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公开(公告)号:US07244617B2
公开(公告)日:2007-07-17
申请号:US10677727
申请日:2003-10-02
申请人: Bingliang Fang , Jack A. Roth
发明人: Bingliang Fang , Jack A. Roth
IPC分类号: C12N15/861 , C12N15/12 , C12N15/34
CPC分类号: C12N7/00 , A61K38/00 , A61K48/00 , C07K14/005 , C07K14/39 , C07K14/475 , C07K2319/00 , C12N15/86 , C12N2710/10322 , C12N2710/10343 , C12N2710/10352 , C12N2830/002 , C12N2830/008 , C12N2830/15 , C12N2830/702
摘要: The present invention provides viral vectors that have been engineered to contain a synthetic promoter that controls at least one essential gene. The synthetic promoter is induced by a specific gene product not normally produced in the cells in which the viral vector is to be transferred. The vectors are propagated in producer or helper cells that express the inducing factor, thereby permitting the virus to replicate to high titer. The lack of the inducing factor in the target cells precludes viral replication, however, meaning that no vector toxicity or immunogenicity arises. Where the virus carries a gene of interest, this should provide for higher level expression for longer periods of time than with current vectors. Methods for making the vectors, helper cells, and their use in protein production, vaccines and gene therapy are disclosed.
摘要翻译: 本发明提供已被工程化以含有控制至少一种必需基因的合成启动子的病毒载体。 合成启动子由病毒载体转移的细胞中通常不产生的特异性基因产物诱导。 载体在表达诱导因子的生产者或辅助细胞中繁殖,从而允许病毒复制至高滴度。 靶细胞缺乏诱导因子排除了病毒复制,但是意味着不会引起载体毒性或免疫原性。 当病毒携带感兴趣的基因时,这应该提供比当前载体更长的时间段的更高级别的表达。 公开了制备载体,辅助细胞及其在蛋白质生产,疫苗和基因治疗中的用途的方法。
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2.
公开(公告)号:US07163925B1
公开(公告)日:2007-01-16
申请号:US09080935
申请日:1998-05-19
申请人: Xiaomei Jin , Jack A. Roth
发明人: Xiaomei Jin , Jack A. Roth
IPC分类号: A61K48/00 , C12N15/63 , C12N15/86 , C12N15/861
CPC分类号: C12N15/86 , A61K48/00 , A61K48/005 , C12N2710/10343
摘要: A variety of genetic constructs are disclosed that will find both in vitro and in vivo use in the area of tumor biology and cancer therapy. In particular, expression constructs are provided that contain a p16 encoding region and other regulatory elements necessary for the expression of a p16 transcript. One version of the expression construct is a replication-deficient adenoviral vector. Also provided are methods for the transformation of cell lines and the inhibition of cancer cell proliferation.
摘要翻译: 公开了在肿瘤生物学和癌症治疗领域中体外和体内使用的多种遗传构建体。 特别地,提供了含有p16编码区和表达p16转录物所必需的其它调节元件的表达构建体。 表达构建体的一个版本是复制缺陷型腺病毒载体。 还提供了转化细胞系和抑制癌细胞增殖的方法。
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公开(公告)号:US07109179B2
公开(公告)日:2006-09-19
申请号:US10784538
申请日:2004-02-23
申请人: Jack A. Roth , Toshiyoshi Fujiwara , Elizabeth A. Grimm , Tapas Mukhopadhyay , Wei-Wei Zhang , Laurie B. Owen-Schaub
发明人: Jack A. Roth , Toshiyoshi Fujiwara , Elizabeth A. Grimm , Tapas Mukhopadhyay , Wei-Wei Zhang , Laurie B. Owen-Schaub
IPC分类号: A61K31/713
CPC分类号: C07K14/82 , A61K31/4745 , A61K31/513 , A61K31/704 , A61K31/7048 , A61K31/7072 , A61K33/24 , A61K38/00 , A61K45/06 , A61K48/00 , C07K14/4746 , C12N15/1135 , C12N15/86 , C12N2710/10332 , C12N2710/10343 , C12N2799/022
摘要: The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.
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公开(公告)号:US07033750B2
公开(公告)日:2006-04-25
申请号:US10170240
申请日:2002-06-11
申请人: Wei-Wei Zhang , Jack A Roth
发明人: Wei-Wei Zhang , Jack A Roth
IPC分类号: C12N15/861 , C12N7/01 , C12N7/02 , C12Q1/70
CPC分类号: C12N15/86 , A61K38/1709 , A61K48/00 , C07K14/4746 , C12N7/00 , C12N2710/10343 , A61K2300/00
摘要: Described are simplified and efficient methods for preparing recombinant adenovirus using liposome-mediated cotransfection and the direct observation of a cytopathic effect (CPE) in the transfected cells. Also disclosed are compositions and methods involving novel p53 adenovirus constructs, including methods for restoring p53 function and tumor suppression in cells and animals having abnormal p53.
摘要翻译: 描述了使用脂质体介导的共转染和直接观察转染细胞中细胞病变效应(CPE)的方法制备重组腺病毒的简化和有效的方法。 还公开了涉及新型p53腺病毒构建体的组合物和方法,包括在具有异常p53的细胞和动物中恢复p53功能和肿瘤抑制的方法。
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公开(公告)号:US06830749B2
公开(公告)日:2004-12-14
申请号:US10180895
申请日:2002-06-25
申请人: Wei-Wei Zhang , Jack A. Roth
发明人: Wei-Wei Zhang , Jack A. Roth
IPC分类号: A61K4300
CPC分类号: C12N15/86 , A61K38/1709 , A61K48/00 , C07K14/4746 , C12N7/00 , C12N2710/10343 , A61K2300/00
摘要: Described are simplified and efficient methods for preparing recombinant adenovirus using liposome-mediated cotransfection and the direct observation of a cytopathic effect (CPE) in the transfected cells. Also disclosed are compositions and methods involving novel p53 adenovirus constructs, including methods for restoring p53 function and tumor suppression in cells and animals having abnormal p53.
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公开(公告)号:US06805858B1
公开(公告)日:2004-10-19
申请号:US09413109
申请日:1999-10-06
申请人: Wei-Wei Zhang , Jack A. Roth
发明人: Wei-Wei Zhang , Jack A. Roth
IPC分类号: A61K4800
CPC分类号: C12N15/86 , A61K38/00 , A61K38/1709 , A61K48/00 , C07K14/4746 , C12N2710/10343 , A61K2300/00
摘要: Described are simplified and efficient methods for preparing recombinant adenovirus using liposome-mediated cotransfection and the direct observation of a cytopathic effect (CPE) in the transfected cells. Also disclosed are compositions and methods involving novel p53 adenovirus constructs, including methods for restoring p53 function and tumor suppression in cells and animals having abnormal p53.
摘要翻译: 描述了使用脂质体介导的共转染和直接观察转染细胞中细胞病变效应(CPE)的方法制备重组腺病毒的简化和有效的方法。 还公开了涉及新型p53腺病毒构建体的组合物和方法,包括在具有异常p53的细胞和动物中恢复p53功能和肿瘤抑制的方法。
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公开(公告)号:US06740320B1
公开(公告)日:2004-05-25
申请号:US08459713
申请日:1995-06-02
申请人: Wei-Wei Zhang , Jack A. Roth
发明人: Wei-Wei Zhang , Jack A. Roth
IPC分类号: A61K4800
CPC分类号: C12N15/86 , A61K38/1709 , A61K48/00 , C07K14/4746 , C12N7/00 , C12N2710/10343 , A61K2300/00
摘要: Described are simplified and efficient methods for preparing recombinant adenovirus using liposome-mediated cotransfection and the direct observation of a cytopathic effect (CPE) in the transfected cells. Also disclosed are compositions and methods involving novel p53 adenovirus constructs, including methods for restoring p53 function and tumor suppression in cells and animals having abnormal p53.
摘要翻译: 描述了使用脂质体介导的共转染和直接观察转染细胞中细胞病变效应(CPE)的方法制备重组腺病毒的简化和有效的方法。 还公开了涉及新型p53腺病毒构建体的组合物和方法,包括在具有异常p53的细胞和动物中恢复p53功能和肿瘤抑制的方法。
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公开(公告)号:US06630344B1
公开(公告)日:2003-10-07
申请号:US09650946
申请日:2000-08-29
申请人: Bingliang Fang , Jack A. Roth
发明人: Bingliang Fang , Jack A. Roth
IPC分类号: C12N15861
CPC分类号: C12N7/00 , A61K38/00 , A61K48/00 , C07K14/005 , C07K14/39 , C07K14/475 , C07K2319/00 , C12N15/86 , C12N2710/10322 , C12N2710/10343 , C12N2710/10352 , C12N2830/002 , C12N2830/008 , C12N2830/15 , C12N2830/702
摘要: The present invention provides viral vectors that have been engineered to contain a synthetic promoter that controls at least one essential gene. The synthetic promoter is induced by a specific gene product not normally produced in the cells in which the viral vector is to be transferred. The vectors are propagated in producer or helper cells that express the inducing factor, thereby permitting the virus to replicate to high titer. The lack of the inducing factor in the target cells precludes viral replication, however, meaning that no vector toxicity or immunogenicity arises. Where the virus carries a gene of interest, this should provide for higher level expression for longer periods of time than with current vectors. Methods for making the vectors, helper cells, and their use in protein production, vaccines and gene therapy are disclosed.
摘要翻译: 本发明提供已被工程化以含有控制至少一种必需基因的合成启动子的病毒载体。 合成启动子由病毒载体转移的细胞中通常不产生的特异性基因产物诱导。 载体在表达诱导因子的生产者或辅助细胞中繁殖,从而允许病毒复制至高滴度。 靶细胞中缺乏诱导因子排除病毒复制,但是意味着不会引起载体毒性或免疫原性。 当病毒携带感兴趣的基因时,这应该提供比当前载体更长的时间段的更高级别的表达。 公开了制备载体,辅助细胞及其在蛋白质生产,疫苗和基因治疗中的用途的方法。
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9.
公开(公告)号:US6069134A
公开(公告)日:2000-05-30
申请号:US953290
申请日:1997-10-17
申请人: Jack A. Roth , Toshiyoshi Fujiwara , Elizabeth A. Grimm , Tapas Mukhopadhyay , Wei-Wei Zhang , Laurie B. Owen-Schaub
发明人: Jack A. Roth , Toshiyoshi Fujiwara , Elizabeth A. Grimm , Tapas Mukhopadhyay , Wei-Wei Zhang , Laurie B. Owen-Schaub
IPC分类号: C12N15/09 , A61K9/08 , A61K31/277 , A61K31/40 , A61K31/407 , A61K31/4745 , A61K31/505 , A61K31/513 , A61K31/70 , A61K31/704 , A61K31/7048 , A61K31/711 , A61K33/24 , A61K35/76 , A61K38/00 , A61K38/17 , A61K45/00 , A61K48/00 , A61K51/00 , A61P35/00 , C07K14/47 , C07K14/82 , C12N15/113 , C12N15/861
CPC分类号: C07K14/82 , A61K31/4745 , A61K31/513 , A61K31/704 , A61K31/7048 , A61K31/7072 , A61K33/24 , A61K45/06 , A61K48/00 , C07K14/4746 , C12N15/1135 , C12N15/86 , A61K38/00 , C12N2710/10332 , C12N2710/10343 , C12N2799/022
摘要: The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.
摘要翻译: 本发明涉及肿瘤抑制基因与DNA损伤剂或因子组合使用,用于杀死细胞,特别是癌细胞。 肿瘤抑制基因p53通过体外和体内的重组腺病毒介导的基因转移与化学治疗剂组合递送。 经特异性DNA断裂处理的细胞经历凋亡。 将p53腺病毒构建体直接注射入肿瘤皮下,然后腹膜内施用DNA损伤剂顺铂,诱导肿瘤的大量凋亡破坏。 本发明还提供了使用复制缺陷型野生型p53腺病毒和DNA损伤药物治疗人类癌症的组合基因置换方案的临床应用。
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公开(公告)号:US5747469A
公开(公告)日:1998-05-05
申请号:US233002
申请日:1994-04-25
申请人: Jack A. Roth , Toshiyoshi Fujiwara , Elizabeth A. Grimm , Tapas Mukhopadhyay , Wei-Wei Zhang , Laurie B. Owen-Schaub
发明人: Jack A. Roth , Toshiyoshi Fujiwara , Elizabeth A. Grimm , Tapas Mukhopadhyay , Wei-Wei Zhang , Laurie B. Owen-Schaub
IPC分类号: C12N15/09 , A61K9/08 , A61K31/277 , A61K31/40 , A61K31/407 , A61K31/4745 , A61K31/505 , A61K31/513 , A61K31/70 , A61K31/704 , A61K31/7048 , A61K31/711 , A61K33/24 , A61K35/76 , A61K38/00 , A61K38/17 , A61K45/00 , A61K48/00 , A61K51/00 , A61P35/00 , C07K14/47 , C07K14/82 , C12N15/113 , C12N15/861 , C12N5/00 , C12N15/00
CPC分类号: C07K14/82 , A61K31/4745 , A61K31/513 , A61K31/704 , A61K31/7048 , A61K31/7072 , A61K33/24 , A61K45/06 , A61K48/00 , C07K14/4746 , C12N15/1135 , C12N15/86 , A61K38/00 , C12N2710/10332 , C12N2710/10343 , C12N2799/022
摘要: The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.
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