CA2971284C - Compositions for introducing nucleic acid into cells - Google Patents
Compositions for introducing nucleic acid into cells Download PDFInfo
- Publication number
- CA2971284C CA2971284C CA2971284A CA2971284A CA2971284C CA 2971284 C CA2971284 C CA 2971284C CA 2971284 A CA2971284 A CA 2971284A CA 2971284 A CA2971284 A CA 2971284A CA 2971284 C CA2971284 C CA 2971284C
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- copolymer
- nucleic acid
- repeating units
- mrna
- composition
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
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| Application Number | Priority Date | Filing Date | Title |
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| EP14199439.2 | 2014-12-19 | ||
| EP14199439.2A EP3034539A1 (en) | 2014-12-19 | 2014-12-19 | Compositions for introducing nucleic acid into cells |
| PCT/EP2015/080669 WO2016097377A1 (en) | 2014-12-19 | 2015-12-18 | Compositions for introducing nucleic acid into cells |
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| CA2971284A1 CA2971284A1 (en) | 2016-06-23 |
| CA2971284C true CA2971284C (en) | 2023-01-10 |
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| CA2971284A Active CA2971284C (en) | 2014-12-19 | 2015-12-18 | Compositions for introducing nucleic acid into cells |
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| EP (2) | EP3034539A1 (enExample) |
| JP (1) | JP6745272B2 (enExample) |
| KR (1) | KR102142180B1 (enExample) |
| CN (1) | CN107001627B (enExample) |
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| BR (1) | BR112017012482B1 (enExample) |
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| ES (1) | ES2887404T3 (enExample) |
| RU (1) | RU2715227C2 (enExample) |
| WO (1) | WO2016097377A1 (enExample) |
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| EP3034539A1 (en) | 2014-12-19 | 2016-06-22 | Ethris GmbH | Compositions for introducing nucleic acid into cells |
| AU2016286364B2 (en) | 2015-06-30 | 2022-07-28 | Ethris Gmbh | ATP-binding cassette family coding polyribonucleotides and formulations thereof |
| WO2018010815A1 (en) * | 2016-07-15 | 2018-01-18 | Biontech Rna Pharmaceuticals Gmbh | Formulation for administration of rna |
| EP3737386A1 (en) * | 2018-01-11 | 2020-11-18 | BioNTech RNA Pharmaceuticals GmbH | Formulation for administration of rna |
| CN112153986B (zh) | 2018-04-25 | 2024-02-09 | 埃泽瑞斯公司 | 用于递送rna的脂质基制剂 |
| IL293911A (en) * | 2019-12-17 | 2022-08-01 | Univ Gent | Non-viral vectors comprising polypropyleneimine |
| CN111249476B (zh) * | 2020-02-19 | 2023-09-26 | 深圳厚存纳米药业有限公司 | 泊洛沙姆和/或泊洛沙胺与脂质组合中性复合物纳米粒 |
| CA3209032A1 (en) | 2021-02-26 | 2022-09-01 | Ethris Gmbh | Formulations for aerosol formation and aerosols for the delivery of nucleic acid |
| CN118510549A (zh) * | 2021-09-22 | 2024-08-16 | 圣诺制药公司 | 具有减小的纳米颗粒尺寸和改善的多分散性指数的纳米颗粒药物组合物 |
| CN116549626A (zh) * | 2022-01-27 | 2023-08-08 | 深圳瑞吉生物科技有限公司 | 一种载核酸脂质纳米颗粒冻干制剂及其制备方法与应用 |
| EP4327829A1 (en) | 2022-08-26 | 2024-02-28 | Ethris GmbH | Stabilization of lipid or lipidoid nanoparticle suspensions |
| JP2025529925A (ja) | 2022-08-26 | 2025-09-09 | エスリス ゲーエムベーハー | 安定な脂質またはリピドイドナノ粒子懸濁液 |
| WO2024240962A1 (en) | 2023-05-25 | 2024-11-28 | Ethris Gmbh | Gm-csf-encoding nucleic acids, pharmaceutical compositions, methods and uses thereof |
| CN116478410B (zh) * | 2023-06-20 | 2023-09-12 | 觅投克(北京)生物医学技术有限公司 | 一种菊糖修饰的聚乙烯亚胺衍生物及其制备方法和应用 |
| WO2025045767A1 (en) | 2023-08-25 | 2025-03-06 | Ethris Gmbh | Stabilized lipid and lipidoid nanoparticle formulations with specific surfactant properties for enhanced pharmaceutical applications |
| WO2025064850A1 (en) | 2023-09-22 | 2025-03-27 | BioNTech SE | Rna constructs with n-terminal degrons to enhance an immune response |
| TW202539697A (zh) | 2023-11-15 | 2025-10-16 | 德商拜恩技術股份公司 | 冠狀病毒疫苗 |
| DE102024133412A1 (de) | 2023-11-15 | 2025-05-15 | BioNTech SE | Sars-cov-2 immunogene zusammensetzungen |
Family Cites Families (35)
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| US4711955A (en) | 1981-04-17 | 1987-12-08 | Yale University | Modified nucleotides and methods of preparing and using same |
| JPS5821590A (ja) | 1981-07-31 | 1983-02-08 | 株式会社東芝 | 制御棒駆動水圧装置 |
| JPS58215490A (ja) * | 1982-06-08 | 1983-12-14 | Nippon Shokubai Kagaku Kogyo Co Ltd | 石炭−水スラリ−用分散剤 |
| CA1223831A (en) | 1982-06-23 | 1987-07-07 | Dean Engelhardt | Modified nucleotides, methods of preparing and utilizing and compositions containing the same |
| US5792608A (en) | 1991-12-12 | 1998-08-11 | Gilead Sciences, Inc. | Nuclease stable and binding competent oligomers and methods for their use |
| US5525711A (en) | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
| FR2722506B1 (fr) * | 1994-07-13 | 1996-08-14 | Rhone Poulenc Rorer Sa | Composition contenant des acides nucleiques, preparation et utilisations |
| US5656611A (en) * | 1994-11-18 | 1997-08-12 | Supratek Pharma Inc. | Polynucleotide compositions |
| DE19527102A1 (de) * | 1995-07-25 | 1997-01-30 | Bayer Ag | Neue Polyamine und ihre Verwendung in Lacken und Beschichtungen |
| US6017700A (en) | 1995-08-04 | 2000-01-25 | Bayer Corporation | Cationic oligonucleotides, and related methods of synthesis and use |
| FR2739292B1 (fr) * | 1995-09-28 | 1997-10-31 | Rhone Poulenc Rorer Sa | Composition pharmaceutique utile pour la transfection d'acides nucleiques et ses utilisations |
| CA2298061A1 (en) * | 1997-08-01 | 1999-02-11 | Supratek Pharma, Inc. | Polynucleotide compositions |
| CA2377207C (en) | 1999-06-25 | 2013-01-08 | Christian Plank | Combinations for introducing nucleic acids into cells |
| DE19933024C2 (de) * | 1999-07-15 | 2003-03-13 | Medinnova Ges Med Innovationen | Kationische Blockcopolymere |
| WO2002000870A2 (en) | 2000-06-26 | 2002-01-03 | Christian Plank | Method for transfecting cells using a magnetic field |
| US20030215395A1 (en) * | 2002-05-14 | 2003-11-20 | Lei Yu | Controllably degradable polymeric biomolecule or drug carrier and method of synthesizing said carrier |
| US20070269891A9 (en) | 2003-01-13 | 2007-11-22 | Yasunobu Tanaka | Solid surface with immobilized degradable cationic polymer for transfecting eukaryotic cells |
| JP4535229B2 (ja) | 2003-05-08 | 2010-09-01 | 国立大学法人 東京大学 | ポリエチレングリコール−ポリカチオンブロック共重合体 |
| JP5061349B2 (ja) | 2005-02-10 | 2012-10-31 | 国立大学法人 東京大学 | ポリカチオン荷電性ポリマー及び核酸のキャリヤーとしての使用 |
| JP5777846B2 (ja) | 2005-06-15 | 2015-09-09 | マサチューセッツ インスティテュート オブ テクノロジー | アミン含有脂質およびその使用 |
| TR201909609T4 (tr) | 2005-08-23 | 2019-07-22 | Univ Pennsylvania | Modifiye edilmiş nükleosidleri içeren rna ve kullanım yöntemleri. |
| CA2633065C (en) | 2005-12-15 | 2016-10-18 | Centre National De La Recherche Scientifique (Cnrs) | Cationic oligonucleotides, automated methods for preparing same and their uses |
| US7700541B2 (en) * | 2006-04-06 | 2010-04-20 | Nitto Denko Corporation | Biodegradable cationic polymers |
| GB0613753D0 (en) * | 2006-07-11 | 2006-08-23 | Norwegian Radium Hospital Res | Method |
| EP2061443A4 (en) * | 2006-08-18 | 2013-07-24 | Arrowhead Res Corp | POLYCONJUGATE FOR IN VIVO ADMINISTRATION OF POLYNUCLEOTIDES |
| US20090042825A1 (en) * | 2007-08-06 | 2009-02-12 | Majed Matar | Composition, method of preparation & application of concentrated formulations of condensed nucleic acids with a cationic lipopolymer |
| WO2009114854A1 (en) * | 2008-03-14 | 2009-09-17 | Egen, Inc. | Biodegradable cross-linked branched poly (alkylene imines) |
| CA3006395C (en) | 2008-11-07 | 2022-05-31 | Massachusetts Institute Of Technology | Aminoalcohol lipidoids and uses thereof |
| US20110263025A1 (en) | 2008-12-02 | 2011-10-27 | University Of Utah Research Foundation | Biodegradable polydisulfide amines for gene delivery |
| BR112012002291A2 (pt) | 2009-07-31 | 2016-11-29 | Ethris Gmbh | "polirribonucleotídeo com uma sequência que codifica uma proteína ou fragmento de proteína, implante, e, processo para a seleção de sequências de nucleotídeos" |
| WO2011154331A1 (en) | 2010-06-10 | 2011-12-15 | F. Hoffmann-La Roche Ag | Polymers for delivery of nucleic acids |
| RS62993B1 (sr) | 2011-10-03 | 2022-03-31 | Modernatx Inc | Modifikovani nukleozidi, nukleotidi, i nukleinske kiseline, i njihove upotrebe |
| WO2014025795A1 (en) | 2012-08-07 | 2014-02-13 | Northeastern University | Compositions for the delivery of rna and drugs into cells |
| EP2971010B1 (en) | 2013-03-14 | 2020-06-10 | ModernaTX, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
| EP3034539A1 (en) | 2014-12-19 | 2016-06-22 | Ethris GmbH | Compositions for introducing nucleic acid into cells |
-
2014
- 2014-12-19 EP EP14199439.2A patent/EP3034539A1/en not_active Withdrawn
-
2015
- 2015-12-18 DK DK15823330.4T patent/DK3242903T3/da active
- 2015-12-18 RU RU2017122022A patent/RU2715227C2/ru active
- 2015-12-18 WO PCT/EP2015/080669 patent/WO2016097377A1/en not_active Ceased
- 2015-12-18 US US15/537,096 patent/US11020487B2/en active Active
- 2015-12-18 CN CN201580068845.7A patent/CN107001627B/zh active Active
- 2015-12-18 BR BR112017012482-3A patent/BR112017012482B1/pt active IP Right Grant
- 2015-12-18 EP EP15823330.4A patent/EP3242903B1/en active Active
- 2015-12-18 KR KR1020177019543A patent/KR102142180B1/ko active Active
- 2015-12-18 CA CA2971284A patent/CA2971284C/en active Active
- 2015-12-18 AU AU2015366220A patent/AU2015366220B2/en active Active
- 2015-12-18 JP JP2017533008A patent/JP6745272B2/ja active Active
- 2015-12-18 ES ES15823330T patent/ES2887404T3/es active Active
Also Published As
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| DK3242903T3 (da) | 2021-09-27 |
| RU2017122022A3 (enExample) | 2019-05-22 |
| BR112017012482A2 (pt) | 2018-02-27 |
| US11020487B2 (en) | 2021-06-01 |
| JP6745272B2 (ja) | 2020-08-26 |
| CN107001627B (zh) | 2020-01-14 |
| ES2887404T3 (es) | 2021-12-22 |
| CN107001627A (zh) | 2017-08-01 |
| CA2971284A1 (en) | 2016-06-23 |
| RU2715227C2 (ru) | 2020-02-26 |
| EP3242903A1 (en) | 2017-11-15 |
| BR112017012482B1 (pt) | 2021-10-19 |
| AU2015366220B2 (en) | 2019-09-19 |
| KR20170097124A (ko) | 2017-08-25 |
| EP3034539A1 (en) | 2016-06-22 |
| US20180236090A1 (en) | 2018-08-23 |
| RU2017122022A (ru) | 2018-12-24 |
| EP3242903B1 (en) | 2021-07-28 |
| JP2018502956A (ja) | 2018-02-01 |
| AU2015366220A1 (en) | 2017-06-01 |
| WO2016097377A1 (en) | 2016-06-23 |
| KR102142180B1 (ko) | 2020-08-07 |
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