CA2996722A1 - Compositions and agents against hepatitis b virus and uses thereof - Google Patents
Compositions and agents against hepatitis b virus and uses thereof Download PDFInfo
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- CA2996722A1 CA2996722A1 CA2996722A CA2996722A CA2996722A1 CA 2996722 A1 CA2996722 A1 CA 2996722A1 CA 2996722 A CA2996722 A CA 2996722A CA 2996722 A CA2996722 A CA 2996722A CA 2996722 A1 CA2996722 A1 CA 2996722A1
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- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1131—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- C12N2310/323—Chemical structure of the sugar modified ring structure
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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| CN108271387B (zh) * | 2015-08-07 | 2023-06-27 | 箭头药业股份有限公司 | 乙型肝炎病毒感染的RNAi疗法 |
| 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 |
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| CN110944675B9 (zh) | 2017-12-01 | 2024-08-09 | 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 |
| CN110997919B (zh) | 2017-12-01 | 2024-04-02 | 苏州瑞博生物技术股份有限公司 | 双链寡核苷酸、含双链寡核苷酸的组合物与缀合物及制备方法和用途 |
| HRP20250192T1 (hr) | 2017-12-01 | 2025-04-11 | Suzhou Ribo Life Science Co., Ltd. | Nukleinska kiselina, sastav i konjugat koji je sadrži, te metoda pripreme i uporaba |
| CN110945130B (zh) | 2017-12-01 | 2024-04-09 | 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 |
| CN110997917B (zh) | 2017-12-01 | 2024-04-09 | 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 |
| CN116375774B (zh) | 2017-12-29 | 2025-09-23 | 苏州瑞博生物技术股份有限公司 | 缀合物及其制备方法和用途 |
| MX2020010383A (es) | 2018-04-05 | 2020-12-10 | Hoffmann La Roche | Uso de inhibidores de fubp1 para el tratamiento de infeccion de virus de hepatitis b. |
| US12247203B2 (en) | 2018-05-16 | 2025-03-11 | Alnylam Pharmaceuticals, Inc. | Modified RNA agents with reduced off-target effect |
| WO2019240504A1 (en) * | 2018-06-12 | 2019-12-19 | Am Sciences Co., Ltd. | Modified oligonucleotides for inhibition of target gene expression |
| WO2019240503A1 (ko) * | 2018-06-12 | 2019-12-19 | 주식회사 에이엠사이언스 | B형 간염 예방 또는 치료용 조성물 |
| US11279929B2 (en) | 2018-07-03 | 2022-03-22 | Hoffmann-La Roche, Inc. | Oligonucleotides for modulating Tau expression |
| CR20210015A (es) | 2018-07-13 | 2021-03-22 | Hoffmann La Roche | Oligonucleótidos para modular la expresión de rtel 1 |
| 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 |
| CN111655297A (zh) | 2018-09-30 | 2020-09-11 | 苏州瑞博生物技术有限公司 | 一种siRNA缀合物及其制备方法和用途 |
| US12496347B2 (en) | 2018-12-28 | 2025-12-16 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, composition and conjugate containing nucleic acid, preparation method therefor and use thereof |
| CN113227376B (zh) | 2019-05-22 | 2024-04-09 | 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 |
| 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 |
| WO2021107097A1 (ja) * | 2019-11-28 | 2021-06-03 | 株式会社ボナック | Ｂ型肝炎治療用核酸分子 |
| WO2021122910A1 (en) | 2019-12-19 | 2021-06-24 | F. Hoffmann-La Roche Ag | Use of sbds inhibitors for treating hepatitis b virus infection |
| EP4077670A1 (en) | 2019-12-19 | 2022-10-26 | F. Hoffmann-La Roche AG | Use of cops3 inhibitors for treating hepatitis b virus infection |
| EP4077667A1 (en) | 2019-12-19 | 2022-10-26 | F. Hoffmann-La Roche AG | Use of sept9 inhibitors for treating hepatitis b virus infection |
| JP2023506540A (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を処置するためのｓｃａｍｐ３阻害剤の使用 |
| CN114867856A (zh) | 2019-12-19 | 2022-08-05 | 豪夫迈·罗氏有限公司 | Saraf抑制剂用于治疗乙型肝炎病毒感染的用途 |
| US20220056451A1 (en) * | 2020-07-27 | 2022-02-24 | Aligos Therapeutics, Inc. | Hbv binding oligonucleotides and methods of use |
| WO2022038211A2 (en) | 2020-08-21 | 2022-02-24 | F. Hoffmann-La Roche Ag | Use of a1cf inhibitors for treating hepatitis b virus infection |
| US20240052349A1 (en) * | 2020-11-06 | 2024-02-15 | Arbutus Biopharma Corporation | Targeted conjugates comprising modified sirna |
| US20240124879A1 (en) * | 2020-12-18 | 2024-04-18 | Olix Pharmaceuticals, Inc. | Rnai agent for inhibiting hbv expression and use thereof |
| US20240309366A1 (en) * | 2020-12-31 | 2024-09-19 | Arcturus Therapeutics, Inc. | Compositions and methods for treating metabolic disorders |
| CN114767704B (zh) * | 2021-01-21 | 2024-06-14 | 圣诺制药公司 | 一种能够靶向乙型肝炎病毒的药物构造及药物组合物 |
| 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 |
| EP4448106A1 (en) | 2021-12-17 | 2024-10-23 | Hoffmann-La Roche Inc. | Combination of oligonucleotides for modulating rtel1 and fubp1 |
| CN115267193B (zh) * | 2022-09-20 | 2022-12-27 | 北京大学 | 用于判断生物样本中HBsAg来源的方法及系统和用途 |
Family Cites Families (29)
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|---|---|---|---|---|
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| 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) |
| CA2485256A1 (en) | 2002-05-10 | 2003-11-20 | Inex Pharmaceuticals Corporation | Pathogen vaccines and methods for using the same |
| US20070027099A1 (en) * | 2003-05-19 | 2007-02-01 | Lin Marie C | Gene therapy of HBV infection via adeno-associated viral vector mediated long term expression of small hairpin RNA (shRNA) |
| US8575327B2 (en) | 2003-06-12 | 2013-11-05 | Alnylam Pharmaceuticals, Inc. | Conserved HBV and HCV sequences useful for gene silencing |
| HUE042261T2 (hu) | 2003-06-12 | 2019-06-28 | Alnylam Pharmaceuticals Inc | Gén kikapcsolásra alkalmas konzervált HBV és HCV szekvenciák |
| WO2005111199A1 (en) | 2004-05-19 | 2005-11-24 | Melbourne Health | Therapeutic, prophylactic and diagnostic agents for hepatitis b |
| WO2006039656A2 (en) | 2004-10-01 | 2006-04-13 | Novartis Vaccines And Diagnostics Inc. | Modified small interfering rna molecules and methods of use |
| US8765704B1 (en) | 2008-02-28 | 2014-07-01 | Novartis Ag | Modified small interfering RNA molecules and methods of use |
| KR20100060018A (ko) | 2005-03-09 | 2010-06-04 | 재단법인 목암생명공학연구소 | 작은 간섭 ｒｎａ 및 이를 포함하는 ｂ형 간염 바이러스 치료용 약학 조성물 |
| US20090226525A1 (en) | 2007-04-09 | 2009-09-10 | Chimeros Inc. | Self-assembling nanoparticle drug delivery system |
| CN104480112B (zh) | 2007-05-22 | 2018-06-12 | 阿克丘勒斯治疗公司 | 用于治疗的una寡聚体 |
| KR20100069679A (ko) | 2007-09-17 | 2010-06-24 | 재단법인 목암생명공학연구소 | ＨＢＶ 또는 ＨＣＶ의 유전자 발현을 하향 조절하는 ｓｉＲＮＡ의 혈청 안정성 향상 및 면역 반응 저감 방법 |
| WO2009106999A2 (en) | 2008-02-28 | 2009-09-03 | Deutsches Krebsforschungszentrum, Stiftung Des Öffentlichen Rechts | Hollow nanoparticles and uses thereof |
| US20100015708A1 (en) * | 2008-06-18 | 2010-01-21 | Mdrna, Inc. | Ribonucleic acids with non-standard bases and uses thereof |
| CA2744093A1 (en) | 2008-12-03 | 2010-06-10 | Marina Biotech, Inc. | Una oligomer structures for therapeutic agents |
| EP2512491B1 (en) | 2009-10-16 | 2017-10-11 | Glaxo Group Limited | Hbv antisense inhibitors |
| EP3587574B1 (en) * | 2010-08-17 | 2022-03-16 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of hepatitis b virus (hbv) gene expression using short interfering nucleic acid (sina) |
| SG10201604074TA (en) | 2011-04-21 | 2016-07-28 | Isis Pharmaceuticals Inc | Modulation of hepatitis b virus (hbv) expression |
| TWI695066B (zh) * | 2011-06-30 | 2020-06-01 | 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 |
| EP2771466A1 (en) | 2011-10-28 | 2014-09-03 | University Of The Witwatersrand, Johannesburg | Inhibition of viral gene expression |
| WO2013159109A1 (en) | 2012-04-20 | 2013-10-24 | Isis Pharmaceuticals, Inc. | Modulation of hepatitis b virus (hbv) expression |
| IN2015DN01087A (enExample) | 2012-08-30 | 2015-06-26 | Replicor Inc | |
| CN105103603A (zh) | 2012-12-05 | 2015-11-25 | 诺基亚通信公司 | 用于流量导向的方法和网络元件 |
| CN105792832B (zh) * | 2013-10-04 | 2021-03-23 | 诺华股份有限公司 | 用于治疗乙肝病毒的有机化合物 |
| EP3071547B1 (en) | 2013-11-18 | 2024-07-10 | Arcturus Therapeutics, Inc. | Ionizable cationic lipid for rna delivery |
| GB201408623D0 (en) | 2014-05-15 | 2014-07-02 | Santaris Pharma As | Oligomers and oligomer conjugates |
| EP3151839A4 (en) | 2014-06-06 | 2018-02-28 | Ionis Pharmaceuticals, Inc. | Compositions and methods for enhanced intestinal absorption of conjugated oligomeric compounds |
| CA2963271A1 (en) | 2014-10-02 | 2016-04-07 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing hepatitis b virus gene expression |
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| AU2016296592A1 (en) | 2018-03-08 |
| WO2017015175A1 (en) | 2017-01-26 |
| US20170016000A1 (en) | 2017-01-19 |
| EP3325097A1 (en) | 2018-05-30 |
| TWI761311B (zh) | 2022-04-21 |
| EP3325097B1 (en) | 2021-09-01 |
| JP2018520685A (ja) | 2018-08-02 |
| EP3325097A4 (en) | 2019-07-10 |
| CN108136206B (zh) | 2021-10-15 |
| US10961535B2 (en) | 2021-03-30 |
| AU2016296592B2 (en) | 2021-08-19 |
| CN108136206A (zh) | 2018-06-08 |
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