CN111511769A - 免疫调节性融合蛋白 - Google Patents
免疫调节性融合蛋白 Download PDFInfo
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- CN111511769A CN111511769A CN201880075263.5A CN201880075263A CN111511769A CN 111511769 A CN111511769 A CN 111511769A CN 201880075263 A CN201880075263 A CN 201880075263A CN 111511769 A CN111511769 A CN 111511769A
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Abstract
提供了一种融合蛋白例如细胞因子受体融合蛋白如IL‑10捕获蛋白(IL‑10trap),其具有新的连接物序列,以允许所述融合蛋白在功能上最优,例如允许细胞因子受体融合蛋白的细胞因子受体部分最优地结合到它的靶细胞因子。所述融合蛋白或编码所述融合蛋白的表达载体可用于治疗细胞增殖性疾病和病变,包括某些形式的癌症和炎性病变。
Description
与相关申请的交叉引用
本申请要求2017年9月27日提交的美国临时专利申请系列号62/564,145的利益和优先权,所述临时申请整体通过引用并入本文。
技术领域
本发明的领域是分子生物学,具体来说是免疫学和融合蛋白,例如细胞因子受体融合蛋白。
背景技术
细胞因子是一种小型、分泌的细胞信号蛋白,其具有广泛的活性,包括细胞生长和分化的调控和免疫功能的调节。细胞因子、细胞因子受体和某些其他免疫调节蛋白已被用作治疗剂来治疗各种不同的医学病症。然而,这些蛋白的施用例如通过皮下或血管途径的给药,可能引起不适当的细胞和细胞外定位,由此限制了治疗活性和/或提高了毒性风险。
IL-10是一种具有免疫调控性质的同二聚体细胞因子,由包括活化的Th2细胞、B细胞、角化细胞、单核细胞和巨噬细胞在内的多种细胞产生(Moore等,(1993)ANNU.REV.IMMUNOL.11:165)。IL-10抑制包括T细胞、单核细胞和巨噬细胞在内的各种不同细胞的活化和效应功能。具体来说,IL-10抑制细胞因子被例如Th1细胞、自然杀伤细胞、单核细胞和巨噬细胞的多种细胞的合成,包括IL-1、IFN-γ和TNF的合成(Fiorentino等,(1989)J.EXP.MED.170:2081-2095;Fiorentino等,(1991)J.IMMUNOL.146:3444;Hsu等,(1992)INT.IMMUNOL.4:563;Hsu等,(1992)INT.IMMUNOL.4:563;D'Andrea等,(1993)J.EXP.MED.178:1041;de Waal Malefyt等,(1991)J.EXP.MED.174:915;Fiorentino等,(1991)J.IMMUNOL.147:3815)。多种病原体,包括细胞内病原体,都会诱发IL-10的产生,使得所述病原体被免疫系统的有效去除速度被减缓或拖延(Moore等,(1993)同上)。
尽管到目前为止在治疗IL-10介导的障碍中已取得进步,但对治疗这些障碍的改进的疗法仍存在需求。
发明内容
本发明部分是基于改进了融合蛋白的功能的连接物序列的发现,所述融合蛋白例如细胞因子受体融合蛋白,例如IL-10受体(IL-10R)融合蛋白,例如IL-10受体亚基α(IL-10RA)融合蛋白如IL-10捕获蛋白(Trap)。所述连接物序列可以允许融合蛋白(例如细胞因子受体)的配体结合部分最优地结合到配体(例如细胞因子),提供融合蛋白的两个或更多个组分(例如二聚体细胞因子的两个亚基)的时空共定位,优化从表达载体(例如病毒载体)的表达,降低免疫原性,或提供切割位点以允许释放所述融合蛋白的组分。例如,所述连接物序列可以提供足够的柔性,以允许细胞因子受体的配体结合结构域在融合蛋白的背景中采取天然构象,并最小化所述融合蛋白作为治疗剂使用的潜在免疫原性。
一方面,本发明提供了一种分离的融合蛋白,其以N-端到C-端的方向包含例如:细胞因子、细胞因子受体或免疫调节蛋白的细胞外结构域、跨膜结构域或细胞内结构域的第一部分;氨基酸连接物;以及下述至少一者:细胞因子、细胞因子受体或免疫调节蛋白的细胞外结构域、跨膜结构域或细胞内结构域的第二部分;免疫球蛋白(Ig)铰链区;和免疫球蛋白(Ig)Fc结构域。在某些实施方式中,所述连接物包含约5至约40个氨基酸残基。在某些实施方式中,所述融合蛋白包含IL-10受体例如人类IL-10受体例如IL-10RA的一部分。
另一方面,本发明提供了一种分离的融合蛋白,其以N-端到C-端的方向包含:细胞因子受体的细胞外结构域的可溶性部分;氨基酸连接物;免疫球蛋白(Ig)铰链区;和免疫球蛋白(Ig)Fc结构域;其中所述连接物包含约5至约40个氨基酸残基。在某些实施方式中,所述细胞因子受体是IL-10受体例如人类IL-10受体例如IL-10RA。
在任何上述融合蛋白的某些实施方式中,所述氨基酸连接物可以包含例如约5至约15个、约5至约20个、约5至约30个、约10至约15个、约10至约20个、约10至约30个、约10至约40个、约15至约20个、约15至约30个或约15至约40个氨基酸残基。
在任何上述融合蛋白的某些实施方式中,所述氨基酸连接物序列源自于内源人类蛋白,例如IgG1、IgG2、IgG3、IgG4、IgA1、IgA2、IgD、IgE、IgM、白蛋白或酪蛋白。在某些实施方式中,所述氨基酸连接物包含免疫球蛋白(Ig)CH1结构域例如IgG1、IgG2、IgG3、IgG4、IgA1、IgA2、IgD、IgE或IgM CH1结构域的C-端部分。在某些实施方式中,所述氨基酸连接物包含选自SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ IDNO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:53、SEQ ID NO:54和SEQ ID NO:57的氨基酸序列。在某些实施方式中,所述氨基酸连接物包含IgG1 CH1结构域的C-端部分,例如所述氨基酸连接物包含选自SEQ ID NO:1、SEQ ID NO:53、SEQ ID NO:54和SEQ ID NO:57的氨基酸序列,例如SEQ ID NO:57的氨基酸序列。
在任何上述融合蛋白的某些实施方式中,所述氨基酸连接物包含源自于细胞因子、信号分子、免疫调节蛋白或肽或生物活性肽的序列。
在任何上述融合蛋白的某些实施方式中,所述氨基酸连接物包含切割位点例如蛋白水解切割位点,例如被存在于真核细胞的内质网或高尔基体中的蛋白酶切割的蛋白水解切割位点。在某些实施方式中,所述蛋白水解切割位点是弗林蛋白酶切割位点例如包含序列RX1X2R(SEQ ID NO:50)的弗林蛋白酶切割位点,其中X1是任何氨基酸并且X2是Lys或Arg,例如包含序列RAKR(SEQ ID NO:51)的弗林蛋白酶切割位点。在任何上述融合蛋白的某些实施方式中,所述氨基酸连接物在哺乳动物或植物中是蛋白水解稳定的。
在任何上述融合蛋白的某些实施方式中,所述细胞因子受体的细胞外结构域的可溶性部分是人类IL-10R例如IL-10RA的细胞外结构域的可溶性部分。例如,在某些实施方式中,所述细胞因子受体的细胞外结构域的可溶性部分包含SEQ ID NO:12的氨基酸序列或SEQ ID NO:12的第22-229位氨基酸残基。
在任何上述融合蛋白的某些实施方式中,所述融合蛋白包含下述一者或多者:IL-10,TGF-β,TGFβ受体例如TGFβII型受体(TβRII),CD80,CD19,CD20,IL-1,IL-2,IL-3,IL-4,IL-5,IL-6,IL-7,IL-8,IL-9,IL-12B/p40,IL-23A/p19,IL27A/p28,IL-27B/EBI3,IL-15,CD154,CD70,TNF-α,CD86,CD137,CD137L,BORIS/CTCFL,FGF,ICAM,IL-24,GM-CSF,MAGE,NY-ESO-1,血管抑素,内皮抑素,乙酰胆碱,干扰素-γ,DKK1/Wnt,p53,Ox40L,GM-CSF,IL-15受体融合蛋白,GITRL,CD40L,CD70,分泌的鞭毛蛋白,IL-12,胸苷激酶,抗PD-1抗体重链或轻链,抗PD-L1抗体重链或轻链和抗CTLA-4抗体重链或轻链,或其功能性片段。
在任何上述融合蛋白的某些实施方式中,所述Ig铰链区选自IgG1、IgG2、IgG3、IgG4、IgA1、IgA2、IgD、IgE和IgM铰链区,并且所述Ig Fc结构域选自IgG1、IgG2、IgG3、IgG4、IgA1、IgA2、IgD、IgE和IgM Fc结构域。在某些实施方式中,所述Ig铰链区和Fc结构域一起包含选自SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ IDNO:18、SEQ ID NO:19、SEQ ID NO:20和SEQ ID NO:21的氨基酸序列。在某些实施方式中,所述Ig Fc、Ig铰链区和Ig CH1结构域源自于单一免疫球蛋白。
在任何上述融合蛋白的某些实施方式中,所述融合蛋白包含选自SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ IDNO:55、SEQ ID NO:56和SEQ ID NO:58的氨基酸序列。在某些实施方式中,所述融合蛋白包含选自SEQ ID NO:22、SEQ ID NO:55、SEQ ID NO:56和SEQ ID NO:58的氨基酸序列。在某些实施方式中,所述融合蛋白包含SEQ ID NO:58的氨基酸序列。
在任何上述融合蛋白的某些实施方式中,所述融合蛋白包含与选自SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ IDNO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ IDNO:55、SEQ ID NO:56和SEQ ID NO:58的序列具有高于80%、85%、90%、95%、96%、97%、98%或99%序列同一性的氨基酸序列。
另一方面,本发明提供了一种二聚体细胞因子结合蛋白,其包含共价连接在一起的任何上述融合蛋白中的两个,其中每个融合蛋白包含细胞因子受体的细胞外结构域,并且其中所述两个细胞外结构域一起定义了用于细胞因子的结合位点。
另一方面,本发明提供了一种核酸,其包含编码任何上述融合蛋白的核苷酸序列。
另一方面,本发明提供了一种表达载体,其包含任何上述核酸。
另一方面,本发明提供了一种宿主细胞,其包含任何上述表达载体。另一方面,本发明提供了一种生产融合蛋白的方法,所述方法包括将宿主细胞在一定条件下生长以表达所述融合蛋白,和纯化所述融合蛋白。另一方面,本发明提供了一种在靶细胞中表达融合蛋白的方法,所述方法包括将所述细胞暴露于有效量的任何上述表达载体。在某些实施方式中,所述融合蛋白在翻译后被切割成两条多肽链。
另一方面,任何上述融合蛋白或表达载体可用于例如在受试者中降低细胞因子活性,由此治疗由细胞因子例如IL-10介导的各种不同的医学指征。另一方面,任何上述融合蛋白或表达载体可用于在体外和/或体内抑制肿瘤细胞的增殖,在需要的受试者中抑制肿瘤生长,或在需要的受试者中治疗癌症。所述受试者可以是例如动物例如哺乳动物,例如人类如人类幼儿。例如,当施用给患有癌症的人类受试者时,所述融合蛋白或表达载体在所述受试者中抑制或减少肿瘤生长或减轻肿瘤负荷。
在某些实施方式中,所述癌症可以选自黑素瘤、皮肤的鳞状细胞癌、基底细胞癌、头颈癌、乳腺癌、肛门癌、宫颈癌、非小细胞肺癌、间皮瘤、小细胞肺癌、肾细胞癌、前列腺癌、胃食管癌、结肠直肠癌、睾丸癌、膀胱癌、卵巢癌、肝癌、肝细胞癌、胆管癌、脑和中枢神经系统癌症、甲状腺癌、甲状旁腺癌(例如甲状旁腺上皮癌)、子宫内膜癌、神经内分泌癌、淋巴瘤(例如霍奇金和非霍奇金)、白血病、梅克尔细胞癌、胃肠道间质肿瘤、多发性骨髓瘤、子宫癌、肉瘤、肾癌、眼癌、胰腺癌和生殖细胞癌(例如卵巢生殖细胞癌)。在某些实施方式中,所述癌症可以选自白血病、乳腺癌、肺癌、胰腺癌、子宫内膜癌、卵巢癌、前列腺癌、宫颈癌、脑癌、皮肤癌、结肠直肠癌、胃癌、头颈癌和白血病。
在某些实施方式中,所述融合蛋白或表达载体与选自手术、放射线、化疗、免疫疗法、激素疗法和病毒疗法的一种或多种疗法相组合施用。在某些实施方式中,所述融合蛋白或表达载体与淋巴细胞例如T-细胞如CAR T-细胞相组合施用。
任何上述融合蛋白或表达载体也可用于在需要的受试者中治疗炎性病症或感染。
本发明的这些和其他方面和优点通过下面的附图、详细描述和权利要求书进行说明。
附图说明
参考下述附图,本发明可以被更充分地理解。
图1A描绘了细胞表面上的二聚体细胞因子受体(左)、抗体(中)和最优地结合靶细胞因子的受体-Fc融合体(右)的示意图。图1B描绘了受体-Fc融合体例如细胞因子捕获蛋白,其被空间约束而不能最优地结合到靶细胞因子(左)或采取最优结合构型(右)。
图2描绘了人类IgG1、IgG2、IgG3、IgG4、IgA1、IgA2、IgD、IgE和IgM CH1结构域(上)和CH2结构域(下)的氨基酸序列的序列比对。
图3描绘了在按照指示用IL-10和/或IL-10RA融合蛋白IL-10R-IgG和IL-10R-Fc处理报告细胞后磷酸化的Stat3的Western印迹。总Stat3被用作内参。与IL-10R-Fc相比,IL-10活性被IL-10R-IgG显著降低。
详细描述
本发明提供了一种重组融合蛋白,其用于在受试者中治疗各种不同的医学病症,例如用于抑制肿瘤细胞的增殖、抑制肿瘤生长、治疗癌症、治疗炎性病症或治疗感染。示例性的融合蛋白包含:细胞因子、细胞因子受体或免疫调节蛋白的细胞外结构域、跨膜结构域或细胞内结构域的第一部分;氨基酸连接物;以及下述至少一者:细胞因子、细胞因子受体或免疫调节蛋白的细胞外结构域、跨膜结构域或细胞内结构域的第二部分;免疫球蛋白(Ig)铰链区;或免疫球蛋白(Ig)Fc结构域。设想了所述第一和第二部分可以是相同蛋白的部分或不同蛋白的部分,并且即使是相同蛋白,所述第一和第二部分也可以是所述相同蛋白的不同部分。在某些实施方式中,所述连接物包含约5至约40个氨基酸残基。本发明的示例性融合蛋白包括细胞因子捕获蛋白。
细胞因子捕获蛋白例如IL-10捕获蛋白是一种含有细胞因子受体例如IL-10受体(IL-10R)例如IL-10受体α亚基(IL-10RA)的细胞外结构域的可溶性部分的分子,其被设计用于结合或以其他方式螯合靶细胞因子。在细胞因子捕获蛋白中,可以将细胞因子受体的细胞外结构域融合到免疫球蛋白(Ig)铰链区和免疫球蛋白(Ig)Fc结构域,这可以允许例如提高稳定性、Fc效应功能和/或多聚体化例如二聚体化。由融合到Ig铰链区和Ig Fc结构域产生的二聚化对于作为二聚体受体复合物存在于细胞表面上的细胞因子受体例如TβRII来说是特别有利的。
常规的细胞因子捕获蛋白例如IL-10捕获蛋白包含两条多肽链,每条多肽链包含融合到Ig铰链区和Ig Fc结构域的细胞因子受体的细胞外结构域的可溶性部分。所述细胞因子受体的细胞外结构域的可溶性部分通常被直接融合到Ig铰链区,没有任何居间序列。所述两条多肽链通过每个所述Ig铰链区中的半胱氨酸残基之间的二硫键共价连接。每条多肽链提供细胞因子受体例如IL-10R例如IL-10RA的细胞外结构域的可溶性部分,并且所述两个细胞因子受体的细胞外结构域的可溶性部分一起定义了用于细胞因子的结合位点。图1A中描绘了二聚体细胞因子受体、免疫球蛋白(抗体)分子和包含两个共价连接的融合蛋白的二聚体蛋白的示意图,每个所述融合蛋白包含融合到Ig铰链区和Ig Fc结构域的细胞因子受体的细胞外结构域的可溶性部分。
本发明部分是基于下述发现,即包含细胞因子受体的细胞外结构域的可溶性部分与Ig铰链区和Ig Fc结构域的融合蛋白的常规的细胞因子捕获蛋白例如IL-10捕获蛋白,不最优地结合它们的靶细胞因子。例如,常规的IL-10捕获蛋白不在两个IL-10配体结合结构域之间提供足够的柔性以允许所述两个IL-10配体结合结构域一起集合成定义IL-10结合位点的最优构型。
因此,一方面,本发明提供了一种分离的融合蛋白,其以N-端到C-端的方向包含:细胞因子受体的细胞外结构域的可溶性部分;氨基酸连接物;免疫球蛋白(Ig)铰链区;和免疫球蛋白(Ig)Fc结构域;其中所述连接物包含约5至约40个氨基酸残基。所述连接物序列允许例如所述细胞因子受体的细胞外结构域的结合结构域最优地结合到它的靶细胞因子。当细胞因子结合蛋白是由上述两种融合蛋白组成的二聚体时,这一点尤为重要,这些融合蛋白共同定义了结合位点以结合所述靶细胞因子。没有所述连接物时,所述两个结合结构域可能在空间上受到约束而不能形成最优结合位点(图1B)。本发明的各种不同特点和方面将在下文中更详细讨论。
I.融合蛋白
示例性的融合蛋白可以包含:细胞因子、细胞因子受体或免疫调节蛋白的细胞外结构域、跨膜结构域或细胞内结构域的第一部分;氨基酸连接物;以及下述至少一者:细胞因子、细胞因子受体或免疫调节蛋白的细胞外结构域、跨膜结构域或细胞内结构域的第二部分;免疫球蛋白(Ig)铰链区;和免疫球蛋白(Ig)Fc结构域。例如,所公开的融合蛋白可以以N-端到C-端的方向包含:细胞因子受体的细胞外结构域的可溶性部分;氨基酸连接物;免疫球蛋白(Ig)铰链区;和免疫球蛋白(Ig)Fc结构域;其中所述连接物包含约5至约40个氨基酸残基。
示例性的细胞因子包括IL-1α、IL-1β、IL-18、IL-2、IL-4、IL-7、IL-9、IL-13、IL-15、IL-3、IL-5、GM-CSF、IL-6、IL-11、G-CSF、IL-12、LIF、OSM、IL-10、IL-20、IL-14、IL-16、IL-17、IFN-α、IFN-β、IFN-γ、CD154、LT-β、TNF-α、TNF-β、4-1BBL APRIL、CD70、CD153、CD178、GITRL、LIGHT、OX40L、TALL-1、TRAIL、TWEAK、TRANCE、TGF-β1、TGF-β2、TGF-β3、Epo、Tpo、Flt-3L、SCF、M-CSF和MSP。
当在本文中使用时,“免疫调节”蛋白是指调节对象的免疫系统的功能的蛋白质。免疫调节蛋白可以例如调节例如B-细胞、T细胞的功能和/或抗体的生产。示例性的免疫调节蛋白包括检查点抑制剂。示例性的免疫调节蛋白可以包括例如CTLA-4、CD70、IL-2、CD40L、OX40L、IL-12、IL-7、PD-1或PD-L1或调节其活性的任何蛋白质。其他示例性的免疫调节蛋白可以包括抗PD-1抗体或抗PD-L1抗体。
当在本文中使用时,“细胞因子受体的细胞外结构域的可溶性部分”是指细胞因子受体的任何细胞外结构域或细胞因子受体的细胞外结构域的片段,其能够结合到靶细胞因子。应该理解,细胞因子受体的细胞外结构域的可溶性部分也设想了所述细胞外结构域的包含结合结构域的部分,所述结合结构域单独地或与第二个结合结构域(例如在二聚体融合蛋白的情况下)相组合能够结合到靶细胞因子。
示例性的细胞因子受体包括I型细胞因子受体(例如GM-CSF受体、G-CSF受体、I型IL受体、Epo受体、LIF受体、CNTF受体或TPO受体)、II型细胞因子受体(例如IL-10受体、IFN-α受体(例如IFNAR1或IFNAR2)、IFN-β受体、IFN-γ受体(例如IFNGR1或IFNGR2)、趋化因子受体(例如CC趋化因子受体、CXC趋化因子受体、CX3C趋化因子受体或XC趋化因子受体)、肿瘤坏死因子超家族受体(TNFR;例如TNFRSF5/CD40、TNFRSF8/CD30、TNFRSF7/CD27、TNFRSF1A/TNFR1/CD120a或TNFRSF1B/TNFR2/CD120b)、TGFβ超家族受体(例如TGFβI型受体或TGFβII型受体)或免疫球蛋白(Ig)超家族受体(例如白介素-1受体、CSF-1R、PDGFR(例如PDGFRA或PDGFRB)或SCFR)。优选的细胞因子受体包括二聚体细胞因子受体例如TGFβ超家族受体例如人类TGFβII型受体(TβRII)。在某些实施方式中,所述细胞因子受体的细胞外结构域的可溶性部分是人类IL-10R例如人类IL-10RA的细胞外结构域的可溶性部分,例如包含SEQ IDNO:12的氨基酸序列或与SEQ ID NO:12具有高于85%、90%、95%、96%、97%、98%或99%的序列同一性的氨基酸序列,和/或其包含结合到IL-10的结合结构域的片段。
所述细胞因子受体的细胞外结构域的可溶性部分保留了它结合其天然配体的能力。在某些实施方式中,所述细胞外结构域的可溶性部分当与全长细胞因子受体相比时,保留了至少50%、60%、70%、80%、90%或95%的对其天然配体的结合能力。
在某些实施方式中,所述融合蛋白可以包含例如下述一者或多者:TβRII,TGF-β,CD80,CD19,CD20,IL-1,IL-2,IL-3,IL-4,IL-5,IL-6,IL-7,IL-8,IL-9,IL-12B/p40,IL-23A/p19,IL-27A/p28,IL-27B/EBI3,IL-15,CD154,CD70,TNF-α,CD86,CD137,CD137L,BORIS/CTCFL,FGF,ICAM,IL-24,GM-CSF,MAGE,NY-ESO-1,血管抑素,内皮抑素,乙酰胆碱,干扰素-γ,DKK1/Wnt,p53,Ox40L,GM-CSF,IL-15受体融合蛋白,GITRL,CD40L,CD70,分泌的鞭毛蛋白,IL-12,胸苷激酶,抗PD-1抗体重链或轻链,抗PD-L1抗体重链或轻链和抗CTLA-4抗体重链或轻链,或其功能性片段。
当在本文中使用时,术语“免疫球蛋白(Ig)铰链区”是指通常连接免疫球蛋白重链恒定区的CH1和CH2结构域的氨基酸序列。Ig铰链区可能包括例如能够与另一个蛋白链中的半胱氨酸残基形成二硫键的一个或多个半胱氨酸残基。当在本文中使用时,术语“免疫球蛋白(Ig)Fc结构域”是指免疫球蛋白重链恒定区的能够结合到Fc受体的片段。Ig Fc结构域可能包括例如免疫球蛋白(Ig)CH2和CH3结构域。Ig CH1、CH2和CH3结构域之间的边界在本领域中是公知的,并且可以在例如PROSITE数据库(可以在万维网上prosite.expasy.org网站处获得)中找到。为清楚起见,在图2中提供了人类IgG1、IgG2、IgG3、IgG4、IgA1、IgA2、IgD、IgE和IgM CH1和CH2结构域的氨基酸序列的比对。
在某些实施方式中,所述Ig铰链区选自IgG1、IgG2、IgG3、IgG4、IgA1、IgA2、IgD、IgE和IgM铰链区,并且所述Ig Fc结构域选自IgG1、IgG2、IgG3、IgG4、IgA1、IgA2、IgD、IgE和IgM Fc结构域。在某些实施方式中,所述Ig铰链区和Fc结构域一起包含选自SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20和SEQ ID NO:21的氨基酸序列。在某些实施方式中,所述Ig铰链区和Fc结构域一起包含与选自SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ IDNO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20和SEQ ID NO:21的序列具有大于85%、90%、95%、96%、97%、98%或99%同一性的氨基酸序列。
所述氨基酸连接物可以允许融合蛋白的配体结合部分(例如细胞因子受体)最优地结合到配体(例如细胞因子),提供融合蛋白的两种或更多种组分(例如二聚体细胞因子的两个亚基)的时空共定位,优化从表达载体(例如病毒载体)的表达,降低免疫原性,或提供切割位点以允许释放出所述融合蛋白的组分。
所述氨基酸连接物可以包含例如约5至约15个、约5至约20个、约5至约25个、约5至约30个、约5至约35个、约5至约40个、约10至约15个、约10至约20个、约10至约25个、约10至约30个、约10至约35个、约10至约40个、约15至约20个、约15至约25个、约15至约30个、约15至约35个或约15至约40个氨基酸残基。所述连接物中的氨基酸可以是天然存在的氨基酸或修饰的氨基酸。
在某些实施方式中,所述氨基酸连接物序列源自于内源人类蛋白例如IgG1、IgG2、IgG3、IgG4、IgA1、IgA2、IgD、IgE、IgM、白蛋白或酪蛋白。在某些实施方式中,所述氨基酸连接物包含免疫球蛋白(Ig)CH1结构域例如IgG1、IgG2、IgG3、IgG4、IgA1、IgA2、IgD、IgE或IgMCH1结构域的C-端部分,例如约5至约40个氨基酸。在某些实施方式中,所述氨基酸连接物包含选自SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9.SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:53、SEQ ID NO:54、SEQ ID NO:57、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63和SEQ ID NO:64的氨基酸序列。在某些实施方式中,所述氨基酸连接物包含与选自SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ IDNO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9.SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:53、SEQ ID NO:54、SEQ ID NO:57、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ IDNO:62、SEQ ID NO:63和SEQ ID NO:64的氨基酸序列具有高于85%、90%、95%、96%、97%、98%或99%的序列同一性的序列。
蛋白质或多肽如果包含与参比蛋白质或多肽的野生型氨基酸序列的全部或相应部分基本上相似的氨基酸序列,则“源自于”所述参比蛋白质或多肽。在某些实施方式中,源自于野生型蛋白质或多肽的蛋白质或多肽相对于所述野生型蛋白质或多肽可能具有一个或多个氨基酸替换。例如,设想了源自于野生型蛋白质或多肽的蛋白质或多肽可能与所述野生型蛋白质或多肽具有高于70%、75%、80%、85%、90%、95%、96%、97%、98%或99%的序列同一性。此外,设想了源自于野生型蛋白质或多肽的蛋白质或多肽相对于所述野生型蛋白质或多肽可能含有一个或多个保守替换。当在本文中使用时,术语“保守替换”是指结构相似的氨基酸的替换。例如,保守替换可以包括在下述组内的替换:Ser和Cys;Leu、Ile和Val;Glu和Asp;Lys和Arg;Phe、Tyr和Trp;和Gln、Asn、Glu、Asp和His。保守替换也可以通过BLAST(基本局部比对搜索工具(Basic Local Alignment Search Tool))算法、BLOSUM替换矩阵(例如BLOSUM 62矩阵)或PAM替换:p矩阵(例如PAM250矩阵)来确定。
在某些实施方式中,所述氨基酸连接物序列源自于细胞因子、信号分子、免疫调节蛋白或肽或生物活性肽。
进一步考虑的连接物序列包括富含甘氨酸和丝氨酸的连接物例如(G4S)3(SEQ IDNO:49)。其他示例性的连接物序列描述在例如George等,(2003)PROTEIN ENGINEERING 15:871–879和美国专利5,482,858和5,525,491中。
在某些实施方式中,所述氨基酸连接物可以包含切割位点例如蛋白水解或非蛋白水解切割位点。在某些实施方式中,所述蛋白水解切割位点被存在于特定组织、细胞器或细胞内区室中的蛋白酶切割。在某些实施方式中,所述连接物包含蛋白水解切割位点和两个半胱氨酸残基,其在蛋白水解切割后产生二硫键连接。在某些实施方式中,所述蛋白水解切割位点被选自基质金属蛋白酶(MMP)、弗林蛋白酶、PC1、PC2、PC3、组织蛋白酶B、蛋白酶3和半胱天冬酶3的蛋白酶切割。在某些实施方式中,所述切割位点是被存在于真核细胞的内质网或高尔基体中的蛋白酶切割的蛋白水解切割位点。在某些实施方式中,所述蛋白水解切割位点是弗林蛋白酶切割位点。弗林蛋白酶是一种广泛表达并集中在高尔基体的蛋白酶,它识别共有序列RX1X2R(SEQ ID NO:50),其中X1是任何氨基酸并且X2是Lys或Arg,并在最后一个Arg之后切割。弗林蛋白酶在切割通过高尔基体运输的蛋白质的前肽中发挥生物学作用。因此,在某些实施方式中,所述蛋白水解切割位点是包含序列RX1X2R(SEQ ID NO:50)的弗林蛋白酶切割位点,其中X1是任何氨基酸并且X2是Lys或Arg,例如包含序列RAKR(SEQ IDNO:51)的弗林蛋白酶切割位点。
在某些实施方式中,所述Ig Fc、Ig铰链区和Ig CH1结构域源自于单一免疫球蛋白。
在某些实施方式中,所述融合蛋白包含选自SEQ ID NO:22、SEQ ID NO:23、SEQ IDNO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ IDNO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:55、SEQ ID NO:56和SEQID NO:58的氨基酸序列。在某些实施方式中,所公开的融合蛋白包含与选自SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ IDNO:55、SEQ ID NO:56和SEQ ID NO:58的序列具有高于85%、90%、95%、96%、97%、98%或99%的序列同一性的氨基酸序列。
序列同一性可以以本领域技术范围之内的各种不同方式来确定,例如使用可公开获得的计算机软件如BLAST、BLAST-2、ALIGN或Megalign(DNASTAR)软件。使用被程序blastp、blastn、blastx、tblastn和tblastx利用的算法的BLAST(基本局部比对搜索工具(Basic Local Alignment Search Tool))分析(Karlin等,(1990)PROC.NATL.ACAD.SCI.USA87:2264-2268;Altschul,(1993)J.MOL.EVOL.36,290-300;Altschul等,(1997)NUCLEICACIDS RES.25:3389-3402,通过参考并入),被定制用于序列相似性搜索。对于搜索序列数据库中的基本问题的讨论,参见Altschul等,(1994)NATURE GENETICS 6:119-129,其全部通过参考并入。本领域技术人员可以为测量比对,包括为了在待比较的序列的全长上获得最大对齐所需的任何算法,确定适合的参数。用于直方图、描述、比对、期望值(即用于针对数据库序列报告匹配的统计学显著性阈值)、截止值、矩阵和筛选器的搜索参数在缺省设置处。blastp、blastx、tblastn和tblastx使用的缺省评分矩阵是BLOSUM62矩阵(Henikoff等,(1992)PROC.NATL.ACAD.SCI.USA 89:10915-10919,全部通过参考并入)。四个blastn参数可以如下调整:Q=10(空隙生成罚分);R=10(空隙扩展罚分);wink=1(在沿着查询的每个wink.sup.th位置处产生词命中率);和gapw=16(设置在其中产生带有空隙的比对的窗口宽度)。等效的Blastp参数设置可以是Q=9;R=2;wink=1;和gapw=32。搜索也可以使用NCBI(National Center for Biotechnology Information)BLAST高级选项参数来进行(例如:-G,开启空隙的成本[Integer]:default=5(对于核苷酸来说)/11(对于蛋白质来说);-E,扩展空隙的成本[Integer]:default=2(对于核苷酸来说)/1(对于蛋白质来说);-q,核苷酸错配的罚分[Integer]:default=-3;-r,核苷酸匹配的奖励[Integer]:default=1;-e,期望值[Real]:default=10;-W,词长[Integer]:default=11(对于核苷酸来说)/28(对于megablast来说)/3(对于蛋白质来说);-y,以比特为单位的blast延长的衰减(X):default=20(对于blastn来说)/7(对于其他来说);-X,带有空隙的比对(以比特为单位)的X衰减值:default=15(对于所有程序来说),不适用于blastn;和–Z,带有空隙的比对(以比特为单位)的最终X衰减值:50(对于blastn来说),25(对于其他来说))。也可以使用用于成对蛋白质比对的ClustalW(缺省参数可以包括例如Blosum62矩阵和空隙开启罚分=10和空隙扩展罚分=0.1)。可以在GCG软件包10.0版中获得的序列之间的Bestfit比较使用DNA参数GAP=50(空隙生成罚分)和LEN=3(空隙扩展罚分),并且在蛋白质比较中的等效设置是GAP=8和LEN=2。
一方面,本发明提供了一种包含两个融合蛋白的细胞因子结合蛋白,其中每个融合蛋白以N-端到C-端的方向包含:细胞因子受体的细胞外结构域的可溶性部分;氨基酸连接物;免疫球蛋白(Ig)铰链区;和免疫球蛋白(Ig)Fc结构域;其中所述连接物包含约5至约40个氨基酸残基,其中所述两个融合蛋白共价连接在一起,并且其中所述两个细胞外结构域一起定义用于细胞因子的结合位点。
所述细胞因子结合蛋白可以包含共价连接在一起的两个上述融合蛋白,其中每个融合蛋白包含细胞因子受体的细胞外结构域,并且其中所述两个细胞外结构域一起定义用于细胞因子的结合位点。所述融合蛋白可以例如通过每个融合蛋白的Ig铰链区中的半胱氨酸残基之间的二硫键共价连接。在某些实施方式中,所述单体或多聚体(例如二聚体)融合蛋白与天然的全长细胞因子受体相比,保留了至少50%、60%、70%、80%、90%或95%的靶配体结合能力。
在某些实施方式中,本发明的细胞因子结合蛋白以200nM、100nM、20nM、15nM、10nM、9nM、8nM、7nM、6nM、5nM、4nM、3nM、2nM、1nM、50pM、25pM或更低的KD结合细胞因子。在某些实施方式中,本发明的细胞因子结合蛋白以200nM至100nM、200nM至20nM、200nM至10nM、200nM至5nM、200nM至1nM、200nM至50pM、200nM至25pM、100nM至20nM、100nM至10nM、100nM至5nM、100nM至1nM、100nM至50pM、100nM至25pM、20nM至10nM、20nM至5nM、20nM至1nM、20nM至50pM、20nM至25pM、10nM至5nM、10nM至1nM、10nM至50pM、10nM至25pM、5nM至1nM、5nM至50pM、5nM至25pM、1nM至50pM、1nM至25pM或50pM至25pM的KD结合细胞因子。在某些实施方式中,本发明的细胞因子结合蛋白以200nM、100nM、20nM、15nM、10nM、9nM、8nM、7nM、6nM、5nM、4nM、3nM、2nM、1nM、50pM、25pM或更低的KD结合IL-10。在某些实施方式中,本发明的细胞因子结合蛋白以200nM至100nM、200nM至20nM、200nM至10nM、200nM至5nM、200nM至1nM、200nM至50pM、200nM至25pM、100nM至20nM、100nM至10nM、100nM至5nM、100nM至1nM、100nM至50pM、100nM至25pM、20nM至10nM、20nM至5nM、20nM至1nM、20nM至50pM、20nM至25pM、10nM至5nM、10nM至1nM、10nM至50pM、10nM至25pM、5nM至1nM、5nM至50pM、5nM至25pM、1nM至50pM、1nM至25pM或50pM至25pM的KD结合IL-10。KD值可以通过本领域中公知的方法包括表面等离子体共振或生物层干涉测量方法来确定。
本发明的示例性融合蛋白包括包含选自SEQ ID NO:22、SEQ ID NO:23、SEQ IDNO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ IDNO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:55、SEQ ID NO:56和SEQID NO:58的氨基酸序列的蛋白。为清楚起见,这些蛋白质的各个元件的序列和所述各个元件包括细胞因子受体的细胞外结构域的可溶性部分、氨基酸连接物、Ig铰链区和Ig Fc结构域的序列所源自的蛋白质,阐述在表1中。
表1
表2
蛋白质序列 | 核酸序列 |
SEQ ID NO:22 | SEQ ID NO:37 |
SEQ ID NO:23 | SEQ ID NO:38 |
SEQ ID NO:24 | SEQ ID NO:39 |
SEQ ID NO:25 | SEQ ID NO:40 |
SEQ ID NO:26 | SEQ ID NO:41 |
SEQ ID NO:27 | SEQ ID NO:42 |
SEQ ID NO:28 | SEQ ID NO:43 |
SEQ ID NO:29 | SEQ ID NO:44 |
SEQ ID NO:30 | SEQ ID NO:45 |
SEQ ID NO:31 | SEQ ID NO:46 |
SEQ ID NO:32 | SEQ ID NO:47 |
II.融合蛋白生产
用于生产本发明的融合蛋白的方法在本领域中是已知的。例如,编码所公开的融合蛋白的DNA分子可以使用本文中提供的序列信息化学合成。合成的DNA分子可以被连接到其他适合的核苷酸序列,包括例如表达控制序列,以产生编码所需融合蛋白的常规基因表达构建体。生产定义的基因构建体在本领域的常规技术范围之内。编码SEQ ID NO:22-32的融合蛋白的示例性核酸序列SEQ ID NO:37-47,可以在表2中找到。
编码所需融合蛋白的核酸可以被并入(连接)到表达载体中,其可以通过常规的转染或转化技术引入到宿主细胞中。示例性的宿主细胞是大肠杆菌细胞、中华仓鼠卵(CHO)细胞、HeLa细胞、幼仓鼠肾(BHK)细胞、猴肾细胞(COS)、人类肝细胞癌细胞(例如Hep G2)和骨髓瘤细胞。转化的宿主细胞可以在允许所述宿主细胞表达编码所需融合蛋白的基因的条件下生长。
具体的表达和纯化条件将随着所使用的表达系统而变。例如,如果基因将在大肠杆菌中表达,首先通过将所述工程化的基因放置在适合的细菌启动子例如Trp或Tac和原核信号序列的下游,将它克隆在表达载体中。所述表达的分泌蛋白积累在折射或包含体中,并且可以在通过弗氏压碎器或超声处理破碎细胞后收获。然后通过本领域中已知的方法将所述折射体溶解,并将蛋白质重新折叠并切开。
如果所述工程化基因将在真核宿主细胞例如CHO细胞中表达,首先将它插入到含有适合的真核启动子、分泌信号、多聚A序列和终止密码子的表达载体中,并且任选地可以含有增强子和各种不同的内含子。所述基因构建体可以使用常规技术引入到真核宿主细胞中。
包含所公开的融合蛋白的多肽可以通过将用编码这些蛋白的表达载体转染的宿主细胞在允许所述多肽表达的条件下生长(培养)来生产。在表达后,所述多肽可以使用本领域中已知的技术收获并纯化或分离,例如亲和标签如蛋白A、蛋白G、谷胱甘肽-S-转移酶(GST)和组氨酸标签。
III.表达载体
通过将编码感兴趣的融合蛋白的基因并入到适合的表达载体中,可以将所述感兴趣的融合蛋白在感兴趣的细胞中表达。当在本文中使用时,“表达载体”是指包含重组多核苷酸的载体,所述多核苷酸包含可操作连接到待表达的核苷酸序列的表达控制序列。表达载体包含用于表达的足够的顺式作用元件,用于表达的其他元件可以由宿主细胞提供或在体外表达系统中。表达载体包括本领域中已知的所有表达载体,例如并入有感兴趣的重组多核苷酸的粘粒、质粒(例如裸露的或包含在脂质体中)、反转录转座子(例如piggyBac、“睡美人”)和病毒(例如慢病毒、反转录病毒、腺病毒和腺相关病毒)。
在某些实施方式中,所公开的表达载体是病毒载体。术语“病毒载体”和“病毒”在本文中可互换使用,是指没有蛋白质合成或能量产生机制的任何专性细胞内寄生物。病毒基因组可以是RNA或DNA。可用于本发明的实践的病毒包括重组修饰的有包膜或无包膜DNA和RNA病毒,优选地选自杆状病毒科、细小病毒科、小核糖核酸病毒科、疱疹病毒科、痘病毒科或腺病毒科。所述病毒可以通过重组DNA技术修饰以包含外源转入基因的表达,并且可以被工程化改造成复制缺陷型、条件复制型或复制型。利用每个亲本载体性质的有利要素的嵌合病毒载体(参见例如Feng等,(1997)NATURE BIOTECHNOLOGY 15:866-870)也可能在本发明的实践中有用。尽管利用来自于待治疗物种的病毒通常是有利的,但在某些情况下使用源自于具有有利的病原学特征的不同物种的载体可能是有利的。例如,用于人类基因疗法的马疱疹病毒载体描述在PCT公开号WO 98/27216中。所述载体被描述为可用于治疗人类,因为所述马病毒对于人类不致病。同样地,绵羊腺病毒载体可用于人类基因疗法,因为它们据宣称避免了针对人类腺病毒载体的抗体。这些载体描述在PCT公开号WO 97/06826中。
在某些实施方式中,所述病毒载体是腺病毒。腺病毒是中等大小(90-100nm)、无包膜(裸露)、二十面体病毒,由核衣壳和双链线性DNA基因组构成。腺病毒在哺乳动物细胞的核中利用宿主的复制机制来复制。术语“腺病毒”是指腺病毒属中的任何病毒,包括但不限于人类、牛、绵羊、马、狗、猪、鼠和猿猴腺病毒亚属。具体来说,人类腺病毒包括A-F亚属及其个体血清型,所述个体血清型和A-F亚属包括但不限于人类腺病毒1、2、3、4、4a、5、6、7、8、9、10、11(Ad11a和Ad11p)、12、13、14、15、16、17、18、19、19a、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、34a、35、35p、36、37、38、39、40、41、42、43、44、45、46、47、48和91型。优选的是源自于人类腺病毒2和5型的载体。除非另有陈述,否则所有腺病毒5型的核苷酸编号是相对于在本文中在SEQ ID NO:52中描绘的NCBI参比序列AC_000008.1。
腺病毒复制周期具有两个阶段:早期阶段,在此期间4个转录单位(E1、E2、E3和E4)表达;以及晚期阶段,其在病毒DNA合成开始之后发生,并且在此期间晚期转录本主要从主要晚期启动子(MLP)表达。所述晚期信息编码大多数病毒的结构蛋白。E1、E2和E4的基因产物负责转录激活、细胞转化、病毒DNA复制以及其他病毒功能,并且是病毒生长必需的。
术语“可操作连接”是指多核苷酸元件以有功能的关系连接。当核酸序列处于与另一个核酸序列功能上相关时,它是“可操作连接”的。例如,如果启动子或增强子影响基因的转录,则它被可操作连接到所述基因。可操作连接的核苷酸序列通常是毗连的。然而,由于增强子通常在与启动子相隔几千碱基时起作用并且内含子序列可能具有可变的长度,因此某些多核苷酸元件可能是可操作连接的但不直接位于侧翼,并且甚至可能从不同的等位基因或染色体反式起作用。
IV.融合蛋白修饰
当用作治疗剂时,融合蛋白可以被优化(例如亲和力成熟)以改善生物化学特性包括亲和性和/或特异性,改善生物物理性质包括聚集、稳定性、沉淀和/或非特异性相互作用,和/或降低免疫原性。亲和力成熟程序在本领域的常规技术范围之内。例如,可以通过DNA改组、链改组、CDR改组、随机突变和/或定点突变,将多样性引入到所公开的融合蛋白中。
通常,优化的融合蛋白具有与它所源自的未优化的(或亲本)融合蛋白至少相同或基本上相同(例如至少85%、90%、95%、96%、97%、98%或99%)的对配体的亲和性。优选地,优化的融合蛋白与亲本融合蛋白相比时具有更高的对配体的亲和性。
融合蛋白(例如亲本和优化的变体)可以被工程化改造以含有某些具有特定效应功能(例如抗体依赖性细胞毒性(ADCC))的恒定(即Fc)区。人类恒定区在本领域中是已知的。
此外,如果所述融合蛋白被用作治疗剂,可以使用标准的体外偶联化学方法将它缀合到效应剂例如小分子毒素或放射性核素。如果所述效应剂是多肽,则所述抗体可以被化学缀合到所述效应物或作为融合蛋白联结到所述效应物。融合蛋白的构建在本领域的常规技术范围之内。
V.治疗方法
上述融合蛋白或表达载体可用于治疗各种不同的医学指征。在某些实施方式中,上述融合蛋白或表达载体可用于治疗由细胞因子例如IL-10介导的医学指征。例如,所述融合蛋白和表达载体可用于治疗各种不同的癌症或炎性疾病。
当在本文中使用时,“治疗”意味着在对象中,例如在哺乳动物中,例如在人类中治疗疾病。这包括:(a)抑制所述疾病,即制止它的发展;和(b)减轻所述疾病,即引起所述疾病状态的减退。当在本文中使用时,术语“受试者”和“患者”是指将被通过本文描述的方法和组合物治疗的生物体。这些生物体优选地包括但不限于哺乳动物(例如鼠类、猿猴、马科动物、牛科动物、猪科动物、犬科动物、猫科动物等),更优选地包括人类。
在某些实施方式中,本文中公开的融合蛋白和表达载体可用于治疗各种不同的癌症。将癌细胞暴露于治疗有效量的所述融合蛋白或表达载体,以便抑制或减少所述癌细胞的增殖。在某些实施方式中,向癌细胞施用治疗有效量的融合蛋白或表达载体,将所述细胞中的IL-10活性降低至少30%、至少40%、至少50%、至少60%、至少70%、至少80%、至少90%或至少95%。IL-10活性可以通过实施例2中所描述的Western印迹来测定。在某些实施方式中,所公开的融合蛋白或表达载体可用于在受试者(例如人类患者,也被称为人类受试者)中抑制肿瘤生长,这可以通过向所述受试者施用有效量的所述融合蛋白或表达载体来实现。在某些实施方式中,向受试者施用有效量的融合蛋白或表达载体将该对象中的肿瘤负荷降低至少30%、至少40%、至少50%、至少60%、至少70%、至少80%或至少90%。
癌症的实例包括实体肿瘤、软组织肿瘤、造血系肿瘤和转移病变。造血系肿瘤的实例包括白血病、急性白血病、急性成淋巴细胞白血病(ALL)、B-细胞、T-细胞或FAB ALL、急性髓性白血病(AML)、慢性髓细胞性白血病(CML)、慢性淋巴细胞性白血病(CLL)例如转化的CLL、弥漫性大B-细胞淋巴瘤(DLBCL)、滤泡性淋巴瘤、毛细胞白血病、骨髓增生异常综合征(MDS)、淋巴瘤、霍奇金病、恶性淋巴瘤、非霍奇金淋巴瘤、伯基特淋巴瘤、多发性骨髓瘤或莱特尔综合征(莱特尔转化)。实体肿瘤的实例包括各种不同器官系统的恶性肿瘤例如肉瘤、腺癌和上皮癌,例如影响头颈部(包括咽)、甲状腺、肺(小细胞或非小细胞肺癌(NSCLC))、乳腺、淋巴、胃肠(例如口腔、食道、胃、肝、胰腺、小肠、结肠和直肠、肛管)、生殖器和泌尿生殖道(例如肾、尿道上皮、膀胱、卵巢、子宫、宫颈、子宫内膜、前列腺、睾丸)、CNS(例如神经或神经胶质细胞例如成神经细胞瘤或神经胶质瘤)或皮肤(例如黑素瘤)的恶性肿瘤。
在某些实施方式中,所述癌症选自黑素瘤、皮肤的鳞状细胞癌、基底细胞癌、头颈癌、乳腺癌、肛门癌、宫颈癌、非小细胞肺癌、间皮瘤、小细胞肺癌、肾细胞癌、前列腺癌、胃食管癌、结肠直肠癌、睾丸癌、膀胱癌、卵巢癌、肝癌、肝细胞癌、胆管癌、脑和中枢神经系统癌症、甲状腺癌、甲状旁腺癌(例如甲状旁腺上皮癌)、子宫内膜癌、神经内分泌癌、淋巴瘤(例如霍奇金和非霍奇金)、白血病、梅克尔细胞癌、胃肠道间质肿瘤、多发性骨髓瘤、子宫癌、肉瘤、肾癌、眼癌、胰腺癌和生殖细胞癌(例如卵巢生殖细胞癌)。在某些实施方式中,所述癌症可以选自白血病、乳腺癌、肺癌、胰腺癌、子宫内膜癌、卵巢癌、前列腺癌、宫颈癌、脑癌、皮肤癌、结肠直肠癌、胃癌、头颈癌和白血病。在某些实施方式中,所述癌症选自白血病、乳腺癌、宫颈癌、结肠直肠癌、肺癌、胰腺癌、前列腺癌、胃癌、头颈癌、子宫内膜癌和卵巢癌。
在某些实施方式中,本公开的融合蛋白或表达载体在需要的受试者(例如具有炎性病症的受试者)中施用以降低一种或多种细胞因子的水平。在某些实施方式中,所公开的融合蛋白或表达载体可用于在受试者(例如人类受试者)中治疗炎性病症,这可以通过向所述受试者施用有效量的所述融合蛋白或表达载体来实现。
当在本文中使用时,炎性病症是完全或部分地以患者中的炎症或炎性反应为特征的疾病或病症。可以使用本发明的融合蛋白或表达载体治疗的炎性病症可以例如根据受影响的原发组织、所述病症隐含的作用机制或免疫系统的调控错误或过度活跃的部分来表征。在某些实施方式中,可以治疗的炎性病症的实例包括肺的炎症(例如哮喘、成人呼吸窘迫综合征、支气管炎、肺部炎症、肺纤维化和囊性纤维化)、关节的炎症(例如类风湿性关节炎、类风湿性脊椎炎、青少年类风湿性关节炎、骨关节炎、痛风性关节炎和其他关节炎病症)、结缔组织的炎症、眼的炎症(例如葡萄膜炎(包括虹膜炎)、结膜炎、巩膜炎和干燥性角膜结膜炎)、鼻的炎症、肠的炎症(例如克罗恩病、溃疡性结肠炎、炎性肠病、炎性肠综合征和远端直肠炎)、肾的炎症(例如肾小球肾炎、间质性肾炎、狼疮性肾炎、韦格纳氏病继发的肾炎、急性肾炎继发的急性肾衰竭、肺出血肾炎综合征、阻塞后综合征和肾小管缺血)、肝的炎症(例如肝炎(由病毒感染、自体免疫反应、药物治疗、毒素、环境因子引起或作为原发性障碍的继发结果)、肥胖症、胆道闭锁、原发性胆汁性肝硬化和原发性硬化性胆管炎)、皮肤的炎症(例如银屑病、湿疹和皮炎例如湿疹性皮炎、特应性和脂溢性皮炎、过敏性或刺激性接触性皮炎、干裂性湿疹、光过敏性皮炎、光毒性皮炎、植物日光性皮炎、放射性皮炎、和瘀滞性皮炎)、中枢神经系统的炎症(例如多发性硬化症和神经变性疾病例如阿兹海默氏病、帕金森氏症或与HIV感染相关的痴呆症)、血管系统的炎症(例如冠状动脉梗塞损伤、外周血管疾病、心肌炎、脉管炎、狭窄血管再生、动脉粥样硬化和与II型糖尿病相关的血管疾病)、内分泌系统的炎症(例如自体免疫性甲状腺炎(桥本病)、I型糖尿病、与II型糖尿病相关的肝脏和脂肪组织中的炎症和肾上腺皮质的急性和慢性炎症)、心脏的炎症或脂肪组织的炎症。本公开设想了某些炎性病症涉及多种组织中的炎症。此外,本公开设想了某些炎性病症可能落于多个类别中。在某些实施方式中,所述炎性病症是自体免疫疾病。示例性的自体免疫疾病包括但不限于类风湿性关节炎、银屑病(包括斑块型银屑病)、银屑病性关节炎、强直性脊柱炎、溃疡性结肠炎、多发性硬化症、狼疮、秃头症、自体免疫性胰腺炎、乳糜泻、白塞病、库欣综合征和格雷夫病。在某些实施方式中,所述炎性病症是类风湿性障碍。示例性的类风湿性障碍包括但不限于类风湿性关节炎、青少年关节炎、粘液囊炎、脊椎炎、痛风、硬皮病、斯提耳氏病和脉管炎。应该指出,病症的某些类别交叠。例如,类风湿性关节炎是炎性类风湿性障碍、炎性关节障碍和自体免疫障碍。
当在本文中使用时,术语“有效量”是指足以实现有益或所需结果的活性组分的量(例如本发明的融合蛋白或表达载体的量)。有效量可以在一次或多次施用、应用或剂量中施用,并且不打算限于特定配方或施用途径。
在某些实施方式中,融合蛋白的治疗有效量在0.1mg/kg至100mg/kg的范围内,例如1mg/kg至100mg/kg、1mg/kg至10mg/kg、1mg/kg至5mg/kg、10mg/kg、7.5mg/kg、5mg/kg或2.5mg/kg。在某些实施方式中,表达载体例如重组病毒的治疗有效量在102至1015噬斑形成单位(pfu)的范围内,例如102至1010、102至105、105至1015、105至1010或1010至1015噬斑形成单位。施用的量取决于多种变量,例如待治疗的疾病或指征的类型和程度、患者的总体健康、所述融合蛋白或表达载体的体内效能、药物配方和施用途径。初始剂量可以提高到超过上限水平,以便快速获得所需的血液水平或组织水平。或者,初始剂量可以低于最适值,并且可以在治疗过程中逐步提高每日剂量。人类剂量可以例如在被设计从0.5mg/kg运行到20mg/kg的常规I期剂量递增研究中进行优化。给药频率可以随着多种因素而变,例如施用途径、剂量、抗体的血清半衰期和待治疗的疾病。示例性的给药频率是每日一次、每周一次和每两周一次。优选的施用途径是肠胃外,例如静脉内输注。基于融合蛋白或表达载体的药物的配制在本领域的常规技术范围之内。在某些实施方式中,将融合蛋白或表达载体冷冻干燥,然后在施用时在缓冲盐水中重构。
对于治疗使用来说,优选地将融合蛋白或表达载体与可药用载体组合。当在本文中使用时,“可药用载体”意味着适合与人类和动物的组织相接触使用而没有过量毒性、刺激性、过敏反应或其他问题或并发症,与合理的利益/风险比相称的缓冲剂、载体和赋形剂。所述载体在与配方的其他成分相容并且对接受者无害的意义上是“可接受的”。可药用载体包括与药物施用相容的缓冲剂、溶剂、分散介质、包衣、等渗和吸收延迟剂等。这些介质和药剂用于制药活性物质的用途,在本领域中是已知的。
含有本文公开的融合蛋白或表达载体的药物组合物可以以剂量单元形式存在,并且可以通过任何适合的方法制备。药物组合物应该被配制成与它计划的施用途径相容。施用途径的实例是静脉内(IV)、真皮内、吸入、眼内、鼻内、透皮、表面、透粘膜和直肠施用。
融合蛋白的优选施用途径是IV输注。可以通过制药领域中已知的方法来制备本发明的制剂。例如参见《Remington制药学》(Remington's Pharmaceutical Sciences),第18版(Mack Publishing Company,1990)。适合于肠胃外施用的配方组分包括无菌稀释剂例如注射用水、盐水溶液、不挥发油、聚乙二醇、甘油、丙二醇或其他合成溶剂,抗细菌剂例如苯甲醇或对羟基苯甲酸甲酯,抗氧化剂例如抗坏血酸或亚硫酸氢钠,螯合剂例如EDTA,缓冲剂例如乙酸盐、柠檬酸盐或磷酸盐,以及张度调节剂例如氯化钠或右旋糖。
对于静脉内施用,适合的载体包括生理盐水、抑菌水、Cremophor ELTM(BASF,Parsippany,NJ)或磷酸盐缓冲盐水(PBS)。所述载体应该在制造和储存的条件下稳定,并且应该被防腐以对抗微生物。所述载体可以是溶剂或分散介质,其含有例如水、乙醇、多元醇(例如甘油、丙二醇和液体聚乙二醇)及其适合的混合物。
药物配方优选是无菌的。灭菌可以通过任何适合的方法来实现,例如通过无菌过滤膜过滤。在所述组合物被冷冻干燥的情况下,过滤除菌可以在冷冻干燥和重构之前或之后进行。在某些实施方式中,本发明的递送介质(例如重组病毒)和/或治疗剂与检查点抑制剂例如抗CTLA-4抗体、抗PD-1抗体或抗PD-L1抗体相组合施用。示例性的抗PD-1抗体包括例如纳武单抗(Bristol-Myers Squibb Co.)、派姆单抗(MerckSharp&Dohme Corp.)、PDR001(Novartis Pharmaceuticals)和匹迪珠单抗(CT-011,CureTech)。示例性的抗PD-L1抗体包括例如阿特珠单抗(Genentech)、德瓦鲁单抗(AstraZeneca)、MEDI4736、阿维鲁单抗(EMD Serono)和BMS 936559(BristolMyers Squibb Co.)。
当在本文中使用时,术语“相组合”施用被理解为意味着在受试者被所述障碍困扰的过程中将两种(或更多种)不同治疗递送到所述受试者,使得在某个时间点所述治疗对所述受试者的效果重叠。在某些实施方式中,一种治疗的递送在第二种治疗的递送开始时仍在进行,使得在施用方面存在交叠。这在本文中有时被称为“同时”或“并行递送”。在其他实施方式中,一种治疗的递送在另一种治疗的递送开始之前结束。在任一种情况的某些实施方式中,治疗由于组合施用而更加有效。例如,所述第二种治疗更加有效,例如使用更少的第二种治疗观察到等同的效果,或者与第二种治疗在不存在第一种治疗的情况下施用的情形中看到的相比,所述第二种治疗以更大的程度减轻症状,或者在使用所述第一种治疗时观察到类似的情况。在某些实施方式中,递送使得症状或与所述障碍相关的其他参数的降低超过在递送一种治疗而不存在另一种治疗的情况下所观察到的。所述两种治疗的效果可以是部分累加、完全累加或高于累加的。所述递送可以使得当第二种治疗被递送时所递送的第一种治疗的效果仍然可检测。
在整个本说明书中,在组合物、装置和系统被描述为具有、包括或包含特定组分的情况下,或者在过程和方法被描述为具有、包括或包含特定步骤的情况下,设想了此外还存在基本上由所叙述的组分构成或由所叙述的组分构成的本发明的组合物、装置和系统,并且存在基本上由所叙述的过程步骤构成或由所叙述的过程步骤构成的符合本发明的过程和方法。
在本申请中,在要素或组分被称为是包含在所叙述的要素或组分的名单中和/或选自所述名单的情况下,应该理解所述要素或组分可以是所叙述的要素或组分中的任一者,或者所述要素或组分可以选自所叙述的要素或组分中的两者或更多者。
此外,应该理解,本文中描述的组合物或方法的要素和/或特点可以以各种不同的方式组合而不背离本发明的精神和范围,不论在本文中是明确说明还是暗示的。例如,在指称特定病毒的情况下,该病毒可用于本发明的组合物的各种不同实施方式和/或本发明的方法中,除非从上下文另有理解。换句话说,在本申请中,实施方式以能够书写并绘制出清楚且简明的申请的方式进行描述和描绘,但计划并且应该认识到实施方式可以进行各种不同的组合或拆分,而不背离本文的教授和发明。例如,应该认识到本文描述和描绘的所有特点可以适用于本文描述和描绘的本发明的所有方面。
应该理解,表述“中的至少一者”各个地包括在所述表述后叙述的每个物体和所叙述的物体中的两者或更多者的各种不同组合,除非从上下文和使用中另有理解。与三个或更多个叙述物体相结合的表述“和/或”应该被理解为具有相同的意义,除非从上下文另有理解。
术语“包括”、“具有”或“含有”、包括其语法等同语的使用,通常应该被理解为开放式和非限制性的,例如不排除另外的未叙述的要素或步骤,除非从上下文另有具体陈述或理解。
当在数量值之前使用术语“约”时,本发明还包括所述特定数量值本身,除非另有具体陈述。当在本文中使用时,术语“约”是指距标称值±10%的变动,除非另有指示或推断。
应该理解,步骤的顺序或执行某些行动的顺序是不重要的,只要本发明仍然可行即可。此外,两个或更多个步骤或行动可以同时进行。
本文中的任何和所有实例或示例性语言如“例如”或“包括”的使用,仅仅旨在更好地说明本发明,并且除非声明,否则不对本发明的范围构成限制。本说明书中的所有语言都不应该被解释为指示任何未提出权利要求的要素对于本发明的实践来说是必不可少的。
实施例
下面的实施例仅仅是说明性的,并且不打算以任何方式限制本发明的范围或内容。
实施例1:IL-10RA融合蛋白质粒构建
本实施例描述了编码IL-10RA融合蛋白的质粒和病毒表达载体的产生。
编码一系列人类IL-10RA融合蛋白的核苷酸序列被生成。第一种融合蛋白hIL-10R-IgG1(SEQ ID NO:58)包括人类IL-10RA的第1-229位核苷酸残基(结束于SLTRQ),随后紧跟人类IgG1序列的第84-330位残基(始于NVNHK)。第二种融合蛋白hIL-10R-Fc(SEQ IDNO:48)包括人类IL-10RA的第1-235位残基(结束于FTVTN),随后紧跟人类IgG1的第104-324位残基(始于DKTHT)。所述融合蛋白的详细情况示出在表3中。
表3
视情况而定将编码所述融合蛋白的核苷酸序列克隆到质粒中,用于下游应用。具体来说,产生了不表达转入基因、表达hIL-10R-IgG1或hIL-10RA-Fc的重组腺病毒载体。
实施例2:IL-10R融合蛋白活性
将A549细胞(人类肺癌细胞)用实施例1中所述不表达转入基因、表达hIL-10R-IgG1或hIL-10RA-Fc的病毒载体以10MOI感染并培养四天。收集来自于所述细胞培养的调制培养基,并将THP-1细胞(人类白血病单核细胞)以5×106个细胞/ml悬浮在所述调制培养基中。将细胞用50ng/ml的人类IL-10在37℃下处理30分钟,或保持原样作为对照。为了测定IL-10活性,将来自于THP-1细胞的提取的细胞内蛋白通过Western印迹探测磷酸化的Stat3。使用总Stat3作为内参。
在来自于用不表达转入基因或表达hIL-10RA-Fc的病毒载体感染的细胞的调制培养基中培养的THP-1细胞中,IL-10诱导Stat3磷酸化。然而,在来自于用表达hIL10R-IgG的病毒感染的细胞的调制培养基中培养的THP-1细胞中,IL-10不诱导Stat3磷酸化。这些结果证实了hIL-10R-IgG1融合蛋白阻断IL-10活化Stat3信号传导级联。
通过参考并入
本文中提高的每个专利文献和科学论文的全部公开内容,为所有目的通过参考并入本文。
等同性
本发明可以以其他特定形式体现而不背离其精神或本质特征。因此,上述实施方式在所有情况下被认为是对本文描述的发明的说明而不是限制。因此,本发明的范围由随附的权利要求书而不是上述描述来指明,并且打算将进入权利要求书的意义和等同性范围之内的所有改变都涵盖在其中。
序列表
<110> 埃皮辛特瑞柯斯公司(EpicentRx, Inc.)
<120> 免疫调节性融合蛋白
<130> AJ4309PT2007
<150> US 62/564,145
<151> 2017-09-27
<160> 64
<170> PatentIn version 3.5
<210> 1
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 1
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
1 5 10
<210> 2
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 2
Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu
1 5 10
<210> 3
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 3
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
1 5 10
<210> 4
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 4
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
1 5 10
<210> 5
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 5
Val Lys His Tyr Thr Asn Pro Ser Gln Asp Val Thr
1 5 10
<210> 6
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 6
Val Lys His Tyr Thr Asn Pro Ser Gln Asp Val Thr
1 5 10
<210> 7
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<400> 7
Thr Ala Ser Lys Ser Lys Lys Glu Ile Phe
1 5 10
<210> 8
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 8
Thr Pro Ser Ser Thr Asp Trp Val Asp Asn Lys Thr Phe Ser
1 5 10
<210> 9
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 9
Val Gln His Pro Asn Gly Asn Lys Glu Lys Asn Val Pro
1 5 10
<210> 10
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 10
Val Gln His Pro Asn Gly Asn Lys Glu Lys Asn Val Pro
1 5 10
<210> 11
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 11
Arg Glu Lys Gln Thr Asp Glu Ile Lys Asp Thr Arg
1 5 10
<210> 12
<211> 229
<212> PRT
<213> 智人(Homo sapiens)
<400> 12
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln
225
<210> 13
<211> 231
<212> PRT
<213> 智人(Homo sapiens)
<400> 13
Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
1 5 10 15
Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
20 25 30
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
35 40 45
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
50 55 60
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
65 70 75 80
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
85 90 95
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
100 105 110
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
115 120 125
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys
130 135 140
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
145 150 155 160
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
165 170 175
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
180 185 190
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
195 200 205
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
210 215 220
Leu Ser Leu Ser Pro Gly Lys
225 230
<210> 14
<211> 227
<212> PRT
<213> 智人(Homo sapiens)
<400> 14
Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
20 25 30
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Lys
225
<210> 15
<211> 278
<212> PRT
<213> 智人(Homo sapiens)
<400> 15
Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys Pro
1 5 10 15
Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu
20 25 30
Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu Pro
35 40 45
Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Ala Pro Glu
50 55 60
Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
65 70 75 80
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
85 90 95
Val Ser His Glu Asp Pro Glu Val Gln Phe Lys Trp Tyr Val Asp Gly
100 105 110
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
115 120 125
Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
130 135 140
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
145 150 155 160
Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu
165 170 175
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
180 185 190
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
195 200 205
Ala Val Glu Trp Glu Ser Ser Gly Gln Pro Glu Asn Asn Tyr Asn Thr
210 215 220
Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
225 230 235 240
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Ile Phe Ser Cys
245 250 255
Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser Leu
260 265 270
Ser Leu Ser Pro Gly Lys
275
<210> 16
<211> 228
<212> PRT
<213> 智人(Homo sapiens)
<400> 16
Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro Ala Pro Glu Phe Leu
1 5 10 15
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
20 25 30
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
35 40 45
Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
50 55 60
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
65 70 75 80
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
85 90 95
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser
100 105 110
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
115 120 125
Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val
130 135 140
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
145 150 155 160
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
165 170 175
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr
180 185 190
Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val
195 200 205
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
210 215 220
Ser Leu Gly Lys
225
<210> 17
<211> 255
<212> PRT
<213> 智人(Homo sapiens)
<400> 17
Val Pro Cys Pro Val Pro Ser Thr Pro Pro Thr Pro Ser Pro Ser Thr
1 5 10 15
Pro Pro Thr Pro Ser Pro Ser Cys Cys His Pro Arg Leu Ser Leu His
20 25 30
Arg Pro Ala Leu Glu Asp Leu Leu Leu Gly Ser Glu Ala Asn Leu Thr
35 40 45
Cys Thr Leu Thr Gly Leu Arg Asp Ala Ser Gly Val Thr Phe Thr Trp
50 55 60
Thr Pro Ser Ser Gly Lys Ser Ala Val Gln Gly Pro Pro Glu Arg Asp
65 70 75 80
Leu Cys Gly Cys Tyr Ser Val Ser Ser Val Leu Pro Gly Cys Ala Glu
85 90 95
Pro Trp Asn His Gly Lys Thr Phe Thr Cys Thr Ala Ala Tyr Pro Glu
100 105 110
Ser Lys Thr Pro Leu Thr Ala Thr Leu Ser Lys Ser Gly Asn Thr Phe
115 120 125
Arg Pro Glu Val His Leu Leu Pro Pro Pro Ser Glu Glu Leu Ala Leu
130 135 140
Asn Glu Leu Val Thr Leu Thr Cys Leu Ala Arg Gly Phe Ser Pro Lys
145 150 155 160
Asp Val Leu Val Arg Trp Leu Gln Gly Ser Gln Glu Leu Pro Arg Glu
165 170 175
Lys Tyr Leu Thr Trp Ala Ser Arg Gln Glu Pro Ser Gln Gly Thr Thr
180 185 190
Thr Phe Ala Val Thr Ser Ile Leu Arg Val Ala Ala Glu Asp Trp Lys
195 200 205
Lys Gly Asp Thr Phe Ser Cys Met Val Gly His Glu Ala Leu Pro Leu
210 215 220
Ala Phe Thr Gln Lys Thr Ile Asp Arg Leu Ala Gly Lys Pro Thr His
225 230 235 240
Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly Thr Cys Tyr
245 250 255
<210> 18
<211> 242
<212> PRT
<213> 智人(Homo sapiens)
<400> 18
Val Pro Cys Pro Val Pro Pro Pro Pro Pro Cys Cys His Pro Arg Leu
1 5 10 15
Ser Leu His Arg Pro Ala Leu Glu Asp Leu Leu Leu Gly Ser Glu Ala
20 25 30
Asn Leu Thr Cys Thr Leu Thr Gly Leu Arg Asp Ala Ser Gly Ala Thr
35 40 45
Phe Thr Trp Thr Pro Ser Ser Gly Lys Ser Ala Val Gln Gly Pro Pro
50 55 60
Glu Arg Asp Leu Cys Gly Cys Tyr Ser Val Ser Ser Val Leu Pro Gly
65 70 75 80
Cys Ala Gln Pro Trp Asn His Gly Glu Thr Phe Thr Cys Thr Ala Ala
85 90 95
His Pro Glu Leu Lys Thr Pro Leu Thr Ala Asn Ile Thr Lys Ser Gly
100 105 110
Asn Thr Phe Arg Pro Glu Val His Leu Leu Pro Pro Pro Ser Glu Glu
115 120 125
Leu Ala Leu Asn Glu Leu Val Thr Leu Thr Cys Leu Ala Arg Gly Phe
130 135 140
Ser Pro Lys Asp Val Leu Val Arg Trp Leu Gln Gly Ser Gln Glu Leu
145 150 155 160
Pro Arg Glu Lys Tyr Leu Thr Trp Ala Ser Arg Gln Glu Pro Ser Gln
165 170 175
Gly Thr Thr Thr Phe Ala Val Thr Ser Ile Leu Arg Val Ala Ala Glu
180 185 190
Asp Trp Lys Lys Gly Asp Thr Phe Ser Cys Met Val Gly His Glu Ala
195 200 205
Leu Pro Leu Ala Phe Thr Gln Lys Thr Ile Asp Arg Met Ala Gly Lys
210 215 220
Pro Thr His Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly Thr
225 230 235 240
Cys Tyr
<210> 19
<211> 286
<212> PRT
<213> 智人(Homo sapiens)
<400> 19
Arg Trp Pro Glu Ser Pro Lys Ala Gln Ala Ser Ser Val Pro Thr Ala
1 5 10 15
Gln Pro Gln Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Pro Ala
20 25 30
Thr Thr Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Lys Glu Lys
35 40 45
Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro
50 55 60
Ser His Thr Gln Pro Leu Gly Val Tyr Leu Leu Thr Pro Ala Val Gln
65 70 75 80
Asp Leu Trp Leu Arg Asp Lys Ala Thr Phe Thr Cys Phe Val Val Gly
85 90 95
Ser Asp Leu Lys Asp Ala His Leu Thr Trp Glu Val Ala Gly Lys Val
100 105 110
Pro Thr Gly Gly Val Glu Glu Gly Leu Leu Glu Arg His Ser Asn Gly
115 120 125
Ser Gln Ser Gln His Ser Arg Leu Thr Leu Pro Arg Ser Leu Trp Asn
130 135 140
Ala Gly Thr Ser Val Thr Cys Thr Leu Asn His Pro Ser Leu Pro Pro
145 150 155 160
Gln Arg Leu Met Ala Leu Arg Glu Pro Ala Ala Gln Ala Pro Val Lys
165 170 175
Leu Ser Leu Asn Leu Leu Ala Ser Ser Asp Pro Pro Glu Ala Ala Ser
180 185 190
Trp Leu Leu Cys Glu Val Ser Gly Phe Ser Pro Pro Asn Ile Leu Leu
195 200 205
Met Trp Leu Glu Asp Gln Arg Glu Val Asn Thr Ser Gly Phe Ala Pro
210 215 220
Ala Arg Pro Pro Pro Gln Pro Gly Ser Thr Thr Phe Trp Ala Trp Ser
225 230 235 240
Val Leu Arg Val Pro Ala Pro Pro Ser Pro Gln Pro Ala Thr Tyr Thr
245 250 255
Cys Val Val Ser His Glu Asp Ser Arg Thr Leu Leu Asn Ala Ser Arg
260 265 270
Ser Leu Glu Val Ser Tyr Val Thr Asp His Gly Pro Met Lys
275 280 285
<210> 20
<211> 325
<212> PRT
<213> 智人(Homo sapiens)
<400> 20
Val Cys Ser Arg Asp Phe Thr Pro Pro Thr Val Lys Ile Leu Gln Ser
1 5 10 15
Ser Cys Asp Gly Gly Gly His Phe Pro Pro Thr Ile Gln Leu Leu Cys
20 25 30
Leu Val Ser Gly Tyr Thr Pro Gly Thr Ile Asn Ile Thr Trp Leu Glu
35 40 45
Asp Gly Gln Val Met Asp Val Asp Leu Ser Thr Ala Ser Thr Thr Gln
50 55 60
Glu Gly Glu Leu Ala Ser Thr Gln Ser Glu Leu Thr Leu Ser Gln Lys
65 70 75 80
His Trp Leu Ser Asp Arg Thr Tyr Thr Cys Gln Val Thr Tyr Gln Gly
85 90 95
His Thr Phe Glu Asp Ser Thr Lys Lys Cys Ala Asp Ser Asn Pro Arg
100 105 110
Gly Val Ser Ala Tyr Leu Ser Arg Pro Ser Pro Phe Asp Leu Phe Ile
115 120 125
Arg Lys Ser Pro Thr Ile Thr Cys Leu Val Val Asp Leu Ala Pro Ser
130 135 140
Lys Gly Thr Val Asn Leu Thr Trp Ser Arg Ala Ser Gly Lys Pro Val
145 150 155 160
Asn His Ser Thr Arg Lys Glu Glu Lys Gln Arg Asn Gly Thr Leu Thr
165 170 175
Val Thr Ser Thr Leu Pro Val Gly Thr Arg Asp Trp Ile Glu Gly Glu
180 185 190
Thr Tyr Gln Cys Arg Val Thr His Pro His Leu Pro Arg Ala Leu Met
195 200 205
Arg Ser Thr Thr Lys Thr Ser Gly Pro Arg Ala Ala Pro Glu Val Tyr
210 215 220
Ala Phe Ala Thr Pro Glu Trp Pro Gly Ser Arg Asp Lys Arg Thr Leu
225 230 235 240
Ala Cys Leu Ile Gln Asn Phe Met Pro Glu Asp Ile Ser Val Gln Trp
245 250 255
Leu His Asn Glu Val Gln Leu Pro Asp Ala Arg His Ser Thr Thr Gln
260 265 270
Pro Arg Lys Thr Lys Gly Ser Gly Phe Phe Val Phe Ser Arg Leu Glu
275 280 285
Val Thr Arg Ala Glu Trp Glu Gln Lys Asp Glu Phe Ile Cys Arg Ala
290 295 300
Val His Glu Ala Ala Ser Pro Ser Gln Thr Val Gln Arg Ala Val Ser
305 310 315 320
Val Asn Pro Gly Lys
325
<210> 21
<211> 351
<212> PRT
<213> 智人(Homo sapiens)
<400> 21
Leu Pro Val Ile Ala Glu Leu Pro Pro Lys Val Ser Val Phe Val Pro
1 5 10 15
Pro Arg Asp Gly Phe Phe Gly Asn Pro Arg Lys Ser Lys Leu Ile Cys
20 25 30
Gln Ala Thr Gly Phe Ser Pro Arg Gln Ile Gln Val Ser Trp Leu Arg
35 40 45
Glu Gly Lys Gln Val Gly Ser Gly Val Thr Thr Asp Gln Val Gln Ala
50 55 60
Glu Ala Lys Glu Ser Gly Pro Thr Thr Tyr Lys Val Thr Ser Thr Leu
65 70 75 80
Thr Ile Lys Glu Ser Asp Trp Leu Ser Gln Ser Met Phe Thr Cys Arg
85 90 95
Val Asp His Arg Gly Leu Thr Phe Gln Gln Asn Ala Ser Ser Met Cys
100 105 110
Val Pro Asp Gln Asp Thr Ala Ile Arg Val Phe Ala Ile Pro Pro Ser
115 120 125
Phe Ala Ser Ile Phe Leu Thr Lys Ser Thr Lys Leu Thr Cys Leu Val
130 135 140
Thr Asp Leu Thr Thr Tyr Asp Ser Val Thr Ile Ser Trp Thr Arg Gln
145 150 155 160
Asn Gly Glu Ala Val Lys Thr His Thr Asn Ile Ser Glu Ser His Pro
165 170 175
Asn Ala Thr Phe Ser Ala Val Gly Glu Ala Ser Ile Cys Glu Asp Asp
180 185 190
Trp Asn Ser Gly Glu Arg Phe Thr Cys Thr Val Thr His Thr Asp Leu
195 200 205
Pro Ser Pro Leu Lys Gln Thr Ile Ser Arg Pro Lys Gly Val Ala Leu
210 215 220
His Arg Pro Asp Val Tyr Leu Leu Pro Pro Ala Arg Glu Gln Leu Asn
225 230 235 240
Leu Arg Glu Ser Ala Thr Ile Thr Cys Leu Val Thr Gly Phe Ser Pro
245 250 255
Ala Asp Val Phe Val Gln Trp Met Gln Arg Gly Gln Pro Leu Ser Pro
260 265 270
Glu Lys Tyr Val Thr Ser Ala Pro Met Pro Glu Pro Gln Ala Pro Gly
275 280 285
Arg Tyr Phe Ala His Ser Ile Leu Thr Val Ser Glu Glu Glu Trp Asn
290 295 300
Thr Gly Glu Thr Tyr Thr Cys Val Val Ala His Glu Ala Leu Pro Asn
305 310 315 320
Arg Val Thr Glu Arg Thr Val Asp Lys Ser Thr Gly Lys Pro Thr Leu
325 330 335
Tyr Asn Val Ser Leu Val Met Ser Asp Thr Ala Gly Thr Cys Tyr
340 345 350
<210> 22
<211> 472
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 22
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val
225 230 235 240
Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
245 250 255
Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
260 265 270
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
275 280 285
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
290 295 300
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
305 310 315 320
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
325 330 335
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
340 345 350
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
355 360 365
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr
370 375 380
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
385 390 395 400
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
405 410 415
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
420 425 430
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
435 440 445
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
450 455 460
Ser Leu Ser Leu Ser Pro Gly Lys
465 470
<210> 23
<211> 468
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 23
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val
225 230 235 240
Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val
245 250 255
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
260 265 270
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
275 280 285
His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
290 295 300
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
305 310 315 320
Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn
325 330 335
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro
340 345 350
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln
355 360 365
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
370 375 380
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ser Val
385 390 395 400
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
405 410 415
Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
420 425 430
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
435 440 445
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
450 455 460
Ser Pro Gly Lys
465
<210> 24
<211> 519
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 24
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val
225 230 235 240
Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys
245 250 255
Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro
260 265 270
Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu
275 280 285
Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Ala Pro
290 295 300
Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
305 310 315 320
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
325 330 335
Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Lys Trp Tyr Val Asp
340 345 350
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
355 360 365
Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
370 375 380
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
385 390 395 400
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg
405 410 415
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys
420 425 430
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
435 440 445
Ile Ala Val Glu Trp Glu Ser Ser Gly Gln Pro Glu Asn Asn Tyr Asn
450 455 460
Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
465 470 475 480
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Ile Phe Ser
485 490 495
Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser
500 505 510
Leu Ser Leu Ser Pro Gly Lys
515
<210> 25
<211> 469
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 25
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val
225 230 235 240
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro Ala Pro Glu Phe
245 250 255
Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
260 265 270
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
275 280 285
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val
290 295 300
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser
305 310 315 320
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
325 330 335
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser
340 345 350
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
355 360 365
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln
370 375 380
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
385 390 395 400
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
405 410 415
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu
420 425 430
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser
435 440 445
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
450 455 460
Leu Ser Leu Gly Lys
465
<210> 26
<211> 496
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 26
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Val Lys His Tyr Thr Asn Pro Ser Gln Asp Val
225 230 235 240
Thr Val Pro Cys Pro Val Pro Ser Thr Pro Pro Thr Pro Ser Pro Ser
245 250 255
Thr Pro Pro Thr Pro Ser Pro Ser Cys Cys His Pro Arg Leu Ser Leu
260 265 270
His Arg Pro Ala Leu Glu Asp Leu Leu Leu Gly Ser Glu Ala Asn Leu
275 280 285
Thr Cys Thr Leu Thr Gly Leu Arg Asp Ala Ser Gly Val Thr Phe Thr
290 295 300
Trp Thr Pro Ser Ser Gly Lys Ser Ala Val Gln Gly Pro Pro Glu Arg
305 310 315 320
Asp Leu Cys Gly Cys Tyr Ser Val Ser Ser Val Leu Pro Gly Cys Ala
325 330 335
Glu Pro Trp Asn His Gly Lys Thr Phe Thr Cys Thr Ala Ala Tyr Pro
340 345 350
Glu Ser Lys Thr Pro Leu Thr Ala Thr Leu Ser Lys Ser Gly Asn Thr
355 360 365
Phe Arg Pro Glu Val His Leu Leu Pro Pro Pro Ser Glu Glu Leu Ala
370 375 380
Leu Asn Glu Leu Val Thr Leu Thr Cys Leu Ala Arg Gly Phe Ser Pro
385 390 395 400
Lys Asp Val Leu Val Arg Trp Leu Gln Gly Ser Gln Glu Leu Pro Arg
405 410 415
Glu Lys Tyr Leu Thr Trp Ala Ser Arg Gln Glu Pro Ser Gln Gly Thr
420 425 430
Thr Thr Phe Ala Val Thr Ser Ile Leu Arg Val Ala Ala Glu Asp Trp
435 440 445
Lys Lys Gly Asp Thr Phe Ser Cys Met Val Gly His Glu Ala Leu Pro
450 455 460
Leu Ala Phe Thr Gln Lys Thr Ile Asp Arg Leu Ala Gly Lys Pro Thr
465 470 475 480
His Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly Thr Cys Tyr
485 490 495
<210> 27
<211> 483
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 27
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Val Lys His Tyr Thr Asn Pro Ser Gln Asp Val
225 230 235 240
Thr Val Pro Cys Pro Val Pro Pro Pro Pro Pro Cys Cys His Pro Arg
245 250 255
Leu Ser Leu His Arg Pro Ala Leu Glu Asp Leu Leu Leu Gly Ser Glu
260 265 270
Ala Asn Leu Thr Cys Thr Leu Thr Gly Leu Arg Asp Ala Ser Gly Ala
275 280 285
Thr Phe Thr Trp Thr Pro Ser Ser Gly Lys Ser Ala Val Gln Gly Pro
290 295 300
Pro Glu Arg Asp Leu Cys Gly Cys Tyr Ser Val Ser Ser Val Leu Pro
305 310 315 320
Gly Cys Ala Gln Pro Trp Asn His Gly Glu Thr Phe Thr Cys Thr Ala
325 330 335
Ala His Pro Glu Leu Lys Thr Pro Leu Thr Ala Asn Ile Thr Lys Ser
340 345 350
Gly Asn Thr Phe Arg Pro Glu Val His Leu Leu Pro Pro Pro Ser Glu
355 360 365
Glu Leu Ala Leu Asn Glu Leu Val Thr Leu Thr Cys Leu Ala Arg Gly
370 375 380
Phe Ser Pro Lys Asp Val Leu Val Arg Trp Leu Gln Gly Ser Gln Glu
385 390 395 400
Leu Pro Arg Glu Lys Tyr Leu Thr Trp Ala Ser Arg Gln Glu Pro Ser
405 410 415
Gln Gly Thr Thr Thr Phe Ala Val Thr Ser Ile Leu Arg Val Ala Ala
420 425 430
Glu Asp Trp Lys Lys Gly Asp Thr Phe Ser Cys Met Val Gly His Glu
435 440 445
Ala Leu Pro Leu Ala Phe Thr Gln Lys Thr Ile Asp Arg Met Ala Gly
450 455 460
Lys Pro Thr His Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly
465 470 475 480
Thr Cys Tyr
<210> 28
<211> 525
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 28
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Thr Ala Ser Lys Ser Lys Lys Glu Ile Phe Arg
225 230 235 240
Trp Pro Glu Ser Pro Lys Ala Gln Ala Ser Ser Val Pro Thr Ala Gln
245 250 255
Pro Gln Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Pro Ala Thr
260 265 270
Thr Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Lys Glu Lys Glu
275 280 285
Lys Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro Ser
290 295 300
His Thr Gln Pro Leu Gly Val Tyr Leu Leu Thr Pro Ala Val Gln Asp
305 310 315 320
Leu Trp Leu Arg Asp Lys Ala Thr Phe Thr Cys Phe Val Val Gly Ser
325 330 335
Asp Leu Lys Asp Ala His Leu Thr Trp Glu Val Ala Gly Lys Val Pro
340 345 350
Thr Gly Gly Val Glu Glu Gly Leu Leu Glu Arg His Ser Asn Gly Ser
355 360 365
Gln Ser Gln His Ser Arg Leu Thr Leu Pro Arg Ser Leu Trp Asn Ala
370 375 380
Gly Thr Ser Val Thr Cys Thr Leu Asn His Pro Ser Leu Pro Pro Gln
385 390 395 400
Arg Leu Met Ala Leu Arg Glu Pro Ala Ala Gln Ala Pro Val Lys Leu
405 410 415
Ser Leu Asn Leu Leu Ala Ser Ser Asp Pro Pro Glu Ala Ala Ser Trp
420 425 430
Leu Leu Cys Glu Val Ser Gly Phe Ser Pro Pro Asn Ile Leu Leu Met
435 440 445
Trp Leu Glu Asp Gln Arg Glu Val Asn Thr Ser Gly Phe Ala Pro Ala
450 455 460
Arg Pro Pro Pro Gln Pro Gly Ser Thr Thr Phe Trp Ala Trp Ser Val
465 470 475 480
Leu Arg Val Pro Ala Pro Pro Ser Pro Gln Pro Ala Thr Tyr Thr Cys
485 490 495
Val Val Ser His Glu Asp Ser Arg Thr Leu Leu Asn Ala Ser Arg Ser
500 505 510
Leu Glu Val Ser Tyr Val Thr Asp His Gly Pro Met Lys
515 520 525
<210> 29
<211> 568
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 29
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Thr Pro Ser Ser Thr Asp Trp Val Asp Asn Lys
225 230 235 240
Thr Phe Ser Val Cys Ser Arg Asp Phe Thr Pro Pro Thr Val Lys Ile
245 250 255
Leu Gln Ser Ser Cys Asp Gly Gly Gly His Phe Pro Pro Thr Ile Gln
260 265 270
Leu Leu Cys Leu Val Ser Gly Tyr Thr Pro Gly Thr Ile Asn Ile Thr
275 280 285
Trp Leu Glu Asp Gly Gln Val Met Asp Val Asp Leu Ser Thr Ala Ser
290 295 300
Thr Thr Gln Glu Gly Glu Leu Ala Ser Thr Gln Ser Glu Leu Thr Leu
305 310 315 320
Ser Gln Lys His Trp Leu Ser Asp Arg Thr Tyr Thr Cys Gln Val Thr
325 330 335
Tyr Gln Gly His Thr Phe Glu Asp Ser Thr Lys Lys Cys Ala Asp Ser
340 345 350
Asn Pro Arg Gly Val Ser Ala Tyr Leu Ser Arg Pro Ser Pro Phe Asp
355 360 365
Leu Phe Ile Arg Lys Ser Pro Thr Ile Thr Cys Leu Val Val Asp Leu
370 375 380
Ala Pro Ser Lys Gly Thr Val Asn Leu Thr Trp Ser Arg Ala Ser Gly
385 390 395 400
Lys Pro Val Asn His Ser Thr Arg Lys Glu Glu Lys Gln Arg Asn Gly
405 410 415
Thr Leu Thr Val Thr Ser Thr Leu Pro Val Gly Thr Arg Asp Trp Ile
420 425 430
Glu Gly Glu Thr Tyr Gln Cys Arg Val Thr His Pro His Leu Pro Arg
435 440 445
Ala Leu Met Arg Ser Thr Thr Lys Thr Ser Gly Pro Arg Ala Ala Pro
450 455 460
Glu Val Tyr Ala Phe Ala Thr Pro Glu Trp Pro Gly Ser Arg Asp Lys
465 470 475 480
Arg Thr Leu Ala Cys Leu Ile Gln Asn Phe Met Pro Glu Asp Ile Ser
485 490 495
Val Gln Trp Leu His Asn Glu Val Gln Leu Pro Asp Ala Arg His Ser
500 505 510
Thr Thr Gln Pro Arg Lys Thr Lys Gly Ser Gly Phe Phe Val Phe Ser
515 520 525
Arg Leu Glu Val Thr Arg Ala Glu Trp Glu Gln Lys Asp Glu Phe Ile
530 535 540
Cys Arg Ala Val His Glu Ala Ala Ser Pro Ser Gln Thr Val Gln Arg
545 550 555 560
Ala Val Ser Val Asn Pro Gly Lys
565
<210> 30
<211> 593
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 30
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Val Gln His Pro Asn Gly Asn Lys Glu Lys Asn
225 230 235 240
Val Pro Leu Pro Val Ile Ala Glu Leu Pro Pro Lys Val Ser Val Phe
245 250 255
Val Pro Pro Arg Asp Gly Phe Phe Gly Asn Pro Arg Lys Ser Lys Leu
260 265 270
Ile Cys Gln Ala Thr Gly Phe Ser Pro Arg Gln Ile Gln Val Ser Trp
275 280 285
Leu Arg Glu Gly Lys Gln Val Gly Ser Gly Val Thr Thr Asp Gln Val
290 295 300
Gln Ala Glu Ala Lys Glu Ser Gly Pro Thr Thr Tyr Lys Val Thr Ser
305 310 315 320
Thr Leu Thr Ile Lys Glu Ser Asp Trp Leu Ser Gln Ser Met Phe Thr
325 330 335
Cys Arg Val Asp His Arg Gly Leu Thr Phe Gln Gln Asn Ala Ser Ser
340 345 350
Met Cys Val Pro Asp Gln Asp Thr Ala Ile Arg Val Phe Ala Ile Pro
355 360 365
Pro Ser Phe Ala Ser Ile Phe Leu Thr Lys Ser Thr Lys Leu Thr Cys
370 375 380
Leu Val Thr Asp Leu Thr Thr Tyr Asp Ser Val Thr Ile Ser Trp Thr
385 390 395 400
Arg Gln Asn Gly Glu Ala Val Lys Thr His Thr Asn Ile Ser Glu Ser
405 410 415
His Pro Asn Ala Thr Phe Ser Ala Val Gly Glu Ala Ser Ile Cys Glu
420 425 430
Asp Asp Trp Asn Ser Gly Glu Arg Phe Thr Cys Thr Val Thr His Thr
435 440 445
Asp Leu Pro Ser Pro Leu Lys Gln Thr Ile Ser Arg Pro Lys Gly Val
450 455 460
Ala Leu His Arg Pro Asp Val Tyr Leu Leu Pro Pro Ala Arg Glu Gln
465 470 475 480
Leu Asn Leu Arg Glu Ser Ala Thr Ile Thr Cys Leu Val Thr Gly Phe
485 490 495
Ser Pro Ala Asp Val Phe Val Gln Trp Met Gln Arg Gly Gln Pro Leu
500 505 510
Ser Pro Glu Lys Tyr Val Thr Ser Ala Pro Met Pro Glu Pro Gln Ala
515 520 525
Pro Gly Arg Tyr Phe Ala His Ser Ile Leu Thr Val Ser Glu Glu Glu
530 535 540
Trp Asn Thr Gly Glu Thr Tyr Thr Cys Val Val Ala His Glu Ala Leu
545 550 555 560
Pro Asn Arg Val Thr Glu Arg Thr Val Asp Lys Ser Thr Gly Lys Pro
565 570 575
Thr Leu Tyr Asn Val Ser Leu Val Met Ser Asp Thr Ala Gly Thr Cys
580 585 590
Tyr
<210> 31
<211> 472
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 31
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe
225 230 235 240
Thr Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
245 250 255
Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
260 265 270
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
275 280 285
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
290 295 300
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
305 310 315 320
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
325 330 335
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
340 345 350
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
355 360 365
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr
370 375 380
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
385 390 395 400
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
405 410 415
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
420 425 430
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
435 440 445
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
450 455 460
Ser Leu Ser Leu Ser Pro Gly Lys
465 470
<210> 32
<211> 472
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 32
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Arg Glu Lys Gln Thr Asp Glu Ile Lys Asp Thr
225 230 235 240
Arg Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
245 250 255
Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
260 265 270
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
275 280 285
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
290 295 300
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
305 310 315 320
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
325 330 335
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
340 345 350
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
355 360 365
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr
370 375 380
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
385 390 395 400
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
405 410 415
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
420 425 430
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
435 440 445
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
450 455 460
Ser Leu Ser Leu Ser Pro Gly Lys
465 470
<210> 33
<211> 467
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 33
Met Leu Ser Arg Leu Leu Pro Phe Leu Val Thr Ile Ser Ser Leu Ser
1 5 10 15
Leu Glu Phe Ile Ala Tyr Gly Thr Glu Leu Pro Ser Pro Ser Tyr Val
20 25 30
Trp Phe Glu Ala Arg Phe Phe Gln His Ile Leu His Trp Lys Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Tyr Tyr Glu Val Ala Leu Lys Gln Tyr
50 55 60
Gly Asn Ser Thr Trp Asn Asp Ile His Ile Cys Arg Lys Ala Gln Ala
65 70 75 80
Leu Ser Cys Asp Leu Thr Thr Phe Thr Leu Asp Leu Tyr His Arg Ser
85 90 95
Tyr Gly Tyr Arg Ala Arg Val Arg Ala Val Asp Asn Ser Gln Tyr Ser
100 105 110
Asn Trp Thr Thr Thr Glu Thr Arg Phe Thr Val Asp Glu Val Ile Leu
115 120 125
Thr Val Asp Ser Val Thr Leu Lys Ala Met Asp Gly Ile Ile Tyr Gly
130 135 140
Thr Ile His Pro Pro Arg Pro Thr Ile Thr Pro Ala Gly Asp Glu Tyr
145 150 155 160
Glu Gln Val Phe Lys Asp Leu Arg Val Tyr Lys Ile Ser Ile Arg Lys
165 170 175
Phe Ser Glu Leu Lys Asn Ala Thr Lys Arg Val Lys Gln Glu Thr Phe
180 185 190
Thr Leu Thr Val Pro Ile Gly Val Arg Lys Phe Cys Val Lys Val Leu
195 200 205
Pro Arg Leu Glu Ser Arg Ile Asn Lys Ala Glu Trp Ser Glu Glu Gln
210 215 220
Cys Leu Leu Ile Thr Thr Glu Gln Ser Thr Lys Val Asp Lys Lys Ile
225 230 235 240
Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu
245 250 255
Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr
260 265 270
Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys
275 280 285
Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val
290 295 300
His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe
305 310 315 320
Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly
325 330 335
Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile
340 345 350
Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val
355 360 365
Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser
370 375 380
Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu
385 390 395 400
Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro
405 410 415
Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val
420 425 430
Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu
435 440 445
His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser
450 455 460
Pro Gly Lys
465
<210> 34
<211> 232
<212> PRT
<213> 小鼠(Mus musculus)
<400> 34
Met Leu Ser Arg Leu Leu Pro Phe Leu Val Thr Ile Ser Ser Leu Ser
1 5 10 15
Leu Glu Phe Ile Ala Tyr Gly Thr Glu Leu Pro Ser Pro Ser Tyr Val
20 25 30
Trp Phe Glu Ala Arg Phe Phe Gln His Ile Leu His Trp Lys Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Tyr Tyr Glu Val Ala Leu Lys Gln Tyr
50 55 60
Gly Asn Ser Thr Trp Asn Asp Ile His Ile Cys Arg Lys Ala Gln Ala
65 70 75 80
Leu Ser Cys Asp Leu Thr Thr Phe Thr Leu Asp Leu Tyr His Arg Ser
85 90 95
Tyr Gly Tyr Arg Ala Arg Val Arg Ala Val Asp Asn Ser Gln Tyr Ser
100 105 110
Asn Trp Thr Thr Thr Glu Thr Arg Phe Thr Val Asp Glu Val Ile Leu
115 120 125
Thr Val Asp Ser Val Thr Leu Lys Ala Met Asp Gly Ile Ile Tyr Gly
130 135 140
Thr Ile His Pro Pro Arg Pro Thr Ile Thr Pro Ala Gly Asp Glu Tyr
145 150 155 160
Glu Gln Val Phe Lys Asp Leu Arg Val Tyr Lys Ile Ser Ile Arg Lys
165 170 175
Phe Ser Glu Leu Lys Asn Ala Thr Lys Arg Val Lys Gln Glu Thr Phe
180 185 190
Thr Leu Thr Val Pro Ile Gly Val Arg Lys Phe Cys Val Lys Val Leu
195 200 205
Pro Arg Leu Glu Ser Arg Ile Asn Lys Ala Glu Trp Ser Glu Glu Gln
210 215 220
Cys Leu Leu Ile Thr Thr Glu Gln
225 230
<210> 35
<211> 12
<212> PRT
<213> 小鼠(Mus musculus)
<400> 35
Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp
1 5 10
<210> 36
<211> 223
<212> PRT
<213> 小鼠(Mus musculus)
<400> 36
Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val
1 5 10 15
Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr
20 25 30
Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu
35 40 45
Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln
50 55 60
Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser
65 70 75 80
Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys
85 90 95
Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile
100 105 110
Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro
115 120 125
Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met
130 135 140
Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn
145 150 155 160
Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr
165 170 175
Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn
180 185 190
Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu
195 200 205
His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 37
<211> 1419
<212> DNA
<213> 人工序列
<220>
<223> 合成的
<400> 37
atgctgccgt gcctcgtagt gctgctggcg gcgctcctca gcctccgtct tggctcagac 60
gctcatggga cagagctgcc cagccctccg tctgtgtggt ttgaagcaga atttttccac 120
cacatcctcc actggacacc catcccaaat cagtctgaaa gtacctgcta tgaagtggcg 180
ctcctgaggt atggaataga gtcctggaac tccatctcca actgtagcca gaccctgtcc 240
tatgacctta ccgcagtgac cttggacctg taccacagca atggctaccg ggccagagtg 300
cgggctgtgg acggcagccg gcactccaac tggaccgtca ccaacacccg cttctctgtg 360
gatgaagtga ctctgacagt tggcagtgtg aacctagaga tccacaatgg cttcatcctc 420
gggaagattc agctacccag gcccaagatg gcccccgcaa atgacacata tgaaagcatc 480
ttcagtcact tccgagagta tgagattgcc attcgcaagg tgccgggaaa cttcacgttc 540
acacacaaga aagtaaaaca tgaaaacttc agcctcctaa cctctggaga agtgggagag 600
ttctgtgtcc aggtgaaacc atctgtcgct tcccgaagta acaaggggat gtggtctaaa 660
gaggagtgca tctccctcac caggcagaag cccagcaaca ccaaggtgga caagagagtt 720
gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 780
gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 840
acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 900
aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 960
tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1020
ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1080
atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg 1140
gatgagctga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1200
gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1260
cccgtgctgg actccgacgg ctccttcttc ctctacagca agctcaccgt ggacaagagc 1320
aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1380
tacacgcaga agagcctctc cctgtctccg ggtaaatga 1419
<210> 38
<211> 1404
<212> DNA
<213> 人工序列
<220>
<223> 合成的
<400> 38
atgctgccgt gcctcgtagt gctgctggcg gcgctcctca gcctccgtct tggctcagac 60
gctcatggga cagagctgcc cagccctccg tctgtgtggt ttgaagcaga atttttccac 120
cacatcctcc actggacacc catcccaaat cagtctgaaa gtacctgcta tgaagtggcg 180
ctcctgaggt atggaataga gtcctggaac tccatctcca actgtagcca gaccctgtcc 240
tatgacctta ccgcagtgac cttggacctg taccacagca atggctaccg ggccagagtg 300
cgggctgtgg acggcagccg gcactccaac tggaccgtca ccaacacccg cttctctgtg 360
gatgaagtga ctctgacagt tggcagtgtg aacctagaga tccacaatgg cttcatcctc 420
gggaagattc agctacccag gcccaagatg gcccccgcaa atgacacata tgaaagcatc 480
ttcagtcact tccgagagta tgagattgcc attcgcaagg tgccgggaaa cttcacgttc 540
acacacaaga aagtaaaaca tgaaaacttc agcctcctaa cctctggaga agtgggagag 600
ttctgtgtcc aggtgaaacc atctgtcgct tcccgaagta acaaggggat gtggtctaaa 660
gaggagtgca tctccctcac caggcagaag cccagcaaca ccaaggtgga caagacagtt 720
gagcgcaaat gttgtgtcga gtgcccaccg tgcccagcac cacctgtggc aggaccgtca 780
gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840
acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tccagttcaa ctggtacgtg 900
gacggcgtgg aggtgcataa tgccaagaca aagccacggg aggagcagtt caacagcacg 960
ttccgtgtgg tcagcgtcct caccgttgtg caccaggact ggctgaacgg caaggagtac 1020
aagtgcaagg tctccaacaa aggcctccca gcccccatcg agaaaaccat ctccaaaacc 1080
aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga ggagatgacc 1140
aagaaccagg tcagcctgac ctgcctggtc aaaggcttct accccagcga catctccgtg 1200
gagtgggaga gcaatgggca gccggagaac aactacaaga ccacacctcc catgctggac 1260
tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320
gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380
agcctctccc tgtctccggg taaa 1404
<210> 39
<211> 1557
<212> DNA
<213> 人工序列
<220>
<223> 合成的
<400> 39
atgctgccgt gcctcgtagt gctgctggcg gcgctcctca gcctccgtct tggctcagac 60
gctcatggga cagagctgcc cagccctccg tctgtgtggt ttgaagcaga atttttccac 120
cacatcctcc actggacacc catcccaaat cagtctgaaa gtacctgcta tgaagtggcg 180
ctcctgaggt atggaataga gtcctggaac tccatctcca actgtagcca gaccctgtcc 240
tatgacctta ccgcagtgac cttggacctg taccacagca atggctaccg ggccagagtg 300
cgggctgtgg acggcagccg gcactccaac tggaccgtca ccaacacccg cttctctgtg 360
gatgaagtga ctctgacagt tggcagtgtg aacctagaga tccacaatgg cttcatcctc 420
gggaagattc agctacccag gcccaagatg gcccccgcaa atgacacata tgaaagcatc 480
ttcagtcact tccgagagta tgagattgcc attcgcaagg tgccgggaaa cttcacgttc 540
acacacaaga aagtaaaaca tgaaaacttc agcctcctaa cctctggaga agtgggagag 600
ttctgtgtcc aggtgaaacc atctgtcgct tcccgaagta acaaggggat gtggtctaaa 660
gaggagtgca tctccctcac caggcagaag cccagcaaca ccaaggtgga caagagagtt 720
gagctcaaaa ccccacttgg tgacacaact cacacatgcc cacggtgccc agagcccaaa 780
tcttgtgaca cacctccccc gtgcccacgg tgcccagagc ccaaatcttg tgacacacct 840
cccccatgcc cacggtgccc agagcccaaa tcttgtgaca cacctccccc gtgcccaagg 900
tgcccagcac ctgaactcct gggaggaccg tcagtcttcc tcttcccccc aaaacccaag 960
gataccctta tgatttcccg gacccctgag gtcacgtgcg tggtggtgga cgtgagccac 1020
gaagaccccg aggtccagtt caagtggtac gtggacggcg tggaggtgca taatgccaag 1080
acaaagccgc gggaggagca gtacaacagc acgttccgtg tggtcagcgt cctcaccgtc 1140
ctgcaccagg actggctgaa cggcaaggag tacaagtgca aggtctccaa caaagccctc 1200
ccagccccca tcgagaaaac catctccaaa accaaaggac agccccgaga accacaggtg 1260
tacaccctgc ccccatcccg ggaggagatg accaagaacc aggtcagcct gacctgcctg 1320
gtcaaaggct tctaccccag cgacatcgcc gtggagtggg agagcagcgg gcagccggag 1380
aacaactaca acaccacgcc tcccatgctg gactccgacg gctccttctt cctctacagc 1440
aagctcaccg tggacaagag caggtggcag caggggaaca tcttctcatg ctccgtgatg 1500
catgaggctc tgcacaaccg cttcacgcag aagagcctct ccctgtctcc gggtaaa 1557
<210> 40
<211> 1407
<212> DNA
<213> 人工序列
<220>
<223> 合成的
<400> 40
atgctgccgt gcctcgtagt gctgctggcg gcgctcctca gcctccgtct tggctcagac 60
gctcatggga cagagctgcc cagccctccg tctgtgtggt ttgaagcaga atttttccac 120
cacatcctcc actggacacc catcccaaat cagtctgaaa gtacctgcta tgaagtggcg 180
ctcctgaggt atggaataga gtcctggaac tccatctcca actgtagcca gaccctgtcc 240
tatgacctta ccgcagtgac cttggacctg taccacagca atggctaccg ggccagagtg 300
cgggctgtgg acggcagccg gcactccaac tggaccgtca ccaacacccg cttctctgtg 360
gatgaagtga ctctgacagt tggcagtgtg aacctagaga tccacaatgg cttcatcctc 420
gggaagattc agctacccag gcccaagatg gcccccgcaa atgacacata tgaaagcatc 480
ttcagtcact tccgagagta tgagattgcc attcgcaagg tgccgggaaa cttcacgttc 540
acacacaaga aagtaaaaca tgaaaacttc agcctcctaa cctctggaga agtgggagag 600
ttctgtgtcc aggtgaaacc atctgtcgct tcccgaagta acaaggggat gtggtctaaa 660
gaggagtgca tctccctcac caggcagaag cccagcaaca ccaaggtgga caagagagtt 720
gagtccaaat atggtccccc atgcccatca tgcccagcac ctgagttcct ggggggacca 780
tcagtcttcc tgttcccccc aaaacccaag gacactctca tgatctcccg gacccctgag 840
gtcacgtgcg tggtggtgga cgtgagccag gaagaccccg aggtccagtt caactggtac 900
gtggatggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gttcaacagc 960
acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa cggcaaggag 1020
tacaagtgca aggtctccaa caaaggcctc ccgtcctcca tcgagaaaac catctccaaa 1080
gccaaagggc agccccgaga gccacaggtg tacaccctgc ccccatccca ggaggagatg 1140
accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctaccccag cgacatcgcc 1200
gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1260
gactccgacg gctccttctt cctctacagc aggctaaccg tggacaagag caggtggcag 1320
gaggggaatg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacacag 1380
aagagcctct ccctgtctct gggtaaa 1407
<210> 41
<211> 1488
<212> DNA
<213> 人工序列
<220>
<223> 合成的
<400> 41
atgctgccgt gcctcgtagt gctgctggcg gcgctcctca gcctccgtct tggctcagac 60
gctcatggga cagagctgcc cagccctccg tctgtgtggt ttgaagcaga atttttccac 120
cacatcctcc actggacacc catcccaaat cagtctgaaa gtacctgcta tgaagtggcg 180
ctcctgaggt atggaataga gtcctggaac tccatctcca actgtagcca gaccctgtcc 240
tatgacctta ccgcagtgac cttggacctg taccacagca atggctaccg ggccagagtg 300
cgggctgtgg acggcagccg gcactccaac tggaccgtca ccaacacccg cttctctgtg 360
gatgaagtga ctctgacagt tggcagtgtg aacctagaga tccacaatgg cttcatcctc 420
gggaagattc agctacccag gcccaagatg gcccccgcaa atgacacata tgaaagcatc 480
ttcagtcact tccgagagta tgagattgcc attcgcaagg tgccgggaaa cttcacgttc 540
acacacaaga aagtaaaaca tgaaaacttc agcctcctaa cctctggaga agtgggagag 600
ttctgtgtcc aggtgaaacc atctgtcgct tcccgaagta acaaggggat gtggtctaaa 660
gaggagtgca tctccctcac caggcaggtg aagcactaca cgaatcccag ccaggatgtg 720
actgtgccct gcccagttcc ctcaactcca cctaccccat ctccctcaac tccacctacc 780
ccatctccct catgctgcca cccccgactg tcactgcacc gaccggccct cgaggacctg 840
ctcttaggtt cagaagcgaa cctcacgtgc acactgaccg gcctgagaga tgcctcaggt 900
gtcaccttca cctggacgcc ctcaagtggg aagagcgctg ttcaaggacc acctgagcgt 960
gacctctgtg gctgctacag cgtgtccagt gtcctgccgg gctgtgccga gccatggaac 1020
catgggaaga ccttcacttg cactgctgcc taccccgagt ccaagacccc gctaaccgcc 1080
accctctcaa aatccggaaa cacattccgg cccgaggtcc acctgctgcc gccgccgtcg 1140
gaggagctgg ccctgaacga gctggtgacg ctgacgtgcc tggcacgtgg cttcagcccc 1200
aaggatgtgc tggttcgctg gctgcagggg tcacaggagc tgccccgcga gaagtacctg 1260
acttgggcat cccggcagga gcccagccag ggcaccacca ccttcgctgt gaccagcata 1320
ctgcgcgtgg cagccgagga ctggaagaag ggggacacct tctcctgcat ggtgggccac 1380
gaggccctgc cgctggcctt cacacagaag accatcgacc gcttggcggg taaacccacc 1440
catgtcaatg tgtctgttgt catggcggag gtggacggca cctgctac 1488
<210> 42
<211> 1449
<212> DNA
<213> 人工序列
<220>
<223> 合成的
<400> 42
atgctgccgt gcctcgtagt gctgctggcg gcgctcctca gcctccgtct tggctcagac 60
gctcatggga cagagctgcc cagccctccg tctgtgtggt ttgaagcaga atttttccac 120
cacatcctcc actggacacc catcccaaat cagtctgaaa gtacctgcta tgaagtggcg 180
ctcctgaggt atggaataga gtcctggaac tccatctcca actgtagcca gaccctgtcc 240
tatgacctta ccgcagtgac cttggacctg taccacagca atggctaccg ggccagagtg 300
cgggctgtgg acggcagccg gcactccaac tggaccgtca ccaacacccg cttctctgtg 360
gatgaagtga ctctgacagt tggcagtgtg aacctagaga tccacaatgg cttcatcctc 420
gggaagattc agctacccag gcccaagatg gcccccgcaa atgacacata tgaaagcatc 480
ttcagtcact tccgagagta tgagattgcc attcgcaagg tgccgggaaa cttcacgttc 540
acacacaaga aagtaaaaca tgaaaacttc agcctcctaa cctctggaga agtgggagag 600
ttctgtgtcc aggtgaaacc atctgtcgct tcccgaagta acaaggggat gtggtctaaa 660
gaggagtgca tctccctcac caggcaggtg aagcactaca cgaatcccag ccaggatgtg 720
actgtgccct gcccagttcc cccacctccc ccatgctgcc acccccgact gtcgctgcac 780
cgaccggccc tcgaggacct gctcttaggt tcagaagcga acctcacgtg cacactgacc 840
ggcctgagag atgcctctgg tgccaccttc acctggacgc cctcaagtgg gaagagcgct 900
gttcaaggac cacctgagcg tgacctctgt ggctgctaca gcgtgtccag tgtcctgcct 960
ggctgtgccc agccatggaa ccatggggag accttcacct gcactgctgc ccaccccgag 1020
ttgaagaccc cactaaccgc caacatcaca aaatccggaa acacattccg gcccgaggtc 1080
cacctgctgc cgccgccgtc ggaggagctg gccctgaacg agctggtgac gctgacgtgc 1140
ctggcacgtg gcttcagccc caaggatgtg ctggttcgct ggctgcaggg gtcacaggag 1200
ctgccccgcg agaagtacct gacttgggca tcccggcagg agcccagcca gggcaccacc 1260
accttcgctg tgaccagcat actgcgcgtg gcagccgagg actggaagaa gggggacacc 1320
ttctcctgca tggtgggcca cgaggccctg ccgctggcct tcacacagaa gaccatcgac 1380
cgcatggcgg gtaaacccac ccatgtcaat gtgtctgttg tcatggcgga ggtggacggc 1440
acctgctac 1449
<210> 43
<211> 1575
<212> DNA
<213> 人工序列
<220>
<223> 合成的
<400> 43
atgctgccgt gcctcgtagt gctgctggcg gcgctcctca gcctccgtct tggctcagac 60
gctcatggga cagagctgcc cagccctccg tctgtgtggt ttgaagcaga atttttccac 120
cacatcctcc actggacacc catcccaaat cagtctgaaa gtacctgcta tgaagtggcg 180
ctcctgaggt atggaataga gtcctggaac tccatctcca actgtagcca gaccctgtcc 240
tatgacctta ccgcagtgac cttggacctg taccacagca atggctaccg ggccagagtg 300
cgggctgtgg acggcagccg gcactccaac tggaccgtca ccaacacccg cttctctgtg 360
gatgaagtga ctctgacagt tggcagtgtg aacctagaga tccacaatgg cttcatcctc 420
gggaagattc agctacccag gcccaagatg gcccccgcaa atgacacata tgaaagcatc 480
ttcagtcact tccgagagta tgagattgcc attcgcaagg tgccgggaaa cttcacgttc 540
acacacaaga aagtaaaaca tgaaaacttc agcctcctaa cctctggaga agtgggagag 600
ttctgtgtcc aggtgaaacc atctgtcgct tcccgaagta acaaggggat gtggtctaaa 660
gaggagtgca tctccctcac caggcagacc gccagcaaga gtaagaagga gatcttccgc 720
tggccagagt ctccaaaggc acaggcctcc tcagtgccca ctgcacaacc ccaagcagag 780
ggcagcctcg ccaaggcaac cacagcccca gccaccaccc gtaacacagg aagaggagga 840
gaagagaaga agaaggagaa ggagaaagag gaacaagaag agagagagac aaagacacca 900
gagtgtccga gccacaccca gcctcttggc gtctacctgc taacccctgc agtgcaggac 960
ctgtggctcc gggacaaagc caccttcacc tgcttcgtgg tgggcagtga cctgaaggat 1020
gctcacctga cctgggaggt ggccgggaag gtccccacag ggggcgtgga ggaagggctg 1080
ctggagcggc acagcaacgg ctcccagagc cagcacagcc gtctgaccct gcccaggtcc 1140
ttgtggaacg cggggacctc cgtcacctgc acactgaacc atcccagcct cccaccccag 1200
aggttgatgg cgctgagaga acccgctgcg caggcacccg tcaagctttc cctgaacctg 1260
ctggcctcgt ctgaccctcc cgaggcggcc tcgtggctcc tgtgtgaggt gtctggcttc 1320
tcgcccccca acatcctcct gatgtggctg gaggaccagc gtgaggtgaa cacttctggg 1380
tttgcccccg cacgcccccc tccacagccc gggagcacca cgttctgggc ctggagtgtg 1440
ctgcgtgtcc cagccccgcc cagccctcag ccagccacct acacgtgtgt ggtcagccac 1500
gaggactccc ggactctgct caacgccagc cggagcctag aagtcagcta tgtaacagac 1560
catggcccca tgaaa 1575
<210> 44
<211> 1704
<212> DNA
<213> 人工序列
<220>
<223> 合成的
<400> 44
atgctgccgt gcctcgtagt gctgctggcg gcgctcctca gcctccgtct tggctcagac 60
gctcatggga cagagctgcc cagccctccg tctgtgtggt ttgaagcaga atttttccac 120
cacatcctcc actggacacc catcccaaat cagtctgaaa gtacctgcta tgaagtggcg 180
ctcctgaggt atggaataga gtcctggaac tccatctcca actgtagcca gaccctgtcc 240
tatgacctta ccgcagtgac cttggacctg taccacagca atggctaccg ggccagagtg 300
cgggctgtgg acggcagccg gcactccaac tggaccgtca ccaacacccg cttctctgtg 360
gatgaagtga ctctgacagt tggcagtgtg aacctagaga tccacaatgg cttcatcctc 420
gggaagattc agctacccag gcccaagatg gcccccgcaa atgacacata tgaaagcatc 480
ttcagtcact tccgagagta tgagattgcc attcgcaagg tgccgggaaa cttcacgttc 540
acacacaaga aagtaaaaca tgaaaacttc agcctcctaa cctctggaga agtgggagag 600
ttctgtgtcc aggtgaaacc atctgtcgct tcccgaagta acaaggggat gtggtctaaa 660
gaggagtgca tctccctcac caggcagact ccatcgtcca cagactgggt cgacaacaaa 720
accttcagcg tctgctccag ggacttcacc ccgcccaccg tgaagatctt acagtcgtcc 780
tgcgacggcg gcgggcactt ccccccgacc atccagctcc tgtgcctcgt ctctgggtac 840
accccaggga ctatcaacat cacctggctg gaggacgggc aggtcatgga cgtggacttg 900
tccaccgcct ctaccacgca ggagggtgag ctggcctcca cacaaagcga gctcaccctc 960
agccagaagc actggctgtc agaccgcacc tacacctgcc aggtcaccta tcaaggtcac 1020
acctttgagg acagcaccaa gaagtgtgca gattccaacc cgagaggggt gagcgcctac 1080
ctaagccggc ccagcccgtt cgacctgttc atccgcaagt cgcccacgat cacctgtctg 1140
gtggtggacc tggcacccag caaggggacc gtgaacctga cctggtcccg ggccagtggg 1200
aagcctgtga accactccac cagaaaggag gagaagcagc gcaatggcac gttaaccgtc 1260
acgtccaccc tgccggtggg cacccgagac tggatcgagg gggagaccta ccagtgcagg 1320
gtgacccacc cccacctgcc cagggccctc atgcggtcca cgaccaagac cagcggcccg 1380
cgtgctgccc cggaagtcta tgcgtttgcg acgccggagt ggccggggag ccgggacaag 1440
cgcaccctcg cctgcctgat ccagaacttc atgcctgagg acatctcggt gcagtggctg 1500
cacaacgagg tgcagctccc ggacgcccgg cacagcacga cgcagccccg caagaccaag 1560
ggctccggct tcttcgtctt cagccgcctg gaggtgacca gggccgaatg ggagcagaaa 1620
gatgagttca tctgccgtgc agtccatgag gcagcgagcc cctcacagac cgtccagcga 1680
gcggtgtctg taaatcccgg taaa 1704
<210> 45
<211> 1779
<212> DNA
<213> 人工序列
<220>
<223> 合成的
<400> 45
atgctgccgt gcctcgtagt gctgctggcg gcgctcctca gcctccgtct tggctcagac 60
gctcatggga cagagctgcc cagccctccg tctgtgtggt ttgaagcaga atttttccac 120
cacatcctcc actggacacc catcccaaat cagtctgaaa gtacctgcta tgaagtggcg 180
ctcctgaggt atggaataga gtcctggaac tccatctcca actgtagcca gaccctgtcc 240
tatgacctta ccgcagtgac cttggacctg taccacagca atggctaccg ggccagagtg 300
cgggctgtgg acggcagccg gcactccaac tggaccgtca ccaacacccg cttctctgtg 360
gatgaagtga ctctgacagt tggcagtgtg aacctagaga tccacaatgg cttcatcctc 420
gggaagattc agctacccag gcccaagatg gcccccgcaa atgacacata tgaaagcatc 480
ttcagtcact tccgagagta tgagattgcc attcgcaagg tgccgggaaa cttcacgttc 540
acacacaaga aagtaaaaca tgaaaacttc agcctcctaa cctctggaga agtgggagag 600
ttctgtgtcc aggtgaaacc atctgtcgct tcccgaagta acaaggggat gtggtctaaa 660
gaggagtgca tctccctcac caggcaggtc cagcacccca acggcaacaa agaaaagaac 720
gtgcctcttc cagtgattgc tgagctgcct cccaaagtga gcgtcttcgt cccaccccgc 780
gacggcttct tcggcaaccc ccgcaagtcc aagctcatct gccaggccac gggtttcagt 840
ccccggcaga ttcaggtgtc ctggctgcgc gaggggaagc aggtggggtc tggcgtcacc 900
acggaccagg tgcaggctga ggccaaagag tctgggccca cgacctacaa ggtgaccagc 960
acactgacca tcaaagagag cgactggctc agccagagca tgttcacctg ccgcgtggat 1020
cacaggggcc tgaccttcca gcagaatgcg tcctccatgt gtgtccccga tcaagacaca 1080
gccatccggg tcttcgccat ccccccatcc tttgccagca tcttcctcac caagtccacc 1140
aagttgacct gcctggtcac agacctgacc acctatgaca gcgtgaccat ctcctggacc 1200
cgccagaatg gcgaagctgt gaaaacccac accaacatct ccgagagcca ccccaatgcc 1260
actttcagcg ccgtgggtga ggccagcatc tgcgaggatg actggaattc cggggagagg 1320
ttcacgtgca ccgtgaccca cacagacctg ccctcgccac tgaagcagac catctcccgg 1380
cccaaggggg tggccctgca caggcccgat gtctacttgc tgccaccagc ccgggagcag 1440
ctgaacctgc gggagtcggc caccatcacg tgcctggtga cgggcttctc tcccgcggac 1500
gtcttcgtgc agtggatgca gagggggcag cccttgtccc cggagaagta tgtgaccagc 1560
gccccaatgc ctgagcccca ggccccaggc cggtacttcg cccacagcat cctgaccgtg 1620
tccgaagagg aatggaacac gggggagacc tacacctgcg tggtggccca tgaggccctg 1680
cccaacaggg tcaccgagag gaccgtggac aagtccaccg gtaaacccac cctgtacaac 1740
gtgtccctgg tcatgtccga cacagctggc acctgctac 1779
<210> 46
<211> 1416
<212> DNA
<213> 人工序列
<220>
<223> 合成的
<400> 46
atgctgccgt gcctcgtagt gctgctggcg gcgctcctca gcctccgtct tggctcagac 60
gctcatggga cagagctgcc cagccctccg tctgtgtggt ttgaagcaga atttttccac 120
cacatcctcc actggacacc catcccaaat cagtctgaaa gtacctgcta tgaagtggcg 180
ctcctgaggt atggaataga gtcctggaac tccatctcca actgtagcca gaccctgtcc 240
tatgacctta ccgcagtgac cttggacctg taccacagca atggctaccg ggccagagtg 300
cgggctgtgg acggcagccg gcactccaac tggaccgtca ccaacacccg cttctctgtg 360
gatgaagtga ctctgacagt tggcagtgtg aacctagaga tccacaatgg cttcatcctc 420
gggaagattc agctacccag gcccaagatg gcccccgcaa atgacacata tgaaagcatc 480
ttcagtcact tccgagagta tgagattgcc attcgcaagg tgccgggaaa cttcacgttc 540
acacacaaga aagtaaaaca tgaaaacttc agcctcctaa cctctggaga agtgggagag 600
ttctgtgtcc aggtgaaacc atctgtcgct tcccgaagta acaaggggat gtggtctaaa 660
gaggagtgca tctccctcac caggcagtac gttcccaaag agtttaatgc tgaaacattc 720
acccccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 780
gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 840
acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 900
aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 960
tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1020
ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1080
atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg 1140
gatgagctga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1200
gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1260
cccgtgctgg actccgacgg ctccttcttc ctctacagca agctcaccgt ggacaagagc 1320
aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1380
tacacgcaga agagcctctc cctgtctccg ggtaaa 1416
<210> 47
<211> 1416
<212> DNA
<213> 人工序列
<220>
<223> 合成的
<400> 47
atgctgccgt gcctcgtagt gctgctggcg gcgctcctca gcctccgtct tggctcagac 60
gctcatggga cagagctgcc cagccctccg tctgtgtggt ttgaagcaga atttttccac 120
cacatcctcc actggacacc catcccaaat cagtctgaaa gtacctgcta tgaagtggcg 180
ctcctgaggt atggaataga gtcctggaac tccatctcca actgtagcca gaccctgtcc 240
tatgacctta ccgcagtgac cttggacctg taccacagca atggctaccg ggccagagtg 300
cgggctgtgg acggcagccg gcactccaac tggaccgtca ccaacacccg cttctctgtg 360
gatgaagtga ctctgacagt tggcagtgtg aacctagaga tccacaatgg cttcatcctc 420
gggaagattc agctacccag gcccaagatg gcccccgcaa atgacacata tgaaagcatc 480
ttcagtcact tccgagagta tgagattgcc attcgcaagg tgccgggaaa cttcacgttc 540
acacacaaga aagtaaaaca tgaaaacttc agcctcctaa cctctggaga agtgggagag 600
ttctgtgtcc aggtgaaacc atctgtcgct tcccgaagta acaaggggat gtggtctaaa 660
gaggagtgca tctccctcac caggcagaga gaaaaacaga ctgatgaaat caaggatact 720
aggcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 780
gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 840
acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 900
aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 960
tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1020
ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1080
atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg 1140
gatgagctga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1200
gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1260
cccgtgctgg actccgacgg ctccttcttc ctctacagca agctcaccgt ggacaagagc 1320
aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1380
tacacgcaga agagcctctc cctgtctccg ggtaaa 1416
<210> 48
<211> 462
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 48
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Tyr Phe Thr Val Thr Asn Asp Lys Thr His Thr
225 230 235 240
Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe
245 250 255
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
260 265 270
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val
275 280 285
Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
290 295 300
Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val
305 310 315 320
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
325 330 335
Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
340 345 350
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
355 360 365
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
370 375 380
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
385 390 395 400
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp
405 410 415
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
420 425 430
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
435 440 445
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 49
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 49
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 50
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 弗林蛋白酶切割位点
<220>
<221> 杂项特点
<222> (2)..(2)
<223> Xaa可以是任何天然存在的氨基酸
<220>
<221> 杂项特点
<222> (3)..(3)
<223> Xaa可以是Lys或Arg
<400> 50
Arg Xaa Xaa Arg
1
<210> 51
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 弗林蛋白酶切割位点
<400> 51
Arg Ala Lys Arg
1
<210> 52
<211> 35938
<212> DNA
<213> 5型腺病毒
<400> 52
catcatcaat aatatacctt attttggatt gaagccaata tgataatgag ggggtggagt 60
ttgtgacgtg gcgcggggcg tgggaacggg gcgggtgacg tagtagtgtg gcggaagtgt 120
gatgttgcaa gtgtggcgga acacatgtaa gcgacggatg tggcaaaagt gacgtttttg 180
gtgtgcgccg gtgtacacag gaagtgacaa ttttcgcgcg gttttaggcg gatgttgtag 240
taaatttggg cgtaaccgag taagatttgg ccattttcgc gggaaaactg aataagagga 300
agtgaaatct gaataatttt gtgttactca tagcgcgtaa tatttgtcta gggccgcggg 360
gactttgacc gtttacgtgg agactcgccc aggtgttttt ctcaggtgtt ttccgcgttc 420
cgggtcaaag ttggcgtttt attattatag tcagctgacg tgtagtgtat ttatacccgg 480
tgagttcctc aagaggccac tcttgagtgc cagcgagtag agttttctcc tccgagccgc 540
tccgacaccg ggactgaaaa tgagacatat tatctgccac ggaggtgtta ttaccgaaga 600
aatggccgcc agtcttttgg accagctgat cgaagaggta ctggctgata atcttccacc 660
tcctagccat tttgaaccac ctacccttca cgaactgtat gatttagacg tgacggcccc 720
cgaagatccc aacgaggagg cggtttcgca gatttttccc gactctgtaa tgttggcggt 780
gcaggaaggg attgacttac tcacttttcc gccggcgccc ggttctccgg agccgcctca 840
cctttcccgg cagcccgagc agccggagca gagagccttg ggtccggttt ctatgccaaa 900
ccttgtaccg gaggtgatcg atcttacctg ccacgaggct ggctttccac ccagtgacga 960
cgaggatgaa gagggtgagg agtttgtgtt agattatgtg gagcaccccg ggcacggttg 1020
caggtcttgt cattatcacc ggaggaatac gggggaccca gatattatgt gttcgctttg 1080
ctatatgagg acctgtggca tgtttgtcta cagtaagtga aaattatggg cagtgggtga 1140
tagagtggtg ggtttggtgt ggtaattttt tttttaattt ttacagtttt gtggtttaaa 1200
gaattttgta ttgtgatttt tttaaaaggt cctgtgtctg aacctgagcc tgagcccgag 1260
ccagaaccgg agcctgcaag acctacccgc cgtcctaaaa tggcgcctgc tatcctgaga 1320
cgcccgacat cacctgtgtc tagagaatgc aatagtagta cggatagctg tgactccggt 1380
ccttctaaca cacctcctga gatacacccg gtggtcccgc tgtgccccat taaaccagtt 1440
gccgtgagag ttggtgggcg tcgccaggct gtggaatgta tcgaggactt gcttaacgag 1500
cctgggcaac ctttggactt gagctgtaaa cgccccaggc cataaggtgt aaacctgtga 1560
ttgcgtgtgt ggttaacgcc tttgtttgct gaatgagttg atgtaagttt aataaagggt 1620
gagataatgt ttaacttgca tggcgtgtta aatggggcgg ggcttaaagg gtatataatg 1680
cgccgtgggc taatcttggt tacatctgac ctcatggagg cttgggagtg tttggaagat 1740
ttttctgctg tgcgtaactt gctggaacag agctctaaca gtacctcttg gttttggagg 1800
tttctgtggg gctcatccca ggcaaagtta gtctgcagaa ttaaggagga ttacaagtgg 1860
gaatttgaag agcttttgaa atcctgtggt gagctgtttg attctttgaa tctgggtcac 1920
caggcgcttt tccaagagaa ggtcatcaag actttggatt tttccacacc ggggcgcgct 1980
gcggctgctg ttgctttttt gagttttata aaggataaat ggagcgaaga aacccatctg 2040
agcggggggt acctgctgga ttttctggcc atgcatctgt ggagagcggt tgtgagacac 2100
aagaatcgcc tgctactgtt gtcttccgtc cgcccggcga taataccgac ggaggagcag 2160
cagcagcagc aggaggaagc caggcggcgg cggcaggagc agagcccatg gaacccgaga 2220
gccggcctgg accctcggga atgaatgttg tacaggtggc tgaactgtat ccagaactga 2280
gacgcatttt gacaattaca gaggatgggc aggggctaaa gggggtaaag agggagcggg 2340
gggcttgtga ggctacagag gaggctagga atctagcttt tagcttaatg accagacacc 2400
gtcctgagtg tattactttt caacagatca aggataattg cgctaatgag cttgatctgc 2460
tggcgcagaa gtattccata gagcagctga ccacttactg gctgcagcca ggggatgatt 2520
ttgaggaggc tattagggta tatgcaaagg tggcacttag gccagattgc aagtacaaga 2580
tcagcaaact tgtaaatatc aggaattgtt gctacatttc tgggaacggg gccgaggtgg 2640
agatagatac ggaggatagg gtggccttta gatgtagcat gataaatatg tggccggggg 2700
tgcttggcat ggacggggtg gttattatga atgtaaggtt tactggcccc aattttagcg 2760
gtacggtttt cctggccaat accaacctta tcctacacgg tgtaagcttc tatgggttta 2820
acaatacctg tgtggaagcc tggaccgatg taagggttcg gggctgtgcc ttttactgct 2880
gctggaaggg ggtggtgtgt cgccccaaaa gcagggcttc aattaagaaa tgcctctttg 2940
aaaggtgtac cttgggtatc ctgtctgagg gtaactccag ggtgcgccac aatgtggcct 3000
ccgactgtgg ttgcttcatg ctagtgaaaa gcgtggctgt gattaagcat aacatggtat 3060
gtggcaactg cgaggacagg gcctctcaga tgctgacctg ctcggacggc aactgtcacc 3120
tgctgaagac cattcacgta gccagccact ctcgcaaggc ctggccagtg tttgagcata 3180
acatactgac ccgctgttcc ttgcatttgg gtaacaggag gggggtgttc ctaccttacc 3240
aatgcaattt gagtcacact aagatattgc ttgagcccga gagcatgtcc aaggtgaacc 3300
tgaacggggt gtttgacatg accatgaaga tctggaaggt gctgaggtac gatgagaccc 3360
gcaccaggtg cagaccctgc gagtgtggcg gtaaacatat taggaaccag cctgtgatgc 3420
tggatgtgac cgaggagctg aggcccgatc acttggtgct ggcctgcacc cgcgctgagt 3480
ttggctctag cgatgaagat acagattgag gtactgaaat gtgtgggcgt ggcttaaggg 3540
tgggaaagaa tatataaggt gggggtctta tgtagttttg tatctgtttt gcagcagccg 3600
ccgccgccat gagcaccaac tcgtttgatg gaagcattgt gagctcatat ttgacaacgc 3660
gcatgccccc atgggccggg gtgcgtcaga atgtgatggg ctccagcatt gatggtcgcc 3720
ccgtcctgcc cgcaaactct actaccttga cctacgagac cgtgtctgga acgccgttgg 3780
agactgcagc ctccgccgcc gcttcagccg ctgcagccac cgcccgcggg attgtgactg 3840
actttgcttt cctgagcccg cttgcaagca gtgcagcttc ccgttcatcc gcccgcgatg 3900
acaagttgac ggctcttttg gcacaattgg attctttgac ccgggaactt aatgtcgttt 3960
ctcagcagct gttggatctg cgccagcagg tttctgccct gaaggcttcc tcccctccca 4020
atgcggttta aaacataaat aaaaaaccag actctgtttg gatttggatc aagcaagtgt 4080
cttgctgtct ttatttaggg gttttgcgcg cgcggtaggc ccgggaccag cggtctcggt 4140
cgttgagggt cctgtgtatt ttttccagga cgtggtaaag gtgactctgg atgttcagat 4200
acatgggcat aagcccgtct ctggggtgga ggtagcacca ctgcagagct tcatgctgcg 4260
gggtggtgtt gtagatgatc cagtcgtagc aggagcgctg ggcgtggtgc ctaaaaatgt 4320
ctttcagtag caagctgatt gccaggggca ggcccttggt gtaagtgttt acaaagcggt 4380
taagctggga tgggtgcata cgtggggata tgagatgcat cttggactgt atttttaggt 4440
tggctatgtt cccagccata tccctccggg gattcatgtt gtgcagaacc accagcacag 4500
tgtatccggt gcacttggga aatttgtcat gtagcttaga aggaaatgcg tggaagaact 4560
tggagacgcc cttgtgacct ccaagatttt ccatgcattc gtccataatg atggcaatgg 4620
gcccacgggc ggcggcctgg gcgaagatat ttctgggatc actaacgtca tagttgtgtt 4680
ccaggatgag atcgtcatag gccattttta caaagcgcgg gcggagggtg ccagactgcg 4740
gtataatggt tccatccggc ccaggggcgt agttaccctc acagatttgc atttcccacg 4800
ctttgagttc agatgggggg atcatgtcta cctgcggggc gatgaagaaa acggtttccg 4860
gggtagggga gatcagctgg gaagaaagca ggttcctgag cagctgcgac ttaccgcagc 4920
cggtgggccc gtaaatcaca cctattaccg ggtgcaactg gtagttaaga gagctgcagc 4980
tgccgtcatc cctgagcagg ggggccactt cgttaagcat gtccctgact cgcatgtttt 5040
ccctgaccaa atccgccaga aggcgctcgc cgcccagcga tagcagttct tgcaaggaag 5100
caaagttttt caacggtttg agaccgtccg ccgtaggcat gcttttgagc gtttgaccaa 5160
gcagttccag gcggtcccac agctcggtca cctgctctac ggcatctcga tccagcatat 5220
ctcctcgttt cgcgggttgg ggcggctttc gctgtacggc agtagtcggt gctcgtccag 5280
acgggccagg gtcatgtctt tccacgggcg cagggtcctc gtcagcgtag tctgggtcac 5340
ggtgaagggg tgcgctccgg gctgcgcgct ggccagggtg cgcttgaggc tggtcctgct 5400
ggtgctgaag cgctgccggt cttcgccctg cgcgtcggcc aggtagcatt tgaccatggt 5460
gtcatagtcc agcccctccg cggcgtggcc cttggcgcgc agcttgccct tggaggaggc 5520
gccgcacgag gggcagtgca gacttttgag ggcgtagagc ttgggcgcga gaaataccga 5580
ttccggggag taggcatccg cgccgcaggc cccgcagacg gtctcgcatt ccacgagcca 5640
ggtgagctct ggccgttcgg ggtcaaaaac caggtttccc ccatgctttt tgatgcgttt 5700
cttacctctg gtttccatga gccggtgtcc acgctcggtg acgaaaaggc tgtccgtgtc 5760
cccgtataca gacttgagag gcctgtcctc gagcggtgtt ccgcggtcct cctcgtatag 5820
aaactcggac cactctgaga caaaggctcg cgtccaggcc agcacgaagg aggctaagtg 5880
ggaggggtag cggtcgttgt ccactagggg gtccactcgc tccagggtgt gaagacacat 5940
gtcgccctct tcggcatcaa ggaaggtgat tggtttgtag gtgtaggcca cgtgaccggg 6000
tgttcctgaa ggggggctat aaaagggggt gggggcgcgt tcgtcctcac tctcttccgc 6060
atcgctgtct gcgagggcca gctgttgggg tgagtactcc ctctgaaaag cgggcatgac 6120
ttctgcgcta agattgtcag tttccaaaaa cgaggaggat ttgatattca cctggcccgc 6180
ggtgatgcct ttgagggtgg ccgcatccat ctggtcagaa aagacaatct ttttgttgtc 6240
aagcttggtg gcaaacgacc cgtagagggc gttggacagc aacttggcga tggagcgcag 6300
ggtttggttt ttgtcgcgat cggcgcgctc cttggccgcg atgtttagct gcacgtattc 6360
gcgcgcaacg caccgccatt cgggaaagac ggtggtgcgc tcgtcgggca ccaggtgcac 6420
gcgccaaccg cggttgtgca gggtgacaag gtcaacgctg gtggctacct ctccgcgtag 6480
gcgctcgttg gtccagcaga ggcggccgcc cttgcgcgag cagaatggcg gtagggggtc 6540
tagctgcgtc tcgtccgggg ggtctgcgtc cacggtaaag accccgggca gcaggcgcgc 6600
gtcgaagtag tctatcttgc atccttgcaa gtctagcgcc tgctgccatg cgcgggcggc 6660
aagcgcgcgc tcgtatgggt tgagtggggg accccatggc atggggtggg tgagcgcgga 6720
ggcgtacatg ccgcaaatgt cgtaaacgta gaggggctct ctgagtattc caagatatgt 6780
agggtagcat cttccaccgc ggatgctggc gcgcacgtaa tcgtatagtt cgtgcgaggg 6840
agcgaggagg tcgggaccga ggttgctacg ggcgggctgc tctgctcgga agactatctg 6900
cctgaagatg gcatgtgagt tggatgatat ggttggacgc tggaagacgt tgaagctggc 6960
gtctgtgaga cctaccgcgt cacgcacgaa ggaggcgtag gagtcgcgca gcttgttgac 7020
cagctcggcg gtgacctgca cgtctagggc gcagtagtcc agggtttcct tgatgatgtc 7080
atacttatcc tgtccctttt ttttccacag ctcgcggttg aggacaaact cttcgcggtc 7140
tttccagtac tcttggatcg gaaacccgtc ggcctccgaa cggtaagagc ctagcatgta 7200
gaactggttg acggcctggt aggcgcagca tcccttttct acgggtagcg cgtatgcctg 7260
cgcggccttc cggagcgagg tgtgggtgag cgcaaaggtg tccctgacca tgactttgag 7320
gtactggtat ttgaagtcag tgtcgtcgca tccgccctgc tcccagagca aaaagtccgt 7380
gcgctttttg gaacgcggat ttggcagggc gaaggtgaca tcgttgaaga gtatctttcc 7440
cgcgcgaggc ataaagttgc gtgtgatgcg gaagggtccc ggcacctcgg aacggttgtt 7500
aattacctgg gcggcgagca cgatctcgtc aaagccgttg atgttgtggc ccacaatgta 7560
aagttccaag aagcgcggga tgcccttgat ggaaggcaat tttttaagtt cctcgtaggt 7620
gagctcttca ggggagctga gcccgtgctc tgaaagggcc cagtctgcaa gatgagggtt 7680
ggaagcgacg aatgagctcc acaggtcacg ggccattagc atttgcaggt ggtcgcgaaa 7740
ggtcctaaac tggcgaccta tggccatttt ttctggggtg atgcagtaga aggtaagcgg 7800
gtcttgttcc cagcggtccc atccaaggtt cgcggctagg tctcgcgcgg cagtcactag 7860
aggctcatct ccgccgaact tcatgaccag catgaagggc acgagctgct tcccaaaggc 7920
ccccatccaa gtataggtct ctacatcgta ggtgacaaag agacgctcgg tgcgaggatg 7980
cgagccgatc gggaagaact ggatctcccg ccaccaattg gaggagtggc tattgatgtg 8040
gtgaaagtag aagtccctgc gacgggccga acactcgtgc tggcttttgt aaaaacgtgc 8100
gcagtactgg cagcggtgca cgggctgtac atcctgcacg aggttgacct gacgaccgcg 8160
cacaaggaag cagagtggga atttgagccc ctcgcctggc gggtttggct ggtggtcttc 8220
tacttcggct gcttgtcctt gaccgtctgg ctgctcgagg ggagttacgg tggatcggac 8280
caccacgccg cgcgagccca aagtccagat gtccgcgcgc ggcggtcgga gcttgatgac 8340
aacatcgcgc agatgggagc tgtccatggt ctggagctcc cgcggcgtca ggtcaggcgg 8400
gagctcctgc aggtttacct cgcatagacg ggtcagggcg cgggctagat ccaggtgata 8460
cctaatttcc aggggctggt tggtggcggc gtcgatggct tgcaagaggc cgcatccccg 8520
cggcgcgact acggtaccgc gcggcgggcg gtgggccgcg ggggtgtcct tggatgatgc 8580
atctaaaagc ggtgacgcgg gcgagccccc ggaggtaggg ggggctccgg acccgccggg 8640
agagggggca ggggcacgtc ggcgccgcgc gcgggcagga gctggtgctg cgcgcgtagg 8700
ttgctggcga acgcgacgac gcggcggttg atctcctgaa tctggcgcct ctgcgtgaag 8760
acgacgggcc cggtgagctt gagcctgaaa gagagttcga cagaatcaat ttcggtgtcg 8820
ttgacggcgg cctggcgcaa aatctcctgc acgtctcctg agttgtcttg ataggcgatc 8880
tcggccatga actgctcgat ctcttcctcc tggagatctc cgcgtccggc tcgctccacg 8940
gtggcggcga ggtcgttgga aatgcgggcc atgagctgcg agaaggcgtt gaggcctccc 9000
tcgttccaga cgcggctgta gaccacgccc ccttcggcat cgcgggcgcg catgaccacc 9060
tgcgcgagat tgagctccac gtgccgggcg aagacggcgt agtttcgcag gcgctgaaag 9120
aggtagttga gggtggtggc ggtgtgttct gccacgaaga agtacataac ccagcgtcgc 9180
aacgtggatt cgttgatatc ccccaaggcc tcaaggcgct ccatggcctc gtagaagtcc 9240
acggcgaagt tgaaaaactg ggagttgcgc gccgacacgg ttaactcctc ctccagaaga 9300
cggatgagct cggcgacagt gtcgcgcacc tcgcgctcaa aggctacagg ggcctcttct 9360
tcttcttcaa tctcctcttc cataagggcc tccccttctt cttcttctgg cggcggtggg 9420
ggagggggga cacggcggcg acgacggcgc accgggaggc ggtcgacaaa gcgctcgatc 9480
atctccccgc ggcgacggcg catggtctcg gtgacggcgc ggccgttctc gcgggggcgc 9540
agttggaaga cgccgcccgt catgtcccgg ttatgggttg gcggggggct gccatgcggc 9600
agggatacgg cgctaacgat gcatctcaac aattgttgtg taggtactcc gccgccgagg 9660
gacctgagcg agtccgcatc gaccggatcg gaaaacctct cgagaaaggc gtctaaccag 9720
tcacagtcgc aaggtaggct gagcaccgtg gcgggcggca gcgggcggcg gtcggggttg 9780
tttctggcgg aggtgctgct gatgatgtaa ttaaagtagg cggtcttgag acggcggatg 9840
gtcgacagaa gcaccatgtc cttgggtccg gcctgctgaa tgcgcaggcg gtcggccatg 9900
ccccaggctt cgttttgaca tcggcgcagg tctttgtagt agtcttgcat gagcctttct 9960
accggcactt cttcttctcc ttcctcttgt cctgcatctc ttgcatctat cgctgcggcg 10020
gcggcggagt ttggccgtag gtggcgccct cttcctccca tgcgtgtgac cccgaagccc 10080
ctcatcggct gaagcagggc taggtcggcg acaacgcgct cggctaatat ggcctgctgc 10140
acctgcgtga gggtagactg gaagtcatcc atgtccacaa agcggtggta tgcgcccgtg 10200
ttgatggtgt aagtgcagtt ggccataacg gaccagttaa cggtctggtg acccggctgc 10260
gagagctcgg tgtacctgag acgcgagtaa gccctcgagt caaatacgta gtcgttgcaa 10320
gtccgcacca ggtactggta tcccaccaaa aagtgcggcg gcggctggcg gtagaggggc 10380
cagcgtaggg tggccggggc tccgggggcg agatcttcca acataaggcg atgatatccg 10440
tagatgtacc tggacatcca ggtgatgccg gcggcggtgg tggaggcgcg cggaaagtcg 10500
cggacgcggt tccagatgtt gcgcagcggc aaaaagtgct ccatggtcgg gacgctctgg 10560
ccggtcaggc gcgcgcaatc gttgacgctc tagaccgtgc aaaaggagag cctgtaagcg 10620
ggcactcttc cgtggtctgg tggataaatt cgcaagggta tcatggcgga cgaccggggt 10680
tcgagccccg tatccggccg tccgccgtga tccatgcggt taccgcccgc gtgtcgaacc 10740
caggtgtgcg acgtcagaca acgggggagt gctccttttg gcttccttcc aggcgcggcg 10800
gctgctgcgc tagctttttt ggccactggc cgcgcgcagc gtaagcggtt aggctggaaa 10860
gcgaaagcat taagtggctc gctccctgta gccggagggt tattttccaa gggttgagtc 10920
gcgggacccc cggttcgagt ctcggaccgg ccggactgcg gcgaacgggg gtttgcctcc 10980
ccgtcatgca agaccccgct tgcaaattcc tccggaaaca gggacgagcc ccttttttgc 11040
ttttcccaga tgcatccggt gctgcggcag atgcgccccc ctcctcagca gcggcaagag 11100
caagagcagc ggcagacatg cagggcaccc tcccctcctc ctaccgcgtc aggaggggcg 11160
acatccgcgg ttgacgcggc agcagatggt gattacgaac ccccgcggcg ccgggcccgg 11220
cactacctgg acttggagga gggcgagggc ctggcgcggc taggagcgcc ctctcctgag 11280
cggtacccaa gggtgcagct gaagcgtgat acgcgtgagg cgtacgtgcc gcggcagaac 11340
ctgtttcgcg accgcgaggg agaggagccc gaggagatgc gggatcgaaa gttccacgca 11400
gggcgcgagc tgcggcatgg cctgaatcgc gagcggttgc tgcgcgagga ggactttgag 11460
cccgacgcgc gaaccgggat tagtcccgcg cgcgcacacg tggcggccgc cgacctggta 11520
accgcatacg agcagacggt gaaccaggag attaactttc aaaaaagctt taacaaccac 11580
gtgcgtacgc ttgtggcgcg cgaggaggtg gctataggac tgatgcatct gtgggacttt 11640
gtaagcgcgc tggagcaaaa cccaaatagc aagccgctca tggcgcagct gttccttata 11700
gtgcagcaca gcagggacaa cgaggcattc agggatgcgc tgctaaacat agtagagccc 11760
gagggccgct ggctgctcga tttgataaac atcctgcaga gcatagtggt gcaggagcgc 11820
agcttgagcc tggctgacaa ggtggccgcc atcaactatt ccatgcttag cctgggcaag 11880
ttttacgccc gcaagatata ccatacccct tacgttccca tagacaagga ggtaaagatc 11940
gaggggttct acatgcgcat ggcgctgaag gtgcttacct tgagcgacga cctgggcgtt 12000
tatcgcaacg agcgcatcca caaggccgtg agcgtgagcc ggcggcgcga gctcagcgac 12060
cgcgagctga tgcacagcct gcaaagggcc ctggctggca cgggcagcgg cgatagagag 12120
gccgagtcct actttgacgc gggcgctgac ctgcgctggg ccccaagccg acgcgccctg 12180
gaggcagctg gggccggacc tgggctggcg gtggcacccg cgcgcgctgg caacgtcggc 12240
ggcgtggagg aatatgacga ggacgatgag tacgagccag aggacggcga gtactaagcg 12300
gtgatgtttc tgatcagatg atgcaagacg caacggaccc ggcggtgcgg gcggcgctgc 12360
agagccagcc gtccggcctt aactccacgg acgactggcg ccaggtcatg gaccgcatca 12420
tgtcgctgac tgcgcgcaat cctgacgcgt tccggcagca gccgcaggcc aaccggctct 12480
ccgcaattct ggaagcggtg gtcccggcgc gcgcaaaccc cacgcacgag aaggtgctgg 12540
cgatcgtaaa cgcgctggcc gaaaacaggg ccatccggcc cgacgaggcc ggcctggtct 12600
acgacgcgct gcttcagcgc gtggctcgtt acaacagcgg caacgtgcag accaacctgg 12660
accggctggt gggggatgtg cgcgaggccg tggcgcagcg tgagcgcgcg cagcagcagg 12720
gcaacctggg ctccatggtt gcactaaacg ccttcctgag tacacagccc gccaacgtgc 12780
cgcggggaca ggaggactac accaactttg tgagcgcact gcggctaatg gtgactgaga 12840
caccgcaaag tgaggtgtac cagtctgggc cagactattt tttccagacc agtagacaag 12900
gcctgcagac cgtaaacctg agccaggctt tcaaaaactt gcaggggctg tggggggtgc 12960
gggctcccac aggcgaccgc gcgaccgtgt ctagcttgct gacgcccaac tcgcgcctgt 13020
tgctgctgct aatagcgccc ttcacggaca gtggcagcgt gtcccgggac acatacctag 13080
gtcacttgct gacactgtac cgcgaggcca taggtcaggc gcatgtggac gagcatactt 13140
tccaggagat tacaagtgtc agccgcgcgc tggggcagga ggacacgggc agcctggagg 13200
caaccctaaa ctacctgctg accaaccggc ggcagaagat cccctcgttg cacagtttaa 13260
acagcgagga ggagcgcatt ttgcgctacg tgcagcagag cgtgagcctt aacctgatgc 13320
gcgacggggt aacgcccagc gtggcgctgg acatgaccgc gcgcaacatg gaaccgggca 13380
tgtatgcctc aaaccggccg tttatcaacc gcctaatgga ctacttgcat cgcgcggccg 13440
ccgtgaaccc cgagtatttc accaatgcca tcttgaaccc gcactggcta ccgccccctg 13500
gtttctacac cgggggattc gaggtgcccg agggtaacga tggattcctc tgggacgaca 13560
tagacgacag cgtgttttcc ccgcaaccgc agaccctgct agagttgcaa cagcgcgagc 13620
aggcagaggc ggcgctgcga aaggaaagct tccgcaggcc aagcagcttg tccgatctag 13680
gcgctgcggc cccgcggtca gatgctagta gcccatttcc aagcttgata gggtctctta 13740
ccagcactcg caccacccgc ccgcgcctgc tgggcgagga ggagtaccta aacaactcgc 13800
tgctgcagcc gcagcgcgaa aaaaacctgc ctccggcatt tcccaacaac gggatagaga 13860
gcctagtgga caagatgagt agatggaaga cgtacgcgca ggagcacagg gacgtgccag 13920
gcccgcgccc gcccacccgt cgtcaaaggc acgaccgtca gcggggtctg gtgtgggagg 13980
acgatgactc ggcagacgac agcagcgtcc tggatttggg agggagtggc aacccgtttg 14040
cgcaccttcg ccccaggctg gggagaatgt tttaaaaaaa aaaaagcatg atgcaaaata 14100
aaaaactcac caaggccatg gcaccgagcg ttggttttct tgtattcccc ttagtatgcg 14160
gcgcgcggcg atgtatgagg aaggtcctcc tccctcctac gagagtgtgg tgagcgcggc 14220
gccagtggcg gcggcgctgg gttctccctt cgatgctccc ctggacccgc cgtttgtgcc 14280
tccgcggtac ctgcggccta ccggggggag aaacagcatc cgttactctg agttggcacc 14340
cctattcgac accacccgtg tgtacctggt ggacaacaag tcaacggatg tggcatccct 14400
gaactaccag aacgaccaca gcaactttct gaccacggtc attcaaaaca atgactacag 14460
cccgggggag gcaagcacac agaccatcaa tcttgacgac cggtcgcact ggggcggcga 14520
cctgaaaacc atcctgcata ccaacatgcc aaatgtgaac gagttcatgt ttaccaataa 14580
gtttaaggcg cgggtgatgg tgtcgcgctt gcctactaag gacaatcagg tggagctgaa 14640
atacgagtgg gtggagttca cgctgcccga gggcaactac tccgagacca tgaccataga 14700
ccttatgaac aacgcgatcg tggagcacta cttgaaagtg ggcagacaga acggggttct 14760
ggaaagcgac atcggggtaa agtttgacac ccgcaacttc agactggggt ttgaccccgt 14820
cactggtctt gtcatgcctg gggtatatac aaacgaagcc ttccatccag acatcatttt 14880
gctgccagga tgcggggtgg acttcaccca cagccgcctg agcaacttgt tgggcatccg 14940
caagcggcaa cccttccagg agggctttag gatcacctac gatgatctgg agggtggtaa 15000
cattcccgca ctgttggatg tggacgccta ccaggcgagc ttgaaagatg acaccgaaca 15060
gggcgggggt ggcgcaggcg gcagcaacag cagtggcagc ggcgcggaag agaactccaa 15120
cgcggcagcc gcggcaatgc agccggtgga ggacatgaac gatcatgcca ttcgcggcga 15180
cacctttgcc acacgggctg aggagaagcg cgctgaggcc gaagcagcgg ccgaagctgc 15240
cgcccccgct gcgcaacccg aggtcgagaa gcctcagaag aaaccggtga tcaaacccct 15300
gacagaggac agcaagaaac gcagttacaa cctaataagc aatgacagca ccttcaccca 15360
gtaccgcagc tggtaccttg catacaacta cggcgaccct cagaccggaa tccgctcatg 15420
gaccctgctt tgcactcctg acgtaacctg cggctcggag caggtctact ggtcgttgcc 15480
agacatgatg caagaccccg tgaccttccg ctccacgcgc cagatcagca actttccggt 15540
ggtgggcgcc gagctgttgc ccgtgcactc caagagcttc tacaacgacc aggccgtcta 15600
ctcccaactc atccgccagt ttacctctct gacccacgtg ttcaatcgct ttcccgagaa 15660
ccagattttg gcgcgcccgc cagcccccac catcaccacc gtcagtgaaa acgttcctgc 15720
tctcacagat cacgggacgc taccgctgcg caacagcatc ggaggagtcc agcgagtgac 15780
cattactgac gccagacgcc gcacctgccc ctacgtttac aaggccctgg gcatagtctc 15840
gccgcgcgtc ctatcgagcc gcactttttg agcaagcatg tccatcctta tatcgcccag 15900
caataacaca ggctggggcc tgcgcttccc aagcaagatg tttggcgggg ccaagaagcg 15960
ctccgaccaa cacccagtgc gcgtgcgcgg gcactaccgc gcgccctggg gcgcgcacaa 16020
acgcggccgc actgggcgca ccaccgtcga tgacgccatc gacgcggtgg tggaggaggc 16080
gcgcaactac acgcccacgc cgccaccagt gtccacagtg gacgcggcca ttcagaccgt 16140
ggtgcgcgga gcccggcgct atgctaaaat gaagagacgg cggaggcgcg tagcacgtcg 16200
ccaccgccgc cgacccggca ctgccgccca acgcgcggcg gcggccctgc ttaaccgcgc 16260
acgtcgcacc ggccgacggg cggccatgcg ggccgctcga aggctggccg cgggtattgt 16320
cactgtgccc cccaggtcca ggcgacgagc ggccgccgca gcagccgcgg ccattagtgc 16380
tatgactcag ggtcgcaggg gcaacgtgta ttgggtgcgc gactcggtta gcggcctgcg 16440
cgtgcccgtg cgcacccgcc ccccgcgcaa ctagattgca agaaaaaact acttagactc 16500
gtactgttgt atgtatccag cggcggcggc gcgcaacgaa gctatgtcca agcgcaaaat 16560
caaagaagag atgctccagg tcatcgcgcc ggagatctat ggccccccga agaaggaaga 16620
gcaggattac aagccccgaa agctaaagcg ggtcaaaaag aaaaagaaag atgatgatga 16680
tgaacttgac gacgaggtgg aactgctgca cgctaccgcg cccaggcgac gggtacagtg 16740
gaaaggtcga cgcgtaaaac gtgttttgcg acccggcacc accgtagtct ttacgcccgg 16800
tgagcgctcc acccgcacct acaagcgcgt gtatgatgag gtgtacggcg acgaggacct 16860
gcttgagcag gccaacgagc gcctcgggga gtttgcctac ggaaagcggc ataaggacat 16920
gctggcgttg ccgctggacg agggcaaccc aacacctagc ctaaagcccg taacactgca 16980
gcaggtgctg cccgcgcttg caccgtccga agaaaagcgc ggcctaaagc gcgagtctgg 17040
tgacttggca cccaccgtgc agctgatggt acccaagcgc cagcgactgg aagatgtctt 17100
ggaaaaaatg accgtggaac ctgggctgga gcccgaggtc cgcgtgcggc caatcaagca 17160
ggtggcgccg ggactgggcg tgcagaccgt ggacgttcag atacccacta ccagtagcac 17220
cagtattgcc accgccacag agggcatgga gacacaaacg tccccggttg cctcagcggt 17280
ggcggatgcc gcggtgcagg cggtcgctgc ggccgcgtcc aagacctcta cggaggtgca 17340
aacggacccg tggatgtttc gcgtttcagc cccccggcgc ccgcgcggtt cgaggaagta 17400
cggcgccgcc agcgcgctac tgcccgaata tgccctacat ccttccattg cgcctacccc 17460
cggctatcgt ggctacacct accgccccag aagacgagca actacccgac gccgaaccac 17520
cactggaacc cgccgccgcc gtcgccgtcg ccagcccgtg ctggccccga tttccgtgcg 17580
cagggtggct cgcgaaggag gcaggaccct ggtgctgcca acagcgcgct accaccccag 17640
catcgtttaa aagccggtct ttgtggttct tgcagatatg gccctcacct gccgcctccg 17700
tttcccggtg ccgggattcc gaggaagaat gcaccgtagg aggggcatgg ccggccacgg 17760
cctgacgggc ggcatgcgtc gtgcgcacca ccggcggcgg cgcgcgtcgc accgtcgcat 17820
gcgcggcggt atcctgcccc tccttattcc actgatcgcc gcggcgattg gcgccgtgcc 17880
cggaattgca tccgtggcct tgcaggcgca gagacactga ttaaaaacaa gttgcatgtg 17940
gaaaaatcaa aataaaaagt ctggactctc acgctcgctt ggtcctgtaa ctattttgta 18000
gaatggaaga catcaacttt gcgtctctgg ccccgcgaca cggctcgcgc ccgttcatgg 18060
gaaactggca agatatcggc accagcaata tgagcggtgg cgccttcagc tggggctcgc 18120
tgtggagcgg cattaaaaat ttcggttcca ccgttaagaa ctatggcagc aaggcctgga 18180
acagcagcac aggccagatg ctgagggata agttgaaaga gcaaaatttc caacaaaagg 18240
tggtagatgg cctggcctct ggcattagcg gggtggtgga cctggccaac caggcagtgc 18300
aaaataagat taacagtaag cttgatcccc gccctcccgt agaggagcct ccaccggccg 18360
tggagacagt gtctccagag gggcgtggcg aaaagcgtcc gcgccccgac agggaagaaa 18420
ctctggtgac gcaaatagac gagcctccct cgtacgagga ggcactaaag caaggcctgc 18480
ccaccacccg tcccatcgcg cccatggcta ccggagtgct gggccagcac acacccgtaa 18540
cgctggacct gcctcccccc gccgacaccc agcagaaacc tgtgctgcca ggcccgaccg 18600
ccgttgttgt aacccgtcct agccgcgcgt ccctgcgccg cgccgccagc ggtccgcgat 18660
cgttgcggcc cgtagccagt ggcaactggc aaagcacact gaacagcatc gtgggtctgg 18720
gggtgcaatc cctgaagcgc cgacgatgct tctgaatagc taacgtgtcg tatgtgtgtc 18780
atgtatgcgt ccatgtcgcc gccagaggag ctgctgagcc gccgcgcgcc cgctttccaa 18840
gatggctacc ccttcgatga tgccgcagtg gtcttacatg cacatctcgg gccaggacgc 18900
ctcggagtac ctgagccccg ggctggtgca gtttgcccgc gccaccgaga cgtacttcag 18960
cctgaataac aagtttagaa accccacggt ggcgcctacg cacgacgtga ccacagaccg 19020
gtcccagcgt ttgacgctgc ggttcatccc tgtggaccgt gaggatactg cgtactcgta 19080
caaggcgcgg ttcaccctag ctgtgggtga taaccgtgtg ctggacatgg cttccacgta 19140
ctttgacatc cgcggcgtgc tggacagggg ccctactttt aagccctact ctggcactgc 19200
ctacaacgcc ctggctccca agggtgcccc aaatccttgc gaatgggatg aagctgctac 19260
tgctcttgaa ataaacctag aagaagagga cgatgacaac gaagacgaag tagacgagca 19320
agctgagcag caaaaaactc acgtatttgg gcaggcgcct tattctggta taaatattac 19380
aaaggagggt attcaaatag gtgtcgaagg tcaaacacct aaatatgccg ataaaacatt 19440
tcaacctgaa cctcaaatag gagaatctca gtggtacgaa actgaaatta atcatgcagc 19500
tgggagagtc cttaaaaaga ctaccccaat gaaaccatgt tacggttcat atgcaaaacc 19560
cacaaatgaa aatggagggc aaggcattct tgtaaagcaa caaaatggaa agctagaaag 19620
tcaagtggaa atgcaatttt tctcaactac tgaggcgacc gcaggcaatg gtgataactt 19680
gactcctaaa gtggtattgt acagtgaaga tgtagatata gaaaccccag acactcatat 19740
ttcttacatg cccactatta aggaaggtaa ctcacgagaa ctaatgggcc aacaatctat 19800
gcccaacagg cctaattaca ttgcttttag ggacaatttt attggtctaa tgtattacaa 19860
cagcacgggt aatatgggtg ttctggcggg ccaagcatcg cagttgaatg ctgttgtaga 19920
tttgcaagac agaaacacag agctttcata ccagcttttg cttgattcca ttggtgatag 19980
aaccaggtac ttttctatgt ggaatcaggc tgttgacagc tatgatccag atgttagaat 20040
tattgaaaat catggaactg aagatgaact tccaaattac tgctttccac tgggaggtgt 20100
gattaataca gagactctta ccaaggtaaa acctaaaaca ggtcaggaaa atggatggga 20160
aaaagatgct acagaatttt cagataaaaa tgaaataaga gttggaaata attttgccat 20220
ggaaatcaat ctaaatgcca acctgtggag aaatttcctg tactccaaca tagcgctgta 20280
tttgcccgac aagctaaagt acagtccttc caacgtaaaa atttctgata acccaaacac 20340
ctacgactac atgaacaagc gagtggtggc tcccgggtta gtggactgct acattaacct 20400
tggagcacgc tggtcccttg actatatgga caacgtcaac ccatttaacc accaccgcaa 20460
tgctggcctg cgctaccgct caatgttgct gggcaatggt cgctatgtgc ccttccacat 20520
ccaggtgcct cagaagttct ttgccattaa aaacctcctt ctcctgccgg gctcatacac 20580
ctacgagtgg aacttcagga aggatgttaa catggttctg cagagctccc taggaaatga 20640
cctaagggtt gacggagcca gcattaagtt tgatagcatt tgcctttacg ccaccttctt 20700
ccccatggcc cacaacaccg cctccacgct tgaggccatg cttagaaacg acaccaacga 20760
ccagtccttt aacgactatc tctccgccgc caacatgctc taccctatac ccgccaacgc 20820
taccaacgtg cccatatcca tcccctcccg caactgggcg gctttccgcg gctgggcctt 20880
cacgcgcctt aagactaagg aaaccccatc actgggctcg ggctacgacc cttattacac 20940
ctactctggc tctataccct acctagatgg aaccttttac ctcaaccaca cctttaagaa 21000
ggtggccatt acctttgact cttctgtcag ctggcctggc aatgaccgcc tgcttacccc 21060
caacgagttt gaaattaagc gctcagttga cggggagggt tacaacgttg cccagtgtaa 21120
catgaccaaa gactggttcc tggtacaaat gctagctaac tacaacattg gctaccaggg 21180
cttctatatc ccagagagct acaaggaccg catgtactcc ttctttagaa acttccagcc 21240
catgagccgt caggtggtgg atgatactaa atacaaggac taccaacagg tgggcatcct 21300
acaccaacac aacaactctg gatttgttgg ctaccttgcc cccaccatgc gcgaaggaca 21360
ggcctaccct gctaacttcc cctatccgct tataggcaag accgcagttg acagcattac 21420
ccagaaaaag tttctttgcg atcgcaccct ttggcgcatc ccattctcca gtaactttat 21480
gtccatgggc gcactcacag acctgggcca aaaccttctc tacgccaact ccgcccacgc 21540
gctagacatg acttttgagg tggatcccat ggacgagccc acccttcttt atgttttgtt 21600
tgaagtcttt gacgtggtcc gtgtgcaccg gccgcaccgc ggcgtcatcg aaaccgtgta 21660
cctgcgcacg cccttctcgg ccggcaacgc cacaacataa agaagcaagc aacatcaaca 21720
acagctgccg ccatgggctc cagtgagcag gaactgaaag ccattgtcaa agatcttggt 21780
tgtgggccat attttttggg cacctatgac aagcgctttc caggctttgt ttctccacac 21840
aagctcgcct gcgccatagt caatacggcc ggtcgcgaga ctgggggcgt acactggatg 21900
gcctttgcct ggaacccgca ctcaaaaaca tgctacctct ttgagccctt tggcttttct 21960
gaccagcgac tcaagcaggt ttaccagttt gagtacgagt cactcctgcg ccgtagcgcc 22020
attgcttctt cccccgaccg ctgtataacg ctggaaaagt ccacccaaag cgtacagggg 22080
cccaactcgg ccgcctgtgg actattctgc tgcatgtttc tccacgcctt tgccaactgg 22140
ccccaaactc ccatggatca caaccccacc atgaacctta ttaccggggt acccaactcc 22200
atgctcaaca gtccccaggt acagcccacc ctgcgtcgca accaggaaca gctctacagc 22260
ttcctggagc gccactcgcc ctacttccgc agccacagtg cgcagattag gagcgccact 22320
tctttttgtc acttgaaaaa catgtaaaaa taatgtacta gagacacttt caataaaggc 22380
aaatgctttt atttgtacac tctcgggtga ttatttaccc ccacccttgc cgtctgcgcc 22440
gtttaaaaat caaaggggtt ctgccgcgca tcgctatgcg ccactggcag ggacacgttg 22500
cgatactggt gtttagtgct ccacttaaac tcaggcacaa ccatccgcgg cagctcggtg 22560
aagttttcac tccacaggct gcgcaccatc accaacgcgt ttagcaggtc gggcgccgat 22620
atcttgaagt cgcagttggg gcctccgccc tgcgcgcgcg agttgcgata cacagggttg 22680
cagcactgga acactatcag cgccgggtgg tgcacgctgg ccagcacgct cttgtcggag 22740
atcagatccg cgtccaggtc ctccgcgttg ctcagggcga acggagtcaa ctttggtagc 22800
tgccttccca aaaagggcgc gtgcccaggc tttgagttgc actcgcaccg tagtggcatc 22860
aaaaggtgac cgtgcccggt ctgggcgtta ggatacagcg cctgcataaa agccttgatc 22920
tgcttaaaag ccacctgagc ctttgcgcct tcagagaaga acatgccgca agacttgccg 22980
gaaaactgat tggccggaca ggccgcgtcg tgcacgcagc accttgcgtc ggtgttggag 23040
atctgcacca catttcggcc ccaccggttc ttcacgatct tggccttgct agactgctcc 23100
ttcagcgcgc gctgcccgtt ttcgctcgtc acatccattt caatcacgtg ctccttattt 23160
atcataatgc ttccgtgtag acacttaagc tcgccttcga tctcagcgca gcggtgcagc 23220
cacaacgcgc agcccgtggg ctcgtgatgc ttgtaggtca cctctgcaaa cgactgcagg 23280
tacgcctgca ggaatcgccc catcatcgtc acaaaggtct tgttgctggt gaaggtcagc 23340
tgcaacccgc ggtgctcctc gttcagccag gtcttgcata cggccgccag agcttccact 23400
tggtcaggca gtagtttgaa gttcgccttt agatcgttat ccacgtggta cttgtccatc 23460
agcgcgcgcg cagcctccat gcccttctcc cacgcagaca cgatcggcac actcagcggg 23520
ttcatcaccg taatttcact ttccgcttcg ctgggctctt cctcttcctc ttgcgtccgc 23580
ataccacgcg ccactgggtc gtcttcattc agccgccgca ctgtgcgctt acctcctttg 23640
ccatgcttga ttagcaccgg tgggttgctg aaacccacca tttgtagcgc cacatcttct 23700
ctttcttcct cgctgtccac gattacctct ggtgatggcg ggcgctcggg cttgggagaa 23760
gggcgcttct ttttcttctt gggcgcaatg gccaaatccg ccgccgaggt cgatggccgc 23820
gggctgggtg tgcgcggcac cagcgcgtct tgtgatgagt cttcctcgtc ctcggactcg 23880
atacgccgcc tcatccgctt ttttgggggc gcccggggag gcggcggcga cggggacggg 23940
gacgacacgt cctccatggt tgggggacgt cgcgccgcac cgcgtccgcg ctcgggggtg 24000
gtttcgcgct gctcctcttc ccgactggcc atttccttct cctataggca gaaaaagatc 24060
atggagtcag tcgagaagaa ggacagccta accgccccct ctgagttcgc caccaccgcc 24120
tccaccgatg ccgccaacgc gcctaccacc ttccccgtcg aggcaccccc gcttgaggag 24180
gaggaagtga ttatcgagca ggacccaggt tttgtaagcg aagacgacga ggaccgctca 24240
gtaccaacag aggataaaaa gcaagaccag gacaacgcag aggcaaacga ggaacaagtc 24300
gggcgggggg acgaaaggca tggcgactac ctagatgtgg gagacgacgt gctgttgaag 24360
catctgcagc gccagtgcgc cattatctgc gacgcgttgc aagagcgcag cgatgtgccc 24420
ctcgccatag cggatgtcag ccttgcctac gaacgccacc tattctcacc gcgcgtaccc 24480
cccaaacgcc aagaaaacgg cacatgcgag cccaacccgc gcctcaactt ctaccccgta 24540
tttgccgtgc cagaggtgct tgccacctat cacatctttt tccaaaactg caagataccc 24600
ctatcctgcc gtgccaaccg cagccgagcg gacaagcagc tggccttgcg gcagggcgct 24660
gtcatacctg atatcgcctc gctcaacgaa gtgccaaaaa tctttgaggg tcttggacgc 24720
gacgagaagc gcgcggcaaa cgctctgcaa caggaaaaca gcgaaaatga aagtcactct 24780
ggagtgttgg tggaactcga gggtgacaac gcgcgcctag ccgtactaaa acgcagcatc 24840
gaggtcaccc actttgccta cccggcactt aacctacccc ccaaggtcat gagcacagtc 24900
atgagtgagc tgatcgtgcg ccgtgcgcag cccctggaga gggatgcaaa tttgcaagaa 24960
caaacagagg agggcctacc cgcagttggc gacgagcagc tagcgcgctg gcttcaaacg 25020
cgcgagcctg ccgacttgga ggagcgacgc aaactaatga tggccgcagt gctcgttacc 25080
gtggagcttg agtgcatgca gcggttcttt gctgacccgg agatgcagcg caagctagag 25140
gaaacattgc actacacctt tcgacagggc tacgtacgcc aggcctgcaa gatctccaac 25200
gtggagctct gcaacctggt ctcctacctt ggaattttgc acgaaaaccg ccttgggcaa 25260
aacgtgcttc attccacgct caagggcgag gcgcgccgcg actacgtccg cgactgcgtt 25320
tacttatttc tatgctacac ctggcagacg gccatgggcg tttggcagca gtgcttggag 25380
gagtgcaacc tcaaggagct gcagaaactg ctaaagcaaa acttgaagga cctatggacg 25440
gccttcaacg agcgctccgt ggccgcgcac ctggcggaca tcattttccc cgaacgcctg 25500
cttaaaaccc tgcaacaggg tctgccagac ttcaccagtc aaagcatgtt gcagaacttt 25560
aggaacttta tcctagagcg ctcaggaatc ttgcccgcca cctgctgtgc acttcctagc 25620
gactttgtgc ccattaagta ccgcgaatgc cctccgccgc tttggggcca ctgctacctt 25680
ctgcagctag ccaactacct tgcctaccac tctgacataa tggaagacgt gagcggtgac 25740
ggtctactgg agtgtcactg tcgctgcaac ctatgcaccc cgcaccgctc cctggtttgc 25800
aattcgcagc tgcttaacga aagtcaaatt atcggtacct ttgagctgca gggtccctcg 25860
cctgacgaaa agtccgcggc tccggggttg aaactcactc cggggctgtg gacgtcggct 25920
taccttcgca aatttgtacc tgaggactac cacgcccacg agattaggtt ctacgaagac 25980
caatcccgcc cgccaaatgc ggagcttacc gcctgcgtca ttacccaggg ccacattctt 26040
ggccaattgc aagccatcaa caaagcccgc caagagtttc tgctacgaaa gggacggggg 26100
gtttacttgg acccccagtc cggcgaggag ctcaacccaa tccccccgcc gccgcagccc 26160
tatcagcagc agccgcgggc ccttgcttcc caggatggca cccaaaaaga agctgcagct 26220
gccgccgcca cccacggacg aggaggaata ctgggacagt caggcagagg aggttttgga 26280
cgaggaggag gaggacatga tggaagactg ggagagccta gacgaggaag cttccgaggt 26340
cgaagaggtg tcagacgaaa caccgtcacc ctcggtcgca ttcccctcgc cggcgcccca 26400
gaaatcggca accggttcca gcatggctac aacctccgct cctcaggcgc cgccggcact 26460
gcccgttcgc cgacccaacc gtagatggga caccactgga accagggccg gtaagtccaa 26520
gcagccgccg ccgttagccc aagagcaaca acagcgccaa ggctaccgct catggcgcgg 26580
gcacaagaac gccatagttg cttgcttgca agactgtggg ggcaacatct ccttcgcccg 26640
ccgctttctt ctctaccatc acggcgtggc cttcccccgt aacatcctgc attactaccg 26700
tcatctctac agcccatact gcaccggcgg cagcggcagc ggcagcaaca gcagcggcca 26760
cacagaagca aaggcgaccg gatagcaaga ctctgacaaa gcccaagaaa tccacagcgg 26820
cggcagcagc aggaggagga gcgctgcgtc tggcgcccaa cgaacccgta tcgacccgcg 26880
agcttagaaa caggattttt cccactctgt atgctatatt tcaacagagc aggggccaag 26940
aacaagagct gaaaataaaa aacaggtctc tgcgatccct cacccgcagc tgcctgtatc 27000
acaaaagcga agatcagctt cggcgcacgc tggaagacgc ggaggctctc ttcagtaaat 27060
actgcgcgct gactcttaag gactagtttc gcgccctttc tcaaatttaa gcgcgaaaac 27120
tacgtcatct ccagcggcca cacccggcgc cagcacctgt cgtcagcgcc attatgagca 27180
aggaaattcc cacgccctac atgtggagtt accagccaca aatgggactt gcggctggag 27240
ctgcccaaga ctactcaacc cgaataaact acatgagcgc gggaccccac atgatatccc 27300
gggtcaacgg aatccgcgcc caccgaaacc gaattctctt ggaacaggcg gctattacca 27360
ccacacctcg taataacctt aatccccgta gttggcccgc tgccctggtg taccaggaaa 27420
gtcccgctcc caccactgtg gtacttccca gagacgccca ggccgaagtt cagatgacta 27480
actcaggggc gcagcttgcg ggcggctttc gtcacagggt gcggtcgccc gggcagggta 27540
taactcacct gacaatcaga gggcgaggta ttcagctcaa cgacgagtcg gtgagctcct 27600
cgcttggtct ccgtccggac gggacatttc agatcggcgg cgccggccgt ccttcattca 27660
cgcctcgtca ggcaatccta actctgcaga cctcgtcctc tgagccgcgc tctggaggca 27720
ttggaactct gcaatttatt gaggagtttg tgccatcggt ctactttaac cccttctcgg 27780
gacctcccgg ccactatccg gatcaattta ttcctaactt tgacgcggta aaggactcgg 27840
cggacggcta cgactgaatg ttaagtggag aggcagagca actgcgcctg aaacacctgg 27900
tccactgtcg ccgccacaag tgctttgccc gcgactccgg tgagttttgc tactttgaat 27960
tgcccgagga tcatatcgag ggcccggcgc acggcgtccg gcttaccgcc cagggagagc 28020
ttgcccgtag cctgattcgg gagtttaccc agcgccccct gctagttgag cgggacaggg 28080
gaccctgtgt tctcactgtg atttgcaact gtcctaacct tggattacat caagatcttt 28140
gttgccatct ctgtgctgag tataataaat acagaaatta aaatatactg gggctcctat 28200
cgccatcctg taaacgccac cgtcttcacc cgcccaagca aaccaaggcg aaccttacct 28260
ggtactttta acatctctcc ctctgtgatt tacaacagtt tcaacccaga cggagtgagt 28320
ctacgagaga acctctccga gctcagctac tccatcagaa aaaacaccac cctccttacc 28380
tgccgggaac gtacgagtgc gtcaccggcc gctgcaccac acctaccgcc tgaccgtaaa 28440
ccagactttt tccggacaga cctcaataac tctgtttacc agaacaggag gtgagcttag 28500
aaaaccctta gggtattagg ccaaaggcgc agctactgtg gggtttatga acaattcaag 28560
caactctacg ggctattcta attcaggttt ctctagaatc ggggttgggg ttattctctg 28620
tcttgtgatt ctctttattc ttatactaac gcttctctgc ctaaggctcg ccgcctgctg 28680
tgtgcacatt tgcatttatt gtcagctttt taaacgctgg ggtcgccacc caagatgatt 28740
aggtacataa tcctaggttt actcaccctt gcgtcagccc acggtaccac ccaaaaggtg 28800
gattttaagg agccagcctg taatgttaca ttcgcagctg aagctaatga gtgcaccact 28860
cttataaaat gcaccacaga acatgaaaag ctgcttattc gccacaaaaa caaaattggc 28920
aagtatgctg tttatgctat ttggcagcca ggtgacacta cagagtataa tgttacagtt 28980
ttccagggta aaagtcataa aacttttatg tatacttttc cattttatga aatgtgcgac 29040
attaccatgt acatgagcaa acagtataag ttgtggcccc cacaaaattg tgtggaaaac 29100
actggcactt tctgctgcac tgctatgcta attacagtgc tcgctttggt ctgtacccta 29160
ctctatatta aatacaaaag cagacgcagc tttattgagg aaaagaaaat gccttaattt 29220
actaagttac aaagctaatg tcaccactaa ctgctttact cgctgcttgc aaaacaaatt 29280
caaaaagtta gcattataat tagaatagga tttaaacccc ccggtcattt cctgctcaat 29340
accattcccc tgaacaattg actctatgtg ggatatgctc cagcgctaca accttgaagt 29400
caggcttcct ggatgtcagc atctgacttt ggccagcacc tgtcccgcgg atttgttcca 29460
gtccaactac agcgacccac cctaacagag atgaccaaca caaccaacgc ggccgccgct 29520
accggactta catctaccac aaatacaccc caagtttctg cctttgtcaa taactgggat 29580
aacttgggca tgtggtggtt ctccatagcg cttatgtttg tatgccttat tattatgtgg 29640
ctcatctgct gcctaaagcg caaacgcgcc cgaccaccca tctatagtcc catcattgtg 29700
ctacacccaa acaatgatgg aatccataga ttggacggac tgaaacacat gttcttttct 29760
cttacagtat gattaaatga gacatgattc ctcgagtttt tatattactg acccttgttg 29820
cgcttttttg tgcgtgctcc acattggctg cggtttctca catcgaagta gactgcattc 29880
cagccttcac agtctatttg ctttacggat ttgtcaccct cacgctcatc tgcagcctca 29940
tcactgtggt catcgccttt atccagtgca ttgactgggt ctgtgtgcgc tttgcatatc 30000
tcagacacca tccccagtac agggacagga ctatagctga gcttcttaga attctttaat 30060
tatgaaattt actgtgactt ttctgctgat tatttgcacc ctatctgcgt tttgttcccc 30120
gacctccaag cctcaaagac atatatcatg cagattcact cgtatatgga atattccaag 30180
ttgctacaat gaaaaaagcg atctttccga agcctggtta tatgcaatca tctctgttat 30240
ggtgttctgc agtaccatct tagccctagc tatatatccc taccttgaca ttggctggaa 30300
acgaatagat gccatgaacc acccaacttt ccccgcgccc gctatgcttc cactgcaaca 30360
agttgttgcc ggcggctttg tcccagccaa tcagcctcgc cccacttctc ccacccccac 30420
tgaaatcagc tactttaatc taacaggagg agatgactga caccctagat ctagaaatgg 30480
acggaattat tacagagcag cgcctgctag aaagacgcag ggcagcggcc gagcaacagc 30540
gcatgaatca agagctccaa gacatggtta acttgcacca gtgcaaaagg ggtatctttt 30600
gtctggtaaa gcaggccaaa gtcacctacg acagtaatac caccggacac cgccttagct 30660
acaagttgcc aaccaagcgt cagaaattgg tggtcatggt gggagaaaag cccattacca 30720
taactcagca ctcggtagaa accgaaggct gcattcactc accttgtcaa ggacctgagg 30780
atctctgcac ccttattaag accctgtgcg gtctcaaaga tcttattccc tttaactaat 30840
aaaaaaaaat aataaagcat cacttactta aaatcagtta gcaaatttct gtccagttta 30900
ttcagcagca cctccttgcc ctcctcccag ctctggtatt gcagcttcct cctggctgca 30960
aactttctcc acaatctaaa tggaatgtca gtttcctcct gttcctgtcc atccgcaccc 31020
actatcttca tgttgttgca gatgaagcgc gcaagaccgt ctgaagatac cttcaacccc 31080
gtgtatccat atgacacgga aaccggtcct ccaactgtgc cttttcttac tcctcccttt 31140
gtatccccca atgggtttca agagagtccc cctggggtac tctctttgcg cctatccgaa 31200
cctctagtta cctccaatgg catgcttgcg ctcaaaatgg gcaacggcct ctctctggac 31260
gaggccggca accttacctc ccaaaatgta accactgtga gcccacctct caaaaaaacc 31320
aagtcaaaca taaacctgga aatatctgca cccctcacag ttacctcaga agccctaact 31380
gtggctgccg ccgcacctct aatggtcgcg ggcaacacac tcaccatgca atcacaggcc 31440
ccgctaaccg tgcacgactc caaacttagc attgccaccc aaggacccct cacagtgtca 31500
gaaggaaagc tagccctgca aacatcaggc cccctcacca ccaccgatag cagtaccctt 31560
actatcactg cctcaccccc tctaactact gccactggta gcttgggcat tgacttgaaa 31620
gagcccattt atacacaaaa tggaaaacta ggactaaagt acggggctcc tttgcatgta 31680
acagacgacc taaacacttt gaccgtagca actggtccag gtgtgactat taataatact 31740
tccttgcaaa ctaaagttac tggagccttg ggttttgatt cacaaggcaa tatgcaactt 31800
aatgtagcag gaggactaag gattgattct caaaacagac gccttatact tgatgttagt 31860
tatccgtttg atgctcaaaa ccaactaaat ctaagactag gacagggccc tctttttata 31920
aactcagccc acaacttgga tattaactac aacaaaggcc tttacttgtt tacagcttca 31980
aacaattcca aaaagcttga ggttaaccta agcactgcca aggggttgat gtttgacgct 32040
acagccatag ccattaatgc aggagatggg cttgaatttg gttcacctaa tgcaccaaac 32100
acaaatcccc tcaaaacaaa aattggccat ggcctagaat ttgattcaaa caaggctatg 32160
gttcctaaac taggaactgg ccttagtttt gacagcacag gtgccattac agtaggaaac 32220
aaaaataatg ataagctaac tttgtggacc acaccagctc catctcctaa ctgtagacta 32280
aatgcagaga aagatgctaa actcactttg gtcttaacaa aatgtggcag tcaaatactt 32340
gctacagttt cagttttggc tgttaaaggc agtttggctc caatatctgg aacagttcaa 32400
agtgctcatc ttattataag atttgacgaa aatggagtgc tactaaacaa ttccttcctg 32460
gacccagaat attggaactt tagaaatgga gatcttactg aaggcacagc ctatacaaac 32520
gctgttggat ttatgcctaa cctatcagct tatccaaaat ctcacggtaa aactgccaaa 32580
agtaacattg tcagtcaagt ttacttaaac ggagacaaaa ctaaacctgt aacactaacc 32640
attacactaa acggtacaca ggaaacagga gacacaactc caagtgcata ctctatgtca 32700
ttttcatggg actggtctgg ccacaactac attaatgaaa tatttgccac atcctcttac 32760
actttttcat acattgccca agaataaaga atcgtttgtg ttatgtttca acgtgtttat 32820
ttttcaattg cagaaaattt caagtcattt ttcattcagt agtatagccc caccaccaca 32880
tagcttatac agatcaccgt accttaatca aactcacaga accctagtat tcaacctgcc 32940
acctccctcc caacacacag agtacacagt cctttctccc cggctggcct taaaaagcat 33000
catatcatgg gtaacagaca tattcttagg tgttatattc cacacggttt cctgtcgagc 33060
caaacgctca tcagtgatat taataaactc cccgggcagc tcacttaagt tcatgtcgct 33120
gtccagctgc tgagccacag gctgctgtcc aacttgcggt tgcttaacgg gcggcgaagg 33180
agaagtccac gcctacatgg gggtagagtc ataatcgtgc atcaggatag ggcggtggtg 33240
ctgcagcagc gcgcgaataa actgctgccg ccgccgctcc gtcctgcagg aatacaacat 33300
ggcagtggtc tcctcagcga tgattcgcac cgcccgcagc ataaggcgcc ttgtcctccg 33360
ggcacagcag cgcaccctga tctcacttaa atcagcacag taactgcagc acagcaccac 33420
aatattgttc aaaatcccac agtgcaaggc gctgtatcca aagctcatgg cggggaccac 33480
agaacccacg tggccatcat accacaagcg caggtagatt aagtggcgac ccctcataaa 33540
cacgctggac ataaacatta cctcttttgg catgttgtaa ttcaccacct cccggtacca 33600
tataaacctc tgattaaaca tggcgccatc caccaccatc ctaaaccagc tggccaaaac 33660
ctgcccgccg gctatacact gcagggaacc gggactggaa caatgacagt ggagagccca 33720
ggactcgtaa ccatggatca tcatgctcgt catgatatca atgttggcac aacacaggca 33780
cacgtgcata cacttcctca ggattacaag ctcctcccgc gttagaacca tatcccaggg 33840
aacaacccat tcctgaatca gcgtaaatcc cacactgcag ggaagacctc gcacgtaact 33900
cacgttgtgc attgtcaaag tgttacattc gggcagcagc ggatgatcct ccagtatggt 33960
agcgcgggtt tctgtctcaa aaggaggtag acgatcccta ctgtacggag tgcgccgaga 34020
caaccgagat cgtgttggtc gtagtgtcat gccaaatgga acgccggacg tagtcatatt 34080
tcctgaagca aaaccaggtg cgggcgtgac aaacagatct gcgtctccgg tctcgccgct 34140
tagatcgctc tgtgtagtag ttgtagtata tccactctct caaagcatcc aggcgccccc 34200
tggcttcggg ttctatgtaa actccttcat gcgccgctgc cctgataaca tccaccaccg 34260
cagaataagc cacacccagc caacctacac attcgttctg cgagtcacac acgggaggag 34320
cgggaagagc tggaagaacc atgttttttt ttttattcca aaagattatc caaaacctca 34380
aaatgaagat ctattaagtg aacgcgctcc cctccggtgg cgtggtcaaa ctctacagcc 34440
aaagaacaga taatggcatt tgtaagatgt tgcacaatgg cttccaaaag gcaaacggcc 34500
ctcacgtcca agtggacgta aaggctaaac ccttcagggt gaatctcctc tataaacatt 34560
ccagcacctt caaccatgcc caaataattc tcatctcgcc accttctcaa tatatctcta 34620
agcaaatccc gaatattaag tccggccatt gtaaaaatct gctccagagc gccctccacc 34680
ttcagcctca agcagcgaat catgattgca aaaattcagg ttcctcacag acctgtataa 34740
gattcaaaag cggaacatta acaaaaatac cgcgatcccg taggtccctt cgcagggcca 34800
gctgaacata atcgtgcagg tctgcacgga ccagcgcggc cacttccccg ccaggaacca 34860
tgacaaaaga acccacactg attatgacac gcatactcgg agctatgcta accagcgtag 34920
ccccgatgta agcttgttgc atgggcggcg atataaaatg caaggtgctg ctcaaaaaat 34980
caggcaaagc ctcgcgcaaa aaagaaagca catcgtagtc atgctcatgc agataaaggc 35040
aggtaagctc cggaaccacc acagaaaaag acaccatttt tctctcaaac atgtctgcgg 35100
gtttctgcat aaacacaaaa taaaataaca aaaaaacatt taaacattag aagcctgtct 35160
tacaacagga aaaacaaccc ttataagcat aagacggact acggccatgc cggcgtgacc 35220
gtaaaaaaac tggtcaccgt gattaaaaag caccaccgac agctcctcgg tcatgtccgg 35280
agtcataatg taagactcgg taaacacatc aggttgattc acatcggtca gtgctaaaaa 35340
gcgaccgaaa tagcccgggg gaatacatac ccgcaggcgt agagacaaca ttacagcccc 35400
cataggaggt ataacaaaat taataggaga gaaaaacaca taaacacctg aaaaaccctc 35460
ctgcctaggc aaaatagcac cctcccgctc cagaacaaca tacagcgctt ccacagcggc 35520
agccataaca gtcagcctta ccagtaaaaa agaaaaccta ttaaaaaaac accactcgac 35580
acggcaccag ctcaatcagt cacagtgtaa aaaagggcca agtgcagagc gagtatatat 35640
aggactaaaa aatgacgtaa cggttaaagt ccacaaaaaa cacccagaaa accgcacgcg 35700
aacctacgcc cagaaacgaa agccaaaaaa cccacaactt cctcaaatcg tcacttccgt 35760
tttcccacgt tacgtaactt cccattttaa gaaaactaca attcccaaca catacaagtt 35820
actccgccct aaaacctacg tcacccgccc cgttcccacg ccccgcgcca cgtcacaaac 35880
tccaccccct cattatcata ttggcttcaa tccaaaataa ggtatattat tgatgatg 35938
<210> 53
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<400> 53
Ser Asn Thr Lys Val Asp Lys Lys Val Glu
1 5 10
<210> 54
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<400> 54
Thr Lys Val Asp Lys Arg Val Glu
1 5
<210> 55
<211> 470
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 55
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro
225 230 235 240
Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
245 250 255
Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
260 265 270
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
275 280 285
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
290 295 300
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
305 310 315 320
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
325 330 335
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
340 345 350
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
355 360 365
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn
370 375 380
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
385 390 395 400
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
405 410 415
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
420 425 430
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
435 440 445
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
450 455 460
Ser Leu Ser Pro Gly Lys
465 470
<210> 56
<211> 468
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 56
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser
225 230 235 240
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
245 250 255
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
260 265 270
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
275 280 285
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
290 295 300
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
305 310 315 320
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
325 330 335
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
340 345 350
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
355 360 365
Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val
370 375 380
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
385 390 395 400
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
405 410 415
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
420 425 430
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
435 440 445
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
450 455 460
Ser Pro Gly Lys
465
<210> 57
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 57
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
1 5 10 15
<210> 58
<211> 476
<212> PRT
<213> 人工序列
<220>
<223> 合成的
<400> 58
Met Leu Pro Cys Leu Val Val Leu Leu Ala Ala Leu Leu Ser Leu Arg
1 5 10 15
Leu Gly Ser Asp Ala His Gly Thr Glu Leu Pro Ser Pro Pro Ser Val
20 25 30
Trp Phe Glu Ala Glu Phe Phe His His Ile Leu His Trp Thr Pro Ile
35 40 45
Pro Asn Gln Ser Glu Ser Thr Cys Tyr Glu Val Ala Leu Leu Arg Tyr
50 55 60
Gly Ile Glu Ser Trp Asn Ser Ile Ser Asn Cys Ser Gln Thr Leu Ser
65 70 75 80
Tyr Asp Leu Thr Ala Val Thr Leu Asp Leu Tyr His Ser Asn Gly Tyr
85 90 95
Arg Ala Arg Val Arg Ala Val Asp Gly Ser Arg His Ser Asn Trp Thr
100 105 110
Val Thr Asn Thr Arg Phe Ser Val Asp Glu Val Thr Leu Thr Val Gly
115 120 125
Ser Val Asn Leu Glu Ile His Asn Gly Phe Ile Leu Gly Lys Ile Gln
130 135 140
Leu Pro Arg Pro Lys Met Ala Pro Ala Asn Asp Thr Tyr Glu Ser Ile
145 150 155 160
Phe Ser His Phe Arg Glu Tyr Glu Ile Ala Ile Arg Lys Val Pro Gly
165 170 175
Asn Phe Thr Phe Thr His Lys Lys Val Lys His Glu Asn Phe Ser Leu
180 185 190
Leu Thr Ser Gly Glu Val Gly Glu Phe Cys Val Gln Val Lys Pro Ser
195 200 205
Val Ala Ser Arg Ser Asn Lys Gly Met Trp Ser Lys Glu Glu Cys Ile
210 215 220
Ser Leu Thr Arg Gln Asn Val Asn His Lys Pro Ser Asn Thr Lys Val
225 230 235 240
Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
245 250 255
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
260 265 270
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
275 280 285
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
290 295 300
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
305 310 315 320
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
325 330 335
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
340 345 350
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
355 360 365
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
370 375 380
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
385 390 395 400
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
405 410 415
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
420 425 430
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
435 440 445
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
450 455 460
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
465 470 475
<210> 59
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 59
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
1 5 10
<210> 60
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 60
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu
1 5 10
<210> 61
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<400> 61
Ser Asn Thr Lys Val Asp Lys Arg Val Glu
1 5 10
<210> 62
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 62
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
1 5 10 15
<210> 63
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 63
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
1 5 10
<210> 64
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<400> 64
Thr Lys Val Asp Lys Lys Val Glu
1 5
Claims (71)
1.一种分离的融合蛋白,其包含:
(i)IL-10受体的一部分;和
(ii)氨基酸连接物;以及下述至少一者:
(iii)细胞因子、细胞因子受体或免疫调节蛋白的细胞外结构域、跨膜结构域或细胞内结构域的一部分;
(iv)免疫球蛋白(Ig)铰链区;或
(v)免疫球蛋白(Ig)Fc结构域。
2.权利要求1所述的分离的融合蛋白,其中所述连接物包含约5至约40个氨基酸残基。
3.一种分离的融合蛋白,其以N-端到C-端的方向包含:
(i)IL-10受体的细胞外结构域的可溶性部分;
(ii)氨基酸连接物;
(iii)免疫球蛋白(Ig)铰链区;和
(iv)免疫球蛋白(Ig)Fc结构域;
其中所述连接物包含约5至约40个氨基酸残基。
4.权利要求1-3中任一项所述的分离的融合蛋白,其中所述连接物包含约5至约30个氨基酸残基。
5.权利要求1-3中任一项所述的分离的融合蛋白,其中所述连接物包含约5至约20个氨基酸残基。
6.权利要求1-3中任一项所述的分离的融合蛋白,其中所述连接物包含约5至约15个氨基酸残基。
7.权利要求1-3中任一项所述的分离的融合蛋白,其中所述连接物包含约10至约40个氨基酸残基。
8.权利要求1-3中任一项所述的分离的融合蛋白,其中所述连接物包含约10至约30个氨基酸残基。
9.权利要求1-3中任一项所述的分离的融合蛋白,其中所述连接物包含约10至约20个氨基酸残基。
10.权利要求1-3中任一项所述的分离的融合蛋白,其中所述连接物包含约10至约15个氨基酸残基。
11.权利要求1-10中任一项所述的分离的融合蛋白,其中所述连接物包含源自于内源人类蛋白的序列。
12.权利要求1-11中任一项所述的分离的融合蛋白,其中所述连接物包含免疫球蛋白(Ig)CH1结构域的C-端部分。
13.权利要求12所述的分离的融合蛋白,其中所述Ig CH1结构域选自IgG1、IgG2、IgG3、IgG4、IgA1、IgA2、IgD、IgE和IgM CH1结构域。
14.权利要求13所述的分离的融合蛋白,其中所述连接物包含选自SEQ ID NO:1、SEQID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ IDNO:8、SEQ ID NO:9、SEQ ID NO:53、SEQ ID NO:54和SEQ ID NO:57的氨基酸序列。
15.权利要求14所述的分离的融合蛋白,其中所述Ig CH1结构域是IgG1 CH1结构域。
16.权利要求15所述的分离的融合蛋白,其中所述连接物包含选自SEQ ID NO:1、SEQID NO:53、SEQ ID NO:54和SEQ ID NO:57的氨基酸序列。
17.权利要求16所述的分离的融合蛋白,其中所述连接物包含SEQ ID NO:57的氨基酸序列。
18.权利要求1-11中任一项所述的分离的融合蛋白,其中所述连接物包含源自于选自白蛋白和酪蛋白的人类蛋白的序列。
19.权利要求18所述的分离的融合蛋白,其中所述连接物包含选自SEQ ID NO:10和SEQID NO:11的氨基酸序列。
20.权利要求1-11中任一项所述的分离的融合蛋白,其中所述连接物包含源自于细胞因子、信号分子、免疫调节蛋白或肽的序列。
21.权利要求1-20中任一项所述的分离的融合蛋白,其中所述连接物包含切割位点。
22.权利要求21所述的分离的融合蛋白,其中所述切割位点是蛋白水解切割位点。
23.权利要求22所述的分离的融合蛋白,其中所述蛋白水解切割位点被存在于真核细胞的内质网或高尔基体中的蛋白酶切开。
24.引起22或23所述的分离的融合蛋白,其中所述蛋白水解切割位点是弗林蛋白酶切割位点。
25.权利要求24所述的分离的融合蛋白,其中所述弗林蛋白酶切割位点包含RX1X2R(SEQID NO:50),其中X1是任何氨基酸,并且X2是Lys或Arg。
26.权利要求22所述的分离的融合蛋白,其中所述弗林蛋白酶切割位点包含RAKR(SEQID NO:51)。
27.权利要求1-20中任一项所述的分离的融合蛋白,其中所述连接物包含在哺乳动物或植物中蛋白水解稳定的氨基酸序列。
28.权利要求1-27在任一项所述的分离的融合蛋白,其中所述IL-10受体是人类IL-10受体。
29.权利要求28所述的分离的融合蛋白,其中所述IL-10受体的细胞外结构域的可溶性部分包含SEQ ID NO:12的氨基酸序列。
30.权利要求28所述的分离的融合蛋白,其中所述IL-10受体的细胞外结构域的可溶性部分包含SEQ ID NO:12的第22至229位氨基酸残基。
31.权利要求1-30中任一项所述的分离的融合蛋白,其中所述Ig Fc结构域和铰链区选自人类IgG1、IgG2、IgG3、IgG4、IgA1、IgA2、IgD、IgE和IgM Fc结构域和铰链区。
32.权利要求31所述的分离的融合蛋白,其中所述Ig Fc结构域和铰链区包含选自SEQID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQID NO:19、SEQ ID NO:20和SEQ ID NO:21的氨基酸序列。
33.权利要求32所述的分离的融合蛋白,其中所述Ig Fc结构域和铰链区是人类IgG1Fc结构域和铰链区。
34.权利要求33所述的分离的融合蛋白,其中所述Ig Fc结构域和铰链区包含SEQ IDNO:13的氨基酸序列。
35.权利要求1-34中任一项所述的分离的融合蛋白,其中所述Ig Fc、Ig铰链区和IgCH1结构域源自于单一免疫球蛋白。
36.权利要求1-35中任一项所述的分离的融合蛋白,其中所述融合蛋白包含选自SEQID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQID NO:55、SEQ ID NO:56和SEQ ID NO:58的氨基酸序列。
37.权利要求36所述的分离的融合蛋白,其中所述融合蛋白包含选自SEQ ID NO:22、SEQ ID NO:55、SEQ ID NO:56和SEQ ID NO:58的氨基酸序列。
38.权利要求37所述的分离的融合蛋白,其中所述融合蛋白包含SEQ ID NO:58的氨基酸序列。
39.一种细胞因子结合蛋白,其包含两个权利要求1-38中任一项所述的融合蛋白,其中每个融合蛋白包含细胞因子受体的细胞外结构域,其中所述两个融合蛋白被共价连接在一起,并且其中所述两个细胞外结构域一起定义了用于结合细胞因子的结合位点。
40.一种分离的核酸,其包含编码权利要求1-39中任一项所述的融合蛋白的核苷酸序列。
41.一种表达载体,其包含权利要求40所述的核酸。
42.一种宿主细胞,其包含权利要求41所述的表达载体。
43.一种生产融合蛋白的方法,所述方法包括:
(a)将权利要求42所述的宿主细胞在一定条件下生长以表达所述融合蛋白;和
(b)纯化所述融合蛋白。
44.一种药物组合物,其包含:(i)权利要求1-39中任一项所述的融合蛋白或权利要求41所述的表达载体;和(ii)至少一种可药用载体或稀释剂。
45.一种在靶细胞中表达融合蛋白的方法,所述方法包括将所述细胞暴露于有效量的权利要求41所述的表达载体,以表达所述融合蛋白。
46.权利要求45所述的方法,其中所述融合蛋白在翻译后被切割成两条多肽链。
47.一种抑制肿瘤细胞增殖的方法,所述方法包括将所述细胞暴露于有效量的权利要求39所述的二聚体融合蛋白,以抑制所述肿瘤细胞的增殖。
48.一种抑制肿瘤细胞增殖的方法,所述方法包括将所述细胞暴露于有效量的权利要求1-38中任一项所述的融合蛋白,以抑制所述肿瘤细胞的增殖。
49.一种在需要的受试者中抑制肿瘤生长的方法,所述方法包括向所述对象施用有效量的权利要求39所述的二聚体融合蛋白,以抑制所述肿瘤的生长。
50.一种在需要的受试者中抑制肿瘤生长的方法,所述方法包括向所述对象施用有效量的权利要求1-38中任一项所述的融合蛋白,以抑制所述肿瘤的生长。
51.一种在需要的受试者中治疗癌症的方法,所述方法包括向所述对象施用有效量的权利要求39所述的二聚体融合蛋白。
52.一种在需要的受试者中治疗癌症的方法,所述方法包括向所述对象施用有效量的权利要求1-38中任一项所述的融合蛋白。
53.一种在细胞中降低IL-10活性的方法,所述方法包括将所述细胞暴露于有效量的权利要求39所述的二聚体融合蛋白,以降低IL-10活性。
54.一种在细胞中降低IL-10活性的方法,所述方法包括将所述细胞暴露于有效量的权利要求1-38中任一项所述的融合蛋白,以降低IL-10活性。
55.一种在需要的受试者中治疗炎性病症的方法,所述方法包括向所述受试者施用有效量的权利要求39所述的二聚体融合蛋白。
56.一种在需要的受试者中治疗炎性病症的方法,所述方法包括向所述受试者施用有效量的权利要求1-38中任一项所述的融合蛋白。
57.一种抑制肿瘤细胞增殖的方法,所述方法包括将所述细胞暴露于有效量的权利要求41所述的表达载体,以抑制所述肿瘤细胞的增殖。
58.一种在需要的受试者中抑制肿瘤生长的方法,所述方法包括向所述受试者施用有效量的权利要求41所述的表达载体,以抑制所述肿瘤的生长。
59.一种在需要的受试者中治疗癌症的方法,所述方法包括向所述受试者施用有效量的权利要求41所述的表达载体。
60.一种在细胞中降低IL-10活性的方法,所述方法包括将所述细胞暴露于有效量的权利要求41所述的表达载体,以降低IL-10活性。
61.一种在需要的受试者中治疗炎性病症的方法,所述方法包括向所述受试者施用有效量的权利要求41所述的表达载体。
62.一种在需要的受试者中治疗感染的方法,所述方法包括向所述受试者施用有效量的权利要求41所述的表达载体。
63.权利要求51、52或59中任一项所述的方法,其中所述癌症选自黑素瘤、皮肤的鳞状细胞癌、基底细胞癌、头颈癌、乳腺癌、肛门癌、宫颈癌、非小细胞肺癌、间皮瘤、小细胞肺癌、肾细胞癌、前列腺癌、胃食管癌、结肠直肠癌、睾丸癌、膀胱癌、卵巢癌、肝癌、肝细胞癌、胆管癌、脑和中枢神经系统癌症、甲状腺癌、甲状旁腺癌(例如甲状旁腺上皮癌)、子宫内膜癌、神经内分泌癌、淋巴瘤(例如霍奇金和非霍奇金)、白血病、梅克尔细胞癌、胃肠道间质肿瘤、多发性骨髓瘤、子宫癌、肉瘤、肾癌、眼癌、胰腺癌和生殖细胞癌(例如卵巢生殖细胞癌)。
64.权利要求51、52或59中任一项所述的方法,其中所述癌症选自白血病、乳腺癌、肺癌、胰腺癌、子宫内膜癌、卵巢癌、前列腺癌、宫颈癌、脑癌、皮肤癌、结肠直肠癌、胃癌、头颈癌和白血病。
65.权利要求64所述的方法,其中所述癌症选自皮肤癌、头颈癌和肺癌。
66.权利要求49-52、55、56、58、59或61-65中任一项所述的方法,其中所述融合蛋白或表达载体与选自手术、放射线、化疗、免疫疗法、激素疗法和病毒疗法的一种或多种疗法相组合施用到所述受试者。
67.权利要求49-52、55、56、58、59或61-65中任一项所述的方法,其中所述融合蛋白或表达载体与淋巴细胞相组合施用到所述受试者。
68.权利要求67所述的方法,其中所述淋巴细胞是T-细胞。
69.权利要求68所述的方法,其中所述T-细胞是嵌合抗原受体T-细胞(CAR T-cell)。
70.权利要求49-52、55、56、58、59或61-69中任一项所述的方法,其中所述受试者是人类或动物。
71.权利要求70所述的方法,其中所述受试者是人类幼儿。
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Publication number | Priority date | Publication date | Assignee | Title |
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Publication number | Priority date | Publication date | Assignee | Title |
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CN113480662B (zh) * | 2021-06-29 | 2022-07-22 | 北京双因生物科技有限公司 | 包含cd40抗体和il-15的融合蛋白及其制备方法和用途 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003066002A2 (en) * | 2002-02-08 | 2003-08-14 | University Of Medicine And Dentistry Of New Jersey | IFN-a/b-INDEPENDENT MECHANISM OF ANTIVIRAL PROTECTION |
WO2006084327A1 (en) * | 2005-02-09 | 2006-08-17 | Apollo Life Sciences Limited | A molecule and chimeric molecules thereof |
CN101146825A (zh) * | 2005-02-14 | 2008-03-19 | 阿波罗生命科学有限公司 | 分子及其嵌合分子 |
US20090111146A1 (en) * | 2003-09-02 | 2009-04-30 | National Institute Of Advanced Industrial Science | Antibody Drug |
WO2016174575A1 (en) * | 2015-04-29 | 2016-11-03 | Mediolanum Farmaceutici S.P.A. | A soluble chimeric interleukin-10 receptor and therapeutic use thereof |
Family Cites Families (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4980286A (en) | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
US5525491A (en) | 1991-02-27 | 1996-06-11 | Creative Biomolecules, Inc. | Serine-rich peptide linkers |
US5262522A (en) | 1991-11-22 | 1993-11-16 | Immunex Corporation | Receptor for oncostatin M and leukemia inhibitory factor |
AU3830895A (en) | 1994-10-07 | 1996-05-02 | Amgen Boulder Inc. | Dimeric il-4 inhibitors |
AUPN477695A0 (en) | 1995-08-14 | 1995-09-07 | Commonwealth Scientific And Industrial Research Organisation | Gene therapy |
GB9626029D0 (en) | 1996-12-14 | 1997-01-29 | Univ Leeds | EVH-1 vectors |
US5998598A (en) | 1997-03-10 | 1999-12-07 | The United States Of America, As Represented By The Department Of Health And Human Services | Immunoadhesins and methods of production and use thereof |
WO1998048024A1 (en) | 1997-04-18 | 1998-10-29 | Biogen, Inc. | Type ii tgf-beta receptor/immunoglobulin constant region fusion proteins |
EP1087998A1 (en) | 1998-06-16 | 2001-04-04 | Biogen, Inc. | Variant type ii tgf-beta receptor fusion proteins and methods |
US7083950B2 (en) | 1998-09-25 | 2006-08-01 | Regeneron Pharmaceuticals, Inc. | High affinity fusion proteins and therapeutic and diagnostic methods for use |
US6472179B2 (en) | 1998-09-25 | 2002-10-29 | Regeneron Pharmaceuticals, Inc. | Receptor based antagonists and methods of making and using |
US7754855B1 (en) | 1999-07-13 | 2010-07-13 | Bolder Biotechnology, Inc. | Immunoglobulin fusion proteins |
ATE316982T1 (de) | 1999-08-09 | 2006-02-15 | Lexigen Pharm Corp | Mehrere zytokin-antikörper komplexen |
US7638604B2 (en) | 2001-02-23 | 2009-12-29 | Genetics Institute, Llc | Monoclonal antibodies against interleukin-22 |
US20030125251A1 (en) | 2001-06-21 | 2003-07-03 | Wakefield Lalage M. | Transforming growth factor beta (TGF-beta) antagonist selectively neutralizes "pathological" TGF-beta |
WO2005028517A2 (en) | 2003-05-09 | 2005-03-31 | The General Hospital Corporation | SOLUBLE TGF-β TYPE III RECEPTOR FUSION PROTEINS |
WO2006084337A1 (en) * | 2005-02-14 | 2006-08-17 | Apollo Life Sciences Limited | A molecule and chimeric molecules thereof |
US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
US20090175819A1 (en) * | 2005-11-15 | 2009-07-09 | Apollo Life Sciences Limited | Molecule and chimeric molecules thereof |
US7867491B2 (en) | 2007-05-30 | 2011-01-11 | Genexine Co., Ltd. | Immunoglobulin fusion proteins |
EP2171062A1 (en) | 2007-06-15 | 2010-04-07 | Genzyme Corporation | Fusion proteins containing two tgf-beta binding domains of tgf-beta type ii receptor |
WO2009154995A2 (en) * | 2008-05-27 | 2009-12-23 | Kyowa Hakko Kirin Co., Ltd. | Interleukin 10 receptor (il-10r) antibodies and methods of use |
NZ590667A (en) | 2008-07-02 | 2013-01-25 | Emergent Product Dev Seattle | Tgf-b antagonist multi-target binding proteins |
EP2326670A4 (en) | 2008-09-17 | 2014-04-16 | Nat Res Council Canada | HETERO MULTIVALENT BINDING AGENT FOR ELEMENTS OF THE TGF-BETA SUPERFAMILY |
WO2010101921A2 (en) | 2009-03-02 | 2010-09-10 | The Regents Of The University Of California | Tumor-selective e1a and e1b mutants |
DK2542590T4 (da) | 2010-03-05 | 2020-07-13 | Univ Johns Hopkins | Sammensætninger og fremgangsmåde til målrettede immunomodulatoriske antistof-fer og fusionproteiner |
PT3489254T (pt) | 2012-04-30 | 2022-12-30 | Biocon Ltd | Proteínas de fusão direcionadas/imunomoduladoras e seus métodos de fabrico |
RU2662991C2 (ru) | 2013-03-12 | 2018-07-31 | Биокон Лтд. | Слитые иммуномодулирующие белки и способы их получения |
JP2016528295A (ja) | 2013-08-22 | 2016-09-15 | アクセルロン ファーマ, インコーポレイテッド | Tgf−ベータ受容体ii型変異体およびその使用 |
EP3071215B1 (en) | 2013-11-21 | 2020-01-08 | The Brigham and Women's Hospital, Inc. | Compositions and methods for treating pulmonary hypertension |
EP3105246B1 (en) | 2014-02-10 | 2021-03-31 | Merck Patent GmbH | Targeted tgf beta inhibition |
EP3233920B1 (en) | 2014-12-19 | 2020-08-26 | Alkermes, Inc. | Single chain fc fusion proteins |
US20200231652A1 (en) | 2015-08-31 | 2020-07-23 | National Research Council Of Canada | Tgf-b-receptor ectodomain fusion molecules and uses thereof |
CN118307682A (zh) | 2016-09-27 | 2024-07-09 | 埃皮辛特瑞柯斯公司 | 免疫调节性融合蛋白 |
US10232053B2 (en) * | 2016-12-30 | 2019-03-19 | Trieza Therapeutics, Inc. | Immunomodulatory oncolytic adenoviral vectors, and methods of production and use thereof for treatment of cancer |
-
2018
- 2018-09-27 CA CA3077223A patent/CA3077223A1/en active Pending
- 2018-09-27 SG SG11202002826VA patent/SG11202002826VA/en unknown
- 2018-09-27 MX MX2020003672A patent/MX2020003672A/es unknown
- 2018-09-27 JP JP2020517588A patent/JP2020536518A/ja not_active Withdrawn
- 2018-09-27 KR KR1020207011933A patent/KR20200057070A/ko not_active Application Discontinuation
- 2018-09-27 EA EA202090838A patent/EA202090838A1/ru unknown
- 2018-09-27 CN CN202410618028.5A patent/CN118652350A/zh active Pending
- 2018-09-27 CN CN201880075263.5A patent/CN111511769B/zh active Active
- 2018-09-27 BR BR112020006115-8A patent/BR112020006115A2/pt unknown
- 2018-09-27 WO PCT/US2018/053197 patent/WO2019067770A1/en active Application Filing
- 2018-09-27 US US16/651,079 patent/US11834492B2/en active Active
- 2018-09-27 EP EP18862997.6A patent/EP3688037A4/en active Pending
- 2018-09-27 AU AU2018338612A patent/AU2018338612A1/en active Pending
-
2020
- 2020-03-26 IL IL273626A patent/IL273626A/en unknown
-
2023
- 2023-05-16 JP JP2023081001A patent/JP2023096044A/ja active Pending
- 2023-10-25 US US18/494,508 patent/US20240052016A1/en active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003066002A2 (en) * | 2002-02-08 | 2003-08-14 | University Of Medicine And Dentistry Of New Jersey | IFN-a/b-INDEPENDENT MECHANISM OF ANTIVIRAL PROTECTION |
US20090111146A1 (en) * | 2003-09-02 | 2009-04-30 | National Institute Of Advanced Industrial Science | Antibody Drug |
WO2006084327A1 (en) * | 2005-02-09 | 2006-08-17 | Apollo Life Sciences Limited | A molecule and chimeric molecules thereof |
CN101146825A (zh) * | 2005-02-14 | 2008-03-19 | 阿波罗生命科学有限公司 | 分子及其嵌合分子 |
WO2016174575A1 (en) * | 2015-04-29 | 2016-11-03 | Mediolanum Farmaceutici S.P.A. | A soluble chimeric interleukin-10 receptor and therapeutic use thereof |
Non-Patent Citations (2)
Title |
---|
JING LI等: "Temporal associations between interleukin 22 and the extracellular domains of IL-22R and IL-10R2", vol. 4, pages 2 * |
MIZUE TERAI等: "Human interleukin 10 receptor 1/IgG1-Fc fusion proteins: immunoadhesins for human IL-10 with therapeutic potential", vol. 58, pages 1309 - 1310 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114945586A (zh) * | 2020-01-21 | 2022-08-26 | 张晋宇 | 一种药物组合物及其用途 |
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US20200223901A1 (en) | 2020-07-16 |
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AU2018338612A1 (en) | 2020-05-07 |
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KR20200057070A (ko) | 2020-05-25 |
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