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1. 发明授权

US07410799B2 In vivo production and delivery of erythropoietin or insulinotropin for gene therapy 有权
标题翻译：红细胞生成素或促胰岛素的体内产生和递送用于基因治疗
公开(公告)号：US07410799B2
公开(公告)日：2008-08-12
申请号：US10885899
申请日：2004-07-07
申请人： Richard F Selden , Douglas Treco , Michael W. Heartlein
发明人： Richard F Selden , Douglas Treco , Michael W. Heartlein
IPC分类号： C12N5/08
CPC分类号： C12N15/907 , A61K47/6901 , A61K48/00 , C07K14/505 , C07K14/605 , C07K14/61 , C07K2319/02 , C12N15/85 , C12N2510/02 , C12N2800/108 , C12N2830/002 , C12N2830/85 , C12N2840/20 , C12N2840/44
摘要： The present invention relates to transfected primary and secondary somatic cells of vertebrate origin, particularly mammalian origin, transfected with exogenous genetic material (DNA) which encodes erythropoietin or an insulinotropin [e.g., derivatives of glucagon-like peptide 1 (GLP-1)], methods by which primary and secondary cells are transfected to include exogenous genetic material encoding erythropoietin or an insulinotropin, methods of producing clonal cell strains or heterogenous cell strains which express erythropoietin or an insulinotropin, methods of gene therapy in which the transfected primary or secondary cells are used, and methods of producing antibodies using the transfected primary or secondary cells. The present invention also includes primary and secondary somatic cells, such as fibroblasts, keratinocytes, epithelial cells, endothelial cells, glial cells, neural cells, formed elements of the blood, muscle cells, other somatic cells, which can be cultured and somatic cell precursors, which have been transfected with exogenous DNA encoding EPO or an insulinotropin, which is stably integrated into their genomes or is expressed in the cells episomally.
摘要翻译：本发明涉及用编码促红细胞生成素或促胰岛素（例如，胰高血糖素样肽1（GLP-1）的衍生物）的外源遗传物质（DNA）转染的脊椎动物来源的转基因和次要体细胞，特别是哺乳动物来源，转染初级细胞和次级细胞的方法包括编码促红细胞生成素或促胰岛激素的外源性遗传物质，产生克隆细胞株或表达促红细胞生成素或促胰岛激素的异源细胞株的方法，转染的原代细胞或次要细胞是基因治疗方法使用，以及使用转染的一次或二次细胞产生抗体的方法。本发明还包括初级和次级体细胞，例如成纤维细胞，角质形成细胞，上皮细胞，内皮细胞，神经胶质细胞，神经细胞，形成的血液元素，肌肉细胞，可培养的其他体细胞和体细胞前体其已经用编码EPO或促胰岛素的外源DNA转染，其稳定整合到其基因组中或者在细胞中以表观形式表达。

2. 发明授权

US06355241B1 In vivo production and delivery of erythropoietin 有权
标题翻译：红细胞生成素的体内生产和递送
公开(公告)号：US06355241B1
公开(公告)日：2002-03-12
申请号：US09420861
申请日：1999-10-19
申请人： Richard F Selden , Douglas Treco , Michael W. Heartlein
发明人： Richard F Selden , Douglas Treco , Michael W. Heartlein
IPC分类号： A01N6300
CPC分类号： C12N15/907 , A61K47/6901 , A61K48/00 , C07K14/505 , C07K14/605 , C07K14/61 , C07K2319/02 , C12N15/85 , C12N2510/02 , C12N2800/108 , C12N2830/002 , C12N2830/85 , C12N2840/20 , C12N2840/44
摘要： The present invention relates to transfected primary and secondary somatic cells of vertebrate origin, particularly mammalian origin, transfected with exogenous genetic material (DNA) which encodes erythropoietin or an insulinotropin [e.g., derivatives of glucagon-like peptide 1(GLP-1)], methods by which primary and secondary cells are transfected to include exogenous genetic material encoding erythropoietin or an insulinotropin, methods of producing clonal cell strains or heterogenous cell strains which express eruthropoietin or an insulinotropin, methods of gene therapy in which the transfected primary or secondary cells are used, and methods of producing antibodies using the transfected primary or secondary cells. The present invention includes primary and secondary somatic cells, such as fibroblasts, keratinocytes, epithelial cells, endothelial cells, glial cells, neural cells, formed elements of the blood, muscle cells, other somatic cells which can be cultured and somatic cell precursors, which have been transfected with exogenous DNA encoding EPO or an insulinotropin, which is stably integrated into their genomes or is expressed in the cells episomally.
摘要翻译：本发明涉及用编码促红细胞生成素或促胰岛素（例如，胰高血糖素样肽1（GLP-1）的衍生物）的外源遗传物质（DNA）转染的脊椎动物来源的转基因和次要体细胞，特别是哺乳动物来源，转染初级细胞和次级细胞的方法包括编码促红细胞生成素或促胰岛激素的外源性遗传物质，产生克隆细胞株的方法或表达促生长素激素或促胰岛激素的异源细胞株，转染的原代细胞或二次细胞是基因治疗方法使用的方法和使用转染的原代细胞或二次细胞产生抗体的方法。本发明包括原代和次要体细胞，例如成纤维细胞，角质形成细胞，上皮细胞，内皮细胞，神经胶质细胞，神经细胞，形成的血液元素，肌肉细胞，可以培养的其他体细胞和体细胞前体已经用编码EPO或促胰岛素的外源DNA转染的游标，其稳定地整合到其基因组中或者在细胞中以表观形式表达。

3. 发明授权

US06303379B1 Vivo protein production and delivery system for gene therapy 有权
标题翻译：用于基因治疗的体内蛋白质生产和递送系统
公开(公告)号：US06303379B1
公开(公告)日：2001-10-16
申请号：US09354883
申请日：1999-07-16
申请人： Richard F Selden , Douglas Treco , Michael W. Heartlein
发明人： Richard F Selden , Douglas Treco , Michael W. Heartlein
IPC分类号： C12N510
CPC分类号： A01K67/0275 , A01K2217/05 , A61K9/0024 , A61K38/27 , A61K38/28 , A61K47/6901 , A61K48/00 , C07K14/505 , C07K14/605 , C07K14/61 , C07K14/62 , C07K16/26 , C07K2319/02 , C12N15/85 , C12N15/907 , C12N2510/02 , C12N2830/002 , C12N2830/85 , C12N2840/44
摘要： The present invention relates to transfected primary and secondary somatic cells of vertebrate origin, particularly mammalian origin, transfected with exogenous genetic material (DNA) which encodes a desired (e.g., a therapeutic) product or is itself a desired (e.g., therapeutic) product, methods by which primary and secondary cells are transfected to include exogenous genetic material, methods of producing clonal cell strains or heterogenous cell strains, methods of gene therapy in which the transfected primary or secondary cells are used, and methods of producing antibodies using the transfected primary or secondary cells. The present invention includes primary and secondary somatic cells, such as fibroblasts, keratinocytes, epithelial cells, endothelial cells, glial cells, neural cells, formed elements of the blood, muscle cells, other somatic cells which can be cultured and somatic cell precursors, which have been transfected with exogenous DNA which is stably integrated into their genomes or is expressed in the cells episomally. The exogenous DNA either encodes a product, such as a translational product (e.g., a protein) or a transcriptional product (e.g., a ribozyme or an anti-sense nucleic acid sequence) which is a therapeutic product or is itself a therapeutic product (e.g., DNA which binds to a cellular regulatory protein or alters gene expression).
摘要翻译：本发明涉及用编码期望（例如治疗性）产品或本身是所需（例如治疗性）产品的外源性遗传物质（DNA）转染的脊椎动物来源的转染的初级和次级体细胞，特别是哺乳动物来源，转染初级细胞和次级细胞以包括外源遗传物质的方法，产生克隆细胞株或异源细胞株的方法，使用转染的原代细胞或次级细胞的基因治疗方法，以及使用转染的原代细胞或二次细胞。本发明包括初级和次级体细胞，例如成纤维细胞，角质形成细胞，上皮细胞，内皮细胞，神经胶质细胞，神经细胞，形成的血液元素，肌肉细胞，可培养的其他体细胞和体细胞细胞前体已被外源DNA转染，其稳定整合到其中基因组或在细胞中表达。外源DNA编码产物，例如翻译产物（例如蛋白质）或转录产物（例如，核酶或反义核酸序列），其是治疗产品或本身是治疗产品（例如，，结合细胞调节蛋白的DNA或改变基因表达）。

4. 发明授权

US5968502A Protein production and protein delivery 失效
公开(公告)号：US5968502A
公开(公告)日：1999-10-19
申请号：US451894
申请日：1995-05-26
申请人： Douglas Treco , Michael W. Heartlein , Richard F Selden
发明人： Douglas Treco , Michael W. Heartlein , Richard F Selden
IPC分类号： A61K38/00 , A61K48/00 , C07K14/505 , C07K14/605 , C07K14/61 , C12N5/08 , C12N15/67 , C12N15/85 , C12N15/90 , A01N63/00
CPC分类号： A61K48/0066 , A61K48/00 , C07K14/505 , C07K14/605 , C07K14/61 , C12N15/67 , C12N15/85 , C12N15/907 , A01K2217/05 , A61K35/12 , A61K38/00 , C07K2319/00 , C07K2319/02 , C12N2510/02 , C12N2800/108 , C12N2830/00 , C12N2830/002 , C12N2830/42 , C12N2830/55 , C12N2830/702 , C12N2830/85 , C12N2840/20 , C12N2840/44
摘要： The present invention relates to transfected primary, secondary, and immortalized cells of vertebrate origin particularly mammalian origin, transfected with exogenous genetic material (DNA) which encodes a desired (e.g., a therapeutic) product or is itself a desired (e.g., therapeutic) product, methods by which primary, secondary and immortalized cells are transfected to include exogenous genetic material, including DNA targeting by homologous recombination, methods for the activation and amplification of endogenous cellular genes, methods by which cells useful for large-scale protein production can be obtained, methods of producing clonal cell strains or heterogenous cell strains, and methods of gene therapy in which transfected primary, secondary or immortalized cells are used.The present invention includes primary, secondary, and immortalized cells, such as fibroblasts, keratinocytes, epithelial cells, endothelial cells, glial cells, neural cells, formed elements of the blood, muscle cells, and other cells which can be cultured.

5. 发明授权

US06846676B2 In Vivo production and delivery of erythropoietin or insulinotropin for gene therapy 失效
标题翻译：体内生产和递送红细胞生成素或促胰岛素用于基因治疗
公开(公告)号：US06846676B2
公开(公告)日：2005-01-25
申请号：US09328130
申请日：1999-06-08
申请人： Richard F. Selden , Douglas Treco , Michael W. Heartlein
发明人： Richard F. Selden , Douglas Treco , Michael W. Heartlein
IPC分类号： A61K31/70 , A61K35/36 , A61K38/22 , A61K38/27 , A61K47/48 , A61K48/00 , A61P3/06 , A61P3/10 , A61P5/06 , A61P5/18 , A61P7/02 , A61P7/04 , A61P37/00 , A61P37/02 , A61P39/06 , A61P43/00 , C07K14/505 , C07K14/605 , C07K14/61 , C12N5/077 , C12N5/10 , C12N15/09 , C12N15/85 , C12N15/90 , C12N15/63 , C12N5/08 , C12N15/00 , C12N15/87
CPC分类号： C12N15/907 , A61K47/6901 , A61K48/00 , C07K14/505 , C07K14/605 , C07K14/61 , C07K2319/02 , C12N15/85 , C12N2510/02 , C12N2800/108 , C12N2830/002 , C12N2830/85 , C12N2840/20 , C12N2840/44
摘要： The invention provides primary and secondary cells that are transfected with a nucleic acid molecule that encodes erythropoietin, clonal or heterogenous strains of such cells, and methods of producing these cell strains.
摘要翻译：本发明提供了用编码促红细胞生成素，这种细胞的克隆或异源株的核酸分子转染的原代细胞和二次细胞，以及产生这些细胞株的方法。

6. 发明授权

US06214622B1 Targeted introduction of DNA into primary or secondary cells and their use for gene therapy 失效
标题翻译：将DNA引入原代细胞或次要细胞，并将其用于基因治疗
公开(公告)号：US06214622B1
公开(公告)日：2001-04-10
申请号：US08446928
申请日：1995-05-18
申请人： Douglas Treco , Michael W. Heartlein , Richard F Selden
发明人： Douglas Treco , Michael W. Heartlein , Richard F Selden
IPC分类号： C12N1587
CPC分类号： A61K48/005 , A61K48/0058
摘要： The present invention relates to a method of gene or DNA targeting in cells of vertebrate, particularly mammalian, origin. That is, it relates to a method of introducing DNA into primary or secondary cells of vertebrate origin through homologous recombination or targeting of the DNA, which is introduced into genomic DNA of the primary or secondary cells at a preselected site. The present invention further relates to primary or secondary cells, referred to as homologously recombinant (HR) primary or secondary cells, produced by the present method and to uses of the homologously recombinant primary or secondary cells. The present invention also relates to a method of turning on a gene present in primary cells, secondary cells or immortalized cells of vertebrate origin, which is normally not expressed in the cells or is not expressed at significant levels in the cells.
摘要翻译：本发明涉及一种在脊椎动物，特别是哺乳动物来源的细胞中靶向的基因或DNA的方法。也就是说，它涉及通过DNA的同源重组或靶向将DNA导入脊椎动物来源的一次或二次细胞的方法，该DNA在预先选择的位点被引入到初级细胞或次级细胞的基因组DNA中。本发明还涉及通过本发明方法产生的称为同源重组（HR）初级或次级细胞的原代细胞或二次细胞，以及同源重组的初级细胞或次级细胞的用途。本发明还涉及一种开放存在于原代细胞，二次细胞或脊椎动物来源的永生化细胞中的基因的方法，其通常不在细胞中表达或不在细胞中以显着水平表达。

7. 发明授权

US6063630A Targeted introduction of DNA into primary or secondary cells and their use for gene therapy 失效
标题翻译：将DNA引入原代细胞或次要细胞，并将其用于基因治疗
公开(公告)号：US6063630A
公开(公告)日：2000-05-16
申请号：US231439
申请日：1994-04-20
申请人： Douglas Treco , Michael W. Heartlein , Richard F Selden
发明人： Douglas Treco , Michael W. Heartlein , Richard F Selden
IPC分类号： A61K48/00 , C12N15/00 , C12N15/09 , C12N15/64 , C12N15/85 , C12N15/87
CPC分类号： A61K48/005 , A61K48/0058
摘要： The present invention relates to a method of gene or DNA targeting in cells of vertebrate, particularly mammalian, origin. That is, it relates to a method of introducing DNA into primary or secondary cells of vertebrate origin through homologous recombination or targeting of the DNA, which is introduced into genomic DNA of the primary or secondary cells at a preselected site. The present invention further relates to primary or secondary cells, referred to as homologously recombinant (HR) primary or secondary cells, produced by the present method and to uses of the homologously recombinant primary or secondary cells. The present invention also relates to a method of turning on a gene present in primary cells, secondary cells or immortalized cells of vertebrate origin, which is normally not expressed in the cells or is not expressed at significant levels in the cells.
摘要翻译：本发明涉及一种在脊椎动物，特别是哺乳动物来源的细胞中靶向的基因或DNA的方法。也就是说，它涉及通过DNA的同源重组或靶向将DNA导入脊椎动物来源的一次或二次细胞的方法，该DNA在预先选择的位点被引入到初级细胞或次级细胞的基因组DNA中。本发明还涉及通过本发明方法产生的称为同源重组（HR）初级或次级细胞的原代细胞或二次细胞，以及同源重组的初级细胞或次级细胞的用途。本发明还涉及一种开放存在于原代细胞，二次细胞或脊椎动物来源的永生化细胞中的基因的方法，其通常不在细胞中表达或不在细胞中以显着水平表达。

8. 发明授权

US6054288A In vivo protein production and delivery system for gene therapy 失效
公开(公告)号：US6054288A
公开(公告)日：2000-04-25
申请号：US443936
申请日：1995-05-18
申请人： Richard F Selden , Douglas Treco , Michael W. Heartlein
发明人： Richard F Selden , Douglas Treco , Michael W. Heartlein
IPC分类号： A61K47/48 , A61K48/00 , C07K14/505 , C07K14/605 , C07K14/61 , C12N15/85 , C12N15/90 , C12P21/06
CPC分类号： C12N15/85 , A61K47/48776 , A61K48/00 , C07K14/505 , C07K14/605 , C07K14/61 , C12N15/907 , C07K2319/02 , C12N2510/02 , C12N2800/108 , C12N2830/002 , C12N2830/85
摘要： The present invention relates to transfected primary and secondary somatic cells of vertebrate origin, particularly mammalian origin, transfected with exogenous genetic material (DNA) which encodes a desired (e.g., a therapeutic) product or is itself a desired (e.g., therapeutic) product, methods by which primary and secondary cells are transfected to include exogenous genetic material, methods of producing clonal cell strains or heterogenous cell strains, methods of gene therapy in which the transfected primary or secondary cells are used, and methods of producing antibodies using the transfected primary or secondary cells.The present invention includes primary and secondary somatic cells, such as fibroblasts, keratinocytes, epithelial cells, endothelial cells, glial cells, neural cells, formed elements of the blood, muscle cells, other somatic cells which can be cultured and somatic cell precursors, which have been transfected with exogenous DNA which is stably integrated into their genomes or is expressed in the cells episomally. The exogenous DNA either encodes a product, such as a translational product (e.g., a protein) or a transcriptional product (e.g., a ribozyme or an anti-sense nucleic acid sequence) which is a therapeutic product or is itself a therapeutic product (e.g., DNA which binds to a cellular regulatory protein or alters gene expression).

9. 发明授权

US06692737B1 In vivo protein production and delivery system for gene therapy 失效
标题翻译：用于基因治疗的体内蛋白质生产和递送系统
公开(公告)号：US06692737B1
公开(公告)日：2004-02-17
申请号：US09549200
申请日：2000-04-13
申请人： Richard F Selden , Douglas Treco , Michael W. Heartlein
发明人： Richard F Selden , Douglas Treco , Michael W. Heartlein
IPC分类号： A61K4800
CPC分类号： C12N15/907 , A61K47/6901 , A61K48/00 , C07K14/505 , C07K14/605 , C07K14/61 , C07K2319/02 , C12N15/85 , C12N2510/02 , C12N2800/108 , C12N2830/002 , C12N2830/85 , C12N2840/44
摘要： The present invention relates to transfected primary and secondary somatic cells of vertebrate origin, particularly mammalian origin, transfected with exogenous genetic material (DNA) which encodes a desired (e.g., a therapeutic) product or is itself a desired (e.g., therapeutic) product, methods by which primary and secondary cells are transfected to include exogenous genetic material, methods of producing clonal cell strains or heterogenous cell strains, methods of gene therapy in which the transfected primary or secondary cells are used, and methods of producing antibodies using the transfected primary or secondary cells. The present invention includes primary and secondary somatic cells, such as fibroblasts, keratinocytes, epithelial cells, endothelial cells, glial cells, neural cells, formed elements of the blood, muscle cells, other somatic cells which can be cultured and somatic cell precursors, which have been transfected with exogenous DNA which is stably integrated into their genomes or is expressed in the cells episomally. The exogenous DNA either encodes a product, such as a translational product (e.g., a protein) or a transcriptional product (e.g., a ribozyme or an anti-sense nucleic acid sequence) which is a therapeutic product or is itself a therapeutic product (e.g., DNA which binds to a cellular regulatory protein or alters gene expression).
摘要翻译：本发明涉及用编码期望（例如治疗性）产品或本身是所需（例如治疗性）产品的外源性遗传物质（DNA）转染的脊椎动物来源的转染的初级和次级体细胞，特别是哺乳动物来源，转染初级细胞和次级细胞以包括外源遗传物质的方法，产生克隆细胞株或异源细胞株的方法，使用转染的原代细胞或次级细胞的基因治疗方法，以及使用转染的原代细胞或二次电池。本发明包括初级和次级体细胞，例如成纤维细胞，角质形成细胞，上皮细胞，内皮细胞，神经胶质细胞，神经细胞，形成的血液元素，肌肉细胞，可培养的其他体细胞和体细胞前体，其中已经用稳定整合到其基因组中的外源DNA转染，或者在细胞中以表观形式表达。外源DNA编码产物，例如翻译产物（例如蛋白质）或转录产物（例如，核酶或反义核酸序列），其是治疗产品或本身是治疗产品（例如，，结合细胞调节蛋白的DNA或改变基因表达）。

10. 发明授权

US06565844B1 Protein production and protein delivery 失效
标题翻译：蛋白质生产和蛋白质递送
公开(公告)号：US06565844B1
公开(公告)日：2003-05-20
申请号：US09312245
申请日：1999-05-14
申请人： Douglas Treco , Michael W. Heartlein , Richard F Selden
发明人： Douglas Treco , Michael W. Heartlein , Richard F Selden
IPC分类号： A61K4800
CPC分类号： A61K48/0066 , A01K2217/05 , A61K35/12 , A61K38/00 , A61K48/00 , C07H21/04 , C07K14/505 , C07K14/605 , C07K14/61 , C07K2319/00 , C07K2319/02 , C12N15/67 , C12N15/85 , C12N15/907 , C12N2510/02 , C12N2800/108 , C12N2830/00 , C12N2830/002 , C12N2830/42 , C12N2830/55 , C12N2830/702 , C12N2830/85 , C12N2840/20 , C12N2840/44
摘要： The present invention relates to DNA constructs that alter the expression of a targeted gene in a cell when the DNA construct is homologously recombined with a target site within the chromosomal DNA of the cell, as well as to a cell into which has been incorporated a new transcription unit containing an exogenous regulatory sequence operatively linked to an endogenous gene of the cell's chromosomal DNA. These constructs and cells can be used in a method of altering expression of the targeted gene.
摘要翻译：本发明涉及当DNA构建体与细胞的染色体DNA内的靶位点同源重组时，以及已经掺入新细胞的细胞中，改变细胞中靶向基因表达的DNA构建体转录单元含有与细胞染色体DNA的内源基因有效连接的外源调节序列。这些构建体和细胞可以用于改变靶基因表达的方法。

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