公开(公告)号：EP3141265A1

公开(公告)日：2017-03-15

申请号：EP16001273.8

申请日：2008-12-04

申请人： Alnylam Pharmaceuticals, Inc.

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

IPC分类号： A61K47/54

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(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.

摘要翻译： 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（RN）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LG，-Linker-LG，或具有如下所示的结构：LG独立地为碳水化合物，例如单糖，二糖，三糖，四糖，寡糖，多糖; RN在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.