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1. 发明授权

US08772471B2 Targeted delivery of siRNA 有权
标题翻译：靶向递送siRNA
公开(公告)号：US08772471B2
公开(公告)日：2014-07-08
申请号：US12524536
申请日：2008-01-25
申请人： Premlata Shankar , Sang-Kyung Lee , Manjunath Narasimhaswamy , Priti Kumar , Haoquan Wu , Hong-Seok Ban
发明人： Premlata Shankar , Sang-Kyung Lee , Manjunath Narasimhaswamy , Priti Kumar , Haoquan Wu , Hong-Seok Ban
IPC分类号： C07H21/04 , C12N15/11
CPC分类号： C12N15/111 , A61K48/00 , C12N15/1135 , C12N15/1136 , C12N15/1138 , C12N15/115 , C12N2310/14 , C12N2310/3513 , C12N2320/32
摘要： The present invention provides a method of delivering RNA interference molecules to a cell or a cell in a subject, which comprises contacting the cell with a protein-double stranded RNA complex, the complex comprising the double stranded RNA segment containing a double stranded RNA of interest and a protein, the protein comprising (1) a targeting moiety, which will specifically bind to a site on a target cell, and (2) a binding moiety linked thereto, which will bind to the double stranded RNA, wherein the double stranded RNA segment is delivered to a cell and effects RNA interference of the target RNA in the cell.
摘要翻译：本发明提供了将RNA干扰分子递送至受试者的细胞或细胞的方法，该方法包括使细胞与蛋白质双链RNA复合物接触，所述复合物包含含有目的双链RNA的双链RNA片段和蛋白质，所述蛋白质包含（1）将特异性结合靶细胞上的位点的靶向部分，和（2）与所述双链RNA结合的与其连接的结合部分，其中所述双链RNA 片段被递送到细胞并且影响目标RNA在细胞中的RNA干扰。

2. 发明申请

US20100209440A1 Targeted Delivery of siRNA 有权
标题翻译：靶向递送siRNA
公开(公告)号：US20100209440A1
公开(公告)日：2010-08-19
申请号：US12524536
申请日：2008-01-25
申请人： Premlata Shankar , Sang-Kyung Lee , Manjunath Narasimhaswamy , Priti Kumar , Haoquan Wu , Hong-Seok Ban
发明人： Premlata Shankar , Sang-Kyung Lee , Manjunath Narasimhaswamy , Priti Kumar , Haoquan Wu , Hong-Seok Ban
IPC分类号： A61K39/395 , A61K38/02 , C07K19/00 , A61P35/00 , A61P31/18 , A61P31/12 , C12N5/07
CPC分类号： C12N15/111 , A61K48/00 , C12N15/1135 , C12N15/1136 , C12N15/1138 , C12N15/115 , C12N2310/14 , C12N2310/3513 , C12N2320/32
摘要： The present invention provides a method of delivering RNA interference molecules to a cell or a cell in a subject, which comprises contacting the cell with a protein-double stranded RNA complex, the complex comprising the double stranded RNA segment containing a double stranded RNA of interest and a protein, the protein comprising (1) a targeting moiety, which will specifically bind to a site on a target cell, and (2) a binding moiety linked thereto, which will bind to the double stranded RNA, wherein the double stranded RNA segment is delivered to a cell and effects RNA interference of the target RNA in the cell.
摘要翻译：本发明提供了将RNA干扰分子递送至受试者的细胞或细胞的方法，该方法包括使细胞与蛋白质双链RNA复合物接触，所述复合物包含含有目的双链RNA的双链RNA片段和蛋白质，所述蛋白质包含（1）将特异性结合靶细胞上的位点的靶向部分，和（2）与所述双链RNA结合的与其连接的结合部分，其中所述双链RNA 片段被递送到细胞并且影响目标RNA在细胞中的RNA干扰。

3. 发明授权

US08748567B2 Method for delivery across the blood brain barrier 有权
标题翻译：穿过血脑屏障的方法
公开(公告)号：US08748567B2
公开(公告)日：2014-06-10
申请号：US12301847
申请日：2007-05-22
申请人： Manjunath Narasimhaswamy , Premlata Shankar , Priti Kumar
发明人： Manjunath Narasimhaswamy , Premlata Shankar , Priti Kumar
IPC分类号： A61K38/00 , A61K39/00 , A61K39/12 , A61K39/205
CPC分类号： A61K47/64 , A61K47/62 , A61K47/645 , A61K47/6455 , A61K47/6911 , A61K47/6921 , A61K47/6951 , A61K49/0056 , B82Y5/00
摘要： The present invention provides compositions and methods useful for delivering agents to target cells or tissues, for example nerve cells and other cells in the central nervous system. The compositions and methods are useful for delivering agents across the blood-brain barrier. The present invention also provides methods of using the compositions provided by the present invention to deliver agents, for example therapeutic agents for the treatment of neurologically related disorders.
摘要翻译：本发明提供了用于将药剂递送至靶细胞或组织例如神经细胞和中枢神经系统中的其它细胞的组合物和方法。组合物和方法可用于递送穿过血脑屏障的药剂。本发明还提供使用本发明提供的组合物递送药物的方法，例如用于治疗神经相关病症的治疗剂。

4. 发明申请

US20100233084A1 Method for Delivery Across the Blood Brain Barrier 有权
标题翻译：交叉血液脑屏障的方法
公开(公告)号：US20100233084A1
公开(公告)日：2010-09-16
申请号：US12301847
申请日：2007-05-22
申请人： Manjunath Narasimhaswamy , Premlata Shankar , Priti Kumar
发明人： Manjunath Narasimhaswamy , Premlata Shankar , Priti Kumar
IPC分类号： A61K49/00 , C07K14/145 , A61K38/16 , C12N5/02 , C07K16/00 , A61K39/395 , C12Q1/02
CPC分类号： A61K47/64 , A61K47/62 , A61K47/645 , A61K47/6455 , A61K47/6911 , A61K47/6921 , A61K47/6951 , A61K49/0056 , B82Y5/00
摘要： The present invention provides compositions and methods useful for delivering agents to target cells or tissues, for example nerve cells and other cells in the central nervous system. The compositions and methods are useful for delivering agents across the blood-brain barrier. The present invention also provides methods of using the compositions provided by the present invention to deliver agents, for example therapeutic agents for the treatment of neurologically related disorders.
摘要翻译：本发明提供了用于将药剂递送至靶细胞或组织例如神经细胞和中枢神经系统中的其它细胞的组合物和方法。组合物和方法可用于递送穿过血脑屏障的药剂。本发明还提供使用本发明提供的组合物递送药物的方法，例如用于治疗神经相关病症的治疗剂。

5. 发明授权

US07696179B2 Inhibition of gene expression using RNA interfering agents 有权
标题翻译：使用RNA干扰剂抑制基因表达
公开(公告)号：US07696179B2
公开(公告)日：2010-04-13
申请号：US10533621
申请日：2003-10-29
申请人： Judy Lieberman , Manjunath Narasimhaswamy , Erwei Song , Sang-Kyung Lee , Premlata Shankar
发明人： Judy Lieberman , Manjunath Narasimhaswamy , Erwei Song , Sang-Kyung Lee , Premlata Shankar
IPC分类号： A01N63/00 , A61K48/00
CPC分类号： C12N15/1138 , A61K38/00 , A61M1/14 , A61M1/16 , A61M1/1609 , A61M1/1617 , A61M1/3406 , A61M1/3609 , A61M1/3612 , A61M2202/0498 , A61M2205/15 , A61M2205/33 , A61M2205/3317 , A61M2205/3324 , A61M2205/50 , A61M2205/52 , C12N15/1132 , C12N2310/111 , C12N2310/14 , C12N2310/53 , Y02A50/465
摘要： The present invention is based, at least in part, on the discovery of compositions and methods for the treatment and prevention of infectious diseases or disorders, e.g., HIV infection, AIDS, and AIDS-related diseases. In particular, the present invention pertains to methods of modulating cellular gene expression or protein activity, e.g., CCR5, gene expression or protein activity and/or gene expression or protein activity of a gene or sequence of an infectious agent, in order to treat or prevent infectious diseases or disorders, HIV infection, AIDS, or an AIDS-related disease or disorder. In one embodiment the combination of an RNA interfering agent targeting a cellular gene in combination with an RNA interfering agent targeting a gene or sequence of an infectious agent results in prolonged prevention of infection by an infectious agent. The present invention is based on the identification of novel RNA interference agents, e.g., siRNA molecules, which target cellular genes, e.g., chemokine receptors, e.g., the CCR5 gene, and result in inhibition of target gene expression on target gene expressing cells, thereby inhibiting entry of infectious agents, e,g., HIV infection into target cells, prevention infection, and/or suppressing replication in established infection.
摘要翻译：本发明至少部分地基于发现用于治疗和预防感染性疾病或病症的组合物和方法，例如HIV感染，AIDS和AIDS相关疾病。特别地，本发明涉及调节细胞基因表达或蛋白质活性的方法，例如CCR5，基因表达或蛋白质活性和/或感染因子的基因或序列的基因表达或蛋白质活性，以便治疗或预防传染病或疾病，艾滋病毒感染，艾滋病或艾滋病相关疾病或病症。在一个实施方案中，靶向细胞基因的RNA干扰剂与靶向感染因子的基因或序列的RNA干扰剂的组合导致长期预防感染性感染的感染。本发明基于鉴定靶向细胞基因（例如趋化因子受体，例如CCR5基因）的新型RNA干扰剂，例如siRNA分子，并导致靶基因表达细胞的靶基因表达的抑制，从而抑制感染因子的侵入，例如艾滋病毒感染进入靶细胞，预防感染和/或抑制确定的感染中的复制。

6. 发明申请

US20070254850A1 Methods for Treating and Preventing Apoptosis-Related Diseases Using Rna Interfering Agents 审中-公开
标题翻译：使用Rna干扰剂治疗和预防凋亡相关疾病的方法
公开(公告)号：US20070254850A1
公开(公告)日：2007-11-01
申请号：US10533622
申请日：2003-10-30
申请人： Judy Lieberman , Manjunath Narasimhaswamy , Erwei Song , Sang-Kyung Lee , Nedim Ince , Premlata Shankar
发明人： Judy Lieberman , Manjunath Narasimhaswamy , Erwei Song , Sang-Kyung Lee , Nedim Ince , Premlata Shankar
IPC分类号： A61K48/00 , C12N15/867 , C12N5/08
CPC分类号： C12N15/1136 , C12N15/1138 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2799/027
摘要： The present invention is based, at least in part, on the discovery of compositions and methods useful in the modulation, e.g., inhibition, of gene expression or protein activity. In particular, the present invention is based on novel RNA interfering agents, e.g., siRNA molecules which target apoptosis-related genes or proinflammatory cytokines, and result in reduction, e.g., prolonged reduction, of apoptosis-related gene expression or proinflammatory cytokine expression in cells. Inhibition of apoptosis-related gene expression or protein activity or proinflammatory cytokine expression or protein activity, e.g., by the siRNAs of the invention, inhibits apoptosis-mediated diseases or disorders and proinflammatory cytokine mediated diseases or disorders, including, for example, transplant rejection, hepatitis, liver injury, sepsis, and cancer.
摘要翻译：本发明至少部分地基于发现可用于调节，例如抑制基因表达或蛋白质活性的组合物和方法。特别地，本发明基于新的RNA干扰剂，例如靶向凋亡相关基因或促炎细胞因子的siRNA分子，并导致细胞凋亡相关基因表达或促炎细胞因子表达的减少，例如延长的减少。抑制凋亡相关基因表达或蛋白质活性或促炎细胞因子表达或蛋白质活性，例如通过本发明的siRNA抑制细胞凋亡介导的疾病或病症和促炎细胞因子介导的疾病或病症，包括例如移植排斥反应，肝炎，肝损伤，败血症和癌症。

7. 发明申请

US20060293262A1 Inhibition of gene expression using rna interfering agents 有权
标题翻译：使用rna干扰剂抑制基因表达
公开(公告)号：US20060293262A1
公开(公告)日：2006-12-28
申请号：US10533621
申请日：2003-10-29
申请人： Judy Lieberman , Manjunath Narasimhaswamy , Erwie Song , Sang-Kyung Lee , Premlata Shankar
发明人： Judy Lieberman , Manjunath Narasimhaswamy , Erwie Song , Sang-Kyung Lee , Premlata Shankar
IPC分类号： A61K48/00
CPC分类号： C12N15/1138 , A61K38/00 , A61M1/14 , A61M1/16 , A61M1/1609 , A61M1/1617 , A61M1/3406 , A61M1/3609 , A61M1/3612 , A61M2202/0498 , A61M2205/15 , A61M2205/33 , A61M2205/3317 , A61M2205/3324 , A61M2205/50 , A61M2205/52 , C12N15/1132 , C12N2310/111 , C12N2310/14 , C12N2310/53 , Y02A50/465
摘要： The present invention is based, at least in part, on the discovery of compositions and methods for the treatment and prevention of infectious diseases or disorders, e.g., HIV infection, AIDS, and AIDS-related diseases. In particular, the present invention pertains to methods of modulating cellular gene expression or protein activity, e.g., CCR5, gene expression or protein activity and/or gene expression or protein activity of a gene or sequence of an infectious agent, in order to treat or prevent infectious diseases or disorders, HIV infection, AIDS, or an AIDS-related disease or disorder. In one embodiment the combination of an RNA interfering agent targeting a cellular gene in combination with an RNA interfering agent targeting a gene or sequence of an infectious agent results in prolonged prevention of infection by an infectious agent The present invention is based on the identification of novel RNA interference agents, e.g., siRNA molecules, which target cellular genes, e.g., chemokine receptors, e.g., the CCR5 gene, and result in inhibition of target gene expression on target gene expressing cells, thereby inhibiting entry of infectious agents, e,g., HIV infection into target cells, prevention infection, and/or suppressing replication in established infection.
摘要翻译：本发明至少部分地基于发现用于治疗和预防感染性疾病或病症的组合物和方法，例如HIV感染，AIDS和AIDS相关疾病。具体地，本发明涉及调节细胞基因表达或蛋白活性的方法，例如CCR5，基因表达或蛋白质活性和/或感染因子的基因或序列的基因表达或蛋白质活性，以便治疗或预防传染病或疾病，艾滋病毒感染，艾滋病或艾滋病相关疾病或病症。在一个实施方案中，靶向细胞基因的RNA干扰剂与靶向感染因子的基因或序列的RNA干扰剂的组合导致长期预防感染因子的感染本发明基于鉴定小鼠 RNA干扰剂，例如siRNA分子，其靶向细胞基因，例如趋化因子受体，例如CCR5基因，并导致靶基因表达细胞上的靶基因表达的抑制，从而抑制感染因子的进入，例如，，HIV感染进入靶细胞，预防感染和/或抑制已建立的感染中的复制。

8. 发明申请

US20090047338A1 Method to Treat Flavivirus Infection with siRNA 审中-公开
标题翻译：用siRNA治疗黄病毒感染的方法
公开(公告)号：US20090047338A1
公开(公告)日：2009-02-19
申请号：US12089015
申请日：2006-10-05
申请人： Manjunath N. Swamy , Premlata Shankar , Priti Kumar , Sang-Kyung Lee
发明人： Manjunath N. Swamy , Premlata Shankar , Priti Kumar , Sang-Kyung Lee
IPC分类号： A61K9/127 , A61K31/7105 , A61P31/00
CPC分类号： C12N15/1131 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2740/15043 , C12N2770/24111
摘要： The present invention is directed to methods of treating flavivirus mediated diseases using siRNAs. The invention is based upon our findings in a mouse model that siRNAs directed against sequences conserved among multiple flaviviruses prevents and treats flavivirus infections. Accordingly, the present invention provides an isolated siRNA comprising a sense RNA and an antisense RNA strand or a single strand. The sense and the antisense RNA strands, or the single RNA strand, form an RNA duplex, and wherein the RNA strand comprises a nucleotide sequence identical to a target sequence of about 15 to about 30 contiguous nucleotides in flavivirus mRNA or mutant or variant thereof.
摘要翻译：本发明涉及使用siRNA治疗黄病毒介导的疾病的方法。本发明基于我们在小鼠模型中的发现，其针对多个黄病毒中保守的序列的siRNA阻止和治疗黄病毒感染。因此，本发明提供了包含有义RNA和反义RNA链或单链的分离的siRNA。有义和反义RNA链或单RNA链形成RNA双链体，其中RNA链包含与黄病毒mRNA或其突变体或变体中约15至约30个连续核苷酸的靶序列相同的核苷酸序列。

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