公开(公告)号：US20230016929A1

公开(公告)日：2023-01-19

申请号：US17774477

申请日：2020-11-06

申请人： ALNYLAM PHARMACEUTICALS, INC.

发明人： Jayaprakash K. NAIR ,  Martin A. MAIER ,  Juan C. SALINAS ,  Shigeo MATSUDA ,  Alexander V. KEL'IN ,  Scott P. LENTINI ,  Guo HE ,  Michelle H. JUNG ,  Justin M. PIERSON ,  Muthiah MANOHARAN ,  Dale C. GUENTHER ,  Ivan ZLATEV ,  Christopher S. THEILE ,  Vasant R. JADHAV ,  Stuart MILSTEIN ,  Maja JANAS ,  Dhrubajyoti DATTA

IPC分类号： A61K31/713 ,  A61K48/00 ,  C12N15/113 ,  A61P25/28

摘要： One aspect of the present invention relates to a compound comprising an antisense strand which is complementary to a target gene; a sense strand which is complementary to said antisense strand; and one or more lipophilic monomers, containing one or more lipophilic moieties, conjugated to one or more positions on at least one strand, optionally via a linker or carrier. Another aspect of the invention relates to a method of gene silencing, comprising administering to a cell or a subject in need thereof a therapeutically effective amount of the lipophilic monomer-conjugated compound.

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.