CA2889540A1 - Improvements in or relating to amphoteric liposomes - Google Patents
Improvements in or relating to amphoteric liposomes Download PDFInfo
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- CA2889540A1 CA2889540A1 CA2889540A CA2889540A CA2889540A1 CA 2889540 A1 CA2889540 A1 CA 2889540A1 CA 2889540 A CA2889540 A CA 2889540A CA 2889540 A CA2889540 A CA 2889540A CA 2889540 A1 CA2889540 A1 CA 2889540A1
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- liposomes
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- mochol
- dope
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Applications Claiming Priority (25)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71719905P | 2005-09-15 | 2005-09-15 | |
| US71729305P | 2005-09-15 | 2005-09-15 | |
| US71729105P | 2005-09-15 | 2005-09-15 | |
| EP05020218.3 | 2005-09-15 | ||
| EP05020217.5 | 2005-09-15 | ||
| EP05020216.7 | 2005-09-15 | ||
| US60/717,291 | 2005-09-15 | ||
| EP05020216A EP1764089A1 (en) | 2005-09-15 | 2005-09-15 | Serum stable liposomes comprising amphoter II lipid mixtures |
| EP05020218 | 2005-09-15 | ||
| US60/717,199 | 2005-09-15 | ||
| US60/717,293 | 2005-09-15 | ||
| EP05020217A EP1764090A1 (en) | 2005-09-15 | 2005-09-15 | Amphoteric liposomes for local drug applications |
| US11/267,423 US20060159737A1 (en) | 2004-11-19 | 2005-11-04 | Pharmaceutical compositions for local administration |
| PCT/EP2005/011905 WO2006048329A1 (en) | 2004-11-05 | 2005-11-04 | Improvements in or relating to pharmaceutical compositions comprising an oligonucleotide as an active agent |
| US11/266,999 US20060216343A1 (en) | 2004-11-05 | 2005-11-04 | Pharmaceutical compositions comprising an oligonucleotide as an active agent |
| US11/266,999 | 2005-11-04 | ||
| EPPCT/EP2005/011905 | 2005-11-04 | ||
| PCT/EP2005/011908 WO2006053646A2 (en) | 2004-11-19 | 2005-11-04 | Improvements in or relating to pharmaceutical compositions for local administration |
| EPPCT/EP2005/011908 | 2005-11-04 | ||
| US11/267,423 | 2005-11-04 | ||
| EP05090322A EP1658839A1 (en) | 2004-11-05 | 2005-11-21 | Oligonucleotide/carrier combinations targeting CD40 |
| EP05090322.8 | 2005-11-21 | ||
| EP06113784.0 | 2006-05-10 | ||
| EP06113784 | 2006-05-10 | ||
| CA2622584A CA2622584C (en) | 2005-09-15 | 2006-09-15 | Improvements in or relating to amphoteric liposomes |
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| CA2622584A Division CA2622584C (en) | 2005-09-15 | 2006-09-15 | Improvements in or relating to amphoteric liposomes |
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| CA2622584A Active CA2622584C (en) | 2005-09-15 | 2006-09-15 | Improvements in or relating to amphoteric liposomes |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2622584A Active CA2622584C (en) | 2005-09-15 | 2006-09-15 | Improvements in or relating to amphoteric liposomes |
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| US (3) | US20070104775A1 (enExample) |
| EP (1) | EP1764091B1 (enExample) |
| JP (1) | JP5571308B2 (enExample) |
| KR (1) | KR20080082956A (enExample) |
| AU (1) | AU2006291429B2 (enExample) |
| CA (2) | CA2889540A1 (enExample) |
| WO (1) | WO2007031333A2 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| DE10109897A1 (de) * | 2001-02-21 | 2002-11-07 | Novosom Ag | Fakultativ kationische Liposomen und Verwendung dieser |
| US8815599B2 (en) | 2004-06-01 | 2014-08-26 | Pronai Therapeutics, Inc. | Methods and compositions for the inhibition of gene expression |
| WO2007031333A2 (en) | 2005-09-15 | 2007-03-22 | Novosom Ag | Improvements in or relating to amphoteric liposomes |
| WO2007107304A2 (en) * | 2006-03-17 | 2007-09-27 | Novosom Ag | An efficient method for loading amphoteric liposomes with nucleic acid active substances |
| JP5122474B2 (ja) | 2005-12-01 | 2013-01-16 | プロネイ・セラピューティクス・インコーポレイテッド | 両性リポソーム製剤 |
| EP2056883B1 (en) * | 2006-08-04 | 2021-09-22 | Baxter International Inc. | Microsphere-based composition for preventing and/or reversing new-onset autoimmune diabetes |
| EP2462924A3 (en) | 2006-10-13 | 2013-01-23 | Marina Biotech, Inc. | Improvements in or relating to amphoteric liposomes. |
| WO2008103431A2 (en) * | 2007-02-23 | 2008-08-28 | Pronai Therapeutics, Inc. | Dnai - liposomes |
| GB0719367D0 (en) | 2007-10-03 | 2007-11-14 | Procarta Biosystems Ltd | Transcription factor decoys, compositions and methods |
| AU2008309880B2 (en) * | 2007-10-12 | 2014-07-10 | Biontech Delivery Technologies Gmbh | Amphoteric liposomes comprising neutral lipids |
| WO2009082491A1 (en) * | 2007-12-26 | 2009-07-02 | Alp Life Sciences, Llc | Nanovesontm: treatment, biomarkers and diagnostic tests for liver diseases and comorbid diseases |
| CN102112110A (zh) * | 2008-06-06 | 2011-06-29 | 米尔纳医疗股份有限公司 | 用于RNAi试剂体内递送的新型组合物 |
| JP5588619B2 (ja) * | 2009-03-11 | 2014-09-10 | 一丸ファルコス株式会社 | pH応答性リポソーム |
| US9937128B2 (en) * | 2009-08-03 | 2018-04-10 | The University Of North Carolina At Chapel Hill | Liposomes comprising a calcium phosphate-containing precipitate |
| GB201002413D0 (en) | 2010-02-12 | 2010-03-31 | Procarta Biosystems Ltd | Nucleic acid complexes |
| GB201005545D0 (en) | 2010-04-01 | 2010-05-19 | Procarta Biosystems Ltd | Transcription factor decoys |
| IT1404011B1 (it) | 2010-12-03 | 2013-11-08 | Uni Degli Studi Magna Graecia Di Catanzaro | Nanovettore coniugato con tsh per il trattamento del cancro della tiroide |
| WO2012135805A2 (en) * | 2011-03-31 | 2012-10-04 | modeRNA Therapeutics | Delivery and formulation of engineered nucleic acids |
| KR102176971B1 (ko) | 2012-07-05 | 2020-11-11 | 타이완 리포좀 캄파니 리미티드 | 관절염의 치료 방법 |
| BE1022518B1 (fr) * | 2014-03-12 | 2016-05-19 | Glaxosmithkline Biologicals S.A. | Formulation liposomale immunogene |
| AU2015301221B2 (en) | 2014-08-04 | 2020-07-02 | MiRagen Therapeutics, Inc. | Inhibitors of MYH7B and uses thereof |
| RU2712511C2 (ru) | 2014-09-08 | 2020-01-29 | Мираген Терапеутикс, Инк. | Миметики mir-29 и пути их применения |
| EP3247716A4 (en) | 2015-01-20 | 2018-10-17 | Miragen Therapeutics, Inc. | Mir-92 inhibitors and uses thereof |
| RU2718534C2 (ru) | 2015-06-05 | 2020-04-08 | Мираджен Терапьютикс, Инк. | Ингибиторы mir-155 для лечения кожной t-клеточной лимфомы (ctcl) |
| CN115537372A (zh) | 2016-07-13 | 2022-12-30 | 哈佛学院院长等 | 抗原呈递细胞模拟支架及其制备和使用方法 |
| RU2746414C1 (ru) * | 2017-05-23 | 2021-04-13 | ТиСиАй КО., ЛТД. | Эмульгированная липосомальная композиция и способ ее получения |
| EP3679140B1 (en) | 2017-09-08 | 2022-11-16 | MiNA Therapeutics Limited | Stabilized cebpa sarna compositions and methods of use |
| US11566246B2 (en) | 2018-04-12 | 2023-01-31 | Mina Therapeutics Limited | SIRT1-saRNA compositions and methods of use |
| WO2020208361A1 (en) | 2019-04-12 | 2020-10-15 | Mina Therapeutics Limited | Sirt1-sarna compositions and methods of use |
| GB2603454A (en) | 2020-12-09 | 2022-08-10 | Ucl Business Ltd | Novel therapeutics for the treatment of neurodegenerative disorders |
| EP4314292A1 (en) | 2021-03-26 | 2024-02-07 | MiNA Therapeutics Limited | Tmem173 sarna compositions and methods of use |
| JP7761921B2 (ja) * | 2021-05-21 | 2025-10-29 | 国立大学法人北海道大学 | 脂質ナノ粒子 |
| WO2023076511A1 (en) | 2021-10-28 | 2023-05-04 | Lyell Immunopharma, Inc. | Methods of generating cells |
| 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 |
| WO2023170435A1 (en) | 2022-03-07 | 2023-09-14 | Mina Therapeutics Limited | Il10 sarna compositions and methods of use |
| WO2024077174A1 (en) | 2022-10-05 | 2024-04-11 | Lyell Immunopharma, Inc. | Methods for culturing nr4a-deficient cells |
| EP4634388A1 (en) | 2022-12-14 | 2025-10-22 | Providence Therapeutics Holdings Inc. | Compositions and methods for infectious diseases |
| WO2024134199A1 (en) | 2022-12-22 | 2024-06-27 | Mina Therapeutics Limited | Chemically modified sarna compositions and methods of use |
| WO2025217398A1 (en) | 2024-04-10 | 2025-10-16 | Lyell Immunopharma, Inc. | Methods for culturing cells with improved culture medium |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5077211A (en) * | 1988-07-06 | 1991-12-31 | Applied Genetics, Inc. | Purification and administration of dna repair enzymes |
| WO1994022468A1 (en) * | 1993-04-02 | 1994-10-13 | Anticancer, Inc. | Method for delivering beneficial compositions to hair follicles |
| US5834012A (en) * | 1995-05-03 | 1998-11-10 | Roman Perez-Soler | Lipid complexed topoisomerase I inhibitors |
| JPH09248182A (ja) * | 1996-03-15 | 1997-09-22 | Oyo Seikagaku Kenkyusho | プラスミド包埋多重膜リポソーム |
| DE19648625A1 (de) | 1996-11-13 | 1998-05-14 | Soft Gene Gmbh | Mikroprojektil für das Einbringen von Substanzen in Zellen durch ballistischen Transfer |
| EP0979311A1 (en) * | 1997-04-30 | 2000-02-16 | Of The University Of Minnesota Regents | $i(IN VIVO) USE OF RECOMBINAGENIC OLIGONUCLEOBASES TO CORRECT GENETIC LESIONS IN HEPATOCYTES |
| DE69841002D1 (de) * | 1997-05-14 | 2009-09-03 | Univ British Columbia | Hochwirksame verkapselung von nukleinsäuren in lipidvesikeln |
| US6506559B1 (en) | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| US20040186071A1 (en) * | 1998-04-13 | 2004-09-23 | Bennett C. Frank | Antisense modulation of CD40 expression |
| US6197584B1 (en) * | 1998-05-01 | 2001-03-06 | Isis Pharmaceuticals, Inc. | Antisense modulation of CD40 expression |
| WO2000021370A1 (en) * | 1998-10-14 | 2000-04-20 | University Of Kentucky Research Foundation | Oligonucleotide delivery systems for camptothecins |
| US6379698B1 (en) * | 1999-04-06 | 2002-04-30 | Isis Pharmaceuticals, Inc. | Fusogenic lipids and vesicles |
| DE10160151A1 (de) | 2001-01-09 | 2003-06-26 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines vorgegebenen Zielgens |
| DE10109898A1 (de) | 2001-02-21 | 2002-09-05 | Novosom Gmbh | Lipide mit veränderlicher Ladung |
| DE10109897A1 (de) * | 2001-02-21 | 2002-11-07 | Novosom Ag | Fakultativ kationische Liposomen und Verwendung dieser |
| US20040086558A1 (en) * | 2001-02-22 | 2004-05-06 | Moshe Baru | Liposome mediated dna administration |
| DE50214201D1 (de) | 2001-06-05 | 2010-03-25 | Curevac Gmbh | Stabilisierte mRNA mit erhöhtem G/C-Gehalt, enkodierend für ein bakterielles Antigen sowie deren Verwendung |
| DE10207177A1 (de) | 2002-02-19 | 2003-09-04 | Novosom Ag | Fakultativ kationische Lipide |
| DE10207178A1 (de) | 2002-02-19 | 2003-09-04 | Novosom Ag | Komponenten für die Herstellung amphoterer Liposomen |
| AU2003237864B2 (en) * | 2002-05-15 | 2008-12-18 | California Pacific Medical Center | Delivery of nucleic acid-like compounds |
| AU2002953285A0 (en) * | 2002-12-12 | 2003-01-02 | Protech Research Pty Ltd | Yeast treatment |
| EP1608735A4 (en) | 2003-04-03 | 2008-11-05 | Alnylam Pharmaceuticals | RNAI CONJUGATES |
| SG190613A1 (en) * | 2003-07-16 | 2013-06-28 | Protiva Biotherapeutics Inc | Lipid encapsulated interfering rna |
| CA2586708A1 (en) * | 2004-11-05 | 2006-05-11 | Novosom Ag | Improvements in or relating to pharmaceutical compositions comprising an oligonucleotide as an active agent |
| JP2008520600A (ja) * | 2004-11-19 | 2008-06-19 | ノヴォソム アクチェンゲゼルシャフト | 局所投与のための医薬組成物におけるまたはそれに関する改善 |
| EP1764090A1 (en) | 2005-09-15 | 2007-03-21 | Novosom AG | Amphoteric liposomes for local drug applications |
| WO2007031333A2 (en) | 2005-09-15 | 2007-03-22 | Novosom Ag | Improvements in or relating to amphoteric liposomes |
| EP1764089A1 (en) | 2005-09-15 | 2007-03-21 | Novosom AG | Serum stable liposomes comprising amphoter II lipid mixtures |
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| WO2007031333A2 (en) | 2007-03-22 |
| AU2006291429B2 (en) | 2013-04-04 |
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| US9066867B2 (en) | 2015-06-30 |
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| EP1764091A2 (en) | 2007-03-21 |
| US9737484B2 (en) | 2017-08-22 |
| EP1764091B1 (en) | 2017-08-30 |
| EP1764091A3 (en) | 2007-06-13 |
| US20110076322A1 (en) | 2011-03-31 |
| US20070104775A1 (en) | 2007-05-10 |
| US20150231073A1 (en) | 2015-08-20 |
| JP5571308B2 (ja) | 2014-08-13 |
| CA2622584A1 (en) | 2007-03-22 |
| AU2006291429A1 (en) | 2007-03-22 |
| KR20080082956A (ko) | 2008-09-12 |
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