD3抗體可活化T細胞。抗CD3抗體可為任何物種,例如小鼠、兔、人類、人源化或駱駝科。例示性抗體包括OKT3、CRIS-7、包括在DYNABEADS人類T-活化劑CD3/CD28 (Thermo Fisher)中之I2C抗CD3抗體,以及已批准及臨床研究之分子的抗CD3域,諸如博納吐單抗(blinatumomab)、卡妥索單抗(catumaxomab)、伏妥珠單抗(fotetuzumab)、特立妥單抗(teclistamab)、厄妥索單抗(ertumaxomab)、艾可瑞妥單抗(epcoritamab)、塔奎妥單抗(talquetamab)、奧尼妥單抗(odronextamab)、賽貝妥單抗(cibistamab)、奧瑞達妥單抗(obrindatamab)、泰妥單抗(tidutamab)、度妥昔珠單抗(duvortuxizumab)、索利托單抗(solitomab)、艾努維妥單抗(eluvixtamab)、帕努妥單抗(pavurutamab)、替坡迪妥單抗(tepoditamab)、維克妥單抗(vibecotamab)、帕拉莫妥單抗(plamotamab)、格菲妥單抗(glofitamab)、艾替瑞妥單抗(etevritamab)及塔拉妥單抗(tarlatamab)。
在一些實施例中,該一個或多個T細胞共刺激分子包括CD28配體(例如,CD80及CD86);與CD28諸如CD28.2結合之抗體,該抗CD28抗體包括在DYNABEADS人類T-活化劑CD3/CD28(賽默飛世爾)中並且抗CD28域揭示於US2020/0199234、US2020/0223925、US2020/0181260、US2020/0239576、US2020/0199233、US2019/0389951、US2020/0299388、US2020/0399369及US2020/0140552中;CD137配體(CD137L);抗CD137抗體,諸如烏瑞蘆單抗(urelumab)及烏托魯單抗(utomilumab);ICOS配體(ICOS-L);以及抗ICOS抗體,諸如菲阿迪利單抗(feladilimab)、伏派利單抗(vopratelimab)以及艾珠利單抗(izuralimab)之抗ICOS域。
在一些實施例中,該一種或多種T細胞活化細胞介素包括IL-2、IL-7、IL-15、IL-21、干擾素(例如,干擾素-γ)以及其功能性變體及修飾形式。
可藉由破壞個體之淋巴細胞及T細胞之各種治療來誘導淋巴清除。例如,淋巴清除可包括清髓性化學療法,諸如氟達拉濱(fludarabine)、環磷醯胺(cyclophosphamide)、苯達莫司汀(bendamustine)以及其組合。亦可藉由對個體之輻射(例如,全身輻射)來誘導淋巴清除。
在一些實施例中,靶向脂質顆粒源來自投與靶向病毒載體組合物之相同個體。在其他實施例中,其係不同的。在一些實施例中,靶向病毒載體及受體組織源可為自體的(來自同一個體)或異源的(來自不同之個體)。在一些實施例中,本文所述之靶向病毒載體組合物之供體組織可為與受體組織不同之組織類型。在一些實施例中,供體組織可為肌肉組織,並且受體組織可為結締組織(例如,脂肪組織)。在其他實施例中,供體組織及受體組織可以係相同或不同之類型,但來自不同之器官系統。
在一些實施例中,可將本文所述之靶向脂質顆粒(例如病毒載體)組合物投與至患有癌症、自身免疫疾病、感染性疾病、代謝疾病、神經退行性疾病或遺傳疾病(例如,酶缺乏症)之個體。在一些實施例中,個體需要再生。
在一些實施例中,癌症係T細胞介導之癌症。在另一個實施例中,CAR之抗原結合部分之部分被設計成治療特定癌症。在一些實施例中,靶向病毒載體可用於治療癌症及病症,包括但不限於非霍奇金淋巴瘤(NHL)、急性淋巴細胞白血病(ALL)、慢性淋巴細胞白血病(CLL)、多發性骨髓瘤等。在一些實施例,靶向病毒載體可用於治療B細胞惡性腫瘤,例如難治性B細胞惡性腫瘤。
在一些實施例中,靶向病毒載體與抑制膜融合之蛋白質之抑制劑共投與。例如,Suppressyn係抑制細胞-細胞融合之人類蛋白質(Sugimoto等人,「A novel human endogenous retroviral protein inhibits cell-cell fusion」Scientific Reports 3: 1462 DOI: 10.1038/srep01462)。在一些實施例中,靶向脂質顆粒與suppressyn之抑制劑(例如,siRNA或抑制性抗體)共投與。
實例
可藉由以下非限制性實例進一步描述本揭示,其中熟習此項技術者已知之標準技術及類似於此等實例中描述之技術之技術可在適當之情況下使用。應當理解,技術人員將設想與本文提供之揭示內容一致之另外的實施例。
實例 1 : CD8 scfv 及 VHH 的 表徵
該實例描述了生成及表徵用CD8特異性scFv或VHH功能化之尼帕G/F假型化慢病毒之功能力價之方法。消除尼帕G與肝配蛋白B2/B3之結合並用CD8特異性結合劑功能化尼帕G允許用慢病毒載體靶向表現CD8之細胞。
慢病毒生產如下進行:轉染前24小時接種HEK-293LX細胞。在轉染當天,用慢病毒包裝質體、編碼GFP之慢病毒轉移質體(pSFFV-GFP),以及編碼重新靶向CD8受體之尼帕G蛋白(NiV-G(CD8))及尼帕F融合蛋白(NiV-Fd22)之質體轉染HEK-293LX細胞。在24小時之後,更換培養基,並且再過24小時之後,收穫慢病毒。為了收穫慢病毒,從HEK293LX細胞中去除上清液並以1000×g離心5分鐘。去除上清液並立即添加至CD8陽性目標細胞或T細胞中,或在-80℃下冷凍以供以後使用。
使用幾種細胞株表徵上述慢病毒載體之特異性及轉導效率。自SupT1人類T淋巴母細胞產生SupT1 CD8αβ基因剔除株。在轉導當天,將SupT1及SupT1 CD8αβ基因剔除細胞、表現南平頂猴CD8αβ及HEK293LX背景株之HEK293LX細胞接種在96孔細胞板中。兩小時之後,慢病毒被連續稀釋並且添加至受體細胞中。將慢病毒及細胞在37℃下於5%CO
2下溫育三天,並且藉由流動式細胞測量術分析GFP表現。簡而言之,藉由胰蛋白酶消化自96孔細胞板中收集過表現南平頂猴CD8αβ細胞之HEK293LX及HEK293LX細胞,轉移至96孔U形底部樣本板中,並且藉由以1000×g離心5分鐘沈澱。然後將細胞重懸於200 µL之PBS中,然後進行流動式細胞測量術分析。藉由離心沈澱SupT1及SupT1 CD8αβ基因剔除細胞並重懸於200 µL之PBS+2% FBS中用於流動式細胞測量術分析。
使用BD Celesta細胞儀量測細胞之GFP螢光。GFP用488nm激光激發並在捕獲513±26nm處的發射。前向及側向散射圈選最初用於捕獲細胞大小之事件並丟棄小碎片。藉由在陰性對照細胞樣本(未用慢病毒處理之細胞)顯示<0.5%之GFP表現陽性事件之最低水準處進行圈選來確定GFP陽性事件。然後評估圈選細胞對GFP螢光呈陽性之總細胞中GFP陽性細胞之%。為了計算慢病毒功能力價,使用顯示介於5%及20%細胞之間的GFP陽性%之轉導細胞孔來確定力價。病毒力價計算之公式:滴定={(F×Cn)/V}×DF。F係藉由流動式細胞測量術確定之GFP陽性細胞之頻率;Cn=感染之目標細胞之總數。V=接種物之體積,並且DF=稀釋因子(參見圖1)。
對具有CD8結合劑97 (VHH)及46 (scFv)之慢病毒在上述另外的非CD8表現細胞株及CD8陽性細胞株SupT1上進行了進一步測試(參見圖2)。細胞在各種稀釋因子下之最大轉導如下所示(表15)。VSV-G用作非細胞特異性對照。此等結果表明結合劑對CD8具有特異性。
表 15.
CD8 結合劑 97 | CD8 結合劑 46 | VSV-G | |
SupT1 | 87.0 | 99.0 | 98.0 |
293 Lenti-X | 6.0 | 3.0 | 81.0 |
Ramos | 9.0 | 4.0 | 68.0 |
HUVEC | 10.0 | 5.0 | 94.0 |
C2C12 | 0 | 0 | 63.0 |
HEL 92.1.7 | 0 | 2.0 | 100.0 |
HeLa | 1.0 | 0 | 97.0 |
HepG2 | 0 | 0 | 99.0 |
hFOB | 0.1 | 0.6 | 68.3 |
HULEC-5a | 2.0 | 4.0 | 83.0 |
Kasumi 1 | 0 | 3.0 | 74.0 |
SK-N-AS | 1.0 | 2.0 | 99.0 |
U-937 | 0 | 0 | 100.0 |
亦評估了與人及南平頂猴CD8的結合。在轉導當天,將SupT1及SupT1 CD8αβ基因剔除細胞株、表現南平頂猴CD8αβ及HEK293LX背景株之HEK293LX細胞接種在96孔細胞板中。兩小時之後,慢病毒被連續稀釋並且添加至受體細胞中。將慢病毒及細胞在37℃下於5%CO
2下溫育三天,並且藉由流動式細胞測量術分析GFP表現。簡而言之,藉由胰蛋白酶消化自96孔細胞板中收集過表現南平頂猴CD8αβ細胞之HEK293LX及HEK293LX細胞,轉移至96孔U形底部樣本板中,並且藉由以1000×g離心5分鐘沈澱。然後將細胞重懸於200 µL之PBS中,然後進行流動式細胞測量術分析。藉由離心沈澱SupT1及SupT1 CD8αβ基因剔除細胞並重懸於200 µL之PBS+2% FBS中用於流動式細胞測量術分析。
使用BD Celesta細胞儀量測細胞之GFP螢光。GFP用488nm激光激發並捕獲513±26nm處捕獲的發射。前向及側向散射圈選最初用於捕獲細胞大小之事件並丟棄小碎片。藉由在陰性對照細胞樣本(未用慢病毒處理之細胞)顯示<0.5%之GFP表現陽性事件之最低水準處進行圈選來確定GFP陽性事件。然後評估圈選細胞對GFP螢光呈陽性之總細胞中GFP陽性細胞之%。為了計算慢病毒功能力價,使用顯示介於5%及20%細胞之間的GFP陽性%之轉導細胞孔來確定力價。病毒力價計算之公式:滴定={(F×Cn)/V}×DF。F係藉由流動式細胞測量術確定之GFP陽性細胞之頻率;Cn=感染之目標細胞之總數。V=接種物之體積,並且DF=稀釋因子。人類CD 8(SupT1)之力價呈現於圖2中。南平頂猴CD8 (表現南平頂猴CD8αβ之HEK293LX細胞)之力價呈現於圖3中。
慢病毒生產如下進行:轉染前24小時接種LV-Max HEK293細胞。在轉染當天,用慢病毒包裝質體、編碼GFP之慢病毒轉移質體(pSFFV-GFP),以及編碼重新靶向CD8受體之尼帕G蛋白(NiV-G(CD8))及尼帕F融合蛋白(NiV-Fd22)之質體轉染LV-Max HEK293細胞。在兩天後,收集轉染細胞之上清液,通過0.45 µm過濾器,並藉由120,000×g超速離心90分鐘進行濃縮。在超速離心後,將慢病毒丸粒重懸浮在PBS中,或者立即用於轉導,或者分裝並在-80℃下冷凍以備後用。
由HEK293LX細胞產生人類CD8α及人類CD8αβ過表現細胞株。在轉導當天,將人類CD8α、人類CD8αβ過表現及HEK293LX背景細胞株接種在96孔細胞板中。兩小時之後,慢病毒被連續稀釋並且添加至受體細胞中。將慢病毒及細胞在37℃下於5%CO
2下溫育三天,並且藉由流動式細胞測量術分析GFP表現。簡而言之,藉由胰蛋白酶消化自96孔細胞板中收集人類CD8α、人類CD8αβ過表現及HEK293LX背景細胞株,轉移至96孔U形底部樣本板中,並且藉由以1000×g離心5分鐘沈澱。然後將細胞重懸於200 µL之PBS中,然後進行流動式細胞測量術分析。
使用BD Celesta細胞儀量測細胞之GFP螢光。GFP用488nm激光激發並捕獲513±26nm處的發射。前向及側向散射圈選最初用於捕獲細胞大小之事件並丟棄小碎片。藉由在陰性對照細胞樣本(未用慢病毒處理之細胞)顯示<0.5%之GFP表現陽性事件之最低水準處進行圈選來確定GFP陽性事件。然後評估圈選細胞對GFP螢光呈陽性之總細胞中GFP陽性細胞之%。為了計算慢病毒功能力價,使用顯示介於5%及20%細胞之間的GFP陽性%之轉導細胞孔來確定力價。病毒力價計算之公式:滴定={(F×Cn)/V}×DF。F係藉由流動式細胞測量術確定之GFP陽性細胞之頻率;Cn=感染之目標細胞之總數。V=接種物之體積,並且DF=稀釋因子。如圖4所示,CD8結合劑46、1、52及17在人類CD8α及人類CD8αβ過表現細胞株中顯示出類似之力價,表明彼等結合劑對CD8α具有特異性。然而,與僅表現CD8α之細胞株相比,CD8結合劑97對人類CD8αβ過表現細胞株具有顯著更高之力價,表明CD8結合劑97對CD8β具有特異性。
與人類 CD8 αβ 異源二聚體的結合評估及親和力
結合劑作為帶有v5標籤之scFv之粗製品生成,並被捕獲至鏈黴親和素BLI感測器上,該感測器用抗V5標籤抗體功能化,用於經由ForteBio Octet HTX儀器進行分析。將感測器暴露於300nM之人類CD8αβ,然後解離成測定緩衝液。藉由用陰性對照scFv之緩衝液扣除並使用1:1 Langmuir模型擬合來參考陽性結合反應,以確定解離速率。
scFv之子集生成為帶有mIgG2a Fc標籤之重組純化scFv。將scFv-mIgG2a蛋白裝載至抗小鼠Fc捕獲感測器上,以經由ForteBio Octet RED96儀器進行分析。將感測器暴露於從500nM開始之人類CD8αβ之系列稀釋,然後解離至測定緩衝液中。藉由緩衝液扣除並使用1:1 Langmuir模型擬合來參考陽性結合反應,以確定締合速率及解離速率並計算K
D。
與人類 CD8 α 的結合評估
結合劑作為帶有v5標籤之scFv之粗製品生成,並被捕獲至HC200M SPRi感測器上,該感測器用抗V5標籤抗體功能化,用於經由Carterra LSA儀器進行分析。在感測器上注射自5 µM開始之人類CD8α系列稀釋,然後注射用於解離之測定緩衝液。藉由用陰性對照scFv之緩衝液扣除並使用1:1 Langmuir模型擬合來參考陽性結合反應,以確定結合反應。
與人類 CD8 β 的結合評估
scFv之子集生成為帶有mIgG2a Fc標籤之重組純化scFv或VHH。將人類CD8β蛋白生物素醯化並裝載至鏈黴親和素感測器上,以經由ForteBio Octet RED96儀器進行分析。將感測器暴露於自500nM開始之scFv-mIgG2a或VHH-mIgG2a濃度之系列稀釋,然後解離至測定緩衝液中。藉由緩衝液扣除並使用1:1 Langmuir模型擬合來參考陽性結合反應,以確定締合速率及解離速率並計算K
D。
與 cyno CD8 α 同源二聚體的結合評估
結合劑作為帶有v5標籤之scFv之粗製品生成,並被捕獲至HC200M SPRi感測器上,該感測器用抗V5標籤抗體功能化,用於經由Carterra LSA儀器進行分析。在感測器上注射自1 µM開始之cyno CD8α-hFc系列稀釋,然後注射用於解離之測定緩衝液。藉由用陰性對照scFv之緩衝液扣除並使用1:1 Langmuir模型擬合來參考陽性結合反應,以確定解離速率。
scFv及VHH之子集生成為帶有mIgG2a Fc標籤之重組純化scFv或VHH。將scFv-mIgG2a或VHH-mIgG2a蛋白裝載至抗小鼠Fc捕獲感測器上,以經由ForteBio Octet RED96儀器進行分析。將感測器暴露於自500 nM開始的cyno CD8α-hFc的濃度的系列稀釋,然後解離至測定緩衝液中。藉由緩衝液扣除並使用1:1 Langmuir模型擬合來參考陽性結合反應,以確定締合速率及解離速率並計算K
D。
選擇CD8結合劑之結合親和力示於
表 16中。
表 16. 選擇 CD8 scfv 的接合彙總。
實例 2 :用 CD8 結合劑假型化的病毒載體的產生及表徵 用於產生尼帕 G 假型化病毒的方法
CD8 結合劑 | 粗力價 Sup1T1(TU/mL) | 最高反應 (nm) | K D(M) | k on ( 1/Ms) | k off(1/s) |
46 | 4.90E+06 | 0.4906 | 9.52E-08 | 8.63E+04 | 8.21E-03 |
1 | 1.05E+06 | 0.1334 | 2.03E-08 | 3.08E+04 | 6.23E-04 |
5 | 1.83E+06 | 0.2201 | 4.01E-07 | 3.84E+04 | 1.54E-02 |
97 | 3.47E+06 | 0.4651 | 5.30E-09 | 5.14E+04 | 2.72E-04 |
該實例描述了生成及表徵用CD8特異性scFv或VHH功能化之尼帕G/F假型化慢病毒之功能力價之方法。消除尼帕G與肝配蛋白B2/B3之結合並用CD8特異性結合劑功能化尼帕G允許用慢病毒載體靶向表現CD8之細胞。藉由在C末端添加甘胺酸/絲胺酸接頭(G
4S×3)及隨後之CD8特異性結合劑(scFv或VHH)對尼帕G(d34、E501A;W504A;Q530A;E533A)進行修飾。尼帕G-接頭-結合劑構築體經密碼子最佳化以在人類細胞中表現,並次选殖至表現載體中用於慢病毒生成。
粗慢病毒生產如下進行:轉染前24小時接種HEK-293LX細胞。在轉染當天,用慢病毒包裝質體(psPAX2)、編碼GFP之慢病毒轉移質體(pSFFV-GFP),以及編碼重新靶向CD8受體之尼帕G蛋白(NiV-G(CD8))及尼帕F融合蛋白(NiV-Fd22)之質體轉染HEK-293LX細胞。在24小時之後,更換培養基,並且再過24小時之後,收穫慢病毒。為了收穫慢病毒,自HEK293LX細胞中去除上清液並以1000×g離心5分鐘。去除上清液並立即添加至CD8陽性目標細胞或T細胞中,或在-80℃下冷凍以供以後使用。
濃縮慢病毒生產如下進行:轉染前24小時接種LV-Max HEK293細胞。在轉染當天,用慢病毒包裝質體(psPAX2)、編碼GFP之慢病毒轉移質體(pSFFV-GFP),以及編碼重新靶向CD8受體之尼帕G蛋白(NiV-G(CD8))及尼帕F融合蛋白(NiV-Fd22)之質體轉染LV-Max HEK293細胞。在兩天後,收集轉染細胞的上清液,通過0.45 µm過濾器,並藉由120,000×g超速離心90分鐘進行濃縮。在超速離心後,將慢病毒丸粒重懸浮在PBS中,或者立即用於轉導,或者分裝並在-80℃下冷凍以備後用。
人類及南平頂猴原代細胞的轉導效率
慢病毒生產如下進行:轉染前24小時接種LV-Max HEK293細胞。在轉染當天,用慢病毒包裝質體(psPAX2)、編碼GFP之慢病毒轉移質體(pSFFV-GFP),以及編碼重新靶向CD8受體之尼帕G蛋白(NiV-G(CD8))及尼帕F融合蛋白(NiV-Fd22)之質體轉染LV-Max HEK293細胞。在兩天後,收集轉染細胞之上清液,通過0.45 µm過濾器,並藉由120,000×g超速離心90分鐘進行濃縮。在超速離心後,將慢病毒丸粒重懸浮在PBS中,或者立即用於轉導,或者分裝並在-80℃下冷凍以備後用。
原代分離之人類PanT細胞或PBMC係自StemCell Technologies公司獲得,並用在培養基中補充有IL-2之抗人類CD3/CD28活化。南平頂猴PBMC係自BioIVT公司獲得,並使用來自Miltenyi Biotec公司之抗CD3/CD28珠粒活化,其中在培養基中補充IL-2。在活化之後72小時,收集細胞並將其接種在96孔板中。對慢病毒進行系列稀釋,並將其添加至原代PanT或PBMC細胞中。在25℃下以1000×g進行90分鐘旋轉感染。然後將細胞在37℃下用5% CO
2溫育72小時。在72小時之後,經由以1000×g離心5分鐘收集細胞,並用活/死排除染料劑及抗體組染色以鑑定CD3陽性、CD8陽性及CD4陽性群體。
使用BD Celesta細胞儀量測細胞之GFP螢光。前向及側向散射圈選最初用於捕獲細胞大小之事件並丟棄小碎片。前向散射高度及前向散射寬度用於捕獲單個細胞。選擇對活/死染色劑呈陰性之事件。對於PanT細胞,對CD8陽性及GFP陽性或CD4陰性及GFP陽性之細胞進行圈選,以評估表現CD8之細胞中的轉導。CD8陽性細胞中的GFP表現係基於來自CD8陽性群體或CD4陰性群體之表現GFP之細胞之百分比計算的。藉由在陰性對照細胞樣本(未用慢病毒處理之細胞)顯示<0.5%之GFP表現陽性事件之最低水準處進行圈選來確定GFP陽性事件。為了計算慢病毒功能力價,使用顯示介於5%及20%細胞之間的CD8陽性細胞之GFP陽性%之轉導細胞孔來確定力價。病毒力價計算之公式:滴定={(F×Cn)/V}×DF。F係藉由流動式細胞測量術確定之GFP陽性細胞之頻率;Cn=感染之目標細胞之總數。V=接種物之體積,並且DF=稀釋因子。
對於PBMC細胞,使用BD Fortessa細胞儀量測細胞之GFP螢光。將細胞圈選為CD3陽性,然後對CD8陽性及GFP陽性或CD4陰性及GFP陽性進行圈選,以評估表現CD8之細胞中的轉導。CD8陽性細胞中的GFP表現係基於來自CD8陽性群體或CD4陰性群體之表現GFP之細胞之百分比計算的。藉由在陰性對照細胞樣本(未用慢病毒處理之細胞)顯示<0.5%之GFP表現陽性事件之最低水準處進行圈選來確定GFP陽性事件。為了計算慢病毒功能力價,使用顯示介於5%及20%細胞之間的CD8陽性細胞之GFP陽性%之轉導細胞孔來確定力價。病毒力價計算之公式:滴定={(F×Cn)/V}×DF。F係藉由流動式細胞測量術確定之GFP陽性細胞之頻率;Cn=感染之目標細胞之總數。V=接種物之體積,並且DF=稀釋因子(參見圖5至圖8)。
活 體內特異性
為了證明特定的活體內轉導,如上產生具有CD8結合劑97及46之表現GFP的慢病毒並將其投與至小鼠。人類PBMC中的T細胞經由CD3/CD28處理活化3天,並將1E7細胞腹膜內注射至NOD-scid-IL2rγ
null小鼠中。一天後,腹膜內注射1E7 TU之CD8融合體(結合劑97或46)或媒劑對照。7天後,藉由腹膜灌洗收集腹膜細胞,並藉由流動式細胞測量術分析在靶GFP表現及脫靶表現。用靶向CD8的慢病毒載體處理後,小鼠中大約35%至55%的CD8+細胞呈GFP陽性(
圖 9A),而只有不到0.2% (圖
9B)的GFP呈陽性,從而表明了小鼠中的CD8特異性轉導。
腫瘤殺傷
為了評估體外腫瘤殺傷,用抗CD3/CD28試劑活化人類PBMC,並用表現CD19CAR或GFP之CD8靶向融合體(VHH結合劑97或scFv結合劑46)轉導細胞。在第3天將RFP+ Nalm6細胞添加至培養物中,並在轉導之後4天在具有兩種CD8融合劑之CD8+細胞中特異性偵測到CD19CAR表現之後18小時藉由流動式細胞測量術評估Nalm6細胞之消除(
圖 10A)。融合劑產生之CD19CAR T細胞(實心符號)介導了對表現CD19之Nalm6細胞之強效及融合劑劑量依賴性殺傷。相反,融合劑產生之GFP+ T細胞(空心符號)未表現出目標細胞殺傷(
圖 10B)。
實例 3 :在 Nalm6 腫瘤模型中 CD8 靶向融合劑的活體內遞送作為 T 細胞活化狀態的函數
該實例描述了對CD8重定向尼帕融合劑及VSV-G之轉導效率的評估。
簡而言之,經由靜脈內(IV)注射給六十二(62)隻雌性NSG小鼠注射1E6 Nalm6-Luc白血病B細胞,三天後接著靜脈內注射2E6人類周邊血液單核細胞(hPBMC),預先用CD3/CD28複合體活化或不活化T細胞。在注射hPBMC之後一天,將表現CD19 CAR之CD8結合劑97尼帕融合劑假型化慢病毒載體(LV)以一系列整合單位(IU) 2E6-5E7中注射至不同之動物組中。在整個研究期間,每週使用Lago X成像系統經由生物發光成像(BLI)跟蹤Nalm6腫瘤進展。CD19CAR包含針對CD19之抗scFv及含有4-1BB及CD3-ζ之細胞內組分的細胞內信號域。對每組一半的小鼠進行周邊血液分析,以評估整個研究期間之循環T及B細胞頻率、循環CAR-T細胞頻率及細胞介素水準。該研究基於個體動物之健康狀況在hPBMC注射後28天或更早結束。處死動物,並且收集來自周邊血液、脾臟及骨髓組織之細胞,並藉由流動式細胞測量術分析CD19CAR表現細胞並進行細胞介素分析。
如
圖 11A所示,CD8-CD19CAR LV及活化之hPBMC處理導致隨時間推移對Nalm6腫瘤生長之穩健控制。如
圖 11B所示,高劑量CD8-CD19CAR LV及非活化hPBMC處理導致對Nalm6腫瘤生長之輕微延遲但穩健之控制。
圖 11C示出了在總回收之活淋巴細胞中在靶CD19CAR表現細胞(CD8
+CD19CAR
+)之百分比,如PBMC對照(上圖)及CD8融合體處理之動物(下圖)中FAC圖之右上象限所示。接受5 E7 IU之CD8-CD19CAR LV之動物骨髓中CAR-T細胞之頻率沒有統計學差異,無論是否活化hPBMC。結果表明,在治療後長達28天之周邊血液、脾臟及骨髓中,可在CD8+ T細胞中偵測到CD19特異性CAR T細胞。
實例 4 :藉由靜脈輸注在幼年雌性平頂猴中的 CD8-SFFV-CD20CAR 的 5 週及 7 週單劑量藥代動力學及藥效學研究
本實例描述了用抗CD8結合蛋白(結合劑46)假型化之慢病毒載體靶向CD8+ T細胞以遞送CD20 CAR轉基因(CD8-SFFV-CD20CAR)。CD20CAR包含針對CD20之抗scFv及含有4-1BB及CD3-ζ之細胞內組分的細胞內信號域。本研究之目的係表徵CD8-SFFV-CD20CAR轉導T細胞及消耗正常、健康CD20+ B細胞之能力、病毒整合之生物分佈以及靜脈投與之耐受性。在1小時內以7.69E8 IU/kg (n=6)之單一最大可行劑量或10mL/kg (n=2)之鹽水對照對八隻幼年雌性平頂猴投與CD8-SFFV-CD20CAR。在基線(第-35天、第-28天及第-21天)評估動物之B細胞及T細胞頻率以及血液學及臨床化學參數之評估。每天監測研究動物之臨床觀察,每週監測體重、溫度、神經性徵兆以及血液學及臨床化學之變化。在研究前、第7天及終止時(第35天至第52天)收集CSF樣本。所有動物在第3天、第5天、第7天、第10天、第14天、第17天、第21天、第28天及第35天進行習知血液採樣及流動式細胞測量術免疫表型分型,以瞭解B及T細胞頻率之變化。在終止時,對動物進行全面屍檢,收集血液、腦脊液及組織用於:淋巴組織之流動式細胞測量術、Luminex之細胞介素分析、PCR之轉基因表現、ddPCR之載體拷貝數(VCN)、深度測序之插入位點分佈(ISD)、臨床病理學(血液學及臨床化學)、組織免疫組織化學及解剖組織病理學。
至第35天之中期數據表明,以7.69E8 IU/kg之單一最大可行劑量投與CD8-SFFV-CD20CAR在所有動物中均具有良好之耐受性。在所有採樣時間內,臨床觀察(包括神經症狀、體溫或臨床化學值)沒有化合物相關之變化。在第7天至第10天血小板及中性粒細胞有短暫之最小之下降,到第14天恢復至基線。兩隻動物之血細胞比容有短暫、最小的下降以及網織紅細胞計數之相關增加,其可能係由於重複採血所致。如
圖 12所示,流動式細胞測量術分析表明,與持續至第35天之動物內預給藥相比,自第7天開始,在6隻治療動物中的4隻周邊血液中CD20+ B細胞顯著降低。至第28/35天之標準化B細胞計數呈現於
圖 13中。此等數據與抗CD20CAR之預期藥理活性一致。
使用ddPCR對來自第-35天及第14天及第35天之2隻對照動物及4隻治療動物之周邊血液單核細胞(PBMC)以及在脾臟及骨髓終止時之樣本進行初步VCN量測。在注射後第-35天及第35天,觀察到PBMC中的VCN,但所有動物中的值均低於定量限(BLQ)。藉由比較,在治療之動物中偵測到脾臟VCN,而對照動物係BLQ。在第35天,0.04%至1.3%之脾細胞(亦即67至1,970個細胞)在所檢查之CD8-SFFV-CD20CAR治療之動物中含有至少一個插入拷貝。亦在治療之猴子之脾臟中偵測到CD20 CAR mRNA,但在對照動物中未偵測到。
使用WPRE (土撥鼠肝炎病毒轉錄後反應元件)擴增子,通過液滴數字聚合酶鏈式反應(ddPCR)量測基因組中轉基因整合之另外的VCN量測。在研究第3天至第9/10天收集之所有(6隻中的6隻)融合體給藥動物之PBMC中轉基因可定量或可偵測到(
表 17),並且在第14天至第27/28天在動物1、4及6之PBMC樣本中可偵測到。
表 17 :藉由載體拷貝數 (VCN) 量測生活中收集的 PBMC 樣本的轉基因整合。
僅當WPRE拷貝在定量範圍內(每個反應50至120,000個拷貝)時才報告載體拷貝數(VCN)。VCN被計算為WPRE拷貝×2/TERT並且報告為VCN (每個二倍體基因組之整合)。若WPRE VCN拷貝低於LLOQ (每個反應之定量下限<50個拷貝)但高於LLOD(每個反應之偵測下限<10個拷貝),則報告WPRE VCN可被偵測到。若WPRE拷貝低於WPRE VCN,則報告不可偵測到。D,可偵測到;U,不可偵測到。
動物 | 第28天 | 第3天 | 第5天 | 第7天 | 第9天/10天 | 第14天 | 第16天至第18天 | 第21天 | 第27天/第28天 | 第35天 |
對照1 | U | U | U | U | U | U | U | U | U | U |
對照2 | U | U | U | U | U | 無樣本 | U | U | U | U |
1 | U | 0.00342 | 0.00273 | D | 0.00220 | U | D | D | D | U |
2 | U | D | D | 0.00207 | 0.00263 | U | U | U | U | U |
3 | U | D | D | D | 0.00283 | U | U | U | U | U |
4 | U | 0.00331 | D | 0.00326 | 0.00230 | D | D | U | U | U |
5 | U | 0.00254 | 0.00179 | 0.00289 | 0.00131 | U | U | U | U | U |
6 | U | 0.00820 | 0.00718 | 無樣本 | 無樣本 | D | D | D | U | U |
此等數據表明CD8-SFFV-CD20CAR在具有良好耐受性之免疫活性動物中的在靶活性,並且與脾臟細胞中載體之存在相關,即使在沒有投與T細胞活化治療之情況下亦係如此。
圖 1A 至圖 1B示出了所揭示之抗CD8抗體在幾種人類細胞株及表現南平頂猴(M. nemestrina) CD8α及CD8β之細胞株中之轉導效率。
圖 2示出了所揭示之抗CD8抗體在SupT1細胞上之力價。
圖 3示出了所揭示之抗CD8抗體在表現南平頂猴CD8α及CD8β之細胞上之力價。
圖 4示出了僅CD8α或CD8αβ過表現細胞上選擇之CD8結合劑之力價。
圖 5示出了本揭示之CD8 scFv (CD8結合劑52)在人類或南平頂猴(NHP)周邊血液單核細胞(PBMC)上之轉導效率。
圖 6示出了本揭示之CD8 scFv (CD8結合劑46)在人類或南平頂猴(NHP) PBMC上之轉導效率。
圖 7A 至圖 7D示出了連接至本揭示之CD8結合劑1 (
圖 7A)、CD8結合劑5 (
圖 7B)、CD8結合劑46 (
圖 7C)及CD8結合劑52 (
圖 7D)之尼帕(Nipah) G假型病毒載體對人類及南平頂猴PBMC (人類供體905C及南平頂猴供體24)之轉導效果。
圖 8A 至圖 8B示出了本揭示之幾種CD8 scFv在人類PBMC上之平均力價(
圖 8A)及供體(905C、703C或2101C)力價(
圖 8B)。
圖 9A 至圖 9B描繪了本揭示之CD8結合劑在活體內使用CD8+ (
圖 9A)及CD8- (
圖 9B)細胞之轉基因小鼠中對人類PBMC之轉導效率。
圖 10A 至圖 10B描繪了使用CD8融合劑產生的CD19CAR T細胞體外殺傷腫瘤。
圖 11A 至圖 11C描繪了注射人類周邊血液單核細胞(hPBMC)
( 圖 11A)後腫瘤隨時間之生長,其中預先用CD3/CD28複合體活化T細胞,並且然後一天後注射CD8-CD19CAR LV,並且隨後注射未活化之hPBMC (沒有預先進行T細胞活化),然後一天後注射CD8-CD19CAR LV (
圖 11B)。
圖 11C示出了在注射CD8-CD19CAR LV後自脾臟、骨髓或周邊血液中回收之總活淋巴細胞中CD8
+CD19CAR
+細胞之百分比,如PBMC對照(上圖)及CD8融合體處理之動物(下圖)中FAC圖的右上象限所示。
圖 12描繪了在投與了用靶向CD8+ T細胞之抗CD8結合蛋白假型化之慢病毒載體以遞送CD20 CAR轉基因後,非人類靈長類動物(NHP)模型中的B細胞含量。
圖 13描繪了在投與媒劑(對照1至2)或用靶向CD8+ T細胞之抗CD8結合蛋白假型化之慢病毒載體以遞送CD20 CAR轉基因(處理1至6)後,非人類靈長類動物中之標準化B細胞計數)。
圖 14描繪了用於向個體投與包含CD8結合劑之慢病毒載體之例示性系統。
<![CDATA[<110> 美商薩那生物科技公司(SANA BIOTECHNOLOGY, INC.)]]> <![CDATA[<120> CD8特異性抗體構築體及其組合物]]> <![CDATA[<130> 15147.0005-00304]]> <![CDATA[<140> TW 111113442]]> <![CDATA[<141> 2022-04-08]]> <![CDATA[<150> 63/299,254]]> <![CDATA[<151> 2022-01-13]]> <![CDATA[<150> 63/172,518]]> <![CDATA[<151> 2021-04-08]]> <![CDATA[<160> 1231 ]]> <![CDATA[<170> PatentIn version 3.5]]> <![CDATA[<210> 1]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1]]> Ser Tyr Ala Ile Ser 1 5 <![CDATA[<210> 2]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 2]]> Thr Tyr Ala Ile Asn 1 5 <![CDATA[<210> 3]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 3]]> Ser Tyr Ala Ile Asn 1 5 <![CDATA[<210> 4]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 4]]> Gly Tyr Tyr Met His 1 5 <![CDATA[<210> 5]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 5]]> Asp Tyr Tyr Ile Gln 1 5 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Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly 1 5 10 15 Gly Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Ser Gly Gly 20 25 30 Gly Gly Gly Ser 35 <![CDATA[<210> 28]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 28]]> Arg Phe Asp Ile Asn 1 5 <![CDATA[<210> 29]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 29]]> Ser His Ala Ile Ser 1 5 <![CDATA[<210> 30]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 30]]> Ser Tyr Gly Ile Asn 1 5 <![CDATA[<210> 31]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 31]]> Asp Tyr Asp Ile Tyr 1 5 <![CDATA[<210> 32]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 32]]> Ser Tyr His Met His 1 5 <![CDATA[<210> 33]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 33]]> Ser Tyr Pro Met Asn 1 5 <![CDATA[<210> 34]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> 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42]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 42]]> Gly Tyr Tyr Leu His 1 5 <![CDATA[<210> 43]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 43]]> Asn His Tyr Met His 1 5 <![CDATA[<210> 44]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 44]]> Asn Tyr Tyr Ile His 1 5 <![CDATA[<210> 45]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 45]]> Asp Tyr Tyr Met His 1 5 <![CDATA[<21]]>0> 46]]> <br/><![CDATA[<211> 5]]> <br/><![CDATA[<212> PRT]]> <br/><![CDATA[<213> 智人]]> <br/> <br/><![CDATA[<400> 46]]> <br/><![CDATA[Glu Asn Glu Met His 1 5 <![CDATA[<210> 47]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 47]]> Ser Tyr Asp Met His 1 5 <![CDATA[<210> 48]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 48]]> Asn Ser Asp Met His 1 5 <![CDATA[<210> 49]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 49]]> Ala Tyr Tyr Met His 1 5 <![CDATA[<210> 50]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 50]]> Asp Tyr His Met His 1 5 <![CDATA[<210> 51]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 51]]> Asp Tyr Tyr Met His 1 5 <![CDATA[<210> 52]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 52]]> Asp Tyr Tyr Met His 1 5 <![CDATA[<210> 53]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 53]]> Thr His Asp Ile Asn 1 5 <![CDATA[<210> 54]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 54]]> Asn Tyr Tyr Ile His 1 5 <![CDATA[<210> 55]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 55]]> Asp Asn Tyr Met His 1 5 <![CDATA[<210> 56]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 56]]> Ser Tyr Ala Ile Ser 1 5 <![CDATA[<210> 57]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 57]]> Thr Tyr Asp Ile Ser 1 5 <![CDATA[<210> 58]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 58]]> Ser Tyr Asp Ile Asn 1 5 <![CDATA[<210> 59]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 59]]> Ser His Trp Ile His 1 5 <![CDATA[<210> 60]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 60]]> Asp Tyr Asp Ile Val 1 5 <![CDATA[<210> 61]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 61]]> Gly His Asp Met His 1 5 <![CDATA[<210> 62]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 62]]> Asn Tyr Asp Met His 1 5 <![CDATA[<210> 63]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 63]]> Ser Tyr Ala Met Thr 1 5 <![CDATA[<210> 64]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 64]]> Thr Tyr Tyr 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<![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 77]]> Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 78]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 78]]> Trp Ile Ser Ala His Asn Gly Val Thr Gln Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 79]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 79]]> Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 80]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 80]]> Trp Ile Ser Pro Tyr Asn Gly Asn Thr Lys Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 81]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 81]]> Ile Ile Asn Pro Asn Ser Gly Asp Thr Lys Tyr Ala His Gln Phe Gln 1 5 10 15 Gly <![CDATA[<210> 82]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 82]]> Ile Ile Asn Pro Ser Asp Gly Asp Thr Lys Tyr Ala Gln Glu Phe Gln 1 5 10 15 Gly <![CDATA[<210> 83]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 83]]> Trp Ile Asn Pro Asn Ser Gly Asp Thr Lys Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 84]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 84]]> Val Ile Asp Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 85]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 85]]> Trp Ile Asp Pro Lys Ser Gly Asp Thr Thr Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 86]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 86]]> Met Ile Asn Pro Gly Ala Gly Ser Ser Thr Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 87]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 87]]> Leu Ile Ser Gly Asp Gly Gly Thr Thr Tyr Tyr Ala Asp Ser Val Lys 1 5 10 15 Gly <![CDATA[<210> 88]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 88]]> Ser Ile Asn Pro Asn Ser Gly Asp Thr Gly Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 89]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 89]]> Arg Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 90]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 90]]> Ala Ile Gly Thr Gly Gly Gly Ile Tyr Tyr Ala Asp Ser Val Lys Gly 1 5 10 15 <![CDATA[<210>]]> 91 <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 91]]> Arg Ile Asn Pro Asn Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 92]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 92]]> Met Ile Asn Pro Ser Asp Gly Ser Thr Arg Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 93]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 93]]> Ile Ile Asn Pro Ser Asp Gly Ser Thr Thr Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 94]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 94]]> Ile Ile Asn Pro Asn Gly Gly Ser Pro Ser Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210>]]> 95 <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 95]]> Ile Ile Asn Pro Ser Asp Gly Ser Thr Asp Tyr Ala Gln Asn Phe Gln 1 5 10 15 Gly <![CDATA[<210> 96]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 96]]> Arg Ile Asn Pro Asn Thr Gly Gly Thr Asn His Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 97]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 97]]> Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 1 5 10 15 Gly <![CDATA[<210> 98]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 98]]> Trp Ile Ser Gly Tyr Asn Gly Asp Thr Asp Tyr Ala Arg Lys Leu Gln 1 5 10 15 Gly <![CDATA[<210> 99]]> <![CDATA[<211]]>> 17]]> <br/><![CDATA[<212> PRT]]> <br/><![CDATA[<213> 智人]]> <br/> <br/><![CDATA[<400> 99]]> <br/><![CDATA[Trp Ile Ser Ala Asp Asn Gly Asn Thr Asn Tyr Glu Gln Lys Val Gln 1 5 10 15 Gly <![CDATA[<210> 100]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 100]]> Trp Ile Ser Pro Asn Ser Gly Ala Thr His Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 101]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 101]]> Trp Ile Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Lys Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 102]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 102]]> Ile Ile Asn Pro Ser Gly Gly Ser Thr Arg Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 103]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 103]]> Trp Ile Asn Pro Lys Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 104]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 104]]> Arg Ile Ser Glu Ser Gly Asp Ser Ser Phe Tyr Ala Asp Ser Val Lys 1 5 10 15 Gly <![CDATA[<210> 105]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 105]]> Ala Ile Gly Thr Gly Gly Gly Thr Tyr Tyr Ala Asp Ser Val Lys Gly 1 5 10 15 <![CDATA[<210> 106]]> <![CDATA[<211> 17]]> <![CDATA[<212> PR]]>T <![CDATA[<213> 智人]]> <![CDATA[<400> 106]]> Trp Met Asn Pro Ser Asn Gly Asp Thr Gly Tyr Ala Arg Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 107]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 107]]> Thr Ile Ser Pro Ser Asp Gly Ser Thr Thr Tyr Ala Gln Arg Phe Gln 1 5 10 15 Gly <![CDATA[<210> 108]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 108]]> Ile Ile Asn Pro Ser Gly Gly Ser Thr Thr Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 109]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 109]]> Gly Phe Asp Pro Glu Asp Gly Glu Thr Ile Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 110]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 110]]> Arg Ile Asn Pro Lys Ser Gly Arg Thr Tyr Tyr Ala Gln Asn Phe Gln 1 5 10 15 Gly <![CDATA[<210> 111]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 111]]> Val Ile Asn Pro Gly Gly Gly Ser Thr Thr Tyr Ala Gln Thr Phe Gln 1 5 10 15 Gly <![CDATA[<210> 112]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 112]]> Leu Met Asn Pro Lys Thr Gly Asp Thr Asn Tyr Ala Glu Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 113]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> ]]>113 Ile Ile Asp Pro Ser Asp Gly Tyr Thr Ser Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 114]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 114]]> Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 115]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 115]]> Gly Ile Met Pro Ile Ser Gly Thr Thr Ile Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 116]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 116]]> Trp Met Ser Pro Thr Ser Gly Asp Thr Gly Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 117]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 117]]> Trp Ile Asn Pro Asn Ser Gly Asp Thr Ser Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 118]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 118]]> Ile Ile Asp Pro Ser Gly Asp Ile Thr Ser Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 119]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 119]]> Ile Ile Glu Thr Ser Gly Gly Ser Thr Asp Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 120]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 120]]> Ile Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Leu Gln 1 5 10 15 Gly <![CDATA[<210> 121]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 121]]> Val Ile Ser Gly Ser Gly Val Thr Thr Tyr Tyr Ala Asp Ser Val Lys 1 5 10 15 Gly <![CDATA[<210> 122]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 122]]> Trp Ile Asn Pro Asn Ser Gly Gly Thr Asp Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 123]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 123]]> Met Ile Asn Pro Ser Gly Gly Ser Thr Thr Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 124]]> <![CDATA[<211>]]> 17 <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 124]]> Trp Ile Asn Pro Asp Ser Gly Gly Thr Asn Tyr Glu Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 125]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 125]]> Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Ser Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 126]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 126]]> Ile Ile Asn Pro Ser Gly Gly Ser Ala Ser Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 127]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 127]]> Ile Ile Ser Pro Ser Asp Gly Ser Thr Ser Tyr Ala Gln Lys Leu Gln 1 5 10 15 Gly <![CDATA[<210> 128]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 128]]> Trp Ile Asn Pro Ile Ser Gly Gly Thr His Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 129]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 129]]> Trp Ile Ser Ala Asp Asn Gly Asp Thr Ser Phe Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 130]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 130]]> Gly Ile Ser Pro Ile Tyr Gly Thr Pro Ala Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 131]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 131]]> Ile Ile Asn Pro Ser Asp Gly Asp Thr Ser Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 132]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 132]]> Thr Ile Asn Pro Ser Gly Gly Thr Thr Thr Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 133]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 133]]> Trp Met Asn Pro Lys Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 134]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 134]]> Ile Ile Asn Pro Gly Gly Gly Asn Ala Arg His Thr Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 135]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 135]]> Gly Phe Asp Pro Glu Asp Gly Glu Thr Val Tyr Ala Gln Asn Phe Gln 1 5 10 15 Gly <![CDATA[<210> 136]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 136]]> Gly Ile Thr Pro Val Phe Gly Ile Ala Asn Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 137]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 137]]> Ile Ile Asn Pro Arg Gly Gly Ser Thr Asn Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 138]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 138]]> Trp Met Asn Pro Asn Asn Gly Asp Thr Asp Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 139]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 139]]> Ile Ile Asn Pro Ser Gly Gly Gly Thr Ser Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 140]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 140]]> Leu Ile Asn Pro Gly Ser Gly Asn Thr Asn Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 141]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 141]]> Gly Ile Ile Pro Ile Phe Gly Thr Pro Asn Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 142]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 142]]> Thr Ile Asn Gly Asp Gly Asp Asp Thr Asp Tyr Ala Asp Ser Val Lys 1 5 10 15 Gly <![CDATA[<210> 143]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 143]]> Gln Ile Asp Pro Asn Ser Gly Asp Thr Ile Tyr Pro Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 144]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 144]]> Ile Val Asn Pro Ser Asp Gly Asn Thr Asn Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 145]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 145]]> Trp Ile Asn Thr Tyr Asn Gly Asn Thr Tyr Tyr Ala Gln Lys Leu Gln 1 5 10 15 Gly <![CDATA[<210> 146]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 146]]> Ile Ile Asn Pro Ser Asp Gly Ile Thr Asp Tyr Ala Gln Arg Phe Gln 1 5 10 15 Gly <![CDATA[<210> 147]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 147]]> Ile Ile Asn Pro Arg Asp Gly Asp Thr Val Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 148]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 148]]> Glu Arg Ala Ala Ala Gly Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 149]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 149]]> Glu His Ala Ala Gly Thr Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 150]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 150]]> Glu Gly Asp Tyr Tyr Tyr Gly Met Asp Ala 1 5 10 <![CDATA[<210> 151]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 151]]> Glu Arg Gly Gly Met Pro Asp Tyr 1 5 <![CDATA[<210> 152]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> ]]>智人 <![CDATA[<400> 152]]> Gly His Gly Ile Pro Lys Tyr 1 5 <![CDATA[<210> 153]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 153]]> Val Arg Ser Gly Ser Pro Gln His 1 5 <![CDATA[<210> 154]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 154]]> Gly Gly Pro Trp Ile Val Asp Ala Phe Asp Ile 1 5 10 <![CDATA[<210> 155]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 155]]> Glu Ala Thr Trp Gly Pro Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 156]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 156]]> Asn Lys Asp Gly Leu Gln His 1 5 <![CDATA[<210> 157]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 157]]> Asp Ala Lys Arg Val Gly Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 158]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 158]]> Leu Val Gly Gly Ser Pro Asp Tyr 1 5 <![CDATA[<210> 159]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 159]]> Gly Ala Met Val Asp Tyr 1 5 <![CDATA[<210> 160]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 160]]> Gly Asn Tyr Val Gly Ser Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 161]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 161]]> Asp Ser Arg Gly Asp Trp Tyr Phe Asp Leu 1 5 10 <![CDATA[<210> 162]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 162]]> His Gly Gly Arg Gly Leu Ala Asp Tyr 1 5 <![CDATA[<210> 163]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 163]]> Leu Lys Glu Leu Ser Ser Ile Leu Asp Ala Phe Asp Ile 1 5 10 <![CDATA[<210> 164]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 164]]> Glu Arg Phe Gly Thr Gly Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 165]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 165]]> Val Ile Gly Glu Met Val Asp Asp Ala Phe Asp Leu 1 5 10 <![CDATA[<210> 166]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 166]]> Glu Arg Leu Phe Gly Thr Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 167]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 167]]> Ala Asp Gly Glu Leu Thr Asp Tyr 1 5 <![CDATA[<210> 168]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 168]]> His His Leu Pro Ala His Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 169]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 169]]> Asp Val Pro Ala Gly Arg Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 170]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 170]]> Asp Arg Gly Val Gly Arg Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 171]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 171]]> Asp Ser Arg Tyr Gly Arg Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 172]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 172]]> Glu Ile Val Val Gly Pro Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 173]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 173]]> Gly Met Val Arg Gly Pro Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 174]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 174]]> Glu Gly Val Thr Gly Pro Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 175]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 175]]> Asp Ala Ala Ala Gly Thr Arg Tyr Tyr Tyr Tyr Tyr Gly Met Asp Val 1 5 10 15 <![CDATA[<210> 176]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 176]]> Glu Leu Tyr Ser Ser Thr Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 177]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 177]]> Ala Leu Tyr Ser Gly Pro Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 178]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 178]]> Asp Ser Leu Val Gly Arg Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 179]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 179]]> Arg Ser Glu Leu Asp Tyr 1 5 <![CDATA[<210> 180]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 180]]> Gly Asp Asp Asn Asp Tyr 1 5 <![CDATA[<210> 181]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 181]]> Gly Glu Glu Val Asp Tyr 1 5 <![CDATA[<210> 182]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 182]]> Gly Arg Arg Val Pro Asp Tyr 1 5 <![CDATA[<210> 183]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 183]]> Gly Lys Val Thr Thr Asp Tyr 1 5 <![CDATA[<210> 184]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 184]]> Gly Arg Glu Leu Ile Glu Tyr 1 5 <![CDATA[<210> 185]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 185]]> Val Tyr Asp Phe Pro Asp Val 1 5 <![CDATA[<210> 186]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 186]]> Ser Thr Tyr Ser His Ile Asp Tyr 1 5 <![CDATA[<210> 187]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 187]]> Glu Asp Ser Ser Gly Phe Asp Tyr 1 5 <![CDATA[<210> 188]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 188]]> Asp Gln Gly Gly Gly Phe Asp Tyr 1 5 <![CDATA[<210> 189]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 189]]> Asp Gln Gly Trp Gly Met Asp Val 1 5 <![CDATA[<210> 190]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 190]]> Leu Thr Glu Gly Ile Pro Asp Tyr 1 5 <![CDATA[<210> 191]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 191]]> Asp Arg Tyr Gly Pro Phe Asp Tyr 1 5 <![CDATA[<210> 192]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 192]]> Leu Val Ala Gly Gly Ala Pro Asp Tyr 1 5 <![CDATA[<210> 193]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 193]]> Asp Gly Phe Thr Gly Asp Ile Ala Tyr 1 5 <![CDATA[<210> 194]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 194]]> Val Asp Asp Ser Ser Ser Pro Asp Tyr 1 5 <![CDATA[<210> 195]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 195]]> Gly Pro Asp Gly Thr Glu Val Asp Tyr 1 5 <![CDATA[<210> 196]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 196]]> Ser Glu Ser Gly Ser Asp Leu Asp Tyr 1 5 <![CDATA[<210> 197]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 197]]> Glu Val Glu Ile Glu Gly Tyr Met Asp Val 1 5 10 <![CDATA[<210> 198]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 198]]> Asp Leu Asp Asp Asp Trp Tyr Met Asp Val 1 5 10 <![CDATA[<210> 199]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 199]]> Asp Ser Thr Thr Trp Asp Ala Phe Asp Ile 1 5 10 <![CDATA[<210> 200]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 200]]> Val Leu Val Gly Ser Gly Ser Pro Asp Tyr 1 5 10 <![CDATA[<210> 201]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 201]]> Glu Ala Ala Ala Gly Leu Asp Phe Gln His 1 5 10 <![CDATA[<210> 202]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 202]]> Ala Asn Ser Trp Asp Ala Asp Tyr 1 5 <![CDATA[<210> 203]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 203]]> Glu His Ser Ser Ser Trp Tyr Thr Phe Asp Tyr 1 5 10 <![CDATA[<210> 204]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 204]]> Asp Asp Asp Ser Ser Gly Tyr Tyr Leu Asp Tyr 1 5 10 <![CDATA[<210> 205]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 205]]> Ala Ser Gly Asp Tyr Met Asp Leu Ile Asp Tyr Met Asp Tyr 1 5 10 <![CDATA[<210> 206]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 206]]> Val Gly Ser Ser Gly Tyr Leu Ala Pro Thr His 1 5 10 <![CDATA[<210> 207]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 207]]> Val Arg Gly Asp Gly Tyr Asn Leu Gly Asp Tyr 1 5 10 <![CDATA[<210> 208]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 208]]> Asp Val Asp Thr Ala Met Gly Ala Gly Asp Tyr 1 5 10 <![CDATA[<210> 209]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 209]]> Val Ala Arg Trp Gly Tyr Gly Asp Tyr Pro Asp Tyr 1 5 10 <![CDATA[<210> 210]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 210]]> Asp Arg Asn Gly Asp Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 211]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 211]]> Glu Gly Leu Gly Ser Ser Trp Tyr Val Leu Asp Tyr 1 5 10 <![CDATA[<210> 212]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 212]]> Asp Gly Ser His Tyr Gly Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 213]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 213]]> Pro Gly Pro Glu Gly Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 214]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 214]]> Tyr His Trp Asp Tyr Gly Asp Tyr Arg Phe Asp Tyr 1 5 10 <![CDATA[<210> 215]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 215]]> Val Glu Ile Asp Tyr Gly Asp Ser Pro Pro Asp Tyr 1 5 10 <![CDATA[<210> 216]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 216]]> Gly Ala Glu Trp Glu Leu Arg Tyr Ala Phe Asp Ile 1 5 10 <![CDATA[<210> 217]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 217]]> Glu Thr Tyr Tyr Gly Leu Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 218]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 218]]> Ala Pro Ser Leu Arg Gly Tyr Ser Tyr Gly Pro Asp Tyr 1 5 10 <![CDATA[<210> 219]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 219]]> Asp Arg Gln Glu Arg Tyr Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 220]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 220]]> Asp Arg Ser Tyr Gly Asp Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 221]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 221]]> Glu Val Phe Ser Glu Asn Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 222]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 222]]> Glu Trp Asp Tyr Thr His Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 223]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 223]]> Gly Asp Ser Ser Gly Tyr Tyr Gln Tyr Tyr Phe Asp Tyr 1 5 10 <![CDATA[<210> 224]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 224]]> Gly Ser Trp Asp Ser Ser Ser Trp Tyr Ile Pro Glu Tyr 1 5 10 <![CDATA[<210> 225]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 225]]> Leu Val Trp Gly Gly Ala Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 226]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 226]]> Pro Val Phe Ser Gly Ser Tyr Tyr Trp Tyr Phe Asp Pro 1 5 10 <![CDATA[<210> 227]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 227]]> Asp Gln Ala Val Ala Gly Pro Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 228]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 228]]> Asp Arg Trp Leu Ala Gly Pro Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 229]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 229]]> Val Met Gly Pro Val Asp Tyr Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 230]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 230]]> Asp Leu Gly Pro Phe Gly Ser Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 231]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 231]]> Glu Gly Val Val Val Pro Pro Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 232]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 232]]> Ser Ser Gly Trp Ser Arg Tyr Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 233]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 233]]> Asp Asn Gly Met Thr Thr Gly Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 <![CDATA[<210> 234]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 234]]> Asp Arg Ala Met Val Thr Gly Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 235]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 235]]> Asp Arg Gly Tyr Gly Asp Arg Gly Tyr Tyr Tyr Gly Met Asp Val 1 5 10 15 <![CDATA[<210> 236]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 236]]> Ser Pro Lys Ala Thr Ala Asp Tyr Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 237]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 237]]> Ser Thr Val Thr Pro Ser Tyr Tyr Tyr Tyr Tyr Gly Met Asp Val 1 5 10 15 <![CDATA[<210> 238]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 238]]> Glu Pro Val Ala Gly Thr Gly Tyr Tyr Tyr Tyr Tyr Gly Met Asp Val 1 5 10 15 <![CDATA[<210> 2]]>39 <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 239]]> Asp Asn Leu Ala Gly Phe Trp Ser Asp Tyr Tyr Tyr Tyr Gly Met Asp 1 5 10 15 Val <![CDATA[<210> 240]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 240]]> Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn 1 5 10 <![CDATA[<210> 241]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 241]]> Gln Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn 1 5 10 <![CDATA[<210> 242]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 242]]> Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp 1 5 10 15 <![CDATA[<210> 243]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 243]]> Arg Ala Ser Gln Ser Ile Ser Arg Asn Leu Asn 1 5 10 <![CDATA[<210> 244]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 244]]> Arg Ala Ser Gln Ser Val Ser Ala Ser Asp Leu Ala 1 5 10 <![CDATA[<210> 245]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 245]]> Gln Ala Ser Gln Asp Ile Gly Asn Tyr Leu Asn 1 5 10 <![CDATA[<210> 246]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 246]]> Arg Ala Ser Gln Ser Ile Ser Thr His Leu Ala 1 5 10 <![CDATA[<210> 247]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 247]]> Arg Ala Ser Gln Thr Ile Ser Asn Tyr Leu Asn 1 5 10 <![CDATA[<210> 248]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 248]]> Arg Ala Ser Gln Gly Ile Arg Asn Asp Leu Gly 1 5 10 <![CDATA[<210> 249]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 249]]> Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu Asn 1 5 10 <![CDATA[<210> 250]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 250]]> Arg Ala Ser Gln Gly Ile Ser Asp Ser Leu Ala 1 5 10 <![CDATA[<210> 251]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 251]]> Gln Ala Ser Gln Asp Ile His Asn Tyr Leu Asn 1 5 10 <![CDATA[<210> 252]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 252]]> Arg Ala Ser Gln Ser Ile Ser Asp Trp Leu Ala 1 5 10 <![CDATA[<210> 253]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 253]]> Arg Ala Ser Gln Ser Ile Ser Thr Trp Leu Ala 1 5 10 <![CDATA[<210> 254]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 254]]> Arg Ala Ser Gln Ser Ile Asn Arg Phe Leu Asn 1 5 10 <![CDATA[<210> 255]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 255]]> Arg Ala Ser Gln Ser Val Ser Thr Tyr Leu Asn 1 5 10 <![CDATA[<210> 256]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 256]]> Gln Ala Ser Gln Asp Ile Ala Lys Tyr Leu Asn 1 5 10 <![CDATA[<210> 257]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 257]]> Gln Ala Ser Gln Gly Ile Thr Asn Tyr Leu Asn 1 5 10 <![CDATA[<210> 258]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 25]]>8 Gln Ala Asn Gln Asp Ile Ser Asn Phe Leu Glu 1 5 10 <![CDATA[<210> 259]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 259]]> Arg Ala Ser Gln Gly Ile Ser Asn Asn Leu Asn 1 5 10 <![CDATA[<210> 260]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 260]]> Arg Ala Ser Gln Ser Ile Ser Arg Ser Leu Val 1 5 10 <![CDATA[<210> 261]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 261]]> Gln Ala Ser His Asp Ile Ser Lys Ser Leu Asn 1 5 10 <![CDATA[<210> 262]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 262]]> Arg Ala Ser Gln Asp Ile Gly Ala Tyr Leu Ala 1 5 10 <![CDATA[<210> 263]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 263]]> Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Ala 1 5 10 <![CDATA[<210> 264]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 264]]> Arg Ala Ser Gln Gly Ile Arg Ser Tyr Leu Ala 1 5 10 <![CDATA[<210> 265]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 265]]> Arg Ala Ser Gln Asn Ile Gly Thr Trp Leu Ala 1 5 10 <![CDATA[<210> 266]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 266]]> Arg Ala Ser Gln Thr Ile Ser Tyr Tyr Leu Asn 1 5 10 <![CDATA[<210> 267]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 267]]> Arg Ala Ser Gln Asn Ile Asn Asn Tyr Leu Asn 1 5 10 <![CDATA[<210> 268]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 268]]> Arg Ala Ser Gln Thr Ile Ser Thr Tyr Leu Asn 1 5 10 <![CDATA[<210> 269]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 269]]> Arg Ala Ser Arg Gly Ile Gly Asn Asp Leu Ala 1 5 10 <![CDATA[<210> 270]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 270]]> Arg Ala Ser Gln Thr Ile Gly Asn Tyr Val Asn 1 5 10 <![CDATA[<210> 271]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 271]]> Arg Ala Ser Gln Phe Ile Gly Ser Trp Leu Ala 1 5 10 <![CDATA[<210> 272]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 272]]> Arg Ala Ser Gln Ser Ile Ser Ser Trp Met Ala 1 5 10 <![CDATA[<210> 273]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 273]]> Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu 1 5 10 15 Ala <![CDATA[<210> 274]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 274]]> Arg Val Ser Gln Gly Ile Ser Ser Tyr Leu Asn 1 5 10 <![CDATA[<210> 275]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 275]]> Arg Ala Ser Gln Gly Ile Ser Asn Tyr Leu Ala 1 5 10 <![CDATA[<210> 276]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 276]]> Arg Ala Ser Gln Ser Ile Arg Asn Tyr Leu Thr 1 5 10 <![CDATA[<210> 277]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 277]]> Arg Ala Ser Gln Asn Ile Arg Leu Tyr Leu Asn 1 5 10 <![CDATA[<210> 278]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 278]]> Gln Ala Ser Gln Asp Ile Arg Lys Phe Leu Asn 1 5 10 <![CDATA[<210> 279]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 279]]> Gln Ala Ser Gln Asp Ile Ser Asn Tyr Leu Ser 1 5 10 <![CDATA[<210> 280]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 280]]> Arg Ala Ser Gln Asn Val Arg Ser Trp Leu Ala 1 5 10 <![CDATA[<210> 281]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 281]]> Arg Ala Ser Gln Gly Ile Gly Asn Asp Leu Gly 1 5 10 <![CDATA[<210> 282]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 282]]> Arg Ala Ser Gln Ser Ile Ser Asn Trp Leu Ala 1 5 10 <![CDATA[<210> 283]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 283]]> Arg Ala Ser Glu Ser Ile Gly Ser Trp Leu Ala 1 5 10 <![CDATA[<210> 284]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 284]]> Arg Ala Ser Gln Ser Val Thr Ser Asn Tyr Leu Ala 1 5 10 <![CDATA[<210> 285]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 285]]> Arg Ala Ser Gln Gly Ile Ser Ser Tyr Leu Ala 1 5 10 <![CDATA[<210> 286]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 286]]> Arg Ala Ser Gln Asp Ile Gly Asn Tyr Leu Asn 1 5 10 <![CDATA[<210> 287]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 287]]> Arg Ala Ser Gln Gly Ile Ser Asn Gly Leu Ser 1 5 10 <![CDATA[<210> 288]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 288]]> Arg Ala Ser Gln Asn Ile Arg Asn Tyr Leu Asn 1 5 10 <![CDATA[<210> 289]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 289]]> Gln Ala Ser Leu Asp Ile Asn Asn Tyr Leu Asn 1 5 10 <![CDATA[<210> 290]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 290]]> Arg Ala Ser Gln Asn Ile Gly Asn Tyr Leu Asn 1 5 10 <![CDATA[<210> 291]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 291]]> Arg Ala Ser Gln Gly Ile Arg Asn Asp Leu Asn 1 5 10 <![CDATA[<210> 292]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 292]]> Arg Ala Ser Gln Gly Ile Asn Thr Trp Leu Ala 1 5 10 <![CDATA[<210> 293]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 293]]> Arg Ala Ser Gln Phe Ile Gly Ser Trp Leu Ala 1 5 10 <![CDATA[<210> 294]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 294]]> Ala Ala Ser Ser Leu Gln Ser 1 5 <![CDATA[<210> 295]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 295]]> Leu Gly Ser Asn Arg Ala Ser 1 5 <![CDATA[<210> 296]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 296]]> Lys Ala Ser Asn Leu Lys Gly 1 5 <![CDATA[<210> 297]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 297]]> Gly Ala Ser Thr Arg Ala Thr 1 5 <![CDATA[<210> 298]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 298]]> Ala Ala Ser Thr Leu Gln Arg 1 5 <![CDATA[<210> 299]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 299]]> Ala Ala Ser Thr Leu Gln Ser 1 5 <![CDATA[<210> 300]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 300]]> Asp Ala Ser Thr Leu Gln Ser 1 5 <![CDATA[<210> 301]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 301]]> Gly Ala Ser Ser Leu Arg Ser 1 5 <![CDATA[<210> 302]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 302]]> Asp Ala Ser Asn Leu Glu Thr 1 5 <![CDATA[<210> 303]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 303]]> Ser Ala Ser Ser Leu Gln Ser 1 5 <![CDATA[<210> 304]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 304]]> Ala Ala Ser Ser Leu Gln Thr 1 5 <![CDATA[<210> 305]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 305]]> Ser Ala Ser Thr Leu Gln Ser 1 5 <![CDATA[<210> 306]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 306]]> Asp Ala Ser His Leu Glu Thr 1 5 <![CDATA[<210> 307]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 307]]> Ala Ala Ser Thr Leu His Ser 1 5 <![CDATA[<210> 308]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 308]]> Ala Ala Ser Ser Leu Gln Asn 1 5 <![CDATA[<210> 309]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 309]]> Gly Ala Ser Ser Leu Gln Ser 1 5 <![CDATA[<210> 310]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 310]]> Ser Ala Phe Ser Leu Gln Ser 1 5 <![CDATA[<210> 311]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 311]]> Ser Ala Ser Asn Leu Gln Ser 1 5 <![CDATA[<210> 312]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 312]]> Asp Ala Ser Ser Leu Glu Ser 1 5 <![CDATA[<210> 313]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 313]]> Glu Ala Ser Thr Leu Glu Ser 1 5 <![CDATA[<210> 314]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> ]]>314 Gly Ala Ser Thr Leu Glu Thr 1 5 <![CDATA[<210> 315]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 315]]> Ala Ala Ser Thr Leu Gln Thr 1 5 <![CDATA[<210> 316]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 316]]> Gly Ala Ser Thr Leu Gln Ser 1 5 <![CDATA[<210> 317]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 317]]> Gly Ala Ser Asn Leu Glu Thr 1 5 <![CDATA[<210> 318]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 318]]> Met Gly Ser Asn Arg Ala Ser 1 5 <![CDATA[<210> 319]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 319]]> Asp Ala Ser Thr Leu Glu Thr 1 5 <![CDATA[<210> 320]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 320]]> Gly Ala Ser Asn Leu His Thr 1 5 <![CDATA[<210> 321]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 321]]> Trp Ala Ser Thr Arg Glu Ser 1 5 <![CDATA[<210> 322]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 322]]> Lys Thr Ser Ser Leu Glu Ser 1 5 <![CDATA[<210> 323]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 323]]> Thr Ala Ser Asn Leu Gln Ser 1 5 <![CDATA[<210> 324]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 324]]> Asp Ala Ser Asn Leu Gln Ser 1 5 <![CDATA[<210> 325]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 325]]> Leu Ala Ser Ser Leu Gln Ser 1 5 <![CDATA[<210> 326]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 326]]> Ser Thr Ser Ser Leu Gln Ser 1 5 <![CDATA[<210> 327]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 327]]> Ala Ala Ser Ser Leu Gln Arg 1 5 <![CDATA[<210> 328]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 328]]> Lys Ala Ser Ser Leu Glu Ser 1 5 <![CDATA[<210> 329]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 329]]> Ala Ala Ser Ser Leu Gln Gly 1 5 <![CDATA[<210> 330]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 330]]> Ala Ala Ser Asn Leu Gln Ser 1 5 <![CDATA[<210> 331]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 331]]> Ala Ala Ser Thr Leu Arg Ser 1 5 <![CDATA[<210> 332]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 332]]> Ala Ala Ser Ser Leu His Ser 1 5 <![CDATA[<210> 333]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 333]]> Gln Gln Ser Tyr Ser Thr Pro Leu Thr 1 5 <![CDATA[<210> 334]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 334]]> Gln Gln Ser Tyr Ser Asn Leu Val Ser 1 5 <![CDATA[<210> 335]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 335]]> Met Gln Ala Leu Gln Thr Pro Phe Thr 1 5 <![CDATA[<210> 3]]>36 <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 336]]> Met Gln Gly Leu Gln Thr Pro His Thr 1 5 <![CDATA[<210> 337]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 337]]> Gln Gln Thr Tyr Ser Ala Pro Leu 1 5 <![CDATA[<210> 338]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 338]]> Met Gln Thr Leu Gln Thr Pro Leu Thr 1 5 <![CDATA[<210> 339]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 339]]> Gln Gln Tyr Gly Asp Ser Pro Gly Ser 1 5 <![CDATA[<210> 340]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 340]]> Gln Gln Ala Asn Ser Phe Pro Pro Thr 1 5 <![CDATA[<210> 341]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 341]]> Gln Gln Tyr Gly Asn Ser Arg Thr 1 5 <![CDATA[<210> 342]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 342]]> Gln Gln Ser Tyr Ser Thr Pro Pro Thr 1 5 <![CDATA[<210> 343]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 343]]> Gln Gln Ser Tyr Ser Ser Pro Tyr Thr 1 5 <![CDATA[<210> 344]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 344]]> Gln Gln Ser Tyr Ser Thr Pro Tyr Thr 1 5 <![CDATA[<210> 345]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 345]]> Met Gln Gly Ala His Trp Pro Pro Thr 1 5 <![CDATA[<210> 346]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> ]]>346 Gln Gln Ser Tyr Arg Thr Pro Tyr Thr 1 5 <![CDATA[<210> 347]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 347]]> Gln Glu Ser Phe Thr Thr Gln Trp Thr 1 5 <![CDATA[<210> 348]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 348]]> Gln Gln Arg Ser Asn Trp Pro Leu Tyr Thr 1 5 10 <![CDATA[<210> 349]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 349]]> Gln Gln Ala Ile Ser Phe Pro Ile Thr 1 5 <![CDATA[<210> 350]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 350]]> Gln Gln Ser Tyr Ser Ser Pro Phe Thr 1 5 <![CDATA[<210> 351]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智]]>人 <![CDATA[<400> 351]]> Gln Gln Ala Ile Ser Phe Pro Leu Thr 1 5 <![CDATA[<210> 352]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 352]]> Gln Gln Ser Tyr Thr Phe Pro Ile Thr 1 5 <![CDATA[<210> 353]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 353]]> Gln Gln Tyr Tyr Ser Tyr Pro Pro Thr 1 5 <![CDATA[<210> 354]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 354]]> Gln Gln Ser Tyr Ser Ala Pro Leu Thr 1 5 <![CDATA[<210> 355]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 355]]> Gln Gln Ser Phe Ser Thr Phe Tyr Thr 1 5 <![CDATA[<210> 356]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 356]]> Gln Gln Ser Tyr Ser Ile Pro Phe Thr 1 5 <![CDATA[<210> 357]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 357]]> Gln Gln Ser Tyr Ser Thr Pro Ile Thr 1 5 <![CDATA[<210> 358]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 358]]> Gln Gln Ser Tyr Thr Ile Pro Ser Thr 1 5 <![CDATA[<210> 359]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 359]]> Gln Gln Ser Tyr Ser Ala Pro Pro Thr 1 5 <![CDATA[<210> 360]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 360]]> Gln Gln Ser Tyr Ser Thr Pro Trp Thr 1 5 <![CDATA[<210> 361]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 361]]> Gln Gln Ser Tyr Thr Thr Pro Leu Thr 1 5 <![CDATA[<210> 362]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 362]]> Gln Gln Ser Tyr Ser Ala Pro Ile Thr 1 5 <![CDATA[<210> 363]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 363]]> Gln Gln Arg Ser Asn Trp Pro Pro Val Thr 1 5 10 <![CDATA[<210> 364]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 364]]> Gln Gln Ser Tyr Ser Ile Pro Ile Thr 1 5 <![CDATA[<210> 365]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 365]]> Met Gln Gly Leu Gln Pro Pro Gly Thr 1 5 <![CDATA[<210> 366]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 366]]> Gln Gln Ser Tyr Asn His Phe Arg Thr 1 5 <![CDATA[<210> 367]]> <![CDATA[<211> 9]]> <![CDATA[<212> ]]>PRT <![CDATA[<213> 智人]]> <![CDATA[<400> 367]]> Gln Arg Ser Asp Ser Thr Pro Leu Thr 1 5 <![CDATA[<210> 368]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 368]]> Gln Gln Leu Asn Ser Tyr Pro Arg Thr 1 5 <![CDATA[<210> 369]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 369]]> Gln Gln Ser Tyr Ser Ile Pro Tyr Thr 1 5 <![CDATA[<210> 370]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 370]]> Gln Gln Thr Tyr Ser Thr Pro Tyr Thr 1 5 <![CDATA[<210> 371]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 371]]> Gln Gln Ser Tyr Ser Thr Pro Gln Thr 1 5 <![CDATA[<210> 372]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 372]]> Met Gln Gly Thr His Trp Pro Thr 1 5 <![CDATA[<210> 373]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 373]]> Gln Gln Thr Phe Ser Leu Pro Tyr Thr 1 5 <![CDATA[<210> 374]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 374]]> Gln Gln Gly Tyr Asn Met Pro Leu Thr 1 5 <![CDATA[<210> 375]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 375]]> Gln Gln Thr Tyr Ser Ala Pro Leu Thr 1 5 <![CDATA[<210> 376]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 376]]> Gln Gln Ser Tyr Ser Phe Pro Trp Thr 1 5 <![CDATA[<210> 377]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 377]]> Gln Gln Thr Tyr Ser Thr Pro Tyr Ile 1 5 <![CDATA[<210> 378]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 378]]> Gln Gln Ser Tyr Ser Ser Pro Trp Thr 1 5 <![CDATA[<210> 379]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 379]]> Gln Gln Tyr Ala Ser Ala Pro Arg Thr 1 5 <![CDATA[<210> 380]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 380]]> Gln Gln Ser Phe Thr Ile Pro Tyr Thr 1 5 <![CDATA[<210> 381]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 381]]> Gln Gln Thr Tyr Arg Thr Pro Pro Thr 1 5 <![CDATA[<210> 382]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 382]]> Gln Gln Ser Leu Thr Thr Pro Phe Thr 1 5 <![CDATA[<210> 383]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 383]]> Gln Gln Leu Asn Gly Tyr Pro Gly Thr 1 5 <![CDATA[<210> 384]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 384]]> Gln Gln Ser Tyr Ser Leu Pro Leu Thr 1 5 <![CDATA[<210> 385]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 385]]> Gln Gln Thr Tyr Thr Thr Pro Arg Thr 1 5 <![CDATA[<210> 386]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 386]]> Gln Gln Ser Tyr Asn Thr Pro Tyr Thr 1 5 <![CDATA[<210> 387]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 387]]> Gln Gln Ser Tyr Ala Pro Pro Pro Thr 1 5 <![CDATA[<210]]>> 388]]> <br/><![CDATA[<211> 9]]> <br/><![CDATA[<212> PRT]]> <br/><![CDATA[<213> 智人]]> <br/> <br/><![CDATA[<400> 388]]> <br/><![CDATA[Met Gln Gly Leu Gln Thr Pro Leu Thr 1 5 <![CDATA[<210> 389]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 389]]> Gln Gln Ser Asp Ser Ile Pro Val Thr 1 5 <![CDATA[<210> 390]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 390]]> Gln Gln Ser Tyr Ser Thr Pro Tyr Asn 1 5 <![CDATA[<210> 391]]> <![CDATA[<211> 8]]> <![CDATA[<212> P]]>RT <![CDATA[<213> 智人]]> <![CDATA[<400> 391]]> Gln His Tyr Gly Ser Ser Pro Ala 1 5 <![CDATA[<210> 392]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 392]]> Gln Gln Ala Tyr Thr Tyr Pro Tyr Thr 1 5 <![CDATA[<210> 393]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 393]]> Gln Gln Ser Tyr Thr Thr Pro Asn Thr 1 5 <![CDATA[<210> 394]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 394]]> Gln Gln Ser Tyr Ser Thr Pro Phe Thr 1 5 <![CDATA[<210> 395]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 395]]> Gln Gln Ser Tyr Ser Met Pro Leu Thr 1 5 <![CDATA[<210> 396]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 396]]> Gln Gln Ser Tyr Thr Thr Pro Trp Thr 1 5 <![CDATA[<210> 397]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 397]]> Gln Gln Ser Tyr Ser Ser Pro Leu Thr 1 5 <![CDATA[<210> 398]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 398]]> Gln Gln Ser Tyr Ser Asp Pro Leu Thr 1 5 <![CDATA[<210> 399]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 399]]> Gln Gln Ser Tyr Ser Thr Pro Pro Trp Thr 1 5 10 <![CDATA[<210> 400]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 400]]> Gln Gln Ser Tyr Gln Thr Pro Leu Thr 1 5 <![CDATA[<210> 401]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 401]]> Gln Gln Ser Tyr Thr Thr Pro Pro Thr 1 5 <![CDATA[<210> 402]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 402]]> Gln Gln Ala Asn Ser Phe Pro Ile Thr 1 5 <![CDATA[<210> 403]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 403]]> Gln Gln Ser Tyr Thr Val Pro Pro Thr 1 5 <![CDATA[<210> 404]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 404]]> Gln Gln Asp Asp Ser Phe Pro Leu Thr 1 5 <![CDATA[<210> 405]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 405]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asp Pro Ser Asp Gly Asn Thr Asn Tyr Ala Gln Asn Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Glu Arg Ala Ala Ala Gly Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 406]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 406]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Asn Thr Tyr 20 25 30 Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Arg Ile Asp Pro Ser Ser Gly Gly Thr Lys Tyr Ala Gln Asn Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Glu His Ala Ala Gly Thr Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 407]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 407]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asp Pro Ser Gly Gly Asn Thr Asn Tyr Ala Gln Asn Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Glu Arg Ala Ala Ala Gly Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 408]]> <![CDATA[<211> 119]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 408]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Tyr Ile Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Glu Gly Asp Tyr Tyr Tyr Gly Met Asp Ala Trp Gly Gln Gly 100 105 110 Thr Met Val Thr Val Ser Ser 115 <![CDATA[<210> 409]]> <![CDATA[<211> 117]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 409]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr 20 25 30 Asp Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Val Ile Asn Pro Asn Asp Gly Ser Thr Arg Tyr Ala Gln Asn Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Arg Gly Gly Met Pro Asp Tyr Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser 115 <![CDATA[<210> 410]]> <![CDATA[<211> 116]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 410]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Arg Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly His Gly Ile Pro Lys Tyr Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser 115 <![CDATA[<210> 411]]> <![CDATA[<211> 117]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 411]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Val Arg Ser Gly Ser Pro Gln His Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser 115 <![CDATA[<210> 412]]> <![CDATA[<211> 120]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 412]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly His Thr Phe Ser Arg His 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Gly Pro Trp Ile Val Asp Ala Phe Asp Ile Trp Gly Gln 100 105 110 Gly Thr Met Val Thr Val Ser Ser 115 120 <![CDATA[<210> 413]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 413]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Asn Thr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Ala Thr Trp Gly Pro Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 414]]> <![CDATA[<211> 116]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 414]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Ser 20 25 30 Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Ser Pro Tyr Asn Gly Asn Thr Lys Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Val Arg Asn Lys Asp Gly Leu Gln His Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser 115 <![CDATA[<210> 415]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 415]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Gly Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Asn Ser Gly Asp Thr Lys Tyr Ala His Gln Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Ala Lys Arg Val Gly Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 416]]> <![CDATA[<211> 117]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 416]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Arg Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Leu Val Gly Gly Ser Pro Asp Tyr Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser 115 <![CDATA[<210> 417]]> <![CDATA[<211> 115]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 417]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Arg Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Glu Asn Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Ala Met Val Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser 115 <![CDATA[<210> 418]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 418]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Asn Thr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Asp Gly Asp Thr Lys Tyr Ala Gln Glu Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Asn Tyr Val Gly Ser Tyr Tyr Tyr Gly Met Asp Val Trp 100 105 110 Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 419]]> <![CDATA[<211> 119]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 419]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 20 25 30 Tyr Leu His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Pro Asn Ser Gly Asp Thr Lys Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Ser Arg Gly Asp Trp Tyr Phe Asp Leu Trp Gly Arg Gly 100 105 110 Thr Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 420]]> <![CDATA[<211> 118]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 420]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Gly Phe Thr Arg Tyr 20 25 30 Ser Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Val Ile Asp Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg His Gly Gly Arg Gly Leu Ala Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 421]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 421]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Arg 20 25 30 Asp Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asp Pro Lys Ser Gly Asp Thr Thr Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Leu Lys Glu Leu Ser Ser Ile Leu Asp Ala Phe Asp Ile Trp 100 105 110 Gly Gln Gly Thr Met Val Thr Val Ser Ser 115 120 <![CDATA[<210> 422]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 422]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Met Ile Asn Pro Gly Ala Gly Ser Ser Thr Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Arg Phe Gly Thr Gly Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Gln Gly Thr Met Val Thr Val Ser Ser 115 120 <![CDATA[<210> 423]]> <![CDATA[<211> 121]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 423]]> Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Ser 20 25 30 Asp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Leu Ile Ser Gly Asp Gly Gly Thr Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Val Ile Gly Glu Met Val Asp Asp Ala Phe Asp Leu Trp Gly 100 105 110 Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 424]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 424]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ser Ile Asn Pro Asn Ser Gly Asp Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Arg Leu Phe Gly Thr Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 425]]> <![CDATA[<211> 117]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 425]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Arg Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Ala Asp Gly Glu Leu Thr Asp Tyr Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser 115 <![CDATA[<210> 426]]> <![CDATA[<211> 121]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 426]]> Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Thr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Gly Thr Gly Gly Gly Ile Tyr Tyr Ala Asp Ser Val Lys 50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 90 95 Arg His His Leu Pro Ala His Tyr Tyr Tyr Tyr Met Asp Val Trp Gly 100 105 110 Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 427]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 427]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Arg Ile Asn Pro Asn Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Val Pro Ala Gly Arg Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 428]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 428]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asn Thr Phe Thr Ser Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Met Ile Asn Pro Ser Asp Gly Ser Thr Arg Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Arg Gly Val Gly Arg Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 429]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 429]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Tyr 20 25 30 Ala Val Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Asp Gly Ser Thr Thr Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Ser Arg Tyr Gly Arg Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 430]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 430]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Asn Tyr 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Asn Gly Gly Ser Pro Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Glu Ile Val Val Gly Pro Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 431]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 431]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Thr Arg Tyr 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Arg Ile Asn Pro Asn Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Met Val Arg Gly Pro Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 432]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 432]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Thr Phe 50 55 60 Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Val Thr Gly Pro Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 433]]> <![CDATA[<211> 125]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400>]]> 433 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Phe 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Asp Gly Ser Thr Asp Tyr Ala Gln Asn Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Ala Ala Ala Gly Thr Arg Tyr Tyr Tyr Tyr Tyr Gly Met 100 105 110 Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 125 <![CDATA[<210> 434]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 434]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser His 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Leu Tyr Ser Ser Thr Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 435]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 435]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Arg Ile Asn Pro Asn Thr Gly Gly Thr Asn His Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Ala Leu Tyr Ser Gly Pro Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 436]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 436]]> Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Ser 20 25 30 Asp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Glu His Ala Ala Gly Thr Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 437]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 437]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Gly Ser Tyr 20 25 30 Gly Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Ser Gly Tyr Asn Gly Asp Thr Asp Tyr Ala Arg Lys Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Ser Leu Val Gly Arg Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 438]]> <![CDATA[<211> 115]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 438]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Thr Asp Tyr 20 25 30 Asp Ile Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Leu 35 40 45 Gly Trp Ile Ser Ala Asp Asn Gly Asn Thr Asn Tyr Glu Gln Lys Val 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Arg Ser Glu Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser 115 <![CDATA[<210> 439]]> <![CDATA[<211> 115]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 439]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 His Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Ser Pro Asn Ser Gly Ala Thr His Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Asp Asp Asn Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser 115 <![CDATA[<210> 440]]> <![CDATA[<211> 115]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 440]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Lys Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Glu Glu Val Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 100 105 110 Val Ser Ser 115 <![CDATA[<210> 441]]> <![CDATA[<211> 116]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 441]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Pro Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Arg Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Arg Arg Val Pro Asp Tyr Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser 115 <![CDATA[<210> 442]]> <![CDATA[<211> 116]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 442]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Pro Lys Ser Gly Ala Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Lys Val Thr Thr Asp Tyr Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser 115 <![CDATA[<210> 443]]> <![CDATA[<211> 116]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 443]]> Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Phe 20 25 30 Glu Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Arg Ile Ser Glu Ser Gly Asp Ser Ser Phe Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ser Gly Arg Glu Leu Ile Glu Tyr Trp Gly Gln Gly Thr Leu Val 100 105 110 Thr Val Ser Ser 115 <![CDATA[<210> 444]]> <![CDATA[<211> 115]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400]]>> 444]]> <br/><![CDATA[Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr 20 25 30 Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Gly Thr Gly Gly Gly Thr Tyr Tyr Ala Asp Ser Val Lys 50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 90 95 Arg Val Tyr Asp Phe Pro Asp Val Trp Gly Gln Gly Thr Thr Val Thr 100 105 110 Val Ser Ser 115 <![CDATA[<210> 445]]> <![CDATA[<211> 117]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 445]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Ser 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Ser Asn Gly Asp Thr Gly Tyr Ala Arg Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Ser Thr Tyr Ser His Ile Asp Tyr Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser 115 <![CDATA[<210> 446]]> <![CDATA[<211> 117]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 446]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Thr Ile Ser Pro Ser Asp Gly Ser Thr Thr Tyr Ala Gln Arg Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Asp Ser Ser Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser 115 <![CDATA[<210> 447]]> <![CDATA[<211> 117]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 447]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Met Asn Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Thr Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Gln Gly Gly Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser 115 <![CDATA[<210> 448]]> <![CDATA[<211> 117]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 448]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Gly Phe Asp Pro Glu Asp Gly Glu Thr Ile Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Gln Gly Trp Gly Met Asp Val Trp Gly Gln Gly Thr Thr 100 105 110 Val Thr Val Ser Ser 115 <![CDATA[<210> 449]]> <![CDATA[<211> 117]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 449]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Arg Ile Asn Pro Lys Ser Gly Arg Thr Tyr Tyr Ala Gln Asn Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Leu Thr Glu Gly Ile Pro Asp Tyr Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser 115 <![CDATA[<210> 450]]> <![CDATA[<211> 117]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 450]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Leu Asn Asp Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Val Ile Asn Pro Gly Gly Gly Ser Thr Thr Tyr Ala Gln Thr Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Tyr Gly Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser 115 <![CDATA[<210> 451]]> <![CDATA[<211> 118]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 451]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Leu Met Asn Pro Lys Thr Gly Asp Thr Asn Tyr Ala Glu Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Leu Val Ala Gly Gly Ala Pro Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 452]]> <![CDATA[<211> 118]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 452]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asp Pro Ser Asp Gly Tyr Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Gly Phe Thr Gly Asp Ile Ala Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 453]]> <![CDATA[<211> 118]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 453]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Val Asp Asp Ser Ser Ser Pro Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 454]]> <![CDATA[<211> 118]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 454]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr 20 25 30 Tyr Leu His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Gly Ile Met Pro Ile Ser Gly Thr Thr Ile Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Thr Gly Pro Asp Gly Thr Glu Val Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 455]]> <![CDATA[<211> 118]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 455]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn His 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ser Ser Glu Ser Gly Ser Asp Leu Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 456]]> <![CDATA[<211> 119]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 456]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Ser Pro Thr Ser Gly Asp Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Val Glu Ile Glu Gly Tyr Met Asp Val Trp Gly Gln Gly 100 105 110 Thr Thr Val Thr Val Ser Ser 115 <![CDATA[<210> 457]]> <![CDATA[<211> 119]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 457]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Pro Asn Ser Gly Asp Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Leu Asp Asp Asp Trp Tyr Met Asp Val Trp Gly Lys Gly 100 105 110 Thr Thr Val Thr Val Ser Ser 115 <![CDATA[<210> 458]]> <![CDATA[<211> 119]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 458]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asp Pro Ser Gly Asp Ile Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Thr Asp Ser Thr Thr Trp Asp Ala Phe Asp Ile Trp Gly Gln Gly 100 105 110 Thr Met Val Thr Val Ser Ser 115 <![CDATA[<210> 459]]> <![CDATA[<211> 119]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 459]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Val Leu Val Gly Ser Gly Ser Pro Asp Tyr Trp Gly Gln Gly 100 105 110 Thr Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 460]]> <![CDATA[<211> 119]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 460]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Glu Asn 20 25 30 Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Glu Thr Ser Gly Gly Ser Thr Asp Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Ala Ala Ala Gly Leu Asp Phe Gln His Trp Gly Gln Gly 100 105 110 Thr Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 461]]> <![CDATA[<211> 120]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 461]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ala Ser Tyr 20 25 30 Asp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Ala Asn Ser Trp Asp Ala Met Val Ile Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 462]]> <![CDATA[<211> 120]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 462]]> Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Ser 20 25 30 Asp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Val Ile Ser Gly Ser Gly Val Thr Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu His Ser Ser Ser Trp Tyr Thr Phe Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 463]]> <![CDATA[<211> 120]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 463]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ala Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Leu 35 40 45 Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asp Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Asp Asp Ser Ser Gly Tyr Tyr Leu Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 464]]> <![CDATA[<211> 120]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 464]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Met Ile Asn Pro Ser Gly Gly Ser Thr Thr Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Ala Ser Gly Asp Tyr Met Asp Leu Ile Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 4]]>65 <![CDATA[<211> 120]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 465]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 His Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Leu 35 40 45 Gly Trp Ile Asn Pro Asp Ser Gly Gly Thr Asn Tyr Glu Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Leu Val Gly Ser Ser Gly Tyr Leu Ala Pro Thr His Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 466]]> <![CDATA[<211> 120]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 466]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Pro Phe Thr Asp Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Val Arg Gly Asp Gly Tyr Asn Leu Gly Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 467]]> <![CDATA[<211> 120]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 467]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Asp Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Ser Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Val Asp Thr Ala Met Gly Ala Gly Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 468]]> <![CDATA[<211> 121]]> <![CDATA[<21]]>2> PRT]]> <br/><![CDATA[<213> 智人]]> <br/> <br/><![CDATA[<400> 468]]> <br/><![CDATA[Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Ala Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Val Ala Arg Trp Gly Tyr Gly Asp Tyr Pro Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 469]]> <![CDATA[<211> 121]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 469]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Thr His 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Ser Pro Ser Asp Gly Ser Thr Ser Tyr Ala Gln Lys Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Asn Gly Asp Tyr Tyr Tyr Gly Met Asp Val Trp Gly 100 105 110 Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 470]]> <![CDATA[<211> 121]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 470]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asn Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Pro Ile Ser Gly Gly Thr His Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Leu Gly Ser Ser Trp Tyr Val Leu Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 471]]> <![CDATA[<211> 121]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 471]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Ser Ala Asp Asn Gly Asp Thr Ser Phe Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Gly Ser His Tyr Gly Tyr Tyr Gly Met Asp Val Trp Gly 100 105 110 Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 472]]> <![CDATA[<211> 121]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 472]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Gly Ile Ser Pro Ile Tyr Gly Thr Pro Ala Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ser Pro Gly Pro Glu Gly Tyr Tyr Tyr Gly Met Asp Val Trp Gly 100 105 110 Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 473]]> <![CDATA[<211> 121]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 473]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Asn 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ser Tyr His Trp Asp Tyr Gly Asp Tyr Arg Phe Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 474]]> <![CDATA[<211> 121]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 474]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Val Glu Ile Asp Tyr Gly Asp Ser Pro Pro Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 475]]> <![CDATA[<211> 121]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 475]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Ser Ser Ser Tyr 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Asp Gly Asp Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Ala Glu Trp Glu Leu Arg Tyr Ala Phe Asp Ile Trp Gly 100 105 110 Gln Gly Thr Met Val Thr Val Ser Ser 115 120 <![CDATA[<210> 476]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 476]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr Tyr 20 25 30 Asp Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Thr Ile Asn Pro Ser Gly Gly Thr Thr Thr Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Thr Tyr Tyr Gly Leu Tyr Tyr Tyr Gly Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 477]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 477]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Lys Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Ala Pro Ser Leu Arg Gly Tyr Ser Tyr Gly Pro Asp Tyr Trp 100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 478]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 478]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Arg Gln Glu Arg Tyr Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 479]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 479]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Asp Gly Ser Thr Asp Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Arg Ser Tyr Gly Asp Tyr Tyr Tyr Gly Met Asp Val Trp 100 105 110 Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 480]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 480]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Gly Gly Gly Asn Ala Arg His Thr Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Val Phe Ser Glu Asn Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 481]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 481]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Asp Gly Ser Thr Thr Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Trp Asp Tyr Thr His Tyr Tyr Tyr Gly Met Asp Val Trp 100 105 110 Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 482]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 482]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asn Thr Phe Thr Ser His 20 25 30 Trp Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Gly Phe Asp Pro Glu Asp Gly Glu Thr Val Tyr Ala Gln Asn Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Asp Ser Ser Gly Tyr Tyr Gln Tyr Tyr Phe Asp Tyr Trp 100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 483]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 483]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Gly Ile Thr Pro Val Phe Gly Ile Ala Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Ser Trp Asp Ser Ser Ser Trp Tyr Ile Pro Glu Tyr Trp 100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 484]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 484]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 25 30 Asp Ile Val Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Arg Gly Gly Ser Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ser Leu Val Trp Gly Gly Ala Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 485]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 485]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Asn Gly Asp Thr Asp Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Thr Pro Val Phe Ser Gly Ser Tyr Tyr Trp Tyr Phe Asp Pro Trp 100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 486]]> <![CDATA[<211> 123]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 486]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Gly Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Thr Asp Gln Ala Val Ala Gly Pro Tyr Tyr Tyr Gly Met Asp Val 100 105 110 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 487]]> <![CDATA[<211> 123]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 487]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Leu Ile Asn Pro Gly Ser Gly Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Trp Leu Ala Gly Pro Tyr Tyr Tyr Gly Met Asp Val 100 105 110 Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 488]]> <![CDATA[<211> 123]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 488]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Met Phe Thr Gly His 20 25 30 Asp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Gly Ile Ile Pro Ile Phe Gly Thr Pro Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Val Met Gly Pro Val Asp Tyr Tyr Tyr Tyr Gly Met Asp Val 100 105 110 Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 489]]> <![CDATA[<211> 123]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 489]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Ser Asn Tyr 20 25 30 Asp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Asp Gly Ser Thr Thr Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Leu Gly Pro Phe Gly Ser Tyr Tyr Tyr Tyr Met Asp Val 100 105 110 Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 490]]> <![CDATA[<211> 123]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 490]]> Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Thr Ile Asn Gly Asp Gly Asp Asp Thr Asp Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Gly Val Val Val Pro Pro Tyr Tyr Tyr Tyr Met Asp Val 100 105 110 Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 491]]> <![CDATA[<211> 123]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 491]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Gln Ile Asp Pro Asn Ser Gly Asp Thr Ile Tyr Pro Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Ser Ser Gly Trp Ser Arg Tyr Tyr Tyr Tyr Tyr Met Asp Val 100 105 110 Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 492]]> <![CDATA[<211> 123]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 492]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asn Tyr 20 25 30 Gln Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Asn Gly Met Thr Thr Gly Tyr Tyr Tyr Tyr Met Asp Val 100 105 110 Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 493]]> <![CDATA[<211> 123]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 493]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Val Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ala Met Val Thr Gly Tyr Tyr Tyr Gly Met Asp Val 100 105 110 Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 494]]> <![CDATA[<211> 124]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 494]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Val Asn Pro Ser Asp Gly Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Gly Tyr Gly Asp Arg Gly Tyr Tyr Tyr Gly Met Asp 100 105 110 Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 495]]> <![CDATA[<211> 124]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 495]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Leu Ser Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Thr Tyr Asn Gly Asn Thr Tyr Tyr Ala Gln Lys Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Thr Ser Pro Lys Ala Thr Ala Asp Tyr Tyr Tyr Tyr Tyr Met Asp 100 105 110 Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 496]]> <![CDATA[<211> 124]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 496]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Asp Gly Ile Thr Asp Tyr Ala Gln Arg Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Thr Ser Thr Val Thr Pro Ser Tyr Tyr Tyr Tyr Tyr Gly Met Asp 100 105 110 Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 497]]> <![CDATA[<211> 125]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 497]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser His 20 25 30 Ala Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Arg Asp Gly Asp Thr Val Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Glu Pro Val Ala Gly Thr Gly Tyr Tyr Tyr Tyr Tyr Gly Met 100 105 110 Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 125 <![CDATA[<210> 498]]> <![CDATA[<211> 126]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 498]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Asn Ser Tyr 20 25 30 Gly Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Asn Leu Ala Gly Phe Trp Ser Asp Tyr Tyr Tyr Tyr Gly 100 105 110 Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 125 <![CDATA[<210> 499]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 499]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 500]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 500]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Asn Leu Val 85 90 95 Ser Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 501]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 501]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 502]]> <![CDATA[<211> 113]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 502]]> Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 1 5 10 15 Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala 85 90 95 Leu Gln Thr Pro Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys 100 105 110 Arg <![CDATA[<210> 503]]> <![CDATA[<211> 113]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 503]]> Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 1 5 10 15 Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly 85 90 95 Leu Gln Thr Pro His Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg <![CDATA[<210> 504]]> <![CDATA[<211> 107]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 504]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Arg Asn 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Lys Ala Ser Asn Leu Lys Gly Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr Ser Ala Pro Leu 85 90 95 Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 505]]> <![CDATA[<211> 113]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 505]]> Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 1 5 10 15 Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Thr 85 90 95 Leu Gln Thr Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg <![CDATA[<210> 506]]> <![CDATA[<211> 109]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 506]]> Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ala Ser 20 25 30 Asp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln 65 70 75 80 Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Asp Ser Pro 85 90 95 Gly Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 507]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 507]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Gly Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Arg Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro Pro 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 508]]> <![CDATA[<211> 107]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 508]]> Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser Thr His 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser 65 70 75 80 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Asn Ser Arg Thr 85 90 95 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 509]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 509]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Thr Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 510]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 510]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Asp 20 25 30 Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ser Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 511]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 511]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 512]]> <![CDATA[<211> 113]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 512]]> Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 1 5 10 15 Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly 85 90 95 Ala His Trp Pro Pro Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 100 105 110 Arg <![CDATA[<210> 513]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 513]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asp Ser 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Ser Leu Arg Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Arg Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 514]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 514]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Glu Ser Phe Thr Thr Gln Trp 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 515]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 515]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile His Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro Pro 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 516]]> <![CDATA[<211> 109]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 516]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Leu 85 90 95 Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 517]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 517]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asp Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Ile Ser Phe Pro Ile 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 518]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 518]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ser Pro Phe 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 519]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 519]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Thr Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Ile Ser Phe Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 520]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 520]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Thr Phe Pro Ile 85 90 95 Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 521]]> <![CDATA[<211> 113]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 521]]> Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 1 5 10 15 Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Asp Ala Ser His Leu Glu Thr Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln Tyr 85 90 95 Tyr Ser Tyr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg <![CDATA[<210> 522]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400]]>> 522]]> <br/><![CDATA[Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ala Pro Leu 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 523]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 523]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Phe Ser Thr Phe Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 524]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 524]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ile Pro Phe 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 525]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 525]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Asn Arg Phe 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Asn Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 526]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 526]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Ile 85 90 95 Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 527]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 527]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Val Ser Thr Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Thr Ile Pro Ser 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 528]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 528]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ala Lys Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ala Pro Pro 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 529]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 529]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Gly Ile Thr Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Trp 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 530]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 530]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile His Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Thr Thr Pro Leu 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 531]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 531]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Phe Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ala Pro Ile 85 90 95 Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 532]]> <![CDATA[<211> 109]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 532]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro 85 90 95 Val Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 533]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 533]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Asn Gln Asp Ile Ser Asn Phe 20 25 30 Leu Glu Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ile Pro Ile 85 90 95 Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 534]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 534]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Asn 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Glu Ala Ser Thr Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 535]]> <![CDATA[<211> 113]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 535]]> Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 1 5 10 15 Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Gly Ala Ser Thr Leu Glu Thr Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly 85 90 95 Leu Gln Pro Pro Gly Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg <![CDATA[<210> 536]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 536]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Arg Ser 20 25 30 Leu Val Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Asn His Phe Arg 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 537]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 537]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Arg Ser Asp Ser Thr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 538]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 538]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser His Asp Ile Ser Lys Ser 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Arg 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 539]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 539]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Ala Tyr 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ile Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 5]]>40 <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 540]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 541]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 541]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Ser Tyr 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 542]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 542]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr Ser Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 543]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 543]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Ile Gly Thr Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Gln 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 544]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 544]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Thr Ile Ser Tyr Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Arg Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 545]]> <![CDATA[<211> 112]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 545]]> Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 1 5 10 15 Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Met Gly Ser Asn Arg Ala Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly 85 90 95 Thr His Trp Pro Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg 100 105 110 <![CDATA[<210> 546]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 546]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Ile Asn Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Phe Ser Leu Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 547]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 547]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Thr Ile Ser Thr Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 548]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 548]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Arg Gly Ile Gly Asn Asp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Thr Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Asn Met Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 549]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 549]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Thr Ile Gly Asn Tyr 20 25 30 Val Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Asn Leu His Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr Ser Ala Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 550]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 550]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Phe Ile Gly Ser Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 551]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智]]>人 <![CDATA[<400> 551]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp 20 25 30 Met Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr Ser Thr Pro Tyr 85 90 95 Ile Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 552]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> ]]>552 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Asn 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ser Pro Trp 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 553]]> <![CDATA[<211> 114]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 553]]> Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 1 5 10 15 Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser 20 25 30 Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 35 40 45 Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 50 55 60 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 65 70 75 80 Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln 85 90 95 Tyr Ala Ser Ala Pro Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 100 105 110 Lys Arg <![CDATA[<210> 554]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 554]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Lys Thr Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Phe Thr Ile Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 555]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 555]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Val Ser Gln Gly Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 556]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 556]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asp Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 557]]> <![CDATA[<211> 108]]> <![CDATA[<21]]>2> PRT]]> <br/><![CDATA[<213> 智人]]> <br/> <br/><![CDATA[<400> 557]]> <br/><![CDATA[Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Tyr 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr Arg Thr Pro Pro 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 558]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 558]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Arg Asn Tyr 20 25 30 Leu Thr Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 559]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 559]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Ile Arg Leu Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Leu Thr Thr Pro Phe 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 560]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 560]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Arg Lys Phe 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Gly Tyr Pro Gly 85 90 95 Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 561]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 561]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Thr Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Leu Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 562]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 562]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr Thr Thr Pro Arg 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 563]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 563]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Arg Ser Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Asn Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 564]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 564]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Gly Asn Asp 20 25 30 Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ala Pro Pro Pro 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 565]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 565]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 566]]> <![CDATA[<211> 113]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 566]]> Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 1 5 10 15 Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly 85 90 95 Leu Gln Thr Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg <![CDATA[<210> 567]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 567]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Leu Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asp Ser Ile Pro Val 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 568]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 568]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr 85 90 95 Asn Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 569]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 569]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Ile Gly Ser Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 570]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 570]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Arg Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 571]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 571]]> Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Thr Ser Asn 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln 65 70 75 80 Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Tyr Gly Ser Ser Pro 85 90 95 Ala Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 572]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 572]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Tyr 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 573]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 573]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Tyr Thr Tyr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 574]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 574]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Thr Thr Pro Asn 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 575]]> <![CDATA[<211> 108]]> <![CDATA[<212> P]]>RT <![CDATA[<213> 智人]]> <![CDATA[<400> 575]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Tyr 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 576]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 576]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Gly 20 25 30 Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Phe 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 577]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 577]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Ile Arg Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 578]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 578]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Leu Asp Ile Asn Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Met Pro Leu 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 579]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 579]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Gly Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Thr Thr Pro Trp 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 580]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 580]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ser Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 581]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 581]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Asp Pro Leu 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 582]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 582]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ala Pro Ile 85 90 95 Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 583]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 583]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Thr Thr Pro Leu 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <![CDATA[<210> 584]]> <![CDATA[<211> 109]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 584]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Ile Gly Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro 85 90 95 Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 585]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 585]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Arg Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Gln Thr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 586]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 586]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Thr Thr Pro Pro 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 587]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 587]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Gln 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 588]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 588]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Asp 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro Ile 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 589]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 589]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Asn Thr Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg 100 105 <![CDATA[<210> 590]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 590]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Thr Val Pro Pro 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 591]]> <![CDATA[<211> 108]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 591]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Arg Tyr Phe 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Asp Asp Ser Phe Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <![CDATA[<210> 592]]> <![CDATA[<211> 546]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 尼]]>帕亨尼帕病毒 <![CDATA[<400> 592]]> Met Val Val Ile Leu Asp Lys Arg Cys Tyr Cys Asn Leu Leu Ile Leu 1 5 10 15 Ile Leu Met Ile Ser Glu Cys Ser Val Gly Ile Leu His Tyr Glu Lys 20 25 30 Leu Ser Lys Ile Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile 35 40 45 Lys Ser Asn Pro Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn 50 55 60 Val Ser Asn Met Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys 65 70 75 80 Thr Arg Leu Asn Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile 85 90 95 Tyr Lys Asn Asn Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly 100 105 110 Val Ile Met Ala Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile 115 120 125 Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile 130 135 140 Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys 145 150 155 160 Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln 165 170 175 Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys 180 185 190 Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser 195 200 205 Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn 210 215 220 Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu 225 230 235 240 Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu 245 250 255 Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser 260 265 270 Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile 275 280 285 Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp 290 295 300 Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn 305 310 315 320 Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg 325 330 335 Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met 340 345 350 Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val 355 360 365 Val Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe 370 375 380 Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala 385 390 395 400 Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr 405 410 415 Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr 420 425 430 Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro 435 440 445 Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn 450 455 460 Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu 465 470 475 480 Leu Asp Thr Val Asn Pro Ser Leu Ile Ser Met Leu Ser Met Ile Ile 485 490 495 Leu Tyr Val Leu Ser Ile Ala Ser Leu Cys Ile Gly Leu Ile Thr Phe 500 505 510 Ile Ser Phe Ile Ile Val Glu Lys Lys Arg Asn Thr Tyr Ser Arg Leu 515 520 525 Glu Asp Arg Arg Val Arg Pro Thr Ser Ser Gly Asp Leu Tyr Tyr Ile 530 535 540 Gly Thr 545 <![CDATA[<210> 593]]> <![CDATA[<211> 520]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 尼帕亨尼帕病毒]]> <![CDATA[<400> 593]]> Ile Leu His Tyr Glu Lys Leu Ser Lys Ile Gly Leu Val Lys Gly Val 1 5 10 15 Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro Leu Thr Lys Asp Ile Val 20 25 30 Ile Lys Met Ile Pro Asn Val Ser Asn Met Ser Gln Cys Thr Gly Ser 35 40 45 Val Met Glu Asn Tyr Lys Thr Arg Leu Asn Gly Ile Leu Thr Pro Ile 50 55 60 Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn Thr His Asp Leu Val Gly 65 70 75 80 Asp Val Arg Leu Ala Gly Val Ile Met Ala Gly Val Ala Ile Gly Ile 85 90 95 Ala Thr Ala Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met 100 105 110 Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr 115 120 125 Asn Glu Ala Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr 130 135 140 Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr 145 150 155 160 Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala 165 170 175 Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu 180 185 190 Gln Asp Pro Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala 195 200 205 Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr 210 215 220 Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile 225 230 235 240 Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe 245 250 255 Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro 260 265 270 Val Ser Phe Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn 275 280 285 Phe Ile Leu Val Arg Asn Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe 290 295 300 Cys Leu Ile Thr Lys Arg Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr 305 310 315 320 Pro Met Thr Asn Asn Met Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys 325 330 335 Cys Pro Arg Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu 340 345 350 Ser Asn Gly Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys 355 360 365 Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu 370 375 380 Met Ile Asp Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile 385 390 395 400 Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly 405 410 415 Ile Ala Ile Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser 420 425 430 Gln Ile Ser Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile 435 440 445 Lys Glu Ala Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Ile Ser 450 455 460 Met Leu Ser Met Ile Ile Leu Tyr Val Leu Ser Ile Ala Ser Leu Cys 465 470 475 480 Ile Gly Leu Ile Thr Phe Ile Ser Phe Ile Ile Val Glu Lys Lys Arg 485 490 495 Asn Thr Tyr Ser Arg Leu Glu Asp Arg Arg Val Arg Pro Thr Ser Ser 500 505 510 Gly Asp Leu Tyr Tyr Ile Gly Thr 515 520 <![CDATA[<210> 594]]> <![CDATA[<211> 83]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 尼帕亨尼帕病毒]]> <![CDATA[<400> 594]]> Ile Leu His Tyr Glu Lys Leu Ser Lys Ile Gly Leu Val Lys Gly Val 1 5 10 15 Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro Leu Thr Lys Asp Ile Val 20 25 30 Ile Lys Met Ile Pro Asn Val Ser Asn Met Ser Gln Cys Thr Gly Ser 35 40 45 Val Met Glu Asn Tyr Lys Thr Arg Leu Asn Gly Ile Leu Thr Pro Ile 50 55 60 Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn Thr His Asp Leu Val Gly 65 70 75 80 Asp Val Arg <![CDATA[<210> 595]]> <![CDATA[<211> 437]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 尼帕]]>亨尼帕病毒 <![CDATA[<400> 595]]> Leu Ala Gly Val Ile Met Ala Gly Val Ala Ile Gly Ile Ala Thr Ala 1 5 10 15 Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala 20 25 30 Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala 35 40 45 Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr 50 55 60 Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys 65 70 75 80 Ile Ser Cys Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys 85 90 95 Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro 100 105 110 Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly 115 120 125 Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe 130 135 140 Asp Asp Leu Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val 145 150 155 160 Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu 165 170 175 Thr Glu Ile Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe 180 185 190 Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu 195 200 205 Val Arg Asn Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile 210 215 220 Thr Lys Arg Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr 225 230 235 240 Asn Asn Met Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg 245 250 255 Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly 260 265 270 Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr 275 280 285 Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp 290 295 300 Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu 305 310 315 320 Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile 325 330 335 Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser 340 345 350 Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala 355 360 365 Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Ile Ser Met Leu Ser 370 375 380 Met Ile Ile Leu Tyr Val Leu Ser Ile Ala Ser Leu Cys Ile Gly Leu 385 390 395 400 Ile Thr Phe Ile Ser Phe Ile Ile Val Glu Lys Lys Arg Asn Thr Tyr 405 410 415 Ser Arg Leu Glu Asp Arg Arg Val Arg Pro Thr Ser Ser Gly Asp Leu 420 425 430 Tyr Tyr Ile Gly Thr 435 <![CDATA[<210> 596]]> <![CDATA[<211> 500]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 596]]> Ile Leu His Tyr Glu Lys Leu Ser Lys Ile Gly Leu Val Lys Gly Val 1 5 10 15 Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro Leu Thr Lys Asp Ile Val 20 25 30 Ile Lys Met Ile Pro Asn Val Ser Asn Met Ser Gln Cys Thr Gly Ser 35 40 45 Val Met Glu Asn Tyr Lys Thr Arg Leu Asn Gly Ile Leu Thr Pro Ile 50 55 60 Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn Thr His Asp Leu Val Gly 65 70 75 80 Asp Val Arg Leu Ala Gly Val Ile Met Ala Gly Val Ala Ile Gly Ile 85 90 95 Ala Thr Ala Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met 100 105 110 Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr 115 120 125 Asn Glu Ala Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr 130 135 140 Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr 145 150 155 160 Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala 165 170 175 Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu 180 185 190 Gln Asp Pro Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala 195 200 205 Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr 210 215 220 Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile 225 230 235 240 Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe 245 250 255 Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro 260 265 270 Val Ser Phe Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn 275 280 285 Phe Ile Leu Val Arg Asn Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe 290 295 300 Cys Leu Ile Thr Lys Arg Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr 305 310 315 320 Pro Met Thr Asn Asn Met Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys 325 330 335 Cys Pro Arg Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu 340 345 350 Ser Asn Gly Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys 355 360 365 Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu 370 375 380 Met Ile Asp Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile 385 390 395 400 Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly 405 410 415 Ile Ala Ile Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser 420 425 430 Gln Ile Ser Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile 435 440 445 Lys Glu Ala Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Ile Ser 450 455 460 Met Leu Ser Met Ile Ile Leu Tyr Val Leu Ser Ile Ala Ser Leu Cys 465 470 475 480 Ile Gly Leu Ile Thr Phe Ile Ser Phe Ile Ile Val Glu Lys Lys Arg 485 490 495 Asn Thr Gly Thr 500 <![CDATA[<210> 597]]> <![CDATA[<211> 417]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 597]]> Leu Ala Gly Val Ile Met Ala Gly Val Ala Ile Gly Ile Ala Thr Ala 1 5 10 15 Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala 20 25 30 Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala 35 40 45 Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr 50 55 60 Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys 65 70 75 80 Ile Ser Cys Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys 85 90 95 Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro 100 105 110 Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly 115 120 125 Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe 130 135 140 Asp Asp Leu Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val 145 150 155 160 Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu 165 170 175 Thr Glu Ile Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe 180 185 190 Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu 195 200 205 Val Arg Asn Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile 210 215 220 Thr Lys Arg Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr 225 230 235 240 Asn Asn Met Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg 245 250 255 Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly 260 265 270 Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr 275 280 285 Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp 290 295 300 Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu 305 310 315 320 Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile 325 330 335 Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser 340 345 350 Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala 355 360 365 Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Ile Ser Met Leu Ser 370 375 380 Met Ile Ile Leu Tyr Val Leu Ser Ile Ala Ser Leu Cys Ile Gly Leu 385 390 395 400 Ile Thr Phe Ile Ser Phe Ile Ile Val Glu Lys Lys Arg Asn Thr Gly 405 410 415 Thr <![CDATA[<210> 598]]> <![CDATA[<211> 500]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 598]]> Ile Leu His Tyr Glu Lys Leu Ser Lys Ile Gly Leu Val Lys Gly Val 1 5 10 15 Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro Leu Thr Lys Asp Ile Val 20 25 30 Ile Lys Met Ile Pro Asn Val Ser Asn Met Ser Gln Cys Thr Gly Ser 35 40 45 Val Met Glu Asn Tyr Lys Thr Arg Leu Asn Gly Ile Leu Thr Pro Ile 50 55 60 Lys Gly Ala Leu Glu Ile Tyr Lys Asn Gln Thr His Asp Leu Val Gly 65 70 75 80 Asp Val Arg Leu Ala Gly Val Ile Met Ala Gly Val Ala Ile Gly Ile 85 90 95 Ala Thr Ala Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met 100 105 110 Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr 115 120 125 Asn Glu Ala Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr 130 135 140 Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr 145 150 155 160 Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala 165 170 175 Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu 180 185 190 Gln Asp Pro Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala 195 200 205 Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr 210 215 220 Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile 225 230 235 240 Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe 245 250 255 Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro 260 265 270 Val Ser Phe Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn 275 280 285 Phe Ile Leu Val Arg Asn Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe 290 295 300 Cys Leu Ile Thr Lys Arg Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr 305 310 315 320 Pro Met Thr Asn Asn Met Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys 325 330 335 Cys Pro Arg Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu 340 345 350 Ser Asn Gly Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys 355 360 365 Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu 370 375 380 Met Ile Asp Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile 385 390 395 400 Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly 405 410 415 Ile Ala Ile Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser 420 425 430 Gln Ile Ser Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile 435 440 445 Lys Glu Ala Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Ile Ser 450 455 460 Met Leu Ser Met Ile Ile Leu Tyr Val Leu Ser Ile Ala Ser Leu Cys 465 470 475 480 Ile Gly Leu Ile Thr Phe Ile Ser Phe Ile Ile Val Glu Lys Lys Arg 485 490 495 Asn Thr Gly Thr 500 <![CDATA[<210> 599]]> <![CDATA[<211> 524]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 599]]> Met Val Val Ile Leu Asp Lys Arg Cys Tyr Cys Asn Leu Leu Ile Leu 1 5 10 15 Ile Leu Met Ile Ser Glu Cys Ser Val Gly Ile Leu His Tyr Glu Lys 20 25 30 Leu Ser Lys Ile Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile 35 40 45 Lys Ser Asn Pro Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn 50 55 60 Val Ser Asn Met Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys 65 70 75 80 Thr Arg Leu Asn Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile 85 90 95 Tyr Lys Asn Asn Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly 100 105 110 Val Ile Met Ala Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile 115 120 125 Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile 130 135 140 Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys 145 150 155 160 Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln 165 170 175 Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys 180 185 190 Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser 195 200 205 Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn 210 215 220 Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu 225 230 235 240 Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu 245 250 255 Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser 260 265 270 Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile 275 280 285 Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp 290 295 300 Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn 305 310 315 320 Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg 325 330 335 Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met 340 345 350 Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val 355 360 365 Val Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe 370 375 380 Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala 385 390 395 400 Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr 405 410 415 Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr 420 425 430 Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro 435 440 445 Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn 450 455 460 Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu 465 470 475 480 Leu Asp Thr Val Asn Pro Ser Leu Ile Ser Met Leu Ser Met Ile Ile 485 490 495 Leu Tyr Val Leu Ser Ile Ala Ser Leu Cys Ile Gly Leu Ile Thr Phe 500 505 510 Ile Ser Phe Ile Ile Val Glu Lys Lys Arg Asn Thr 515 520 <![CDATA[<210> 600]]> <![CDATA[<211]]>> 602]]> <br/><![CDATA[<212> PRT]]> <br/><![CDATA[<213> 尼帕亨尼帕病毒]]> <br/> <br/><![CDATA[<400> 600]]> <br/><![CDATA[Met Gly Pro Ala Glu Asn Lys Lys Val Arg Phe Glu Asn Thr Thr Ser 1 5 10 15 Asp Lys Gly Lys Ile Pro Ser Lys Val Ile Lys Ser Tyr Tyr Gly Thr 20 25 30 Met Asp Ile Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu 35 40 45 Ser Ala Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile 50 55 60 Val Met Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn 65 70 75 80 Gln Ala Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys 85 90 95 Gly Leu Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu 100 105 110 Ile Asp Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu 115 120 125 Gly Ser Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn 130 135 140 Glu Lys Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn 145 150 155 160 Ile Ser Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr 165 170 175 Glu Gly Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln 180 185 190 Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu 195 200 205 Pro Val Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala 210 215 220 Met Asp Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser 225 230 235 240 Cys Ser Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val 245 250 255 Leu Asp Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp 260 265 270 Thr Pro Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn 275 280 285 Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro 290 295 300 Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu 305 310 315 320 Ala Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu 325 330 335 Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr 340 345 350 Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val 355 360 365 Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro 370 375 380 Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met 385 390 395 400 Gly Ile Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys 405 410 415 Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile 420 425 430 Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser 435 440 445 Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met 450 455 460 Ile Lys Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp 465 470 475 480 Arg Asn Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg 485 490 495 Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala 500 505 510 Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp 515 520 525 Ser Asn Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn 530 535 540 Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln 545 550 555 560 Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile 565 570 575 Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys 580 585 590 Leu Phe Ala Val Lys Ile Pro Glu Gln Cys 595 600 <![CDATA[<210> 601]]> <![CDATA[<211> 597]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 601]]> Met Gly Lys Val Arg Phe Glu Asn Thr Thr Ser Asp Lys Gly Lys Ile 1 5 10 15 Pro Ser Lys Val Ile Lys Ser Tyr Tyr Gly Thr Met Asp Ile Lys Lys 20 25 30 Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala Phe Asn Thr 35 40 45 Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met Asn Ile Met 50 55 60 Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala Val Ile Lys 65 70 75 80 Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu Ala Asp Lys 85 90 95 Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp Thr Ser Ser 100 105 110 Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser Lys Ile Ser 115 120 125 Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys Cys Lys Phe 130 135 140 Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser Cys Pro Asn 145 150 155 160 Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly Val Ser Asn 165 170 175 Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln 180 185 190 Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln 195 200 205 Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr 210 215 220 Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val 225 230 235 240 Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp 245 250 255 Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro 260 265 270 Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr 275 280 285 Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr 290 295 300 Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys 305 310 315 320 Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile 325 330 335 Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile 340 345 350 Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg 355 360 365 Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln 370 375 380 Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn 385 390 395 400 Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp 405 410 415 Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu 420 425 430 Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val 435 440 445 Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp 450 455 460 Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val 465 470 475 480 Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro 485 490 495 Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg 500 505 510 Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala 515 520 525 Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg 530 535 540 Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn 545 550 555 560 Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile 565 570 575 Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys 580 585 590 Ile Pro Glu Gln Cys 595 <![CDATA[<210> 602]]> <![CDATA[<211> 592]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 602]]> Met Gly Asn Thr Thr Ser Asp Lys Gly Lys Ile Pro Ser Lys Val Ile 1 5 10 15 Lys Ser Tyr Tyr Gly Thr Met Asp Ile Lys Lys Ile Asn Glu Gly Leu 20 25 30 Leu Asp Ser Lys Ile Leu Ser Ala Phe Asn Thr Val Ile Ala Leu Leu 35 40 45 Gly Ser Ile Val Ile Ile Val Met Asn Ile Met Ile Ile Gln Asn Tyr 50 55 60 Thr Arg Ser Thr Asp Asn Gln Ala Val Ile Lys Asp Ala Leu Gln Gly 65 70 75 80 Ile Gln Gln Gln Ile Lys Gly Leu Ala Asp Lys Ile Gly Thr Glu Ile 85 90 95 Gly Pro Lys Val Ser Leu Ile Asp Thr Ser Ser Thr Ile Thr Ile Pro 100 105 110 Ala Asn Ile Gly Leu Leu Gly Ser Lys Ile Ser Gln Ser Thr Ala Ser 115 120 125 Ile Asn Glu Asn Val Asn Glu Lys Cys Lys Phe Thr Leu Pro Pro Leu 130 135 140 Lys Ile His Glu Cys Asn Ile Ser Cys Pro Asn Pro Leu Pro Phe Arg 145 150 155 160 Glu Tyr Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val Gly Leu Pro 165 170 175 Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys 180 185 190 Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr Cys Ile 195 200 205 Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser His 210 215 220 Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln Arg Ile 225 230 235 240 Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro Ser Leu 245 250 255 Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr His 260 265 270 Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val 275 280 285 Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser 290 295 300 Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly 305 310 315 320 Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr 325 330 335 Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr 340 345 350 Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr 355 360 365 Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu 370 375 380 Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu 385 390 395 400 Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys 405 410 415 Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro 420 425 430 Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser 435 440 445 Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn 450 455 460 Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro Gly 465 470 475 480 Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu 485 490 495 Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser 500 505 510 Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe 515 520 525 Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser 530 535 540 Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys 545 550 555 560 Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp 565 570 575 Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys 580 585 590 <![CDATA[<210> 603]]> <![CDATA[<211> 587]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 603]]> Met Gly Lys Gly Lys Ile Pro Ser Lys Val Ile Lys Ser Tyr Tyr Gly 1 5 10 15 Thr Met Asp Ile Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile 20 25 30 Leu Ser Ala Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile 35 40 45 Ile Val Met Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp 50 55 60 Asn Gln Ala Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile 65 70 75 80 Lys Gly Leu Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser 85 90 95 Leu Ile Asp Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu 100 105 110 Leu Gly Ser Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val 115 120 125 Asn Glu Lys Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys 130 135 140 Asn Ile Ser Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln 145 150 155 160 Thr Glu Gly Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu 165 170 175 Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr 180 185 190 Leu Pro Val Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu 195 200 205 Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly 210 215 220 Ser Cys Ser Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu 225 230 235 240 Val Leu Asp Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val 245 250 255 Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr 260 265 270 Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp 275 280 285 Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg 290 295 300 Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln 305 310 315 320 Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro 325 330 335 Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala 340 345 350 Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys 355 360 365 Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser 370 375 380 Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu 385 390 395 400 Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu 405 410 415 Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp 420 425 430 Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr 435 440 445 Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn 450 455 460 Trp Arg Asn Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro 465 470 475 480 Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp 485 490 495 Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu 500 505 510 Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp 515 520 525 Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala 530 535 540 Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys 545 550 555 560 Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro 565 570 575 Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys 580 585 <![CDATA[<210> 604]]> <![CDATA[<211> 582]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 604]]> Met Gly Ser Lys Val Ile Lys Ser Tyr Tyr Gly Thr Met Asp Ile Lys 1 5 10 15 Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala Phe Asn 20 25 30 Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met Asn Ile 35 40 45 Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala Val Ile 50 55 60 Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu Ala Asp 65 70 75 80 Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp Thr Ser 85 90 95 Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser Lys Ile 100 105 110 Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys Cys Lys 115 120 125 Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser Cys Pro 130 135 140 Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly Val Ser 145 150 155 160 Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn 165 170 175 Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly 180 185 190 Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly 195 200 205 Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly 210 215 220 Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly 225 230 235 240 Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn 245 250 255 Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr 260 265 270 Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser 275 280 285 Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro 290 295 300 Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser 305 310 315 320 Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly 325 330 335 Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val 340 345 350 Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys 355 360 365 Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro 370 375 380 Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser 385 390 395 400 Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg 405 410 415 Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro 420 425 430 Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly 435 440 445 Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr 450 455 460 Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys 465 470 475 480 Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp 485 490 495 Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr 500 505 510 Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr 515 520 525 Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr 530 535 540 Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu 545 550 555 560 Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val 565 570 575 Lys Ile Pro Glu Gln Cys 580 <![CDATA[<210> 605]]> <![CDATA[<211> 577]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 605]]> Met Gly Ser Tyr Tyr Gly Thr Met Asp Ile Lys Lys Ile Asn Glu Gly 1 5 10 15 Leu Leu Asp Ser Lys Ile Leu Ser Ala Phe Asn Thr Val Ile Ala Leu 20 25 30 Leu Gly Ser Ile Val Ile Ile Val Met Asn Ile Met Ile Ile Gln Asn 35 40 45 Tyr Thr Arg Ser Thr Asp Asn Gln Ala Val Ile Lys Asp Ala Leu Gln 50 55 60 Gly Ile Gln Gln Gln Ile Lys Gly Leu Ala Asp Lys Ile Gly Thr Glu 65 70 75 80 Ile Gly Pro Lys Val Ser Leu Ile Asp Thr Ser Ser Thr Ile Thr Ile 85 90 95 Pro Ala Asn Ile Gly Leu Leu Gly Ser Lys Ile Ser Gln Ser Thr Ala 100 105 110 Ser Ile Asn Glu Asn Val Asn Glu Lys Cys Lys Phe Thr Leu Pro Pro 115 120 125 Leu Lys Ile His Glu Cys Asn Ile Ser Cys Pro Asn Pro Leu Pro Phe 130 135 140 Arg Glu Tyr Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val Gly Leu 145 150 155 160 Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro 165 170 175 Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr Cys 180 185 190 Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser 195 200 205 His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln Arg 210 215 220 Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro Ser 225 230 235 240 Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr 245 250 255 His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala 260 265 270 Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly 275 280 285 Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly 290 295 300 Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg 305 310 315 320 Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp 325 330 335 Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys 340 345 350 Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro 355 360 365 Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile 370 375 380 Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro 385 390 395 400 Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser 405 410 415 Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala 420 425 430 Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val 435 440 445 Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro 450 455 460 Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp 465 470 475 480 Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile 485 490 495 Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro Val 500 505 510 Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala 515 520 525 Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu 530 535 540 Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly 545 550 555 560 Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln 565 570 575 Cys <![CDATA[<210> 606]]> <![CDATA[<211> 573]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 606]]> Met Gly Thr Met Asp Ile Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser 1 5 10 15 Lys Ile Leu Ser Ala Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile 20 25 30 Val Ile Ile Val Met Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser 35 40 45 Thr Asp Asn Gln Ala Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln 50 55 60 Gln Ile Lys Gly Leu Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys 65 70 75 80 Val Ser Leu Ile Asp Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile 85 90 95 Gly Leu Leu Gly Ser Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu 100 105 110 Asn Val Asn Glu Lys Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His 115 120 125 Glu Cys Asn Ile Ser Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg 130 135 140 Pro Gln Thr Glu Gly Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile 145 150 155 160 Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser 165 170 175 Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro 180 185 190 Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg 195 200 205 Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val 210 215 220 Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr 225 230 235 240 Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala 245 250 255 Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val 260 265 270 Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met 275 280 285 Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln 290 295 300 His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val 305 310 315 320 Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe 325 330 335 Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser 340 345 350 Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg 355 360 365 Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly 370 375 380 Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe 385 390 395 400 Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile 405 410 415 Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp 420 425 430 Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val 435 440 445 Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln 450 455 460 Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr 465 470 475 480 Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val 485 490 495 Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe 500 505 510 Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr 515 520 525 Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile 530 535 540 Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile 545 550 555 560 Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys 565 570 <![CDATA[<210> 607]]> <![CDATA[<211> 569]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 607]]> Met Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala 1 5 10 15 Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met 20 25 30 Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala 35 40 45 Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu 50 55 60 Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp 65 70 75 80 Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser 85 90 95 Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys 100 105 110 Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser 115 120 125 Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly 130 135 140 Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr 145 150 155 160 Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val 165 170 175 Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp 180 185 190 Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser 195 200 205 Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp 210 215 220 Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro 225 230 235 240 Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu 245 250 255 Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu 260 265 270 Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val 275 280 285 Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu 290 295 300 Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro 305 310 315 320 Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe 325 330 335 Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr 340 345 350 Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile 355 360 365 Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn 370 375 380 Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp 385 390 395 400 Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly 405 410 415 Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys 420 425 430 Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn 435 440 445 Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn 450 455 460 Thr Cys Pro Ala Ile Cys Ala Glu Gly Val Tyr Asn Asp Ala Phe Leu 465 470 475 480 Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn 485 490 495 Ala Thr Ala Ala Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile 500 505 510 Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr 515 520 525 Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu 530 535 540 Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe 545 550 555 560 Ala Val Lys Ile Pro Glu Gln Cys Thr 565 <![CDATA[<210> 608]]> <![CDATA[<211> 546]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 亨德拉亨尼帕病毒]]> <![CDATA[<400> 608]]> Met Ala Thr Gln Glu Val Arg Leu Lys Cys Leu Leu Cys Gly Ile Ile 1 5 10 15 Val Leu Val Leu Ser Leu Glu Gly Leu Gly Ile Leu His Tyr Glu Lys 20 25 30 Leu Ser Lys Ile Gly Leu Val Lys Gly Ile Thr Arg Lys Tyr Lys Ile 35 40 45 Lys Ser Asn Pro Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn 50 55 60 Val Ser Asn Val Ser Lys Cys Thr Gly Thr Val Met Glu Asn Tyr Lys 65 70 75 80 Ser Arg Leu Thr Gly Ile Leu Ser Pro Ile Lys Gly Ala Ile Glu Leu 85 90 95 Tyr Asn Asn Asn Thr His Asp Leu Val Gly Asp Val Lys Leu Ala Gly 100 105 110 Val Val Met Ala Gly Ile Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile 115 120 125 Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile 130 135 140 Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys 145 150 155 160 Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln 165 170 175 Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Gln Ile Ser Cys 180 185 190 Lys Gln Thr Glu Leu Ala Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser 195 200 205 Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn 210 215 220 Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu 225 230 235 240 Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu 245 250 255 Leu Glu Ser Asp Ser Ile Ala Gly Gln Ile Val Tyr Val Asp Leu Ser 260 265 270 Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile 275 280 285 Gln Gln Ala Tyr Val Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp 290 295 300 Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Val Leu Ile Arg Asn 305 310 315 320 Thr Leu Ile Ser Asn Ile Glu Val Lys Tyr Cys Leu Ile Thr Lys Lys 325 330 335 Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr Ala Ser Val 340 345 350 Arg Glu Cys Leu Thr Gly Ser Thr Asp Lys Cys Pro Arg Glu Leu Val 355 360 365 Val Ser Ser His Val Pro Arg Phe Ala Leu Ser Gly Gly Val Leu Phe 370 375 380 Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala 385 390 395 400 Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr 405 410 415 Cys Thr Thr Val Val Leu Gly Asn Ile Ile Ile Ser Leu Gly Lys Tyr 420 425 430 Leu Gly Ser Ile Asn Tyr Asn Ser Glu Ser Ile Ala Val Gly Pro Pro 435 440 445 Val Tyr Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn 450 455 460 Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Lys Ile 465 470 475 480 Leu Asp Thr Val Asn Pro Ser Leu Ile Ser Met Leu Ser Met Ile Ile 485 490 495 Leu Tyr Val Leu Ser Ile Ala Ala Leu Cys Ile Gly Leu Ile Thr Phe 500 505 510 Ile Ser Phe Val Ile Val Glu Lys Lys Arg Gly Asn Tyr Ser Arg Leu 515 520 525 Asp Asp Arg Gln Val Arg Pro Val Ser Asn Gly Asp Leu Tyr Tyr Ile 530 535 540 Gly Thr 545 <![CDATA[<210> 609]]> <![CDATA[<211> 604]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 亨德拉亨尼帕病毒]]> <![CDATA[<400> 609]]> Met Met Ala Asp Ser Lys Leu Val Ser Leu Asn Asn Asn Leu Ser Gly 1 5 10 15 Lys Ile Lys Asp Gln Gly Lys Val Ile Lys Asn Tyr Tyr Gly Thr Met 20 25 30 Asp Ile Lys Lys Ile Asn Asp Gly Leu Leu Asp Ser Lys Ile Leu Gly 35 40 45 Ala Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Ile Ile Ile Val 50 55 60 Met Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Thr Thr Asp Asn Gln 65 70 75 80 Ala Leu Ile Lys Glu Ser Leu Gln Ser Val Gln Gln Gln Ile Lys Ala 85 90 95 Leu Thr Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile 100 105 110 Asp Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly 115 120 125 Ser Lys Ile Ser Gln Ser Thr Ser Ser Ile Asn Glu Asn Val Asn Asp 130 135 140 Lys Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile 145 150 155 160 Ser Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Ile Ser Gln 165 170 175 Gly Val Ser Asp Leu Val Gly Leu Pro Asn Gln Ile Cys Leu Gln Lys 180 185 190 Thr Thr Ser Thr Ile Leu Lys Pro Arg Leu Ile Ser Tyr Thr Leu Pro 195 200 205 Ile Asn Thr Arg Glu Gly Val Cys Ile Thr Asp Pro Leu Leu Ala Val 210 215 220 Asp Asn Gly Phe Phe Ala Tyr Ser His Leu Glu Lys Ile Gly Ser Cys 225 230 235 240 Thr Arg Gly Ile Ala Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu 245 250 255 Asp Arg Gly Asp Lys Val Pro Ser Met Phe Met Thr Asn Val Trp Thr 260 265 270 Pro Pro Asn Pro Ser Thr Ile His His Cys Ser Ser Thr Tyr His Glu 275 280 285 Asp Phe Tyr Tyr Thr Leu Cys Ala Val Ser His Val Gly Asp Pro Ile 290 295 300 Leu Asn Ser Thr Ser Trp Thr Glu Ser Leu Ser Leu Ile Arg Leu Ala 305 310 315 320 Val Arg Pro Lys Ser Asp Ser Gly Asp Tyr Asn Gln Lys Tyr Ile Ala 325 330 335 Ile Thr Lys Val Glu Arg Gly Lys Tyr Asp Lys Val Met Pro Tyr Gly 340 345 350 Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly 355 360 365 Phe Leu Pro Arg Thr Glu Phe Gln Tyr Asn Asp Ser Asn Cys Pro Ile 370 375 380 Ile His Cys Lys Tyr Ser Lys Ala Glu Asn Cys Arg Leu Ser Met Gly 385 390 395 400 Val Asn Ser Lys Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr 405 410 415 Asn Leu Ser Leu Gly Gly Asp Ile Ile Leu Gln Phe Ile Glu Ile Ala 420 425 430 Asp Asn Arg Leu Thr Ile Gly Ser Pro Ser Lys Ile Tyr Asn Ser Leu 435 440 445 Gly Gln Pro Val Phe Tyr Gln Ala Ser Tyr Ser Trp Asp Thr Met Ile 450 455 460 Lys Leu Gly Asp Val Asp Thr Val Asp Pro Leu Arg Val Gln Trp Arg 465 470 475 480 Asn Asn Ser Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe 485 490 495 Asn Val Cys Pro Glu Val Cys Trp Glu Gly Thr Tyr Asn Asp Ala Phe 500 505 510 Leu Ile Asp Arg Leu Asn Trp Val Ser Ala Gly Val Tyr Leu Asn Ser 515 520 525 Asn Gln Thr Ala Glu Asn Pro Val Phe Ala Val Phe Lys Asp Asn Glu 530 535 540 Ile Leu Tyr Gln Val Pro Leu Ala Glu Asp Asp Thr Asn Ala Gln Lys 545 550 555 560 Thr Ile Thr Asp Cys Phe Leu Leu Glu Asn Val Ile Trp Cys Ile Ser 565 570 575 Leu Val Glu Ile Tyr Asp Thr Gly Asp Ser Val Ile Arg Pro Lys Leu 580 585 590 Phe Ala Val Lys Ile Pro Ala Gln Cys Ser Glu Ser 595 600 <![CDATA[<210> 610]]> <![CDATA[<211> 526]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 610]]> Met Val Val Ile Leu Asp Lys Arg Cys Tyr Cys Asn Leu Leu Ile Leu 1 5 10 15 Ile Leu Met Ile Ser Glu Cys Ser Val Gly Ile Leu His Tyr Glu Lys 20 25 30 Leu Ser Lys Ile Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile 35 40 45 Lys Ser Asn Pro Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn 50 55 60 Val Ser Asn Met Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys 65 70 75 80 Thr Arg Leu Asn Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile 85 90 95 Tyr Lys Asn Asn Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly 100 105 110 Val Ile Met Ala Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile 115 120 125 Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile 130 135 140 Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys 145 150 155 160 Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln 165 170 175 Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys 180 185 190 Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser 195 200 205 Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn 210 215 220 Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu 225 230 235 240 Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu 245 250 255 Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser 260 265 270 Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile 275 280 285 Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp 290 295 300 Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn 305 310 315 320 Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg 325 330 335 Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met 340 345 350 Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val 355 360 365 Val Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe 370 375 380 Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala 385 390 395 400 Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr 405 410 415 Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr 420 425 430 Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro 435 440 445 Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn 450 455 460 Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu 465 470 475 480 Leu Asp Thr Val Asn Pro Ser Leu Ile Ser Met Leu Ser Met Ile Ile 485 490 495 Leu Tyr Val Leu Ser Ile Ala Ser Leu Cys Ile Gly Leu Ile Thr Phe 500 505 510 Ile Ser Phe Ile Ile Val Glu Lys Lys Arg Asn Thr Gly Thr 515 520 525 <![CDATA[<210> 611]]> <![CDATA[<211> 526]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 611]]> Met Val Val Ile Leu Asp Lys Arg Cys Tyr Cys Asn Leu Leu Ile Leu 1 5 10 15 Ile Leu Met Ile Ser Glu Cys Ser Val Gly Ile Leu His Tyr Glu Lys 20 25 30 Leu Ser Lys Ile Gly Leu Val Lys Gly Val Thr Arg Lys Tyr Lys Ile 35 40 45 Lys Ser Asn Pro Leu Thr Lys Asp Ile Val Ile Lys Met Ile Pro Asn 50 55 60 Val Ser Asn Met Ser Gln Cys Thr Gly Ser Val Met Glu Asn Tyr Lys 65 70 75 80 Thr Arg Leu Asn Gly Ile Leu Thr Pro Ile Lys Gly Ala Leu Glu Ile 85 90 95 Tyr Lys Asn Gln Thr His Asp Leu Val Gly Asp Val Arg Leu Ala Gly 100 105 110 Val Ile Met Ala Gly Val Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile 115 120 125 Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala Asp Asn Ile 130 135 140 Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala Val Val Lys 145 150 155 160 Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr Ala Leu Gln 165 170 175 Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys Ile Ser Cys 180 185 190 Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys Tyr Leu Ser 195 200 205 Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro Val Ser Asn 210 215 220 Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly Asn Tyr Glu 225 230 235 240 Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe Asp Asp Leu 245 250 255 Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Leu Ser 260 265 270 Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu Thr Glu Ile 275 280 285 Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe Asn Asn Asp 290 295 300 Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu Val Arg Asn 305 310 315 320 Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile Thr Lys Arg 325 330 335 Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr Asn Asn Met 340 345 350 Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg Glu Leu Val 355 360 365 Val Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly Val Leu Phe 370 375 380 Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr Gly Arg Ala 385 390 395 400 Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp Asn Thr Thr 405 410 415 Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu Gly Lys Tyr 420 425 430 Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile Gly Pro Pro 435 440 445 Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser Ser Met Asn 450 455 460 Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala Gln Arg Leu 465 470 475 480 Leu Asp Thr Val Asn Pro Ser Leu Ile Ser Met Leu Ser Met Ile Ile 485 490 495 Leu Tyr Val Leu Ser Ile Ala Ser Leu Cys Ile Gly Leu Ile Thr Phe 500 505 510 Ile Ser Phe Ile Ile Val Glu Lys Lys Arg Asn Thr Gly Thr 515 520 525 <![CDATA[<210> 612]]> <![CDATA[<211> 569]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 612]]> Met Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala 1 5 10 15 Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met 20 25 30 Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala 35 40 45 Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu 50 55 60 Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp 65 70 75 80 Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser 85 90 95 Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys 100 105 110 Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser 115 120 125 Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly 130 135 140 Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr 145 150 155 160 Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val 165 170 175 Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp 180 185 190 Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser 195 200 205 Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp 210 215 220 Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro 225 230 235 240 Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu 245 250 255 Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu 260 265 270 Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val 275 280 285 Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu 290 295 300 Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro 305 310 315 320 Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe 325 330 335 Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr 340 345 350 Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile 355 360 365 Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn 370 375 380 Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp 385 390 395 400 Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly 405 410 415 Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys 420 425 430 Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn 435 440 445 Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn 450 455 460 Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu 465 470 475 480 Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn 485 490 495 Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile 500 505 510 Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr 515 520 525 Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu 530 535 540 Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe 545 550 555 560 Ala Val Lys Ile Pro Glu Gln Cys Thr 565 <![CDATA[<210> 613]]> <![CDATA[<211> 498]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 613]]> Ile Leu His Tyr Glu Lys Leu Ser Lys Ile Gly Leu Val Lys Gly Val 1 5 10 15 Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro Leu Thr Lys Asp Ile Val 20 25 30 Ile Lys Met Ile Pro Asn Val Ser Asn Met Ser Gln Cys Thr Gly Ser 35 40 45 Val Met Glu Asn Tyr Lys Thr Arg Leu Asn Gly Ile Leu Thr Pro Ile 50 55 60 Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn Thr His Asp Leu Val Gly 65 70 75 80 Asp Val Arg Leu Ala Gly Val Ile Met Ala Gly Val Ala Ile Gly Ile 85 90 95 Ala Thr Ala Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met 100 105 110 Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr 115 120 125 Asn Glu Ala Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr 130 135 140 Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr 145 150 155 160 Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala 165 170 175 Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu 180 185 190 Gln Asp Pro Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala 195 200 205 Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr 210 215 220 Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile 225 230 235 240 Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe 245 250 255 Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro 260 265 270 Val Ser Phe Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn 275 280 285 Phe Ile Leu Val Arg Asn Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe 290 295 300 Cys Leu Ile Thr Lys Arg Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr 305 310 315 320 Pro Met Thr Asn Asn Met Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys 325 330 335 Cys Pro Arg Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu 340 345 350 Ser Asn Gly Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys 355 360 365 Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu 370 375 380 Met Ile Asp Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile 385 390 395 400 Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly 405 410 415 Ile Ala Ile Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser 420 425 430 Gln Ile Ser Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile 435 440 445 Lys Glu Ala Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Ile Ser 450 455 460 Met Leu Ser Met Ile Ile Leu Tyr Val Leu Ser Ile Ala Ser Leu Cys 465 470 475 480 Ile Gly Leu Ile Thr Phe Ile Ser Phe Ile Ile Val Glu Lys Lys Arg 485 490 495 Asn Thr <![CDATA[<210> 614]]> <![CDATA[<211> 557]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 松灣亨尼帕病毒]]> <![CDATA[<400> 614]]> Met Ser Asn Lys Arg Thr Thr Val Leu Ile Ile Ile Ser Tyr Thr Leu 1 5 10 15 Phe Tyr Leu Asn Asn Ala Ala Ile Val Gly Phe Asp Phe Asp Lys Leu 20 25 30 Asn Lys Ile Gly Val Val Gln Gly Arg Val Leu Asn Tyr Lys Ile Lys 35 40 45 Gly Asp Pro Met Thr Lys Asp Leu Val Leu Lys Phe Ile Pro Asn Ile 50 55 60 Val Asn Ile Thr Glu Cys Val Arg Glu Pro Leu Ser Arg Tyr Asn Glu 65 70 75 80 Thr Val Arg Arg Leu Leu Leu Pro Ile His Asn Met Leu Gly Leu Tyr 85 90 95 Leu Asn Asn Thr Asn Ala Lys Met Thr Gly Leu Met Ile Ala Gly Val 100 105 110 Ile Met Gly Gly Ile Ala Ile Gly Ile Ala Thr Ala Ala Gln Ile Thr 115 120 125 Ala Gly Phe Ala Leu Tyr Glu Ala Lys Lys Asn Thr Glu Asn Ile Gln 130 135 140 Lys Leu Thr Asp Ser Ile Met Lys Thr Gln Asp Ser Ile Asp Lys Leu 145 150 155 160 Thr Asp Ser Val Gly Thr Ser Ile Leu Ile Leu Asn Lys Leu Gln Thr 165 170 175 Tyr Ile Asn Asn Gln Leu Val Pro Asn Leu Glu Leu Leu Ser Cys Arg 180 185 190 Gln Asn Lys Ile Glu Phe Asp Leu Met Leu Thr Lys Tyr Leu Val Asp 195 200 205 Leu Met Thr Val Ile Gly Pro Asn Ile Asn Asn Pro Val Asn Lys Asp 210 215 220 Met Thr Ile Gln Ser Leu Ser Leu Leu Phe Asp Gly Asn Tyr Asp Ile 225 230 235 240 Met Met Ser Glu Leu Gly Tyr Thr Pro Gln Asp Phe Leu Asp Leu Ile 245 250 255 Glu Ser Lys Ser Ile Thr Gly Gln Ile Ile Tyr Val Asp Met Glu Asn 260 265 270 Leu Tyr Val Val Ile Arg Thr Tyr Leu Pro Thr Leu Ile Glu Val Pro 275 280 285 Asp Ala Gln Ile Tyr Glu Phe Asn Lys Ile Thr Met Ser Ser Asn Gly 290 295 300 Gly Glu Tyr Leu Ser Thr Ile Pro Asn Phe Ile Leu Ile Arg Gly Asn 305 310 315 320 Tyr Met Ser Asn Ile Asp Val Ala Thr Cys Tyr Met Thr Lys Ala Ser 325 330 335 Val Ile Cys Asn Gln Asp Tyr Ser Leu Pro Met Ser Gln Asn Leu Arg 340 345 350 Ser Cys Tyr Gln Gly Glu Thr Glu Tyr Cys Pro Val Glu Ala Val Ile 355 360 365 Ala Ser His Ser Pro Arg Phe Ala Leu Thr Asn Gly Val Ile Phe Ala 370 375 380 Asn Cys Ile Asn Thr Ile Cys Arg Cys Gln Asp Asn Gly Lys Thr Ile 385 390 395 400 Thr Gln Asn Ile Asn Gln Phe Val Ser Met Ile Asp Asn Ser Thr Cys 405 410 415 Asn Asp Val Met Val Asp Lys Phe Thr Ile Lys Val Gly Lys Tyr Met 420 425 430 Gly Arg Lys Asp Ile Asn Asn Ile Asn Ile Gln Ile Gly Pro Gln Ile 435 440 445 Ile Ile Asp Lys Val Asp Leu Ser Asn Glu Ile Asn Lys Met Asn Gln 450 455 460 Ser Leu Lys Asp Ser Ile Phe Tyr Leu Arg Glu Ala Lys Arg Ile Leu 465 470 475 480 Asp Ser Val Asn Ile Ser Leu Ile Ser Pro Ser Val Gln Leu Phe Leu 485 490 495 Ile Ile Ile Ser Val Leu Ser Phe Ile Ile Leu Leu Ile Ile Ile Val 500 505 510 Tyr Leu Tyr Cys Lys Ser Lys His Ser Tyr Lys Tyr Asn Lys Phe Ile 515 520 525 Asp Asp Pro Asp Tyr Tyr Asn Asp Tyr Lys Arg Glu Arg Ile Asn Gly 530 535 540 Lys Ala Ser Lys Ser Asn Asn Ile Tyr Tyr Val Gly Asp 545 550 555 <![CDATA[<210> 615]]> <![CDATA[<211> 545]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 墨江亨尼帕病毒]]> <![CDATA[<400> 615]]> Met Ala Leu Asn Lys Asn Met Phe Ser Ser Leu Phe Leu Gly Tyr Leu 1 5 10 15 Leu Val Tyr Ala Thr Thr Val Gln Ser Ser Ile His Tyr Asp Ser Leu 20 25 30 Ser Lys Val Gly Val Ile Lys Gly Leu Thr Tyr Asn Tyr Lys Ile Lys 35 40 45 Gly Ser Pro Ser Thr Lys Leu Met Val Val Lys Leu Ile Pro Asn Ile 50 55 60 Asp Ser Val Lys Asn Cys Thr Gln Lys Gln Tyr Asp Glu Tyr Lys Asn 65 70 75 80 Leu Val Arg Lys Ala Leu Glu Pro Val Lys Met Ala Ile Asp Thr Met 85 90 95 Leu Asn Asn Val Lys Ser Gly Asn Asn Lys Tyr Arg Phe Ala Gly Ala 100 105 110 Ile Met Ala Gly Val Ala Leu Gly Val Ala Thr Ala Ala Thr Val Thr 115 120 125 Ala Gly Ile Ala Leu His Arg Ser Asn Glu Asn Ala Gln Ala Ile Ala 130 135 140 Asn Met Lys Ser Ala Ile Gln Asn Thr Asn Glu Ala Val Lys Gln Leu 145 150 155 160 Gln Leu Ala Asn Lys Gln Thr Leu Ala Val Ile Asp Thr Ile Arg Gly 165 170 175 Glu Ile Asn Asn Asn Ile Ile Pro Val Ile Asn Gln Leu Ser Cys Asp 180 185 190 Thr Ile Gly Leu Ser Val Gly Ile Arg Leu Thr Gln Tyr Tyr Ser Glu 195 200 205 Ile Ile Thr Ala Phe Gly Pro Ala Leu Gln Asn Pro Val Asn Thr Arg 210 215 220 Ile Thr Ile Gln Ala Ile Ser Ser Val Phe Asn Gly Asn Phe Asp Glu 225 230 235 240 Leu Leu Lys Ile Met Gly Tyr Thr Ser Gly Asp Leu Tyr Glu Ile Leu 245 250 255 His Ser Glu Leu Ile Arg Gly Asn Ile Ile Asp Val Asp Val Asp Ala 260 265 270 Gly Tyr Ile Ala Leu Glu Ile Glu Phe Pro Asn Leu Thr Leu Val Pro 275 280 285 Asn Ala Val Val Gln Glu Leu Met Pro Ile Ser Tyr Asn Ile Asp Gly 290 295 300 Asp Glu Trp Val Thr Leu Val Pro Arg Phe Val Leu Thr Arg Thr Thr 305 310 315 320 Leu Leu Ser Asn Ile Asp Thr Ser Arg Cys Thr Ile Thr Asp Ser Ser 325 330 335 Val Ile Cys Asp Asn Asp Tyr Ala Leu Pro Met Ser His Glu Leu Ile 340 345 350 Gly Cys Leu Gln Gly Asp Thr Ser Lys Cys Ala Arg Glu Lys Val Val 355 360 365 Ser Ser Tyr Val Pro Lys Phe Ala Leu Ser Asp Gly Leu Val Tyr Ala 370 375 380 Asn Cys Leu Asn Thr Ile Cys Arg Cys Met Asp Thr Asp Thr Pro Ile 385 390 395 400 Ser Gln Ser Leu Gly Ala Thr Val Ser Leu Leu Asp Asn Lys Arg Cys 405 410 415 Ser Val Tyr Gln Val Gly Asp Val Leu Ile Ser Val Gly Ser Tyr Leu 420 425 430 Gly Asp Gly Glu Tyr Asn Ala Asp Asn Val Glu Leu Gly Pro Pro Ile 435 440 445 Val Ile Asp Lys Ile Asp Ile Gly Asn Gln Leu Ala Gly Ile Asn Gln 450 455 460 Thr Leu Gln Glu Ala Glu Asp Tyr Ile Glu Lys Ser Glu Glu Phe Leu 465 470 475 480 Lys Gly Val Asn Pro Ser Ile Ile Thr Leu Gly Ser Met Val Val Leu 485 490 495 Tyr Ile Phe Met Ile Leu Ile Ala Ile Val Ser Val Ile Ala Leu Val 500 505 510 Leu Ser Ile Lys Leu Thr Val Lys Gly Asn Val Val Arg Gln Gln Phe 515 520 525 Thr Tyr Thr Gln His Val Pro Ser Met Glu Asn Ile Asn Tyr Val Ser 530 535 540 His 545 <![CDATA[<210> 616]]> <![CDATA[<211> 662]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 未知]]> <![CDATA[<220>]]> <![CDATA[<223> 未知之描述:蝙蝠副黏病毒Eid_hel/GH-M74a/GHA/2009序列]]> <![CDATA[<400> 616]]> Met Lys Lys Lys Thr Asp Asn Pro Thr Ile Ser Lys Arg Gly His Asn 1 5 10 15 His Ser Arg Gly Ile Lys Ser Arg Ala Leu Leu Arg Glu Thr Asp Asn 20 25 30 Tyr Ser Asn Gly Leu Ile Val Glu Asn Leu Val Arg Asn Cys His His 35 40 45 Pro Ser Lys Asn Asn Leu Asn Tyr Thr Lys Thr Gln Lys Arg Asp Ser 50 55 60 Thr Ile Pro Tyr Arg Val Glu Glu Arg Lys Gly His Tyr Pro Lys Ile 65 70 75 80 Lys His Leu Ile Asp Lys Ser Tyr Lys His Ile Lys Arg Gly Lys Arg 85 90 95 Arg Asn Gly His Asn Gly Asn Ile Ile Thr Ile Ile Leu Leu Leu Ile 100 105 110 Leu Ile Leu Lys Thr Gln Met Ser Glu Gly Ala Ile His Tyr Glu Thr 115 120 125 Leu Ser Lys Ile Gly Leu Ile Lys Gly Ile Thr Arg Glu Tyr Lys Val 130 135 140 Lys Gly Thr Pro Ser Ser Lys Asp Ile Val Ile Lys Leu Ile Pro Asn 145 150 155 160 Val Thr Gly Leu Asn Lys Cys Thr Asn Ile Ser Met Glu Asn Tyr Lys 165 170 175 Glu Gln Leu Asp Lys Ile Leu Ile Pro Ile Asn Asn Ile Ile Glu Leu 180 185 190 Tyr Ala Asn Ser Thr Lys Ser Ala Pro Gly Asn Ala Arg Phe Ala Gly 195 200 205 Val Ile Ile Ala Gly Val Ala Leu Gly Val Ala Ala Ala Ala Gln Ile 210 215 220 Thr Ala Gly Ile Ala Leu His Glu Ala Arg Gln Asn Ala Glu Arg Ile 225 230 235 240 Asn Leu Leu Lys Asp Ser Ile Ser Ala Thr Asn Asn Ala Val Ala Glu 245 250 255 Leu Gln Glu Ala Thr Gly Gly Ile Val Asn Val Ile Thr Gly Met Gln 260 265 270 Asp Tyr Ile Asn Thr Asn Leu Val Pro Gln Ile Asp Lys Leu Gln Cys 275 280 285 Ser Gln Ile Lys Thr Ala Leu Asp Ile Ser Leu Ser Gln Tyr Tyr Ser 290 295 300 Glu Ile Leu Thr Val Phe Gly Pro Asn Leu Gln Asn Pro Val Thr Thr 305 310 315 320 Ser Met Ser Ile Gln Ala Ile Ser Gln Ser Phe Gly Gly Asn Ile Asp 325 330 335 Leu Leu Leu Asn Leu Leu Gly Tyr Thr Ala Asn Asp Leu Leu Asp Leu 340 345 350 Leu Glu Ser Lys Ser Ile Thr Gly Gln Ile Thr Tyr Ile Asn Leu Glu 355 360 365 His Tyr Phe Met Val Ile Arg Val Tyr Tyr Pro Ile Met Thr Thr Ile 370 375 380 Ser Asn Ala Tyr Val Gln Glu Leu Ile Lys Ile Ser Phe Asn Val Asp 385 390 395 400 Gly Ser Glu Trp Val Ser Leu Val Pro Ser Tyr Ile Leu Ile Arg Asn 405 410 415 Ser Tyr Leu Ser Asn Ile Asp Ile Ser Glu Cys Leu Ile Thr Lys Asn 420 425 430 Ser Val Ile Cys Arg His Asp Phe Ala Met Pro Met Ser Tyr Thr Leu 435 440 445 Lys Glu Cys Leu Thr Gly Asp Thr Glu Lys Cys Pro Arg Glu Ala Val 450 455 460 Val Thr Ser Tyr Val Pro Arg Phe Ala Ile Ser Gly Gly Val Ile Tyr 465 470 475 480 Ala Asn Cys Leu Ser Thr Thr Cys Gln Cys Tyr Gln Thr Gly Lys Val 485 490 495 Ile Ala Gln Asp Gly Ser Gln Thr Leu Met Met Ile Asp Asn Gln Thr 500 505 510 Cys Ser Ile Val Arg Ile Glu Glu Ile Leu Ile Ser Thr Gly Lys Tyr 515 520 525 Leu Gly Ser Gln Glu Tyr Asn Thr Met His Val Ser Val Gly Asn Pro 530 535 540 Val Phe Thr Asp Lys Leu Asp Ile Thr Ser Gln Ile Ser Asn Ile Asn 545 550 555 560 Gln Ser Ile Glu Gln Ser Lys Phe Tyr Leu Asp Lys Ser Lys Ala Ile 565 570 575 Leu Asp Lys Ile Asn Leu Asn Leu Ile Gly Ser Val Pro Ile Ser Ile 580 585 590 Leu Phe Ile Ile Ala Ile Leu Ser Leu Ile Leu Ser Ile Ile Thr Phe 595 600 605 Val Ile Val Met Ile Ile Val Arg Arg Tyr Asn Lys Tyr Thr Pro Leu 610 615 620 Ile Asn Ser Asp Pro Ser Ser Arg Arg Ser Thr Ile Gln Asp Val Tyr 625 630 635 640 Ile Ile Pro Asn Pro Gly Glu His Ser Ile Arg Ser Ala Ala Arg Ser 645 650 655 Ile Asp Arg Asp Arg Asp 660 <![CDATA[<210> 617]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 617]]> Arg Tyr Ala Ile Ser 1 5 <![CDATA[<210> 618]]> <![CDATA[<211> 602]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 尼帕亨尼帕病毒]]> <![CDATA[<400> 618]]> Met Pro Ala Glu Asn Lys Lys Val Arg Phe Glu Asn Thr Thr Ser Asp 1 5 10 15 Lys Gly Lys Ile Pro Ser Lys Val Ile Lys Ser Tyr Tyr Gly Thr Met 20 25 30 Asp Ile Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser 35 40 45 Ala Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val 50 55 60 Met Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln 65 70 75 80 Ala Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly 85 90 95 Leu Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile 100 105 110 Asp Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly 115 120 125 Ser Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu 130 135 140 Lys Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile 145 150 155 160 Ser Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu 165 170 175 Gly Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys 180 185 190 Thr Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro 195 200 205 Val Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met 210 215 220 Asp Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys 225 230 235 240 Ser Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu 245 250 255 Asp Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr 260 265 270 Pro Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn 275 280 285 Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile 290 295 300 Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala 305 310 315 320 Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala 325 330 335 Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly 340 345 350 Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly 355 360 365 Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile 370 375 380 Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly 385 390 395 400 Ile Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr 405 410 415 Asn Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser 420 425 430 Asp Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu 435 440 445 Gly Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile 450 455 460 Lys Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg 465 470 475 480 Asn Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe 485 490 495 Asn Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe 500 505 510 Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser 515 520 525 Asn Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu 530 535 540 Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys 545 550 555 560 Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser 565 570 575 Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu 580 585 590 Phe Ala Val Lys Ile Pro Glu Gln Cys Thr 595 600 <![CDATA[<210> 619]]> <![CDATA[<211> 622]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 松灣亨尼帕病毒]]> <![CDATA[<400> 619]]> Met Leu Ser Gln Leu Gln Lys Asn Tyr Leu Asp Asn Ser Asn Gln Gln 1 5 10 15 Gly Asp Lys Met Asn Asn Pro Asp Lys Lys Leu Ser Val Asn Phe Asn 20 25 30 Pro Leu Glu Leu Asp Lys Gly Gln Lys Asp Leu Asn Lys Ser Tyr Tyr 35 40 45 Val Lys Asn Lys Asn Tyr Asn Val Ser Asn Leu Leu Asn Glu Ser Leu 50 55 60 His Asp Ile Lys Phe Cys Ile Tyr Cys Ile Phe Ser Leu Leu Ile Ile 65 70 75 80 Ile Thr Ile Ile Asn Ile Ile Thr Ile Ser Ile Val Ile Thr Arg Leu 85 90 95 Lys Val His Glu Glu Asn Asn Gly Met Glu Ser Pro Asn Leu Gln Ser 100 105 110 Ile Gln Asp Ser Leu Ser Ser Leu Thr Asn Met Ile Asn Thr Glu Ile 115 120 125 Thr Pro Arg Ile Gly Ile Leu Val Thr Ala Thr Ser Val Thr Leu Ser 130 135 140 Ser Ser Ile Asn Tyr Val Gly Thr Lys Thr Asn Gln Leu Val Asn Glu 145 150 155 160 Leu Lys Asp Tyr Ile Thr Lys Ser Cys Gly Phe Lys Val Pro Glu Leu 165 170 175 Lys Leu His Glu Cys Asn Ile Ser Cys Ala Asp Pro Lys Ile Ser Lys 180 185 190 Ser Ala Met Tyr Ser Thr Asn Ala Tyr Ala Glu Leu Ala Gly Pro Pro 195 200 205 Lys Ile Phe Cys Lys Ser Val Ser Lys Asp Pro Asp Phe Arg Leu Lys 210 215 220 Gln Ile Asp Tyr Val Ile Pro Val Gln Gln Asp Arg Ser Ile Cys Met 225 230 235 240 Asn Asn Pro Leu Leu Asp Ile Ser Asp Gly Phe Phe Thr Tyr Ile His 245 250 255 Tyr Glu Gly Ile Asn Ser Cys Lys Lys Ser Asp Ser Phe Lys Val Leu 260 265 270 Leu Ser His Gly Glu Ile Val Asp Arg Gly Asp Tyr Arg Pro Ser Leu 275 280 285 Tyr Leu Leu Ser Ser His Tyr His Pro Tyr Ser Met Gln Val Ile Asn 290 295 300 Cys Val Pro Val Thr Cys Asn Gln Ser Ser Phe Val Phe Cys His Ile 305 310 315 320 Ser Asn Asn Thr Lys Thr Leu Asp Asn Ser Asp Tyr Ser Ser Asp Glu 325 330 335 Tyr Tyr Ile Thr Tyr Phe Asn Gly Ile Asp Arg Pro Lys Thr Lys Lys 340 345 350 Ile Pro Ile Asn Asn Met Thr Ala Asp Asn Arg Tyr Ile His Phe Thr 355 360 365 Phe Ser Gly Gly Gly Gly Val Cys Leu Gly Glu Glu Phe Ile Ile Pro 370 375 380 Val Thr Thr Val Ile Asn Thr Asp Val Phe Thr His Asp Tyr Cys Glu 385 390 395 400 Ser Phe Asn Cys Ser Val Gln Thr Gly Lys Ser Leu Lys Glu Ile Cys 405 410 415 Ser Glu Ser Leu Arg Ser Pro Thr Asn Ser Ser Arg Tyr Asn Leu Asn 420 425 430 Gly Ile Met Ile Ile Ser Gln Asn Asn Met Thr Asp Phe Lys Ile Gln 435 440 445 Leu Asn Gly Ile Thr Tyr Asn Lys Leu Ser Phe Gly Ser Pro Gly Arg 450 455 460 Leu Ser Lys Thr Leu Gly Gln Val Leu Tyr Tyr Gln Ser Ser Met Ser 465 470 475 480 Trp Asp Thr Tyr Leu Lys Ala Gly Phe Val Glu Lys Trp Lys Pro Phe 485 490 495 Thr Pro Asn Trp Met Asn Asn Thr Val Ile Ser Arg Pro Asn Gln Gly 500 505 510 Asn Cys Pro Arg Tyr His Lys Cys Pro Glu Ile Cys Tyr Gly Gly Thr 515 520 525 Tyr Asn Asp Ile Ala Pro Leu Asp Leu Gly Lys Asp Met Tyr Val Ser 530 535 540 Val Ile Leu Asp Ser Asp Gln Leu Ala Glu Asn Pro Glu Ile Thr Val 545 550 555 560 Phe Asn Ser Thr Thr Ile Leu Tyr Lys Glu Arg Val Ser Lys Asp Glu 565 570 575 Leu Asn Thr Arg Ser Thr Thr Thr Ser Cys Phe Leu Phe Leu Asp Glu 580 585 590 Pro Trp Cys Ile Ser Val Leu Glu Thr Asn Arg Phe Asn Gly Lys Ser 595 600 605 Ile Arg Pro Glu Ile Tyr Ser Tyr Lys Ile Pro Lys Tyr Cys 610 615 620 <![CDATA[<210> 620]]> <![CDATA[<211> 632]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 未知]]> <![CDATA[<220>]]> <![CDATA[<223> 未知之描述:蝙蝠副黏病毒Eid_hel/GH-M74a/GHA/2009序列]]> <![CDATA[<400> 620]]> Met Pro Gln Lys Thr Val Glu Phe Ile Asn Met Asn Ser Pro Leu Glu 1 5 10 15 Arg Gly Val Ser Thr Leu Ser Asp Lys Lys Thr Leu Asn Gln Ser Lys 20 25 30 Ile Thr Lys Gln Gly Tyr Phe Gly Leu Gly Ser His Ser Glu Arg Asn 35 40 45 Trp Lys Lys Gln Lys Asn Gln Asn Asp His Tyr Met Thr Val Ser Thr 50 55 60 Met Ile Leu Glu Ile Leu Val Val Leu Gly Ile Met Phe Asn Leu Ile 65 70 75 80 Val Leu Thr Met Val Tyr Tyr Gln Asn Asp Asn Ile Asn Gln Arg Met 85 90 95 Ala Glu Leu Thr Ser Asn Ile Thr Val Leu Asn Leu Asn Leu Asn Gln 100 105 110 Leu Thr Asn Lys Ile Gln Arg Glu Ile Ile Pro Arg Ile Thr Leu Ile 115 120 125 Asp Thr Ala Thr Thr Ile Thr Ile Pro Ser Ala Ile Thr Tyr Ile Leu 130 135 140 Ala Thr Leu Thr Thr Arg Ile Ser Glu Leu Leu Pro Ser Ile Asn Gln 145 150 155 160 Lys Cys Glu Phe Lys Thr Pro Thr Leu Val Leu Asn Asp Cys Arg Ile 165 170 175 Asn Cys Thr Pro Pro Leu Asn Pro Ser Asp Gly Val Lys Met Ser Ser 180 185 190 Leu Ala Thr Asn Leu Val Ala His Gly Pro Ser Pro Cys Arg Asn Phe 195 200 205 Ser Ser Val Pro Thr Ile Tyr Tyr Tyr Arg Ile Pro Gly Leu Tyr Asn 210 215 220 Arg Thr Ala Leu Asp Glu Arg Cys Ile Leu Asn Pro Arg Leu Thr Ile 225 230 235 240 Ser Ser Thr Lys Phe Ala Tyr Val His Ser Glu Tyr Asp Lys Asn Cys 245 250 255 Thr Arg Gly Phe Lys Tyr Tyr Glu Leu Met Thr Phe Gly Glu Ile Leu 260 265 270 Glu Gly Pro Glu Lys Glu Pro Arg Met Phe Ser Arg Ser Phe Tyr Ser 275 280 285 Pro Thr Asn Ala Val Asn Tyr His Ser Cys Thr Pro Ile Val Thr Val 290 295 300 Asn Glu Gly Tyr Phe Leu Cys Leu Glu Cys Thr Ser Ser Asp Pro Leu 305 310 315 320 Tyr Lys Ala Asn Leu Ser Asn Ser Thr Phe His Leu Val Ile Leu Arg 325 330 335 His Asn Lys Asp Glu Lys Ile Val Ser Met Pro Ser Phe Asn Leu Ser 340 345 350 Thr Asp Gln Glu Tyr Val Gln Ile Ile Pro Ala Glu Gly Gly Gly Thr 355 360 365 Ala Glu Ser Gly Asn Leu Tyr Phe Pro Cys Ile Gly Arg Leu Leu His 370 375 380 Lys Arg Val Thr His Pro Leu Cys Lys Lys Ser Asn Cys Ser Arg Thr 385 390 395 400 Asp Asp Glu Ser Cys Leu Lys Ser Tyr Tyr Asn Gln Gly Ser Pro Gln 405 410 415 His Gln Val Val Asn Cys Leu Ile Arg Ile Arg Asn Ala Gln Arg Asp 420 425 430 Asn Pro Thr Trp Asp Val Ile Thr Val Asp Leu Thr Asn Thr Tyr Pro 435 440 445 Gly Ser Arg Ser Arg Ile Phe Gly Ser Phe Ser Lys Pro Met Leu Tyr 450 455 460 Gln Ser Ser Val Ser Trp His Thr Leu Leu Gln Val Ala Glu Ile Thr 465 470 475 480 Asp Leu Asp Lys Tyr Gln Leu Asp Trp Leu Asp Thr Pro Tyr Ile Ser 485 490 495 Arg Pro Gly Gly Ser Glu Cys Pro Phe Gly Asn Tyr Cys Pro Thr Val 500 505 510 Cys Trp Glu Gly Thr Tyr Asn Asp Val Tyr Ser Leu Thr Pro Asn Asn 515 520 525 Asp Leu Phe Val Thr Val Tyr Leu Lys Ser Glu Gln Val Ala Glu Asn 530 535 540 Pro Tyr Phe Ala Ile Phe Ser Arg Asp Gln Ile Leu Lys Glu Phe Pro 545 550 555 560 Leu Asp Ala Trp Ile Ser Ser Ala Arg Thr Thr Thr Ile Ser Cys Phe 565 570 575 Met Phe Asn Asn Glu Ile Trp Cys Ile Ala Ala Leu Glu Ile Thr Arg 580 585 590 Leu Asn Asp Asp Ile Ile Arg Pro Ile Tyr Tyr Ser Phe Trp Leu Pro 595 600 605 Thr Asp Cys Arg Thr Pro Tyr Pro His Thr Gly Lys Met Thr Arg Val 610 615 620 Pro Leu Arg Ser Thr Tyr Asn Tyr 625 630 <![CDATA[<210> 621]]> <![CDATA[<211> 625]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 墨江亨尼帕病毒]]> <![CDATA[<400> 621]]> Met Ala Thr Asn Arg Asp Asn Thr Ile Thr Ser Ala Glu Val Ser Gln 1 5 10 15 Glu Asp Lys Val Lys Lys Tyr Tyr Gly Val Glu Thr Ala Glu Lys Val 20 25 30 Ala Asp Ser Ile Ser Gly Asn Lys Val Phe Ile Leu Met Asn Thr Leu 35 40 45 Leu Ile Leu Thr Gly Ala Ile Ile Thr Ile Thr Leu Asn Ile Thr Asn 50 55 60 Leu Thr Ala Ala Lys Ser Gln Gln Asn Met Leu Lys Ile Ile Gln Asp 65 70 75 80 Asp Val Asn Ala Lys Leu Glu Met Phe Val Asn Leu Asp Gln Leu Val 85 90 95 Lys Gly Glu Ile Lys Pro Lys Val Ser Leu Ile Asn Thr Ala Val Ser 100 105 110 Val Ser Ile Pro Gly Gln Ile Ser Asn Leu Gln Thr Lys Phe Leu Gln 115 120 125 Lys Tyr Val Tyr Leu Glu Glu Ser Ile Thr Lys Gln Cys Thr Cys Asn 130 135 140 Pro Leu Ser Gly Ile Phe Pro Thr Ser Gly Pro Thr Tyr Pro Pro Thr 145 150 155 160 Asp Lys Pro Asp Asp Asp Thr Thr Asp Asp Asp Lys Val Asp Thr Thr 165 170 175 Ile Lys Pro Ile Glu Tyr Pro Lys Pro Asp Gly Cys Asn Arg Thr Gly 180 185 190 Asp His Phe Thr Met Glu Pro Gly Ala Asn Phe Tyr Thr Val Pro Asn 195 200 205 Leu Gly Pro Ala Ser Ser Asn Ser Asp Glu Cys Tyr Thr Asn Pro Ser 210 215 220 Phe Ser Ile Gly Ser Ser Ile Tyr Met Phe Ser Gln Glu Ile Arg Lys 225 230 235 240 Thr Asp Cys Thr Ala Gly Glu Ile Leu Ser Ile Gln Ile Val Leu Gly 245 250 255 Arg Ile Val Asp Lys Gly Gln Gln Gly Pro Gln Ala Ser Pro Leu Leu 260 265 270 Val Trp Ala Val Pro Asn Pro Lys Ile Ile Asn Ser Cys Ala Val Ala 275 280 285 Ala Gly Asp Glu Met Gly Trp Val Leu Cys Ser Val Thr Leu Thr Ala 290 295 300 Ala Ser Gly Glu Pro Ile Pro His Met Phe Asp Gly Phe Trp Leu Tyr 305 310 315 320 Lys Leu Glu Pro Asp Thr Glu Val Val Ser Tyr Arg Ile Thr Gly Tyr 325 330 335 Ala Tyr Leu Leu Asp Lys Gln Tyr Asp Ser Val Phe Ile Gly Lys Gly 340 345 350 Gly Gly Ile Gln Lys Gly Asn Asp Leu Tyr Phe Gln Met Tyr Gly Leu 355 360 365 Ser Arg Asn Arg Gln Ser Phe Lys Ala Leu Cys Glu His Gly Ser Cys 370 375 380 Leu Gly Thr Gly Gly Gly Gly Tyr Gln Val Leu Cys Asp Arg Ala Val 385 390 395 400 Met Ser Phe Gly Ser Glu Glu Ser Leu Ile Thr Asn Ala Tyr Leu Lys 405 410 415 Val Asn Asp Leu Ala Ser Gly Lys Pro Val Ile Ile Gly Gln Thr Phe 420 425 430 Pro Pro Ser Asp Ser Tyr Lys Gly Ser Asn Gly Arg Met Tyr Thr Ile 435 440 445 Gly Asp Lys Tyr Gly Leu Tyr Leu Ala Pro Ser Ser Trp Asn Arg Tyr 450 455 460 Leu Arg Phe Gly Ile Thr Pro Asp Ile Ser Val Arg Ser Thr Thr Trp 465 470 475 480 Leu Lys Ser Gln Asp Pro Ile Met Lys Ile Leu Ser Thr Cys Thr Asn 485 490 495 Thr Asp Arg Asp Met Cys Pro Glu Ile Cys Asn Thr Arg Gly Tyr Gln 500 505 510 Asp Ile Phe Pro Leu Ser Glu Asp Ser Glu Tyr Tyr Thr Tyr Ile Gly 515 520 525 Ile Thr Pro Asn Asn Gly Gly Thr Lys Asn Phe Val Ala Val Arg Asp 530 535 540 Ser Asp Gly His Ile Ala Ser Ile Asp Ile Leu Gln Asn Tyr Tyr Ser 545 550 555 560 Ile Thr Ser Ala Thr Ile Ser Cys Phe Met Tyr Lys Asp Glu Ile Trp 565 570 575 Cys Ile Ala Ile Thr Glu Gly Lys Lys Gln Lys Asp Asn Pro Gln Arg 580 585 590 Ile Tyr Ala His Ser Tyr Lys Ile Arg Gln Met Cys Tyr Asn Met Lys 595 600 605 Ser Ala Thr Val Thr Val Gly Asn Ala Lys Asn Ile Thr Ile Arg Arg 610 615 620 Tyr 625 <![CDATA[<210> 622]]> <![CDATA[<211> 552]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 亨德拉亨尼帕病毒]]> <![CDATA[<400> 622]]> Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met 1 5 10 15 Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala 20 25 30 Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu 35 40 45 Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp 50 55 60 Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser 65 70 75 80 Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys 85 90 95 Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser 100 105 110 Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly 115 120 125 Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr 130 135 140 Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val 145 150 155 160 Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp 165 170 175 Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser 180 185 190 Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp 195 200 205 Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro 210 215 220 Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu 225 230 235 240 Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu 245 250 255 Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val 260 265 270 Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu 275 280 285 Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro 290 295 300 Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe 305 310 315 320 Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr 325 330 335 Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile 340 345 350 Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn 355 360 365 Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp 370 375 380 Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly 385 390 395 400 Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys 405 410 415 Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn 420 425 430 Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn 435 440 445 Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu 450 455 460 Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn 465 470 475 480 Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile 485 490 495 Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr 500 505 510 Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu 515 520 525 Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe 530 535 540 Ala Val Lys Ile Pro Glu Gln Cys 545 550 <![CDATA[<210> 623]]> <![CDATA[<211> 555]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 亨德拉亨尼帕病毒]]> <![CDATA[<400> 623]]> Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Ile Ile Ile Val Met 1 5 10 15 Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Thr Thr Asp Asn Gln Ala 20 25 30 Leu Ile Lys Glu Ser Leu Gln Ser Val Gln Gln Gln Ile Lys Ala Leu 35 40 45 Thr Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp 50 55 60 Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser 65 70 75 80 Lys Ile Ser Gln Ser Thr Ser Ser Ile Asn Glu Asn Val Asn Asp Lys 85 90 95 Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser 100 105 110 Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Ile Ser Gln Gly 115 120 125 Val Ser Asp Leu Val Gly Leu Pro Asn Gln Ile Cys Leu Gln Lys Thr 130 135 140 Thr Ser Thr Ile Leu Lys Pro Arg Leu Ile Ser Tyr Thr Leu Pro Ile 145 150 155 160 Asn Thr Arg Glu Gly Val Cys Ile Thr Asp Pro Leu Leu Ala Val Asp 165 170 175 Asn Gly Phe Phe Ala Tyr Ser His Leu Glu Lys Ile Gly Ser Cys Thr 180 185 190 Arg Gly Ile Ala Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp 195 200 205 Arg Gly Asp Lys Val Pro Ser Met Phe Met Thr Asn Val Trp Thr Pro 210 215 220 Pro Asn Pro Ser Thr Ile His His Cys Ser Ser Thr Tyr His Glu Asp 225 230 235 240 Phe Tyr Tyr Thr Leu Cys Ala Val Ser His Val Gly Asp Pro Ile Leu 245 250 255 Asn Ser Thr Ser Trp Thr Glu Ser Leu Ser Leu Ile Arg Leu Ala Val 260 265 270 Arg Pro Lys Ser Asp Ser Gly Asp Tyr Asn Gln Lys Tyr Ile Ala Ile 275 280 285 Thr Lys Val Glu Arg Gly Lys Tyr Asp Lys Val Met Pro Tyr Gly Pro 290 295 300 Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe 305 310 315 320 Leu Pro Arg Thr Glu Phe Gln Tyr Asn Asp Ser Asn Cys Pro Ile Ile 325 330 335 His Cys Lys Tyr Ser Lys Ala Glu Asn Cys Arg Leu Ser Met Gly Val 340 345 350 Asn Ser Lys Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn 355 360 365 Leu Ser Leu Gly Gly Asp Ile Ile Leu Gln Phe Ile Glu Ile Ala Asp 370 375 380 Asn Arg Leu Thr Ile Gly Ser Pro Ser Lys Ile Tyr Asn Ser Leu Gly 385 390 395 400 Gln Pro Val Phe Tyr Gln Ala Ser Tyr Ser Trp Asp Thr Met Ile Lys 405 410 415 Leu Gly Asp Val Asp Thr Val Asp Pro Leu Arg Val Gln Trp Arg Asn 420 425 430 Asn Ser Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn 435 440 445 Val Cys Pro Glu Val Cys Trp Glu Gly Thr Tyr Asn Asp Ala Phe Leu 450 455 460 Ile Asp Arg Leu Asn Trp Val Ser Ala Gly Val Tyr Leu Asn Ser Asn 465 470 475 480 Gln Thr Ala Glu Asn Pro Val Phe Ala Val Phe Lys Asp Asn Glu Ile 485 490 495 Leu Tyr Gln Val Pro Leu Ala Glu Asp Asp Thr Asn Ala Gln Lys Thr 500 505 510 Ile Thr Asp Cys Phe Leu Leu Glu Asn Val Ile Trp Cys Ile Ser Leu 515 520 525 Val Glu Ile Tyr Asp Thr Gly Asp Ser Val Ile Arg Pro Lys Leu Phe 530 535 540 Ala Val Lys Ile Pro Ala Gln Cys Ser Glu Ser 545 550 555 <![CDATA[<210> 624]]> <![CDATA[<211> 26]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 尼帕亨尼帕病毒]]> <![CDATA[<400> 624]]> Met Val Val Ile Leu Asp Lys Arg Cys Tyr Cys Asn Leu Leu Ile Leu 1 5 10 15 Ile Leu Met Ile Ser Glu Cys Ser Val Gly 20 25 <![CDATA[<210> 625]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 625]]> Gly Gly Gly Gly Gly Ser 1 5 <![CDATA[<210> 626]]> <![CDATA[<211> 50]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<220>]]> <![CDATA[<221> SITE]]> <![CDATA[<222> (1)..(50) ]]> <![CDATA[<223> 此序列可包含1至10個「Gly Gly Gly Gly Ser」重複單元]]> <![CDATA[<400> 626]]> Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 1 5 10 15 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 20 25 30 Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 35 40 45 Gly Ser 50 <![CDATA[<210> 627]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 627]]> Gly Gly Gly Gly Ser 1 5 <![CDATA[<210> 628]]> <![CDATA[<211> 600]]> <![CDATA[<212>]]> PRT <![CDATA[<213> 尼帕亨尼帕病毒]]> <![CDATA[<400> 628]]> Pro Ala Glu Asn Lys Lys Val Arg Phe Glu Asn Thr Thr Ser Asp Lys 1 5 10 15 Gly Lys Ile Pro Ser Lys Val Ile Lys Ser Tyr Tyr Gly Thr Met Asp 20 25 30 Ile Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala 35 40 45 Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met 50 55 60 Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala 65 70 75 80 Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu 85 90 95 Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp 100 105 110 Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser 115 120 125 Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys 130 135 140 Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser 145 150 155 160 Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly 165 170 175 Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr 180 185 190 Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val 195 200 205 Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp 210 215 220 Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser 225 230 235 240 Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp 245 250 255 Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro 260 265 270 Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu 275 280 285 Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu 290 295 300 Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val 305 310 315 320 Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu 325 330 335 Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro 340 345 350 Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe 355 360 365 Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr 370 375 380 Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile 385 390 395 400 Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn 405 410 415 Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp 420 425 430 Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly 435 440 445 Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys 450 455 460 Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn 465 470 475 480 Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn 485 490 495 Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu 500 505 510 Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn 515 520 525 Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile 530 535 540 Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr 545 550 555 560 Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu 565 570 575 Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe 580 585 590 Ala Val Lys Ile Pro Glu Gln Cys 595 600 <![CDATA[<210> 629]]> <![CDATA[<211> 595]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 629]]> Lys Val Arg Phe Glu Asn Thr Thr Ser Asp Lys Gly Lys Ile Pro Ser 1 5 10 15 Lys Val Ile Lys Ser Tyr Tyr Gly Thr Met Asp Ile Lys Lys Ile Asn 20 25 30 Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala Phe Asn Thr Val Ile 35 40 45 Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met Asn Ile Met Ile Ile 50 55 60 Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala Val Ile Lys Asp Ala 65 70 75 80 Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu Ala Asp Lys Ile Gly 85 90 95 Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp Thr Ser Ser Thr Ile 100 105 110 Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser Lys Ile Ser Gln Ser 115 120 125 Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys Cys Lys Phe Thr Leu 130 135 140 Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser Cys Pro Asn Pro Leu 145 150 155 160 Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val 165 170 175 Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu 180 185 190 Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly 195 200 205 Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala 210 215 220 Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys 225 230 235 240 Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val 245 250 255 Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr 260 265 270 Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu 275 280 285 Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp 290 295 300 Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn 305 310 315 320 Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys 325 330 335 Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln 340 345 350 Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu 355 360 365 Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser 370 375 380 Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His 385 390 395 400 Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu 405 410 415 Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile 420 425 430 Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr 435 440 445 Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu 450 455 460 Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser 465 470 475 480 Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile 485 490 495 Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn 500 505 510 Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn 515 520 525 Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln 530 535 540 Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe 545 550 555 560 Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp 565 570 575 Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro 580 585 590 Glu Gln Cys 595 <![CDATA[<210> 630]]> <![CDATA[<211> 590]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 630]]> Asn Thr Thr Ser Asp Lys Gly Lys Ile Pro Ser Lys Val Ile Lys Ser 1 5 10 15 Tyr Tyr Gly Thr Met Asp Ile Lys Lys Ile Asn Glu Gly Leu Leu Asp 20 25 30 Ser Lys Ile Leu Ser Ala Phe Asn Thr Val Ile Ala Leu Leu Gly Ser 35 40 45 Ile Val Ile Ile Val Met Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg 50 55 60 Ser Thr Asp Asn Gln Ala Val Ile Lys Asp Ala Leu Gln Gly Ile Gln 65 70 75 80 Gln Gln Ile Lys Gly Leu Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro 85 90 95 Lys Val Ser Leu Ile Asp Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn 100 105 110 Ile Gly Leu Leu Gly Ser Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn 115 120 125 Glu Asn Val Asn Glu Lys Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile 130 135 140 His Glu Cys Asn Ile Ser Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr 145 150 155 160 Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val Gly Leu Pro Asn Asn 165 170 175 Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile 180 185 190 Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr Cys Ile Thr Asp 195 200 205 Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu 210 215 220 Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln Arg Ile Ile Gly 225 230 235 240 Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro Ser Leu Phe Met 245 250 255 Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr His Cys Ser 260 265 270 Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr 275 280 285 Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met 290 295 300 Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn 305 310 315 320 Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys 325 330 335 Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr 340 345 350 Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp 355 360 365 Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys 370 375 380 Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu Arg Ser 385 390 395 400 Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys Val Val 405 410 415 Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys 420 425 430 Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser 435 440 445 Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn Pro Leu 450 455 460 Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro Gly Gln Ser 465 470 475 480 Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu Gly Val 485 490 495 Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly 500 505 510 Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe Thr Val 515 520 525 Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp 530 535 540 Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys 545 550 555 560 Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn Val 565 570 575 Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys 580 585 590 <![CDATA[<210> 631]]> <![CDATA[<211> 585]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 631]]> Lys Gly Lys Ile Pro Ser Lys Val Ile Lys Ser Tyr Tyr Gly Thr Met 1 5 10 15 Asp Ile Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser 20 25 30 Ala Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val 35 40 45 Met Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln 50 55 60 Ala Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly 65 70 75 80 Leu Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile 85 90 95 Asp Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly 100 105 110 Ser Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu 115 120 125 Lys Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile 130 135 140 Ser Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu 145 150 155 160 Gly Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys 165 170 175 Thr Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro 180 185 190 Val Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met 195 200 205 Asp Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys 210 215 220 Ser Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu 225 230 235 240 Asp Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr 245 250 255 Pro Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn 260 265 270 Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile 275 280 285 Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala 290 295 300 Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala 305 310 315 320 Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly 325 330 335 Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly 340 345 350 Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile 355 360 365 Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly 370 375 380 Ile Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr 385 390 395 400 Asn Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser 405 410 415 Asp Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu 420 425 430 Gly Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile 435 440 445 Lys Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg 450 455 460 Asn Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe 465 470 475 480 Asn Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe 485 490 495 Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser 500 505 510 Asn Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu 515 520 525 Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys 530 535 540 Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser 545 550 555 560 Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu 565 570 575 Phe Ala Val Lys Ile Pro Glu Gln Cys 580 585 <![CDATA[<210> 632]]> <![CDATA[<211> 580]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 632]]> Ser Lys Val Ile Lys Ser Tyr Tyr Gly Thr Met Asp Ile Lys Lys Ile 1 5 10 15 Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala Phe Asn Thr Val 20 25 30 Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met Asn Ile Met Ile 35 40 45 Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala Val Ile Lys Asp 50 55 60 Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu Ala Asp Lys Ile 65 70 75 80 Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp Thr Ser Ser Thr 85 90 95 Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser Lys Ile Ser Gln 100 105 110 Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys Cys Lys Phe Thr 115 120 125 Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser Cys Pro Asn Pro 130 135 140 Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly Val Ser Asn Leu 145 150 155 160 Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile 165 170 175 Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser 180 185 190 Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe 195 200 205 Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser 210 215 220 Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu 225 230 235 240 Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn 245 250 255 Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val 260 265 270 Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr 275 280 285 Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser 290 295 300 Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu 305 310 315 320 Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys 325 330 335 Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr 340 345 350 Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr 355 360 365 Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser 370 375 380 His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly 385 390 395 400 Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser 405 410 415 Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe 420 425 430 Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val 435 440 445 Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile 450 455 460 Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu 465 470 475 480 Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile 485 490 495 Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu 500 505 510 Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala 515 520 525 Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys 530 535 540 Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr 545 550 555 560 Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile 565 570 575 Pro Glu Gln Cys 580 <![CDATA[<210> 633]]> <![CDATA[<211> 575]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 633]]> Ser Tyr Tyr Gly Thr Met Asp Ile Lys Lys Ile Asn Glu Gly Leu Leu 1 5 10 15 Asp Ser Lys Ile Leu Ser Ala Phe Asn Thr Val Ile Ala Leu Leu Gly 20 25 30 Ser Ile Val Ile Ile Val Met Asn Ile Met Ile Ile Gln Asn Tyr Thr 35 40 45 Arg Ser Thr Asp Asn Gln Ala Val Ile Lys Asp Ala Leu Gln Gly Ile 50 55 60 Gln Gln Gln Ile Lys Gly Leu Ala Asp Lys Ile Gly Thr Glu Ile Gly 65 70 75 80 Pro Lys Val Ser Leu Ile Asp Thr Ser Ser Thr Ile Thr Ile Pro Ala 85 90 95 Asn Ile Gly Leu Leu Gly Ser Lys Ile Ser Gln Ser Thr Ala Ser Ile 100 105 110 Asn Glu Asn Val Asn Glu Lys Cys Lys Phe Thr Leu Pro Pro Leu Lys 115 120 125 Ile His Glu Cys Asn Ile Ser Cys Pro Asn Pro Leu Pro Phe Arg Glu 130 135 140 Tyr Arg Pro Gln Thr Glu Gly Val Ser Asn Leu Val Gly Leu Pro Asn 145 150 155 160 Asn Ile Cys Leu Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys Leu 165 170 175 Ile Ser Tyr Thr Leu Pro Val Val Gly Gln Ser Gly Thr Cys Ile Thr 180 185 190 Asp Pro Leu Leu Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser His Leu 195 200 205 Glu Arg Ile Gly Ser Cys Ser Arg Gly Val Ser Lys Gln Arg Ile Ile 210 215 220 Gly Val Gly Glu Val Leu Asp Arg Gly Asp Glu Val Pro Ser Leu Phe 225 230 235 240 Met Thr Asn Val Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr His Cys 245 250 255 Ser Ala Val Tyr Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser 260 265 270 Thr Val Gly Asp Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu 275 280 285 Met Met Thr Arg Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr 290 295 300 Asn Gln His Gln Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp 305 310 315 320 Lys Val Met Pro Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu 325 330 335 Tyr Phe Pro Ala Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn 340 345 350 Asp Ser Asn Cys Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn 355 360 365 Cys Arg Leu Ser Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu Arg 370 375 380 Ser Gly Leu Leu Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys Val 385 390 395 400 Val Phe Ile Glu Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro Ser 405 410 415 Lys Ile Tyr Asp Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser Phe 420 425 430 Ser Trp Asp Thr Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn Pro 435 440 445 Leu Val Val Asn Trp Arg Asn Asn Thr Val Ile Ser Arg Pro Gly Gln 450 455 460 Ser Gln Cys Pro Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu Gly 465 470 475 480 Val Tyr Asn Asp Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala 485 490 495 Gly Val Phe Leu Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe Thr 500 505 510 Val Phe Lys Asp Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu 515 520 525 Asp Thr Asn Ala Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn 530 535 540 Lys Ile Trp Cys Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn 545 550 555 560 Val Ile Arg Pro Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys 565 570 575 <![CDATA[<210> 634]]> <![CDATA[<211> 571]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 634]]> Thr Met Asp Ile Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile 1 5 10 15 Leu Ser Ala Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile 20 25 30 Ile Val Met Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp 35 40 45 Asn Gln Ala Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile 50 55 60 Lys Gly Leu Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser 65 70 75 80 Leu Ile Asp Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu 85 90 95 Leu Gly Ser Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val 100 105 110 Asn Glu Lys Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys 115 120 125 Asn Ile Ser Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln 130 135 140 Thr Glu Gly Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu 145 150 155 160 Gln Lys Thr Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr 165 170 175 Leu Pro Val Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu 180 185 190 Ala Met Asp Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly 195 200 205 Ser Cys Ser Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu 210 215 220 Val Leu Asp Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val 225 230 235 240 Trp Thr Pro Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr 245 250 255 Asn Asn Glu Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp 260 265 270 Pro Ile Leu Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg 275 280 285 Leu Ala Val Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln 290 295 300 Leu Ala Leu Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro 305 310 315 320 Tyr Gly Pro Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala 325 330 335 Val Gly Phe Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys 340 345 350 Pro Ile Thr Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser 355 360 365 Met Gly Ile Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu 370 375 380 Lys Tyr Asn Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu 385 390 395 400 Ile Ser Asp Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp 405 410 415 Ser Leu Gly Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr 420 425 430 Met Ile Lys Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn 435 440 445 Trp Arg Asn Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro 450 455 460 Arg Phe Asn Thr Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp 465 470 475 480 Ala Phe Leu Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu 485 490 495 Asp Ser Asn Gln Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp 500 505 510 Asn Glu Ile Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala 515 520 525 Gln Lys Thr Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys 530 535 540 Ile Ser Leu Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro 545 550 555 560 Lys Leu Phe Ala Val Lys Ile Pro Glu Gln Cys 565 570 <![CDATA[<210> 635]]> <![CDATA[<211> 568]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 635]]> Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala Phe 1 5 10 15 Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met Asn 20 25 30 Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala Val 35 40 45 Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu Ala 50 55 60 Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp Thr 65 70 75 80 Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser Lys 85 90 95 Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys Cys 100 105 110 Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser Cys 115 120 125 Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly Val 130 135 140 Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser 145 150 155 160 Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val 165 170 175 Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu 180 185 190 Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg 195 200 205 Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg 210 215 220 Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro 225 230 235 240 Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe 245 250 255 Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn 260 265 270 Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys 275 280 285 Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg 290 295 300 Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser 305 310 315 320 Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu 325 330 335 Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys 340 345 350 Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg 355 360 365 Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu 370 375 380 Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln 385 390 395 400 Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln 405 410 415 Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe 420 425 430 Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn 435 440 445 Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr 450 455 460 Cys Pro Ala Ile Cys Ala Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile 465 470 475 480 Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Ala 485 490 495 Thr Ala Ala Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu 500 505 510 Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile 515 520 525 Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val 530 535 540 Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala 545 550 555 560 Val Lys Ile Pro Glu Gln Cys Thr 565 <![CDATA[<210> 636]]> <![CDATA[<211> 603]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 亨德拉亨尼帕病毒]]> <![CDATA[<400> 636]]> Met Ala Asp Ser Lys Leu Val Ser Leu Asn Asn Asn Leu Ser Gly Lys 1 5 10 15 Ile Lys Asp Gln Gly Lys Val Ile Lys Asn Tyr Tyr Gly Thr Met Asp 20 25 30 Ile Lys Lys Ile Asn Asp Gly Leu Leu Asp Ser Lys Ile Leu Gly Ala 35 40 45 Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Ile Ile Ile Val Met 50 55 60 Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Thr Thr Asp Asn Gln Ala 65 70 75 80 Leu Ile Lys Glu Ser Leu Gln Ser Val Gln Gln Gln Ile Lys Ala Leu 85 90 95 Thr Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp 100 105 110 Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser 115 120 125 Lys Ile Ser Gln Ser Thr Ser Ser Ile Asn Glu Asn Val Asn Asp Lys 130 135 140 Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser 145 150 155 160 Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Ile Ser Gln Gly 165 170 175 Val Ser Asp Leu Val Gly Leu Pro Asn Gln Ile Cys Leu Gln Lys Thr 180 185 190 Thr Ser Thr Ile Leu Lys Pro Arg Leu Ile Ser Tyr Thr Leu Pro Ile 195 200 205 Asn Thr Arg Glu Gly Val Cys Ile Thr Asp Pro Leu Leu Ala Val Asp 210 215 220 Asn Gly Phe Phe Ala Tyr Ser His Leu Glu Lys Ile Gly Ser Cys Thr 225 230 235 240 Arg Gly Ile Ala Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp 245 250 255 Arg Gly Asp Lys Val Pro Ser Met Phe Met Thr Asn Val Trp Thr Pro 260 265 270 Pro Asn Pro Ser Thr Ile His His Cys Ser Ser Thr Tyr His Glu Asp 275 280 285 Phe Tyr Tyr Thr Leu Cys Ala Val Ser His Val Gly Asp Pro Ile Leu 290 295 300 Asn Ser Thr Ser Trp Thr Glu Ser Leu Ser Leu Ile Arg Leu Ala Val 305 310 315 320 Arg Pro Lys Ser Asp Ser Gly Asp Tyr Asn Gln Lys Tyr Ile Ala Ile 325 330 335 Thr Lys Val Glu Arg Gly Lys Tyr Asp Lys Val Met Pro Tyr Gly Pro 340 345 350 Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe 355 360 365 Leu Pro Arg Thr Glu Phe Gln Tyr Asn Asp Ser Asn Cys Pro Ile Ile 370 375 380 His Cys Lys Tyr Ser Lys Ala Glu Asn Cys Arg Leu Ser Met Gly Val 385 390 395 400 Asn Ser Lys Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn 405 410 415 Leu Ser Leu Gly Gly Asp Ile Ile Leu Gln Phe Ile Glu Ile Ala Asp 420 425 430 Asn Arg Leu Thr Ile Gly Ser Pro Ser Lys Ile Tyr Asn Ser Leu Gly 435 440 445 Gln Pro Val Phe Tyr Gln Ala Ser Tyr Ser Trp Asp Thr Met Ile Lys 450 455 460 Leu Gly Asp Val Asp Thr Val Asp Pro Leu Arg Val Gln Trp Arg Asn 465 470 475 480 Asn Ser Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn 485 490 495 Val Cys Pro Glu Val Cys Trp Glu Gly Thr Tyr Asn Asp Ala Phe Leu 500 505 510 Ile Asp Arg Leu Asn Trp Val Ser Ala Gly Val Tyr Leu Asn Ser Asn 515 520 525 Gln Thr Ala Glu Asn Pro Val Phe Ala Val Phe Lys Asp Asn Glu Ile 530 535 540 Leu Tyr Gln Val Pro Leu Ala Glu Asp Asp Thr Asn Ala Gln Lys Thr 545 550 555 560 Ile Thr Asp Cys Phe Leu Leu Glu Asn Val Ile Trp Cys Ile Ser Leu 565 570 575 Val Glu Ile Tyr Asp Thr Gly Asp Ser Val Ile Arg Pro Lys Leu Phe 580 585 590 Ala Val Lys Ile Pro Ala Gln Cys Ser Glu Ser 595 600 <![CDATA[<210> 637]]> <![CDATA[<211> 568]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 637]]> Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala Phe 1 5 10 15 Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met Asn 20 25 30 Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala Val 35 40 45 Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu Ala 50 55 60 Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp Thr 65 70 75 80 Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser Lys 85 90 95 Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys Cys 100 105 110 Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser Cys 115 120 125 Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly Val 130 135 140 Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser 145 150 155 160 Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val 165 170 175 Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu 180 185 190 Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg 195 200 205 Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg 210 215 220 Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro 225 230 235 240 Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe 245 250 255 Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn 260 265 270 Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys 275 280 285 Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg 290 295 300 Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser 305 310 315 320 Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu 325 330 335 Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys 340 345 350 Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg 355 360 365 Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu 370 375 380 Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln 385 390 395 400 Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln 405 410 415 Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe 420 425 430 Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn 435 440 445 Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr 450 455 460 Cys Pro Glu Ile Cys Trp Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile 465 470 475 480 Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Gln 485 490 495 Thr Ala Glu Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu 500 505 510 Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile 515 520 525 Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val 530 535 540 Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala 545 550 555 560 Val Lys Ile Pro Glu Gln Cys Thr 565 <![CDATA[<210> 638]]> <![CDATA[<211> 621]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 松灣亨尼帕病毒]]> <![CDATA[<400> 638]]> Leu Ser Gln Leu Gln Lys Asn Tyr Leu Asp Asn Ser Asn Gln Gln Gly 1 5 10 15 Asp Lys Met Asn Asn Pro Asp Lys Lys Leu Ser Val Asn Phe Asn Pro 20 25 30 Leu Glu Leu Asp Lys Gly Gln Lys Asp Leu Asn Lys Ser Tyr Tyr Val 35 40 45 Lys Asn Lys Asn Tyr Asn Val Ser Asn Leu Leu Asn Glu Ser Leu His 50 55 60 Asp Ile Lys Phe Cys Ile Tyr Cys Ile Phe Ser Leu Leu Ile Ile Ile 65 70 75 80 Thr Ile Ile Asn Ile Ile Thr Ile Ser Ile Val Ile Thr Arg Leu Lys 85 90 95 Val His Glu Glu Asn Asn Gly Met Glu Ser Pro Asn Leu Gln Ser Ile 100 105 110 Gln Asp Ser Leu Ser Ser Leu Thr Asn Met Ile Asn Thr Glu Ile Thr 115 120 125 Pro Arg Ile Gly Ile Leu Val Thr Ala Thr Ser Val Thr Leu Ser Ser 130 135 140 Ser Ile Asn Tyr Val Gly Thr Lys Thr Asn Gln Leu Val Asn Glu Leu 145 150 155 160 Lys Asp Tyr Ile Thr Lys Ser Cys Gly Phe Lys Val Pro Glu Leu Lys 165 170 175 Leu His Glu Cys Asn Ile Ser Cys Ala Asp Pro Lys Ile Ser Lys Ser 180 185 190 Ala Met Tyr Ser Thr Asn Ala Tyr Ala Glu Leu Ala Gly Pro Pro Lys 195 200 205 Ile Phe Cys Lys Ser Val Ser Lys Asp Pro Asp Phe Arg Leu Lys Gln 210 215 220 Ile Asp Tyr Val Ile Pro Val Gln Gln Asp Arg Ser Ile Cys Met Asn 225 230 235 240 Asn Pro Leu Leu Asp Ile Ser Asp Gly Phe Phe Thr Tyr Ile His Tyr 245 250 255 Glu Gly Ile Asn Ser Cys Lys Lys Ser Asp Ser Phe Lys Val Leu Leu 260 265 270 Ser His Gly Glu Ile Val Asp Arg Gly Asp Tyr Arg Pro Ser Leu Tyr 275 280 285 Leu Leu Ser Ser His Tyr His Pro Tyr Ser Met Gln Val Ile Asn Cys 290 295 300 Val Pro Val Thr Cys Asn Gln Ser Ser Phe Val Phe Cys His Ile Ser 305 310 315 320 Asn Asn Thr Lys Thr Leu Asp Asn Ser Asp Tyr Ser Ser Asp Glu Tyr 325 330 335 Tyr Ile Thr Tyr Phe Asn Gly Ile Asp Arg Pro Lys Thr Lys Lys Ile 340 345 350 Pro Ile Asn Asn Met Thr Ala Asp Asn Arg Tyr Ile His Phe Thr Phe 355 360 365 Ser Gly Gly Gly Gly Val Cys Leu Gly Glu Glu Phe Ile Ile Pro Val 370 375 380 Thr Thr Val Ile Asn Thr Asp Val Phe Thr His Asp Tyr Cys Glu Ser 385 390 395 400 Phe Asn Cys Ser Val Gln Thr Gly Lys Ser Leu Lys Glu Ile Cys Ser 405 410 415 Glu Ser Leu Arg Ser Pro Thr Asn Ser Ser Arg Tyr Asn Leu Asn Gly 420 425 430 Ile Met Ile Ile Ser Gln Asn Asn Met Thr Asp Phe Lys Ile Gln Leu 435 440 445 Asn Gly Ile Thr Tyr Asn Lys Leu Ser Phe Gly Ser Pro Gly Arg Leu 450 455 460 Ser Lys Thr Leu Gly Gln Val Leu Tyr Tyr Gln Ser Ser Met Ser Trp 465 470 475 480 Asp Thr Tyr Leu Lys Ala Gly Phe Val Glu Lys Trp Lys Pro Phe Thr 485 490 495 Pro Asn Trp Met Asn Asn Thr Val Ile Ser Arg Pro Asn Gln Gly Asn 500 505 510 Cys Pro Arg Tyr His Lys Cys Pro Glu Ile Cys Tyr Gly Gly Thr Tyr 515 520 525 Asn Asp Ile Ala Pro Leu Asp Leu Gly Lys Asp Met Tyr Val Ser Val 530 535 540 Ile Leu Asp Ser Asp Gln Leu Ala Glu Asn Pro Glu Ile Thr Val Phe 545 550 555 560 Asn Ser Thr Thr Ile Leu Tyr Lys Glu Arg Val Ser Lys Asp Glu Leu 565 570 575 Asn Thr Arg Ser Thr Thr Thr Ser Cys Phe Leu Phe Leu Asp Glu Pro 580 585 590 Trp Cys Ile Ser Val Leu Glu Thr Asn Arg Phe Asn Gly Lys Ser Ile 595 600 605 Arg Pro Glu Ile Tyr Ser Tyr Lys Ile Pro Lys Tyr Cys 610 615 620 <![CDATA[<210> 639]]> <![CDATA[<211> 631]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 未知]]> <![CDATA[<220>]]> <![CDATA[<223> 未知之描述:蝙蝠副黏病毒Eid_hel/GH-M74a/GHA/2009序列]]> <![CDATA[<400> 639]]> Pro Gln Lys Thr Val Glu Phe Ile Asn Met Asn Ser Pro Leu Glu Arg 1 5 10 15 Gly Val Ser Thr Leu Ser Asp Lys Lys Thr Leu Asn Gln Ser Lys Ile 20 25 30 Thr Lys Gln Gly Tyr Phe Gly Leu Gly Ser His Ser Glu Arg Asn Trp 35 40 45 Lys Lys Gln Lys Asn Gln Asn Asp His Tyr Met Thr Val Ser Thr Met 50 55 60 Ile Leu Glu Ile Leu Val Val Leu Gly Ile Met Phe Asn Leu Ile Val 65 70 75 80 Leu Thr Met Val Tyr Tyr Gln Asn Asp Asn Ile Asn Gln Arg Met Ala 85 90 95 Glu Leu Thr Ser Asn Ile Thr Val Leu Asn Leu Asn Leu Asn Gln Leu 100 105 110 Thr Asn Lys Ile Gln Arg Glu Ile Ile Pro Arg Ile Thr Leu Ile Asp 115 120 125 Thr Ala Thr Thr Ile Thr Ile Pro Ser Ala Ile Thr Tyr Ile Leu Ala 130 135 140 Thr Leu Thr Thr Arg Ile Ser Glu Leu Leu Pro Ser Ile Asn Gln Lys 145 150 155 160 Cys Glu Phe Lys Thr Pro Thr Leu Val Leu Asn Asp Cys Arg Ile Asn 165 170 175 Cys Thr Pro Pro Leu Asn Pro Ser Asp Gly Val Lys Met Ser Ser Leu 180 185 190 Ala Thr Asn Leu Val Ala His Gly Pro Ser Pro Cys Arg Asn Phe Ser 195 200 205 Ser Val Pro Thr Ile Tyr Tyr Tyr Arg Ile Pro Gly Leu Tyr Asn Arg 210 215 220 Thr Ala Leu Asp Glu Arg Cys Ile Leu Asn Pro Arg Leu Thr Ile Ser 225 230 235 240 Ser Thr Lys Phe Ala Tyr Val His Ser Glu Tyr Asp Lys Asn Cys Thr 245 250 255 Arg Gly Phe Lys Tyr Tyr Glu Leu Met Thr Phe Gly Glu Ile Leu Glu 260 265 270 Gly Pro Glu Lys Glu Pro Arg Met Phe Ser Arg Ser Phe Tyr Ser Pro 275 280 285 Thr Asn Ala Val Asn Tyr His Ser Cys Thr Pro Ile Val Thr Val Asn 290 295 300 Glu Gly Tyr Phe Leu Cys Leu Glu Cys Thr Ser Ser Asp Pro Leu Tyr 305 310 315 320 Lys Ala Asn Leu Ser Asn Ser Thr Phe His Leu Val Ile Leu Arg His 325 330 335 Asn Lys Asp Glu Lys Ile Val Ser Met Pro Ser Phe Asn Leu Ser Thr 340 345 350 Asp Gln Glu Tyr Val Gln Ile Ile Pro Ala Glu Gly Gly Gly Thr Ala 355 360 365 Glu Ser Gly Asn Leu Tyr Phe Pro Cys Ile Gly Arg Leu Leu His Lys 370 375 380 Arg Val Thr His Pro Leu Cys Lys Lys Ser Asn Cys Ser Arg Thr Asp 385 390 395 400 Asp Glu Ser Cys Leu Lys Ser Tyr Tyr Asn Gln Gly Ser Pro Gln His 405 410 415 Gln Val Val Asn Cys Leu Ile Arg Ile Arg Asn Ala Gln Arg Asp Asn 420 425 430 Pro Thr Trp Asp Val Ile Thr Val Asp Leu Thr Asn Thr Tyr Pro Gly 435 440 445 Ser Arg Ser Arg Ile Phe Gly Ser Phe Ser Lys Pro Met Leu Tyr Gln 450 455 460 Ser Ser Val Ser Trp His Thr Leu Leu Gln Val Ala Glu Ile Thr Asp 465 470 475 480 Leu Asp Lys Tyr Gln Leu Asp Trp Leu Asp Thr Pro Tyr Ile Ser Arg 485 490 495 Pro Gly Gly Ser Glu Cys Pro Phe Gly Asn Tyr Cys Pro Thr Val Cys 500 505 510 Trp Glu Gly Thr Tyr Asn Asp Val Tyr Ser Leu Thr Pro Asn Asn Asp 515 520 525 Leu Phe Val Thr Val Tyr Leu Lys Ser Glu Gln Val Ala Glu Asn Pro 530 535 540 Tyr Phe Ala Ile Phe Ser Arg Asp Gln Ile Leu Lys Glu Phe Pro Leu 545 550 555 560 Asp Ala Trp Ile Ser Ser Ala Arg Thr Thr Thr Ile Ser Cys Phe Met 565 570 575 Phe Asn Asn Glu Ile Trp Cys Ile Ala Ala Leu Glu Ile Thr Arg Leu 580 585 590 Asn Asp Asp Ile Ile Arg Pro Ile Tyr Tyr Ser Phe Trp Leu Pro Thr 595 600 605 Asp Cys Arg Thr Pro Tyr Pro His Thr Gly Lys Met Thr Arg Val Pro 610 615 620 Leu Arg Ser Thr Tyr Asn Tyr 625 630 <![CDATA[<210> 640]]> <![CDATA[<211> 624]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 墨江亨尼帕病毒]]> <![CDATA[<400> 640]]> Ala Thr Asn Arg Asp Asn Thr Ile Thr Ser Ala Glu Val Ser Gln Glu 1 5 10 15 Asp Lys Val Lys Lys Tyr Tyr Gly Val Glu Thr Ala Glu Lys Val Ala 20 25 30 Asp Ser Ile Ser Gly Asn Lys Val Phe Ile Leu Met Asn Thr Leu Leu 35 40 45 Ile Leu Thr Gly Ala Ile Ile Thr Ile Thr Leu Asn Ile Thr Asn Leu 50 55 60 Thr Ala Ala Lys Ser Gln Gln Asn Met Leu Lys Ile Ile Gln Asp Asp 65 70 75 80 Val Asn Ala Lys Leu Glu Met Phe Val Asn Leu Asp Gln Leu Val Lys 85 90 95 Gly Glu Ile Lys Pro Lys Val Ser Leu Ile Asn Thr Ala Val Ser Val 100 105 110 Ser Ile Pro Gly Gln Ile Ser Asn Leu Gln Thr Lys Phe Leu Gln Lys 115 120 125 Tyr Val Tyr Leu Glu Glu Ser Ile Thr Lys Gln Cys Thr Cys Asn Pro 130 135 140 Leu Ser Gly Ile Phe Pro Thr Ser Gly Pro Thr Tyr Pro Pro Thr Asp 145 150 155 160 Lys Pro Asp Asp Asp Thr Thr Asp Asp Asp Lys Val Asp Thr Thr Ile 165 170 175 Lys Pro Ile Glu Tyr Pro Lys Pro Asp Gly Cys Asn Arg Thr Gly Asp 180 185 190 His Phe Thr Met Glu Pro Gly Ala Asn Phe Tyr Thr Val Pro Asn Leu 195 200 205 Gly Pro Ala Ser Ser Asn Ser Asp Glu Cys Tyr Thr Asn Pro Ser Phe 210 215 220 Ser Ile Gly Ser Ser Ile Tyr Met Phe Ser Gln Glu Ile Arg Lys Thr 225 230 235 240 Asp Cys Thr Ala Gly Glu Ile Leu Ser Ile Gln Ile Val Leu Gly Arg 245 250 255 Ile Val Asp Lys Gly Gln Gln Gly Pro Gln Ala Ser Pro Leu Leu Val 260 265 270 Trp Ala Val Pro Asn Pro Lys Ile Ile Asn Ser Cys Ala Val Ala Ala 275 280 285 Gly Asp Glu Met Gly Trp Val Leu Cys Ser Val Thr Leu Thr Ala Ala 290 295 300 Ser Gly Glu Pro Ile Pro His Met Phe Asp Gly Phe Trp Leu Tyr Lys 305 310 315 320 Leu Glu Pro Asp Thr Glu Val Val Ser Tyr Arg Ile Thr Gly Tyr Ala 325 330 335 Tyr Leu Leu Asp Lys Gln Tyr Asp Ser Val Phe Ile Gly Lys Gly Gly 340 345 350 Gly Ile Gln Lys Gly Asn Asp Leu Tyr Phe Gln Met Tyr Gly Leu Ser 355 360 365 Arg Asn Arg Gln Ser Phe Lys Ala Leu Cys Glu His Gly Ser Cys Leu 370 375 380 Gly Thr Gly Gly Gly Gly Tyr Gln Val Leu Cys Asp Arg Ala Val Met 385 390 395 400 Ser Phe Gly Ser Glu Glu Ser Leu Ile Thr Asn Ala Tyr Leu Lys Val 405 410 415 Asn Asp Leu Ala Ser Gly Lys Pro Val Ile Ile Gly Gln Thr Phe Pro 420 425 430 Pro Ser Asp Ser Tyr Lys Gly Ser Asn Gly Arg Met Tyr Thr Ile Gly 435 440 445 Asp Lys Tyr Gly Leu Tyr Leu Ala Pro Ser Ser Trp Asn Arg Tyr Leu 450 455 460 Arg Phe Gly Ile Thr Pro Asp Ile Ser Val Arg Ser Thr Thr Trp Leu 465 470 475 480 Lys Ser Gln Asp Pro Ile Met Lys Ile Leu Ser Thr Cys Thr Asn Thr 485 490 495 Asp Arg Asp Met Cys Pro Glu Ile Cys Asn Thr Arg Gly Tyr Gln Asp 500 505 510 Ile Phe Pro Leu Ser Glu Asp Ser Glu Tyr Tyr Thr Tyr Ile Gly Ile 515 520 525 Thr Pro Asn Asn Gly Gly Thr Lys Asn Phe Val Ala Val Arg Asp Ser 530 535 540 Asp Gly His Ile Ala Ser Ile Asp Ile Leu Gln Asn Tyr Tyr Ser Ile 545 550 555 560 Thr Ser Ala Thr Ile Ser Cys Phe Met Tyr Lys Asp Glu Ile Trp Cys 565 570 575 Ile Ala Ile Thr Glu Gly Lys Lys Gln Lys Asp Asn Pro Gln Arg Ile 580 585 590 Tyr Ala His Ser Tyr Lys Ile Arg Gln Met Cys Tyr Asn Met Lys Ser 595 600 605 Ala Thr Val Thr Val Gly Asn Ala Lys Asn Ile Thr Ile Arg Arg Tyr 610 615 620 <![CDATA[<210> 641]]> <![CDATA[<211> 530]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 松灣亨尼帕病毒]]> <![CDATA[<400> 641]]> Asp Phe Asp Lys Leu Asn Lys Ile Gly Val Val Gln Gly Arg Val Leu 1 5 10 15 Asn Tyr Lys Ile Lys Gly Asp Pro Met Thr Lys Asp Leu Val Leu Lys 20 25 30 Phe Ile Pro Asn Ile Val Asn Ile Thr Glu Cys Val Arg Glu Pro Leu 35 40 45 Ser Arg Tyr Asn Glu Thr Val Arg Arg Leu Leu Leu Pro Ile His Asn 50 55 60 Met Leu Gly Leu Tyr Leu Asn Asn Thr Asn Ala Lys Met Thr Gly Leu 65 70 75 80 Met Ile Ala Gly Val Ile Met Gly Gly Ile Ala Ile Gly Ile Ala Thr 85 90 95 Ala Ala Gln Ile Thr Ala Gly Phe Ala Leu Tyr Glu Ala Lys Lys Asn 100 105 110 Thr Glu Asn Ile Gln Lys Leu Thr Asp Ser Ile Met Lys Thr Gln Asp 115 120 125 Ser Ile Asp Lys Leu Thr Asp Ser Val Gly Thr Ser Ile Leu Ile Leu 130 135 140 Asn Lys Leu Gln Thr Tyr Ile Asn Asn Gln Leu Val Pro Asn Leu Glu 145 150 155 160 Leu Leu Ser Cys Arg Gln Asn Lys Ile Glu Phe Asp Leu Met Leu Thr 165 170 175 Lys Tyr Leu Val Asp Leu Met Thr Val Ile Gly Pro Asn Ile Asn Asn 180 185 190 Pro Val Asn Lys Asp Met Thr Ile Gln Ser Leu Ser Leu Leu Phe Asp 195 200 205 Gly Asn Tyr Asp Ile Met Met Ser Glu Leu Gly Tyr Thr Pro Gln Asp 210 215 220 Phe Leu Asp Leu Ile Glu Ser Lys Ser Ile Thr Gly Gln Ile Ile Tyr 225 230 235 240 Val Asp Met Glu Asn Leu Tyr Val Val Ile Arg Thr Tyr Leu Pro Thr 245 250 255 Leu Ile Glu Val Pro Asp Ala Gln Ile Tyr Glu Phe Asn Lys Ile Thr 260 265 270 Met Ser Ser Asn Gly Gly Glu Tyr Leu Ser Thr Ile Pro Asn Phe Ile 275 280 285 Leu Ile Arg Gly Asn Tyr Met Ser Asn Ile Asp Val Ala Thr Cys Tyr 290 295 300 Met Thr Lys Ala Ser Val Ile Cys Asn Gln Asp Tyr Ser Leu Pro Met 305 310 315 320 Ser Gln Asn Leu Arg Ser Cys Tyr Gln Gly Glu Thr Glu Tyr Cys Pro 325 330 335 Val Glu Ala Val Ile Ala Ser His Ser Pro Arg Phe Ala Leu Thr Asn 340 345 350 Gly Val Ile Phe Ala Asn Cys Ile Asn Thr Ile Cys Arg Cys Gln Asp 355 360 365 Asn Gly Lys Thr Ile Thr Gln Asn Ile Asn Gln Phe Val Ser Met Ile 370 375 380 Asp Asn Ser Thr Cys Asn Asp Val Met Val Asp Lys Phe Thr Ile Lys 385 390 395 400 Val Gly Lys Tyr Met Gly Arg Lys Asp Ile Asn Asn Ile Asn Ile Gln 405 410 415 Ile Gly Pro Gln Ile Ile Ile Asp Lys Val Asp Leu Ser Asn Glu Ile 420 425 430 Asn Lys Met Asn Gln Ser Leu Lys Asp Ser Ile Phe Tyr Leu Arg Glu 435 440 445 Ala Lys Arg Ile Leu Asp Ser Val Asn Ile Ser Leu Ile Ser Pro Ser 450 455 460 Val Gln Leu Phe Leu Ile Ile Ile Ser Val Leu Ser Phe Ile Ile Leu 465 470 475 480 Leu Ile Ile Ile Val Tyr Leu Tyr Cys Lys Ser Lys His Ser Tyr Lys 485 490 495 Tyr Asn Lys Phe Ile Asp Asp Pro Asp Tyr Tyr Asn Asp Tyr Lys Arg 500 505 510 Glu Arg Ile Asn Gly Lys Ala Ser Lys Ser Asn Asn Ile Tyr Tyr Val 515 520 525 Gly Asp 530 <![CDATA[<210> 642]]> <![CDATA[<211> 640]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 未知]]> <![CDATA[<220>]]> <![CDATA[<223> 未知之描述:蝙蝠副黏病毒Eid_hel/GH-M74a/GHA/2009序列]]> <![CDATA[<400> 642]]> Ser Arg Ala Leu Leu Arg Glu Thr Asp Asn Tyr Ser Asn Gly Leu Ile 1 5 10 15 Val Glu Asn Leu Val Arg Asn Cys His His Pro Ser Lys Asn Asn Leu 20 25 30 Asn Tyr Thr Lys Thr Gln Lys Arg Asp Ser Thr Ile Pro Tyr Arg Val 35 40 45 Glu Glu Arg Lys Gly His Tyr Pro Lys Ile Lys His Leu Ile Asp Lys 50 55 60 Ser Tyr Lys His Ile Lys Arg Gly Lys Arg Arg Asn Gly His Asn Gly 65 70 75 80 Asn Ile Ile Thr Ile Ile Leu Leu Leu Ile Leu Ile Leu Lys Thr Gln 85 90 95 Met Ser Glu Gly Ala Ile His Tyr Glu Thr Leu Ser Lys Ile Gly Leu 100 105 110 Ile Lys Gly Ile Thr Arg Glu Tyr Lys Val Lys Gly Thr Pro Ser Ser 115 120 125 Lys Asp Ile Val Ile Lys Leu Ile Pro Asn Val Thr Gly Leu Asn Lys 130 135 140 Cys Thr Asn Ile Ser Met Glu Asn Tyr Lys Glu Gln Leu Asp Lys Ile 145 150 155 160 Leu Ile Pro Ile Asn Asn Ile Ile Glu Leu Tyr Ala Asn Ser Thr Lys 165 170 175 Ser Ala Pro Gly Asn Ala Arg Phe Ala Gly Val Ile Ile Ala Gly Val 180 185 190 Ala Leu Gly Val Ala Ala Ala Ala Gln Ile Thr Ala Gly Ile Ala Leu 195 200 205 His Glu Ala Arg Gln Asn Ala Glu Arg Ile Asn Leu Leu Lys Asp Ser 210 215 220 Ile Ser Ala Thr Asn Asn Ala Val Ala Glu Leu Gln Glu Ala Thr Gly 225 230 235 240 Gly Ile Val Asn Val Ile Thr Gly Met Gln Asp Tyr Ile Asn Thr Asn 245 250 255 Leu Val Pro Gln Ile Asp Lys Leu Gln Cys Ser Gln Ile Lys Thr Ala 260 265 270 Leu Asp Ile Ser Leu Ser Gln Tyr Tyr Ser Glu Ile Leu Thr Val Phe 275 280 285 Gly Pro Asn Leu Gln Asn Pro Val Thr Thr Ser Met Ser Ile Gln Ala 290 295 300 Ile Ser Gln Ser Phe Gly Gly Asn Ile Asp Leu Leu Leu Asn Leu Leu 305 310 315 320 Gly Tyr Thr Ala Asn Asp Leu Leu Asp Leu Leu Glu Ser Lys Ser Ile 325 330 335 Thr Gly Gln Ile Thr Tyr Ile Asn Leu Glu His Tyr Phe Met Val Ile 340 345 350 Arg Val Tyr Tyr Pro Ile Met Thr Thr Ile Ser Asn Ala Tyr Val Gln 355 360 365 Glu Leu Ile Lys Ile Ser Phe Asn Val Asp Gly Ser Glu Trp Val Ser 370 375 380 Leu Val Pro Ser Tyr Ile Leu Ile Arg Asn Ser Tyr Leu Ser Asn Ile 385 390 395 400 Asp Ile Ser Glu Cys Leu Ile Thr Lys Asn Ser Val Ile Cys Arg His 405 410 415 Asp Phe Ala Met Pro Met Ser Tyr Thr Leu Lys Glu Cys Leu Thr Gly 420 425 430 Asp Thr Glu Lys Cys Pro Arg Glu Ala Val Val Thr Ser Tyr Val Pro 435 440 445 Arg Phe Ala Ile Ser Gly Gly Val Ile Tyr Ala Asn Cys Leu Ser Thr 450 455 460 Thr Cys Gln Cys Tyr Gln Thr Gly Lys Val Ile Ala Gln Asp Gly Ser 465 470 475 480 Gln Thr Leu Met Met Ile Asp Asn Gln Thr Cys Ser Ile Val Arg Ile 485 490 495 Glu Glu Ile Leu Ile Ser Thr Gly Lys Tyr Leu Gly Ser Gln Glu Tyr 500 505 510 Asn Thr Met His Val Ser Val Gly Asn Pro Val Phe Thr Asp Lys Leu 515 520 525 Asp Ile Thr Ser Gln Ile Ser Asn Ile Asn Gln Ser Ile Glu Gln Ser 530 535 540 Lys Phe Tyr Leu Asp Lys Ser Lys Ala Ile Leu Asp Lys Ile Asn Leu 545 550 555 560 Asn Leu Ile Gly Ser Val Pro Ile Ser Ile Leu Phe Ile Ile Ala Ile 565 570 575 Leu Ser Leu Ile Leu Ser Ile Ile Thr Phe Val Ile Val Met Ile Ile 580 585 590 Val Arg Arg Tyr Asn Lys Tyr Thr Pro Leu Ile Asn Ser Asp Pro Ser 595 600 605 Ser Arg Arg Ser Thr Ile Gln Asp Val Tyr Ile Ile Pro Asn Pro Gly 610 615 620 Glu His Ser Ile Arg Ser Ala Ala Arg Ser Ile Asp Arg Asp Arg Asp 625 630 635 640 <![CDATA[<210> 643]]> <![CDATA[<211> 520]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 亨德拉亨尼帕病毒]]> <![CDATA[<400> 643]]> Ile Leu His Tyr Glu Lys Leu Ser Lys Ile Gly Leu Val Lys Gly Ile 1 5 10 15 Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro Leu Thr Lys Asp Ile Val 20 25 30 Ile Lys Met Ile Pro Asn Val Ser Asn Val Ser Lys Cys Thr Gly Thr 35 40 45 Val Met Glu Asn Tyr Lys Ser Arg Leu Thr Gly Ile Leu Ser Pro Ile 50 55 60 Lys Gly Ala Ile Glu Leu Tyr Asn Asn Asn Thr His Asp Leu Val Gly 65 70 75 80 Asp Val Lys Leu Ala Gly Val Val Met Ala Gly Ile Ala Ile Gly Ile 85 90 95 Ala Thr Ala Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met 100 105 110 Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr 115 120 125 Asn Glu Ala Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr 130 135 140 Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr 145 150 155 160 Ile Asp Gln Ile Ser Cys Lys Gln Thr Glu Leu Ala Leu Asp Leu Ala 165 170 175 Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu 180 185 190 Gln Asp Pro Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala 195 200 205 Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr 210 215 220 Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp Ser Ile Ala Gly Gln Ile 225 230 235 240 Val Tyr Val Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe 245 250 255 Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr Val Gln Glu Leu Leu Pro 260 265 270 Val Ser Phe Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn 275 280 285 Phe Val Leu Ile Arg Asn Thr Leu Ile Ser Asn Ile Glu Val Lys Tyr 290 295 300 Cys Leu Ile Thr Lys Lys Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr 305 310 315 320 Pro Met Thr Ala Ser Val Arg Glu Cys Leu Thr Gly Ser Thr Asp Lys 325 330 335 Cys Pro Arg Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu 340 345 350 Ser Gly Gly Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys 355 360 365 Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu 370 375 380 Met Ile Asp Asn Thr Thr Cys Thr Thr Val Val Leu Gly Asn Ile Ile 385 390 395 400 Ile Ser Leu Gly Lys Tyr Leu Gly Ser Ile Asn Tyr Asn Ser Glu Ser 405 410 415 Ile Ala Val Gly Pro Pro Val Tyr Thr Asp Lys Val Asp Ile Ser Ser 420 425 430 Gln Ile Ser Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile 435 440 445 Lys Glu Ala Gln Lys Ile Leu Asp Thr Val Asn Pro Ser Leu Ile Ser 450 455 460 Met Leu Ser Met Ile Ile Leu Tyr Val Leu Ser Ile Ala Ala Leu Cys 465 470 475 480 Ile Gly Leu Ile Thr Phe Ile Ser Phe Val Ile Val Glu Lys Lys Arg 485 490 495 Gly Asn Tyr Ser Arg Leu Asp Asp Arg Gln Val Arg Pro Val Ser Asn 500 505 510 Gly Asp Leu Tyr Tyr Ile Gly Thr 515 520 <![CDATA[<210> 644]]> <![CDATA[<211> 519]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 墨江亨尼帕病毒]]> <![CDATA[<400> 644]]> Ile His Tyr Asp Ser Leu Ser Lys Val Gly Val Ile Lys Gly Leu Thr 1 5 10 15 Tyr Asn Tyr Lys Ile Lys Gly Ser Pro Ser Thr Lys Leu Met Val Val 20 25 30 Lys Leu Ile Pro Asn Ile Asp Ser Val Lys Asn Cys Thr Gln Lys Gln 35 40 45 Tyr Asp Glu Tyr Lys Asn Leu Val Arg Lys Ala Leu Glu Pro Val Lys 50 55 60 Met Ala Ile Asp Thr Met Leu Asn Asn Val Lys Ser Gly Asn Asn Lys 65 70 75 80 Tyr Arg Phe Ala Gly Ala Ile Met Ala Gly Val Ala Leu Gly Val Ala 85 90 95 Thr Ala Ala Thr Val Thr Ala Gly Ile Ala Leu His Arg Ser Asn Glu 100 105 110 Asn Ala Gln Ala Ile Ala Asn Met Lys Ser Ala Ile Gln Asn Thr Asn 115 120 125 Glu Ala Val Lys Gln Leu Gln Leu Ala Asn Lys Gln Thr Leu Ala Val 130 135 140 Ile Asp Thr Ile Arg Gly Glu Ile Asn Asn Asn Ile Ile Pro Val Ile 145 150 155 160 Asn Gln Leu Ser Cys Asp Thr Ile Gly Leu Ser Val Gly Ile Arg Leu 165 170 175 Thr Gln Tyr Tyr Ser Glu Ile Ile Thr Ala Phe Gly Pro Ala Leu Gln 180 185 190 Asn Pro Val Asn Thr Arg Ile Thr Ile Gln Ala Ile Ser Ser Val Phe 195 200 205 Asn Gly Asn Phe Asp Glu Leu Leu Lys Ile Met Gly Tyr Thr Ser Gly 210 215 220 Asp Leu Tyr Glu Ile Leu His Ser Glu Leu Ile Arg Gly Asn Ile Ile 225 230 235 240 Asp Val Asp Val Asp Ala Gly Tyr Ile Ala Leu Glu Ile Glu Phe Pro 245 250 255 Asn Leu Thr Leu Val Pro Asn Ala Val Val Gln Glu Leu Met Pro Ile 260 265 270 Ser Tyr Asn Ile Asp Gly Asp Glu Trp Val Thr Leu Val Pro Arg Phe 275 280 285 Val Leu Thr Arg Thr Thr Leu Leu Ser Asn Ile Asp Thr Ser Arg Cys 290 295 300 Thr Ile Thr Asp Ser Ser Val Ile Cys Asp Asn Asp Tyr Ala Leu Pro 305 310 315 320 Met Ser His Glu Leu Ile Gly Cys Leu Gln Gly Asp Thr Ser Lys Cys 325 330 335 Ala Arg Glu Lys Val Val Ser Ser Tyr Val Pro Lys Phe Ala Leu Ser 340 345 350 Asp Gly Leu Val Tyr Ala Asn Cys Leu Asn Thr Ile Cys Arg Cys Met 355 360 365 Asp Thr Asp Thr Pro Ile Ser Gln Ser Leu Gly Ala Thr Val Ser Leu 370 375 380 Leu Asp Asn Lys Arg Cys Ser Val Tyr Gln Val Gly Asp Val Leu Ile 385 390 395 400 Ser Val Gly Ser Tyr Leu Gly Asp Gly Glu Tyr Asn Ala Asp Asn Val 405 410 415 Glu Leu Gly Pro Pro Ile Val Ile Asp Lys Ile Asp Ile Gly Asn Gln 420 425 430 Leu Ala Gly Ile Asn Gln Thr Leu Gln Glu Ala Glu Asp Tyr Ile Glu 435 440 445 Lys Ser Glu Glu Phe Leu Lys Gly Val Asn Pro Ser Ile Ile Thr Leu 450 455 460 Gly Ser Met Val Val Leu Tyr Ile Phe Met Ile Leu Ile Ala Ile Val 465 470 475 480 Ser Val Ile Ala Leu Val Leu Ser Ile Lys Leu Thr Val Lys Gly Asn 485 490 495 Val Val Arg Gln Gln Phe Thr Tyr Thr Gln His Val Pro Ser Met Glu 500 505 510 Asn Ile Asn Tyr Val Ser His 515 <![CDATA[<210> 645]]> <![CDATA[<211> 40]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<220>]]> <![CDATA[<221> SITE]]> <![CDATA[<222> (1)..(40) ]]> <![CDATA[<223> 此序列可包含1至10個「Gly Gly Gly Se」重複單元]]> <![CDATA[<400> 645]]> Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser 1 5 10 15 Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser 20 25 30 Gly Gly Gly Ser Gly Gly Gly Ser 35 40 <![CDATA[<210> 646]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 646]]> Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 15 <![CDATA[<210> 647]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 647]]> Thr Thr Ala Ala Ser Gly Ser Ser Gly Gly Ser Ser Ser Gly Ala 1 5 10 15 <![CDATA[<210> 648]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 648]]> Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr 1 5 10 15 Lys Gly <![CDATA[<210> 649]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 649]]> Glu Gly Tyr Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 650]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 650]]> Gly Ile Ala Val Ala Gly Thr Asp Tyr 1 5 <![CDATA[<210> 651]]> <![CDATA[<211> 119]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 651]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly His Ile Asn Pro Asn Asn Gly Asp Thr Asn Tyr Ala Gln Asn Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Glu Gly Tyr Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly 100 105 110 Thr Thr Val Thr Val Ser Ser 115 <![CDATA[<210> 652]]> <![CDATA[<211> 118]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 652]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Ser Ala His Asn Gly Val Thr Gln Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Ile Ala Val Ala Gly Thr Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 653]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 653]]> Gly Gly Thr Phe Ser Ser Tyr 1 5 <![CDATA[<210> 654]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 654]]> Gly Gly Thr Phe Asn Thr Tyr 1 5 <![CDATA[<210> 655]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 655]]> Gly Tyr Thr Phe Thr Gly Tyr 1 5 <![CDATA[<210> 656]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 656]]> Gly Tyr Thr Phe Thr Asp Tyr 1 5 <![CDATA[<210> 657]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 657]]> Gly Tyr Thr Phe Thr Arg Tyr 1 5 <![CDATA[<210> 658]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 658]]> Gly Tyr Thr Phe Thr Ser Tyr 1 5 <![CDATA[<210> 659]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 659]]> Gly His Thr Phe Ser Arg His 1 5 <![CDATA[<210> 660]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 660]]> Gly Gly Thr Phe Ser Asn Thr 1 5 <![CDATA[<210> 661]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 661]]> Gly Tyr Thr Phe Thr Arg Ser 1 5 <![CDATA[<210> 662]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 662]]> Gly Asp Thr Phe Thr Gly Tyr 1 5 <![CDATA[<210> 663]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 663]]> Gly Tyr Thr Phe Thr Asn Tyr 1 5 <![CDATA[<210> 664]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 664]]> Gly Tyr Gly Phe Thr Arg Tyr 1 5 <![CDATA[<210> 665]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 665]]> Gly Tyr Thr Phe Thr Ser Arg 1 5 <![CDATA[<210> 666]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 666]]> Gly Phe Thr Phe Ser Asn Ser 1 5 <![CDATA[<210> 667]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 667]]> Gly Tyr Thr Phe Thr Thr Tyr 1 5 <![CDATA[<210> 668]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 668]]> Gly Phe Thr Phe Ser Ser Tyr 1 5 <![CDATA[<210> 669]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 669]]> Gly Gly Thr Phe Ser Arg Tyr 1 5 <![CDATA[<210> 670]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 670]]> Gly Asn Thr Phe Thr Ser Tyr 1 5 <![CDATA[<210> 671]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 671]]> Gly Gly Thr Phe Ser Asn Tyr 1 5 <![CDATA[<210> 672]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 672]]> Gly Gly Thr Phe Thr Arg Tyr 1 5 <![CDATA[<210> 673]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 673]]> Gly Gly Thr Phe Ser Arg Phe 1 5 <![CDATA[<210> 674]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 674]]> Gly Gly Thr Phe Ser Ser His 1 5 <![CDATA[<210> 675]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 675]]> Gly Gly Thr Phe Gly Ser Tyr 1 5 <![CDATA[<210> 676]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 676]]> Gly Tyr Ile Phe Thr Asp Tyr 1 5 <![CDATA[<210> 677]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 677]]> Gly Phe Thr Phe Ser Ser Phe 1 5 <![CDATA[<210> 678]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213]]>> 智人]]> <br/> <br/><![CDATA[<400> 678]]> <br/><![CDATA[Gly Phe Thr Phe Asp Asp Tyr 1 5 <![CDATA[<210> 679]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 679]]> Gly Tyr Thr Phe Thr Asp Ser 1 5 <![CDATA[<210> 680]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 680]]> Gly Tyr Thr Phe Met Asn Tyr 1 5 <![CDATA[<210> 681]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 681]]> Gly Tyr Thr Leu Asn Asp Tyr 1 5 <![CDATA[<210> 682]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 682]]> Gly Tyr Thr Phe Thr Asn His 1 5 <![CDATA[<210> 683]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 683]]> Gly Tyr Thr Phe Thr Glu Asn 1 5 <![CDATA[<210> 684]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 684]]> Gly Tyr Thr Phe Ala Ser Tyr 1 5 <![CDATA[<210> 685]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 685]]> Gly Tyr Thr Phe Thr Ala Tyr 1 5 <![CDATA[<210> 686]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 686]]> Gly Tyr Pro Phe Thr Asp Tyr 1 5 <![CDATA[<210> 687]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 687]]> Gly Tyr Thr Phe Ser Asp Tyr 1 5 <![CDATA[<210> 688]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 688]]> Gly Asp Thr Phe Thr Thr His 1 5 <![CDATA[<210> 689]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 689]]> Gly Asp Thr Phe Thr Asn Tyr 1 5 <![CDATA[<210> 690]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 690]]> Gly Tyr Thr Phe Thr Asp Asn 1 5 <![CDATA[<210> 691]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 691]]> Gly Gly Thr Ser Ser Ser Tyr 1 5 <![CDATA[<210> 692]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 692]]> Gly Gly Thr Phe Thr Ser Tyr 1 5 <![CDATA[<210> 693]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 693]]> Gly Asn Thr Phe Thr Ser His 1 5 <![CDATA[<210> 694]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 694]]> Gly Phe Thr Phe Ser Asp Tyr 1 5 <![CDATA[<210> 695]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 695]]> Gly Tyr Met Phe Thr Gly His 1 5 <![CDATA[<210> 696]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 696]]> Gly Tyr Ile Phe Ser Asn Tyr 1 5 <![CDATA[<210> 697]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 697]]> Gly Ser Thr Phe Thr Asn Tyr 1 5 <![CDATA[<210> 698]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 698]]> Gly Gly Thr Leu Ser Ser Tyr 1 5 <![CDATA[<210> 699]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 699]]> Gly Tyr Thr Phe Thr Ser His 1 5 <![CDATA[<210> 700]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 700]]> Gly Gly Thr Phe Asn Ser Tyr 1 5 <![CDATA[<210> 701]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 701]]> Asp Pro Ser Asp Gly Asn 1 5 <![CDATA[<210> 702]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 702]]> Asp Pro Ser Ser Gly Gly 1 5 <![CDATA[<210> 703]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 703]]> Asp Pro Ser Gly Gly Asn 1 5 <![CDATA[<210> 704]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 704]]> Asn Pro Asn Asn Gly Asp 1 5 <![CDATA[<210> 705]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 705]]> Asn Pro Asn Ser Gly Gly 1 5 <![CDATA[<210> 706]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 706]]> Asn Pro Asn Asp Gly Ser 1 5 <![CDATA[<210> 707]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 707]]> Asn Pro Asn Ser Gly Asn 1 5 <![CDATA[<210> 708]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 708]]> Ser Ala His Asn Gly Val 1 5 <![CDATA[<210> 709]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 709]]> Asn Pro Ser Gly Gly Ser 1 5 <![CDATA[<210> 710]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 710]]> Ser Pro Tyr Asn Gly Asn 1 5 <![CDATA[<210> 711]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 711]]> Asn Pro Asn Ser Gly Asp 1 5 <![CDATA[<210> 712]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 712]]> Asn Pro Ser Asp Gly Asp 1 5 <![CDATA[<210> 713]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 713]]> Asp Pro Ser Gly Gly Ser 1 5 <![CDATA[<210> 714]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 714]]> Asp Pro Lys Ser Gly Asp 1 5 <![CDATA[<210> 715]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 715]]> Asn Pro Gly Ala Gly Ser 1 5 <![CDATA[<210> 716]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 716]]> Ser Gly Asp Gly Gly Thr 1 5 <![CDATA[<210> 717]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 717]]> Ile Pro Ile Phe Gly Thr 1 5 <![CDATA[<210> 718]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 718]]> Gly Thr Gly Gly Gly 1 5 <![CDATA[<210> 719]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 719]]> Asn Pro Ser Asp Gly Ser 1 5 <![CDATA[<210> 720]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 720]]> Asn Pro Asn Gly Gly Ser 1 5 <![CDATA[<210> 721]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 721]]> Asn Pro Asn Thr Gly Gly 1 5 <![CDATA[<210> 722]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 722]]> Ser Gly Ser Gly Gly Ser 1 5 <![CDATA[<210> 723]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 723]]> Ser Gly Tyr Asn Gly Asp 1 5 <![CDATA[<210> 724]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 724]]> Ser Ala Asp Asn Gly Asn 1 5 <![CDATA[<210> 725]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 725]]> Ser Pro Asn Ser Gly Ala 1 5 <![CDATA[<210> 726]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 726]]> Asn Pro Lys Ser Gly Ala 1 5 <![CDATA[<210> 727]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 727]]> Ser Glu Ser Gly Asp Ser 1 5 <![CDATA[<210> 728]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 728]]> Asn Pro Ser Asn Gly Asp 1 5 <![CDATA[<210> 729]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 729]]> Ser Pro Ser Asp Gly Ser 1 5 <![CDATA[<210> 730]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 730]]> Asp Pro Glu Asp Gly Glu 1 5 <![CDATA[<210> 731]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 731]]> Asn Pro Lys Ser Gly Arg 1 5 <![CDATA[<210> 732]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 732]]> Asn Pro Gly Gly Gly Ser 1 5 <![CDATA[<210> 733]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 733]]> Asn Pro Lys Thr Gly Asp 1 5 <![CDATA[<210> 734]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 734]]> Asp Pro Ser Asp Gly Tyr 1 5 <![CDATA[<210> 735]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 735]]> Met Pro Ile Ser Gly Thr 1 5 <![CDATA[<210> 736]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 736]]> Ser Pro Thr Ser Gly Asp 1 5 <![CDATA[<210> 737]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 737]]> Asp Pro Ser Gly Asp Ile 1 5 <![CDATA[<210> 738]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 738]]> Glu Thr Ser Gly Gly Ser 1 5 <![CDATA[<210> 739]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 739]]> Ser Gly Ser Gly Val Thr 1 5 <![CDATA[<210> 740]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 740]]> Asn Pro Asp Ser Gly Gly 1 5 <![CDATA[<210> 741]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 741]]> Asn Pro Ile Ser Gly Gly 1 5 <![CDATA[<210> 742]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 742]]> Ser Ala Asp Asn Gly Asp 1 5 <![CDATA[<210> 743]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 743]]> Ser Pro Ile Tyr Gly Thr 1 5 <![CDATA[<210> 744]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 744]]> Asn Pro Ser Gly Gly Thr 1 5 <![CDATA[<210> 745]]> <![CDATA[<211> 6]]> <![CDATA[<212]]>> PRT]]> <br/><![CDATA[<213> 智人]]> <br/> <br/><![CDATA[<400> 745]]> <br/><![CDATA[Asn Pro Lys Ser Gly Asn 1 5 <![CDATA[<210> 746]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 746]]> Asn Pro Gly Gly Gly Asn 1 5 <![CDATA[<210> 747]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 747]]> Thr Pro Val Phe Gly Ile 1 5 <![CDATA[<210> 748]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 748]]> Asn Pro Arg Gly Gly Ser 1 5 <![CDATA[<210> 749]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 749]]> Asn Pro Ser Gly Gly Gly 1 5 <![CDATA[<210> 750]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 750]]> Asn Pro Gly Ser Gly Asn 1 5 <![CDATA[<210> 751]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 751]]> Asn Gly Asp Gly Asp Asp 1 5 <![CDATA[<210> 752]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 752]]> Asp Pro Asn Ser Gly Asp 1 5 <![CDATA[<210> 753]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 753]]> Asn Pro Ser Asp Gly Asn 1 5 <![CDATA[<210> 754]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 754]]> Asn Thr Tyr Asn Gly Asn 1 5 <![CDATA[<210> 755]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 755]]> Asn Pro Ser Asp Gly Ile 1 5 <![CDATA[<210> 756]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 756]]> Asn Pro Arg Asp Gly Asp 1 5 <![CDATA[<210> 757]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 757]]> Gln Ala Ser Gln Asp Ile Arg Tyr Phe Leu Asn 1 5 10 <![CDATA[<210> 758]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 758]]> Gly Gly Thr Phe Ser Ser Tyr Ala 1 5 <![CDATA[<210> 759]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 759]]> Gly Gly Thr Phe Asn Thr Tyr Ala 1 5 <![CDATA[<210> 760]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 760]]> Gly Tyr Thr Phe Thr Gly Tyr Tyr 1 5 <![CDATA[<210> 761]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 761]]> Gly Tyr Thr Phe Thr Asp Tyr Tyr 1 5 <![CDATA[<210> 762]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 762]]> Gly Tyr Thr Phe Thr Arg Tyr Asp 1 5 <![CDATA[<210> 763]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 763]]> Gly Tyr Thr Phe Thr Ser Tyr Ala 1 5 <![CDATA[<210> 764]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 764]]> Gly Tyr Thr Phe Thr Ser Tyr Tyr 1 5 <![CDATA[<210> 765]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 765]]> Gly His Thr Phe Ser Arg His Tyr 1 5 <![CDATA[<210> 766]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 766]]> Gly Tyr Thr Phe Thr Ser Tyr Gly 1 5 <![CDATA[<210> 767]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 767]]> Gly Gly Thr Phe Ser Asn Thr Asp 1 5 <![CDATA[<210> 768]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 768]]> Gly Tyr Thr Phe Thr Arg Ser Tyr 1 5 <![CDATA[<210> 769]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 769]]> Gly Asp Thr Phe Thr Gly Tyr Tyr 1 5 <![CDATA[<210> 770]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 770]]> Gly Tyr Thr Phe Thr Arg Tyr Tyr 1 5 <![CDATA[<210> 771]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 771]]> Gly Tyr Thr Phe Thr Asn Tyr Asp 1 5 <![CDATA[<210> 772]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 772]]> Gly Tyr Thr Phe Thr Asn Tyr Tyr 1 5 <![CDATA[<210> 773]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 773]]> Gly Tyr Gly Phe Thr Arg Tyr Ser 1 5 <![CDATA[<210> 774]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 774]]> Gly Tyr Thr Phe Thr Ser Arg Asp 1 5 <![CDATA[<210> 775]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 775]]> Gly Tyr Thr Phe Thr Ser Tyr Asp 1 5 <![CDATA[<210> 776]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 776]]> Gly Phe Thr Phe Ser Asn Ser Asp 1 5 <![CDATA[<210> 777]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 777]]> Gly Tyr Thr Phe Thr Thr Tyr Asp 1 5 <![CDATA[<210> 778]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 778]]> Gly Phe Thr Phe Ser Ser Tyr Thr 1 5 <![CDATA[<210> 779]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 779]]> Gly Gly Thr Phe Ser Arg Tyr Asp 1 5 <![CDATA[<210> 780]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 780]]> Gly Asn Thr Phe Thr Ser Tyr Tyr 1 5 <![CDATA[<210> 781]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 781]]> Gly Gly Thr Phe Ser Arg Tyr Ala 1 5 <![CDATA[<210> 782]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 782]]> Gly Gly Thr Phe Ser Asn Tyr Ala 1 5 <![CDATA[<210> 783]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 783]]> Gly Gly Thr Phe Thr Arg Tyr Ala 1 5 <![CDATA[<210> 784]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 784]]> Gly Gly Thr Phe Ser Arg Phe Asp 1 5 <![CDATA[<210> 785]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 785]]> Gly Gly Thr Phe Ser Ser His Ala 1 5 <![CDATA[<210> 786]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 786]]> Gly Gly Thr Phe Gly Ser Tyr Gly 1 5 <![CDATA[<210> 787]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 787]]> Gly Tyr Ile Phe Thr Asp Tyr Asp 1 5 <![CDATA[<210> 788]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 788]]> Gly Tyr Thr Phe Thr Ser Tyr His 1 5 <![CDATA[<210> 789]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 789]]> Gly Tyr Thr Phe Thr Ser Tyr Pro 1 5 <![CDATA[<210> 790]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 790]]> Gly Phe Thr Phe Ser Ser Phe Glu 1 5 <![CDATA[<210> 791]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 791]]> Gly Phe Thr Phe Asp Asp Tyr Ala 1 5 <![CDATA[<210> 792]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 792]]> Gly Tyr Thr Phe Thr Asp Ser Tyr 1 5 <![CDATA[<210> 793]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 793]]> Gly Tyr Thr Phe Met Asn Tyr Tyr 1 5 <![CDATA[<210> 794]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 794]]> Gly Tyr Thr Leu Asn Asp Tyr Tyr 1 5 <![CDATA[<210> 795]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 795]]> Gly Tyr Thr Phe Thr Asn His Tyr 1 5 <![CDATA[<210> 796]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 796]]> Gly Tyr Thr Phe Thr Glu Asn Glu 1 5 <![CDATA[<210> 797]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 797]]> Gly Tyr Thr Phe Ala Ser Tyr Asp 1 5 <![CDATA[<210> 798]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 798]]> Gly Tyr Thr Phe Thr Ala Tyr Tyr 1 5 <![CDATA[<210> 799]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 799]]> Gly Tyr Thr Phe Thr Asp Tyr His 1 5 <![CDATA[<210> 800]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 800]]> Gly Tyr Pro Phe Thr Asp Tyr Tyr 1 5 <![CDATA[<210> 801]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 801]]> Gly Tyr Thr Phe Ser Asp Tyr Tyr 1 5 <![CDATA[<210> 802]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 802]]> Gly Asp Thr Phe Thr Thr His Asp 1 5 <![CDATA[<210> 803]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 803]]> Gly Asp Thr Phe Thr Asn Tyr Tyr 1 5 <![CDATA[<210> 804]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 804]]> Gly Tyr Thr Phe Thr Asp Asn Tyr 1 5 <![CDATA[<210> 805]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 805]]> Gly Gly Thr Ser Ser Ser Tyr Ala 1 5 <![CDATA[<210> 806]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 806]]> Gly Gly Thr Phe Thr Ser Tyr Asp 1 5 <![CDATA[<210> 807]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 807]]> Gly Asn Thr Phe Thr Ser His Trp 1 5 <![CDATA[<210> 808]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 808]]> Gly Phe Thr Phe Ser Asp Tyr Asp 1 5 <![CDATA[<210> 809]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 809]]> Gly Tyr Met Phe Thr Gly His Asp 1 5 <![CDATA[<210> 810]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 810]]> Gly Tyr Ile Phe Ser Asn Tyr Asp 1 5 <![CDATA[<210> 811]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 811]]> Gly Phe Thr Phe Ser Ser Tyr Ala 1 5 <![CDATA[<210> 812]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 812]]> Gly Tyr Thr Phe Thr Thr Tyr Tyr 1 5 <![CDATA[<210> 813]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 813]]> Gly Ser Thr Phe Thr Asn Tyr Gln 1 5 <![CDATA[<210> 814]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 814]]> Gly Gly Thr Leu Ser Ser Tyr Asp 1 5 <![CDATA[<210> 815]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 815]]> Gly Tyr Thr Phe Thr Ser His Ala 1 5 <![CDATA[<210> 816]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 816]]> Gly Gly Thr Phe Asn Ser Tyr Gly 1 5 <![CDATA[<210> 817]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 817]]> Ile Asp Pro Ser Asp Gly Asn Thr 1 5 <![CDATA[<210> 818]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 818]]> Ile Asp Pro Ser Ser Gly Gly Thr 1 5 <![CDATA[<210> 819]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 819]]> Ile Asp Pro Ser Gly Gly Asn Thr 1 5 <![CDATA[<210> 820]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 820]]> Ile Asn Pro Asn Asn Gly Asp Thr 1 5 <![CDATA[<210> 821]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 821]]> Ile Asn Pro Asn Ser Gly Gly Thr 1 5 <![CDATA[<210> 822]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 822]]> Ile Asn Pro Asn Asp Gly Ser Thr 1 5 <![CDATA[<210> 823]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 823]]> Met Asn Pro Asn Ser Gly Asn Thr 1 5 <![CDATA[<210> 824]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 824]]> Ile Ser Ala His Asn Gly Val Thr 1 5 <![CDATA[<210> 825]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 825]]> Ile Asn Pro Ser Gly Gly Ser Thr 1 5 <![CDATA[<210> 826]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 826]]> Ile Ser Pro Tyr Asn Gly Asn Thr 1 5 <![CDATA[<210> 827]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 827]]> Ile Asn Pro Asn Ser Gly Asp Thr 1 5 <![CDATA[<210> 828]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 828]]> Ile Asn Pro Ser Asp Gly Asp Thr 1 5 <![CDATA[<210> 829]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 829]]> Ile Asp Pro Ser Gly Gly Ser Thr 1 5 <![CDATA[<210> 830]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 830]]> Ile Asp Pro Lys Ser Gly Asp Thr 1 5 <![CDATA[<210> 831]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 831]]> Ile Asn Pro Gly Ala Gly Ser Ser 1 5 <![CDATA[<210> 832]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 832]]> Ile Ser Gly Asp Gly Gly Thr Thr 1 5 <![CDATA[<210> 833]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 833]]> Ile Ile Pro Ile Phe Gly Thr Ala 1 5 <![CDATA[<210> 834]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 834]]> Ile Gly Thr Gly Gly Gly Ile 1 5 <![CDATA[<210> 835]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 835]]> Ile Asn Pro Ser Asp Gly Ser Thr 1 5 <![CDATA[<210> 836]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 836]]> Ile Asn Pro Asn Gly Gly Ser Pro 1 5 <![CDATA[<210> 837]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 837]]> Ile Asn Pro Asn Thr Gly Gly Thr 1 5 <![CDATA[<210> 838]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 838]]> Ile Ser Gly Ser Gly Gly Ser Thr 1 5 <![CDATA[<210> 839]]> <![CDATA[<211> ]]>8 <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 839]]> Ile Ser Gly Tyr Asn Gly Asp Thr 1 5 <![CDATA[<210> 840]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 840]]> Ile Ser Ala Asp Asn Gly Asn Thr 1 5 <![CDATA[<210> 841]]> <![CDATA[<21]]>1> 8]]> <br/><![CDATA[<212> PRT]]> <br/><![CDATA[<213> 智人]]> <br/> <br/><![CDATA[<400> 841]]> <br/><![CDATA[Ile Ser Pro Asn Ser Gly Ala Thr 1 5 <![CDATA[<210> 842]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 842]]> Ile Asn Pro Asn Ser Gly Asn Thr 1 5 <![CDATA[<210> 843]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 843]]> Ile Asn Pro Lys Ser Gly Ala Thr 1 5 <![CDATA[<210> 844]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 844]]> Ile Ser Glu Ser Gly Asp Ser Ser 1 5 <![CDATA[<210> 845]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 845]]> Ile Gly Thr Gly Gly Gly Thr 1 5 <![CDATA[<210> 846]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 846]]> Met Asn Pro Ser Asn Gly Asp Thr 1 5 <![CDATA[<210> 847]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 847]]> Ile Ser Pro Ser Asp Gly Ser Thr 1 5 <![CDATA[<210> 848]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 848]]> Phe Asp Pro Glu Asp Gly Glu Thr 1 5 <![CDATA[<210> 849]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 849]]> Ile Asn Pro Lys Ser Gly Arg Thr 1 5 <![CDATA[<210> 850]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 850]]> Ile Asn Pro Gly Gly Gly Ser Thr 1 5 <![CDATA[<210> 851]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 851]]> Met Asn Pro Lys Thr Gly Asp Thr 1 5 <![CDATA[<210> 852]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 852]]> Ile Asp Pro Ser Asp Gly Tyr Thr 1 5 <![CDATA[<210> 853]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 853]]> Ile Met Pro Ile Ser Gly Thr Thr 1 5 <![CDATA[<210> 854]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 854]]> Met Ser Pro Thr Ser Gly Asp Thr 1 5 <![CDATA[<210> 855]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 855]]> Ile Asp Pro Ser Gly Asp Ile Thr 1 5 <![CDATA[<210> 856]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 856]]> Ile Glu Thr Ser Gly Gly Ser Thr 1 5 <![CDATA[<210> 857]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 857]]> Ile Ser Gly Ser Gly Val Thr Thr 1 5 <![CDATA[<210> 858]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 858]]> Ile Asn Pro Asp Ser Gly Gly Thr 1 5 <![CDATA[<210> 859]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 859]]> Ile Asn Pro Ser Gly Gly Ser Ala 1 5 <![CDATA[<210> 860]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 860]]> Ile Asn Pro Ile Ser Gly Gly Thr 1 5 <![CDATA[<210> 861]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 861]]> Ile Ser Ala Asp Asn Gly Asp Thr 1 5 <![CDATA[<210> 862]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 86]]>2 Ile Ser Pro Ile Tyr Gly Thr Pro 1 5 <![CDATA[<210> 863]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 863]]> Ile Asn Pro Ser Gly Gly Thr Thr 1 5 <![CDATA[<210> 864]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 864]]> Met Asn Pro Lys Ser Gly Asn Thr 1 5 <![CDATA[<210> 865]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 865]]> Ile Asn Pro Gly Gly Gly Asn Ala 1 5 <![CDATA[<210> 866]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 866]]> Ile Thr Pro Val Phe Gly Ile Ala 1 5 <![CDATA[<210> 867]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 867]]> Ile Asn Pro Arg Gly Gly Ser Thr 1 5 <![CDATA[<210> 868]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 868]]> Met Asn Pro Asn Asn Gly Asp Thr 1 5 <![CDATA[<210> 869]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 869]]> Ile Asn Pro Ser Gly Gly Gly Thr 1 5 <![CDATA[<210> 870]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 870]]> Ile Asn Pro Gly Ser Gly Asn Thr 1 5 <![CDATA[<210> 871]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 871]]> Ile Ile Pro Ile Phe Gly Thr Pro 1 5 <![CDATA[<210> 872]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 872]]> Ile Asn Gly Asp Gly Asp Asp Thr 1 5 <![CDATA[<210> 873]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 873]]> Ile Asp Pro Asn Ser Gly Asp Thr 1 5 <![CDATA[<210> 874]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 874]]> Val Asn Pro Ser Asp Gly Asn Thr 1 5 <![CDATA[<210> 875]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 875]]> Ile Asn Thr Tyr Asn Gly Asn Thr 1 5 <![CDATA[<210> 876]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 876]]> Ile Asn Pro Ser Asp Gly Ile Thr 1 5 <![CDATA[<210> 877]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 877]]> Ile Asn Pro Arg Asp Gly Asp Thr 1 5 <![CDATA[<210> 878]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 878]]> Ala Lys Glu Arg Ala Ala Ala Gly Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 879]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 879]]> Ala Lys Glu His Ala Ala Gly Thr Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 880]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 880]]> Ala Lys Glu Gly Tyr Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 881]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 881]]> Ala Lys Glu Gly Asp Tyr Tyr Tyr Gly Met Asp Ala 1 5 10 <![CDATA[<210> 882]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 882]]> Ala Arg Glu Arg Gly Gly Met Pro Asp Tyr 1 5 10 <![CDATA[<210> 883]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 883]]> Ala Arg Gly His Gly Ile Pro Lys Tyr 1 5 <![CDATA[<210> 884]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 884]]> Ala Arg Val Arg Ser Gly Ser Pro Gln His 1 5 10 <![CDATA[<210> 885]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 885]]> Ala Arg Gly Gly Pro Trp Ile Val Asp Ala Phe Asp Ile 1 5 10 <![CDATA[<210> 886]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 886]]> Ala Arg Gly Ile Ala Val Ala Gly Thr Asp Tyr 1 5 10 <![CDATA[<210> 887]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 887]]> Ala Arg Glu Ala Thr Trp Gly Pro Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 888]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 888]]> Val Arg Asn Lys Asp Gly Leu Gln His 1 5 <![CDATA[<210> 889]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 889]]> Ala Lys Asp Ala Lys Arg Val Gly Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 890]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 890]]> Ala Arg Leu Val Gly Gly Ser Pro Asp Tyr 1 5 10 <![CDATA[<210> 891]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 891]]> Ala Arg Gly Ala Met Val Asp Tyr 1 5 <![CDATA[<210> 892]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 892]]> Ala Arg Gly Asn Tyr Val Gly Ser Tyr Tyr Tyr Gly Met Asp Val 1 5 10 15 <![CDATA[<210> 893]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 893]]> Ala Arg Asp Ser Arg Gly Asp Trp Tyr Phe Asp Leu 1 5 10 <![CDATA[<210> 894]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 894]]> Thr Arg His Gly Gly Arg Gly Leu Ala Asp Tyr 1 5 10 <![CDATA[<210> 895]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 895]]> Ala Arg Leu Lys Glu Leu Ser Ser Ile Leu Asp Ala Phe Asp Ile 1 5 10 15 <![CDATA[<210> 896]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 896]]> Ala Arg Glu Arg Phe Gly Thr Gly Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 897]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 897]]> Ala Arg Val Ile Gly Glu Met Val Asp Asp Ala Phe Asp Leu 1 5 10 <![CDATA[<210> 898]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 898]]> Ala Arg Glu Arg Leu Phe Gly Thr Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 899]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 899]]> Ala Arg Ala Asp Gly Glu Leu Thr Asp Tyr 1 5 10 <![CDATA[<210> 900]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 900]]> Ala Arg His His Leu Pro Ala His Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 901]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 901]]> Ala Arg Asp Val Pro Ala Gly Arg Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 902]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 902]]> Ala Lys Asp Arg Gly Val Gly Arg Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 903]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 903]]> Ala Lys Asp Ser Arg Tyr Gly Arg Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 904]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 904]]> Ala Lys Glu Ile Val Val Gly Pro Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210]]>> 905]]> <br/><![CDATA[<211> 15]]> <br/><![CDATA[<212> PRT]]> <br/><![CDATA[<213> 智人]]> <br/> <br/><![CDATA[<400> 905]]> <br/><![CDATA[Ala Arg Gly Met Val Arg Gly Pro Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 906]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 906]]> Ala Arg Glu Gly Val Thr Gly Pro Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 9]]>07 <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 907]]> Ala Arg Asp Ala Ala Ala Gly Thr Arg Tyr Tyr Tyr Tyr Tyr Gly Met 1 5 10 15 Asp Val <![CDATA[<210> 908]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 908]]> Ala Arg Glu Leu Tyr Ser Ser Thr Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 909]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 909]]> Ala Arg Ala Leu Tyr Ser Gly Pro Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 910]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 910]]> Ala Arg Asp Ser Leu Val Gly Arg Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 911]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 911]]> Ala Arg Arg Ser Glu Leu Asp Tyr 1 5 <![CDATA[<210> 912]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 912]]> Ala Arg Gly Asp Asp Asn Asp Tyr 1 5 <![CDATA[<210> 913]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 913]]> Ala Arg Gly Glu Glu Val Asp Tyr 1 5 <![CDATA[<210> 914]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 914]]> Ala Arg Gly Arg Arg Val Pro Asp Tyr 1 5 <![CDATA[<210> 915]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213>]]> 智人 <![CDATA[<400> 915]]> Ala Arg Gly Lys Val Thr Thr Asp Tyr 1 5 <![CDATA[<210> 916]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 916]]> Ala Ser Gly Arg Glu Leu Ile Glu Tyr 1 5 <![CDATA[<210> 917]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 917]]> Ala Arg Val Tyr Asp Phe Pro Asp Val 1 5 <![CDATA[<210> 918]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 918]]> Ala Arg Ser Thr Tyr Ser His Ile Asp Tyr 1 5 10 <![CDATA[<210> 919]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 919]]> Ala Arg Glu Asp Ser Ser Gly Phe Asp Tyr 1 5 10 <![CDATA[<210> 920]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 920]]> Ala Arg Asp Gln Gly Gly Gly Phe Asp Tyr 1 5 10 <![CDATA[<210> 921]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 921]]> Ala Arg Asp Gln Gly Trp Gly Met Asp Val 1 5 10 <![CDATA[<210> 922]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 922]]> Ala Arg Leu Thr Glu Gly Ile Pro Asp Tyr 1 5 10 <![CDATA[<210> 923]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 923]]> Ala Arg Asp Arg Tyr Gly Pro Phe Asp Tyr 1 5 10 <![CDATA[<210> 924]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 924]]> Thr Arg Leu Val Ala Gly Gly Ala Pro Asp Tyr 1 5 10 <![CDATA[<210> 925]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 925]]> Ala Arg Asp Gly Phe Thr Gly Asp Ile Ala Tyr 1 5 10 <![CDATA[<210> 926]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 926]]> Ala Arg Val Asp Asp Ser Ser Ser Pro Asp Tyr 1 5 10 <![CDATA[<210> 927]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 927]]> Thr Thr Gly Pro Asp Gly Thr Glu Val Asp Tyr 1 5 10 <![CDATA[<210> 928]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 928]]> Ala Ser Ser Glu Ser Gly Ser Asp Leu Asp Tyr 1 5 10 <![CDATA[<210> 929]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 929]]> Ala Arg Glu Val Glu Ile Glu Gly Tyr Met Asp Val 1 5 10 <![CDATA[<210> 930]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 930]]> Ala Lys Asp Leu Asp Asp Asp Trp Tyr Met Asp Val 1 5 10 <![CDATA[<210> 931]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 931]]> Thr Thr Asp Ser Thr Thr Trp Asp Ala Phe Asp Ile 1 5 10 <![CDATA[<210> 932]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 932]]> Ala Arg Val Leu Val Gly Ser Gly Ser Pro Asp Tyr 1 5 10 <![CDATA[<210> 933]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 933]]> Ala Arg Glu Ala Ala Ala Gly Leu Asp Phe Gln His 1 5 10 <![CDATA[<210> 934]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 934]]> Ala Arg Ala Asn Ser Trp Asp Ala Met Val Ile Asp Tyr 1 5 10 <![CDATA[<210> 935]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 935]]> Ala Arg Glu His Ser Ser Ser Trp Tyr Thr Phe Asp Tyr 1 5 10 <![CDATA[<210> 936]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 936]]> Ala Arg Asp Asp Asp Ser Ser Gly Tyr Tyr Leu Asp Tyr 1 5 10 <![CDATA[<210> 937]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 937]]> Ala Arg Ala Ser Gly Asp Tyr Met Asp Leu Ile Asp Tyr 1 5 10 <![CDATA[<210> 938]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 938]]> Ala Leu Val Gly Ser Ser Gly Tyr Leu Ala Pro Thr His 1 5 10 <![CDATA[<210> 939]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 939]]> Ala Arg Val Arg Gly Asp Gly Tyr Asn Leu Gly Asp Tyr 1 5 10 <![CDATA[<210> 940]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 940]]> Ala Arg Asp Val Asp Thr Ala Met Gly Ala Gly Asp Tyr 1 5 10 <![CDATA[<210> 941]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 941]]> Ala Arg Val Ala Arg Trp Gly Tyr Gly Asp Tyr Pro Asp Tyr 1 5 10 <![CDATA[<210> 942]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 942]]> Ala Arg Asp Arg Asn Gly Asp Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 943]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 943]]> Ala Arg Glu Gly Leu Gly Ser Ser Trp Tyr Val Leu Asp Tyr 1 5 10 <![CDATA[<210> 944]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 944]]> Ala Arg Asp Gly Ser His Tyr Gly Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 945]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 945]]> Ala Ser Pro Gly Pro Glu Gly Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <![CDATA[<210> 946]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 946]]> Ala Ser Tyr His Trp Asp Tyr Gly Asp Tyr Arg Phe Asp Tyr 1 5 10 <![CDATA[<210> 947]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 947]]> Ala Arg Val Glu Ile Asp Tyr Gly Asp Ser Pro Pro Asp Tyr 1 5 10 <![CDATA[<210> 948]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 948]]> Ala Arg Gly Ala Glu Trp Glu Leu Arg Tyr Ala Phe Asp Ile 1 5 10 <![CDATA[<210> 949]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 949]]> Ala Arg Glu Thr Tyr Tyr Gly Leu Tyr Tyr Tyr Gly Met Asp Val 1 5 10 15 <![CDATA[<210> 950]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 950]]> Ala Arg Ala Pro Ser Leu Arg Gly Tyr Ser Tyr Gly Pro Asp Tyr 1 5 10 15 <![CDATA[<210> 951]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 951]]> Ala Lys Asp Arg Gln Glu Arg Tyr Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 952]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 952]]> Ala Lys Asp Arg Ser Tyr Gly Asp Tyr Tyr Tyr Gly Met Asp Val 1 5 10 15 <![CDATA[<210> 953]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 953]]> Ala Arg Glu Val Phe Ser Glu Asn Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 954]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 954]]> Ala Arg Glu Trp Asp Tyr Thr His Tyr Tyr Tyr Gly Met Asp Val 1 5 10 15 <![CDATA[<210> 955]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 955]]> Ala Arg Gly Asp Ser Ser Gly Tyr Tyr Gln Tyr Tyr Phe Asp Tyr 1 5 10 15 <![CDATA[<210> 956]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 956]]> Ala Arg Gly Ser Trp Asp Ser Ser Ser Trp Tyr Ile Pro Glu Tyr 1 5 10 15 <![CDATA[<210> 957]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 957]]> Ala Ser Leu Val Trp Gly Gly Ala Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 958]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 958]]> Thr Thr Pro Val Phe Ser Gly Ser Tyr Tyr Trp Tyr Phe Asp Pro 1 5 10 15 <![CDATA[<210> 959]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 959]]> Thr Thr Asp Gln Ala Val Ala Gly Pro Tyr Tyr Tyr Gly Met Asp Val 1 5 10 15 <![CDATA[<210> 960]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 960]]> Ala Arg Asp Arg Trp Leu Ala Gly Pro Tyr Tyr Tyr Gly Met Asp Val 1 5 10 15 <![CDATA[<210> 961]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 961]]> Ala Arg Val Met Gly Pro Val Asp Tyr Tyr Tyr Tyr Gly Met Asp Val 1 5 10 15 <![CDATA[<210> 962]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 962]]> Ala Arg Asp Leu Gly Pro Phe Gly Ser Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 963]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 963]]> Ala Arg Glu Gly Val Val Val Pro Pro Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 964]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 964]]> Ala Arg Ser Ser Gly Trp Ser Arg Tyr Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 965]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 965]]> Ala Arg Asp Asn Gly Met Thr Thr Gly Tyr Tyr Tyr Tyr Met Asp Val 1 5 10 15 <![CDATA[<210> 966]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 966]]> Ala Arg Asp Arg Ala Met Val Thr Gly Tyr Tyr Tyr Gly Met Asp Val 1 5 10 15 <![CDATA[<210> 967]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 967]]> Ala Arg Asp Arg Gly Tyr Gly Asp Arg Gly Tyr Tyr Tyr Gly Met Asp 1 5 10 15 Val <![CDATA[<210> 968]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 968]]> Ala Thr Ser Pro Lys Ala Thr Ala Asp Tyr Tyr Tyr Tyr Tyr Met Asp 1 5 10 15 Val <![CDATA[<210> 969]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 969]]> Thr Thr Ser Thr Val Thr Pro Ser Tyr Tyr Tyr Tyr Tyr Gly Met Asp 1 5 10 15 Val <![CDATA[<210> 970]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 970]]> Ala Arg Glu Pro Val Ala Gly Thr Gly Tyr Tyr Tyr Tyr Tyr Gly Met 1 5 10 15 Asp Val <![CDATA[<210> 971]]> <![CDATA[<211>]]> 19 <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 971]]> Ala Arg Asp Asn Leu Ala Gly Phe Trp Ser Asp Tyr Tyr Tyr Tyr Gly 1 5 10 15 Met Asp Val <![CDATA[<210> 972]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 972]]> Gln Ser Ile Ser Ser Tyr 1 5 <![CDATA[<210> 973]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 973]]> Gln Asp Ile Ser Asn Tyr 1 5 <![CDATA[<210> 974]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 974]]> Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr 1 5 10 <![CDATA[<210> 975]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 975]]> Gln Ser Ile Ser Arg Asn 1 5 <![CDATA[<210> 976]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 976]]> Gln Ser Val Ser Ala Ser Asp 1 5 <![CDATA[<210> 977]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 977]]> Gln Asp Ile Gly Asn Tyr 1 5 <![CDATA[<210> 978]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 978]]> Gln Ser Ile Ser Thr His 1 5 <![CDATA[<210> 979]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 979]]> Gln Thr Ile Ser Asn Tyr 1 5 <![CDATA[<210> 980]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 980]]> Gln Gly Ile Arg Asn Asp 1 5 <![CDATA[<210> 981]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 981]]> Gln Ser Ile Ser Asn Tyr 1 5 <![CDATA[<210> 982]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 982]]> Gln Gly Ile Ser Asp Ser 1 5 <![CDATA[<210> 983]]> <![CDATA[<211>]]> 6 <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 983]]> Gln Asp Ile His Asn Tyr 1 5 <![CDATA[<210> 984]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 984]]> Gln Ser Ile Ser Asp Trp 1 5 <![CDATA[<210> 985]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 985]]> Gln Ser Ile Ser Thr Trp 1 5 <![CDATA[<210> 986]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 986]]> Gln Ser Ile Asn Arg Phe 1 5 <![CDATA[<210> 987]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 987]]> Gln Ser Val Ser Thr Tyr 1 5 <![CDATA[<210> 988]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 988]]> Gln Asp Ile Ala Lys Tyr 1 5 <![CDATA[<210> 989]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 989]]> Gln Gly Ile Thr Asn Tyr 1 5 <![CDATA[<210> 990]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 990]]> Gln Asp Ile Ser Asn Phe 1 5 <![CDATA[<210> 991]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 991]]> Gln Gly Ile Ser Asn Asn 1 5 <![CDATA[<210> 992]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 992]]> Gln Ser Ile Ser Arg Ser 1 5 <![CDATA[<210> 993]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 993]]> His Asp Ile Ser Lys Ser 1 5 <![CDATA[<210> 994]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 994]]> Gln Asp Ile Gly Ala Tyr 1 5 <![CDATA[<210> 995]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 995]]> Gln Gly Ile Arg Ser Tyr 1 5 <![CDATA[<210> 996]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 996]]> Gln Asn Ile Gly Thr Trp 1 5 <![CDATA[<210> 997]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 997]]> Gln Thr Ile Ser Tyr Tyr 1 5 <![CDATA[<210> 998]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 998]]> Gln Asn Ile Asn Asn Tyr 1 5 <![CDATA[<210> 999]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 999]]> Gln Thr Ile Ser Thr Tyr 1 5 <![CDATA[<210> 1000]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1000]]> Arg Gly Ile Gly Asn Asp 1 5 <![CDATA[<210> 1001]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1001]]> Gln Thr Ile Gly Asn Tyr 1 5 <![CDATA[<210> 1002]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1002]]> Gln Phe Ile Gly Ser Trp 1 5 <![CDATA[<210> 1003]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1003]]> Gln Ser Ile Ser Ser Trp 1 5 <![CDATA[<210> 1004]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1004]]> Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr 1 5 10 <![CDATA[<210> 1005]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1005]]> Gln Gly Ile Ser Ser Tyr 1 5 <![CDATA[<210> 1006]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1006]]> Gln Gly Ile Ser Asn Tyr 1 5 <![CDATA[<210> 1007]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1007]]> Gln Ser Ile Arg Asn Tyr 1 5 <![CDATA[<210> 1008]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1]]>008 Gln Asn Ile Arg Leu Tyr 1 5 <![CDATA[<210> 1009]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1009]]> Gln Asp Ile Arg Lys Phe 1 5 <![CDATA[<210> 1010]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1010]]> Gln Asn Val Arg Ser Trp 1 5 <![CDATA[<210> 1011]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1011]]> Gln Gly Ile Gly Asn Asp 1 5 <![CDATA[<210> 1012]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1012]]> Gln Ser Ile Ser Asn Trp 1 5 <![CDATA[<210> 1013]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1013]]> Glu Ser Ile Gly Ser Trp 1 5 <![CDATA[<210> 1014]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1014]]> Gln Ser Val Thr Ser Asn Tyr 1 5 <![CDATA[<210> 1015]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1015]]> Gln Gly Ile Ser Asn Gly 1 5 <![CDATA[<210> 1016]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1016]]> Gln Asn Ile Arg Asn Tyr 1 5 <![CDATA[<210> 1017]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1017]]> Leu Asp Ile Asn Asn Tyr 1 5 <![CDATA[<210> 1018]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1018]]> Gln Asn Ile Gly Asn Tyr 1 5 <![CDATA[<210> 1]]>019 <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1019]]> Gln Gly Ile Asn Thr Trp 1 5 <![CDATA[<210> 1020]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1020]]> Gln Asp Ile Arg Tyr Phe 1 5 <![CDATA[<210> 1021]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1021]]> Ala Ala Ser 1 <![CDATA[<210> 1022]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1022]]> Leu Gly Ser 1 <![CDATA[<210> 1023]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1023]]> Lys Ala Ser 1 <![CDATA[<210> 1024]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1024]]> Gly Ala Ser 1 <![CDATA[<210> 1025]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1025]]> Asp Ala Ser 1 <![CDATA[<210> 1026]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1026]]> Ser Ala Ser 1 <![CDATA[<210> 1027]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1027]]> Ser Ala Phe 1 <![CDATA[<210> 1028]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1028]]> Glu Ala Ser 1 <![CDATA[<210> 1029]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1029]]> Met Gly Ser 1 <![CDATA[<210> 1030]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1030]]> Trp Ala Ser 1 <![CDATA[<210> 1031]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1031]]> Lys Thr Ser 1 <![CDATA[<210> 1032]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1032]]> Thr Ala Ser 1 <![CDATA[<210> 1033]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1033]]> Leu Ala Ser 1 <![CDATA[<210> 1034]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1034]]> Ser Thr Ser 1 <![CDATA[<210> 1035]]> <![CDATA[<211> 245]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1035]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asp Pro Ser Asp Gly Asn Thr Asn Tyr Ala Gln Asn Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Glu Arg Ala Ala Ala Gly Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly 115 120 125 Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser 130 135 140 Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys 145 150 155 160 Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys 165 170 175 Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln 180 185 190 Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 195 200 205 Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 210 215 220 Cys Gln Gln Ser Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys 225 230 235 240 Val Glu Ile Lys Arg 245 <![CDATA[<210> 1036]]> <![CDATA[<211> 245]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1036]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly Gly 100 105 110 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val 115 120 125 Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser 130 135 140 Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val 145 150 155 160 Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Ile Ile Asp Pro 165 170 175 Ser Asp Gly Asn Thr Asn Tyr Ala Gln Asn Phe Gln Gly Arg Val Thr 180 185 190 Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser 195 200 205 Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Glu Arg Ala 210 215 220 Ala Ala Gly Tyr Tyr Tyr Tyr Met Asp Val Trp Gly Gln Gly Thr Thr 225 230 235 240 Val Thr Val Ser Ser 245 <![CDATA[<210> 1037]]> <![CDATA[<211> 245]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1037]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met 35 40 45 Gly Ile Ile Asp Pro Ser Asp Gly Asn Thr Asn Tyr Ala Gln Asn Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Glu Arg Ala Ala Ala Gly Tyr Tyr Tyr Tyr Met Asp Val Trp 100 105 110 Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly 115 120 125 Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser 130 135 140 Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys 145 150 155 160 Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys 165 170 175 Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln 180 185 190 Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 195 200 205 Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 210 215 220 Cys Gln Gln Ser Tyr Ser Thr Pro Leu Thr Phe Gly Cys Gly Thr Lys 225 230 235 240 Val Glu Ile Lys Arg 245 <![CDATA[<210> 1038]]> <![CDATA[<211> 245]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1038]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 85 90 95 Thr Phe Gly Cys Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly Gly 100 105 110 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val 115 120 125 Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser 130 135 140 Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val 145 150 155 160 Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Ile Ile Asp Pro 165 170 175 Ser Asp Gly Asn Thr Asn Tyr Ala Gln Asn Phe Gln Gly Arg Val Thr 180 185 190 Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser 195 200 205 Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Glu Arg Ala 210 215 220 Ala Ala Gly Tyr Tyr Tyr Tyr Met Asp Val Trp Gly Gln Gly Thr Thr 225 230 235 240 Val Thr Val Ser Ser 245 <![CDATA[<210> 1039]]> <![CDATA[<211> 247]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1039]]> Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 1 5 10 15 Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly 85 90 95 Leu Gln Thr Pro His Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 115 120 125 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 130 135 140 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 145 150 155 160 Tyr Ile Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 165 170 175 Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Ser Tyr Ala Gln Lys Phe 180 185 190 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 195 200 205 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 210 215 220 Ala Lys Glu Gly Asp Tyr Tyr Tyr Gly Met Asp Ala Trp Gly Gln Gly 225 230 235 240 Thr Met Val Thr Val Ser Ser 245 <![CDATA[<210> 1040]]> <![CDATA[<211> 247]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1040]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Tyr Ile Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Glu Gly Asp Tyr Tyr Tyr Gly Met Asp Ala Trp Gly Gln Gly 100 105 110 Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 115 120 125 Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Ser Pro Leu Ser 130 135 140 Leu Pro Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser 145 150 155 160 Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu 165 170 175 Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn 180 185 190 Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr 195 200 205 Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val 210 215 220 Tyr Tyr Cys Met Gln Gly Leu Gln Thr Pro His Thr Phe Gly Gln Gly 225 230 235 240 Thr Lys Val Glu Ile Lys Arg 245 <![CDATA[<210> 1041]]> <![CDATA[<211> 247]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1041]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Tyr Ile Gln Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Glu Gly Asp Tyr Tyr Tyr Gly Met Asp Ala Trp Gly Gln Gly 100 105 110 Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 115 120 125 Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Ser Pro Leu Ser 130 135 140 Leu Pro Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser 145 150 155 160 Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu 165 170 175 Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn 180 185 190 Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr 195 200 205 Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val 210 215 220 Tyr Tyr Cys Met Gln Gly Leu Gln Thr Pro His Thr Phe Gly Cys Gly 225 230 235 240 Thr Lys Val Glu Ile Lys Arg 245 <![CDATA[<210> 1042]]> <![CDATA[<211> 247]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1042]]> Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 1 5 10 15 Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly 85 90 95 Leu Gln Thr Pro His Thr Phe Gly Cys Gly Thr Lys Val Glu Ile Lys 100 105 110 Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 115 120 125 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 130 135 140 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 145 150 155 160 Tyr Ile Gln Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met 165 170 175 Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Ser Tyr Ala Gln Lys Phe 180 185 190 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 195 200 205 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 210 215 220 Ala Lys Glu Gly Asp Tyr Tyr Tyr Gly Met Asp Ala Trp Gly Gln Gly 225 230 235 240 Thr Met Val Thr Val Ser Ser 245 <![CDATA[<210> 1043]]> <![CDATA[<211> 240]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1043]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met 35 40 45 Gly Gly Phe Asp Pro Glu Asp Gly Glu Thr Ile Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Gln Gly Trp Gly Met Asp Val Trp Gly Gln Gly Thr Thr 100 105 110 Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 115 120 125 Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser 130 135 140 Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser 145 150 155 160 Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 165 170 175 Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser 180 185 190 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 195 200 205 Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr 210 215 220 Ser Thr Pro Tyr Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Arg 225 230 235 240 <![CDATA[<210> 1044]]> <![CDATA[<211> 240]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1044]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Gly Phe Asp Pro Glu Asp Gly Glu Thr Ile Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Gln Gly Trp Gly Met Asp Val Trp Gly Gln Gly Thr Thr 100 105 110 Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 115 120 125 Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser 130 135 140 Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser 145 150 155 160 Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 165 170 175 Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser 180 185 190 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 195 200 205 Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr 210 215 220 Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 225 230 235 240 <![CDATA[<210> 1045]]> <![CDATA[<211> 240]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1045]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr Ser Thr Pro Tyr 85 90 95 Thr Phe Gly Cys Gly Thr Lys Leu Glu Ile Lys Arg Gly Gly Gly Gly 100 105 110 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val 115 120 125 Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser 130 135 140 Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Tyr Met His Trp Val 145 150 155 160 Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Gly Phe Asp Pro 165 170 175 Glu Asp Gly Glu Thr Ile Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr 180 185 190 Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser 195 200 205 Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Gln Gly 210 215 220 Trp Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 225 230 235 240 <![CDATA[<210> 1046]]> <![CDATA[<211> 240]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1046]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr Ser Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Gly Gly Gly Gly 100 105 110 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val 115 120 125 Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser 130 135 140 Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Tyr Met His Trp Val 145 150 155 160 Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Phe Asp Pro 165 170 175 Glu Asp Gly Glu Thr Ile Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr 180 185 190 Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser 195 200 205 Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Gln Gly 210 215 220 Trp Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 225 230 235 240 <![CDATA[<210> 1047]]> <![CDATA[<211> 241]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1047]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Thr Ile Gly Asn Tyr 20 25 30 Val Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Asn Leu His Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr Ser Ala Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly Gly 100 105 110 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val 115 120 125 Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser 130 135 140 Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn His Tyr Met His Trp Val 145 150 155 160 Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Met Asn Pro 165 170 175 Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr 180 185 190 Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser 195 200 205 Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ser Ser Glu Ser 210 215 220 Gly Ser Asp Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 225 230 235 240 Ser <![CDATA[<210> 1048]]> <![CDATA[<211> 241]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<22]]>3> 人工序列之描述:合成]]> <br/><![CDATA[ 多肽 <![CDATA[<400> 1048]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn His 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ser Ser Glu Ser Gly Ser Asp Leu Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 115 120 125 Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 130 135 140 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln 145 150 155 160 Thr Ile Gly Asn Tyr Val Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 165 170 175 Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Leu His Thr Gly Val Pro 180 185 190 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 195 200 205 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr 210 215 220 Tyr Ser Ala Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 225 230 235 240 Arg <![CDATA[<210> 1049]]> <![CDATA[<211> 241]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1049]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn His 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ser Ser Glu Ser Gly Ser Asp Leu Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 115 120 125 Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 130 135 140 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln 145 150 155 160 Thr Ile Gly Asn Tyr Val Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 165 170 175 Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Leu His Thr Gly Val Pro 180 185 190 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 195 200 205 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr 210 215 220 Tyr Ser Ala Pro Leu Thr Phe Gly Cys Gly Thr Lys Val Glu Ile Lys 225 230 235 240 Arg <![CDATA[<210> 1050]]> <![CDATA[<211> 241]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1050]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Thr Ile Gly Asn Tyr 20 25 30 Val Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Asn Leu His Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr Ser Ala Pro Leu 85 90 95 Thr Phe Gly Cys Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly Gly 100 105 110 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val 115 120 125 Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser 130 135 140 Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn His Tyr Met His Trp Val 145 150 155 160 Arg Gln Ala Pro Gly Gln Cys Leu Glu Trp Met Gly Trp Met Asn Pro 165 170 175 Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr 180 185 190 Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser 195 200 205 Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ser Ser Glu Ser 210 215 220 Gly Ser Asp Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 225 230 235 240 Ser <![CDATA[<210> 1051]]> <![CDATA[<211> 241]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1051]]> Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn His 20 25 30 Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ser Ser Glu Ser Gly Ser Asp Leu Asp Tyr Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 115 120 125 Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 130 135 140 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln 145 150 155 160 Thr Ile Gly Asn Tyr Val Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 165 170 175 Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Leu His Thr Gly Val Pro 180 185 190 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 195 200 205 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr 210 215 220 Tyr Ser Ala Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 225 230 235 240 Arg <![CDATA[<210> 1052]]> <![CDATA[<211> 241]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1052]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Thr Ile Gly Asn Tyr 20 25 30 Val Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Asn Leu His Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr Ser Ala Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly Gly 100 105 110 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val 115 120 125 Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser 130 135 140 Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn His Tyr Met His Trp Val 145 150 155 160 Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Ile Ile Asn Pro 165 170 175 Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr 180 185 190 Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser 195 200 205 Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ser Ser Glu Ser 210 215 220 Gly Ser Asp Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 225 230 235 240 Ser <![CDATA[<210> 1053]]> <![CDATA[<211> 829]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1053]]> Met Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala 1 5 10 15 Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met 20 25 30 Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala 35 40 45 Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu 50 55 60 Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp 65 70 75 80 Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser 85 90 95 Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys 100 105 110 Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser 115 120 125 Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly 130 135 140 Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr 145 150 155 160 Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val 165 170 175 Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp 180 185 190 Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser 195 200 205 Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp 210 215 220 Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro 225 230 235 240 Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu 245 250 255 Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu 260 265 270 Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val 275 280 285 Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu 290 295 300 Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro 305 310 315 320 Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe 325 330 335 Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr 340 345 350 Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile 355 360 365 Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn 370 375 380 Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp 385 390 395 400 Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly 405 410 415 Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys 420 425 430 Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn 435 440 445 Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn 450 455 460 Thr Cys Pro Ala Ile Cys Ala Glu Gly Val Tyr Asn Asp Ala Phe Leu 465 470 475 480 Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn 485 490 495 Ala Thr Ala Ala Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile 500 505 510 Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr 515 520 525 Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu 530 535 540 Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe 545 550 555 560 Ala Val Lys Ile Pro Glu Gln Cys Thr Gly Gly Gly Gly Ser Gly Gly 565 570 575 Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly 580 585 590 Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala 595 600 605 Ser Gly Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala 610 615 620 Pro Gly Gln Gly Leu Glu Trp Met Gly Ile Ile Asp Pro Ser Asp Gly 625 630 635 640 Asn Thr Asn Tyr Ala Gln Asn Phe Gln Gly Arg Val Thr Met Thr Arg 645 650 655 Asp Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser 660 665 670 Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Glu Arg Ala Ala Ala Gly 675 680 685 Tyr Tyr Tyr Tyr Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val 690 695 700 Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 705 710 715 720 Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val 725 730 735 Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser 740 745 750 Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu 755 760 765 Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser 770 775 780 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln 785 790 795 800 Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro 805 810 815 Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 820 825 <![CDATA[<210> 1054]]> <![CDATA[<211> 831]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1054]]> Met Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala 1 5 10 15 Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met 20 25 30 Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala 35 40 45 Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu 50 55 60 Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp 65 70 75 80 Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser 85 90 95 Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys 100 105 110 Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser 115 120 125 Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly 130 135 140 Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr 145 150 155 160 Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val 165 170 175 Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp 180 185 190 Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser 195 200 205 Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp 210 215 220 Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro 225 230 235 240 Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu 245 250 255 Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu 260 265 270 Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val 275 280 285 Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu 290 295 300 Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro 305 310 315 320 Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe 325 330 335 Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr 340 345 350 Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile 355 360 365 Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn 370 375 380 Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp 385 390 395 400 Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly 405 410 415 Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys 420 425 430 Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn 435 440 445 Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn 450 455 460 Thr Cys Pro Ala Ile Cys Ala Glu Gly Val Tyr Asn Asp Ala Phe Leu 465 470 475 480 Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn 485 490 495 Ala Thr Ala Ala Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile 500 505 510 Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr 515 520 525 Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu 530 535 540 Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe 545 550 555 560 Ala Val Lys Ile Pro Glu Gln Cys Thr Gly Gly Gly Gly Ser Gly Gly 565 570 575 Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly 580 585 590 Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala 595 600 605 Ser Gly Tyr Thr Phe Thr Asp Tyr Tyr Ile Gln Trp Val Arg Gln Ala 610 615 620 Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly 625 630 635 640 Gly Thr Ser Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg 645 650 655 Asp Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser 660 665 670 Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Glu Gly Asp Tyr Tyr Tyr 675 680 685 Gly Met Asp Ala Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly 690 695 700 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile 705 710 715 720 Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly Glu Pro 725 730 735 Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly 740 745 750 Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln 755 760 765 Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro Asp Arg 770 775 780 Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg 785 790 795 800 Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly Leu Gln 805 810 815 Thr Pro His Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 820 825 830 <![CDATA[<210> 1055]]> <![CDATA[<211> 824]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1055]]> Met Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala 1 5 10 15 Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met 20 25 30 Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala 35 40 45 Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu 50 55 60 Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp 65 70 75 80 Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser 85 90 95 Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys 100 105 110 Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser 115 120 125 Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly 130 135 140 Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr 145 150 155 160 Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val 165 170 175 Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp 180 185 190 Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser 195 200 205 Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp 210 215 220 Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro 225 230 235 240 Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu 245 250 255 Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu 260 265 270 Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val 275 280 285 Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu 290 295 300 Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro 305 310 315 320 Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe 325 330 335 Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr 340 345 350 Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile 355 360 365 Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn 370 375 380 Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp 385 390 395 400 Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly 405 410 415 Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys 420 425 430 Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn 435 440 445 Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn 450 455 460 Thr Cys Pro Ala Ile Cys Ala Glu Gly Val Tyr Asn Asp Ala Phe Leu 465 470 475 480 Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn 485 490 495 Ala Thr Ala Ala Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile 500 505 510 Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr 515 520 525 Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu 530 535 540 Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe 545 550 555 560 Ala Val Lys Ile Pro Glu Gln Cys Thr Gly Gly Gly Gly Ser Gly Gly 565 570 575 Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly 580 585 590 Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala 595 600 605 Ser Gly Tyr Thr Phe Thr Ser Tyr Tyr Met His Trp Val Arg Gln Ala 610 615 620 Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Phe Asp Pro Glu Asp Gly 625 630 635 640 Glu Thr Ile Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg 645 650 655 Asp Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser 660 665 670 Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Gln Gly Trp Gly Met 675 680 685 Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly 690 695 700 Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met 705 710 715 720 Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr 725 730 735 Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr 740 745 750 Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser 755 760 765 Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly 770 775 780 Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala 785 790 795 800 Thr Tyr Tyr Cys Gln Gln Thr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln 805 810 815 Gly Thr Lys Leu Glu Ile Lys Arg 820 <![CDATA[<210> 1056]]> <![CDATA[<211> 825]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1056]]> Met Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala 1 5 10 15 Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met 20 25 30 Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala 35 40 45 Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu 50 55 60 Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp 65 70 75 80 Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser 85 90 95 Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys 100 105 110 Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser 115 120 125 Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly 130 135 140 Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr 145 150 155 160 Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val 165 170 175 Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp 180 185 190 Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser 195 200 205 Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp 210 215 220 Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro 225 230 235 240 Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu 245 250 255 Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu 260 265 270 Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val 275 280 285 Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu 290 295 300 Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro 305 310 315 320 Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe 325 330 335 Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr 340 345 350 Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile 355 360 365 Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn 370 375 380 Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp 385 390 395 400 Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly 405 410 415 Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys 420 425 430 Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn 435 440 445 Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn 450 455 460 Thr Cys Pro Ala Ile Cys Ala Glu Gly Val Tyr Asn Asp Ala Phe Leu 465 470 475 480 Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn 485 490 495 Ala Thr Ala Ala Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile 500 505 510 Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr 515 520 525 Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu 530 535 540 Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe 545 550 555 560 Ala Val Lys Ile Pro Glu Gln Cys Thr Gly Gly Gly Gly Ser Gly Gly 565 570 575 Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly 580 585 590 Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala 595 600 605 Ser Gly Tyr Thr Phe Thr Asn His Tyr Met His Trp Val Arg Gln Ala 610 615 620 Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Met Asn Pro Asn Ser Gly 625 630 635 640 Asn Thr Gly Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg 645 650 655 Asp Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser 660 665 670 Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ser Ser Glu Ser Gly Ser Asp 675 680 685 Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly 690 695 700 Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln 705 710 715 720 Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val 725 730 735 Thr Ile Thr Cys Arg Ala Ser Gln Thr Ile Gly Asn Tyr Val Asn Trp 740 745 750 Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Gly Ala 755 760 765 Ser Asn Leu His Thr Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser 770 775 780 Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe 785 790 795 800 Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr Ser Ala Pro Leu Thr Phe Gly 805 810 815 Gly Gly Thr Lys Val Glu Ile Lys Arg 820 825 <![CDATA[<210> 1057]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1057]]> Arg Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Glu Asn Phe Gln 1 5 10 15 Gly <![CDATA[<210> 1058]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1058]]> Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Thr Phe Gln 1 5 10 15 Gly <![CDATA[<210> 1059]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1059]]> Ile Ile Asn Pro Ser Asp Gly Ser Thr Asp Tyr Ala Gln Lys Phe Gln 1 5 10 15 Gly <![CDATA[<210> 1060]]> <![CDATA[<211> 125]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1060]]> Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Gly Tyr 20 25 30 Val Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Lys Phe Val 35 40 45 Ala Ala Ile Ser Arg Gly Gly Leu Ser Thr Ser Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Phe 65 70 75 80 Leu Gln Met Asn Thr Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ala Asp Arg Ser Asp Leu Tyr Glu Ile Thr Ala Ala Ser Asn Ile 100 105 110 Asp Ser Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 125 <![CDATA[<210> 1061]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1061]]> Gly Tyr Val Met Gly 1 5 <![CDATA[<210> 1062]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1062]]> Ala Ile Ser Arg Gly Gly Leu Ser Thr Ser Tyr Ala Asp Ser Val Lys 1 5 10 15 Gly <![CDATA[<210> 1063]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1063]]> Asp Arg Ser Asp Leu Tyr Glu Ile Thr Ala Ala Ser Asn Ile Asp Ser 1 5 10 15 <![CDATA[<210> 1064]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1064]]> Gly Arg Thr Phe Ser Gly Tyr 1 5 <![CDATA[<210> 1065]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1065]]> Ser Arg Gly Gly Leu Ser 1 5 <![CDATA[<210> 1066]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1066]]> Gly Arg Thr Phe Ser Gly Tyr Val 1 5 <![CDATA[<210> 1067]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1067]]> Ile Ser Arg Gly Gly Leu Ser Thr 1 5 <![CDATA[<210> 1068]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1068]]> Ala Ala Asp Arg Ser Asp Leu Tyr Glu Ile Thr Ala Ala Ser Asn Ile 1 5 10 15 Asp Ser <![CDATA[<210> 1069]]> <![CDATA[<211> 709]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1069]]> Met Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala 1 5 10 15 Phe Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met 20 25 30 Asn Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala 35 40 45 Val Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu 50 55 60 Ala Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp 65 70 75 80 Thr Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser 85 90 95 Lys Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys 100 105 110 Cys Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser 115 120 125 Cys Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly 130 135 140 Val Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr 145 150 155 160 Ser Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val 165 170 175 Val Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp 180 185 190 Glu Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser 195 200 205 Arg Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp 210 215 220 Arg Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro 225 230 235 240 Pro Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu 245 250 255 Phe Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu 260 265 270 Asn Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val 275 280 285 Lys Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu 290 295 300 Arg Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro 305 310 315 320 Ser Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe 325 330 335 Leu Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr 340 345 350 Lys Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile 355 360 365 Arg Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn 370 375 380 Leu Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp 385 390 395 400 Gln Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly 405 410 415 Gln Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys 420 425 430 Phe Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn 435 440 445 Asn Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn 450 455 460 Thr Cys Pro Ala Ile Cys Ala Glu Gly Val Tyr Asn Asp Ala Phe Leu 465 470 475 480 Ile Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn 485 490 495 Ala Thr Ala Ala Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile 500 505 510 Leu Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr 515 520 525 Ile Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu 530 535 540 Val Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe 545 550 555 560 Ala Val Lys Ile Pro Glu Gln Cys Thr Gly Gly Gly Gly Ser Gly Gly 565 570 575 Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly 580 585 590 Gly Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala 595 600 605 Ser Gly Arg Thr Phe Ser Gly Tyr Val Met Gly Trp Phe Arg Gln Ala 610 615 620 Pro Gly Lys Gln Arg Lys Phe Val Ala Ala Ile Ser Arg Gly Gly Leu 625 630 635 640 Ser Thr Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg 645 650 655 Asp Asn Ala Lys Asn Thr Val Phe Leu Gln Met Asn Thr Leu Lys Pro 660 665 670 Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Asp Arg Ser Asp Leu Tyr 675 680 685 Glu Ile Thr Ala Ala Ser Asn Ile Asp Ser Trp Gly Gln Gly Thr Leu 690 695 700 Val Thr Val Ser Ser 705 <![CDATA[<210> 1070]]> <![CDATA[<211> 828]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1070]]> Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala Phe 1 5 10 15 Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met Asn 20 25 30 Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala Val 35 40 45 Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu Ala 50 55 60 Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp Thr 65 70 75 80 Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser Lys 85 90 95 Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys Cys 100 105 110 Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser Cys 115 120 125 Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly Val 130 135 140 Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser 145 150 155 160 Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val 165 170 175 Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu 180 185 190 Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg 195 200 205 Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg 210 215 220 Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro 225 230 235 240 Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe 245 250 255 Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn 260 265 270 Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys 275 280 285 Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg 290 295 300 Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser 305 310 315 320 Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu 325 330 335 Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys 340 345 350 Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg 355 360 365 Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu 370 375 380 Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln 385 390 395 400 Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln 405 410 415 Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe 420 425 430 Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn 435 440 445 Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr 450 455 460 Cys Pro Ala Ile Cys Ala Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile 465 470 475 480 Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Ala 485 490 495 Thr Ala Ala Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu 500 505 510 Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile 515 520 525 Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val 530 535 540 Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala 545 550 555 560 Val Lys Ile Pro Glu Gln Cys Thr Gly Gly Gly Gly Ser Gly Gly Gly 565 570 575 Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala 580 585 590 Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser 595 600 605 Gly Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro 610 615 620 Gly Gln Gly Leu Glu Trp Met Gly Ile Ile Asp Pro Ser Asp Gly Asn 625 630 635 640 Thr Asn Tyr Ala Gln Asn Phe Gln Gly Arg Val Thr Met Thr Arg Asp 645 650 655 Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu 660 665 670 Asp Thr Ala Val Tyr Tyr Cys Ala Lys Glu Arg Ala Ala Ala Gly Tyr 675 680 685 Tyr Tyr Tyr Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser 690 695 700 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 705 710 715 720 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 725 730 735 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 740 745 750 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 755 760 765 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 770 775 780 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 785 790 795 800 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 805 810 815 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 820 825 <![CDATA[<210> 1071]]> <![CDATA[<211> 830]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1071]]> Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala Phe 1 5 10 15 Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met Asn 20 25 30 Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala Val 35 40 45 Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu Ala 50 55 60 Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp Thr 65 70 75 80 Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser Lys 85 90 95 Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys Cys 100 105 110 Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser Cys 115 120 125 Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly Val 130 135 140 Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser 145 150 155 160 Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val 165 170 175 Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu 180 185 190 Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg 195 200 205 Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg 210 215 220 Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro 225 230 235 240 Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe 245 250 255 Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn 260 265 270 Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys 275 280 285 Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg 290 295 300 Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser 305 310 315 320 Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu 325 330 335 Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys 340 345 350 Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg 355 360 365 Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu 370 375 380 Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln 385 390 395 400 Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln 405 410 415 Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe 420 425 430 Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn 435 440 445 Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr 450 455 460 Cys Pro Ala Ile Cys Ala Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile 465 470 475 480 Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Ala 485 490 495 Thr Ala Ala Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu 500 505 510 Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile 515 520 525 Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val 530 535 540 Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala 545 550 555 560 Val Lys Ile Pro Glu Gln Cys Thr Gly Gly Gly Gly Ser Gly Gly Gly 565 570 575 Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala 580 585 590 Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser 595 600 605 Gly Tyr Thr Phe Thr Asp Tyr Tyr Ile Gln Trp Val Arg Gln Ala Pro 610 615 620 Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly 625 630 635 640 Thr Ser Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp 645 650 655 Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu 660 665 670 Asp Thr Ala Val Tyr Tyr Cys Ala Lys Glu Gly Asp Tyr Tyr Tyr Gly 675 680 685 Met Asp Ala Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly 690 695 700 Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val 705 710 715 720 Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly Glu Pro Ala 725 730 735 Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr 740 745 750 Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu 755 760 765 Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro Asp Arg Phe 770 775 780 Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val 785 790 795 800 Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly Leu Gln Thr 805 810 815 Pro His Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 820 825 830 <![CDATA[<210> 1072]]> <![CDATA[<211> 823]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1072]]> Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala Phe 1 5 10 15 Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met Asn 20 25 30 Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala Val 35 40 45 Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu Ala 50 55 60 Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp Thr 65 70 75 80 Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser Lys 85 90 95 Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys Cys 100 105 110 Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser Cys 115 120 125 Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly Val 130 135 140 Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser 145 150 155 160 Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val 165 170 175 Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu 180 185 190 Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg 195 200 205 Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg 210 215 220 Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro 225 230 235 240 Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe 245 250 255 Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn 260 265 270 Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys 275 280 285 Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg 290 295 300 Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser 305 310 315 320 Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu 325 330 335 Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys 340 345 350 Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg 355 360 365 Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu 370 375 380 Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln 385 390 395 400 Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln 405 410 415 Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe 420 425 430 Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn 435 440 445 Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr 450 455 460 Cys Pro Ala Ile Cys Ala Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile 465 470 475 480 Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Ala 485 490 495 Thr Ala Ala Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu 500 505 510 Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile 515 520 525 Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val 530 535 540 Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala 545 550 555 560 Val Lys Ile Pro Glu Gln Cys Thr Gly Gly Gly Gly Ser Gly Gly Gly 565 570 575 Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala 580 585 590 Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser 595 600 605 Gly Tyr Thr Phe Thr Ser Tyr Tyr Met His Trp Val Arg Gln Ala Pro 610 615 620 Gly Gln Gly Leu Glu Trp Met Gly Gly Phe Asp Pro Glu Asp Gly Glu 625 630 635 640 Thr Ile Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp 645 650 655 Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu 660 665 670 Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Gln Gly Trp Gly Met Asp 675 680 685 Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly 690 695 700 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr 705 710 715 720 Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile 725 730 735 Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln 740 745 750 Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser 755 760 765 Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 770 775 780 Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr 785 790 795 800 Tyr Tyr Cys Gln Gln Thr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly 805 810 815 Thr Lys Leu Glu Ile Lys Arg 820 <![CDATA[<210> 1073]]> <![CDATA[<211> 824]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1073]]> Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala Phe 1 5 10 15 Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met Asn 20 25 30 Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala Val 35 40 45 Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu Ala 50 55 60 Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp Thr 65 70 75 80 Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser Lys 85 90 95 Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys Cys 100 105 110 Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser Cys 115 120 125 Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly Val 130 135 140 Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser 145 150 155 160 Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val 165 170 175 Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu 180 185 190 Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg 195 200 205 Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg 210 215 220 Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro 225 230 235 240 Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe 245 250 255 Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn 260 265 270 Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys 275 280 285 Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg 290 295 300 Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser 305 310 315 320 Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu 325 330 335 Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys 340 345 350 Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg 355 360 365 Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu 370 375 380 Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln 385 390 395 400 Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln 405 410 415 Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe 420 425 430 Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn 435 440 445 Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr 450 455 460 Cys Pro Ala Ile Cys Ala Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile 465 470 475 480 Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Ala 485 490 495 Thr Ala Ala Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu 500 505 510 Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile 515 520 525 Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val 530 535 540 Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala 545 550 555 560 Val Lys Ile Pro Glu Gln Cys Thr Gly Gly Gly Gly Ser Gly Gly Gly 565 570 575 Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala 580 585 590 Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser 595 600 605 Gly Tyr Thr Phe Thr Asn His Tyr Met His Trp Val Arg Gln Ala Pro 610 615 620 Gly Gln Gly Leu Glu Trp Met Gly Trp Met Asn Pro Asn Ser Gly Asn 625 630 635 640 Thr Gly Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp 645 650 655 Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu 660 665 670 Asp Thr Ala Val Tyr Tyr Cys Ala Ser Ser Glu Ser Gly Ser Asp Leu 675 680 685 Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly 690 695 700 Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met 705 710 715 720 Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr 725 730 735 Ile Thr Cys Arg Ala Ser Gln Thr Ile Gly Asn Tyr Val Asn Trp Tyr 740 745 750 Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Gly Ala Ser 755 760 765 Asn Leu His Thr Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly 770 775 780 Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala 785 790 795 800 Thr Tyr Tyr Cys Gln Gln Thr Tyr Ser Ala Pro Leu Thr Phe Gly Gly 805 810 815 Gly Thr Lys Val Glu Ile Lys Arg 820 <![CDATA[<210> 1074]]> <![CDATA[<211> 708]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1074]]> Lys Lys Ile Asn Glu Gly Leu Leu Asp Ser Lys Ile Leu Ser Ala Phe 1 5 10 15 Asn Thr Val Ile Ala Leu Leu Gly Ser Ile Val Ile Ile Val Met Asn 20 25 30 Ile Met Ile Ile Gln Asn Tyr Thr Arg Ser Thr Asp Asn Gln Ala Val 35 40 45 Ile Lys Asp Ala Leu Gln Gly Ile Gln Gln Gln Ile Lys Gly Leu Ala 50 55 60 Asp Lys Ile Gly Thr Glu Ile Gly Pro Lys Val Ser Leu Ile Asp Thr 65 70 75 80 Ser Ser Thr Ile Thr Ile Pro Ala Asn Ile Gly Leu Leu Gly Ser Lys 85 90 95 Ile Ser Gln Ser Thr Ala Ser Ile Asn Glu Asn Val Asn Glu Lys Cys 100 105 110 Lys Phe Thr Leu Pro Pro Leu Lys Ile His Glu Cys Asn Ile Ser Cys 115 120 125 Pro Asn Pro Leu Pro Phe Arg Glu Tyr Arg Pro Gln Thr Glu Gly Val 130 135 140 Ser Asn Leu Val Gly Leu Pro Asn Asn Ile Cys Leu Gln Lys Thr Ser 145 150 155 160 Asn Gln Ile Leu Lys Pro Lys Leu Ile Ser Tyr Thr Leu Pro Val Val 165 170 175 Gly Gln Ser Gly Thr Cys Ile Thr Asp Pro Leu Leu Ala Met Asp Glu 180 185 190 Gly Tyr Phe Ala Tyr Ser His Leu Glu Arg Ile Gly Ser Cys Ser Arg 195 200 205 Gly Val Ser Lys Gln Arg Ile Ile Gly Val Gly Glu Val Leu Asp Arg 210 215 220 Gly Asp Glu Val Pro Ser Leu Phe Met Thr Asn Val Trp Thr Pro Pro 225 230 235 240 Asn Pro Asn Thr Val Tyr His Cys Ser Ala Val Tyr Asn Asn Glu Phe 245 250 255 Tyr Tyr Val Leu Cys Ala Val Ser Thr Val Gly Asp Pro Ile Leu Asn 260 265 270 Ser Thr Tyr Trp Ser Gly Ser Leu Met Met Thr Arg Leu Ala Val Lys 275 280 285 Pro Lys Ser Asn Gly Gly Gly Tyr Asn Gln His Gln Leu Ala Leu Arg 290 295 300 Ser Ile Glu Lys Gly Arg Tyr Asp Lys Val Met Pro Tyr Gly Pro Ser 305 310 315 320 Gly Ile Lys Gln Gly Asp Thr Leu Tyr Phe Pro Ala Val Gly Phe Leu 325 330 335 Val Arg Thr Glu Phe Lys Tyr Asn Asp Ser Asn Cys Pro Ile Thr Lys 340 345 350 Cys Gln Tyr Ser Lys Pro Glu Asn Cys Arg Leu Ser Met Gly Ile Arg 355 360 365 Pro Asn Ser His Tyr Ile Leu Arg Ser Gly Leu Leu Lys Tyr Asn Leu 370 375 380 Ser Asp Gly Glu Asn Pro Lys Val Val Phe Ile Glu Ile Ser Asp Gln 385 390 395 400 Arg Leu Ser Ile Gly Ser Pro Ser Lys Ile Tyr Asp Ser Leu Gly Gln 405 410 415 Pro Val Phe Tyr Gln Ala Ser Phe Ser Trp Asp Thr Met Ile Lys Phe 420 425 430 Gly Asp Val Leu Thr Val Asn Pro Leu Val Val Asn Trp Arg Asn Asn 435 440 445 Thr Val Ile Ser Arg Pro Gly Gln Ser Gln Cys Pro Arg Phe Asn Thr 450 455 460 Cys Pro Ala Ile Cys Ala Glu Gly Val Tyr Asn Asp Ala Phe Leu Ile 465 470 475 480 Asp Arg Ile Asn Trp Ile Ser Ala Gly Val Phe Leu Asp Ser Asn Ala 485 490 495 Thr Ala Ala Asn Pro Val Phe Thr Val Phe Lys Asp Asn Glu Ile Leu 500 505 510 Tyr Arg Ala Gln Leu Ala Ser Glu Asp Thr Asn Ala Gln Lys Thr Ile 515 520 525 Thr Asn Cys Phe Leu Leu Lys Asn Lys Ile Trp Cys Ile Ser Leu Val 530 535 540 Glu Ile Tyr Asp Thr Gly Asp Asn Val Ile Arg Pro Lys Leu Phe Ala 545 550 555 560 Val Lys Ile Pro Glu Gln Cys Thr Gly Gly Gly Gly Ser Gly Gly Gly 565 570 575 Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly 580 585 590 Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser 595 600 605 Gly Arg Thr Phe Ser Gly Tyr Val Met Gly Trp Phe Arg Gln Ala Pro 610 615 620 Gly Lys Gln Arg Lys Phe Val Ala Ala Ile Ser Arg Gly Gly Leu Ser 625 630 635 640 Thr Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp 645 650 655 Asn Ala Lys Asn Thr Val Phe Leu Gln Met Asn Thr Leu Lys Pro Glu 660 665 670 Asp Thr Ala Val Tyr Tyr Cys Ala Ala Asp Arg Ser Asp Leu Tyr Glu 675 680 685 Ile Thr Ala Ala Ser Asn Ile Asp Ser Trp Gly Gln Gly Thr Leu Val 690 695 700 Thr Val Ser Ser 705 <![CDATA[<210> 1075]]> <![CDATA[<211> 245]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1075]]> Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly 1 5 10 15 Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile 35 40 45 Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 65 70 75 80 Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Ser Thr Ser Gly 100 105 110 Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys 115 120 125 Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser 130 135 140 Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 145 150 155 160 Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile 165 170 175 Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu 180 185 190 Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn 195 200 205 Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr 210 215 220 Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser 225 230 235 240 Val Thr Val Ser Ser 245 <![CDATA[<210> 1076]]> <![CDATA[<211> 242]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1076]]> Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly 1 5 10 15 Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile 35 40 45 Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 65 70 75 80 Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Gly Gly Gly Ser 100 105 110 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Lys Leu Gln Glu 115 120 125 Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys 130 135 140 Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg 145 150 155 160 Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser 165 170 175 Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile 180 185 190 Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln 195 200 205 Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly 210 215 220 Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val 225 230 235 240 Ser Ser <![CDATA[<210> 1077]]> <![CDATA[<211> 118]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1077]]> Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Asn His 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Leu Val 35 40 45 Ser Ser Ile Ser Gly Asn Gly Arg Thr Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Ile Ser Lys Asn Thr Leu Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Gly Gly Glu Thr Leu Val Asp Ser Arg Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 1078]]> <![CDATA[<211> 119]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1078]]> Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser His 20 25 30 Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Ala Ile Ser Gly Ser Gly Asp Phe Thr His Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Val Ser 65 70 75 80 Leu Gln Met Asn Asn Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Glu Asp Gly Gly Ser Leu Leu Gly Tyr Arg Gly Gln Gly 100 105 110 Thr Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 1079]]> <![CDATA[<211> 121]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1079]]> Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ser Ile Ser Gly Ser Gly Asp Tyr Ile Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Ile Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Glu Gly Thr Gly Ala Asn Ser Ser Leu Ala Asp Tyr Arg Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 1080]]> <![CDATA[<211> 119]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1080]]> Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser His 20 25 30 Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ser Gly Ser Gly Asp Tyr Thr His Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Val Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Ser Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Glu Asp Gly Gly Ser Leu Leu Gly His Arg Gly Gln Gly 100 105 110 Thr Leu Val Thr Val Ser Ser 115 <![CDATA[<210> 1081]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1081]]> Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro 1 5 10 <![CDATA[<210> 1082]]> <![CDATA[<211> 25]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1082]]> Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala 1 5 10 15 Ser Gln Pro Leu Ser Leu Arg Pro Glu 20 25 <![CDATA[<210> 1083]]> <![CDATA[<211> 39]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1083]]> Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser Asn 1 5 10 15 Gly Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro Leu 20 25 30 Phe Pro Gly Pro Ser Lys Pro 35 <![CDATA[<210> 1084]]> <![CDATA[<211> 44]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1084]]> Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp 1 5 10 15 Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly 20 25 30 Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys 35 40 <![CDATA[<210> 1085]]> <![CDATA[<211> 27]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1085]]> Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu 1 5 10 15 Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val 20 25 <![CDATA[<210> 1086]]> <![CDATA[<211> 41]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1086]]> Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr 1 5 10 15 Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro 20 25 30 Pro Arg Asp Phe Ala Ala Tyr Arg Ser 35 40 <![CDATA[<210> 1087]]> <![CDATA[<211> 42]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1087]]> Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met 1 5 10 15 Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe 20 25 30 Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu 35 40 <![CDATA[<210> 1088]]> <![CDATA[<211> 112]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1088]]> Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly 1 5 10 15 Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr 20 25 30 Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys 35 40 45 Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys 50 55 60 Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg 65 70 75 80 Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala 85 90 95 Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 100 105 110 <![CDATA[<210> 1089]]> <![CDATA[<211> 112]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1089]]> Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly 1 5 10 15 Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr 20 25 30 Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys 35 40 45 Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys 50 55 60 Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg 65 70 75 80 Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala 85 90 95 Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 100 105 110 <![CDATA[<210> 1090]]> <![CDATA[<211> 21]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1090]]> Met Glu Phe Gly Leu Ser Trp Leu Phe Leu Val Ala Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Ser Arg 20 <![CDATA[<210> 1091]]> <![CDATA[<211> 41]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1091]]> Arg Ser Lys Arg Ser Arg Gly Gly His Ser Asp Tyr Met Asn Met Thr 1 5 10 15 Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro 20 25 30 Pro Arg Asp Phe Ala Ala Tyr Arg Ser 35 40 <![CDATA[<210> 1092]]> <![CDATA[<211> 498]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1092]]> Ile Leu His Tyr Glu Lys Leu Ser Lys Ile Gly Leu Val Lys Gly Val 1 5 10 15 Thr Arg Lys Tyr Lys Ile Lys Ser Asn Pro Leu Thr Lys Asp Ile Val 20 25 30 Ile Lys Met Ile Pro Asn Val Ser Asn Met Ser Gln Cys Thr Gly Ser 35 40 45 Val Met Glu Asn Tyr Lys Thr Arg Leu Asn Gly Ile Leu Thr Pro Ile 50 55 60 Lys Gly Ala Leu Glu Ile Tyr Lys Asn Asn Thr His Asp Leu Val Gly 65 70 75 80 Asp Val Arg Leu Ala Gly Val Ile Met Ala Gly Val Ala Ile Gly Ile 85 90 95 Ala Thr Ala Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met 100 105 110 Lys Asn Ala Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr 115 120 125 Asn Glu Ala Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr 130 135 140 Val Leu Thr Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr 145 150 155 160 Ile Asp Lys Ile Ser Cys Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala 165 170 175 Leu Ser Lys Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu 180 185 190 Gln Asp Pro Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala 195 200 205 Phe Gly Gly Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr 210 215 220 Glu Asp Phe Asp Asp Leu Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile 225 230 235 240 Ile Tyr Val Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe 245 250 255 Pro Ile Leu Thr Glu Ile Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro 260 265 270 Val Ser Phe Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn 275 280 285 Phe Ile Leu Val Arg Asn Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe 290 295 300 Cys Leu Ile Thr Lys Arg Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr 305 310 315 320 Pro Met Thr Asn Asn Met Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys 325 330 335 Cys Pro Arg Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu 340 345 350 Ser Asn Gly Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys 355 360 365 Gln Thr Thr Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu 370 375 380 Met Ile Asp Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile 385 390 395 400 Ile Ser Leu Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly 405 410 415 Ile Ala Ile Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser 420 425 430 Gln Ile Ser Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile 435 440 445 Lys Glu Ala Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Ile Ser 450 455 460 Met Leu Ser Met Ile Ile Leu Tyr Val Leu Ser Ile Ala Ser Leu Cys 465 470 475 480 Ile Gly Leu Ile Thr Phe Ile Ser Phe Ile Ile Val Glu Lys Lys Arg 485 490 495 Asn Thr <![CDATA[<210> 1093]]> <![CDATA[<211> 415]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1093]]> Leu Ala Gly Val Ile Met Ala Gly Val Ala Ile Gly Ile Ala Thr Ala 1 5 10 15 Ala Gln Ile Thr Ala Gly Val Ala Leu Tyr Glu Ala Met Lys Asn Ala 20 25 30 Asp Asn Ile Asn Lys Leu Lys Ser Ser Ile Glu Ser Thr Asn Glu Ala 35 40 45 Val Val Lys Leu Gln Glu Thr Ala Glu Lys Thr Val Tyr Val Leu Thr 50 55 60 Ala Leu Gln Asp Tyr Ile Asn Thr Asn Leu Val Pro Thr Ile Asp Lys 65 70 75 80 Ile Ser Cys Lys Gln Thr Glu Leu Ser Leu Asp Leu Ala Leu Ser Lys 85 90 95 Tyr Leu Ser Asp Leu Leu Phe Val Phe Gly Pro Asn Leu Gln Asp Pro 100 105 110 Val Ser Asn Ser Met Thr Ile Gln Ala Ile Ser Gln Ala Phe Gly Gly 115 120 125 Asn Tyr Glu Thr Leu Leu Arg Thr Leu Gly Tyr Ala Thr Glu Asp Phe 130 135 140 Asp Asp Leu Leu Glu Ser Asp Ser Ile Thr Gly Gln Ile Ile Tyr Val 145 150 155 160 Asp Leu Ser Ser Tyr Tyr Ile Ile Val Arg Val Tyr Phe Pro Ile Leu 165 170 175 Thr Glu Ile Gln Gln Ala Tyr Ile Gln Glu Leu Leu Pro Val Ser Phe 180 185 190 Asn Asn Asp Asn Ser Glu Trp Ile Ser Ile Val Pro Asn Phe Ile Leu 195 200 205 Val Arg Asn Thr Leu Ile Ser Asn Ile Glu Ile Gly Phe Cys Leu Ile 210 215 220 Thr Lys Arg Ser Val Ile Cys Asn Gln Asp Tyr Ala Thr Pro Met Thr 225 230 235 240 Asn Asn Met Arg Glu Cys Leu Thr Gly Ser Thr Glu Lys Cys Pro Arg 245 250 255 Glu Leu Val Val Ser Ser His Val Pro Arg Phe Ala Leu Ser Asn Gly 260 265 270 Val Leu Phe Ala Asn Cys Ile Ser Val Thr Cys Gln Cys Gln Thr Thr 275 280 285 Gly Arg Ala Ile Ser Gln Ser Gly Glu Gln Thr Leu Leu Met Ile Asp 290 295 300 Asn Thr Thr Cys Pro Thr Ala Val Leu Gly Asn Val Ile Ile Ser Leu 305 310 315 320 Gly Lys Tyr Leu Gly Ser Val Asn Tyr Asn Ser Glu Gly Ile Ala Ile 325 330 335 Gly Pro Pro Val Phe Thr Asp Lys Val Asp Ile Ser Ser Gln Ile Ser 340 345 350 Ser Met Asn Gln Ser Leu Gln Gln Ser Lys Asp Tyr Ile Lys Glu Ala 355 360 365 Gln Arg Leu Leu Asp Thr Val Asn Pro Ser Leu Ile Ser Met Leu Ser 370 375 380 Met Ile Ile Leu Tyr Val Leu Ser Ile Ala Ser Leu Cys Ile Gly Leu 385 390 395 400 Ile Thr Phe Ile Ser Phe Ile Ile Val Glu Lys Lys Arg Asn Thr 405 410 415 <![CDATA[<210> 1094]]> <![CDATA[<400> 1094]]> 000 <![CDATA[<210> 1095]]> <![CDATA[<400> 1095]]> 000 <![CDATA[<210> 1096]]> <![CDATA[<400> 1096]]> 000 <![CDATA[<210> 1097]]> <![CDATA[<400> 1097]]> 000 <![CDATA[<210> 1098]]> <![CDATA[<400> 1098]]> 000 <![CDATA[<210> 1099]]> <![CDATA[<400> 1099]]> 000 <![CDATA[<210> 1100]]> <![CDATA[<400> 1100]]> 000 <![CDATA[<210> 1101]]> <![CDATA[<400> 1101]]> 000 <![CDATA[<210> 1102]]> <![CDATA[<400> 1102]]> 000 <![CDATA[<210> 1103]]> <![CDATA[<400> 1103]]> 000 <![CDATA[<210> 1104]]> <![CDATA[<400> 1104]]> 000 <![CDATA[<210> 1105]]> <![CDATA[<400> 1105]]> 000 <![CDATA[<210> 1106]]> <![CDATA[<211> 21]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1106]]> Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 1 5 10 15 His Ala Ala Arg Pro 20 <![CDATA[<210> 1107]]> <![CDATA[<211> 20]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 未知]]> <![CDATA[<220>]]> <![CDATA[<223> 未知之描述:IgK信號肽序列]]> <![CDATA[<400> 1107]]> Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 1 5 10 15 Gly Ser Thr Gly 20 <![CDATA[<210> 1108]]> <![CDATA[<211> 22]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1108]]> Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 1 5 10 15 Ala Phe Leu Leu Ile Pro 20 <![CDATA[<210> 1109]]> <![CDATA[<211> 45]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1109]]> Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala 1 5 10 15 Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly 20 25 30 Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp 35 40 45 <![CDATA[<210> 1110]]> <![CDATA[<211> 39]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1110]]> Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser Asn 1 5 10 15 Gly Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro Leu 20 25 30 Phe Pro Gly Pro Ser Lys Pro 35 <![CDATA[<210> 1111]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1111]]> Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro 1 5 10 <![CDATA[<210> 1112]]> <![CDATA[<211> 12]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1112]]> Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro 1 5 10 <![CDATA[<210> 1113]]> <![CDATA[<211> 229]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1113]]> Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe 1 5 10 15 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 20 25 30 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 35 40 45 Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 50 55 60 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 65 70 75 80 Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 85 90 95 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 100 105 110 Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 115 120 125 Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 130 135 140 Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 145 150 155 160 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 165 170 175 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu 180 185 190 Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 195 200 205 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 210 215 220 Leu Ser Leu Gly Lys 225 <![CDATA[<210> 1114]]> <![CDATA[<211> 24]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1114]]> Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu 1 5 10 15 Ser Leu Val Ile Thr Leu Tyr Cys 20 <![CDATA[<210> 1115]]> <![CDATA[<211> 27]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1115]]> Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu 1 5 10 15 Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val 20 25 <![CDATA[<210> 1116]]> <![CDATA[<211> 42]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1116]]> Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met 1 5 10 15 Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe 20 25 30 Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu 35 40 <![CDATA[<210> 1117]]> <![CDATA[<211> 41]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1117]]> Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr 1 5 10 15 Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro 20 25 30 Pro Arg Asp Phe Ala Ala Tyr Arg Ser 35 40 <![CDATA[<210> 1118]]> <![CDATA[<211> 112]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1118]]> Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly 1 5 10 15 Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr 20 25 30 Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys 35 40 45 Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys 50 55 60 Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg 65 70 75 80 Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala 85 90 95 Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 100 105 110 <![CDATA[<210> 1119]]> <![CDATA[<211> 245]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1119]]> Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly 1 5 10 15 Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile 35 40 45 Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 65 70 75 80 Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Ser Thr Ser Gly 100 105 110 Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys 115 120 125 Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser 130 135 140 Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 145 150 155 160 Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile 165 170 175 Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu 180 185 190 Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn 195 200 205 Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr 210 215 220 Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser 225 230 235 240 Val Thr Val Ser Ser 245 <![CDATA[<210> 1120]]> <![CDATA[<211> 107]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1120]]> Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly 1 5 10 15 Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile 35 40 45 Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 65 70 75 80 Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr 100 105 <![CDATA[<210> 1121]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1121]]> Gln Asp Ile Ser Lys Tyr 1 5 <![CDATA[<210> 1122]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1122]]> His Thr Ser 1 <![CDATA[<210> 1123]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1123]]> Gln Gln Gly Asn Thr Leu Pro Tyr Thr 1 5 <![CDATA[<210> 1124]]> <![CDATA[<211> 18]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1124]]> Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr 1 5 10 15 Lys Gly <![CDATA[<210> 1125]]> <![CDATA[<211> 120]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1125]]> Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln 1 5 10 15 Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr 20 25 30 Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu 35 40 45 Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys 50 55 60 Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu 65 70 75 80 Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala 85 90 95 Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Ser Val Thr Val Ser Ser 115 120 <![CDATA[<210> 1126]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1126]]> Gly Val Ser Leu Pro Asp Tyr Gly 1 5 <![CDATA[<210> 1127]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1127]]> Ile Trp Gly Ser Glu Thr Thr 1 5 <![CDATA[<210> 1128]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1128]]> Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 1 5 10 <![CDATA[<210> 1129]]> <![CDATA[<211> 242]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1129]]> Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly 1 5 10 15 Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile 35 40 45 Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 65 70 75 80 Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Gly Gly Gly Ser 100 105 110 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Lys Leu Gln Glu 115 120 125 Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys 130 135 140 Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg 145 150 155 160 Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser 165 170 175 Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile 180 185 190 Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln 195 200 205 Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly 210 215 220 Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val 225 230 235 240 Ser Ser <![CDATA[<210> 1130]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1130]]> Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 15 <![CDATA[<210> 1131]]> <![CDATA[<211> 1458]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 聚核苷酸 <![CDATA[<400> 1131]]> atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg 60 ccggacatcc agatgacaca gactacatcc tccctgtctg cctctctggg agacagagtc 120 accatcagtt gcagggcaag tcaggacatt agtaaatatt taaattggta tcagcagaaa 180 ccagatggaa ctgttaaact cctgatctac catacatcaa gattacactc aggagtccca 240 tcaaggttca gtggcagtgg gtctggaaca gattattctc tcaccattag caacctggag 300 caagaagata ttgccactta cttttgccaa cagggtaata cgcttccgta cacgttcgga 360 ggggggacca agctggagat cacaggtggc ggtggctcgg gcggtggtgg gtcgggtggc 420 ggcggatctg aggtgaaact gcaggagtca ggacctggcc tggtggcgcc ctcacagagc 480 ctgtccgtca catgcactgt ctcaggggtc tcattacccg actatggtgt aagctggatt 540 cgccagcctc cacgaaaggg tctggagtgg ctgggagtaa tatggggtag tgaaaccaca 600 tactataatt cagctctcaa atccagactg accatcatca aggacaactc caagagccaa 660 gttttcttaa aaatgaacag tctgcaaact gatgacacag ccatttacta ctgtgccaaa 720 cattattact acggtggtag ctatgctatg gactactggg gccaaggaac ctcagtcacc 780 gtctcctcaa ccacgacgcc agcgccgcga ccaccaacac cggcgcccac catcgcgtcg 840 cagcccctgt ccctgcgccc agaggcgtgc cggccagcgg cggggggcgc agtgcacacg 900 agggggctgg acttcgcctg tgatatctac atctgggcgc ccttggccgg gacttgtggg 960 gtccttctcc tgtcactggt tatcaccctt tactgcaaac ggggcagaaa gaaactcctg 1020 tatatattca aacaaccatt tatgagacca gtacaaacta ctcaagagga agatggctgt 1080 agctgccgat ttccagaaga agaagaagga ggatgtgaac tgagagtgaa gttcagcagg 1140 agcgcagacg cccccgcgta caagcagggc cagaaccagc tctataacga gctcaatcta 1200 ggacgaagag aggagtacga tgttttggac aagagacgtg gccgggaccc tgagatgggg 1260 ggaaagccga gaaggaagaa ccctcaggaa ggcctgtaca atgaactgca gaaagataag 1320 atggcggagg cctacagtga gattgggatg aaaggcgagc gccggagggg caaggggcac 1380 gatggccttt accagggtct cagtacagcc accaaggaca cctacgacgc ccttcacatg 1440 caggccctgc cccctcgc 1458 <![CDATA[<210> 1132]]> <![CDATA[<211> 486]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1132]]> Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 1 5 10 15 His Ala Ala Arg Pro Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu 20 25 30 Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln 35 40 45 Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr 50 55 60 Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro 65 70 75 80 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile 85 90 95 Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly 100 105 110 Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr 115 120 125 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 130 135 140 Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser 145 150 155 160 Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly 165 170 175 Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly 180 185 190 Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser 195 200 205 Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys 210 215 220 Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys 225 230 235 240 His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly 245 250 255 Thr Ser Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro 260 265 270 Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu 275 280 285 Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp 290 295 300 Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly 305 310 315 320 Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg 325 330 335 Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln 340 345 350 Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu 355 360 365 Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala 370 375 380 Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu 385 390 395 400 Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp 405 410 415 Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu 420 425 430 Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile 435 440 445 Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr 450 455 460 Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met 465 470 475 480 Gln Ala Leu Pro Pro Arg 485 <![CDATA[<210> 1133]]> <![CDATA[<211> 1383]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<22]]>0>]]> <br/><![CDATA[<223> 人工序列之描述:合成]]> <br/><![CDATA[ 聚核苷酸 <![CDATA[<400> 1133]]> atgctgctgc tggtgaccag cctgctgctg tgcgagctgc cccaccccgc ctttctgctg 60 atccccgaca tccagatgac ccagaccacc tccagcctga gcgccagcct gggcgaccgg 120 gtgaccatca gctgccgggc cagccaggac atcagcaagt acctgaactg gtatcagcag 180 aagcccgacg gcaccgtcaa gctgctgatc taccacacca gccggctgca cagcggcgtg 240 cccagccggt ttagcggcag cggctccggc accgactaca gcctgaccat ctccaacctg 300 gaacaggaag atatcgccac ctacttttgc cagcagggca acacactgcc ctacaccttt 360 ggcggcggaa caaagctgga aatcaccggc agcacctccg gcagcggcaa gcctggcagc 420 ggcgagggca gcaccaaggg cgaggtgaag ctgcaggaaa gcggccctgg cctggtggcc 480 cccagccaga gcctgagcgt gacctgcacc gtgagcggcg tgagcctgcc cgactacggc 540 gtgagctgga tccggcagcc ccccaggaag ggcctggaat ggctgggcgt gatctggggc 600 agcgagacca cctactacaa cagcgccctg aagagccggc tgaccatcat caaggacaac 660 agcaagagcc aggtgttcct gaagatgaac agcctgcaga ccgacgacac cgccatctac 720 tactgcgcca agcactacta ctacggcggc agctacgcca tggactactg gggccagggc 780 accagcgtga ccgtgagcag cgaatctaag tacggaccgc cctgcccccc ttgccctatg 840 ttctgggtgc tggtggtggt cggaggcgtg ctggcctgct acagcctgct ggtcaccgtg 900 gccttcatca tcttttgggt gaaacggggc agaaagaaac tcctgtatat attcaaacaa 960 ccatttatga gaccagtaca aactactcaa gaggaagatg gctgtagctg ccgatttcca 1020 gaagaagaag aaggaggatg tgaactgcgg gtgaagttca gcagaagcgc cgacgcccct 1080 gcctaccagc agggccagaa tcagctgtac aacgagctga acctgggcag aagggaagag 1140 tacgacgtcc tggataagcg gagaggccgg gaccctgaga tgggcggcaa gcctcggcgg 1200 aagaaccccc aggaaggcct gtataacgaa ctgcagaaag acaagatggc cgaggcctac 1260 agcgagatcg gcatgaaggg cgagcggagg cggggcaagg gccacgacgg cctgtatcag 1320 ggcctgtcca ccgccaccaa ggatacctac gacgccctgc acatgcaggc cctgccccca 1380 agg 1383 <![CDATA[<210> 1134]]> <![CDATA[<211> 461]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1134]]> Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 1 5 10 15 Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Thr Thr Ser Ser 20 25 30 Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser 35 40 45 Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly 50 55 60 Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val 65 70 75 80 Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr 85 90 95 Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln 100 105 110 Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile 115 120 125 Thr Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser 130 135 140 Thr Lys Gly Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala 145 150 155 160 Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu 165 170 175 Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu 180 185 190 Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser 195 200 205 Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln 210 215 220 Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr 225 230 235 240 Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 245 250 255 Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Glu Ser Lys Tyr Gly 260 265 270 Pro Pro Cys Pro Pro Cys Pro Met Phe Trp Val Leu Val Val Val Gly 275 280 285 Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile 290 295 300 Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln 305 310 315 320 Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser 325 330 335 Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys 340 345 350 Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln 355 360 365 Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu 370 375 380 Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg 385 390 395 400 Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met 405 410 415 Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly 420 425 430 Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp 435 440 445 Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 450 455 460 <![CDATA[<210> 1135]]> <![CDATA[<211> 1467]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 聚核苷酸 <![CDATA[<400> 1135]]> atgcttctcc tggtgacaag ccttctgctc tgtgagttac cacacccagc attcctcctg 60 atcccagaca tccagatgac acagactaca tcctccctgt ctgcctctct gggagacaga 120 gtcaccatca gttgcagggc aagtcaggac attagtaaat atttaaattg gtatcagcag 180 aaaccagatg gaactgttaa actcctgatc taccatacat caagattaca ctcaggagtc 240 ccatcaaggt tcagtggcag tgggtctgga acagattatt ctctcaccat tagcaacctg 300 gagcaagaag atattgccac ttacttttgc caacagggta atacgcttcc gtacacgttc 360 ggagggggga ctaagttgga aataacaggc tccacctctg gatccggcaa gcccggatct 420 ggcgagggat ccaccaaggg cgaggtgaaa ctgcaggagt caggacctgg cctggtggcg 480 ccctcacaga gcctgtccgt cacatgcact gtctcagggg tctcattacc cgactatggt 540 gtaagctgga ttcgccagcc tccacgaaag ggtctggagt ggctgggagt aatatggggt 600 agtgaaacca catactataa ttcagctctc aaatccagac tgaccatcat caaggacaac 660 tccaagagcc aagttttctt aaaaatgaac agtctgcaaa ctgatgacac agccatttac 720 tactgtgcca aacattatta ctacggtggt agctatgcta tggactactg gggtcaagga 780 acctcagtca ccgtctcctc agcggccgca attgaagtta tgtatcctcc tccttaccta 840 gacaatgaga agagcaatgg aaccattatc catgtgaaag ggaaacacct ttgtccaagt 900 cccctatttc ccggaccttc taagcccttt tgggtgctgg tggtggttgg gggagtcctg 960 gcttgctata gcttgctagt aacagtggcc tttattattt tctgggtgag gagtaagagg 1020 agcaggctcc tgcacagtga ctacatgaac atgactcccc gccgccccgg gcccacccgc 1080 aagcattacc agccctatgc cccaccacgc gacttcgcag cctatcgctc cagagtgaag 1140 ttcagcagga gcgcagacgc ccccgcgtac cagcagggcc agaaccagct ctataacgag 1200 ctcaatctag gacgaagaga ggagtacgat gttttggaca agagacgtgg ccgggaccct 1260 gagatggggg gaaagccgag aaggaagaac cctcaggaag gcctgtacaa tgaactgcag 1320 aaagataaga tggcggaggc ctacagtgag attgggatga aaggcgagcg ccggaggggc 1380 aaggggcacg atggccttta ccagggtctc agtacagcca ccaaggacac ctacgacgcc 1440 cttcacatgc aggccctgcc ccctcgc 1467 <![CDATA[<210> 1136]]> <![CDATA[<211> 489]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1136]]> Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 1 5 10 15 Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Thr Thr Ser Ser 20 25 30 Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser 35 40 45 Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly 50 55 60 Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val 65 70 75 80 Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr 85 90 95 Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln 100 105 110 Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile 115 120 125 Thr Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser 130 135 140 Thr Lys Gly Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala 145 150 155 160 Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu 165 170 175 Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu 180 185 190 Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser 195 200 205 Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln 210 215 220 Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr 225 230 235 240 Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 245 250 255 Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Ala Ala Ile Glu 260 265 270 Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser Asn Gly Thr 275 280 285 Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro Leu Phe Pro 290 295 300 Gly Pro Ser Lys Pro Phe Trp Val Leu Val Val Val Gly Gly Val Leu 305 310 315 320 Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val 325 330 335 Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr 340 345 350 Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro 355 360 365 Pro Arg Asp Phe Ala Ala Tyr Arg Ser Arg Val Lys Phe Ser Arg Ser 370 375 380 Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu 385 390 395 400 Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg 405 410 415 Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln 420 425 430 Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr 435 440 445 Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp 450 455 460 Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala 465 470 475 480 Leu His Met Gln Ala Leu Pro Pro Arg 485 <![CDATA[<210> 1137]]> <![CDATA[<211> 246]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1137]]> Asp Ile Val Leu Thr Gln Ser Pro Ala Ile Leu Ser Ala Ser Pro Gly 1 5 10 15 Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Asn Tyr Met 20 25 30 Asp Trp Tyr Gln Lys Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Tyr 35 40 45 Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser 50 55 60 Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Val Glu Ala Glu 65 70 75 80 Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Phe Asn Pro Pro Thr 85 90 95 Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly Ser Thr Ser Gly Ser 100 105 110 Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Gln Leu 115 120 125 Gln Gln Ser Gly Ala Glu Leu Val Lys Pro Gly Ala Ser Val Lys Met 130 135 140 Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Asn Met His Trp 145 150 155 160 Val Lys Gln Thr Pro Gly Gln Gly Leu Glu Trp Ile Gly Ala Ile Tyr 165 170 175 Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe Lys Gly Lys Ala 180 185 190 Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser 195 200 205 Ser Leu Thr Ser Glu Asp Ser Ala Asp Tyr Tyr Cys Ala Arg Ser Asn 210 215 220 Tyr Tyr Gly Ser Ser Tyr Trp Phe Phe Asp Val Trp Gly Ala Gly Thr 225 230 235 240 Thr Val Thr Val Ser Ser 245 <![CDATA[<210> 1138]]> <![CDATA[<211> 106]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1138]]> Asp Ile Val Leu Thr Gln Ser Pro Ala Ile Leu Ser Ala Ser Pro Gly 1 5 10 15 Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Asn Tyr Met 20 25 30 Asp Trp Tyr Gln Lys Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Tyr 35 40 45 Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser 50 55 60 Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Val Glu Ala Glu 65 70 75 80 Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Phe Asn Pro Pro Thr 85 90 95 Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 <![CDATA[<210> 1139]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1139]]> Arg Ala Ser Ser Ser Val Asn Tyr Met Asp 1 5 10 <![CDATA[<210> 1140]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1140]]> Ala Thr Ser Asn Leu Ala Ser 1 5 <![CDATA[<210> 1141]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序]]>列之描述:合成 肽 <![CDATA[<400> 1141]]> Gln Gln Trp Ser Phe Asn Pro Pro Thr 1 5 <![CDATA[<210> 1142]]> <![CDATA[<211> 122]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1142]]> Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asn Met His Trp Val Lys Gln Thr Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe 50 55 60 Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr 65 70 75 80 Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Asp Tyr Tyr Cys 85 90 95 Ala Arg Ser Asn Tyr Tyr Gly Ser Ser Tyr Trp Phe Phe Asp Val Trp 100 105 110 Gly Ala Gly Thr Thr Val Thr Val Ser Ser 115 120 <![CDATA[<210> 1143]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1143]]> Ser Tyr Asn Met His 1 5 <![CDATA[<210> 1144]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1144]]> Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe Lys 1 5 10 15 Gly <![CDATA[<210> 1145]]> <![CDATA[<211> 246]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1145]]> Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 1 5 10 15 Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asn 20 25 30 Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu 35 40 45 Trp Leu Gly Arg Thr Tyr Tyr Arg Ser Lys Trp Tyr Asn Asp Tyr Ala 50 55 60 Val Ser Val Lys Ser Arg Ile Thr Ile Asn Pro Asp Thr Ser Lys Asn 65 70 75 80 Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Val 85 90 95 Tyr Tyr Cys Ala Arg Glu Val Thr Gly Asp Leu Glu Asp Ala Phe Asp 100 105 110 Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly 115 120 125 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr 130 135 140 Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile 145 150 155 160 Thr Cys Arg Ala Ser Gln Thr Ile Trp Ser Tyr Leu Asn Trp Tyr Gln 165 170 175 Gln Arg Pro Gly Lys Ala Pro Asn Leu Leu Ile Tyr Ala Ala Ser Ser 180 185 190 Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Arg Gly Ser Gly Thr 195 200 205 Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Phe Ala Thr 210 215 220 Tyr Tyr Cys Gln Gln Ser Tyr Ser Ile Pro Gln Thr Phe Gly Gln Gly 225 230 235 240 Thr Lys Leu Glu Ile Lys 245 <![CDATA[<210> 1146]]> <![CDATA[<211> 124]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1146]]> Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 1 5 10 15 Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asn 20 25 30 Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu 35 40 45 Trp Leu Gly Arg Thr Tyr Tyr Arg Ser Lys Trp Tyr Asn Asp Tyr Ala 50 55 60 Val Ser Val Lys Ser Arg Ile Thr Ile Asn Pro Asp Thr Ser Lys Asn 65 70 75 80 Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Val 85 90 95 Tyr Tyr Cys Ala Arg Glu Val Thr Gly Asp Leu Glu Asp Ala Phe Asp 100 105 110 Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser 115 120 <![CDATA[<210> 1147]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1147]]> Gly Asp Ser Val Ser Ser Asn Ser Ala Ala 1 5 10 <![CDATA[<210> 1148]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1148]]> Thr Tyr Tyr Arg Ser Lys Trp Tyr Asn 1 5 <![CDATA[<210> 1149]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1149]]> Ala Arg Glu Val Thr Gly Asp Leu Glu Asp Ala Phe Asp Ile 1 5 10 <![CDATA[<210> 1150]]> <![CDATA[<211> 107]]> <![CDATA[<212> PR]]>T <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述]]>:合成 多肽 <![CDATA[<400> 1150]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Thr Ile Trp Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Arg Pro Gly Lys Ala Pro Asn Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Arg Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ile Pro Gln 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 100 105 <![CDATA[<210> 1151]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1151]]> Gln Thr Ile Trp Ser Tyr 1 5 <![CDATA[<210> 1152]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1152]]> Ala Ala Ser 1 <![CDATA[<210> 1153]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1153]]> Gln Gln Ser Tyr Ser Ile Pro Gln Thr 1 5 <![CDATA[<210> 1154]]> <![CDATA[<211> 246]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1154]]> Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Met Val Lys Pro Ser Gln 1 5 10 15 Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asn 20 25 30 Ser Val Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu 35 40 45 Trp Leu Gly Arg Thr Tyr Tyr Arg Ser Thr Trp Tyr Asn Asp Tyr Ala 50 55 60 Val Ser Met Lys Ser Arg Ile Thr Ile Asn Pro Asp Thr Asn Lys Asn 65 70 75 80 Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Val 85 90 95 Tyr Tyr Cys Ala Arg Glu Val Thr Gly Asp Leu Glu Asp Ala Phe Asp 100 105 110 Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly 115 120 125 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Ile 130 135 140 Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile 145 150 155 160 Thr Cys Arg Ala Ser Gln Thr Ile Trp Ser Tyr Leu Asn Trp Tyr Arg 165 170 175 Gln Arg Pro Gly Glu Ala Pro Asn Leu Leu Ile Tyr Ala Ala Ser Ser 180 185 190 Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Arg Gly Ser Gly Thr 195 200 205 Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Phe Ala Thr 210 215 220 Tyr Tyr Cys Gln Gln Ser Tyr Ser Ile Pro Gln Thr Phe Gly Gln Gly 225 230 235 240 Thr Lys Leu Glu Ile Lys 245 <![CDATA[<210> 1155]]> <![CDATA[<211> 124]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1155]]> Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Met Val Lys Pro Ser Gln 1 5 10 15 Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asn 20 25 30 Ser Val Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu 35 40 45 Trp Leu Gly Arg Thr Tyr Tyr Arg Ser Thr Trp Tyr Asn Asp Tyr Ala 50 55 60 Val Ser Met Lys Ser Arg Ile Thr Ile Asn Pro Asp Thr Asn Lys Asn 65 70 75 80 Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Val 85 90 95 Tyr Tyr Cys Ala Arg Glu Val Thr Gly Asp Leu Glu Asp Ala Phe Asp 100 105 110 Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser 115 120 <![CDATA[<210> 1156]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1156]]> Gly Asp Ser Val Ser Ser Asn Ser Val Ala 1 5 10 <![CDATA[<210> 1157]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1157]]> Thr Tyr Tyr Arg Ser Thr Trp Tyr Asn 1 5 <![CDATA[<210> 1158]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1158]]> Ala Arg Glu Val Thr Gly Asp Leu Glu Asp Ala Phe Asp Ile 1 5 10 <![CDATA[<210> 1159]]> <![CDATA[<211> 107]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1159]]> Asp Ile Gln Met Ile Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Thr Ile Trp Ser Tyr 20 25 30 Leu Asn Trp Tyr Arg Gln Arg Pro Gly Glu Ala Pro Asn Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Arg Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ile Pro Gln 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 100 105 <![CDATA[<210> 1160]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1160]]> Gln Thr Ile Trp Ser Tyr 1 5 <![CDATA[<210> 1161]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1161]]> Ala Ala Ser 1 <![CDATA[<210> 1162]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1162]]> Gln Gln Ser Tyr Ser Ile Pro Gln Thr 1 5 <![CDATA[<210> 1163]]> <![CDATA[<211> 246]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1163]]> Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Met Ser Leu Gly 1 5 10 15 Lys Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Ser Val Ile 20 25 30 Gly Ala His Leu Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 35 40 45 Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu Thr Gly Val Pro Ala 50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asp 65 70 75 80 Pro Val Glu Glu Asp Asp Val Ala Ile Tyr Ser Cys Leu Gln Ser Arg 85 90 95 Ile Phe Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly 100 105 110 Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys 115 120 125 Gly Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly 130 135 140 Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp 145 150 155 160 Tyr Ser Ile Asn Trp Val Lys Arg Ala Pro Gly Lys Gly Leu Lys Trp 165 170 175 Met Gly Trp Ile Asn Thr Glu Thr Arg Glu Pro Ala Tyr Ala Tyr Asp 180 185 190 Phe Arg Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala 195 200 205 Tyr Leu Gln Ile Asn Asn Leu Lys Tyr Glu Asp Thr Ala Thr Tyr Phe 210 215 220 Cys Ala Leu Asp Tyr Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Ser Val Thr Val Ser Ser 245 <![CDATA[<210> 1164]]> <![CDATA[<211> 111]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1164]]> Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Met Ser Leu Gly 1 5 10 15 Lys Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Ser Val Ile 20 25 30 Gly Ala His Leu Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 35 40 45 Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu Thr Gly Val Pro Ala 50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asp 65 70 75 80 Pro Val Glu Glu Asp Asp Val Ala Ile Tyr Ser Cys Leu Gln Ser Arg 85 90 95 Ile Phe Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 110 <![CDATA[<210> 1165]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1165]]> Arg Ala Ser Glu Ser Val Ser Val Ile Gly Ala His Leu Ile His 1 5 10 15 <![CDATA[<210> 1166]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1166]]> Leu Ala Ser Asn Leu Glu Thr 1 5 <![CDATA[<210> 1167]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1167]]> Leu Gln Ser Arg Ile Phe Pro Arg Thr 1 5 <![CDATA[<210> 1168]]> <![CDATA[<211> 117]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1168]]> Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu 1 5 10 15 Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Ser Ile Asn Trp Val Lys Arg Ala Pro Gly Lys Gly Leu Lys Trp Met 35 40 45 Gly Trp Ile Asn Thr Glu Thr Arg Glu Pro Ala Tyr Ala Tyr Asp Phe 50 55 60 Arg Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala Tyr 65 70 75 80 Leu Gln Ile Asn Asn Leu Lys Tyr Glu Asp Thr Ala Thr Tyr Phe Cys 85 90 95 Ala Leu Asp Tyr Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser 100 105 110 Val Thr Val Ser Ser 115 <![CDATA[<210> 1169]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1169]]> Asp Tyr Ser Ile Asn 1 5 <![CDATA[<210> 1170]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1170]]> Trp Ile Asn Thr Glu Thr Arg Glu Pro Ala Tyr Ala Tyr Asp Phe Arg 1 5 10 15 Gly <![CDATA[<210> 1171]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1171]]> Asp Tyr Ser Tyr Ala Met Asp Tyr 1 5 <![CDATA[<210> 11]]>72 <![CDATA[<211> 246]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1172]]> Asp Ile Val Leu Thr Gln Ser Pro Pro Ser Leu Ala Met Ser Leu Gly 1 5 10 15 Lys Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Thr Ile Leu 20 25 30 Gly Ser His Leu Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 35 40 45 Thr Leu Leu Ile Gln Leu Ala Ser Asn Val Gln Thr Gly Val Pro Ala 50 55 60 Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu Thr Ile Asp 65 70 75 80 Pro Val Glu Glu Asp Asp Val Ala Val Tyr Tyr Cys Leu Gln Ser Arg 85 90 95 Thr Ile Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly 100 105 110 Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys 115 120 125 Gly Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly 130 135 140 Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Arg His 145 150 155 160 Tyr Ser Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp 165 170 175 Met Gly Arg Ile Asn Thr Glu Ser Gly Val Pro Ile Tyr Ala Asp Asp 180 185 190 Phe Lys Gly Arg Phe Ala Phe Ser Val Glu Thr Ser Ala Ser Thr Ala 195 200 205 Tyr Leu Val Ile Asn Asn Leu Lys Asp Glu Asp Thr Ala Ser Tyr Phe 210 215 220 Cys Ser Asn Asp Tyr Leu Tyr Ser Leu Asp Phe Trp Gly Gln Gly Thr 225 230 235 240 Ala Leu Thr Val Ser Ser 245 <![CDATA[<210> 1173]]> <![CDATA[<211> 111]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223]]>> 人工序列之描述:合成]]> <br/><![CDATA[ 多肽 <![CDATA[<400> 1173]]> Asp Ile Val Leu Thr Gln Ser Pro Pro Ser Leu Ala Met Ser Leu Gly 1 5 10 15 Lys Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Thr Ile Leu 20 25 30 Gly Ser His Leu Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 35 40 45 Thr Leu Leu Ile Gln Leu Ala Ser Asn Val Gln Thr Gly Val Pro Ala 50 55 60 Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu Thr Ile Asp 65 70 75 80 Pro Val Glu Glu Asp Asp Val Ala Val Tyr Tyr Cys Leu Gln Ser Arg 85 90 95 Thr Ile Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 110 <![CDATA[<210> ]]>1174 <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1174]]> Arg Ala Ser Glu Ser Val Thr Ile Leu Gly Ser His Leu Ile Tyr 1 5 10 15 <![CDATA[<210> 1175]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1175]]> Leu Ala Ser Asn Val Gln Thr 1 5 <![CDATA[<210> 1176]]> <![CDATA[<211> 9]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1176]]> Leu Gln Ser Arg Thr Ile Pro Arg Thr 1 5 <![CDATA[<210> 1177]]> <![CDATA[<211> 117]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1177]]> Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu 1 5 10 15 Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Arg His Tyr 20 25 30 Ser Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp Met 35 40 45 Gly Arg Ile Asn Thr Glu Ser Gly Val Pro Ile Tyr Ala Asp Asp Phe 50 55 60 Lys Gly Arg Phe Ala Phe Ser Val Glu Thr Ser Ala Ser Thr Ala Tyr 65 70 75 80 Leu Val Ile Asn Asn Leu Lys Asp Glu Asp Thr Ala Ser Tyr Phe Cys 85 90 95 Ser Asn Asp Tyr Leu Tyr Ser Leu Asp Phe Trp Gly Gln Gly Thr Ala 100 105 110 Leu Thr Val Ser Ser 115 <![CDATA[<210> 1178]]> <![CDATA[<211> 5]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1178]]> His Tyr Ser Met Asn 1 5 <![CDATA[<210> 1179]]> <![CDATA[<211> 17]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1179]]> Arg Ile Asn Thr Glu Ser Gly Val Pro Ile Tyr Ala Asp Asp Phe Lys 1 5 10 15 Gly <![CDATA[<210> 1180]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1180]]> Asp Tyr Leu Tyr Ser Leu Asp Phe 1 5 <![CDATA[<210> 1181]]> <![CDATA[<211> 121]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1181]]> Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ser Ile Ser Gly Ser Gly Asp Tyr Ile Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Ile Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Glu Gly Thr Gly Ala Asn Ser Ser Leu Ala Asp Tyr Arg Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <![CDATA[<210> 1182]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1182]]> Gly Phe Thr Phe Ser Ser Tyr Ala 1 5 <![CDATA[<210> 1183]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1183]]> Ile Ser Gly Ser Gly Asp Tyr Ile 1 5 <![CDATA[<210> 1184]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1184]]> Ala Lys Glu Gly Thr Gly Ala Asn Ser Ser Leu Ala Asp Tyr 1 5 10 <![CDATA[<210> 1185]]> <![CDATA[<400> 1185]]> 000 <![CDATA[<210> 1186]]> <![CDATA[<400> 1186]]> 000 <![CDATA[<210> 1187]]> <![CDATA[<400> 1187]]> 000 <![CDATA[<210> 1188]]> <![CDATA[<400> 1188]]> 000 <![CDATA[<210> 1189]]> <![CDATA[<400> 1189]]> 000 <![CDATA[<210> 1190]]> <![CDATA[<400> 1190]]> 000 <![CDATA[<210> 1191]]> <![CDATA[<400> 1191]]> 000 <![CDATA[<210> 1192]]> <![CDATA[<400> 1192]]> 000 <![CDATA[<210> 1193]]> <![CDATA[<400> 1193]]> 000 <![CDATA[<210> 1194]]> <![CDATA[<400> 1194]]> 000 <![CDATA[<210> 1195]]> <![CDATA[<400> 1195]]> 000 <![CDATA[<210> 1196]]> <![CDATA[<400> 1196]]> 000 <![CDATA[<210> 1197]]> <![CDATA[<400> 1197]]> 000 <![CDATA[<210> 1198]]> <![CDATA[<400> 1198]]> 000 <![CDATA[<210> 1199]]> <![CDATA[<400> 1199]]> 000 <![CDATA[<210> 1200]]> <![CDATA[<400> 1200]]> 000 <![CDATA[<210> 1201]]> <![CDATA[<400> 1201]]> 000 <![CDATA[<210> 1202]]> <![CDATA[<400> 1202]]> 000 <![CDATA[<210> 1203]]> <![CDATA[<400> 1203]]> 000 <![CDATA[<210> 1204]]> <![CDATA[<400> 1204]]> 000 <![CDATA[<210> 1205]]> <![CDATA[<400> 1205]]> 000 <![CDATA[<210> 1206]]> <![CDATA[<400> 1206]]> 000 <![CDATA[<210> 1207]]> <![CDATA[<400> 1207]]> 000 <![CDATA[<210> 1208]]> <![CDATA[<400> 1208]]> 000 <![CDATA[<210> 1209]]> <![CDATA[<400> 1209]]> 000 <![CDATA[<210> 1210]]> <![CDATA[<400> 1210]]> 000 <![CDATA[<210> 1211]]> <![CDATA[<400> 1211]]> 000 <![CDATA[<210> 1212]]> <![CDATA[<400> 1212]]> 000 <![CDATA[<210> 1213]]> <![CDATA[<211> 42]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1213]]> Ala Ala Ala Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu 1 5 10 15 Lys Ser Asn Gly Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro 20 25 30 Ser Pro Leu Phe Pro Gly Pro Ser Lys Pro 35 40 <![CDATA[<210> 1214]]> <![CDATA[<211> 28]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 智人]]> <![CDATA[<400> 1214]]> Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser 1 5 10 15 Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val 20 25 <![CDATA[<210> 1215]]> <![CDATA[<211> 1]]>12 <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1215]]> Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly 1 5 10 15 Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr 20 25 30 Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys 35 40 45 Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys 50 55 60 Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg 65 70 75 80 Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala 85 90 95 Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 100 105 110 <![CDATA[<210> 1216]]> <![CDATA[<211> 1467]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 聚核苷酸 <![CDATA[<400> 1216]]> atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg 60 ccggacatcc agatgacaca gactacatcc tccctgtctg cctctctggg agacagagtc 120 accatcagtt gcagggcaag tcaggacatt agtaaatatt taaattggta tcagcagaaa 180 ccagatggaa ctgttaaact cctgatctac catacatcaa gattacactc aggagtccca 240 tcaaggttca gtggcagtgg gtctggaaca gattattctc tcaccattag caacctggag 300 caagaagata ttgccactta cttttgccaa cagggtaata cgcttccgta cacgttcgga 360 ggggggacca agctggagat cacaggctcc acctctggat ccggcaagcc cggatctggc 420 gagggatcca ccaagggcga ggtgaaactg caggagtcag gacctggcct ggtggcgccc 480 tcacagagcc tgtccgtcac atgcactgtc tcaggggtct cattacccga ctatggtgta 540 agctggattc gccagcctcc acgaaagggt ctggagtggc tgggagtaat atggggtagt 600 gaaaccacat actataattc agctctcaaa tccagactga ccatcatcaa ggacaactcc 660 aagagccaag ttttcttaaa aatgaacagt ctgcaaactg atgacacagc catttactac 720 tgtgccaaac attattacta cggtggtagc tatgctatgg actactgggg ccaaggaacc 780 tcagtcaccg tctcctcaac cacgacgcca gcgccgcgac caccaacacc ggcgcccacc 840 atcgcgtcgc agcccctgtc cctgcgccca gaggcgtgcc ggccagcggc ggggggcgca 900 gtgcacacga gggggctgga cttcgcctgt gatatctaca tctgggcgcc cttggccggg 960 acttgtgggg tccttctcct gtcactggtt atcacccttt actgcaaacg gggcagaaag 1020 aaactcctgt atatattcaa acaaccattt atgagaccag tacaaactac tcaagaggaa 1080 gatggctgta gctgccgatt tccagaagaa gaagaaggag gatgtgaact gagagtgaag 1140 ttcagcagga gcgcagacgc ccccgcgtac cagcagggcc agaaccagct ctataacgag 1200 ctcaatctag gacgaagaga ggagtacgat gttttggaca agagacgtgg ccgggaccct 1260 gagatggggg gaaagccgag aaggaagaac cctcaggaag gcctgtacaa tgaactgcag 1320 aaagataaga tggcggaggc ctacagtgag attgggatga aaggcgagcg ccggaggggc 1380 aaggggcacg atggccttta ccagggtctc agtacagcca ccaaggacac ctacgacgcc 1440 cttcacatgc aggccctgcc ccctcgc 1467 <![CDATA[<210> 1217]]> <![CDATA[<211> 489]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1217]]> Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 1 5 10 15 His Ala Ala Arg Pro Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu 20 25 30 Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln 35 40 45 Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr 50 55 60 Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro 65 70 75 80 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile 85 90 95 Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly 100 105 110 Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr 115 120 125 Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr 130 135 140 Lys Gly Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro 145 150 155 160 Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro 165 170 175 Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu 180 185 190 Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala 195 200 205 Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val 210 215 220 Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr 225 230 235 240 Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp 245 250 255 Gly Gln Gly Thr Ser Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro 260 265 270 Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu 275 280 285 Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg 290 295 300 Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly 305 310 315 320 Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys 325 330 335 Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg 340 345 350 Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro 355 360 365 Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser 370 375 380 Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu 385 390 395 400 Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg 405 410 415 Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln 420 425 430 Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr 435 440 445 Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp 450 455 460 Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala 465 470 475 480 Leu His Met Gln Ala Leu Pro Pro Arg 485 <![CDATA[<210> 1218]]> <![CDATA[<211> 243]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1218]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Lys Tyr Asp Leu Leu Thr 85 90 95 Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Ser Thr Ser Gly Ser 100 105 110 Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Gln Leu Gln Leu 115 120 125 Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu 130 135 140 Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser Ser Tyr Tyr Trp 145 150 155 160 Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Ser 165 170 175 Ile Ser Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg 180 185 190 Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu 195 200 205 Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp 210 215 220 Arg Gly Asp Thr Ile Leu Asp Val Trp Gly Gln Gly Thr Met Val Thr 225 230 235 240 Val Ser Ser <![CDATA[<210> 1219]]> <![CDATA[<211> 106]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1219]]> Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Lys Tyr Asp Leu Leu Thr 85 90 95 Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 <![CDATA[<210> 1220]]> <![CDATA[<211> 6]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1220]]> Gln Ser Ile Ser Ser Tyr 1 5 <![CDATA[<210> 1221]]> <![CDATA[<211> 3]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1221]]> Ala Ala Ser 1 <![CDATA[<210> 1222]]> <![CDATA[<211> 8]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1222]]> Gln Gln Lys Tyr Asp Leu Leu Thr 1 5 <![CDATA[<210> 1223]]> <![CDATA[<211> 119]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1223]]> Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu 1 5 10 15 Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser 20 25 30 Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu 35 40 45 Trp Ile Gly Ser Ile Ser Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser 50 55 60 Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe 65 70 75 80 Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 85 90 95 Cys Ala Arg Asp Arg Gly Asp Thr Ile Leu Asp Val Trp Gly Gln Gly 100 105 110 Thr Met Val Thr Val Ser Ser 115 <![CDATA[<210> 1224]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1224]]> Gly Gly Ser Ile Ser Ser Ser Ser Tyr Tyr 1 5 10 <![CDATA[<210> 1225]]> <![CDATA[<211> 7]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1225]]> Ile Ser Tyr Ser Gly Ser Thr 1 5 <![CDATA[<210> 1226]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 肽 <![CDATA[<400> 1226]]> Ala Arg Asp Arg Gly Asp Thr Ile Leu Asp Val 1 5 10 <![CDATA[<210> 1227]]> <![CDATA[<211> 1503]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 聚核苷酸 <![CDATA[<400> 1227]]> atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg 60 ccggacatcc agatgaccca gtctccatcc tccctgtctg catctgtagg agacagagtc 120 accatcactt gccgggcaag tcagagcatt agcagctatt taaattggta tcagcagaaa 180 ccagggaaag cccctaagct cctgatctat gctgcatcca gtttgcaaag tggggtccca 240 tcaaggttca gtggcagtgg atctgggaca gatttcactc tcaccatcag cagtctgcaa 300 cctgaagatt ttgcaactta ctactgtcag caaaaatacg acctcctcac ttttggcgga 360 gggaccaagg ttgagatcaa aggcagcacc agcggctccg gcaagcctgg ctctggcgag 420 ggcagcacaa agggacagct gcagctgcag gagtcgggcc caggactggt gaagccttcg 480 gagaccctgt ccctcacctg cactgtctct ggtggctcca tcagcagtag tagttactac 540 tggggctgga tccgccagcc cccagggaag gggctggagt ggattgggag tatctcctat 600 agtgggagca cctactacaa cccgtccctc aagagtcgag tcaccatatc cgtagacacg 660 tccaagaacc agttctccct gaagctgagt tctgtgaccg ccgcagacac ggcggtgtac 720 tactgcgcca gagatcgtgg agacaccata ctagacgtat ggggtcaggg tacaatggtc 780 accgtcagct cattcgtgcc cgtgttcctg cccgccaaac ctaccaccac ccctgcccct 840 agacctccca ccccagcccc aacaatcgcc agccagcctc tgtctctgcg gcccgaagcc 900 tgtagacctg ctgccggcgg agccgtgcac accagaggcc tggacttcgc ctgcgacatc 960 tacatctggg cccctctggc cggcacctgt ggcgtgctgc tgctgagcct ggtgatcacc 1020 ctgtactgca accaccggaa caaacggggc agaaagaaac tcctgtatat attcaaacaa 1080 ccatttatga gaccagtaca aactactcaa gaggaagatg gctgtagctg ccgatttcca 1140 gaagaagaag aaggaggatg tgaactgaga gtgaagttca gcagatccgc cgacgcccct 1200 gcctaccagc agggacagaa ccagctgtac aacgagctga acctgggcag acgggaagag 1260 tacgacgtgc tggacaagcg gagaggccgg gaccccgaga tgggcggaaa gcccagacgg 1320 aagaaccccc aggaaggcct gtataacgaa ctgcagaaag acaagatggc cgaggcctac 1380 agcgagatcg gcatgaaggg cgagcggagg cgcggcaagg gccacgatgg cctgtaccag 1440 ggcctgagca ccgccaccaa ggacacctac gacgccctgc acatgcaggc cctgcccccc 1500 aga 1503 <![CDATA[<210> 1228]]> <![CDATA[<211> 501]]> <![CDATA[<212> PR]]>T <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1228]]> Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 1 5 10 15 His Ala Ala Arg Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 20 25 30 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln 35 40 45 Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 50 55 60 Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro 65 70 75 80 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 85 90 95 Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Lys 100 105 110 Tyr Asp Leu Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly 115 120 125 Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys 130 135 140 Gly Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser 145 150 155 160 Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser 165 170 175 Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu 180 185 190 Glu Trp Ile Gly Ser Ile Ser Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro 195 200 205 Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln 210 215 220 Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 225 230 235 240 Tyr Cys Ala Arg Asp Arg Gly Asp Thr Ile Leu Asp Val Trp Gly Gln 245 250 255 Gly Thr Met Val Thr Val Ser Ser Phe Val Pro Val Phe Leu Pro Ala 260 265 270 Lys Pro Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr 275 280 285 Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala 290 295 300 Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile 305 310 315 320 Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser 325 330 335 Leu Val Ile Thr Leu Tyr Cys Asn His Arg Asn Lys Arg Gly Arg Lys 340 345 350 Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr 355 360 365 Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu 370 375 380 Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro 385 390 395 400 Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly 405 410 415 Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro 420 425 430 Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr 435 440 445 Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly 450 455 460 Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln 465 470 475 480 Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln 485 490 495 Ala Leu Pro Pro Arg 500 <![CDATA[<210> 1229]]> <![CDATA[<400> 1229]]> 000 <![CDATA[<210> 1230]]> <![CDATA[<400> 1230]]> 000 <![CDATA[<210> 1231]]> <![CDATA[<211> 468]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 人工序列之描述:合成]]> 多肽 <![CDATA[<400> 1231]]> Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly 1 5 10 15 Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile 35 40 45 Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 65 70 75 80 Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Ser Thr Ser Gly 100 105 110 Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys 115 120 125 Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser 130 135 140 Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 145 150 155 160 Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile 165 170 175 Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu 180 185 190 Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn 195 200 205 Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr 210 215 220 Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser 225 230 235 240 Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro 245 250 255 Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys 260 265 270 Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala 275 280 285 Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu 290 295 300 Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys 305 310 315 320 Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr 325 330 335 Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly 340 345 350 Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala 355 360 365 Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg 370 375 380 Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu 385 390 395 400 Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn 405 410 415 Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met 420 425 430 Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly 435 440 445 Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala 450 455 460 Leu Pro Pro Arg 465
Claims (121)
- 一種特異性結合CD8α或CD8β之抗體或其抗原結合片段,該抗體或其抗原結合片段包含重鏈可變區及/或輕鏈可變區,其中該重鏈可變區包含三個重鏈互補決定區(HCDR1、HCDR2及HCDR3),並且該輕鏈可變區包含三個輕鏈互補決定區(LCDR1、LCDR2及LCDR3),其中該HCDR1、HCDR2、HCDR3、LCDR1、LCDR2及LCDR3分別包含: a) SEQ ID NO: 1、70、148、240、294及333; b) SEQ ID NO: 2、71、149、241、294及334; c) SEQ ID NO: 3、72、148、240、294及333; d) SEQ ID NO: 4、73、649、242、295及335; e) SEQ ID NO: 5、74、150、242、295及336; f) SEQ ID NO: 6、75、151、243、296及337; g) SEQ ID NO: 7、76、152、242、295及338; h) SEQ ID NO: 8、77、153、244、297及339; i) SEQ ID NO: 9、77、154、245、298及340; j) SEQ ID NO: 10、78、650、246、297及341; k) SEQ ID NO: 11、79、155、247、299及342; l) SEQ ID NO: 12、80、156、248、300及343; m) SEQ ID NO: 13、81、157、249、294及344; n) SEQ ID NO: 14、76、158、242、295及345; o) SEQ ID NO: 15、76、159、250、301及346; p) SEQ ID NO: 11、82、160、249、294及347; q) SEQ ID NO: 16、83、161、251、302及340; r) SEQ ID NO: 17、84、162、241、303及348; s) SEQ ID NO: 18、85、163、252、304及349; t) SEQ ID NO: 19、86、164、241、305及350; u) SEQ ID NO: 20、87、165、253、299及351; v) SEQ ID NO: 4、88、166、249、299及352; w) SEQ ID NO: 21、89、167、242、306及353; x) SEQ ID NO: 22、90、168、241、307及354; y) SEQ ID NO: 23、91、169、241、299及355; z) SEQ ID NO: 24、92、170、241、299及356; aa) SEQ ID NO: 25、93、171、254、308及344; bb) SEQ ID NO: 26、94、172、240、294及333; cc) SEQ ID NO: 617、91、173、241、299及357; dd) SEQ ID NO: 1、79、174、255、294及358; ee) SEQ ID NO: 28、95、175、256、294及359; ff) SEQ ID NO: 29、79、176、257、309及360; gg) SEQ ID NO: 1、96、177、240、294及333; hh) SEQ ID NO: 20、97、149、251、299及361; ii) SEQ ID NO: 30、98、178、241、310及362; jj) SEQ ID NO: 31、99、179、240、311及363; kk) SEQ ID NO: 32、100、180、258、312及364; ll) SEQ ID NO: 19、101、181、259、313及333; mm) SEQ ID NO: 33、102、182、242、314及365; nn) SEQ ID NO: 34、103、183、260、315及366; oo) SEQ ID NO: 35、104、184、241、302及367; pp) SEQ ID NO: 36、105、185、261、316及368; qq) SEQ ID NO: 37、106、186、262、294及369; rr) SEQ ID NO: 38、107、187、263、294及344; ss) SEQ ID NO: 39、108、188、264、317及344; tt) SEQ ID NO: 40、109、189、240、294及370; uu) SEQ ID NO: 8、110、190、265、299及371; vv) SEQ ID NO: 41、111、191、266、299及346; ww) SEQ ID NO: 19、112、192、242、318及372; xx) SEQ ID NO: 4、113、193、267、309及373; yy) SEQ ID NO: 4、114、194、268、302、344及453; zz) SEQ ID NO: 42、115、195、269、319、374及454; aaa) SEQ ID NO: 43、77、196、270、320及375; bbb) SEQ ID NO: 44、116、197、271、299及376; ccc) SEQ ID NO: 40、117、198、272、302及377; ddd) SEQ ID NO: 40、118、199、259、302及378; eee) SEQ ID NO: 45、114、200、273、321及379; fff) SEQ ID NO: 46、119、201、240、322及380; ggg) SEQ ID NO: 47、120、202、274、309及333; hhh) SEQ ID NO: 48、121、203、252、302及333; iii) SEQ ID NO: 49、122、204、275、311及381; jjj) SEQ ID NO: 44、123、205、276、311及333; kkk) SEQ ID NO: 50、124、206、277、299及382; lll) SEQ ID NO: 51、77、207、278、294及383; mmm) SEQ ID NO: 52、125、208、240、323及384; nnn) SEQ ID NO: 34、126、209、279、324及385; ooo) SEQ ID NO: 53、127、210、280、294及386; ppp) SEQ ID NO: 54、128、211、281、294及387; qqq) SEQ ID NO: 19、129、212、282、317及342; rrr) SEQ ID NO: 19、130、213、242、295及388; sss) SEQ ID NO: 55、77、214、240、325及389; ttt) SEQ ID NO: 8、77、215、241、326及390; uuu) SEQ ID NO: 56、131、216、283、294及344; vvv) SEQ ID NO: 57、132、217、249、327及333; www) SEQ ID NO: 19、133、218、284、297及391; xxx) SEQ ID NO: 58、79、219、240、294及333; yyy) SEQ ID NO: 19、95、220、285、299及342; zzz) SEQ ID NO: 58、134、221、286、294及392; aaaa) SEQ ID NO: 40、93、222、241、309及393; bbbb) SEQ ID NO: 59、135、223、275、299及344; cccc) SEQ ID NO: 19、136、224、287、302及394; dddd) SEQ ID NO: 60、137、225、288、309及333; eeee) SEQ ID NO: 10、138、226、289、328及395; ffff) SEQ ID NO: 19、139、227、241、329及396; gggg) SEQ ID NO: 1、140、228、241、294及397; hhhh) SEQ ID NO: 61、141、229、241、328及395; iiii) SEQ ID NO: 62、93、230、241、316及362; jjjj) SEQ ID NO: 63、142、231、249、330、361及490; kkkk) SEQ ID NO: 64、143、232、290、299及399; llll) SEQ ID NO: 65、79、233、241、331及400; mmmm) SEQ ID NO: 66、79、234、241、299及401; nnnn) SEQ ID NO: 19、144、235、241、332及371; oooo) SEQ ID NO: 67、145、236、291、330及402; pppp) SEQ ID NO: 19、146、237、292、294及344; qqqq) SEQ ID NO: 68、147、238、241、299及403; rrrr) SEQ ID NO: 69、77、239、293、299及404;及 ssss) SEQ ID NO: 1061、1062及1063。
- 如請求項1之抗體或其抗原結合片段,其中該抗體或其抗原結合片段包含具有與選自SEQ ID NO: 405-498或1060之序列有至少90%、95%、96%、97%、98%、99%或100%同一性之胺基酸序列的重鏈可變區(VH)。
- 如請求項1或2之抗體或其抗原結合片段,其中該抗體或其抗原結合片段包含具有與選自SEQ ID NO: 499-591之序列有至少90%、95%、96%、97%、98%、99%或100%同一性之胺基酸序列之輕鏈可變區(VL)。
- 如請求項2或3之抗體或其抗原結合片段,其中該抗體或其抗原結合片段包含具有與選自SEQ ID NO: 405-498之序列有至少90%、95%、96%、97%、98%、99%或100%同一性之胺基酸序列之VH及具有與選自SEQ ID NO: 499-591之序列有至少90%、95%、96%、97%、98%、99%或100%同一性之胺基酸序列之VL。
- 如請求項2至4中任一項之抗體或其抗原結合片段,其中該VH選自SEQ ID NO: 405、408、448、455及1060,並且該VL選自499、503、542及549。
- 如請求項1之抗體或其抗原結合片段,其中該HCDR1、HCDR2、HCDR3、LCDR1、LCDR2及LCDR3分別包含: a) SEQ ID NO: 1、70、148、240、294、333; b) SEQ ID NO: 5、74、150、242、295、336; c) SEQ ID NO: 40、109、189、240、294、370; d) SEQ ID NO: 43、77、196、270、320、375。
- 如請求項1至6中任一項之抗體或其抗原結合片段,其中該抗體或其抗原結合片段與人類CD8α或CD8β結合。
- 如請求項1至7中任一項之抗體或其抗原結合片段,其中該抗體或其抗原結合片段與由兩條α鏈構成之人類CD8α同源二聚體結合。
- 如請求項1至7中任一項之抗體或其抗原結合片段,其中該抗體或其抗原結合片段與由一條α鏈及一條β鏈構成之人類CD8異源二聚體結合。
- 如請求項1至9中任一項之抗體或其抗原結合片段,其中該抗原結合片段係Fab、Fab'、F(ab')2、Fd、scFv、(scFv) 2、scFv-Fc、sdAb、VHH或Fv片段。
- 如請求項10之抗體或其抗原結合片段,其中該抗原結合片段係scFv。
- 如請求項11之抗體或其抗原結合片段,其中該VH位於該LH之N末端側。
- 如請求項11之抗體或其抗原結合片段,其中該VL位於該VH之N末端側。
- 如請求項11至13中任一項之抗體或其抗原結合片段,其中該scFv包含連接該VH及該VL之接頭。
- 如請求項14之抗體或其抗原結合片段,其中該接頭包含SEQ ID NO: 625-627及645-648所示之胺基酸序列。
- 如請求項1至15中任一項之抗體或其抗原結合片段,其中該抗體或其抗原結合片段以約400nM或更低之K D與人類CD8α或人類CD8β結合。
- 如請求項1至15中任一項之抗體或其抗原結合片段,其中該抗體或其抗原結合片段以約5nM至約500nM之K D與南平頂猴(M. nemestrina) CD8α或南平頂猴CD8β結合。
- 如請求項1至15中任一項之抗體或其抗原結合片段,其中該抗體或其抗原結合片段以約5nM至約500nM之K D與人類CD8α或CD8β結合。
- 一種分離的聚核苷酸,其編碼如請求項1至18中任一項之抗體或其抗原結合片段。
- 一種分離之載體,其包含如請求項19之聚核苷酸。
- 一種分離之宿主細胞,其包含如請求項19之聚核苷酸及/或如請求項20之載體。
- 一種融合蛋白,其包含亨尼帕病毒糖蛋白G(G蛋白)或其生物活性部分以及如請求項1至18中任一項之至少一種抗體或其抗原結合片段,其中該抗體或抗原結合片段與該G蛋白或其生物活性部分之C末端融合。
- 如請求項22之融合蛋白,其中該抗體或其抗原結合片段經由肽接頭與該G蛋白融合。
- 如請求項23之融合蛋白,其中該肽接頭包含長度為至多65個胺基酸之多肽。
- 如請求項22至24中任一項之融合蛋白,其中該肽接頭包含約2至65個胺基酸。
- 如請求項22至25中任一項之融合蛋白,其中該肽接頭包含長度為3個、4個、5個、6個、7個、8個、9個、10個、11個、12個、13個、14個、15個、16個、17個、18個、19個、20個、21個、22個、23個、24個、25個、26個、27個、28個、29個、30個、31個、32個、33個、34個、35個、36個、37個、38個、39個、40個、41個、42個、43個、44個、45個、46個、47個、48個、49個、50個、51個、52個、53個、54個、55個、56個、57個、58個、59個、60個、61個、62個、63個、64個或65個胺基酸之多肽。
- 如請求項22至26中任一項之融合蛋白,其中該肽接頭包含GS、GGS、GGGS (SEQ ID NO: 645)、GGGGS (SEQ ID NO: 626及627)、GGGGGS (SEQ ID NO: 625)或其組合。
- 如請求項22至27中任一項之融合蛋白,其中該肽接頭包含(GGS)n,其中n為1至10。
- 如請求項22至27中任一項之融合蛋白,其中該肽接頭包含(GGS)n,其中n為1、2、3、4、5、6、7、8、9或10。
- 如請求項22至27中任一項之融合蛋白,其中該肽接頭包含(GGGS)n (SEQ ID NO: 645),其中n為1至10。
- 如請求項22至27中任一項之融合蛋白,其中該肽接頭包含(GGGS)n (SEQ ID NO: 645),其中n為1、2、3、4、5、6、7、8、9或10。
- 如請求項22至27中任一項之融合蛋白,其中該肽接頭包含(GGGGS)n (SEQ ID NO: 626),其中n為1至10。
- 如請求項22至27中任一項之融合蛋白,其中該肽接頭包含(GGGGS)n (SEQ ID NO: 626),其中n為1、2、3、4、5、6、7、8、9或10。
- 如請求項22至27中任一項之融合蛋白,其中該肽接頭包含(GGGGGS)n (SEQ ID NO: 27),其中n為1至6。
- 如請求項22至27中任一項之融合蛋白,其中該肽接頭包含(GGGGGS)n (SEQ ID NO: 27),其中n為1、2、3、4、5或6。
- 如請求項22至35中任一項之融合蛋白,其中該抗原結合片段係scFv。
- 如請求項22至36中任一項之融合蛋白,其中該G蛋白或其生物活性部分係野生型尼帕病毒G糖蛋白(NiV-G)或其功能性活性變體或生物活性部分。
- 如請求項22至37中任一項之融合蛋白,其中該NiV-G變體或其生物活性部分包含與SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628有至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少89%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%序列同一性之胺基酸序列。
- 如請求項22至38中任一項之融合蛋白,其中該NiV-G蛋白係生物活性部分,該生物活性部分在野生型NiV-G蛋白SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628之N末端處或附近被截短並且缺乏至多40個連續胺基酸殘基。
- 如請求項22至37中任一項之融合蛋白,其中該NiV-G蛋白係生物活性部分,該生物活性部分在野生型NiV-G之N末端處被截短並且具有SEQ ID NO: 601-606或629-634中任一者所示之序列或者與SEQ ID NO: 601-606或629-634有至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少89%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%序列同一性之胺基酸序列。
- 如請求項22至39中任一項之融合蛋白,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之該N末端處或附近具有5個胺基酸截短。
- 如請求項22至39中任一項之融合蛋白,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之該N末端處或附近具有10個胺基酸截短。
- 如請求項22至39中任一項之融合蛋白,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之該N末端處或附近具有15個胺基酸截短。
- 如請求項22至39中任一項之融合蛋白,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之該N末端處或附近具有20個胺基酸截短。
- 如請求項22至39中任一項之融合蛋白,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之該N末端處或附近具有25個胺基酸截短。
- 如請求項22至39中任一項之融合蛋白,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之該N末端處或附近具有30個胺基酸截短。
- 如請求項22至39中任一項之融合蛋白,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之該N末端處或附近具有34個胺基酸截短。
- 如請求項22至47中任一項之融合蛋白,其中該NiV-G變體或其生物活性部分表現出與肝配蛋白B2或肝配蛋白B3之結合降低。
- 如請求項22至39中任一項之融合蛋白,其中該NiV-G變體或其生物活性部分包含對應於選自參考SEQ ID NO: 618所示之編號的之E501A、W504A、Q530A及E533A之胺基酸取代的一個或多個胺基酸取代。
- 如請求項22至39中任一項之融合蛋白,其中該NiV-G變體或其生物活性部分包含對應於選自參考SEQ ID NO: 618所示之該編號的E501A、W504A、Q530A及E533A之胺基酸取代的胺基酸取代。
- 如請求項22至39中任一項之融合蛋白,其中該NiV-G變體或其生物活性部分包含與SEQ ID NO: 607有至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少89%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%序列同一性之胺基酸序列。
- 如請求項22至39中任一項之融合蛋白,其中該NiV-G變體或其生物活性部分包含與SEQ ID NO: 635有至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少89%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%序列同一性之胺基酸序列。
- 如請求項22至39中任一項之融合蛋白,其中該NiV-G蛋白具有在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之該N末端處或附近之34個胺基酸截短以及對應於選自參考SEQ ID NO: 618所示之編號之E501A、W504A、Q530A及E533A之胺基酸取代之一個或多個胺基酸取代。
- 如請求項22至54中任一項之融合蛋白,其中該蛋白經假型化至慢病毒顆粒上。
- 如請求項22至55中任一項之融合蛋白,其中該抗體或其抗原結合片段與存在於CD8+ T細胞上之細胞表面分子結合。
- 一種病毒載體,其包含: i) 亨尼帕病毒F蛋白分子或其生物活性部分; ii) 亨尼帕病毒包膜糖蛋白G (G蛋白)或其生物活性部分;及 iii) 如請求項1至18中任一項之至少一種抗體或其抗原結合片段, 其中該抗體或其抗原結合片段與該G蛋白或其生物活性部分的C末端連接。
- 如請求項56之病毒載體,其中該抗體或其抗原結合片段結合存在於目標細胞上之細胞表面分子。
- 如請求項57之病毒載體,其中該目標細胞係CD8+ T細胞。
- 如請求項56至58中任一項之病毒載體,其中該抗體或其抗原結合片段結合存在於目標細胞上之抗原或其部分。
- 如請求項56至59中任一項之病毒載體,其中該抗原結合片段係scFv。
- 如請求項56至59中任一項之病毒載體,其中該F蛋白或其生物活性部分係野生型尼帕病毒F(NiV-F)蛋白或其功能性活性變體或生物活性部分。
- 如請求項56至59中任一項之病毒載體,其中該NiV-F蛋白或其功能性活性變體或生物活性部分包含SEQ ID NO: 593所示之胺基酸序列或者與SEQ ID NO: 593有至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少89%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%序列同一性之胺基酸序列。
- 如請求項56至62中任一項之病毒載體,其中該NiV-F蛋白係其生物活性部分,該生物活性部分在該野生型NiV-F蛋白(SEQ ID NO: 593)之C末端處或附近具有20個胺基酸截短。
- 如請求項56至62中任一項之病毒載體,其中該NiV-F蛋白具有與SEQ ID NO: 596有至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少89%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%序列同一性之胺基酸序列。
- 如請求項56至62中任一項之病毒載體,其中該NiV-F蛋白係其生物活性部分,該生物活性部分包含: i) 該野生型NiV-F蛋白(SEQ ID NO: 593)之C末端處或附近之20個胺基酸截短;及 ii) N-連接糖基化位點上之點突變。
- 如請求項56至62中任一項之病毒載體,其中該NiV-F蛋白係其生物活性部分,該生物活性部分在該野生型NiV-F蛋白(SEQ ID NO: 593)之C末端處或附近具有22個胺基酸截短。
- 如請求項66之病毒載體,其中該NiV-F蛋白具有由編碼與SEQ ID NO: 599有至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少89%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%序列同一性之序列之核苷酸序列編碼之胺基酸序列。
- 如請求項57之病毒載體,其中該NiV-F蛋白具有與SEQ ID NO: 613有至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少89%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%序列同一性之胺基酸序列。
- 如請求項56至68中任一項之病毒載體,其中該F蛋白或其生物活性部分包含F1次單元或其融合部分。
- 如請求項69之病毒載體,其中該F1次單元係F0前體之蛋白水解裂解部分。
- 如請求項70之病毒載體,其中該F1次單元包含SEQ ID NO: 595所示之序列或者與SEQ ID NO: 595有至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少9%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%序列同一性之胺基酸序列。
- 如請求項56至71中任一項之病毒載體,其中該G蛋白或其生物活性部分係野生型尼帕病毒G糖蛋白(NiV-G)或其功能性活性變體或生物活性部分。
- 如請求項56至72中任一項之病毒載體,其中該NiV-G變體或其生物活性部分包含與SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628有至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少89%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%序列同一性之胺基酸序列。
- 如請求項56至73中任一項之病毒載體,其中該NiV-G蛋白係生物活性部分,該生物活性部分在該野生型NiV-G蛋白SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628之N末端處或附近被截短並且缺乏至多40個連續胺基酸殘基。
- 如請求項56至72中任一項之病毒載體,其中該NiV-G蛋白係生物活性部分,該生物活性部分在野生型NiV-G之N末端處被截短並且具有SEQ ID NO: 601-606或629-634中任一者所示之序列或者與SEQ ID NO: 601-606或629-634有至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少89%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%序列同一性之胺基酸序列。
- 如請求項56至73中任一項之病毒載體,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有5個胺基酸截短。
- 如請求項56至73中任一項之病毒載體,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有10個胺基酸截短。
- 如請求項56至73中任一項之病毒載體,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有15個胺基酸截短。
- 如請求項56至73中任一項之病毒載體,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有20個胺基酸截短。
- 如請求項56至73中任一項之病毒載體,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有25個胺基酸截短。
- 如請求項56至73中任一項之病毒載體,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有30個胺基酸截短。
- 如請求項56至73中任一項之病毒載體,其中該NiV-G蛋白在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近具有34個胺基酸截短。
- 如請求項56至82中任一項之病毒載體,其中該NiV-G變體或其生物活性部分表現出與肝配蛋白B2或肝配蛋白B3之結合降低。
- 如請求項56至83中任一項之病毒載體,其中該NiV-G變體或其生物活性部分包含對應於選自參考SEQ ID NO: 618所示之編號之E501A、W504A、Q530A及E533A之胺基酸取代之一個或多個胺基酸取代。
- 如請求項56至84中任一項之病毒載體,其中該NiV-G變體或其生物活性部分包含對應於選自參考SEQ ID NO: 618所示之編號之E501A、W504A、Q530A及E533A之胺基酸取代之胺基酸取代。
- 如請求項56至85中任一項之病毒載體,其中該NiV-G變體或其生物活性部分包含與SEQ ID NO: 607有至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少89%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%序列同一性之胺基酸序列。
- 如請求項56至73中任一項之病毒載體,其中該NiV-G變體或其生物活性部分包含與SEQ ID NO: 635有至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少89%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%序列同一性之胺基酸序列。
- 如請求項56至87中任一項之病毒載體,其中該NiV-G蛋白具有在該野生型NiV-G蛋白(SEQ ID NO: 600、SEQ ID NO: 618或SEQ ID NO: 628)之N末端處或附近之34個胺基酸截短以及對應於選自參考SEQ ID NO: 618所示之編號之E501A、W504A、Q530A及E533A之胺基酸取代之一個或多個胺基酸取代。
- 如請求項88之病毒載體,其中該NiV-F蛋白係其生物活性部分,該生物活性部分在該野生型NiV-F蛋白(SEQ ID NO: 593)之C末端處或附近具有22個胺基酸截短。
- 如請求項56至89中任一項之病毒載體,其中該NiV-G變體或其生物活性部分表現出與肝配蛋白B2或肝配蛋白B3之結合降低。
- 如請求項56至90中任一項之病毒載體,其中該病毒載體係慢病毒載體。
- 如請求項56至91中任一項之病毒載體,其中該病毒載體係逆轉錄病毒載體。
- 如請求項56至92中任一項之病毒載體,其中該病毒載體包含除該F蛋白分子及該G蛋白之外的一種或多種病毒組分。
- 如請求項93之病毒載體,其中該一種或多種病毒組分包含選自Gag、Pol、Rev及Tat中的一者或多者之病毒蛋白。
- 如請求項93或94之病毒載體,其中該一種或多種病毒組分包含編碼嵌合抗原受體(CAR)之一種或多種內源性核酸序列。
- 如請求項93或94之病毒載體,其中該一種或多種病毒組分包含編碼T細胞受體(TCR)之一種或多種內源性核酸序列。
- 如請求項94至96中任一項之病毒載體,其中該一種或多種病毒組分包含以下核酸序列中的一者或多者:5' LTR (例如,包含U5並且缺乏功能性U3域)、Psi包裝元件(Psi)、中央聚嘌呤束(cPPT)/中央終止序列(CTS)(例如DNA瓣)、Poly A尾部序列、轉錄後調控元件(例如,WPRE)、Rev反應元件(RRE)及3' LTR (例如,包含U5並且缺乏功能性U3)。
- 一種用於選擇性調節CD8+ T細胞活性之方法,其包含使如請求項56至96中任一項之病毒載體與包含CD8+ T細胞之細胞接觸。
- 一種向個體遞送外源藥劑之方法,其包含向該個體投與如請求項56至96中任一項之病毒載體,其中該病毒載體進一步包含外源藥劑。
- 如請求項99之方法,其中該外源藥劑編碼治療劑或診斷劑。
- 如請求項100之方法,其中該治療劑係嵌合抗原受體(CAR)或T細胞受體(TCR)。
- 如請求項101之方法,其中該CAR靶向選自CD19、CD20、CD22或BCMA之腫瘤抗原。
- 如請求項101或102之方法,其中該CAR包含選自CD137 (4-1BB)信號傳導域、CD28信號傳導域及CD3ζ信號傳導域之一個或多個細胞內域。
- 一種治療個體之癌症之方法,其包含向該個體投與如請求項56至97中任一項之病毒載體,其中該病毒載體進一步包含外源藥劑。
- 如請求項104之方法,其中該外源藥劑編碼治療劑或診斷劑。
- 如請求項105之方法,其中該治療劑係嵌合抗原受體(CAR)或T細胞受體(TCR)。
- 如請求項106之方法,其中該CAR靶向選自CD19、CD20、CD22或BCMA之腫瘤抗原。
- 如請求項106或107之方法,其中該CAR包含選自CD137(4-1BB)信號傳導域、CD28信號傳導域及CD3ζ信號傳導域之一個或多個細胞內域。
- 一種轉導表現CD8之細胞之方法,其包含使該細胞與如請求項56至97中任一項之病毒載體接觸。
- 如請求項109之方法,其中該細胞係CD8+ T細胞。
- 如請求項109或110之方法,其中該病毒載體包含嵌合抗原受體(CAR)或T細胞受體(TCR)。
- 如請求項110或111之方法,其中該CD8+ T細胞不與外源活化藥劑接觸。
- 一種如請求項56至97中任一項之病毒載體用於選擇性調節CD8+ T細胞之活性之用途。
- 一種如請求項56至97中任一項之病毒載體用於選擇性轉導CD8+ T細胞之用途。
- 如請求項56至97中任一項之病毒載體,其用作藥物。
- 一種如請求項56至97中任一項之病毒載體用於基因遞送之用途。
- 如請求項89之用途,其中該病毒載體用於遞送嵌合抗原受體(CAR)或T細胞受體(TCR)。
- 一種如請求項56至97中任一項之病毒載體用於治療B細胞惡性腫瘤之用途,該B細胞惡性腫選自由以下組成之群組:非霍奇金淋巴瘤(NHL)、急性淋巴細胞白血病(ALL)、慢性淋巴細胞白血病(CLL)及多發性骨髓瘤。
- 如請求項98至112中任一項之方法,其中該接觸或投與係藉由使用閉合流體迴路將慢病毒載體離體投與至個體來進行的。
- 如請求項119之方法,其中該離體投與包含: (a) 自個體獲得全血; (b) 收集含有包含T細胞(例如CD8+ T細胞)之白細胞組分的血液部分; (c) 使包含T細胞(例如CD8+ T細胞)之該白細胞組分與包含該慢病毒載體之組合物接觸;以及 (d) 將包含T細胞(例如CD8+ T細胞)之所接觸之白細胞組分再輸注至該個體中,其中步驟(a)至(d)在閉合流體迴路中在線進行。
- 如請求項120之方法,其中步驟(c)中之該接觸不超過24小時、不超過18小時、不超過12小時、不超過6小時、不超過4小時、不超過2小時或不超過1小時。
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WO2022216915A1 (en) | 2022-10-13 |
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