公开(公告)号：WO2022056286A1

公开(公告)日：2022-03-17

申请号：PCT/US2021/049905

申请日：2021-09-10

Applicant: ARROWHEAD PHARMACEUTICALS, INC.

Inventor： LI, Xiaokai ,  PEI, Tao ,  PHAN, Susan ,  BLOKHIN, Andrei, V.

IPC: C07C13/47 ,  C12N15/09 ,  C12N15/111

Abstract: Synthetic ανβ6 integrin ligands of Formula (I) having serum stability and affinity for integrin ανβ6, which is a receptor expressed in a variety of cell types, are described. The described ligands are usful for delivering cargo molecules, such as RNAi agents or other oligonucleotide-based compounds, to cells that express integrin ανβ6, and thereby facilitating the uptake of the cargo molecules into these cells. Compositions that include ανβ6 integrin ligands and methods of use are also described Formula (I).

公开(公告)号：WO2020163747A1

公开(公告)日：2020-08-13

申请号：PCT/US2020/017264

申请日：2020-02-07

Applicant: ARROWHEAD PHARMACEUTICALS, INC. ,  JANSSEN PHARMACEUTICALS, INC.

Inventor： GIVEN, Bruce D. ,  HAMILTON, James C. ,  SCHLUEP, Thomas ,  BEUMONT-MAUVIEL, Maria ,  LENZ, Oliver ,  KALMEIJER, Ronald

IPC: A61K9/00 ,  A61K31/713 ,  C12N15/113 ,  A61P31/20 ,  A61P1/16

Abstract: Described are methods for inhibition of Hepatitis B virus gene expression or treating symptoms and/or diseases associated with Hepatitis B virus infection. Dosing regimens for administering these RNAi agents are also described. RNA interference (RNAi) agents for inhibiting the expression of Hepatitis B vims gene are described. The HBV RNAi agents disclosed herein may be targeted to cells, such as hepatocytes, for example, by using conjugated targeting ligands. Pharmaceutical compositions comprising one or more HBV RNAi agents optionally with one or more additional therapeutics are also described. Delivery of the described HBV RNAi agents to infected liver in vivo provides for inhibition of HBV gene expression and treatment of diseases and conditions associated with HBV infection.

公开(公告)号：WO2020146521A2

公开(公告)日：2020-07-16

申请号：PCT/US2020/012775

申请日：2020-01-08

Applicant: ARROWHEAD PHARMACEUTICALS, INC.

Inventor： LI, Zhen ,  SHU, Dongxu ,  NICHOLAS, Anthony ,  ZHU, Rui ,  CARLSON, Jeffrey ,  WONG, So ,  LI, Xiaokai ,  ALTENHOFER, Erich ,  FOWLER-WATTERS, Matthew ,  CHEN, Bo

IPC: A61K48/00

Abstract: The present disclosure relates to RNAi agents, for example, double stranded RNAi agents, able to inhibit HIF-2 alpha ( EPAS1 ) gene expression. Also disclosed are pharmaceutical compositions that include HIF-2 alpha RNAi agents and methods of use thereof. The HIF-2 alpha RNAi agents disclosed herein may be linked or conjugated to targeting ligands (such as compounds that have affinity for integrins, including alpha-v-beta-3 and alpha-v-beta-5 integrins) and pharmacokinetic (PK) enhancers, to facilitate the delivery to cells and tissues, including to clear cell renal cell carcinoma (ccRCC) cells and tumors. Delivery of compositions comprising the HIF-2 alpha RNAi agents in vivo provides for inhibition of HIF-2 alpha gene expression. The HIF-2 alpha RNAi agents can be used in methods of treatment of various diseases and disorders, including ccRCC.

公开(公告)号：WO2020061177A1

公开(公告)日：2020-03-26

申请号：PCT/US2019/051707

申请日：2019-09-18

Applicant: ARROWHEAD PHARMACEUTICALS, INC.

Inventor： LI, Zhen ,  ZHU, Rui ,  MORALES, Shawn A.

IPC: A61K31/7105 ,  A61K31/713 ,  C12N15/113

Abstract: The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit l7P-hydroxy steroid dehydrogenase type 13 (HSD17B13 or 17β-Η8013) gene expression. Also disclosed are pharmaceutical compositions that include HSD17B13 RNAi agents and methods of use thereof. The HSD17B13 RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery' to cells, including to hepatocytes. Delivery7 of the HSD17B13 RNAi agents in vivo provides for inhibition of HSD17B13 gene expression. The RNAi agents can be used in methods of treatment of HSD17B13-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.

公开(公告)号：WO2019051402A1

公开(公告)日：2019-03-14

申请号：PCT/US2018/050248

申请日：2018-09-10

Applicant: ARROWHEAD PHARMACEUTICALS, INC.

Inventor： LI, Zhen ,  ZHU, Rui ,  PEI, Tao ,  KANNER, Steven ,  WONG, So

IPC: A61K31/7125

Abstract: The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, capable of inhibiting Apolipoprotein C-III (also called APOC3, apoC-III, APOC-III, and APO C- III) gene expression, and compositions that include APOC3 RNAi agents. The APOC3 RNAi agents disclosed herein may be conjugated to targeting ligands. including ligands that include N -acetylgalactosamine, to facilitate the delivery to cells, including to hepatocytes. Pharmaceutical compositions that include one or more APOC3 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the APOC3 RNAi agents in vivo provides for inhibition of APOC3 gene expression, and can result in lower triglycerides and or cholesterol levels in the subject. The APOC3 RNAi agents can be used in methods of treatment of APOC3-related diseases and disorders, including hypertriglyceridemia, cardiovascular disease, and other metabolic-related disorders and diseases.

公开(公告)号：WO2018132432A1

公开(公告)日：2018-07-19

申请号：PCT/US2018/013102

申请日：2018-01-10

Applicant: ARROWHEAD PHARMACEUTICALS, INC.

Inventor： LI, Zhen ,  ZHU, Rui ,  WOODDELL, Christine, L. ,  PEI, Tao

IPC: C12N15/113

Abstract: RNAi agents for inhibiting the expression of the alpha- 1 antitrypsin (AAT) gene, compositions including AAT RNAi agents, and methods of use are described. Also disclosed are pharmaceutical compositions including one or more AAT RNAi agents together with one or more excipients capable of delivering the RNAi agent(s) to a liver cell in vivo. Deliver)' of the AAT RNAi agent(s) to liver cells in vivo inhibits AAT gene expression and treats diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, and fulminant hepatic failure.

公开(公告)号：WO2018027106A2

公开(公告)日：2018-02-08

申请号：PCT/US2017/045446

申请日：2017-08-04

Applicant: ARROWHEAD PHARMACEUTICALS, INC.

Inventor： LI, Zhen ,  ZHU, Rui ,  WOODDELL, Christine I. ,  GIVEN, Bruce D. ,  PEI, Tao ,  LEWIS, David L. ,  ALMEIDA, Lauren J. ,  ROZEMA, David B. ,  WAKEFIELD, Darren H.

Abstract: Described are compositions and methods for inhibition of Hepatitis B virus gene expression. RNA interference (RNAi) agents for inhibiting the expression of Hepatitis B virus gene are described. The HBV RNAi agents disclosed herein may be targeted to cells, such as hepatocytes, for example, by using conjugated targeting ligands. Pharmaceutical compositions comprising one or more HBV RNAi agents optionally with one or more additional therapeutics are also described. Delivery of the described HBV RNAi agents to infected liver in vivo provides for inhibition of HBV gene expression and treatment of diseases and conditions associated with HBV infection.

Abstract translation: 描述了用于抑制乙型肝炎病毒基因表达的组合物和方法。 描述了用于抑制乙型肝炎病毒基因表达的RNA干扰（RNAi）剂。 本文公开的HBV RNAi剂可以例如通过使用缀合的靶向配体靶向细胞，例如肝细胞。 还描述了包含一种或多种HBV RNAi剂任选地具有一种或多种另外的治疗剂的药物组合物。 所描述的HBV RNAi试剂在体内传递到受感染的肝脏提供了对HBV基因表达的抑制和与HBV感染相关的疾病和病症的治疗。

公开(公告)号：WO2017027350A3

公开(公告)日：2017-03-23

申请号：PCT/US2016045714

申请日：2016-08-05

Applicant: ARROWHEAD PHARMACEUTICALS INC

Inventor： WOODDELL CHRISTINE I ,  ROZEMA DAVID B ,  LEWIS DAVID L ,  WAKEFIELD DARREN H ,  ALMEIDA LAUREN J

IPC: C12N15/113 ,  A61K31/7115 ,  A61K31/713 ,  C07H21/02 ,  C12N15/51

CPC classification number: A61K31/713 ,  A61K38/16 ,  A61K47/549 ,  A61K47/554 ,  A61K47/59 ,  A61K2300/00

Abstract: Described are compositions and methods for inhibition of Hepatitis B virus gene expression. RNA interference (RN Ai) triggers and RNAi trigger conjugates for inhibiting the expression of Hepatitis B virus gene are described. Pharmaceutical compositions comprising one or more HBV RNAi triggers optionally with one or more additional therapeutics are also described. Delivery of the described HBV RNAi triggers to infected liver in vivo provides for inhibition of HBV gene expression and treatment.

Abstract translation: 描述了用于抑制乙型肝炎病毒基因表达的组合物和方法。 描述了用于抑制乙型肝炎病毒基因表达的RNA干扰（RN Ai）触发和RNAi触发偶联物。 还描述了包含一种或多种HBV RNAi的药物组合物任选地与一种或多种另外的治疗剂触发。 所描述的HBV RNAi在体内传染给感染的肝脏可以抑制HBV基因的表达和治疗。

公开(公告)号：WO2016196243A1

公开(公告)日：2016-12-08

申请号：PCT/US2016/034517

申请日：2016-05-27

Applicant: ARROWHEAD PHARMACEUTICALS, INC.

Inventor： CARLSON, Jeffrey, C. ,  BLOKHIN, Andrei, V.

IPC: A61K38/07 ,  C07K1/06 ,  C07K5/10 ,  C07K5/107

CPC classification number: C07K5/1008 ,  A61K38/00 ,  C07K5/101 ,  C07K5/1016

Abstract: Tetrapeptide linkers for reversibly linking a first compound to a amine-containing second compound are described. Compounds containing the tetrapeptide linkers and methods of using the tetrapeptide linkers are also described.

Abstract translation: 描述了用于可逆地连接第一化合物与含胺的第二化合物的四肽接头。 还描述了含有四肽接头的化合物和使用四肽接头的方法。

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

Applicant: ARROWHEAD PHARMACEUTICALS, INC.

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

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

Abstract: 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.