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1. 发明公开

US20240327801A1 EFFICIENT CELL CULTURE SYSTEM FOR HEPATITIS C VIRUS GENOTYPE 4a 审中-公开
公开(公告)号：US20240327801A1
公开(公告)日：2024-10-03
申请号：US18276852
申请日：2022-02-11
申请人： Hvidovre Hospital
发明人： Martin Schou Pedersen , Jens Bukh , Long Van Pham , Santseharay Ramirez Almeida , Ulrik Fahnøe , Carlota Fernandez-Antunez , Daryl Grant Humes , Kristian Schønning
IPC分类号： C12N7/00 , A61K39/00
CPC分类号： C12N7/00 , A61K39/00 , A61K2039/525 , C12N2770/24221 , C12N2770/24234 , C12N2770/24251
摘要： The present invention relates to nucleic acid sequences that encode hepatitis C viruses (HCV) of genotype da that are useful in the fundamental research of HCV as well as in the search of antivirals and vaccines against HCV. In particular, the present invention relates to nucleic acid sequences that comprise HCV, which are capable of expressing the virus when transfected into cells and are capable of replication or infectivity in cultured cells.

2. 发明申请

US20160244729A1 NOVEL HCV CULTURE SYSTEMS AND DIRECT-ACTING ANTIVIRAL SENSITIVITY 审中-公开
标题翻译：新型HCV文化系统和直接作用的抗病毒敏感性
公开(公告)号：US20160244729A1
公开(公告)日：2016-08-25
申请号：US15025833
申请日：2014-10-21
申请人： HVIDOVRE HOSPITAL
发明人： Yiping Li , Santseharay Ramirez Almeida , Daryl Grant Humes , Judith M. Gottwein , Jens Bukh
IPC分类号： C12N7/00 , C12Q1/02
CPC分类号： C12N7/00 , C12N2770/24221 , C12N2770/24234 , C12N2770/24251 , C12N2770/24252 , C12Q1/025
摘要： The present invention relates to hepatitis C virus (HCV) culture systems of genotypes 1a, 3a, 4a, 5a, and 6a that directly contribute to HCV drug and vaccine development, to HCV basic research and better-individualized treatment of HCV infected patients.
摘要翻译：本发明涉及直接有助于HCV药物和疫苗开发的基因型1a，3a，4a，5a和6a的丙型肝炎病毒（HCV）培养系统，HCV基因研究和HCV感染患者的更好个体化治疗。

3. 发明授权

US09234184B2 Nucleic acid construct comprising nucleic acid derived from genome of hepatitis C virus of genotype 1B, hepatitis C virus genome-replicating cells transfected with the same, and method for producing infectious hepatitis C virus particles 有权
标题翻译：包含来自基因型1B的丙型肝炎病毒基因组的核酸的核酸构建体，用其转染的丙型肝炎病毒基因组复制细胞和用于产生感染性丙型肝炎病毒颗粒的方法
公开(公告)号：US09234184B2
公开(公告)日：2016-01-12
申请号：US14009049
申请日：2012-03-30
申请人： Takaji Wakita , Tomoko Date , Yasuhito Tanaka , Masashi Mizokami
发明人： Takaji Wakita , Tomoko Date , Yasuhito Tanaka , Masashi Mizokami
IPC分类号： C12N7/08 , C12N7/00 , C12N7/04 , C12N15/86 , C07K16/10 , C12Q1/70 , C07K16/08 , C07K14/005 , A61K39/12 , A61K39/00
CPC分类号： C12N7/00 , A61K39/00 , A61K39/12 , C07K14/005 , C07K16/082 , C07K16/109 , C12N15/86 , C12N2770/24221 , C12N2770/24222 , C12N2770/24231 , C12N2770/24234 , C12N2770/24243 , C12N2770/24251 , C12Q1/707 , C12Q2600/136 , C12Q2600/156
摘要： A subgenomic replicon RNA (nucleic acid) having an excellent autonomously replicating ability and a fullgenomic replicon RNA (nucleic acid) having an excellent autonomously replicating ability and infectious HCV particle-producing ability, each derived from a novel HCV of genotype 1b, are provided. Particularly, a subgenomic replicon RNA (nucleic acid) and a fullgenomic replicon RNA (nucleic acid), each derived from an HCV genome of the NC1 strain which is a novel HCV genotype 1b isolated from a patient with acute severe hepatitis C, are provided.
摘要翻译：提供了具有优异的自主复制能力的亚基因组复制子RNA（核酸）和具有优异的自主复制能力和感染性HCV颗粒产生能力的全基因组复制子RNA（核酸），各自源自基因型1b的新型HCV。特别地，提供了从NC1菌株的HCV基因组衍生的亚基因组复制子RNA（核酸）和全基因组复制子RNA（核酸），其是从急性重症丙型肝炎患者分离的新型HCV基因型1b。

4. 发明授权

US08604179B2 Nucleic acid comprising chimeric gene derived from hepatitis C virus 失效
标题翻译：包含源自丙型肝炎病毒的嵌合基因的核酸
公开(公告)号：US08604179B2
公开(公告)日：2013-12-10
申请号：US12989592
申请日：2009-04-24
申请人： Daisuke Akazawa , Takaji Wakita
发明人： Daisuke Akazawa , Takaji Wakita
IPC分类号： A61K39/29 , C07K14/005 , C12N7/00
CPC分类号： A61K39/29 , A61K39/12 , A61K2039/5252 , A61K2039/5254 , C07K14/005 , C07K16/109 , C07K2319/00 , C12N7/00 , C12N2770/24222 , C12N2770/24234 , C12N2770/24251 , C12Q1/707 , C12Q2600/136 , C12Q2600/156
摘要： This invention provides infectious chimeric HCV particles that can be used for vaccines. This invention further provides a nucleic acid comprising a chimeric gene derived from the hepatitis C virus comprising regions each encoding Core protein, E1 protein, E2 protein and p7 protein derived from a hepatitis C virus strain other than JFH-1 strain; NS2 protein derived from JFH-1 strain or a hepatitis C virus strain other than JFH-1 strain, or a chimeric NS2 protein of NS2 protein derived from JFH-1 strain and NS2 protein derived from a hepatitis C virus strain other than JFH-1 strain; and NS3 protein, NS4A protein, NS4B protein, NS5A protein, and NS5B protein derived from JFH-1 strain in that order in 5′ to 3′ direction, wherein the 328th proline residue from the amino acid residue at N-terminus of the Core protein is substituted with an amino acid residue other than proline. This invention further provides chimeric HCV particles comprising such nucleic acid, and use of such HCV particles for vaccines.
摘要翻译：本发明提供可用于疫苗的感染性嵌合HCV颗粒。本发明还提供了包含源自丙型肝炎病毒的嵌合基因的核酸，其包含各自编码来自除了JFH-1株之外的丙型肝炎病毒株的核心蛋白质，E1蛋白质，E2蛋白质和p7蛋白质的区域; 衍生自JFH-1株或除JFH-1株以外的丙型肝炎病毒株的NS2蛋白或源自JFH-1株的NS2蛋白的嵌合NS2蛋白和来自除JFH-1以外的丙型肝炎病毒株的NS2蛋白应变; 和NS3蛋白，NS4A蛋白，NS4B蛋白，NS5A蛋白和NS5B蛋白，其在5'至3'方向上按顺序从JFH-1菌株衍生，其中来自核心N末端的氨基酸残基的第328位脯氨酸残基蛋白质被除脯氨酸以外的氨基酸残基取代。本发明进一步提供了包含这种核酸的嵌合HCV颗粒，以及这种HCV颗粒用于疫苗的用途。

5. 发明授权

US07759087B1 Method of indefinite culture of hepatitis C virus 有权
标题翻译：丙型肝炎病毒无限培养方法
公开(公告)号：US07759087B1
公开(公告)日：2010-07-20
申请号：US11536324
申请日：2006-09-28
申请人： Hengli Tang
发明人： Hengli Tang
IPC分类号： A01N1/02 , C12P21/00
CPC分类号： C12N7/00 , C12N2770/24251
摘要： The invention discloses a method of maintaining hepatitis C virus (HCV) growing indefinitely in cell culture. The method includes providing a culture of cells susceptible to infection by HCV; introducing to the cell culture an inoculum containing an infective dose of HCV; contacting the inoculated cell culture with a growth medium containing an excess of uridine and cytidine; and changing spent growth medium with fresh growth medium containing the excess of uridine and cytidine on a predetermined schedule.
摘要翻译：本发明公开了一种在细胞培养物中无限期地维持丙型肝炎病毒（HCV）的方法。该方法包括提供对HCV感染敏感的细胞培养物; 向细胞培养物中引入含有感染性HCV的接种物; 使接种的细胞培养物与含有过量尿苷和胞苷的生长培养基接触; 并且以预定的时间表改变含有过量的尿苷和胞苷的新鲜生长培养基的消费生长培养基。

6. 发明申请

US20100093841A1 CELL CULTURE SYSTEM OF A HEPATITIS C GENOTYPE 3A AND 2A CHIMERA 有权
标题翻译：乙型肝炎病毒基因组3A和2A型细胞培养系统
公开(公告)号：US20100093841A1
公开(公告)日：2010-04-15
申请号：US12595822
申请日：2008-04-11
申请人： Judith M. Gottwein , Troels Kasper Høyer Scheel , Jesper Eugen-Olsen , Jens Bukh
发明人： Judith M. Gottwein , Troels Kasper Høyer Scheel , Jesper Eugen-Olsen , Jens Bukh
IPC分类号： A61K31/7052 , C07H21/00 , C12N15/63 , C12P21/00 , C12Q1/70 , C12Q1/68 , C12N7/00 , C07K16/00 , A61P31/12
CPC分类号： C12N7/00 , A61K2039/5254 , C12N2770/24251
摘要： The present inventors have developed a culture system for genotype 3a, which has a high prevalence worldwide. Since intergenotypic recombinant genomes exploiting the replication characteristics of JFH1 will be a valuable tool for the genotype specific study of the replaced genes and related therapeutics, the present inventors constructed a genotype 3a/2a (S52/JFH1) recombinant containing the structural genes (Core, E1, E2), p7 and NS2 of strain S52 and characterized it in Huh7.5 cells. S52/JFH1 and J6/JFH viruses passaged in cell culture had comparable growth kinetics and yielded similar peak HCV RNA titers and infectivity titers. Direct genome sequencing of cell culture derived S52/JFH1 viruses identified putative adaptive mutations in Core, E2, p7, NS3 and NS5A; clonal analysis revealed, that all genomes analyzed exhibited different combinations of these mutations. Finally, viruses resulting from transfection with RNA transcripts of five S52/JFH1 recombinant containing these combinations of putative adaptive mutations performed as efficiently as J6/JFH viruses in Huh7.5 15 cells and were all genetically stable after viral passage. In conclusion, the present inventors have developed a robust and genetically stable cell culture system for HCV genotype 3a.
摘要翻译：本发明人已经开发了一种在全球范围内具有高流行性的基因型3a的培养系统。由于利用JFH1的复制特征的基因型重组基因组将成为替代基因和相关治疗剂的基因型特异性研究的有价值的工具，本发明人构建了一种含有结构基因（核心，核苷酸）的基因型3a / 2a（S52 / JFH1） E1，E2），p7和NS2，并在Huh7.5细胞中表征。在细胞培养物中传代的S52 / JFH1和J6 / JFH病毒具有相似的生长动力学，并产生相似的HCV RNA滴度和感染性滴度。来自S52 / JFH1病毒的细胞培养物的直接基因组测序鉴定了核心，E2，p7，NS3和NS5A中的推定适应性突变; 克隆分析显示，所有分析的基因组都显示出这些突变的不同组合。最后，含有这些组合推定的适应性突变的5种S52 / JFH1重组RNA转录物转染的病毒与Huh7.515细胞中的J6 / JFH病毒一样有效地进行，并且在病毒传代后都具有遗传稳定性。总之，本发明人已经开发了用于HCV基因型3a的稳健和遗传稳定的细胞培养系统。

7. 发明申请

US20100068698A1 PRODUCTION OF INFECTIOUS HEPATITIS C VIRUS PARTICLES IN CELL CULTURE 审中-公开
标题翻译：在细胞培养中生产感染性HEPATITIS C病毒颗粒
公开(公告)号：US20100068698A1
公开(公告)日：2010-03-18
申请号：US12557716
申请日：2009-09-11
申请人： Matthew F. McCown , Isabel Najera
发明人： Matthew F. McCown , Isabel Najera
IPC分类号： C12Q1/70 , C12N7/00
CPC分类号： C12N7/00 , C12N2770/24251
摘要： The present invention provides for novel methods of producing high levels of infectious HCV genotype 1 virus particles in cell culture systems. The availability of HCV genotype 1 virus (principally associated with liver disease in most regions of the world) that can undergo the complete viral cycle in cultured cells is beneficial for the discovery and development of novel therapies for the treatment of HCV.
摘要翻译：本发明提供了在细胞培养系统中产生高水平感染性HCV基因型1病毒颗粒的新方法。可以在培养细胞中经历完整病毒循环的HCV基因型1病毒（主要与世界大多数地区的肝病相关）的可用性有利于发现和开发用于治疗HCV的新疗法。

8. 发明申请

US20100062419A1 Infectious, Chimeric Hepatitis C Virus, Methods of Producing the Same and Methods of Use Thereof 审中-公开
标题翻译：传染性，嵌合丙型肝炎病毒，其生产方法及其使用方法
公开(公告)号：US20100062419A1
公开(公告)日：2010-03-11
申请号：US12581597
申请日：2009-10-19
申请人： Charles Rice , Matthew J. Evans , Brett D. Lindenbach , Christopher Jones
发明人： Charles Rice , Matthew J. Evans , Brett D. Lindenbach , Christopher Jones
IPC分类号： C12Q1/70 , C12N7/00 , C07H21/04
CPC分类号： C12N7/00 , A61K2039/525 , C07K2319/61 , C12N15/86 , C12N2770/24243 , C12N2770/24251 , C12N2840/203 , C12Q1/18 , G01N33/5767 , G01N2333/18 , G01N2500/00
摘要： The present invention provides infectious recombinant Hepatitis C Viruses (HCV), and vectors, cells and animals comprising the same. The present invention provides methods of producing infectious recombinant HCV, and their use in identifying anti-HCV therapeutic agents, as well as sequences of HCV associated with HCV pathogenesis.
摘要翻译：本发明提供感染性重组丙型肝炎病毒（HCV），以及包含其的载体，细胞和动物。本发明提供生产感染性重组HCV的方法及其在鉴定抗HCV治疗剂中的用途以及与HCV发病机制相关的HCV序列。

9. 发明申请

US20100028973A1 METHOD FOR PROLIFERATING HEPATITIS VIRUS, HOLLOW FIBER FOR CULTURING HEPATITIS VIRUS-INFECTED CELLS, AND USE THEREOF 审中-公开
标题翻译：用于增殖乙型肝炎病毒的方法，用于培养乙型肝炎病毒感染细胞的中空纤维及其用途
公开(公告)号：US20100028973A1
公开(公告)日：2010-02-04
申请号：US12442695
申请日：2007-09-26
申请人： Tatsuya Yamaguchi , Masaya Segawa , Masashi Mizokami , Yasuhito Tanaka , Kunitada Shimotohno , Makoto Hijikata
发明人： Tatsuya Yamaguchi , Masaya Segawa , Masashi Mizokami , Yasuhito Tanaka , Kunitada Shimotohno , Makoto Hijikata
IPC分类号： C12N7/00
CPC分类号： C12Q1/045 , C12N7/00 , C12N2730/10151 , C12N2730/10152 , C12N2770/24251 , C12N2770/24252 , C12Q1/025
摘要： The present invention provides (i) a method for proliferating a hepatitis virus, the method including the steps of: infecting, with the hepatitis virus, cells packed into a lumen of a hollow fiber made of a permeabilized membrane; and culturing the cells or (ii) a method for proliferating a hepatitis virus, the method including the steps of: infecting cells with the hepatitis virus; packing the cells into a lumen of a hollow fiber made of a permeabilized membrane; and culturing the cells. This provides an experimental system for infecting in vitro culture cells with a hepatitis virus such as HBV or HCV and then proliferating the hepatitis virus.
摘要翻译：本发明提供（i）一种增加肝炎病毒的方法，其特征在于，包括以下步骤：用肝炎病毒感染填充在由透化膜构成的中空纤维的内腔中的细胞; 和（ii）增殖型肝炎病毒的方法，所述方法包括以下步骤：用所述肝炎病毒感染细胞; 将细胞包装到由透化膜制成的中空纤维的内腔中; 并培养细胞。这提供了用肝炎病毒如HBV或HCV感染体外培养细胞，然后增殖肝炎病毒的实验系统。

10. 发明申请

US20090148832A1 Compositions and Methods for Generation of Infectious Hepatitis C Virus in Immortalized Human Hepatocytes 审中-公开
标题翻译：在永生化人肝细胞中产生传染性丙型肝炎病毒的组合物和方法
公开(公告)号：US20090148832A1
公开(公告)日：2009-06-11
申请号：US12365523
申请日：2009-02-04
申请人： RATNA RAY , RANJIT RAY , ARNAB BASU , TATSUO KANDA
发明人： RATNA RAY , RANJIT RAY , ARNAB BASU , TATSUO KANDA
IPC分类号： C12Q1/70 , C12N7/00
CPC分类号： C12N7/00 , A61K2039/525 , C12N2770/24251 , C12Q1/18 , G01N33/5067 , G01N2333/18
摘要： The present invention provides a cell line capable producing infectious hepatitis C virus 1a (HCV 1a) particles in culture. Disclosed are compositions and methods for an HCV 1a (clone H77) transfected immortal human hepatocyte (IHH) capable of generating infectious HCV 1a virus particles in culture. Also disclosed are methods of using the cell line, or HCV 1a virus particles derived from said cell line, to screen for potential therapeutic agents which interfere with HCV 1a virus propagation to treat hepatic disease.
摘要翻译：本发明提供了一种在培养中能够产生感染性丙型肝炎病毒1a（HCV1a）颗粒的细胞系。公开了能够在培养中产生感染性HCV 1a病毒颗粒的HCV 1a（克隆H77）转染的永生人肝细胞（IHH）的组合物和方法。还公开了使用细胞系或源自所述细胞系的HCV 1a病毒颗粒筛选干扰HCV 1a病毒繁殖以治疗肝脏疾病的潜在治疗剂的方法。

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