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1. 发明授权

US5981273A Composition comprising an endosomolytic agent for introducing nucleic acid complexes into higher eucaryotic cells 失效
标题翻译：组合物，其包含用于将核酸复合物引入高级真核细胞的内体分解剂
公开(公告)号：US5981273A
公开(公告)日：1999-11-09
申请号：US450417
申请日：1995-05-25
申请人： David T. Curiel , Max L. Birnstiel , Matthew Cotten , Ernst Wagner , Kurt Zatloukal , Christian Plank , Berndt Oberhauser , Walter G. M. Schmidt
发明人： David T. Curiel , Max L. Birnstiel , Matthew Cotten , Ernst Wagner , Kurt Zatloukal , Christian Plank , Berndt Oberhauser , Walter G. M. Schmidt
IPC分类号： A61K47/48 , A61K48/00 , C07K14/11 , C07K14/775 , C07K14/79 , C12N15/87 , C07H21/02 , C12N7/00
CPC分类号： A61K47/48776 , A61K48/00 , C07K14/005 , C07K14/775 , C07K14/79 , C12N15/87 , C07K2319/00 , C12N2740/16022
摘要： A composition for the transfection of higher eucaryotic cells, comprising complexes of nucleic acid, a substance having an affinity for nucleic acid and optionally an internalizing factor, contains an endosomolytic agent, e.g. a virus or virus component, which may be conjugated. The endosomolytic agent, which is optionally part of the nucleic acid complex, is internalized into the cells together with the complex and releases the contents of the endosomes into the cytoplasm, thereby increasing the gene transfer capacity. Pharmaceutical preparations, transfection kits and methods for introducing nucleic acid into higher eucaryotic cells by treating the cells with the composition are also disclosed.
摘要翻译：用于转染高等真核细胞的组合物，其包含核酸复合物，对核酸和任选的内在因子具有亲和力的物质，含有内体细胞溶解剂可以结合的病毒或病毒组分。任选地是核酸复合物的一部分的内体细胞溶解剂与复合物一起被内化到细胞中，并将内体的内容物释放到细胞质中，从而增加基因转移能力。还公开了药物制剂，转染试剂盒和通过用组合物处理细胞将核酸引入高级真核细胞的方法。

2. 发明授权

US06274322B1 Composition for introducing nucleic acid complexes into higher eucaryotic cells 有权
标题翻译：用于将核酸复合物引入高级真核细胞的组合物
公开(公告)号：US06274322B1
公开(公告)日：2001-08-14
申请号：US09465646
申请日：1999-12-16
申请人： David T. Curiel , Max L. Birnstiel , Matthew Cotten , Ernst Wagner , Kurt Zatloukal , Christian Plank , Berndt Oberhauser , Walter G. M. Schmidt
发明人： David T. Curiel , Max L. Birnstiel , Matthew Cotten , Ernst Wagner , Kurt Zatloukal , Christian Plank , Berndt Oberhauser , Walter G. M. Schmidt
IPC分类号： C12Q168
CPC分类号： C12N15/87 , A61K38/00 , A61K47/50 , A61K47/6901 , A61K48/00 , C07K14/005 , C07K14/56 , C07K14/775 , C07K14/79 , C07K16/00 , C07K16/2803 , C07K2317/77 , C07K2319/00 , C12N7/00 , C12N2710/10251 , C12N2710/10261 , C12N2710/10322 , C12N2710/10351 , C12N2710/10361 , C12N2710/10363 , C12N2740/11022 , C12N2740/15022 , C12N2740/16022 , C12N2740/16122 , C12N2760/16122 , C12N2770/32722 , C12N2770/32761 , Y10T436/143333
摘要： A composition for the transfection of higher eucaryotic cells, comprising complexes of nucleic acid, a substance having an affinity for nucleic acid and optionally an internalizing factor, contains an endosomolytic agent, e.g. a virus or virus component, which may be conjugated. The endosomolytic agent, which is optionally part of the nucleic acid complex, is internalized into the cells together with the complex and releases the contents of the endosomes into the cytoplasm, thereby increasing the gene transfer capacity. Pharmaceutical preparations, transfection kits and methods for introducing nucleic acid into higher eucaryotic cells by treating the cells with the composition are also disclosed.
摘要翻译：用于转染高等真核细胞的组合物，其包含核酸复合物，对核酸和任选的内在因子具有亲和力的物质，含有内体细胞溶解剂可以结合的病毒或病毒组分。任选地是核酸复合物的一部分的内体细胞溶解剂与复合物一起被内化到细胞中，并将内体的内容物释放到细胞质中，从而增加基因转移能力。还公开了药物制剂，转染试剂盒和通过用组合物处理细胞将核酸引入高级真核细胞的方法。

3. 发明授权

US6022735A Composition for introducing nucleic acid complexes into higher eucaryotic cells 失效
公开(公告)号：US6022735A
公开(公告)日：2000-02-08
申请号：US449741
申请日：1995-05-25
申请人： David T. Curiel , Max L. Birnstiel , Matthew Cotten , Ernst Wagner , Kurt Zatloukal , Christian Plank , Berndt Oberhauser , Walter G. M. Schmidt
发明人： David T. Curiel , Max L. Birnstiel , Matthew Cotten , Ernst Wagner , Kurt Zatloukal , Christian Plank , Berndt Oberhauser , Walter G. M. Schmidt
IPC分类号： C12N15/09 , A61K35/76 , A61K38/00 , A61K38/21 , A61K38/36 , A61K39/44 , A61K47/48 , A61K48/00 , A61P31/12 , A61P35/00 , C07K14/005 , C07K14/075 , C07K14/095 , C07K14/11 , C07K14/15 , C07K14/16 , C07K14/56 , C07K14/775 , C07K14/79 , C07K16/00 , C07K16/28 , C12N5/10 , C12N7/04 , C12N15/34 , C12N15/41 , C12N15/44 , C12N15/87 , G01N33/00 , C12N15/63 , C07H21/04 , C12N15/00 , C12Q1/70
CPC分类号： C12N15/87 , A61K47/48 , A61K47/48776 , A61K48/00 , C07K14/005 , C07K14/56 , C07K14/775 , C07K14/79 , C07K16/00 , C07K16/2803 , C12N7/00 , A61K38/00 , C07K2317/77 , C07K2319/00 , C12N2710/10251 , C12N2710/10261 , C12N2710/10322 , C12N2710/10351 , C12N2710/10361 , C12N2710/10363 , C12N2740/11022 , C12N2740/15022 , C12N2740/16022 , C12N2740/16122 , C12N2760/16122 , C12N2770/32722 , C12N2770/32761 , Y10T436/143333
摘要： A composition for the transfection of higher eucaryotic cells, comprising complexes of nucleic acid, a substance having an affinity for nucleic acid and optionally an internalizing factor, contains an endosomolytic agent, e.g. a virus or virus component, which may be conjugated. The endosomolytic agent, which is optionally part of the nucleic acid complex, is internalized into the cells together with the complex and releases the contents of the endosomes into the cytoplasm, thereby increasing the gene transfer capacity. Pharmaceutical preparations, transfection kits and methods for introducing nucleic acid into higher eucaryotic cells by treating the cells with the composition are also disclosed.

4. 发明授权

US5547932A Composition for introducing nucleic acid complexes into higher eucaryotic cells 失效
公开(公告)号：US5547932A
公开(公告)日：1996-08-20
申请号：US948357
申请日：1992-09-23
申请人： David T. Curiel , Max L. Birnstiel , Matthew Cotten , Ernst Wagner , Kurt Zatloukal , Christian Plank , Berndt Oberhauser , Walter G. M. Schmidt
发明人： David T. Curiel , Max L. Birnstiel , Matthew Cotten , Ernst Wagner , Kurt Zatloukal , Christian Plank , Berndt Oberhauser , Walter G. M. Schmidt
IPC分类号： C12N15/09 , A61K35/76 , A61K38/00 , A61K38/21 , A61K38/36 , A61K39/44 , A61K47/48 , A61K48/00 , A61P31/12 , A61P35/00 , C07K14/005 , C07K14/075 , C07K14/095 , C07K14/11 , C07K14/15 , C07K14/16 , C07K14/56 , C07K14/775 , C07K14/79 , C07K16/00 , C07K16/28 , C12N5/10 , C12N7/04 , C12N15/34 , C12N15/41 , C12N15/44 , C12N15/87 , G01N33/00 , C12Q1/70 , A01N63/00 , C07H21/04 , C12N15/00
CPC分类号： C12N15/87 , A61K47/48 , A61K47/48776 , A61K48/00 , C07K14/005 , C07K14/56 , C07K14/775 , C07K14/79 , C07K16/00 , C07K16/2803 , C12N7/00 , A61K38/00 , C07K2317/77 , C07K2319/00 , C12N2710/10251 , C12N2710/10261 , C12N2710/10322 , C12N2710/10351 , C12N2710/10361 , C12N2710/10363 , C12N2740/11022 , C12N2740/15022 , C12N2740/16022 , C12N2740/16122 , C12N2760/16122 , C12N2770/32722 , C12N2770/32761 , Y10T436/143333
摘要： A composition for the transfection of higher eucaryotic cells, comprising complexes of nucleic acid, a substance having an affinity for nucleic acid and optionally an internalizing factor, contains an endosomolytic agent, e.g. a virus or virus component, which may be conjugated. The endosomolytic agent, which is optionally part of the nucleic acid complex, is internalized into the cells together with the complex and releases the contents of the endosomes into the cytoplasm, thereby increasing the gene transfer capacity. Pharmaceutical preparations, transfection kits and methods for introducing nucleic acid into higher eucaryotic cells by treating the cells with the composition are also disclosed.

5. 发明授权

US6077663A Composition for introducing nucleic acid complexes into higher eucaryotic cells 失效
标题翻译：用于将核酸复合物引入高级真核细胞的组合物
公开(公告)号：US6077663A
公开(公告)日：2000-06-20
申请号：US449754
申请日：1995-05-25
申请人： David T. Curiel , Max L. Birnstiel , Matthew Cotten , Ernst Wagner , Kurt Zatloukal , Christian Plank , Berndt Oberhauser , Walter G.M. Schmidt
发明人： David T. Curiel , Max L. Birnstiel , Matthew Cotten , Ernst Wagner , Kurt Zatloukal , Christian Plank , Berndt Oberhauser , Walter G.M. Schmidt
IPC分类号： C12N15/09 , A61K35/76 , A61K38/00 , A61K38/21 , A61K38/36 , A61K39/44 , A61K47/48 , A61K48/00 , A61P31/12 , A61P35/00 , C07K14/005 , C07K14/075 , C07K14/095 , C07K14/11 , C07K14/15 , C07K14/16 , C07K14/56 , C07K14/775 , C07K14/79 , C07K16/00 , C07K16/28 , C12N5/10 , C12N7/04 , C12N15/34 , C12N15/41 , C12N15/44 , C12N15/87 , G01N33/00 , C12Q1/68
CPC分类号： C12N15/87 , A61K47/48 , A61K47/48776 , A61K48/00 , C07K14/005 , C07K14/56 , C07K14/775 , C07K14/79 , C07K16/00 , C07K16/2803 , C12N7/00 , A61K38/00 , C07K2317/77 , C07K2319/00 , C12N2710/10251 , C12N2710/10261 , C12N2710/10322 , C12N2710/10351 , C12N2710/10361 , C12N2710/10363 , C12N2740/11022 , C12N2740/15022 , C12N2740/16022 , C12N2740/16122 , C12N2760/16122 , C12N2770/32722 , C12N2770/32761 , Y10T436/143333
摘要： A composition for the transfection of higher eucaryotic cells, comprising complexes of nucleic acid, a substance having an affinity for nucleic acid and optionally an internalizing factor, contains an endosomolytic agent, e.g. a virus or virus component, which may be conjugated. The endosomolytic agent, which is optionally part of the nucleic acid complex, is internalized into the cells together with the complex and releases the contents of the endosomes into the cytoplasm, thereby increasing the gene transfer capacity. Pharmaceutical preparations, transfection kits and methods for introducing nucleic acid into higher eucaryotic cells by treating the cells with the composition are also disclosed.
摘要翻译：用于转染高等真核细胞的组合物，其包含核酸复合物，对核酸和任选的内在因子具有亲和力的物质，含有内体细胞溶解剂可以结合的病毒或病毒组分。任选地是核酸复合物的一部分的内体细胞溶解剂与复合物一起被内化到细胞中，并将内体的内容物释放到细胞质中，从而增加基因转移能力。还公开了药物制剂，转染试剂盒和通过用组合物处理细胞将核酸引入高级真核细胞的方法。

6. 发明授权

US5521291A Conjugates for introducing nucleic acid into higher eucaryotic cells 失效
标题翻译：用于将核酸引入高级真核细胞的缀合物
公开(公告)号：US5521291A
公开(公告)日：1996-05-28
申请号：US166899
申请日：1993-12-15
申请人： David T. Curiel , Ping-chuan Hu , Max L. Birnstiel , Matthew Cotten , Ernst Wagner
发明人： David T. Curiel , Ping-chuan Hu , Max L. Birnstiel , Matthew Cotten , Ernst Wagner
IPC分类号： A61K47/48 , C07K16/08 , C12N15/87 , A61K39/42 , C07H19/00 , C12N7/00
CPC分类号： C12N15/87 , A61K47/48692 , A61K47/48776 , C07K16/081
摘要： Conjugates in which a virus is bound via an antibody to a substance having an affinity for nucleic acid, for transporting gene constructs into higher eucaryotic cells. Complexes of the conjugates and nucleic acid are internalized in the cell, whilst the virus as part of the complex brings about the internalization and the release of the contents of the endosomes, in which the complexes are located after entering the cell. Pharmaceutical preparations in which the nucleic acid is a therapeutically active gene construct, particularly for use in gene therapy.
摘要翻译：通过抗体将病毒结合到对核酸具有亲和性的物质，用于将基因构建体转运到较高真核细胞中的缀合物。缀合物和核酸的复合物被内化在细胞中，而作为复合物的一部分的病毒导致内含体的内化和释放，其中复合物在进入细胞后位于其中。其中核酸是治疗活性基因构建体，特别是用于基因治疗的药物制剂。

7. 发明授权

US06613563B1 Viral vectors with modified tropism 失效
标题翻译：具有改良趋向性的病毒载体
公开(公告)号：US06613563B1
公开(公告)日：2003-09-02
申请号：US09039060
申请日：1998-03-13
申请人： Barbara A. Sosnowski , Andrew Baird , Glenn F. Pierce , David T. Curiel , Joanne T. Douglas , Buck E. Rogers
发明人： Barbara A. Sosnowski , Andrew Baird , Glenn F. Pierce , David T. Curiel , Joanne T. Douglas , Buck E. Rogers
IPC分类号： C12N1500
CPC分类号： C12N15/86 , A61K48/00 , C07K14/50 , C07K16/081 , C07K2317/74 , C12N2710/10343 , C12N2710/10345 , C12N2810/851 , C12N2810/859
摘要： The present invention relates to gene therapy. In particular, therapeutic agents, therapeutic gene products, and compositions are disclosed. Various systems and methods useful in targeting and delivering non-native nucleotide sequences to specific cells are disclosed, wherein virus-antibody-ligand conjugates are used to facilitate targeting and delivery.
摘要翻译：本发明涉及基因治疗。特别地，公开了治疗剂，治疗基因产物和组合物。公开了用于将非天然核苷酸序列靶向和递送至特定细胞的各种系统和方法，其中使用病毒 - 抗体 - 配体缀合物来促进靶向和递送。

8. 发明授权

US06468547B1 Enhancement of tumor cell chemosensitivity and radiosensitivity using single chain secretory antibodies 失效
标题翻译：使用单链分泌抗体增强肿瘤细胞化学敏感性和放射敏感性
公开(公告)号：US06468547B1
公开(公告)日：2002-10-22
申请号：US09499543
申请日：2000-02-07
申请人： Donald J. Buchsbaum , David T. Curiel , Murray Stackhouse
发明人： Donald J. Buchsbaum , David T. Curiel , Murray Stackhouse
IPC分类号： A61K3900
CPC分类号： C07K16/30 , A61K48/00 , A61K2039/505 , A61K2039/51 , C07K16/18 , C07K16/2863 , C07K16/32 , C07K16/40 , C07K2317/622 , C07K2317/73 , C12N2799/022
摘要： The present invention provides a method of enhancing the chemosensitivity and radiosensitivity of a neoplastic cell expressing an oncoprotein that stimulates proliferation of the cell, comprising introducing into the cell a nucleic acid molecule encoding an antibody homologue, wherein the antibody homologue is expressed intracellularly and binds to the oncoprotein intracellularly in the endoplasmic reticulum of the cell. The present invention is also directed to a method for enhancing the inhibition of proliferation of a neoplastic cell expressing an oncoprotein that stimulates proliferation of the cell, comprising the steps of: introducing into the cell a nucleic acid molecule encoding an antibody homologue, wherein the antibody homologue is expressed intracellularly and binds to the protein intracellularly; and contacting said cell with an anti-neoplastic agent.
摘要翻译：本发明提供增强表达刺激细胞增殖的癌蛋白的肿瘤细胞的化学敏感性和放射敏感性的方法，包括将编码抗体同系物的核酸分子导入细胞，其中抗体同系物在细胞内表达并结合胞内胞内蛋白质细胞内质网。本发明还涉及一种用于增强表达癌细胞增殖的肿瘤细胞增殖抑制的方法，所述方法包括以下步骤：将编码抗体同系物的核酸分子导入细胞，其中所述抗体同源物在细胞内表达并在细胞内结合蛋白; 并使所述细胞与抗肿瘤剂接触。

9. 发明授权

US06824771B1 Infectivity-enhanced conditionally-replicative adenovirus and uses thereof 有权
标题翻译：感染性增强的条件复制型腺病毒及其用途
公开(公告)号：US06824771B1
公开(公告)日：2004-11-30
申请号：US09569789
申请日：2000-05-12
申请人： David T. Curiel , Victor Krasnykh , Ramon Alemany , Igor Dmitriev
发明人： David T. Curiel , Victor Krasnykh , Ramon Alemany , Igor Dmitriev
IPC分类号： A61K3576
CPC分类号： C12N15/86 , A61K31/522 , A61K31/70 , A61K31/7076 , A61K35/761 , A61K38/45 , A61K45/06 , A61K48/00 , A61K48/0058 , A61K2300/00 , C12N7/00 , C12N2710/10332 , C12N2710/10343 , C12N2710/10345 , C12N2810/40 , C12N2810/405 , C12N2810/6018 , C12N2810/851 , C12N2810/859 , C12N2830/008
摘要： A modified adenovirus capable of overcoming the problem of low level of coxsackle-adenovirus receptor (CAR) expression on tumor cells and methods of using such adenovirus are provided. The fiber protein of the adenovirus is modified by insertion or replacement so as to target the adenovirus to tumor cells, and the replication of the modified adenovirus is limited to tumor cells due to mutations in E1a or E1b genes.
摘要翻译：提供能够克服肿瘤细胞上的柯萨奇 - 腺病毒受体（CAR）表达低水平的问题的修饰的腺病毒和使用这种腺病毒的方法。通过插入或替换来修饰腺病毒的纤维蛋白，以将腺病毒靶向肿瘤细胞，由于E1a或E1b基因突变，修饰的腺病毒的复制受到肿瘤细胞的限制。

10. 发明授权

US06716823B1 Noninvasive genetic immunization, expression products therefrom, and uses thereof 有权
公开(公告)号：US06716823B1
公开(公告)日：2004-04-06
申请号：US09533149
申请日：2000-03-23
申请人： De-chu C. Tang , Donald H. Marks , David T. Curiel , Zhongkai Shi
发明人： De-chu C. Tang , Donald H. Marks , David T. Curiel , Zhongkai Shi
IPC分类号： A61K3170
CPC分类号： A61K39/00 , A61K39/0011 , A61K39/08 , A61K39/12 , A61K39/145 , A61K48/00 , A61K2039/53 , A61K2039/54 , A61K2039/541 , A61K2039/542 , A61K2039/543 , A61K2039/55522 , A61K2039/55555 , A61K2039/60 , C12N2710/10043 , C12N2760/16134 , C12N2760/16171
摘要： Disclosed and claimed are methods of non-invasive genetic immunization in an animal and/or methods of inducing a systemic immune or therapeutic response in an animal, products therefrom and uses for the methods and products therefrom. The methods can include contacting skin of the animal with a vector in an amount effective to induce the systemic immune or therapeutic response in the animal. The vector can include and express an exogenous nucleic acid molecule encoding an epitope or gene product of interest. The systemic immune response can be to or from the epitope or gene product. The nucleic acid molecule can encode an epitope of interest and/or an antigen of interest and/or a nucleic acid molecule that stimulates and/or modulates an immunological response and/or stimulates and/or modulates expression, e.g., transcription and/or translation, such as transcription and/or translation of an endogenous and/or exogenous nucleic acid molecule; e.g., one or more of influenza hemagglutinin, influenza nuclear protein, influenza M2, tetanus toxin C-fragment, anthrax protective antigen, anthrax lethal factor, rabies glycoprotein, HBV surface antigen, HIV gp 120, HIV gp 160, human carcinoembryonic antigen, malaria CSP, malaria SSP, malaria MSP, malaria pfg, and mycobacterium tuberculosis HSP; and/or a therapeutic, an immunomodulatory gene, such as co-stimulatory gene and/or a cytokine gene. The immune response can be induced by the vector expressing the nucleic acid molecule in the animal's cells. The animal's cells can be epidermal cells. The immune response can be against a pathogen or a neoplasm. A prophylactic vaccine or a therapeutic vaccine or an immunological composition can include the vector. The animal can be a vertebrate, e.g., a mammal, such as human, a cow, a horse, a dog, a cat, a goat, a sheep or a pig; or fowl such as turkey, chicken or duck. The vector can be one or more of a viral vector, including viral coat, e.g., with some or all viral genes deleted therefrom, bacterial, protozoan, transposon, retrotransposon, and DNA vector, e.g., a recombinant vector; for instance, an adenovirus, such as an adenovirus defective in its E1 and/or E3 and/or E4 region(s). The method can encompass applying a delivery device including the vector to the skin of the animal, as well as such a method further including disposing the vector in and/or on the delivery device. The vector can have all viral genes deleted therefrom. The vector can induce a therapeutic and/or an anti-tumor effect in the animal, e.g., by expressing an oncogene, a tumor-suppressor gene, or a tumor-associated gene. Immunological products generated by the expression, e.g., antibodies, cells from the methods, and the expression products, are likewise useful in in vitro and ex vivo applications, and such immunological and expression products and cells and applications are disclosed and claimed. Methods for expressing a gene product in vivo and products therefor and therefrom including mucosal and/or intranasal administration of an adenovirus, advantageously an E1 and/or E3 and/or E4 defective or deleted adenovirus, such as a human adenovirus or canine adenovirus, are also disclosed and claimed.

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