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1. 发明公开

EP2828382A1 HCV FULL-LENGTH INFECTIOUS CELL CULTURE SYSTEMS AND APPLICATIONS THEREOF 有权
标题翻译：用全长与感染HCV -ZELLKULTURSYSTEME及其用途
公开(公告)号：EP2828382A1
公开(公告)日：2015-01-28
申请号：EP13712475.6
申请日：2013-03-15
申请人： Hvidovre Hospital , Københavns Universitet
发明人： LI, Yiping , SCHEEL, Troels Kasper Høyer , ALMEIDA, Santseharay Ramirez , GOTTWEIN, Judith M. , BUKH, Jens
IPC分类号： C12N7/00 , G01N33/576
CPC分类号： C12N7/00 , C12N2770/24221 , C12N2770/24234 , C12N2770/24252 , C12N2770/24271 , C12Q1/707 , C12Q2600/156 , C12Q2600/158
摘要： The present invention relates to nucleic acid sequences that encode hepatitis C viruses (HCV) that are useful in the fundamental research of HCV as well as in the search of a vaccine against HCV. In particular the present invention relates to nucleic acid sequences that comprises HCVs which are capable of expressing said virus when transfected into cells and are capable of infectivity in vivo.

2. 发明公开

EP3212775A1 OPTIMIZED HCV FULL-LENGTH INFECTIOUS CELL CULTURE SYSTEMS AND APPLICATIONS THEREOF 有权
标题翻译：优化的HCV全长感染细胞培养系统及其应用
公开(公告)号：EP3212775A1
公开(公告)日：2017-09-06
申请号：EP15790825.2
申请日：2015-10-23
申请人： Hvidovre Hospital , Københavns Universitet
发明人： BUKH, Jens , LI, Yiping , ALMEIDA, Santseharay Ramirez
IPC分类号： C12N7/00 , C12N15/40 , C12N5/10 , G01N33/50
CPC分类号： C12N7/00 , C12N2770/24221 , C12N2770/24222 , C12N2770/24251 , C12Q1/70 , G01N2500/04
摘要： The present invention relates to nucleic acid sequences that encode hepatitis C viruses (HCV) that are useful in the fundamental research of HCV as well as in the search of a vaccine against HCV. In particular the present invention relates to nucleic acid sequences that comprises HCVs which are capable of expressing said virus when transfected into cells and are capable of infectivity in vivo.
摘要翻译：本发明涉及编码丙型肝炎病毒（HCV）的核酸序列，其可用于HCV的基础研究以及寻找针对HCV的疫苗。特别地，本发明涉及包含当转染到细胞中时能够表达所述病毒且能够在体内感染的HCV的核酸序列。

3. 发明授权

EP2828382B1 HCV FULL-LENGTH INFECTIOUS CELL CULTURE SYSTEMS AND APPLICATIONS THEREOF 有权
标题翻译：用全长与感染HCV -ZELLKULTURSYSTEME及其用途
公开(公告)号：EP2828382B1
公开(公告)日：2016-10-26
申请号：EP13712475.6
申请日：2013-03-15
申请人： Hvidovre Hospital , Københavns Universitet
发明人： LI, Yiping , SCHEEL, Troels Kasper Høyer , ALMEIDA, Santseharay Ramirez , GOTTWEIN, Judith M. , BUKH, Jens
IPC分类号： C12N7/00 , G01N33/576
CPC分类号： C12N7/00 , C12N2770/24221 , C12N2770/24234 , C12N2770/24252 , C12N2770/24271 , C12Q1/707 , C12Q2600/156 , C12Q2600/158

5. 发明公开

EP2483396A2 JFH-1 BASED HCV CELL CULTURE SYSTEMS FOR NS5A OF GENOTYPES 1-7 审中-公开
标题翻译： JFH-1 HCV-BASED细胞培养系统NS5A基因型1-7
公开(公告)号：EP2483396A2
公开(公告)日：2012-08-08
申请号：EP10793294.9
申请日：2010-10-01
申请人： Hvidovre Hospital , Københavns Universitet
发明人： SCHEEL, Troels Kasper, Hoyer , GOTTWEIN, Judith, M. , JENSEN, Tanja, Bertelsen , BUKH, Jens
IPC分类号： C12N7/00 , C07K14/18 , A61K39/29 , G01N33/50 , C12N7/02
CPC分类号： C12N7/00 , A61K39/00 , C07K14/005 , C12N2770/24222 , C12N2770/24251 , C12Q1/18 , G01N33/56983 , G01N2333/18
摘要： The present inventors developed hepatitis C virus recombinants expressing NS5A from genotype Ia, 1b, 2a, 3a, 4a, 5a, 6a or 7a in the context of a genotype 2a backbone. Additional recombinants express NS5A and the structural proteins (Core, E1 and E2), p7 and NS2 from genotype 1a, 1b, 3a, 4a, 5a, 6a or 7a in the genotype 2a backbone. Sequence analysis of the recombinants recovered after viral passage in Huh7.5 cells revealed adaptive mutations in NS5A and/or NS3. The importance of these mutations for improved growth kinetics was shown in reverse genetic studies.

6. 发明公开

EP2344647A1 HEPATITIS C VIRUS EXPRESSING REPORTER TAGGED NS5A PROTEIN 审中-公开
标题翻译： NS5A-PROTEIN MIT REPORTER-TAG EXPRIMIERENDES HEPATITIS-C-VIRUS
公开(公告)号：EP2344647A1
公开(公告)日：2011-07-20
申请号：EP09736116.6
申请日：2009-10-05
申请人： Hvidovre Hospital , Københavns Universitet
发明人： GOTTWEIN, Judith M. , SCHEEL, Troels Kasper Høyer , BUKH, Jens , PRENTØ, Jannick , JENSEN, Tanja Bertelsen , LADEMANN, Jacob Bo , LI, Yiping
IPC分类号： C12N15/86 , C12N7/02 , A61K39/29 , C07K14/18
CPC分类号： C12N15/86 , A61K2039/525 , C07K14/005 , C12N7/00 , C12N2770/24222 , C12N2770/24243 , C12N2770/24251
摘要： The present inventors developed hepatitis C reporter viruses containing Core through NS2 of prototype isolates of all major HCV genotypes and the remaining genes of isolate JFH1, by insertion of reporter genes in domain III of HCV NS5A. The inventors have identified a deletion upstream of the inserted reporter gene sequence, which conferred favourable growth kinetics in Huh7.5 cells to these viruses. These reporter viruses can be used for high throughput analysis of drug and vaccine candidates as well as patient samples. Drugs could be evaluated for their potential to prevent infection or cure infected cells. The neutralizing capacity of antibodies induced by vaccine candidates could be evaluated in order to define successful vaccination strategies. Broadly neutralizing antibodies could be identified testing engineered antibodies and antibodies derived from serum of HCV infected individuals; thus this technique could contribute to the development of immunotherapy. The developed systems could aid individualized treatment of HCV infected: Patient isolates could be tested for resistance to drugs by introduction of genome regions involved in drug resistance in the developed constructs and subsequent treatment with the drug of interest. The present inventorsalso developed JFH1-based intergenotypic recombinants with genotype specific homotypic 5UTR, or heterotypic 5'UTR (either of genotype 1a (strain H77) or of genotype 3a (strain S52)). The present inventors additionallydeveloped J6/JFH1 recombinants with the 5'UTR of genotypes 1-6. These recombinants with different 5UTRs are a useful to study the function of the 5'UTR in a genotype specific manner.
摘要翻译：开发了通过在HCV NS5A的结构域III插入报道基因，通过NS2的核心通过NS2的所有主要HCV基因型的原型分离物和分离物JFH1的剩余基因的丙型肝炎报告病毒。插入的报道基因序列上游的缺失在Huh7.5细胞中赋予这些病毒有利的生长动力学。这些报告病毒可用于药物和疫苗候选物以及患者样品的高通量分析。还开发了具有基因型特异性同型5'UTR或异型5'UTR（基因型1a（菌株H77）或基因型3a（菌株S52））的基于JFH1的间基型重组体。本发明人还开发了具有基因型1-6的5'UTR的J6 / JFH1重组体。具有不同5'UTR的这些重组体可用于以基因型特异性方式研究5'UTR的功能。

7. 发明授权

EP3027740B1 HIGH-TITER HCV FULL-LENGTH GENOTYPE 2B INFECTIOUS CELL CULTURE SYSTEMS AND APPLICATIONS THEREOF 有权
公开(公告)号：EP3027740B1
公开(公告)日：2019-10-09
申请号：EP14750437.7
申请日：2014-07-28
申请人： Hvidovre Hospital
发明人： ALMEIDA, Santseharay Ramirez , LI, Yiping , GOTTWEIN, Judith M. , BUKH, Jens
IPC分类号： C12N7/00 , C07K14/005

8. 发明公开

EP2235164A1 EFFICIENT CELL CULTURE SYSTEM FOR HEPATITIS C VIRUS GENOTYPE 1A AND 1B 审中-公开
标题翻译：高效的培养体系丙肝病毒基因型1a和1b
公开(公告)号：EP2235164A1
公开(公告)日：2010-10-06
申请号：EP08863498.5
申请日：2008-12-19
申请人： Hvidovre Hospital
发明人： SCHEEL, Troels Kasper Høyer , GOTTWEIN, Judith M. , PRENTØ, Jannick , JENSEN, Tanja Bertelsen , BUKH, Jens
IPC分类号： C12N7/00 , A61K39/29 , C07K14/18
CPC分类号： C12N7/00 , A61K39/12 , A61K39/29 , A61K2039/525 , A61K2039/53 , C07K14/005 , C12N2770/24221 , C12N2770/24222 , C12N2770/24234
摘要： The present inventors developed hepatitis C virus la/2a and lb/2a intergenotypic recombinants in which the JFHl structural genes (Core, El and E2), p7 and NS2 were replaced by the corresponding genes of the genotype Ia reference strain H77C or TN or the corresponding genes of the genotype Ib reference strain J4. Sequence analysis of recovered la/2a and lb/2a recombinants from 2 serial passages and subsequent reverse genetic studies revealed adaptive mutations in e.g. p7, NS2 and/or NS3. In addition, the inventors demonstrate the possibility of using adaptive mutations identified for one HCV isolate in generating efficient cell culture systems for other isolates by transfer of mutations across isolates, subtypes or major genotypes. Furthermore neutralization studies showed that viruses of e.g. genotype 1 were efficiently neutralized by genotype Ia, 4a and 5a serum, an effect that could be utilized e.g. in vaccine development and immunological prophylaxis. The inventors in addition demonstrate the use of the developed systems for screening of antiviral substances in vitro and functional studies of the virus, e.g. identification of receptors required for HCV entry,

9. 发明公开

EP2482846A1 INFECTIOUS HEPATITIS C VIRUSES OF GENOTYPE 3A AND 4A AND USES THEREOF 有权
标题翻译：感染性丙型肝炎病毒基因型3a和4a及其使用
公开(公告)号：EP2482846A1
公开(公告)日：2012-08-08
申请号：EP10754407.4
申请日：2010-09-16
申请人： Hvidovre Hospital , The United States Of America, As Represented By The Secretary, Department of Health and Human Services
发明人： GOTTWEIN, Judith, M. , SCHEEL, Troels Kasper Høyer , PURCELL, Robert , BUKH, Jens
IPC分类号： A61K39/29 , C12N7/00
CPC分类号： C12Q1/18 , C12N7/00 , C12N15/86 , C12N2770/24221 , C12N2770/24243 , C12Q1/707 , G01N33/5008
摘要： The present invention relates to molecular approaches to the production of nucleic acid sequences, which comprises the genome of infectious hepatitis C virus. In particular, invention provides nucleic acid sequences which comprise the genomes of infectious hepatitis C viruses of either genotype 3a (strain S52) or genotype 4a (strain ED43). The invention therefore relates to the use of the nucleic acid sequences and polypeptides encoded by all or part of the sequences in the development of vaccines and diagnostic assays for HCV and in the development of screening assays for the identification of antiviral agents for HCV. The invention therefore also relates to the use of viral particles derived from laboratory animals infected with S52 and ED43 viruses.

10. 发明公开

EP3060655A2 NOVEL HCV CULTURE SYSTEMS AND DIRECT-ACTING ANTIVIRAL SENSITIVITY 有权
标题翻译：新HCV培养系统和直接作用的抗病灵敏度
公开(公告)号：EP3060655A2
公开(公告)日：2016-08-31
申请号：EP14792379.1
申请日：2014-10-21
申请人： Hvidovre Hospital
发明人： LI, Yiping , ALMEIDA, Santseharay Ramirez , HUMES, Daryl Grant , GOTTWEIN, Judith M. , BUKH, Jens
IPC分类号： C12N7/00 , A61K39/12 , G01N33/53 , C07K16/10
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.

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