JP6640079B2 - 小容積の粒子を調製するためのデバイス及び方法 - Google Patents
小容積の粒子を調製するためのデバイス及び方法 Download PDFInfo
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- B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
- B01J2/06—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops in a liquid medium
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Landscapes
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| US201361891758P | 2013-10-16 | 2013-10-16 | |
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| PCT/US2014/060961 WO2015057998A1 (en) | 2013-10-16 | 2014-10-16 | Device for formulating particles at small volumes |
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| EP4481401A3 (en) | 2015-02-24 | 2025-04-23 | The University of British Columbia | Continuous flow microfluidic system and method |
| EP3283059B1 (en) | 2015-04-13 | 2024-01-03 | CureVac Manufacturing GmbH | Method for producing rna compositions |
| WO2016176505A1 (en) | 2015-04-28 | 2016-11-03 | The University Of British Columbia | Disposable microfluidic cartridge |
| USD772427S1 (en) | 2015-04-28 | 2016-11-22 | University Of British Columbia | Microfluidic cartridge |
| USD771834S1 (en) | 2015-04-28 | 2016-11-15 | University Of British Columbia | Microfluidic cartridge |
| USD771833S1 (en) | 2015-04-28 | 2016-11-15 | University Of British Columbia | Microfluidic cartridge |
| WO2017048770A1 (en) * | 2015-09-15 | 2017-03-23 | Regulus Therapeutics, Inc. | Systems, compositions, and methods for formulating nucleic acid compositions |
| KR102361123B1 (ko) * | 2016-01-06 | 2022-02-09 | 더 유니버시티 오브 브리티쉬 콜롬비아 | 분기 혼합기들 및 그 사용 및 제조 방법 |
| WO2018006166A1 (en) | 2016-07-06 | 2018-01-11 | Precision Nanosystems Inc | Smart microfluidic mixing instrument and cartridges |
| US20210284998A1 (en) * | 2016-10-03 | 2021-09-16 | Precision Nanosystems Inc. | Compositions for Transfecting Resistant Cell Types |
| EP3554478B1 (en) * | 2016-12-16 | 2022-01-26 | Delphi Scientific, LLC | Layered particles and processes thereof |
| US20190298857A1 (en) * | 2018-01-09 | 2019-10-03 | Trucode Gene Repair, Inc. | Polymer-based nanoparticles, related formulations methods, and apparatus |
| CN112105389B (zh) * | 2018-04-29 | 2024-10-18 | 环球生命科学解决方案加拿大有限公司 | 用于转染抵抗细胞类型的组合物 |
| WO2020081933A1 (en) * | 2018-10-19 | 2020-04-23 | Translate Bio, Inc. | Pumpless encapsulation of messenger rna |
| EP3956459A4 (en) * | 2019-04-15 | 2023-01-11 | Precision Nanosystems Inc | NONVIRAL MODIFICATION OF T LYMPHOCYTE GENE EXPRESSION |
| CA3165471A1 (en) * | 2019-12-23 | 2021-07-01 | Nutcracker Therapeutics, Inc. | Microfluidic apparatus and methods of use thereof |
| EP4132478A1 (en) | 2020-04-09 | 2023-02-15 | Finncure Oy | Mimetic nanoparticles for preventing the spreading and lowering the infection rate of novel coronaviruses |
| US12194157B2 (en) | 2020-04-09 | 2025-01-14 | Finncure Oy | Carrier for targeted delivery to a host |
| DE102020214601A1 (de) * | 2020-11-19 | 2022-05-19 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein | Verfahren und Vorrichtung zur Herstellung einer Flüssigkeit enthaltend Liposomen und hergestellte Flüssigkeit |
| WO2022109721A1 (en) | 2020-11-30 | 2022-06-02 | Precision Nanosystems Inc. | Non aggregating microfluidic mixer and methods therefor |
| CN114247398A (zh) * | 2021-12-17 | 2022-03-29 | 沈磊 | 一种脂质纳米颗粒制备系统及设备 |
| WO2024006863A1 (en) | 2022-06-30 | 2024-01-04 | Precision NanoSystems ULC | Lipid nanoparticle formulations for vaccines |
| CN120390635A (zh) | 2022-12-12 | 2025-07-29 | 环球生命科学解决方案加拿大有限公司 | 脂质纳米颗粒冻干方法和组合物 |
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Family Cites Families (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
| US5216141A (en) | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
| JP3119871B2 (ja) | 1990-07-26 | 2000-12-25 | 株式会社医薬分子設計研究所 | オリゴデオキシリボヌクレオチド類 |
| US5386023A (en) | 1990-07-27 | 1995-01-31 | Isis Pharmaceuticals | Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
| DK51092D0 (da) | 1991-05-24 | 1992-04-15 | Ole Buchardt | Oligonucleotid-analoge betegnet pna, monomere synthoner og fremgangsmaade til fremstilling deraf samt anvendelser deraf |
| US5641625A (en) | 1992-05-22 | 1997-06-24 | Isis Pharmaceuticals, Inc. | Cleaving double-stranded DNA with peptide nucleic acids |
| US5766855A (en) | 1991-05-24 | 1998-06-16 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity and sequence specificity |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
| US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
| US5644048A (en) | 1992-01-10 | 1997-07-01 | Isis Pharmaceuticals, Inc. | Process for preparing phosphorothioate oligonucleotides |
| GB9211979D0 (en) | 1992-06-05 | 1992-07-15 | Buchard Ole | Uses of nucleic acid analogues |
| US5417956A (en) * | 1992-08-18 | 1995-05-23 | Worcester Polytechnic Institute | Preparation of nanophase solid state materials |
| US5527675A (en) | 1993-08-20 | 1996-06-18 | Millipore Corporation | Method for degradation and sequencing of polymers which sequentially eliminate terminal residues |
| DE4331012A1 (de) | 1993-09-13 | 1995-03-16 | Bayer Ag | Nukleinsäuren-bindende Oligomere mit N-Verzweigung für Therapie und Diagnostik |
| GB2284209A (en) | 1993-11-25 | 1995-05-31 | Ole Buchardt | Nucleic acid analogue-induced transcription of RNA from a double-stranded DNA template |
| US5637684A (en) | 1994-02-23 | 1997-06-10 | Isis Pharmaceuticals, Inc. | Phosphoramidate and phosphorothioamidate oligomeric compounds |
| US5705333A (en) | 1994-08-05 | 1998-01-06 | The Regents Of The University Of California | Peptide-based nucleic acid mimics(PENAMS) |
| US5753789A (en) | 1996-07-26 | 1998-05-19 | Yale University | Oligonucleotides containing L-nucleosides |
| ES2192672T3 (es) | 1996-11-18 | 2003-10-16 | Takeshi Imanishi | Nuevos analogos de nucleotidos. |
| JP3756313B2 (ja) | 1997-03-07 | 2006-03-15 | 武 今西 | 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体 |
| US6251666B1 (en) | 1997-03-31 | 2001-06-26 | Ribozyme Pharmaceuticals, Inc. | Nucleic acid catalysts comprising L-nucleotide analogs |
| US6107470A (en) | 1997-05-29 | 2000-08-22 | Nielsen; Peter E. | Histidine-containing peptide nucleic acids |
| JP4236812B2 (ja) | 1997-09-12 | 2009-03-11 | エクシコン エ／エス | オリゴヌクレオチド類似体 |
| KR100694914B1 (ko) | 1998-07-09 | 2007-03-14 | 바이오셉트 인코포레이티드 | 디엔에이 서열 하이브리드화를 최적화하기 위한 개선된펩티드 핵산 유니버셜 라이브러리의 사용방법 |
| JP2002026134A (ja) | 2000-07-12 | 2002-01-25 | Seiko Epson Corp | 半導体集積回路の製造方法及びこの方法により製造した半導体集積回路 |
| WO2003011443A2 (en) | 2001-07-27 | 2003-02-13 | President And Fellows Of Harvard College | Laminar mixing apparatus and methods |
| GB0126716D0 (en) | 2001-11-07 | 2002-01-02 | Advanced Phytonics Ltd | Method for the production of particles |
| JP3775305B2 (ja) * | 2002-01-31 | 2006-05-17 | コニカミノルタホールディングス株式会社 | 液体混合機構及び液体混合方法 |
| US7718099B2 (en) | 2002-04-25 | 2010-05-18 | Tosoh Corporation | Fine channel device, fine particle producing method and solvent extraction method |
| EP1391237B1 (en) | 2002-08-01 | 2011-09-21 | Tosoh Corporation | Fine channel device, desksize chemical plant and fine particle producing apparatus employing them |
| ES2327231T3 (es) * | 2003-03-10 | 2009-10-27 | The Regents Of The University Of Michigan | Control microfluidico integrado que emplea accionadores tactiles programables. |
| JP4346456B2 (ja) | 2004-01-19 | 2009-10-21 | 株式会社Ｋｒｉ | 微粒子製造装置 |
| GB0418447D0 (en) | 2004-08-19 | 2004-09-22 | Advanced Phytonics Ltd | Process for preparing particles and apparatus |
| JP4822689B2 (ja) | 2004-10-29 | 2011-11-24 | 株式会社Ｋｒｉ | 微生物単離装置、微生物の単離方法および該方法で得られた微生物含有微粒子 |
| JP4713397B2 (ja) * | 2006-01-18 | 2011-06-29 | 株式会社リコー | 微小流路構造体及び微小液滴生成システム |
| US9381477B2 (en) * | 2006-06-23 | 2016-07-05 | Massachusetts Institute Of Technology | Microfluidic synthesis of organic nanoparticles |
| EP2069733A4 (en) | 2006-10-02 | 2013-07-10 | Nanomaterials Tech Pte Ltd | PROCESS FOR PRODUCING MICROPARTICLES AND PRECIPITATION NANOPARTICLES |
| EP2496700B1 (en) * | 2009-11-04 | 2017-03-01 | The University Of British Columbia | Nucleic acid-containing lipid particles and related methods |
| WO2012016184A2 (en) | 2010-07-30 | 2012-02-02 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for delivery of active agents |
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- 2014-10-16 JP JP2016523932A patent/JP6640079B2/ja active Active
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| EP3057693A1 (en) | 2016-08-24 |
| CN105813721B (zh) | 2019-11-05 |
| CA2927358C (en) | 2021-12-21 |
| US10159652B2 (en) | 2018-12-25 |
| WO2015057998A1 (en) | 2015-04-23 |
| JP2017500279A (ja) | 2017-01-05 |
| US20190076372A1 (en) | 2019-03-14 |
| CA2927358A1 (en) | 2015-04-23 |
| US20160235688A1 (en) | 2016-08-18 |
| CN105813721A (zh) | 2016-07-27 |
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