CN110642948B - B7-h3纳米抗体、其制备方法及用途 - Google Patents
B7-h3纳米抗体、其制备方法及用途 Download PDFInfo
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- CN110642948B CN110642948B CN201910953967.4A CN201910953967A CN110642948B CN 110642948 B CN110642948 B CN 110642948B CN 201910953967 A CN201910953967 A CN 201910953967A CN 110642948 B CN110642948 B CN 110642948B
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Abstract
本发明提供了一种B7‑H3纳米抗体，其制备方法及用途。所述B7‑H3纳米抗体包括框架区(FR)和互补决定区(CDR)，所述互补决定区包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)。所述B7‑H3纳米抗体可以特异性地与B7‑H3结合，灵敏地检测B7‑H3分子，并有望作为治疗性抗体用于各种B7‑H3分子高表达的恶性肿瘤的治疗。
Description
技术领域
本发明涉及针对于B7-H3多肽分子抗原表位的纳米抗体，该纳米抗体的制备方法以及该纳米抗体的用途。
背景技术
B7-H3(又称CD276)是B7家族成员，其序列与PD-L1(B7-H1)胞外区域相似，是一种具有多种生物学功能的系统发育保守蛋白。B7-H3是一种I型跨膜蛋白，在小鼠中其胞外结构域由一对免疫球蛋白可变结构域(IgV)和免疫球蛋白恒定结构域(IgC)组成(2IgB7-H3亚型)；在人体中则因外显子复制而产生了两对完全相同的免疫球蛋白(4IgB7-H3亚型)，该亚型为更常见的形式表达。B7-H3在mRNA水平上表达较为广泛，在非淋巴器官如肝脏、心脏、前列腺以及淋巴器官如脾脏和胸腺中都能够检测到，但蛋白表达受到严格的调控。B7-H3结构性表达在非免疫静息期成纤维细胞、内皮细胞、成骨细胞和羊水干细胞上。经诱导B7-H3能够表达在免疫细胞特别是抗原呈递细胞上。和调节性T细胞(Treg)共培养，IFN-γ、脂多糖(LPS)或anti-CD40体外刺激都能够诱导树突状细胞表达B7-H3蛋白。此外，单核细胞和单核细胞来源的DCs分别在LPS刺激或细胞因子诱导分化后会上调B7-H3表达水平；经PMA/Ionomycin刺激后在NK细胞、B细胞和少量T细胞上也可以检测到B7-H3蛋白。与在正常细胞中严格的调控不同，B7-H3在多种恶性肿瘤，包括黑素瘤、白血病、乳腺癌、前列腺癌、卵巢癌、胰腺癌、直肠癌等癌症中呈现异常过表达。B7-H3的高表达也与预后不良和临床疗效差有关，开发靶向B7-H3的抗体药物成为一种有前景的肿瘤治疗策略。
纳米抗体技术，是生物医学科学家在传统抗体的基础上，运用分子生物学技术结合纳米粒子科学的概念进行的抗体工程革命，从而研发出的最新和最小的抗体分子，最初由比利时科学家Hamers,R在骆驼血液中发现。普通抗体蛋白由两条重链和两条轻链组成，而从骆驼血液中发现新型抗体只有两条重链，这些“重链抗体”能像正常抗体一样与抗原等靶标紧紧结合，但不像单链抗体那样相互黏连聚集成块。以该“重链抗体”为基础的纳米抗体不仅分子量只是普通抗体的1/10，而且化学性质也更加灵活，稳定性好，可溶性高，表达容易，肿瘤组织穿透性高，且容易偶联其它分子。因此应用纳米抗体技术研发B7-H3的治疗性抗体具有广阔的前景。
发明内容
鉴于以上问题，一方面，本发明提供一种B7-H3纳米抗体，其包括框架区(FR)和互补决定区(CDR)，所述互补决定区包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为选自SEQ ID NO:5、SEQ ID NO:12、SEQ ID NO:19、SEQID NO:24、SEQ ID NO:29、SEQ ID NO:34、SEQ ID NO:41、SEQ ID NO:46、SEQ ID NO:51、SEQID NO:58、SEQ ID NO:63和SEQ ID NO:68中的任一种；
所述互补决定区2(CDR2)为选自SEQ ID NO:6、SEQ ID NO:13、SEQ ID NO:20、SEQID NO:25、SEQ ID NO:30、SEQ ID NO:35、SEQ ID NO:42、SEQ ID NO:47、SEQ ID NO:52、SEQID NO:59、SEQ ID NO:64和SEQ ID NO:69中的任一种；以及
所述互补决定区3(CDR3)为选自SEQ ID NO:7、SEQ ID NO:14、SEQ ID NO:21、SEQID NO:26、SEQ ID NO:31、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:43、SEQ ID NO:48、SEQID NO:53、SEQ ID NO:60、SEQ ID NO:65和SEQ ID NO:70中的任一种。
在具体实施方式中，所述B7-H3纳米抗体依次包含以下区域：框架区1(FR1)、互补决定区1(CDR1)、框架区2(FR2)、互补决定区2(CDR2)、框架区3(FR3)、互补决定区3(CDR3)和框架区4(FR4)，其中，
所述框架区1(FR1)为选自SEQ ID NO:1、SEQ ID NO:8、SEQ ID NO:15、SEQ ID NO:22、SEQ ID NO:27、SEQ ID NO:32、SEQ ID NO:38、SEQ ID NO:44、SEQ ID NO:49、SEQ IDNO:54、SEQ ID NO:61和SEQ ID NO:66中的任一种；
所述互补决定区1(CDR1)为选自SEQ ID NO:5、SEQ ID NO:12、SEQ ID NO:19、SEQID NO:24、SEQ ID NO:29、SEQ ID NO:34、SEQ ID NO:41、SEQ ID NO:46、SEQ ID NO:51、SEQID NO:58、SEQ ID NO:63和SEQ ID NO:68中的任一种；
所述框架区2(FR2)为选自SEQ ID NO:2、SEQ ID NO:9、SEQ ID NO:16、SEQ ID NO:39、SEQ ID NO:55中的任一种；
所述互补决定区2(CDR2)为选自SEQ ID NO:6、SEQ ID NO:13、SEQ ID NO:20、SEQID NO:25、SEQ ID NO:30、SEQ ID NO:35、SEQ ID NO:42、SEQ ID NO:47、SEQ ID NO:52、SEQID NO:59、SEQ ID NO:64和SEQ ID NO:69中的任一种；
所述框架区3(FR3)选自为SEQ ID NO:3、SEQ ID NO:10、SEQ ID NO:17、SEQ IDNO:23、SEQ ID NO:28、SEQ ID NO:33、SEQ ID NO:40、SEQ ID NO:45、SEQ ID NO:50、SEQ IDNO:56、SEQ ID NO:62和SEQ ID NO:67中的任一种；
所述互补决定区3(CDR3)为选自SEQ ID NO:7、SEQ ID NO:14、SEQ ID NO:21、SEQID NO:26、SEQ ID NO:31、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:43、SEQ ID NO:48、SEQID NO:53、SEQ ID NO:60、SEQ ID NO:65和SEQ ID NO:70中的任一种；和
所述框架区4(FR4)为选自SEQ ID NO:4、SEQ ID NO:11、SEQ ID NO:18和SEQ IDNO:57中的任一种。
在一个具体实例中，所述B7-H3纳米抗体包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:5，
所述互补决定区2(CDR2)为SEQ ID NO:6，
所述互补决定区3(CDR3)为SEQ ID NO:7。
在一个具体实例中，所述B7-H3纳米抗体包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:12，
所述互补决定区2(CDR2)为SEQ ID NO:13，
所述互补决定区3(CDR3)为SEQ ID NO:14。
在一个具体实例中，所述B7-H3纳米抗体包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:19，
所述互补决定区2(CDR2)为SEQ ID NO:20，
所述互补决定区3(CDR3)为SEQ ID NO:21。
在一个具体实例中，所述B7-H3纳米抗体包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:24，
所述互补决定区2(CDR2)为SEQ ID NO:25，
所述互补决定区3(CDR3)为SEQ ID NO:26。
在一个具体实例中，所述B7-H3纳米抗体包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:29，
所述互补决定区2(CDR2)为SEQ ID NO:30，
所述互补决定区3(CDR3)为SEQ ID NO:31。
在一个具体实例中，所述B7-H3纳米抗体包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:34，
所述互补决定区2(CDR2)为SEQ ID NO:35，
所述互补决定区3(CDR3)为SEQ ID NO:36。
在一个具体实例中，所述B7-H3纳米抗体包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:12，
所述互补决定区2(CDR2)为SEQ ID NO:13，
所述互补决定区3(CDR3)为SEQ ID NO:37。
在一个具体实例中，所述B7-H3纳米抗体包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:41，
所述互补决定区2(CDR2)为SEQ ID NO:42，
所述互补决定区3(CDR3)为SEQ ID NO:43。
在一个具体实例中，所述B7-H3纳米抗体包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:46，
所述互补决定区2(CDR2)为SEQ ID NO:47，
所述互补决定区3(CDR3)为SEQ ID NO:48。
在一个具体实例中，所述B7-H3纳米抗体包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:51，
所述互补决定区2(CDR2)为SEQ ID NO:52，
所述互补决定区3(CDR3)为SEQ ID NO:53。
在一个具体实例中，所述B7-H3纳米抗体包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:58，
所述互补决定区2(CDR2)为SEQ ID NO:59，
所述互补决定区3(CDR3)为SEQ ID NO:60。
在一个具体实例中，所述B7-H3纳米抗体包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:63，
所述互补决定区2(CDR2)为SEQ ID NO:64，
所述互补决定区3(CDR3)为SEQ ID NO:65。
在一个具体实例中，所述B7-H3纳米抗体包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:68，
所述互补决定区2(CDR2)为SEQ ID NO:69，
所述互补决定区3(CDR3)为SEQ ID NO:70。
在具体实施方式中，所述B7-H3纳米抗体具有选自以下任一种的氨基酸序列：
SEQ ID NO:71、SEQ ID NO:72、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQID NO:76、SEQ ID NO:77、SEQ ID NO:78、SEQ ID NO:79、SEQ ID NO:80、SEQ ID NO:81、SEQID NO:82和SEQ ID NO:83。
另一方面，本发明提供一种制备前述B7-H3纳米抗体的方法，包括以下步骤：
1).构建B7-H3分子纳米抗体文库；
2).筛选B7-H3纳米抗体；
3).用免疫印迹法检测单个阳性克隆；
4).用phage Elisa对阳性克隆进一步验证；以及
5).在真核表达系统中表达纯化B7-H3纳米抗体。
再一方面，本发明提供了一种DNA分子，其编码上述B7-H3纳米抗体。
再一方面，本发明提供了一种表达载体，其包含上述DNA分子。
又一方面，本发明提供了上述B7-H3纳米抗体在制备B7-H3分子检测试剂中的用途。
又一方面，本发明提供了上述B7-H3纳米抗体在制备用于治疗B7-H3分子高表达的恶性肿瘤的药物中的用途。
本发明的效果
本发明的B7-H3纳米抗体可以特异性地与B7-H3结合，灵敏地检测B7-H3分子，并有望作为治疗性抗体用于各种B7-H3分子高表达的恶性肿瘤的治疗。
附图说明
图1为实施例3中的Output phage免疫印迹图。
图2为实施例4中用phage Elisa对阳性克隆进一步验证的结果。
图3为实施例5中1-13#纳米抗体纯化的SDS-PAGE图。
具体实施方式
以下通过具体实施例来描述本申请的纳米抗体的具体制备过程，然而本领域的技术人员应当了解，本申请的范围不应受这些实施例的限制，而是包含本领域的技术人员可以做出的各种等同变换形式。
完全/不完全弗氏佐剂(sigma,F5506),链霉亲和素磁珠(invitrogen,65002),casein(Thermo,37528),PROTRAN BA85(Whatman,10401116),酶标板(greiner,650061),羊抗M13HRP(GE,279421)。
实施例1：针对B7-H3分子纳米抗体文库的构建
(1)蛋白表达hu4IgB7-H3抗原分子，将1mg hu4IgB7-H3抗原与完全弗氏佐剂等体积混合，免疫一只新疆单峰驼；
(2)第二周开始，将1mg hu4IgB7-H3抗原与不完全弗氏佐剂等体积混合，共免疫7次，刺激B细胞表达抗原特异性的纳米抗体；
(3)7次免疫结束后，提取100ml骆驼外周血淋巴细胞并提取总RNA；
(4)反转录获得cDNA并用巢式PCR扩增VHH片段；
(5)利用kunkel反应将VHH单链DNA退火到噬菌体载体中；
(6)将kunkel产物转化至电转化感受态DH10B中，构建B7-H3纳米抗体文库并测定库容，库容大小为1.07×10e9。
实施例2：针对B7-H3纳米抗体的筛选过程
(1)液相淘选：
1.用终浓度0.5％casein封闭缓冲液封闭10e12pfu input phage，室温孵育1h；
2.同时取100μl链霉亲和素磁珠用无菌PBS洗三次，弃上清，用500μl 1％casein封闭缓冲液室温封闭1h；
3.弃掉步骤2中的封闭液，将1ml封闭好的phage加至磁珠中，充分混匀，旋转混匀结合15min；(阴性筛选)
4.取上清至新的无菌EP管中，加入终浓度为100nM hu4IgB7-H3-biotin抗原，室温旋转混匀结合2h；
5.同时取100μl链霉亲和素磁珠用无菌PBS洗三次，弃上清，用500μl 1％casein封闭缓冲液室温封闭1h；
6.弃掉步骤5中的封闭液，将1ml phage-hu hu4IgB7-H3-biotin混合物加至磁珠中，充分混匀，旋转混匀结合15min；
7.弃上清，用1×PBS洗10次，收集磁珠；
8.将400μl新鲜配置的洗脱缓冲液100mM Triethylamine加到步骤7的磁珠中，旋转洗脱10min；
9.将400μl上清转移至无菌EP管中，加入200μl pH6.4Tris-HCl中和，筛选获得output phage。
(2)固相淘选：
1.用1ml终浓度为100nM hu-hu4IgB7-H3抗原溶液包被免疫管，4℃孵育过夜；
2.第二天，用1×PBS冲洗未包被的免疫管3次，甩干，加4ml 1％casein封闭缓冲液室温旋转封闭1h；
3.用终浓度1％的BSA封闭5×10e12pfu第一轮input phage，用1×PBS补充到1ml终体积，室温旋转封闭1h；
4.弃去未包被抗原的免疫管中的封闭液，将封闭好的phage投入未包被抗原的免疫管中，旋转结合2h(阴性筛选)；
5.同时弃去包被抗原的免疫管中的包被液，用1×PBS冲洗3次，甩干，加4ml封闭缓冲液室温旋转封闭1h；
6.弃去包被抗原的免疫管中的封闭液，将阴性筛选后的phage转移到免疫管中，旋转结合2h；
7.弃去上清，用1×PBST冲洗免疫管10次，甩干；
8.将1ml新鲜配置的洗脱缓冲液100mM Triethylamine加到免疫管中，室温静置孵育10min；
9.将1ml洗脱液转移至无菌EP管中，加入500μl pH6.4Tris-HCl中和，筛选获得output phage。
实施例3：用免疫印迹法检测单个阳性克隆(Mccafferty J,Griffiths A D,Winter G,et al.Phage antibodies:filamentous phage displaying antibodyvariable domains[J].Nature,1990,348(6301):552-554.Huse W,Sastry L,Iverson S,et al.Generation of a large combinatorial library of the immunoglobulinrepertoire in phage lambda[J].Biotechnology,1989,246(4935):1275-1281.)
(1)每块LB平板铺2000pfu output phage，37℃培养6-8h；
(2)用5ml 2μg/ml anti-M13抗体包被Whatman 0.45μm NC膜，室温孵育2.5h；
(3)弃去包被液，用5ml 1％casein封闭缓冲液封闭NC膜，室温孵育1h；
(4)弃去封闭液，用1×PBS洗3次，晾干；
(5)将NC膜贴于长有phage的LB平板上，打孔定位，室温培养过夜；
(6)第二天揭膜置于新的培养皿中，1×PBS冲洗3次，加入100nM的hu4IgB7-H3-biotin室温孵育1h；
(7)0.1％PBST冲洗8次，加入1:1000稀释的Neutravidin-AP室温孵育30min；
(8)0.1％PBST冲洗8次，加入10ml AP显色底物(100μl BCIP+100μl NBT),室温显色10-30min；
(9)将阳性克隆挑取出来，做plaque PCR，待测序；
(10)通过DNAman序列比对软件比对序列，将CDR1、CDR2、CDR3相同的克隆视为同一克隆。
实施例4：用phage Elisa对阳性克隆进一步验证
(1)phage的扩增：1:100接种XL1blue大肠杆菌于LB液体培养基中(含10μg/ml四环素)，长至OD60＝0.6；将Xl1blue分装到96孔深孔板中，600μl/孔，加入15μl挑取的phageelution；过夜扩增，4000rpm离心30min，取上清，即可用来做phage Elisa；
(2)Elisa检测：
1.将hu4IgB7-H3抗原用1×PBS稀释至100nM,按每孔50μl包被ELISA板，4℃过夜；
2.弃去包被液，甩干ELISA板，用1×PBS冲洗3次；
3.每孔加入200μl1％casein封闭缓冲液,室温封闭1h；
4.弃去封闭液，在每孔中加入50μl高滴度phage，室温孵育2h；
5.用0.1％PBST冲洗6次，甩干；
6.加入1:5000稀释的羊抗M13-HRP抗体，50μl/孔，室温孵育1h。用0.1％PBST冲洗6次，甩干；
7.每孔加入50μlTMB显色液，室温显色5min。加入50μl 2M的H2SO4终止反应，测OD450值；
8.当样品孔OD值大于对照孔OD值3倍视为阳性，最终得到13个阳性克隆株。(所得到的13个纳米抗体的DNA序列分别为SEQ ID No.:84-96。)实施例5：纳米抗体在真核表达系统中的表达、纯化
(1)将前面测序分析获得不同克隆株的VHH片段克隆到PINfuse真核表达载体中；
(2)测序正确后，提取质粒；
(3)将HEK293F悬浮细胞培养在Freestyle 293表达培养基中，密度达到1×10e6/ml,成活率＞90％时，用于转染；
(4)PEI:质粒的质量比为3:1，按照1μg质粒/1ml HEK293F细胞的比例转染；
(5)转染后5-6天，收集细胞上清，用proteinA株纯化获得高纯度的抗体蛋白，并用超滤柱将洗脱缓冲液置换成PBS。(所得到的13个纳米抗体的氨基酸序列分别为SEQ IDNo.:71-83)。
序列表
<110> 达石药业（广东）有限公司，上海迈石生物技术有限公司，深圳创石生物医药有限公司
<120> B7-H3纳米抗体、其制备方法及用途
<130> DI19-1476-XC03
<160> 96
<170> PatentIn version 3.5
<210> 1
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1
<400> 1
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Ala His Arg
20 25 30
<210> 2
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> FR2
<400> 2
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val Ala
1 5 10
<210> 3
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3
<400> 3
Arg Phe Thr Ile Ser Gln Asp Asn Ala Asn Asp Met Val Tyr Leu Gln
1 5 10 15
Met Leu Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Ala Ala
20 25 30
<210> 4
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> FR4
<400> 4
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 5
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR1
<400> 5
Arg Tyr Tyr Met Ser
1 5
<210> 6
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR2
<400> 6
Ser Ile Tyr Ile Gly Ser Gly Ser Thr Asp Tyr Val Asp Ser Val Lys
1 5 10 15
Gly
<210> 7
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> CDR3
<400> 7
Gly Leu Tyr Gly Gly Arg Trp Asp Arg Ala Gln Tyr Lys Tyr
1 5 10
<210> 8
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1
<400> 8
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Tyr Thr Arg Ser
20 25 30
<210> 9
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> FR2
<400> 9
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val Ala Ala
1 5 10 15
<210> 10
<211> 35
<212> PRT
<213> 人工序列
<220>
<223> FR3
<400> 10
Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Ala Lys Asn Thr Val
1 5 10 15
Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr
20 25 30
Cys Ala Ala
35
<210> 11
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> FR4
<400> 11
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 12
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR1
<400> 12
Thr Ile Trp Ile Gly
1 5
<210> 13
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> CDR2
<400> 13
Ile Tyr Ile Gly Ser Gly Ala Thr Tyr Tyr Val Asp Ser Val Lys Gly
1 5 10 15
<210> 14
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> CDR3
<400> 14
Thr Gly Gly Thr Val Gly Ser Met Val Arg Phe Ser Pro Val Gly Asp
1 5 10 15
Phe Gly Tyr
<210> 15
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1
<400> 15
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr
20 25 30
<210> 16
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> FR2
<400> 16
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser
1 5 10
<210> 17
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3
<400> 17
Arg Ser Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln
1 5 10 15
Leu Asn Ser Leu Glu Thr Glu Asp Thr Ala Met Tyr Tyr Cys Ala Lys
20 25 30
<210> 18
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> FR4
<400> 18
Arg Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 19
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR1
<400> 19
Asn Tyr Ala Met Ser
1 5
<210> 20
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> CDR2
<400> 20
Gly Ile Asn Ser Asp Gly Gly Thr Tyr Tyr Ser Asn Ser Val Lys Gly
1 5 10 15
<210> 21
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> CDR3
<400> 21
Gly Asn Gly Pro Ser Trp Thr Leu Gly Ser Val Asp Val Asn Ser
1 5 10 15
<210> 22
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1
<400> 22
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Asp Thr Tyr Arg
20 25 30
<210> 23
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3
<400> 23
Arg Phe Thr Ile Ser Gln Asp Ser Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
20 25 30
<210> 24
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR1
<400> 24
Arg Asn Thr Met Gly
1 5
<210> 25
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR2
<400> 25
Ala Ile Tyr Thr Gly Gly Thr Ser Thr Ala Tyr Ala Asp Ser Val Arg
1 5 10 15
Gly
<210> 26
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR3
<400> 26
Gly Ser Val Trp Ser Arg Tyr Thr Trp Ser Trp Pro Ser Thr Tyr Ser
1 5 10 15
Tyr
<210> 27
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1
<400> 27
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Glu Tyr Ser Tyr Ser
20 25 30
<210> 28
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3
<400> 28
Arg Phe Thr Ile Ser Gln Asp Ile Ala Glu Asn Thr Val Tyr Leu Arg
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Ala Ala
20 25 30
<210> 29
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR1
<400> 29
Arg Lys Trp Met Gly
1 5
<210> 30
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> CDR2
<400> 30
Ala Ile Tyr Thr Ser Gly Arg Thr Ala Val Ala Asp Ser Val Lys Gly
1 5 10 15
<210> 31
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> CDR3
<400> 31
Leu Thr Gly Ala Ser Asp Ser Pro Leu Arg Pro Ser Glu Tyr Asn Tyr
1 5 10 15
<210> 32
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1
<400> 32
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
20 25 30
<210> 33
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3
<400> 33
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Met Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Ala Ala
20 25 30
<210> 34
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR1
<400> 34
Ser Tyr Asp Met Ser
1 5
<210> 35
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR2
<400> 35
Ala Ile Asn Ser Gly Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 36
<211> 21
<212> PRT
<213> 人工序列
<220>
<223> CDR3
<400> 36
Asp Pro Gly Ser Ser Leu Ala Val Gly Ala Trp Leu Lys Ala Ala Asp
1 5 10 15
Pro Phe Tyr Gly Tyr
20
<210> 37
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> CDR3
<400> 37
Thr Ser Gly Thr Val Gly Ser Met Val Arg Phe Ser Pro Val Gly Asp
1 5 10 15
Phe Gly Tyr
<210> 38
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1
<400> 38
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
20 25 30
<210> 39
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> FR2
<400> 39
Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val Ser
1 5 10
<210> 40
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3
<400> 40
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Lys Met Leu Tyr Leu Gln
1 5 10 15
Met Asp Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr
20 25 30
<210> 41
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR1
<400> 41
Gly Val Asp Met Ser
1 5
<210> 42
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR2
<400> 42
Gly Phe Gly Ser Gly Gly Glu Ser Pro Ser Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 43
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> CDR3
<400> 43
Arg Trp Ala Glu Gly Tyr
1 5
<210> 44
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1
<400> 44
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Leu Phe Ser
20 25 30
<210> 45
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3
<400> 45
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Thr Leu Gln
1 5 10 15
Leu Asn Ser Leu Lys Thr Glu Asp Thr Ala Met Tyr Tyr Cys Ala Lys
20 25 30
<210> 46
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR1
<400> 46
Arg Tyr Ser Met Ser
1 5
<210> 47
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR2
<400> 47
Gly Ile Thr Asn Gly Gly Ser Ile Thr Lys Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 48
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> CDR3
<400> 48
Gly Ala Gly Glu Tyr Gly Pro Val Ser Asp Tyr Val Phe Ser Leu
1 5 10 15
<210> 49
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1
<400> 49
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Ile Gly
20 25 30
<210> 50
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3
<400> 50
Arg Phe Ala Ile Ser Glu Asp Asn Ala Lys Asn Thr Val Tyr Leu His
1 5 10 15
Met Asn Leu Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Ala Ala
20 25 30
<210> 51
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR1
<400> 51
Ser Asn Tyr Met Gly
1 5
<210> 52
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR2
<400> 52
Ala Ile Tyr Thr Gly Gly Gly Asn Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 53
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> CDR3
<400> 53
Asp Leu Arg Leu Arg Val Ala Val Leu His Pro Tyr Gly Tyr Asn Tyr
1 5 10 15
<210> 54
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1
<400> 54
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr Phe Ser
20 25 30
<210> 55
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> FR2
<400> 55
Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser
1 5 10 15
<210> 56
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3
<400> 56
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln
1 5 10 15
Leu Asn Asn Leu Lys Thr Glu Asp Thr Ala Met Tyr Tyr Cys Thr Lys
20 25 30
<210> 57
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> FR4
<400> 57
Gly Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 58
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> CDR1
<400> 58
Asn Tyr Ala Met
1
<210> 59
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> CDR2
<400> 59
Arg Ile Ser Ser Ser Gly Ile Thr Tyr Tyr Ala Asp Ser Val Lys Gly
1 5 10 15
<210> 60
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR3
<400> 60
Ser Ser Glu Ala Pro
1 5
<210> 61
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1
<400> 61
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ala Ile Tyr Arg
20 25 30
<210> 62
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3
<400> 62
Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Asp Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Ala Ala
20 25 30
<210> 63
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR1
<400> 63
Gly Asn Tyr Met Gly
1 5
<210> 64
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR2
<400> 64
Ala Ile Ala Thr Asn Gly Arg Thr Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 65
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> CDR3
<400> 65
Asp Asn Ser Trp Ser Cys Thr Val Val Gly Gly Leu Leu Ala Pro Ala
1 5 10 15
Tyr Asn Tyr
<210> 66
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1
<400> 66
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Arg Phe Thr Tyr Ser
20 25 30
<210> 67
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3
<400> 67
Arg Phe Thr Ile Ser Leu Asp Ile Ala Lys Lys Thr Leu Ser Leu Gln
1 5 10 15
Met Asp Ser Leu Lys Ser Glu Asp Thr Ala Met Tyr Tyr Cys Ala Ala
20 25 30
<210> 68
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR1
<400> 68
Trp Tyr Cys Met Gly
1 5
<210> 69
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR2
<400> 69
Ala Ile Cys Thr Thr Pro Ser Arg Thr Tyr Ala Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 70
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> CDR3
<400> 70
Asp Thr Arg Gly Ala Ile Gly Phe Phe Lys Gly Ser Gly Pro Ala Ile
1 5 10 15
Pro Tyr
<210> 71
<211> 123
<212> PRT
<213> 人工序列
<220>
<223> 1#纳米抗体
<400> 71
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Ala His Arg Arg Tyr
20 25 30
Tyr Met Ser Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val
35 40 45
Ala Ser Ile Tyr Ile Gly Ser Gly Ser Thr Asp Tyr Val Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Asn Asp Met Val Tyr
65 70 75 80
Leu Gln Met Leu Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Ala Gly Leu Tyr Gly Gly Arg Trp Asp Arg Ala Gln Tyr Lys Tyr
100 105 110
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
115 120
<210> 72
<211> 131
<212> PRT
<213> 人工序列
<220>
<223> 2#纳米抗体
<400> 72
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Tyr Thr Arg Ser Thr Ile
20 25 30
Trp Ile Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val
35 40 45
Ala Ala Ile Tyr Ile Gly Ser Gly Ala Thr Tyr Tyr Val Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Ala Lys Asn
65 70 75 80
Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met
85 90 95
Tyr Tyr Cys Ala Ala Thr Gly Gly Thr Val Gly Ser Met Val Arg Phe
100 105 110
Ser Pro Val Gly Asp Phe Gly Tyr Trp Gly Gln Gly Thr Gln Val Thr
115 120 125
Val Ser Ser
130
<210> 73
<211> 123
<212> PRT
<213> 人工序列
<220>
<223> 3#纳米抗体
<400> 73
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Asn Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Gly Ile Asn Ser Asp Gly Gly Thr Tyr Tyr Ser Asn Ser Val Lys
50 55 60
Gly Arg Ser Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Leu Asn Ser Leu Glu Thr Glu Asp Thr Ala Met Tyr Tyr Cys Ala
85 90 95
Lys Gly Asn Gly Pro Ser Trp Thr Leu Gly Ser Val Asp Val Asn Ser
100 105 110
Arg Gly Gln Gly Thr Gln Val Thr Val Ser Ser
115 120
<210> 74
<211> 126
<212> PRT
<213> 人工序列
<220>
<223> 4#纳米抗体
<400> 74
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Asp Thr Tyr Arg Arg Asn
20 25 30
Thr Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val
35 40 45
Ala Ala Ile Tyr Thr Gly Gly Thr Ser Thr Ala Tyr Ala Asp Ser Val
50 55 60
Arg Gly Arg Phe Thr Ile Ser Gln Asp Ser Ala Lys Asn Thr Val Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Gly Ser Val Trp Ser Arg Tyr Thr Trp Ser Trp Pro Ser Thr
100 105 110
Tyr Ser Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
115 120 125
<210> 75
<211> 124
<212> PRT
<213> 人工序列
<220>
<223> 5#纳米抗体
<400> 75
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Glu Tyr Ser Tyr Ser Arg Lys
20 25 30
Trp Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val
35 40 45
Ala Ala Ile Tyr Thr Ser Gly Arg Thr Ala Val Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Gln Asp Ile Ala Glu Asn Thr Val Tyr Leu
65 70 75 80
Arg Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Ala
85 90 95
Ala Leu Thr Gly Ala Ser Asp Ser Pro Leu Arg Pro Ser Glu Tyr Asn
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
115 120
<210> 76
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 6#纳米抗体
<400> 76
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Asp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ala Ile Asn Ser Gly Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Met Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Ala Asp Pro Gly Ser Ser Leu Ala Val Gly Ala Trp Leu Lys Ala
100 105 110
Ala Asp Pro Phe Tyr Gly Tyr Trp Gly Gln Gly Thr Gln Val Thr Val
115 120 125
Ser Ser
130
<210> 77
<211> 131
<212> PRT
<213> 人工序列
<220>
<223> 7#纳米抗体
<400> 77
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Tyr Thr Arg Ser Thr Ile
20 25 30
Trp Ile Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val
35 40 45
Ala Ala Ile Tyr Ile Gly Ser Gly Ala Thr Tyr Tyr Val Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Ala Lys Asn
65 70 75 80
Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met
85 90 95
Tyr Tyr Cys Ala Ala Thr Ser Gly Thr Val Gly Ser Met Val Arg Phe
100 105 110
Ser Pro Val Gly Asp Phe Gly Tyr Trp Gly Gln Gly Thr Gln Val Thr
115 120 125
Val Ser Ser
130
<210> 78
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 8#纳米抗体
<400> 78
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Gly Val
20 25 30
Asp Met Ser Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val
35 40 45
Ser Gly Phe Gly Ser Gly Gly Glu Ser Pro Ser Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Lys Met Leu Tyr
65 70 75 80
Leu Gln Met Asp Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Arg Trp Ala Glu Gly Tyr Trp Gly Gln Gly Thr Gln Val Thr
100 105 110
Val Ser Ser
115
<210> 79
<211> 124
<212> PRT
<213> 人工序列
<220>
<223> 9#纳米抗体
<400> 79
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Leu Phe Ser Arg Tyr
20 25 30
Ser Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Gly Ile Thr Asn Gly Gly Ser Ile Thr Lys Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Thr
65 70 75 80
Leu Gln Leu Asn Ser Leu Lys Thr Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Lys Gly Ala Gly Glu Tyr Gly Pro Val Ser Asp Tyr Val Phe Ser
100 105 110
Leu Arg Gly Gln Gly Thr Gln Val Thr Val Ser Ser
115 120
<210> 80
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 10#纳米抗体
<400> 80
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Ile Gly Ser Asn
20 25 30
Tyr Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val
35 40 45
Ala Ala Ile Tyr Thr Gly Gly Gly Asn Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Ala Ile Ser Glu Asp Asn Ala Lys Asn Thr Val Tyr
65 70 75 80
Leu His Met Asn Leu Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Ala Asp Leu Arg Leu Arg Val Ala Val Leu His Pro Tyr Gly Tyr
100 105 110
Asn Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
115 120 125
<210> 81
<211> 113
<212> PRT
<213> 人工序列
<220>
<223> 11#纳米抗体
<400> 81
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr Phe Ser Asn Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Arg Ile Ser Ser Ser Gly Ile Thr Tyr Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Leu Asn Asn Leu Lys Thr Glu Asp Thr Ala Met Tyr Tyr Cys Thr
85 90 95
Lys Ser Ser Glu Ala Pro Gly Gly Gln Gly Thr Gln Val Thr Val Ser
100 105 110
Ser
<210> 82
<211> 128
<212> PRT
<213> 人工序列
<220>
<223> 12#纳米抗体
<400> 82
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ala Ile Tyr Arg Gly Asn
20 25 30
Tyr Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val
35 40 45
Ala Ala Ile Ala Thr Asn Gly Arg Thr Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Val Tyr
65 70 75 80
Leu Gln Met Asn Asp Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Ala Asp Asn Ser Trp Ser Cys Thr Val Val Gly Gly Leu Leu Ala
100 105 110
Pro Ala Tyr Asn Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
115 120 125
<210> 83
<211> 127
<212> PRT
<213> 人工序列
<220>
<223> 13#纳米抗体
<400> 83
Asp Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Arg Phe Thr Tyr Ser Trp Tyr
20 25 30
Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val
35 40 45
Ala Ala Ile Cys Thr Thr Pro Ser Arg Thr Tyr Ala Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Leu Asp Ile Ala Lys Lys Thr Leu Ser
65 70 75 80
Leu Gln Met Asp Ser Leu Lys Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Ala Asp Thr Arg Gly Ala Ile Gly Phe Phe Lys Gly Ser Gly Pro
100 105 110
Ala Ile Pro Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
115 120 125
<210> 84
<211> 369
<212> DNA
<213> 人工序列
<220>
<223> 1#纳米抗体DNA
<400> 84
gatgtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60
tcctgtgcag cctctggtgt cgcccacagg cgctactaca tgtcctggtt ccgccaggct 120
ccagggaagg agcgcgaggg ggtcgcatcc atttatattg gtagtggtag cacagactat 180
gtcgactccg tgaagggccg attcaccatc tcccaagaca acgccaacga catggtgtat 240
ctgcaaatgc tcagcctcaa acctgaggac actgccatgt actactgtgc ggcaggcctt 300
tacggtggta gatgggatcg ggcccagtat aagtactggg gccaggggac ccaggtcacc 360
gtctcctca 369
<210> 85
<211> 393
<212> DNA
<213> 人工序列
<220>
<223> 2#纳米抗体DNA
<400> 85
gatgtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60
tcctgtacag cctccggata cacccgcagt accatttgga taggctggtt ccgccaggct 120
ccagggaagg agcgcgaggg ggtcgcagct atttatattg gtagtggcgc gacatactat 180
gtggactccg tgaagggccg attcaccatc tcccaagaca acgccaagaa cgccaagaac 240
acggtgtatc tgcagatgaa cagcctgaaa cctgaggaca ctgccatgta ctactgtgcg 300
gcaacgggcg gtactgtagg aagtatggtc cgattctccc cagtgggcga ctttggttat 360
tggggccagg ggacccaggt caccgtctcc tca 393
<210> 86
<211> 369
<212> DNA
<213> 人工序列
<220>
<223> 3#纳米抗体DNA
<400> 86
gatgtgcagc tgcaggagtc tggaggaggc ttggtgcagc ctggggggtc tctgagactc 60
tcctgtgcag cctctggatt caccttcaca aactatgcca tgagctgggt ccgccaggct 120
ccagggaagg gactcgagtg ggtctcaggt attaatagtg atggtggcac atactattca 180
aactccgtga agggccgaag caccatctcc agagacaacg ccaagaacac gctgtatctg 240
caattgaaca gcctggagac tgaggacacg gccatgtatt actgtgcaaa aggaaacggc 300
ccgtcttgga ccctggggag cgtggacgtt aactcccggg gccaggggac ccaggtcacc 360
gtctcctca 369
<210> 87
<211> 378
<212> DNA
<213> 人工序列
<220>
<223> 4#纳米抗体DNA
<400> 87
gatgtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60
tcctgtgcag cctctggaga cacttacagg cgcaacacca tgggctggtt ccgccaggct 120
ccggggaagg agcgcgaggg ggtcgcagct atttatactg gtggtactag tacagcctat 180
gccgactccg tgaggggccg attcaccatc tcccaagaca gcgccaagaa cacggtgtat 240
ctgcaaatga acagcctgaa acctgaggac actgccatat actactgtgc ggcaggctca 300
gtgtggtccc gttatacatg gtcctggccc agtacgtata gctactgggg ccaggggacc 360
caggtcaccg tctcctca 378
<210> 88
<211> 372
<212> DNA
<213> 人工序列
<220>
<223> 5#纳米抗体DNA
<400> 88
gatgtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60
tcctgtgcag cctctgaata cagctacagt aggaagtgga tgggctggtt ccgccaggct 120
ccagggaagg agcgcgaggg ggtcgcagct atttatacta gtggtaggac agccgttgcc 180
gactccgtga agggccgatt caccatctcc caagacatcg ccgagaacac ggtgtatctg 240
cgtatgaaca gcctgaaacc tgaggacact gccatgtact actgtgcggc actcacaggt 300
gctagcgact caccgctacg cccaagcgag tataactact ggggccaggg gacccaggtc 360
accgtctcct ca 372
<210> 89
<211> 390
<212> DNA
<213> 人工序列
<220>
<223> 6#纳米抗体DNA
<400> 89
gatgtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60
tcctgtgcag cctctggatt cacattcagt agctacgaca tgagctgggt ccgccaggct 120
ccagggaagg ggctcgagtg ggtctcagct attaatagtg gtggtggtag cacatactat 180
gcagactccg tgaagggccg attcaccatc tccagagaca acgccaagaa cacgatgtat 240
ctgcaaatga acagcctgaa acctgaggac actgccatgt actactgtgc ggcagatcct 300
ggttcaagtt tggcggtggg agcttggttg aaggcggcgg atcccttcta tggttactgg 360
ggccagggga cccaggtcac cgtctcctca 390
<210> 90
<211> 393
<212> DNA
<213> 人工序列
<220>
<223> 7#纳米抗体DNA
<400> 90
gatgtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60
tcctgtacag cctccggata cacccgcagt accatttgga taggctggtt ccgccaggct 120
ccagggaagg agcgcgaggg ggtcgcagct atttatattg gtagtggcgc gacatactat 180
gtggactccg tgaagggccg attcaccatc tcccaagaca acgccaagaa cgccaagaac 240
acggtgtatc tgcagatgaa cagcctgaaa cctgaggaca ctgccatgta ctactgtgcg 300
gcaacgagcg gtactgtagg aagtatggtc cgattctccc cagtgggcga ctttggttat 360
tggggccagg ggacccaggt caccgtctcc tca 393
<210> 91
<211> 345
<212> DNA
<213> 人工序列
<220>
<223> 8#纳米抗体DNA
<400> 91
gatgtgcagc tgcaggagtc tggaggaggc ttggtgcagc ctggggggtc tctgagactc 60
tcctgtgcag cctctggatt cacattcagt ggcgtcgaca tgagctgggt ccgccaggct 120
ccagggaggg ggctcgagtg ggtctcaggg tttggtagtg gtggtgaaag cccatcatat 180
gcagactccg tgaagggccg attcaccatc tccagagaca acgccaagaa aatgctgtat 240
ctgcagatgg acagtttgaa acctgaggac acagccgtgt attactgcgc cacccgctgg 300
gctgagggct actggggcca ggggacccag gtcaccgtct cctca 345
<210> 92
<211> 372
<212> DNA
<213> 人工序列
<220>
<223> 9#纳米抗体DNA
<400> 92
gatgtgcagc tgcaggagtc tggaggaggc ttggtgcagc ctggggggtc tctgagactc 60
tcctgtgcag cctctggatt cctcttcagt agatattcca tgagttgggt ccgccaggct 120
ccagggaagg gactcgagtg ggtctcaggt attacgaatg gtggtagcat tacaaagtat 180
gcagactccg tgaagggccg attcaccatc tccagagaca acgccaagaa cacactgact 240
ctgcaactga acagcctgaa aactgaggac acggccatgt attactgtgc caaaggcgcg 300
ggggagtatg gccctgttag tgactatgtc ttctctctca ggggccaggg gacccaggtc 360
accgtctcct ca 372
<210> 93
<211> 375
<212> DNA
<213> 人工序列
<220>
<223> 10#纳米抗体DNA
<400> 93
gatgtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60
tcctgtgcag cctctggata caccatcggt agcaactaca tgggctggtt ccgccaggct 120
ccagggaagg agcgcgaggg ggtcgcagct atttatactg gtggtggtaa tacatactat 180
gccgactccg tgaagggccg attcgccatc tccgaagaca acgccaagaa cacggtgtat 240
ctgcacatga acctcctgaa acctgaggac actgccatgt actactgtgc ggcagacttg 300
agactacggg ttgctgtact ccacccgtat gggtataact actggggcca ggggacccag 360
gtcaccgtct cctca 375
<210> 94
<211> 339
<212> DNA
<213> 人工序列
<220>
<223> 11#纳米抗体DNA
<400> 94
gatgtgcagc tgcaggagtc tggaggaggc ttggtgcagc ctggggggtc tctgagactc 60
tcctgtgcag tctctggatt caccttcagt aactatgcca tgagctgggt ccgccaggct 120
ccagggaagg ggctcgagtg ggtctcacgt attagtagta gtggtattac atactatgca 180
gactccgtga agggccgatt caccatctcc agagacaacg ccaagaacac gctgtatcta 240
caattgaaca acctgaaaac tgaggacacg gccatgtatt actgtacaaa aagttccgag 300
gccccgggtg gccaggggac ccaggtcacc gtctcctca 339
<210> 95
<211> 384
<212> DNA
<213> 人工序列
<220>
<223> 12#纳米抗体DNA
<400> 95
gatgtgcagc tgcaggagtc tggaggaggc tcggtacagg ctggagggtc tctgagactc 60
tcctgtgcag cctctggagc catctacaga ggcaactaca tgggctggtt ccgccaggct 120
ccagggaagg agcgcgaggg ggtcgcggct atcgctacta atggtcgtac aacatactat 180
gccgactccg tgaagggccg attcaccatc tcccaagaca acgccaagaa cacggtgtat 240
ctgcaaatga acgacctgaa acctgaggac actgccatgt actactgtgc ggcagacaac 300
tcttggtcct gtacggtggt aggtgggcta ctggcgcctg cctataacta ctggggccag 360
gggacccagg tcaccgtctc ctca 384
<210> 96
<211> 381
<212> DNA
<213> 人工序列
<220>
<223> 13#纳米抗体DNA
<400> 96
gatgtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60
tcctgtgcag cctctagatt tacctacagt tggtactgca tgggctggtt ccgccaggct 120
ccggggaagg agcgcgaggg ggtcgcagct atttgcacga caccgagccg cacatacgct 180
gccgactccg tgaagggtcg attcaccatc tccctagaca tcgccaagaa gacgctgtct 240
ctgcaaatgg acagcctgaa atctgaggac actgccatgt actactgtgc ggcagataca 300
agaggagcta tagggttctt caagggcagt gggcccgcca tcccctactg gggccagggg 360
acccaggtca ccgtctcctc a 381
Claims (5)
1.一种B7-H3纳米抗体，其包括框架区(FR)和互补决定区(CDR)，所述互补决定区包含互补决定区1(CDR1)、互补决定区2(CDR2)和互补决定区3(CDR3)，其中，
所述互补决定区1(CDR1)为SEQ ID NO:5，
所述互补决定区2(CDR2)为SEQ ID NO:6，
所述互补决定区3(CDR3)为SEQ ID NO:7；或者
所述互补决定区1(CDR1)为SEQ ID NO:12，
所述互补决定区2(CDR2)为SEQ ID NO:13，
所述互补决定区3(CDR3)为SEQ ID NO:14；或者
所述互补决定区1(CDR1)为SEQ ID NO:19，
所述互补决定区2(CDR2)为SEQ ID NO:20，
所述互补决定区3(CDR3)为SEQ ID NO:21；或者
所述互补决定区1(CDR1)为SEQ ID NO:24，
所述互补决定区2(CDR2)为SEQ ID NO:25，
所述互补决定区3(CDR3)为SEQ ID NO:26；或者
所述互补决定区1(CDR1)为SEQ ID NO:29，
所述互补决定区2(CDR2)为SEQ ID NO:30，
所述互补决定区3(CDR3)为SEQ ID NO:31；或者
所述互补决定区1(CDR1)为SEQ ID NO:34，
所述互补决定区2(CDR2)为SEQ ID NO:35，
所述互补决定区3(CDR3)为SEQ ID NO:36；或者
所述互补决定区1(CDR1)为SEQ ID NO:12，
所述互补决定区2(CDR2)为SEQ ID NO:13，
所述互补决定区3(CDR3)为SEQ ID NO:37；或者
所述互补决定区1(CDR1)为SEQ ID NO:41，
所述互补决定区2(CDR2)为SEQ ID NO:42，
所述互补决定区3(CDR3)为SEQ ID NO:43；或者
所述互补决定区1(CDR1)为SEQ ID NO:46，
所述互补决定区2(CDR2)为SEQ ID NO:47，
所述互补决定区3(CDR3)为SEQ ID NO:48；或者
所述互补决定区1(CDR1)为SEQ ID NO:51，
所述互补决定区2(CDR2)为SEQ ID NO:52，
所述互补决定区3(CDR3)为SEQ ID NO:53；或者
所述互补决定区1(CDR1)为SEQ ID NO:58，
所述互补决定区2(CDR2)为SEQ ID NO:59，
所述互补决定区3(CDR3)为SEQ ID NO:60；或者
所述互补决定区1(CDR1)为SEQ ID NO:63，
所述互补决定区2(CDR2)为SEQ ID NO:64，
所述互补决定区3(CDR3)为SEQ ID NO:65；或者
所述互补决定区1(CDR1)为SEQ ID NO:68，
所述互补决定区2(CDR2)为SEQ ID NO:69，
所述互补决定区3(CDR3)为SEQ ID NO:70。
2.根据权利要求1所述的B7-H3纳米抗体，其中，所述B7-H3纳米抗体具有选自以下任一种的氨基酸序列：
SEQ ID NO:71、SEQ ID NO:72、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ IDNO:76、SEQ ID NO:77、SEQ ID NO:78、SEQ ID NO:79、SEQ ID NO:80、SEQ ID NO:81、SEQ IDNO:82和SEQ ID NO:83。
3.一种DNA分子，其编码如权利要求1或2所述的B7-H3纳米抗体。
4.一种表达载体，其包含如权利要求3所述的DNA分子。
5.如权利要求1或2所述的B7-H3纳米抗体在制备B7-H3分子检测试剂中的用途。
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| US17/767,444 US20240092910A1 (en) | 2019-10-09 | 2020-10-09 | B7-h3 nanobody, preparation method and use thereof |
| PCT/CN2020/119893 WO2021068871A1 (zh) | 2019-10-09 | 2020-10-09 | B7-h3纳米抗体、其制备方法及用途 |
| JP2022521665A JP2022551318A (ja) | 2019-10-09 | 2020-10-09 | Ｂ７－ｈ３ナノ抗体、その製造方法および使用 |
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| US20240108745A1 (en) | 2021-02-09 | 2024-04-04 | Medilink Therapeutics (Suzhou) Co., Ltd. | Bioactive substance conjugate, preparation method therefor and use thereof |
| CN117362434A (zh) * | 2022-06-30 | 2024-01-09 | 南京北恒生物科技有限公司 | 靶向b7-h3的抗体及其用途 |
| WO2024077547A1 (zh) * | 2022-10-13 | 2024-04-18 | 达石药业(广东)有限公司 | 一种b7h3/pdl1双特异性抗体及其药物组合物及应用 |
| CN118105508A (zh) * | 2022-11-29 | 2024-05-31 | 四川科伦博泰生物医药股份有限公司 | 药物连接子化合物及其制备方法和用途 |
| CN116239691B (zh) * | 2022-12-30 | 2024-04-02 | 兰州大学第二医院 | 一种抗b7-h3纳米抗体及其应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101104639A (zh) * | 2006-07-10 | 2008-01-16 | 苏州大学 | 抗人b7-h3单克隆抗体的制备及其应用 |
| CN103687945A (zh) * | 2011-04-25 | 2014-03-26 | 第一三共株式会社 | 抗-b7-h3抗体 |
| WO2015181267A1 (en) * | 2014-05-29 | 2015-12-03 | Spring Bioscience Corporation | Anti-b7-h3 antibodies and diagnostic uses thereof |
| CN110305213A (zh) * | 2018-11-09 | 2019-10-08 | 上海复旦张江生物医药股份有限公司 | 一种抗b7-h3抗体及其制备方法、其偶联物和应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8013125B2 (en) * | 2008-03-03 | 2011-09-06 | Dyax Corp. | Metalloproteinase 9 and metalloproteinase 2 binding proteins |
| GB2461546B (en) * | 2008-07-02 | 2010-07-07 | Argen X Bv | Antigen binding polypeptides |
| WO2014160627A1 (en) * | 2013-03-25 | 2014-10-02 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anti-cd276 polypeptides, proteins, and chimeric antigen receptors |
| CA2959356C (en) * | 2014-08-27 | 2024-02-20 | Memorial Sloan Kettering Cancer Center | Novel antibodies that bind to b7h3 |
| WO2018161872A1 (zh) * | 2017-03-06 | 2018-09-13 | 江苏恒瑞医药股份有限公司 | 抗b7-h3抗体、其抗原结合片段及其医药用途 |
| CN110642948B (zh) * | 2019-10-09 | 2021-06-29 | 达石药业(广东)有限公司 | B7-h3纳米抗体、其制备方法及用途 |
-
2019
- 2019-10-09 CN CN201910953967.4A patent/CN110642948B/zh active Active
-
2020
- 2020-10-09 US US17/767,444 patent/US20240092910A1/en active Pending
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101104639A (zh) * | 2006-07-10 | 2008-01-16 | 苏州大学 | 抗人b7-h3单克隆抗体的制备及其应用 |
| CN103687945A (zh) * | 2011-04-25 | 2014-03-26 | 第一三共株式会社 | 抗-b7-h3抗体 |
| WO2015181267A1 (en) * | 2014-05-29 | 2015-12-03 | Spring Bioscience Corporation | Anti-b7-h3 antibodies and diagnostic uses thereof |
| CN110305213A (zh) * | 2018-11-09 | 2019-10-08 | 上海复旦张江生物医药股份有限公司 | 一种抗b7-h3抗体及其制备方法、其偶联物和应用 |
Non-Patent Citations (1)
| Title |
|---|
| 大容量人源 Fab 噬菌体展示抗体库的构建及抗CD276抗体筛选;刘婕等;《中国医药生物技术》;20140810;第9卷(第4期);第273-276页 * |
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| Publication number | Publication date |
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| JP2022551318A (ja) | 2022-12-08 |
| WO2021068871A1 (zh) | 2021-04-15 |
| EP4043491B1 (en) | 2024-07-03 |
| EP4043491A1 (en) | 2022-08-17 |
| EP4043491A4 (en) | 2022-12-07 |
| CN110642948A (zh) | 2020-01-03 |
| US20240092910A1 (en) | 2024-03-21 |
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