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1. 发明申请

US20110076760A1 Viral expression plasmids for production of proteins, antibodies, enzymes, virus-like particles and for use in cell-based assays 有权
标题翻译：用于生产蛋白质，抗体，酶，病毒样颗粒和用于基于细胞的测定中的病毒表达质粒
公开(公告)号：US20110076760A1
公开(公告)日：2011-03-31
申请号：US12803831
申请日：2010-07-07
申请人： Toomas Silla , Ingrid Tagen , Anne Kalling , Radi Tegova , Mart Ustav , Tiiu Mandel , Urve Toots , Andres Tover , Aare Abroi , Ene Ustav , Jelizaveta Geimanen , Kadri Janikson
发明人： Toomas Silla , Ingrid Tagen , Anne Kalling , Radi Tegova , Mart Ustav , Tiiu Mandel , Urve Toots , Andres Tover , Aare Abroi , Ene Ustav , Jelizaveta Geimanen , Kadri Janikson
IPC分类号： C12N5/10 , C12N15/63
CPC分类号： C12N15/85 , A61K48/00 , C07K14/005 , C12N7/00 , C12N15/86 , C12N2710/16222 , C12N2710/16244 , C12N2710/22022 , C12N2710/22044 , C12N2740/16023 , C12N2800/108 , C12N2800/40 , C12N2820/10 , C12N2820/60
摘要： This disclosure shows that the EBV FR-element comprised of EBNA1 multimeric binding sites can provide the stable maintenance replication function to the mouse polyomavirus (PyV) core origin plasmids in the presence of BPV-1 E2 protein and PyV large T-antigen (LT).
摘要翻译：本公开显示，在BPV-1 E2蛋白和PyV大T抗原（LT）存在下，由EBNA1多聚体结合位点组成的EBV FR元件可以为小鼠多瘤病毒（PyV）核心起始质粒提供稳定的维持复制功能，。

2. 发明授权

US08377653B2 Viral expression plasmids for production of proteins, antibodies, enzymes, virus-like particles and for use in cell-based assays 有权
公开(公告)号：US08377653B2
公开(公告)日：2013-02-19
申请号：US12803831
申请日：2010-07-07
申请人： Toomas Silla , Ingrid Tagen , Anne Kalling , Radi Tegova , Mart Ustav , Tiiu Mandel , Urve Toots , Andres Tover , Aare Abroi , Ene Ustav , Jelizaveta Geimanen , Kadri Janikson
发明人： Toomas Silla , Ingrid Tagen , Anne Kalling , Radi Tegova , Mart Ustav , Tiiu Mandel , Urve Toots , Andres Tover , Aare Abroi , Ene Ustav , Jelizaveta Geimanen , Kadri Janikson
IPC分类号： C12N5/10 , C12N15/00
CPC分类号： C12N15/85 , A61K48/00 , C07K14/005 , C12N7/00 , C12N15/86 , C12N2710/16222 , C12N2710/16244 , C12N2710/22022 , C12N2710/22044 , C12N2740/16023 , C12N2800/108 , C12N2800/40 , C12N2820/10 , C12N2820/60
摘要： This disclosure shows that the EBV FR-element comprised of EBNA1 multimeric binding sites can provide the stable maintenance replication function to the mouse polyomavirus (PyV) core origin plasmids in the presence of BPV-1 E2 protein and PyV large T-antigen (LT).

3. 发明授权

US07790446B2 Vectors, cell lines and their use in obtaining extended episomal maintenance replication of hybrid plasmids and expression of gene products 有权
标题翻译：载体，细胞系及其用于获得杂交质粒的延长的附加型维持复制和基因产物的表达
公开(公告)号：US07790446B2
公开(公告)日：2010-09-07
申请号：US11351809
申请日：2006-02-10
申请人： Toomas Silla , Ingrid Tagen , Jelizaveta Geimanen , Kadri Janikson , Aare Abroi , Ene Ustav , Mart Ustav , Tiiu Mandel
发明人： Toomas Silla , Ingrid Tagen , Jelizaveta Geimanen , Kadri Janikson , Aare Abroi , Ene Ustav , Mart Ustav , Tiiu Mandel
IPC分类号： C12N15/00 , C12N15/113 , C07H21/04
CPC分类号： C12N15/85 , A61K48/00 , C07K14/005 , C12N7/00 , C12N15/86 , C12N2510/02 , C12N2710/20022 , C12N2710/22022 , C12N2800/108 , C12N2820/60
摘要： This disclosure shows that the BPV-1 E2 protein-dependent minichromosome maintenance element (MME) comprised of E2 multimeric binding sites can provide the stable maintenance replication function to the mouse polyomavirus (PyV) core origin plasmids in the presence of BPV-1 E2 protein and PyV large T-antigen (LT). MME dependent plasmids are lost with the frequency of 6% per generation. Significantly long stable maintenance replication can also be provided without selection pressure. We also demonstrate that PyV core origin maintenance function/replication activation could be provided by Epstein-Barr virus Family of repeats and EBNA1 protein. The maintenance of the Polyomavirus core origin plasmid was characterized by 13% loss of the plasmid during one cell generation in the case of EBV FR harboring plasmids. Our data clearly indicate that maintenance functions from different viruses can provide segregation/partitioning function to different heterologous origins in variety of cells and can be used in expression of gene products.
摘要翻译：本公开显示，由E2多聚体结合位点组成的BPV-1 E2蛋白依赖性微染色体维持元件（MME）可在BPV-1 E2蛋白存在下为小鼠多瘤病毒（PyV）核心质粒提供稳定的维持复制功能和PyV大T抗原（LT）。 MME依赖质粒以每代6％的频率丢失。也可以在没有选择压力的情况下提供显着长的稳定维护复制。我们还证明，可以由Epstein-Barr病毒家族重复和EBNA1蛋白提供PyV核心起源维持功能/复制激活。在EBV FR携带质粒的情况下，在单细胞产生期间，多瘤病毒核心起源质粒的维持表征为质粒损失13％。我们的数据清楚地表明，不同病毒的维护功能可以为多种细胞中的不同异源起源提供分离/分配功能，可用于基因产物的表达。

4. 发明申请

US20060183230A1 Vectors, cell lines and their use in obtaining extended episomal maintenance replication of hybrid plasmids and expression of gene products 有权
标题翻译：载体，细胞系及其用于获得杂交质粒的延长的附加型维持复制和基因产物的表达
公开(公告)号：US20060183230A1
公开(公告)日：2006-08-17
申请号：US11351809
申请日：2006-02-10
申请人： Toomas Silla , Ingrid Tagen , Jelizaveta Geimanen , Kadri Janikson , Aare Abroi , Ene Ustav , Mart Ustav , Tiiu Mandel
发明人： Toomas Silla , Ingrid Tagen , Jelizaveta Geimanen , Kadri Janikson , Aare Abroi , Ene Ustav , Mart Ustav , Tiiu Mandel
IPC分类号： C12N15/86
CPC分类号： C12N15/85 , A61K48/00 , C07K14/005 , C12N7/00 , C12N15/86 , C12N2510/02 , C12N2710/20022 , C12N2710/22022 , C12N2800/108 , C12N2820/60
摘要： This disclosure shows that the BPV-1 E2 protein-dependent minichromosome maintenance element (MME) comprised of E2 multimeric binding sites can provide the stable maintenance replication function to the mouse polyomavirus (PyV) core origin plasmids in the presence of BPV-1 E2 protein and PyV large T-antigen (LT). MME dependent plasmids are lost with the frequency of 6% per generation. Significantly long stable maintenance replication can also be provided without selection pressure. We also demonstrate that PyV core origin maintenance function/replication activation could be provided by Epstein-Barr virus Family of repeats and EBNA1 protein. The maintenance of the Polyomavirus core origin plasmid was characterized by 13% loss of the plasmid during one cell generation in the case of EBV FR harboring plasmids. Our data clearly indicate that maintenance functions from different viruses can provide segregation/partitioning function to different heterologous origins in variety of cells and can be used in expression of gene products.
摘要翻译：本公开显示，由E2多聚体结合位点组成的BPV-1 E2蛋白依赖性微染色体维持元件（MME）可在BPV-1 E2蛋白存在下为小鼠多瘤病毒（PyV）核心质粒提供稳定的维持复制功能和PyV大T抗原（LT）。 MME依赖质粒以每代6％的频率丢失。也可以在没有选择压力的情况下提供显着长的稳定维护复制。我们还证明，可以由Epstein-Barr病毒家族重复和EBNA1蛋白提供PyV核心起源维持功能/复制激活。在EBV FR携带质粒的情况下，在单细胞产生期间，多瘤病毒核心起源质粒的维持表征为质粒损失13％。我们的数据清楚地表明，不同病毒的维护功能可以为多种细胞中的不同异源起源提供分离/分配功能，可用于基因产物的表达。

5. 发明申请

US20050026137A1 Novel expression vectors and uses thereof 有权
标题翻译：新型表达载体及其用途
公开(公告)号：US20050026137A1
公开(公告)日：2005-02-03
申请号：US10476615
申请日：2002-05-03
申请人： Kai Krohn , Vesna Blazevic , Marja Tahtinen , Mart Ustav , Urve Toots , Andres Mannjk , Annamari Ranki , Ene Ustav
发明人： Kai Krohn , Vesna Blazevic , Marja Tahtinen , Mart Ustav , Urve Toots , Andres Mannjk , Annamari Ranki , Ene Ustav
IPC分类号： A61K48/00 , C12N15/85 , C12Q1/70 , C12N15/86
CPC分类号： C07K14/005 , A61K48/00 , A61K2039/53 , C12N15/85 , C12N2800/108 , C12N2830/42 , C12N2840/20 , C12N2840/203
摘要： The present invention relates to novel vectors, to DNA vaccines and gene therapeutics containing said vectors, to methods for the preparation of the vectors and DNA vaccines and gene therapeutics containing the vectors, and to therapeutic uses of said vectors. More specifically, the present invention relates to novel vectors comprising (a) an expression cassette of a gene of a nuclear-anchoring protein, which contains (i) a DNA binding domain capable of binding to a specific DNA sequence and (ii) a functional domain capable of binding to a nuclear component and (b) a multimerized DNA sequence forming a binding site for the anchoring protein, and optionally (c) one or more expression cassettes of a DNA sequence of interest. In particular the invention relates to vectors that lack a papilloma virus origin of replication. The nuclear-anchoring protein might be the E2 protein of Bovine Papilloma Virus type 1 or Epstein-Barr Virus Nuclear Antigen 1. The invention also relates to vectors that lack an origin of replication functional in a mammalian cell. The invention further relates to methods for expressing a DNA sequence of interest in a subject.
摘要翻译：本发明涉及新载体，DNA疫苗和含有所述载体的基因治疗剂，用于制备载体和DNA疫苗的方法以及含有载体的基因治疗剂以及所述载体的治疗用途。更具体地说，本发明涉及包含（a）核锚定蛋白基因的表达盒的新载体，其包含（i）能够结合特定DNA序列的DNA结合结构域和（ii）功能性能够结合核组分的结构域和（b）形成锚定蛋白的结合位点的多聚化DNA序列，以及任选（c）感兴趣的DNA序列的一个或多个表达盒。特别地，本发明涉及缺乏乳头瘤病毒复制起点的载体。核锚定蛋白可能是牛乳头瘤病毒1型或爱泼斯坦 - 巴尔病毒核抗原1的E2蛋白。本发明还涉及在哺乳动物细胞中缺乏复制起点的载体。本发明还涉及在受试者中表达感兴趣的DNA序列的方法。

6. 发明授权

US07510718B2 Expression vectors and uses thereof 有权
标题翻译：表达载体及其用途
公开(公告)号：US07510718B2
公开(公告)日：2009-03-31
申请号：US10476615
申请日：2002-05-03
申请人： Kai Krohn , Vesna Blazevic , Marja Tahtinen , Mart Ustav , Urve Toots , Andres Mannik , Annamari Ranki , Ene Ustav
发明人： Kai Krohn , Vesna Blazevic , Marja Tahtinen , Mart Ustav , Urve Toots , Andres Mannik , Annamari Ranki , Ene Ustav
IPC分类号： A61K39/00 , A61K39/40 , A61K39/42 , A61K39/295 , A61K39/385 , A61K49/00 , C12Q1/70 , C12N15/00
CPC分类号： C07K14/005 , A61K48/00 , A61K2039/53 , C12N15/85 , C12N2800/108 , C12N2830/42 , C12N2840/20 , C12N2840/203
摘要： The present invention relates to novel vectors, to DNA vaccines and gene therapeutics containing the vectors, to methods for the preparation of the vectors and DNA vaccines and gene therapeutics containing the vectors, and to therapeutic uses of the vectors. The novel vectors comprise (a) an expression cassette of a gene of a nuclear-anchoring protein, which contains (i) a DNA binding domain capable of binding to a specific DNA sequence and (ii) a functional domain capable of binding to a nuclear component and (b) a multimerized DNA sequence forming a binding site for the anchoring protein, and optionally (c) one or more expression cassettes of a DNA sequence of interest. The vectors lack a papilloma virus origin of replication.
摘要翻译：本发明涉及新载体，DNA疫苗和含有载体的基因治疗剂，载体和DNA疫苗的制备方法和含有载体的基因治疗剂以及载体的治疗用途。新载体包含（a）核锚定蛋白基因的表达盒，其包含（i）能够结合特异性DNA序列的DNA结合结构域和（ii）能够结合核的功能结构域组分和（b）形成锚定蛋白的结合位点的多聚DNA序列，以及（c）感兴趣的DNA序列的一个或多个表达盒。载体缺乏乳头瘤病毒复制起点。

7. 发明授权

US07498314B2 Expression vectors and uses thereof 有权
标题翻译：表达载体及其用途
公开(公告)号：US07498314B2
公开(公告)日：2009-03-03
申请号：US10138098
申请日：2002-05-03
申请人： Kai Krohn , Vesna Blazevic , Marja Tähtinen , Mart Ustav , Urve Toots , Andres Männik , Annamari Ranki , Ene Ustav
发明人： Kai Krohn , Vesna Blazevic , Marja Tähtinen , Mart Ustav , Urve Toots , Andres Männik , Annamari Ranki , Ene Ustav
IPC分类号： A61K48/00 , A61K31/711 , C07H21/04 , C12N5/10 , C12N1/21 , C12P21/00
CPC分类号： C07K14/005 , A61K48/00 , A61K2039/53 , C12N15/85 , C12N2800/108 , C12N2830/42 , C12N2840/20 , C12N2840/203
摘要： The present invention relates to novel vectors, to DNA vaccines and gene therapeutics containing said vectors, to methods for the preparation of the vectors and DNA vaccines and gene therapeutics, and to therapeutic uses of said vectors. More specifically, the present invention relates to novel vectors comprising an expression cassette of a gene of a nuclear-anchoring protein, which contains a DNA binding domain capable of binding to a specific DNA sequence and a functional domain capable of binding to a nuclear component and a multimerized DNA sequence forming a binding site for the nuclear-anchoring protein, and optionally an expression cassette of a gene, genes or a DNA sequence or DNA sequences of interest. The present invention further relates to DNA vaccines and gene therapeutics containing the novel vectors, to methods for the preparation of the novel vectors and the DNA vaccines and gene therapeutics.
摘要翻译：本发明涉及新型载体，DNA疫苗和含有所述载体的基因治疗剂，用于制备载体和DNA疫苗和基因治疗剂的方法以及所述载体的治疗用途。更具体地，本发明涉及包含核锚定蛋白的基因的表达盒的新载体，其包含能够结合特定DNA序列的DNA结合结构域和能够结合核成分的功能结构域，形成核 - 锚定蛋白的结合位点的多聚DNA序列，以及任选的基因的表达盒，感兴趣的DNA序列或DNA序列。本发明还涉及含有新载体的DNA疫苗和基因治疗剂，用于制备新载体和DNA疫苗和基因治疗剂的方法。

8. 发明申请

US20100279416A1 METHOD FOR INTRODUCING CHANGES INTO A EUKARYOTIC GENOME IN VIVO AND A KIT 审中-公开
标题翻译：将变化引入体内和体内的原核生物基因组的方法
公开(公告)号：US20100279416A1
公开(公告)日：2010-11-04
申请号：US12593558
申请日：2008-03-27
申请人： Mart Ustav , Ene Ustav , Meelis Kadaja , Alina Sumerina
发明人： Mart Ustav , Ene Ustav , Meelis Kadaja , Alina Sumerina
IPC分类号： C12N15/86 , C12N15/63
CPC分类号： C12N15/86 , C12N2510/00 , C12N2710/20043 , C12N2800/80
摘要： The invention relates to a method for introducing changes into a eukaryotic genome in vivo wherein the HPV genome, which comprises HPV replication origin sequence, is used together with HPV early proteins in order to achieve DNA replication in vivo. There is also disclosed a kit for in vivo amplification, excision, translocation and/or inversion of a DNA sequence, which comprises a vector carrying HPV genome or a part of HPV genome including HPV replication origin sequence, and expression vector or vectors encoding HPV early proteins.
摘要翻译：本发明涉及一种用于将体内引入变体进入体内的真核基因组的方法，其中包含HPV复制起始序列的HPV基因组与HPV早期蛋白一起使用以在体内实现DNA复制。还公开了用于DNA序列的体内扩增，切除，易位和/或倒位的试剂盒，其包含携带HPV基因组的载体或包含HPV复制起始序列的HPV基因组的一部分，以及编码HPV早期的表达载体或载体蛋白质。

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