CN116948025A - 一种抗Tau蛋白的抗体 - Google Patents
一种抗Tau蛋白的抗体 Download PDFInfo
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- CN116948025A CN116948025A CN202311186566.3A CN202311186566A CN116948025A CN 116948025 A CN116948025 A CN 116948025A CN 202311186566 A CN202311186566 A CN 202311186566A CN 116948025 A CN116948025 A CN 116948025A
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- tau protein
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Abstract
本发明公开了一种抗Tau蛋白的抗体,本发明提供的抗Tau蛋白的抗体对于Tau蛋白具有很强的亲和活性及特异性,为Tau蛋白的检测以及Tau蛋白相关疾病的治疗提供了新的思路,具有广阔的应用前景。
Description
技术领域
本发明属于生物医药领域,具体涉及一种抗Tau蛋白的抗体。
背景技术
微管相关蛋白Tau(microtubule-associated protein-tau,MAPT)又称为Tau蛋白,是神经系统内神经元表达水平最高的蛋白质,对稳定神经元微管系统、调控神经细胞生长发育以及神经传导等功能具有重要作用,是维持神经元生存和功能的必需物质。其表达水平可用来辅助阿尔兹海默症的诊治和预测轻度认知障碍到阿尔茨海默症的进展。因此,研发新的抗Tau蛋白的抗体对于实现Tau蛋白相关疾病的检测和治疗具有重要的作用。
发明内容
为弥补现有技术的不足,本发明提供了一种抗Tau蛋白的抗体。
为实现上述目的,本发明采用如下技术方案:
本发明的第一方面提供了一种抗Tau蛋白的抗体,所述抗体包括如SEQ ID NO:1、2、3所示的氨基酸序列的重链可变区互补决定区CDR1、CDR2、CDR3;
以及如SEQ ID NO:9、10、11所示的氨基酸序列的轻链可变区互补决定区CDR1、CDR2、CDR3。
进一步,所述抗体还包括如SEQ ID NO:4、5、6、7所示的氨基酸序列的重链可变区框架区FR1、FR2、FR3、FR4;
以及如SEQ ID NO:12、13、14、15所示的氨基酸序列的轻链可变区框架区FR1、FR2、FR3、FR4。
进一步,所述抗体的重链可变区具有与SEQ ID NO:8所示的氨基酸序列至少80%、至少85%、至少90%、至少92%、至少93%、95%、至少96%、至少97%、至少98%、至少99%的序列同一性,轻链可变区具有与SEQ ID NO:16所示的氨基酸序列至少80%、至少85%、至少90%、至少92%、至少93%、95%、至少96%、至少97%、至少98%、至少99%序列同一性。
进一步,所述抗体的重链可变区具有如SEQ ID NO:8所示的氨基酸序列,轻链可变区具有如SEQ ID NO:16所示的氨基酸序列。
进一步,所述CDR是根据Kabat、IMGT、Chothia、AbM或Contact编号系统定义的。
进一步,所述CDR是根据Kabat编号系统定义的。
进一步,所述抗体的重链可操作的连接第一信号肽,所述抗体的轻链可操作的连接第二信号肽。
进一步,所述第一信号肽的氨基酸序列如SEQ ID NO:33所示,第二信号肽的氨基酸序列如SEQ ID NO:34所示。
进一步,所述信号肽与抗体的5’端连接。
本发明的第二方面提供了如下任一项物质:
(1)核酸分子,所述核酸分子编码本发明第一方面所述的抗体;
(2)载体,所述载体包括(1)中所述的核酸分子;
(3)宿主细胞,所述宿主细胞包括(1)中所述的核酸分子或(2)中所述的载体;
(4)检测Tau蛋白的产品,所述产品包括本发明第一方面所述的抗体;
(5)药物组合物,所述药物组合物包括本发明第一方面所述的抗体;
(6)一种衍生物,所述衍生物包括在本发明第一方面所述的抗体上连接可检测试剂、治疗试剂,或所述抗体是去岩藻糖基化的抗体。
进一步,(1)中编码重链可变区互补决定区CDR1、CDR2、CDR3的核酸分子的核苷酸序列分别如SEQ ID NO:17、18、19所示;
编码轻链可变区互补决定区CDR1、CDR2、CDR3的核酸分子的核苷酸序列分别如SEQID NO:25、26、27所示。
进一步,(1)中编码重链的核酸分子可操作的连接第一信号肽,编码轻链的核酸分子可操作的连接第二信号肽。
进一步,所述第一信号肽的核苷酸序列如SEQ ID NO:35所示,所述第二信号肽的核苷酸序列如SEQ ID NO:36所示。
进一步,所述信号肽与核酸分子的5’端连接。
进一步,(2)中所述的载体还包括用于控制表达的元件。
进一步,所述载体还包括有助于其进入细胞的材料。
进一步,(3)中所述的宿主细胞包括原核细胞、真核细胞。
进一步,所述原核细胞包括真细菌。
进一步,所述真核细胞包括原生生物细胞、动物细胞、植物细胞或真菌细胞。
进一步,所述动物细胞包括哺乳动物细胞、鸟类细胞、昆虫细胞。
进一步,(4)中所述的产品包括试剂盒、试纸条。
进一步,所述试剂盒包括连接有信号产生化合物的抗体的缀合物。
进一步,(5)中所述的药物组合物还包括药学上可接受的载体。
进一步,(6)中所述的可检测试剂包括荧光染料、放射性标记、金属离子、酶、磁珠、比色标记。
进一步,(6)中所述的治疗试剂包括细胞毒素、治疗剂。
本发明的第三方面提供了本发明第一方面所述的抗体,或本发明第二方面所述的物质在检测Tau蛋白或在制备诊断Tau蛋白相关疾病的产品中的应用。
进一步,Tau蛋白相关疾病包括神经退化性疾病。
本发明的第四方面提供了本发明第一方面所述的抗体,或本发明第二方面所述的物质在制备预防和/或治疗Tau蛋白相关疾病的药物组合物中的应用。
本发明的第五方面提供了一种制备本发明第一方面所述的抗体的方法,所述方法包括:培养本发明第二方面中(3)所述的宿主细胞,回收单克隆抗体。
进一步,所述的方法还包括纯化所述的抗体。
本发明的第六方面提供了一种检测样本中Tau蛋白的方法,所述方法包括:使本发明第一方面所述的抗体与待测样本接触,从而检测待测样本中Tau蛋白的水平。
进一步,所述方法为非诊断目的的方法。
本发明的优点和有益效果:
本发明提供的抗Tau蛋白的抗体对于Tau蛋白具有很强的亲和活性及特异性,为Tau蛋白的检测以及Tau蛋白相关疾病的治疗提供了新的思路,具有广阔的应用前景。
附图说明
图1是抗体识别Tau蛋白的Western结果图;
图2是纯化抗体与抗原结合的特异性图。
具体实施方式
下文提供了本说明书中使用的一些术语的定义。除非另有说明,本文中使用的所有技术和科学用语通常具有和本发明所属领域的普通技术人员通常理解的意思相同的意思。
本发明提供了一种抗Tau蛋白的抗体,所述抗体包括如SEQ ID NO:1、2、3所示的氨基酸序列的重链可变区互补决定区CDR1、CDR2、CDR3;
以及如SEQ ID NO:9、10、11所示的氨基酸序列的轻链可变区互补决定区CDR1、CDR2、CDR3。
在本发明中,抗体是指免疫球蛋白和免疫球蛋白片段,无论天然的或者部分或全部合成(例如重组)产生的,其至少包括免疫球蛋白分子的部分可变区的保留全长免疫球蛋白的结合特异性能力的任何片段。因此,抗体包括具有与免疫球蛋白抗原结合结构域(抗体结合位点)同源或基本上同源的结合结构域的任何蛋白。抗体包括抗体片段,例如抗Tau蛋白抗体片段。如本发明所用,因此术语抗体包括合成抗体、重组产生的抗体、多特异性抗体(例如双特异性抗体)、人抗体、非人抗体、人源化抗体、嵌合抗体、胞内抗体以及抗体片段,包括但不限于Fab片段、Fab′片段、F(ab’)2片段、Fv片段、二硫键连接的Fv(dsFv)、Fd片段、Fd’片段、单链Fv(scFv)、单链Fab(scFab)、双抗体、抗独特型(抗Id)抗体、或者上述任何抗体的抗原结合片段。本发明所提供的抗体包括任何免疫球蛋白类型(例如,IgG、IgM、IgD、IgE、IgA和IgY)、任何类别(例如IgG1、IgG2、IgG3、IgG4、IgA1和IgA2)或亚类(例如,IgG2a和IgG2b)的成员,抗体包括单克隆抗体、多克隆抗体,本发明的抗体为单克隆抗体。
对于抗体的互补决定区CDR的精确氨基酸序列边界,可根据公知方法来定义,例如基于抗体的三维结构和CDR环的拓扑学的Chothia(Chothia等,Nature 342:877-883,1989;Al-Lazikani等,Journal of Molecular Biology,273:927-948,1997);或者基于抗体序列可变性的Kabat(Kabat等,Sequences of Proteins of Immunological Interest,第4版,U.S .Department of Health and Human Services,National Institutes of Health,1987)、AbM(University of Bath)、Contact(University College London)以及IMGT(theinternational ImMunoGeneTics database,1999Nucleic Acids Research ,27 ,209-212);或者基于利用大量晶体结构的近邻传播聚类(affinity propagation clustering)的North CDR定义。本申请中抗体的CDR可以由本领域技术人员根据本领域的任何方案(例如上述任选的定义方法)确定边界。
应该注意的是,基于不同定义方式获得的同一抗体的CDR的边界可能有所差异,即不同定义方式下获得的同一抗体可变区的CDR序列有所不同。因此,当采用本申请定义的具体CDR序列限定抗体时,所述抗体还包括其互补决定区序列包含本申请所述的CDR的序列,只是由于采用了不同的CDR边界定义方式而导致其所声称的CDR边界与本申请所定义的具体CDR边界不同的抗体。
在本发明的具体实施方案中,抗体的互补决定区CDR根据Kabat方式确定。
本发明提供了如下任一项物质:
(1)核酸分子,所述核酸分子编码上述抗体;
(2)载体,所述载体包括(1)中所述的核酸分子;
(3)宿主细胞,所述宿主细胞包括(1)中所述的核酸分子或(2)中所述的载体;
(4)检测Tau蛋白的产品,所述产品包括上述抗体;
(5)药物组合物,所述药物组合物包括上述抗体;
(6)一种衍生物,所述衍生物包括在上述抗体上连接可检测试剂、治疗试剂,或所述抗体是去岩藻糖基化的抗体。
在本发明中,核酸分子或核酸是指包括至少两个连接的核苷酸或核苷酸衍生物的寡聚体或聚合物,包括通常通过磷酸二酯键连接在一起的脱氧核糖核酸(DNA)和核糖核酸(RNA)。多核苷酸还包括DNA和RNA衍生物,其包括例如核苷酸类似物或除磷酸二酯键之外的“骨架”键,例如磷酸三酯键、氨基磷酸酯键、硫代磷酸酯键、硫酯键或肽键(肽核酸)。多核苷酸(核酸分子)包括单链和/或双链多核苷酸,例如脱氧核糖核酸(DNA)和核糖核酸(RNA)以及RNA或DNA的类似物或衍生物。该术语还包括由核苷酸类似物组成的RNA或DNA的等同物、衍生物、变体和类似物,单链(正义或反义)和双链多核苷酸。脱氧核糖核苷酸包括脱氧腺苷、脱氧胞苷、脱氧鸟苷和脱氧胸苷。对于RNA,尿嘧啶碱基为尿苷。多核苷酸可以包含核苷酸类似物,包括例如质量修饰核苷酸,其允许质量区分多核苷酸;包括可检测标记的核苷酸,例如荧光、放射性、发光或化学发光标记,其允许检测多核苷酸;或者包含反应基团的核苷酸,例如生物素或硫醇基,其促进多核苷酸固定至固体支持物。多核苷酸还可以包含一个或多个可选择性切割的骨架键,例如,可化学、酶促或光解切割。例如,多核苷酸可以包括一个或多个脱氧核糖核苷酸,之后是一个或多个核糖核苷酸,其后可以是一个或多个脱氧核糖核苷酸,这样的序列可以通过碱水解在核糖核苷酸序列处切割。多核苷酸还可以包括一个或多个对切割相对耐受的键,例如嵌合寡核苷酸引物,其可以包括通过肽核酸键连接的核苷酸以及在3′端通过磷酸二酯键或其他合适的键连接的至少一个核苷酸,并且能够通过聚合酶延伸。肽核酸序列可以利用公知的方法来制备。本发明所提供的核酸分子(多核苷酸)的实例为寡核苷酸,包括合成寡核苷酸、寡核苷酸双链体、引物(包括补平引物)以及寡核苷酸双链体盒。
在本发明中,载体是指可以将编码蛋白质的多核苷酸可操作地插入其中以引起所述蛋白质表达的媒介物。载体可用于转化、转导或转染宿主细胞,以使其在宿主细胞内表达携带的遗传元件。载体可以含有多种用于控制表达的元件,包括启动子序列、转录起始序列、增强子序列、选择元件和报告基因。另外,载体可以含有复制起点。复制起点是指当在载体中存在时其起始复制的序列。复制起点可被复制起始因子或替代地被DNA解螺旋酶识别。载体还可以包括有助于其进入细胞的材料,包括但不限于病毒颗粒、脂质体或蛋白质包膜。
作为本发明的一种可选方式,载体是病毒。病毒载体用于引入编码靶标特异性多肽的非内源性核酸序列。病毒载体可以是逆转录病毒载体或慢病毒载体。病毒载体还可以包括编码转导标记的核酸序列。合适的病毒载体包括基于RNA病毒的载体,例如逆转录病毒来源的载体,例如莫洛尼鼠白血病病毒(MLV)来源的载体,并且包括更复杂的逆转录病毒来源的载体,例如慢病毒来源的载体。HIV-1衍生的载体属于这一类。
病毒载体包括逆转录病毒,腺病毒,细小病毒(如腺相关病毒),冠状病毒,负链RNA病毒(如正粘病毒(如流感病毒),弹状病毒(如狂犬病和水疱性口炎病毒),副粘病毒(如,麻疹和仙台病毒),正链RNA病毒(例如小核糖核酸病毒和甲型病毒)以及双链DNA病毒,包括腺病毒,疱疹病毒(例如1型和2型单纯疱疹病毒和爱泼斯坦-巴尔病毒和巨细胞病毒)和痘病毒(例如,牛痘,鸡痘和金丝雀痘)。其他病毒包括但不限于诺沃克病毒、披膜病毒、黄病毒、呼肠孤病毒、乳头瘤病毒、肝炎病毒和肝炎病毒。逆转录病毒的例子包括禽类白血病肉瘤、哺乳动物C型、B型病毒、D型病毒、HTLV-BLV组、慢病毒或泡沫病毒。
作为本发明的一种可选方式,载体是表达载体。根据本发明的表达载体能够指导本发明的核酸分子在宿主中的复制和表达。
载体的非限制性实例包括pQE-12、pUC-系列、pBluescript(Stratagene)、pET-系列表达载体(Novagen)或pCRTOPO(Invitrogen)、λgt11、pJOE、pBBR1-MCS系列、pJB861、pBSMuL、pBC2、pUCPKS、pTACT1、pTRE、pCAL-n-EK、pESP-1、pOP13CAT、E-027 pCAG Kosak-Cherry(L45a)载体系统、pREP(Invitrogen)、pCEP4(Invitrogen)、pMC1neo(Stratagene)、pXT1(Stratagene)、pSG5(Stratagene)、EBO-pSV2neo、pBPV-1、pdBPVMMTneo、pRSVgpt、pRSVneo、pSV2-dhfr、pIZD35、Okayama-Berg cDNA表达载体pcDV1(Pharmacia)、pRc/CMV、pcDNA1、pcDNA3(Invitrogen)、pcDNA3.1、pSPORT1(GIBCO BRL)、pGEMHE(Promega)、pLXIN、pSIR(Clontech)、pIRES-EGFP(Clontech)、pEAK-10(EdgeBiosystems)pTriEx-Hygro(Novagen)和pCINeo(Promega)。适合于巴斯德毕赤氏酵母(Pichia pastoris)的质粒载体的非限制性实例包括例如质粒pAO815、pPIC9K和pPIC3.5K(全部为Invitrogen)。适合于在爪蟾属(Xenopus)胚胎、斑马鱼胚胎以及各种各样的哺乳动物和禽类细胞中表达蛋白质的另一种载体是多用途表达载体pCS2+。
在本发明中,宿主细胞是用于接受、保持、复制和扩增载体的细胞。宿主细胞还可以用来表达载体所编码的多肽。当宿主细胞分裂时,载体中所含的核酸复制,从而扩增核酸。在一个实施方案中,宿主细胞为遗传包装(genetic package),可以诱导在其表面上表达变体多肽。在另一实施方案中,用遗传包装感染宿主细胞。
宿主细胞实际上可以是表达载体可用的任何细胞。包括原核细胞、真核细胞,所述原核细胞包括但不限于真细菌,如革兰氏阴性或革兰氏阳性生物体,例如肠内菌科(Enterobacteriaceae),如埃希氏菌属(Escherichia),例如大肠杆菌(DH5α、BL21DE3、BL21DE3pLysS、JM109、TOP10、HB101、SCS110、E.coli JM110);肠杆菌属(Enterobacter);肠杆菌属(Erwinia);克雷伯氏菌属(Klebsiella);变形杆菌属(Proteus);沙门氏菌属(Salmonella),例如鼠伤寒沙门氏菌(Salmonella typhimurium);沙雷氏菌属(Serratia),例如粘质沙雷氏菌(Serratia marcescans);和志贺杆菌属(Shigella),以及芽孢杆菌属(Bacilli),如枯草芽孢杆菌(B.subtilis)和地衣芽孢杆菌(B.licheniformis);假单胞菌属(Pseudomonas),如绿脓杆菌(P.aeruginosa);和链霉菌属(Streptomyces)。
真核细胞包括但不限于原生生物细胞、动物细胞、植物细胞或真菌细胞,所述动物细胞包括哺乳动物细胞、鸟类细胞、昆虫细胞。其中,哺乳动物细胞包括但不限于CHO细胞、F2N细胞、CSO细胞、BHK细胞、Bowes黑色素瘤细胞、HeLa细胞、911细胞、AT1080细胞、A549细胞、293T细胞、293F细胞。
在本发明中,试剂盒包括用于各种检测测定的一种或多种试剂,所述检测测定包括例如免疫测定如ELISA(夹心型或竞争性形式)。试剂盒的组分可以预先附着至固体支持物,或者当使用该试剂盒时,可以应用于固体支持物的表面。在本发明的一些实施方案中,信号生成手段可以与本发明的抗体或片段预先结合,或者可能需要在使用之前与一种或多种组分例如缓冲液、抗体-酶缀合物、酶底物等等组合。试剂盒还可以包括另外的试剂,例如用于减少与固相表面的非特异性结合的封闭试剂、洗涤试剂、酶底物等等。固相表面可以是管、珠、微量滴定板、微球或适合于固定蛋白质、肽或多肽的其他材料的形式。在特定方面,催化化学发光或显色产物形成或者化学发光或显色底物还原的酶是信号生成手段的组分。这样的酶是本领域众所周知的。试剂盒可以包括本发明所述的任何捕获试剂和检测试剂。任选地,试剂盒还可以包含用于进行本发明的方法的说明书。
在本发明中,所述药物组合物还包括药学上可接受的载体,通常,这样的药物组合物使用不会明显破坏所述抗体或其抗原结合片段的生物学性质的组分,所述生物学性质例如结合其特异性表位(例如,结合Tau蛋白上的表位)。每种组分在与其他成分相容并且不伤害患者的意义上是药学和生理学可接受的。药物组合物可以常规地以单位剂型存在,并且可以通过药学领域公知的方法制备,包括但不限于片剂、丸剂、散剂、液体溶液剂或混悬剂(例如,包括可注射、可吸收和体表制剂(例如,滴眼液、凝胶剂或软膏剂)、气雾剂(例如,鼻腔喷雾剂)、脂质体、栓剂、可注射和可灌注的溶液以及缓释形式。药学上可接受的载体包括但不限于水、缓冲剂、盐水溶液、磷酸缓冲盐溶液、各种类型的湿润剂、无菌溶液、醇、阿拉伯树胶、植物油、苄醇、明胶、甘油、碳水化合物(如乳糖、蔗糖、直链淀粉或淀粉)、硬脂酸镁、滑石、硅酸、粘性石蜡、芳香油、脂肪酸单甘油酯和二甘油酯、季戊四醇脂肪酸酯、羟甲基纤维素、粉末等。本发明提供的药物组合物可以包含其他添加剂,包括例如抗氧化剂、防腐剂、抗微生物剂、镇痛剂、粘合剂、崩解剂、着色剂、稀释剂、赋形剂、增量剂、助流剂、增溶剂、稳定剂、张力剂、媒介物、增稠剂、调味剂、乳剂(如油/水乳剂)、乳化和悬浮剂(如阿拉伯胶、琼脂、藻酸、藻酸钠、膨润土、卡波姆、卡拉胶、羧甲基纤维素、纤维素、胆固醇、明胶、羟乙基纤维素、羟丙基纤维素、羟丙基甲基纤维素、甲基纤维素、辛基酚聚醚-9(octoxynol 9)、油醇、聚乙烯吡咯烷酮、丙二醇单硬脂酸酯、十二烷基硫酸钠、山梨聚糖酯、硬脂醇、黄蓍胶、黄原胶及其衍生物)、溶剂以及各种成分,例如晶体纤维素、微晶纤维素、柠檬酸、糊精、葡萄糖、液体葡萄糖、乳酸、乳糖、氯化镁、偏磷酸钾、淀粉。这样的载体和/或添加剂可以通过常规方法配制,并且可以以合适的剂量给对象施用。
在本发明中,可检测试剂可以是具有可检测的物理或化学特性的任何物质。这类可检测的试剂在免疫测定领域已良好开发,并且一般来说,在这类方法中有用的任何标记的大部分可以应用于所提供的方法。因此,标记可以是通过光谱、光化学、生化、免疫化学、电学、光学或化学方法可检测的任何组合物。可检测试剂包括但不限于荧光染料(例如,异硫氰酸荧光素、德克萨斯红、罗丹明等),放射性标记(例如,3H、125I、35S、14C或32P),特别地,放射性标记(例如,157Gd、55Mn、162Dy、52Cr和56Fe),金属离子(例如,111In、97Ru、67Ga、68Ga、72As、89Zr和201Tl),酶(例如,辣根过氧化物酶、碱性磷酸酶以及ELISA中常用的其他酶),电子转移剂(例如,包括金属结合蛋白和化合物),发光和化学发光标记(例如,萤光素和2,3-二氢酞嗪(2,3-dihydrophtahlazinediones),例如,鲁米诺),磁珠(例如,DYNABEADSTM),以及比色标记,例如胶体金或有色玻璃或塑料珠(例如,聚苯乙烯、聚丙烯、胶乳)。
治疗试剂包括但不限于细胞毒素、治疗剂或放射性金属离子,其中,细胞毒素包括但不限于紫杉醇、细胞松弛素B、短杆菌肽D、溴化乙锭、依米丁、丝裂霉素、依托泊苷、替尼泊苷(tenoposide)、长春新碱、长春碱、秋水仙碱、多柔比星、柔红霉素、二氢蒽二酮(dihydroxy anthracin dione)、米托蒽醌、光神霉素、放线菌素D、1-去氢睾酮、糖皮质激素、普鲁卡因、丁卡因、利多卡因、普萘洛尔和嘌呤霉素,以及它们的类似物或同系物。治疗剂包括但不限于抗代谢药(例如,甲氨蝶呤、6-巯基嘌呤、6-硫代鸟嘌呤、阿糖胞苷、5-氟尿嘧啶达卡巴嗪(decarbazine)),烷化剂(例如,氮芥、thioepa苯丁酸氮芥、美法仑、卡莫司汀(BSNU)和洛莫司汀(CCNU)、环磷酰胺(cyclothosphamide)、白消安、二溴甘露醇、链佐星、丝裂霉素C以及顺铂(cis-dichlorodiamine platinum)(II)(DDP)顺铂(cisplatin)),蒽环类(例如,柔红霉素(原来为道诺霉素)和多柔比星),抗生素(例如,放线菌素D(dactinomycin)(原来为放线菌素)、博来霉素、光神霉素和安曲霉素(AMC)),抗有丝分裂剂(例如,长春新碱和长春碱),以及抗病毒药,例如但不限于核苷类似物,如齐多夫定、阿昔洛韦、更昔洛韦(gangcyclovir)、阿糖腺苷、碘苷、曲氟尿苷和利巴韦林;膦甲酸(foscamet)、金刚烷胺、金刚乙胺、沙奎那韦、茚地那韦、利托那韦和α-干扰素。
在本发明中,去岩藻糖基化是指基本上缺少直接或间接与N-糖基化位点(例如,人IgG1 Fc区的氨基酸残基位置297,根据EU索引编号)或非IgG1或非人IgG1免疫球蛋白中的对应的残基共价连接的N-聚糖的核心岩藻糖基化。
去岩藻糖基化的抗体或其抗原结合片段是指在其恒定区糖基化中缺少岩藻糖的IgG1或IgG3同种型抗体。人IgG1或IgG3的糖基化在Asn297处发生,呈核心岩藻糖基化双分支复合寡糖糖基化的形式,以最多2个Gal残基作为末端。在一些实施方案中,去岩藻糖基化的抗体在Asn297缺少岩藻糖。这些结构被标记为G0,G1(α1,6或α1,3)或G2聚糖残基,取决于末端Gal残基的量。
本发明提供了上述抗体,或上述物质在检测Tau蛋白或在制备诊断Tau蛋白相关疾病的产品中的应用。
在本发明中,Tau蛋白相关疾病包括神经退化性疾病或病症的异源性组,包括显示Tau病理学与类淀粉蛋白病理学共存的疾病或病症,包括但不限于阿兹海默氏症、库贾氏病(Creutzfeldt-Jacob disease)、拳击手型痴呆、唐氏综合征、杰茨曼-斯脱司勒-史茵克氏病、包涵体肌炎及朊病毒蛋白(prion protein)大脑类淀粉蛋白血管病、外伤性脑损伤,且进一步包括不显示独特类淀粉蛋白病理学的疾病或病症,包括但不限于关岛型肌肉萎缩性脊髓侧索硬化症/帕金森氏病-痴呆复合症(amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam)、非关岛型运动神经元病(Non-Guamanianmotor neuron disease)伴随神经纤维缠结、嗜银颗粒性痴呆(argyrophilic graindementia)、皮质基底核退化(corticobasal degeneration)、弥漫性神经纤维缠结伴随钙化、因第17对染色体异常导致的额颞叶痴呆伴随帕金森氏病、哈勒沃登-施帕茨病(Hallevorden-Spatz disease)、多系统萎缩、C型尼曼-匹克二氏病(Niemann-Pickdisease)、苍白球脑桥黑质退化(Pallido-ponto-nigral degeneration)、匹克症(Pick’sdisease)、进行性皮质下胶质增生、进行性核上麻痹、亚急性硬化性泛脑炎、单纯缠结型痴呆(Tangle only dementia)、脑炎后帕金森氏病、肌强直性营养不良(Myotonicdystrophy)。
下面结合具体实施例进一步阐述此发明。应理解的是,在此描述的特定实施方式通过举例的方式来表示,并不作为对本发明的限制。在不偏离本发明范围的情况下,本发明的主要特征可以用于各种实施方式。
实施例
1、免疫原处理:免疫原为重组Tau蛋白,经SDS-PAGE鉴定蛋白纯度和分子量,经过ImmunoPlus技术处理,增强免疫原性。
2、动物免疫:选取BALB/c小鼠,常规方法免疫。经三次免疫后,用间接ELISA方法测试抗血清效价,选取效价高的小鼠进行后续实验,使用western测试抗血清对重组抗原的识别。
3、脾细胞制备:引颈处死小鼠,无菌条件下取出脾脏,置于已消毒的90~100目不锈钢网中。用注射器向脾脏内注入3 ml无血清培养液,反复抽吸数次获取细胞,再制成细胞悬液。把细胞悬液注入50ml离心管中,加10~20ml培养液,轻轻吹打数次,室温中静置5分钟。离心(800~1000转/分)计数,备用。
4、细胞融合:将小鼠骨髓瘤细胞和小鼠脾细胞按1:5比例混合,离心弃去上清,并以消毒滤纸吸净多余上清。将1ml 40%的PEG溶液60秒内逐滴加入到细胞团中,同时并不断轻微转动离心管。在不断转动的离心管中,60秒内逐滴加入1ml无血清培养液。而后于5分钟内缓慢加完20ml无血清培养基。离心(800 转/分,8 分钟),去上清,用完全培养液10ml悬浮,轻轻混匀。将细胞悬液加入96孔板内,每孔50微升。37℃ CO2培养箱中培养24小时后更换成HAT选择性培养液。
5、融合后细胞培养:融合后7~10天用HAT培养液半量换液,以后每隔2~3天半量换液一次。2~3周后出现杂交细胞集落。待集落增殖生长至1/3孔时,应用间接ELISA方法,对小鼠杂交瘤细胞培养上清中的单克隆抗体进行亲和力测试。以重组Tau蛋白作为抗原包被酶标板,包被抗原浓度为1μg/ml,100μl/孔。包被缓冲液为PBS(PH=7.4)。4℃放置过夜。次日PBS洗涤3次,每次5分钟。以1% BSA封闭,每孔加入200μl。37℃恒温箱孵育2小时。弃去BSA,加入含有单克隆抗体的细胞培养上清,每孔100μl。以小鼠的阳性抗血清作为阳性对照,以空白培养上清作为阴性对照。37℃恒温箱孵育2小时。弃去一抗,洗涤液洗5次,加Peroxidase-AffiniPure Goat Anti-Mouse IgG,37℃恒温箱孵育1小时。加入底物显色后,以酶标仪测定吸光值。
结果显示,在1:10的稀释条件下,抗体的吸光值>2.9,远远大于阴性对照值0.069,说明抗体对重组Tau蛋白抗原有很好的亲和力(表2),抗体的序列如表1所示。
表 1 24F1H2抗体序列
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表 2抗体识别重组Tau蛋白
6、以临床样本中的人Tau蛋白作为抗原,以含有单克隆抗体的小鼠杂交瘤细胞培养上清进行检测。
结果显示,在目标位置,出现强阳性条带,说明抗体对临床样本中的抗原有很强的结合力(图1)。
7、应用双抗体夹心ELISA方法,以2.5μg/ml的纯化抗体包被酶标板,包被液为PBS(pH=7.4),4℃放置过夜。洗涤液洗涤3次,加入重组Tau蛋白作为抗原,抗原浓度分别为0、1、10、100ng/ml。37℃孵育1小时。洗涤3次,加入生物素标记的检测抗体,浓度为1μg/ml。37℃孵育1小时。洗涤3次,加入HRP标记的链酶亲和素,与检测抗体结合,浓度为1mg/ml,1:10,000稀释,每孔加入100μl。37℃孵育30分钟。加底物显色,酶标仪测定吸光值。
结果显示,23H9E4与24F1H2配对成功,随着抗体含量的增加,吸光值随之上升。抗原浓度为100ng/ml时,吸光值>1.7,明显高于阴性对照。说明抗体对抗原有很强的识别和捕获作用(表3)。
表 3纯化抗体对抗原的识别
8、将23H9E4与24F1H2配对组合,对重组Tau蛋白进行检测。将抗原浓度进行倍比稀释,根据抗原浓度与吸光值进行绘图。
结果显示,随着抗原浓度升高,吸光值也随之升高,说明抗体与抗原结合具有特异性(图2)。
上述实施例的说明只是用于理解本发明的方法及其核心思想。应当指出,对于本领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以对本发明进行若干改进和修饰,这些改进和修饰也将落入本发明权利要求的保护范围内。
Claims (10)
1.一种抗Tau蛋白的抗体,其特征在于,所述抗体包括如SEQ ID NO:1、2、3所示的氨基酸序列的重链可变区互补决定区CDR1、CDR2、CDR3;
以及如SEQ ID NO:9、10、11所示的氨基酸序列的轻链可变区互补决定区CDR1、CDR2、CDR3。
2.根据权利要求1所述的抗体,其特征在于,所述抗体还包括如SEQ ID NO:4、5、6、7所示的氨基酸序列的重链可变区框架区FR1、FR2、FR3、FR4;
以及如SEQ ID NO:12、13、14、15所示的氨基酸序列的轻链可变区框架区FR1、FR2、FR3、FR4。
3.根据权利要求2所述的抗体,其特征在于,所述抗体的重链可变区具有与SEQ ID NO:8所示的氨基酸序列至少80%、至少85%、至少90%、至少92%、至少93%、95%、至少96%、至少97%、至少98%、至少99%的序列同一性,轻链可变区具有与SEQ ID NO:16所示的氨基酸序列至少80%、至少85%、至少90%、至少92%、至少93%、95%、至少96%、至少97%、至少98%、至少99%序列同一性。
4.根据权利要求3所述的抗体,其特征在于,所述抗体的重链可操作的连接第一信号肽,所述抗体的轻链可操作的连接第二信号肽。
5.如下任一项物质:
(1)核酸分子,其特征在于,所述核酸分子编码权利要求1-4任一项所述的抗体;
(2)载体,其特征在于,所述载体包括(1)中所述的核酸分子;
(3)宿主细胞,其特征在于,所述宿主细胞包括(1)中所述的核酸分子或(2)中所述的载体;
(4)检测Tau蛋白的产品,其特征在于,所述产品包括权利要求1-4任一项所述的抗体;
(5)药物组合物,其特征在于,所述药物组合物包括权利要求1-4任一项所述的抗体;
(6)一种衍生物,其特征在于,所述衍生物包括在权利要求1-4任一项所述的抗体上连接可检测试剂、治疗试剂,或所述抗体是去岩藻糖基化的抗体。
6.根据权利要求5所述的物质,其特征在于,(1)中编码重链可变区互补决定区CDR1、CDR2、CDR3的核酸分子的核苷酸序列分别如SEQ ID NO:17、18、19所示;
编码轻链可变区互补决定区CDR1、CDR2、CDR3的核酸分子的核苷酸序列分别如SEQ IDNO:25、26、27所示。
7.权利要求1-4任一项所述的抗体,或权利要求5或6所述的物质在检测Tau蛋白或在制备诊断Tau蛋白相关疾病的产品中的应用。
8.权利要求1-4任一项所述的抗体,或权利要求5或6所述的物质在制备预防和/或治疗Tau蛋白相关疾病的药物组合物中的应用。
9.一种制备权利要求1-4任一项所述的抗体的方法,其特征在于,所述方法包括:培养权利要求5中(3)所述的宿主细胞,回收单克隆抗体。
10.一种检测样本中Tau蛋白的方法,其特征在于,所述方法包括:使权利要求1-4任一项所述的抗体与待测样本接触,从而检测待测样本中Tau蛋白的水平。
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CN117402251A (zh) * | 2023-12-15 | 2024-01-16 | 中国医学科学院基础医学研究所 | 一种抗小g蛋白rbj的抗体及其应用 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102596221A (zh) * | 2009-06-10 | 2012-07-18 | 纽约大学 | 病理tau蛋白的免疫靶向 |
CN103339146A (zh) * | 2010-10-11 | 2013-10-02 | 比奥根艾迪克国际神经科学公司 | 人抗tau抗体 |
CN104520322A (zh) * | 2012-04-05 | 2015-04-15 | Ac免疫有限公司 | 人源化tau抗体 |
CN104736185A (zh) * | 2012-08-16 | 2015-06-24 | 埃匹瑞恩股份有限公司 | 治疗Tau病变的方法 |
CN107810196A (zh) * | 2015-06-24 | 2018-03-16 | 豪夫迈·罗氏有限公司 | 人源化的抗‑Tau(pS422)抗体和使用方法 |
CN114430744A (zh) * | 2019-07-15 | 2022-05-03 | 阿德尔公司 | 抗Tau抗体及其用途 |
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102596221A (zh) * | 2009-06-10 | 2012-07-18 | 纽约大学 | 病理tau蛋白的免疫靶向 |
CN103339146A (zh) * | 2010-10-11 | 2013-10-02 | 比奥根艾迪克国际神经科学公司 | 人抗tau抗体 |
CN104520322A (zh) * | 2012-04-05 | 2015-04-15 | Ac免疫有限公司 | 人源化tau抗体 |
CN104736185A (zh) * | 2012-08-16 | 2015-06-24 | 埃匹瑞恩股份有限公司 | 治疗Tau病变的方法 |
CN107810196A (zh) * | 2015-06-24 | 2018-03-16 | 豪夫迈·罗氏有限公司 | 人源化的抗‑Tau(pS422)抗体和使用方法 |
CN114430744A (zh) * | 2019-07-15 | 2022-05-03 | 阿德尔公司 | 抗Tau抗体及其用途 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117402251A (zh) * | 2023-12-15 | 2024-01-16 | 中国医学科学院基础医学研究所 | 一种抗小g蛋白rbj的抗体及其应用 |
CN117402251B (zh) * | 2023-12-15 | 2024-02-23 | 中国医学科学院基础医学研究所 | 一种抗小g蛋白rbj的抗体及其应用 |
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