ES2690538T3 - Composiciones y métodos para inhibir la expresión génica del virus de la hepatitis B - Google Patents
Composiciones y métodos para inhibir la expresión génica del virus de la hepatitis B Download PDFInfo
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- ES2690538T3 ES2690538T3 ES12804876.6T ES12804876T ES2690538T3 ES 2690538 T3 ES2690538 T3 ES 2690538T3 ES 12804876 T ES12804876 T ES 12804876T ES 2690538 T3 ES2690538 T3 ES 2690538T3
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| EP11172235 | 2011-06-30 | ||
| US13/535,454 US8809293B2 (en) | 2011-06-30 | 2012-06-28 | Compositions and methods for inhibiting gene expression of hepatitis B virus |
| US201213535454 | 2012-06-28 | ||
| PCT/US2012/044505 WO2013003520A1 (en) | 2011-06-30 | 2012-06-28 | Compositions and methods for inhibiting gene expression of hepatitis b virus |
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| ZA (1) | ZA201307914B (OSRAM) |
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| LT2606134T (lt) | 2010-08-17 | 2019-07-25 | Sirna Therapeutics, Inc. | Hepatito b viruso (hbv) geno raiškos slopinimas, tarpininkaujant rnr interferencijai naudojant mažą interferuojančią nukleorūgštį (sina) |
| MX340408B (es) | 2011-04-21 | 2016-07-07 | Ionis Pharmaceuticals Inc | Modulacion de la expresion del virus de hepatitis b (vhb). |
| TW202244278A (zh) * | 2011-06-30 | 2022-11-16 | 美商艾羅海德製藥公司 | 用於抑制ｂ型肝炎病毒基因表現之組合物及方法 |
| WO2014032176A1 (en) | 2012-08-30 | 2014-03-06 | Replicor Inc. | Methods for the treatment of hepatitis b and hepatitis d infections |
| CA2889044A1 (en) | 2012-11-15 | 2014-05-22 | Roche Innovation Center Copenhagen A/S | Anti apob antisense conjugate compounds |
| MX2015009056A (es) | 2013-01-30 | 2015-10-05 | Hoffmann La Roche | Conjugados de oligonucleotidos de acido nucleico bloqueado y carbohidratos. |
| JP6694811B2 (ja) | 2013-10-04 | 2020-05-20 | ノバルティス アーゲー | ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ |
| WO2015051366A2 (en) | 2013-10-04 | 2015-04-09 | Novartis Ag | Novel formats for organic compounds for use in rna interference |
| WO2015050871A2 (en) * | 2013-10-04 | 2015-04-09 | Novartis Ag | Organic compounds to treat hepatitis b virus |
| GB201408623D0 (en) | 2014-05-15 | 2014-07-02 | Santaris Pharma As | Oligomers and oligomer conjugates |
| WO2016011123A1 (en) * | 2014-07-16 | 2016-01-21 | Arrowhead Research Corporation | Organic compositions to treat apoc3-related diseases |
| RU2017114964A (ru) | 2014-10-02 | 2018-11-07 | Протива Байотерапьютикс, Инк. | Композиции и способы для подавления экспрессии гена вируса гепатита в |
| JOP20200092A1 (ar) * | 2014-11-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها |
| DK3237636T3 (da) * | 2014-12-22 | 2021-01-25 | Anapa Biotech As | Dobbelt-quenching analyse til multiplex detektion af målnukleinsyrer |
| KR20170141257A (ko) * | 2015-05-06 | 2017-12-22 | 베니텍 바이오파마 리미티드 | B형 간염 바이러스 (hbv) 감염의 치료를 위한 시약 및 이의 용도 |
| US20170137821A1 (en) | 2015-07-17 | 2017-05-18 | Arcturus Therapeutics, Inc. | Molecules and agents for treating hepatitis b virus |
| CN108136206B (zh) * | 2015-07-17 | 2021-10-15 | 阿克丘勒斯治疗公司 | 抗乙型肝炎病毒的组合物和药剂及其用途 |
| US20180208932A1 (en) * | 2015-07-29 | 2018-07-26 | Arbutus Biopharma Corporation | Compositions and methods for silencing hepatitis b virus gene expression |
| JO3769B1 (ar) * | 2015-08-07 | 2021-01-31 | Arrowhead Pharmaceuticals Inc | علاج RNAi لعدوى فيروس التهاب الكبد B |
| AU2016306275A1 (en) | 2015-08-07 | 2018-02-08 | Arrowhead Pharmaceuticals, Inc. | RNAi therapy for Hepatitis B virus infection |
| CN113797348A (zh) * | 2016-03-07 | 2021-12-17 | 箭头药业股份有限公司 | 用于治疗性化合物的靶向配体 |
| CN108713061B (zh) * | 2016-03-09 | 2022-04-05 | 学校法人东京理科大学 | Rna杂交形成用核酸低聚物 |
| HRP20210315T1 (hr) | 2016-03-14 | 2021-04-16 | F. Hoffmann - La Roche Ag | Oligonukleotidi za smanjenje ekspresije pd-l1 |
| CA3023185A1 (en) * | 2016-05-05 | 2017-11-09 | Benitec Biopharma Limited | Reagents for treatment of hepatitis b virus (hbv) infection and use thereof |
| MA45496A (fr) | 2016-06-17 | 2019-04-24 | Hoffmann La Roche | Molécules d'acide nucléique pour la réduction de l'arnm de padd5 ou pad7 pour le traitement d'une infection par l'hépatite b |
| JOP20170161A1 (ar) * | 2016-08-04 | 2019-01-30 | Arrowhead Pharmaceuticals Inc | عوامل RNAi للعدوى بفيروس التهاب الكبد ب |
| WO2018053185A1 (en) | 2016-09-14 | 2018-03-22 | Alios Biopharma, Inc. | Modified oligonucleotides and methods of use |
| BR112019007450A2 (pt) * | 2016-10-14 | 2020-07-07 | Precision Biosciences, Inc. | meganucleases modificadas específicas para sequências de reconhecimento no genoma do vírus da hepatite b |
| CN110114071B (zh) | 2016-11-07 | 2023-07-04 | 爱彼特生物制药公司 | 含有取代的吡啶酮的三环化合物以及使用其的方法 |
| AU2017368050A1 (en) | 2016-11-29 | 2019-06-20 | Puretech Lyt, Inc. | Exosomes for delivery of therapeutic agents |
| MA49014A (fr) | 2017-03-21 | 2020-02-05 | Arbutus Biopharma Corp | Dihydroindène-4-carboxamides substitués, leurs analogues et procédés d'utilisation correspondant |
| IL321221A (en) | 2017-04-05 | 2025-07-01 | Silence Therapeutics Gmbh | Products and compositions |
| CN118384268A (zh) * | 2017-04-18 | 2024-07-26 | 阿尔尼拉姆医药品有限公司 | 具有乙肝病毒（hbv）感染的受试者的治疗方法 |
| US11324820B2 (en) | 2017-04-18 | 2022-05-10 | Alnylam Pharmaceuticals, Inc. | Methods for the treatment of subjects having a hepatitis b virus (HBV) infection |
| PE20200868A1 (es) | 2017-10-16 | 2020-08-31 | Hoffmann La Roche | OLIGONUCLEOTIDOS ANTISENTIDO Y CONJUGADOS QUE LOS COMPRENDEN PARA LA REDUCCION DEL ARNm DE PAPD5 Y PAPD7 |
| PL3684377T3 (pl) * | 2017-10-20 | 2023-04-17 | Dicerna Pharmaceuticals, Inc. | Sposoby leczenia zakażenia wirusem zapalenia wątroby typu b |
| JP7360716B2 (ja) | 2017-12-01 | 2023-10-13 | スーチョウ リボ ライフ サイエンス カンパニー、リミテッド | 核酸、当該核酸を含む組成物および複合体ならびに調製方法と使用 |
| CN118291456A (zh) | 2017-12-01 | 2024-07-05 | 苏州瑞博生物技术股份有限公司 | 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途 |
| JP7261494B2 (ja) | 2017-12-01 | 2023-04-20 | スーチョウ リボ ライフ サイエンス カンパニー、リミテッド | 核酸、当該核酸を含む組成物及び複合体ならびに調製方法と使用 |
| EP3719128B1 (en) | 2017-12-01 | 2025-01-15 | Suzhou Ribo Life Science Co., Ltd. | Double-stranded oligonucleotide, composition and conjugate comprising double-stranded oligonucleotide, preparation method therefor and use thereof |
| EP3718572B1 (en) | 2017-12-01 | 2024-07-31 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, composition and conjugate containing nucleic acid, preparation method and use |
| EA202091513A1 (ru) | 2017-12-19 | 2020-09-09 | Янссен Сайенсиз Айрлэнд Анлимитед Компани | Вакцины против вируса гепатита b (hbv) и их применение |
| JP7436030B2 (ja) | 2017-12-29 | 2024-02-21 | スーチョウ リボ ライフ サイエンス カンパニー、リミテッド | 複合体及びその調製方法と使用 |
| PE20211912A1 (es) | 2018-04-05 | 2021-09-28 | Centre Nat Rech Scient | Uso de inhibidores de fubp1 para el tratamiento de infeccion de virus de hepatitis b |
| KR102585973B1 (ko) | 2018-07-03 | 2023-10-10 | 에프. 호프만-라 로슈 아게 | 타우 발현을 조절하기 위한 올리고뉴클레오티드 |
| CR20210015A (es) | 2018-07-13 | 2021-03-22 | Hoffmann La Roche | Oligonucleótidos para modular la expresión de rtel 1 |
| TWI826492B (zh) | 2018-07-27 | 2023-12-21 | 加拿大商愛彼特生物製藥公司 | 經取代四氫環戊[c]吡咯、經取代二氫吡咯，其類似物及使用其之方法 |
| BR112021001613A2 (pt) | 2018-08-13 | 2021-05-04 | Alnylam Pharmaceuticals, Inc. | agentes de ácido ribonucleico de fita dupla, célula, composições farmacêuticas, métodos de inibição da expressão gênica, de inibição da replicação e de tratar um sujeito, métodos para reduzir o nível de um antígeno e para reduzir a carga viral e uso de um agente de dsrna |
| WO2020038377A1 (zh) | 2018-08-21 | 2020-02-27 | 苏州瑞博生物技术有限公司 | 一种核酸、含有该核酸的药物组合物和缀合物及其用途 |
| US11896674B2 (en) | 2018-09-30 | 2024-02-13 | Suzhou Ribo Life Science Co., Ltd. | SiRNA conjugate, preparation method therefor and use thereof |
| CN109385459A (zh) * | 2018-10-18 | 2019-02-26 | 大连理工大学 | 一种细胞分裂素通过抑制dna聚合酶活性抑制细胞增殖的方法 |
| TWI827760B (zh) | 2018-12-12 | 2024-01-01 | 加拿大商愛彼特生物製藥公司 | 經取代之芳基甲基脲類及雜芳基甲基脲類、其類似物及其使用方法 |
| JP7507495B2 (ja) | 2018-12-28 | 2024-06-28 | スーチョウ リボ ライフ サイエンス カンパニー、リミテッド | 核酸、当該核酸を含む組成物及び複合体ならびに調製方法と使用 |
| TWI872048B (zh) | 2019-02-07 | 2025-02-11 | 美商艾羅海德製藥公司 | 用於Ｂ型肝炎病毒感染之ＲＮＡｉ劑 |
| CN114072142A (zh) | 2019-04-18 | 2022-02-18 | 杨森制药公司 | 用于治疗乙型肝炎病毒感染的组合疗法 |
| TW202106294A (zh) | 2019-04-18 | 2021-02-16 | 美商健生醫藥公司 | 用於治療ｂ型肝炎病毒感染的組合療法（一） |
| CN118256498A (zh) | 2019-05-22 | 2024-06-28 | 苏州瑞博生物技术股份有限公司 | 核酸、药物组合物与缀合物及制备方法和用途 |
| US20220305107A1 (en) * | 2019-06-18 | 2022-09-29 | Janssen Sciences Ireland Unlimited Company | COMBINATION OF HEPATITIS B VIRUS (HBV) VACCINES AND HBV-TARGETING RNAi |
| US20220305117A1 (en) | 2019-06-18 | 2022-09-29 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and hbv-targeting rnai |
| CN110218728A (zh) * | 2019-06-28 | 2019-09-10 | 厦门甘宝利生物医药有限公司 | 一种新化合物及其应用 |
| CN114829599A (zh) | 2019-12-19 | 2022-07-29 | 豪夫迈·罗氏有限公司 | Scamp3抑制剂用于治疗乙型肝炎病毒感染的用途 |
| JP7653997B2 (ja) | 2019-12-19 | 2025-03-31 | エフ． ホフマン－ラ ロシュ アーゲー | Ｂ型肝炎ウイルス感染を処置するためのｃｏｐｓ３阻害剤の使用 |
| JP7634542B2 (ja) | 2019-12-19 | 2025-02-21 | エフ． ホフマン－ラ ロシュ アーゲー | Ｂ型肝炎ウイルス感染症を処置するためのｓｅｐｔ９阻害剤の使用 |
| EP4077671A1 (en) | 2019-12-19 | 2022-10-26 | F. Hoffmann-La Roche AG | Use of saraf inhibitors for treating hepatitis b virus infection |
| JP2023506550A (ja) | 2019-12-19 | 2023-02-16 | エフ． ホフマン－ラ ロシュ エージー． | Ｂ型肝炎ウイルス感染症を処置するためのｓｂｄｓ阻害剤の使用 |
| US20210285000A1 (en) | 2020-03-05 | 2021-09-16 | Janssen Pharmaceuticals, Inc. | Combination therapy for treating hepatitis b virus infection |
| KR20220163960A (ko) * | 2020-03-06 | 2022-12-12 | 알리고스 테라퓨틱스 인코포레이티드 | 변경된 짧은 개재성 핵산(siNA) 분자 및 이의 용도 |
| CN116157522A (zh) | 2020-08-21 | 2023-05-23 | 豪夫迈·罗氏有限公司 | A1cf抑制剂用于治疗乙型肝炎病毒感染的用途 |
| KR102798766B1 (ko) * | 2020-12-18 | 2025-04-23 | 올릭스 주식회사 | HBV 발현을 억제하는 RNAi 제제 및 이의 용도 |
| TW202245809A (zh) | 2020-12-18 | 2022-12-01 | 美商詹森藥物公司 | 用於治療b型肝炎病毒感染之組合療法 |
| US20240299557A1 (en) * | 2021-01-22 | 2024-09-12 | Taibidi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. | Compound for degrading deoxyribonucleic acid (dna) polymerase, and use thereof |
| TW202246500A (zh) | 2021-02-02 | 2022-12-01 | 瑞士商赫孚孟拉羅股份公司 | 用於抑制 ｒｔｅｌ１ 表現之增強型寡核苷酸 |
| CA3240651A1 (en) * | 2021-12-16 | 2023-06-22 | Yunfei Li | Dsrna, preparation method therefor and use thereof |
| WO2023111210A1 (en) | 2021-12-17 | 2023-06-22 | F. Hoffmann-La Roche Ag | Combination of oligonucleotides for modulating rtel1 and fubp1 |
| WO2023233290A1 (en) | 2022-05-31 | 2023-12-07 | Janssen Sciences Ireland Unlimited Company | Rnai agents targeting pd-l1 |
| CN119452087A (zh) * | 2022-06-21 | 2025-02-14 | 正大天晴药业集团股份有限公司 | 用于抑制乙型肝炎病毒的双链核糖核酸 |
| WO2024125636A1 (zh) * | 2022-12-16 | 2024-06-20 | 上海拓界生物医药科技有限公司 | Toll样受体调节剂与dsRNA的联合治疗 |
| CN119331868A (zh) * | 2023-07-18 | 2025-01-21 | 复旦大学 | 一种核酸、含有该核酸的药物组合物和缀合物及其应用 |
| WO2025067544A1 (zh) * | 2023-09-28 | 2025-04-03 | 北京凯因科技股份有限公司 | 用于抑制乙型肝炎病毒的siRNA及其用途 |
| CN119799706A (zh) * | 2024-07-08 | 2025-04-11 | 杭州天龙药业有限公司 | 靶向调控HBV基因表达的siRNA及其应用 |
Family Cites Families (114)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
| US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| JP2828642B2 (ja) | 1987-06-24 | 1998-11-25 | ハワード フローレイ インスティテュト オブ イクスペリメンタル フィジオロジー アンド メディシン | ヌクレオシド誘導体 |
| US4924624A (en) | 1987-10-22 | 1990-05-15 | Temple University-Of The Commonwealth System Of Higher Education | 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof |
| US5278302A (en) | 1988-05-26 | 1994-01-11 | University Patents, Inc. | Polynucleotide phosphorodithioates |
| US5216141A (en) | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
| US5328470A (en) | 1989-03-31 | 1994-07-12 | The Regents Of The University Of Michigan | Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor |
| US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
| US5591722A (en) | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
| US5399676A (en) | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
| DE69034150T2 (de) | 1989-10-24 | 2005-08-25 | Isis Pharmaceuticals, Inc., Carlsbad | 2'-Modifizierte Oligonukleotide |
| US5264562A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences, Inc. | Oligonucleotide analogs with novel linkages |
| DK0452457T3 (da) | 1989-11-03 | 1998-03-02 | Univ Vanderbilt | Fremgangsmåde til in vivo fjernelse af funktionelle fremmede gener |
| US5177198A (en) | 1989-11-30 | 1993-01-05 | University Of N.C. At Chapel Hill | Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates |
| US5587470A (en) | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| US5212295A (en) | 1990-01-11 | 1993-05-18 | Isis Pharmaceuticals | Monomers for preparation of oligonucleotides having chiral phosphorus linkages |
| US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
| US5506351A (en) | 1992-07-23 | 1996-04-09 | Isis Pharmaceuticals | Process for the preparation of 2'-O-alkyl guanosine and related compounds |
| US5578718A (en) | 1990-01-11 | 1996-11-26 | Isis Pharmaceuticals, Inc. | Thiol-derivatized nucleosides |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| US5321131A (en) | 1990-03-08 | 1994-06-14 | Hybridon, Inc. | Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling |
| US5470967A (en) | 1990-04-10 | 1995-11-28 | The Dupont Merck Pharmaceutical Company | Oligonucleotide analogs with sulfamate linkages |
| US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
| US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
| US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
| US5218105A (en) | 1990-07-27 | 1993-06-08 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| US6262241B1 (en) | 1990-08-13 | 2001-07-17 | Isis Pharmaceuticals, Inc. | Compound for detecting and modulating RNA activity and gene expression |
| US5214134A (en) | 1990-09-12 | 1993-05-25 | Sterling Winthrop Inc. | Process of linking nucleosides with a siloxane bridge |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| AU2916292A (en) | 1991-10-24 | 1993-05-21 | Isis Pharmaceuticals, Inc. | Derivatized oligonucleotides having improved uptake and other properties |
| US5594121A (en) | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
| US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| US20030206887A1 (en) * | 1992-05-14 | 2003-11-06 | David Morrissey | RNA interference mediated inhibition of hepatitis B virus (HBV) using short interfering nucleic acid (siNA) |
| EP0577558A2 (de) | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
| GB9304618D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Chemical compounds |
| HU9501974D0 (en) | 1993-03-31 | 1995-09-28 | Sterling Winthrop Inc | Oligonucleotides with amide linkages replacing phosphodiester linkages |
| US5571902A (en) | 1993-07-29 | 1996-11-05 | Isis Pharmaceuticals, Inc. | Synthesis of oligonucleotides |
| US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
| US5554746A (en) | 1994-05-16 | 1996-09-10 | Isis Pharmaceuticals, Inc. | Lactam nucleic acids |
| US5597909A (en) | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
| US6166197A (en) | 1995-03-06 | 2000-12-26 | Isis Pharmaceuticals, Inc. | Oligomeric compounds having pyrimidine nucleotide (S) with 2'and 5 substitutions |
| US5856459A (en) * | 1995-06-06 | 1999-01-05 | Hybridon, Inc. | Oligonucleotides specific for hepatitis B virus |
| US5985662A (en) * | 1995-07-13 | 1999-11-16 | Isis Pharmaceuticals Inc. | Antisense inhibition of hepatitis B virus replication |
| US6172209B1 (en) | 1997-02-14 | 2001-01-09 | Isis Pharmaceuticals Inc. | Aminooxy-modified oligonucleotides and methods for making same |
| US6127533A (en) | 1997-02-14 | 2000-10-03 | Isis Pharmaceuticals, Inc. | 2'-O-aminooxy-modified oligonucleotides |
| CN1057302C (zh) * | 1997-08-27 | 2000-10-11 | 中国科学院上海生物化学研究所 | 抑制乙型肝炎病毒复制的反义脱氧寡核苷酸 |
| US6271358B1 (en) | 1998-07-27 | 2001-08-07 | Isis Pharmaceuticals, Inc. | RNA targeted 2′-modified oligonucleotides that are conformationally preorganized |
| BR9914772A (pt) | 1998-10-09 | 2001-12-11 | Ingene Inc | Conjunto de elementos genéticos, vetor, célulahospedeira, conjunto para a produção de umasequência de ácido nucléico, método para aprodução in vivo ou in vitro de uma sequência deácido nucléico, transcrição de cdna, molécula deácido nucléico inibidor, transcrição de mrna,molécula heteroduplex e composiçãofarmacêutica |
| US5977341A (en) | 1998-11-20 | 1999-11-02 | Isis Pharmaceuticals Inc. | Antisense modulation of inhibitor-kappa B kinase-beta expression |
| US20050032733A1 (en) * | 2001-05-18 | 2005-02-10 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SiNA) |
| US8202979B2 (en) * | 2002-02-20 | 2012-06-19 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid |
| WO2003070918A2 (en) * | 2002-02-20 | 2003-08-28 | Ribozyme Pharmaceuticals, Incorporated | Rna interference by modified short interfering nucleic acid |
| US8273866B2 (en) | 2002-02-20 | 2012-09-25 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SINA) |
| CA2442092A1 (en) | 2001-03-26 | 2002-10-17 | Ribozyme Pharmaceuticals, Inc. | Oligonucleotide mediated inhibition of hepatitis b virus and hepatitis c virus replication |
| US9994853B2 (en) | 2001-05-18 | 2018-06-12 | Sirna Therapeutics, Inc. | Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference |
| EP1627061B1 (en) * | 2001-05-18 | 2009-08-12 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING CHEMICALLY MODIFIED SHORT INTERFERING NUCLEIC ACID (siNA) |
| 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 |
| US20030198627A1 (en) | 2001-09-01 | 2003-10-23 | Gert-Jan Arts | siRNA knockout assay method and constructs |
| US6635428B2 (en) | 2001-12-04 | 2003-10-21 | Quest Diagnostics Investments Incorporated | Oligonucleotides and methods for detecting hepatitis B viral nucleic acids |
| US9181551B2 (en) | 2002-02-20 | 2015-11-10 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
| EP1432724A4 (en) | 2002-02-20 | 2006-02-01 | Sirna Therapeutics Inc | INTERFERENCE MEDIATION INHIBITION OF GENE RNA FROM MAP KINASE |
| US8232383B2 (en) | 2002-02-20 | 2012-07-31 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
| US7452987B2 (en) | 2002-08-05 | 2008-11-18 | Silence Therapeutics Aktiengesellschaft (Ag) | Interfering RNA molecules |
| US7923547B2 (en) | 2002-09-05 | 2011-04-12 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
| EP2957568B1 (en) | 2002-11-05 | 2016-12-21 | Ionis Pharmaceuticals, Inc. | Compositions comprising alternating 2'-modified nucleosides for use in gene modulation |
| EP1636385A4 (en) | 2003-06-24 | 2010-06-02 | Mirus Bio Corp | INHIBITION OF GENE FUNCTION BY IN VIVO DISTRIBUTION OF GENE EXPRESSION INHIBITORS BASED ON POLYNUCLEOTIDES IN MAMMALIAN CELLS |
| EP1709178A4 (en) * | 2003-12-16 | 2008-01-09 | Agency Science Tech & Res | METHODS AND COMPOUNDS FOR MODIFYING MICROBIAL CONTAMINATION DEGREE OF HEPATITIS VIRUS |
| CA2553211A1 (en) | 2004-01-12 | 2005-07-21 | Genesense Technologies Inc. | Antisense oligonucleotides directed to ribonucleotide reductase r2 and uses thereof in combination therapies for the treatment of cancer |
| CA2566286A1 (en) | 2004-05-11 | 2005-12-08 | Rnai Co., Ltd. | Polynucleotide causing rna interfere and method of regulating gene expression with the use of the same |
| US20080255065A1 (en) | 2004-08-18 | 2008-10-16 | Genesense Technologies, Inc. | Small Interfering Rna Molecules Against Ribonucleotide Reductase and Uses Thereof |
| KR20100060018A (ko) * | 2005-03-09 | 2010-06-04 | 재단법인 목암생명공학연구소 | 작은 간섭 ｒｎａ 및 이를 포함하는 ｂ형 간염 바이러스 치료용 약학 조성물 |
| AU2006279454B2 (en) | 2005-08-17 | 2011-12-15 | Sirna Therapeutics, Inc. | Chemically modified short interfering nucleic acid molecules that mediate rna interference |
| RU2418068C2 (ru) * | 2005-08-17 | 2011-05-10 | Сирна Терапьютикс, Инк. | Молекулы химически модифицированной короткой интерферирующей нуклеиновой кислоты, которые опосредуют интерференцию рнк |
| CN101426912A (zh) * | 2005-08-17 | 2009-05-06 | 瑟纳治疗公司 | 介导rna干扰的化学修饰短干扰核酸分子 |
| CA2627585A1 (en) | 2005-11-01 | 2007-05-10 | Alnylam Pharmaceuticals, Inc. | Rnai inhibition of influenza virus replication |
| US8877917B2 (en) | 2007-04-23 | 2014-11-04 | Alnylam Pharmaceuticals, Inc. | Glycoconjugates of RNA interference agents |
| EP2164965B1 (en) * | 2007-05-29 | 2013-09-11 | University Of The Witwatersrand, Johannesburg | A primary micro rna expression cassette |
| US20100209491A1 (en) | 2007-09-17 | 2010-08-19 | Mogam Biotechnology Research Institute | Method for enhancing serum stability and lowering immune response of sirna down-regulating gene expression of hbv or hcv |
| WO2009082607A2 (en) | 2007-12-04 | 2009-07-02 | Alnylam Pharmaceuticals, Inc. | Targeting lipids |
| US8207138B2 (en) | 2009-05-19 | 2012-06-26 | Medtronic, Inc. | Methods and devices for improved efficiency of RNA delivery to cells |
| US9050375B2 (en) | 2009-07-06 | 2015-06-09 | Hoffmann-La Roche, Inc. | Bi-specific digoxigenin binding antibodies |
| US20110152349A1 (en) * | 2009-12-18 | 2011-06-23 | Anke Geick | Compositions and methods for inhibiting expression of il-18 genes |
| US9198972B2 (en) | 2010-01-28 | 2015-12-01 | Alnylam Pharmaceuticals, Inc. | Monomers and oligonucleotides comprising cycloaddition adduct(s) |
| EP2390327A1 (en) | 2010-05-27 | 2011-11-30 | Sylentis S.A. | siRNA and their use in methods and compositions for the treatment and/or prevention of eye conditions |
| LT2606134T (lt) | 2010-08-17 | 2019-07-25 | Sirna Therapeutics, Inc. | Hepatito b viruso (hbv) geno raiškos slopinimas, tarpininkaujant rnr interferencijai naudojant mažą interferuojančią nukleorūgštį (sina) |
| EP2616543A1 (en) | 2010-09-15 | 2013-07-24 | Alnylam Pharmaceuticals, Inc. | MODIFIED iRNA AGENTS |
| CN101948834B (zh) * | 2010-09-16 | 2012-07-04 | 山东大学 | 用于治疗HBV的siRNA |
| EP2632472B1 (en) | 2010-10-29 | 2017-12-13 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of gene expression using short interfering nucleic acids (sina) |
| US8501930B2 (en) | 2010-12-17 | 2013-08-06 | Arrowhead Madison Inc. | Peptide-based in vivo siRNA delivery system |
| MX340408B (es) | 2011-04-21 | 2016-07-07 | Ionis Pharmaceuticals Inc | Modulacion de la expresion del virus de hepatitis b (vhb). |
| TW202244278A (zh) | 2011-06-30 | 2022-11-16 | 美商艾羅海德製藥公司 | 用於抑制ｂ型肝炎病毒基因表現之組合物及方法 |
| WO2013159109A1 (en) | 2012-04-20 | 2013-10-24 | Isis Pharmaceuticals, Inc. | Modulation of hepatitis b virus (hbv) expression |
| SI3401400T1 (sl) | 2012-05-25 | 2019-10-30 | Univ California | Postopki in sestavki za RNA usmerjeno modifikacijo tarčne DNA in za RNA usmerjeno modulacijo prepisovanja |
| GB201215857D0 (en) | 2012-09-05 | 2012-10-24 | Sylentis Sau | siRNA and their use in methods and compositions for the treatment and/or prevention of eye conditions |
| US9943604B2 (en) | 2013-09-20 | 2018-04-17 | Ionis Pharmaceuticals, Inc. | Targeted therapeutic nucleosides and their use |
| WO2015050871A2 (en) | 2013-10-04 | 2015-04-09 | Novartis Ag | Organic compounds to treat hepatitis b virus |
| EP3811977B1 (en) | 2014-05-01 | 2025-12-03 | Ionis Pharmaceuticals, Inc. | Method for synthesis of reactive conjugate clusters |
| JOP20200115A1 (ar) | 2014-10-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات وطرق لتثبيط التعبير الجيني عن hao1 (حمض أوكسيداز هيدروكسيلي 1 (أوكسيداز جليكولات)) |
| JOP20200092A1 (ar) | 2014-11-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها |
| CN108136206B (zh) | 2015-07-17 | 2021-10-15 | 阿克丘勒斯治疗公司 | 抗乙型肝炎病毒的组合物和药剂及其用途 |
| US20170137821A1 (en) | 2015-07-17 | 2017-05-18 | Arcturus Therapeutics, Inc. | Molecules and agents for treating hepatitis b virus |
| US20180208932A1 (en) | 2015-07-29 | 2018-07-26 | Arbutus Biopharma Corporation | Compositions and methods for silencing hepatitis b virus gene expression |
| AU2016306275A1 (en) | 2015-08-07 | 2018-02-08 | Arrowhead Pharmaceuticals, Inc. | RNAi therapy for Hepatitis B virus infection |
| MA45478A (fr) | 2016-04-11 | 2019-02-20 | Arbutus Biopharma Corp | Compositions de conjugués d'acides nucléiques ciblés |
| JOP20170161A1 (ar) | 2016-08-04 | 2019-01-30 | Arrowhead Pharmaceuticals Inc | عوامل RNAi للعدوى بفيروس التهاب الكبد ب |
| US10294474B2 (en) | 2016-09-02 | 2019-05-21 | Arrowhead Pharmaceuticals, Inc. | Targeting ligands |
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