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1. 发明申请

WO2010080909A9 COMPOSITIONS AND METHODS OF USE OF AN ONCOLYTIC VESICULAR STOMATITIS VIRUS 审中-公开
公开(公告)号：WO2010080909A9
公开(公告)日：2010-07-15
申请号：PCT/US2010/020370
申请日：2010-01-07
申请人： YALE UNIVERSITY , VAN DEN POL, Anthony, N. , WOLLMANN, Guido
发明人： VAN DEN POL, Anthony, N. , WOLLMANN, Guido
IPC分类号： C07K14/145 , A61K35/76
摘要： Oncolytic VSV viruses have been developed as a strategy for combating cancer. The present invention includes mutant VSV that have one or more mutations in the nucleic acid sequence encoding the viral genome that increase the oncolytic potential of the virus. Pharmaceutical compositions including oncolytic virus disclosed herein are also provided. Pharmaceutical compositions containing virus and one or more excipients may be for systemic or local administration. Methods of administering an effective amount of the compositions for treating cancer are disclosed. Preferred routes of administration include intratumeral and intravenous injection, and intranasal delivery. Administration of the disclosed compositions containing oncolytic viruses may be coupled with surgical, radiologic, other therapeutic approaches to treatment of cancer. Methods of manufacturing mutant VSV viruses exhibiting desired properties include applying selective pressure, and through directed or random mutagenesis.

2. 发明申请

WO2015077714A1 CHIMERIC VSV VIRUS COMPOSITIONS AND METHODS OF USE THEREOF FOR TREATMENT OF CANCER 审中-公开
标题翻译： CHIMERIC VSV病毒组合物及其用于治疗癌症的方法
公开(公告)号：WO2015077714A1
公开(公告)日：2015-05-28
申请号：PCT/US2014/067137
申请日：2014-11-24
申请人： YALE UNIVERSITY
发明人： VAN DEN POL, Anthony N. , WOLLMANN, Guido
IPC分类号： A61K35/766 , A61K39/00 , A61P35/00 , C12N15/86
CPC分类号： A61K35/766 , A61K9/0019 , A61K9/0043 , A61K9/007 , A61K35/12 , A61K39/205 , A61K45/06 , A61K2039/5152 , A61K2039/5256 , C12N7/00 , C12N7/04 , C12N2760/20133 , C12N2760/20222 , C12N2760/20223 , C12N2760/20232 , C12N2760/20234
摘要： Methods of treating cancer including administering to a subject with cancer a pharmaceutical composition including an effective amount of a chimeric VSV virus are disclosed. The chimeric viruses are based on a VSV background where the VSV G protein is replaced with one or more heterologous viral glycoproteins. In the most preferred embodiment, the VSV G protein is replaced with the glycoprotein from Lassa virus or a functional fragment thereof. The resulting chimeric virus is an oncolytic virus that is attenuated and safe in the brain, yet still retains sufficient oncolytic activity to infect and destroy cancer cells such glioblastoma, and to generate an immune response against infected cancer cells. Methods of using chimeric viruses as a platform for immunization against other pathogenic microbes are also provided.
摘要翻译：公开了治疗癌症的方法，包括向受试者施用包含有效量的嵌合VSV病毒的药物组合物。嵌合病毒基于VSV背景，其中VSV G蛋白被一种或多种异源病毒糖蛋白替代。在最优选的实施方案中，VSV G蛋白被来自Lassa病毒的糖蛋白或其功能片段替代。所得到的嵌合病毒是在脑中减毒和安全的溶瘤病毒，但仍保留足够的溶瘤活性以感染和破坏癌细胞如胶质母细胞瘤，并产生针对感染的癌细胞的免疫应答。还提供了使用嵌合病毒作为免疫其他致病微生物的平台的方法。

3. 发明申请

WO2011056993A1 COMPOSITIONS AND METHODS FOR TREATING CANCER WITH ATTENUATED ONCOLYTIC VIRUSES 审中-公开
标题翻译：用于治疗患有衰老的光感病毒的癌症的组合物和方法
公开(公告)号：WO2011056993A1
公开(公告)日：2011-05-12
申请号：PCT/US2010/055480
申请日：2010-11-04
申请人： YALE UNIVERSITY , VAN DEN POL, Anthony, N. , WOLLMANN, Guido
发明人： VAN DEN POL, Anthony, N. , WOLLMANN, Guido
IPC分类号： C07K14/145 , A61K35/76 , C12N7/04
CPC分类号： A61K38/21 , A61K35/766 , C12N7/00 , C12N2760/20232 , C12N2760/20261 , A61K2300/00
摘要： Compositions including attenuated oncolytic viruses and methods of their use for the treatment of cancer are disclosed. Some attenuated virus exhibit potential as tumor therapies by exhibiting characteristics including, but not limited to, high selectivity, infectivity, cytotoxicity, or replication index for tumor cells, and/or low infectivity, cytotoxicity, or replication index for normal cells. In preferred embodiments, the ratio of replication of virus in normal cells-tumor cells is about 1:100 or greater. Preferred viruses have two or more mechanisms of attenuation including insertion of a transgene such as GFP or an interferon, preferably at position 1 of the viral genome. The compositions can be administered to subjects having tumors, in an effective amount to delay or inhibit the growth of a tumor, reduce the growth or size of the tumor, and/or inhibit or reduce metastasis of the tumor. Methods for manufacturing viruses and methods of testing their oncolytic potential are also disclosed.
摘要翻译：公开了包括减毒的溶瘤病毒及其用于治疗癌症的方法的组合物。一些减毒病毒通过表现出特征，包括但不限于肿瘤细胞的高选择性，感染性，细胞毒性或复制指数，和/或正常细胞的低感染性，细胞毒性或复制指数，具有肿瘤治疗的潜力。在优选的实施方案中，病毒在正常细胞 - 肿瘤细胞中的复制比例为约1:100或更高。优选的病毒具有两种或更多种衰减机制，包括插入转基因例如GFP或干扰素，优选在病毒基因组的位置1。组合物可以以有效量施用于具有肿瘤的受试者，以延缓或抑制肿瘤的生长，减少肿瘤的生长或大小，和/或抑制或减少肿瘤的转移。还公开了制造病毒的方法和测试其溶瘤潜力的方法。

4. 发明申请

WO2010080909A1 COMPOSITIONS AND METHODS OF USE OF AN ONCOLYTIC VESICULAR STOMATITIS VIRUS 审中-公开
标题翻译：组合物和使用粘膜炎症性STOMATITIV病毒的方法
公开(公告)号：WO2010080909A1
公开(公告)日：2010-07-15
申请号：PCT/US2010/020370
申请日：2010-01-07
申请人： YALE UNIVERSITY , VAN DEN POL, Anthony, N. , WOLLMANN, Guido
发明人： VAN DEN POL, Anthony, N. , WOLLMANN, Guido
IPC分类号： C07K14/145 , A61K35/76
CPC分类号： C07K14/005 , A61K38/00 , C12N2760/20222 , C12N2760/20232
摘要： Oncolytic VSV viruses have been developed as a strategy for combating cancer. The present invention includes mutant VSV that have one or more mutations in the nucleic acid sequence encoding the viral genome that increase the oncolytic potential of the virus. Pharmaceutical compositions including oncolytic virus disclosed herein are also provided. Pharmaceutical compositions containing virus and one or more excipients may be for systemic or local administration. Methods of administering an effective amount of the compositions for treating cancer are disclosed. Preferred routes of administration include intratumeral and intravenous injection, and intranasal delivery. Administration of the disclosed compositions containing oncolytic viruses may be coupled with surgical, radiologic, other therapeutic approaches to treatment of cancer. Methods of manufacturing mutant VSV viruses exhibiting desired properties include applying selective pressure, and through directed or random mutagenesis.
摘要翻译：已经开发了溶瘤VSV病毒作为防治癌症的策略。本发明包括突变体VSV，其在编码病毒基因组的核酸序列中具有增加病毒溶瘤潜力的一个或多个突变。还提供了包括本文公开的溶瘤病毒的药物组合物。含有病毒和一种或多种赋形剂的药物组合物可用于全身或局部施用。公开了施用有效量的治疗癌症的组合物的方法。优选的给药途径包括瘤内和静脉内注射，以及鼻内递送。所公开的含有溶瘤病毒的组合物的施用可与用于治疗癌症的手术，放射学，其它治疗方法相结合。显示所需性质的突变VSV病毒的制备方法包括施加选择压力，并通过定向或随机诱变。

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