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1.发明授权Methods and compositions for enhancing delivery of double-stranded RNA or a double-stranded hybrid nucleic acid to regulate gene expression in mammalian cells 有权用于增强双链RNA或双链杂交核酸的转运以调节哺乳动物细胞中的基因表达的方法和组合物公开(公告)号：US08940857B2
公开(公告)日：2015-01-27
申请号：US12870989
申请日：2010-08-30
CPC分类号： A61K47/48123 , A61K31/713 , A61K38/00 , A61K45/06 , A61K47/554 , A61K48/005 , C07K14/00 , C12N15/111 , C12N15/113 , C12N15/1137 , C12N15/87 , C12N2310/14 , C12N2310/3513 , C12N2310/3515 , C12N2320/30 , C12N2320/32 , C12Y302/01023
摘要： A delivery-enhancing peptide comprising the amino acid sequence of SEQ ID NO:11 or salt thereof. This invention is directed towards methods and compositions to administer a double-stranded ribonucleic acid to a mammal so as to effectuate transfection of the double-stranded RNA into a desired tissue of the mammal.
摘要翻译： 包含SEQ ID NO：11的氨基酸序列的递送增强肽或其盐。 本发明涉及向哺乳动物施用双链核糖核酸的方法和组合物，以便将双链RNA转染到哺乳动物的所需组织中。
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2.发明申请METHODS AND COMPOSITIONS FOR ENHANCING DELIVERY OF DOUBLE-STRANDED RNA OR A DOUBLE-STRANDED HYBRID NUCLEIC ACID TO REGULATE GENE EXPRESSION IN MAMMALIAN CELLS 有权用于增强递送双链RNA或双重混合核酸以调节哺乳动物细胞中基因表达的方法和组合物公开(公告)号：US20100316707A1
公开(公告)日：2010-12-16
申请号：US12870989
申请日：2010-08-30
CPC分类号： A61K47/48123 , A61K31/713 , A61K38/00 , A61K45/06 , A61K47/554 , A61K48/005 , C07K14/00 , C12N15/111 , C12N15/113 , C12N15/1137 , C12N15/87 , C12N2310/14 , C12N2310/3513 , C12N2310/3515 , C12N2320/30 , C12N2320/32 , C12Y302/01023
摘要： A delivery-enhancing peptide comprising the amino acid sequence of SEQ ID NO:11 or salt thereof. This invention is directed towards methods and compositions to administer a double-stranded ribonucleic acid to a mammal so as to effectuate transfection of the double-stranded RNA into a desired tissue of the mammal.
摘要翻译： 包含SEQ ID NO：11的氨基酸序列的递送增强肽或其盐。 本发明涉及向哺乳动物施用双链核糖核酸的方法和组合物，以便将双链RNA转染到哺乳动物的所需组织中。
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3.发明申请METHODS AND COMPOSITIONS FOR ENHANCING DELIVERY OF DOUBLE-STRANDED RNA OR A DOUBLE-STRANDED HYBRID NUCLEIC ACID TO REGULATE GENE EXPRESSION IN MAMMALIAN CELLS 审中-公开用于增强递送双链RNA或双重混合核酸以调节哺乳动物细胞中基因表达的方法和组合物公开(公告)号：US20080261304A1
公开(公告)日：2008-10-23
申请号：US12013274
申请日：2008-01-11
CPC分类号： A61K45/06 , A61K31/713 , A61K38/00 , A61K47/554 , A61K48/005 , C07K14/00 , C12N15/111 , C12N15/113 , C12N15/1137 , C12N15/87 , C12N2310/14 , C12N2310/3513 , C12N2310/3515 , C12N2320/30 , C12N2320/32 , C12Y302/01023
摘要： A double-stranded RNA, preferably a small, interfering (si)RNA or a siHybrid, to which cholesterol moieties are linked.
摘要翻译： 胆固醇部分连接的双链RNA，优选小的干扰（si）RNA或siHybrid。
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4.发明申请Methods and compositions for enhancing delivery of double-stranded RNA or a double-stranded hybrid nucleic acid to regulate gene expression in mammalian cells 审中-公开用于增强双链RNA或双链杂交核酸的转运以调节哺乳动物细胞中的基因表达的方法和组合物公开(公告)号：US20060014289A1
公开(公告)日：2006-01-19
申请号：US11107371
申请日：2005-04-15
申请人： Mohammad Ahmadian , Kunyuan Cui , Lishan Chen , Shu-Chih Chen , Michael Houston
发明人： Mohammad Ahmadian , Kunyuan Cui , Lishan Chen , Shu-Chih Chen , Michael Houston
CPC分类号： A61K45/06 , A61K31/713 , A61K38/00 , A61K47/554 , A61K48/005 , C07K14/00 , C12N15/111 , C12N15/113 , C12N15/1137 , C12N15/87 , C12N2310/14 , C12N2310/3513 , C12N2310/3515 , C12N2320/30 , C12N2320/32 , C12Y302/01023
摘要： Cholesterol moieties are linked to specific ends of double-stranded RNA, preferably a small, interfering (si)RNA or to a dsHybrid. The dsHybrid has one strand comprised of DNA and one strand comprised of RNA. Preferably the sense strand is the DNA strand and the antisense strand is the RNA strand of the dsHybrid. The present invention is based upon the discovery that a cholesterol moiety, if linked to a specific end or ends of the sense or antisense strands of a siRNA, can enhance the delivery and silencing efficiency of the siRNA directed against its target message, in comparison with a corresponding, non-conjugated siRNA. Conjugated siRNAs and dsHybrids of the invention are optionally formulated with, or coordinately administered with, a secondary delivery-enhancing agent, such as a delivery-enhancing peptide, to enhance intracellular delivery and uptake of the conjugated siRNAs or dsHybrid.
摘要翻译： 胆固醇部分连接到双链RNA的特异性末端，优选小的干扰（si）RNA或dsHybrid。 dsHybrid具有由DNA组成的一条链和由RNA组成的一条链。 优选地，有义链是DNA链，反义链是dsHybrid的RNA链。 本发明基于以下发现：与siRNA的有义链或反义链的特定末端或末端连接的胆固醇部分可以提高针对其目标信息的siRNA的递送和沉默效率，与 相应的非共轭siRNA。 本发明的共轭siRNA和dsHybrids任选地与二次递送增强剂（例如递送增强肽）一起配制或配位施用，以增强缀合siRNA或dsHybrid的细胞内递送和摄取。
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5.发明授权Compositions and methods for enhancing delivery of nucleic acids into cells and for modifying expression of target genes in cells 失效用于增强核酸转运到细胞中并用于修饰细胞中靶基因表达的组合物和方法公开(公告)号：US08299236B2
公开(公告)日：2012-10-30
申请号：US12206165
申请日：2008-09-08
IPC分类号： C07H21/04
CPC分类号： C12N15/1136 , A61K47/64 , A61K2121/00 , C07K14/001 , C07K14/43572 , C07K14/47 , C12N15/111 , C12N15/87 , C12N2310/14 , C12N2310/3513 , C12N2320/32
摘要： Polynucleotide delivery-enhancing polypeptides are admixed or complexed with, or conjugated to, nucleic acids for enhancing delivery the nucleic acids into cells. The transported nucleic acids are active in target cells as small inhibitory nucleic acids (siNAs) that modulate expression of target genes, mediated at least in part by RNA interference (RNAi). The siNA/polypeptide compositions and methods of the invention provide effective tools to modulate gene expression and alter phenotype in mammalian cells, including by altering phenotype in a manner that eliminates disease symptoms or alters disease potential in targeted cells or subject individuals to which the siNA/polypeptide compositions are administered.
摘要翻译： 多核苷酸递送增强多肽与核酸混合或复合或缀合到核酸上，以增强将核酸递送到细胞中。 运输的核酸作为调节目标基因表达的小抑制性核酸（siNA）在靶细胞中是活性的，至少部分地通过RNA干扰（RNAi）介导。 本发明的siNA /多肽组合物和方法提供了有效的工具来调节哺乳动物细胞中的基因表达和改变表型，包括通过以消除疾病症状或改变目标细胞或受试个体的疾病潜力的方式改变表型，其中siNA / 施用多肽组合物。
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6.发明申请COMPOSITIONS AND METHODS FOR ENHANCING DELIVERY OF NUCLEIC ACIDS INTO CELLS AND FOR MODIFYING EXPRESSION OF TARGET GENES IN CELLS 失效用于增强核酸转运到细胞中并用于修饰细胞中目标基因表达的组合物和方法公开(公告)号：US20090042298A1
公开(公告)日：2009-02-12
申请号：US12206165
申请日：2008-09-08
CPC分类号： C12N15/1136 , A61K47/64 , A61K2121/00 , C07K14/001 , C07K14/43572 , C07K14/47 , C12N15/111 , C12N15/87 , C12N2310/14 , C12N2310/3513 , C12N2320/32
摘要： Polynucleotide delivery-enhancing polypeptides are admixed or complexed with, or conjugated to, nucleic acids for enhancing delivery the nucleic acids into cells. The transported nucleic acids are active in target cells as small inhibitory nucleic acids (siNAs) that modulate expression of target genes, mediated at least in part by RNA interference (RNAi). The siNA/polypeptide compositions and methods of the invention provide effective tools to modulate gene expression and alter phenotype in mammalian cells, including by altering phenotype in a manner that eliminates disease symptoms or alters disease potential in targeted cells or subject individuals to which the siNA/polypeptide compositions are administered.
摘要翻译： 多核苷酸递送增强多肽与核酸混合或复合或缀合到核酸上，以增强将核酸递送到细胞中。 运输的核酸作为调节目标基因表达的小抑制性核酸（siNA）在靶细胞中是活性的，至少部分地通过RNA干扰（RNAi）介导。 本发明的siNA /多肽组合物和方法提供了有效的工具来调节哺乳动物细胞中的基因表达和改变表型，包括通过以消除疾病症状或改变目标细胞或受试个体的疾病潜力的方式改变表型，其中siNA / 施用多肽组合物。
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7.发明申请METHOD OF TREATING AN INFLAMMATORY DISEASE BY DOUBLE STRANDED RIBONUCLEIC ACID 审中-公开通过双重拉唑酸处理炎症疾病的方法公开(公告)号：US20100113332A1
公开(公告)日：2010-05-06
申请号：US11576139
申请日：2005-09-27
CPC分类号： C12N15/1136 , A61K47/64 , A61K2121/00 , C07K14/001 , C07K14/43572 , C07K14/47 , C12N15/111 , C12N15/87 , C12N2310/14 , C12N2310/3513 , C12N2320/32
摘要： What is disclosed is the use of a formulation comprising double stranded ribonucleic acid (dsRNA) in the manufacture of a medicament for treating an inflammatory disease in a mammal and inhibiting production of tumor necrosis factor-α (TNF-α) in the mammal.
摘要翻译： 所公开的是使用包含双链核糖核酸（dsRNA）的制剂在制备用于治疗哺乳动物炎症性疾病和抑制哺乳动物肿瘤坏死因子-α（TNF-α）产生的药物中的用途。
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8.发明申请COMPOUNDS AND METHODS FOR PEPTIDE RIBONUCLEIC ACID CONDENSATE PARTICLES FOR RNA THERAPEUTICS 审中-公开用于RNA治疗的肽类抗坏血酸浓缩颗粒的化合物和方法公开(公告)号：US20100129460A1
公开(公告)日：2010-05-27
申请号：US12445575
申请日：2006-10-13
申请人： Roger C. Adami , Tianying Zhu , Kunyuan Cui , Michael E. Houston, JR. , Lishan Chen , Yuching Chen
发明人： Roger C. Adami , Tianying Zhu , Kunyuan Cui , Michael E. Houston, JR. , Lishan Chen , Yuching Chen
IPC分类号： A61K31/713 , A61K9/14
CPC分类号： C07K14/003 , A61K9/14 , A61K47/6455 , A61K48/00 , C07K2319/10 , C12N15/111 , C12N15/1136 , C12N15/87 , C12N15/88 , C12N2310/14 , C12N2320/32 , Y10T428/2982
摘要： Compounds comprising condensed particles having diameters less than 1000 nm, wherein the particles comprise one or more double stranded ribonucleic acids (dsKNAs) and one or more peptides. The compounds, compositions and methods are useful for modulating gene expression by RNA Interference.
摘要翻译： 包含直径小于1000nm的冷凝颗粒的化合物，其中颗粒包含一种或多种双链核糖核酸（dsKNA）和一种或多种肽。 化合物，组合物和方法可用于通过RNA干扰调节基因表达。
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9.发明申请COMPOUNDS AND METHODS FOR PEPTIDE RIBONUCLEIC ACID CONDENSATE PARTICLES FOR RNA THERAPEUTICS 审中-公开用于RNA治疗的肽类抗坏血酸浓缩颗粒的化合物和方法公开(公告)号：US20130072424A1
公开(公告)日：2013-03-21
申请号：US13475892
申请日：2012-05-18
申请人： Roger C. Adami , Tianying Zhu , Kunyuan Cui , Michael E. Houston, JR. , Lishan Chen , Yuching Chen
发明人： Roger C. Adami , Tianying Zhu , Kunyuan Cui , Michael E. Houston, JR. , Lishan Chen , Yuching Chen
CPC分类号： C07K14/003 , A61K9/14 , A61K47/6455 , A61K48/00 , C07K2319/10 , C12N15/111 , C12N15/1136 , C12N15/87 , C12N15/88 , C12N2310/14 , C12N2320/32 , Y10T428/2982
摘要： Compounds comprising condensed particles having diameters less than 1000 nm, wherein the particles comprise one or more double stranded ribonucleic acids (dsRNAs) and one or more peptides. The compounds, compositions and methods are useful for modulating gene expression by RNA interference.
摘要翻译： 包含直径小于1000nm的冷凝颗粒的化合物，其中所述颗粒包含一种或多种双链核糖核酸（dsRNA）和一种或多种肽。 化合物，组合物和方法可用于通过RNA干扰调节基因表达。
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公开(公告)号：US20090018097A1
公开(公告)日：2009-01-15
申请号：US12065604
申请日：2006-05-25
申请人： Steven C. Quay , Kunyuan Cui , Paul H. Johnson , Lishan Chen , Mohammad Ahmadian
发明人： Steven C. Quay , Kunyuan Cui , Paul H. Johnson , Lishan Chen , Mohammad Ahmadian
IPC分类号： A61K31/713 , C07H21/02 , C12N5/10 , A61P35/00
CPC分类号： C12N15/111 , C12N15/113 , C12N2310/14 , C12N2310/321 , C12N2310/33 , C12N2310/331 , C12N2320/50 , C12N2320/51 , C12N2310/3521
摘要： A double-stranded RNA (dsRNA) molecule comprising between about 15 base pairs and about 40 base pairs, wherein at least one ribonucleotide of the dsRNA is a 5′-methyl-pyrimidine and/or at least one 2′-O-methyl ribonucleotide, and a method of improving ribonuclease stability, reducing off-target effects of a double stranded siRNA molecule, or of reducing interferon responsiveness of a double stranded siRNA molecule using such dsRNA.
摘要翻译： 包含约15个碱基对和约40个碱基对的双链RNA（dsRNA）分子，其中dsRNA的至少一个核糖核苷酸是5'-甲基 - 嘧啶和/或至少一个2'-O-甲基核糖核苷酸 ，以及使用这种dsRNA，提高核糖核酸酶稳定性，降低双链siRNA分子的脱靶效应或降低双链siRNA分子的干扰素反应性的方法。
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