CA2984026C - Improved amino lipids and methods for the delivery of nucleic acids - Google Patents
Improved amino lipids and methods for the delivery of nucleic acids Download PDFInfo
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- CA2984026C CA2984026C CA2984026A CA2984026A CA2984026C CA 2984026 C CA2984026 C CA 2984026C CA 2984026 A CA2984026 A CA 2984026A CA 2984026 A CA2984026 A CA 2984026A CA 2984026 C CA2984026 C CA 2984026C
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- lipid
- dma
- dlin
- nucleic acid
- sirna
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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| US10421908P | 2008-10-09 | 2008-10-09 | |
| US10421208P | 2008-10-09 | 2008-10-09 | |
| US61/104,212 | 2008-10-09 | ||
| US61/104,219 | 2008-10-09 | ||
| US22066609P | 2009-06-26 | 2009-06-26 | |
| US61/220,666 | 2009-06-26 | ||
| CA2740000A CA2740000C (en) | 2008-10-09 | 2009-10-09 | Improved amino lipids and methods for the delivery of nucleic acids |
Related Parent Applications (1)
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| CA2740000A Division CA2740000C (en) | 2008-10-09 | 2009-10-09 | Improved amino lipids and methods for the delivery of nucleic acids |
Publications (2)
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| CA2984026A1 CA2984026A1 (en) | 2010-04-15 |
| CA2984026C true CA2984026C (en) | 2020-02-11 |
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| CA2984026A Expired - Fee Related CA2984026C (en) | 2008-10-09 | 2009-10-09 | Improved amino lipids and methods for the delivery of nucleic acids |
| CA2740000A Expired - Fee Related CA2740000C (en) | 2008-10-09 | 2009-10-09 | Improved amino lipids and methods for the delivery of nucleic acids |
Family Applications After (1)
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| CA2740000A Expired - Fee Related CA2740000C (en) | 2008-10-09 | 2009-10-09 | Improved amino lipids and methods for the delivery of nucleic acids |
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| US (2) | US9139554B2 (OSRAM) |
| EP (3) | EP2743265B1 (OSRAM) |
| JP (5) | JP5777519B2 (OSRAM) |
| CN (2) | CN102245590B (OSRAM) |
| AU (1) | AU2009303345B2 (OSRAM) |
| CA (2) | CA2984026C (OSRAM) |
| ES (1) | ES2475065T3 (OSRAM) |
| PL (1) | PL2350043T3 (OSRAM) |
| WO (1) | WO2010042877A1 (OSRAM) |
Families Citing this family (564)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9228186B2 (en) | 2002-11-14 | 2016-01-05 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
| EP3067046B1 (en) | 2005-12-08 | 2020-03-25 | Insmed Incorporated | Lipid-based compositions of antiinfectives for treating pulmonary infections |
| US9119783B2 (en) | 2007-05-07 | 2015-09-01 | Insmed Incorporated | Method of treating pulmonary disorders with liposomal amikacin formulations |
| WO2009017802A1 (en) | 2007-08-01 | 2009-02-05 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Nitro-fattyacid modulation of type ii diabetes |
| ES2535419T3 (es) | 2007-12-27 | 2015-05-11 | Protiva Biotherapeutics Inc. | Silenciamiento de expresión de quinasa tipo polo usando ARN interferente |
| ES2638448T3 (es) | 2008-04-15 | 2017-10-20 | Protiva Biotherapeutics Inc. | Novedosas formulaciones de lípidos para la administración de ácidos nucleicos |
| US20090326070A1 (en) | 2008-05-01 | 2009-12-31 | Complexa Inc. | Vinyl substituted fatty acids |
| CN102099024B (zh) | 2008-06-19 | 2015-11-25 | 犹他大学研究基金会 | 硝化脂质在毒性医疗疗法的副作用的治疗上的用途 |
| US20140024713A1 (en) | 2008-06-19 | 2014-01-23 | University Of Utah Research Foundation | Use of nitrated lipids for treatment of side effects of toxic medical therapies |
| EP2743265B1 (en) * | 2008-10-09 | 2017-03-15 | Arbutus Biopharma Corporation | Improved amino lipids and methods for the delivery of nucleic acids |
| AU2015249072C1 (en) * | 2008-10-20 | 2022-10-27 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of transthyretin |
| PT2937418T (pt) * | 2008-10-20 | 2018-01-23 | Alnylam Pharmaceuticals Inc | Composições e métodos de inibição da expressão de transtirretina |
| US8969353B2 (en) | 2008-11-07 | 2015-03-03 | Massachusetts Institute Of Technology | Aminoalcohol lipidoids and uses thereof |
| EA037404B1 (ru) | 2008-11-10 | 2021-03-24 | Арбутус Биофарма Корпорэйшн | Липиды и композиции для доставки лекарственных средств |
| WO2010054384A1 (en) | 2008-11-10 | 2010-05-14 | Alnylam Pharmaceuticals, Inc. | Lipids and compositions for the delivery of therapeutics |
| US20100233270A1 (en) | 2009-01-08 | 2010-09-16 | Northwestern University | Delivery of Oligonucleotide-Functionalized Nanoparticles |
| EP2391343B1 (en) * | 2009-01-29 | 2017-03-01 | Arbutus Biopharma Corporation | Improved lipid formulation for the delivery of nucleic acids |
| NZ594995A (en) * | 2009-03-12 | 2013-06-28 | Alnylam Pharmaceuticals Inc | LIPID FORMULATED COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF HUMAN KINESIN FAMILY MEMBER 11 (Eg5) AND VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) GENES |
| AU2010245933B2 (en) * | 2009-05-05 | 2016-06-16 | Arbutus Biopharma Corporation | Methods of delivering oligonucleotides to immune cells |
| HRP20211619T1 (hr) * | 2009-06-10 | 2022-02-04 | Arbutus Biopharma Corporation | Poboljšana formulacija lipida |
| US9051567B2 (en) | 2009-06-15 | 2015-06-09 | Tekmira Pharmaceuticals Corporation | Methods for increasing efficacy of lipid formulated siRNA |
| NZ597504A (en) * | 2009-06-15 | 2013-10-25 | Alnylam Pharmaceuticals Inc | Lipid formulated dsrna targeting the pcsk9 gene |
| CA2767129C (en) | 2009-07-01 | 2015-01-06 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein b |
| JP5766188B2 (ja) | 2009-07-01 | 2015-08-19 | プロチバ バイオセラピューティクス インコーポレイティッド | 固形腫瘍に治療剤を送達するための脂質製剤 |
| US8716464B2 (en) | 2009-07-20 | 2014-05-06 | Thomas W. Geisbert | Compositions and methods for silencing Ebola virus gene expression |
| JP2013500966A (ja) | 2009-07-31 | 2013-01-10 | ユニバーシティー オブ ピッツバーグ − オブ ザ コモンウェルス システム オブ ハイヤー エデュケーション | 抗炎症剤としての脂肪酸 |
| US9181295B2 (en) | 2009-08-20 | 2015-11-10 | Sirna Therapeutics, Inc. | Cationic lipids with various head groups for oligonucleotide delivery |
| EP2480668A2 (en) | 2009-09-23 | 2012-08-01 | Protiva Biotherapeutics Inc. | Compositions and methods for silencing genes expressed in cancer |
| CA2781276A1 (en) | 2009-10-02 | 2011-04-07 | Complexa, Inc. | Heteroatom containing substituted fatty acids |
| EP2496238A4 (en) * | 2009-11-03 | 2013-10-02 | Alnylam Pharmaceuticals Inc | FORMULATED LIPID COMPOSITIONS AND METHODS FOR INHIBITING TRANSTHYRETIN EXPRESSION (TTR) |
| DK3338765T3 (en) | 2009-12-01 | 2019-03-04 | Translate Bio Inc | STEROID DERIVATIVE FOR THE SUPPLY OF MRNA IN HUMANGENETIC DISEASES |
| WO2011088309A1 (en) | 2010-01-14 | 2011-07-21 | Regulus Therapeutics Inc. | Microrna compositions and methods |
| EP2525781A1 (en) | 2010-01-22 | 2012-11-28 | Schering Corporation | Novel cationic lipids for oligonucleotide delivery |
| US20130037977A1 (en) | 2010-04-08 | 2013-02-14 | Paul A. Burke | Preparation of Lipid Nanoparticles |
| JP5902617B2 (ja) * | 2010-04-28 | 2016-04-13 | 協和発酵キリン株式会社 | カチオン性脂質 |
| US9408914B2 (en) | 2010-04-28 | 2016-08-09 | Kyowa Hakko Kirin Co., Ltd. | Cationic lipid |
| US10077232B2 (en) | 2010-05-12 | 2018-09-18 | Arbutus Biopharma Corporation | Cyclic cationic lipids and methods of use |
| US8865675B2 (en) | 2010-05-12 | 2014-10-21 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein B |
| EP2569276B1 (en) | 2010-05-12 | 2021-02-24 | Arbutus Biopharma Corporation | Novel cationic lipids and methods of use thereof |
| JP2013531634A (ja) | 2010-05-24 | 2013-08-08 | メルク・シャープ・エンド・ドーム・コーポレイション | オリゴヌクレオチド送達のための新規なアミノアルコールカチオン性脂質 |
| MX341332B (es) | 2010-06-03 | 2016-08-16 | Alnylam Pharmaceuticals Inc | Lipidos biodegradables para la administracion de agentes activos. |
| WO2012000104A1 (en) | 2010-06-30 | 2012-01-05 | Protiva Biotherapeutics, Inc. | Non-liposomal systems for nucleic acid delivery |
| ES2557382T3 (es) * | 2010-07-06 | 2016-01-25 | Glaxosmithkline Biologicals Sa | Liposomas con lípidos que tienen un valor de pKa ventajoso para el suministro de ARN |
| PL3243526T3 (pl) | 2010-07-06 | 2020-05-18 | Glaxosmithkline Biologicals S.A. | Dostarczanie rna w celu wyzwolenia wielu szlaków immunologicznych |
| FI4005592T3 (fi) | 2010-07-06 | 2023-01-13 | Virionin kaltaisia kuljetuspartikkeleita itsereplikoituville rna-molekyyleille | |
| PL2591114T3 (pl) | 2010-07-06 | 2017-08-31 | Glaxosmithkline Biologicals Sa | Immunizacja dużych ssaków małymi dawkami rna |
| WO2012016184A2 (en) * | 2010-07-30 | 2012-02-02 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for delivery of active agents |
| EP3578205A1 (en) | 2010-08-06 | 2019-12-11 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
| RU2624045C2 (ru) | 2010-08-17 | 2017-06-30 | Сирна Терапьютикс,Инк | ОПОСРЕДУЕМОЕ РНК-ИНТЕРФЕРЕНЦИЕЙ ИНГИБИРОВАНИЕ ЭКСПРЕССИИ ГЕНОВ ВИРУСА ГЕПАТИТА B (HBV) С ПРИМЕНЕНИЕМ МАЛОЙ ИНТЕРФЕРИРУЮЩЕЙ НУКЛЕИНОВОЙ КИСЛОТЫ (миНК) |
| US9233997B2 (en) | 2010-08-26 | 2016-01-12 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of prolyl hydroxylase domain 2 (PHD2) gene expression using short interfering nucleic acid (siNA) |
| EP2609135A4 (en) | 2010-08-26 | 2015-05-20 | Massachusetts Inst Technology | POLY (BETA AMINO ALCOHOLS), THEIR PREPARATION AND USES THEREOF |
| HUE061068T2 (hu) | 2010-08-31 | 2023-05-28 | Glaxosmithkline Biologicals Sa | Pegilált liposzómák immunogént kódoló RNS szállítására |
| EP3406730B1 (en) | 2010-08-31 | 2022-02-23 | Sirna Therapeutics, Inc. | Novel single chemical entities and methods for delivery of oligonucleotides |
| US9549901B2 (en) | 2010-09-03 | 2017-01-24 | The Brigham And Women's Hospital, Inc. | Lipid-polymer hybrid particles |
| US8466122B2 (en) | 2010-09-17 | 2013-06-18 | Protiva Biotherapeutics, Inc. | Trialkyl cationic lipids and methods of use thereof |
| BR112013004585B1 (pt) | 2010-09-20 | 2021-09-08 | Merck Sharp & Dohme Corp | Lipídeo catiônico, composição de lnp, e, uso de um lipídeo catiônico |
| JP2013545723A (ja) | 2010-09-30 | 2013-12-26 | メルク・シャープ・エンド・ドーム・コーポレイション | オリゴヌクレオチドの送達のための低分子量カチオン性脂質 |
| CN103429606A (zh) | 2010-10-01 | 2013-12-04 | 现代治疗公司 | 设计核酸及其使用方法 |
| EP4098324A1 (en) | 2010-10-11 | 2022-12-07 | GlaxoSmithKline Biologicals S.A. | Antigen delivery platforms |
| EP2629802B1 (en) | 2010-10-21 | 2019-12-04 | Sirna Therapeutics, Inc. | Low molecular weight cationic lipids for oligonucleotide delivery |
| EP3327125B1 (en) | 2010-10-29 | 2020-08-05 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of gene expression using short interfering nucleic acids (sina) |
| WO2012061259A2 (en) | 2010-11-05 | 2012-05-10 | Merck Sharp & Dohme Corp. | Novel low molecular weight cyclic amine containing cationic lipids for oligonucleotide delivery |
| US8853377B2 (en) | 2010-11-30 | 2014-10-07 | 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 |
| CA2831613A1 (en) | 2011-03-31 | 2012-10-04 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
| JP6184945B2 (ja) | 2011-06-08 | 2017-08-23 | 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 | ｍＲＮＡ送達のための脂質ナノ粒子組成物および方法 |
| ES2987057T3 (es) | 2011-06-08 | 2024-11-13 | Translate Bio Inc | Lípidos escindibles |
| CA2840989A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Immunogenic combination compositions and uses thereof |
| EP4115875A1 (en) | 2011-07-06 | 2023-01-11 | GlaxoSmithKline Biologicals S.A. | Liposomes having useful n:p ratio for delivery of rna molecules |
| WO2013028501A1 (en) | 2011-08-19 | 2013-02-28 | The University Of Utah Research Foundation | Combination therapy with nitrated lipids and inhibitors of the renin-angiotensin-aldosterone system |
| US9126966B2 (en) * | 2011-08-31 | 2015-09-08 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods of use thereof |
| US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| KR20190099538A (ko) | 2011-10-03 | 2019-08-27 | 모더나 세라퓨틱스, 인코포레이티드 | 변형된 뉴클레오사이드, 뉴클레오타이드, 및 핵산, 및 이들의 용도 |
| US9271952B2 (en) * | 2011-10-11 | 2016-03-01 | Complexa, Inc. | Compositions and methods for treating nephropathy |
| EA032088B1 (ru) | 2011-10-27 | 2019-04-30 | Массачусетс Инститьют Оф Текнолоджи | Аминокислотные производные, функционализованные на n-конце, способные образовывать микросферы, инкапсулирующие лекарственное средство |
| PE20142362A1 (es) * | 2011-11-18 | 2015-01-30 | Alnylam Pharmaceuticals Inc | Agentes de iarn, composiciones y metodos de uso de los mismos para tratar enfermedades asociadas con transtiretina (ttr) |
| US9061063B2 (en) | 2011-12-07 | 2015-06-23 | Alnylam Pharmaceuticals, Inc. | Biodegradable lipids for the delivery of active agents |
| US20140308304A1 (en) | 2011-12-07 | 2014-10-16 | Alnylam Pharmaceuticals, Inc. | Lipids for the delivery of active agents |
| AU2012347605B2 (en) * | 2011-12-07 | 2017-09-21 | Alnylam Pharmaceuticals, Inc. | Branched alkyl and cycloalkyl terminated biodegradable lipids for the delivery of active agents |
| EP4144378A1 (en) | 2011-12-16 | 2023-03-08 | ModernaTX, Inc. | Modified nucleoside, nucleotide, and nucleic acid compositions |
| US9035039B2 (en) | 2011-12-22 | 2015-05-19 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing SMAD4 |
| RU2624732C2 (ru) | 2012-01-27 | 2017-07-06 | Ф.Хоффманн-Ля Рош Аг | Конъюгаты антагонистов интегрина для нацеленной доставки к клеткам, экспрессирующим lfa-1 |
| CN104039356B (zh) | 2012-01-27 | 2018-08-17 | 弗·哈夫曼-拉罗切有限公司 | 用于靶向递送的、与小分子整联蛋白拮抗剂共价连接的壳聚糖 |
| BR112014016736A8 (pt) | 2012-01-27 | 2017-07-04 | Hoffmann La Roche | composto, composição farmacêutica, método para tratamento, uso de um composto e invenção |
| BR112014013135A2 (pt) | 2012-01-27 | 2017-12-05 | Hoffmann La Roche | composto, composição farmacêutica, método para o tratamento da inflamação, uso de um composto e invenção |
| SI2817287T1 (sl) | 2012-02-24 | 2019-02-28 | Arbutus Biopharma Corporation | Trialkilni kationski lipidi in postopki za njihovo uporabo |
| CN102600173B (zh) * | 2012-03-02 | 2013-05-29 | 海南美兰史克制药有限公司 | 氨氯地平/贝那普利药物组合物脂质体固体制剂 |
| US10322089B2 (en) * | 2012-03-14 | 2019-06-18 | The Board Of Trustees Of The Leland Stanford Junior University | Nanoparticles, nanoparticle delivery methods, and systems of delivery |
| WO2013143555A1 (en) * | 2012-03-26 | 2013-10-03 | Biontech Ag | Rna formulation for immunotherapy |
| ES2762873T3 (es) | 2012-03-29 | 2020-05-26 | Translate Bio Inc | Lípidos catiónicos ionizables |
| CA2868030C (en) | 2012-03-29 | 2021-05-25 | Shire Human Genetic Therapies, Inc. | Lipid-derived neutral nanoparticles |
| AU2013243954A1 (en) * | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
| US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
| US9254311B2 (en) | 2012-04-02 | 2016-02-09 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins |
| US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
| US10501513B2 (en) | 2012-04-02 | 2019-12-10 | Modernatx, Inc. | Modified polynucleotides for the production of oncology-related proteins and peptides |
| AU2013243949A1 (en) * | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of biologics and proteins associated with human disease |
| EP2838877B1 (en) | 2012-04-19 | 2018-09-12 | Sirna Therapeutics, Inc. | Novel diester and triester based low molecular weight, biodegradable cationic lipids for oligonucleotide delivery |
| WO2013163628A2 (en) | 2012-04-27 | 2013-10-31 | Duke University | Genetic correction of mutated genes |
| US10245229B2 (en) | 2012-06-08 | 2019-04-02 | Translate Bio, Inc. | Pulmonary delivery of mRNA to non-lung target cells |
| EP3536787A1 (en) | 2012-06-08 | 2019-09-11 | Translate Bio, Inc. | Nuclease resistant polynucleotides and uses thereof |
| TW201726599A (zh) | 2012-07-06 | 2017-08-01 | 協和醱酵麒麟有限公司 | 陽離子性脂質 |
| US9415109B2 (en) | 2012-07-06 | 2016-08-16 | Alnylam Pharmaceuticals, Inc. | Stable non-aggregating nucleic acid lipid particle formulations |
| EP2882706A1 (en) | 2012-08-13 | 2015-06-17 | Massachusetts Institute of Technology | Amine-containing lipidoids and uses thereof |
| US9512456B2 (en) | 2012-08-14 | 2016-12-06 | Modernatx, Inc. | Enzymes and polymerases for the synthesis of RNA |
| DK2922554T3 (en) | 2012-11-26 | 2022-05-23 | Modernatx Inc | Terminalt modificeret rna |
| US10124066B2 (en) | 2012-11-29 | 2018-11-13 | Insmed Incorporated | Stabilized vancomycin formulations |
| EP4331620A3 (en) | 2012-12-07 | 2024-12-04 | Translate Bio, Inc. | Lipidic nanoparticles for mrna delivery |
| EP2971010B1 (en) | 2013-03-14 | 2020-06-10 | ModernaTX, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
| IL305374A (en) | 2013-03-14 | 2023-10-01 | Ethris Gmbh | Cftr mrna compositions and related methods and uses |
| EA201591293A1 (ru) | 2013-03-14 | 2016-02-29 | Шир Хьюман Дженетик Терапис, Инк. | Способы и композиции для доставки антител, кодируемых мрнк |
| JP6586075B2 (ja) | 2013-03-14 | 2019-10-02 | トランスレイト バイオ， インコーポレイテッド | メッセンジャーｒｎａの精製方法 |
| ES3032013T3 (en) | 2013-03-15 | 2025-07-14 | Translate Bio Inc | Synergistic enhancement of the delivery of nucleic acids via blended formulations |
| US8980864B2 (en) * | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
| US9828582B2 (en) | 2013-03-19 | 2017-11-28 | Duke University | Compositions and methods for the induction and tuning of gene expression |
| WO2014179562A1 (en) | 2013-05-01 | 2014-11-06 | Massachusetts Institute Of Technology | 1,3,5-triazinane-2,4,6-trione derivatives and uses thereof |
| TW201534578A (zh) | 2013-07-08 | 2015-09-16 | Daiichi Sankyo Co Ltd | 新穎脂質 |
| US10023626B2 (en) | 2013-09-30 | 2018-07-17 | Modernatx, Inc. | Polynucleotides encoding immune modulating polypeptides |
| BR112016007255A2 (pt) | 2013-10-03 | 2017-09-12 | Moderna Therapeutics Inc | polinucleotídeos que codificam receptor de lipoproteína de baixa densidade |
| WO2015061461A1 (en) | 2013-10-22 | 2015-04-30 | Shire Human Genetic Therapies, Inc. | Cns delivery of mrna and uses thereof |
| AU2014340155B2 (en) | 2013-10-22 | 2018-11-01 | Massachusetts Institute Of Technology | Lipid formulations for delivery of messenger RNA |
| BR112016009014B1 (pt) | 2013-10-22 | 2024-02-06 | Translate Bio, Inc | USO DE COMPOSIÇÃO COMPREENDENDO mRNA PARA DEFICIÊNCIA DE ARGININOSSUCINATO SINTETASE |
| EA034103B1 (ru) | 2013-10-22 | 2019-12-27 | Транслейт Био, Инк. | СПОСОБ ЛЕЧЕНИЯ ФЕНИЛКЕТОНУРИИ С ПРИМЕНЕНИЕМ мРНК |
| AU2014351482B2 (en) | 2013-11-22 | 2020-08-20 | Mina Therapeutics Limited | C/EBP alpha short activating RNA compositions and methods of use |
| CN105939699B (zh) | 2013-12-03 | 2020-10-02 | 西北大学 | 脂质体颗粒、制备所述脂质体颗粒的方法以及其用途 |
| JP6389477B2 (ja) * | 2014-01-09 | 2018-09-12 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | カチオン性脂質 |
| EP3556353A3 (en) | 2014-02-25 | 2020-03-18 | Merck Sharp & Dohme Corp. | Lipid nanoparticle vaccine adjuvants and antigen delivery systems |
| ES2774552T3 (es) | 2014-03-24 | 2020-07-21 | Translate Bio Inc | Terapia de ARNm para el tratamiento de enfermedades oculares |
| PT3981437T (pt) | 2014-04-23 | 2025-01-15 | Modernatx Inc | Vacinas de ácidos nucleicos |
| MX373952B (es) | 2014-04-25 | 2020-07-13 | Shire Human Genetic Therapies | Métodos de purificación de arn mensajero. |
| CN106535877A (zh) | 2014-05-15 | 2017-03-22 | 英斯梅德股份有限公司 | 用于治疗肺部非结核性分枝杆菌感染的方法 |
| CN105085292B (zh) * | 2014-05-23 | 2017-12-15 | 上海交通大学 | 3‑((2‑(二甲氨基)乙烷基)(甲基)氨基)丙酸的两亲性衍生物及其用途 |
| CN105085295A (zh) * | 2014-05-23 | 2015-11-25 | 上海交通大学 | 氨甲环酸的两亲性衍生物及其用途 |
| MA48050A (fr) | 2014-05-30 | 2020-02-12 | Translate Bio Inc | Lipides biodégradables pour l'administration d'acides nucléiques |
| US10434064B2 (en) | 2014-06-04 | 2019-10-08 | Exicure, Inc. | Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications |
| EA033966B1 (ru) | 2014-06-24 | 2019-12-13 | Транслейт Био, Инк. | Стереохимически обогащенные композиции для доставки нуклеиновых кислот |
| HUE060907T2 (hu) * | 2014-06-25 | 2023-04-28 | Acuitas Therapeutics Inc | Új lipidek és lipid nanorészecske formulációk nukleinsavak bevitelére |
| TW201619137A (zh) | 2014-06-30 | 2016-06-01 | 協和醱酵麒麟有限公司 | 陽離子性脂質 |
| US9840479B2 (en) | 2014-07-02 | 2017-12-12 | Massachusetts Institute Of Technology | Polyamine-fatty acid derived lipidoids and uses thereof |
| AU2015283954B2 (en) | 2014-07-02 | 2020-11-12 | Translate Bio, Inc. | Encapsulation of messenger RNA |
| GB201414464D0 (en) | 2014-08-14 | 2014-10-01 | Technion Res & Dev Foundation | Compositions and methods for therapeutics prescreening |
| CN106794256B (zh) | 2014-08-19 | 2021-04-30 | 西北大学 | 蛋白质/寡核苷酸核-壳纳米颗粒治疗剂 |
| DK3185957T3 (da) | 2014-08-29 | 2022-08-29 | Alnylam Pharmaceuticals Inc | Patisiran til anvendelse ved behandlingen af transthyretin-medieret amyloidosis |
| ES2861597T3 (es) | 2014-12-05 | 2021-10-06 | Translate Bio Inc | Terapia de ARN mensajero para el tratamiento de enfermedad articular |
| JP6929791B2 (ja) | 2015-02-09 | 2021-09-01 | デューク ユニバーシティ | エピゲノム編集のための組成物および方法 |
| EP3900702A1 (en) | 2015-03-19 | 2021-10-27 | Translate Bio, Inc. | Mrna therapy for pompe disease |
| JP6910947B2 (ja) * | 2015-03-24 | 2021-07-28 | 協和キリン株式会社 | 核酸含有脂質ナノ粒子 |
| SG11201707663SA (en) | 2015-04-17 | 2017-11-29 | Curevac Ag | Lyophilization of rna |
| CA2984125A1 (en) | 2015-04-27 | 2016-11-03 | The Trustees Of The University Of Pennsylvania | Nucleoside-modified rna for inducing an adaptive immune response |
| HK1251010A1 (zh) | 2015-05-06 | 2019-01-18 | Benitec IP Holdings Inc. | 用於治疗乙型肝炎病毒(hbv)感染的试剂及用途 |
| CN104803863B (zh) * | 2015-05-08 | 2016-07-20 | 厦门成坤生物技术有限公司 | 阳离子类脂化合物及其制备方法 |
| SG11201708541QA (en) | 2015-05-20 | 2017-12-28 | Curevac Ag | Dry powder composition comprising long-chain rna |
| SG11201708540VA (en) | 2015-05-20 | 2017-12-28 | Curevac Ag | Dry powder composition comprising long-chain rna |
| CN107848988B (zh) | 2015-06-19 | 2021-10-22 | 麻省理工学院 | 烯基取代的2,5-哌嗪二酮和其在组合物中用于向个体或细胞递送药剂的用途 |
| US10221127B2 (en) | 2015-06-29 | 2019-03-05 | Acuitas Therapeutics, Inc. | Lipids and lipid nanoparticle formulations for delivery of nucleic acids |
| HRP20210543T1 (hr) | 2015-07-07 | 2021-05-14 | H. Lundbeck A/S | Inhibitori pde9 s imidazo triazinonskom okosnicom i imidazo pirazinonskom okosnicom za liječenje perifernih bolesti |
| JP6884714B2 (ja) * | 2015-07-09 | 2021-06-09 | インスメッド インコーポレイテッド | 肺疾患及び肺損傷を治療するための組成物及び方法 |
| US11364292B2 (en) | 2015-07-21 | 2022-06-21 | Modernatx, Inc. | CHIKV RNA vaccines |
| TW201718638A (zh) | 2015-07-21 | 2017-06-01 | 現代治療公司 | 傳染病疫苗 |
| ES2842300T3 (es) | 2015-07-31 | 2021-07-13 | Alnylam Pharmaceuticals Inc | Composiciones de ARNi de transtiretina (TTR) y métodos para su uso para el tratamiento o la prevención de enfermedades asociadas con TTR |
| US11564893B2 (en) | 2015-08-17 | 2023-01-31 | Modernatx, Inc. | Methods for preparing particles and related compositions |
| CA2995995A1 (en) | 2015-08-24 | 2017-03-02 | Halo-Bio Rnai Therapeutics, Inc. | Polynucleotide nanoparticles for the modulation of gene expression and uses thereof |
| SMT202200178T1 (it) | 2015-09-17 | 2022-05-12 | Modernatx Inc | Composti e composizioni per il rilascio intracellulare di agenti terapeutici |
| CN108430466A (zh) | 2015-10-02 | 2018-08-21 | 康普莱克夏公司 | 使用治疗有效量的活化脂肪酸预防、治疗和逆转疾病 |
| JP6990176B2 (ja) | 2015-10-05 | 2022-02-03 | モデルナティエックス インコーポレイテッド | メッセンジャーリボ核酸薬物の治療投与のための方法 |
| WO2017066497A2 (en) | 2015-10-13 | 2017-04-20 | Duke University | Genome engineering with type i crispr systems in eukaryotic cells |
| AU2016338559B2 (en) | 2015-10-14 | 2022-11-24 | Translate Bio, Inc. | Modification of RNA-related enzymes for enhanced production |
| MA45209A (fr) | 2015-10-22 | 2019-04-17 | Modernatx Inc | Vaccins contre les maladies sexuellement transmissibles |
| US11643441B1 (en) | 2015-10-22 | 2023-05-09 | Modernatx, Inc. | Nucleic acid vaccines for varicella zoster virus (VZV) |
| EP3718565B1 (en) | 2015-10-22 | 2022-04-27 | ModernaTX, Inc. | Respiratory virus vaccines |
| JP6921833B2 (ja) | 2015-10-22 | 2021-08-18 | モデルナティーエックス， インコーポレイテッド | ヒトサイトメガロウイルスワクチン |
| WO2017070624A1 (en) | 2015-10-22 | 2017-04-27 | Modernatx, Inc. | Tropical disease vaccines |
| IL307179A (en) | 2015-10-28 | 2023-11-01 | Acuitas Therapeutics Inc | Novel lipids and lipid nanoparticle formulations for delivery of nucleic acids |
| WO2017095967A2 (en) | 2015-11-30 | 2017-06-08 | Duke University | Therapeutic targets for the correction of the human dystrophin gene by gene editing and methods of use |
| PL3386484T3 (pl) | 2015-12-10 | 2022-07-25 | Modernatx, Inc. | Kompozycje i sposoby dostarczania środków terapeutycznych |
| CN106883158B (zh) * | 2015-12-15 | 2019-08-23 | 中国科学院广州生物医药与健康研究院 | 生物可降解的氨基脂质类化合物及其制备方法和应用 |
| PL3394030T3 (pl) | 2015-12-22 | 2022-04-11 | Modernatx, Inc. | Związki i kompozycje do wewnątrzkomórkowego dostarczania środków |
| CA3009131C (en) | 2015-12-25 | 2024-06-04 | Kyowa Hakko Kirin Co., Ltd. | Compounds as cationic lipids and their use in nucleic acid delivery compositions |
| CN105622473B (zh) * | 2016-02-06 | 2017-07-25 | 吴国球 | 一种阳离子氨基脂质及其合成方法和用途 |
| US20190046638A1 (en) | 2016-04-01 | 2019-02-14 | Checkmate Pharmaceuticals, Inc. | Fc RECEPTOR-MEDIATED DRUG DELIVERY |
| KR102475301B1 (ko) | 2016-04-08 | 2022-12-09 | 트랜슬레이트 바이오 인코포레이티드 | 다량체 코딩 핵산 및 그 용도 |
| US20190127713A1 (en) | 2016-04-13 | 2019-05-02 | Duke University | Crispr/cas9-based repressors for silencing gene targets in vivo and methods of use |
| CA3020754C (en) | 2016-04-14 | 2023-07-25 | Benitec Biopharma Limited | Reagents for treatment of oculopharyngeal muscular dystrophy (opmd) and use thereof |
| US11866700B2 (en) | 2016-05-06 | 2024-01-09 | Exicure Operating Company | Liposomal spherical nucleic acid (SNA) constructs presenting antisense oligonucleotides (ASO) for specific knockdown of interleukin 17 receptor mRNA |
| CN114656378A (zh) * | 2016-05-16 | 2022-06-24 | 得克萨斯州大学系统董事会 | 阳离子磺酰胺氨基脂质和两亲性两性离子氨基脂质 |
| PL3458074T3 (pl) * | 2016-05-16 | 2024-11-12 | Board Of Regents Of The University Of Texas System | KOMPOZYCJA DO DOSTARCZANIA tRNA W POSTACI NANOCZĄSTEK I SPOSOBY ICH STOSOWANIA |
| IL263079B2 (en) | 2016-05-18 | 2024-05-01 | Modernatx Inc | Polynucleotides encoding relaxin |
| EP3458107B1 (en) | 2016-05-18 | 2024-03-13 | ModernaTX, Inc. | Polynucleotides encoding jagged1 for the treatment of alagille syndrome |
| CN109312313A (zh) | 2016-06-13 | 2019-02-05 | 川斯勒佰尔公司 | 用于治疗鸟氨酸转氨甲酰酶缺乏症的信使rna疗法 |
| US10501416B2 (en) | 2016-06-24 | 2019-12-10 | Eisai R&D Management Co., Ltd. | Cationic lipid |
| WO2018006052A1 (en) * | 2016-06-30 | 2018-01-04 | Protiva Biotherapeutics, Inc. | Compositions and methods for delivering messenger rna |
| EP4275747A3 (en) | 2016-07-19 | 2024-01-24 | Duke University | Therapeutic applications of cpf1-based genome editing |
| AU2017314067A1 (en) | 2016-08-19 | 2018-12-20 | CureVac SE | RNA for cancer therapy |
| TW201815736A (zh) | 2016-09-27 | 2018-05-01 | 日商協和醱酵麒麟有限公司 | 作為陽離子性脂質之化合物 |
| TW201813632A (zh) * | 2016-09-28 | 2018-04-16 | 日商協和醱酵麒麟有限公司 | 含有核酸之脂質奈米粒子 |
| AU2017345766A1 (en) | 2016-10-21 | 2019-05-16 | Modernatx, Inc. | Human cytomegalovirus vaccine |
| US20190314486A1 (en) | 2016-10-21 | 2019-10-17 | Merck Sharp & Dohme Corp. | Influenza hemagglutinin protein vaccines |
| US12491261B2 (en) | 2016-10-26 | 2025-12-09 | Acuitas Therapeutics, Inc. | Lipid nanoparticle formulations |
| US11583504B2 (en) | 2016-11-08 | 2023-02-21 | Modernatx, Inc. | Stabilized formulations of lipid nanoparticles |
| WO2018089846A1 (en) | 2016-11-10 | 2018-05-17 | Translate Bio, Inc. | Subcutaneous delivery of messenger rna |
| MA46762A (fr) | 2016-11-10 | 2019-09-18 | Translate Bio Inc | Procédé amélioré de préparation de nanoparticules lipidiques chargées d'arnm |
| EP3538146A4 (en) | 2016-11-11 | 2020-07-15 | ModernaTX, Inc. | INFLUENZA VACCINE |
| US11542490B2 (en) | 2016-12-08 | 2023-01-03 | CureVac SE | RNAs for wound healing |
| US11103578B2 (en) | 2016-12-08 | 2021-08-31 | Modernatx, Inc. | Respiratory virus nucleic acid vaccines |
| JP2020501545A (ja) | 2016-12-08 | 2020-01-23 | キュアバック アーゲー | 肝疾患の処置または予防のためのｒｎａ |
| EP3558355A2 (en) | 2016-12-23 | 2019-10-30 | CureVac AG | Henipavirus vaccine |
| WO2018115527A2 (en) | 2016-12-23 | 2018-06-28 | Curevac Ag | Mers coronavirus vaccine |
| US11464847B2 (en) | 2016-12-23 | 2022-10-11 | Curevac Ag | Lassa virus vaccine |
| EP3565891B1 (en) | 2017-01-09 | 2023-04-12 | Whitehead Institute for Biomedical Research | Methods of altering gene expression by perturbing transcription factor multimers that structure regulatory loops |
| JP7317715B2 (ja) | 2017-01-11 | 2023-07-31 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | ジカウイルスに対する免疫応答を誘導するためのヌクレオシド改変ｒｎａ |
| MA47515A (fr) | 2017-02-16 | 2019-12-25 | Modernatx Inc | Compositions immunogènes très puissantes |
| EP3585417B1 (en) | 2017-02-27 | 2023-02-22 | Translate Bio, Inc. | Method of making a codon-optimized cftr mrna |
| MA47824A (fr) | 2017-03-07 | 2020-01-15 | Translate Bio Inc | Administration polyanionique d'acides nucléiques |
| AU2018234814B2 (en) | 2017-03-15 | 2022-06-30 | Modernatx, Inc. | Crystal forms of amino lipids |
| LT3596041T (lt) | 2017-03-15 | 2023-01-25 | Modernatx, Inc. | Terapinių medžiagų, skirtų intraląsteliniam tiekimui, junginys ir sudėtys |
| WO2018170270A1 (en) | 2017-03-15 | 2018-09-20 | Modernatx, Inc. | Varicella zoster virus (vzv) vaccine |
| WO2018170256A1 (en) | 2017-03-15 | 2018-09-20 | Modernatx, Inc. | Herpes simplex virus vaccine |
| WO2018170245A1 (en) | 2017-03-15 | 2018-09-20 | Modernatx, Inc. | Broad spectrum influenza virus vaccine |
| AU2018234828A1 (en) | 2017-03-15 | 2019-09-19 | Modernatx, Inc. | Lipid nanoparticle formulation |
| US11464848B2 (en) | 2017-03-15 | 2022-10-11 | Modernatx, Inc. | Respiratory syncytial virus vaccine |
| JP2020514370A (ja) | 2017-03-17 | 2020-05-21 | キュアバック アーゲー | 組合せ抗癌療法のためのｒｎａワクチン及び免疫チェックポイント阻害剤 |
| WO2018170347A1 (en) | 2017-03-17 | 2018-09-20 | Modernatx, Inc. | Zoonotic disease rna vaccines |
| EP3601576A1 (en) | 2017-03-24 | 2020-02-05 | CureVac AG | Nucleic acids encoding crispr-associated proteins and uses thereof |
| US11357856B2 (en) | 2017-04-13 | 2022-06-14 | Acuitas Therapeutics, Inc. | Lipids for delivery of active agents |
| WO2018200892A1 (en) | 2017-04-27 | 2018-11-01 | The Trustees Of The University Of Pennsylvania | NUCLEOSIDE-MODIFIED mRNA-LIPID NANOPARTICLE LINEAGE VACCINE FOR HEPATITIS C VIRUS |
| CN116693411A (zh) | 2017-04-28 | 2023-09-05 | 爱康泰生治疗公司 | 用于递送核酸的新型羰基脂质和脂质纳米颗粒制剂 |
| WO2018209270A1 (en) | 2017-05-11 | 2018-11-15 | Northwestern University | Adoptive cell therapy using spherical nucleic acids (snas) |
| EP3624824B1 (en) | 2017-05-16 | 2024-07-10 | Translate Bio, Inc. | Codon-optimized mrna encoding cftr for use in treating cystic fibrosis |
| US11015204B2 (en) | 2017-05-31 | 2021-05-25 | Arcturus Therapeutics, Inc. | Synthesis and structure of high potency RNA therapeutics |
| CA3063907A1 (en) | 2017-05-31 | 2018-12-06 | Ultragenyx Pharmaceutical Inc. | Therapeutics for glycogen storage disease type iii |
| EP3630200A4 (en) | 2017-05-31 | 2021-02-24 | Arcturus Therapeutics, Inc. | THERAPEUTICS FOR PHENYLKETONURIA |
| EP3638678B1 (en) | 2017-06-14 | 2025-12-03 | ModernaTX, Inc. | Compounds and compositions for intracellular delivery of agents |
| EP3638215A4 (en) | 2017-06-15 | 2021-03-24 | Modernatx, Inc. | RNA FORMULATIONS |
| US10780183B2 (en) | 2017-06-19 | 2020-09-22 | Translate Bio, Inc. | Messenger RNA therapy for the treatment of Friedreich's ataxia |
| SG11201911430PA (en) | 2017-07-04 | 2020-01-30 | Curevac Ag | Novel nucleic acid molecules |
| US20210228738A1 (en) | 2017-07-17 | 2021-07-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Compositions and methods for increasing or enhancing transduction of gene therapy vectors and for removing or reducing immunoglobulins |
| EP3662913A4 (en) | 2017-08-04 | 2021-06-30 | Kyowa Kirin Co., Ltd. | Nucleic-acid-containing lipid nanoparticles |
| US11639329B2 (en) | 2017-08-16 | 2023-05-02 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
| US11524932B2 (en) | 2017-08-17 | 2022-12-13 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
| WO2019036028A1 (en) | 2017-08-17 | 2019-02-21 | Acuitas Therapeutics, Inc. | LIPIDS FOR USE IN LIPID NANOPARTICULAR FORMULATIONS |
| US12065396B2 (en) | 2017-08-17 | 2024-08-20 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
| EP3673069A1 (en) | 2017-08-22 | 2020-07-01 | CureVac AG | Bunyavirales vaccine |
| CN111315359A (zh) | 2017-08-31 | 2020-06-19 | 摩登纳特斯有限公司 | 制备脂质纳米颗粒的方法 |
| EP3679140B1 (en) | 2017-09-08 | 2022-11-16 | MiNA Therapeutics Limited | Stabilized cebpa sarna compositions and methods of use |
| AU2018330495A1 (en) | 2017-09-08 | 2020-03-26 | Mina Therapeutics Limited | Stabilized hnf4a sarna compositions and methods of use |
| US10653767B2 (en) | 2017-09-14 | 2020-05-19 | Modernatx, Inc. | Zika virus MRNA vaccines |
| US11806360B2 (en) | 2017-09-19 | 2023-11-07 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for treating transthyretin (TTR) mediated amyloidosis |
| JP2021501572A (ja) | 2017-10-19 | 2021-01-21 | キュアバック アーゲー | 新規な人工核酸分子 |
| CN111511924A (zh) | 2017-11-08 | 2020-08-07 | 库瑞瓦格股份公司 | Rna序列调整 |
| WO2019115635A1 (en) | 2017-12-13 | 2019-06-20 | Curevac Ag | Flavivirus vaccine |
| WO2019126593A1 (en) | 2017-12-20 | 2019-06-27 | Translate Bio, Inc. | Improved composition and methods for treatment of ornithine transcarbamylase deficiency |
| BR112020013201A2 (pt) | 2017-12-27 | 2020-12-01 | Takeda Pharmaceutical Company Limited | nanopartícula lipídica, medicamento, métodos para expressar um receptor, para prevenir ou tratar câncer e para produzir um medicamento, uso da nanopartícula lipídica e do imunócito ex vivo, composição, imunócito ex vivo, e, célula ex vivo |
| EP3733647B1 (en) | 2017-12-27 | 2022-06-15 | Eisai R&D Management Co., Ltd. | Cationic lipid |
| WO2019148101A1 (en) | 2018-01-29 | 2019-08-01 | Modernatx, Inc. | Rsv rna vaccines |
| MA51230A (fr) | 2018-01-29 | 2021-05-05 | Merck Sharp & Dohme | Protéines f rsv stabilisées et leurs utilisations |
| WO2019152802A1 (en) | 2018-02-02 | 2019-08-08 | Translate Bio, Inc. | Cationic polymers |
| JP2021513508A (ja) * | 2018-02-12 | 2021-05-27 | インテアールエヌエー テクノロジーズ ビー．ヴイ．ＩｎｔｅＲＮＡ Ｔｅｃｈｎｏｌｏｇｉｅｓ Ｂ．Ｖ． | 抗がんマイクロｒｎａ及びその脂質製剤 |
| EP3752194A4 (en) | 2018-02-13 | 2022-03-16 | Checkmate Pharmaceuticals, Inc. | COMPOSITIONS AND METHODS FOR TUMOR IMMUNOTHERAPY |
| WO2019191627A1 (en) | 2018-03-30 | 2019-10-03 | Insmed Incorporated | Methods for continuous manufacture of liposomal drug products |
| EP3773702A2 (en) | 2018-04-05 | 2021-02-17 | CureVac AG | Novel yellow fever nucleic acid molecules for vaccination |
| KR102890791B1 (ko) | 2018-04-09 | 2025-11-24 | 체크메이트 파마슈티칼스, 인크. | 바이러스-유사 입자 내로의 올리고뉴클레오타이드의 포장 |
| WO2019197845A1 (en) | 2018-04-12 | 2019-10-17 | Mina Therapeutics Limited | Sirt1-sarna compositions and methods of use |
| JP7613685B2 (ja) | 2018-04-17 | 2025-01-15 | キュアバック エスイー | 新規ｒｓｖ ｒｎａ分子及びワクチン接種用組成物 |
| WO2019222277A1 (en) | 2018-05-15 | 2019-11-21 | Translate Bio, Inc. | Subcutaneous delivery of messenger rna |
| EP3794008A1 (en) | 2018-05-16 | 2021-03-24 | Translate Bio, Inc. | Ribose cationic lipids |
| JP7488193B2 (ja) | 2018-05-24 | 2024-05-21 | トランスレイト バイオ， インコーポレイテッド | チオエステルカチオン性脂質 |
| JP2021526134A (ja) | 2018-05-25 | 2021-09-30 | イマラ インク． | ６−［（３Ｓ，４Ｓ）−４−メチル−ｌ−（ピリミジン−２−イルメチル）ピロリジン−３−イル］−３−テトラヒドロピラン−４−イル−７Ｈ−イミダゾ［ｌ，５−Ａ］ピラジン−８−オンの一水和物および結晶形態 |
| JP2021525743A (ja) | 2018-05-30 | 2021-09-27 | トランスレイト バイオ， インコーポレイテッド | リン酸エステルカチオン性脂質 |
| WO2019232103A1 (en) | 2018-05-30 | 2019-12-05 | Translate Bio, Inc. | Messenger rna vaccines and uses thereof |
| CN112533909B (zh) | 2018-05-30 | 2024-11-15 | 川斯勒佰尔公司 | 维生素阳离子脂质 |
| US11547666B2 (en) | 2018-05-30 | 2023-01-10 | Translate Bio, Inc. | Cationic lipids comprising a steroidal moiety |
| EP3813874A1 (en) | 2018-06-27 | 2021-05-05 | CureVac AG | Novel lassa virus rna molecules and compositions for vaccination |
| CN112638362B (zh) | 2018-07-23 | 2025-06-13 | 川斯勒佰尔公司 | 信使rna的干粉制剂 |
| CA3108544A1 (en) | 2018-08-24 | 2020-02-27 | Translate Bio, Inc. | Methods for purification of messenger rna |
| US11357726B2 (en) | 2018-08-29 | 2022-06-14 | Translate Bio, Inc. | Process of preparing mRNA-loaded lipid nanoparticles |
| EP3843737A4 (en) | 2018-08-31 | 2022-06-01 | Imara Inc. | PDE9 INHIBITORS FOR THE TREATMENT OF SICKLE CELL DISEASE |
| WO2020056294A1 (en) | 2018-09-14 | 2020-03-19 | Translate Bio, Inc. | Composition and methods for treatment of methylmalonic acidemia |
| CA3113436A1 (en) | 2018-09-19 | 2020-03-26 | Modernatx, Inc. | Compounds and compositions for intracellular delivery of therapeutic agents |
| EP3852732A1 (en) | 2018-09-19 | 2021-07-28 | ModernaTX, Inc. | Peg lipids and uses thereof |
| AU2019345067A1 (en) | 2018-09-19 | 2021-04-08 | Modernatx, Inc. | High-purity peg lipids and uses thereof |
| WO2020061457A1 (en) | 2018-09-20 | 2020-03-26 | Modernatx, Inc. | Preparation of lipid nanoparticles and methods of administration thereof |
| US12329857B2 (en) | 2018-09-21 | 2025-06-17 | Acuitas Therapeutics, Inc. | Systems and methods for manufacturing lipid nanoparticles and liposomes |
| CA3114435A1 (en) | 2018-10-01 | 2020-04-09 | Alnylam Pharmaceuticals, Inc. | Biodegradable lipids for the delivery of active agents |
| PT3864163T (pt) | 2018-10-09 | 2024-04-30 | Univ British Columbia | Composições e sistemas que compreendem vesículas competentes para transfeção isentas de solventes orgânicos e detergentes e métodos relacionados com as mesmas |
| BR112021007360A2 (pt) | 2018-10-18 | 2021-07-20 | Takeda Pharmaceutical Company Limited | métodos para ativar/proliferar células t, para distribuir um ácido nucleico em células t e para produzir um medicamento, célula t, medicamento, cultura de células, composição, e, kit para distribuir um ácido nucleico em células t |
| KR20210090634A (ko) | 2018-10-19 | 2021-07-20 | 트랜슬레이트 바이오 인코포레이티드 | 전령 rna의 무펌프 캡슐화 |
| WO2020097379A2 (en) | 2018-11-09 | 2020-05-14 | Translate Bio, Inc. | Peg lipidoid compounds |
| BR112021008974A2 (pt) | 2018-11-09 | 2021-08-03 | Translate Bio, Inc. | lipídios de 2,5-dioxopiperazina com frações éster, tioéster, dissulfeto e anidrido intercaladas |
| EP3876914A2 (en) | 2018-11-09 | 2021-09-15 | Translate Bio, Inc. | Messenger rna therapy for treatment of ocular diseases |
| US12350383B2 (en) * | 2018-11-09 | 2025-07-08 | Arbutus Biopharma Corporation | Cationic lipids containing silicon |
| AU2019377525B2 (en) | 2018-11-09 | 2025-10-16 | Translate Bio, Inc. | Multi-PEG lipid compounds |
| US20220096612A1 (en) | 2018-11-12 | 2022-03-31 | Translatebioinc | Methods for inducing immune tolerance |
| AU2019384557B2 (en) | 2018-11-21 | 2025-07-17 | Translate Bio, Inc. | Treatment of cystic fibrosis by delivery of nebulized mRNA encoding CFTR |
| EP3883917B1 (en) | 2018-11-21 | 2024-01-24 | Translate Bio, Inc. | Cationic lipid compounds and compositions thereof for use in the delivery of messenger rna |
| WO2020118115A1 (en) | 2018-12-06 | 2020-06-11 | Arcturus Therapeutics, Inc. | Compositions and methods for treating ornithine transcarbamylase deficiency |
| TW202039534A (zh) | 2018-12-14 | 2020-11-01 | 美商美國禮來大藥廠 | KRAS變體mRNA分子 |
| AU2019410737A1 (en) | 2018-12-21 | 2021-06-10 | CureVac SE | RNA for malaria vaccines |
| CA3125588A1 (en) | 2019-01-07 | 2020-07-16 | Translate Bio, Inc. | Composition and methods for treatment of primary ciliary dyskinesia |
| AU2020205717B2 (en) | 2019-01-11 | 2025-09-11 | Acuitas Therapeutics, Inc. | Lipids for lipid nanoparticle delivery of active agents |
| AU2020214843A1 (en) * | 2019-01-31 | 2021-08-19 | Modernatx, Inc. | Methods of preparing lipid nanoparticles |
| US20220133908A1 (en) | 2019-02-08 | 2022-05-05 | Curevac Ag | Coding rna administered into the suprachoroidal space in the treatment of ophthalmic diseases |
| US11351242B1 (en) | 2019-02-12 | 2022-06-07 | Modernatx, Inc. | HMPV/hPIV3 mRNA vaccine composition |
| WO2020190750A1 (en) | 2019-03-15 | 2020-09-24 | Modernatx, Inc. | Hiv rna vaccines |
| CA3136265A1 (en) | 2019-04-05 | 2020-10-08 | Precision Biosciences, Inc. | Methods of preparing populations of genetically-modified immune cells |
| WO2020208361A1 (en) | 2019-04-12 | 2020-10-15 | Mina Therapeutics Limited | Sirt1-sarna compositions and methods of use |
| WO2020214946A1 (en) | 2019-04-18 | 2020-10-22 | Translate Bio, Inc. | Cystine cationic lipids |
| EP3959195B1 (en) | 2019-04-22 | 2023-11-08 | Translate Bio, Inc. | Thioester cationic lipids |
| US12453759B2 (en) | 2019-05-03 | 2025-10-28 | Translate Bio, Inc. | Di-thioester cationic lipids |
| CA3140423A1 (en) | 2019-05-14 | 2020-11-19 | Translate Bio, Inc. | Improved process of preparing mrna-loaded lipid nanoparticles |
| JP7686574B2 (ja) | 2019-05-22 | 2025-06-02 | 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 | 環状ｒｎａ組成物及び方法 |
| WO2020243540A1 (en) | 2019-05-31 | 2020-12-03 | Translate Bio, Inc. | Macrocyclic lipids |
| WO2020254535A1 (en) | 2019-06-18 | 2020-12-24 | Curevac Ag | Rotavirus mrna vaccine |
| JP7724161B2 (ja) | 2019-06-21 | 2025-08-15 | トランスレイト バイオ， インコーポレイテッド | トリシンおよびクエン酸脂質 |
| WO2020257611A1 (en) | 2019-06-21 | 2020-12-24 | Translate Bio, Inc. | Cationic lipids comprising an hydroxy moiety |
| KR20220039719A (ko) * | 2019-07-03 | 2022-03-29 | 팩터 바이오사이언스 인크. | 양이온성 지질 및 이의 용도 |
| KR20220078557A (ko) | 2019-07-08 | 2022-06-10 | 트랜슬레이트 바이오 인코포레이티드 | 개선된 mrna 로딩된 지질 나노입자 및 이의 제조 방법 |
| JP7759311B2 (ja) | 2019-07-19 | 2025-10-23 | フラッグシップ パイオニアリング イノベーションズ シックス，エルエルシー | リコンビナーゼ組成物及び使用方法 |
| JP7630904B2 (ja) * | 2019-07-23 | 2025-02-18 | 株式会社東芝 | 核酸導入キャリア、核酸導入キャリアセット、核酸導入組成物及び核酸導入方法 |
| JP7764363B2 (ja) | 2019-07-23 | 2025-11-05 | トランスレイト バイオ， インコーポレイテッド | ｍＲＮＡ担持脂質ナノ粒子の安定性組成物および作製のプロセス |
| WO2021021988A1 (en) | 2019-07-30 | 2021-02-04 | Translate Bio, Inc. | Treatment of cystic fibrosis by delivery of nebulized mrna encoding cftr |
| US10501404B1 (en) | 2019-07-30 | 2019-12-10 | Factor Bioscience Inc. | Cationic lipids and transfection methods |
| EP4013880A1 (en) | 2019-08-14 | 2022-06-22 | CureVac AG | Rna combinations and compositions with decreased immunostimulatory properties |
| BR112022004759A2 (pt) | 2019-09-19 | 2022-06-21 | Modernatx Inc | Composições e compostos lipídicos com cauda ramificada para entrega intracelular de agentes terapêuticos |
| AU2020348376A1 (en) | 2019-09-20 | 2022-04-07 | Translate Bio, Inc. | mRNA encoding engineered CFTR |
| CA3147643A1 (en) | 2019-09-23 | 2021-04-01 | Omega Therapeutics, Inc. | Compositions and methods for modulating hepatocyte nuclear factor 4-alpha (hnf4.alpha.) gene expression |
| WO2021061707A1 (en) | 2019-09-23 | 2021-04-01 | Omega Therapeutics, Inc. | Compositions and methods for modulating apolipoprotein b (apob) gene expression |
| US12076438B2 (en) | 2019-10-09 | 2024-09-03 | Translate Bio, Inc. | Compositions, methods and uses of messenger RNA |
| CA3155074A1 (en) * | 2019-10-18 | 2021-04-22 | The Trustees Of The University Of Pennsylvania | Lipid and lipid nanoparticle formulation for drug delivery |
| JP2022553042A (ja) | 2019-10-21 | 2022-12-21 | トランスレイト バイオ， インコーポレイテッド | メッセンジャーｒｎａの組成物、方法および使用 |
| EP3920976B1 (en) | 2019-12-04 | 2023-07-19 | Orna Therapeutics, Inc. | Circular rna compositions and methods |
| EP4076400A1 (en) | 2019-12-20 | 2022-10-26 | Translate Bio, Inc. | Improved process of preparing mrna-loaded lipid nanoparticles |
| US20230090515A1 (en) | 2019-12-20 | 2023-03-23 | Curevac Ag | Lipid nanoparticles for delivery of nucleic acids |
| KR20220142432A (ko) | 2019-12-20 | 2022-10-21 | 트랜슬레이트 바이오 인코포레이티드 | 메신저 rna의 직장 전달 |
| WO2021142245A1 (en) | 2020-01-10 | 2021-07-15 | Translate Bio, Inc. | Compounds, pharmaceutical compositions and methods for modulating expression of muc5b in lung cells and tissues |
| DE202021003575U1 (de) | 2020-02-04 | 2022-01-17 | Curevac Ag | Coronavirus-Vakzine |
| EP4103227A1 (en) | 2020-02-14 | 2022-12-21 | Merck Sharp & Dohme LLC | Hpv vaccine |
| CA3173035A1 (en) | 2020-02-25 | 2021-09-02 | Translate Bio, Inc. | Improved processes of preparing mrna-loaded lipid nanoparticles |
| US12351834B2 (en) | 2020-03-03 | 2025-07-08 | Arcturus Therapeutics, Inc. | Compositions and methods for the treatment of ornithine transcarbamylase deficiency |
| US11744887B2 (en) | 2020-03-09 | 2023-09-05 | Arcturus Therapeutics, Inc. | Coronavirus vaccine compositions and methods |
| WO2021183720A1 (en) | 2020-03-11 | 2021-09-16 | Omega Therapeutics, Inc. | Compositions and methods for modulating forkhead box p3 (foxp3) gene expression |
| JP2023520763A (ja) | 2020-03-24 | 2023-05-19 | ジェネレーション バイオ カンパニー | ゴーシェ治療薬を発現するための非ウイルス性ｄｎａベクター及びその使用 |
| CN115667530A (zh) | 2020-03-24 | 2023-01-31 | 世代生物公司 | 非病毒dna载体和其用于表达因子ix治疗剂的用途 |
| AU2021252164A1 (en) | 2020-04-09 | 2022-12-15 | 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 |
| JP2023524071A (ja) | 2020-05-01 | 2023-06-08 | アークトゥラス・セラピューティクス・インコーポレイテッド | 嚢胞性線維症を治療するための核酸及び方法 |
| WO2021226463A1 (en) | 2020-05-07 | 2021-11-11 | Translate Bio, Inc. | Composition and methods for treatment of primary ciliary dyskinesia |
| WO2021226468A1 (en) | 2020-05-07 | 2021-11-11 | Translate Bio, Inc. | Improved compositions for cftr mrna therapy |
| WO2021226436A1 (en) | 2020-05-07 | 2021-11-11 | Translate Bio, Inc. | Optimized nucleotide sequences encoding sars-cov-2 antigens |
| WO2021231697A1 (en) | 2020-05-14 | 2021-11-18 | Translate Bio, Inc. | Peg lipidoid compounds |
| CA3183399A1 (en) | 2020-05-15 | 2021-11-18 | Translate Bio, Inc. | Lipid nanoparticle formulations for mrna delivery |
| US20240042015A1 (en) | 2020-05-19 | 2024-02-08 | Orna Therapeutics, Inc. | Circular rna compositions and methods |
| TW202208629A (zh) | 2020-05-20 | 2022-03-01 | 美商旗艦先鋒創新有限責任公司 | 免疫原性組成物及其用途 |
| MX2022014653A (es) | 2020-05-20 | 2023-02-16 | Flagship Pioneering Innovations Vi Llc | Composiciones de antigeno de coronavirus y sus usos. |
| WO2021239880A1 (en) | 2020-05-29 | 2021-12-02 | Curevac Ag | Nucleic acid based combination vaccines |
| AU2021281453A1 (en) | 2020-05-29 | 2022-11-17 | Flagship Pioneering Innovations Vi, Llc. | Trem compositions and methods relating thereto |
| EP4158031A1 (en) | 2020-05-29 | 2023-04-05 | Flagship Pioneering Innovations VI, LLC | Trem compositions and methods relating thereto |
| WO2022006527A1 (en) | 2020-07-02 | 2022-01-06 | Maritime Therapeutics, Inc. | Compositions and methods for reverse gene therapy |
| EP4178613A1 (en) | 2020-07-08 | 2023-05-17 | Janssen Sciences Ireland Unlimited Company | Rna replicon vaccines against hbv |
| AU2021308681A1 (en) | 2020-07-16 | 2023-03-09 | Acuitas Therapeutics, Inc. | Cationic lipids for use in lipid nanoparticles |
| JP2023535632A (ja) | 2020-07-27 | 2023-08-18 | アンジャリウム バイオサイエンシズ エージー | Ｄｎａ分子の組成物、その作製方法、及びその使用方法 |
| US20230272052A1 (en) | 2020-07-31 | 2023-08-31 | CureVac SE | Nucleic acid encoded antibody mixtures |
| IL300404A (en) * | 2020-08-06 | 2023-04-01 | Modernatx Inc | Methods for preparing fat nanoparticles |
| AU2021325945A1 (en) | 2020-08-14 | 2023-04-06 | Arcturus Therapeutics, Inc. | Method of lyophilizing lipid nanoparticles |
| US11406703B2 (en) | 2020-08-25 | 2022-08-09 | Modernatx, Inc. | Human cytomegalovirus vaccine |
| EP4157344A2 (en) | 2020-08-31 | 2023-04-05 | CureVac SE | Multivalent nucleic acid based coronavirus vaccines |
| CN116157148A (zh) | 2020-09-03 | 2023-05-23 | 旗舰创业创新第六有限责任公司 | 免疫原性组合物及其用途 |
| CA3194863A1 (en) | 2020-10-06 | 2022-04-14 | Shrirang KARVE | Improved process and formulation of lipid nanoparticles |
| US20230365995A1 (en) | 2020-10-07 | 2023-11-16 | Precision Biosciences, Inc. | Lipid nanoparticle compositions |
| AU2021361986A1 (en) | 2020-10-12 | 2023-06-15 | Translate Bio, Inc. | Improved process of preparing mrna-loaded lipid nanoparticles |
| WO2022081548A1 (en) | 2020-10-12 | 2022-04-21 | Translate Bio, Inc. | Improved process of preparing ice-based lipid nanoparticles |
| WO2022081750A1 (en) | 2020-10-14 | 2022-04-21 | George Mason Research Foundation, Inc. | Ionizable lipids and methods of manufacture and use thereof |
| JP2023548587A (ja) | 2020-11-09 | 2023-11-17 | トランスレイト バイオ， インコーポレイテッド | コドン最適化したｍＲＮＡの送達のための改善された組成物 |
| IL303165A (en) | 2020-11-25 | 2023-07-01 | Translate Bio Inc | Stable liquid lipid nanoparticle formulations |
| MX2023006056A (es) | 2020-11-25 | 2023-06-06 | Akagera Medicines Inc | Nanoparticulas lipidicas para suministro de acidos nucleicos y metodos de uso de las mismas. |
| PH12023500013A1 (en) | 2020-12-04 | 2024-03-11 | Tidal Therapeutics Inc | Ionizable cationic lipids and lipi nanoparticles, and methods of synthesis and use thereof |
| GB2603454A (en) | 2020-12-09 | 2022-08-10 | Ucl Business Ltd | Novel therapeutics for the treatment of neurodegenerative disorders |
| CA3171051A1 (en) | 2020-12-22 | 2022-06-30 | Curevac Ag | Pharmaceutical composition comprising lipid-based carriers encapsulating rna for multidose administration |
| WO2022137133A1 (en) | 2020-12-22 | 2022-06-30 | Curevac Ag | Rna vaccine against sars-cov-2 variants |
| WO2022140702A1 (en) | 2020-12-23 | 2022-06-30 | Flagship Pioneering, Inc. | Compositions of modified trems and uses thereof |
| WO2022146654A1 (en) | 2020-12-28 | 2022-07-07 | Janssen Pharmaceuticals, Inc. | Transcription activator-like effector nucleases (talens) targeting hbv |
| WO2022155404A1 (en) | 2021-01-14 | 2022-07-21 | Translate Bio, Inc. | Methods and compositions for delivering mrna coded antibodies |
| WO2022162027A2 (en) | 2021-01-27 | 2022-08-04 | Curevac Ag | Method of reducing the immunostimulatory properties of in vitro transcribed rna |
| TW202245835A (zh) | 2021-02-04 | 2022-12-01 | 美商默沙東有限責任公司 | 用於肺炎球菌結合物疫苗之奈米乳化液佐劑組合物 |
| US11524023B2 (en) | 2021-02-19 | 2022-12-13 | Modernatx, Inc. | Lipid nanoparticle compositions and methods of formulating the same |
| EP4313115A1 (en) | 2021-03-25 | 2024-02-07 | Translate Bio, Inc. | Optimized nucleotide sequences encoding the extracellular domain of human ace2 protein or a portion thereof |
| US20240181037A1 (en) | 2021-03-26 | 2024-06-06 | Glaxosmithkline Biologicals Sa | Immunogenic compositions |
| JP2024511092A (ja) | 2021-03-26 | 2024-03-12 | ミナ セラピューティクス リミテッド | ＴＭＥＭ１７３ｓａＲＮＡ組成物及び使用方法 |
| CA3171429A1 (en) | 2021-03-31 | 2022-09-30 | Alexander SCHWENGER | Syringes containing pharmaceutical compositions comprising rna |
| JP2024512669A (ja) | 2021-03-31 | 2024-03-19 | フラグシップ パイオニアリング イノベーションズ ブイ，インコーポレーテッド | タノトランスミッションポリペプチド及び癌の処置におけるそれらの使用 |
| CA3215606A1 (en) | 2021-04-19 | 2022-10-27 | Shrirang KARVE | Improved compositions for delivery of mrna |
| AU2022260111A1 (en) | 2021-04-20 | 2023-11-30 | Anjarium Biosciences Ag | Compositions of dna molecules encoding amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase, methods of making thereof, and methods of use thereof |
| WO2022232286A1 (en) | 2021-04-27 | 2022-11-03 | Generation Bio Co. | Non-viral dna vectors expressing anti-coronavirus antibodies and uses thereof |
| EP4329885A1 (en) | 2021-04-27 | 2024-03-06 | Generation Bio Co. | Non-viral dna vectors expressing therapeutic antibodies and uses thereof |
| EP4334446A1 (en) | 2021-05-03 | 2024-03-13 | CureVac SE | Improved nucleic acid sequence for cell type specific expression |
| CA3220358A1 (en) * | 2021-05-28 | 2022-12-01 | Nanovation Therapeutics Inc. | Kc2-type lipids |
| CN117460542A (zh) | 2021-06-11 | 2024-01-26 | 纳米智能生物医学工程有限公司 | 包含用于将寡核苷酸递送至靶细胞内的肽-脂质缀合物的纳米颗粒以及包含其的药物组合物 |
| WO2023278754A1 (en) | 2021-07-01 | 2023-01-05 | Translate Bio, Inc. | Compositions for delivery of mrna |
| WO2023278811A1 (en) | 2021-07-01 | 2023-01-05 | Indapta Therapeutics, Inc. | Engineered natural killer (nk) cells and related methods |
| EP4367242A2 (en) | 2021-07-07 | 2024-05-15 | Omega Therapeutics, Inc. | Compositions and methods for modulating secreted frizzled receptor protein 1 (sfrp1) gene expression |
| US20240336945A1 (en) | 2021-07-26 | 2024-10-10 | Flagship Pioneering Innovations Vi, Llc | Trem compositions and uses thereof |
| US20240252684A1 (en) | 2021-07-30 | 2024-08-01 | Tune Therapeutics, Inc. | Compositions and methods for modulating expression of methyl-cpg binding protein 2 (mecp2) |
| CA3227103A1 (en) | 2021-07-30 | 2023-02-02 | Matthew P. GEMBERLING | Compositions and methods for modulating expression of frataxin (fxn) |
| CA3171750A1 (en) | 2021-07-30 | 2023-02-02 | Tim SONNTAG | Mrnas for treatment or prophylaxis of liver diseases |
| AR126675A1 (es) | 2021-08-03 | 2023-11-01 | Alnylam Pharmaceuticals Inc | COMPOSICIONES DE ARNi CONTRA LA TRANSTIRRETINA (TTR) Y SUS MÉTODOS DE USO |
| KR20240046247A (ko) | 2021-08-19 | 2024-04-08 | 머크 샤프 앤드 돔 엘엘씨 | 열안정성 지질 나노입자 및 그의 사용 방법 |
| CN113461577B (zh) * | 2021-09-01 | 2021-12-14 | 中山大学附属第七医院(深圳) | 一种氨基脂质及其应用 |
| MX2024002725A (es) | 2021-09-03 | 2024-03-15 | CureVac SE | Nuevas nanoparticulas lipidicas para la administracion de acidos nucleicos que comprenden fosfatidilserina. |
| CN115745942B (zh) * | 2021-09-03 | 2025-06-10 | 广州谷森制药有限公司 | 阳离子脂质化合物 |
| AU2022336209B2 (en) | 2021-09-03 | 2025-10-16 | CureVac SE | Novel lipid nanoparticles for delivery of nucleic acids |
| CN115745941B (zh) * | 2021-09-03 | 2025-07-01 | 广州谷森制药有限公司 | 阳离子脂质化合物 |
| CN115772089B (zh) * | 2021-09-07 | 2025-06-10 | 广州谷森制药有限公司 | 阳离子脂质化合物 |
| AR127073A1 (es) | 2021-09-17 | 2023-12-13 | Flagship Pioneering Innovations Vi Llc | Composiciones y métodos para producir polirribonucleótidos circulares |
| EP4419706A1 (en) | 2021-10-18 | 2024-08-28 | Flagship Pioneering Innovations VI, LLC | Compositions and methods for purifying polyribonucleotides |
| US20250027108A1 (en) | 2021-10-29 | 2025-01-23 | CureVac SE | Improved circular rna for expressing therapeutic proteins |
| CN118541346A (zh) | 2021-11-08 | 2024-08-23 | 奥纳治疗公司 | 用于递送环状多核苷酸的脂质纳米颗粒组合物 |
| AU2022388747A1 (en) | 2021-11-10 | 2024-06-20 | Translate Bio, Inc. | Composition and methods for treatment of primary ciliary dyskinesia |
| AU2022397292A1 (en) | 2021-11-24 | 2024-05-30 | Flagship Pioneering Innovations Vi, Llc | Varicella-zoster virus immunogen compositions and their uses |
| AU2022397300A1 (en) | 2021-11-24 | 2024-06-27 | Flagship Pioneering Innovations Vi, Llc | Immunogenic compositions and their uses |
| CN118900845A (zh) | 2021-11-24 | 2024-11-05 | 旗舰创业创新六公司 | 冠状病毒免疫原组合物及其用途 |
| WO2023099884A1 (en) | 2021-12-01 | 2023-06-08 | Mina Therapeutics Limited | Pax6 sarna compositions and methods of use |
| GB202117758D0 (en) | 2021-12-09 | 2022-01-26 | Ucl Business Ltd | Therapeutics for the treatment of neurodegenerative disorders |
| KR20240123832A (ko) | 2021-12-16 | 2024-08-14 | 아퀴타스 테라퓨틱스 인크. | 지질 나노입자 제형에 사용하기 위한 지질 |
| MX2024007307A (es) | 2021-12-17 | 2024-08-06 | Flagship Pioneering Innovations Vi Llc | Métodos de enriquecimiento de arn circular en condiciones desnaturalizantes. |
| US20250051386A1 (en) | 2021-12-22 | 2025-02-13 | Flagship Pioneering Innovations Vi, Llc | Compositions and methods for purifying polyribonucleotides |
| KR20240118881A (ko) | 2021-12-23 | 2024-08-05 | 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 | 항푸소제닉 폴리펩티드를 인코딩하는 원형 폴리리보뉴클레오티드 |
| EP4463135A2 (en) | 2022-01-10 | 2024-11-20 | Sana Biotechnology, Inc. | Methods of ex vivo dosing and administration of lipid particles or viral vectors and related systems and uses |
| WO2023135273A2 (en) | 2022-01-14 | 2023-07-20 | Anjarium Biosciences Ag | Compositions of dna molecules encoding factor viii, methods of making thereof, and methods of use thereof |
| WO2023144193A1 (en) | 2022-01-25 | 2023-08-03 | CureVac SE | Mrnas for treatment of hereditary tyrosinemia type i |
| US20250099614A1 (en) | 2022-01-28 | 2025-03-27 | CureVac SE | Nucleic acid encoded transcription factor inhibitors |
| EP4473097A1 (en) | 2022-02-02 | 2024-12-11 | Sana Biotechnology, Inc. | Methods of repeat dosing and administration of lipid particles or viral vectors and related systems and uses |
| WO2023170435A1 (en) | 2022-03-07 | 2023-09-14 | Mina Therapeutics Limited | Il10 sarna compositions and methods of use |
| JP2025509607A (ja) | 2022-03-14 | 2025-04-11 | ジェネレーション バイオ カンパニー | 異種プライムブーストワクチン組成物及び使用の方法 |
| CN119072464A (zh) | 2022-03-25 | 2024-12-03 | 赛欧生物医药股份有限公司 | 新型可电离脂质和脂质纳米颗粒以及其使用方法 |
| EP4501317A1 (en) * | 2022-03-28 | 2025-02-05 | NOF Corporation | Method for producing nucleic acid-encapsulated lipid nanoparticles, method for producing pharmaceutical composition containing said lipid nanoparticles, and method for introducing nucleic acid into cell or target cell |
| AU2023244571A1 (en) | 2022-04-01 | 2024-10-10 | Nanovation Therapeutics Inc. | Mrna delivery method and composition thereof |
| WO2023196634A2 (en) | 2022-04-08 | 2023-10-12 | Flagship Pioneering Innovations Vii, Llc | Vaccines and related methods |
| EP4519685A1 (en) | 2022-05-01 | 2025-03-12 | Yeda Research and Development Co. Ltd | Reexpression of hnf4a to alleviate cancer-associated cachexia |
| EP4522743A1 (en) | 2022-05-09 | 2025-03-19 | Flagship Pioneering Innovations VI, LLC | Trem compositions and methods of use for treating proliferative disorders |
| WO2023218420A1 (en) | 2022-05-13 | 2023-11-16 | Janssen Pharmaceuticals, Inc. | Mrna compositions for inducing latent hiv-1 reversal |
| WO2023220729A2 (en) | 2022-05-13 | 2023-11-16 | Flagship Pioneering Innovations Vii, Llc | Double stranded dna compositions and related methods |
| WO2023230587A2 (en) | 2022-05-25 | 2023-11-30 | Akagera Medicines, Inc. | Lipid nanoparticles for delivery of nucleic acids and methods of use thereof |
| CN119212720A (zh) | 2022-05-25 | 2024-12-27 | 库瑞瓦格欧洲股份公司 | 编码大肠杆菌FimH抗原性多肽的基于核酸的疫苗 |
| WO2023239756A1 (en) | 2022-06-07 | 2023-12-14 | Generation Bio Co. | Lipid nanoparticle compositions and uses thereof |
| IL317461A (en) | 2022-06-08 | 2025-02-01 | Tidal Therapeutics Inc | Ionized Cationic Lipids and Lipid Nanoparticles and Methods of Synthesis and Use thereof |
| US20250179492A1 (en) | 2022-06-22 | 2025-06-05 | Flagship Pioneering Innovations Vi, Llc | Compositions of modified trems and uses thereof |
| US12297285B2 (en) | 2022-06-24 | 2025-05-13 | Orna Therapeutics, Inc. | Circular RNA encoding chimeric antigen receptors targeting BCMA |
| JP2025524469A (ja) | 2022-06-24 | 2025-07-30 | チューン セラピューティクス インコーポレイテッド | 標的を定めた遺伝子抑制を介して低密度リポタンパク質を低減するための組成物、系、及び方法 |
| KR20250060188A (ko) | 2022-06-30 | 2025-05-07 | 인답타 세라뷰틱스 인코포레이티드 | 조작된 자연 살해(nk) 세포 및 항체 요법의 조합 및 관련 방법 |
| CA3261865A1 (en) | 2022-07-12 | 2024-01-18 | Tune Therapeutics, Inc. | TARGETED TRANSCRIPTIONAL ACTIVATION COMPOSITIONS, SYSTEMS AND METHODS |
| KR20250044720A (ko) | 2022-08-01 | 2025-04-01 | 플래그쉽 파이어니어링 이노베이션스 Vii, 엘엘씨 | 면역조절 단백질 및 관련 방법 |
| EP4569112A1 (en) | 2022-08-12 | 2025-06-18 | Remix Therapeutics Inc. | Methods and compositions for modulating splicing at alternative splice sites |
| WO2024040194A1 (en) | 2022-08-17 | 2024-02-22 | Capstan Therapeutics, Inc. | Conditioning for in vivo immune cell engineering |
| WO2024040222A1 (en) | 2022-08-19 | 2024-02-22 | Generation Bio Co. | Cleavable closed-ended dna (cedna) and methods of use thereof |
| AU2023325407A1 (en) | 2022-08-19 | 2025-02-20 | Tune Therapeutics, Inc. | Compositions, systems, and methods for regulation of hepatitis b virus through targeted gene repression |
| AU2023334610A1 (en) | 2022-08-31 | 2025-03-13 | Sail Biomedicines, Inc. | Novel ionizable lipids and lipid nanoparticles and methods of using the same |
| WO2024053648A1 (ja) | 2022-09-06 | 2024-03-14 | 国立大学法人九州大学 | 脂質ナノ粒子 |
| EP4590821A2 (en) | 2022-09-19 | 2025-07-30 | Tune Therapeutics, Inc. | Compositions, systems, and methods for modulating t cell function |
| WO2024068545A1 (en) | 2022-09-26 | 2024-04-04 | Glaxosmithkline Biologicals Sa | Influenza virus vaccines |
| EP4598946A1 (en) | 2022-10-05 | 2025-08-13 | Flagship Pioneering Innovations V, Inc. | Nucleic acid molecules encoding trif and additionalpolypeptides and their use in treating cancer |
| WO2024086929A1 (en) * | 2022-10-25 | 2024-05-02 | Nanovation Therapeutics Inc. | Lipid nanoparticle formulations for anti-sense oligonucleotide delivery |
| WO2024089638A1 (en) | 2022-10-28 | 2024-05-02 | Glaxosmithkline Biologicals Sa | Nucleic acid based vaccine |
| AU2023372397A1 (en) | 2022-10-31 | 2025-05-08 | Flagship Pioneering Innovations Vi, Llc | Compositions and methods for purifying polyribonucleotides |
| CN120435298A (zh) | 2022-11-08 | 2025-08-05 | 旗舰创业创新第六有限责任公司 | 用于产生环状多核糖核苷酸的组合物和方法 |
| WO2024102762A1 (en) | 2022-11-08 | 2024-05-16 | Orna Therapeutics, Inc. | Lipids and lipid nanoparticle compositions for delivering polynucleotides |
| AU2023375897A1 (en) | 2022-11-08 | 2025-06-12 | Orna Therapeutics, Inc. | Circular rna compositions |
| TW202425959A (zh) | 2022-11-08 | 2024-07-01 | 美商歐納醫療公司 | 遞送多核苷酸的脂質及奈米顆粒組合物 |
| CN120265279A (zh) | 2022-11-21 | 2025-07-04 | 翻译生物公司 | 信使rna的干粉配制品的组合物及其使用方法 |
| WO2024119103A1 (en) | 2022-12-01 | 2024-06-06 | Generation Bio Co. | Lipid nanoparticles comprising nucleic acids and lipid-anchored polymers |
| KR20250129819A (ko) | 2022-12-01 | 2025-08-29 | 제너레이션 바이오 컴퍼니 | 핵산, 이온화 가능한 지질, 스테롤, 지질에 고정된 중합체, 및 헬퍼 지질을 포함하는 지질 나노입자 및 이의 용도 |
| KR20250131271A (ko) | 2022-12-01 | 2025-09-02 | 제너레이션 바이오 컴퍼니 | 신규한 폴리글리세롤-접합된 지질 및 이를 포함하는 지질 나노입자 조성물 |
| KR20250114116A (ko) | 2022-12-01 | 2025-07-28 | 제너레이션 바이오 컴퍼니 | 세포 표적화를 위한 스텔스 지질 나노입자 조성물 |
| WO2024123134A1 (ko) | 2022-12-09 | 2024-06-13 | 서울대학교산학협력단 | B 세포 및 t 세포 내로 mrna를 전달하기 위한 펩타이드 기반 결합체를 포함하는 나노입자 및 이의 용도 |
| WO2024123139A1 (ko) | 2022-12-09 | 2024-06-13 | 주식회사 나이벡 | 타겟 세포 내로 올리고뉴클레오티드를 전달하기 위한 펩타이드 기반 결합체를 포함하는 나노입자 및 이를 포함하는 약학적 조성물 |
| WO2024121814A1 (en) | 2022-12-09 | 2024-06-13 | Takeda Pharmaceutical Company Limited | Modified immunomodulators |
| TW202430215A (zh) | 2022-12-14 | 2024-08-01 | 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 | 用於將治療劑遞送至骨之組成物和方法 |
| WO2024125597A1 (en) | 2022-12-14 | 2024-06-20 | Providence Therapeutics Holdings Inc. | Compositions and methods for infectious diseases |
| AU2023394992A1 (en) | 2022-12-15 | 2025-07-31 | Sanofi Pasteur Inc. | Mrna encoding influenza virus-like particle |
| AU2023398825A1 (en) | 2022-12-15 | 2025-06-26 | Orna Therapeutics, Inc. | Circular rna compositions and methods |
| CN120475991A (zh) | 2022-12-20 | 2025-08-12 | 赛诺菲巴斯德有限公司 | 鼻病毒mRNA疫苗 |
| WO2024134199A1 (en) | 2022-12-22 | 2024-06-27 | Mina Therapeutics Limited | Chemically modified sarna compositions and methods of use |
| WO2024141786A2 (en) | 2022-12-29 | 2024-07-04 | Popvax Private Limited | Multitarget vaccines and therapeutics |
| WO2024141784A2 (en) | 2022-12-29 | 2024-07-04 | Popvax Private Limited | Broadly protective betacoronavirus vaccines and compositions |
| US12410394B2 (en) * | 2023-01-06 | 2025-09-09 | Athergen, Inc. | Composition comprising nicotinamide mononucleotide and leucomethylene blue |
| US20240238473A1 (en) | 2023-01-09 | 2024-07-18 | Beth Israel Deaconess Medical Center, Inc. | Recombinant nucleic acid molecules and their use in wound healing |
| US20240252520A1 (en) | 2023-01-09 | 2024-08-01 | Beth Israel Deaconess Medical Center, Inc. | Therapeutic agents and their use for treating chronic wounds |
| TW202438673A (zh) | 2023-01-09 | 2024-10-01 | 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 | 疫苗及相關方法 |
| US20240269251A1 (en) | 2023-01-09 | 2024-08-15 | Flagship Pioneering Innovations V, Inc. | Genetic switches and their use in treating cancer |
| WO2024163683A2 (en) | 2023-02-01 | 2024-08-08 | Tune Therapeutics, Inc. | Systems, compositions, and methods for modulating expression of methyl-cpg binding protein 2 (mecp2) and x-inactive specific transcript (xist) |
| WO2024163678A2 (en) | 2023-02-01 | 2024-08-08 | Tune Therapeutics, Inc. | Fusion proteins and systems for targeted activation of frataxin (fxn) and related methods |
| TW202448516A (zh) | 2023-02-03 | 2024-12-16 | 美商健臻公司 | 接合hsc特異性抗體的脂質奈米粒子及其用途 |
| EP4658239A1 (en) | 2023-02-03 | 2025-12-10 | GlaxoSmithKline Biologicals S.A. | Rna formulation |
| TW202438515A (zh) | 2023-02-06 | 2024-10-01 | 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 | 免疫調節組合物及相關方法 |
| EP4662196A1 (en) * | 2023-02-09 | 2025-12-17 | Seqirus Inc. | Ionizable cationic compound |
| KR20250151427A (ko) | 2023-02-13 | 2025-10-21 | 플래그쉽 파이어니어링 이노베이션스 Vii, 엘엘씨 | 치료적 조성물을 위한 절단성 링커 함유 이온화 가능한 지질 및 지질 담체 |
| GB202302092D0 (en) | 2023-02-14 | 2023-03-29 | Glaxosmithkline Biologicals Sa | Analytical method |
| EP4665405A1 (en) | 2023-02-17 | 2025-12-24 | Flagship Pioneering Innovations VII, LLC | Dna compositions comprising modified uracil |
| EP4665856A2 (en) | 2023-02-17 | 2025-12-24 | Flagship Pioneering Innovations VII, LLC | Dna compositions comprising modified cytosine |
| WO2024184500A1 (en) | 2023-03-08 | 2024-09-12 | CureVac SE | Novel lipid nanoparticle formulations for delivery of nucleic acids |
| AU2024235803A1 (en) | 2023-03-15 | 2025-09-25 | Flagship Pioneering Innovations Vi, Llc | Compositions comprising polyribonucleotides and uses thereof |
| WO2024192422A1 (en) | 2023-03-15 | 2024-09-19 | Flagship Pioneering Innovations Vi, Llc | Immunogenic compositions and uses thereof |
| WO2024205657A2 (en) | 2023-03-29 | 2024-10-03 | Orna Therapeutics, Inc. | Lipids and lipid nanoparticle compositions for delivering polynucleotides |
| WO2024200820A1 (en) | 2023-03-30 | 2024-10-03 | Ose Immunotherapeutics | Method of synthesis of targeted lipid nanoparticle and uses thereof |
| WO2024200823A1 (en) | 2023-03-30 | 2024-10-03 | Ose Immunotherapeutics | Lipid-based nanoparticle targeted at activated immune cells for the expression of immune cell enhancing molecule and use thereof |
| AR132276A1 (es) | 2023-04-07 | 2025-06-11 | Takeda Pharmaceuticals Co | Complejo de conjugación |
| AU2024255972A1 (en) | 2023-04-12 | 2025-10-23 | Flagship Pioneering Innovations Vi, Llc | Modified trems, compositions, and related methods thereof |
| KR20250171373A (ko) | 2023-04-12 | 2025-12-08 | 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 | 미스센스 돌연변이 교정용 trem |
| WO2024218166A1 (en) | 2023-04-17 | 2024-10-24 | Sanofi | Reconstitutable dry powder formulations and methods of use thereof |
| WO2024220746A2 (en) | 2023-04-21 | 2024-10-24 | Flagship Pioneering Innovations Vii, Llc | Rnai agents targeting fatty acid synthase and related methods |
| WO2024223728A1 (en) | 2023-04-27 | 2024-10-31 | Glaxosmithkline Biologicals Sa | Influenza virus vaccines |
| WO2024223724A1 (en) | 2023-04-27 | 2024-10-31 | Glaxosmithkline Biologicals Sa | Influenza virus vaccines |
| AU2024269222A1 (en) | 2023-05-05 | 2025-10-09 | Orna Therapeutics, Inc. | Circular rna compositions and methods |
| AU2024269676A1 (en) | 2023-05-08 | 2025-11-06 | Merck Sharp & Dohme Llc | Polynucleotides encoding norovirus vp1 antigens and uses thereof |
| WO2024230934A1 (en) | 2023-05-11 | 2024-11-14 | CureVac SE | Therapeutic nucleic acid for the treatment of ophthalmic diseases |
| DE102023001946A1 (de) | 2023-05-12 | 2024-11-14 | Friedrich-Schiller-Universität Jena, Körperschaft des öffentlichen Rechts | Nanopartikel für den Transport von Wirkstoffen mit anionischen Gruppen, Verfahren zu deren Herstellung und deren Verwendung |
| WO2024236504A1 (en) | 2023-05-15 | 2024-11-21 | Takeda Pharmaceutical Company Limited | Sequences and methods for delivery of dna and rna |
| WO2024236361A1 (en) | 2023-05-15 | 2024-11-21 | Takeda Pharmaceutical Company Limited | Compositions and methods for delivery of nucleic acids to cells |
| CN116270543B (zh) * | 2023-05-19 | 2023-09-26 | 清华大学 | 脂质纳米颗粒在制备通过雾吸或鼻滴给药递送核酸的药物中的用途 |
| WO2024243438A2 (en) | 2023-05-23 | 2024-11-28 | Omega Therapeutics, Inc. | Compositions and methods for reducing cxcl9, cxcl10, and cxcl11 gene expression |
| WO2024249954A1 (en) | 2023-05-31 | 2024-12-05 | Capstan Therapeutics, Inc. | Lipid nanoparticle formulations and compositions |
| WO2024254226A1 (en) | 2023-06-09 | 2024-12-12 | Merck Sharp & Dohme Llc | Nanoemulsion adjuvant compositions for human papillomavirus vaccines |
| WO2024258829A1 (en) | 2023-06-12 | 2024-12-19 | Flagship Pioneering Innovations Vii, Llc | Sars-cov-2 vaccine compositions and related methods |
| WO2025006799A1 (en) | 2023-06-27 | 2025-01-02 | Capstan Therapeutics, Inc. | Extracorporeal and ex vivo engineering of select cell populations from peripheral blood |
| WO2025006684A1 (en) | 2023-06-28 | 2025-01-02 | Flagship Pioneering Innovations Vi, Llc | Circular polyribonucleotides encoding antifusogenic polypeptides |
| WO2025008774A1 (en) | 2023-07-05 | 2025-01-09 | Takeda Pharmaceutical Company Limited | Viral vectors encoding recombinant fviii variants with increased expression for gene therapy of hemophilia a |
| TW202515531A (zh) | 2023-07-07 | 2025-04-16 | 美商輝瑞股份有限公司 | 兩親性ｔｌｒ７／８佐劑及其用途 |
| WO2025011529A2 (en) | 2023-07-07 | 2025-01-16 | Shanghai Circode Biomed Co., Ltd. | Circular rna vaccines for seasonal flu and methods of uses |
| US20250092426A1 (en) | 2023-07-25 | 2025-03-20 | Flagship Pioneering Innovations Vii, Llc | Cas endonucleases and related methods |
| WO2025029840A1 (en) | 2023-07-31 | 2025-02-06 | Tune Therapeutics, Inc. | Compositions and methods for multiplexed activation and repression of t cell gene expression |
| WO2025029835A1 (en) | 2023-07-31 | 2025-02-06 | Tune Therapeutics, Inc. | Compositions and methods for modulating il-2 gene expression |
| US20250243274A1 (en) * | 2023-07-31 | 2025-07-31 | Jibe Therapeutics, Inc. | Compositions for Redirecting Immunoglobulins to Immune Cells |
| WO2025027116A1 (en) | 2023-08-01 | 2025-02-06 | Institut Curie | Nanoparticles comprising nucleic acid sequences encoding cyclic gmp-amp synthase |
| WO2025038494A1 (en) | 2023-08-11 | 2025-02-20 | Tune Therapeutics, Inc. | Compositions, systems, and methods for lymphoid cell differentiation using targeted gene activation |
| WO2025042786A1 (en) | 2023-08-18 | 2025-02-27 | Flagship Pioneering Innovations Vi, Llc | Compositions comprising circular polyribonucleotides and uses thereof |
| WO2025049690A1 (en) | 2023-08-29 | 2025-03-06 | Orna Therapeutics, Inc. | Circular polyethylene glycol lipids |
| WO2025045142A1 (en) | 2023-08-29 | 2025-03-06 | Shanghai Circode Biomed Co., Ltd. | Circular rna encoding vegf polypeptides, formulations, and methods of uses |
| WO2025054236A2 (en) | 2023-09-06 | 2025-03-13 | Flagship Pioneering Innovations Vii, Llc | Sars-cov-2 vaccine compositions and related methods |
| WO2025052180A2 (en) | 2023-09-07 | 2025-03-13 | Axelyf ehf. | Lipids and lipid nanoparticles |
| WO2025059073A1 (en) | 2023-09-11 | 2025-03-20 | Tune Therapeutics, Inc. | Epigenetic editing methods and systems for differentiating stem cells |
| TW202525266A (zh) | 2023-09-18 | 2025-07-01 | 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 | 可電離類脂質組成物及其治療用途 |
| WO2025063214A1 (ja) * | 2023-09-22 | 2025-03-27 | 国立大学法人東北大学 | 核酸を内封したリガンド修飾脂質ナノ粒子の製造方法 |
| WO2025072331A1 (en) | 2023-09-26 | 2025-04-03 | Flagship Pioneering Innovations Vii, Llc | Cas nucleases and related methods |
| WO2025096807A2 (en) | 2023-10-31 | 2025-05-08 | Flagship Pioneering Innovations Vii, Llc | Novel therapeutic dna forms |
| WO2025101501A1 (en) | 2023-11-07 | 2025-05-15 | Orna Therapeutics, Inc. | Circular rna compositions |
| US20250162981A1 (en) | 2023-11-14 | 2025-05-22 | Flagship Pioneering Innovations Vii, Llc | Ionizable lipidoid compositions and therapeutic uses thereof |
| WO2025111526A1 (en) | 2023-11-22 | 2025-05-30 | Flagship Pioneering Innovations Vii, Llc | Methods and compositions for treating non-alcoholic fatty liver disease |
| WO2025117877A2 (en) | 2023-12-01 | 2025-06-05 | Flagship Pioneering Innovations Vii, Llc | Cas nucleases and related methods |
| WO2025129128A1 (en) | 2023-12-15 | 2025-06-19 | Vivasor, Inc. | Compositions and methods for non-viral delivery of therapeutic compounds |
| WO2025132839A1 (en) | 2023-12-21 | 2025-06-26 | Glaxosmithkline Biologicals Sa | Influenza virus vaccines |
| WO2025133115A1 (en) | 2023-12-21 | 2025-06-26 | Ose Immunotherapeutics | Lipid-based nanoparticles comprising il-35 |
| US20250375499A1 (en) | 2024-01-26 | 2025-12-11 | Flagship Pioneering Innovations Vii, Llc | Immunoreceptor inhibitory proteins and related methods |
| WO2025174825A2 (en) | 2024-02-12 | 2025-08-21 | Aera Therapeutics, Inc. | Delivery compositions |
| WO2025180874A1 (en) * | 2024-02-27 | 2025-09-04 | Basf Se | Substituted 1,3-dioxolane sulfates and their use |
| WO2025190300A1 (zh) * | 2024-03-13 | 2025-09-18 | 仁景(苏州)生物科技有限公司 | 脂质纳米颗粒及脂质纳米颗粒组合物 |
| WO2025194019A1 (en) | 2024-03-14 | 2025-09-18 | Flagship Pioneering Innovations Vii, Llc | Methods for treating liver fibrosis and non-alcoholic fatty liver disease |
| WO2025196065A1 (en) | 2024-03-20 | 2025-09-25 | Sanofi | Novel homocysteine based lipids and their use for delivery of nucleic acids |
| GB202404607D0 (en) | 2024-03-29 | 2024-05-15 | Glaxosmithkline Biologicals Sa | RNA formulation |
| WO2025217275A2 (en) | 2024-04-10 | 2025-10-16 | Flagship Pioneering Innovations Vii, Llc | Immune cell targeted compositions and related methods |
| CN118388360B (zh) | 2024-04-17 | 2025-04-04 | 北京悦康科创医药科技股份有限公司 | 含有苯环结构的长效脾靶向阳离子脂质化合物、包含其的组合物及用途 |
| US20250353881A1 (en) | 2024-05-16 | 2025-11-20 | Flagship Pioneering Innovations Vii, Llc | Immunoreceptor inhibitory proteins and related methods |
| WO2025245188A2 (en) | 2024-05-21 | 2025-11-27 | Flagship Pioneering Innovations Vii, Llc | Methods of treating liver steatosis and non-alcoholic fatty liver disease |
| WO2025245111A1 (en) | 2024-05-22 | 2025-11-27 | Flagship Pioneering Innovations Vii, Llc | Immunoreceptor targeting proteins and related methods |
| WO2025250751A1 (en) | 2024-05-31 | 2025-12-04 | Orna Therapeutics, Inc. | Circular rna compositions and methods |
| WO2025252759A1 (en) | 2024-06-03 | 2025-12-11 | Bio-Sourcing | Transient expression by lipid nanoparticle formulations |
| WO2025259931A1 (en) | 2024-06-14 | 2025-12-18 | Orbital Therapeutics, Inc. | Compositions and methods for rna circularization |
Family Cites Families (230)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US3993754A (en) | 1974-10-09 | 1976-11-23 | The United States Of America As Represented By The United States Energy Research And Development Administration | Liposome-encapsulated actinomycin for cancer chemotherapy |
| US4086257A (en) | 1976-10-12 | 1978-04-25 | Sears Barry D | Phosphatidyl quaternary ammonium compounds |
| CH624011A5 (OSRAM) | 1977-08-05 | 1981-07-15 | Battelle Memorial Institute | |
| US4394448A (en) | 1978-02-24 | 1983-07-19 | Szoka Jr Francis C | Method of inserting DNA into living cells |
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| EP0032578B1 (de) | 1980-01-16 | 1984-07-25 | Hans Georg Prof. Dr. Weder | Verfahren und Dialysiereinrichtung zur Herstellung von Bilayer-Vesikeln und Verwendung der Bilayer-Vesikel |
| US4598051A (en) | 1980-03-12 | 1986-07-01 | The Regents Of The University Of California | Liposome conjugates and diagnostic methods therewith |
| 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 |
| US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
| US4522803A (en) | 1983-02-04 | 1985-06-11 | The Liposome Company, Inc. | Stable plurilamellar vesicles, their preparation and use |
| US4476301A (en) | 1982-04-29 | 1984-10-09 | Centre National De La Recherche Scientifique | Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon |
| US4603044A (en) | 1983-01-06 | 1986-07-29 | Technology Unlimited, Inc. | Hepatocyte Directed Vesicle delivery system |
| US4588578A (en) | 1983-08-08 | 1986-05-13 | The Liposome Company, Inc. | Lipid vesicles prepared in a monophase |
| US4515736A (en) | 1983-05-12 | 1985-05-07 | The Regents Of The University Of California | Method for encapsulating materials into liposomes |
| US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| US5550111A (en) | 1984-07-11 | 1996-08-27 | Temple University-Of The Commonwealth System Of Higher Education | Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof |
| FR2567892B1 (fr) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
| US5367066A (en) | 1984-10-16 | 1994-11-22 | Chiron Corporation | Oligonucleotides with selectably cleavable and/or abasic sites |
| 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 |
| US5550289A (en) | 1985-01-07 | 1996-08-27 | Syntex (U.S.A.) Inc. | N-(1,(1-1)-dialkyloxy)-and N-(1,(1-1)-dialkenyloxy alk-1-yl-N-N,N-tetrasubstituted ammonium lipids and uses therefor |
| US5208036A (en) | 1985-01-07 | 1993-05-04 | 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 |
| FR2575751B1 (fr) | 1985-01-08 | 1987-04-03 | Pasteur Institut | Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques |
| US5405938A (en) | 1989-12-20 | 1995-04-11 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
| US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US4737323A (en) | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
| US5453566A (en) | 1986-03-28 | 1995-09-26 | Calgene, Inc. | Antisense regulation of gene expression in plant/cells |
| US4839175A (en) * | 1986-07-28 | 1989-06-13 | Liposome Technology, Inc. | Liposomes with enhanced retention on mucosal tissue |
| WO1988000824A1 (en) * | 1986-07-28 | 1988-02-11 | Liposome Technology, Inc. | Liposomes with enhanced retention on mucosal tissue |
| US4987071A (en) | 1986-12-03 | 1991-01-22 | University Patents, Inc. | RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods |
| US5320906A (en) | 1986-12-15 | 1994-06-14 | Vestar, Inc. | Delivery vehicles with amphiphile-associated active ingredient |
| US5276019A (en) | 1987-03-25 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| CA1340032C (en) | 1987-06-24 | 1998-09-08 | Jim Haralambidis | Lucleoside derivatives |
| US4924624A (en) | 1987-10-22 | 1990-05-15 | Temple University-Of The Commonwealth System Of Higher Education | 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof |
| US5188897A (en) | 1987-10-22 | 1993-02-23 | Temple University Of The Commonwealth System Of Higher Education | Encapsulated 2',5'-phosphorothioate oligoadenylates |
| WO1989009221A1 (en) | 1988-03-25 | 1989-10-05 | University Of Virginia Alumni Patents Foundation | Oligonucleotide n-alkylphosphoramidates |
| US5278302A (en) | 1988-05-26 | 1994-01-11 | University Patents, Inc. | Polynucleotide phosphorodithioates |
| US5216141A (en) | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
| US5175273A (en) | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
| CA1340323C (en) | 1988-09-20 | 1999-01-19 | Arnold E. Hampel | Rna catalyst for cleaving specific rna sequences |
| GB8822492D0 (en) | 1988-09-24 | 1988-10-26 | Considine J | Apparatus for removing tumours from hollow organs of body |
| US4957773A (en) | 1989-02-13 | 1990-09-18 | Syracuse University | Deposition of boron-containing films from decaborane |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| FR2645866B1 (fr) | 1989-04-17 | 1991-07-05 | Centre Nat Rech Scient | Nouvelles lipopolyamines, leur preparation et leur emploi |
| US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
| AU637800B2 (en) | 1989-08-31 | 1993-06-10 | City Of Hope | Chimeric dna-rna catalytic sequences |
| US5591722A (en) | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
| US5286634A (en) | 1989-09-28 | 1994-02-15 | Stadler Joan K | Synergistic method for host cell transformation |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5225212A (en) | 1989-10-20 | 1993-07-06 | Liposome Technology, Inc. | Microreservoir liposome composition and method |
| US5399676A (en) | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
| US5264562A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences, Inc. | Oligonucleotide analogs with novel linkages |
| ATE190981T1 (de) | 1989-10-24 | 2000-04-15 | Isis Pharmaceuticals Inc | 2'-modifizierte nukleotide |
| US5264564A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences | Oligonucleotide analogs with novel linkages |
| US5177198A (en) | 1989-11-30 | 1993-01-05 | University Of N.C. At Chapel Hill | Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates |
| US5130302A (en) | 1989-12-20 | 1992-07-14 | Boron Bilogicals, Inc. | Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same |
| US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
| US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
| US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| US5321131A (en) | 1990-03-08 | 1994-06-14 | Hybridon, Inc. | Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling |
| US5279833A (en) | 1990-04-04 | 1994-01-18 | Yale University | Liposomal transfection of nucleic acids into animal cells |
| US5470967A (en) | 1990-04-10 | 1995-11-28 | The Dupont Merck Pharmaceutical Company | Oligonucleotide analogs with sulfamate linkages |
| US5264618A (en) | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
| GB9009980D0 (en) | 1990-05-03 | 1990-06-27 | Amersham Int Plc | Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides |
| DE69032425T2 (de) | 1990-05-11 | 1998-11-26 | Microprobe Corp., Bothell, Wash. | Teststreifen zum Eintauchen für Nukleinsäure-Hybridisierungsassays und Verfahren zur kovalenten Immobilisierung von Oligonucleotiden |
| US6465188B1 (en) | 1990-06-11 | 2002-10-15 | Gilead Sciences, Inc. | Nucleic acid ligand complexes |
| US6365730B1 (en) | 1990-06-19 | 2002-04-02 | Gene Shears Pty. Limited | DNA-Armed ribozymes and minizymes |
| US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
| US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
| US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
| US5614617A (en) | 1990-07-27 | 1997-03-25 | Isis Pharmaceuticals, Inc. | Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression |
| US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| PT98562B (pt) | 1990-08-03 | 1999-01-29 | Sanofi Sa | Processo para a preparacao de composicoes que compreendem sequencias de nucleo-sidos com cerca de 6 a cerca de 200 bases resistentes a nucleases |
| US5789573A (en) | 1990-08-14 | 1998-08-04 | Isis Pharmaceuticals, Inc. | Antisense inhibition of ICAM-1, E-selectin, and CMV IE1/IE2 |
| US5177196A (en) | 1990-08-16 | 1993-01-05 | Microprobe Corporation | Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof |
| US5214134A (en) | 1990-09-12 | 1993-05-25 | Sterling Winthrop Inc. | Process of linking nucleosides with a siloxane bridge |
| US5561225A (en) | 1990-09-19 | 1996-10-01 | Southern Research Institute | Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages |
| AU662298B2 (en) | 1990-09-20 | 1995-08-31 | Gilead Sciences, Inc. | Modified internucleoside linkages |
| 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 |
| PL169576B1 (pl) | 1990-10-12 | 1996-08-30 | Max Planck Gesellschaft | Sposób wytwarzania czasteczki RNA o aktywnosci katalitycznej PL PL |
| US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
| DE4216134A1 (de) | 1991-06-20 | 1992-12-24 | Europ Lab Molekularbiolog | Synthetische katalytische oligonukleotidstrukturen |
| DE4120916A1 (de) * | 1991-06-25 | 1993-01-07 | Basf Ag | Omega-3 mehrfach ungesaettigte fettsaeurederivate, ihre herstellung und verwendung |
| US5571799A (en) | 1991-08-12 | 1996-11-05 | Basco, Ltd. | (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response |
| US5283185A (en) | 1991-08-28 | 1994-02-01 | University Of Tennessee Research Corporation | Method for delivering nucleic acids into cells |
| ES2103918T3 (es) | 1991-10-17 | 1997-10-01 | Ciba Geigy Ag | Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios. |
| US5594121A (en) | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
| US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
| US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| EP0625207A1 (en) | 1991-12-17 | 1994-11-23 | The Regents Of The University Of California | Gene therapy for cystic fibrosis transmembrane conductance regulator activity (cftr) |
| US5858784A (en) | 1991-12-17 | 1999-01-12 | The Regents Of The University Of California | Expression of cloned genes in the lung by aerosol- and liposome-based delivery |
| US5652094A (en) | 1992-01-31 | 1997-07-29 | University Of Montreal | Nucleozymes |
| FR2687679B1 (fr) | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | Oligothionucleotides. |
| WO1993017125A1 (en) | 1992-02-19 | 1993-09-02 | Baylor College Of Medicine | Oligonucleotide modulation of cell growth |
| US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
| EP0642589A4 (en) | 1992-05-11 | 1997-05-21 | Ribozyme Pharm Inc | METHOD AND REAGENT TO INHIBIT VIRAL REPLICATION. |
| US5434257A (en) | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
| IL105914A0 (en) | 1992-06-04 | 1993-10-20 | Univ California | Methods and compositions for in vivo gene therapy |
| EP0577558A2 (de) | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
| CA2140343A1 (en) | 1992-07-17 | 1994-02-03 | Sean M. Sullivan | Method and reagent for treatment of animal diseases |
| US5334761A (en) | 1992-08-28 | 1994-08-02 | Life Technologies, Inc. | Cationic lipids |
| IL108367A0 (en) | 1993-01-27 | 1994-04-12 | Hektoen Inst For Medical Resea | Antisense polynzcleotide inhibition of human growth factor-sensitive cancer cells |
| US5476925A (en) | 1993-02-01 | 1995-12-19 | Northwestern University | Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups |
| GB9304618D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Chemical compounds |
| DE69404289T2 (de) | 1993-03-30 | 1998-02-19 | Sanofi Sa | Acyclische nucleosid analoge und sie enthaltende oligonucleotidsequenzen |
| ATE160572T1 (de) | 1993-03-31 | 1997-12-15 | Sanofi Sa | Oligonucleotide mit amidverkettungen die phosphoesterverkettungen einsetzen |
| DE4311944A1 (de) | 1993-04-10 | 1994-10-13 | Degussa | Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen |
| US5578475A (en) | 1993-07-12 | 1996-11-26 | Life Technologies, Inc. | Composition and methods for transfecting eukaryotic cells |
| US5532130A (en) | 1993-07-20 | 1996-07-02 | Dyad Pharmaceutical Corporation | Methods and compositions for sequence-specific hybridization of RNA by 2'-5' oligonucleotides |
| US5502177A (en) | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
| US5801154A (en) | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
| US5457187A (en) | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
| US5446137B1 (en) | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
| US5674908A (en) | 1993-12-20 | 1997-10-07 | Life Technologies, Inc. | Highly packed polycationic ammonium, sulfonium and phosphonium lipids |
| US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US6989434B1 (en) | 1994-02-11 | 2006-01-24 | Invitrogen Corporation | Reagents for intracellular delivery of macromolecules |
| US6075012A (en) | 1994-02-11 | 2000-06-13 | Life Technologies, Inc. | Reagents for intracellular delivery of macromolecules |
| US5591317A (en) | 1994-02-16 | 1997-01-07 | Pitts, Jr.; M. Michael | Electrostatic device for water treatment |
| US5631359A (en) | 1994-10-11 | 1997-05-20 | Ribozyme Pharmaceuticals, Inc. | Hairpin ribozymes |
| US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
| US5627053A (en) | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
| US5625050A (en) | 1994-03-31 | 1997-04-29 | Amgen Inc. | Modified oligonucleotides and intermediates useful in nucleic acid therapeutics |
| 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 |
| US5534499A (en) | 1994-05-19 | 1996-07-09 | The University Of British Columbia | Lipophilic drug derivatives for use in liposomes |
| CA2194221C (en) | 1994-06-22 | 2001-01-02 | Timothy D. Heath | Cationic amphiphiles |
| FR2722506B1 (fr) | 1994-07-13 | 1996-08-14 | Rhone Poulenc Rorer Sa | Composition contenant des acides nucleiques, preparation et utilisations |
| US5597909A (en) | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
| EP1179340A3 (en) | 1994-09-30 | 2003-05-07 | INEX Pharmaceutical Corp. | Compositions for the introduction of polyanionic materials into cells |
| US5820873A (en) | 1994-09-30 | 1998-10-13 | The University Of British Columbia | Polyethylene glycol modified ceramide lipids and liposome uses thereof |
| US5885613A (en) | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
| US6027726A (en) | 1994-09-30 | 2000-02-22 | Inex Phamaceuticals Corp. | Glycosylated protein-liposome conjugates and methods for their preparation |
| US5753613A (en) | 1994-09-30 | 1998-05-19 | Inex Pharmaceuticals Corporation | Compositions for the introduction of polyanionic materials into cells |
| WO1996011266A2 (en) | 1994-10-05 | 1996-04-18 | Amgen Inc. | Method for inhibiting smooth muscle cell proliferation and oligonucleotides for use therein |
| US5627159A (en) | 1994-10-27 | 1997-05-06 | Life Technologies, Inc. | Enhancement of lipid cationic transfections in the presence of serum |
| US5783683A (en) | 1995-01-10 | 1998-07-21 | Genta Inc. | Antisense oligonucleotides which reduce expression of the FGFRI gene |
| JP3583505B2 (ja) * | 1995-05-10 | 2004-11-04 | 花王株式会社 | 新規な第４級アンモニウム塩及びそれを含有する柔軟剤組成物 |
| AU701106B2 (en) | 1995-06-07 | 1999-01-21 | Promega Biosciences, Inc. | Novel carbamate-based cationic lipids |
| US20030069173A1 (en) | 1998-03-16 | 2003-04-10 | Life Technologies, Inc. | Peptide-enhanced transfections |
| EP0874910A4 (en) | 1995-06-07 | 1999-04-21 | Life Technologies Inc | ENHANCED CATIONIC LIPID TRANSFECTION BY PEPTIDES |
| 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 |
| 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 |
| US5811406A (en) | 1995-06-07 | 1998-09-22 | Regents Of The University Of California | Dry powder formulations of polynucleotide complexes |
| 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 |
| US5981501A (en) | 1995-06-07 | 1999-11-09 | Inex Pharmaceuticals Corp. | Methods for encapsulating plasmids in lipid bilayers |
| US6051429A (en) | 1995-06-07 | 2000-04-18 | Life Technologies, Inc. | Peptide-enhanced cationic lipid transfections |
| US5747470A (en) | 1995-06-07 | 1998-05-05 | Gen-Probe Incorporated | Method for inhibiting cellular proliferation using antisense oligonucleotides to gp130 mRNA |
| AU705549B2 (en) | 1995-06-07 | 1999-05-27 | Promega Biosciences, Inc. | Phosphonic acid-based cationic lipids |
| JPH11510489A (ja) | 1995-07-21 | 1999-09-14 | ジンタ・インコーポレイテッド | 新規アミド基本カチオン性脂質 |
| US6339173B1 (en) | 1996-07-22 | 2002-01-15 | Promega Biosciences, Inc. | Amide-based cationic lipids |
| US5739119A (en) | 1996-11-15 | 1998-04-14 | Galli; Rachel L. | Antisense oligonucleotides specific for the muscarinic type 2 acetylcholine receptor MRNA |
| US5877220A (en) | 1997-03-06 | 1999-03-02 | Genta, Incorporated | Amide-based oligomeric cationic lipids |
| US6034135A (en) | 1997-03-06 | 2000-03-07 | Promega Biosciences, Inc. | Dimeric cationic lipids |
| US6406705B1 (en) | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
| US6743171B1 (en) | 1997-04-02 | 2004-06-01 | Henry M. Bowles | Relocatable mental function testing gateway |
| US6235310B1 (en) * | 1997-04-04 | 2001-05-22 | Valentis, Inc. | Methods of delivery using cationic lipids and helper lipids |
| US6835395B1 (en) | 1997-05-14 | 2004-12-28 | The University Of British Columbia | Composition containing small multilamellar oligodeoxynucleotide-containing lipid vesicles |
| DE69841002D1 (de) | 1997-05-14 | 2009-09-03 | Univ British Columbia | Hochwirksame verkapselung von nukleinsäuren in lipidvesikeln |
| WO1999005303A1 (en) | 1997-07-24 | 1999-02-04 | Inex Pharmaceuticals Corporation | Preparation of lipid-nucleic acid particles using a solvent extraction and direct hydration method |
| US6320017B1 (en) | 1997-12-23 | 2001-11-20 | Inex Pharmaceuticals Corp. | Polyamide oligomers |
| DE69937964T2 (de) | 1998-11-12 | 2009-01-02 | Invitrogen Corp., Carlsbad | Transportreagentien |
| US6656498B1 (en) * | 1998-11-25 | 2003-12-02 | Vanderbilt University | Cationic liposomes for gene transfer |
| US6649780B1 (en) | 1998-12-22 | 2003-11-18 | Valentis, Inc. | Cationic lipids |
| RU2148349C1 (ru) * | 1999-01-05 | 2000-05-10 | Всероссийский научно-исследовательский институт консервной и овощесушильной промышленности | Способ производства комбикормового премикса |
| US6852334B1 (en) | 1999-04-20 | 2005-02-08 | The University Of British Columbia | Cationic peg-lipids and methods of use |
| CA2378438C (en) | 1999-07-15 | 2010-05-04 | Inex Pharmaceuticals Corp. | Methods for preparation of lipid-encapsulated therapeutic agents |
| US7094423B1 (en) | 1999-07-15 | 2006-08-22 | Inex Pharmaceuticals Corp. | Methods for preparation of lipid-encapsulated therapeutic agents |
| DE60036950T2 (de) | 1999-08-27 | 2008-08-07 | Inex Pharmaceuticals Corp., Burnaby | Zusammensetzungen zur stimulation der zytokin sekretion und zur induktion einer immunantwort |
| AU2001247951A1 (en) * | 2000-02-07 | 2001-08-14 | Roche Diagnostics Corporation | Novel cationic amphiphiles |
| WO2002081628A2 (en) | 2001-04-05 | 2002-10-17 | Ribozyme Pharmaceuticals, Incorporated | Modulation of gene expression associated with inflammation proliferation and neurite outgrowth, using nucleic acid based technologies |
| US7189705B2 (en) | 2000-04-20 | 2007-03-13 | The University Of British Columbia | Methods of enhancing SPLP-mediated transfection using endosomal membrane destabilizers |
| US6543484B1 (en) | 2000-08-15 | 2003-04-08 | Roderick Highsmith | Waste water disposal system |
| JP2004511572A (ja) | 2000-10-25 | 2004-04-15 | ザ ユニバーシティ オブ ブリティッシュ コロンビア | 標的化送達のための脂質製剤 |
| EP1337664A4 (en) | 2000-10-27 | 2005-01-19 | Invitrogen Corp | METHOD FOR INTRODUCING ANTISENSE OLIGONUCLEOTIDES IN EUKARYOTIC CELLS |
| CZ302719B6 (cs) | 2000-12-01 | 2011-09-21 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Izolovaná molekula dvouretezcové RNA, zpusob její výroby a její použití |
| ES2307568T3 (es) | 2000-12-08 | 2008-12-01 | Coley Pharmaceutical Gmbh | Acidos nucleicos de tipo cpg y metodos de uso de los mismos. |
| US20040142892A1 (en) | 2001-04-30 | 2004-07-22 | The University Of British Columbia | Autogene nucleic acids encoding a secretable RNA polymerase |
| WO2002087541A1 (en) | 2001-04-30 | 2002-11-07 | Protiva Biotherapeutics Inc. | Lipid-based formulations for gene transfer |
| US20040063654A1 (en) | 2001-11-02 | 2004-04-01 | Davis Mark E. | Methods and compositions for therapeutic use of RNA interference |
| US7223887B2 (en) | 2001-12-18 | 2007-05-29 | The University Of British Columbia | Multivalent cationic lipids and methods of using same in the production of lipid particles |
| CA2486007C (en) | 2002-05-15 | 2011-11-22 | California Pacific Medical Center | Delivery of nucleic acid-like compounds |
| ATE485031T1 (de) | 2002-06-28 | 2010-11-15 | Protiva Biotherapeutics Inc | Verfahren und vorrichtung zur herstellung von liposomen |
| AU2004205895B2 (en) | 2003-01-16 | 2009-02-26 | The Trustees Of The University Of Pennsylvania | Compositions and methods for siRNA inhibition of ICAM-1 |
| US7803781B2 (en) | 2003-02-28 | 2010-09-28 | Isis Pharmaceuticals, Inc. | Modulation of growth hormone receptor expression and insulin-like growth factor expression |
| US8242089B2 (en) | 2003-06-18 | 2012-08-14 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Sphingolipids polyalkylamine conjugates for use in transfection |
| ES2559828T3 (es) | 2003-07-16 | 2016-02-16 | Protiva Biotherapeutics Inc. | ARN de interferencia encapsulado en lípidos |
| AU2004272646B2 (en) | 2003-09-15 | 2011-11-24 | Arbutus Biopharma Corporation | Polyethyleneglycol-modified lipid compounds and uses thereof |
| EP1766035B1 (en) | 2004-06-07 | 2011-12-07 | Protiva Biotherapeutics Inc. | Lipid encapsulated interfering rna |
| EP1781593B1 (en) | 2004-06-07 | 2011-12-14 | Protiva Biotherapeutics Inc. | Cationic lipids and methods of use |
| EP1773857A4 (en) | 2004-07-02 | 2009-05-13 | Protiva Biotherapeutics Inc | THE IMMUNE SYSTEM STIMULATING SIRNA MOLECULES AND APPLICATIONS THEREOF |
| WO2006007712A1 (en) | 2004-07-19 | 2006-01-26 | Protiva Biotherapeutics, Inc. | Methods comprising polyethylene glycol-lipid conjugates for delivery of therapeutic agents |
| NZ554214A (en) | 2004-09-24 | 2009-10-30 | Alnylam Pharmaceuticals Inc | Rnai modulation of apob and uses thereof |
| AU2005306533B2 (en) | 2004-11-17 | 2012-05-31 | Arbutus Biopharma Corporation | siRNA silencing of apolipoprotein B |
| WO2006074546A1 (en) | 2005-01-13 | 2006-07-20 | Protiva Biotherapeutics, Inc. | Lipid encapsulated interfering rna |
| US20060228406A1 (en) | 2005-03-17 | 2006-10-12 | Invitrogen Corporation | Transfection reagent for non-adherent suspension cells |
| 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 |
| EP1937213B1 (en) | 2005-07-27 | 2017-10-25 | Protiva Biotherapeutics Inc. | Systems and methods for manufacturing liposomes |
| CA2628300C (en) | 2005-11-02 | 2018-04-17 | Protiva Biotherapeutics, Inc. | Modified sirna molecules and uses thereof |
| MX2009003548A (es) * | 2006-10-03 | 2009-04-15 | Alnylam Pharmaceuticals Inc | Formulaciones que contienen lipidos. |
| WO2009088891A1 (en) | 2008-01-02 | 2009-07-16 | Alnylam Pharmaceuticals, Inc. | Screening method for selected amino lipid-containing compositions |
| WO2009086558A1 (en) | 2008-01-02 | 2009-07-09 | Tekmira Pharmaceuticals Corporation | Improved compositions and methods for the delivery of nucleic acids |
| US20110065774A1 (en) | 2008-01-31 | 2011-03-17 | Alnylam Pharmaceuticals | Chemically modified oligonucleotides and uses thereof |
| ES2638448T3 (es) * | 2008-04-15 | 2017-10-20 | Protiva Biotherapeutics Inc. | Novedosas formulaciones de lípidos para la administración de ácidos nucleicos |
| WO2009129319A2 (en) * | 2008-04-15 | 2009-10-22 | Protiva Biotherapeutics, Inc. | Silencing of csn5 gene expression using interfering rna |
| WO2009132131A1 (en) * | 2008-04-22 | 2009-10-29 | Alnylam Pharmaceuticals, Inc. | Amino lipid based improved lipid formulation |
| EP3584320A1 (en) * | 2008-09-25 | 2019-12-25 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of serum amyloid a gene |
| EP2743265B1 (en) * | 2008-10-09 | 2017-03-15 | Arbutus Biopharma Corporation | Improved amino lipids and methods for the delivery of nucleic acids |
| EA037404B1 (ru) | 2008-11-10 | 2021-03-24 | Арбутус Биофарма Корпорэйшн | Липиды и композиции для доставки лекарственных средств |
| AU2010245933B2 (en) | 2009-05-05 | 2016-06-16 | Arbutus Biopharma Corporation | Methods of delivering oligonucleotides to immune cells |
| US20110071208A1 (en) | 2009-06-05 | 2011-03-24 | Protiva Biotherapeutics, Inc. | Lipid encapsulated dicer-substrate interfering rna |
| WO2011000106A1 (en) | 2009-07-01 | 2011-01-06 | Protiva Biotherapeutics, Inc. | Improved cationic lipids and methods for the delivery of therapeutic agents |
| CA2767129C (en) | 2009-07-01 | 2015-01-06 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein b |
| JP5766188B2 (ja) | 2009-07-01 | 2015-08-19 | プロチバ バイオセラピューティクス インコーポレイティッド | 固形腫瘍に治療剤を送達するための脂質製剤 |
| WO2011066651A1 (en) | 2009-12-01 | 2011-06-09 | Protiva Biotherapeutics, Inc. | Snalp formulations containing antioxidants |
| US10077232B2 (en) | 2010-05-12 | 2018-09-18 | Arbutus Biopharma Corporation | Cyclic cationic lipids and methods of use |
| US8865675B2 (en) | 2010-05-12 | 2014-10-21 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein B |
| EP2569276B1 (en) | 2010-05-12 | 2021-02-24 | Arbutus Biopharma Corporation | Novel cationic lipids and methods of use thereof |
| WO2012000104A1 (en) | 2010-06-30 | 2012-01-05 | Protiva Biotherapeutics, Inc. | Non-liposomal systems for nucleic acid delivery |
| CN113214102A (zh) | 2010-11-15 | 2021-08-06 | 生命技术公司 | 含胺的转染试剂及其制备和使用方法 |
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| JP2016196508A (ja) | 2016-11-24 |
| CA2984026A1 (en) | 2010-04-15 |
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| CA2740000A1 (en) | 2010-04-15 |
| US20160095924A1 (en) | 2016-04-07 |
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| CN102245590A (zh) | 2011-11-16 |
| JP5777519B2 (ja) | 2015-09-09 |
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| EP2743265A1 (en) | 2014-06-18 |
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| JP6077509B2 (ja) | 2017-02-08 |
| EP2350043B1 (en) | 2014-03-26 |
| JP2019137688A (ja) | 2019-08-22 |
| CN104119242A (zh) | 2014-10-29 |
| JP6505912B2 (ja) | 2019-04-24 |
| US9139554B2 (en) | 2015-09-22 |
| WO2010042877A1 (en) | 2010-04-15 |
| HK1160459A1 (en) | 2012-08-17 |
| US10653780B2 (en) | 2020-05-19 |
| JP2012505250A (ja) | 2012-03-01 |
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| ES2475065T3 (es) | 2014-07-10 |
| JP2015028054A (ja) | 2015-02-12 |
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| CA2740000C (en) | 2017-12-12 |
| AU2009303345A1 (en) | 2010-04-15 |
| EP2743265B1 (en) | 2017-03-15 |
| CN104119242B (zh) | 2017-07-07 |
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