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75 条记录 (耗时 0.049 秒)

    iRNA AGENTS WITH BIOCLEAVABLE TETHERS
    51.
    发明申请
    iRNA AGENTS WITH BIOCLEAVABLE TETHERS 有权
    具有可生物降解性能的iRNA试剂

    公开(公告)号：US20150073133A1

    公开(公告)日：2015-03-12

    申请号：US14485255

    申请日：2014-09-12

    申请人： Alnylam Pharmaceuticals, Inc.

    发明人： Muthiah MANOHARAN ,  Kallanthottathil G. Rajeev

    IPC分类号： C12N15/113

    CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/323 ,  C12N2310/3511 ,  C12N2320/51

    摘要： The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent.

    摘要翻译： 本发明涉及iRNA试剂，其优选包括其中核糖部分已被核糖替代的单体，其进一步包括具有一个或多个连接基团的系链，其中至少一个连接基团是可切割的 连接组。 系链又可以连接到所选择的部分，例如配体，例如靶向或递送部分，或改变物理性质的部分。 可切割连接基团是在细胞外部足够稳定的连接基团，使得其允许靶向治疗有益量的iRNA试剂（例如，单链或双链iRNA试剂），其通过可切割连接基团连接至 靶向细胞靶向细胞，但是在进入靶细胞时被切割以从靶向剂释放iRNA试剂。

    iRNA AGENTS WITH BIOCLEAVABLE TETHERS
    53.
    发明申请
    iRNA AGENTS WITH BIOCLEAVABLE TETHERS 有权
    具有可生物降解性能的iRNA试剂

    公开(公告)号：US20130281685A1

    公开(公告)日：2013-10-24

    申请号：US13849017

    申请日：2013-03-22

    申请人： Alnylam Pharmaceuticals, Inc.

    发明人： Muthiah MANOHARAN ,  Kallanthottathil G. RAJEEV

    IPC分类号： C12N15/113

    CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/323 ,  C12N2310/3511 ,  C12N2320/51

    摘要： The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent.

    摘要翻译： 本发明涉及iRNA试剂，其优选包括其中核糖部分已被核糖替代的单体，其进一步包括具有一个或多个连接基团的系链，其中至少一个连接基团是可切割的 连接组。 系链又可以连接到所选择的部分，例如配体，例如靶向或递送部分，或改变物理性质的部分。 可切割连接基团是在细胞外部足够稳定的连接基团，使得其允许靶向治疗有益量的iRNA试剂（例如，单链或双链iRNA试剂），其通过可切割连接基团连接至 靶向细胞靶向细胞，但是在进入靶细胞时被切割以从靶向剂释放iRNA试剂。

    ENHANCEMENT OF siRNA SILENCING ACTIVITY USING UNIVERSAL BASES OR MISMATCHES IN THE SENSE STRAND
    54.
    发明申请
    ENHANCEMENT OF siRNA SILENCING ACTIVITY USING UNIVERSAL BASES OR MISMATCHES IN THE SENSE STRAND 审中-公开
    使用通用基因或者错觉信号的siRNA沉默活性的增强

    公开(公告)号：US20130196434A1

    公开(公告)日：2013-08-01

    申请号：US13847955

    申请日：2013-03-20

    申请人： Alnylam Pharmaceuticals, Inc.

    发明人： Martin MAIER ,  Haripriya ADDEPALLI ,  Muthiah MANOHARAN

    IPC分类号： C07H21/02

    CPC分类号： C07H21/02 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/33 ,  C12N2310/331 ,  C12N2310/332 ,  C12N2320/50

    摘要： One aspect of the present invention relates to a double stranded nucleic acid useful as an siRNA, that has a sense strand and an antisense strand relative to a target nucleic acid, where the sense strand contains one or more modified nucleobases, or one or more mismatch base pairings with the antisense strand. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one nucleoside comprising a non-natural nucleobase. Another aspect of the invention relates to a method of gene silencing, comprising administering to a mammal in need thereof a therapeutically effective amount of a double-stranded oligonucleotides containing a sense strand and an antisense strand, where the sense strand contains one or more modified nucleobases, or one or more mismatch base pairings with the antisense strand.

    摘要翻译： 本发明的一个方面涉及可用作siRNA的双链核酸，其相对于靶核酸具有有义链和反义链，其中有义链含有一个或多个修饰的核碱基或一个或多个错配 与反义链的碱基配对。 本发明的另一方面涉及包含至少一种包含非天然核碱基的核苷的单链寡核苷酸。 本发明的另一方面涉及一种基因沉默方法，包括向有需要的哺乳动物施用治疗有效量的含有义链和反义链的双链寡核苷酸，其中有义链含有一个或多个修饰的核碱基 或与反义链的一个或多个错配碱基配对。

    CARBOHYDRATE CONJUGATES AS DELIVERY AGENTS FOR OLIGONUCLEOTIDES
    55.
    发明申请
    CARBOHYDRATE CONJUGATES AS DELIVERY AGENTS FOR OLIGONUCLEOTIDES 有权
    碳氢化合物作为交付剂的交付代理

    公开(公告)号：US20130178512A1

    公开(公告)日：2013-07-11

    申请号：US13693478

    申请日：2012-12-04

    申请人： Alnylam Pharmaceuticals, Inc.

    发明人： Muthiah MANOHARAN ,  Kallanthottathil G. RAJEEV ,  Narayanannair K. JAYAPRAKASH ,  Martin MAIER

    IPC分类号： C07H21/02

    CPC分类号： A61K47/28 ,  A61K31/70 ,  A61K31/7004 ,  A61K31/7052 ,  A61K31/7088 ,  A61K31/713 ,  A61K47/16 ,  A61K47/22 ,  A61K47/543 ,  A61K47/549 ,  A61K47/60 ,  A61K48/00 ,  C07H21/02 ,  Y02A50/385 ,  Y02A50/411 ,  Y02A50/467 ,  Y02P20/55

    摘要： The present invention provides iRNA agents comprising at least one subunit of the formula (I): wherein: A and B are each independently for each occurrence O, N(RN) or S; X and Y are each independently for each occurrence H, OH, a hydroxyl protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z′)(Z″)O-nucleoside, —P(Z′)(Z″)O-oligonucleotide, a lipid, a PEG, a steroid, a lipophile, a polymer, —P(Z′)(Z″)O-Linker-OP(Z′″)(Z″″)O-oligonucleotide, a nucleotide, an oligonucleotide, —P(Z′)(Z″)-formula (I), —P(Z′)(Z″)— or -Linker-R; R is LG, -Linker-LG, or has the structure shown below: LG is independently for each occurrence a carbohydrate, e.g., monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide, polysaccharide; RN is independently for each occurrence H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl; and Z′, Z″, Z′″ and Z″″ are each independently for each occurrence O or S.

    摘要翻译： 本发明提供包含至少一个式（I）亚基的iRNA试剂：其中：A和B各自独立地为O，N（RN）或S; X和Y各自独立地为H，OH，羟基保护基，磷酸基，磷酸二酯基，活化磷酸酯基，活化亚磷酸酯基，亚磷酰胺，固体载体，-P（Z'）（ Z'）（Z“）O - 寡核苷酸，脂质，PEG，类固醇，亲脂体，聚合物，-P（Z'）（Z”）O （Z'）（Z“） - （Z”）（Z“）（Z”）（Z“）（Z”） （Z“） - 或-Linker-R; R是LG，-Linker-LG，或具有如下结构：每次出现LG独立为碳水化合物，例如单糖，二糖，三糖，四糖，寡糖，多糖; 乙烯基，丙基，异丙基，丁基或苄基各自独立地为N， Z'，Z“，Z”“和Z”“各自独立地为O或S.