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1. 发明授权

US06573090B1 Enhanced packaging of herpes virus amplicons and generation of recombinant virus vectors 失效
标题翻译：增强疱疹病毒扩增子的包装和重组病毒载体的产生
公开(公告)号：US06573090B1
公开(公告)日：2003-06-03
申请号：US09458068
申请日：1999-12-09
申请人： Xandra O. Breakefield , E. Antonio Chiocca , Yoshinaga Saeki , Cornel Fraefel , Kurt Tobler , Mathias Ackermann , Mark Suter , Gosse J. Adema , Ken Shortman
发明人： Xandra O. Breakefield , E. Antonio Chiocca , Yoshinaga Saeki , Cornel Fraefel , Kurt Tobler , Mathias Ackermann , Mark Suter , Gosse J. Adema , Ken Shortman
IPC分类号： C12N1581
CPC分类号： C12N15/86 , A61K39/00 , A61K39/12 , A61K39/245 , A61K48/00 , A61K2039/5256 , A61K2039/53 , A61K2039/545 , C12N2710/16634 , C12N2710/16643 , C12N2800/204
摘要： The present invention relates to an enhanced and simplified herpes virus amplicon packaging system. The packaging system comprises a herpes virus amplicon vector and a packaging vector. In one embodiment, the packaging vector comprises a bacterial artificial chromosome (BAC) containing the HSV-1 genome. The packaging vector contains an intact pac site but is otherwise rendered packaging defective. The packaging vector can be rendered packaging defective by inserting nucleotides into the pac site, or by otherwise interfering with the capsid's ability to close, for example, by increasing the size of the DNA fragment upon which the herpes virus genome is cloned. This system can be used to package a wide range of nucleotide sequences (e.g., a therapeutic or antigenic gene) into an empty herpes virus particle taking advantage of the large transgene capacity of herpes viruses. This system can also be used as a vaccine to induce protective immunity against HSV-1, or other complex pathogens.
摘要翻译：本发明涉及增强和简化的疱疹病毒扩增子包装系统。包装系统包括疱疹病毒扩增子载体和包装载体。在一个实施方案中，包装载体包含含有HSV-1基因组的细菌人造染色体（BAC）。包装载体包含完整的pac位点，否则会导致包装有缺陷。包装载体可以通过将核苷酸插入pac位点而被包装有缺陷，或以其它方式干扰衣壳关闭的能力，例如通过增加克隆疱疹病毒基因组的DNA片段的大小。该系统可用于利用疱疹病毒的大转基因能力将大范围的核苷酸序列（例如，治疗或抗原基因）包装到空疱疹病毒颗粒中。该系统也可以用作疫苗来诱导针对HSV-1或其他复杂病原体的保护性免疫。

2. 发明授权

US06602499B1 Combination viral-based and gene-based therapy of tumors 有权
标题翻译：组合病毒和基于肿瘤的基因治疗
公开(公告)号：US06602499B1
公开(公告)日：2003-08-05
申请号：US09302952
申请日：1999-04-30
申请人： E. Antonio Chiocca , Xandra O. Breakefield
发明人： E. Antonio Chiocca , Xandra O. Breakefield
IPC分类号： A61K3500
CPC分类号： B82Y5/00 , A61K31/675 , A61K35/763 , A61K38/415 , A61K38/44 , A61K45/06 , A61K47/6891 , A61K48/00 , C12N7/00 , C12N15/86 , C12N2710/16332 , C12N2710/16632 , C12N2710/16643 , C12Y114/14 , C12Y117/04001 , A61K2300/00
摘要： The present invention relates to viral mutants and methods of using these viral mutants for selectively killing neoplastic cells. The viral mutants of the invention are capable of selectively killing neoplastic cells by a combination of viral mediated oncolysis and anti-cancer (“suicide”) gene therapy.
摘要翻译：本发明涉及病毒突变体和使用这些病毒突变体选择性杀死肿瘤细胞的方法。本发明的病毒突变体能够通过病毒介导的溶瘤和抗癌（“自杀”）基因治疗的组合选择性地杀死肿瘤细胞。

3. 发明授权

US5688773A Method of selectively destroying neoplastic cells 失效
标题翻译：选择性破坏肿瘤细胞的方法
公开(公告)号：US5688773A
公开(公告)日：1997-11-18
申请号：US330523
申请日：1994-10-28
申请人： E. Antonio Chiocca , David J. Waxman , Ming X. Wei , Xandra O. Breakefield , Ling Chen
发明人： E. Antonio Chiocca , David J. Waxman , Ming X. Wei , Xandra O. Breakefield , Ling Chen
IPC分类号： C12N15/09 , A61K31/675 , A61K35/76 , A61K38/00 , A61K48/00 , A61P25/00 , A61P35/00 , C12N5/10 , C12N9/02 , C12N5/00 , C12N15/00 , C07N14/00
CPC分类号： C12N9/0079 , A61K48/00 , A61K38/00 , C12N2799/027
摘要： A method for selectively killing nervous system and peripheral neoplastic cells is provided. Viral vectors are used to selectively express a cytochrome P450 gene in neoplastic cells, whose gene product targets the cells for selective killing, by rendering the cells sensitive to a chemotherapeutic agent.
摘要翻译：提供了选择性地杀死神经系统和外周肿瘤细胞的方法。病毒载体用于通过使细胞对化学治疗剂敏感的肿瘤细胞中选择性表达细胞色素P450基因，其肿瘤细胞的基因产物靶向选择性杀伤细胞。

4. 发明授权

US07214515B2 Viral delivery system for infectious transfer of large genomic DNA inserts 有权
标题翻译：用于传染性大基因组DNA插入片段的病毒递送系统
公开(公告)号：US07214515B2
公开(公告)日：2007-05-08
申请号：US10035216
申请日：2002-01-04
申请人： E. Antonio Chiocca , Yoshinaga Saeki , Richard Wade-Martins
发明人： E. Antonio Chiocca , Yoshinaga Saeki , Richard Wade-Martins
IPC分类号： C12N15/64 , C12N15/70 , C12N15/79
CPC分类号： C12N7/00 , A61K38/177 , A61K38/45 , A61K48/00 , C12N15/86 , C12N2710/10343 , C12N2710/16643 , C12N2800/108 , C12N2800/204 , C12N2800/206 , C12N2800/30
摘要： The present invention relates to HSV-based amplicon vectors carrying a genomic DNA fragment, and methods of constructing and using the same. Included within the present invention is a method of converting any large capacity DNA cloning vector, such as a BAC or PAC, into an HSV amplicon or hybrid HSV amplicon using site-specific, or other types of recombination, so that genomic DNA inserts within the BAC or PAC clone can be delivered by infection to a cell, and efficiently expressed. The present invention also relates to a system for the rapid creation of viral vectors carrying transgenes of interest. This aspect of the invention is accomplished through recombination between: (a) a large-capacity cloning vector carrying a viral genome, and (b) a transfer vector containing the transgene of interest. Finally, an expression-ready genomic DNA library is disclosed.
摘要翻译：本发明涉及携带基因组DNA片段的基于HSV的扩增子载体及其构建和使用方法。本发明中包括使用位点特异性或其他类型的重组将任何大容量DNA克隆载体（例如BAC或PAC）转化成HSV扩增子或杂交HSV扩增子的方法，使得基因组DNA插入到 BAC或PAC克隆可通过感染递送至细胞，并有效表达。本发明还涉及快速产生携带转基因的病毒载体的系统。本发明的这个方面是通过以下之间的重组来实现的：（a）携带病毒基因组的大容量克隆载体和（b）含有感兴趣的转基因的转移载体。最后，公开了一种表达基因组DNA文库。

5. 发明申请

US20100143500A1 Methods and Compositions for Inhibiting GSK-3 In Glial Cell Related Disorders 审中-公开
标题翻译：抑制GSK-3胶质细胞相关疾病的方法和组合
公开(公告)号：US20100143500A1
公开(公告)日：2010-06-10
申请号：US12447811
申请日：2007-10-31
申请人： Sean E. Lawler , Michal Oskar Nowicki , E. Antonio Chiocca
发明人： Sean E. Lawler , Michal Oskar Nowicki , E. Antonio Chiocca
IPC分类号： A61K33/14 , A61K31/4015 , A61K31/426 , C12Q1/48 , C12N9/12 , C07D207/24 , C07D277/38 , C01D15/04 , A61P35/00
CPC分类号： A61K33/14 , A61K31/4015 , A61K31/426 , C12Q1/485 , G01N33/57407 , G01N2333/912 , G01N2500/00 , A61K2300/00
摘要： A method of treating a glial cell related disorder in a mammalian subject includes administering a drug which enhances or prolongs GSK-3 α or β inactivation.
摘要翻译：在哺乳动物受试者中治疗神经胶质细胞相关病症的方法包括施用增强或延长GSK-3α或bgr的药物; 灭活。

6. 发明授权

US06897057B1 Cell-specific and/or tumor-specific promoter retargeting of herpes γ 34.5 gene expression 有权
标题翻译：细胞特异性和/或肿瘤特异性启动子重新靶向疱疹γ34.5基因表达
公开(公告)号：US06897057B1
公开(公告)日：2005-05-24
申请号：US09653277
申请日：2000-08-31
申请人： E. Antonio Chiocca , Richard Y. Chung
发明人： E. Antonio Chiocca , Richard Y. Chung
IPC分类号： A61K48/00 , C07K14/035 , C12N7/00 , C12N15/869 , C12N5/00 , A61K31/70 , C12P21/06
CPC分类号： C12N15/86 , A61K48/00 , A61K2039/525 , A61K2039/5256 , C07K14/005 , C12N7/00 , C12N2710/16622 , C12N2710/16643 , C12N2830/00
摘要： The present invention relates to herpes viral mutants and methods of using these viral mutants for selectively targeting tumor cells or other populations of target cells. The viral mutants of the invention are capable of selective targeting due to the use of tumor-specific and/or cell-specific promoters to drive expression of the herpes γ34.5 gene.
摘要翻译：本发明涉及疱疹病毒突变体和使用这些病毒突变体选择性靶向靶细胞肿瘤细胞或其他群体的方法。由于使用肿瘤特异性和/或细胞特异性启动子驱动疱疹γ34.5基因的表达，本发明的病毒突变体能够进行选择性靶向。

7. 发明授权

US06602701B2 Three-dimensional cell growth assay 失效
标题翻译：三维细胞生长测定
公开(公告)号：US06602701B2
公开(公告)日：2003-08-05
申请号：US09758644
申请日：2001-01-11
申请人： Thomas S. Deisboeck , E. Antonio Chiocca , John D. Wright
发明人： Thomas S. Deisboeck , E. Antonio Chiocca , John D. Wright
IPC分类号： C12M300
CPC分类号： C12M41/36 , C12M23/34
摘要： The invention relates to devices and methods for growing cells in vitro in an enclosed device that allows for a three-dimensional measurement over time of both their proliferative and/or invasive properties. By growing the cells in an enclosed matrix that resembles the environment that the cells confront in vivo, the cells can divide, invade, and form branched networks as they do in living tissue, e.g., in an individual. The devices of the invention include a test chamber in which cells, e.g., tumor cells, are placed and permitted to divide and/or invade. Cells can be placed within an insert within a chamber of the device. A delivery chamber that connects to the test chamber enables the delivery of agents that can be studied, e.g., for their therapeutic potential. The assay devices of the invention can be used as model systems to study cancer biology and to evaluate the efficacy of anti-cancer therapeutics.
摘要翻译：本发明涉及用于在封闭装置中体外培养细胞的装置和方法，所述装置和方法允许随着时间的推移进行三维测量，包括它们的增殖和/或侵入性质。通过将细胞生长在类似于细胞在体内所面临的环境的封闭的基质中，细胞可如在活组织中例如在个体中分开，侵入并形成分支的网络。本发明的装置包括测试室，其中放置例如肿瘤细胞的细胞并允许分裂和/或侵入细胞。细胞可以放置在装置的腔室内的插入物内。连接到测试室的输送室能够输送可以研究的药剂，例如用于其治疗潜力。本发明的测定装置可用作模型系统来研究癌症生物学并评估抗癌治疗剂的功效。

8. 发明申请

US20100273258A1 Interactive Microenvironment System 审中-公开
标题翻译：交互式微环境系统
公开(公告)号：US20100273258A1
公开(公告)日：2010-10-28
申请号：US12766328
申请日：2010-04-23
申请人： John J. Lannutti , Jed K. Johnson , E. Antonio Chiocca , Sara Nicole Fischer , Sean E. Lawler , Young C. Lin , Clay B. Marsh
发明人： John J. Lannutti , Jed K. Johnson , E. Antonio Chiocca , Sara Nicole Fischer , Sean E. Lawler , Young C. Lin , Clay B. Marsh
IPC分类号： C12N5/071 , C12M3/00
CPC分类号： C12M23/12 , C12M23/34 , C12M25/04 , C12M35/04 , C12M35/08 , C12N5/0068 , C12N2533/40 , D01D5/003 , D01F6/625
摘要： A culture cell for growing animal cells in vitro has sides and a bottom forming a volume. The volume contains a layer of nanofiber upon which animal cells can be cultured. The layer of nanofiber can be oriented or non-oriented. Multiple layers can be placed in the volume, where the layers have different composition and/or different porosity. The nanofiber can be, for example, surface treated or of a core-shell construction.
摘要翻译：用于在体外生长动物细胞的培养细胞具有形成体积的侧面和底部。体积包含一层可以培养动物细胞的纳米纤维。纳米纤维层可以定向或不定向。多层可以放置在体积中，其中层具有不同的组成和/或不同的孔隙率。纳米纤维可以是例如表面处理的或核 - 壳结构。

9. 发明授权

US07514252B2 Cell-specific and/or tumor-specific promoter retargeting of herpes γ 34.5 gene expression 有权
标题翻译：细胞特异性和/或肿瘤特异性启动子重新靶向疱疹γ34.5基因表达
公开(公告)号：US07514252B2
公开(公告)日：2009-04-07
申请号：US11042189
申请日：2005-01-26
申请人： E. Antonio Chiocca , Richard Y. Chung
发明人： E. Antonio Chiocca , Richard Y. Chung
IPC分类号： C12N7/00 , C12N15/63 , A61K35/00
CPC分类号： C12N15/86 , A61K48/00 , A61K2039/525 , A61K2039/5256 , C07K14/005 , C12N7/00 , C12N2710/16622 , C12N2710/16643 , C12N2830/00
摘要： The present invention relates to herpes viral mutants and methods of using these viral mutants for selectively targeting tumor cells or other populations of target cells. The viral mutants of the invention are capable of selective targeting due to the use of tumor-specific and/or cell-specific promoters to drive expression of the herpes γ34.5 gene.
摘要翻译：本发明涉及疱疹病毒突变体和使用这些病毒突变体选择性靶向靶细胞肿瘤细胞或其他群体的方法。由于使用肿瘤特异性和/或细胞特异性启动子驱动疱疹γ34.5基因的表达，本发明的病毒突变体能够进行选择性靶向。

10. 发明授权

US06849424B2 Three-dimensional cell growth assay 失效
标题翻译：三维细胞生长测定
公开(公告)号：US06849424B2
公开(公告)日：2005-02-01
申请号：US10365677
申请日：2003-02-12
申请人： Thomas S. Deisboeck , E. Antonio Chiocca , John D. Wright
发明人： Thomas S. Deisboeck , E. Antonio Chiocca , John D. Wright
IPC分类号： C12M1/12 , C12M1/34 , C12Q1/02
CPC分类号： C12M41/36 , C12M23/34
摘要： The invention relates to devices and methods for growing cells in vitro in an enclosed device that allows for a three-dimensional measurement over time of both their proliferative and/or invasive properties. By growing the cells in an enclosed matrix that resembles the environment that the cells confront in vivo, the cells can divide, invade, and form branched networks as they do in living tissue, e.g., in an individual. The devices of the invention include a test chamber in which cells, e.g., tumor cells, are placed and permitted to divide and/or invade. Cells can be placed within an insert within a chamber of the device. A delivery chamber that connects to the test chamber enables the delivery of agents that can be studied, e.g., for their therapeutic potential. The assay devices of the invention can be used as model systems to study cancer biology and to evaluate the efficacy of anti-cancer therapeutics.
摘要翻译：本发明涉及用于在封闭装置中体外培养细胞的装置和方法，所述装置和方法允许随着时间的推移进行三维测量，包括它们的增殖和/或侵入性质。通过将细胞生长在类似于细胞在体内所面临的环境的封闭的基质中，细胞可如在活组织中例如在个体中分开，侵入并形成分支的网络。本发明的装置包括测试室，其中放置例如肿瘤细胞的细胞并允许分裂和/或侵入细胞。细胞可以放置在装置的腔室内的插入物内。连接到测试室的输送室能够输送可以研究的药剂，例如用于其治疗潜力。本发明的测定装置可用作模型系统来研究癌症生物学并评估抗癌治疗剂的功效。

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