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    Carbohydrate conjugates as delivery agents for oligonucleotides
    47.
    发明授权
    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：US08106022B2

    公开(公告)日：2012-01-31

    申请号：US12328528

    申请日：2008-12-04

    申请人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Jayaprakash K. Narayanannair ,  Martin Maier

    发明人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Jayaprakash K. Narayanannair ,  Martin Maier

    IPC分类号： A01N43/04 ,  A61K31/70

    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“）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.

    Oligonucleotides comprising a non-phosphate backbone linkage
    50.
    发明授权
    Oligonucleotides comprising a non-phosphate backbone linkage 有权
    包含非磷酸骨架键的寡核苷酸

    公开(公告)号：US07723512B2

    公开(公告)日：2010-05-25

    申请号：US12496250

    申请日：2009-07-01

    申请人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev

    发明人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev

    IPC分类号： C07H19/00 ,  C07H19/22

    CPC分类号： C12N15/111 ,  C07H19/04 ,  C07H19/12 ,  C07H19/16 ,  C07H19/167 ,  C07H19/173 ,  C07H21/02 ,  C12N15/1136 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/312 ,  C12N2320/51

    摘要： One aspect of the present invention relates to a ribonucleoside substituted with a phosphonamidite group at the 3′-position. In certain embodiments, the phosphonamidite is an alkyl phosphonamidite. Another aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a non-phosphate linkage occurs in only one strand. In certain embodiments, a non-phosphate linkage occurs in both strands. In certain embodiments, a ligand is bound to one of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, a ligand is bound to both of the oligonucleotide strands comprising the double-stranded oligonucleotide. 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-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a ligand is bound to the oligonucleotide strand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety.

    摘要翻译： 本发明的一个方面涉及在3'-位被亚磷酰胺基取代的核糖核苷。 在某些实施方案中，亚磷酰胺是烷基亚磷酰胺。 本发明的另一方面涉及包含至少一种非磷酸键的双链寡核苷酸。 代表性的非磷酸酯键包括膦酸酯，羟胺，羟基肼基，酰胺和氨基甲酸酯键。 在某些实施方案中，非磷酸酯键是膦酸酯键。 在某些实施方案中，非磷酸酯键仅出现在一条链中。 在某些实施方案中，在两条链中都发生非磷酸连接。 在某些实施方案中，配体与包含双链寡核苷酸的寡核苷酸链之一结合。 在某些实施方案中，配体与包含双链寡核苷酸的两条寡核苷酸链结合。 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磷酸键的单链寡核苷酸。 代表性的非磷酸酯键包括膦酸酯，羟胺，羟基肼基，酰胺和氨基甲酸酯键。 在某些实施方案中，非磷酸酯键是膦酸酯键。 在某些实施方案中，配体与寡核苷酸链结合。 在某些实施方案中，寡核苷酸包含至少一个修饰的糖部分。