ES2804764T3 - Polinucleótidos para la interferencia de ARN multivalente, composiciones y métodos de uso de los mismos - Google Patents
Polinucleótidos para la interferencia de ARN multivalente, composiciones y métodos de uso de los mismos Download PDFInfo
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- ES2804764T3 ES2804764T3 ES10783959T ES10783959T ES2804764T3 ES 2804764 T3 ES2804764 T3 ES 2804764T3 ES 10783959 T ES10783959 T ES 10783959T ES 10783959 T ES10783959 T ES 10783959T ES 2804764 T3 ES2804764 T3 ES 2804764T3
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18301109P | 2009-06-01 | 2009-06-01 | |
| PCT/US2010/036962 WO2010141511A2 (en) | 2009-06-01 | 2010-06-01 | Polynucleotides for multivalent rna interference, compositions and methods of use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2804764T3 true ES2804764T3 (es) | 2021-02-09 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10783959T Active ES2804764T3 (es) | 2009-06-01 | 2010-06-01 | Polinucleótidos para la interferencia de ARN multivalente, composiciones y métodos de uso de los mismos |
Country Status (7)
| Country | Link |
|---|---|
| US (3) | US9200276B2 (https=) |
| EP (1) | EP2438168B1 (https=) |
| JP (2) | JP5875976B2 (https=) |
| CN (1) | CN102575252B (https=) |
| CA (1) | CA2764158A1 (https=) |
| ES (1) | ES2804764T3 (https=) |
| WO (1) | WO2010141511A2 (https=) |
Families Citing this family (152)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010141511A2 (en) | 2009-06-01 | 2010-12-09 | Halo-Bio Rnai Therapeutics, Inc. | Polynucleotides for multivalent rna interference, compositions and methods of use thereof |
| US9115167B2 (en) * | 2011-03-10 | 2015-08-25 | Biomics Biotechnologies Co., Ltd. | Multi-targets interfering RNA molecules and their applications |
| SI3366775T2 (sl) | 2011-11-18 | 2025-12-31 | Alnylam Pharmaceuticals, Inc. | Modificirana sredstva RNAI |
| EP3730618A1 (en) | 2011-11-18 | 2020-10-28 | Alnylam Pharmaceuticals, Inc. | Rnai agents, compositions and methods of use thereof for treating transthyretin (ttr) associated diseases |
| AU2013202315A1 (en) * | 2012-01-04 | 2013-07-18 | Halo-Bio Rnai Therapeutics, Inc. | Nicked polynucleotide complexes for multivalent RNA interference |
| WO2013180038A1 (ja) | 2012-05-26 | 2013-12-05 | 株式会社ボナック | デリバリー機能を有する遺伝子発現制御用の一本鎖核酸分子 |
| AU2013296321B2 (en) | 2012-08-03 | 2019-05-16 | Alnylam Pharmaceuticals, Inc. | Modified RNAi agents |
| IL292159B1 (en) | 2012-12-05 | 2026-04-01 | Alnylam Pharmaceuticals Inc | PCSK9 iRNA compositions and methods of using them |
| IL288931B2 (en) | 2013-03-14 | 2025-05-01 | Alnylam Pharmaceuticals Inc | Compositions comprising a complementary portion of C5 IRNA and methods of using them |
| DK2992098T3 (da) | 2013-05-01 | 2019-06-17 | Ionis Pharmaceuticals Inc | Sammensætninger og fremgangsmåder til modulering af hbv- og ttr-ekspression |
| KR102234623B1 (ko) | 2013-05-22 | 2021-04-02 | 알닐람 파마슈티칼스 인코포레이티드 | Tmprss6 조성물 및 이의 사용 방법 |
| EA038792B1 (ru) | 2013-05-22 | 2021-10-20 | Элнилэм Фармасьютикалз, Инк. | КОМПОЗИЦИИ НА ОСНОВЕ RNAi Serpina1 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
| WO2015042564A1 (en) | 2013-09-23 | 2015-03-26 | Alnylam Pharmaceuticals, Inc. | Methods for treating or preventing transthyretin (ttr) associated diseases |
| SG10201804960RA (en) | 2013-12-12 | 2018-07-30 | Alnylam Pharmaceuticals Inc | Complement component irna compositions and methods of use thereof |
| WO2015099122A1 (ja) | 2013-12-26 | 2015-07-02 | 学校法人東京医科大学 | 遺伝子発現制御のための人工ミミックmiRNAおよびその用途 |
| CN106068324B (zh) | 2013-12-27 | 2020-12-29 | 株式会社博纳克 | 控制基因表达的人工匹配型miRNA及其用途 |
| US10119136B2 (en) | 2014-01-09 | 2018-11-06 | Alnylam Pharmaceuticals, Inc. | RNAi agents modified at the 4′-C position |
| CN113057959B (zh) | 2014-02-11 | 2024-07-16 | 阿尔尼拉姆医药品有限公司 | 己酮糖激酶(KHK)iRNA组合物及其使用方法 |
| WO2015134528A1 (en) * | 2014-03-04 | 2015-09-11 | Donald Danforth Plant Science Center | New generation of artificial micrornas |
| CN103820442B (zh) * | 2014-03-07 | 2015-10-21 | 中国农业科学院植物保护研究所 | 水稻黑条矮缩病毒RNAi多价靶基因序列及应用 |
| TW201607559A (zh) | 2014-05-12 | 2016-03-01 | 阿尼拉製藥公司 | 治療serpinc1相關疾患之方法和組成物 |
| AU2015264038B2 (en) | 2014-05-22 | 2021-02-11 | Alnylam Pharmaceuticals, Inc. | Angiotensinogen (AGT) iRNA compositions and methods of use thereof |
| IL316808A (en) | 2014-08-20 | 2025-01-01 | Alnylam Pharmaceuticals Inc | Modified double-stranded RNA materials and their uses |
| TW202503057A (zh) | 2014-10-10 | 2025-01-16 | 美商艾爾妮蘭製藥公司 | 用於抑制hao1(羥酸氧化酶1(乙醇酸鹽氧化酶))基因表現的組合物及方法 |
| KR102545316B1 (ko) | 2014-11-10 | 2023-06-22 | 알닐람 파마슈티칼스 인코포레이티드 | B형 간염 바이러스(hbv) irna 조성물 및 그의 이용 방법 |
| JP2017535552A (ja) | 2014-11-17 | 2017-11-30 | アルナイラム ファーマシューティカルズ, インコーポレイテッドAlnylam Pharmaceuticals, Inc. | アポリポタンパク質C3(APOC3)iRNA組成物およびその使用方法 |
| JP2018504380A (ja) | 2014-12-18 | 2018-02-15 | アルナイラム ファーマシューティカルズ, インコーポレイテッドAlnylam Pharmaceuticals, Inc. | Reversir(商標)化合物 |
| KR20170098914A (ko) | 2014-12-27 | 2017-08-30 | 가부시키가이샤 보낙 | 유전자 발현 제어를 위한 천연형 miRNA 및 그의 용도 |
| CA2976445A1 (en) | 2015-02-13 | 2016-08-18 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof |
| WO2016158809A1 (ja) | 2015-03-27 | 2016-10-06 | 株式会社ボナック | デリバリー機能と遺伝子発現制御能を有する一本鎖核酸分子 |
| WO2016201301A1 (en) | 2015-06-12 | 2016-12-15 | Alnylam Pharmaceuticals, Inc. | Complement component c5 irna compositions and methods of use thereof |
| WO2017011286A1 (en) | 2015-07-10 | 2017-01-19 | Alnylam Pharmaceuticals, Inc. | Insulin-like growth factor binding protein, acid labile subunit (igfals) and insulin-like growth factor 1 (igf-1) irna compositions and methods of use thereof |
| WO2017035278A1 (en) * | 2015-08-24 | 2017-03-02 | Halo-Bio Rnai Therapeutics, Inc. | Polynucleotide nanoparticles for the modulation of gene expression and uses thereof |
| CA2996873A1 (en) | 2015-09-02 | 2017-03-09 | Alnylam Pharmaceuticals, Inc. | Programmed cell death 1 ligand 1 (pd-l1) irna compositions and methods of use thereof |
| KR20250078597A (ko) | 2015-11-06 | 2025-06-02 | 아이오니스 파마수티컬즈, 인코포레이티드 | 아포리포프로테인 (a) 발현 조정 |
| KR20180095843A (ko) | 2015-12-07 | 2018-08-28 | 젠자임 코포레이션 | Serpinc1-연관 장애의 치료를 위한 방법 및 조성물 |
| EP3469083A1 (en) | 2016-06-10 | 2019-04-17 | Alnylam Pharmaceuticals, Inc. | COMPLEMENT COMPONENT C5 iRNA COMPOSITIONS AND METHODS OF USE THEREOF FOR TREATING PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) |
| TWI788312B (zh) | 2016-11-23 | 2023-01-01 | 美商阿尼拉製藥公司 | 絲胺酸蛋白酶抑制因子A1 iRNA組成物及其使用方法 |
| WO2018112320A1 (en) | 2016-12-16 | 2018-06-21 | Alnylam Pharmaceuticals, Inc. | Methods for treating or preventing ttr-associated diseases using transthyretin (ttr) irna compositions |
| CN108342386B (zh) * | 2017-01-22 | 2022-04-15 | 广州市锐博生物科技有限公司 | 一种多聚寡核酸分子及其在多靶标干扰中的应用 |
| TW202434265A (zh) | 2017-07-10 | 2024-09-01 | 美商健贊公司 | 於患有血友病之個體中治療出血事件之方法及組成物 |
| EP3652317A1 (en) | 2017-07-13 | 2020-05-20 | Alnylam Pharmaceuticals, Inc. | Lactate dehydrogenase a (ldha) irna compositions and methods of use thereof |
| WO2019014688A1 (en) * | 2017-07-14 | 2019-01-17 | Halo-Bio Rnai Therapeutics, Inc. | METHODS AND COMPOSITIONS FOR APNAMOND-ACTIVATED FORMULATION OF NANOPARTICLES OF SELF-FORMING POLYNUCLEOTIDES |
| US20200385719A1 (en) | 2017-11-16 | 2020-12-10 | Alnylam Pharmaceuticals, Inc. | Kisspeptin 1 (kiss1) irna compositions and methods of use thereof |
| WO2019100039A1 (en) | 2017-11-20 | 2019-05-23 | Alnylam Pharmaceuticals, Inc. | Serum amyloid p component (apcs) irna compositions and methods of use thereof |
| EP3728593A1 (en) | 2017-12-18 | 2020-10-28 | Alnylam Pharmaceuticals, Inc. | High mobility group box-1 (hmgb1) irna compositions and methods of use thereof |
| MX2020011570A (es) | 2018-05-07 | 2020-11-24 | Alnylam Pharmaceuticals Inc | Administracion extrahepatica. |
| TWI851574B (zh) | 2018-05-14 | 2024-08-11 | 美商阿尼拉製藥公司 | 血管收縮素原(AGT)iRNA組成物及其使用方法 |
| AU2018433363B2 (en) * | 2018-07-20 | 2022-12-08 | Guangzhou Ribobio Co., Ltd. | Nucleic acid unit and polymeric nucleic acid and application thereof |
| CA3110014A1 (en) * | 2018-08-27 | 2020-03-05 | Sirnaomics, Inc. | Products and compositions |
| US20210332367A1 (en) | 2018-09-18 | 2021-10-28 | Alnylam Pharmaceuticals, Inc. | KETOHEXOKINASE (KHK) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| CA3110300A1 (en) * | 2018-09-28 | 2020-04-02 | Sirnaomics, Inc. | Products and compositions |
| WO2020069055A1 (en) | 2018-09-28 | 2020-04-02 | Alnylam Pharmaceuticals, Inc. | Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases |
| WO2020232430A1 (en) * | 2019-05-16 | 2020-11-19 | University Of South Florida | Methods of downregulating ccl20 genes for treatment of traumatic brain injuries |
| AU2020279101B2 (en) | 2019-05-17 | 2025-07-24 | Alnylam Pharmaceuticals, Inc. | Oral delivery of oligonucleotides |
| EP4007811A2 (en) | 2019-08-01 | 2022-06-08 | Alnylam Pharmaceuticals, Inc. | Carboxypeptidase b2 (cpb2) irna compositions and methods of use thereof |
| EP4007812A1 (en) | 2019-08-01 | 2022-06-08 | Alnylam Pharmaceuticals, Inc. | Serpin family f member 2 (serpinf2) irna compositions and methods of use thereof |
| EP4013870A1 (en) | 2019-08-13 | 2022-06-22 | Alnylam Pharmaceuticals, Inc. | Small ribosomal protein subunit 25 (rps25) irna agent compositions and methods of use thereof |
| US12503699B2 (en) | 2019-10-04 | 2025-12-23 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing UGT1a1 gene expression |
| EP4045652A1 (en) | 2019-10-18 | 2022-08-24 | Alnylam Pharmaceuticals, Inc. | Solute carrier family member irna compositions and methods of use thereof |
| WO2021081026A1 (en) | 2019-10-22 | 2021-04-29 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof |
| EP4051795A1 (en) | 2019-11-01 | 2022-09-07 | Alnylam Pharmaceuticals, Inc. | Huntingtin (htt) irna agent compositions and methods of use thereof |
| US20230040920A1 (en) | 2019-11-01 | 2023-02-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing dnajb1-prkaca fusion gene expression |
| WO2021092145A1 (en) | 2019-11-06 | 2021-05-14 | Alnylam Pharmaceuticals, Inc. | Transthyretin (ttr) irna composition and methods of use thereof for treating or preventing ttr-associated ocular diseases |
| BR112022007795A2 (pt) | 2019-11-06 | 2022-07-05 | Alnylam Pharmaceuticals Inc | Administração extra-hepática |
| BR112022009216A2 (pt) | 2019-11-13 | 2022-08-02 | Alnylam Pharmaceuticals Inc | Métodos e composições para tratar um distúrbio associado a angiotensinogênio (agt) |
| US12565653B2 (en) | 2019-11-22 | 2026-03-03 | Alnylam Pharmaceuticals, Inc. | ATAXIN3 (ATXN3) RNAi agent compositions and methods of use thereof |
| KR20220115995A (ko) | 2019-12-13 | 2022-08-19 | 알닐람 파마슈티칼스 인코포레이티드 | 인간 염색체 9 개방 판독 프레임 72 (C9orf72) iRNA 제제 조성물 및 이의 사용 방법 |
| WO2021126734A1 (en) | 2019-12-16 | 2021-06-24 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof |
| WO2021154941A1 (en) | 2020-01-31 | 2021-08-05 | Alnylam Pharmaceuticals, Inc. | Complement component c5 irna compositions for use in the treatment of amyotrophic lateral sclerosis (als) |
| IL295445A (en) | 2020-02-10 | 2022-10-01 | Alnylam Pharmaceuticals Inc | Preparations and methods for silencing vegf-a expression |
| JP7735288B2 (ja) | 2020-02-18 | 2025-09-08 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | アポリポタンパク質C3(APOC3)iRNA組成物およびその使用法 |
| EP4114947A1 (en) | 2020-03-05 | 2023-01-11 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases |
| BR112022017822A2 (pt) | 2020-03-06 | 2022-11-08 | Alnylam Pharmaceuticals Inc | Composições de irna de cetoexocinase (khk) e métodos de uso das mesmas |
| US20210363523A1 (en) * | 2020-03-18 | 2021-11-25 | University Of Massachusetts | Oligonucleotides for mapt modulation |
| US20210363524A1 (en) * | 2020-03-18 | 2021-11-25 | University Of Massachusetts | Oligonucleotides for snca modulation |
| EP4121534A1 (en) | 2020-03-18 | 2023-01-25 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for treating subjects having a heterozygous alanine-glyoxylate aminotransferase gene (agxt) variant |
| TW202204615A (zh) | 2020-03-26 | 2022-02-01 | 美商阿尼拉製藥公司 | 冠狀病毒iRNA組成物及其使用方法 |
| US20230190785A1 (en) | 2020-03-30 | 2023-06-22 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing dnajc15 gene expression |
| US12534731B2 (en) | 2020-04-01 | 2026-01-27 | Alnylam Pharmaceuticals, Inc. | Alpha-2A adrenergic receptor (ADRA2A) iRNA agent compositions and methods of use thereof |
| KR20230008729A (ko) | 2020-04-06 | 2023-01-16 | 알닐람 파마슈티칼스 인코포레이티드 | Myoc 발현을 사일런싱하기 위한 조성물 및 방법 |
| EP4133077A1 (en) | 2020-04-07 | 2023-02-15 | Alnylam Pharmaceuticals, Inc. | Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof |
| EP4133076A1 (en) | 2020-04-07 | 2023-02-15 | Alnylam Pharmaceuticals, Inc. | Angiotensin-converting enzyme 2 (ace2) irna compositions and methods of use thereof |
| JP2023521094A (ja) | 2020-04-07 | 2023-05-23 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | Scn9a発現をサイレンシングするための組成物および方法 |
| IL297702A (en) | 2020-04-27 | 2022-12-01 | Alnylam Pharmaceuticals Inc | Apolipoprotein e (apoe) irna agent compositions and methods of use thereof |
| JP2023523790A (ja) | 2020-04-30 | 2023-06-07 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | 補体因子B(CFB)iRNA組成物およびその使用方法 |
| US20230183707A1 (en) | 2020-05-21 | 2023-06-15 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting marc1 gene expression |
| WO2021252649A2 (en) | 2020-06-09 | 2021-12-16 | Alnylam Pharmaceuticals, Inc. | Sirna compositions and methods for silencing gpam (glycerol-3-phosphate acyltransferase 1, mitochondrial) expression |
| EP4162050A1 (en) | 2020-06-09 | 2023-04-12 | Alnylam Pharmaceuticals, Inc. | Rnai compositions and methods of use thereof for delivery by inhalation |
| WO2021257782A1 (en) | 2020-06-18 | 2021-12-23 | Alnylam Pharmaceuticals, Inc. | XANTHINE DEHYDROGENASE (XDH) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| WO2022011214A1 (en) | 2020-07-10 | 2022-01-13 | Alnylam Pharmaceuticals, Inc. | Circular sirnas |
| WO2022066847A1 (en) | 2020-09-24 | 2022-03-31 | Alnylam Pharmaceuticals, Inc. | Dipeptidyl peptidase 4 (dpp4) irna compositions and methods of use thereof |
| EP4225917A1 (en) | 2020-10-05 | 2023-08-16 | Alnylam Pharmaceuticals, Inc. | G protein-coupled receptor 75 (gpr75) irna compositions and methods of use thereof |
| CA3198823A1 (en) | 2020-10-21 | 2022-04-28 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating primary hyperoxaluria |
| EP4232582A1 (en) | 2020-10-23 | 2023-08-30 | Alnylam Pharmaceuticals, Inc. | Mucin 5b (muc5b) irna compositions and methods of use thereof |
| KR20230107625A (ko) | 2020-11-13 | 2023-07-17 | 알닐람 파마슈티칼스 인코포레이티드 | 응고 인자 V(F5) iRNA 조성물 및 이의 사용 방법 |
| TW202237150A (zh) | 2020-12-01 | 2022-10-01 | 美商艾拉倫製藥股份有限公司 | 用於抑制hao1(羥基酸氧化酶1(乙醇酸氧化酶))基因表現的方法及組成物 |
| CN114606196A (zh) * | 2020-12-04 | 2022-06-10 | 南京大学 | 一种进行siRNA表达和体内递送的细胞疗法 |
| WO2022125490A1 (en) | 2020-12-08 | 2022-06-16 | Alnylam Pharmaceuticals, Inc. | Coagulation factor x (f10) irna compositions and methods of use thereof |
| EP4271695A2 (en) | 2020-12-31 | 2023-11-08 | Alnylam Pharmaceuticals, Inc. | 2'-modified nucleoside based oligonucleotide prodrugs |
| EP4271696A2 (en) | 2020-12-31 | 2023-11-08 | Alnylam Pharmaceuticals, Inc. | Cyclic-disulfide modified phosphate based oligonucleotide prodrugs |
| EP4274896A1 (en) | 2021-01-05 | 2023-11-15 | Alnylam Pharmaceuticals, Inc. | Complement component 9 (c9) irna compositions and methods of use thereof |
| JP2024506042A (ja) * | 2021-02-08 | 2024-02-08 | ラクティゲン セラピューティクス | 多価オリゴヌクレオチド薬剤およびその使用方法 |
| EP4291654A2 (en) | 2021-02-12 | 2023-12-20 | Alnylam Pharmaceuticals, Inc. | Superoxide dismutase 1 (sod1) irna compositions and methods of use thereof for treating or preventing superoxide dismutase 1- (sod1-) associated neurodegenerative diseases |
| EP4298220A1 (en) | 2021-02-25 | 2024-01-03 | Alnylam Pharmaceuticals, Inc. | Prion protein (prnp) irna compositions and methods of use thereof |
| AU2022226098A1 (en) | 2021-02-26 | 2023-08-24 | Alnylam Pharmaceuticals, Inc. | KETOHEXOKINASE (KHK) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| JP2024508896A (ja) | 2021-03-04 | 2024-02-28 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | アンジオポエチン様3(ANGPTL3)iRNA組成物およびその使用方法 |
| WO2022192519A1 (en) | 2021-03-12 | 2022-09-15 | Alnylam Pharmaceuticals, Inc. | Glycogen synthase kinase 3 alpha (gsk3a) irna compositions and methods of use thereof |
| EP4314296A2 (en) | 2021-03-29 | 2024-02-07 | Alnylam Pharmaceuticals, Inc. | Huntingtin (htt) irna agent compositions and methods of use thereof |
| EP4314293A1 (en) | 2021-04-01 | 2024-02-07 | Alnylam Pharmaceuticals, Inc. | Proline dehydrogenase 2 (prodh2) irna compositions and methods of use thereof |
| EP4330392A1 (en) | 2021-04-26 | 2024-03-06 | Alnylam Pharmaceuticals, Inc. | Transmembrane protease, serine 6 (tmprss6) irna compositions and methods of use thereof |
| WO2022232343A1 (en) | 2021-04-29 | 2022-11-03 | Alnylam Pharmaceuticals, Inc. | Signal transducer and activator of transcription factor 6 (stat6) irna compositions and methods of use thereof |
| EP4341401A1 (en) | 2021-05-18 | 2024-03-27 | Alnylam Pharmaceuticals, Inc. | Sodium-glucose cotransporter-2 (sglt2) irna compositions and methods of use thereof |
| EP4347823A1 (en) | 2021-06-02 | 2024-04-10 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof |
| EP4347822A2 (en) | 2021-06-04 | 2024-04-10 | Alnylam Pharmaceuticals, Inc. | Human chromosome 9 open reading frame 72 (c9orf72) irna agent compositions and methods of use thereof |
| AR126070A1 (es) | 2021-06-08 | 2023-09-06 | Alnylam Pharmaceuticals Inc | Composiciones y métodos para tratar o prevenir la enfermedad de stargardt y/o trastornos asociados con la proteína transportadora de retinol 4 (rbp4) |
| CA3221985A1 (en) * | 2021-06-21 | 2022-12-29 | Chad PECOT | Inverted chimeric sirna molecules and methods of use thereof |
| AU2022303164A1 (en) | 2021-06-30 | 2024-01-18 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating an angiotensinogen- (agt-) associated disorder |
| WO2023283403A2 (en) | 2021-07-09 | 2023-01-12 | Alnylam Pharmaceuticals, Inc. | Bis-rnai compounds for cns delivery |
| WO2023003805A1 (en) | 2021-07-19 | 2023-01-26 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating subjects having or at risk of developing a non-primary hyperoxaluria disease or disorder |
| MX2024000981A (es) | 2021-07-21 | 2024-02-12 | Alnylam Pharmaceuticals Inc | Composiciones de acido ribonucleico de interferencia (arni) de gen diana asociado con trastorno metabolico y sus metodos de uso. |
| AU2022316139A1 (en) | 2021-07-23 | 2024-01-18 | Alnylam Pharmaceuticals, Inc. | Beta-catenin (ctnnb1) irna compositions and methods of use thereof |
| WO2023009687A1 (en) | 2021-07-29 | 2023-02-02 | Alnylam Pharmaceuticals, Inc. | 3-hydroxy-3-methylglutaryl-coa reductase (hmgcr) irna compositions and methods of use thereof |
| CA3227852A1 (en) | 2021-08-03 | 2023-02-09 | Alnylam Pharmaceuticals, Inc. | Transthyretin (ttr) irna compositions and methods of use thereof |
| EP4381071A1 (en) | 2021-08-04 | 2024-06-12 | Alnylam Pharmaceuticals, Inc. | Irna compositions and methods for silencing angiotensinogen (agt) |
| CN118076737A (zh) | 2021-08-13 | 2024-05-24 | 阿尔尼拉姆医药品有限公司 | 因子XII(F12)iRNA组合物及其使用方法 |
| JP2024538859A (ja) | 2021-08-31 | 2024-10-24 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | 細胞死誘導DFFA様エフェクターB(CIDEB)iRNA組成物およびその使用方法 |
| WO2023041508A2 (en) * | 2021-09-14 | 2023-03-23 | Argonaute RNA Limited | Treatment of cardiovascular disease |
| JP2024535850A (ja) | 2021-09-17 | 2024-10-02 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | 補体成分(C3)をサイレンシングするためのiRNA組成物および方法 |
| AU2022345881A1 (en) | 2021-09-20 | 2024-03-21 | Alnylam Pharmaceuticals, Inc. | Inhibin subunit beta e (inhbe) modulator compositions and methods of use thereof |
| TW202328449A (zh) | 2021-09-24 | 2023-07-16 | 美商艾拉倫製藥公司 | 微管相關蛋白TAU(MAPT)iRNA試劑組合物及其使用方法 |
| CN118369427A (zh) | 2021-10-15 | 2024-07-19 | 阿尔尼拉姆医药品有限公司 | 肝外递送irna组合物及其使用方法 |
| US20250295755A1 (en) | 2021-10-22 | 2025-09-25 | Sail Biomedicines, Inc. | Mrna vaccine composition |
| EP4423272A2 (en) | 2021-10-29 | 2024-09-04 | Alnylam Pharmaceuticals, Inc. | Huntingtin (htt) irna agent compositions and methods of use thereof |
| CN118302525A (zh) | 2021-10-29 | 2024-07-05 | 阿尔尼拉姆医药品有限公司 | 补体因子B(CFB)iRNA组合物及其使用方法 |
| CA3238764A1 (en) | 2021-11-23 | 2023-06-01 | Siddharth Patel | A bacteria-derived lipid composition and use thereof |
| EP4452239A1 (en) | 2021-12-20 | 2024-10-30 | Sail Biomedicines, Inc. | Compositions comprising mrna and lipid reconstructed plant messenger packs |
| WO2023141314A2 (en) | 2022-01-24 | 2023-07-27 | Alnylam Pharmaceuticals, Inc. | Heparin sulfate biosynthesis pathway enzyme irna agent compositions and methods of use thereof |
| JP2025522880A (ja) | 2022-06-30 | 2025-07-17 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | 環状ジスルフィド修飾リン酸ベースのオリゴヌクレオチドプロドラッグ |
| EP4569113A1 (en) | 2022-09-15 | 2025-06-18 | Regeneron Pharmaceuticals, Inc. | 17b-hydroxysteroid dehydrogenase type 13 (hsd17b13) irna compositions and methods of use thereof |
| WO2024073732A1 (en) | 2022-09-30 | 2024-04-04 | Alnylam Pharmaceuticals, Inc. | Modified double-stranded rna agents |
| WO2024102434A1 (en) | 2022-11-10 | 2024-05-16 | Senda Biosciences, Inc. | Rna compositions comprising lipid nanoparticles or lipid reconstructed natural messenger packs |
| CN121057577A (zh) | 2023-01-27 | 2025-12-02 | 赛欧生物医药股份有限公司 | 经修饰的脂质组合物及其用途 |
| KR20260009305A (ko) | 2023-04-12 | 2026-01-19 | 알닐람 파마슈티칼스 인코포레이티드 | 이중 가닥 rna 제제의 간외 전달 |
| WO2024220712A2 (en) | 2023-04-19 | 2024-10-24 | Sail Biomedicines, Inc. | Vaccine compositions |
| WO2024220752A2 (en) | 2023-04-19 | 2024-10-24 | Sail Biomedicines, Inc. | Rna therapeutic compositions |
| WO2024220625A1 (en) | 2023-04-19 | 2024-10-24 | Sail Biomedicines, Inc. | Delivery of polynucleotides from lipid nanoparticles comprising rna and ionizable lipids |
| WO2024228030A2 (en) | 2023-05-04 | 2024-11-07 | Argonaute RNA Limited | Dual silencing |
| KR20260049597A (ko) | 2023-08-04 | 2026-04-14 | 알닐람 파마슈티칼스 인코포레이티드 | Ctnnb1-관련 질환을 치료하기 위한 방법 및 조성물 |
| WO2025064660A2 (en) | 2023-09-21 | 2025-03-27 | Alnylam Pharmaceuticals, Inc. | Activin a receptor type 1c (acvr1c) irna compositions and methods of use thereof |
| WO2025076031A2 (en) | 2023-10-03 | 2025-04-10 | Alnylam Pharmaceuticals, Inc. | Peritoneal macrophages comprising a nanoparticle encapsulating a nucleic acid molecule and methods of use thereof |
| WO2026036000A1 (en) | 2024-08-08 | 2026-02-12 | Invaio Sciences, Inc. | Nature-derived lipid particles for use in agriculture |
Family Cites Families (124)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5506337A (en) | 1985-03-15 | 1996-04-09 | Antivirals Inc. | Morpholino-subunit combinatorial library and method |
| WO1986005519A1 (en) | 1985-03-15 | 1986-09-25 | James Summerton | Polynucleotide assay reagent and method |
| US5217866A (en) | 1985-03-15 | 1993-06-08 | Anti-Gene Development Group | Polynucleotide assay reagent and method |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US5521063A (en) | 1985-03-15 | 1996-05-28 | Antivirals Inc. | Polynucleotide reagent containing chiral subunits and methods of use |
| US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
| US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
| JPH09500526A (ja) | 1993-06-14 | 1997-01-21 | ベーアーエスエフ アクツィエンゲゼルシャフト | テトラサイクリン反応性プロモーターによる真核細胞の遺伝子発現の厳密な制御 |
| US5814618A (en) | 1993-06-14 | 1998-09-29 | Basf Aktiengesellschaft | Methods for regulating gene expression |
| US5856174A (en) | 1995-06-29 | 1999-01-05 | Affymetrix, Inc. | Integrated nucleic acid diagnostic device |
| US6013516A (en) | 1995-10-06 | 2000-01-11 | The Salk Institute For Biological Studies | Vector and method of use for nucleic acid delivery to non-dividing cells |
| US20040171031A1 (en) | 1996-06-06 | 2004-09-02 | Baker Brenda F. | Sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
| US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
| US5874554A (en) | 1996-12-13 | 1999-02-23 | Incyte Pharmaceuticals, Inc. | Methods and solvent vehicles for reagent delivery in oligonucleotide synthesis using automated pulse jetting devices |
| US7572582B2 (en) | 1997-09-12 | 2009-08-11 | Exiqon A/S | Oligonucleotide analogues |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| US6506559B1 (en) | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| US6218181B1 (en) | 1998-03-18 | 2001-04-17 | The Salk Institute For Biological Studies | Retroviral packaging cell line |
| DK1144616T4 (da) | 1999-01-19 | 2009-03-30 | Unilever Nv | Fremgangsmåde til fremstilling af antistoffragmenter |
| DE19956568A1 (de) | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
| US7084125B2 (en) | 1999-03-18 | 2006-08-01 | Exiqon A/S | Xylo-LNA analogues |
| US7053207B2 (en) | 1999-05-04 | 2006-05-30 | Exiqon A/S | L-ribo-LNA analogues |
| GB9927444D0 (en) | 1999-11-19 | 2000-01-19 | Cancer Res Campaign Tech | Inhibiting gene expression |
| DE10100586C1 (de) | 2001-01-09 | 2002-04-11 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines Ziegens |
| ES2336887T5 (es) | 2000-03-30 | 2019-03-06 | Whitehead Inst Biomedical Res | Mediadores de interferencia por ARN específicos de secuencias de ARN |
| CA2429814C (en) | 2000-12-01 | 2014-02-18 | Thomas Tuschl | Rna interference mediating small rna molecules |
| US7767802B2 (en) | 2001-01-09 | 2010-08-03 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of anti-apoptotic genes |
| US7423142B2 (en) | 2001-01-09 | 2008-09-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of anti-apoptotic genes |
| US20050191618A1 (en) * | 2001-05-18 | 2005-09-01 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of human immunodeficiency virus (HIV) gene expression using short interfering nucleic acid (siNA) |
| US20070173473A1 (en) * | 2001-05-18 | 2007-07-26 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA) |
| US20070270579A1 (en) | 2001-05-18 | 2007-11-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA) |
| US20050196781A1 (en) * | 2001-05-18 | 2005-09-08 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of STAT3 gene expression using short interfering nucleic acid (siNA) |
| DK2280070T3 (en) | 2001-07-23 | 2015-08-24 | Univ Leland Stanford Junior | Methods and compositions for use in RNAi-mediated inhibition of gene expression in mammals |
| US10590418B2 (en) | 2001-07-23 | 2020-03-17 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for RNAi mediated inhibition of gene expression in mammals |
| CA2459347C (en) | 2001-09-04 | 2012-10-09 | Exiqon A/S | Locked nucleic acid (lna) compositions and uses thereof |
| US7745418B2 (en) | 2001-10-12 | 2010-06-29 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting viral replication |
| DE10163098B4 (de) | 2001-10-12 | 2005-06-02 | Alnylam Europe Ag | Verfahren zur Hemmung der Replikation von Viren |
| DE10202419A1 (de) | 2002-01-22 | 2003-08-07 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines durch eine Chromosomen-Aberration entstandenen Zielgens |
| KR100464261B1 (ko) | 2002-01-24 | 2005-01-03 | 주식회사 파나진 | Pna 올리고머를 합성하기 위한 신규한 단량체 및 그의제조방법 |
| US20100240730A1 (en) | 2002-02-20 | 2010-09-23 | Merck Sharp And Dohme Corp. | RNA Interference Mediated Inhibition of Gene Expression Using Chemically Modified Short Interfering Nucleic Acid (siNA) |
| KR20030084444A (ko) | 2002-04-26 | 2003-11-01 | 주식회사 파나진 | Pna 올리고머를 합성하기 위한 신규한 단량체 및 그의제조방법 |
| US7569575B2 (en) | 2002-05-08 | 2009-08-04 | Santaris Pharma A/S | Synthesis of locked nucleic acid derivatives |
| WO2004030634A2 (en) | 2002-10-02 | 2004-04-15 | Alnylam Pharmaceuticals Inc. | Therapeutic compositions |
| CA2502649A1 (en) | 2002-10-18 | 2004-04-29 | Nucleonics Inc. | Double-stranded rna structures and constructs, and methods for generating and using the same |
| AU2003299864A1 (en) * | 2002-12-27 | 2004-07-29 | P. Radhakrishnan | Sirna compounds and methods for the downregulation of gene expression |
| JP2004261002A (ja) * | 2003-01-08 | 2004-09-24 | Tsutomu Suzuki | siRNAの製造方法 |
| WO2004064737A2 (en) | 2003-01-17 | 2004-08-05 | Alnylam Pharmaceuticals | Therapeutics compositions |
| CA2518475C (en) | 2003-03-07 | 2014-12-23 | Alnylam Pharmaceuticals, Inc. | Irna agents comprising asymmetrical modifications |
| WO2004090108A2 (en) | 2003-04-03 | 2004-10-21 | Alnylam Pharmaceuticals | Irna conjugates |
| US20050233342A1 (en) | 2003-03-07 | 2005-10-20 | Muthiah Manoharan | Methods of preventing off-target gene silencing |
| CA2521464C (en) | 2003-04-09 | 2013-02-05 | Alnylam Pharmaceuticals, Inc. | Irna conjugates |
| US20070179100A1 (en) | 2003-04-09 | 2007-08-02 | Muthiah Manoharan | Protected monomers |
| WO2004091572A2 (en) * | 2003-04-09 | 2004-10-28 | Biodelivery Sciences International, Inc. | Cochleate compositions directed against expression of proteins |
| ES2702942T3 (es) | 2003-04-17 | 2019-03-06 | Alnylam Pharmaceuticals Inc | Agentes de ARNi modificados |
| JP4991288B2 (ja) | 2003-04-17 | 2012-08-01 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | 二本鎖iRNA剤、および二本鎖iRNA剤の対合の安定性を調節する方法。 |
| US20050148531A1 (en) * | 2003-05-15 | 2005-07-07 | Todd Hauser | Modulation of gene expression using DNA-DNA hybrids |
| US7595306B2 (en) | 2003-06-09 | 2009-09-29 | Alnylam Pharmaceuticals Inc | Method of treating neurodegenerative disease |
| WO2005004794A2 (en) | 2003-06-09 | 2005-01-20 | Alnylam Pharmaceuticals Inc. | Method of treating neurodegenerative disease |
| AU2004263830B2 (en) | 2003-06-13 | 2008-12-18 | Alnylam Pharmaceuticals, Inc. | Double-stranded ribonucleic acid with increased effectiveness in an organism |
| US7211668B2 (en) | 2003-07-28 | 2007-05-01 | Panagene, Inc. | PNA monomer and precursor |
| DE602004030923D1 (de) * | 2003-09-17 | 2011-02-17 | Rodos Biotarget Gmbh | Lipid-arzneimittel-formulierungen zur gezielten pharmakotherapie von myeloiden und lymphoiden immunzellen |
| ES2423060T3 (es) | 2004-03-12 | 2013-09-17 | Alnylam Pharmaceuticals, Inc. | Agentes iRNA que tienen como diana al VEGF |
| JP2007531794A (ja) | 2004-04-05 | 2007-11-08 | アルニラム ファーマスーティカルズ インコーポレイテッド | オリゴヌクレオチドの合成および精製に使用する方法および反応試薬 |
| EP1768998A2 (en) | 2004-04-27 | 2007-04-04 | Alnylam Pharmaceuticals Inc. | Single-stranded and double-stranded oligonucleotides comprising a 2-arylpropyl moiety |
| AU2005323437B2 (en) | 2004-04-30 | 2011-10-06 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a C5-modified pyrimidine |
| AU2005247509C1 (en) | 2004-05-27 | 2012-09-20 | Alnylam Pharmaceuticals, Inc. | Nuclease resistant double-stranded ribonucleic acid |
| EP1789553B1 (en) | 2004-06-30 | 2014-03-26 | Alnylam Pharmaceuticals Inc. | Oligonucleotides comprising a non-phosphate backbone linkage |
| US20080213891A1 (en) | 2004-07-21 | 2008-09-04 | Alnylam Pharmaceuticals, Inc. | RNAi Agents Comprising Universal Nucleobases |
| WO2006093526A2 (en) | 2004-07-21 | 2006-09-08 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a modified or non-natural nucleobase |
| AU2005330637B2 (en) | 2004-08-04 | 2012-09-20 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase |
| EP1791567B1 (en) | 2004-08-10 | 2015-07-29 | Alnylam Pharmaceuticals Inc. | Chemically modified oligonucleotides |
| EP2377873B1 (en) * | 2004-09-24 | 2014-08-20 | Alnylam Pharmaceuticals, Inc. | RNAi modulation of ApoB and uses thereof |
| CA2587697A1 (en) | 2004-11-24 | 2006-07-13 | Alnylam Pharmaceuticals, Inc. | Rnai modulation of the bcr-abl fusion gene and uses thereof |
| US8003619B2 (en) | 2004-12-09 | 2011-08-23 | Alnylam Pharmaceuticals, Inc. | Method of stimulating an immune response and inhibiting expression of a gene using an oligonucleotide |
| EP1824872B1 (en) | 2004-12-14 | 2012-02-08 | Alnylam Pharmaceuticals Inc. | Rnai modulation of mll-af4 and uses thereof |
| EP2765189A1 (en) | 2004-12-21 | 2014-08-13 | Monsanto Technology LLC | Recombinant DNA constructs and methods for controlling gene expression |
| US7169561B2 (en) * | 2004-12-29 | 2007-01-30 | Applera Corporation | Methods, compositions, and kits for forming self-complementary polynucleotides |
| US20090005332A1 (en) * | 2004-12-30 | 2009-01-01 | Hauser Todd M | Compositions and Methods for Modulating Gene Expression Using Self-Protected Oligonucleotides |
| CN102600480B (zh) | 2005-01-07 | 2015-07-22 | 阿尔尼拉姆医药品有限公司 | RSV的RNAi调节及其治疗应用 |
| EP1841464B1 (en) | 2005-01-24 | 2012-06-27 | Alnylam Pharmaceuticals Inc. | Rnai modulation of the nogo-l or nogo-r gene and uses thereof |
| US7718625B2 (en) * | 2005-01-27 | 2010-05-18 | University Of South Florida | Polynucleotides targeted against the extended 5′-UTR region of argininosuccinate synthase and uses thereof |
| NZ560936A (en) * | 2005-02-03 | 2010-04-30 | Benitec Inc | RNAI expression constructs |
| WO2007002718A2 (en) | 2005-06-27 | 2007-01-04 | Alnylam Pharmaceuticals, Inc. | Rnai modulation of hif-1 and theraputic uses thereof |
| AU2006272808C1 (en) | 2005-07-21 | 2010-10-21 | Alnylam Pharmaceuticals, Inc. | RNAi modulation of the Rho-A gene and uses thereof |
| AU2006275579B2 (en) * | 2005-08-01 | 2012-10-04 | Purdue Research Foundation | Multivalent RNA nanoparticles for delivery of active agents to a cell |
| AU2006279906B2 (en) | 2005-08-10 | 2012-05-10 | Alnylam Pharmaceuticals, Inc. | Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof |
| US20070213292A1 (en) | 2005-08-10 | 2007-09-13 | The Rockefeller University | Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof |
| US20070148246A1 (en) * | 2005-08-11 | 2007-06-28 | Dan Luo | Nucleic Acid-Based Matrixes |
| EP1937066A4 (en) | 2005-08-18 | 2008-12-24 | Alnylam Pharmaceuticals Inc | METHOD AND COMPOSITIONS FOR THE TREATMENT OF NERVOUS DISEASES |
| JP5111385B2 (ja) | 2005-10-28 | 2013-01-09 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | ハンチンチン遺伝子の発現を抑制するための組成物および方法 |
| WO2007053696A2 (en) | 2005-11-01 | 2007-05-10 | Alnylam Pharmaceuticals, Inc. | Rnai inhibition of influenza virus replication |
| CA2626584A1 (en) | 2005-11-04 | 2007-05-18 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of nav1.8 gene |
| US20100069461A1 (en) | 2005-11-09 | 2010-03-18 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of factor v leiden mutant gene |
| CA2527144C (en) | 2005-11-15 | 2014-04-29 | Queen's University At Kingston | Reversibly switchable surfactants and methods of use thereof |
| RU2410431C2 (ru) | 2005-11-25 | 2011-01-27 | Мологен Аг | Днк-конструкции для специфического ингибирования экспрессии генов посредством рнк-интерференции |
| EP1989307B1 (en) | 2006-02-08 | 2012-08-08 | Quark Pharmaceuticals, Inc. | NOVEL TANDEM siRNAS |
| EP1993611A4 (en) | 2006-03-16 | 2013-05-22 | Alnylam Pharmaceuticals Inc | RNAi MODULATION OF TGF-BETA AND THERAPEUTIC USES |
| NZ571568A (en) | 2006-03-31 | 2010-11-26 | Alnylam Pharmaceuticals Inc | Double-stranded RNA molecule compositions and methods for inhibiting expression of Eg5 gene |
| WO2007127919A2 (en) | 2006-04-28 | 2007-11-08 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a gene from the jc virus |
| PL2735568T3 (pl) | 2006-05-10 | 2018-02-28 | Sarepta Therapeutics, Inc. | Analogi oligonukleotydowe mające kationowe połączenia pomiędzy podjednostkami |
| CN101484588B (zh) | 2006-05-11 | 2013-11-06 | 阿尔尼拉姆医药品有限公司 | 抑制pcsk9基因表达的组合物和方法 |
| WO2007134037A2 (en) | 2006-05-15 | 2007-11-22 | Immunomedics, Inc. | Methods and compositions for treatment of human immunodeficiency virus infection with conjugated antibodies or antibody fragments |
| CN101489566B (zh) | 2006-05-19 | 2012-04-18 | 阿尔尼拉姆医药品有限公司 | Aha基因的RNAi调控及其治疗性应用 |
| KR20090019790A (ko) | 2006-05-19 | 2009-02-25 | 더 스크립스 리서치 인스티튜트 | 단백질 미스폴딩의 치료 |
| WO2007137220A2 (en) | 2006-05-22 | 2007-11-29 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of ikk-b gene |
| WO2008008719A2 (en) | 2006-07-10 | 2008-01-17 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the myc gene |
| US20080039415A1 (en) | 2006-08-11 | 2008-02-14 | Gregory Robert Stewart | Retrograde transport of sirna and therapeutic uses to treat neurologic disorders |
| AU2007297388A1 (en) | 2006-09-18 | 2008-03-27 | Alnylam Pharmaceuticals, Inc. | RNAi modulation of scap and therapeutic uses thereof |
| EP2066687A4 (en) | 2006-09-21 | 2010-12-08 | Alnylam Pharmaceuticals Inc | COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF HAMP GENE |
| WO2008036929A2 (en) | 2006-09-21 | 2008-03-27 | Alnylam Pharmaceuticals, Inc. | Complex for transferring an anionic substance into a cell |
| CA2927045A1 (en) | 2006-10-03 | 2008-04-10 | Muthiah Manoharan | Lipid containing formulations |
| US8034921B2 (en) | 2006-11-21 | 2011-10-11 | Alnylam Pharmaceuticals, Inc. | IRNA agents targeting CCR5 expressing cells and uses thereof |
| EP2905336A1 (en) | 2007-03-29 | 2015-08-12 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inhibiting expression of a gene from the ebola |
| CA2685127C (en) | 2007-04-23 | 2019-01-08 | Alnylam Pharmaceuticals, Inc. | Glycoconjugates of rna interference agents |
| WO2009018332A1 (en) | 2007-08-01 | 2009-02-05 | Alnylam Pharmaceuticals, Inc. | Single-stranded and double-stranded oligonucleotides comprising a metal-chelating ligand |
| RU2606627C2 (ru) | 2007-11-15 | 2017-01-10 | Серепта Терапьютикс,Инк. | Способ синтеза морфолиновых олигомеров |
| WO2009073809A2 (en) | 2007-12-04 | 2009-06-11 | Alnylam Pharmaceuticals, Inc. | Carbohydrate conjugates as delivery agents for oligonucleotides |
| US8298765B2 (en) * | 2009-01-01 | 2012-10-30 | Cornell University | Multifunctional nucleic acid nano-structures |
| JP5529895B2 (ja) | 2009-02-04 | 2014-06-25 | ソンギュングヮン ユニバーシティ ファウンデーション フォー コーポレート コラボレーション | 細胞内の伝達能が増加した低分子干渉rna複合体 |
| EP2432794B1 (en) | 2009-05-22 | 2017-08-30 | The Research Foundation of State University of New York | Trans-acting rna switches |
| WO2010141511A2 (en) | 2009-06-01 | 2010-12-09 | Halo-Bio Rnai Therapeutics, Inc. | Polynucleotides for multivalent rna interference, compositions and methods of use thereof |
-
2010
- 2010-06-01 WO PCT/US2010/036962 patent/WO2010141511A2/en not_active Ceased
- 2010-06-01 CN CN201080034204.7A patent/CN102575252B/zh active Active
- 2010-06-01 JP JP2012513363A patent/JP5875976B2/ja not_active Expired - Fee Related
- 2010-06-01 ES ES10783959T patent/ES2804764T3/es active Active
- 2010-06-01 US US13/375,460 patent/US9200276B2/en active Active
- 2010-06-01 CA CA2764158A patent/CA2764158A1/en not_active Abandoned
- 2010-06-01 EP EP10783959.9A patent/EP2438168B1/en active Active
-
2015
- 2015-07-31 JP JP2015151507A patent/JP2015192674A/ja active Pending
- 2015-11-30 US US14/954,653 patent/US9957505B2/en not_active Expired - Fee Related
-
2018
- 2018-04-30 US US15/967,052 patent/US20180346908A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN102575252A (zh) | 2012-07-11 |
| US20120184598A1 (en) | 2012-07-19 |
| EP2438168B1 (en) | 2020-02-12 |
| JP5875976B2 (ja) | 2016-03-02 |
| WO2010141511A3 (en) | 2011-04-21 |
| JP2012528572A (ja) | 2012-11-15 |
| US20180346908A1 (en) | 2018-12-06 |
| EP2438168A4 (en) | 2014-01-22 |
| EP2438168A2 (en) | 2012-04-11 |
| CN102575252B (zh) | 2016-04-20 |
| CA2764158A1 (en) | 2010-12-09 |
| JP2015192674A (ja) | 2015-11-05 |
| US20160160215A1 (en) | 2016-06-09 |
| US9957505B2 (en) | 2018-05-01 |
| US9200276B2 (en) | 2015-12-01 |
| WO2010141511A2 (en) | 2010-12-09 |
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