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    • 5. 发明授权
    • TARGETING LIPIDS
    • 靶向脂质体
    • EP2231195B1
    • 2017-03-29
    • EP08865121.1
    • 2008-12-04
    • Arbutus Biopharma Corporation
    • MANOHARAN, MuthiahRAJEEV, Kallanthottathil, G.NARAYANANNAIR, Jayaprakash, K.JAYARAMAN, Muthusamy
    • A61K47/56A61K31/70A61K31/713
    • A61K47/28A61K31/70A61K31/7004A61K31/7052A61K31/7088A61K31/713A61K47/16A61K47/22A61K47/543A61K47/549A61K47/60A61K48/00C07H21/02Y02A50/385Y02A50/411Y02A50/467Y02P20/55
    • 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(R N ) 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")0- 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 L G , -Linker-L G , or has the structure shown below: L G is independently for each occurence a carbohydrate, e.g., monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide, polysaccharide; R N 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.
    • 本发明提供了包含至少一个式(I)的亚基的iRNA试剂:其中:A和B各自独立为O,N(R N)或S; X和Y各自独立为H,OH,羟基保护基,磷酸酯基,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,亲脂体,聚合物,P(Z')(Z“)O-连接体-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L G, - 接头-L G,或具有如下所示的结构:L G独立地为碳水化合物,例如单糖,二糖,三糖,四糖,寡糖,多糖; R N每次出现时独立地为H,甲基,乙基,丙基,异丙基,丁基或苄基; 和Z',Z“,Z”'和Z“”各自独立地为O或S.