公开(公告)号：EP2999785B1

公开(公告)日：2018-04-04

申请号：EP14730051.1

申请日：2014-05-22

申请人： Alnylam Pharmaceuticals, Inc.

发明人： SEHGAL, Alfica ,  CHARISSE, Klaus ,  BETTENCOURT, Brian ,  MAIER, Martin ,  RAJEEV, Kallanthottathil G. ,  HINKLE, Gregory ,  MANOHARAN, Muthiah

IPC分类号： C12N15/113 ,  A61K31/712 ,  A61K31/713 ,  A61P1/16 ,  A61P11/00 ,  A61P35/00

CPC分类号： C12N15/113 ,  A61K31/712 ,  A61K31/713 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/331 ,  C12N2310/332 ,  C12N2310/343 ,  C12N2310/344 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2320/32 ,  C12N2320/34 ,  C12N2320/51 ,  C12N2330/30 ,  C12N2310/322 ,  C12N2310/3533 ,  C12N2310/3521

摘要： 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：EP3284824A1

公开(公告)日：2018-02-21

申请号：EP17175148.0

申请日：2013-04-10

申请人： Alnylam Pharmaceuticals, Inc. ,  Icahn School of Medicine at Mount Sinai

发明人： BETTENCOURT, Brian ,  FITZGERALD, Kevin ,  QUERBES, William ,  YASUDA, Makiko ,  DESNICK, Robert J.

IPC分类号： C12N15/113 ,  A61K31/713

CPC分类号： C12N15/113 ,  A61K31/713 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/343 ,  C12N2310/344 ,  C12N2310/351 ,  C12N2310/3521 ,  C12N2310/3533 ,  C12N2310/50 ,  C12N2310/533 ,  C12N2320/30 ,  C12Y203/01037

摘要： The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ALAS1 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of ALAS1.

公开(公告)号：EP2321414B1

公开(公告)日：2018-01-10

申请号：EP09790796.8

申请日：2009-07-24

申请人： Alnylam Pharmaceuticals, Inc.

发明人： MAIER, Martin ,  ADDEPALLI, Haripriya ,  MANOHARAN, Muthiah

IPC分类号： C12N15/113 ,  C07H21/02

CPC分类号： C07H21/02 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/33 ,  C12N2310/331 ,  C12N2310/332 ,  C12N2320/50

摘要： One aspect of the present invention relates to a double stranded nucleic acid useful as an siRNA, that has a sense strand and an antisense strand relative to a target nucleic acid, where the sense strand contains one or more modified nucleobases, or one or more mismatch base pairings with the antisense strand. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one nucleoside comprising a non-natural nucleobase. Another aspect of the invention relates to a method of gene silencing, comprising administering to a mammal in need thereof a therapeutically effective amount of a double-stranded oligonucleotides containing a sense strand and an antisense strand, where the sense strand contains one or more modified nucleobases, or one or more mismatch base pairings with the antisense strand.

公开(公告)号：EP2723390B1

公开(公告)日：2017-12-27

申请号：EP12802392.6

申请日：2012-06-22

申请人： Alnylam Pharmaceuticals, Inc.

发明人： SEHGAL, Alfica ,  BUMCROT, David ,  BETTENCOURT, Brian

IPC分类号： A61K48/00 ,  A61K38/17

CPC分类号： G03G15/556 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/3515 ,  C12N2310/3521 ,  G03G15/0853 ,  G03G15/086 ,  G03G2215/0888

摘要： The technology described herein relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the Serpinal gene, and methods of using such dsRNA compositions to inhibit expression of Serpinal. In one embodiment, an iRNA for inhibiting expression of a Serpinal gene includes at least two sequences that are complementary to each other. The iRNA includes a sense strand having a first sequence and an antisense strand having a second sequence. The antisense strand includes a nucleotide sequence that is substantially complementary to at least part of an mRNA encoding Serpinal, and the region of complementarity is 30 nucleotides or less, and at least 15 nucleotides in length. Generally, the iRNA is 19 to 24, e.g., 19 to 21 nucleotides in length.

公开(公告)号：EP3256587A2

公开(公告)日：2017-12-20

申请号：EP16706299.1

申请日：2016-02-11

申请人： Alnylam Pharmaceuticals, Inc.

发明人： FITZGERALD, Kevin ,  HINKLE, Gregory

IPC分类号： C12N15/113 ,  A61K31/713

CPC分类号： A61K31/7125 ,  C07H19/067 ,  C07H19/167 ,  C07H21/02 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3515 ,  C12P19/34 ,  C12N2310/3521 ,  C12N2310/3533

摘要： The present invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting the Patatin-Like Phospholipase Domain Containing 3 (PNPLA3) gene, and methods of using such RNAi agents to inhibit expression of a PNPLA3 gene and methods of treating subjects having Nonalcoholic Fatty Liver Disease (NAFLD) and/or a PNPLA3-associated disorder.

公开(公告)号：EP3254672A1

公开(公告)日：2017-12-13

申请号：EP17000656.3

申请日：2011-06-03

申请人： Alnylam Pharmaceuticals, Inc.

发明人： Manoharan, Muthiah ,  Maier, Martin ,  Jayaraman, Muthusamy ,  Matsuda, Shigeo ,  Jayaprakash, Narayanannair, K. ,  Rajeev, Kallanthottathil, G. ,  Akinc, Akin ,  Baillie, Thomas, A.

IPC分类号： A61K9/10 ,  A61K39/00 ,  A61K48/00 ,  C07C69/02 ,  C07C211/62 ,  C07C211/63 ,  C12N15/87 ,  A61K31/713 ,  A61K47/44 ,  C07C229/12 ,  C12N15/113 ,  C12N15/88

CPC分类号： C07C229/12 ,  A61K31/713 ,  A61K39/0005 ,  A61K47/44 ,  C12N15/113 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/30

摘要： The present invention relates to a cationic lipid having one or more biodegradable groups located in the mid- or distal section of a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid.

摘要翻译： 本发明涉及阳离子脂质，其具有位于阳离子脂质的脂质部分（例如疏水链）的中部或远端部分的一个或多个生物可降解基团。 可以将这些阳离子脂质掺入用于递送活性剂（例如核酸）的脂质颗粒中。 本发明还涉及包含中性脂质，能够减少聚集的脂质，本发明的阳离子脂质和任选的甾醇的脂质颗粒。 脂质颗粒可以进一步包含治疗剂例如核酸。

公开(公告)号：EP3249052A1

公开(公告)日：2017-11-29

申请号：EP17162101.4

申请日：2007-05-10

申请人： Alnylam Pharmaceuticals, Inc.

发明人： TAN, Pamela ,  BRAMLAGE, Birgit ,  FRANK-KAMENETSKY, Maria ,  FITZGERALD, Kevin ,  AKINC, Akin ,  KOTELIANSKI, Victor E.

IPC分类号： C12Q1/68 ,  A01N43/04 ,  C07H21/04 ,  A61K31/07 ,  C12N15/113

CPC分类号： C12N15/1137 ,  A61K31/713 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/332 ,  C12N2310/3515 ,  C12N2310/3521

摘要： The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the PCSK9 gene (PCSK9 gene), comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the PCSK9 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by PCSK9 gene expression and the expression of the PCSK9 gene using the pharmaceutical composition.

摘要翻译： 本发明涉及用于抑制PCSK9基因（PCSK9基因）表达的双链核糖核酸（dsRNA），其包含具有长度小于30个核苷酸，通常长度为19-25个核苷酸的核苷酸序列的反义链 并且其与PCSK9基因的至少一部分基本上互补。 本发明还涉及包含dsRNA和药学上可接受的载体的药物组合物; 使用该药物组合物治疗由PCSK9基因表达引起的疾病和PCSK9基因表达的方法。

公开(公告)号：EP3207138A1

公开(公告)日：2017-08-23

申请号：EP15791083.7

申请日：2015-10-16

申请人： Alnylam Pharmaceuticals, Inc.

发明人： HINKLE, Gregory

IPC分类号： C12N15/113 ,  A61K31/712 ,  A61K31/713 ,  A61P43/00

摘要： The invention relates to polynucleotide agents, e.g., antisense polunucleotide agents, targeting the ALAS1 gene, and methods of using such agents to alter (e.g., inhibit) expression of ALAS1 and to treat ALAS1 associated diseases, e.g., porphyria.

摘要翻译： 本发明涉及靶向ALAS1基因的多核苷酸试剂，例如反义多核苷酸试剂，以及使用这些试剂来改变（例如，抑制）ALAS1表达和治疗ALAS1相关疾病（例如卟啉症）的方法。

公开(公告)号：EP3185957A2

公开(公告)日：2017-07-05

申请号：EP15835924.0

申请日：2015-08-27

申请人： Alnylam Pharmaceuticals, Inc.

发明人： BETTENCOURT, Brian

IPC分类号： A61P25/02 ,  A61P25/28 ,  C12N15/00

CPC分类号： G01N33/566 ,  C07D263/57 ,  C07K1/00 ,  C12N15/113 ,  C12N2310/14 ,  G01N33/50 ,  G01N33/53 ,  G01N33/567 ,  G01N33/6896

摘要： Disclosed herein are methods for reducing or arresting an increase in a Neuropathy Impairment Score (NIS) or a modified NIS (mNIS+7) in a human subject by administering an effective amount of a transthyretin (TTR)-inhibiting composition.

摘要翻译： 本文公开了通过施用有效量的转甲状腺素蛋白（TTR）抑制组合物来减少或阻止人受试者中的神经病损伤评分（NIS）或修饰的NIS（mNIS + 7）增加的方法。

公开(公告)号：EP2836595B1

公开(公告)日：2017-06-14

申请号：EP13721433.4

申请日：2013-04-10

申请人： Alnylam Pharmaceuticals, Inc. ,  Icahn School of Medicine at Mount Sinai

发明人： BETTENCOURT, Brian ,  FITZGERALD, Kevin ,  QUERBES, William ,  YASUDA, Makiko ,  DESNICK, Robert, J.

IPC分类号： C12N15/113 ,  A61K31/713 ,  A61P43/00

CPC分类号： C12N15/113 ,  A61K31/713 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/343 ,  C12N2310/344 ,  C12N2310/351 ,  C12N2310/3521 ,  C12N2310/3533 ,  C12N2310/50 ,  C12N2310/533 ,  C12N2320/30 ,  C12Y203/01037

摘要： The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ALAS1 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of ALAS1.

摘要翻译： 本发明涉及靶向ALAS1基因的双链核糖核酸（dsRNA）组合物，以及使用这种dsRNA组合物改变（例如抑制）ALAS1表达的方法。