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    Carbohydrate Conjugates as Delivery Agents for Oligonucleotides
    1.
    发明申请
    Carbohydrate Conjugates as Delivery Agents for Oligonucleotides 审中-公开
    碳水化合物缀合物作为寡核苷酸的递送剂

    公开(公告)号：US20150119445A1

    公开(公告)日：2015-04-30

    申请号：US14338161

    申请日：2014-07-22

    Applicant: ALNYLAM PHARMACEUTICALS, INC.

    Inventor： Muthiah MANOHARAN ,  Kallanthottathil G. RAJEEV ,  Jayaprakash NAIR ,  Martin MAIER

    IPC: A61K47/48 ,  A61K31/713

    CPC classification number: 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

    Abstract: 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.

    Abstract translation: 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“）O-核苷，-P（Z'）（Z”）O-寡核苷酸，脂质，PEG，类固醇，亲脂性，聚合物，-P（Z'）（Z“）O-Linker- OP（Z'）（Z“）O-寡核苷酸，核苷酸，寡核苷酸，-P（Z'）（Z”） - 式（I），-P（Z'）（Z“） - 或 - -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， 和Z'，Z“，Z”“和Z”“各自独立地为O或S.

    CARBOHYDRATE CONJUGATES AS DELIVERY AGENTS FOR OLIGONUCLEOTIDES
    3.
    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：US20160051691A1

    公开(公告)日：2016-02-25

    申请号：US14835272

    申请日：2015-08-25

    Applicant: Alnylam Pharmaceuticals, Inc.

    Inventor： Muthiah MANOHARAN ,  Kallanthottathil G. RAJEEV ,  Jayaprakash NAIR ,  Martin MAIER

    IPC: A61K47/48 ,  A61K31/713 ,  A61K31/7088

    CPC classification number: 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

    Abstract: 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.

    Abstract translation: 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“）O-核苷，-P（Z'）（Z”）O-寡核苷酸，脂质，PEG，类固醇，亲脂性，聚合物，-P（Z'）（Z“）O-Linker- OP（Z'“）（Z”“） - 寡核苷酸，寡核苷酸，-P（Z'）（Z”） - 式（I），-P（Z'）（Z“） - 链接器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， 和Z'，Z“，Z”“和Z”“各自独立地为O或S.

    Carbohydrate Conjugates as Delivery Agents for Oligonucleotides
    4.
    发明申请
    Carbohydrate Conjugates as Delivery Agents for Oligonucleotides 有权
    碳水化合物缀合物作为寡核苷酸的递送剂

    公开(公告)号：US20150119444A1

    公开(公告)日：2015-04-30

    申请号：US14329557

    申请日：2014-07-11

    Applicant: ALNYLAM PHARMACEUTICALS, INC.

    Inventor： Muthiah MANOHARAN ,  Kallanthottathil G. RAJEEV ,  Jayaprakash NAIR ,  Martin MAIER

    IPC: A61K47/48 ,  A61K31/713

    CPC classification number: 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

    Abstract: 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.

    Abstract translation: 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“）O-核苷，-P（Z'）（Z”）O-寡核苷酸，脂质，PEG，类固醇，亲脂性，聚合物，-P（Z'）（Z“）O-Linker- OP（Z'“）（Z”“） - 寡核苷酸，寡核苷酸，-P（Z'）（Z”） - 式（I），-P（Z'）（Z“） - 链接器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， 和Z'，Z“，Z”“和Z”“各自独立地为O或S.

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