公开(公告)号：US11597932B2

公开(公告)日：2023-03-07

申请号：US16956271

申请日：2018-12-21

Applicant: ALNYLAM PHARMACEUTICALS, INC.

Inventor： Muthiah Manoharan ,  Nate Taneja ,  Hartmut Ingo Jahns ,  Shigeo Matsuda ,  Klaus Charisse ,  Guo He ,  Jayaprakash K. Nair ,  Christopher Brown ,  Mark K. Schlegel ,  Vasant Jadhav ,  Martin Maier

IPC: C12N15/113

Abstract: The present invention relates to a chirally-modified dsRNA agent capable of inhibiting the expression of a target gene. The sense and antisense strands of chirally-modified dsRNA agent independently or in combination comprises one or more site specific-site specific/position specific, chirally-modified internucleotide linkages.

公开(公告)号：US20230002772A1

公开(公告)日：2023-01-05

申请号：US17586850

申请日：2022-01-28

Applicant: Alnylam Pharmaceuticals, Inc.

Inventor： Anna Borodovsky ,  Kallanthottathil G. Rajeev ,  Kevin Fitzgerald ,  Maria Frank-Kamenetsky ,  William Querbes ,  Martin A. Maier ,  Klaus Charisse ,  Satyanarayana Kuchimanchi ,  Muthiah Manoharan ,  Stuart Milstein

IPC: C12N15/113 ,  A61K31/713 ,  A61K47/54

Abstract: The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the PCSK9 gene, and methods of using such RNAi agents to inhibit expression of PCSK9 and methods of treating subjects having a lipid disorder, such as a hyperlipidemia.

公开(公告)号：US11406716B2

公开(公告)日：2022-08-09

申请号：US16850555

申请日：2020-04-16

Applicant: Alnylam Pharmaceuticals, Inc.

Inventor： Kallanthottathil G. Rajeev ,  Tracy Zimmermann ,  Muthiah Manoharan ,  Martin Maier ,  Satyanarayana Kuchimanchi ,  Klaus Charisse

IPC: C12N15/113 ,  A61K48/00 ,  C07H21/02 ,  C12N15/85

Abstract: One aspect of the present invention relates to double-stranded RNAi (dsRNA) duplex agent capable of inhibiting the expression of a target gene. The dsRNA duplex comprises one or more motifs of three identical modifications on three consecutive nucleotides in one or both strand, particularly at or near the cleavage site of the strand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

公开(公告)号：US20220213475A1

公开(公告)日：2022-07-07

申请号：US17402459

申请日：2021-08-13

Applicant: Alnylam Pharmaceuticals, Inc.

Inventor： Kevin Fitzgerald ,  Maria Frank-Kamenetsky ,  Klaus Charisse

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

Abstract: The invention relates to dual targeting siRNA agents targeting a PCSK9 gene and a second gene, and methods of using dual targeting siRNA agents to inhibit expression of PCSK9 and to treat PCSK9 related disorders, e.g., hyperlipidemia.

公开(公告)号：US20210317452A1

公开(公告)日：2021-10-14

申请号：US17141275

申请日：2021-01-05

Applicant: Alnylam Pharmaceuticals, Inc.

Inventor： Alfica Sehgal ,  Klaus Charisse ,  Brian Bettencourt ,  Martin A. Maier ,  Kallanthottathil G. Rajeev ,  Gregory Hinkle ,  Muthiah Manoharan

IPC: C12N15/113 ,  A61K31/712 ,  A61K31/713

Abstract: The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the Serpina1 gene, and methods of using such RNAi agents to inhibit expression of Serpina1 and methods of treating subjects having a Serpina1 associated disease, such as a liver disorder.

公开(公告)号：US20210269796A1

公开(公告)日：2021-09-02

申请号：US17194431

申请日：2021-03-08

Applicant: Alnylam Pharmaceuticals, Inc.

Inventor： Mark K. Schlegel ,  Maja Janas ,  Vasant R. Jadhav ,  Donald Foster ,  Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Alexander V. Kel'in ,  Klaus Charisse ,  Jayaprakash K. Nair ,  Martin A. Maier ,  Shigeo Matsuda ,  Muthusamy Jayaraman ,  Alfica Sehgal ,  Christopher Brown ,  Kevin Fitzgerald ,  Stuart Milstein

IPC: C12N15/113

Abstract: The invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting the Serpina1 gene, and methods of using such RNAi agents to inhibit expression of Serpina1 and methods of treating subjects having a Serpina1 associated disease, such as a liver disorder.

公开(公告)号：US20180362978A1

公开(公告)日：2018-12-20

申请号：US15948624

申请日：2018-04-09

Applicant: Alnylam Pharmaceuticals, Inc.

Inventor： Brian Bettencourt ,  Kevin Fitzgerald ,  Stuart Milstein ,  Martin A. Maier ,  Klaus Charisse ,  Kallanthottathil Rajeev ,  Satyanarayana Kuchimanchi ,  Muthiah Manoharan ,  Tuyen Nguyen

IPC: C12N15/113

Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) targeting an APOC3 gene, and methods of using the dsRNA to inhibit expression of APOC3.

公开(公告)号：US10125369B2

公开(公告)日：2018-11-13

申请号：US14650128

申请日：2013-12-05

Applicant: Alnylam Pharmaceuticals, Inc.

Inventor： Anna Borodovsky ,  Kallanthottathil G. Rajeev ,  Kevin Fitzgerald ,  Maria Frank-Kamenetsky ,  William Querbes ,  Martin Maier ,  Klaus Charisse ,  Satyanarayana Kuchimanchi ,  Muthiah Manoharan ,  Stuart Milstein

IPC: C07H21/04 ,  A61K48/00 ,  C12N15/11 ,  C12N15/113 ,  A61K31/713 ,  A61K47/54

Abstract: The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the PCSK9 gene, and methods of using such RNAi agents to inhibit expression of PCSK9 and methods of treating subjects having a lipid disorder, such as a hyperlipidemia.

公开(公告)号：US20160145629A1

公开(公告)日：2016-05-26

申请号：US14947025

申请日：2015-11-20

Applicant: ALNYLAM PHARMACEUTICALS, INC.

Inventor： James Butler ,  Brian Bettencourt ,  Kallanthottathil G. Rajeev ,  Martin Maier ,  Klaus Charisse

IPC: C12N15/113

CPC classification number: C12N15/1138 ,  C12N9/6424 ,  C12N15/1137 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/316 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/343 ,  C12N2310/351 ,  C12N2310/3521 ,  C12N2310/3533 ,  C12N2320/30

Abstract: The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the TMPRSS6 gene, and methods of using such RNAi agents to inhibit expression of TMPRSS6 and methods of treating subjects having a TMPRSS6 associated disorder, e.g., an iron overload associated disorder, such as β-thalassemia or hemochromatosis.

Abstract translation: 本发明涉及RNAi试剂，例如靶向TMPRSS6基因的双链RNAi试剂，以及使用这种RNAi试剂抑制TMPRSS6表达的方法和治疗患有TMPRSS6相关病症的受试者的方法，例如铁超载相关病症 ，如“地中海贫血症”或“血色素沉着症”。

公开(公告)号：US09249415B2

公开(公告)日：2016-02-02

申请号：US14699140

申请日：2015-04-29

Applicant: Alnylam Pharmaceuticals, Inc.

Inventor： Kevin Fitzgerald ,  James Butler ,  Brian Bettencourt ,  Anna Borodovsky ,  Satyanarayana Kuchimanchi ,  Klaus Charisse ,  Muthiah Manoharan ,  Martin Maier ,  Kallanthottathil G. Rajeev ,  Donald Foster

IPC: C12N15/113

CPC classification number: C12N15/113 ,  A61K31/713 ,  A61K39/3955 ,  C07K16/18 ,  C07K2317/24 ,  C07K2317/76 ,  C12N2310/14 ,  C12N2310/3125 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/351 ,  C12N2310/3527 ,  C12N2320/30

Abstract: The invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the complement component C5 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.

Abstract translation: 本发明涉及iRNA，例如双链核糖核酸（dsRNA），针对补体成分C5基因的组合物，以及使用这种iRNA的方法，例如dsRNA，组合物抑制C5的表达并治疗具有补体成分的受试者 C5相关疾病，例如阵发性夜间血红蛋白尿。