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31. 发明授权

US6074640A Enhancement of tumor cell radiosensitivity using single chain intracellular antibodies 失效
标题翻译：使用单链细胞内抗体增强肿瘤细胞放射敏感性
公开(公告)号：US6074640A
公开(公告)日：2000-06-13
申请号：US961327
申请日：1997-10-30
申请人： David T. Curiel , Murray Stackhouse , Donald J. Buchsbaum
发明人： David T. Curiel , Murray Stackhouse , Donald J. Buchsbaum
IPC分类号： A61K48/00 , A61P35/00 , C07K16/18 , C07K16/30 , C07K16/32 , A61K39/395 , C07H21/04
CPC分类号： C07K16/32 , C07K16/18 , C07K16/30 , A61K2039/505 , A61K48/00 , C07K2317/622 , C07K2317/73
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。

32. 发明授权

US06028059A Methods for modulating protein function in cells using intracellular antibody homologues 失效
标题翻译：使用细胞内抗体同系物调节细胞中蛋白质功能的方法
公开(公告)号：US06028059A
公开(公告)日：2000-02-22
申请号：US668706
申请日：1996-06-24
申请人： David T. Curiel , Jessy Deshane
发明人： David T. Curiel , Jessy Deshane
IPC分类号： A61K48/00 , C07K16/32
CPC分类号： C07K16/32 , A61K2039/505 , A61K48/00 , C07K2317/622 , C12N2799/022
摘要： Methods and compositions for modulating protein function in a cell involving intracellular expression of an antibody homologue that binds to the protein within the cell are disclosed. In a preferred embodiment, an antibody homologue, such as a single chain Fv (sFv) fragment, is expressed within an intracellular compartment of a cell, such as the endoplasmic reticulum (ER), to inhibit cell surface expression of a membrane protein. Preferably, the cell is a malignant mammalian cell and the protein is a cell surface receptor oncoprotein, such as erbB2. Intracellular binding of the antibody homologue to the receptor oncoprotein inhibits its surface expression and, moreover, inhibits cell proliferation and cell survival. Isolated nucleic acid molecules encoding anti-c-erbB2 antibody homologues, as well as recombinant expression ventors and host cells incorporating these nucleic acid molecules, are also disclosed.
摘要翻译：公开了涉及在细胞内与蛋白质结合的抗体同系物的细胞内表达的细胞中调节蛋白质功能的方法和组合物。在优选的实施方案中，抗体同系物，例如单链Fv（sFv）片段在细胞的细胞内隔室（例如内质网（ER））内表达，以抑制膜蛋白的细胞表面表达。优选地，细胞是恶性哺乳动物细胞，并且蛋白质是细胞表面受体癌蛋白，例如erbB2。抗体同源物与受体癌蛋白的细胞内结合抑制其表面表达，此外抑制细胞增殖和细胞存活。还公开了编码抗c-erbB2抗体同系物的分离的核酸分子以及掺入这些核酸分子的重组表达细胞和宿主细胞。

33. 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.

34. 发明授权

US5981504A Genetic induction of receptors for targeted radiotherapy 失效
标题翻译：用于靶向放射治疗的受体的遗传诱导
公开(公告)号：US5981504A
公开(公告)日：1999-11-09
申请号：US948132
申请日：1997-10-09
申请人： Donald J. Buchsbaum , David Raben , Mohammad B. Khazaeli , David T. Curiel , Murray Stackhouse
发明人： Donald J. Buchsbaum , David Raben , Mohammad B. Khazaeli , David T. Curiel , Murray Stackhouse
IPC分类号： A61K51/08 , A61K51/10 , A61P35/00 , A61K48/00
CPC分类号： A61K51/1036 , A61K51/08 , A61K51/083 , A61K51/10 , A61K2123/00
摘要： The present invention provides a method to achieve radioisotopic localization at tumor sites, i.e., a method of enhancing radiolabeled ligand localization to a tumor in an individual in need of such treatment, comprising the steps of: transducing said tumor with a gene encoding a membrane expressed protein unique to said tumor; and administering to said individual a radiolabeled ligand which specifically binds to said protein. The use of gene therapy technology to induce expression of high affinity membrane molecules/receptors can enhance the specificity of radioisotope localization while the use of radioactive isotopes with the ability to deliver radiation damage across several cell diameters will compensate for less than perfect transduction efficiency.
摘要翻译：本发明提供了一种在肿瘤部位实现放射性同位素定位的方法，即在需要这种治疗的个体中增强对肿瘤的放射性标记配体定位的方法，包括以下步骤：用编码膜表达的基因转导所述肿瘤所述肿瘤独特的蛋白质; 并向所述个体施用特异性结合所述蛋白质的放射性标记的配体。使用基因治疗技术诱导高亲和力膜分子/受体的表达可以增强放射性同位素定位的特异性，而使用具有在几个细胞直径上传递辐射损伤的能力的放射性同位素将补偿不到完美的转导效率。

35. 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.

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