公开(公告)号：WO2023069754A2

公开(公告)日：2023-04-27

申请号：PCT/US2022/047491

申请日：2022-10-21

申请人： AMGEN INC.

发明人： RULIFSON, Ingrid ,  MEADE, Bryan ,  LONG, Jason C. ,  MURRAY, Justin K.

IPC分类号： C12N15/113 ,  C12N9/10 ,  A61K31/713 ,  A61K31/7115 ,  A61K31/712 ,  A61K31/7125 ,  A61P1/16 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/343 ,  C12N2310/351 ,  C12N2320/11 ,  C12N2320/32

摘要： The disclosure relates to RNAi constructs, such as siRNA, for reducing expression of the GPAM gene. Methods of using such RNAi constructs to treat or prevent liver disease, such as nonalcoholic fatty liver disease (NAFLD), are also described.

公开(公告)号：WO2022256290A2

公开(公告)日：2022-12-08

申请号：PCT/US2022/031519

申请日：2022-05-31

申请人： ALNYLAM PHARMACEUTICALS, INC. ,  REGENERON PHARMACEUTICALS, INC. ,  DANG, Lan, Thi Hoang ,  MCININCH, James, D. ,  NGUYEN, Tuyen, M. ,  DUBOSE, Brittany

发明人： FRENDEWEY, David ,  SHARMA-KANNING, Aarti

IPC分类号： C12N15/113 ,  A61K31/713 ,  A61P25/28 ,  C12N2310/14 ,  C12N2310/3183 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/351 ,  C12N2310/3515

摘要： The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a human chromosome 9 open reading frame 72 (C9orf72) gene, as well as methods of inhibiting expression of a C9orf72 gene and methods of treating subjects having a C9orf72-associated disease or disorder, e.g., C9orf72 amyotrophic lateral sclerosis, frontotemporal dementia or Huntington-Like Syndrome Due To C9orf72 Expansions, using such dsRNAi agents and compositions.

公开(公告)号：WO2022212153A1

公开(公告)日：2022-10-06

申请号：PCT/US2022/021635

申请日：2022-03-24

申请人： ALNYLAM PHARMACEUTICALS, INC.

发明人： ERBE, David ,  MCININCH, James, D.

IPC分类号： C12N15/113 ,  A61K31/713 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/351 ,  C12Y105/05

摘要： The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the proline dehydrogenase 2 (PRODH2) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a PRODH2 gene and to methods of preventing and treating a PRODH2-associated disorder, e.g., primary hyperoxalurias and/or kidney stone diseases.

公开(公告)号：WO2022060721A2

公开(公告)日：2022-03-24

申请号：PCT/US2021/050247

申请日：2021-09-14

申请人： ARROWHEAD PHARMACEUTICALS, INC.

发明人： CHRISTIANSON, Dawn ,  HAMILTON, James C. ,  GIVEN, Bruce ,  SAN MARTIN, Javier

IPC分类号： C12N15/113 ,  A61K31/713 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/344 ,  C12N2310/351 ,  C12N2320/35

摘要： Described are methods of reducing liver Z-AAT protein levels in a human subject with a PiZZ genotype of alpha-1 antitrypsin (AAT) by using pharmaceutical compositions that include AAT RNAi agents. The pharmaceutical compositions disclosed herein that include AAT RNAi agents, when administered to a human subject with a PiZZ mutation, lead to a reduction in liver Z-AAT protein levels, including both soluble and insoluble Z-AAT protein. Such reductions can lead to the treatment of liver diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, increased risk of hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, fulminant hepatic failure, and other liver-related diseases.

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：WO2022031591A2

公开(公告)日：2022-02-10

申请号：PCT/US2021/044158

申请日：2021-08-02

申请人： UNIVERSITY OF MASSACHUSETTS ,  KHVOROVA, Anastasia ,  ALTERMAN, Julia ,  LY, Socheata ,  CONROY, Faith ,  O'REILLY, Daniel

发明人： KHVOROVA, Anastasia ,  ALTERMAN, Julia ,  LY, Socheata ,  CONROY, Faith ,  O'REILLY, Daniel

IPC分类号： A61P25/28 ,  C12N15/113 ,  A61K9/0019 ,  C12N15/11 ,  C12N15/86 ,  C12N2310/111 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/343 ,  C12N2310/344 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/3533 ,  C12N2310/52 ,  C12N2320/32 ,  C12N2750/14142

摘要： This disclosure relates to novel HTT-1A targeting sequences. Novel HTT-1A targeting oligonucleotides for the treatment of neurodegenerative diseases are also provided.

公开(公告)号：WO2021252649A2

公开(公告)日：2021-12-16

申请号：PCT/US2021/036643

申请日：2021-06-09

申请人： ALNYLAM PHARMACEUTICALS, INC.

发明人： MCININCH, James D. ,  BONDURANT, Lucas ,  DEATON, Aimee

IPC分类号： C12N9/10 ,  C12N15/113 ,  A61K31/713 ,  A61K31/7105 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/3183 ,  C12N2310/344 ,  C12N2310/351 ,  C12N2310/3515 ,  C12N2320/11 ,  C12Y203/01015

摘要： The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the GPAM gene, as well as methods of inhibiting expression of GPAM, and methods of treating subjects that would benefit from reduction in expression of GPAM, such as subjects having a GPAM-associated disease, disorder, or condition, using such dsRNA compositions.

公开(公告)号：WO2021231771A2

公开(公告)日：2021-11-18

申请号：PCT/US2021/032311

申请日：2021-05-13

申请人： ARIZ PRECISION MEDICINE

发明人： BOOKBINDER, Lonnie L. ,  VAISH, Narendra K. ,  NILES, Brad J. ,  FLYNN, Jonathan ,  NUNEZ, Nicole

IPC分类号： C12N15/113 ,  A61K31/713 ,  C07K14/47 ,  C12N15/87 ,  C12N2310/14 ,  C12N2310/351 ,  C12N2310/3513 ,  C12N2320/31 ,  C12N2320/32 ,  C12Y201/01043

摘要： Inhibitory RNA molecules that specifically inhibit mammalian RIZ2 expression, with therapeutic effect in cell proliferative diseases, such as cancer.

公开(公告)号：WO2022272108A2

公开(公告)日：2022-12-29

申请号：PCT/US2022/034965

申请日：2022-06-24

申请人： SIRNAOMICS, INC.

发明人： SAMARSKY, Dmitry

IPC分类号： C12N15/113 ,  A61K31/712 ,  A61K31/7125 ,  A61P3/06 ,  C12N2310/14 ,  C12N2310/351

摘要： Nucleic acid products and compositions and their uses are provided. In particular, nucleic acid products are provided that modulate, interfere with, or inhibit APOC3 gene expression. The products can be oligomeric compounds that comprise at least a first region of linked nucleosides having at least a first nucleobase sequence that is at least partially complementary to at least a portion of RNA transcribed from a APOC3 gene, wherein said first nucleobase sequence is selected from the following sequences, or a portion thereof: SEQ ID NOs 1 to 39.

公开(公告)号：WO2022269346A2

公开(公告)日：2022-12-29

申请号：PCT/IB2022/000337

申请日：2022-06-17

申请人： HORIZON THERAPEUTICS IRELAND DAC

发明人： BROWN, Duncan ,  NYBORG, Andrew ,  BOWERS, Michael, Scott

IPC分类号： C12N15/113 ,  C12N15/1137 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/31 ,  C12N2310/32 ,  C12N2310/351 ,  C12Y117/01004

摘要： Compositions, methods for making and using polynucleotide inhibitors modulating xanthine dehydrogenase expression or activity are provided.