AU2012217685B2 - Compositions and methods for delivering nucleic acid to a cell - Google Patents
Compositions and methods for delivering nucleic acid to a cell Download PDFInfo
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- AU2012217685B2 AU2012217685B2 AU2012217685A AU2012217685A AU2012217685B2 AU 2012217685 B2 AU2012217685 B2 AU 2012217685B2 AU 2012217685 A AU2012217685 A AU 2012217685A AU 2012217685 A AU2012217685 A AU 2012217685A AU 2012217685 B2 AU2012217685 B2 AU 2012217685B2
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- Prior art keywords
- lipid
- nucleic acid
- liposome
- dna
- composition
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/531—Stem-loop; Hairpin
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- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/32—Special delivery means, e.g. tissue-specific
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| US61/443,246 | 2011-02-15 | ||
| PCT/US2012/025324 WO2012112730A2 (en) | 2011-02-15 | 2012-02-15 | Compositions and methods for delivering nucleic acid to a cell |
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| AU2012217685B2 true AU2012217685B2 (en) | 2017-05-18 |
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| WO (1) | WO2012112730A2 (https=) |
Families Citing this family (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012019168A2 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| RU2013120302A (ru) | 2010-10-01 | 2014-11-20 | Модерна Терапьютикс, Инк. | Сконструированные нуклеиновые кислоты и способы их применения |
| EP2691101A2 (en) | 2011-03-31 | 2014-02-05 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
| US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| RU2648950C2 (ru) | 2011-10-03 | 2018-04-02 | Модерна Терапьютикс, Инк. | Модифицированные нуклеозиды, нуклеотиды и нуклеиновые кислоты и их применение |
| CN104114572A (zh) | 2011-12-16 | 2014-10-22 | 现代治疗公司 | 经修饰的核苷、核苷酸和核酸组合物 |
| US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
| AU2013243948A1 (en) | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins associated with human disease |
| US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
| US9254311B2 (en) | 2012-04-02 | 2016-02-09 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins |
| AU2013202947B2 (en) | 2012-06-13 | 2016-06-02 | Ipsen Biopharm Ltd. | Methods for treating pancreatic cancer using combination therapies comprising liposomal irinotecan |
| US9717724B2 (en) | 2012-06-13 | 2017-08-01 | Ipsen Biopharm Ltd. | Methods for treating pancreatic cancer using combination therapies |
| ITRM20120480A1 (it) * | 2012-10-09 | 2014-04-10 | Uni Degli Studi Camerino | Nanoparticelle lipidiche multicomponenti e procedimenti per la loro preparazione. |
| WO2014081507A1 (en) | 2012-11-26 | 2014-05-30 | Moderna Therapeutics, Inc. | Terminally modified rna |
| US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
| US10023626B2 (en) | 2013-09-30 | 2018-07-17 | Modernatx, Inc. | Polynucleotides encoding immune modulating polypeptides |
| JP2016538829A (ja) | 2013-10-03 | 2016-12-15 | モデルナ セラピューティクス インコーポレイテッドＭｏｄｅｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | 低密度リポタンパク質受容体をコードするポリヌクレオチド |
| SG10201912038TA (en) | 2014-04-23 | 2020-02-27 | Modernatx Inc | Nucleic acid vaccines |
| WO2016007644A1 (en) | 2014-07-08 | 2016-01-14 | The Children's Medical Center Corporation | Compositions and methods for treating diabetes |
| US11318131B2 (en) | 2015-05-18 | 2022-05-03 | Ipsen Biopharm Ltd. | Nanoliposomal irinotecan for use in treating small cell lung cancer |
| WO2016191547A1 (en) * | 2015-05-26 | 2016-12-01 | Comfort Care For Animals Llc | Liposome loading |
| EP3337467B1 (en) | 2015-08-20 | 2020-12-09 | Ipsen Biopharm Ltd. | Combination therapy using liposomal irinotecan and a parp inhibitor for cancer treatment |
| MX385425B (es) | 2015-08-21 | 2025-03-18 | Ipsen Biopharm Ltd | Irinotecán liposomal y oxaliplatino, 5-fluoroacilo y leucovorina para usarse en el tratamiento de cáncer pancreático metastásico. |
| EP4286012A3 (en) | 2015-09-17 | 2024-05-29 | ModernaTX, Inc. | Compounds and compositions for intracellular delivery of therapeutic agents |
| CN108291227A (zh) | 2015-10-14 | 2018-07-17 | 拜奥-帕斯控股股份有限公司 | 用于脂质体制剂的对乙氧基核酸 |
| MX382522B (es) | 2015-10-16 | 2025-03-13 | Ipsen Biopharm Ltd | Composiciones farmaceuticas estabilizantes de camptotecina. |
| HRP20220652T1 (hr) | 2015-12-10 | 2022-06-24 | Modernatx, Inc. | Pripravci i postupci unosa terapijskih sredstava |
| HUE057877T2 (hu) | 2015-12-22 | 2022-06-28 | Modernatx Inc | Vegyületek és készítmények terápiás szerek intracelluláris bejuttatására |
| AU2017325971A1 (en) | 2016-09-16 | 2019-04-11 | Bio-Path Holdings, Inc. | Combination therapy with liposomal antisense oligonucleotides |
| EP3535026A1 (en) | 2016-11-02 | 2019-09-11 | Ipsen Biopharm Limited | Treating gastric cancer using combination therapies comprising liposomal irinotecan, oxaliplatin, 5-fluoruracil (and leucovorin) |
| US11583504B2 (en) | 2016-11-08 | 2023-02-21 | Modernatx, Inc. | Stabilized formulations of lipid nanoparticles |
| WO2018170322A1 (en) | 2017-03-15 | 2018-09-20 | Modernatx, Inc. | Crystal forms of amino lipids |
| SMT202300097T1 (it) | 2017-03-15 | 2023-05-12 | Modernatx Inc | Composto e composizioni per il rilascio intracellulare di agenti terapeutici |
| US11969506B2 (en) | 2017-03-15 | 2024-04-30 | Modernatx, Inc. | Lipid nanoparticle formulation |
| KR102723213B1 (ko) * | 2017-03-29 | 2024-10-30 | 인스티튜트 오브 베이직 메디컬 사이언시즈, 차이니즈 아카데미 오브 메디컬 사이언시즈 | 핵산 전달제 및 그의 관련 제품의 제조에 있어서의 화합물 또는 전통 중국 의약 추출물의 적용 |
| EA201992485A1 (ru) | 2017-04-19 | 2020-02-17 | Байо-Пат Холдингз, Инк. | Р-этокси нуклеиновые кислоты для ингибирования stat3 |
| EA201992490A1 (ru) | 2017-04-19 | 2020-03-03 | Байо-Пат Холдингз, Инк. | Р-этокси нуклеиновые кислоты для ингибирования bcl2 |
| US12077501B2 (en) | 2017-06-14 | 2024-09-03 | Modernatx, Inc. | Compounds and compositions for intracellular delivery of agents |
| WO2019046809A1 (en) | 2017-08-31 | 2019-03-07 | Modernatx, Inc. | METHODS OF MANUFACTURING LIPID NANOPARTICLES |
| JP6462073B1 (ja) * | 2017-09-04 | 2019-01-30 | 一丸ファルコス株式会社 | ｐＨ感受性リポソームの製造方法 |
| TW201927288A (zh) | 2017-10-20 | 2019-07-16 | 德商拜恩迪克Ｒｎａ製藥有限公司 | 適用於治療之微脂體ｒｎａ配製物的製備及儲存 |
| US12280114B2 (en) | 2018-03-29 | 2025-04-22 | Institute Of Basic Medical Sciences | Extraction of plant source “medicinal soup” and manual preparation of “herbal medicine” and related products |
| EP3778556A4 (en) * | 2018-03-29 | 2022-04-20 | Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences | APPLICATION OF A TRADITIONAL CHINESE MEDICINE COMPOUND OR EXTRACT IN THE MANUFACTURE OF A NUCLEIC ACID RELEASE AGENT AND RELATED PRODUCTS |
| AU2019345067A1 (en) | 2018-09-19 | 2021-04-08 | Modernatx, Inc. | High-purity peg lipids and uses thereof |
| MA53650A (fr) | 2018-09-19 | 2021-07-28 | Modernatx Inc | Lipides peg et leurs utilisations |
| US12263248B2 (en) | 2018-09-19 | 2025-04-01 | Modernatx, Inc. | Compounds and compositions for intracellular delivery of therapeutic agents |
| CN113271926A (zh) | 2018-09-20 | 2021-08-17 | 摩登纳特斯有限公司 | 脂质纳米颗粒的制备及其施用方法 |
| US11197827B2 (en) * | 2018-10-31 | 2021-12-14 | Microsoft Technology Licensing, Llc | Polynucleotide encapsulation and preservation using self-assembling membranes |
| WO2020200472A1 (en) * | 2019-04-05 | 2020-10-08 | Biontech Rna Pharmaceuticals Gmbh | Preparation and storage of liposomal rna formulations suitable for therapy |
| AU2020350759A1 (en) | 2019-09-19 | 2022-03-31 | Modernatx, Inc. | Branched tail lipid compounds and compositions for intracellular delivery of therapeutic agents |
| BR112022004936A2 (pt) | 2019-09-19 | 2022-06-14 | Modernatx Inc | Compostos lipídicos contendo carbonato e composições para distribuição intracelular de agentes terapêuticos |
| US20230372397A1 (en) | 2020-10-06 | 2023-11-23 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
| WO2022076606A1 (en) | 2020-10-06 | 2022-04-14 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
| US20240123067A1 (en) | 2020-12-17 | 2024-04-18 | Iovance Biotherapeutics, Inc. | Treatment of cancers with tumor infiltrating lymphocyte therapies |
| CA3202483A1 (en) | 2020-12-17 | 2022-06-23 | Maria Fardis | Treatment with tumor infiltrating lymphocyte therapies in combination with ctla-4 and pd-1 inhibitors |
| US11524023B2 (en) | 2021-02-19 | 2022-12-13 | Modernatx, Inc. | Lipid nanoparticle compositions and methods of formulating the same |
| EP4326287A2 (en) | 2021-04-19 | 2024-02-28 | Iovance Biotherapeutics, Inc. | Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies |
| US20240342285A1 (en) | 2021-07-28 | 2024-10-17 | Iovance Biotherapeutics, Inc. | Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with kras inhibitors |
| WO2023077015A2 (en) | 2021-10-27 | 2023-05-04 | Iovance Biotherapeutics, Inc. | Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy |
| EP4430167A1 (en) | 2021-11-10 | 2024-09-18 | Iovance Biotherapeutics, Inc. | Methods of expansion treatment utilizing cd8 tumor infiltrating lymphocytes |
| CA3248034A1 (en) | 2022-04-15 | 2023-10-19 | Iovance Biotherapeutics, Inc. | METHODS FOR EXPANSION OF TIL CELLS BY MEANS OF SPECIFIC CYTOKINE COMBINATIONS AND/OR AKT INHIBITOR TREATMENT |
| CN114984236B (zh) * | 2022-04-29 | 2023-03-24 | 深圳近邻生物科技有限公司 | 一种响应型核酸递送系统及其制备方法、交联聚合物载体 |
| WO2025108545A1 (en) * | 2023-11-22 | 2025-05-30 | Danmarks Tekniske Universitet | Delivery of nucleotides from injectable biomaterial |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009061515A1 (en) * | 2007-11-09 | 2009-05-14 | Northeastern University | Self-assembling micelle-like nanoparticles for systemic gene delivery |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5908635A (en) * | 1994-08-05 | 1999-06-01 | The United States Of America As Represented By The Department Of Health And Human Services | Method for the liposomal delivery of nucleic acids |
| US5885613A (en) | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
| US6214388B1 (en) | 1994-11-09 | 2001-04-10 | The Regents Of The University Of California | Immunoliposomes that optimize internalization into target cells |
| US6210707B1 (en) | 1996-11-12 | 2001-04-03 | The Regents Of The University Of California | Methods of forming protein-linked lipidic microparticles, and compositions thereof |
| US7244826B1 (en) | 1998-04-24 | 2007-07-17 | The Regents Of The University Of California | Internalizing ERB2 antibodies |
| US6794128B2 (en) | 1998-04-24 | 2004-09-21 | The Regents Of The University Of California | Methods of selecting internalizing antibodies |
| US7780882B2 (en) * | 1999-02-22 | 2010-08-24 | Georgetown University | Simplified and improved method for preparing an antibody or an antibody fragment targeted immunoliposome for systemic administration of a therapeutic or diagnostic agent |
| DE602004027655D1 (de) * | 2003-11-03 | 2010-07-22 | Yissum Res Dev Co | Verfahren zur auswahl von kationischen oder anionischen liposomen zur behandlung einer schleimhautmembran und diese enthaltendes set |
| JP4651276B2 (ja) * | 2003-11-12 | 2011-03-16 | テルモ株式会社 | リポソームを体内より排泄する抗体およびリポソームの血中クリアランス促進剤 |
| JP3941808B2 (ja) | 2004-10-28 | 2007-07-04 | 株式会社日立製作所 | 動画像の変化点検出方法及び装置 |
| US20070171077A1 (en) | 2006-01-26 | 2007-07-26 | Behrouz Kawarizadeh | License Plate Incorporating RFID Device |
| WO2008096779A1 (ja) * | 2007-02-09 | 2008-08-14 | National University Corporation NARA Institute of Science and Technology | Ｃ７０含有リポソームおよびその製造方法、並びにその利用 |
| SG178789A1 (en) | 2007-02-16 | 2012-03-29 | Merrimack Pharmaceuticals Inc | Antibodies against erbb3 and uses thereof |
| CA2702103A1 (en) | 2007-10-12 | 2009-04-16 | Novosom Ag | Improvements in or relating to amphotaric liposomes comprising neutral lipids |
| CN102231979B (zh) * | 2008-10-16 | 2014-10-29 | 玛瑞纳生物技术有限公司 | 基因沉默治疗剂的脂质体有效递送方法和组合物 |
| JP5532635B2 (ja) * | 2009-03-11 | 2014-06-25 | 凸版印刷株式会社 | 核酸含有リポソームを用いた遺伝子解析方法及び遺伝子解析キット |
| EP2453911A1 (en) | 2009-04-30 | 2012-05-23 | Genetic Immunity Kft | Immunogenic nanomedicine composition and preparation and uses thereof |
| US8420118B2 (en) * | 2009-09-10 | 2013-04-16 | The Board Of Regents Of The University Of Oklahoma | Anionic lipids and lipid nano-structures and methods of producing and using same |
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| WO2009061515A1 (en) * | 2007-11-09 | 2009-05-14 | Northeastern University | Self-assembling micelle-like nanoparticles for systemic gene delivery |
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| JP2017093436A (ja) | 2017-06-01 |
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