公开(公告)号：US20240358738A1

公开(公告)日：2024-10-31

申请号：US18651230

申请日：2024-04-30

申请人： ALNYLAM PHARMACEUTICALS, INC.

发明人： Jayaprakash K. NAIR ,  Martin MAIER ,  Vasant JADHAV ,  Stuart MILSTEIN ,  Kirk BROWN ,  Rubina G. PARMAR ,  Kallanthottathil G. RAJEEV ,  Muthiah MANOHARAN ,  Alexander V. KEL'IN ,  Muthusamy JAYARAMAN ,  Klaus CHARISSE ,  Adam CASTORENO ,  Christopher S. THEILE ,  Kevin FITZGERALD

IPC分类号： A61K31/713 ,  A61K9/00 ,  A61K47/54 ,  C12N15/113

CPC分类号： A61K31/713 ,  A61K9/0019 ,  A61K47/543 ,  C12N15/1137 ,  C12N15/1138 ,  C12N2310/14 ,  C12N2310/3515

摘要： One aspect of the present invention relates to a double stranded iRNA agent comprising an antisense strand which is complementary to a target gene; a sense strand which is complementary to said antisense strand; and one or more lipophilic moieties conjugated to one or more internal positions on at least one strand, optionally via a linker or carrier. Another aspect of the invention relates to a method of gene silencing, comprising administering to a cell or a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs.

公开(公告)号：US20230068339A1

公开(公告)日：2023-03-02

申请号：US17741550

申请日：2022-05-11

申请人： Alnylam Pharmaceuticals, Inc.

发明人： Kevin FITZGERALD ,  William QUERBES ,  James BUTLER ,  Stephanie WILLIAMS ,  Abigail LIEBOW ,  Gregory HINKLE ,  Martin A. MAIER ,  Stuart MILSTEIN ,  Satyanarayana KUCHIMANCHI ,  Muthiah MANOHARAN

IPC分类号： C12N15/113 ,  A61P3/04 ,  A61P43/00 ,  A61P13/12 ,  A61P1/18 ,  A61P3/10 ,  A61P9/12 ,  A61P15/08 ,  A61P9/10 ,  A61P1/16 ,  A61P3/06 ,  A61K31/713

摘要： The present invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the apolipoprotein C3 (APOC3) gene, and methods of using such RNAi agents to inhibit expression of APOC3 and methods of treating subjects having an APOC3 associated disorder, e.g., hypertriglyceridemia.

公开(公告)号：US20220125823A1

公开(公告)日：2022-04-28

申请号：US17052945

申请日：2019-05-07

申请人： ALNYLAM PHARMACEUTICALS, INC.

发明人： Jayaprakash K. NAIR ,  Martin MAIER ,  Vasant JADHAV ,  Stuart MILSTEIN ,  Kirk BROWN ,  Rubina G. PARMAR ,  Kallanthottathil G. RAJEEV ,  Muthiah MANOHARAN ,  Alexander V. KEL'IN ,  Muthusamy JAYARAMAN ,  Klaus CHARISSE ,  Adam CASTORENO ,  Christopher S. THEILE ,  Kevin FITZGERALD

IPC分类号： A61K31/713 ,  C12N15/113 ,  A61K47/54 ,  A61K9/00

摘要： The invention relates to a method of gene silencing, comprising administering to a cell or a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs at one or more internal positions on at least one strand, optionally via a linker or carrier.

公开(公告)号：US20240009225A1

公开(公告)日：2024-01-11

申请号：US18311484

申请日：2023-05-03

申请人： ALNYLAM PHARMACEUTICALS, INC.

发明人： Jayaprakash K. NAIR ,  Martin MAIER ,  Vasant JADHAV ,  Stuart MILSTEIN ,  Kirk BROWN ,  Rubina G. PARMAR ,  Kallanthottathil G. RAJEEV ,  Muthiah MANOHARAN ,  Alexander V. KEL'IN ,  Muthusamy JAYARAMAN ,  Klaus CHARISSE ,  Adam CASTORENO ,  Christopher THEILE ,  Kevin FITZGERALD

IPC分类号： A61K31/713 ,  A61K47/54 ,  A61K9/00 ,  C12N15/113

CPC分类号： A61K31/713 ,  A61K47/543 ,  A61K9/0019 ,  C12N15/1137 ,  C12N15/1138 ,  C12N2310/14 ,  C12N2310/3515

摘要： One aspect of the present invention relates to a double stranded iRNA agent comprising an antisense strand which is complementary to a target gene; a sense strand which is complementary to said antisense strand; and one or more lipophilic moieties conjugated to one or more internal positions on at least one strand, optionally via a linker or carrier. Another aspect of the invention relates to a method of gene silencing, comprising administering to a cell or a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs.

公开(公告)号：US20230049529A1

公开(公告)日：2023-02-16

申请号：US17621029

申请日：2020-06-18

申请人： Alnylam Pharmaceuticals, Inc. ,  THE SCRIPPS RESEARCH INSTITUTE

发明人： Alexander V. KEL'IN ,  Alex R. NANNA ,  Christopher RADER ,  Christopher THEILE ,  Justin PIERSON ,  Kevin FITZGERALD ,  Zhi Xiang VOO

IPC分类号： A61K47/68 ,  C12N15/113 ,  A61K47/54 ,  C07K16/28 ,  C07K16/32

摘要： The disclosure is directed to dual variable domain immunoglobulin double-stranded RNA conjugates that are advantageous for inhibition of target gene expression, as well as compositions suitable for therapeutic use. The dual variable domain immunoglobulin comprises a first variable domain that binds to a binding target, and a second variable domain that comprises a reactive residue, where the linker is covalently conjugated to the reactive residue. The dsRNA is linked to the linker and is capable of inhibiting the expression of the target gene by RNA interference. The disclosure also provides pharmaceutical compositions comprising these conjugate and methods of inhibiting the expression of a target gene by administering these conjugates, e.g., for the treatment of various disease conditions.