公开(公告)号：WO2022266753A1

公开(公告)日：2022-12-29

申请号：PCT/CA2022/050991

申请日：2022-06-20

Applicant: RISEN (SUZHOU) PHARMA TECH CO., LTD. ,  LV, Jiasheng ,  SIYANG, Haixiao ,  YIN, Yijie ,  GUO, Wantao ,  LI, Haiming ,  CHEN, Dawei ,  GU, Jiamin ,  KONG, Xianqi ,  PAN, Jun ,  MA, Xinxin ,  SONG, Peiming ,  WU, Chun ,  FENG, Hui ,  YAO, Sheng

Inventor： LV, Jiasheng ,  SIYANG, Haixiao ,  YIN, Yijie ,  GUO, Wantao ,  LI, Haiming ,  CHEN, Dawei ,  GU, Jiamin ,  KONG, Xianqi ,  PAN, Jun ,  MA, Xinxin ,  SONG, Peiming ,  WU, Chun ,  FENG, Hui ,  YAO, Sheng

IPC: C07C275/16 ,  A61K47/54 ,  A61P3/00 ,  A61P9/00 ,  C07C233/47 ,  C07C237/22 ,  C07C271/02 ,  C07C279/14 ,  C07C323/59 ,  C07D207/416 ,  C07D249/04 ,  C07K16/00 ,  C12N15/113 ,  A61K47/542 ,  A61K47/545 ,  A61K47/549

Abstract: There are provided conjugates of Formula (V) wherein R1 is a triantennary targeting moiety comprising N-acetyl galactosamine and R2 is a bioactive agent which is preferably an oligonucleotide, as well as pharmaceutical compositions and methods of use of the conjugates for the treatment, inhibition, or prevention of diseases and disorders which are therapeutic targets of the bioactive agent. In preferred embodiments the conjugate preferentially binds to asiaglycoprotein receptors (ASGPR). In preferred embodiments, the oligonucleotide is SiRNA which targets the PCSK9 gene, providing treatment options for lipid disorders such as hyperlipidemia.