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1.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：US09725479B2
公开(公告)日：2017-08-08
申请号：US13696796
申请日：2011-04-22
申请人： Muthiah Manoharan , Kallanthottathil G. Rajeev , Ivan Zlatev , Eric E. Swayze , Thazha P. Prakash , Walter F. Lima
发明人： Muthiah Manoharan , Kallanthottathil G. Rajeev , Ivan Zlatev , Eric E. Swayze , Thazha P. Prakash , Walter F. Lima
IPC分类号： C07H17/02 , C07H19/067 , C07H21/02 , C12N15/113
CPC分类号： C07H17/02 , C07H19/067 , C07H21/02 , C12N15/113 , C12N15/1137 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/344 , C12N2310/3521 , C12N2310/3525
摘要： The present invention provides compounds of formula (1). 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.
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公开(公告)号：US20130323836A1
公开(公告)日：2013-12-05
申请号：US13696796
申请日：2011-04-22
申请人： Muthiah Manoharan , Kallanthottathil G. Rajeev , Ivan Zlatev , Eric E. Swayze , Thazha P. Prakash , Walter F. Lima
发明人： Muthiah Manoharan , Kallanthottathil G. Rajeev , Ivan Zlatev , Eric E. Swayze , Thazha P. Prakash , Walter F. Lima
IPC分类号： C07H17/02 , C12N15/113
CPC分类号： C07H17/02 , C07H19/067 , C07H21/02 , C12N15/113 , C12N15/1137 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/344 , C12N2310/3521 , C12N2310/3525
摘要： The present invention provides compounds of formula (1). 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）的化合物。 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：US20130203836A1
公开(公告)日：2013-08-08
申请号：US13638891
申请日：2011-03-31
IPC分类号： C12N15/113 , C07H19/16 , A61K48/00 , C07H19/06
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：US20130156845A1
公开(公告)日：2013-06-20
申请号：US13643940
申请日：2011-04-29
申请人： Muthiah Manoharan , Sayda Elbashir , Kallanthottathil G. Rajeev , Thazha P. Prakash , Walter F. Lima , Eric E. Swayze
发明人： Muthiah Manoharan , Sayda Elbashir , Kallanthottathil G. Rajeev , Thazha P. Prakash , Walter F. Lima , Eric E. Swayze
IPC分类号： A61K9/127 , A61K31/7088
CPC分类号： A61K9/1272 , A61K9/1275 , A61K31/7088 , C12N15/111 , C12N15/88 , C12N2310/11 , C12N2320/32
摘要： The present invention provides compositions comprising a nucleic acid lipid particle and an oligomeric compound and uses thereof. In certain embodiments, such compositions are useful as antisense compounds. Certain such antisense compounds are useful as RNase H antisense compounds or as RNAi compounds.
摘要翻译： 本发明提供了包含核酸脂质颗粒和寡聚化合物的组合物及其用途。 在某些实施方案中，这样的组合物可用作反义化合物。 某些这样的反义化合物可用作RNase H反义化合物或作为RNAi化合物。
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7.发明申请MODIFIED 5' DIPHOSPHATE NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM 有权改良的5'二磷酸核苷和其制备的低聚物公开(公告)号：US20130109850A1
公开(公告)日：2013-05-02
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： 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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8.发明授权2′-substituted oligomeric compounds and compositions for use in gene modulations 有权2'-取代的寡聚化合物和用于基因调节的组合物公开(公告)号：US07919612B2
公开(公告)日：2011-04-05
申请号：US10701316
申请日：2003-11-04
申请人： Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke , Thazha P. Prakash
发明人： Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke , Thazha P. Prakash
CPC分类号： C12N15/113 , A61K38/00 , C07H21/00 , C12N9/22 , C12N15/1135 , C12N2310/311 , C12N2310/312 , C12N2310/314 , C12N2310/315 , C12N2310/316 , C12N2310/318 , C12N2310/3181 , C12N2310/321 , C12N2310/322 , C12N2310/3341 , C12N2310/335 , C12N2310/341 , C12N2310/346 , Y02A50/395 , Y02P20/582 , C12N2310/3527 , C12N2310/3525 , C12N2310/3521
摘要： Compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes a modified sugar and/or backbone modification. In some embodiments the modification is a 2′ substituent group on a sugar moiety that is not H or OH. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleotide of the oligomer has a modified sugar and/or backbone modification.
摘要翻译： 提供包含第一和第二寡聚体的组合物，其中至少一部分第一寡聚体能够与至少一部分第二寡聚物杂交，至少一部分第一寡聚体与选定的靶互补并能够与选定的靶 核酸，并且第一或第二寡聚体中的至少一种包括修饰的糖和/或骨架修饰。 在一些实施方案中，修饰是糖部分上不是H或OH的2'取代基。 还提供低聚物/蛋白质组合物，其包含与选定的靶核酸互补并且能够与选定的靶核酸杂交的寡聚体和至少一种包含至少一部分RNA诱导的沉默复合物（RISC）的蛋白质，其中至少一个核苷酸 低聚物具有修饰的糖和/或骨架修饰。
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9.发明申请公开(公告)号：US20130260460A1
公开(公告)日：2013-10-03
申请号：US13643062
申请日：2011-04-22
申请人： Jeremy Lackey , Muthiah Manoharan , Kallanthottathil Rajeev , Ivan Zlatev , Eric E. Swayze , Thazha P. Prakash
发明人： Jeremy Lackey , Muthiah Manoharan , Kallanthottathil Rajeev , Ivan Zlatev , Eric E. Swayze , Thazha P. Prakash
IPC分类号： C12N15/113 , C07H21/00
CPC分类号： C12N15/113 , C07H19/06 , C07H19/10 , C07H19/20 , C07H21/00 , C07H21/02 , C07H21/04 , C07H23/00
摘要： This invention relates to conformationally locked dinucleotide motifs for exo- and phosphate stabilization. For instance, oligonucleotides can be prepared having one or more of the following formulas (IV-IX).
摘要翻译： 本发明涉及用于外切和磷酸酯稳定化的构象锁定二核苷酸基序。 例如，可以制备具有一个或多个下式（IV-IX）的寡核苷酸。
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10.发明授权2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations 有权2'-氟取代低聚化合物和用于基因调控的组合物公开(公告)号：US07812149B2
公开(公告)日：2010-10-12
申请号：US10700689
申请日：2003-11-04
申请人： Thazha P. Prakash , Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke
发明人： Thazha P. Prakash , Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke
CPC分类号： C12N15/111 , C12N2310/14 , C12N2310/321 , C12N2310/322 , C12N2310/341 , C12N2310/346 , C12N2310/3521 , C12N2310/3533 , C12N2310/531 , C12N2320/51
摘要： Compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes a modified sugar and/or backbone modification. In some embodiments the modification is a 2′-F substituent group on a sugar moiety. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleoside of the oligomer has a modified sugar and/or backbone modification.
摘要翻译： 提供包含第一和第二寡聚体的组合物，其中至少一部分第一寡聚体能够与至少一部分第二寡聚物杂交，至少一部分第一寡聚体与选定的靶互补并能够与选定的靶 核酸，并且第一或第二寡聚体中的至少一种包括修饰的糖和/或骨架修饰。 在一些实施方案中，修饰是糖部分上的2'-F取代基。 还提供寡聚物/蛋白质组合物，其包含与选定的靶核酸互补并且能够与选定的靶核酸杂交的寡聚体和至少一种包含至少一部分RNA诱导的沉默复合物（RISC）的蛋白质，其中至少一种核苷 低聚物具有修饰的糖和/或骨架修饰。
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