公开(公告)号：US11590156B2

公开(公告)日：2023-02-28

申请号：US16990916

申请日：2020-08-11

申请人： Arrowhead Pharmaceuticals, Inc.

发明人： Zhen Li ,  Rui Zhu ,  Christine I. Wooddell ,  Bruce D. Given ,  Tao Pei ,  David L. Lewis ,  Lauren J. Almeida ,  David B. Rozema ,  Darren H. Wakefield

IPC分类号： C12N15/113 ,  A61K31/7105 ,  A61P31/14 ,  A61K9/00 ,  A61K31/675 ,  A61P31/20 ,  A61K31/7088

摘要： 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.

公开(公告)号：US20210180066A1

公开(公告)日：2021-06-17

申请号：US17179605

申请日：2021-02-19

申请人： Arrowhead Pharmaceuticals, Inc.

发明人： So Wong ,  David L. Lewis ,  David B. Rozema ,  Darren H. Wakefield ,  Steven B. Kanner ,  Weijun Cheng ,  Lauren J. Almeida ,  Andrei V. Blokhin ,  Jeffrey C. Carlson ,  Anthony L. Nicholas ,  Aaron Almeida ,  Jonathan D. Benson ,  Justin Woods

IPC分类号： C12N15/113 ,  A61K31/713 ,  A61K45/06 ,  A61K47/60 ,  A61K47/64

摘要： RNA interference (RNAi) triggers and RNAi trigger conjugates for inhibiting the expression of Hif2α (EPAS1) gene are described. Pharmaceutical compositions comprising one or more Hif2α RNAi triggers optionally with one or more additional therapeutics are also described. Delivery of the described Hif2α RNAi triggers to tumor cells in vivo provides for inhibition of Hif2α gene expression and treatment of cancer.

公开(公告)号：US20190062748A1

公开(公告)日：2019-02-28

申请号：US16189550

申请日：2018-11-13

申请人： Arrowhead Pharmaceuticals, Inc.

发明人： David B. Rozema ,  So Wong ,  Weijun Cheng ,  Aaron M. Almeida ,  Andrei V. Blokhin ,  Jeffrey C. Carlson

IPC分类号： C12N15/113 ,  C07K5/078 ,  A61K47/18 ,  C07K5/06 ,  C07K5/062 ,  A61K31/713 ,  C07K5/065 ,  C07K5/09

摘要： The present invention is directed compositions for delivery of RNA interference (RNAi) triggers to integrin positive tumor cells in vivo. The compositions comprise RGD ligand-targeted amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or conjugate) are further covalently linked to an RNAi trigger.

公开(公告)号：US20170253875A1

公开(公告)日：2017-09-07

申请号：US15452423

申请日：2017-03-07

申请人： Arrowhead Pharmaceuticals, Inc.

发明人： David B. Rozema ,  Darren H. Wakefield ,  Andrei V. Blokhin ,  Jonathan D. Benson ,  Zhen Li ,  Tao Pei ,  Fred Fleitz

IPC分类号： C12N15/113 ,  A61K31/713 ,  C07H15/04

CPC分类号： C12N15/113 ,  A61K31/713 ,  A61K47/549 ,  C07H15/04 ,  C12N2310/14 ,  C12N2310/317 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/351 ,  C12N2310/3515 ,  C12N2310/3521 ,  C12N2310/3533 ,  C12N2310/3525

摘要： Described are novel targeting ligands that may be linked to compounds, such therapeutic compounds, that are useful in directing the compounds to the target in vivo. The targeting ligands disclosed herein can serve to target expression-inhibiting oligomeric compounds, such as RNAi agents, to liver cells to modulate gene expression. The targeting ligands disclosed herein, when conjugated to an expression-inhibiting oligomeric compound, may be used in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Compositions including the targeting ligands disclosed herein when linked to expression-inhibiting oligomeric compounds are capable of mediating expression of target nucleic acid sequences in liver cells, such as hepatocytes, which may be useful in the treatment of diseases or conditions that respond to inhibition of gene expression or activity in a cell, tissue, or organism.

公开(公告)号：US20170096665A1

公开(公告)日：2017-04-06

申请号：US15281309

申请日：2016-09-30

申请人： Arrowhead Pharmaceuticals, Inc.

发明人： Stacey Melquist ,  Steven Kanner ,  David B. Rozema ,  David L. Lewis ,  Lauren J. Almeida ,  Darren H. Wakefield ,  Vladimir S. Trubetskoy ,  Tao Pei ,  Zhen Li ,  Aaron Almeida

IPC分类号： C12N15/113

CPC分类号： C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/351 ,  C12N2310/3517 ,  C12Y304/21

摘要： RNA interference (RNAi) agents and RNAi agent conjugates for inhibiting the expression of the LPA (apo(a)) gene are described. Pharmaceutical compositions comprising one or more LPA RNAi agents optionally with one or more additional therapeutics are also described. Delivery of the described LPA RNAi agents to liver cells in vivo provides for inhibition of LPA gene expression and treatment of cardiovascular and cardiovascular-related diseases.

公开(公告)号：US20170035796A1

公开(公告)日：2017-02-09

申请号：US15229314

申请日：2016-08-05

申请人： Arrowhead Pharmaceuticals, Inc.

发明人： Christine I. Wooddell ,  David B. Rozema ,  David L. Lewis ,  Darren H. Wakefield ,  Lauren J. Almeida

IPC分类号： A61K31/713 ,  A61K38/16

CPC分类号： A61K31/713 ,  A61K38/16 ,  A61K47/549 ,  A61K47/554 ,  A61K47/59 ,  A61K2300/00

摘要： Described are compositions and methods for inhibition of Hepatitis B virus gene expression. RNA interference (RNAi) 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.

摘要翻译： 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）触发剂和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：US20170022497A1

公开(公告)日：2017-01-26

申请号：US15278518

申请日：2016-09-28

申请人： Arrowhead Pharmaceuticals, Inc.

发明人： David B. Rozema ,  So Wong ,  Weijun Cheng ,  Aaron M. Almeida ,  Andrei V. Blokhin ,  Jeffrey C. Carlson

IPC分类号： C12N15/113 ,  A61K47/18 ,  A61K31/713

CPC分类号： C12N15/113 ,  A61K31/713 ,  A61K47/183 ,  C07K5/06008 ,  C07K5/06026 ,  C07K5/06043 ,  C07K5/06052 ,  C07K5/06078 ,  C07K5/06156 ,  C07K5/0817 ,  C12N2310/14 ,  C12N2310/322 ,  C12N2310/3513 ,  C12N2310/3535 ,  C12N2320/32

摘要： The present invention is directed compositions for delivery of RNA interference (RNAi) triggers to integrin positive tumor cells in vivo. The compositions comprise RGD ligand-targeted amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or conjugate) are further covalently linked to an RNAi trigger.

摘要翻译： 本发明涉及用于在体内递送RNA干扰（RNAi）触发剂至整联蛋白阳性肿瘤细胞的组合物。 组合物包含可用酶切割的二肽 - 氨基苄基 - 碳酸酯掩蔽剂可逆地修饰的RGD配体靶向的两亲膜活性多胺。 改性掩盖聚合物的膜活性，而可逆性提供生理反应性。 可逆修饰的多胺（动态多偶联物或缀合物）进一步与RNAi触发共价连接。