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公开(公告)号：US5994134A
公开(公告)日：1999-11-30
申请号：US73076
申请日：1998-05-04
CPC分类号： C12N7/00 , A61K48/0091 , C12N15/86 , C12N2531/00 , C12N2710/10043 , C12N2710/10343 , Y10S435/948
摘要： The present invention is directed to a method of producing recombinant viral vectors at high titers incorporating a variety of important advancements over the art. The method of the present invention incorporates multiple features which provide enhanced production of viruses, particularly those viruses encoding exogenous transgenes. The specifically illustrated method describes a method for the high titer serum-free media production of recombinant replication defective adenoviruses containing an exogenous transgene. The invention provides methods of preparing microcarriers, methods for seeding bioreactors at high cell density, increasing the infectivity of the producer cells to the virus, methods to increase product yield through synchronization of the cell cycle of the producer cells, and methods to minimize the deleterious effects of exogenous transgenes. The invention further provides producer cells prepared by the process of the invention. The invention further provides viruses produced by the process.
摘要翻译： 本发明涉及以高滴度生产重组病毒载体的方法，其结合了本领域的各种重要进展。 本发明的方法结合了多个特征，其提供增强的病毒生产，特别是编码外源转基因的那些病毒。 具体说明的方法描述了含有外源转基因的重组复制缺陷型腺病毒的高滴度无血清培养基的制备方法。 本发明提供了制备微载体的方法，用于以高细胞密度接种生物反应器的方法，增加生产细胞对病毒的感染性，通过生产细胞的细胞周期同步来提高产量的方法，以及使有害细菌最小化的方法 外源转基因的作用。 本发明还提供了通过本发明的方法制备的生产细胞。 本发明还提供了通过该方法产生的病毒。
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公开(公告)号：US07691370B2
公开(公告)日：2010-04-06
申请号：US10062216
申请日：2002-01-30
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10332 , C12N2710/10343 , C12N2830/00 , C12N2830/001 , C12N2830/15
摘要： The present invention provides recombinant viruses which replicate the viral genome selectively in response to the intracellular conditions of the target cell through the use a pathway-responsive promoter which substantially inhibits viral replication in the host cell based on the phenotypic or genotypic of the infected cell. In the target cell, the promoter element of the pathway-responsive promoter is inactive and thus the virus is permitted to replicate. This results in: (1) killing the cells by natural lytic nature of the virus, and/or (2) provides a therapeutic dose of a transgene product (amplified in comparison to replication incompetent vectors) to the target cell, and (3) producing a localized concentration of the virus facilitating the infection of surrounding cells to the recombinant virus. The invention further provides therapeutic and diagnostic methods of use of the vectors, pharmaceutical formulations comprising the vectors, methods of making the vectors and transformed cells comprising the vectors.
摘要翻译： 本发明提供了通过使用基于感染细胞的表型或基因型基本上抑制宿主细胞中的病毒复制的途径反应性启动子来响应于靶细胞的细胞内条件而选择性复制病毒基因的重组病毒。 在靶细胞中，途径反应性启动子的启动子元件是无活性的，因此病毒被允许复制。 这导致：（1）通过病毒的天然裂解性质杀死细胞，和/或（2）向靶细胞提供治疗剂量的转基因产物（与复制无能载体相比扩增），和（3） 产生该病毒的局部浓度，促进周围细胞感染重组病毒。 本发明还提供了使用载体的治疗和诊断方法，包含载体的药物制剂，制备载体的方法和包含载体的转化细胞。
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公开(公告)号：US08133481B2
公开(公告)日：2012-03-13
申请号：US12706134
申请日：2010-02-16
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10332 , C12N2710/10343 , C12N2830/00 , C12N2830/001 , C12N2830/15
摘要： The present invention provides recombinant viruses which replicate the viral genome selectively in response to the intracellular conditions of the target cell through the use a pathway-responsive promoter which substantially inhibits viral replication in the host cell based on the phenotypic or genotypic of the infected cell. In the target cell, the promoter element of the pathway-responsive promoter is inactive and thus the virus is permitted to replicate. This results in: (1) killing the cells by natural lytic nature of the virus, and/or (2) provides a therapeutic dose of a transgene product (amplified in comparison to replication incompetent vectors) to the target cell, and (3) producing a localized concentration of the virus facilitating the infection of surrounding cells to the recombinant virus. The invention further provides therapeutic and diagnostic methods of use of the vectors, pharmaceutical formulations comprising the vectors, methods of making the vectors and transformed cells comprising the vectors.
摘要翻译： 本发明提供了通过使用基于感染细胞的表型或基因型基本上抑制宿主细胞中的病毒复制的途径反应性启动子来响应于靶细胞的细胞内条件而选择性复制病毒基因的重组病毒。 在靶细胞中，途径反应性启动子的启动子元件是无活性的，因此病毒被允许复制。 这导致：（1）通过病毒的天然裂解性质杀死细胞，和/或（2）向靶细胞提供治疗剂量的转基因产物（与复制无能载体相比扩增），和（3） 产生该病毒的局部浓度，促进周围细胞感染重组病毒。 本发明还提供了使用载体的治疗和诊断方法，包含载体的药物制剂，制备载体的方法和包含载体的转化细胞。
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公开(公告)号：US20100266546A1
公开(公告)日：2010-10-21
申请号：US12706134
申请日：2010-02-16
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10332 , C12N2710/10343 , C12N2830/00 , C12N2830/001 , C12N2830/15
摘要： The present invention provides recombinant viruses which replicate the viral genome selectively in response to the intracellular conditions of the target cell through the use a pathway-responsive promoter which substantially inhibits viral replication in the host cell based on the phenotypic or genotypic of the infected cell. In the target cell, the promoter element of the pathway-responsive promoter is inactive and thus the virus is permitted to replicate. This results in: (1) killing the cells by natural lytic nature of the virus, and/or (2) provides a therapeutic dose of a transgene product (amplified in comparison to replication incompetent vectors) to the target cell, and (3) producing a localized concentration of the virus facilitating the infection of surrounding cells to the recombinant virus. The invention further provides therapeutic and diagnostic methods of use of the vectors, pharmaceutical formulations comprising the vectors, methods of making the vectors and transformed cells comprising the vectors.
摘要翻译： 本发明提供了通过使用基于感染细胞的表型或基因型基本上抑制宿主细胞中的病毒复制的途径反应性启动子来响应于靶细胞的细胞内条件而选择性复制病毒基因的重组病毒。 在靶细胞中，途径反应性启动子的启动子元件是无活性的，因此病毒被允许复制。 这导致：（1）通过病毒的天然裂解性质杀死细胞，和/或（2）向靶细胞提供治疗剂量的转基因产物（与复制无能载体相比扩增），和（3） 产生该病毒的局部浓度，促进周围细胞感染重组病毒。 本发明还提供了使用载体的治疗和诊断方法，包含载体的药物制剂，制备载体的方法和包含载体的转化细胞。
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公开(公告)号：US07001770B1
公开(公告)日：2006-02-21
申请号：US09416735
申请日：1999-10-13
CPC分类号： C12N15/86 , A61K38/1709 , A61K38/1758 , A61K45/06 , C12N2710/10332 , C12N2710/10343
摘要： The present invention provides a method to enhance apoptosis in a cell by the administration of p53 in combination with a calpain inhibitor. The present invention provides a method of increasing the infectivity of a cell to a viral vector by treatment of the cell with a calpain inhibitor. the present invention further provides a method of enhancing transciption of a therapeutic transgene from the CMV promoter. The present invention also provides a method of suppress the in vivo CTL response to viral vectors by the use of calpain inhibitors. The present invention further provides a pharmaceutical formulations of p53 and a calpain inhibitor in a pharmaceutically acceptable carrier. The present invention provides a method of ablating neoplastic cells in a mammalian organism in vivo by the co-administration of a calpain inhibitor and p53. The present invention also provides a method of ablating neoplastic cells in a population of normal cells contaminated by said neoplastic cells ex vivo by the administration of a recombinant adenovirus in combination with a calpain inhibitor to said population.
摘要翻译： 本发明提供了通过与钙蛋白酶抑制剂组合施用p53来增强细胞凋亡的方法。 本发明提供了通过用钙蛋白酶抑制剂处理细胞来增加细胞对病毒载体的感染性的方法。 本发明还提供了增强来自CMV启动子的治疗性转基因的转录的方法。 本发明还提供了通过使用钙蛋白酶抑制剂抑制对病毒载体的体内CTL应答的方法。 本发明进一步提供药学上可接受的载体中的p53和钙蛋白酶抑制剂的药物制剂。 本发明提供了通过共同给予钙蛋白酶抑制剂和p53来体内在哺乳动物生物体内消化肿瘤细胞的方法。 本发明还提供了一种通过将重组腺病毒与钙蛋白酶抑制剂组合给所述群体而在体外从所述赘生性细胞污染的正常细胞群体中消化肿瘤细胞的方法。
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公开(公告)号：US06464976B1
公开(公告)日：2002-10-15
申请号：US09653474
申请日：2000-08-31
申请人： Drake M. LaFace , Amena Rahman , Paul W. Shabram , Van T. Tsai
发明人： Drake M. LaFace , Amena Rahman , Paul W. Shabram , Van T. Tsai
IPC分类号： A61K3900
CPC分类号： C12N15/86 , A61K35/16 , A61K35/30 , A61K48/00 , A61M1/3486 , A61M1/3496 , C12N2710/10343 , Y10S514/885
摘要： The present invention provides an apparatus and method to diminish the pre-existing immune response to the administration of a therapeutic virus by the selective elimination of antiviral antibodies from the serum. The present invention provides a chromatographic material for the elimination of such antibodies. The invention further provides plasmapheresis apparatus comprising this material. The invention further provides methods for the employment of such apparatus as part of therapeutic treatment regiments.
摘要翻译： 本发明提供了通过从血清中选择性消除抗病毒抗体来减少预先存在的对施用治疗性病毒的免疫应答的装置和方法。 本发明提供了用于消除这种抗体的色谱材料。 本发明进一步提供了包含该材料的血浆去除装置。 本发明还提供了使用这种装置作为治疗治疗团的一部分的方法。
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公开(公告)号：US20120219590A1
公开(公告)日：2012-08-30
申请号：US13404950
申请日：2012-02-24
申请人： Amish A. Patel , Paul W. Shabram
发明人： Amish A. Patel , Paul W. Shabram
IPC分类号： A61K39/235 , A61P31/20 , A61P37/04 , A61K39/12 , A61P31/12
CPC分类号： A61K39/235 , A61K39/12 , C12N2710/10334
摘要： The present invention is directed to formulations for spray-drying viral particles, methods for spray drying such compositions, and pharmaceutical compositions and vaccines comprising the present spray-dried powders. The present formulations advantageously provide for spray-drying viral particles at low temperatures, thereby producing spray-dried viral powders having viral infectivities comparable to those of powders prepared by lyophilization of comparable formulations. The methods and compositions described herein advantageously provide substantially higher throughput and production rates for the production of viral powders. Further, spray-dried viral powders incorporating enteric polymers can be produced at low temperatures.
摘要翻译： 本发明涉及用于喷雾干燥病毒颗粒的制剂，用于喷雾干燥该组合物的方法，以及包含本发明喷雾干燥粉末的药物组合物和疫苗。 本发明的制剂有利地在低温下提供喷雾干燥病毒颗粒，由此产生具有与通过冻干可比较的制剂制备的粉末相当的病毒感染性的喷雾干燥的病毒粉末。 本文所述的方法和组合物有利地提供了用于生产病毒粉末的显着更高的产量和生产速率。 此外，可以在低温下生产掺入肠溶聚合物的喷雾干燥的病毒粉末。
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公开(公告)号：US5837520A
公开(公告)日：1998-11-17
申请号：US400793
申请日：1995-03-07
IPC分类号： C08L101/02 , A61K48/00 , C07K14/82 , C08F2/22 , C08F2/44 , C08F8/30 , C08F265/02 , C08L101/00 , C09D11/10 , C12N7/02 , C12N15/09 , C12N15/86 , C12Q1/00 , F23D14/20 , F23D14/48 , F23D14/70 , F23D14/84 , C12N7/00 , C12N15/00
CPC分类号： C12N7/00 , C07K14/82 , C08F265/02 , C09D11/106 , C12N15/86 , C12Q1/00 , A01K2217/05 , A61K48/00 , C12N2710/10343 , C12N2710/10351 , Y10S435/803
摘要： The invention provides a method for purifying viral vectors containing therapeutic genes for use in gene therapy. The invention comprises a method of purification from a cell lysate of a recombinant viral vector containing a therapeutic gene, which comprises: a) treating said lysate with an enzymatic agent that selectively degrades both unencapsulated DNA and RNA; b) chromatographing the treated lysate from step a) on a first resin; and c) chromatographing the eluant from step b) on a second resin; wherein one resin is an anion exchange resin and the other is an immobilized metal ion chromatography (IMAC) resin.
摘要翻译： 本发明提供了一种用于纯化含有用于基因治疗的治疗基因的病毒载体的方法。 本发明包括从包含治疗基因的重组病毒载体的细胞裂解物中纯化的方法，其包括：a）用选择性降解未包封的DNA和RNA的酶试剂处理所述裂解物; b）将经处理的来自步骤a）的裂解物色谱分离在第一树脂上; 和c）将来自步骤b）的洗脱液层析到第二树脂上; 其中一种树脂是阴离子交换树脂，另一种是固定金属离子色谱（IMAC）树脂。
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