公开(公告)号：US20240343746A1

公开(公告)日：2024-10-17

申请号：US18259884

申请日：2021-12-30

申请人： ALNYLAM PHARMACEUTICALS, INC.

发明人： Alexander V. KEL’IN ,  Justin M. PIERSON ,  Jayaprakash k. NAIR ,  Martin A. MAIER ,  Anna BISBE ,  Cheng TANG

IPC分类号： C07F9/6553 ,  C07F9/6558 ,  C07F9/6561 ,  C07H21/02

CPC分类号： C07F9/655345 ,  C07F9/655363 ,  C07F9/655381 ,  C07F9/65586 ,  C07F9/6561 ,  C07H21/02

摘要： This invention relates to a compound comprising a structure of formula (I): cyclic disulfide moiety-phosphorus coupling group (I). The cyclic disulfide moiety has the structure of (C-I), (C-II), or (C-III). This invention also relates to an oligonucleotide comprising one or more compounds that comprise the structure of formula (I), wherein at least one phosphorus coupling group contains a nucleoside or oligonucleotide. The invention also relates to a pharmaceutical composition comprising the oligonucleotide described herein and a method of reducing or inhibiting the expression of a target gene by administering to the subject a therapeutically effective amount of the oligonucleotide described herein.

公开(公告)号：US20240336914A1

公开(公告)日：2024-10-10

申请号：US18259887

申请日：2021-12-30

申请人： ALNYLAM PHARMACEUTICALS, INC.

发明人： Shigeo MATSUDA ,  Jayaprakash K. NAIR ,  Martin A. MAIER ,  Michelle H. JUNG ,  Anna BISBE ,  Ivan ZLATEV ,  Mark K. SCHLEGEL ,  Christopher BROWN ,  Vasant R. JADHAV

IPC分类号： C12N15/113

CPC分类号： C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/351

摘要： This invention relates to an oligonucleotide comprising one or more 2′-modified nucleosides, wherein the 2′-position of the nucleoside has a structure of formula (I). The invention also relates to a pharmaceutical composition comprising the oligonucleotide described herein and a method of reducing or inhibiting the expression of a target gene by administering to the subject a therapeutically effective amount of the oligonucleotide described herein. The invention also relates to a method of bioactivating an oligonucleotide comprising one or more 2′-modified nucleosides, wherein the 2′-position of the nucleoside is modified by a bio-cleavable linking group, wherein the bio-cleavable linking group comprises acetal, disulfide, carbamate, amide, sulfonamide, a biocleavable carbohydrate linker, or combinations thereof, said method comprising the step of: exposing the oligonucleotide to a physiological condition that causes the bio-cleavable linking group to be cleaved from the 2′-modified nucleoside, thereby regenerating the 2′-OH group of the nucleoside.