UA121863C2 - Стереохімічно збагачені композиції для доставки нуклеїнових кислот - Google Patents
Стереохімічно збагачені композиції для доставки нуклеїнових кислот Download PDFInfo
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- UA121863C2 UA121863C2 UAA201612749A UAA201612749A UA121863C2 UA 121863 C2 UA121863 C2 UA 121863C2 UA A201612749 A UAA201612749 A UA A201612749A UA A201612749 A UAA201612749 A UA A201612749A UA 121863 C2 UA121863 C2 UA 121863C2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
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Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3354644A1 (en) | 2011-06-08 | 2018-08-01 | Translate Bio, Inc. | Cleavable lipids |
| MX2016005238A (es) * | 2013-10-22 | 2016-08-12 | Shire Human Genetic Therapies | Formulaciones de lipidos para la administracion de acido ribonucleico mensajero. |
| JP6557722B2 (ja) | 2014-05-30 | 2019-08-07 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | 核酸の送達のための生分解性脂質 |
| WO2018144709A2 (en) * | 2017-02-01 | 2018-08-09 | The Trustees Of The University Of Pennsylvania | Gene therapy for treating citrullenemia |
| WO2018157133A1 (en) | 2017-02-27 | 2018-08-30 | Translate Bio, Inc. | Methods for purification of messenger rna |
| EP3585892B8 (en) | 2017-02-27 | 2022-07-13 | Translate Bio, Inc. | Methods for purification of messenger rna |
| WO2019152802A1 (en) | 2018-02-02 | 2019-08-08 | Translate Bio, Inc. | Cationic polymers |
| US20210220449A1 (en) * | 2018-05-15 | 2021-07-22 | Translate Bio, Inc. | Subcutaneous Delivery of Messenger RNA |
| CA3108544A1 (en) | 2018-08-24 | 2020-02-27 | Translate Bio, Inc. | Methods for purification of messenger rna |
| CN113166783B (zh) | 2018-10-09 | 2024-10-11 | 不列颠哥伦比亚大学 | 包含无有机溶剂和去污剂的转染活性囊泡的组合物和系统以及与之相关的方法 |
| KR20210089648A (ko) | 2018-11-08 | 2021-07-16 | 트랜슬레이트 바이오 인코포레이티드 | 메신저 rna 정제를 위한 방법 및 조성물 |
| WO2020219427A1 (en) * | 2019-04-22 | 2020-10-29 | Translate Bio, Inc. | Thioester cationic lipids |
| KR20220121246A (ko) | 2019-12-20 | 2022-08-31 | 큐어백 아게 | 핵산 전달용 신규한 지질 나노입자 |
| CN111658782A (zh) * | 2020-06-10 | 2020-09-15 | 深圳近邻生物科技有限公司 | mRNA疫苗递送载体及制备方法、mRNA疫苗及制备方法 |
| CA3193347A1 (en) * | 2020-09-23 | 2022-03-31 | Saswata KARMAKAR | Piperazine-based cationic lipids |
| 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 |
| JP2023546175A (ja) | 2020-10-14 | 2023-11-01 | ジョージ・メイソン・リサーチ・ファウンデーション・インコーポレイテッド | 脂質ナノ粒子製造の方法及びそれに由来する組成物 |
| WO2022099003A1 (en) | 2020-11-06 | 2022-05-12 | Sanofi | Lipid nanoparticles for delivering mrna vaccines |
| CZ310443B6 (cs) | 2021-07-19 | 2025-06-25 | Ústav organické chemie a biochemie AV ČR, v. v. i. | Cyklohexanové lipidoidy pro transfekci nukleových kyselin a jejich použití |
| MX2024002726A (es) | 2021-09-03 | 2024-03-20 | CureVac SE | Nuevas nanoparticulas lipidicas para la administracion de acidos nucleicos. |
| WO2023073228A1 (en) | 2021-10-29 | 2023-05-04 | CureVac SE | Improved circular rna for expressing therapeutic proteins |
| US20250099614A1 (en) | 2022-01-28 | 2025-03-27 | CureVac SE | Nucleic acid encoded transcription factor inhibitors |
| WO2023227608A1 (en) | 2022-05-25 | 2023-11-30 | Glaxosmithkline Biologicals Sa | Nucleic acid based vaccine encoding an escherichia coli fimh antigenic polypeptide |
| WO2024089638A1 (en) | 2022-10-28 | 2024-05-02 | Glaxosmithkline Biologicals Sa | Nucleic acid based vaccine |
| KR20250153298A (ko) | 2023-03-08 | 2025-10-24 | 큐어백 에스이 | 핵산 전달을 위한 신규의 지질 나노입자 제형 |
| WO2024230934A1 (en) | 2023-05-11 | 2024-11-14 | CureVac SE | Therapeutic nucleic acid for the treatment of ophthalmic diseases |
| CN118852328A (zh) * | 2024-07-02 | 2024-10-29 | 北京大学 | 肽基可离子化脂质合成及其应用 |
Family Cites Families (334)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2647121A (en) | 1951-02-02 | 1953-07-28 | Ruth P Jacoby | Diamine-bis-acetamides |
| US2819718A (en) | 1953-07-16 | 1958-01-14 | Isidore H Goldman | Drainage tube |
| US2717909A (en) | 1953-09-24 | 1955-09-13 | Monsanto Chemicals | Hydroxyethyl-keryl-alkylene-ammonium compounds |
| US2844629A (en) | 1956-04-25 | 1958-07-22 | American Home Prod | Fatty acid amides and derivatives thereof |
| US3096560A (en) | 1958-11-21 | 1963-07-09 | William J Liebig | Process for synthetic vascular implants |
| FR1378382A (fr) | 1962-12-01 | 1964-11-13 | Sandoz Sa | Amides de l'acide amino-propionique, utilisables en particulier pour le traitement des fibres textiles |
| GB1072118A (en) | 1962-12-01 | 1967-06-14 | Sandoz Ag | Amides of aminopropionic acid |
| JPS5141663B1 (https=) | 1966-03-12 | 1976-11-11 | ||
| JPS4822365B1 (https=) | 1968-10-25 | 1973-07-05 | ||
| NL143127B (nl) | 1969-02-04 | 1974-09-16 | Rhone Poulenc Sa | Versterkingsorgaan voor een defecte hartklep. |
| US3614954A (en) | 1970-02-09 | 1971-10-26 | Medtronic Inc | Electronic standby defibrillator |
| US3614955A (en) | 1970-02-09 | 1971-10-26 | Medtronic Inc | Standby defibrillator and method of operation |
| JPS5024216B1 (https=) | 1970-12-29 | 1975-08-14 | ||
| JPS5012146Y2 (https=) | 1971-07-27 | 1975-04-15 | ||
| US3945052A (en) | 1972-05-01 | 1976-03-23 | Meadox Medicals, Inc. | Synthetic vascular graft and method for manufacturing the same |
| US3805301A (en) | 1972-07-28 | 1974-04-23 | Meadox Medicals Inc | Tubular grafts having indicia thereon |
| US4022833A (en) | 1973-02-14 | 1977-05-10 | Sterling Drug Inc. | N,N'-bridged-bis[2-alkyl-2-hydroxyethylamines] |
| JPS49127908A (https=) | 1973-04-20 | 1974-12-07 | ||
| JPS5624664B2 (https=) | 1973-06-28 | 1981-06-08 | ||
| US4013507A (en) | 1973-09-18 | 1977-03-22 | California Institute Of Technology | Ionene polymers for selectively inhibiting the vitro growth of malignant cells |
| JPS5123537A (ja) | 1974-04-26 | 1976-02-25 | Adeka Argus Chemical Co Ltd | Kasozaisoseibutsu |
| GB1527592A (en) | 1974-08-05 | 1978-10-04 | Ici Ltd | Wound dressing |
| US3995623A (en) | 1974-12-23 | 1976-12-07 | American Hospital Supply Corporation | Multipurpose flow-directed catheter |
| JPS5813576B2 (ja) | 1974-12-27 | 1983-03-14 | アデカ ア−ガスカガク カブシキガイシヤ | 安定化された合成高分子組成物 |
| US4281669A (en) | 1975-05-09 | 1981-08-04 | Macgregor David C | Pacemaker electrode with porous system |
| DE2520814A1 (de) | 1975-05-09 | 1976-11-18 | Bayer Ag | Lichtstabilisierung von polyurethanen |
| JPS5210847A (en) | 1975-07-16 | 1977-01-27 | Nippon Steel Corp | Pinch roll |
| US4096860A (en) | 1975-10-08 | 1978-06-27 | Mclaughlin William F | Dual flow encatheter |
| CA1069652A (en) | 1976-01-09 | 1980-01-15 | Alain F. Carpentier | Supported bioprosthetic heart valve with compliant orifice ring |
| US4134402A (en) | 1976-02-11 | 1979-01-16 | Mahurkar Sakharam D | Double lumen hemodialysis catheter |
| US4072146A (en) | 1976-09-08 | 1978-02-07 | Howes Randolph M | Venous catheter device |
| US4335723A (en) | 1976-11-26 | 1982-06-22 | The Kendall Company | Catheter having inflatable retention means |
| US4099528A (en) | 1977-02-17 | 1978-07-11 | Sorenson Research Co., Inc. | Double lumen cannula |
| US4140126A (en) | 1977-02-18 | 1979-02-20 | Choudhury M Hasan | Method for performing aneurysm repair |
| US4265745A (en) | 1977-05-25 | 1981-05-05 | Teijin Limited | Permselective membrane |
| US4182833A (en) | 1977-12-07 | 1980-01-08 | Celanese Polymer Specialties Company | Cationic epoxide-amine reaction products |
| US4180068A (en) | 1978-04-13 | 1979-12-25 | Motion Control, Incorporated | Bi-directional flow catheter with retractable trocar/valve structure |
| EP0005035B1 (en) | 1978-04-19 | 1981-09-23 | Imperial Chemical Industries Plc | A method of preparing a tubular product by electrostatic spinning |
| US4284459A (en) | 1978-07-03 | 1981-08-18 | The Kendall Company | Method for making a molded catheter |
| US4227533A (en) | 1978-11-03 | 1980-10-14 | Bristol-Myers Company | Flushable urinary catheter |
| US4375817A (en) | 1979-07-19 | 1983-03-08 | Medtronic, Inc. | Implantable cardioverter |
| US5132418A (en) | 1980-02-29 | 1992-07-21 | University Patents, Inc. | Process for preparing polynucleotides |
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US4500707A (en) | 1980-02-29 | 1985-02-19 | University Patents, Inc. | Nucleosides useful in the preparation of polynucleotides |
| DE3010841A1 (de) | 1980-03-21 | 1981-10-08 | Ulrich Dr.med. 6936 Haag Uthmann | Katheder |
| US4308085A (en) | 1980-07-28 | 1981-12-29 | Jenoptik Jena Gmbh | Process for the preparation of high molecular thermoplastic epoxide-amine-polyadducts |
| US4415732A (en) | 1981-03-27 | 1983-11-15 | University Patents, Inc. | Phosphoramidite compounds and processes |
| US4668777A (en) | 1981-03-27 | 1987-05-26 | University Patents, Inc. | Phosphoramidite nucleoside compounds |
| US4973679A (en) | 1981-03-27 | 1990-11-27 | University Patents, Inc. | Process for oligonucleo tide synthesis using phosphormidite intermediates |
| US4339369A (en) | 1981-04-23 | 1982-07-13 | Celanese Corporation | Cationic epoxide-amine reaction products |
| US4401796A (en) | 1981-04-30 | 1983-08-30 | City Of Hope Research Institute | Solid-phase synthesis of polynucleotides |
| US4373071A (en) | 1981-04-30 | 1983-02-08 | City Of Hope Research Institute | Solid-phase synthesis of polynucleotides |
| US4406656A (en) | 1981-06-01 | 1983-09-27 | Brack Gillium Hattler | Venous catheter having collapsible multi-lumens |
| US4475972A (en) | 1981-10-01 | 1984-10-09 | Ontario Research Foundation | Implantable material |
| US4401472A (en) | 1982-02-26 | 1983-08-30 | Martin Marietta Corporation | Hydraulic cement mixes and processes for improving hydraulic cement mixes |
| US4568329A (en) | 1982-03-08 | 1986-02-04 | Mahurkar Sakharam D | Double lumen catheter |
| US4546499A (en) | 1982-12-13 | 1985-10-15 | Possis Medical, Inc. | Method of supplying blood to blood receiving vessels |
| US4530113A (en) | 1983-05-20 | 1985-07-23 | Intervascular, Inc. | Vascular grafts with cross-weave patterns |
| US4550447A (en) | 1983-08-03 | 1985-11-05 | Shiley Incorporated | Vascular graft prosthesis |
| US4647416A (en) | 1983-08-03 | 1987-03-03 | Shiley Incorporated | Method of preparing a vascular graft prosthesis |
| US5104399A (en) | 1986-12-10 | 1992-04-14 | Endovascular Technologies, Inc. | Artificial graft and implantation method |
| US4571241A (en) | 1983-12-16 | 1986-02-18 | Christopher T Graham | Urinary catheter with collapsible urethral tube |
| US4710169A (en) | 1983-12-16 | 1987-12-01 | Christopher T Graham | Urinary catheter with collapsible urethral tube |
| US4737518A (en) | 1984-04-03 | 1988-04-12 | Takeda Chemical Industries, Ltd. | Lipid derivatives, their production and use |
| US4562596A (en) | 1984-04-25 | 1986-01-07 | Elliot Kornberg | Aortic graft, device and method for performing an intraluminal abdominal aortic aneurysm repair |
| US4782836A (en) | 1984-05-24 | 1988-11-08 | Intermedics, Inc. | Rate adaptive cardiac pacemaker responsive to patient activity and temperature |
| US4897355A (en) | 1985-01-07 | 1990-01-30 | Syntex (U.S.A.) Inc. | N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US4662382A (en) | 1985-01-16 | 1987-05-05 | Intermedics, Inc. | Pacemaker lead with enhanced sensitivity |
| US4762915A (en) | 1985-01-18 | 1988-08-09 | Liposome Technology, Inc. | Protein-liposome conjugates |
| US4860751A (en) | 1985-02-04 | 1989-08-29 | Cordis Corporation | Activity sensor for pacemaker control |
| CA1320724C (en) | 1985-07-19 | 1993-07-27 | Koichi Kanehira | Terpene amino alcohols and medicinal uses thereof |
| ATE77806T1 (de) | 1985-08-05 | 1992-07-15 | Miyoshi Yushi Kk | Verfahren fuer die abscheidung von metallen. |
| US4701162A (en) | 1985-09-24 | 1987-10-20 | The Kendall Company | Foley catheter assembly |
| US4737323A (en) | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
| US5153319A (en) | 1986-03-31 | 1992-10-06 | University Patents, Inc. | Process for preparing polynucleotides |
| DE3616824A1 (de) | 1986-05-17 | 1987-11-19 | Schering Ag | Verwendung von haertbaren kunstharzmischungen fuer oberflaechenbeschichtungen und druckfarben und verfahren zu ihrer herstellung |
| EP0255899B1 (de) | 1986-07-31 | 1992-07-15 | Werner Prof. Dr.-Ing. Irnich | Frequenzadaptierender Herzschrittmacher |
| US4960409A (en) | 1986-09-11 | 1990-10-02 | Catalano Marc L | Method of using bilumen peripheral venous catheter with adapter |
| JPH0829776B2 (ja) | 1986-10-29 | 1996-03-27 | 東燃化学株式会社 | 合成樹脂製容器及びその製造用金型 |
| US4720517A (en) | 1986-11-24 | 1988-01-19 | Ciba-Geigy Corporation | Compositions stabilized with N-hydroxyiminodiacetic and dipropionic acids and esters thereof |
| US4873370A (en) | 1987-03-03 | 1989-10-10 | Pennzoil Products Company | Alkylene diamines for use in friction and wear reducing compositions |
| DE3728917A1 (de) | 1987-08-29 | 1989-03-09 | Roth Hermann J | Neue lipide mit unsymmetrisch substituierter disulfidbruecke |
| US5138067A (en) | 1987-12-17 | 1992-08-11 | Shionogi & Co. Ltd. | Lipid derivatives |
| US5047540A (en) | 1987-12-17 | 1991-09-10 | Shionogi & Co., Ltd. | Lipid derivatives |
| US4892540A (en) | 1988-04-21 | 1990-01-09 | Sorin Biomedica S.P.A. | Two-leaflet prosthetic heart valve |
| US5176661A (en) | 1988-09-06 | 1993-01-05 | Advanced Cardiovascular Systems, Inc. | Composite vascular catheter |
| US5024671A (en) | 1988-09-19 | 1991-06-18 | Baxter International Inc. | Microporous vascular graft |
| US5200395A (en) | 1988-10-18 | 1993-04-06 | Ajinomoto Company, Inc. | Pharmaceutical composition of BUF-5 for treating anemia |
| CA2001401A1 (en) | 1988-10-25 | 1990-04-25 | Claude Piantadosi | Quaternary amine containing ether or ester lipid derivatives and therapeutic compositions |
| US5047524A (en) | 1988-12-21 | 1991-09-10 | Applied Biosystems, Inc. | Automated system for polynucleotide synthesis and purification |
| US5262530A (en) | 1988-12-21 | 1993-11-16 | Applied Biosystems, Inc. | Automated system for polynucleotide synthesis and purification |
| FR2645866B1 (fr) | 1989-04-17 | 1991-07-05 | Centre Nat Rech Scient | Nouvelles lipopolyamines, leur preparation et leur emploi |
| US5101824A (en) | 1990-04-16 | 1992-04-07 | Siemens-Pacesetter, Inc. | Rate-responsive pacemaker with circuitry for processing multiple sensor inputs |
| WO1992001425A1 (en) | 1990-07-26 | 1992-02-06 | Rodney James Lane | Self expanding vascular endoprosthesis for aneurysms |
| US5693338A (en) | 1994-09-29 | 1997-12-02 | Emisphere Technologies, Inc. | Diketopiperazine-based delivery systems |
| DE9117152U1 (de) | 1990-10-09 | 1996-07-11 | Cook Inc., Bloomington, Ind. | Stent |
| ATE120971T1 (de) | 1990-12-19 | 1995-04-15 | Osypka Peter | Herzschrittmacherleitung mit einem inneren kanal und mit einem elektrodenkopf. |
| US5116360A (en) | 1990-12-27 | 1992-05-26 | Corvita Corporation | Mesh composite graft |
| US5405363A (en) | 1991-03-15 | 1995-04-11 | Angelon Corporation | Implantable cardioverter defibrillator having a smaller displacement volume |
| US5330768A (en) | 1991-07-05 | 1994-07-19 | Massachusetts Institute Of Technology | Controlled drug delivery using polymer/pluronic blends |
| US5545449A (en) | 1991-10-02 | 1996-08-13 | Weyerhaeuser Company | Polyether-reinforced fiber-based materials |
| US5151105A (en) | 1991-10-07 | 1992-09-29 | Kwan Gett Clifford | Collapsible vessel sleeve implant |
| US5284491A (en) | 1992-02-27 | 1994-02-08 | Medtronic, Inc. | Cardiac pacemaker with hysteresis behavior |
| US5352461A (en) | 1992-03-11 | 1994-10-04 | Pharmaceutical Discovery Corporation | Self assembling diketopiperazine drug delivery system |
| SE9200951D0 (sv) | 1992-03-27 | 1992-03-27 | Kabi Pharmacia Ab | Pharmaceutical composition containing a defined lipid system |
| EP0657534A4 (en) | 1992-08-04 | 1997-06-04 | Green Cross Corp | ANTIALLERGIC AGING. |
| US5334761A (en) | 1992-08-28 | 1994-08-02 | Life Technologies, Inc. | Cationic lipids |
| US5380778A (en) | 1992-09-30 | 1995-01-10 | Minnesota Mining And Manufacturing Company | Fluorochemical aminoalcohols |
| US5461223A (en) | 1992-10-09 | 1995-10-24 | Eastman Kodak Company | Bar code detecting circuitry |
| JPH06211978A (ja) | 1992-10-28 | 1994-08-02 | Takeda Chem Ind Ltd | 新規ポリエーテルポリオール及びそれを用いる軟質ウレタンフォームの製造法 |
| US5300022A (en) | 1992-11-12 | 1994-04-05 | Martin Klapper | Urinary catheter and bladder irrigation system |
| US5496362A (en) | 1992-11-24 | 1996-03-05 | Cardiac Pacemakers, Inc. | Implantable conformal coil patch electrode with multiple conductive elements for cardioversion and defibrillation |
| US5716395A (en) | 1992-12-11 | 1998-02-10 | W.L. Gore & Associates, Inc. | Prosthetic vascular graft |
| US6020317A (en) | 1993-02-19 | 2000-02-01 | Nippon Shinyaku Co. Ltd. | Glycerol derivative, device and pharmaceutical composition |
| US5395619A (en) | 1993-03-03 | 1995-03-07 | Liposome Technology, Inc. | Lipid-polymer conjugates and liposomes |
| US5697953A (en) | 1993-03-13 | 1997-12-16 | Angeion Corporation | Implantable cardioverter defibrillator having a smaller displacement volume |
| US5624976A (en) | 1994-03-25 | 1997-04-29 | Dentsply Gmbh | Dental filling composition and method |
| US5314430A (en) | 1993-06-24 | 1994-05-24 | Medtronic, Inc. | Atrial defibrillator employing transvenous and subcutaneous electrodes and method of use |
| DE4325848A1 (de) | 1993-07-31 | 1995-02-02 | Basf Ag | Verfahren zur Herstellung von N-(2-Hydroxyethyl)-piperazin |
| EP0647462A1 (en) | 1993-10-06 | 1995-04-12 | The Kansai Electric Power Co., Inc. | Method for removing carbon dioxide from combustion exhaust gas |
| US5609624A (en) | 1993-10-08 | 1997-03-11 | Impra, Inc. | Reinforced vascular graft and method of making same |
| SE9303481L (sv) | 1993-10-22 | 1995-04-23 | Berol Nobel Ab | Hygienkomposition |
| WO1995013033A1 (en) | 1993-11-08 | 1995-05-18 | Lazarus Harrison M | Intraluminal vascular graft and method |
| NZ277614A (en) | 1993-11-24 | 1998-05-27 | Megabios Corp | Piperazine-containing amphiphiles and their use in liposomes for delivering genetic material intracellularly |
| US5464924A (en) | 1994-01-07 | 1995-11-07 | The Dow Chemical Company | Flexible poly(amino ethers) for barrier packaging |
| US5840576A (en) | 1994-07-20 | 1998-11-24 | Cytotherapeutics, Inc. | Methods and compositions of growth control for cells encapsulated within bioartificial organs |
| US5885613A (en) | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
| GB9524630D0 (en) | 1994-12-24 | 1996-01-31 | Zeneca Ltd | Chemical compounds |
| US5965434A (en) | 1994-12-29 | 1999-10-12 | Wolff; Jon A. | Amphipathic PH sensitive compounds and delivery systems for delivering biologically active compounds |
| US5830430A (en) | 1995-02-21 | 1998-11-03 | Imarx Pharmaceutical Corp. | Cationic lipids and the use thereof |
| EP0822835A1 (en) | 1995-04-17 | 1998-02-11 | Imarx Pharmaceutical Corp. | Hybrid magnetic resonance contrast agents |
| US6428771B1 (en) | 1995-05-15 | 2002-08-06 | Pharmaceutical Discovery Corporation | Method for drug delivery to the pulmonary system |
| US5772694A (en) | 1995-05-16 | 1998-06-30 | Medical Carbon Research Institute L.L.C. | Prosthetic heart valve with improved blood flow |
| US5700642A (en) | 1995-05-22 | 1997-12-23 | Sri International | Oligonucleotide sizing using immobilized cleavable primers |
| US5609629A (en) | 1995-06-07 | 1997-03-11 | Med Institute, Inc. | Coated implantable medical device |
| US5981501A (en) | 1995-06-07 | 1999-11-09 | Inex Pharmaceuticals Corp. | Methods for encapsulating plasmids in lipid bilayers |
| ATE285477T1 (de) | 1995-06-07 | 2005-01-15 | Inex Pharmaceutical Corp | Herstellung von lipid-nukleinsäure partikeln duch ein hydrophobische lipid-nukleinsäuree komplexe zwischenprodukt und zur verwendung in der gentransfer |
| US5705385A (en) | 1995-06-07 | 1998-01-06 | Inex Pharmaceuticals Corporation | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
| US7422902B1 (en) | 1995-06-07 | 2008-09-09 | The University Of British Columbia | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
| US5607385A (en) | 1995-08-17 | 1997-03-04 | Medtronic, Inc. | Device and algorithm for a combined cardiomyostimulator and a cardiac pacer-carioverter-defibrillator |
| US5728844A (en) | 1995-08-29 | 1998-03-17 | Celgene Corporation | Immunotherapeutic agents |
| US5744335A (en) | 1995-09-19 | 1998-04-28 | Mirus Corporation | Process of transfecting a cell with a polynucleotide mixed with an amphipathic compound and a DNA-binding protein |
| FR2740978B1 (fr) | 1995-11-10 | 1998-01-02 | Ela Medical Sa | Dispositif medical actif du type defibrillateur/cardioverteur implantable |
| US5874105A (en) | 1996-01-31 | 1999-02-23 | Collaborative Laboratories, Inc. | Lipid vesicles formed with alkylammonium fatty acid salts |
| US6667053B1 (en) | 1996-02-16 | 2003-12-23 | Elan Pharmaceuticals, Inc. | D and L etherlipid stereoisomers and liposomes |
| US5913848A (en) | 1996-06-06 | 1999-06-22 | Luther Medical Products, Inc. | Hard tip over-the-needle catheter and method of manufacturing the same |
| US5736573A (en) | 1996-07-31 | 1998-04-07 | Galat; Alexander | Lipid and water soluble derivatives of drugs |
| TW520297B (en) | 1996-10-11 | 2003-02-11 | Sequus Pharm Inc | Fusogenic liposome composition and method |
| US6887665B2 (en) | 1996-11-14 | 2005-05-03 | Affymetrix, Inc. | Methods of array synthesis |
| US6204297B1 (en) | 1996-11-26 | 2001-03-20 | Rhodia Inc. | Nonionic gemini surfactants |
| JPH10197978A (ja) | 1997-01-09 | 1998-07-31 | Mitsubishi Paper Mills Ltd | ハロゲン化銀写真感光材料 |
| FR2760193B1 (fr) | 1997-02-28 | 1999-05-28 | Transgene Sa | Lipides et complexes de lipides cationiques et de substances actives, notamment pour la transfection de cellules |
| US5837283A (en) | 1997-03-12 | 1998-11-17 | The Regents Of The University Of California | Cationic lipid compositions targeting angiogenic endothelial cells |
| US5945326A (en) | 1997-03-20 | 1999-08-31 | New England Biolabs, Inc. | Method for cloning and producing the Spel restriction endonuclease |
| IL133087A0 (en) * | 1997-05-28 | 2001-03-19 | Nielsen Peter E | Conjugated peptide nucleic acids having enhanced cellular uptake |
| JPH115786A (ja) | 1997-06-13 | 1999-01-12 | Pola Chem Ind Inc | 新規アミノヒドロキシプロピルピペラジン誘導体 |
| US6067471A (en) | 1998-08-07 | 2000-05-23 | Cardiac Pacemakers, Inc. | Atrial and ventricular implantable cardioverter-defibrillator and lead system |
| JPH1180142A (ja) | 1997-09-05 | 1999-03-26 | Pola Chem Ind Inc | ジフェニルアルキル化合物の製造法 |
| US6096075A (en) | 1998-01-22 | 2000-08-01 | Medical Carbon Research Institute, Llc | Prosthetic heart valve |
| US6271209B1 (en) | 1998-04-03 | 2001-08-07 | Valentis, Inc. | Cationic lipid formulation delivering nucleic acid to peritoneal tumors |
| US6176877B1 (en) | 1998-04-20 | 2001-01-23 | St. Jude Medical, Inc. | Two piece prosthetic heart valve |
| DE19822602A1 (de) | 1998-05-20 | 1999-11-25 | Goldschmidt Ag Th | Verfahren zur Herstellung von Polyaminosäureestern durch Veresterung von sauren Polyaminosäuren oder Umesterung von Polyaminosäureestern |
| NO313244B1 (no) | 1998-07-08 | 2002-09-02 | Crew Dev Corp | Fremgangsmåte for isolering og produksjon av magnesitt eller magnesiumklorid |
| US6055454A (en) | 1998-07-27 | 2000-04-25 | Cardiac Pacemakers, Inc. | Cardiac pacemaker with automatic response optimization of a physiologic sensor based on a second sensor |
| CA2340652C (en) | 1998-08-20 | 2013-09-24 | Cook Incorporated | Coated implantable medical device comprising paclitaxel |
| US6379698B1 (en) | 1999-04-06 | 2002-04-30 | Isis Pharmaceuticals, Inc. | Fusogenic lipids and vesicles |
| US6169923B1 (en) | 1999-04-23 | 2001-01-02 | Pacesetter, Inc. | Implantable cardioverter-defibrillator with automatic arrhythmia detection criteria adjustment |
| KR100669053B1 (ko) | 1999-04-23 | 2007-01-15 | 알자 코포레이션 | 리포좀에 사용하기 위한 절단가능 결합을 갖는 콘쥬게이트 |
| US6696424B1 (en) | 1999-05-28 | 2004-02-24 | Vical Incorporated | Cytofectin dimers and methods of use thereof |
| ES2569916T3 (es) | 1999-06-29 | 2016-05-13 | Mannkind Corporation | Formulaciones farmacéuticas que comprenden insulina complejada con una dicetopiperazina |
| EP1202714A1 (en) | 1999-07-16 | 2002-05-08 | Purdue Research Foundation | Vinyl ether lipids with cleavable hydrophilic headgroups |
| US6358278B1 (en) | 1999-09-24 | 2002-03-19 | St. Jude Medical, Inc. | Heart valve prosthesis with rotatable cuff |
| US6371983B1 (en) | 1999-10-04 | 2002-04-16 | Ernest Lane | Bioprosthetic heart valve |
| CN101041079A (zh) | 1999-12-30 | 2007-09-26 | 诺瓦提斯公司 | 用于基因治疗的新的胶体合成载体 |
| US6370434B1 (en) | 2000-02-28 | 2002-04-09 | Cardiac Pacemakers, Inc. | Cardiac lead and method for lead implantation |
| US6331381B1 (en) | 2000-04-14 | 2001-12-18 | International Business Machines Corporation | Method for making a liquid crystal alignment layer |
| US6565960B2 (en) | 2000-06-01 | 2003-05-20 | Shriners Hospital Of Children | Polymer composite compositions |
| WO2002000870A2 (en) | 2000-06-26 | 2002-01-03 | Christian Plank | Method for transfecting cells using a magnetic field |
| IL138474A0 (en) | 2000-09-14 | 2001-10-31 | Epox Ltd | Highly branched water-soluble polyamine oligomers, process for their preparation and applications thereof |
| USRE43612E1 (en) | 2000-10-10 | 2012-08-28 | Massachusetts Institute Of Technology | Biodegradable poly(β-amino esters) and uses thereof |
| US6998115B2 (en) | 2000-10-10 | 2006-02-14 | Massachusetts Institute Of Technology | Biodegradable poly(β-amino esters) and uses thereof |
| US7427394B2 (en) | 2000-10-10 | 2008-09-23 | Massachusetts Institute Of Technology | Biodegradable poly(β-amino esters) and uses thereof |
| US20020094528A1 (en) | 2000-11-29 | 2002-07-18 | Salafsky Joshua S. | Method and apparatus using a surface-selective nonlinear optical technique for detection of probe-target interations |
| JP2002167368A (ja) | 2000-12-01 | 2002-06-11 | Nitto Denko Corp | アルキル置換デンドリマーおよびその製造法 |
| US20020192721A1 (en) | 2001-03-28 | 2002-12-19 | Engeneos, Inc. | Modular molecular clasps and uses thereof |
| US7084303B2 (en) | 2001-04-23 | 2006-08-01 | Shin-Etsu Chemical Co., Ltd. | Tertiary amine compounds having an ester structure and processes for preparing same |
| US6656977B2 (en) | 2001-07-20 | 2003-12-02 | Air Products And Chemical, Inc. | Alkyl glycidyl ether-capped polyamine foam control agents |
| EP2390331B1 (en) | 2001-09-28 | 2018-04-25 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | MicroRNA molecules |
| WO2003040288A2 (de) | 2001-11-09 | 2003-05-15 | Bayer Healthcare Ag | Isotopencodierte affinitätsmarker 3 |
| DE10207178A1 (de) | 2002-02-19 | 2003-09-04 | Novosom Ag | Komponenten für die Herstellung amphoterer Liposomen |
| US20030215395A1 (en) | 2002-05-14 | 2003-11-20 | Lei Yu | Controllably degradable polymeric biomolecule or drug carrier and method of synthesizing said carrier |
| US7601367B2 (en) | 2002-05-28 | 2009-10-13 | Mirus Bio Llc | Compositions and processes using siRNA, amphipathic compounds and polycations |
| US7901708B2 (en) | 2002-06-28 | 2011-03-08 | Protiva Biotherapeutics, Inc. | Liposomal apparatus and manufacturing methods |
| US20040028804A1 (en) | 2002-08-07 | 2004-02-12 | Anderson Daniel G. | Production of polymeric microarrays |
| WO2004018654A2 (en) | 2002-08-22 | 2004-03-04 | Celltran Limited | Cell culture surface |
| CN100457804C (zh) | 2002-11-04 | 2009-02-04 | Ge拜尔硅股份有限公司 | 线性聚氨基-和/或聚铵聚硅氧烷共聚物ⅰ |
| CA2506843A1 (en) | 2002-11-22 | 2004-06-10 | Novo-Nordisk A/S | 2,5-diketopiperazines for the treatment of obesity |
| US6998508B2 (en) | 2003-03-10 | 2006-02-14 | Air Products And Chemicals, Inc. | Tertiary alkanolamines containing surface active alkyl groups |
| US7619017B2 (en) | 2003-05-19 | 2009-11-17 | Wacker Chemical Corporation | Polymer emulsions resistant to biodeterioration |
| EP1644479A4 (en) | 2003-06-16 | 2008-04-23 | Mark W Grinstaff | FUNCTIONAL SYNTHETIC MOLECULES AND MACROMOLECULES FOR GENERAL FEEDING |
| WO2005028619A2 (en) | 2003-09-15 | 2005-03-31 | Massachusetts Institute Of Technology | Nanoliter-scale synthesis of arrayed biomaterials and screening thereof |
| NZ592917A (en) | 2003-09-15 | 2012-12-21 | Protiva Biotherapeutics Inc | Stable polyethyleneglycol (PEG) dialkyloxypropyl (DAA) lipid conjugates |
| US20050069590A1 (en) | 2003-09-30 | 2005-03-31 | Buehler Gail K. | Stable suspensions for medicinal dosages |
| KR20060111471A (ko) | 2003-11-10 | 2006-10-27 | 니폰 가야꾸 가부시끼가이샤 | 디이모늄염 화합물 및 그의 용도 |
| US7022214B2 (en) | 2004-01-21 | 2006-04-04 | Bio-Rad Laboratories, Inc. | Carrier ampholytes of high pH range |
| US7556684B2 (en) | 2004-02-26 | 2009-07-07 | Construction Research & Technology Gmbh | Amine containing strength improvement admixture |
| US20060228404A1 (en) | 2004-03-04 | 2006-10-12 | Anderson Daniel G | Compositions and methods for treatment of hypertrophic tissues |
| BRPI0510093B8 (pt) | 2004-04-20 | 2022-12-27 | Dendritic Nanotechnologies Inc | polímeros dendríticos |
| US7799565B2 (en) | 2004-06-07 | 2010-09-21 | Protiva Biotherapeutics, Inc. | Lipid encapsulated interfering RNA |
| US7745651B2 (en) | 2004-06-07 | 2010-06-29 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods of use |
| DE102004043342A1 (de) | 2004-09-08 | 2006-03-09 | Bayer Materialscience Ag | Blockierte Polyurethan-Prepolymere als Klebstoffe |
| GB0502482D0 (en) | 2005-02-07 | 2005-03-16 | Glaxo Group Ltd | Novel compounds |
| JP5042863B2 (ja) | 2005-02-14 | 2012-10-03 | サーナ・セラピューティクス・インコーポレイテッド | 生物学的に活性な分子をデリバリーするための脂質ナノ粒子系組成物および方法 |
| EP1869106B1 (en) | 2005-03-28 | 2014-06-25 | Dendritic Nanotechnologies, Inc. | Janus dendrimers and dendrons |
| US9006487B2 (en) | 2005-06-15 | 2015-04-14 | Massachusetts Institute Of Technology | Amine-containing lipids and uses thereof |
| EP3611266B1 (en) | 2005-08-23 | 2022-11-09 | The Trustees of the University of Pennsylvania | Rna containing modified nucleosides and methods of use thereof |
| MX373000B (es) | 2005-09-14 | 2020-05-21 | Mannkind Corp | Metodo para formulacion de farmaco basado en el aumento de la afinidad de agentes activos hacia las superficies de microparticulas cristalinas. |
| WO2007031091A2 (en) | 2005-09-15 | 2007-03-22 | Santaris Pharma A/S | Rna antagonist compounds for the modulation of p21 ras expression |
| US8101741B2 (en) | 2005-11-02 | 2012-01-24 | Protiva Biotherapeutics, Inc. | Modified siRNA molecules and uses thereof |
| WO2007073489A2 (en) | 2005-12-22 | 2007-06-28 | Trustees Of Boston University | Molecules for gene delivery and gene therapy, and methods of use thereof |
| CN100569877C (zh) | 2005-12-30 | 2009-12-16 | 财团法人工业技术研究院 | 含多uv交联反应基的分枝状结构化合物及其应用 |
| EP1986679B1 (en) | 2006-02-22 | 2017-10-25 | MannKind Corporation | A method for improving the pharmaceutic properties of microparticles comprising diketopiperazine and an active agent |
| WO2007096662A2 (en) | 2006-02-27 | 2007-08-30 | Technische Universität München | Cancer imaging and treatment |
| US20070275923A1 (en) | 2006-05-25 | 2007-11-29 | Nastech Pharmaceutical Company Inc. | CATIONIC PEPTIDES FOR siRNA INTRACELLULAR DELIVERY |
| WO2007143659A2 (en) | 2006-06-05 | 2007-12-13 | Massachusetts Institute Of Technology | Crosslinked, degradable polymers and uses thereof |
| ES2293834B1 (es) | 2006-07-20 | 2009-02-16 | Consejo Superior Investig. Cientificas | Compuesto con actividad inhibidora de las interacciones ubc13-uev, composiciones farmaceuticas que lo comprenden y sus aplicaciones terapeuticas. |
| CA2658768C (en) | 2006-07-21 | 2016-05-17 | Massachusetts Institute Of Technology | End-modified poly(beta-amino esters) and uses thereof |
| EP2049665A2 (en) | 2006-07-28 | 2009-04-22 | Applera Corporation | Dinucleotide mrna cap analogs |
| EP3192788A1 (en) | 2006-10-03 | 2017-07-19 | Arbutus Biopharma Corporation | Lipid containing formulations |
| WO2008113364A2 (en) | 2007-03-20 | 2008-09-25 | Recepticon Aps | Amino derivatives to prevent nephrotoxicity and cancer |
| JP5186126B2 (ja) | 2007-03-29 | 2013-04-17 | 公益財団法人地球環境産業技術研究機構 | 新規トリアジン誘導体ならびにその製法およびそのガス分離膜としての用途 |
| US8678686B2 (en) | 2007-05-01 | 2014-03-25 | Pgr-Solutions | Multi-chain lipophilic polyamines |
| GB0716897D0 (en) | 2007-08-30 | 2007-10-10 | Univ Muenchen Tech | Cancer imaging and treatment |
| WO2009030254A1 (en) | 2007-09-04 | 2009-03-12 | Curevac Gmbh | Complexes of rna and cationic peptides for transfection and for immunostimulation |
| CA2701274A1 (en) | 2007-10-02 | 2009-04-09 | Mdrna, Inc. | Lipopeptides for delivery of nucleic acids |
| WO2009058911A2 (en) | 2007-10-31 | 2009-05-07 | Applied Biosystems Inc. | Preparation and isolation of 5' capped mrna |
| WO2009082607A2 (en) | 2007-12-04 | 2009-07-02 | Alnylam Pharmaceuticals, Inc. | Targeting lipids |
| WO2009082817A1 (en) | 2007-12-27 | 2009-07-09 | Protiva Biotherapeutics, Inc. | Silencing of polo-like kinase expression using interfering rna |
| WO2009126933A2 (en) | 2008-04-11 | 2009-10-15 | Alnylam Pharmaceuticals, Inc. | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components |
| AU2009238175C1 (en) | 2008-04-15 | 2023-11-30 | Arbutus Biopharma Corporation | Novel lipid formulations for nucleic acid delivery |
| US20090263407A1 (en) | 2008-04-16 | 2009-10-22 | Abbott Laboratories | Cationic Lipids and Uses Thereof |
| WO2009127230A1 (en) | 2008-04-16 | 2009-10-22 | Curevac Gmbh | MODIFIED (m)RNA FOR SUPPRESSING OR AVOIDING AN IMMUNOSTIMULATORY RESPONSE AND IMMUNOSUPPRESSIVE COMPOSITION |
| JP5024216B2 (ja) | 2008-07-23 | 2012-09-12 | トヨタ自動車株式会社 | 内燃機関の点火時期制御装置及び点火時期制御方法 |
| WO2010037408A1 (en) | 2008-09-30 | 2010-04-08 | Curevac Gmbh | Composition comprising a complexed (m)rna and a naked mrna for providing or enhancing an immunostimulatory response in a mammal and uses thereof |
| CN104119242B (zh) | 2008-10-09 | 2017-07-07 | 泰米拉制药公司 | 改善的氨基脂质和递送核酸的方法 |
| CN102231979B (zh) | 2008-10-16 | 2014-10-29 | 玛瑞纳生物技术有限公司 | 基因沉默治疗剂的脂质体有效递送方法和组合物 |
| WO2010062322A2 (en) | 2008-10-27 | 2010-06-03 | Massachusetts Institute Of Technology | Modulation of the immune response |
| ES2646630T3 (es) * | 2008-11-07 | 2017-12-14 | Massachusetts Institute Of Technology | Lipidoides aminoalcohólicos y usos de los mismos |
| HUE037082T2 (hu) | 2008-11-10 | 2018-08-28 | Arbutus Biopharma Corp | Új lipidek és készítmények terápiás hatóanyagok szállítására |
| US8314106B2 (en) | 2008-12-29 | 2012-11-20 | Mannkind Corporation | Substituted diketopiperazine analogs for use as drug delivery agents |
| CA2750561C (en) | 2009-01-26 | 2017-10-10 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein c-iii expression |
| US20100222489A1 (en) | 2009-02-27 | 2010-09-02 | Jiang Dayue D | Copolymer composition, membrane article, and methods thereof |
| PT2414322T (pt) * | 2009-03-20 | 2022-12-07 | Egen Inc | Derivados de poliamina |
| WO2010114789A1 (en) | 2009-04-02 | 2010-10-07 | The Siemon Company | Telecommunications patch panel |
| KR20180094137A (ko) | 2009-05-05 | 2018-08-22 | 알닐람 파마슈티칼스 인코포레이티드 | 지질 조성물 |
| WO2010132876A1 (en) | 2009-05-15 | 2010-11-18 | Arizona Board Of Regents For And On Behalf Of Arizona State University | Polymers for delivering a substance into a cell |
| MX342785B (es) | 2009-06-10 | 2016-10-12 | Alnylam Pharmaceuticals Inc | Formulacion mejorada de lipido. |
| WO2010147992A1 (en) | 2009-06-15 | 2010-12-23 | Alnylam Pharmaceuticals, Inc. | Methods for increasing efficacy of lipid formulated sirna |
| US9018187B2 (en) | 2009-07-01 | 2015-04-28 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods for the delivery of therapeutic agents |
| US8569256B2 (en) | 2009-07-01 | 2013-10-29 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods for the delivery of therapeutic agents |
| US8236943B2 (en) | 2009-07-01 | 2012-08-07 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein B |
| WO2011011447A1 (en) | 2009-07-20 | 2011-01-27 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing ebola virus gene expression |
| BR112012002134B8 (pt) | 2009-07-30 | 2021-05-25 | Salvat Lab Sa | compostos inibidores de apaf-1 |
| 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" |
| DE102009043342A1 (de) | 2009-09-29 | 2011-03-31 | Bayer Technology Services Gmbh | Stoffe für selbstorganisierte Träger zur kontrollierten Freisetzung eines Wirkstoffs |
| HUE042177T2 (hu) | 2009-12-01 | 2019-06-28 | Translate Bio Inc | Szteroidszármazék mRNS szállítására humán genetikai betegségekben |
| EP2338520A1 (de) | 2009-12-21 | 2011-06-29 | Ludwig Maximilians Universität | Konjugat mit Zielfindungsligand und dessen Verwendung |
| WO2011076807A2 (en) | 2009-12-23 | 2011-06-30 | Novartis Ag | Lipids, lipid compositions, and methods of using them |
| WO2011141705A1 (en) | 2010-05-12 | 2011-11-17 | Protiva Biotherapeutics, Inc. | Novel cationic lipids and methods of use thereof |
| CN101863544B (zh) | 2010-06-29 | 2011-09-28 | 湖南科技大学 | 一种氰尿酸基重金属螯合絮凝剂及其制备方法 |
| WO2012019168A2 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| EP2609135A4 (en) | 2010-08-26 | 2015-05-20 | Massachusetts Inst Technology | POLY (BETA AMINO ALCOHOLS), THEIR PREPARATION AND USES THEREOF |
| RU2013120302A (ru) | 2010-10-01 | 2014-11-20 | Модерна Терапьютикс, Инк. | Сконструированные нуклеиновые кислоты и способы их применения |
| WO2012075040A2 (en) | 2010-11-30 | 2012-06-07 | Shire Human Genetic Therapies, Inc. | mRNA FOR USE IN TREATMENT OF HUMAN GENETIC DISEASES |
| US9238716B2 (en) | 2011-03-28 | 2016-01-19 | Massachusetts Institute Of Technology | Conjugated lipomers and uses thereof |
| WO2012133737A1 (ja) | 2011-03-31 | 2012-10-04 | 公益財団法人地球環境産業技術研究機構 | 架橋性アミン化合物、該化合物を用いた高分子膜及びその製造方法 |
| EP2691101A2 (en) | 2011-03-31 | 2014-02-05 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
| WO2012158736A1 (en) | 2011-05-17 | 2012-11-22 | modeRNA Therapeutics | Engineered nucleic acids and methods of use thereof for non-human vertebrates |
| EP2532649B1 (en) | 2011-06-07 | 2015-04-08 | Incella GmbH | Amino lipids, their synthesis and uses thereof |
| PL3586861T3 (pl) | 2011-06-08 | 2022-05-23 | Translate Bio, Inc. | Kompozycje nanocząstek lipidowych i sposoby dostarczania mrna |
| EP3354644A1 (en) | 2011-06-08 | 2018-08-01 | Translate Bio, Inc. | Cleavable lipids |
| US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| EP3384938A1 (en) | 2011-09-12 | 2018-10-10 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| EP2755986A4 (en) | 2011-09-12 | 2015-05-20 | Moderna Therapeutics Inc | MANIPULATED NUCLEIC ACIDS AND METHOD OF APPLICATION THEREFOR |
| RU2648950C2 (ru) * | 2011-10-03 | 2018-04-02 | Модерна Терапьютикс, Инк. | Модифицированные нуклеозиды, нуклеотиды и нуклеиновые кислоты и их применение |
| US8999950B2 (en) | 2011-10-05 | 2015-04-07 | Protiva Biotherapeutics Inc. | Compositions and methods for silencing aldehyde dehydrogenase |
| KR102451116B1 (ko) | 2011-10-27 | 2022-10-06 | 메사추세츠 인스티튜트 오브 테크놀로지 | 약물 캡슐화 마이크로스피어를 형성할 수 있는, n-말단 상에 관능화된 아미노산 유도체 |
| US20140378538A1 (en) | 2011-12-14 | 2014-12-25 | Moderma Therapeutics, Inc. | Methods of responding to a biothreat |
| WO2013090186A1 (en) | 2011-12-14 | 2013-06-20 | modeRNA Therapeutics | Modified nucleic acids, and acute care uses thereof |
| CN104114572A (zh) | 2011-12-16 | 2014-10-22 | 现代治疗公司 | 经修饰的核苷、核苷酸和核酸组合物 |
| JP2015510495A (ja) | 2011-12-21 | 2015-04-09 | モデルナ セラピューティクス インコーポレイテッドModerna Therapeutics,Inc. | 器官または器官移植片の生存可能性または寿命を延長する方法 |
| EP2797634A4 (en) | 2011-12-29 | 2015-08-05 | Moderna Therapeutics Inc | MODIFIED MRNAS FOR THE CODING OF CELL-PENETRATING POLYPEPTIDES |
| SG11201405157PA (en) | 2012-02-24 | 2014-10-30 | Protiva Biotherapeutics Inc | Trialkyl cationic lipids and methods of use thereof |
| ES2762873T3 (es) | 2012-03-29 | 2020-05-26 | Translate Bio Inc | Lípidos catiónicos ionizables |
| US9254311B2 (en) | 2012-04-02 | 2016-02-09 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins |
| US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
| CA2868391A1 (en) | 2012-04-02 | 2013-10-10 | Stephane Bancel | Polynucleotides comprising n1-methyl-pseudouridine and methods for preparing the same |
| US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
| US20140275229A1 (en) | 2012-04-02 | 2014-09-18 | Moderna Therapeutics, Inc. | Modified polynucleotides encoding udp glucuronosyltransferase 1 family, polypeptide a1 |
| AU2013243948A1 (en) | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins associated with human disease |
| US20150050354A1 (en) | 2012-04-02 | 2015-02-19 | Moderna Therapeutics, Inc. | Modified polynucleotides for the treatment of otic diseases and conditions |
| EP2882706A1 (en) | 2012-08-13 | 2015-06-17 | Massachusetts Institute of Technology | Amine-containing lipidoids and uses thereof |
| WO2014081507A1 (en) | 2012-11-26 | 2014-05-30 | Moderna Therapeutics, Inc. | Terminally modified rna |
| EP4331620A3 (en) | 2012-12-07 | 2024-12-04 | Translate Bio, Inc. | Lipidic nanoparticles for mrna delivery |
| WO2014093574A1 (en) | 2012-12-13 | 2014-06-19 | Moderna Therapeutics, Inc. | Modified polynucleotides for altering cell phenotype |
| US20140200261A1 (en) | 2013-01-17 | 2014-07-17 | Moderna Therapeutics, Inc. | Signal-sensor polynucleotides for the alteration of cellular phenotypes |
| JP5991937B2 (ja) | 2013-03-06 | 2016-09-14 | Jxエネルギー株式会社 | 摩擦調整剤および潤滑油組成物 |
| US20160022774A1 (en) | 2013-03-12 | 2016-01-28 | Moderna Therapeutics, Inc. | Diagnosis and treatment of fibrosis |
| EP2968391A1 (en) | 2013-03-13 | 2016-01-20 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
| EP2971010B1 (en) | 2013-03-14 | 2020-06-10 | ModernaTX, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
| WO2014144767A1 (en) | 2013-03-15 | 2014-09-18 | Moderna Therapeutics, Inc. | Ion exchange purification of mrna |
| WO2014152031A1 (en) | 2013-03-15 | 2014-09-25 | Moderna Therapeutics, Inc. | Ribonucleic acid purification |
| WO2014152030A1 (en) | 2013-03-15 | 2014-09-25 | Moderna Therapeutics, Inc. | Removal of dna fragments in mrna production process |
| WO2014144711A1 (en) | 2013-03-15 | 2014-09-18 | Moderna Therapeutics, Inc. | Analysis of mrna heterogeneity and stability |
| US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
| US20160032273A1 (en) | 2013-03-15 | 2016-02-04 | Moderna Therapeutics, Inc. | Characterization of mrna molecules |
| WO2014152027A1 (en) | 2013-03-15 | 2014-09-25 | Moderna Therapeutics, Inc. | Manufacturing methods for production of rna transcripts |
| WO2014179562A1 (en) | 2013-05-01 | 2014-11-06 | Massachusetts Institute Of Technology | 1,3,5-triazinane-2,4,6-trione derivatives and uses thereof |
| US9895443B2 (en) | 2013-06-26 | 2018-02-20 | Massachusetts Institute Of Technology | Multi-tailed lipids and uses thereof |
| SMT202100691T1 (it) | 2013-07-11 | 2022-01-10 | Modernatx Inc | Composizioni 5 comprendenti polinucleotidi sintetici che codificano proteine correlate a crispr e sgrna sintetici e metodi d'uso |
| WO2015011633A1 (en) | 2013-07-23 | 2015-01-29 | Protiva Biotherapeutics, Inc. | Compositions and methods for delivering messenger rna |
| US20160194368A1 (en) | 2013-09-03 | 2016-07-07 | Moderna Therapeutics, Inc. | Circular polynucleotides |
| US20160194625A1 (en) | 2013-09-03 | 2016-07-07 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
| US10023626B2 (en) | 2013-09-30 | 2018-07-17 | Modernatx, Inc. | Polynucleotides encoding immune modulating polypeptides |
| WO2015051169A2 (en) | 2013-10-02 | 2015-04-09 | Moderna Therapeutics, Inc. | Polynucleotide molecules and uses thereof |
| EP3052479A4 (en) | 2013-10-02 | 2017-10-25 | Moderna Therapeutics, Inc. | Polynucleotide molecules and uses thereof |
| KR101355583B1 (ko) | 2013-10-04 | 2014-01-24 | 한국지질자원연구원 | 간이 유용광물 분리 장치 및 이를 이용한 유용광물 분리 방법 |
| AU2014337156A1 (en) | 2013-10-18 | 2016-05-12 | Modernatx, Inc. | Compositions and methods for tolerizing cellular systems |
| BR112017006679A2 (pt) | 2014-10-02 | 2017-12-26 | Protiva Biotherapeutics Inc | moléculas, composição, partícula, composição farmacêutica, métodos para silenciar a expressão de um gene, usos de uma partícula, métodos para melhorar um ou mais sintomas, métodos para tratar uma infecção, usos de uma composição, método para inibir a replicação do vírus da hepatite d |
| WO2016071857A1 (en) | 2014-11-07 | 2016-05-12 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing ebola virus expression |
| WO2016077123A1 (en) | 2014-11-10 | 2016-05-19 | Moderna Therapeutics, Inc. | Multiparametric nucleic acid optimization |
| EP3461904A1 (en) | 2014-11-10 | 2019-04-03 | ModernaTX, Inc. | Alternative nucleic acid molecules containing reduced uracil content and uses thereof |
| US20180000953A1 (en) | 2015-01-21 | 2018-01-04 | Moderna Therapeutics, Inc. | Lipid nanoparticle compositions |
| WO2016118725A1 (en) | 2015-01-23 | 2016-07-28 | Moderna Therapeutics, Inc. | Lipid nanoparticle compositions |
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