ES2898340T3 - Composiciones y métodos para tratar neumopatías y lesión pulmonar - Google Patents
Composiciones y métodos para tratar neumopatías y lesión pulmonar Download PDFInfo
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| US9119783B2 (en) | 2007-05-07 | 2015-09-01 | Insmed Incorporated | Method of treating pulmonary disorders with liposomal amikacin formulations |
| WO2014085526A1 (en) | 2012-11-29 | 2014-06-05 | Insmed Incorporated | Stabilized vancomycin formulations |
| PL3060041T3 (pl) | 2013-10-25 | 2021-08-02 | Insmed Incorporated | Związki prostacykliny |
| PL3142643T3 (pl) | 2014-05-15 | 2019-12-31 | Insmed Incorporated | Sposoby leczenia zakażeń płuc prątkami niegruźliczymi |
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| WO2020018959A1 (en) * | 2018-07-19 | 2020-01-23 | Impel Neuropharma, Inc. | Respiratory tract delivery of levodopa and dopa decarboxylase inhibitor for treatment of parkinson's disease |
| GB2592505B (en) * | 2018-09-04 | 2023-05-03 | Univ Texas | Compositions and methods for organ specific delivery of nucleic acids |
| JP7555123B2 (ja) | 2018-10-09 | 2024-09-24 | ザ ユニヴァーシティ オブ ブリティッシュ コロンビア | 有機溶媒不含かつ劣化剤不含のトランスフェクション・コンピテント・ベシクルを含む組成物及びシステム並びにそれらに関連する方法 |
| CN109432047B (zh) * | 2018-10-29 | 2021-07-20 | 中国药科大学 | 一种逆转肺纤维化纳米制剂及其制备方法 |
| JP7455144B2 (ja) | 2019-04-29 | 2024-03-25 | インスメッド インコーポレイテッド | トレプロスチニルプロドラッグの乾燥粉末組成物およびその使用方法 |
| JP7674354B2 (ja) * | 2019-12-05 | 2025-05-09 | ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | 肝線維症および線維症に関連する他の疾患に対するエキソソームベースの療法 |
| MX2022012683A (es) | 2020-04-09 | 2023-01-11 | Verve Therapeutics Inc | Edicion de bases de pcsk9 y metodos de uso de la misma para el tratamiento de enfermedades. |
| CN115768438A (zh) * | 2020-07-10 | 2023-03-07 | 盖纳万科学有限公司 | 用于向肺递送治疗剂的脂质纳米颗粒 |
| JP2023549011A (ja) | 2020-09-15 | 2023-11-22 | ヴァーヴ・セラピューティクス，インコーポレーテッド | 遺伝子編集のための脂質製剤 |
| CZ310613B6 (cs) | 2020-09-23 | 2026-01-28 | Ústav organické chemie a biochemie AV ČR, v. v. i. | Lipidoidy pro transfekci nukleových kyselin a jejich použití |
| TW202233232A (zh) | 2020-11-06 | 2022-09-01 | 法商賽諾菲公司 | 遞送mRNA疫苗的脂質奈米顆粒 |
| WO2022204219A1 (en) | 2021-03-22 | 2022-09-29 | Recode Therapeutics, Inc. | Compositions and methods for targeted delivery to cells |
| CN113058042B (zh) * | 2021-04-01 | 2023-06-30 | 易慧生物技术(上海)有限公司 | 一种可鼻喷的稳定递载rna分子的脂质纳米颗粒制备方法 |
| CN115245559A (zh) * | 2021-04-25 | 2022-10-28 | 上海萨美细胞技术有限公司 | 一种用于治疗肺损伤的药物 |
| CN117881789A (zh) * | 2021-06-09 | 2024-04-12 | 瑞科德治疗公司 | 多核苷酸组合物、相关制剂、及其使用方法 |
| US20230057155A1 (en) * | 2021-08-11 | 2023-02-23 | Board Of Regents, The University Of Texas System | Dry liposome formulations and related methods thereof |
| PL438742A1 (pl) * | 2021-08-14 | 2023-02-20 | Bs Biotechna Spółka Z Ograniczoną Odpowiedzialnością | Liposom kationowy wiążący i stabilizujący RNA, jego zastosowanie i sposób ładowania liposomu emetyną |
| EP4226949A1 (en) * | 2022-02-14 | 2023-08-16 | Pantherna Therapeutics GmbH | Preparation for use in a method for the treatment and/or prevention of a disease |
| WO2024242216A1 (ko) * | 2023-05-23 | 2024-11-28 | 주식회사 케이더블유바이오 | 대식세포 표적화 리포좀 및 이의 용도 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4721612A (en) * | 1984-04-12 | 1988-01-26 | The Liposome Company, Inc. | Steroidal liposomes |
| US4861580A (en) * | 1985-10-15 | 1989-08-29 | The Liposome Company, Inc. | Composition using salt form of organic acid derivative of alpha-tocopheral |
| DE19746287A1 (de) * | 1997-10-20 | 1999-04-22 | Hoechst Marion Roussel De Gmbh | Substituierte Isochinolin-2-Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| KR20060036119A (ko) * | 2003-08-20 | 2006-04-27 | 가부시키가이샤 로코모젠 | 시노비올린 활성 조절 작용의 검출 방법 |
| US20060134189A1 (en) * | 2004-11-17 | 2006-06-22 | Protiva Biotherapeutics, Inc | siRNA silencing of apolipoprotein B |
| JP5777519B2 (ja) * | 2008-10-09 | 2015-09-09 | テクミラ ファーマシューティカルズ コーポレイション | 改良されたアミノ脂質および核酸の送達方法 |
| WO2011108955A1 (en) * | 2010-03-03 | 2011-09-09 | Universidade De Coimbra | Multi -targeting system comprising a nanocarrier, nucleic acid(s) and non-nucleic acid based drug(s) |
| AU2011261434B2 (en) * | 2010-06-02 | 2015-11-26 | Alnylam Pharmaceuticals, Inc. | Compositions and methods directed to treating liver fibrosis |
| US20140308304A1 (en) * | 2011-12-07 | 2014-10-16 | Alnylam Pharmaceuticals, Inc. | Lipids for the delivery of active agents |
| WO2014052634A1 (en) * | 2012-09-27 | 2014-04-03 | The University Of North Carolina At Chapel Hill | Lipid coated nanoparticles containing agents having low aqueous and lipid solubilities and methods thereof |
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- 2016-07-11 EP EP16822088.7A patent/EP3319976B1/en active Active
- 2016-07-11 WO PCT/US2016/041776 patent/WO2017008076A1/en not_active Ceased
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- 2016-07-11 ES ES16822088T patent/ES2898340T3/es active Active
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2020
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| AU2020203367A1 (en) | 2020-06-11 |
| CA2989884A1 (en) | 2017-01-12 |
| JP2018519818A (ja) | 2018-07-26 |
| EP3319976A1 (en) | 2018-05-16 |
| EP3319976A4 (en) | 2019-03-20 |
| WO2017008076A1 (en) | 2017-01-12 |
| EP3319976B1 (en) | 2021-09-01 |
| AU2016291228A1 (en) | 2017-12-07 |
| AU2016291228B2 (en) | 2020-04-09 |
| JP6884714B2 (ja) | 2021-06-09 |
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