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71.发明申请Chemically Modified Oligonucleotides for Use in Modulating Micro RNA and Uses Thereof 有权用于调节微RNA的化学修饰的寡核苷酸及其用途公开(公告)号：US20100222413A1
公开(公告)日：2010-09-02
申请号：US12714863
申请日：2010-03-01
IPC分类号： A61K31/7088
CPC分类号： C12N15/113 , C12N2310/11 , C12N2310/315 , C12N2310/321 , C12N2310/345 , C12N2310/346 , C12N2310/3515 , C12N2310/3521 , C12N2310/3527 , C12N2310/3531 , C12N2310/3533
摘要： This invention relates generally to chemically modified oligonuceotides useful for modulating expression of microRNAs and pre-microRNAs. More particularly, the invention relates to single stranded chemically modified oligonuceotides for inhibiting microRNA and pre-microRNA expression and to methods of making and using the modified oligonucleotides. Also included in the invention are compositions and methods for silencing microRNAs in the central nervous system.
摘要翻译： 本发明一般涉及可用于调节微小RNA和pre-microRNAs表达的化学修饰的寡核苷酸。 更具体地说，本发明涉及用于抑制微小RNA和pre-microRNA表达的单链化学修饰的寡核苷酸以及制备和使用修饰的寡核苷酸的方法。 本发明还包括在中枢神经系统中沉默微小RNA的组合物和方法。
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公开(公告)号：US09254327B2
公开(公告)日：2016-02-09
申请号：US13697229
申请日：2011-05-10
IPC分类号： C12N15/11 , A61K9/127 , A61K31/13 , A61K47/18 , C12N15/88 , A61K31/7088 , C07C219/08 , C07C229/12 , C07C233/38 , C07C237/06 , C07C271/12 , C07C271/64 , C07C275/20
CPC分类号： A61K47/18 , A61K9/1272 , A61K9/1278 , A61K31/7088 , C07C219/08 , C07C229/12 , C07C233/38 , C07C237/06 , C07C271/12 , C07C271/64 , C07C275/20 , C12N15/88
摘要： A lipid particle can include a cationic lipid. Synthesis of the cationic lipid can include a ylide-based reaction, such as a Wittig reaction or sulfur ylide reaction. In some cases, the synthesis can also include a Michael addition or a related addition reaction.
摘要翻译： 脂质颗粒可以包括阳离子脂质。 阳离子脂质的合成可以包括基于叶立德的反应，例如Wittig反应或硫叶立德反应。 在某些情况下，合成还可以包括迈克尔加成或相关的加成反应。
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73.发明授权Modified 5′ diphosphate nucleosides and oligomeric compounds prepared therefrom 有权修饰的5'二磷酸核苷和由其制备的低聚化合物公开(公告)号：US09156873B2
公开(公告)日：2015-10-13
申请号：US13642804
申请日：2011-04-26
申请人： Thazha P. Prakash , Punit P. Seth , Muthiah Manoharan , Eric E. Swayze , Kallanthottathil G. Rajeev , Ivan Zlatev
发明人： Thazha P. Prakash , Punit P. Seth , Muthiah Manoharan , Eric E. Swayze , Kallanthottathil G. Rajeev , Ivan Zlatev
IPC分类号： C07H21/04 , C07H19/00 , C07H19/04 , C07H19/10 , C12N15/113
CPC分类号： C07H19/10 , C12N15/113
摘要： Provided herein are modified 5′ diphosphate nucleosides and oligomeric compounds prepared therefrom. More particularly, modified 5′ diphosphate nucleosides are provided that can be further modified at the 2′ and 5′ positions. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The oligomeric compounds are also expected to be useful as primers and probes in diagnostic applications.
摘要翻译： 本文提供修饰的5'二磷酸核苷和由其制备的低聚化合物。 更具体地，提供修饰的5'-二磷酸核苷，其可以在2'和5'位置进一步修饰。 在一些实施方案中，预期本文提供的寡聚化合物与靶RNA的一部分杂交，导致靶RNA的正常功能丧失。 还预期寡聚化合物可用作诊断应用中的引物和探针。
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公开(公告)号：US09102938B2
公开(公告)日：2015-08-11
申请号：US13638891
申请日：2011-03-31
IPC分类号： C07H21/02 , C12N15/113 , C07H19/067 , A61K48/00 , C07H19/06 , C07H19/16
CPC分类号： C12N15/113 , A61K48/00 , C07H19/06 , C07H19/067 , C07H19/16
摘要： The present invention provides nucleosides of formula (1) and oligonucleotides comprising at least on nucleoside of formula (2):Formula (1) and Formula (2). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene.
摘要翻译： 本发明提供式（1）的核苷和至少包含式（2）核苷的寡核苷酸：式（1）和式（2）。 本发明的另一方面涉及一种抑制基因表达的方法，所述方法包括（a）使本发明的寡核苷酸与细胞接触; 和（b）将来自步骤（a）的细胞维持足以获得靶基因的mRNA降解的时间。
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公开(公告)号：US08993746B2
公开(公告)日：2015-03-31
申请号：US13431376
申请日：2012-03-27
申请人： Hans-Peter Vornlocher , Ingo Roehl , Philipp Hadwiger , Tracy Stage Zimmermann , Muthiah Manoharan , Kallanthottathil G. Rajeev , Akin Akinc
发明人： Hans-Peter Vornlocher , Ingo Roehl , Philipp Hadwiger , Tracy Stage Zimmermann , Muthiah Manoharan , Kallanthottathil G. Rajeev , Akin Akinc
IPC分类号： C07H21/00 , C07H21/02 , C12N15/11 , C12N15/113
CPC分类号： C07H21/02 , C12N15/111 , C12N15/113 , C12N2310/14 , C12N2310/315 , C12N2310/318 , C12N2310/321 , C12N2310/322 , C12N2310/323 , C12N2310/3231 , C12N2310/53 , C12N2320/51 , C12N2310/3521 , C12N2310/3525 , C12N2310/3527
摘要： This invention relates to modified double-stranded oligoribonucleic acid (dsRNA) having improved stability in cells and biological fluids, and methods of making and identifying dsRNA having improved stability, and of using the dsRNA to inhibit the expression or function of a target gene.
摘要翻译： 本发明涉及在细胞和生物流体中具有改善的稳定性的修饰的双链寡核糖核酸（dsRNA），以及制备和鉴定具有改善的稳定性的dsRNA的方法，以及使用dsRNA抑制靶基因的表达或功能。
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76.发明授权Chemically modified oligonucleotides for use in modulation micro RNA and uses thereof 有权用于调节微RNA的化学修饰的寡核苷酸及其用途公开(公告)号：US08541385B2
公开(公告)日：2013-09-24
申请号：US12714863
申请日：2010-03-01
IPC分类号： A61K48/00
CPC分类号： C12N15/113 , C12N2310/11 , C12N2310/315 , C12N2310/321 , C12N2310/345 , C12N2310/346 , C12N2310/3515 , C12N2310/3521 , C12N2310/3527 , C12N2310/3531 , C12N2310/3533
摘要： This invention relates generally to chemically modified oligonuceotides useful for modulating expression of microRNAs and pre-microRNAs. More particularly, the invention relates to single stranded chemically modified oligonuceotides for inhibiting microRNA and pre-microRNA expression and to methods of making and using the modified oligonucleotides. Also included in the invention are compositions and methods for silencing microRNAs in the central nervous system.
摘要翻译： 本发明一般涉及可用于调节微小RNA和pre-microRNAs表达的化学修饰的寡核苷酸。 更具体地说，本发明涉及用于抑制微小RNA和pre-microRNA表达的单链化学修饰的寡核苷酸以及制备和使用修饰的寡核苷酸的方法。 本发明还包括在中枢神经系统中沉默微小RNA的组合物和方法。
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77.发明申请CHEMICALLY MODIFIED OLIGONUCLEOTIDES AND SMALL MOLECULES FOR USE IN REDUCING MICRO RNA ACTIVITY LEVELS AND USES THEREOF 审中-公开化学修饰的寡核苷酸和用于减少微RNA活性水平的小分子及其用途公开(公告)号：US20110257244A1
公开(公告)日：2011-10-20
申请号：US12863369
申请日：2009-01-16
IPC分类号： A61K31/713 , A61P35/00 , A61P19/06 , A61P7/06 , A61P25/28
CPC分类号： C12N15/113 , C12N2310/113 , C12N2310/14 , C12N2310/33 , C12N2310/351
摘要： This invention relates generally to chemically modified oligonucleotides useful for modulating activity of microRNAs and pre-microRNAs. More particularly, the invention relates to single stranded chemically modified oligonucleotides for inhibiting microRNA and pre-microRNA activity and to methods of making and using the modified oligonucleotides.
摘要翻译： 本发明一般涉及可用于调节微小RNA和pre-microRNAs的活性的化学修饰的寡核苷酸。 更具体地说，本发明涉及用于抑制微小RNA和pre-microRNA活性的单链化学修饰的寡核苷酸以及制备和使用经修饰的寡核苷酸的方法。
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公开(公告)号：US20110130440A1
公开(公告)日：2011-06-02
申请号：US12934323
申请日：2009-03-26
CPC分类号： C07H19/073 , C07H19/173 , C07H19/23 , C07H21/04 , C12N15/111 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2320/51 , C12N2310/3521 , C12N2310/3525
摘要： One aspect of the present invention relates to modified nucleosides and oligonucleotides comprising such modified nucleosides. Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene.
摘要翻译： 本发明的一个方面涉及修饰的核苷和包含这种修饰的核苷的寡核苷酸。 本发明的另一方面涉及一种抑制基因表达的方法，所述方法包括（a）使本发明的寡核苷酸与细胞接触; 和（b）将来自步骤（a）的细胞维持足以获得靶基因的mRNA降解的时间。
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79.发明授权Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase 有权包含与修饰或非天然核碱基连接的配体的寡核苷酸公开(公告)号：US07893224B2
公开(公告)日：2011-02-22
申请号：US12533710
申请日：2009-07-31
CPC分类号： C07H21/00 , A61K31/7115 , C07F9/6561 , C07H21/02 , C12Q1/6883 , Y02A50/385 , Y02A50/387 , Y02A50/393 , Y02A50/395 , Y02A50/411 , Y02A50/463 , Y02A50/465 , Y02A50/467
摘要： One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.
摘要翻译： 本发明的一个方面涉及包含至少一个与改变的或非天然核碱基连接的配体的双链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吡咯基或硝基咪唑基。 在某些实施方案中，配体是类固醇或芳族化合物。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链中只有一条含有与改变的或非天然核碱基连接的配体。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链都独立地包含与改变的或非天然核碱基连接的配体。 在某些实施方案中，寡核苷酸链包含至少一个修饰的糖部分。 本发明的另一方面涉及包含至少一个与改变的或非天然核碱基连接的配体的单链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吡咯基或硝基咪唑基。 在某些实施方案中，配体是类固醇或芳族化合物。 在某些实施方案中，在核苷中天然存在的核糖部分被己糖，多环杂烷基环或环己烯基取代。 在某些实施方案中，寡核苷酸中的至少一个磷酸键被硫代磷酸酯键取代。
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公开(公告)号：US07772387B2
公开(公告)日：2010-08-10
申请号：US12495932
申请日：2009-07-01
CPC分类号： C07H21/00 , A61K31/7115 , C07F9/65515 , C07F9/65586 , C07F9/6561 , C07H21/02 , Y02A50/385 , Y02A50/387 , Y02A50/393 , Y02A50/395 , Y02A50/411 , Y02A50/463 , Y02A50/465 , Y02A50/467
摘要： One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-natural nucleobase. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.
摘要翻译： 本发明的一个方面涉及包含至少一种非天然核碱基的双链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吲哚基，硝基吡咯基或硝基咪唑基。 在优选的实施方案中，非天然核碱基是二氟苯甲酰基。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链中只有一条含有非天然核碱基。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链都独立地含有非天然核碱基。 在某些实施方案中，寡核苷酸链包含至少一个修饰的糖部分。 本发明的另一方面涉及包含至少一种非天然核碱基的单链寡核苷酸。 在优选的实施方案中，非天然核碱基是二氟苯甲酰基。 在某些实施方案中，在核苷中天然存在的核糖部分被己糖，多环杂烷基环或环己烯基取代。 在某些实施方案中，寡核苷酸中的至少一个磷酸键被硫代磷酸酯键取代。
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