公开(公告)号：WO2022056266A2

公开(公告)日：2022-03-17

申请号：PCT/US2021/049871

申请日：2021-09-10

申请人： ARROWHEAD PHARMACEUTICALS, INC.

发明人： DING, Zhi-Ming ,  VAN DYKE, Jonathan ,  LI, Xiaokai ,  NICHOLAS, Anthony ,  SCHIENEBECK, Casi, M. ,  PEI, Tao ,  XU, Zhao ,  AL, Teng ,  PHAN, Susan ,  RAMOS-HUNTER, Susan

IPC分类号： C12N15/113 ,  A61K31/7088 ,  A61P21/00 ,  C12N2310/14 ,  C12N2310/312 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/351 ,  C12N2310/3513 ,  C12N2320/32

摘要： Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a double homeobox 4 ( DUX4 ) gene. The DUX4 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a DUX4 gene. Pharmaceutical compositions that include one or more DUX4 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described DUX4 RNAi agents to skeletal muscle cells in vivo, provides for inhibition of DUX4 gene expression and a reduction in DUX4 levels, which can provide a therapeutic benefit to subjects, including human subjects, suffering from certain skeletal muscle-related diseases or disorders including Facioscapulohumeral Muscular Dystrophy (FSHD).

公开(公告)号：WO2022271573A1

公开(公告)日：2022-12-29

申请号：PCT/US2022/034102

申请日：2022-06-17

申请人： ARROWHEAD PHARMACEUTICALS, INC.

发明人： NICHOLAS, Anthony ,  PEI, Tao ,  XU, Zhao ,  BRAAS, Daniel ,  DING, Zhi-Ming

IPC分类号： A61K31/713 ,  A61K47/14 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/3515

摘要： The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed arc pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytcs. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.

公开(公告)号：WO2022056266A8

公开(公告)日：2022-03-17

申请号：PCT/US2021/049871

申请日：2021-09-10

申请人： ARROWHEAD PHARMACEUTICALS, INC.

发明人： DING, Zhi-Ming ,  VAN DYKE, Jonathan ,  LI, Xiaokai ,  NICHOLAS, Anthony ,  SCHIENEBECK, Casi, M. ,  PEI, Tao ,  XU, Zhao ,  AI, Teng ,  PHAN, Susan ,  RAMOS-HUNTER, Susan

IPC分类号： C12N15/113 ,  A61K31/7088 ,  A61P21/00 ,  C12N2310/14 ,  C12N2310/312 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/351 ,  C12N2310/3513 ,  C12N2320/32

摘要： Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a double homeobox 4 ( DUX4 ) gene. The DUX4 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a DUX4 gene. Pharmaceutical compositions that include one or more DUX4 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described DUX4 RNAi agents to skeletal muscle cells in vivo, provides for inhibition of DUX4 gene expression and a reduction in DUX4 levels, which can provide a therapeutic benefit to subjects, including human subjects, suffering from certain skeletal muscle-related diseases or disorders including Facioscapulohumeral Muscular Dystrophy (FSHD).

公开(公告)号：WO2021195467A2

公开(公告)日：2021-09-30

申请号：PCT/US2021/024299

申请日：2021-03-26

申请人： ARROWHEAD PHARMACEUTICALS, INC.

发明人： NICHOLAS, Anthony ,  PEI, Tao ,  XU, Zhao ,  SCHIENEBECK, Casi ,  DING, Zhi-Ming

IPC分类号： A61K31/713 ,  C12N15/113 ,  A61P3/06 ,  A61K47/549 ,  A61P1/16 ,  C12N15/1137 ,  C12N15/1138 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2320/35

摘要： The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene expression. Also disclosed are pharmaceutical compositions that include PNPLA3 RNAi agents and methods of use thereof. The PNPLA3 RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the PNPLA3 RNAi agents in vivo provides for inhibition of PNPLA3 gene expression. The RNAi agents can be used in methods of treatment of PNPLA3 -related diseases and disorders, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatic fibrosis, and alcoholic or non-alcoholic liver diseases, including cirrhosis.