CN101918446B - 抑制内皮唾液酸蛋白与配体结合的方法 - Google Patents
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Abstract
本发明提供了抑制内皮唾液酸蛋白与内皮唾液酸蛋白配体相互作用的方法。所述抑制通过用抗内皮唾液酸蛋白抗体阻断细胞表面表达的内皮唾液酸蛋白与配体例如纤连蛋白或胶原蛋白的相互作用而实现。
Description
与相关申请的交叉引用
本申请要求2007年4月5日提交的美国临时申请No.60/910,362和2007年10月15日提交的美国临时申请No.60/980,026的优先权,这二者都合并在此作为参考。
技术领域
本发明总体上涉及免疫治疗学。更具体地说,本发明涉及破坏内皮唾液酸蛋白与其底物相互作用以抑制细胞功能的组合物和方法,所述细胞功能包括血管生成和细胞运动性。
背景
本说明书通篇引用了多种出版物,包括专利、公布的申请、技术论文和学术论文。这些引用的出版物每一篇都以其全文和出于所有目的合并在此作为参考。
血管生成是涉及新血管形成的受调控的过程。它在正常生长、胚胎发育、伤口愈合和其它生理过程中发挥着重要的作用(Yancopoulos等(2000)Nature,407:242-8)。正在发育的毛细血管内,细胞外基质(ECM)蛋白充当了内皮和肿瘤组织的结构支架并为肿瘤细胞的生长提供支撑。在几种疾病状态包括癌症中涉及血管重新生成,此时形成的新的“胚胎样”血管(本文称作心血管形成)在结构和功能上显得不同于正常的脉管系统(Hanahan等(2000)Cell,100:57-70)。利用各种各样的血管生成模型系统,许多体内和体外研究已经证明了正常和疾病相关的脉管系统之间的生物学差异,从而提出了新的抗血管生成化合物的可能性,所述化合物能够选择性抑制胚胎类型的血管、肿瘤相关的内皮细胞的形成来治疗新生血管性疾病。考虑到这些治疗机会,对 于能够特异性抑制肿瘤和其他新生血管性疾病相关的内皮或基质(成纤维细胞,周细胞等等)细胞生长和功能的潜在靶,正在进行热切的研究。
在鉴别这样的靶的尝试中,已经设计了策略来鉴别肿瘤基质的细胞表面抗原以及来分离在肿瘤基质细胞中表达的特异性蛋白或RNA(Rettig等(1992)Proc.Natl.Acad.Sci.USA,89:10832-6;St.Croix等(2000)Science,289:1197-1202)。这些策略已经鉴别了看来是在肿瘤基质细胞中特异性表达的细胞表面蛋白,称为内皮唾液酸蛋白(或肿瘤内皮标记1(TEM1)或CD248)。
在正常和瘤组织中考查基因表达模式表明,内皮唾液酸蛋白mRNA的表达在肿瘤新生血管中的上调(St Croix等(2000)Science,289:1197-1202)。类似的内皮唾液酸蛋白表达水平也在人结肠直肠癌(Rmali等(2005)World J.Gastroenterol.,11:1283-1286)、乳腺癌组织(Davies等(2004)Clin.Exp.Metastasis,21:31-37)和组织细胞瘤(Dolznig等(2005)Cancer Immun.,5:10)中注意到。在高度浸润的胶质母细胞瘤、间变性星形细胞瘤和转移癌包括黑素瘤中已经观察到人内皮唾液酸蛋白表达(Brady等(2004)J.Neuropathol.Exp.Neurol.,63:1274-1283;Huber等(2006)J.Cutan.Pathol.,33:145-155)。
在免疫组化研究中使出抗体,已经发现了内皮唾液酸蛋白在恶性组织的许多新生血管的内皮细胞、成纤维细胞和/或周细胞中的大量表达(Virgintino等(2007)Angiogenesis,10:35-45),而在来源于胚胎样内皮培养物的细胞系,例如但不限于HUVEC(人脐静脉内皮细胞)或HMVEC-(初生儿皮肤微血管内皮细胞)中,表达是有限的。分析能够与内皮唾液酸蛋白结合的抗体、多肽或非蛋白质配体,已经鉴别了这类分子亚组,其能够抑制内皮唾液酸蛋白与其底物结合和/或抑制导致细胞停滞或死亡的细胞内活性。
Rettig等描述了在多种癌症类型内识别血管上抗原的单克隆抗体 (Rettig等(1992)Proc.Natl.Acad.Sci.USA,89:10832-6)。其中之一被命名为FB5并通过用人胚胎成纤维细胞免疫小鼠而产生。FB5识别神经母细胞瘤细胞系表面上~100kDa的蛋白,LA1-5s(美国专利No.5,342,757)。FB5是与内皮唾液酸蛋白结合的鼠类抗体(IgG1),并已经显示出识别与多种不同癌症类型有关的内皮细胞。结构评估已经将内皮唾液酸蛋白分类为C-型凝集素样组成膜蛋白质,包含五个球状胞外结构域(包括C-型凝集素结构域,一个与Sushi/ccp/scr模式类似的结构域,和三个EGF重复序列)。该蛋白还包含粘蛋白样区域、跨膜区段和短的胞质尾区。该蛋白看来是糖蛋白。碳水化合物分析显示,内皮唾液酸蛋白核心蛋白具有丰富的O-连接的糖基化(Christian等(2001)J.Biol.Chem.,276:48588-48595)。后续的工作将小鼠FB5的互补决定区(CDRs)合并到人IgG1框架中,产生与恶性组织内的血管以及HMVEC培养物中的细胞亚组结合的人源化抗体。
TEM1敲除的小鼠发育正常并展现出正常的伤口愈合,提示内皮唾液酸蛋白不是胎儿发育或伤口修复期间新生血管形成所需要的(Nanda等(2006)Proc.Natl.Acad.Sci USA,103:3351-3356)。但是,当将结肠直肠癌细胞植入TEM1敲除小鼠的腹部位置中时,与亲代动物相比,丧失内皮唾液酸蛋白表达与降低肿瘤生长、浸润和转移相关。内皮唾液酸蛋白表达的缺失已经显示出降低了内皮唾液酸蛋白敲除小鼠中人异种移植肿瘤的生长、浸润和转移(Nanda等(2006)Proc.Natl.Acad.Sci USA,103:3351-3356)。另外,缺少内皮唾液酸蛋白导致不成熟的小血管增加以及中等和大的肿瘤血管减少。
新生血管形成与许多疾病状态有关。在癌症中,据认为,新生血管形成对于给肿瘤供应血液是重要的。在非肿瘤的癌症或恶性病例如视网膜病和黄斑变性中,失控的新生血管形成导致失明(Wilkinson-Berka(2004)Curr.Pharm.Des.,10:3331-48;Das和McGuire(2003)Prog.Retin.Eye Res.,22:721-48)。此外,若干报告已经鉴别出新生血管形成在炎性疾病中的作用(Paleolog and Miotla(1998) Angiogenesis,2(4):295-307)。更好地了解胚胎样内皮和前体细胞以及与这些疾病状态有关的内皮相关细胞(周细胞,成纤维细胞等)中的分子途经的方法,将促使用于治疗这些疾病的新药的开发。反之,新生血管形成与伤口愈合有关(Galiano等(2004)Am.J.Pathol.,164:1935-47)。鉴别促进伤口愈合的血管形成的分子途经,能够提供鉴别促进这些过程的药物和因子的能力,以提高与外伤、烧伤和感染有关的伤口治疗。
有效的抗血管生成和促血管生成(proangiogenic)治疗的难题是,对于与新生血管形成有关的活化细胞过程重要的分子和相关途经的生物过程的性质不确定(Bagley等(2003)Cancer Res.,63:5866-73)。鉴别和阐明分子和它们调节给定途径的功能,能够产生在新生血管相关的疾病例如癌症、炎症、眼病、心血管疾病和伤口愈合中具有刺激或抑制活性的有效化合物的分离。与正常成年人组织中血管有关的成年人样内皮细胞相反,通过基于分子的分析分离和研究这些化合物的能力,还将在评价它们对新生血管形成中所涉及细胞的正常生物学的特异性抑制或刺激作用中提供用处(Asahara和Kawamoto(2004)Am.J.Physiol.Cell Physiol,287:C572-9)。
发明内容
本发明特征在于抑制表达内皮唾液酸蛋白的细胞与内皮唾液酸蛋白配体相互作用的方法。
一方面,所述方法包括在基因水平抑制表达内皮唾液酸蛋白的细胞中内皮唾液酸蛋白的表达。内皮唾液酸蛋白的配体可以是细胞外基质蛋白,例如胶原蛋白或纤连蛋白。在一些实施方案中,配体是胶原蛋白I或胶原蛋白IV。在优选的实施方案中,细胞是哺乳动物细胞。在基因水平调节内皮唾液酸蛋白表达可以通过本技术领域任何适当的手段来实行,例如反义核酸分子、双链RNA、核酶、锤头状核酶、诱捕(decoy)寡核苷酸等等。调节内皮唾液酸蛋白表达还可以通过敲除编码内皮唾液酸蛋白的基因来实现。
在另一方面,方法包括物理阻断表达内皮唾液酸蛋白的细胞表面上表达的内皮唾液酸蛋白,从而抑制细胞与内皮唾液酸蛋白配体的相互作用。内皮唾液酸蛋白的配体可以是细胞外基质蛋白,例如胶原蛋白(例如,胶原蛋白I或胶原蛋白IV)或纤连蛋白。
阻断细胞表面的内皮唾液酸蛋白可以通过本技术领域任何适当的手段实现,例如小分子抑制剂、多肽抑制剂、与内皮唾液酸蛋白特异性结合的抗体、与内皮唾液酸蛋白配体特异性结合的抗体等等。在一些实施方案中,竞争性抑制剂用于抑制内皮唾液酸蛋白或表达内皮唾液酸蛋白的细胞与内皮唾液酸蛋白配体的相互作用。在一些实施方案中,竞争性抑制剂可以是内皮唾液酸蛋白配体、内皮唾液酸蛋白配体的内皮唾液酸蛋白结合性片段,例如,胶原蛋白或纤连蛋白的内皮唾液酸蛋白结合性片段。优选的竞争性抑制剂是胶原蛋白I、胶原蛋白IV或纤连蛋白的内皮唾液酸蛋白结合性片段。最优选的竞争性抑制剂是纤连蛋白的70kDa的N-末端片段、纤连蛋白的45kDa的明胶结合片段、和纤连蛋白的30kDa的肝素结合片段。
合适的抗体可以是嵌合抗体、人源化抗体、完全的人类抗体、特异性结合抗原的抗原结合片段等等。在一些实施方案中,抗体对于抗原的亲合力优选小于大约1×10-7M,更优选小于大约1×10-8M,更加优选小于大约1×10-9M,和最优选小于大约1×10-10M。在一些优选的实施方案中,抗体是抗内皮唾液酸蛋白抗体或特异性识别内皮唾液酸蛋白的抗原结合片段。在一些实施方案中,抗体或抗原结合片段包含的重链分别含有SEQ ID NO:28、30和32的CDR1、CDR2、和CDR3,而轻链分别包含SEQ ID NO:13、15和17的CDR1、CDR2和CDR3。在一些实施方案中,抗体或抗原结合片段可以包括的重链含有SEQ IDNO:34的可变结构域,包括的轻链含有SEQ ID NO:19的可变结构域。在一些实施方案中,抗体或抗原结合片段可以包括的重链含有SEQ IDNO:22或26的氨基酸序列,包括的轻链含有SEQ ID NO:11的氨基酸序列。抗体M4和M4.1是针对人类内皮唾液酸蛋白的人源化抗体。虽然抗体M4和M4.1共有轻链序列,但它们在例如它们的重链上SEQ ID NO:20的429位残基处,相对于SEQ ID NO:24的429位残基,显示有单个氨基酸序列的不同。氨基酸变化是例如SEQ ID NO:19的1286位核苷酸处,相对于SEQ ID NO:23的1286位核苷酸,有单个核苷酸改变的结果。在一些实施方案中,能够依照本发明使用的抗体是由ATCC登录号PTA-7554的细胞产生的。
抑制内皮唾液酸蛋白与内皮唾液酸蛋白配体相互作用,能够影响该正常相互作用带来的途经、级联和下游效应。例如,阻断或抑制表达内皮唾液酸蛋白的细胞与内皮唾液酸蛋白配体的相互作用能够抑制整联蛋白的活化、基质金属蛋白酶的活化、和/或基质金属蛋白酶的表达。能够抑制细胞运动性。最优选的是抑制血管生成或新生血管形成。
在一些实施方案中,抑制表达内皮唾液酸蛋白的细胞与其配体的相互作用抑制了整联蛋白β1、β2或β3的活化。在一些实施方案中,抑制表达内皮唾液酸蛋白的细胞与其配体的相互作用抑制细胞的迁移。在一些实施方案中,抑制表达内皮唾液酸蛋白的细胞与其配体的相互作用抑制了基质金属蛋白酶的活化或表达。在优选的实施方案中,基质金属蛋白酶是MMP-9。
本发明的特征还在于抑制血管生成或新生血管形成的方法。方法包括体外和体内抑制血管生成或新生血管形成。在一些方面,方法包括给对象施用治疗有效量的特异性结合内皮唾液酸蛋白的抗体或抗原结合片段,或者阻断细胞表面上表达的内皮唾液酸蛋白的组合物,致使细胞与内皮唾液酸蛋白配体的相互作用被抑制。这种抑制扼制了施用组合物的对象的组织、器官或瘤的血管生成和/或新生血管形成。内皮唾液酸蛋白的配体可以是细胞外基质蛋白,例如胶原蛋白(例如,胶原蛋白I或胶原蛋白IV)或纤连蛋白。组合物可以包含任何能够物理阻断细胞表面内皮唾液酸蛋白与至少一种内皮唾液酸蛋白配体相互作 用的分子,例如在此描述和例示的那些。这样的分子的例子包括但不限于,小分子抑制剂、多肽抑制剂、与内皮唾液酸蛋白特异性结合的抗体、与内皮唾液酸蛋白配体特异性结合的抗体、抗原结合片段等等。合适的抗体可以是嵌合抗体、人源化抗体、完全的人类抗体、抗体片段等等。
另外的特征是鉴别增强(“激动剂”)或降低(“拮抗剂”)内皮唾液酸蛋白与内皮唾液酸蛋白配体相互作用的药剂的分析和方法。在鉴别这样拮抗剂的方法的一个方面中,该方法包括将内皮唾液酸蛋白与测试化合物接触,从而形成内皮唾液酸蛋白-测试化合物复合物,将内皮唾液酸蛋白-测试化合物复合物与内皮唾液酸蛋白的配体接触,和定量测量在存在和不存在测试化合物的情况下,内皮唾液酸蛋白与配体的相互作用,其中在测试化合物存在下,内皮唾液酸蛋白与配体的相互作用水平减少,表明该测试化合物是内皮唾液酸蛋白与配体相互作用的拮抗剂。在一种实施方案中,鉴别内皮唾液酸蛋白与内皮唾液酸蛋白配体相互作用的激动剂或拮抗剂的方法包括,在存在和不存在测试化合物的情况下,将内皮唾液酸蛋白与内皮唾液酸蛋白配体接触,并定量测量内皮唾液酸蛋白与配体的相互作用,其中在测试化合物的存在下,内皮唾液酸蛋白与配体的相互作用水平增加或减少,分别表明该测试化合物是内皮唾液酸蛋白与配体相互作用的激动剂或拮抗剂。在本发明的分析中,内皮唾液酸蛋白能够与细胞膜、细胞膜片段、人工脂质双层或固体支持物结合。在一些方面中,配体能够与固体支持物结合。内皮唾液酸蛋白的配体可以是细胞外基质蛋白,例如胶原蛋白或纤连蛋白。
附图简述
图1A和1B显示了恶性组织的内皮唾液酸蛋白阳性细胞的免疫组织化学分析。肿瘤从结肠直肠癌患者分离并在液氮中急冻(flashfrozen)。样品切薄片并用抗内皮唾液酸蛋白或同种型对照抗体染色。如所示,肿瘤中的血管(图1A)对于内皮唾液酸蛋白呈阳性染色,而同 种型对照抗体染色的连续切片为阴性(图1B)。
图2A和2B显示了正常组织的内皮唾液酸蛋白阳性细胞的免疫组织化学分析。正常组织通过活组织检查从患者分离,并急冻在液氮中。样品切薄片并用抗内皮唾液酸蛋白或同种型对照抗体染色。如所示,正常组织包含少数内皮唾液酸蛋白阳性细胞(EPCs)(箭头,图2A),而同种型对照抗体染色的连续部分是阴性的(图2B)。通过原位或抗体染色,测试的许多正常组织具有一些内皮唾液酸蛋白阳性细胞。
图3显示从初级内皮培养物中分离内皮唾液酸蛋白阳性细胞。HMVEC培养物通过淘选富集内皮唾液酸蛋白阳性细胞。然后,将经内皮唾液酸蛋白淘选的培养物与HMVEC亲代培养物比较表达内皮唾液酸蛋白的细胞的百分比。如所示,通过抗-内皮唾液酸蛋白抗体、然后是荧光结合的二抗进行免疫染色来测定,淘选的培养物具有比未淘选的亲代培养物高得多的内皮唾液酸蛋白阳性细胞数量。每个视野的细胞数量通过光学显微镜检查确定。
图4显示重组内皮唾液酸蛋白(Fc-TEM1)与细胞外基质蛋白(EMPs)结合。ELISA板,用EMP纤连蛋白(FN)、胶原蛋白(COL;包括I型胶原蛋白(COLI)和IV型胶原蛋白(COL IV))、玻连蛋白(VN)、层粘连蛋白(LN)或明胶(Ge1)预包被,在加入递增浓度的纯化Fc-TEM1蛋白之前,用ELISA分析缓冲液阻断。温育两个小时之后,洗板,并利用对于该Fc尾特异性的HRP-连接的山羊-抗小鼠二级mAb,采用标准ELISA条件,分析结合。洗板并显影,然后利用读板器在OD 450nm处进行分析。如图4A所示,Fc-TEM1与FN和COL牢固结合,而与LM、VN或Ge1观察到弱结合。对于图4B,ELISA板用以下抗原预包被过夜:葡萄球菌肠毒素B(STEB)、卵清蛋白(OVA)、牛γ球蛋白(BGG)、大多数黑素瘤细胞上表达的肿瘤相关90-kD糖蛋白抗原(TA90)、鸡蛋溶菌酶(HEL)、破伤风类毒素(TT)、1%BSA、人类间皮素、人类GM-CSF、山羊IgG和小鼠IgG。Fc-TEM1以递增量加入(5,10,50μg/ml)并使其粘附2小时。然后洗板,并加入HRP-结合的山羊-抗-小鼠抗体,检测结合的Fc-TEM1。
图5显示纤连蛋白(FN)与内皮唾液酸蛋白结合的结构域的作图。 评估来源于纤连蛋白(FN)的蛋白水解和重组的片段支持TEM-1结合的能力。评价的FN片段包括:N-末端70kDa片段(Sigma Cat.No.F0287)(通过组织蛋白酶D消化纤连蛋白获得);30kDa肝素结合片段(Sigma Cat.No.F9911);45kDa明胶结合片段(Sigma Cat.No.F0162)(二者均从胰蛋白酶消化的70kDa片段获得);包含细胞粘附结构域的120kDa片段(“120kDa片段”);和两个重组片段:Fn2,其含有第一III型7FN结构域,和Fn4,其含有链间二硫键和α4β1整联蛋白结合结构域的位点。FN结构的图改编自Wierzbicka-Patynowski等(2003)J.Cell Sci,116:3269-76。
图6显示在抑制剂的存在下,重组Fc-TEM1与EMP和纤连蛋白结合。M4是针对人类内皮唾液酸蛋白的人源化抗体,而rbtTEM1是针对人类内皮唾液酸蛋白的兔抗体。按图4所示进行分析,除了加入抗体来测量干扰或阻断Fc-TEM1与FN结合的能力。如本图所示,M4能够抑制Fc-TEM1与FN结合,而非特异性对照(HuIgG)则不能。
图7显示内皮唾液酸蛋白与EMP结合和其被内皮唾液酸蛋白-EMP抑制剂化合物抑制。纤连蛋白片段在图5中说明。图7A显示与来源于天然FN的蛋白片段结合。图7B显示与来源于变性的FN的蛋白片段结合。对于图7A和7B,FN片段以指定的浓度包被在ELISA板上。使用抗FN多克隆抗体,然后加入HRP-结合的山羊-抗-兔二抗,检测完整的结合蛋白。加入Fc-TEM1(1.25μg/ml),并使其结合2小时。然后洗板,并加入HRP-结合的山羊-抗-小鼠抗体,检测结合的Fc-TEM1。图7B中带细线条的棒(Fc-TEM1-天然)代表与未变性FN结合的Fc-TEM1。如所示,内皮唾液酸蛋白与纤连蛋白的N-末端区域结合,对于与FN-2、FN-4或120kDa的片段的结合,很少检测到或没有结合。纤连蛋白的多克隆抗体与所有片段结合。图7C和7D显示,Fc-TEM1与FN的70kDa片段结合,并通过内皮唾液酸蛋白-EMP抑制剂化合物抑制相互作用。将完整的FN和70kDa FN蛋白以两种蛋白均~15nmol/孔的固定浓度包被在ELISA板上。Fc-TEM1(1.25μg/ml)用递增量的抗内皮唾液酸蛋白抗体M4或同种型对照IgG在4℃预温育1小时。Fc-TEM1/M4(图7C)或Fc-TEM1/IgG(图7D)复合物被加到 FN-和70kDa-包被的孔中并在室温下温育2小时。结合的Fc-TEM1蛋白通过加入HRP-结合的山羊-抗-小鼠二抗进行检测。
图8示出了在以商品名MATRIGEL(BD Biosciences)销售的凝胶状蛋白混合物上,经表达内皮唾液酸蛋白后,细胞形态学的改变。CHO-K1或CHO-TEM1的8E4个细胞被种在用MATRIGEL包被的96-孔板上,并在37℃温育。温育过夜之后,细胞照相,肉眼检查小管形成。
图9显示内皮唾液酸蛋白介导的、细胞与EMP片段的结合。CHO细胞用表达内皮唾液酸蛋白或假cDNA的载体进行转染。经证实细胞表达细胞表面内皮唾液酸蛋白(CHOTEM1),而用假的进行转染者(CHOK1)则不表达。对于图9A,中华仓鼠卵巢(CHO)细胞被加到含有各种ECM蛋白的预包被的96-孔板。使细胞在37℃粘附1小时,并彻底洗孔以除去任何松散结合的细胞。利用CELLTITER-GLO荧光细胞活力分析,确定附着细胞的数量。缩写:Co1,胶原蛋白;FN,纤连蛋白;LN,层粘连蛋白;TN,生腱蛋白;VN,玻连蛋白;Neg,牛血清白蛋白。对于图9B,中华仓鼠卵巢(CHO)细胞用表达内皮唾液酸蛋白或假cDNA的载体转染。细胞通过FACS分析证实表达细胞表面内皮唾液酸蛋白(CHOTEM1),而用假的进行转染者(CHOK1)则不表达。然后测试细胞单独或者与抗内皮唾液酸蛋白抗体M4或对照IgG相组合,结合EMP纤连蛋白的能力。图9B证明,抗内皮唾液酸蛋白抗体M4降低细胞与FN的内皮唾液酸蛋白介导的粘附。细胞(1.5E5)在4℃与抗体M4(100μg/ml)或IgG同种型对照抗体(100μg/ml)预温育1小时。至于图9C,测试细胞结合全长FN或纤连蛋白片段的能力。如图9A所示,包被FN的孔中,粘附的CHO-TEM1细胞的数量比亲代CHO-K1细胞高6倍。在包被层粘连蛋白或玻连蛋白的表面上,观察到CHO-K1和CHO-TEM1的附着之间没有显著差异,而与胶原蛋白和生腱蛋白的附着弱到不能评定任何有价值的差异(图9A)。用M4抗体预处理CHO-TEM1细胞,导致TEM1-FN-依赖性细胞粘附减少50%,而IgG对照抗体没有作用(图9B)。M4抗体处理不影响亲代的CHO-K1细胞的FN-依赖性、内皮唾液酸蛋白-不依赖性细胞粘附(基准粘附)。CHO-TEM1细胞显示与亲代CHO-K1细胞比较,与FN、70kDa和30kDa 片段的附着增强了3-至5-倍,而45kDa或FN2片段则没有发现明显的附着。CHO-TEM1细胞结合MATRIGEL比CHO-K1好五倍(图9C)。
图10显示内皮唾液酸蛋白-EMP胶原蛋白抑制剂化合物的鉴定。CHO细胞用表达内皮唾液酸蛋白或假cDNA的载体进行转染。经证实细胞表达细胞表面内皮唾液酸蛋白(CHOTEM1),而用假的进行转染者(CHOK1)则不表达。然后测试细胞单独或者与抗内皮唾液酸蛋白抗体M4或对照IgG相组合,结合EMP I型胶原蛋白(COL I)的能力。如所示,内皮唾液酸蛋白过表达导致细胞与COL I的结合增加,与对照分子(IgG)相比,这可以通过内皮唾液酸蛋白抑制剂例如M4来阻断。RbtTEM1还抑制Fc-TEM1与COL I结合(数据未显示)。
图11显示内皮唾液酸蛋白介导的、细胞与EMP胶原蛋白的结合。CHO细胞用表达内皮唾液酸蛋白或假cDNA的载体进行转染。经证实细胞表达细胞表面内皮唾液酸蛋白(CHOTEM1),而用假的进行转染者(CHOK1)则不表达。然后测试细胞结合EMP I型胶原蛋白(COL I)的能力。如所示,内皮唾液酸蛋白过表达导致细胞与COL I结合增加。
图12显示内皮唾液酸蛋白介导的细胞迁移及其被抗内皮唾液酸蛋白抗体M4抑制。测定了M4抑制CHO-TEM1和CHO-K1细胞迁移通过MATRIGEL=(图12A)或FN-(图12B)包被的膜的能力。细胞被加到顶部小室并使其在37℃迁移48小时。除去膜,并利用CELLTITER-GLO荧光细胞活力分析测定迁移细胞的数量。在指定的情况下,实验期间细胞用M4或IgG同种型对照处理。如图12A所示,CHO-K1细胞展现出适中的细胞迁移,而CHO-TEM1细胞显示出提高了>10-倍的迁移。M4抗体处理,而不是对照IgG,消除了CHO-TEM1细胞迁移。在利用FN包被的穿膜(transwell)小室的迁移试验中,观察到类似的结果(图12B)。
图13显示细胞途经的内皮唾液酸蛋白提高。CHO细胞用表达内皮唾液酸蛋白或假cDNA的载体进行转染。经证实细胞表达细胞表面内皮唾液酸蛋白(CHOTEM1),而用假的进行转染者(CHOK1)则不然。然后测试细胞上调细胞途经的能力。一个这样的途径是MMP9途径,其在细胞迁移中发挥作用。如所示,与对照细胞相比,内皮唾液酸蛋 白过表达导致MMP-9活性增加。
图14显示阻断内皮唾液酸蛋白对β整联蛋白活化的影响。人胚肾293(HEK293)细胞用表达内皮唾液酸蛋白或假cDN A的载体转染。经证实细胞表达细胞表面内皮唾液酸蛋白(293 TEM1),而用假的进行转染者(293T)则不表达。然后测试细胞上调细胞途经的能力。一个这样的途径是整联蛋白途径,在细胞迁移中发挥作用。如所示,与对照细胞相比,内皮唾液酸蛋白过表达导致整联蛋白β1活性增加(图14B),而对细胞表面β1表达的直接影响不变(图14A)。用内皮唾液酸蛋白抑制剂M4处理细胞,导致整联蛋白活性抑制,而对细胞表面水平没有观察到影响(图14B)。这些数据显示了使用内皮唾液酸蛋白抑制剂抑制表达内皮唾液酸蛋白的细胞中整联蛋白功能的能力。
图15图解了抗体M4.1识别CHO-TEM-1细胞和人初级周细胞中未还原的人TEM-1,而不是小鼠2H11细胞中的鼠TEM-1。人TEM-1的兔多克隆抗体(rabPAb TEM-1)识别CHO-TEM-1细胞和人周细胞中的人TEM-1,还有小鼠2H11细胞中的鼠TEM-1。由于这些细胞中缺乏TEM-1表达,M4.1或rabPAb TEM-1都不对来自亲代CHO-K1细胞或小鼠NS0和MS1细胞的裂解物发生反应。只有rabPAb TEM-1与还原的人TEM-1起反应,虽然与未还原的TEM-1比较,反应程度较少。
说明性实施方案的具体描述
说明书和权利要求通篇使用与本发明的方法和其它方面有关的各种术语。这样的术语赋予了它们在本技术领域中的一般含意,除非另有陈述。其它专门定义的术语的解释与在此提供的定义一致。
要理解,本发明不局限于具体的方法、试剂、化合物、组合物或生物学体系,其当然可以改变。还要理解,在此使用的术语只是为了描述具体的实施方案,而不是打算进行限制。
在本说明书和所附权利要求中使用,不含量词的单数形式包括复数指示物,除非内容明确地另有表示。因此,例如,提及“细胞”包 括两个或多个细胞的组合等等。
在此叙述的每个范围包括范围的所有组合和子组合,以及其中包含的具体数字。
术语“大约”在此使用,当指示可测值例如量、时间期限等等时,意味着包涵该特定值±20%或±10%的变化,更优选±5%,更加优选±1%,和更进一步优选±0.1%,因为这样的变化适于执行本公开的方法。
“内皮唾液酸蛋白特异性分析”(ESA)是指可用于鉴别下述化合物的分析,所述化合物能够通过内皮唾液酸蛋白或整联蛋白介导的机制,直接或间接干扰内皮唾液酸蛋白表达或者导致表达内皮唾液酸蛋白的细胞或内皮唾液酸蛋白与EMPs的直接或间接结合改变的生物活性,以及改变细胞内源途经例如但不限于基质金属蛋白酶(MMPs)和/或细胞增殖或存活。
“多核苷酸”,同义也称为“核酸”或“核酸分子”,是指任何多核苷酸或多脱氧核糖核苷酸,其可以是未修饰的RNA或DNA,或者修饰的RNA或DNA。“多核苷酸”包括但不限于单链和双链DNA、单链和双链区域混合物单一的DNA、单链和双链RNA、和单链和双链区域混合物的RNA、所含的DNA和RNA可以是单链或更典型为双链或者单链和双链区域的混合物的杂交分子。另外,“多核苷酸”是指含有RNA或DNA或者RNA和DNA二者的三链区域。术语多核苷酸还包括含有一个或多个修饰碱基的DNAs或RNAs,和出于稳定性或其它原因进行骨架修饰的DNAs或RNAs。“修饰的”碱基包括例如,三苯甲基化碱基和稀有碱基例如次黄嘌呤核苷。对DNA和RNA能够做出多种修饰;因此,“多核苷酸”包括通常在自然界中发现的多核苷酸的化学、酶学或代谢修饰形式,以及病毒和细胞特征性DNA和RNA的化学形式。“多核苷酸”还包括相对短的核酸链,经常称为寡核苷酸。
“载体”是复制子,例如质粒、噬菌体、粘粒或病毒,另一种核酸区段可以可操作地插入其中,从而造成该区段的复制或表达。
“多肽”、“肽”和“蛋白质”在此可互换使用,以指代氨基酸残基的聚合物。所述术语应用于其中一个或多个氨基酸残基是自然界存在的相应氨基酸的人工化学模拟物的氨基酸聚合物,以及应用于自然界存在的氨基酸聚合物和非自然界存在的氨基酸聚合物。本发明的多肽包括保守修饰的变体。技术人员将认识到,对核酸、肽、多肽或蛋白质序列的取代、缺失或添加使得编码序列中单个氨基酸或小百分比的氨基酸改变、添加或缺失,是“保守修饰的变体”,其中所述改变导致了将氨基酸用化学类似的氨基酸取代氨基酸。提供功能类似的氨基酸的保守取代表是本技术领域中公知的。这样的保守修饰变体是在本发明的多态性变体、种间同系物和等位基因以外的,并且不排除多态性变体、种间同系物和等位基因。
术语核酸分子的“表达”是指基因产物的生物合成。该术语包涵基因转录成为RNA。举例,而不是作为限制,调节基因例如反义核酸或干扰核酸,能够通过转录成反义RNA或RNAi或shRNA来表达。该术语还包涵将RNA翻译成一种或多种多肽,并包涵自然界所有存在的转录后和翻译后修饰。
当外来或异种核酸例如DNA已经导入细胞内部时,则细胞已经被这样的DNA“转化”或“转染”。转化DNA可以被或可以不被整合(共价连接)到细胞的基因组中。在例如原核生物、酵母和哺乳动物细胞中,转化DNA可以保留在附加元件例如质粒上。至于真核细胞,稳定转化的细胞、或“稳定细胞”,是其中转化DNA已经变得整合到染色体中、以致它通过染色体复制被子细胞继承的细胞。这种稳定性通过真核细胞建立由含有转化DNA的子细胞群组成的细胞系或克隆的能力进行证明。“克隆”是通过有丝分裂来源于单个细胞或共同祖先的细胞群。 “细胞系”是能够在体外稳定生长许多代的初级细胞。
用在这里,“测试化合物”是指任何纯化的分子、基本上纯化的分子、作为化合物混合物的一种或多种组分的分子、化合物与能够在本发明方法中利用的任何其它材料的混合物。测试化合物可以是有机或无机化学物质、或生物分子、及其所有片段、类似物、同系物、结合物和衍生物。“生物分子”包括蛋白、多肽、核酸、脂质、单糖、多糖、及其所有片段、类似物、同系物、结合物和衍生物。测试化合物可以是天然或合成来源,并可以从它们的自然界存在源中分离或纯化,或可以重新合成。测试化合物可以依据结构或组成进行限定,或可以不限定。化合物可以是未知结构的分离产物、若干已知产物的混合物、或含有一种或多种化合物的不限定的组合物。不限定的组合物的例子包括细胞和组织提取液;其中培养着原核、真核和古细菌细胞的生长培养基;发酵肉汤;蛋白质表达文库;等等。
“击倒(Knockdown)”是指一种或多种基因表达降低的细胞或生物体。本领域技术人员将会理解,击倒将展现出至少大约50%的表达降低,优选将展现出至少大约67%的表达降低,并更优选将展现出至少大约75%的表达降低,虽然降低更多也是可能的,包括至少大约80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或更多的表达降低。
“抑制”或“干扰”意味着降低、减少、阻断、阻止、延迟、抑制、失活、脱敏、停止或下调目的基因、基因产物(例如,多肽)或途径的生物活性或表达。在本发明的一些优选实施方案中,抑制目的蛋白质或途径例如内皮唾液酸蛋白或细胞迁移途径的表达或生物活性,是指减少(抑制或下调)大于大约50%至大约99%,更具体地说,大约50%、51%、52%、53%、54%、55%、56%、57%、58%、59%、60%、61%、62%、63%、64%、65%、66%、67%、68%、69%、70%、71%、72%、 73%、74%、75%、76%、77%、78%、79%、80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或更高。抑制可以是直接的,即对目的分子或途径本身进行起作用,或间接的,即对影响目的分子或途径的分子或途径起作用。
“重组”,当涉及例如细胞、或核酸、蛋白质或载体使用时,表明所述细胞、核酸、蛋白质或载体已经通过引入异源核酸或蛋白质或者改变天然核酸或蛋白质加以修饰,或该细胞源自如此修饰的细胞。因此,例如,重组细胞表达在细胞的天然(非重组)形式中未发现的基因、或表达原本不正常表达、低下表达或根本不表达的天然基因。
“有效量”和“治疗有效量”在此可互换使用,是指在此描述的抗体、抗原结合片段或组合物有效达到具体生物学结果例如但不限于在此公开、描述或例示的生物学结果的量。这样的结果可以包括但是不局限于,治疗通过本技术领域任何合适的手段测定的、与血管生成或新生血管形成有关的疾病。
用在这里,“测量”或“测定”是指任何定性或定量测定。
“内皮唾液酸蛋白配体”是指能够与内皮唾液酸蛋白结合、与其相互作用、对其进行刺激和/或改变其表达的任何化学物质、生物分子、复合物或其类似物、同系物或衍生物。
除有注解的时候,“对象”或“患者”可互换地使用,并且是指哺乳动物例如人类患者和非人类灵长动物,以及试验动物例如兔子、狗、猫、大鼠、小鼠及其他动物。因此,“对象”或“患者”用在这里意味着能够对其施用本发明组合物的任何哺乳动物患者或对象。
“血管生成”是指形成新血管。
“新生血管形成”是指正常情况下不含血管的组织或器官中新血管的病理性增殖,或与具体组织或器官的正常状态相比,类型或数量不同的血管的病理性增殖。
“表位”是指作为抗体结合位点的抗原免疫决定簇。用在这里,术语“构象表位”是指非连续表位,由未打断的氨基酸序列以外的抗原氨基酸之间的空间关系形成。
“分离的”是指“通过人工”从自然状态改变。如果分子或组合物在自然界中存在,如果它已经从其原来的环境中改变或取出或这二者,则它已经被“分离”。例如,活的植物或动物中天然存在的多核苷酸或多肽不是“分离的”,但是与其自然状态的共存材料分离开的同样的多核苷酸或多肽,根据在此使用的术语而言,是“分离的”。
“基本相同”对于核酸或氨基酸序列而言,是指两种或多种序列之间至少大约65%的同一性。优选,该术语是指两种或多种序列之间至少大约70%同一性,更优选至少大约75%同一性,更优选至少大约80%同一性,更优选至少大约85%同一性,更优选至少大约90%同一性,更优选至少大约91%同一性,更优选至少大约92%同一性,更优选至少大约93%同一性,更优选至少大约94%同一性,更优选至少大约95%同一性,更优选至少大约96%同一性,更优选至少大约97%同一性,更优选至少大约98%同一性,和更优选至少大约99%或更高的同一性。
根据本发明已经发现,内皮唾液酸蛋白与细胞外基质蛋白包括纤连蛋白或胶原蛋白特异性相互作用。还已经发现,这种相互作用促进细胞迁移并还促进和便于血管生成。这些观察之外,进一步发现,破坏内皮唾液酸蛋白和细胞外基质蛋白之间的相互作用能够抑制细胞迁移并能够抑制血管生成。因此,本发明的特征在于抑制内皮唾液酸蛋白与内皮唾液酸蛋白配体相互作用的方法。
一方面,本发明的特征在于抑制表达内皮唾液酸蛋白的细胞表达的内皮唾液酸蛋白与内皮唾液酸蛋白配体相互作用的方法。在一些优选的实施方案中,该方法包括抑制该细胞的内皮唾液酸蛋白表达。抑制内皮唾液酸蛋白表达能够发生在基因水平或蛋白水平。例如,抑制内皮唾液酸蛋白的表达可以包括靶定编码内皮唾液酸蛋白的DNA,或靶定内皮唾液酸蛋白基因的mRNA转录物。
基因调节的方法在本技术领域中是已知的并且容易实施,并且全部都适合在本发明的方法中使用。例如,在专门工程化以表达编码内皮唾液酸蛋白(例如,SEQ ID NO:1、3或5)的转基因的细胞中,该转基因可以置于诱导型启动子的控制之下。本发明中适用的诱导型启动子是本领域技术人员所知的。
在一些优选的实施方案中,编码内皮唾液酸蛋白的基因可以通过使用多种其它的转录后基因沉默(RNA沉默)技术加以抑制。RNA沉默包括通过基于RNase H的酶(“切丁酶(Dicer)”或“类切丁酶”),把双链RNA(dsRNA)加工成21-28个核苷酸的小片段。分裂产物是siRNA(小干扰RNA)或miRNA(微小RNA),被掺入以序列特异性方式调节基因表达的蛋白效应器复合物中。
RNA干扰(RNAi)是双链RNA(dsRNA)介导的转录后基因沉默机制,与基于反义和核酶的途径不同(关于RNAi和siRNA的综述,参见Jain,Pharmacogenomics(2004)5:239-42)。通过细胞转化,或通过给动物施用在严紧条件下与编码内皮唾液酸蛋白的基因杂交、并减弱该靶基因表达的核酸(例如,dsRNA),RNA干扰在抑制细胞或动物例如人类的内皮唾液酸蛋白表达的方法中是有用的。RNA干扰提供的shRNA或siRNA包含了靶定内皮唾液酸蛋白基因中一个或多个区域的多重序列。双链RNA(dsRNA)分子(shRNA或siRNA)首先经过被称为切丁酶的类RNase III酶加工(Bernstein E等(2001)Nature 409:363-366),成为包含 两个21nt链的较小dsRNA分子,每个具有5′磷酸基和3′羟基,并且包括与另一条链精确互补的19nt区域,使得产生侧翼带有2nt的-3′突出端的19nt双链体区域,在此之后,认为其指导各种类型细胞中mRNA的序列特异性降解。因此,RNAi通过短干扰RNAs(siRNA)介导,其一般包含大约19个核苷酸长度的双链区域,每条链上具有1-2个核苷酸的3′突出端,致使总长度在大约21和23个核苷酸之间。在哺乳动物细胞中,长于大约30个核苷酸的dsRNA通常通过干扰素响应,引起非特异性的mRNA降解。但是,哺乳动物细胞中存在的siRNA,不是引起干扰素响应,而是导致序列特异性的基因沉默。
病毒载体或DNA载体编码短发夹RNA(shRNA),其在细胞的细胞质中加工成短干扰RNA(siRNA)。短干扰RNA(siRNA)通常包含优选大约19个碱基对长的RNA双链体,并任选还包含一个或两个单链突出端或环。siRNA可以包含两条杂交在一起的RNA链,或者可以包含其中包括自身杂交部分的RNA单链。siRNAs可以包括一个或多个自由的链末端,链末端可以包括磷酸和/或羟基基团。siRNAs一般包括在严紧条件下与靶转录物杂交的部分。siRNA的一条链(或siRNA的自身杂交部分)通常与靶转录物的区域精确互补,意味着siRNA与靶转录物的杂交没有一个错配。在本发明的某些没有达到完美互补性的实施方案中,一般优选任何错配位于siRNA末端或者末端附近。
siRNAs当通过诸如转染、电穿孔、阳离子脂质体介导的转染或显微注射的方法转入哺乳动物细胞中时,或当通过多种基于质粒的途径在细胞中表达时,已经显示出下调基因表达。利用siRNA的RNA干扰的综述例如如下:Tuschl(2002)Nat.Biotechnol.20:446-8;Yu J-Y等(2002)Proc.Natl.Acad.Sci.USA,99:6047-52;Sui G等(2002)Proc.Natl.Acad.Sci.USA,99:5515-20;Paddison等(2002)Genes and Dev.,16:948-58;Brummelkamp等(2002)Science,296:550-3,2002;Miyagashi等(2002)Nat.Biotechnol,20:497-500;和Paul等(2002)Nat.Biotechnol,20:505-8。如这些和其他参考文献所述,siRNA可以由两条 个体核酸链组成,或由带有能够形成发夹(茎-环)结构的自身互补区域的单链组成。结构、长度、错配数、环的大小、突出端中核苷酸的同一性等的许多变化与有效的siRNA引发的基因沉默相一致。虽然不希望受任何理论的约束,但认为,多种不同前体的细胞内加工(例如,通过切丁酶)导致能够有效介导基因沉默的siRNA产生。一般优选靶定外显子而不是内含子,并且还可以优选选择与靶转录物的3′部分内区域互补的序列。一般优选选择包含大约等摩尔比率的不同核苷酸的序列,并且优选避免其中单个残基重复多次的序列段。
因此,siRNAs可以包含具有大约19个核苷酸长的双链区域并且每条链上带有1-2个核苷酸的3′突出端的RNA分子,致使总长度在大约21和23个核苷酸之间。用在这里,siRNAs还包括各种可以在体内加工以产生这样的分子的各种RNA结构。这样的结构包括含有两个互补元件的RNA链,所述互补元件彼此杂交形成茎、环和任选的突出端,优选为3′突出端。优选,茎大约19bp长,环大约1-20、更优选大约4-10、和最优选大约6-8nt长,和/或突出端大约1-20、和更优选大约2-15nt长。在本发明的某些实施方案中,茎最小19个核苷酸长度,并可以直至大约29个核苷酸长度。4个核苷酸或更大的环比短的环受到的空间约束的可能性低,因此可能是优选的。突出端可以包括5′磷酸和3′羟基。突出端可以但是不必包含多个U残基,例如1和5个U残基之间。上面描述的标准siRNAs引发它们靶定的mRNAs的降解,从而还减低蛋白质合成的速率。除了通过经典途径起作用的siRNAs之外,某些与模板转录物的3′UTR结合的siRNAs可以通过与经典的RNA干扰有关但是不相同的机制,例如减少转录物的翻译而不是降低其稳定性,来抑制模板转录物编码的蛋白质的表达。这样的RNAs称为微小RNAs(miRNAs),通常长度在大约20和26个核苷酸之间,例如,22nt长度。据认为,它们源自被称为小时序RNAs(stRNAs)或mRNA前体的较大前体,其一般为大约70nt长,带有大约4-15nt的环(Grishok等(2001)Cell,106:23-4;Hutvagner等(2001)Science,293:834-8;Ketting等(2001)Genes Dev.,15:2654-9)。已经在许多生物体包括哺乳动物中 鉴定到了这种类型的内源RNAs,提示这种转录后基因沉默的机制可能是普遍的(Lagos-Quintana等(2001)Science,294:853-8,2001;Pasquinelli(2002)Trends Gen.,18:171-3)。微小RNAs已经表现出在哺乳动物细胞中阻断含有靶位点的靶转录物的翻译(Zeng等(2002)Mol.Cell,9:1327-33)。
在3′UTR(或靶转录物中其它地方)内结合并抑制翻译的siRNAs,例如天然存在的或人工的(即,由人类设计)mRNAs,可以耐受在siRNA/模板双链体中较大数量的错配,特别可以耐受双链体中央区域内的错配。事实上,有证据说明,一些错配可能是可取的或需要的,因为天然存在的stRNAs频繁呈现这样的错配,已经表现出抑制体外翻译的mRNAs也是一样。例如,当与靶转录物杂交时,这样的siRNAs常常包括由错配区域分开的两段完美互补的序列。多种结构都是可能的。例如,mRNA可以包括不同一性(错配)的多个区域。从靶和mRNA二者包含未配对的核苷酸这一意义上说,不同一性(错配)的区域不必是对称的。通常,完美互补的一段序列长度至少5个核苷酸,例如,6、7或更多核苷酸的长度,而错配区域长度可以是例如1、2、3或4个核苷酸。
设计成模拟siRNAs和mRNA前体的发夹结构,在细胞内加工成能够减少或抑制靶转录物表达的分子(McManus等(2002)RNA8:842-50)。这些发夹结构以两条RNA链形成19bp双链体结构构成的经典siRNAs为基准,分为I类或II类发夹。I类发夹在反义siRNA链的5′或3′末端合并有环(即,该链与需要抑制的靶转录物互补),但是在其它方面与经典的siRNAs相同。II类发夹由于它们在茎中除了一个或多个核苷酸错配之外,还包含19nt的双链体区域和双链体反义链的3′或5′末端处的环,从而类似mRNA前体。这些分子细胞内加工成能够介导沉默的小RNA双链体结构。它们看起来通过降解靶mRNA、而不是通过所认为的天然存在的mRNAs和siRNAs情况下的翻译抑制,来发挥它们的作用。
因此,显然,含有双链体结构的多样化的RNA分子组,能够通过各种机制介导沉默。出于本发明的目的,任何这样的RNA,一部分与靶转录物结合并无论是通过引发降解、抑制翻译或通过其它方式降低其表达,均被认为是是siRNA,并且任何产生这样的siRNA的结构(即,作为该RNA的前体),在本发明的实施中都是有用的。
本发明使用的另一种RNA干扰方法是使用短发夹RNAs(shRNA)。含有编码特定目的siRNA序列的DNA序列的质粒,通过转染或病毒介导的感染,被递送到靶细胞中。一旦在细胞中,该DNA序列连续转录成自己环回并通过分子内碱基配对形成发夹结构的RNA分子。这些发夹结构,一旦由细胞加工,等价于转染的siRNA分子,并被细胞用于介导目的蛋白质的RNAi。使用shRNA比siRNA转染有优势,因为前者可以引起蛋白表达的长期稳定抑制。通过转染的siRNAs抑制蛋白表达是暂时现象,存在的时期不会长于数天。在一些情况下,这可能是优选和希望的。在需要蛋白抑制时期较长的情况下,shRNA介导的抑制是优选的。特别优选使用shRNA。通常,siRNA-编码载体是包含启动子、在“正义”方向上沉默的靶基因序列、间隔子、反义的靶基因序列和终止子的构建物。
抑制内皮唾液酸蛋白的表达,还可以通过本技术领域已知的和容易实施的其它方法来实现。例如,可以使用反义核酸。反义RNA转录物具有与相同细胞中任何其它RNA转录物部分或全部互补的碱基序列。这样的转录物已经表现出通过多种机制调节基因表达,包括调节RNA剪接、调节RNA转运和调节mRNA的翻译(Denhardt(1992)Ann.N Y Acad.Sci,660:70-6,1992;Nellen等(1993)Trends Biochem.Sci.,18:419-23;和Baker等(1999)Biochim.Biophys.Acta.,1489:3-18)。因此,在本发明的某些实施方案中,在细胞中抑制内皮唾液酸蛋白通过在细胞中表达反义核酸分子来实现。
反义核酸一般是与靶核酸(例如,mRNA转录物)的一部分互补、并因此能够与该靶结合以形成双链体的单链核酸(DNA,RNA,修饰的DNA或修饰的RNA)。通常,它们是长度范围为15至35个核苷酸、但长度范围可以从10直至大约50个核苷酸的寡核苷酸。结合通常降低或抑制靶核酸例如编码内皮唾液酸蛋白的基因的功能。例如,反义寡核苷酸当结合基因组DNA时可以阻断转录,当结合mRNA时抑制翻译,和/或引起核酸降解。抑制内皮唾液酸蛋白的表达,可以通过施用所包含的序列与编码内皮唾液酸蛋白的mRNA的序列互补的反义核酸或肽核酸来实现。反义技术及其应用在本技术领域中是公知的并记载于Phillips(主编)的反义技术,方法酶学(Antisense Technology,Methods Enzymol.),2000,313和314卷,Academic Press,San Diego,以及其中提到的参考文献中。还参见Crooke(主编)的“反义药物技术:原理,策略和应用(ANTISENSE DRUG TECHNOLOGY:PRINCIPLES,STRATEGIES,AND APPLICATIONS)”(第一版)Marcel Dekker,以及其中提到的参考文献。
反义寡核苷酸可以用与细胞中任何RNA转录物的一部分互补的碱基序列合成。反义寡核苷酸可以通过多种机制调节基因表达,包括调节RNA剪接、调节RNA转运和调节mRNA翻译。反义寡核苷酸的各种性质包括稳定性、毒性、组织分布以及细胞摄取和结合亲合力可以通过化学修饰改变,所述化学修饰包括:(i)替换磷酸二酯骨架(例如,肽核酸,硫代磷酸酯寡核苷酸,以及氨基磷酸酯寡核苷酸);(ii)修饰糖碱基(例如2′-O-丙基核糖和2′-甲氧基乙氧基核糖);和(iii)修饰核苷(例如,C-5丙炔基U,C-5噻唑U,和吩噁嗪C)(Wagner(1995)Nat.Medicine,1:1116-8;Varga等(1999)Immun.Lett.,69:217-24;Neilsen(1999)Curr.Opin.Biotech.,10:71-5;和Woolf(1990)Nucleic Acids Res.,18:1763-9)。
抑制内皮唾液酸蛋白基因表达还可以通过利用核酶实现。某些称为核酶或脱氧核酶的核酸分子,已经表现出催化RNA分子的序列特异 性切割。切割位点通过RNA或DNA酶中的核苷酸与靶RNA中的核苷酸互补配对进行确定。因此,RNA和DNA酶可以设计成切开任何RNA分子,从而增加其降解速率(Cotten等(1989)EMBO J,8:861-6;和Usman等(1996)Curr.Opin.Struct.Biol.,1:527-33)。锤头状核酶也常规用于基因调节(Lyngstadaas(2001)Crit.Rev.Oral Biol.Med.,12:469-78)。
在本发明的优选方面,本发明方法针对的细胞可以用转录-沉默核酸例如shRNA或siRNA特异性转化,或可以用编码这样的核酸的载体转化,致使细胞表达抑制性核酸分子。细胞的转化可以根据本技术领域任何合适的方法进行,包括在此描述和例示的方法。
诱捕寡核苷酸也适合于调节内皮唾液酸蛋白编码基因的表达。最近的临床试验已经测试了诱捕寡核苷酸隔离病原性蛋白的能力。诱捕寡核苷酸一般含有能够穿透细胞的增强子元件,一旦进入细胞内部,诱捕寡核苷酸与序列特异性DNA结合蛋白相结合并干扰转录(Fichou等(2006)Trends BiotechnoL,24:563-70;Nakamura等(2002)In Vivo,16:45-8;Tomita等(1997)Exp.Nephrol,5:429-34)。
内皮唾液酸蛋白表达的遗传调节还可以通过击倒编码内皮唾液酸蛋白的基因来实现。本领域技术人员将会理解,内皮唾液酸蛋白基因的序列(来自任何所目的生物体),例如SEQ ID NO:1、3或5,可用于产生击倒内皮唾液酸蛋白基因表达的核酸分子和载体。根据它们的序列考虑,编码来源于SEQ ID NOs:1、3和5的调节性、特别是抑制性序列的核酸分子,包括SEQ ID NOs:1、3和5的等位基因变体、同系物和自然突变体。因为预期这样的变体和同系物在核苷酸序列中拥有某些差异,本发明提供的分离多核苷酸与来源于SEQ ID NOs:1、3或5的任何击倒核酸具有至少大约60%,优选至少大约61%、62%、63%、64%、65%、66%、67%、68%、69%或70%,更优选至少大约71%、72%、73%、74%、75%、76%、77%.78%、79%或80%,更加优选81%、 82%、83%、84%、85%、86%、87%、88%、89%,并且甚至更优选90%、91%、92%、93%、94%、95%,和最优选96%、97%、98%或99%或更高的同一性。因为在不同生物体的编码这些调节序列的基因当中,可能存在天然的序列变异,本领域技术人员预期会发现这种变异水平,而仍然保持所述击倒多核苷酸的独特性质。因此,这样的变体和同系物被认为是彼此基本相同,并包含在本发明的范围内。
击倒核酸分子能够通过两种一般方法制备:(1)它们可以从适当的三磷酸核苷合成,或(2)它们可以从生物学来源分离。这两种方法采用的方案是本技术领域公知的。
核苷酸序列信息例如内皮唾液酸蛋白整个核酸序列比如SEQ IDNOs:1、3和5的可用性,使得能够通过寡核苷酸合成制备本发明的分离核酸分子。合成寡核苷酸可以通过在Applied Biosystems 38A DNA合成仪或类似装置上应用亚磷酰胺(phosphoramadite)法制备。生成的构建物可以根据本技术领域已知的方法例如高效液相色谱法(HPLC)纯化。如此构建的合成DNA分子然后可以在适当的载体中克隆并放大。
击倒核酸可以在任何便利的克隆载体中,保持为DNA。在一些优选的方面,克隆保持在质粒克隆/表达载体中,两种都可以在合适的原核或真核宿主细胞中增殖。
击倒核酸分子包括cDNA、基因组DNA、RNA及其可以是单链、双链乃至三链的片段。因此,本发明提供的寡核苷酸(DNA或RNA的正义或反义链)具有能够与至少一种本发明的核酸分子序列、特别是SEQ ID NOs:1、3或5杂交的序列。这样的寡核苷酸可用作检测编码内皮唾液酸蛋白的基因的探针,或可用作mRNA翻译成蛋白时或之前,正性或负性调节编码内皮唾液酸蛋白的基因表达的探针。其中寡核苷酸或多核苷酸可以用作这类分析的探针的方法包括但是不局限于:(1)原位杂交;(2)Southern杂交;(3)Northern杂交;和(4)各种放大反应, 例如聚合酶链式反应(PCR)和连接酶链式反应(LCR)。
本发明的特征还在于,用于产生转基因宿主细胞载体和试剂盒,所述转基因宿主细胞包含在正义或反义方向抑制内皮唾液酸蛋白、或其同系物、类似物或变体表达的调节序列的编码多核苷酸,或在细胞或组织特异性启动子和/或其它调节序列控制之下的构建物。这样的载体适于调控,并优选抑制内皮唾液酸蛋白的表达。
合适的宿主细胞包括,但是不局限于,表达内皮唾液酸蛋白的植物细胞、细菌细胞、酵母及其他真菌细胞、昆虫细胞和哺乳动物细胞。细胞可以是致瘤性转化的。更优选是人类细胞。
用于转化多种多样的这些宿主细胞的载体对本领域技术人员是公知的。它们包括但是不局限于,质粒、噬粒、粘粒、杆状病毒、杆粒、细菌人工染色体(BACs)、酵母人工染色体(YACs)以及其它的细菌、酵母和病毒载体。
调节序列的编码区可以置于有效的组成性启动子之下,例如以下基因的启动子:次黄嘌呤磷酸核糖基转移酶(HPRT),腺苷脱氨酶,丙酮酸激酶,β-肌动蛋白,人肌球蛋白,人血红蛋白,人肌肉肌酸及其他。另外,许多病毒启动子在真核细胞中发挥组成性功能,适用于本发明。这样的病毒启动子包括但不限于,巨细胞病毒(CMV)立即早期启动子,SV 40的早期和晚期启动子,小鼠乳腺肿瘤病毒(MMTV)启动子,马洛尼(Maloney)白血病病毒的长末端重复序列(LTRs),人类免疫缺陷病毒(HIV),E-B病毒(EBV),劳氏(Rous)肉瘤病毒(RSV),及其他逆转录病毒,和单纯疱疹病毒的胸苷激酶启动子。其它启动子是本领域普通技术人员所知的。在一种实施方案中,调节序列的编码区置于诱导型启动子之下,例如金属硫蛋白启动子,四环素诱导型启动子,强力霉素诱导型启动子,含有一个或多个干扰素刺激响应元件(ISRE)例如蛋白激酶R2′,5′-寡腺苷酸合成酶的启动子,Mx基因,ADAR1,等等。其 它合适的诱导型启动子将是本领域技术人员所知的。
击倒载体可用于以调节性核酸序列转化各种表达内皮唾液酸蛋白的细胞。本技术领域中对于将外源基因引入细胞的许多技术是已知的,并可以为了实施本发明的方法,根据本发明的各种实施方案,用于构建重组细胞。所用的技术应该为宿主细胞提供稳定转移的异源基因序列,致使异源基因序列可遗传并可被后代细胞表达,并使得受体细胞的必要发育和生理功能不受破坏。可以使用的技术包括但是不限于,染色体转移(例如,细胞融合,染色体介导的基因转移,微细胞介导的基因转移),物理方法(例如,转染,原生质球融合,显微注射,电穿孔,脂质体载体),病毒载体转移(例如,重组DNA病毒,重组RNA病毒)等等(记载于Cline(1985)Pharmac.Ther.,29:69-92)。
抑制内皮唾液酸蛋白表达的击倒细胞可以通过转录后基因沉默,抑制编码转运蛋白的mRNA的翻译而产生。来自靶物种的供下调节的基因,或其片段,可以用来控制所编码的蛋白的产生。全长反义分子可以用于本目的。或者,可以利用靶定翻译关键性的特定mRNA区域的反义寡核苷酸。反义分子可以由带有DNA构建物的转化细胞原位提供,所述细胞经转录产生反义RNA序列。这样的构建物可以设计成产生全长或部分反义序列。这种基因沉默作用可以通过转基因过度生产基因编码序列的正义和反义RNA进行增强,以致产生大量的dsRNA(例如,参见Waterhouse等(1998)Proc.Natl.Acad.Sci.U.S.A.,95:13959-64)。在这方面,已经发现含有与至少一个内含子的部分或全部相对应的序列的dsRNA特别有效。在一种实施方案中,编码序列反义链的部分或全部通过转基因表达。在另一种实施方案中,一种内皮唾液酸蛋白编码序列的部分或全部的杂交正义和反义链是转基因表达的。
作为本发明方法的对象或以其它方式用于本发明方法的细胞,包括天然表达内皮唾液酸蛋白的表达内皮唾液酸蛋白的细胞,或用表达内皮唾液酸蛋白的重组质粒转染的细胞。本发明的初级表达内皮唾液 酸蛋白的细胞可以从组织分离、或从销售内皮细胞的出售者购买,例如但不限于HUVEC或HMVEC,以及初级和培养的成纤维细胞。本发明的转染细胞包括任何已知的昆虫表达细胞系,例如草地贪夜蛾(Spodoptera frugiperda)细胞。表达细胞系也可以是酵母细胞系,例如酿酒酵母(Saccharomyces cerevisiae)和粟酒裂殖酵母(Schizosaccharomyces pombe)细胞。表达细胞也可以是哺乳动物细胞,例如中华仓鼠卵巢,幼仓鼠肾细胞,人胚肾细胞系293,正常狗肾细胞系,正常猫肾细胞系,猴肾细胞,非洲绿猴肾细胞,COS细胞,和非致癌性小鼠成肌细胞G8细胞,成纤维细胞系,骨髓瘤细胞系,小鼠NIH/3T3细胞,LMTK细胞,小鼠足细胞,人宫颈癌细胞,buffalo大鼠肝细胞,人肺细胞,人肝细胞,小鼠乳腺肿瘤细胞,TRI细胞,MRC5细胞,和FS4细胞。
抑制内皮唾液酸蛋白表达抑制了内皮唾液酸蛋白与任何内皮唾液酸蛋白配体的相互作用。内皮唾液酸蛋白配体包括细胞外基质蛋白,例如纤连蛋白和胶原蛋白。
本发明的特征还在于,抑制表达内皮唾液酸蛋白的细胞表达的内皮唾液酸蛋白与内皮唾液酸蛋白配体相互作用的方法包括,阻断或阻碍细胞的内皮唾液酸蛋白表达。因此,例如,物理屏障用来抑制、妨碍、或以其它方式阻止所表达的内皮唾液酸蛋白与内皮唾液酸蛋白配体相互作用。任何化学物质或生物分子可以用来阻碍这一相互作用。例如,与内皮唾液酸蛋白特异性结合、或者说与内皮唾液酸蛋白配体特异性结合的小分子、多肽、抗体及其抗原结合片段,可以用于本方法。
在一些优选的实施方案中,抑制表达内皮唾液酸蛋白的细胞与内皮唾液酸蛋白配体的相互作用,包括抑制内皮唾液酸蛋白配体与表达的内皮唾液酸蛋白结合。例如,用分子屏障阻止、阻断、妨碍或以其它方式阻碍内皮唾液酸蛋白和其配体之间相互作用。以这种方法,从 而阻止、抑制、阻断、妨碍、阻碍或者阻止了细胞被配体接近。阻碍内皮唾液酸蛋白可以通过本技术领域合适的任何手段发生,例如用化学物质或者生物分子。
例如,适合本发明方法使用的化学物质包括但是不局限于,氨基酸结构,类固醇,细胞周期蛋白,蒽,重金属,喹诺酮(quinilone),萜烯,酚醛,葡糖苷,生物碱(alkyloids),脂质等等,或其能够对表达内皮唾液酸蛋白的细胞发挥生物效应的混合物。化学物质可通过化学合成产生或来源于生物催化或来源于生物流体。化学物质可源于人类、非人类哺乳动物、植物、酵母、真菌和/或和/或原核来源。
在一些实施方案中,竞争性抑制剂用于抑制内皮唾液酸蛋白或表达内皮唾液酸蛋白的细胞与内皮唾液酸蛋白配体的相互作用。“竞争性抑制剂”与配体竞争内皮唾液酸蛋白的结合位点。在一些实施方案中,竞争性抑制剂是内皮唾液酸蛋白配体,例如,胶原蛋白(例如,胶原蛋白I或IV)或纤连蛋白,或其内皮唾液酸蛋白结合片段。最优选的竞争性抑制剂是纤连蛋白的70kDa的N-末端片段、纤连蛋白的45kDa的明胶结合片段、和纤连蛋白的30kDa的肝素结合片段。
在高度优选的实施方案中,抗体或其抗原结合片段用丁阻碍表达的内皮唾液酸蛋白与内皮唾液酸蛋白配体相互作用。抗体或抗原结合片段可以是对内皮唾液酸蛋白上的表位特异性的,或可以是对内皮唾液酸蛋白配体上的表位特异性的。更优选对内皮唾液酸蛋白特异性的抗体和其抗原结合片段。针对配体例如纤连蛋白、胶原蛋白等等的抗体市场上可买到。
合适的抗体可以是多克隆或单克隆抗体,或可以是保持了对内皮唾液酸蛋白或内皮唾液酸蛋白配体特异性的抗体衍生物或片段。抗体可以来自五类抗体的任一种,即IgA、IgD、IgE、IgG和IgM同种型。合适的抗体还包括一般在母鸡或火鸡血清和母鸡或火鸡蛋黄中发现的 IgY同种型。
抗体衍生物和抗原结合片段适合在本发明方法中使用,这样的衍生物包括保持了亲本抗体分子抗原结合特异性的完整抗体的部分。例如,衍生物可以包括至少一个可变区(重链或轻链可变区)。合适的抗体衍生物和片段的例子包括但不限于,具有多表位特异性的抗体,双特异性抗体,双抗体和单链分子,以及Fab、F(ab′)2、Fd、Fabc和Fv分子,单链(Sc)抗体,单个抗体轻链,单个抗体重链,抗体链和其它分子的嵌合融合体,重链单体或二聚体,轻链单体或二聚体,由一条重链和一条轻链构成的二聚体,等等。所有的抗体同种型可用于产生抗体衍生物和片段。抗体衍生物和片段可以重组产生。
本发明方法适用的抗体可以源自任何物种。例如,抗体可以是小鼠、大鼠、山羊、马、猪、牛、鸡、兔、驴、人等等的。为了用于治疗方法、或为了施用于人类,非人类起源的抗体可以改变结构,使得在给人类患者施用时抗原性较小。
因而,在本发明的一些实施方案中,用于本发明方法的抗体是嵌合抗体。嵌合抗体及其生产方法是本技术领域公知的和确立的。例如,嵌合抗体可以包括带有人类Fc的小鼠抗原结合结构域或其它这样的结构域。
在一些实施方案中,抗体是人源化抗体。人源化抗体可以是嵌合的免疫球蛋白、免疫球蛋白链或其片段(例如Fv,Fab,Fab′,F(ab′)2或抗体的其它抗原结合子序列),其含有来源于非人免疫球蛋白的最小序列。就绝大部分而言,人源化抗体是人免疫球蛋白(接受者抗体),其中来自接受者的互补决定区(CDR)的残基被来自具有所需特异性、亲合力和能力的非人类物种(供体抗体)例如小鼠、大鼠或兔子的CDR的残基替代。一些情况下,人免疫球蛋白Fv框架区(FWR)的残基被相应的非人类残基替代。此外,人源化抗体可以包含在接受者抗体或引入的 CDR或框架序列中均未发现的残基。进行这些修饰,以进一步改善和优化抗体性能。通常,人源化抗体将包含至少一个、并通常是两个可变结构域的基本上全部,其中所有CDR区域的全部或基本上全部对应于非人免疫球蛋白的CDR区域,并且所有或基本上所有的FWR区域是人免疫球蛋白序列的FWR区域。人源化抗体还将最好包含免疫球蛋白恒定区(Fc)、通常是人免疫球蛋白的恒定区的至少一部分。进一步的细节参见Jones等(1986)Nature,321:522-5;Reichmann等(1988)Nature,332:323-9;和Presta(1992)Curr.Op.Struct.Biol,2:593-6。
在本发明的优选方面,抗体是完全人类的。这意味着抗体只来自人类来源,或者由与抗体的人类形式一致的氨基酸序列组成。
本发明的抗体能够被标记或以其它方式与各种化学物质或生物分子部分结合,例如,供治疗或诊断应用。所述部分可以是细胞毒素,例如细菌毒素、病毒毒素、放射性同位素等等。所述部分可以是可检测出的注记,例如荧光注记、放射标记、生物素等等。其他的部分包括但是不限于糖基化、乙酰化、聚乙二醇化、磷酸化和酰胺化。对本发明方法有用的抗体可以通过已知的保护/封闭基团、蛋白水解裂解、与细胞配体或其它蛋白连接等等,自身衍生化。
本领域技术人员将认识到,抗体特异性主要是通过六个CDR区域确定的,尤其是H链CDR3(Kala等(2002)J.Biochem.,132:535-41;Morea等(1998)J.MoL Biol,275:269-94;和Chothia等(1987)J.MoIBiol,196:901-17)。但是,抗体构架区可以在抗原-抗体相互作用中起作用(Panka等(1988)Proc.Natl Acad.Sci.USA,85:3080-4),特别是就它们在CDR环构象中的作用而言(Foote等(1992)J.Mol.Biol,224:487-99)。因此,本发明方法中适用的抗体可以包含赋予抗体对内皮唾液酸蛋白或内皮唾液酸蛋白配体特异性的H或L链CDR或FWR区域的任何组合。
在一些实施方案中,本发明构思了利用与内皮唾液酸蛋白特异性结合的分离的人类抗体及其抗原结合片段。在一些实施方案中,合适的抗体或抗原结合片段可以包含的重链分别含有SEQ ID NO:28、30和32的CDR1、CDR2、和CDR3,而轻链分别包含SEQ ID NO:13、15和17的CDR1、CDR2和CDR3。在一些实施方案中,重链CDR1、CDR2和CDR3分别由SEQ ID NO:27、29和31的核苷酸序列编码。在一些实施方案中,轻链CDR1、CDR2和CDR3分别由SEQ ID NO:12、14和16的核苷酸序列编码。在一些实施方案中,抗体或抗原结合片段可以包括的重链含有SEQ ID NO:34的可变结构域,包括的轻链含有SEQ ID NO:19的可变结构域。在一些实施方案中,重链可变结构域由SEQ ID NO:33的核苷酸序列编码。在一些实施方案中,轻链可变结构域由SEQ ID NO:18的核苷酸序列编码。在一些实施方案中,抗体或抗原结合片段可以包括的重链含有SEQ ID NO:22或26的氨基酸序列,包括的轻链含有SEQ ID NO:11的氨基酸序列。
在一些实施方案中,重链由SEQ ID NO:21或25的核苷酸序列编码,而轻链由SEQ ID NO:10的核苷酸序列编码。在一些实施方案中,抗体或抗原结合片段包括的重链含有SEQ ID NO:20或24,包括的轻链含有SEQ ID NO:9。在一些实施方案中,抗体包含由SEQ ID NO:8或23的核酸序列编码的重链。抗体或抗原结合片段可以包含由含有SEQ ID NO:7的核酸序列编码的轻链。
可以根据本发明使用的生产抗体的抗体生产细胞已经于2006年4月24日和2008年3月11日保藏在美国典型培养物保藏中心(Amer.Type Cult.Coll.)(10801University Blvd.,Manassas,Virginia20110-2209),并已经指定保藏号PTA-7554。
要理解,因为重链和轻链以及它们的编码基因当中可能存在天然的序列变异,本领域技术人员将预料到会在所述氨基酸序列或它们的编码基因之内发现一些变异水平,但是却仍然保持本发明抗体的独特结合性质(例如,特异性和亲合力)。这样的预料部分是由于遗传密码的简并性,以及保守氨基酸序列变异的已知进化成就,这些不会明显改变所编码的蛋白的性质。因此,这样的变体和同系物被认为是彼此基本相同,并包含在本发明的范围内。
具有单个或多个氨基酸取代、缺失、添加或替换并仍然保持在此描述的抗体的生物学性质(例如,结合亲合力或免疫效应器活性)的变体,考虑用于本发明。技术人员可以生产具有单个或多个氨基酸取代、缺失、添加或替换的变体。这些变体可以包括,例如(a)其中一个或多个被保守或非保守的氨基酸取代的变体,(b)从多肽添加或缺失一个或多个氨基酸的变体,(c)其中一个或多个氨基酸包括取代基的变体,和(d)其中多肽与另一种肽或多肽例如融合伴侣、蛋白标签或其它的化学部分融合的变体,这可以赋予所述多肽有用的性质,例如对抗体的表位、聚组氨酸序列、生物素部分等等。本发明的抗体可以包括其中在保守的或非保守的位置上,来自一个物种的氨基酸残基取代另一个物种的相应残基的变体。在其它实施方案中,非保守位置上的氨基酸残基被保守或非保守的残基取代。用于获得这些变体的技术,包括基因(抑制,缺失,突变等等)、化学和酶技术,是本领域的普通技术人员所知的。
本发明构思了具有与前述的氨基酸序列基本相同的氨基酸序列的抗体或其抗原结合片段。例如,这样的抗体或抗原结合片段可以包括其中重链CDR1、CDR2和CDR3分别与SEQ ID NO:28、30和32至少90%同一、和/或其中轻链CDR1、CDR2和CDR3分别与SEQ ID NO:13、15和17至少90%同一者。在一些实施方案中,这样的抗体或抗原结合片段可以包括其中重链可变结构域与SEQ ID NO:34至少90%同一、和/或其中轻链可变结构域与SEQ ID NO:19至少90%同一者。在一些实施方案中,抗体或抗原结合片段可以包括其中重链与SEQ ID NO:22或26至少90%同一和/或其中轻链与SEQ ID NO:11至少90%同一者。在一些实施方案中,抗体或抗原结合片段可以包括其中重链与SEQ ID NO:20或24至少90%同一和/或其中轻链与SEQ ID NO:9至少90%同一者。例如,抗体M4和M4.1是针对人类内皮唾液酸蛋白的人源化抗体。虽然抗体M4和M4.1共有轻链序列,但它们在它们的重链上,例如,SEQ ID NO:20的429位残基相对于SEQ ID NO:24的429位残基,显示有单个氨基酸序列的不同。本发明进一步构思了与抗体M4或M4.1竞争与内皮唾液酸蛋白结合的抗体或其抗原结合片段。本发明进一步构思了与抗体M4或M4.1结合的内皮唾液酸蛋白表位相同的抗体或其抗原结合片段。
适合用于本发明方法中的抗体可以具有对靶抗原例如内皮唾液酸蛋白或内皮唾液酸蛋白配体的结合亲合力,解离常数(KD)小于1×10-2M。在一些实施方案中,KD小于1×10-3M。在其它实施方案中,KD小于1×10-4M。在一些实施方案中,KD小于1×10-5M。在另外的其它实施方案中,KD小于1×10-6M。在其它实施方案中,KD小于1×10-7M。在其它实施方案中,KD小于1×10-8M。在其它实施方案中,KD小于1×10-9M。在其它实施方案中,KD小于1×10-10M。在另外的其它实施方案中,KD小于1×10-11M。在一些实施方案中,KD小于1×10-12M。在其它实施方案中,KD小于1×10-13M。在其它实施方案中,KD小于1×10-14M。在另外的其它实施方案中,KD小于1×10-15M。
与内皮唾液酸蛋白结合的抗体特异性和/或亲合力可以任选通过利用被引入抗体生产细胞的错配修复基因,例如PMS1、PMS2、PMS2-134、PMSR2、PMSR3、MLH1、MLH2、MLH3、MLH4、MLH5、MLH6、PMSL9、MSH1和MSH2的显性失活等位基因,直接演变所述生产抗体的细胞来进行优化。含有显性失活突变体的细胞将变得可高突变,并以比未转染的对照细胞高的速率积累突变。突变细胞库可以是筛选生产更高亲合力/特异性的抗体或结合蛋白的克隆,或生产更高滴度的抗体或结合蛋白的克隆,或只是在一定条件下生长更快或更好的克隆。利用错配修复基因的显性失活等位基因,产生可高突变的细胞的技术,描述于美国专利No.6,146,894。或者,错配修复可以是利用 WO 02/054856中描述的错配修复的化学抑制剂进行抑制。利用错配修复基因显性失活等位基因或错配修复的化学抑制剂来提高抗体的技术,也可以应用于表达克隆免疫球蛋白或蛋白基因的哺乳动物、酵母、植物或原核生物表达细胞。表达显性失活的等位基因或小分子的细胞可以被“治愈”,因为所述显性失活的等位基因如果可诱导的话,可以被关掉、从细胞中消除,而小的化学物质可以从生长培养物中去除,致使细胞再次遗传学稳定并且不再以异常的高速率积累突变。
抑制内皮唾液酸蛋白的表达抑制了内皮唾液酸蛋白与任何内皮唾液酸蛋白配体的相互作用。内皮唾液酸蛋白配体包括细胞外基质蛋白,例如纤连蛋白和胶原蛋白。任何胶原蛋白亚型可以充当内皮唾液酸蛋白的配体。更优选胶原蛋白I和胶原蛋白IV。
抑制内皮唾液酸蛋白与内皮唾液酸蛋白配体的相互作用,抑制了作为这一相互作用结果的上调或以其它方式激活的途经和级联。例如,内皮唾液酸蛋白与内皮唾液酸蛋白配体相互作用,可以促进粘附分子例如整联蛋白的表达和/或活化,粘附分子特别介导细胞与细胞外基质或与其它细胞粘附,并介导细胞信号途经。
整联蛋白倾向于作为含有两种不同链α(alpha)和β(beta)亚单位的异源二聚体存在。已经辨别了大约18α和8β亚单位。另外,许多整联蛋白亚单位经差别剪接,作为变体存在。α和β整联蛋白亚单位的各种组合产生了超过24种独特的活性整联蛋白复合物(Hynes(2002)Cell,110:673)。整联蛋白亚单位穿透质膜,并通常含有大约40-70个氨基酸的短的细胞质结构域。细胞质膜外面,α和β链在沿着大约23nm的长度上,处于彼此紧密接近。每条整联蛋白链的氨基末端在彼此5nm之内毗邻,以形成用于EMP相互作用的配体结合区。整联蛋白利用几种标准分类。α链被这样分类,是因为α链的亚组具有插入到氨基末端附近的结构元件,被称为α-A结构域,因为它具有与von Willebrand因子内的A-结构域相似的结构基序。携带这种结构域的整联蛋白可以与 胶原蛋白结合(整联蛋白复合物α1β1和α2β1),或用那些含有β2家族的整联蛋白的复合物担当细胞-细胞粘附分子。整联蛋白的两个主要功能是细胞与细胞外基质蛋白的粘附,以及与细胞结合的EMP-整联蛋白介导的信号转导。另外,整联蛋白还涉及范围广泛的其它生物活性,包括结合病毒例如腺病毒、埃可病毒、汉坦病毒、口蹄疫病毒,以及结合涉及免疫巡查的细胞和用于细胞迁移的细胞-细胞接触。整联蛋白将EMPs与细胞内的细胞骨架结合(这取决于整联蛋白复合物)。已经鉴定了几种整联蛋白的配体。较常见的配体是纤连蛋白、玻连蛋白、胶原蛋白和层粘连蛋白。整联蛋白、EMP和细胞内部微丝之间的相互作用通过支架蛋白包括踝蛋白、桩蛋白和α-辅肌动蛋白连接。这些相互作用导致调节激酶像FAK(粘附斑激酶)和Src激酶家族成员对底物例如p130CAS的磷酸化,从而募集信号适体例如Crk来介导细胞响应,包括途径活化、细胞增殖和/或存活。任何这些整联蛋白相关的功能都可以作为用于分析的内皮唾液酸蛋白活性的函数,被组合成筛选分析,来监测整联蛋白活性,以鉴定本发明的药剂或有效的内皮唾液酸蛋白靶定分子。况且,根据这里公开的本发明,在表达内皮唾液酸蛋白的细胞中用针对内皮唾液酸蛋白的药剂靶定整联蛋白,具有很大的机会抑制整联蛋白介导的病毒感染和其它病理。
因此,抑制内皮唾液酸蛋白与内皮唾液酸蛋白配体的相互作用,抑制了表达内皮唾液酸蛋白的细胞上整联蛋白分子的表达和/或活化。在一些优选的实施方案中,整联蛋白β1、β2或β3的表达或活化通过所述抑制进行遏制。
表达和/或活化受到抑制内皮唾液酸蛋白与内皮唾液酸蛋白配体相互作用的影响的其它分子和途经包括基质金属蛋白酶(MMPs)。MMPs是锌依赖性蛋白酶,尤其在降解细胞外基质蛋白、细胞表面受体等中起作用。MMPs尤其在细胞迁移、增殖和血管生成中起作用。MMP家族的酶在它们的活性位点内具有共同的锌结合基序(HExxHxxGxxH),和活性位点之后的保守甲硫氨酸。MMPs通过它们 的彼此同源性、底物特异性并部分通过它们的细胞定位来进行分类。它们广义上分为4类:胶原蛋白酶,溶基质蛋白酶,明胶酶和膜型MMPs(MT-MMPs)。胶原蛋白酶型MMPs能够将三螺旋丝状胶原蛋白降解成区别性片段。这些胶原蛋白是骨和软骨的主要组分,这类MMPs是唯一已知能够降解它们的哺乳动物酶。它们包括MMP-I(间质胶原蛋白酶);MMP-8(中性粒细胞胶原蛋白酶);MMP-13(胶原蛋白酶3);和MMP-18。溶基质蛋白酶型MMP酶对切开EMPs表现出显著的能力,但是不能切开三螺旋丝状胶原蛋白。这一类包括MMP-3(溶基质蛋白酶1);MMP-10(溶基质蛋白酶2);MMP-11(溶基质蛋白酶3);MMP-12(巨噬细胞金属弹力酶);MMP-19(RASI-I,也称为溶基质蛋白酶-4);和MMP-20(釉质溶解素);MMP-22(C-MMP)和MMP-27。明胶酶型MMPs主要降解IV型胶原蛋白和明胶,并通过存在插入到催化结构域中的其他结构域来区别。明胶结合区的位置紧挨锌结合基序之前,形成分开的折叠单位,不破坏催化结构域的结构。这一类包括MMP-2(72kDa明胶酶,明胶酶-A);MMP-9(92kDa明胶酶,明胶酶-B)。最后,膜结合的MMPs是附着于细胞膜外面的MMPs。它们包括:II型跨膜半胱氨酸阵列MMP-23;糖基磷脂酰肌醇-附连的MMPs 17和25(分别为MT4-MMP和MT6-MMP);和I型跨膜MMPs 14、15、16、24(分别为MT1-MMP、MT2-MMP、MT3-MMP、和MT5-MMP)。所有这些MMPs都在前肽中具有弗林蛋白酶切割位点,这个特征也是MMP-11共有的。
因此,抑制内皮唾液酸蛋白与内皮唾液酸蛋白配体的相互作用,抑制了表达内皮唾液酸蛋白的细胞上MMPs的表达和/或活化。在一些优选的实施方案中,MMP-1、MMP-2、MMP-8、MMP-9、MMP-12、MMP-13或MMP-18的表达或活化通过所述抑制进行遏制。
不打算受任何具体的作用理论或机制的制约,但据认为,内皮唾液酸蛋白在血管生成中直接或间接发挥功能,特别是就新生血管形成和疾病例如癌症而言。因此,据认为,破坏内皮唾液酸蛋白或表达内皮唾液酸蛋白的细胞与内皮唾液酸蛋白配体的结合,或破坏内皮唾液 酸蛋白介导的整联蛋白活化、MMPs表达和/或细胞增殖/存活可以抑制与新生血管性疾病有关的血管形成。
因此,本发明的特征还在于抑制血管生成的方法。所述方法可以体外或体内进行。一方面,抑制血管生成的方法包括对对象施用治疗有效量的阻碍细胞表面上表达的内皮唾液酸蛋白的组合物,其中所述阻碍抑制了所述细胞与内皮唾液酸蛋白配体的相互作用,并且其中抑制所述细胞与所述配体的所述相互作用抑制了对象的组织、器官或瘤的血管生成。
另一个方面,抑制血管生成的方法包括将细胞、细胞培养物、组织或器官与阻碍细胞表面上表达的内皮唾液酸蛋白的组合物接触,其中所述阻碍抑制了所述细胞与内皮唾液酸蛋白的配体的相互作用,并且其中抑制所述细胞与所述配体的相互作用抑制了所述细胞、细胞培养物、组织或器官的血管生成。
在一些优选的实施方案中,组合物包含至少一种在此描述的竞争性抑制剂。在一些实施方案中,竞争性抑制剂是内皮唾液酸蛋白配体,例如,胶原蛋白、纤连蛋白、或其内皮唾液酸蛋白结合片段。优选的竞争性抑制剂是胶原蛋白I、胶原蛋白IV或纤连蛋白的片段。最优选的竞争性抑制剂是纤连蛋白的70kDa的N-末端片段、纤连蛋白的45kDa的明胶结合片段、和纤连蛋白的30kDa的肝素结合片段。
在优选的实施方案中,组合物包含至少一种特异性结合内皮唾液酸蛋白的抗体。这样的抗体优选具有对内皮唾液酸蛋白的亲合力小于大约1×10-7M,更优选小于大约1×10-8M,更优选小于大约1×10-9M,和并更优选小于大约1×10-10M。与内皮唾液酸蛋白特异性结合的抗体可以包括其特征在此描述并且举例说明的那些抗体。例如,在一些优选的方面,特异性结合内皮唾液酸蛋白抗体包含的重链分别含有SEQ ID NO:28、30和32的CDR1、CDR2、和CDR3,而轻链分别包含SEQ ID NO:13、15和17的CDR1、CDR2和CDR3。在一些实施方案中,重链CDR1、CDR2和CDR3分别由SEQ ID NO:27、29和31的核苷酸序列编码。在一些实施方案中,轻链CDR1、CDR2和CDR3分别由SEQ ID NO:12、14和16的核苷酸序列编码。在一些实施方案中,抗体可以包括的重链含有SEQ ID NO:34的可变结构域,包括的轻链含有SEQ ID NO:19的可变结构域。在一些实施方案中,重链可变结构域由SEQ ID NO:33的核苷酸序列编码。在一些实施方案中,轻链可变结构域由SEQ ID NO:18的核苷酸序列编码。在一些实施方案中,抗体可以包括的重链含有SEQ ID NO:22或26的氨基酸序列,包括的轻链含有SEQ ID NO:11的氨基酸序列。在一些实施方案中,重链由SEQ ID NO:21或25的核苷酸序列编码,而轻链由SEQ ID NO:10的核苷酸序列编码。在一些实施方案中,抗体包括的重链含有SEQ ID NO:20或24,包括的轻链含有SEQ ID NO:9。在一些实施方案中,抗体包含的重链由SEQ ID NO:8或23的核酸序列编码。抗体可以包含由含有SEQ ID NO:7的核酸序列编码的轻链。可以根据本发明使用的生产抗体的抗体生产细胞已经于2006年4月24日和2008年3月11日保藏在美国典型培养物保藏中心(Amer.Type Cult.Coll.)(10801University Blvd.,Manassas,Virginia 20110-2209),并分别指定保藏号PTA-7554。抗体可以是在此描述的多克隆、单克隆、抗原结合片段、嵌合、人源化、完全人类的抗体等等。
抑制内皮唾液酸蛋白的表达抑制了内皮唾液酸蛋白与任何内皮唾液酸蛋白配体的相互作用。内皮唾液酸蛋白配体包括细胞外基质蛋白,例如纤连蛋白和胶原蛋白。
本发明的特征还在于抑制新生血管形成的方法。所述方法可以体外或体内进行。一方面,抑制新生血管形成的方法包括对对象施用治疗有效量的阻碍细胞表面上表达的内皮唾液酸蛋白的组合物,其中所述阻碍抑制了所述细胞与内皮唾液酸蛋白配体的相互作用,并且其中抑制所述细胞与所述配体的所述相互作用抑制了对象的组织、器官或瘤的新生血管形成。
另一个方面,抑制新生血管形成的方法包括将细胞、细胞培养物、组织或器官与阻碍细胞表面上表达的内皮唾液酸蛋白的组合物接触,其中所述阻碍抑制所述细胞与内皮唾液酸蛋白的配体的相互作用,并且其中抑制所述细胞与所述配体的相互作用,抑制了所述细胞、细胞培养物、组织或器官的新生血管形成。
在一些优选的实施方案中,组合物包含至少一种在此描述的竞争性抑制剂。在一些实施方案中,竞争性抑制剂是内皮唾液酸蛋白配体,例如,胶原蛋白、纤连蛋白、或其内皮唾液酸蛋白结合片段。优选的竞争性抑制剂是胶原蛋白I、胶原蛋白IV或纤连蛋白的片段。最优选的竞争性抑制剂是纤连蛋白的70kDa的N-末端片段、纤连蛋白的45kDa的明胶结合片段、和纤连蛋白的30kDa的肝素结合片段。
在优选的实施方案中,组合物包含至少一种特异性结合内皮唾液酸蛋白的抗体。这样的抗体优选具有对内皮唾液酸蛋白的亲合力小于大约1×10-7M,更优选小于大约1×10-8M,更优选小于大约1×10-9M,和并更优选小于大约1×10-10M。与内皮唾液酸蛋白特异性结合的抗体可以包括其特征在此描述并且举例说明的那些抗体。例如,在一些优选的方面,特异性结合内皮唾液酸蛋白抗体包含的重链分别含有SEQ ID NO:28、30和32的CDR1、CDR2、和CDR3,而轻链分别包含SEQ ID NO:13、15和17的CDR1、CDR2和CDR3。在一些实施方案中,重链CDR1、CDR2和CDR3分别由SEQ ID NO:27、29和31的核苷酸序列编码。在一些实施方案中,轻链CDR1、CDR2和CDR3分别由SEQ ID NO:12、14和16的核苷酸序列编码。在一些实施方案中,抗体可以包括的重链含有SEQ ID NO:34的可变结构域,包括的轻链含有SEQ ID NO:19的可变结构域。在一些实施方案中,重链可变结构域由SEQ ID NO:33的核苷酸序列编码。在一些实施方案中,轻链可变结构域由SEQ ID NO:18的核苷酸序列编码。在一些实施方案中,抗体可以包括的重链含有SEQ ID NO:22或26的氨基酸序列,包括的轻链含有SEQ ID NO:11的氨基酸序列。在一些实施方案中,重链由SEQ ID NO:21或25的核苷酸序列编码,而轻链由SEQ ID NO:10的核苷酸序列编码。在一些实施方案中,抗体包括的重链含有SEQ ID NO:20或24,包括的轻链含有SEQ ID NO:9。在一些实施方案中,抗体包含的重链由SEQ ID NO:8或23的核酸序列编码。抗体可以包含由含有SEQ ID NO:7的核酸序列编码的轻链。可以根据本发明使用的生产抗体的抗体生产细胞已经于2006年4月24日和2008年3月11日保藏在美国典型培养物保藏中心(Amer.Type Cult.Coll.)(10801University Blvd.,Manassas,Virginia 20110-2209),并分别指定保藏号PTA-7554。抗体可以是在此描述的多克隆、单克隆、抗原结合片段、嵌合、人源化、完全人类的抗体等等。
抑制内皮唾液酸蛋白的表达抑制了内皮唾液酸蛋白与任何内皮唾液酸蛋白配体的相互作用。内皮唾液酸蛋白配体包括细胞外基质蛋白,例如纤连蛋白比如人类纤连蛋白(SEQ ID NO:35)和胶原蛋白。
本发明的特征还在于鉴别内皮唾液酸蛋白与内皮唾液酸蛋白配体的相互作用的激动剂和拮抗剂的分析和方法。在一些实施方案中,方法包括将内皮唾液酸蛋白与测试化合物接触,将内皮唾液酸蛋白-测试化合物复合物与内皮唾液酸蛋白的配体接触,和在存在和不存在所述测试化合物下,定量测量内皮唾液酸蛋白与配体的相互作用。在测试化合物的存在下,内皮唾液酸蛋白与配体的相互作用水平增加或减少,表明所述测试化合物分别是内皮唾液酸蛋白与配体的相互作用的激动剂或拮抗剂。
在一些实施方案中,方法包括将表达内皮唾液酸蛋白的细胞与测试化合物接触,将所述表达内皮唾液酸蛋白的细胞与内皮唾液酸蛋白的配体接触,和在存在和不存在所述测试化合物下,定量测量细胞上整联蛋白分子例如整联蛋白β1、β2或β3的表达或活化。在测试化合物的存在下,细胞上整联蛋白分子的表达或活化水平增加或减少,表明所述测试化合物分别是内皮唾液酸蛋白与所述配体的相互作用的激动剂或拮抗剂。
在一些实施方案中,方法包括将表达内皮唾液酸蛋白的细胞与测试化合物接触,将所述表达内皮唾液酸蛋白的细胞与内皮唾液酸蛋白的配体接触,并在存在和不存在所述测试化合物下,定量测量细胞上MMPs例如MMP-I、MMP-2、MMP-8、MMP-9、MMP-12、MMP-13或MMP-18的表达或活化。在测试化合物的存在下,细胞上MMP分子的表达或活化水平增加或减少,表明所述测试化合物分别是内皮唾液酸蛋白与所述配体的相互作用的激动剂或拮抗剂。
在本发明的分析中,内皮唾液酸蛋白能够与细胞膜、优选哺乳动物细胞膜、细胞膜片段、人工脂质双层或合适的固体支撑物结合。内皮唾液酸蛋白配体可以是细胞外基质蛋白,包括但不限于纤连蛋白或胶原蛋白。
产生对内皮唾液酸蛋白或表达内皮唾液酸蛋白的细胞具有潜在生物活性、即与内皮唾液酸蛋白可能相互作用的测试化合物的一个策略,包括但是不局限于,筛选生产噬菌体衣壳肽的噬菌体文库,所述文库可以被筛选,以在文库中鉴定能够有可能用来抑制内皮唾液酸蛋白和内皮唾液酸蛋白配体之间相互作用的多肽。
提供下列实施例更详细描述本发明。它们是用来举例说明,而不是限制本发明。
实施例1
恶性组织上内皮唾液酸蛋白表达的免疫组化分析
通过恶性组织的免疫组化显示了利用抗体检测表达内皮唾液酸蛋白的细胞。抗内皮唾液酸蛋白或标准IgG抗体以两个浓度(0.5μg/mL和 2.5μg/mL)用于新鲜冷冻的人类结肠直肠癌组织。磷酸盐缓冲盐水[PBS(0.15M NaCl,pH 7.2)]+1%牛血清白蛋白用作一级抗体的稀释剂。组织包埋在Tissue- O.C.T.介质中,干冰冷冻,并保存在低于-70℃的密封塑料袋中。组织切成大约5μm的切片,并在室温丙酮中固定10分钟。载玻片低于-70℃保存直到染色。马上要染色之前,将载玻片在10%中性缓冲的福尔马林中固定10秒。
将冷冻切片在磷酸盐缓冲盐水(PBS[0.15M NaCl,pH 7.2])中漂洗两次。通过将载玻片与Dako En VisionTM试剂盒中提供的过氧化物酶溶液一起温育5分钟并在PBS(0.15M NaCl,pH 7.2)中漂洗两次,阻断内源性过氧化物酶。接下来,将载玻片用设计用于降低非特异性结合的蛋白质封闭剂处理20分钟。蛋白质封闭剂的制备如下:PBS(0.15M NaCl,pH 7.2);0.5%酪蛋白;1%牛血清白蛋白(BSA);和1.5%标准山羊血清。蛋白质封闭剂之后,在室温下施加一级抗体(测试物品M4、阴性对照抗体或没有抗体[只有缓冲液作为分析对照])一小时。接下来,将载玻片用PBS漂洗两次(0.15M NaCl,pH 7.2),用Dako EnVisionTM试剂盒提供的过氧化物酶标记的山羊抗-IgG聚合物处理30分钟(EnVisionTM聚合物以制造商提供的浓度使用),用PBS(0.15M NaCl,pH 7.2)漂洗两次,并用Dako EnVisionTM试剂盒中提供的底物-色原(DAB)溶液处理8分钟。所有的载玻片在水中漂洗,用苏木精复染,脱水并加上盖玻片用于说明。如所示,肿瘤中的血管(图1A)对于内皮唾液酸蛋白呈阳性染色,而同种型对照抗体染色的连续切片为阴性(图IB)。
实施例2
健康组织上内皮唾液酸蛋白表达的免疫组化分析
通过正常组织的免疫组化显示了利用抗体检测表达内皮唾液酸蛋白的细胞。简单说,正常组织样品通过低温恒温器切片,如上所述分析内皮唾液酸蛋白表达。正常组织包含的表达内皮唾液酸蛋白的成纤维细胞/树枝状细胞非常少,也不像在肿瘤内血管中观察到的强大和同质(图2A和2B)。这些细胞对研究新生血管形成的作用有用处,并 且能够分离用于基因表达,以研究细胞生长、分化、迁移或特征鉴别的情形。它们可以利用本领域技术人员已知的方法以及下列方法,进行体内、离体(ex vivo)或体外研究。
实施例3
表达内皮唾液酸蛋白的细胞的分离和富集
为了证明与内皮唾液酸蛋白结合的蛋白能够充当富集内皮或成纤维细胞样表达内皮唾液酸蛋白的细胞的有效方式,利用能够结合内皮唾液酸蛋白的抗体淘选人类微血管内皮细胞(HMVECs),以从含有5-10%表达内皮唾液酸蛋白的细胞的起始库分离富集的表达内皮唾液酸蛋白的细胞群。不想被下面的方法或特异性试剂局限,本实施例证明了内皮唾液酸蛋白抗体的用途在于能够分离表达内皮唾液酸蛋白的细胞。
简单地说,在无菌条件下用山羊抗人IgG Fcγ包被96-孔板。接下来,20μg/ml人抗-内皮唾液酸蛋白抗体M4被加到板上,三个孔(A、B、C)作为对照,没有抗体,并在4℃温育1hr。从10cm陪替氏培养皿的培养物中收获HMVECs,培养物带有DPBS/EDTA而不是胰蛋白酶以避免对细胞膜的任何损害,从而保持内皮唾液酸蛋白细胞表面蛋白完整。在抽吸和洗去任何非结合的抗内皮唾液酸蛋白抗体以后,合并的细胞以两个不同的浓度,100,000细胞/孔或50,000/孔在96-孔板中铺板。细胞在4℃下在板中温育一小时。然后,板用DPBS/FBS洗四次(直到对照孔A、B和C显示孔内没有细胞为止)。50,000细胞/孔的板显示细胞非常少,而100,000细胞/孔的孔包含许多附着于板的细胞。然后细胞在适当的生长培养基中温育三天。从100,000细胞/孔板挑选对照B和C孔用于免疫染色。钙荧光素,AM染料用于染色所述细胞,以供利用 Eclipse TS100荧光显微镜时可见。扩大阳性淘选的培养物供生长和如下所述进一步分析同源内皮唾液酸蛋白表达。
为了进一步确定分离表达内皮唾液酸蛋白的细胞的能力,制备抗 内皮唾液酸蛋白抗体淘选的HMVEC细胞和未淘选的HMVEC培养物供免疫染色,利用荧光抗内皮唾液酸蛋白抗体或荧光α-β1-整联蛋白抗体作为对照。正如预期,淘选和未淘选的培养物(未显示)中大于90%的细胞对α-β1-整联蛋白染色阳性,而淘选的培养物中大于90%的细胞对内皮唾液酸蛋白染色阳性,但是未淘选的HMVEC培养物中只有5-7%的细胞对内皮唾液酸蛋白染色阳性。这些资料证明了利用内皮唾液酸蛋白-结合蛋白例如抗体分离和富集活表达内皮唾液酸蛋白的细胞的能力。
如图3所示,通过抗内皮唾液酸蛋白抗体然后是荧光结合的二抗进行免疫染色来测定,淘选的培养物与未淘选的亲代培养物相比,具有高得多的内皮唾液酸蛋白阳性细胞数量。每个视野的细胞数量通过光学显微镜检查确定。
实施例4
内皮唾液酸蛋白与细胞外基质蛋白相互作用
构建TEM1和Fc-TEM-1表达质粒.用PCR扩增来自LA1-5S基因组DNA中代表TEM1开放阅读框的1-685位氨基酸的DNA片段(GenBank#AF279142)。产生的扩增子用EcoRI和XbaI消化并连接到pEF6-V5-HisA(Invitrogen)中。为了产生Fc-TEM-1,TEM1的细胞外区域与单体的鼠IgG2b Fcγ结构域融合并连接到衍生的pEF6-EK-Mm-IgG2b-Fcγ-ND载体中,所述载体含有肠激酶识别区(DDDD),跟着是修饰的鼠IgG2b Fcγ(通过CH3的铰链区)结构域。为了阻止二聚化,负责重链间二硫键的四个半胱氨酸残基变成丝氨酸。由此产生的单体、分泌的融合蛋白由全长TEM1胞外结构域和鼠IgG2bFcγ组成。所有质粒序列的完整性用 DTCS化学(BeckmanCoulter,Fullerton,CA)验证。原始数据用CEQ 8000 DNA测序仪获得并用 软件(Invitrogen)分析。
纯化Fc-TEM-1.CHO-TEM1-Fcγ细胞在与 (GE Healthcare,Piscataway,NJ)相配的Wave20/50EH平台上,在IS-CHO-CD培养基(Irvine Scientific,Santa Ana,CA)中以25L规模培养,所述培养基补充有2mM L-谷氨酰胺,1X青霉素/链霉素,6g/L大豆水解产物和2.2g/L碳酸氢钠(Irvine Scientific),直到培养物的成活力达到50-70%。使用装备有0.2μm中空纤维筒(GE Healthcare)的 BenchtopPilot中空纤维系统(GE Healthcare)澄清细胞外条件培养基,直到储存容器中剩余0.5L培养物。此时,将浓缩的细胞团用4L磷酸盐缓冲盐水(PBS,20mM磷酸钾,150mM NaCl pH 7.2)清洗,以回收残余的细胞外液。将4L清洗液与澄清的原料合并。然后,利用设置在Prep/ 架(Millipore,Billerica,MA)中的Prep/ Spiral Wound 2.5 ft2 100k超滤筒,并由入口压力20PSI的蠕动泵驱动,以及重复循环的速率为大约400mL/min,将澄清的培养基浓缩12倍(29L到2.5L)。由此产生的浓缩原料通过配备了0.2μm膜的瓶顶过滤器(Nalgene)进行过滤除菌。通过蛋白A亲合色谱,过10×100mm ProSep- (Millipore)柱,并通过加入5个柱体积的洗脱缓冲液(100mM柠檬酸盐/10mM乙酸盐pH3.0)进行洗脱,来俘获TEM1-Fcγ。洗脱的材料对缓冲液QA(20mMTris-Cl pH 8.0)进行透析,并通过离子交换色谱经5mL Q-FF柱(GE Healthcare)进一步纯化。结合的蛋白用15%缓冲液QB(20mMTris-Cl,1M NaCl pH 8.0)清洗,然后使用35%缓冲液QB洗脱结合的Fc-TEM-1。洗脱的蛋白在配有100kDa MWCO膜(Millipore)的8400型正压超滤组件(Millipore)中,通过超滤浓缩至总体积大约5mL。浓缩的Fc-TEM-1在用PBS平衡的 S-300HR 26×60柱(GEHealthcare)上,通过制备型体积排阻色谱进行纯化。含有纯化的Fc-TEM-1的级份被合并,通过使用100kDa MWCO膜经超滤浓缩到0.1-1mg/mL之间的额定范围,并以单次使用的等份小样保存在-80℃。
纯化的Fc-TEM-1(2.9μg)上样到4-12%Bis-Tris凝胶(Invitrogen,Inc.)上,并在MOPS运行缓冲液中(50mM MOPS,50mM Tris,3.5mMSDS,1mM EDTA pH 7.7)电泳40分钟。为了染色,将凝胶在Fix溶液(50%甲醇,10%乙酸)中固定15分钟,在去离子水中清洗两次,各10 分钟,并使用GelCode蓝色胶体考马斯亮蓝染色剂(Pierce)至少染色1小时。凝胶通过重复用去离子水清洗来脱染色。
预包被了纤连蛋白(FN)、胶原蛋白I(Col I)、胶原蛋白IV(Col IV)、层粘连蛋白(LN)(BD Biosciences,San Diego CA)、玻连蛋白(VN)、或明胶(Gel)(Chemicon Intl.)的96-孔板用于评价Fc-TEM-1结合。TEM 1与Col I、Col IV和FN的结合不是由于来自人血浆的纯化蛋白中的痕量污染物,因为Col I或Col IV都没有通过抗Col抗体ELISA在FN中检测到,Col中也没有检测到FN(数据未显示)。在加入Fc-TEM-1融合蛋白之前,用分析缓冲液(PBS中0.5%BSA,0.5%Tween-20)将所有的板封闭2小时,通过内皮唾液酸蛋白的N-末端前导序列和整个胞外结构域与鼠γ重链融合,产生可溶的内皮唾液酸蛋白。室温温育1h后,洗版,并加入HRP-山羊抗人IgG(H+L)抗体(JacksonImmunoresearch Laboratories,West Grove,PA)1小时。用SureBlueTMTMB过氧化物酶底物(KPL,Gaithersburg,MD)评价显色。BSA和人同种型对照抗体二者用作阴性对照。Fc-TEM-1不结合BSA,人同种型也不结合任何ECM蛋白(数据未显示)。
如图4A所示,Fc-TEM1以剂量依赖性方式结合纤连蛋白以及胶原蛋白I和IV,而在整个剂量范围内没有观察到与LN或VN的结合。有趣的是,虽然Fc-TEM1结合胶原蛋白,但与明胶(热变性的胶原蛋白)没有观察到可检测出的结合。所测试的四种鼠同种型IgG抗体均不能与任何ECM蛋白结合,排除了相互作用是由Fc-TEM1融合蛋白的鼠Fc骨架(数据未显示)介导的可能性。含有鼠γ重链并只有内皮唾液酸蛋白的凝集素结构域的融合蛋白也结合FN(数据未显示)。
为了证实Fc-TEM1和ECM蛋白质相互作用的选择性,将Fc-TEM1施加于涂有不同纯化蛋白的ELISA板上。通过用溶解在碳酸氢盐包被缓冲液(pH 9.6)(Sigma)中的1μg/ml STEB(葡萄球菌肠毒素B疫苗)、2μg/ml牛γ球蛋白、2μg/ml大多数黑素瘤细胞上表达的肿瘤相关90kD 糖蛋白抗原(TA 90)、2μg/ml鸡蛋溶菌酶、1∶500稀释的破伤风类毒素、1%BSA、0.2μg/ml人间皮素、2μg/ml卵清蛋白(OVA)、1μg/ml人GM-CSF、2μg/ml山羊IgG、2μg/ml小鼠IgG在4℃下包被TP免疫小ELISA板过夜,进行抗原特异性ELISAs。板用清洗缓冲液(含有0.5%TWEEN-20)清洗三次,用1x分析缓冲液在室温下封闭2小时,如上所述进行ELISA。如图4B所示,除了用作阳性对照的抗小鼠Fc之外,Fc-TEM1Fc-TEM1不与任何测试蛋白结合。
实施例5
抑制TEM1与人血浆纤连蛋白
96-孔板用纤连蛋白(FN)预包被,抗TEM-1抗体阻断Fc-TEM-1介导的附着的能力通过ELISA评估。简单地说,在加入融合蛋白之前,FN包被的板用分析缓冲液(PBS中0.5%BSA,0.5%Tween-20)封闭2h。Fc-TEM-1在4℃与抗体M4(人源化抗内皮唾液酸蛋白抗体,在美国专利公布No.20060239911中描述为ES1)、人同种型(HuIgG)或在兔子中产生的抗TEM-1抗体(RbtTEM1)预先温育1h。M4不与除非人类灵长类动物之外的内皮唾液酸蛋白的物种同系物结合。已经对内皮唾液酸蛋白的细胞外凝集素结构域中做出了M4结合表位的图。蛋白/抗体复合物被加到FN包被的板上,并使其在室温下粘附1h,在这时洗板并加入HRP-山羊抗人IgG(H+L)抗体(Jackson ImmunoresearchLaboratories,West Grove,PA)1h。显色利用SureBlueTM TMB过氧化物酶底物(KPL,Gaithersburg,MD)进行评估。如图6所示,M4抑制Fc-TEM1与纤连蛋白结合,而非特异性对照(HuIgG)不抑制结合。RbtTEM1也抑制Fc-TEM1与纤连蛋白结合(数据未显示)。
实施例6
内皮唾液酸蛋白介导与纤连蛋白的附着
产生了稳定表达内皮唾液酸蛋白的CHO-TEM1细胞(通过FACS与M4抗体证实,数据未显示)。CHO-K1细胞培养在补充有L-谷氨酰胺、1%最低必需氨基酸、丙酮酸钠、非必需氨基酸、和10%热灭活的 FBS(Invitrogen,Carlsbad,CA)的RMPI中。CHO-K1细胞(3E6)(ATCC,Manassas,VA)在0.4mm电穿孔杯中用10μg线性质粒DNA电穿孔。用GENE PULSER(BioRad,Hercules,CA)投送70V/1000uF的脉冲。令电穿孔的细胞恢复24小时,之后选择杀稻瘟菌素(5μg/ml)抗性克隆。内皮唾液酸蛋白表达是通过FACS证实的,挑选高度表达的细胞。
清洗细胞(1.5×105细胞/孔)并悬浮在含有Mg2+/Ca2+的PBS中,并一式四份加入涂有纤连蛋白的96-孔板中,使其粘附1h。在指明的情况下,细胞在开始分析之前与抗体(100μg/mL)M4或人同种型(IgG)预先温育1h。使用CellTiter- (Promega,Madison,WI),在使细胞与板粘附之后,用PBS洗板5次并测量成活力。图9B显示,内皮唾液酸蛋白的过表达导致细胞与纤连蛋白的结合增加,与对照例如非特异性的IgG相反,这可以通过内皮唾液酸蛋白抑制剂例如抗体M4进行阻断。
实施例7
内皮唾液酸蛋白与纤连蛋白和纤连蛋白片段结合
纤连蛋白是以蛋白C末端二硫键共价连接的二聚体存在的大复合糖蛋白(Ruoslahti等(1981)J.Biol.Chem.,256:7277-7281;Wierzbicka-Patynowski&Schwarzbauer(2003)J.Cell Sci,116:3269-3276;Magnusson&Mosher(1998)Arterioscler.Thromb.Vasc.Biol,18:1363-1370)。已经报道了来源于酶法降解或可变剪接的纤连蛋白片段与某些疾病状态有关,并具有截然不同的生物学功能(Magnusson&Mosher(1998)Arterioscler.Thromb.Vasc.Biol,18:1363-1370;Labat-Robert(2002)Semin.Cancer Biol,12:187-195;Homandberg(1999)Front Biosci,4:D713-730)。
评估Fc-TEM-1与不同纤连蛋白片段结合的能力。等摩尔量的蛋白在包被缓冲液(50mM碳酸盐-碳酸氢盐,pH 9.4)中进行稀释,被加到ELISA板(Greiner Bio-one,Monroe,NC)并在4℃温育过夜。在加入Fc-TEM-1之前,用分析缓冲液(PBS中0.5%BSA,0.5% Tween-20)将 所有板封闭2小时。在室温下温育1h之后,洗板并加入HRP-山羊抗-人IgG(H+L)抗体(Jackson Immunoresearch Laboratories,West Grove,PA)1h。用SureBlueTM TMB过氧化物酶底物(KPL,Gaithersburg,MD)评估显色。为了评估包被的纤连蛋白的完整性,直接针对纤连蛋白(FNAb)的兔多克隆抗体用于检测可识别的并且被均匀包被的所有FN片段。
全长人血浆纯化的纤连蛋白和120kDa的细胞粘附FN片段蛋白购自Chemicon Intl.(Temucula,CA),蛋白水解的30kDa、45kDa、70kDa片段来自Sigma(St.Louis,MO),和重组人纤连蛋白片段2和4(分别为FN2和FN4)来自R&D Systems(Minneapolis,MN)。
如图7A所示,Fc-TEM1结合FN氨基末端70kDa和其蛋白水解断裂产物(45kDa和30kDa片段)。在不同的片段之中,结合程度多变,并小于在完整FN中所见到的。相反,Fc-TEM1不结合120kDa的FN片段或者重组片段Fn2或Fn4。这种缺乏结合不太可能是由于包被不均匀或降解,因为所有的FN片段都是由抗FN多克隆抗体来有力检测到。这证明,涉及与内皮唾液酸蛋白相互作用的FN结构域存在于70kDa氨基末端部分。为了确定70kDa片段在进一步消化之后的结合能力降低是否表明Fc-TEM1与位于紧密接近蛋白水解裂解位点的区域结合、或是TEM1识别在进一步消化以后改变的FN氨基末端内的构象依赖性表位,检查Fc-TEM1与FN蛋白的还原形式结合的能力。虽然抗-FN抗体能够识别还原的FN,表明包被相当,但如图7B所示,Fc-TEM1的结合被完全除去了。与完整的FN类似,抗内皮唾液酸蛋白抗体M4以剂量依赖性方式阻断Fc-TEM1与70kDa片段结合(图7C),而同种型对照抗体没有效果(图7D)。这些结果表明,Fc-TEM1识别位于FN的氨基末端内的构象依赖性表位,在进一步蛋白水解降解后可以被削弱。
实施例8
细胞表面纤连蛋白与内皮唾液酸蛋白结合
稳定表达内皮唾液酸蛋白的CHO-TEM1细胞(通过FACS与M4抗体证实,数据未显示)产生。CHO-K1细胞培养在补充有L-谷氨酰胺、1%最低必需氨基酸、丙酮酸钠、非必需氨基酸、和10%热灭活的FBS(Invitrogen,Carlsbad,CA)的RPMI中。CHO-K1细胞(3E6)(ATCC,Manassas,VA)在0.4mm电穿孔杯中用10ug线性质粒DNA电穿孔。利用GENE PULSER(BioRad,Hercules,CA)输送170V/1000uF的脉冲。令电穿孔的细胞恢复24小时,之后选择杀稻瘟菌素(5ug/ml)抗性克隆。内皮唾液酸蛋白表达是通过FACS证实的,并挑选高度表达的细胞。
在亲代CHO-K1和CHO-TEM1细胞中,利用多克隆抗FN抗体,通过流式细胞术检查细胞表面FN水平。细胞收获在细胞解离缓冲液(Invitrogen,Carlsbad,CA)中,清洗,并再悬浮于冰冷的PBS+1%FBS中。细胞在冰上与一级抗体M4(10μg/ml)一起温育1小时,清洗并与FITC结合的山羊-抗-人二抗(Southern Biotech,Birmingham,AL)一起温育,并在EASYCYTE流式细胞仪上(Guava Technologies,Hayward,CA)分析。持续观察到,与CHO-K1细胞相比,CHO-TEM1细胞中表面FN的水平要高出15-20%。检查细胞表面FN与内皮唾液酸蛋白的结合。
利用抗FN抗体,将FN从CHO-K1和CHO-TEM1裂解物中进行免疫沉淀,然后利用相同的抗体抗TEM1抗体(M4)进行Western印迹。细胞(10E7)在补充有Complete Mini蛋白酶抑制剂混合物(RocheDiagnostics,Indianapolis,IN)的放免沉淀(RIPA)缓冲液(50mMTris-HCl,pH 7.4,1%NP-40,0.5%去氧胆酸钠,150mM NaCl,0.1%十二烷基硫酸钠[SDS])中裂解,并在13,000rpm下离心15min以除去碎屑。G蛋白Sepharose 6 Fast Flow珠(Amersham Biosciences,Piscataway,NJ)用PBS清洗3次,在4℃通过温和摇动俘获抗FN抗体(1μg)。每个样品的等量蛋白通过加入未结合的G蛋白进行预清理。温育2小时后,去除G蛋白,上清液被加到抗体-Sepharose复合物上,在4℃温育过夜。用RIPA缓冲液彻底清洗后,结合的蛋白通过在含有5%β-巯基乙 醇的 LDS样品缓冲液(Invitrogen)中煮沸10分钟而去除。蛋白利用SDS-聚丙烯酰胺凝胶电泳在4-12% Bis-Tris凝胶上(Invitrogen)分离,并转移到PVDF膜上。使用对纤连蛋白(Abcam,Cambridge,MA)或内皮唾液酸蛋白(Morphotek,Inc.,Exton,PA)具有特异性的兔多克隆抗体进行免疫印迹,用山羊-抗-兔HRP-结合的抗体检测,并利用SUPERSIGNAL West Pico化学发光底物(Pierce,Rockford,IL)显现。可溶性Fc-TEM1的完整性和纯度也通过Western印迹监测。蛋白(5ug)在含有5%β-巯基乙醇的4x NUPAGE LDS样品缓冲液(Invitrogen)中煮沸5min,在NUPAGE 4-12%Bis-Tris凝胶(Invitrogen)上进行电泳,并转移到PVDF膜和如上所述进行免疫印迹。
结果发现,FN可以从CHO-TEM1裂解物中免疫沉淀内皮唾液酸蛋白(数据未显示)。相反,在用不下拉FN的标准IgG进行免疫沉淀的细胞裂解物中,不能检测到内皮唾液酸蛋白(数据未显示)。至少两种不同的途径(ELISA和共免疫沉淀)提供了FN和内皮唾液酸蛋白相互作用的强有力证据。利用异位表达内皮唾液酸蛋白的HEK-293T细胞获得了类似的结果(数据未显示)。
实施例9
培养在MATRIGEL上表达内皮唾液酸蛋白的细胞形成网样结构
虽然培养在塑性表面上的亲代CHO-K1和CHO-TEM1细胞之间没有观察到生长或存活的差异,但当这些细胞培养在MATRIGEL上时,观察到形态的强烈不同。培养2天后,亲代CHO-K1细胞成长为伸出最小的分离细胞簇(图8,上图),而CHO-TEM1细胞成长为形成网样网络的簇(图8,下左图)。另外,簇内的CHO-TEM1细胞显示出伸出到其它簇的突出(图8,下右图)。随着时间,CHO-TEM1细胞而不是CHO-K1细胞彼此移动得更靠近,形成较大的簇(数据未显示)。
实施例10
内皮唾液酸蛋白表达增加细胞与纤连蛋白、和纤连蛋白N末端的70kD或30kD的粘附
为了评估与FN片段的粘附,等摩尔量的蛋白片段预先包被过夜,然后用含有10mg/mL BSA的PBS封闭2h。MATRIGEL用作阳性对照。清洗收获在细胞解离缓冲液中的CHO-K1或CHO-TEM1细胞(1.5×105细胞/孔),悬浮在含有Mg2+/Ca2+的PBS中,并一式四份加入到ECM细胞粘附阵列试剂盒(Millipore)或在个别包被的FN、LN、Ge1和Co1I板(BD Biosciences)上铺板,使其粘附1小时。温育之后,每个孔用PBS清洗5次,并使用CellTiter- 测量成活力。在指明的情况下,细胞在开始分析之前用抗体预先温育1小时。如图9A所示,包被FN的孔中,粘附的CHO-TEM1细胞的数量比亲代CHO-K1细胞高6倍。在包被层粘连蛋白或玻连蛋白的表面上,观察到CHO-K1和CHO-TEM1的粘附之间没有显著差异,而与胶原蛋白和生腱蛋白的粘附弱到不能评定任何有价值的差异(图9A)。用M4抗体预处理CHO-TEM1细胞,导致TEM1-FN-依赖性细胞粘附减少50%,而IgG对照抗体没有影响(图9B)。M4抗体处理不影响亲代的CHO-K1细胞的FN-依赖性、内皮唾液酸蛋白-不依赖性细胞粘附(基准粘附)。
板用等摩尔量的完整FN、FN蛋白水解片段和MATRIGEL预包被。CHO-TEM1细胞显示,与亲代CHO-K1细胞比较,与FN、70kDa和30kDa片段的粘附增强了3-至5-倍,而45kDa或Fn2片段则没有发现明显的粘附。CHO-TEM1细胞结合的MATRIGEL比CHO-K1好五倍(图9C)。这些数据表明,内皮唾液酸蛋白提高细胞与细胞外基质的粘附,和FN的氨基末端涉及这些相互作用。
实施例11
内皮唾液酸蛋白结合胶原蛋白I和M4抑制这一结合
使用胶原蛋白I预包被的96-孔板评估M4阻断Fc-TEM-1结合的能力。板用分析缓冲液(PBS中0.5%BSA,0.5%Tween-20)封闭2h,然后加入指定浓度的蛋白(μg/mL)。Fc-TEM-1在4℃用抗体M4或人同种型(人IgG)预先温育1h。蛋白/抗体复合物被加到Co1 I包被的板上, 并使其在室温下粘附1h,在这时洗板并加入HRP-山羊抗人IgG(H+L)抗体(Jackson Immunoresearch Laboratories,West Grove,PA)1h。使用SureBlueTM TMB过氧化物酶底物(KPL,Gaithersburg,MD)评估显色。图10显示,内皮唾液酸蛋白的过表达导致细胞与COL I的结合增加,与对照例如非特异性的IgG相反,这可以通过内皮唾液酸蛋白抑制剂例如M4进行阻断。RbtTEM1还抑制Fc-TEM1与COL I结合(数据未显示)。
实施例12
内皮唾液酸蛋白增加细胞与胶原蛋白的粘附
清洗CHO-K1或CHO-TEM1细胞(1.5×105细胞/孔),悬浮在含有Mg2+/Ca2+的PBS中,并一式四份加入到胶原蛋白I包被的96孔板中,使其粘附到指定的时间点。在使细胞与板粘附之后,用PBS洗板5次并使用CellTiter- 测量成活力。如图11所示,内皮唾液酸蛋白过表达导致细胞与COL I结合增加。
实施例13
细胞迁移分析
使用BD BioCoat肿瘤浸润系统TM(BD Bioscience)和人类纤连蛋白细胞培养物插入物(BD Bioscience),评估TEM1介导的细胞迁移。细胞用非酶细胞解离缓冲液收获,并在补充有2%胎牛血清(FBS)的生长培养基中稀释到4E5个细胞/ml的浓度,500μl细胞悬液被加到膜插入物的顶部室。为了产生梯度,含有20%FBS的生长培养基被加到底部室。细胞温育48小时,其后去除插入物,使用CELLTITER-GLO(Promega)计算迁移通过包被的膜的细胞。细胞用图12的说明中指定的抗体预处理,并在连续存在的抗体中评估迁移。为了检查MATRIGEL上的小管形成,细胞(8E4个细胞/孔)被加到包被有MATRIGEL(BD Bioscience)的96-孔板,温育过夜并以200-400倍放大照相。
如图12A所示,CHO-K1细胞展现出中度细胞迁移,而CHO-TEM1 细胞显示出迁移增强了>10-倍。M4抗体处理,而不是对照IgG,消除了CHO-TEM1细胞迁移。在利用FN包被的穿膜(transwell)小室的迁移实验中,观察到类似的结果(图12B)。
实施例14
内皮唾液酸蛋白增加MMP-9活性
内皮唾液酸蛋白、MMP-2和COL IV已经显示出在以早期血管形成过程的手指样伸出为特征的组织区域中共区域化(colocalize)(Virgintino等(2007)Angiogenesis,10:35-45)。为了评估MMP活性,细胞接种在6-孔板中,和血清饥饿48小时。收集培养物上清液,并在4℃通过离心(13,000rpm,15min)澄清以除去任何碎屑。等量的蛋白根据制造商说明书,在非还原条件下(Invitrogen)进行明胶和酪蛋白酶谱分析。阳性对照人类MMP-2和9(Chemicon,International)用于指示MMP-2和MMP-9的迁移,并用作我们的CHOK1和CHO-TEM-1上清液的参照。如图13所示,与亲代CHO-K1细胞相比,CHO-TEM1细胞中MMP-9活性显著提高。通过MMP特异性ELISA测量,MMP-9活性提高与CHO-TEM1细胞上清液中MMP-9蛋白的分泌增加相关。这些数据表明,诱导MMP-9分泌有助于提高在此证明的CHO-TEM1细胞迁移通过MATRIGEL和FN包被的穿膜的能力。
实施例15
内皮唾液酸蛋白增加β整联蛋白的活性
整联蛋白(例如,α4β1,α5β1)是表征明确的介导FN依赖性细胞粘附的受体(Wierzbicka-Patynowski&Schwarzbauer 2003;Magnusson&Mosher 1998)。另外,已经对未鉴别的细胞受体描述了结合FN的N-末端70kDa区域的功能(McKeown-Longo&Mosher(1983)J.Cell Biol.,97:466-472)并需要暴露与FN-整联蛋白和FN-FN相互作用有关的可溶性FN中隐藏的整联蛋白结合位点(RGD基序)(Tomasini-Johansson等(2006)Matrix Biol.,25:282-293;McKeown-Longo&Mosher(1985)J.Cell Biol,100:364-374)。内皮唾液酸蛋白在此鉴定为与N-末端70kDa FN区域相互作用并提高FN依赖性细胞粘附的新受体。在这些细胞体系中体外测量的FN结合提高可能是与内皮唾液酸蛋白和整联蛋白相继相互作用的结果。
人胚肾293(HEK293)细胞用表达内皮唾液酸蛋白或假cDNA的载体转染。经证实细胞表达细胞表面内皮唾液酸蛋白(293 TEM1),而用假的进行转染者(293T)则不表达。测试细胞上调整联蛋白表达的能力和在抗体M4存在下的活性。图14B显示,内皮唾液酸蛋白的过表达导致整联蛋白β1活性相对于对照细胞提高。图14A显示,细胞表面β1整联蛋白表达不变。用内皮唾液酸蛋白抑制剂M4处理细胞,导致整联蛋白活性抑制,而对细胞表面水平没有观察到影响(图14B)。虽然不希望受到任何一个理论的制约,但内皮唾液酸蛋白和可溶性FN的N-末端70kDa片段之间的相互作用,可以担负起启动FN装配成能结合整联蛋白的多聚体高亲合力形式的任务。
实施例16
M4.1识别未还原的人类TEM-1而不是鼠TEM-1
CHO-TEM-1细胞、小鼠2H11细胞、亲代CHO-K1细胞、小鼠NS0细胞、和小鼠MS1细胞在完全RPMI 1640(RPMI 1640;丙酮酸钠;非必需氨基酸;L-谷氨酰胺和FBS;Invitrogen Corp.)中培养。人类初级周细胞培养在周细胞培养基中(500ml基础培养基(Cat#1201),10ml(2%)胎牛血清(FBS,Cat.No.0025),5ml周细胞生长补加剂(PGS,Cat.No.1252)和5ml青霉素/链霉素溶液(P/S,Cat.No.0503);InvitogenCorp.)。细胞在湿润的培育箱中于37℃和5%CO2中生长。细胞用TrypLETM Select(Invitrogen Corp.,catalog no.12563-011)去粘附(deadhered),清洗和计数。细胞以2×107细胞在含有蛋白酶抑制剂的RIPA裂解缓冲液中裂解,并在冰上温育10分钟。不溶性物质在40℃下10,000xG沉淀10分钟,上清液转移到新管中。等分样品与等体积的有或者没有10%2-巯基乙醇(还原剂)的2x蛋白加样缓冲液混合。15μL(1.5×105个细胞)裂解液上样到15孔4-12%Bis/Tris SDS-PAGE凝 胶上,并在MES电泳缓冲液中200V下电泳30分钟。凝胶被电印迹在PVDF上,然后在5%乳-TBST(5%M-TBST)中室温下通过摇动阻断1小时。M4.1印迹用5%M-TBST中3.3μg/mL的M4.1在40℃探查过夜。
用在5%M-TBST中1∶300稀释(4.5mg/ml存货#:NB 487-76)的抗体4℃下探查兔抗-tem-1多克隆抗体印迹过夜。抗体M4.1,像抗体M4,是针对人类内皮唾液酸蛋白的人源化抗体。膜用30mL TBST在室温下清洗5次,每次5分钟。HRP-结合的山羊抗-人IgG(H+L)(JacksonImmuno,1mg/mL原液)在5%M-TBST中1∶20,000稀释,作为二抗在室温下探测M4.1印迹30分钟。HRP-结合的山羊抗-兔(H+L)二抗用于在室温下印迹多克隆抗TEM-1印迹30分钟。膜用30mL TBST在室温下清洗5次,每次5分钟。使用Femto Western印迹检测系统(Pierce),按照手册,通过化学发光检测信号。
如图15所示,M4.1识别CHO-TEM-1细胞中未还原的人TEM-1以及人初级周细胞,而不是小鼠2H11细胞中的鼠TEM-1(SEQ IDNO:2)(图15)。针对人TEM-1的兔多克隆抗体(rabPAb TEM-1)识别CHO-TEM-1细胞中的人TEM-1以及人周细胞,还有小鼠2H11细胞中的鼠TEM-1。M4.1或rabPAbTEM-1由于在这些细胞中缺乏TEM-1表达,都不对来自亲代CHO-K1细胞或小鼠NS0和MS1细胞裂解物发生反应。只有rabPAb TEM-1与还原的人TEM-1起反应,虽然与未还原的TEM-1相比程度较低。
本发明不局限于以上描述和举例说明的实施方案,而是能够在所附权利要求内进行变化和修改。
序列表
<110>诺福泰克公司(Morphotek,Inc.)
<120>抑制内皮唾液酸蛋白与配体结合的方法
(METHODS FOR INHIBITING THE BINDING OF ENDOSIALIN TO LIGANDS)
<130>SCT093512-40
<150>US 60/910,362
<151>2007-04-05
<150>US 60/980,026
<151>2007-10-15
<160>35
<170>PatentIn version 3.3
<210>1
<211>2660
<212>DNA
<213>Mus musculus
<400>1
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ctgctgctgg cctgggtggc cgcggtgccc gcactgggcc aggtcccctg gacgccggag 120
cctcgagccg cgtgcggccc cagcagctgc tacgcgctct ttccccggcg ccgcacattc 180
ctggaagctt ggcgggcgtg ccgcgaattg gggggcaacc tggccacacc gcggacccca 240
gaggaggccc agcgtgtgga cagcctggtg ggggtcgggc cggccaacgg gctgctatgg 300
attgggttgc agcggcaggc taggcaatgc cagccgcagc gcccactgcg gggcttcata 360
tggaccacgg gagaccagga caccgccttc accaactggg cccagccggc tacggaagga 420
ccctgcccag cccagcgctg tgcagccctt gaggccagcg gagagcatcg ctggctcgaa 480
ggctcgtgca cactggctgt cgatggctac ctctgccagt ttggttttga gggtgcctgc 540
cctgccttgc cgcttgaggt gggtcaggcc ggtcccgctg tctacaccac acccttcaac 600
ctggtttcca gcgagttcga atggctgccc tttggctccg tggcagctgt gcagtgccaa 660
gctggcaggg gagcttctct gctgtgcgtg aaacagcctt caggtggcgt gggctggtcc 720
cagactggcc cgctgtgccc agggactggc tgtggtcctg acaatggggg ttgcgaacat 780
gagtgtgtgg aagaggtgga cggtgctgtg tcctgccgct gcagtgaagg cttccgtcta 840
gcagcagatg ggcacagttg tgaagacccc tgtgcccagg ccccctgtga gcagcagtgt 900
gaacctggag ggccacaagg ctatagctgc cactgtcgcc ttggcttccg gccagctgag 960
gatgatccac accgctgcgt ggacacggat gagtgccaga ttgctggtgt gtgccagcag 1020
atgtgtgtca actatgttgg tggctttgag tgttactgca gcgagggtca cgagcttgag 1080
gcagatggta tcagctgtag ccctgcagga gccatgggtg cccaggcttc ccaggatctc 1140
agagatgagt tgctggatga tggagaagaa ggggaggatg aagaggagcc ctgggaggac 1200
tttgatggca cctggacaga ggaacagggg atcctatggc tggcacctac acatccacct 1260
gactttggcc tgccctatag gcccaacttc ccacaggatg gagagcctca gagattgcac 1320
ctggagccta cctggccacc cccacttagt gcccccaggg gcccctacca ctcctcagtg 1380
gtgtctgcca cacggcccat ggtgatctct gccactcgac ccacactacc ttctgcccac 1440
aagacctctg ttatttcagc tacacgccca cccctgagcc ctgtccaccc acctgccatg 1500
gcccctgcca cacctccagc tgtgttctct gagcaccaga tccccaaaat caaggccaat 1560
tatccagacc tgccttttgg ccacaagcct gggataacct cggccactca cccagcacgg 1620
tctcctccgt accagccccc cattatctca accaactatc cccaagtctt ccctccccac 1680
caggccccta tgtctccaga tacccacact atcacttatt tgcctccagt cccccctcac 1740
cttgatcctg gggataccac ttctaaagcc catcaacacc ctttgctccc agatgctcca 1800
ggtatcagaa cccaggcccc ccagctttct gtctcagctc tccagccccc tcttcctacc 1860
aactccaggt cttctgtcca tgaaactcct gtgcctgctg ccaaccagcc cccagccttc 1920
ccttcttctc ccctcccccc tcagaggccc actaaccaga cctcatctat cagccctaca 1980
cattcctatt ccagagcccc tctagtccca agggaaggag ttcccagtcc caaatcagtg 2040
ccacagctgc cctcggtgcc ctccacagca gctccaacag ccctggcaga gtcaggtctt 2100
gcaggccaaa gccaaaggga tgaccgctgg ctgctggtgg cactcctggt gccaacatgt 2160
gtcttcttgg tggtgctgct tgccctgggc attgtgtact gcactcgctg tggctcccac 2220
gcacccaaca agcggatcac ggactgctat cgctgggtca cacatgctgg gaacaagagc 2280
tcaacagaac ccatgccccc cagaggcagc cttacagggg tacagacctg tagaaccagt 2340
gtgtgatggg gtgcagatgc ccctttgtgg gatagaagaa aaggacttgc tttggacaca 2400
tggctgagac cacaccaagg acttatgggg gctgcccagc tgacagagga ggttctgttc 2460
tttgagccca gcatccatgg caaaggacac accaggactc caggacctca aggggtgggt 2520
gctgggatct tctccaataa atggggtgcc aacctcaccc aaaaaaaaaa aaaaaaaaaa 2580
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2640
aaaaaaaaaa aaaaaaaaaa 2660
<210>2
<211>765
<212>PRT
<213>Mus musculus
<400>2
Met Leu Leu Arg Leu Leu Leu Ala Trp Val Ala Ala Val Pro Ala Leu
1 5 10 15
Gly Gln Val Pro Trp Thr Pro Glu Pro Arg Ala Ala Cys Gly Pro Ser
20 25 30
Ser Cys Tyr Ala Leu Phe Pro Arg Arg Arg Thr Phe Leu Glu Ala Trp
35 40 45
Arg Ala Cys Arg Glu Leu Gly Gly Asn Leu Ala Thr Pro Arg Thr Pro
50 55 60
Glu Glu Ala Gln Arg Val Asp Ser Leu Val Gly Val Gly Pro Ala Asn
65 70 75 80
Gly Leu Leu Trp Ile Gly Leu Gln Arg Gln Ala Arg Gln Cys Gln Pro
85 90 95
Gln Arg Pro Leu Arg Gly Phe Ile Trp Thr Thr Gly Asp Gln Asp Thr
100 105 110
Ala Phe Thr Asn Trp Ala Gln Pro Ala Thr Glu Gly Pro Cys Pro Ala
115 120 125
Gln Arg Cys Ala Ala Leu Glu Ala Ser Gly Glu His Arg Trp Leu Glu
130 135 140
Gly Ser Cys Thr Leu Ala Val Asp Gly Tyr Leu Cys Gln Phe Gly Phe
145 150 155 160
Glu Gly Ala Cys Pro Ala Leu Pro Leu Glu Val Gly Gln Ala Gly Pro
165 170 175
Ala Val Tyr Thr Thr Pro Phe Asn Leu Val Ser Ser Glu Phe Glu Trp
180 185 190
Leu Pro Phe Gly Ser Val Ala Ala Val Gln Cys Gln Ala Gly Arg Gly
195 200 205
Ala Ser Leu Leu Cys Val Lys Gln Pro Ser Gly Gly Val Gly Trp Ser
210 215 220
Gln Thr Gly Pro Leu Cys Pro Gly Thr Gly Cys Gly Pro Asp Asn Gly
225 230 235 240
Gly Cys Glu His Glu Cys Val Glu Glu Val Asp Gly Ala Val Ser Cys
245 250 255
Arg Cys Ser Glu Gly Phe Arg Leu Ala Ala Asp Gly His Ser Cys Glu
260 265 270
Asp Pro Cys Ala Gln Ala Pro Cys Glu Gln Gln Cys Glu Pro Gly Gly
275 280 285
Pro Gln Gly Tyr Ser Cys His Cys Arg Leu Gly Phe Arg Pro Ala Glu
290 295 300
Asp Asp Pro His Arg Cys Val Asp Thr Asp Glu Cys Gln Ile Ala Gly
305 310 315 320
Val Cys Gln Gln Met Cys Val Asn Tyr Val Gly Gly Phe Glu Cys Tyr
325 330 335
Cys Ser Glu Gly His Glu Leu Glu Ala Asp Gly Ile Ser Cys Ser Pro
340 345 350
Ala Gly Ala Met Gly Ala Gln Ala Ser Gln Asp Leu Arg Asp Glu Leu
355 360 365
Leu Asp Asp Gly Glu Glu Gly Glu Asp Glu Glu Glu Pro Trp Glu Asp
370 375 380
Phe Asp Gly Thr Trp Thr Glu Glu Gln Gly Ile Leu Trp Leu Ala Pro
385 390 395 400
Thr His Pro Pro Asp Phe Gly Leu Pro Tyr Arg Pro Asn Phe Pro Gln
405 410 415
Asp Gly Glu Pro Gln Arg Leu His Leu Glu Pro Thr Trp Pro Pro Pro
420 425 430
Leu Ser Ala Pro Arg Gly Pro Tyr His Ser Ser Val Val Ser Ala Thr
435 440 445
Arg Pro Met Val Ile Ser Ala Thr Arg Pro Thr Leu Pro Ser Ala His
450 455 460
Lys Thr Ser Val Ile Ser Ala Thr Arg Pro Pro Leu Ser Pro Val His
465 470 475 480
Pro Pro Ala Met Ala Pro Ala Thr Pro Pro Ala Val Phe Ser Glu His
485 490 495
Gln Ile Pro Lys Ile Lys Ala Asn Tyr Pro Asp Leu Pro Phe Gly His
500 505 510
Lys Pro Gly Ile Thr Ser Ala Thr His Pro Ala Arg Ser Pro Pro Tyr
515 520 525
Gln Pro Pro Ile Ile Ser Thr Asn Tyr Pro Gln Val Phe Pro Pro His
530 535 540
Gln Ala Pro Met Ser Pro Asp Thr His Thr Ile Thr Tyr Leu Pro Pro
545 550 555 560
Val Pro Pro His Leu Asp Pro Gly Asp Thr Thr Ser Lys Ala His Gln
565 570 575
His Pro Leu Leu Pro Asp Ala Pro Gly Ile Arg Thr Gln Ala Pro Gln
580 585 590
Leu Ser Val Ser Ala Leu Gln Pro Pro Leu Pro Thr Asn Ser Arg Ser
595 600 605
Ser Val His Glu Thr Pro Val Pro Ala Ala Asn Gln Pro Pro Ala Phe
610 615 620
Pro Ser Ser Pro Leu Pro Pro Gln Arg Pro Thr Asn Gln Thr Ser Ser
625 630 635 640
Ile Ser Pro Thr His Ser Tyr Ser Arg Ala Pro Leu Val Pro Arg Glu
645 650 655
Gly Val Pro Ser Pro Lys Ser Val Pro Gln Leu Pro Ser Val Pro Ser
660 665 670
Thr Ala Ala Pro Thr Ala Leu Ala Glu Ser Gly Leu Ala Gly Gln Ser
675 680 685
Gln Arg Asp Asp Arg Trp Leu Leu Val Ala Leu Leu Val Pro Thr Cys
690 695 700
Val Phe Leu Val Val Leu Leu Ala Leu Gly Ile Val Tyr Cys Thr Arg
705 710 715 720
Cys Gly Ser His Ala Pro Asn Lys Arg Ile Thr Asp Cys Tyr Arg Trp
725 730 735
Val Thr His Ala Gly Asn Lys Ser Ser Thr Glu Pro Met Pro Pro Arg
740 745 750
Gly Ser Leu Thr Gly Val Gln Thr Cys Arg Thr Ser Val
755 760 765
<210>3
<211>2576
<212>DNA
<213>Homo sapiens
<400>3
agtccggggg catcgcgatg ctgctgcgcc tgttgctggc ctgggcggcc gcagggccca 60
cactgggcca ggacccctgg gctgctgagc cccgtgccgc ctgcggcccc agcagctgct 120
acgctctctt cccacggcgc cgcaccttcc tggaggcctg gcgggcctgc cgcgagctgg 180
ggggcgacct ggccactcct cggacccccg aggaggccca gcgtgtggac agcctggtgg 240
gtgcgggccc agccagccgg ctgctgtgga tcgggctgca gcggcaggcc cggcaatgcc 300
agctgcagcg cccactgcgc ggcttcacgt ggaccacagg ggaccaggac acggctttca 360
ccaactgggc ccagccagcc tctggaggcc cctgcccggc ccagcgctgt gtggccctgg 420
aggcaagtgg cgagcaccgc tggctggagg gctcgtgcac gctggctgtc gacggctacc 480
tgtgccagtt tggcttcgag ggcgcctgcc cggcgctgca agatgaggcg ggccaggccg 540
gcccagccgt gtataccacg cccttccacc tggtctccac agagtttgag tggctgccct 600
tcggctctgt ggccgctgtg cagtgccagg ctggcagggg agcctctctg ctctgcgtga 660
agcagcctga gggaggtgtg ggctggtcac gggctgggcc cctgtgcctg gggactggct 720
gcagccctga caacgggggc tgcgaacacg aatgtgtgga ggaggtggat ggtcacgtgt 780
cctgccgctg cactgagggc ttccggctgg cagcagacgg gcgcagttgc gaggacccct 840
gtgcccaggc tccgtgcgag cagcagtgtg agcccggtgg gccacaaggc tacagctgcc 900
actgtcgcct gggtttccgg ccagcggagg atgatccgca ccgctgtgtg gacacagatg 960
agtgccagat tgccggtgtg tgccagcaga tgtgtgtcaa ctacgttggt ggcttcgagt 1020
gttattgtag cgagggacat gagctggagg ctgatggcat cagctgcagc cctgcagggg 1080
ccatgggtgc ccaggcttcc caggacctcg gagatgagtt gctggatgac ggggaggatg 1140
aggaagatga agacgaggcc tggaaggcct tcaacggtgg ctggacggag atgcctggga 1200
tcctgtggat ggagcctacg cagccgcctg actttgccct ggcctataga ccgagcttcc 1260
cagaggacag agagccacag ataccctacc cggagcccac ctggccaccc ccgctcagtg 1320
cccccagggt cccctaccac tcctcagtgc tctccgtcac ccggcctgtg gtggtctctg 1380
ccacgcatcc cacactgcct tctgcccacc agcctcctgt gatccctgcc acacacccag 1440
ctttgtcccg tgaccaccag atccccgtga tcgcagccaa ctatccagat ctgccttctg 1500
cctaccaacc cggtattctc tctgtctctc attcagcaca gcctcctgcc caccagcccc 1560
ctatgatctc aaccaaatat ccggagctct tccctgccca ccagtccccc atgtttccag 1620
acacccgggt cgctggcacc cagaccacca ctcatttgcc tggaatccca cctaaccatg 1680
cccctctggt caccaccctc ggtgcccagc taccccctca agccccagat gcccttgtcc 1740
tcagaaccca ggccacccag cttcccatta tcccaactgc ccagccctct ctgaccacca 1800
cctccaggtc ccctgtgtct cctgcccatc aaatctctgt gcctgctgcc acccagcccg 1860
cagccctccc caccctcctg ccctctcaga gccccactaa ccagacctca cccatcagcc 1920
ctacacatcc ccattccaaa gccccccaaa tcccaaggga agatggcccc agtcccaagt 1980
tggccctgtg gctgccctca ccagctccca cagcagcccc aacagccctg ggggaggctg 2040
gtcttgccga gcacagccag agggatgacc ggtggctgct ggtggcactc ctggtgccaa 2100
cgtgtgtctt tttggtggtc ctgcttgcac tgggcatcgt gtactgcacc cgctgtggcc 2160
cccatgcacc caacaagcgc atcactgact gctatcgctg ggtcatccat gctgggagca 2220
agagcccaac agaacccatg ccccccaggg gcagcctcac aggggtgcag acctgcagaa 2280
ccagcgtgtg atggggtgca gacccccctc atggagtatg gggcgctgga cacatggccg 2340
gggctgcacc agggacccat gggggctgcc cagctggaca gatggcttcc tgctccccag 2400
gcccagccag ggtcctctct caaccactag acttggctct caggaactct gcttcctggc 2460
ccagcgctcg tgaccaagga tacaccaaag cccttaagac ctcagggggc gggtgctggg 2520
gtcttctcca ataaatgggg tgtcaacctt acccaaggaa aaaaaaaaaa aaaaaa 2576
<210>4
<211>757
<212>PRT
<213>Homo sapiens
<400>4
Met Leu Leu Arg Leu Leu Leu Ala Trp Ala Ala Ala Gly Pro Thr Leu
1 5 10 15
Gly Gln Asp Pro Trp Ala Ala Glu Pro Arg Ala Ala Cys Gly Pro Ser
20 25 30
Ser Cys Tyr Ala Leu Phe Pro Arg Arg Arg Thr Phe Leu Glu Ala Trp
35 40 45
Arg Ala Cys Arg Glu Leu Gly Gly Asp Leu Ala Thr Pro Arg Thr Pro
50 55 60
Glu Glu Ala Gln Arg Val Asp Ser Leu Val Gly Ala Gly Pro Ala Ser
65 70 75 80
Arg Leu Leu Trp Ile Gly Leu Gln Arg Gln Ala Arg Gln Cys Gln Leu
85 90 95
Gln Arg Pro Leu Arg Gly Phe Thr Trp Thr Thr Gly Asp Gln Asp Thr
100 105 110
Ala Phe Thr Asn Trp Ala Gln Pro Ala Ser Gly Gly Pro Cys Pro Ala
115 120 125
Gln Arg Cys Val Ala Leu Glu Ala Ser Gly Glu His Arg Trp Leu Glu
130 135 140
Gly Ser Cys Thr Leu Ala Val Asp Gly Tyr Leu Cys Gln Phe Gly Phe
145 150 155 160
Glu Gly Ala Cys Pro Ala Leu Gln Asp Glu Ala Gly Gln Ala Gly Pro
165 170 175
Ala Val Tyr Thr Thr Pro Phe His Leu Val Ser Thr Glu Phe Glu Trp
180 185 190
Leu Pro Phe Gly Ser Val Ala Ala Val Gln Cys Gln Ala Gly Arg Gly
195 200 205
Ala Ser Leu Leu Cys Val Lys Gln Pro Glu Gly Gly Val Gly Trp Ser
210 215 220
Arg Ala Gly Pro Leu Cys Leu Gly Thr Gly Cys Ser Pro Asp Asn Gly
225 230 235 240
Gly Cys Glu His Glu Cys Val Glu Glu Val Asp Gly His Val Ser Cys
245 250 255
Arg Cys Thr Glu Gly Phe Arg Leu Ala Ala Asp Gly Arg Ser Cys Glu
260 265 270
Asp Pro Cys Ala Gln Ala Pro Cys Glu Gln Gln Cys Glu Pro Gly Gly
275 280 285
Pro Gln Gly Tyr Ser Cys His Cys Arg Leu Gly Phe Arg ProAla Glu
290 295 300
Asp Asp Pro His Arg Cys Val Asp Thr Asp Glu Cys Gln Ile Ala Gly
305 310 315 320
Val Cys Gln Gln Met Cys Val Asn Tyr Val Gly Gly Phe Glu Cys Tyr
325 330 335
Cys Ser Glu Gly His Glu Leu Glu Ala Asp Gly Ile Ser Cys Ser Pro
340 345 350
Ala Gly Ala Met Gly Ala Gln Ala Ser Gln Asp Leu Gly Asp Glu Leu
355 360 365
Leu Asp Asp Gly Glu Asp Glu Glu Asp Glu Asp Glu Ala Trp Lys Ala
370 375 380
Phe Asn Gly Gly Trp Thr Glu Met Pro Gly Ile Leu Trp Met Glu Pro
385 390 395 400
Thr Gln Pro Pro Asp Phe Ala Leu Ala Tyr Arg Pro Ser Phe Pro Glu
405 410 415
Asp Arg Glu Pro Gln Ile Pro Tyr Pro Glu Pro Thr Trp Pro Pro Pro
420 425 430
Leu Ser Ala Pro Arg Val Pro Tyr His Ser Ser Val Leu Ser Val Thr
440 440 445
Arg Pro Val Val Val Ser Ala Thr His Pro Thr Leu Pro Ser Ala His
450 455 460
Gln Pro Pro Val Ile Pro Ala Thr His Pro Ala Leu Ser Arg Asp His
465 470 475 480
Gln Ile Pro Val Ile Ala Ala Asn Tyr Pro Asp Leu Pro Ser Ala Tyr
485 490 495
Gln Pro Gly Ile Leu Ser Val Ser His Ser Ala Gln Pro Pro Ala His
500 505 510
Gln Pro Pro Met Ile Ser Thr Lys Tyr Pro Glu Leu Phe Pro Ala His
515 520 525
Gln Ser Pro Met Phe Pro Asp Thr Arg Val Ala Gly Thr Gln Thr Thr
530 535 540
Thr His Leu Pro Gly Ile Pro Pro Asn His Ala Pro Leu Val Thr Thr
545 550 555 560
Leu Gly Ala Gln Leu Pro Pro Gln Ala Pro Asp Ala Leu Val Leu Arg
565 570 575
Thr Gln Ala Thr Gln Leu Pro Ile Ile Pro Thr Ala Gln Pro Ser Leu
580 585 590
Thr Thr Thr Ser Arg Ser Pro Val Ser Pro Ala His Gln Ile Ser Val
595 600 605
Pro Ala Ala Thr Gln Pro Ala Ala Leu Pro Thr Leu Leu Pro Ser Gln
610 615 620
Ser Pro Thr Asn Gln Thr Ser Pro Ile Ser Pro Thr His Pro His Ser
625 630 635 640
Lys Ala Pro Gln Ile Pro Arg Glu Asp Gly Pro Ser Pro Lys Leu Ala
645 650 655
Leu Trp Leu Pro Ser Pro Ala Pro Thr Ala Ala Pro Thr Ala Leu Gly
660 665 670
Glu Ala Gly Leu Ala Glu His Ser Gln Arg Asp Asp Arg Trp Leu Leu
675 680 685
Val Ala Leu Leu Val Pro Thr Cys Val Phe Leu Val Val Leu Leu Ala
690 695 700
Leu Gly Ile Val Tyr Cys Thr Arg Cys Gly Pro His Ala Pro Asn Lys
705 710 715 720
Arg Ile Thr Asp Cys Tyr Arg Trp Val Ile His Ala Gly Ser Lys Ser
725 730 735
Pro Thr Glu Pro Met Pro Pro Arg Gly Ser Leu Thr Gly Val Gln Thr
740 745 750
Cys Arg Thr Ser Val
755
<210>5
<211>2397
<212>DNA
<213>Rattus rattus
<400>5
atgctgctgc gcctgctgct ggcctgggcg gccgcggtgc ccgcactggg ccaggccccc 60
tggacgccgg agcctagagc cgectgcggc cccagcagct gctacgctct ctttccccgg 120
cgccgcacat tcctggaggc ttggcggtcg tgccgcgaat tggggggcaa cctggccaca 180
ccgaggaccc cggaggaggc ccgacgtgtg gacagcctgg tgggcgtcgg acccgccaac 240
gggctgctat ggattgggtt gcagcggcag gctcggcaat gccagccaca gcgcccactg 300
cggggcttca tatggaccac gggagaccag gacaccgcct tcactaactg ggcccagccg 360
gctacggaag gaccctgccc ggcccagcgc tgtgctgccc ttgaggccag cggagaacat 420
cgctggctcg aaggctcgtg cacactggct gtcgatggct acctctgcca gtttggtttt 480
gagggtgcct gtcctgcctt gccgcttgag gtgggccaag ccggtccagc tatctacacc 540
acacccttca acctggtttc cagtgagttc gaatggctac cctttggctc cgtggcagct 600
gtgcagtgcc aagctggcag gggaacgtct ctgttgtgtg tgaaacaacc ttcaggtggc 660
gttggctggt cccagactgg cccactgtgt ccagggactg gctgtggtcc tgacaatggg 720
ggttgcgaac atgaatgtgt ggaagagttg gatggcggta tgtcctgccg ctgcagtgaa 780
ggcttccgtc tagcagcaga tgggcacagt tgtgaagacc cttgtgccca ggccccctgt 840
gagcagcagt gtgagcctgg tgggccacaa ggctacagct gccactgtcg cctaggcttc 900
cggccagctg aggatgagcc acaccgctgc gtggacacgg atgagtgcca gattgctggt 960
gtgtgccagc agatgtgtgt caactatgtt ggtggctttg agtgttactg cagggagggt 1020
catgagcttg aggcagatgg tatcagttgt agccctgcag gagctatggg tgcccaggct 1080
tcccaggatc ttagagacga gttgctggat gatggagaag aaggggagga tgaagaggag 1140
ccctgggagg acttcgatgg cacctggaca gaggagcagg ggaccctatg gatggcacct 1200
acacatccgc ctgactttgg cctgccctat aggcccaact tcccacagga tggagagcct 1260
cagagattgc acctggagcc tacctggcca cccccactta gcgcccccag gggcccctac 1320
cactcctcag tggtgtctgc cacacggccc atggtaatct ctgccactcg acccacacaa 1380
ccttctgccc gaaagacctc tgttatttca gccacacacc taccccttaa ccctgtccac 1440
ccacctgccc tagcccctac cacacctcca gccgtgctcc etgagcacca gatccccaaa 1500
atcaaggcca gttatccaga cttgcctttt ggccacaagc ctgggataac ctcagccact 1560
cacccagcac agcctcctcc tcaccagccc cccatcatct caacgaaata tccccaagtc 1620
ttccctcccc agcaggcccc tatgtctcca gacacccaca ctatcactaa tttgcctcta 1680
atcccatctc accttgaccc tggggatacc acttcccaag ccggtcacca tcctttgctc 1740
ccagatgttc caggtatcag aacccaggct ccccaggttt ctgtctcagc tctccagccc 1800
tctctgccta ccaactccag gtcttctgtc catgaacccc ctgtgcctac tgccaaccag 1860
cccccagcct tcccttctcc cctgccccct cagagcccca ttaaccagac ctcatctatc 1920
agccctacac actcctattc cagagcccct caggtcccaa gggaaggagc tcccagtccc 1980
aaatcagtgc caaggctgca ctcagtggcc cccacagcag ctccaacagc cctggcagag 2040
ttgggtcttg caggccaaag ccagagagat gaccgatggc tgctggtggc actcttggta 2100
ccaacgtgtg tcttcttggt ggtcctgctc gcattgggca ttgtgtactg cactcgctgt 2160
ggctcccata cgcccaacaa gcgtatcact gactgctatc gctgggtcac gcatgctggg 2220
aacaagagct caacagaacc catgcccccc agatggacag agaaggttct gttccttgaa 2280
cccagcattc atggcaaagg acacactgaa ggactccagg acctcaaggg gtgggtgctg 2340
ggatcttctc caataaatgg cgtgccaacc tcacccaaag tccgtgatcc ccgctga 2397
<210>6
<211>798
<212>PRT
<213>Rattus rattus
<400>6
Met Leu Leu Arg Leu Leu Leu Ala Trp Ala Ala Ala Val Pro Ala Leu
1 5 10 15
Gly Gln Ala Pro Trp Thr Pro Glu Pro Arg Ala Ala Cys Gly Pro Ser
20 25 30
Ser Cys Tyr Ala Leu Phe Pro Arg Arg Arg Thr Phe Leu Glu Ala Trp
35 40 45
Arg Ser Cys Arg Glu Leu Gly Gly Asn Leu Ala Thr Pro Arg Thr Pro
50 55 60
Glu Glu Ala Arg Arg Val Asp Ser Leu Val Gly Val Gly Pro Ala Asn
65 70 75 80
Gly Leu Leu Trp Ile Gly Leu Gln Arg Gln Ala Arg Gln Cys Gln Pro
85 90 95
Gln Arg Pro Leu Arg Gly Phe Ile Trp Thr Thr Gly Asp Gln Asp Thr
100 105 110
Ala Phe Thr Asn Trp Ala Gln Pro Ala Thr Glu Gly Pro Cys Pro Ala
115 120 125
Gln Arg Cys Ala Ala Leu Glu Ala Ser Gly Glu His Arg Trp Leu Glu
130 135 140
Gly Ser Cys Thr Leu Ala Val Asp Gly Tyr Leu Cys Gln Phe Gly Phe
145 150 155 160
Glu Gly Ala Cys Pro Ala Leu Pro Leu Glu Val Gly Gln Ala Gly Pro
165 170 175
Ala Ile Tyr Thr Thr Pro Phe Asn Leu Val Ser Ser Glu Phe Glu Trp
180 185 190
Leu Pro Phe Gly Ser Val Ala Ala Val Gln Cys Gln Ala Gly Arg Gly
195 200 205
Thr Ser Leu Leu Cys Val Lys Gln Pro Ser Gly Gly Val Gly Trp Ser
210 215 220
Gln Thr Gly Pro Leu Cys Pro Gly Thr Gly Cys Gly Pro Asp Asn Gly
225 230 235 240
Gly Cys Glu His Glu Cys Val Glu Glu Leu Asp Gly Gly Met Ser Cys
245 250 255
Arg Cys Ser Glu Gly Phe Arg Leu Ala Ala Asp Gly His Ser Cys Glu
260 265 270
Asp Pro Cys Ala Gln Ala Pro Cys Glu Gln Gln Cys Glu Pro Gly Gly
275 280 285
Pro Gln Gly Tyr Ser Cys His Cys Arg Leu Gly Phe Arg Pro Ala Glu
290 295 300
Asp Glu Pro His Arg Cys Val Asp Thr Asp Glu Cys Gln Ile Ala Gly
305 310 315 320
Val Cys Gln Gln Met Cys Val Asn Tyr Val Gly Gly Phe Glu Cys Tyr
325 330 335
Cys Arg Glu Gly His Glu Leu Glu Ala Asp Gly Ile Ser Cys Ser Pro
340 345 350
Ala Gly Ala Met Gly Ala Gln Ala Ser Gln Asp Leu Arg Asp Glu Leu
355 360 365
Leu Asp Asp Gly Glu Glu Gly Glu Asp Glu Glu Glu Pro Trp Glu Asp
370 375 380
Phe Asp Gly Thr Trp Thr Glu Glu Gln Gly Thr Leu Trp Met Ala Pro
385 390 395 400
Thr His Pro Pro Asp Phe Gly Leu Pro Tyr Arg Pro Asn Phe Pro Gln
405 410 415
Asp Gly Glu Pro Gln Arg Leu His Leu Glu Pro Thr Trp Pro Pro Pro
420 425 430
Leu Ser Ala Pro Arg Gly Pro Tyr His Ser Ser Val Val Ser Ala Thr
435 440 445
Arg Pro Met Val Ile Ser Ala Thr Arg Pro Thr Gln Pro Ser Ala Arg
450 455 460
Lys Thr Ser Val Ile Ser Ala Thr His Leu Pro Leu Asn Pro Val His
465 470 475 480
Pro Pro Ala Leu Ala Pro Thr Thr Pro Pro Ala Val Leu Pro Glu His
485 490 495
Gln Ile Pro Lys Ile Lys Ala Ser Tyr Pro Asp Leu Pro Phe Gly His
500 505 510
Lys Pro Gly Ile Thr Ser Ala Thr His Pro Ala Gln Pro Pro Pro His
515 520 525
Gln Pro Pro Ile Ile Ser Thr Lys Tyr Pro Gln Val Phe Pro Pro Gln
530 535 540
Gln Ala Pro Met Ser Pro Asp Thr His Thr Ile Thr Asn Leu Pro Leu
545 550 555 560
Ile Pro Ser His Leu Asp Pro Gly Asp Thr Thr Ser Gln Ala Gly His
565 570 575
His Pro Leu Leu Pro Asp Val Pro Gly Ile Arg Thr Gln Ala Pro Gln
580 585 590
Val Ser Val Ser Ala Leu Gln Pro Ser Leu Pro Thr Asn Ser Arg Ser
595 600 605
Ser Val His Glu Pro Pro Val Pro Thr Ala Asn Gln Pro Pro Ala Phe
610 615 620
Pro Ser Pro Leu Pro Pro Gln Ser Pro Ile Asn Gln Thr Ser Ser Ile
625 630 635 640
Ser Pro Thr His Ser Tyr Ser Arg Ala Pro Gln Val Pro Arg Glu Gly
645 650 655
Ala Pro Ser Pro Lys Ser Val Pro Arg Leu His Ser Val Ala Pro Thr
660 665 670
Ala Ala Pro Thr Ala Leu Ala Glu Leu Gly Leu Ala Gly Gln Ser Gln
675 680 685
Arg Asp Asp Arg Trp Leu Leu Val Ala Leu Leu Val Pro Thr Cys Val
690 695 700
Phe Leu Val Val Leu Leu Ala Leu Gly Ile Val Tyr Cys Thr Arg Cys
705 710 715 720
Gly Ser His Thr Pro Asn Lys Arg Ile Thr Asp Cys Tyr Arg Trp Val
725 730 735
Thr His Ala Gly Asn Lys Ser Ser Thr Glu Pro Met Pro Pro Arg Trp
740 745 750
Thr Glu Lys Val Leu Phe Leu Glu Pro Ser Ile His Gly Lys Gly His
755 760 765
Thr Glu Gly Leu Gln Asp Leu Lys Gly Trp Val Leu Gly Ser Ser Pro
770 775 780
Ile Asn Gly Val Pro Thr Ser Pro Lys Val Arg Asp Pro Arg
785 790 795
<210>7
<211>705
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleic Acid Sequence encoding light chain of antibodies M4and
M4.1with leader sequence
<400>7
atgggatgga gctgtatcat cctcttcttg gtagcaacag ctacaggtgt ccactccgac 60
atccagatga cccagagccc aagcagcctg agcgccagcg tgggtgacag agtgaccatc 120
acctgtagag ccagccagaa tgtgggtact gctgtagcct ggctacagca gaccccaggt 180
aaggctccaa agctgctgat ctactcggca tcgaatcggt acactggtgt gccaagcaga 240
ttcagcggta gcggtagcgg taccgactac accttcacca tcagcagcct ccagccagag 300
gacatcgcca cctactactg ccagcaatat accaactatc ccatgtacac gttcggccaa 360
gggaccaagg tgcaaatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600
ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 660
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttaa 705
<210>8
<211>1422
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleic Acid Sequence encoding heavy chain of antibody M4with
leader sequenc e
<400>8
atgggatgga gctgtatcat cctcttcttg gtagcaacag ctacaggtgt ccactcccag 60
gtccaactgc aggagagcgg tccaggtctt gtgagaccta gccagaccct gagcctgacc 120
tgcaccgcgt ctggctacac cttcactgac tatgttatac actgggtgaa acagccacct 180
ggacgaggtc ttgagtggat tggatatatt aatccttatg atgatgatac tacctacaac 240
cagaagttca agggcagagt gacaatgctg gtagacacca gctccaacac agcctacctg 300
agactcagca gcgtgacagc cgaggacacc gcggtctatt attgtgcaag aagggggaat 360
tcctatgatg gttactttga ctactctatg gactactggg gatccgggac cccggtcacc 420
gtctcctcag cctccaccaa gggcccatcg gtcttccccc tggcaccctc ctccaagagc 480
acctctgggg gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 540
acggtgtcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta 600
cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttgggc 660
acccagacct acatctgcaa cgtgaatcac aagcccagca acaccaaggt ggacaagaaa 720
gttgagccca aatcttgtga caaaactcac acatgcccac cgtgcccagc acctgaactc 780
ctggggggac cgtcagtctt cctcttcccc ccaaaaccca aggacaccct catgatctcc 840
cggacccctg aggtcacatg cgtggtggtg gacgtgagcc acgaagaccc tgaggtcaag 900
ttcaactggt acgtggacgg cgtggaggtg cataatgcca agacaaagcc gcgggaggag 960
cagtacaaca gcacgtaccg tgtggtcagc gtcctcaccg tcctgcacca ggactggctg 1020
aatggcaagg agtacaagtg caaggtctcc aacaaagccc tcccagcccc catcgagaaa 1080
accatctcca aagccaaagg gcagccccga gaaccacagg tgtacaccct gcccccatcc 1140
cgggatgagc tgaccaagaa ccaggtcagc ctgacctgcc tggtcaaagg cttctatccc 1200
agcgacatcg ccgtggagtg ggagagcaat gggcagccgg agaacaacta caagaccacg 1260
cctcccgtgc tggactccga cggctccttc ttcctctaca gcaagctcac cgtggacaag 1320
agcaggtggc agcaggggaa cgtcttctca tgctccgtga tgcatgaggc tctgcacaac 1380
cactacacgc agaagagcct ctccctgtct cccgggaaat ga 1422
<210>9
<211>234
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Acid Sequence of light chain of antibodies M4and M4.1with
leader sequence
<400>9
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala
20 25 30
Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val
35 40 45
Gly Thr Ala Val Ala Trp Leu Gln Gln Thr Pro Gly Lys Ala Pro Lys
50 55 60
Leu Leu Ile Tyr Ser Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg
65 70 75 80
Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Phe Thr Ile Ser Ser
85 90 95
Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Thr Asn
100 105 110
Tyr Pro Met Tyr Thr Phe Gly Gln Gly Thr Lys Val Gln Ile Lys Arg
115 120 125
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
130 135 140
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
145 150 155 160
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
165 170 175
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
195 200 205
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
210 215 220
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230
<210>10
<211>648
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleotide Sequence encoding light chain of antibodies M4and
M4.1without leader sequence
<400>10
gacatccaga tgacccagag cccaagcagc ctgagcgcca gcgtgggtga cagagtgacc 60
atcacctgta gagccagcca gaatgtgggt actgctgtag cctggctaca gcagacccca 120
ggtaaggctc caaagctgct gatctactcg gcatcgaatc ggtacactgg tgtgccaagc 180
agattcagcg gtagcggtag cggtaccgac tacaccttca ccatcagcag cctccagcca 240
gaggacatcg ccacctacta ctgccagcaa tataccaact atcccatgta cacgttcggc 300
caagggacca aggtgcaaat caaacgaact gtggctgcac catctgtctt catcttcccg 360
ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttaa 648
<210>11
<211>215
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Acid Sequence of light chain of antibodies M4and M4.1
without leader sequence
<400>11
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Gly Thr Ala
20 25 30
Val Ala Trp Leu Gln Gln Thr Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ser Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Thr Asn Tyr Pro Met
85 90 95
Tyr Thr Phe Gly Gln Gly Thr Lys Val Gln Ile Lys Arg Thr Val Ala
100 105 110
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser
115 120 125
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu
130 135 140
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
145 150 155 160
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
165 170 175
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
180 185 190
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
195 200 205
Ser Phe Asn Arg Gly Glu Cys
210 215
<210>12
<211>33
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleic Acid Sequence encoding CDR1of light chain of antibodies
M4and M4.1
<400>12
agagccagcc agaatgtggg tactgctgta gcc 33
<210>13
<211>11
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Acid Sequence of CDR1of light chain of antibodies M4and
M4.1
<400>13
Arg Ala Ser Gln Asn Val Gly Thr Ala Val Ala
1 5 10
<210>14
<211>21
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleotide Sequence encoding CDR2of light chain of antibodies M4
and M4.1
<400>14
tcggcatcga atcggtacac t 21
<210>15
<211>7
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Acid Sequence of CDR2of light chain of antibodies M4and
M4.1
<400>15
Ser Ala Ser Asn Arg Tyr Thr
1 5
<210>16
<211>30
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleotide Sequence encoding CDR3of light chain of antibodies M4
and M4.1
<400>16
cagcaatata ccaactatcc catgtacacg 30
<210>17
<211>10
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Acid Sequence of CDR3of light chain of antibodies M4and
M4.1
<400>17
Gln Gln Tyr Thr Asn Tyr Pro Met Tyr Thr
1 5 10
<210>18
<211>294
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleotide Sequence encoding variable domain of light chain of
antibodies M4and M4.1
<400>18
gacatccaga tgacccagag cccaagcagc ctgagcgcca gcgtgggtga cagagtgacc 60
atcacctgta gagccagcca gaatgtgggt actgctgtag cctggctaca gcagacccca 120
ggtaaggctc caaagctgct gatctactcg gcatcgaatc ggtacactgg tgtgccaagc 180
agattcagcg gtagcggtag cggtaccgac tacaccttca ccatcagcag cctccagcca 240
gaggacatcg ccacctacta ctgccagcaa tataccaact atcccatgta cacg 294
<210>19
<211>98
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Acid Sequence of variable domain of light chain of
antibodies M4and M4.1
<400>19
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Gly Thr Ala
20 25 30
Val Ala Trp Leu Gln Gln Thr Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ser Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Thr Asn Tyr Pro Met
85 90 95
Tyr Thr
<210>20
<211>473
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Acid Sequence of heavy chain of antibody M4plus leader
seauence
<400>20
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg
20 25 30
Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Val Ile His Trp Val Lys Gln Pro Pro Gly Arg Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Tyr Asp Asp Asp Thr Thr Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Arg Val Thr Met Leu Val Asp Thr Ser Ser Asn
85 90 95
Thr Ala Tyr Leu Arg Leu Ser Ser Val Thr Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Arg Gly Asn Ser Tyr Asp Gly Tyr Phe Asp Tyr
115 120 125
Ser Met Asp Tyr Trp Gly Ser Gly Thr Pro Val Thr Val Ser Ser Ala
130 135 140
Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser
145 150 155 160
Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe
165 170 175
Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly
180 185 190
Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu
195 200 205
Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr
210 215 220
Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys
225 230 235 240
Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro
245 250 255
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
260 265 270
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
275 280 285
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
290 295 300
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
305 310 315 320
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
325 330 335
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
340 345 350
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
355 360 365
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
370 375 380
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
385 390 395 400
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
405 410 415
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
420 425 430
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
435 440 445
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
450 455 460
Lys Ser Leu Ser Leu Ser Pro Gly Lys
465 470
<210>21
<211>1365
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleotide Sequence encoding heavy chain of antibody M4without
leader sequence
<400>21
caggtccaac tgcaggagag cggtccaggt cttgtgagac ctagccagac cctgagcctg 60
acctgcaccg cgtctggcta caccttcact gactatgtta tacactgggt gaaacagcca 120
cctggacgag gtcttgagtg gattggatat attaatcctt atgatgatga tactacctac 180
aaccagaagt tcaagggcag agtgacaatg ctggtagaca ccagctccaa cacagcctac 240
ctgagactca gcagcgtgac agccgaggac accgcggtct attattgtgc aagaaggggg 300
aattcctatg atggttactt tgactactct atggactact ggggatccgg gaccccggtc 360
accgtctcct cagcctccac caagggccca tcggtcttcc ccctggcacc ctcctccaag 420
agcacctctg ggggcacagc ggccctgggc tgcctggtca aggactactt ccccgaaccg 480
gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 540
ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg 600
ggcacccaga cctacatctg caacgtgaat cacaagccca gcaacaccaa ggtggacaag 660
aaagttgagc ccaaatcttg tgacaaaact cacacatgcc caccgtgccc agcacctgaa 720
ctcctggggg gaccgtcagt cttcctcttc cccccaaaac ccaaggacac cctcatgatc 780
tcccggaccc ctgaggtcac atgcgtggtg gtggacgtga gccacgaaga ccctgaggtc 840
aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa gccgcgggag 900
gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccaggactgg 960
ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag ccctcccagc ccccatcgag 1020
aaaaccatct ccaaagccaa agggcagccc cgagaaccac aggtgtacac cctgccccca 1080
tcccgggatg agctgaccaa gaaccaggtc agcctgacct gcctggtcaa aggcttctat 1140
cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa ctacaagacc 1200
acgcctcccg tgctggactc cgacggctcc ttcttcctct acagcaagct caccgtggac 1260
aagagcaggt ggcagcaggg gaacgtcttc tcatgctccg tgatgcatga ggctctgcac 1320
aaccactaca cgcagaagag cctctccctg tctcccggga aatga 1365
<210>22
<211>454
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Acid Sequence of heavy chain of antibody M4without leader
sequence
<400>22
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Val Ile His Trp Val Lys Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Tyr Asp Asp Asp Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Met Leu Val Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Arg Leu Ser Ser Val Thr Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Gly Asn Ser Tyr Asp Gly Tyr Phe Asp Tyr Ser Met Asp
100 105 110
Tyr Trp Gly Ser Gly Thr Pro Val Thr Val Ser Ser Ala Ser Thr Lys
115 120 125
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
130 135 140
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
145 150 155 160
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
165 170 175
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
180 185 190
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
195 200 205
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215 220
Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
225 230 235 240
Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
245 250 255
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
260 265 270
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
275 280 285
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
290 295 300
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
305 310 315 320
Leu Asn Gly Lys G1u Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
325 330 335
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
340 345 350
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn
355 360 365
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
370 375 380
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
385 390 395 400
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
405 410 415
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
420 425 430
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
435 440 445
Ser Leu Ser Pro Gly Lys
450
<210>23
<211>1422
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleotide Sequence encoding heavychain of antibody M4.1wi th
leader sequence
<400>23
atgggatgga gctgtatcat cctcttcttg gtagcaacag ctacaggtgt ccactcccag 60
gtccaactgc aggagagcgg tccaggtctt gtgagaccta gccagaccct gagcctgacc 120
tgcaccgcgt ctggctacac cttcactgac tatgttatac actgggtgaa acagccacct 180
ggacgaggtc ttgagtggat tggatatatt aatccttatg atgatgatac tacctacaac 240
cagaagttca agggcagagt gacaatgctg gtagacacca gctccaacac agcctacctg 300
agactcagca gcgtgacagc cgaggacacc gcggtctatt attgtgcaag aagggggaat 360
tcctatgatg gttactttga ctactctatg gactactggg gatccgggac cccggtcacc 420
gtctcctcag cctccaccaa gggcccatcg gtcttccccc tggcaccctc ctccaagagc 480
acctctgggg gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 540
acggtgtcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta 600
cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttgggc 660
acccagacct acatctgcaa cgtgaatcac aagcccagca acaccaaggt ggacaagaaa 720
gttgagccca aatcttgtga caaaactcac acatgcccac cgtgcccagc acctgaactc 780
ctggggggac cgtcagtctt cctcttcccc ccaaaaccca aggacaccct catgatctcc 840
cggacccctg aggtcacatg cgtggtggtg gacgtgagcc acgaagaccc tgaggtcaag 900
ttcaactggt acgtggacgg cgtggaggtg cataatgcea agacaaagcc gcgggaggag 960
cagtacaaca gcacgtaccg tgtggtcagc gtcctcaccg tcctgcacca ggactggctg 1020
aatggcaagg agtacaagtg caaggtctcc aacaaagccc tcccagcccc catcgagaaa 1080
accatctcca aagccaaagg gcagccccga gaaccacagg tgtacaccct gcccccatcc 1140
cgggatgagc tgaccaagaa ccaggtcagc ctgacctgcc tggtcaaagg cttctatccc 1200
agcgacatcg ccgtggagtg ggagagcaat gggcagccgg agaacaacta caagaccacg 1260
cctcccgtgc tggactccga cggcttcttc ttcctctaca gcaagctcac cgtggacaag 1320
agcaggtggc agcaggggaa cgtcttctca tgctccgtga tgcatgaggc tctgcacaac 1380
cactacacgc agaagagcct ctccctgtct cccgggaaat ga 1422
<210>24
<211>473
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Acid Sequence of heavy chain of antibody M4.1with leader
sequence
<400>24
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg
20 25 30
Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Val Ile His Trp Val Lys Gln Pro Pro Gly Arg Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Tyr Asp Asp Asp Thr Thr Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Arg Val Thr Met Leu Val Asp Thr Ser Ser Asn
85 90 95
Thr Ala Tyr Leu Arg Leu Ser Ser Val Thr Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Arg Gly Asn Ser Tyr Asp Gly Tyr Phe Asp Tyr
115 120 125
Ser Met Asp Tyr Trp Gly Ser Gly Thr Pro Val Thr Val Ser Ser Ala
130 135 140
Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser
145 150 155 160
Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe
165 170 175
Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly
180 185 190
Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu
195 200 205
Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr
210 215 220
Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys
225 230 235 240
Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro
245 250 255
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
260 265 270
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
275 280 285
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
290 295 300
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
305 310 315 320
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
325 330 335
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
340 345 350
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
355 360 365
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
370 375 380
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
385 390 395 400
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
405 410 415
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Phe Phe Phe Leu
420 425 430
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln GlnGly AsnVal
435 440 445
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
450 455 460
Lys Ser Leu Ser Leu Ser Pro Gly Lys
465 470
<210>25
<211>1365
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleotide Sequence encoding heavy chain of antibody M4.1without
leader sequence
<400>25
caggtccaac tgcaggagag cggtccaggt cttgtgagac ctagccagac cctgagcctg 60
acctgcaccg cgtctggcta caccttcact gactatgtta tacactgggt gaaacagcca 120
cctggacgag gtcttgagtg gattggatat attaatcctt atgatgatga tactacctac 180
aaccagaagt tcaagggcag agtgacaatg ctggtagaca ccagctccaa cacagcctac 240
ctgagactca gcagcgtgac agccgaggac accgcggtct attattgtgc aagaaggggg 300
aattcctatg atggttactt tgactactct atggactact ggggatccgg gaccccggtc 360
accgtctcct cagcctccac caagggccca tcggtcttcc ccctggcacc ctcctccaag 420
agcacctctg ggggcacagc ggccctgggc tgcctggtca aggactactt ccccgaaccg 480
gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 540
ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg 600
ggcacccaga cctacatctg caacgtgaat cacaagccca gcaacaccaa ggtggacaag 660
aaagttgagc ccaaatcttg tgacaaaact cacacatgcc caccgtgccc agcacctgaa 720
ctcctggggg gaccgtcagt cttcctcttc cccccaaaac ccaaggacac cctcatgatc 780
tcccggaccc ctgaggtcac atgcgtggtg gtggacgtga gccacgaaga ccctgaggtc 840
aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa gccgcgggag 900
gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccaggactgg 960
ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag ccctcccagc ccccatcgag 1020
aaaaccatct ccaaagccaa agggcagccc cgagaaccac aggtgtacac cctgccccca 1080
tcccgggatg agctgaccaa gaaccaggtc agcctgacct gcctggtcaa aggcttctat 1140
cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa ctacaagacc 1200
acgcctcccg tgctggactc cgacggcttc ttcttcctct acagcaagct caccgtggac 1260
aagagcaggt ggcagcaggg gaacgtcttc tcatgctccg tgatgcatga ggctctgcac 1320
aaccactaca cgcagaagag cctctccctg tctcccggga aatga 1365
<210>26
<211>454
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Acid Sequence of heavy chain of antibody M4.1without
leader sequence
<400>26
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Val Ile His Trp Val Lys Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Tyr Asp Asp Asp Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Met Leu Val Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Arg Leu Ser Ser Val Thr Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Gly Asn Ser Tyr Asp Gly Tyr Phe Asp Tyr Ser Met Asp
100 105 110
Tyr Trp Gly Ser Gly Thr Pro Val Thr Val Ser Ser Ala Ser Thr Lys
115 120 125
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
130 135 140
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
145 150 155 160
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
165 170 175
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
180 185 190
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
195 200 205
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215 220
Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
225 230 235 240
Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
245 250 255
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
260 265 270
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
275 280 285
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
290 295 300
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
305 310 315 320
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
325 330 335
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
340 345 350
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn
355 360 365
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
370 375 380
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
385 390 395 400
Thr Pro Pro Val Leu Asp Ser Asp Gly Phe Phe Phe Leu Tyr Ser Lys
405 410 415
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
420 425 430
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
435 440 445
Ser Leu Ser Pro Gly Lys
450
<210>27
<211>30
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleotide Sequence encoding CDR1of heavy chain of antibodies M4
and M4.1
<400>27
ggctacacct tcactgacta tgttatacac 30
<210>28
<211>10
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Acid Sequence of CDR1of heavy chain of antibodies M4and
M4.1
<400>28
Gly Tyr Thr Phe Thr Asp Tyr Val Ile His
1 5 10
<210>29
<211>51
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleotide Sequence encoding CDR2of heavy chain of antibodies M4
and M4.1
<400>29
tatattaatc cttatgatga tgatactacc tacaaccaga agttcaaggg c 51
<210>30
<211>17
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Acid Sequence of CDR2of heavy chain of antibodies M4and
M4.1
<400>30
Tyr Ile Asn Pro Tyr Asp Asp Asp Thr Thr Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210>31
<211>51
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleotide Sequence encoding CDR3of heavy chain of Antibodies M4
and M4.1
<400>31
gcaagaaggg ggaattccta tgatggttac tttgactact ctatggacta c 51
<210>32
<211>17
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Acid Sequence of heavy chain CDR3of antibodies M4and M4.1
<400>32
Ala Arg Arg Gly Asn Ser Tyr Asp Gly Tyr Phe Asp Tyr Ser Met Asp
1 5 10 15
Tyr
<210>33
<211>339
<212>DNA
<213>Artificial Sequence
<220>
<223>Nucleotide Sequence encoding variable domain of heavy chain of
antibodies M4and M4.1
<400>33
caggtccaac tgcaggagag cggtccaggt cttgtgagac ctagccagac cctgagcctg 60
acctgcaccg cgtctggcta caccttcact gactatgtta tacactgggt gaaacagcca 120
cctggacgag gtcttgagtg gattggatat attaatcctt atgatgatga tactacctac 180
aaccagaagt tcaagggcag agtgacaatg ctggtagaca ccagctccaa cacagcctac 240
ctgagactca gcagcgtgac agccgaggac accgcggtct attattgtgc aagaaggggg 300
aattcctatg atggttactt tgactactct atggactac 339
<210>34
<211>113
<212>PRT
<213>Artificial Sequence
<220>
<223>Amino Ac id Sequence of variable domain of heavy chain of
antibodies M4and M4.1
<400>34
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Val Ile His Trp Val Lys Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Tyr Asp Asp Asp Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Met Leu Val Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Arg Leu Ser Ser Val Thr Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Gly Asn Ser Tyr Asp Gly Tyr Phe Asp Tyr Ser Met Asp
100 105 110
Tyr
<210>35
<211>2477
<212>PRT
<213>Homo sapiens
<400>35
Met Leu Arg Gly Pro Gly Pro Gly Leu Leu Leu Leu Ala Val Gln Cys
1 5 10 15
Leu Gly Thr Ala Val Pro Ser Thr Gly Ala Ser Lys Ser Lys Arg Gln
20 25 30
Ala Gln Gln Met Val Gln Pro Gln Ser Pro Val Ala Val Ser Gln Ser
35 40 45
Lys Pro Gly Cys Tyr Asp Asn Gly Lys His Tyr Gln Ile Asn Gln Gln
50 55 60
Trp Glu Arg Thr Tyr Leu Gly Asn Ala Leu Val Cys Thr Cys Tyr Gly
65 70 75 80
Gly Ser Arg Gly Phe Asn Cys Glu Ser Lys Pro Glu Ala Glu Glu Thr
85 90 95
Cys Phe Asp Lys Tyr Thr Gly Asn Thr Tyr Arg Val Gly Asp Thr Tyr
100 105 110
Glu Arg Pro Lys Asp Ser Met Ile Trp Asp Cys Thr Cys Ile Gly Ala
115 120 125
Gly Arg Gly Arg Ile Ser Cys Thr Ile Ala Asn Arg Cys His Glu Gly
130 135 140
Gly Gln Ser Tyr Lys Ile Gly Asp Thr Trp Arg Arg Pro His Glu Thr
145 150 155 160
Gly Gly Tyr Met Leu Glu Cys Val Cys Leu Gly Asn Gly Lys Gly Glu
165 170 175
Trp Thr Cys Lys Pro Ile Ala Glu Lys Cys Phe Asp His Ala Ala Gly
180 185 190
Thr Ser Tyr Val Val Gly Glu Thr Trp Glu Lys Pro Tyr Gln Gly Trp
195 200 205
Met Met Val Asp Cys Thr Cys Leu Gly Glu Gly Ser Gly Arg Ile Thr
210 215 220
Cys Thr Ser Arg Asn Arg Cys Asn Asp Gln Asp Thr Arg Thr Ser Tyr
225 230 235 240
Arg Ile Gly Asp Thr Trp Ser Lys Lys Asp Asn Arg Gly Asn Leu Leu
245 250 255
Gln Cys Ile Cys Thr Gly Asn Gly Arg Gly Glu Trp Lys Cys Glu Arg
260 265 270
His Thr Ser Val Gln Thr Thr Ser Ser Gly Ser Gly Pro Phe Thr Asp
275 280 285
Val Arg Ala Ala Val Tyr Gln Pro Gln Pro His Pro Gln Pro Pro Pro
290 295 300
Tyr Gly His Cys Val Thr Asp Ser Gly Val Val Tyr Ser Val Gly Met
305 310 315 320
Gln Trp Leu Lys Thr Gln Gly Asn Lys Gln Met Leu Cys Thr Cys Leu
325 330 335
Gly Asn Gly Val Ser Cys Gln Glu Thr Ala Val Thr Gln Thr Tyr Gly
340 345 350
Gly Asn Ser Asn Gly Glu Pro Cys Val Leu Pro Phe Thr Tyr Asn Gly
355 360 365
Arg Thr Phe Tyr Ser Cys Thr Thr Glu Gly Arg Gln Asp Gly His Leu
370 375 380
Trp Cys Ser Thr Thr Ser Asn Tyr Glu Gln Asp Gln Lys Tyr Ser Phe
385 390 395 400
Cys Thr Asp His Thr Val Leu Val Gln Thr Arg Gly Gly Asn Ser Asn
405 410 415
Gly Ala Leu Cys His Phe Pro Phe Leu Tyr Asn Asn His Asn Tyr Thr
420 425 430
Asp Cys Thr Ser Glu Gly Arg Arg Asp Asn Met Lys Trp Cys Gly Thr
435 440 445
Thr Gln Asn Tyr Asp Ala Asp Gln Lys Phe Gly Phe Cys Pro Met Ala
450 455 460
Ala His Glu Glu Ile Cys Thr Thr Asn Glu Gly Val Met Tyr Arg Ile
465 470 475 480
Gly Asp Gln Trp Asp Lys Gln His Asp Met Gly His Met Met Arg Cys
485 490 495
Thr Cys Val Gly Asn Gly Arg Gly Glu Trp Thr Cys Ile Ala Tyr Ser
500 505 510
Gln Leu Arg Asp Gln Cys Ile Val Asp Asp Ile Thr Tyr Asn Val Asn
515 520 525
Asp Thr Phe His Lys Arg His Glu Glu Gly His Met Leu Asn Cys Thr
530 535 540
Cys Phe Gly Gln Gly Arg Gly Arg Trp Lys Cys Asp Pro Val Asp Gln
545 550 555 560
Cys Gln Asp Ser Glu Thr Gly Thr Phe Tyr Gln Ile Gly Asp Ser Trp
565 570 575
Glu Lys Tyr Val His Gly Val Arg Tyr Gln Cys Tyr Cys Tyr Gly Arg
580 585 590
Gly Ile Gly Glu Trp His Cys Gln Pro Leu Gln Thr Tyr Pro Ser Ser
595 600 605
Ser Gly Pro Val Glu Val Phe Ile Thr Glu Thr Pro Ser Gln Pro Asn
610 615 620
Ser His Pro Ile Gln Trp Asn Ala Pro Gln Pro Ser His Ile Ser Lys
625 630 635 640
Tyr Ile Leu Arg Trp Arg Pro Lys Asn Ser Val Gly Arg Trp Lys Glu
645 650 655
Ala Thr Ile Pro Gly His Leu Asn Ser Tyr Thr Ile Lys Gly Leu Lys
660 665 670
Pro Gly Val Val Tyr Glu Gly Gln Leu Ile Ser Ile Gln Gln Tyr Gly
675 680 685
His Gln Glu Val Thr Arg Phe Asp Phe Thr Thr Thr Ser Thr Ser Thr
690 695 700
Pro Val Thr Ser Asn Thr Val Thr Gly Glu Thr Thr Pro Phe Ser Pro
705 710 715 720
Leu Val Ala Thr Ser Glu Ser Val Thr Glu Ile Thr Ala Ser Ser Phe
725 730 735
Val Val Ser Trp Val Ser Ala Ser Asp Thr Val Ser Gly Phe Arg Val
740 745 750
Glu Tyr Glu Leu Ser Glu Glu Gly Asp Glu Pro Gln Tyr Leu Asp Leu
755 760 765
Pro Ser Thr Ala Thr Ser Val Asn Ile Pro Asp Leu Leu Pro Gly Arg
770 775 780
Lys Tyr Ile Val Asn Val Tyr Gln Ile Ser Glu Asp Gly Glu Gln Ser
785 790 795 800
LeuIle Leu Ser Thr Ser Gln Thr Thr Ala Pro Asp Ala Pro Pro Asp
805 810 815
Pro Thr Val Asp Gln Val Asp Asp Thr Ser Ile Val Val Arg Trp Ser
820 825 830
Arg Pro Gln Ala Pro Ile Thr Gly Tyr Arg Ile Val Tyr Ser Pro Ser
835 840 845
Val Glu Gly Ser Ser Thr Glu Leu Asn Leu Pro Glu Thr Ala Asn Ser
850 855 860
Val Thr Leu Ser Asp Leu Gln Pro Gly Val Gln Tyr Asn Ile Thr Ile
865 870 875 880
Tyr Ala Val Glu Glu Asn Gln Glu Ser Thr Pro Val Val Ile Gln Gln
885 890 895
Glu Thr Thr Gly Thr Pro Arg Ser Asp Thr Val Pro Ser Pro Arg Asp
900 905 910
Leu Gln Phe Val Glu Val Thr Asp Val Lys Val Thr Ile Met Trp Thr
915 920 925
Pro Pro Glu Ser Ala Val Thr Gly Tyr Arg Val Asp Val Ile Pro Val
930 935 940
Asn Leu Pro Gly Glu His Gly Gln Arg Leu Pro Ile Ser Arg Asn Thr
945 950 955 960
Phe Ala Glu Val Thr Gly Leu Ser Pro Gly Val Thr Tyr Tyr Phe Lys
965 970 975
Val Phe Ala Val Ser His Gly Arg Glu Ser Lys Pro Leu Thr Ala Gln
980 985 990
Gln Thr Thr Lys Leu Asp Ala Pro Thr Asn Leu Gln Phe Val Asn Glu
995 1000 1005
Thr Asp Ser Thr Val Leu Val Arg Trp Thr Pro Pro Arg Ala Gln
1010 1015 1020
Ile Thr Gly Tyr Arg Leu Thr Val Gly Leu Thr Arg Arg Gly Gln
1025 1030 1035
Pro Arg Gln Tyr Asn Val Gly Pro Ser Val Ser Lys Tyr Pro Leu
1040 1045 1050
Arg Asn Leu Gln Pro Ala Ser Glu Tyr Thr Val Ser Leu Val Ala
1055 1060 1065
Ile Lys Gly Asn Gln Glu Ser Pro Lys Ala Thr Gly Val Phe Thr
1070 1075 1080
Thr Leu Gln Pro Gly Ser Ser Ile Pro Pro Tyr Asn Thr Glu Val
1085 1090 1095
Thr Glu Thr Thr Ile Val Ile Thr Trp Thr Pro Ala Pro Arg Ile
1100 1105 1110
Gly Phe Lys Leu Gly Val Arg Pro Ser Gln Gly Gly Glu Ala Pro
1115 1120 1125
Arg Glu Val Thr Ser Asp Ser Gly Ser Ile Val Val Ser Gly Leu
1130 1135 1140
Thr Pro Gly Val Glu Tyr Val Tyr Thr Ile Gln Val Leu Arg Asp
1145 1150 1155
Gly Gln Glu Arg Asp Ala Pro Ile Val Asn Lys Val Val Thr Pro
1160 1165 1170
Leu Ser Pro Pro Thr Asn Leu His Leu Glu Ala Asn Pro Asp Thr
1175 1180 1185
Gly Val Leu Thr Val Ser Trp Glu Arg Ser Thr Thr Pro Asp Ile
1190 1195 1200
Thr Gly Tyr Arg Ile Thr Thr Thr Pro Thr Asn Gly Gln Gln Gly
1205 1210 1215
Asn Ser Leu Glu Glu Val Val His Ala Asp Gln Ser Ser Cys Thr
1220 1225 1230
Phe Asp Asn Leu Ser Pro Gly Leu Glu Tyr Asn Val Ser Val Tyr
1235 1240 1245
Thr Val Lys Asp Asp Lys Glu Ser Val Pro Ile Ser Asp Thr Ile
1250 1255 1260
Ile Pro Glu Val Pro Gln Leu Thr Asp Leu Ser Phe Val Asp Ile
1265 1270 1275
Thr Asp Ser Ser Ile Gly Leu Arg Trp Thr Pro Leu Asn Ser Ser
1280 1285 1290
Thr Ile Ile Gly Tyr Arg Ile Thr Val Val Ala Ala Gly Glu Gly
1295 1300 1305
Ile Pro Ile Phe Glu Asp Phe Val Asp Ser Ser Val Gly Tyr Tyr
1310 1315 1320
Thr Val Thr Gly Leu Glu Pro Gly Ile Asp Tyr Asp Ile Ser Val
1325 1330 1335
Ile Thr Leu Ile Asn Gly Gly Glu Ser Ala Pro Thr Thr Leu Thr
1340 1345 1350
Gln Gln Thr Ala Val Pro Pro Pro Thr Asp Leu Arg Phe Thr Asn
1355 1360 1365
Ile Gly Pro Asp Thr Met Arg Val Thr Trp Ala Pro Pro Pro Ser
1370 1375 1380
Ile Asp Leu Thr Asn Phe Leu Val Arg Tyr Ser Pro Val Lys Asn
1385 1390 1395
Glu Glu Asp Val Ala Glu Leu Ser Ile Ser Pro Ser Asp Asn Ala
1400 1405 1410
Val Val Leu Thr Asn Leu Leu Pro Gly Thr Glu Tyr Val Val Ser
1415 1420 1425
Val Ser Ser Val Tyr Glu Gln His Glu Ser Thr Pro Leu Arg Gly
1430 1435 1440
Arg Gln Lys Thr Gly Leu Asp Ser Pro Thr Gly Ile Asp Phe Ser
1445 1450 1455
Asp Ile Thr Ala Asn Ser Phe Thr Val His Trp Ile Ala Pro Arg
1460 1465 1470
Ala Thr Ile Thr Gly Tyr Arg Ile Arg His His Pro Glu His Phe
1475 1480 1485
Ser Gly Arg Pro Arg Glu Asp Arg Val Pro His Ser Arg Asn Ser
1490 1495 1500
Ile Thr Leu Thr Asn Leu Thr Pro Gly Thr Glu Tyr Val Val Ser
1505 1510 1515
Ile Val Ala Leu Asn Gly Arg Glu Glu Ser Pro Leu Leu Ile Gly
1520 1525 1530
Gln Gln Ser Thr Val Ser Asp Val Pro Arg Asp Leu Glu Val Val
1535 1540 1545
Ala Ala Thr Pro Thr Ser Leu Leu Ile Ser Trp Asp Ala Pro Ala
1550 1555 1560
Val Thr Val Arg Tyr Tyr Arg Ile Thr Tyr Gly Glu Thr Gly Gly
1565 1570 1575
Asn Ser Pro Val Gln Glu Phe Thr Val Pro Gly Ser Lys Ser Thr
1580 1585 1590
Ala Thr Ile Ser Gly Leu Lys Pro Gly Val Asp Tyr Thr Ile Thr
1595 1600 1605
Val Tyr Ala Val Thr Gly Arg Gly Asp Ser Pro Ala Ser Ser Lys
1610 1615 1620
Pro Ile Ser Ile Asn Tyr Arg Thr Glu Ile Asp Lys Pro Ser Gln
1625 1630 1635
Met Gln Val Thr Asp Val Gln Asp Asn Ser Ile Ser Val Lys Trp
1640 1645 1650
Leu Pro Ser Ser Ser Pro Val Thr Gly Tyr Arg Val Thr Thr Thr
1655 1660 1665
Pro Lys Asn Gly Pro Gly Pro Thr Lys Thr Lys Thr Ala Gly Pro
1670 1675 1680
Asp Gln Thr Glu Met Thr Ile Glu Gly Leu Gln Pro Thr Val Glu
1685 1690 1695
Tyr Val Val Ser Val Tyr Ala Gln Asn Pro Ser Gly Glu Ser Gln
1700 1705 1710
Pro Leu Val Gln Thr Ala Val Thr Asn Ile Asp Arg Pro Lys Gly
1715 1720 1725
Leu Ala Phe Thr Asp Val Asp Val Asp Ser Ile Lys Ile Ala Trp
1730 1735 1740
Glu Ser Pro Gln Gly Gln Val Ser Arg Tyr Arg Val Thr Tyr Ser
1745 1750 1755
Ser Pro Glu Asp Gly Ile His Glu Leu Phe Pro Ala Pro Asp Gly
1760 1765 1770
Glu Glu Asp Thr Ala Glu Leu Gln Gly Leu Arg Pro Gly Ser Glu
1775 1780 1785
Tyr Thr Val Ser Val Val Ala Leu His Asp Asp Met Glu Ser Gln
1790 1795 1800
Pro Leu Ile Gly Thr Gln Ser Thr Ala Ile Pro Ala Pro Thr Asp
1805 1810 1815
Leu Lys Phe Thr Gln Val Thr Pro Thr Ser Leu Ser Ala Gln Trp
1820 1825 1830
Thr Pro Pro Asn Val Gln Leu Thr Gly Tyr Arg Val Arg Val Thr
1835 1840 1845
Pro Lys Glu Lys Thr Gly Pro Met Lys Glu Ile Asn Leu Ala Pro
1850 1855 1860
Asp Ser Ser Ser Val Val Val Ser Gly Leu Met Val Ala Thr Lys
1865 1870 1875
Tyr Glu Val Ser Val Tyr Ala Leu Lys Asp Thr Leu Thr Ser Arg
1880 1885 1890
Pro Ala Gln Gly Val Val Thr Thr Leu Glu Asn Val Ser Pro Pro
1895 1900 1905
Arg Arg Ala Arg Val Thr Asp Ala Thr Glu Thr Thr Ile Thr Ile
1910 1915 1920
Ser Trp Arg Thr Lys Thr Glu Thr Ile Thr Gly Phe Gln Val Asp
1925 1930 1935
Ala Val Pro Ala Asn Gly Gln Thr ProIle Gln Arg ThrIle Lys
1940 1945 1950
Pro Asp Val Arg Ser Tyr Thr Ile Thr Gly Leu Gln Pro Gly Thr
1955 1960 1965
Asp Tyr Lys Ile Tyr Leu Tyr Thr Leu Asn Asp Asn Ala Arg Ser
1970 1975 1980
Ser Pro Val Val Ile Asp Ala Ser Thr Ala Ile Asp Ala Pro Ser
1985 1990 1995
Asn Leu Arg Phe Leu Ala Thr Thr Pro Asn Ser Leu Leu Val Ser
2000 2005 2010
Trp Gln Pro Pro Arg Ala Arg Ile Thr Gly Tyr Ile Ile Lys Tyr
2015 2020 2025
Glu Lys Pro Gly Ser Pro Pro Arg Glu Val Val Pro Arg Pro Arg
2030 2035 2040
Pro Gly Val Thr Glu Ala Thr Ile Thr Gly Leu Glu Pro Gly Thr
2045 2050 2055
Glu Tyr Thr Ile Tyr Val Ile Ala Leu Lys Asn Asn Gln Lys Ser
2060 2065 2070
Glu Pro Leu Ile Gly Arg Lys Lys Thr Asp Glu Leu Pro Gln Leu
2075 2080 2085
Val Thr Leu Pro His Pro Asn Leu His Gly Pro Glu Ile Leu Asp
2090 2095 2100
Val Pro Ser Thr Val Gln Lys Thr Pro Phe Val Thr His Pro Gly
2105 2110 2115
Tyr Asp Thr Gly Asn Gly Ile Gln Leu Pro Gly Thr Ser Gly Gln
2120 2125 2130
Gln Pro Ser Val Gly Gln Gln Met Ile Phe Glu Glu His Gly Phe
2135 2140 2145
Arg Arg Thr Thr Pro Pro Thr Thr Ala Thr Pro Ile Arg His Arg
2150 2155 2160
Pro Arg Pro Tyr Pro Pro Asn Val Gly Glu Glu Ile Gln Ile Gly
2165 2170 2175
His Ile Pro Arg Glu Asp Val Asp Tyr His Leu Tyr Pro His Gly
2180 2185 2190
Pro Gly Leu Asn Pro Asn Ala Ser Thr Gly Gln Glu Ala Leu Ser
2195 2200 2205
Gln Thr Thr Ile Ser Trp Ala Pro Phe Gln Asp Thr Ser Glu Tyr
2210 2215 2220
Ile Ile Ser Cys His Pro Val Gly Thr Asp Glu Glu Pro Leu Gln
2225 2230 2235
Phe Arg Val Pro Gly Thr Ser Thr Ser Ala Thr Leu Thr Gly Leu
2240 2245 2250
Thr Arg Gly Ala Thr Tyr Asn Ile Ile Val Glu Ala Leu Lys Asp
2255 2260 2265
Gln Gln Arg His Lys Val Arg Glu Glu Val Val Thr Val Gly Asn
2270 2275 2280
Ser Val Asn Glu Gly Leu Asn Gln Pro Thr Asp Asp Ser Cys Phe
2285 2290 2295
Asp Pro Tyr Thr Val Ser His Tyr Ala Val Gly Asp Glu Trp Glu
2300 2305 2310
Arg Met Ser Glu Ser Gly Phe Lys Leu Leu Cys Gln Cys Leu Gly
2315 2320 2325
Phe Gly Ser Gly His Phe Arg Cys Asp Ser Ser Arg Trp Cys His
2330 2335 2340
Asp Asn Gly Val Asn Tyr Lys Ile Gly Glu Lys Trp Asp Arg Gln
2345 2350 2355
Gly Glu Asn Gly Gln Met Met Ser Cys Thr Cys Leu Gly Asn Gly
2360 2365 2370
Lys Gly Glu Phe Lys Cys Asp Pro His Glu Ala Thr Cys Tyr Asp
2375 2380 2385
Asp Gly Lys Thr Tyr His Val Gly Glu Gln Trp Gln Lys Glu Tyr
2390 2395 2400
Leu Gly Ala Ile Cys Ser Cys Thr Cys Phe Gly Gly Gln Arg Gly
2405 2410 2415
Trp Arg Cys Asp Asn Cys Arg Arg Pro Gly Gly Glu Pro Ser Pro
2420 2425 2430
Glu Gly Thr Thr Gly Gln Ser Tyr Asn Gln Tyr Ser Gln Arg Tyr
2435 2440 2445
His Gln Arg Thr Asn Thr Asn Val Asn Cys Pro Ile Glu Cys Phe
2450 2455 2460
Met Pro Leu Asp Val Gln Ala Asp Arg Glu Asp Ser Arg Glu
2465 2470 2475
Claims (9)
1.抗体在制备用于抑制对象瘤中的新生血管形成或血管生成的药物中的应用,所述抗体特异性结合内皮唾液酸蛋白并抑制细胞表面上表达的内皮唾液酸蛋白与胶原蛋白或纤连蛋白的相互作用,其中抗体由两条氨基酸序列为SEQ ID NO:22的重链和两条氨基酸序列为SEQID NO:11的轻链构成。
2.权利要求1的应用,其中所述抗体不结合鼠内皮唾液酸蛋白。
3.权利要求1或2的应用,其中所述细胞是哺乳动物细胞。
4.权利要求1或2的应用,其中所述细胞是瘤性细胞。
5.权利要求3的应用,其中所述细胞是瘤性细胞。
6.抗体在制备用于治疗对象中的癌症的药物中的应用,所述抗体特异性结合内皮唾液酸蛋白并抑制细胞表面上表达的内皮唾液酸蛋白与胶原蛋白或纤连蛋白的相互作用,其中抗体由两条氨基酸序列为SEQ ID NO:22的重链和两条氨基酸序列为SEQ ID NO:11的轻链构成。
7.抗体在制备用于治疗对象中的视网膜病的药物中的应用,所述抗体特异性结合内皮唾液酸蛋白并抑制细胞表面上表达的内皮唾液酸蛋白与胶原蛋白或纤连蛋白的相互作用,其中抗体由两条氨基酸序列为SEQ ID NO:22的重链和两条氨基酸序列为SEQ ID NO:11的轻链构成。
8.抗体在制备用于治疗对象中的黄斑变性的药物中的应用,所述抗体特异性结合内皮唾液酸蛋白并抑制细胞表面上表达的内皮唾液酸蛋白与胶原蛋白或纤连蛋白的相互作用,其中抗体由两条氨基酸序列为SEQ ID NO:22的重链和两条氨基酸序列为SEQ ID NO:11的轻链构成。
9.抗体在制备用于治疗对象中的炎性疾病的药物中的应用,所述抗体特异性结合内皮唾液酸蛋白并抑制细胞表面上表达的内皮唾液酸蛋白与胶原蛋白或纤连蛋白的相互作用,其中抗体由两条氨基酸序列为SEQ ID NO:22的重链和两条氨基酸序列为SEQ ID NO:11的轻链构成。
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Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008538700A (ja) * | 2005-04-22 | 2008-11-06 | モルフォテック、インク. | 免疫エフェクター活性を有するエンドシアリン細胞に内部移行する抗体 |
DK2137217T3 (en) * | 2007-04-05 | 2014-03-17 | Morphotek Inc | Methods of inhibiting the binding of endosialin to ligands |
US8697081B2 (en) * | 2008-04-09 | 2014-04-15 | The Regents Of The University Of Michigan | Method of modulating neovascularization |
US20100260769A1 (en) * | 2009-04-09 | 2010-10-14 | Morphotek, Inc. | Endosialin binding molecules |
US9556272B2 (en) | 2009-11-11 | 2017-01-31 | The Trustees Of The University Of Pennsylvania | Anti-TEM1 antibodies and uses thereof |
EP2621946A1 (en) | 2010-09-29 | 2013-08-07 | Morphotek, Inc. | Engineered human endosialin-expressing rodents |
EP2831114B1 (en) | 2012-03-30 | 2019-05-08 | Eisai R&D Management Co., Ltd. | Tem-1 diagnostic antibodies |
WO2013162748A1 (en) * | 2012-04-27 | 2013-10-31 | The Trustees Of The University Of Pennsylvania | Anti-tumor endothelial marker-1 (tem1) antibody variants and uses thereof |
EP2964764A1 (en) | 2013-03-09 | 2016-01-13 | Baylor College Of Medicine | Vascular-targeted t-cell therapy |
GB201702926D0 (en) * | 2017-02-23 | 2017-04-12 | Univ Birmingham | Modulators |
MX2020001057A (es) | 2017-07-28 | 2020-11-24 | Applied Therapeutics Inc | Composiciones y metodos para tratar la galactosemia. |
CN110531077B (zh) * | 2018-05-25 | 2023-07-07 | 荣昌生物制药(烟台)股份有限公司 | 间皮素免疫组化检测试剂盒 |
CN111026023A (zh) * | 2020-01-12 | 2020-04-17 | 安徽楚江科技新材料股份有限公司 | 基于s7-400控制系统的铜带轧机PLC组态方法 |
CN116790744B (zh) * | 2023-06-30 | 2024-04-26 | 浙江大学 | 一种缺血性心脏病晚期纤维化干预靶点及其应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6090930A (en) * | 1994-03-08 | 2000-07-18 | Ludwig Institute For Cancer Research | Recombinant human anti-FB5 antibodies |
WO2005086713A2 (en) * | 2004-03-04 | 2005-09-22 | Kirin Brewery Co., Ltd. | Role of human endothelial precursor cells and vascular pericytes tumor in angiogenesis |
Family Cites Families (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5965132A (en) | 1992-03-05 | 1999-10-12 | Board Of Regents, The University Of Texas System | Methods and compositions for targeting the vasculature of solid tumors |
US5342757A (en) | 1992-11-13 | 1994-08-30 | Ludwig Institute For Cancer Research | Monoclonal antibodies which specifically binds to endosialin, a 165 Kd glycoprotein found on tumor vascular endothelium, and uses thereof |
ATE244888T1 (de) | 1993-02-05 | 2003-07-15 | Epigen Inc | Humanes carcinoma-antigen (hca), hca antikörper, hca immunoassays, aufzeichnungsmethoden und therapy |
DE19541844C1 (de) | 1995-11-09 | 1997-07-24 | Gsf Forschungszentrum Umwelt | Verfahren zur Herstellung von menschlichen Antikörpern und deren Verwendung |
US6146894A (en) | 1998-04-14 | 2000-11-14 | The Johns Hopkins University | Method for generating hypermutable organisms |
CA2355337A1 (en) | 1998-09-09 | 2000-03-16 | U.S. Army Institute Of Surgical Research | Method for monitoring arterial oxygen saturation |
AU2001248352A1 (en) | 2000-03-15 | 2001-09-24 | Epigenomics Ag | Diagnosis of diseases associated with the cell cycle |
WO2002010217A2 (en) | 2000-08-02 | 2002-02-07 | The Johns Hopkins University | Endothelial cell expression patterns |
ATE501635T1 (de) | 2001-01-15 | 2011-04-15 | Morphotek Inc | Chemische hemmstoffe des mismatch-repair |
US20040043928A1 (en) | 2001-08-02 | 2004-03-04 | Ramesh Kekuda | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
US20030124579A1 (en) | 2001-09-05 | 2003-07-03 | Eos Biotechnology, Inc. | Methods of diagnosis of ovarian cancer, compositions and methods of screening for modulators of ovarian cancer |
US20040014058A1 (en) | 2001-10-05 | 2004-01-22 | Alsobrook John P. | Novel human proteins, polynucleotides encoding them and methods of using the same |
US20060127902A1 (en) | 2002-08-15 | 2006-06-15 | Genzyme Corporation | Brain endothelial cell expression patterns |
AU2003298786A1 (en) | 2002-11-26 | 2004-06-18 | Protein Design Labs, Inc. | Methods of detecting soft tissue sarcoma, compositions and methods of screening for soft tissue sarcoma modulators |
EP2267031A1 (en) | 2003-03-04 | 2010-12-29 | Kirin Beer Kabushiki Kaisha | Endothelial cell specific antibodies and uses thereof |
WO2006017759A2 (en) | 2004-08-05 | 2006-02-16 | Kirin Brewery Co., Ltd. | Tumor endothelial marker-1 (tem1) binding antibodies and uses thereof |
WO2006029045A2 (en) | 2004-09-03 | 2006-03-16 | Kirin Brewery Co., Ltd. | Endothelial cell specific antibodies and uses thereof |
EP1793868B1 (en) | 2004-09-23 | 2010-12-29 | Guerbet | Liposomal contrast agents for cest imaging |
WO2006060719A2 (en) | 2004-12-03 | 2006-06-08 | Morphotek, Inc. | Use of endosialin binding proteins to isolate endosialin positive cells |
EP1856278A2 (en) | 2005-02-10 | 2007-11-21 | Oncotherapy Science, Inc. | Method of diagnosing bladder cancer |
JP2008538700A (ja) | 2005-04-22 | 2008-11-06 | モルフォテック、インク. | 免疫エフェクター活性を有するエンドシアリン細胞に内部移行する抗体 |
US7315372B1 (en) * | 2005-09-29 | 2008-01-01 | The United States Of America As Represented By The Secretary Of The Navy | Instrument using near-field intensity correlation measurements for characterizing scattering of light by suspensions |
DE102005050933A1 (de) | 2005-10-21 | 2007-04-26 | Justus-Liebig-Universität Giessen | Erfindung betreffend Expressionsprofile zur Vorhersage von septischen Zuständen |
US7908090B2 (en) | 2005-11-30 | 2011-03-15 | The Board Of Trustees Of The Leland Stanford Junior University | Signatures for human aging |
JP2009523709A (ja) | 2005-12-16 | 2009-06-25 | ジェネンテック・インコーポレーテッド | 神経膠腫の診断、予後の予測及び治療の方法 |
WO2008084331A2 (en) | 2006-06-21 | 2008-07-17 | Hopitaux Universitaires De Geneve | Biomarkers for renal disorders |
WO2008006517A2 (en) | 2006-07-13 | 2008-01-17 | Siemens Healthcare Diagnostics Gmbh | Prediction of breast cancer response to taxane-based chemotherapy |
EP2049713A4 (en) | 2006-07-21 | 2010-06-16 | Univ Alberta | TISSUE REJECTION |
WO2008021288A2 (en) | 2006-08-11 | 2008-02-21 | Johns Hopkins University | Consensus coding sequences of human breast and colorectal cancers |
US20080300170A1 (en) | 2006-09-01 | 2008-12-04 | Cohava Gelber | Compositions and methods for diagnosis and treatment for type 2 diabetes |
WO2008063479A2 (en) | 2006-11-17 | 2008-05-29 | Fred Hutchinson Cancer Research Center | Pancreatic cancer biomarkers |
US20110119776A1 (en) | 2007-02-05 | 2011-05-19 | Wong Kwok-Kin | Methods of diagnosing and prognosing lung cancer |
WO2008101118A2 (en) | 2007-02-14 | 2008-08-21 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | A gene expression signature identifying pro-angiogenic genes in ovarian tumor endothelial cell isolates |
EP1986010A1 (en) | 2007-04-05 | 2008-10-29 | Vereniging voor christelijk hoger onderwijs, wetenschappelijk onderzoek en patiëntenzorg | Methods and tools for discriminating colorectal adenomas and adenocarcinomas |
DK2137217T3 (en) * | 2007-04-05 | 2014-03-17 | Morphotek Inc | Methods of inhibiting the binding of endosialin to ligands |
JP5769417B2 (ja) | 2007-08-16 | 2015-08-26 | ザ ロイヤル インスティチューション フォー ザ アドバンスメント オブ ラーニング/マギル ユニバーシティ | 腫瘍細胞由来微小胞 |
CN102084000B (zh) | 2008-02-01 | 2016-03-16 | 总医院有限公司 | 微泡在医学疾病和病况的诊断、预后以及治疗中的用途 |
WO2009105549A2 (en) | 2008-02-19 | 2009-08-27 | Oncomethylome Sciences Sa | Detection and prognosis of lung cancer |
WO2009120877A2 (en) | 2008-03-26 | 2009-10-01 | The Johns Hopkins University | Microrna-based diagnostic testing and therapies for inflammatory bowel disease and related diseases |
US20100136584A1 (en) | 2008-09-22 | 2010-06-03 | Icb International, Inc. | Methods for using antibodies and analogs thereof |
US20100092470A1 (en) | 2008-09-22 | 2010-04-15 | Icb International, Inc. | Antibodies, analogs and uses thereof |
WO2010045714A1 (en) | 2008-10-20 | 2010-04-29 | University Health Network | Methods and compositions for the detection of ovarian cancer |
AU2010204741B2 (en) | 2009-01-14 | 2016-01-07 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Ratio based biomarkers and methods of use thereof |
US20100260769A1 (en) | 2009-04-09 | 2010-10-14 | Morphotek, Inc. | Endosialin binding molecules |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6090930A (en) * | 1994-03-08 | 2000-07-18 | Ludwig Institute For Cancer Research | Recombinant human anti-FB5 antibodies |
US6391302B1 (en) * | 1994-03-08 | 2002-05-21 | Ludwig Institute For Cancer Research | Method for treating cancers which present antigen FB5 with humanized antibodies |
WO2005086713A2 (en) * | 2004-03-04 | 2005-09-22 | Kirin Brewery Co., Ltd. | Role of human endothelial precursor cells and vascular pericytes tumor in angiogenesis |
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