TWI225412B - Liposome-entrapped polynucleotide composition and method - Google Patents
Liposome-entrapped polynucleotide composition and method Download PDFInfo
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- TWI225412B TWI225412B TW087109984A TW87109984A TWI225412B TW I225412 B TWI225412 B TW I225412B TW 087109984 A TW087109984 A TW 087109984A TW 87109984 A TW87109984 A TW 87109984A TW I225412 B TWI225412 B TW I225412B
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- fat
- polynucleotide
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- solvent
- fatty
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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
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- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers
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- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
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| US5855911A (en) * | 1995-08-29 | 1999-01-05 | Board Of Regents, The University Of Texas System | Liposomal phosphodiester, phosphorothioate, and P-ethoxy oligonucleotides |
| US7309692B1 (en) * | 1996-07-08 | 2007-12-18 | Board Of Regents, The University Of Texas System | Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to GRB2 or CRK1 |
| US6977244B2 (en) | 1996-10-04 | 2005-12-20 | Board Of Regents, The University Of Texas Systems | Inhibition of Bcl-2 protein expression by liposomal antisense oligodeoxynucleotides |
| US6056973A (en) * | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
| US7262173B2 (en) * | 1997-03-21 | 2007-08-28 | Georgetown University | Chemosensitizing with liposomes containing oligonucleotides |
| US6126965A (en) * | 1997-03-21 | 2000-10-03 | Georgetown University School Of Medicine | Liposomes containing oligonucleotides |
| US6559129B1 (en) * | 1997-03-21 | 2003-05-06 | Georgetown University | Cationic liposomal delivery system and therapeutic use thereof |
| US20030229040A1 (en) * | 1997-03-21 | 2003-12-11 | Georgetown University | Cationic liposomal delivery system and therapeutic use thereof |
| US7285288B1 (en) | 1997-10-03 | 2007-10-23 | Board Of Regents, The University Of Texas System | Inhibition of Bcl-2 protein expression by liposomal antisense oligodeoxynucleotides |
| US7704962B1 (en) | 1997-10-03 | 2010-04-27 | Board Of Regents, The University Of Texas System | Small oligonucleotides with anti-tumor activity |
| AU773515B2 (en) * | 1999-02-08 | 2004-05-27 | Alza Corporation | Method for controlling liposome size |
| EP1365794A2 (en) * | 2000-07-21 | 2003-12-03 | Lue, Tom | Prevention and treatment of sexual arousal disorders |
| US7223406B2 (en) | 2000-07-21 | 2007-05-29 | The Regents Of The University Of California | Methods and compositions for preventing and treating male erectile dysfunction and female sexual arousal disorder |
| US20020146829A1 (en) * | 2000-11-29 | 2002-10-10 | Aventis Pharmaceuticals Products Inc. | Neutral and anionic colloidal particles for gene delivery |
| US6610322B1 (en) * | 2000-12-20 | 2003-08-26 | Brian Charles Keller | Self forming, thermodynamically stable liposomes and their applications |
| WO2002087541A1 (en) * | 2001-04-30 | 2002-11-07 | Protiva Biotherapeutics Inc. | Lipid-based formulations for gene transfer |
| KR100411234B1 (ko) * | 2001-08-14 | 2003-12-18 | 한국과학기술원 | 올리고뉴클레오티드 혼성화 미셀 및 그의 제조방법 |
| CA2471967A1 (en) * | 2002-01-03 | 2003-07-31 | Board Of Regents, The University Of Texas System | Wt1 antisense oligos for the inhibition of breast cancer |
| KR100466254B1 (ko) * | 2002-02-25 | 2005-01-14 | 한국과학기술원 | 세포내 전달을 위한 올리고뉴클레오티드와 친수성 고분자로 구성되는 유전자 전달용 접합체, 고분자 전해질 복합 미셀 및 그의 제조방법 |
| AU2003237864B2 (en) * | 2002-05-15 | 2008-12-18 | California Pacific Medical Center | Delivery of nucleic acid-like compounds |
| US20030219696A1 (en) * | 2002-05-23 | 2003-11-27 | Moreland Gerald W. | Method and apparatus for preventing backflow in dental saliva evacuators |
| WO2004002468A1 (en) * | 2002-06-26 | 2004-01-08 | Medigene Oncology Gmbh | Method of producing a cationic liposomal preparation comprising a lipophilic compound |
| US7901708B2 (en) | 2002-06-28 | 2011-03-08 | Protiva Biotherapeutics, Inc. | Liposomal apparatus and manufacturing methods |
| AU2002953285A0 (en) * | 2002-12-12 | 2003-01-02 | Protech Research Pty Ltd | Yeast treatment |
| ES2366617T3 (es) | 2003-04-21 | 2011-10-21 | Epeius Biotechnologies Corporation | Métodos y composiciones para el tratamiento de transtornos. |
| US20070178066A1 (en) | 2003-04-21 | 2007-08-02 | Hall Frederick L | Pathotropic targeted gene delivery system for cancer and other disorders |
| DK1765294T3 (da) * | 2004-05-12 | 2008-11-10 | Baxter Int | Nukleinsyremikrokugler samt deres fremstilling og afgivelse |
| EP1904111A4 (en) | 2005-06-03 | 2009-08-19 | Univ Johns Hopkins | COMPOSITIONS AND METHODS FOR REDUCING MICRORNA EXPRESSION FOR THE TREATMENT OF NEOPLASIA |
| US20070087045A1 (en) * | 2005-10-14 | 2007-04-19 | Industrial Technology Research Institute | Lipid carrier and method of preparing the same |
| WO2007080902A1 (ja) | 2006-01-11 | 2007-07-19 | Kyowa Hakko Kogyo Co., Ltd. | 眼球において標的遺伝子の発現を抑制する組成物および眼球における疾患の治療剤 |
| EP2639315A1 (en) | 2007-05-11 | 2013-09-18 | The Johns Hopkins University | Biomarkers for melanoma |
| PL208054B1 (pl) * | 2007-09-06 | 2011-03-31 | Akademia Medyczna Im Piastow Śląskich We Wrocławiu | Kompozycja lipidowa do wytwarzania lipidowego nośnika dla leków genetycznych i jej zastosowanie |
| US20110038941A1 (en) * | 2007-12-27 | 2011-02-17 | The Ohio State University Research Foundation | Lipid Nanoparticle Compositions and Methods of Making and Using the Same |
| WO2009137095A2 (en) | 2008-05-08 | 2009-11-12 | The Johns Hopkins University | Compositions and methods for modulating an immune response |
| WO2010013815A1 (ja) | 2008-08-01 | 2010-02-04 | 協和発酵キリン株式会社 | 標的遺伝子の発現を抑制する組成物 |
| EP2408916A2 (en) | 2009-03-19 | 2012-01-25 | Merck Sharp&Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF CONNECTIVE TISSUE GROWTH FACTOR (CTGF) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| US20120029054A1 (en) | 2009-03-19 | 2012-02-02 | Merck Sharp & Dohme Corp. | RNA Interference Mediated Inhibition of GATA Binding Protein 3 (GATA3) Gene Expression Using Short Intefering Nucleic Acid (siNA) |
| EP2408458A1 (en) | 2009-03-19 | 2012-01-25 | Merck Sharp&Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 6 (STAT6) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| SG174452A1 (en) | 2009-03-19 | 2011-10-28 | Merck Sharp & Dohme | RNA INTERFERENCE MEDIATED INHIBITION OF BTB AND CNC HOMOLOGY 1, BASIC LEUCINE ZIPPER TRANSCRIPTION FACTOR 1 (BACH 1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) SEQUENCE LISTING |
| CN102439152A (zh) | 2009-03-27 | 2012-05-02 | 默沙东公司 | 使用短干扰核酸（siNA）的RNA干扰介导的细胞间粘附分子1（ICAM-1）基因表达的抑制 |
| WO2010111471A2 (en) | 2009-03-27 | 2010-09-30 | Merck Sharp & Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 1 (STAT1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| WO2010111468A2 (en) | 2009-03-27 | 2010-09-30 | Merck Sharp & Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF THE NERVE GROWTH FACTOR BETA CHAIN (NGFß) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (SINA) |
| US20120022143A1 (en) | 2009-03-27 | 2012-01-26 | Merck Sharp & Dohme Corp | RNA Interference Mediated Inhibition of the Thymic Stromal Lymphopoietin (TSLP) Gene Expression Using Short Interfering Nucliec Acid (siNA) |
| US20120010272A1 (en) | 2009-03-27 | 2012-01-12 | Merck Sharp & Dohme Corp. | RNA Interference Mediated Inhibition of Apoptosis Signal-Regulating Kinase 1 (ASK1) Gene Expression Using Short Interfering Nucleic Acid (siNA) |
| KR101689787B1 (ko) | 2009-08-31 | 2016-12-26 | 나노캐리어 가부시키가이샤 | 입자 조성물 및 이를 가진 의약 조성물 |
| JP4653242B1 (ja) | 2010-02-12 | 2011-03-16 | ナノキャリア株式会社 | 粒子状医薬組成物 |
| WO2011119995A2 (en) | 2010-03-26 | 2011-09-29 | Cerulean Pharma Inc. | Formulations and methods of use |
| US9408914B2 (en) | 2010-04-28 | 2016-08-09 | Kyowa Hakko Kirin Co., Ltd. | Cationic lipid |
| EP2567952A4 (en) | 2010-04-28 | 2015-11-25 | Kyowa Hakko Kirin Co Ltd | CATIONIC LIPID |
| CA2799403C (en) | 2010-05-14 | 2020-01-21 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for treating leukemia |
| CN103119160B (zh) | 2010-05-14 | 2016-06-01 | 达那-法伯癌症研究所 | 用于调节代谢的组合物和方法 |
| US8518907B2 (en) | 2010-08-02 | 2013-08-27 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of catenin (cadherin-associated protein), beta 1 (CTNNB1) gene expression using short interfering nucleic acid (siNA) |
| EP3587574B1 (en) | 2010-08-17 | 2022-03-16 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of hepatitis b virus (hbv) gene expression using short interfering nucleic acid (sina) |
| JP6106085B2 (ja) | 2010-08-24 | 2017-03-29 | サーナ・セラピューティクス・インコーポレイテッドＳｉｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | 内部非核酸スペーサーを含む一本鎖ＲＮＡｉ剤 |
| EP2609106A4 (en) | 2010-08-26 | 2014-03-19 | Merck Sharp & Dohme | RNA INTERFERENCE MEDIATED INHIBITION OF PROLYL HYDROXYLASE DOMAIN 2 (PHD2) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| US9260471B2 (en) | 2010-10-29 | 2016-02-16 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acids (siNA) |
| JP5952197B2 (ja) | 2011-01-19 | 2016-07-13 | 協和発酵キリン株式会社 | 標的遺伝子の発現を抑制する組成物 |
| JP2013095755A (ja) | 2011-11-02 | 2013-05-20 | Kyowa Hakko Kirin Co Ltd | カチオン性脂質 |
| CA2856117A1 (en) | 2011-11-17 | 2013-05-23 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Auto-recognizing therapeutic rna/dna chimeric nanoparticles (np) |
| CA2856116A1 (en) | 2011-11-17 | 2013-05-23 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Therapeutic rna switches compositions and methods of use |
| TW201330874A (zh) | 2011-12-12 | 2013-08-01 | Kyowa Hakko Kirin Co Ltd | 含有陽離子性脂質之組合之脂質奈米粒子 |
| TWI594767B (zh) | 2011-12-12 | 2017-08-11 | 協和醱酵麒麟有限公司 | 含有陽離子性脂質之藥物傳遞系統用脂質奈米粒子 |
| WO2013106358A1 (en) | 2012-01-10 | 2013-07-18 | Hussain M Mahmood | Method of treating hyperlipidemia and atherosclerosis with mir-30c |
| EP2830596B1 (en) * | 2012-03-29 | 2020-12-30 | Translate Bio, Inc. | Lipid-derived neutral nanoparticles |
| EP2852381B1 (en) | 2012-05-23 | 2020-10-07 | The Ohio State University | Lipid nanoparticle compositions and methods of making and methods of using the same |
| EP2856172A4 (en) | 2012-05-25 | 2016-03-02 | Univ Vermont | COMPOSITIONS AND METHODS FOR TESTING THROMBOCYTE REACTIVITY AND TREATMENT SELECTION |
| TW201726600A (zh) | 2012-07-06 | 2017-08-01 | 協和醱酵麒麟有限公司 | 陽離子性脂質 |
| US9913907B2 (en) | 2012-07-16 | 2018-03-13 | Kyowa Hakko Kirin Co., Ltd. | RNAi pharmaceutical composition for suppressing expression of KRAS gene |
| JP6000033B2 (ja) * | 2012-09-18 | 2016-09-28 | 株式会社ピカソ美化学研究所 | 内包物質に耐熱性を与えたリポソーム及びその製造方法 |
| EP2970945B1 (en) | 2013-03-14 | 2024-05-01 | GenVivo, Inc. | Improved thymidine kinase gene |
| EP3158992A1 (en) * | 2015-10-21 | 2017-04-26 | Universität Heidelberg | Liposomes containing cell penetrating peptides and tetraetherlipids for the oral delivery of macromolecules |
| EP3373939A4 (en) | 2015-11-10 | 2019-06-26 | B.G. Negev Technologies and Applications Ltd., at Ben-Gurion University | MEDIUM AND METHOD FOR REDUCING TUMORIGENITY OF CANCER STEM CELLS |
| WO2017099829A1 (en) | 2015-12-11 | 2017-06-15 | The General Hospital Corporation | Compositions and methods for treating drug-tolerant glioblastoma |
| WO2017111172A1 (ja) | 2015-12-25 | 2017-06-29 | 協和発酵キリン株式会社 | カチオン性脂質としての化合物 |
| WO2019195738A1 (en) | 2018-04-06 | 2019-10-10 | Children's Medical Center Corporation | Compositions and methods for somatic cell reprogramming and modulating imprinting |
| EP3628309A1 (en) | 2018-09-28 | 2020-04-01 | Universität Heidelberg | Method of making oral dosage forms |
| EP4085137A4 (en) * | 2019-12-31 | 2024-06-12 | Fred Hutchinson Cancer Center | Nanoparticle systems to stimulate and maintain immune system responsiveness at treatment sites |
| EP4161552A1 (en) | 2020-06-05 | 2023-04-12 | The Broad Institute, Inc. | Compositions and methods for treating neoplasia |
| WO2022053130A1 (en) | 2020-09-09 | 2022-03-17 | Sid Alex Group, S.R.O. | Antago-mir-155 for treatment of v-src, c-src-tyrosine kinase-induced cancers |
| US20230241118A1 (en) | 2021-10-20 | 2023-08-03 | University Of Rochester | Rejuvenation treatment of age-related white matter loss |
| EP4658294A2 (en) | 2023-02-02 | 2025-12-10 | University of Rochester | Competitive replacement of glial cells |
| WO2024226499A1 (en) | 2023-04-24 | 2024-10-31 | The Broad Institute, Inc. | Compositions and methods for modifying fertility |
| WO2025090427A1 (en) | 2023-10-23 | 2025-05-01 | University Of Rochester | Glial-targeted relief of hyperexcitability in neurodegenerative diseases |
| WO2025096975A1 (en) | 2023-11-02 | 2025-05-08 | The Regents Of The University Of Colorado, A Body Corporate | Compositions and methods of enhancing immune cell therapies by runx2 modulation |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4394448A (en) * | 1978-02-24 | 1983-07-19 | Szoka Jr Francis C | Method of inserting DNA into living cells |
| DE69634084T2 (de) * | 1995-06-07 | 2005-12-08 | Inex Pharmaceuticals Corp. | Herstellung von lipid-nukleinsäure partikeln duch ein hydrophobische lipid-nukleinsäuree komplexe zwischenprodukt und zur verwendung in der gentransfer |
| US5705385A (en) * | 1995-06-07 | 1998-01-06 | Inex Pharmaceuticals Corporation | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
| WO1997004748A2 (en) * | 1995-08-01 | 1997-02-13 | Advanced Therapies, Inc. | Enhanced artificial viral envelopes for cellular delivery of therapeutic substances |
| US5855911A (en) * | 1995-08-29 | 1999-01-05 | Board Of Regents, The University Of Texas System | Liposomal phosphodiester, phosphorothioate, and P-ethoxy oligonucleotides |
| FR2751222B1 (fr) * | 1996-07-16 | 1998-10-09 | Capsulis | Compositions contenant au moins un acide nucleique et leurs applications dans le domaine biomedical, en particulier en therapie genique |
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1998
- 1998-06-22 DE DE69820465T patent/DE69820465T2/de not_active Expired - Fee Related
- 1998-06-22 AT AT98930447T patent/ATE255882T1/de not_active IP Right Cessation
- 1998-06-22 CA CA002294579A patent/CA2294579C/en not_active Expired - Fee Related
- 1998-06-22 JP JP50493699A patent/JP2002508765A/ja not_active Abandoned
- 1998-06-22 AU AU79837/98A patent/AU7983798A/en not_active Abandoned
- 1998-06-22 WO PCT/US1998/012937 patent/WO1998058630A1/en not_active Ceased
- 1998-06-22 DK DK98930447T patent/DK1017365T3/da active
- 1998-06-22 ES ES98930447T patent/ES2212305T3/es not_active Expired - Lifetime
- 1998-06-22 EP EP98930447A patent/EP1017365B1/en not_active Expired - Lifetime
- 1998-06-22 TW TW087109984A patent/TWI225412B/zh not_active IP Right Cessation
- 1998-06-23 US US09/103,341 patent/US6120798A/en not_active Expired - Lifetime
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|---|---|
| US6120798A (en) | 2000-09-19 |
| WO1998058630A1 (en) | 1998-12-30 |
| JP2002508765A (ja) | 2002-03-19 |
| DE69820465T2 (de) | 2004-09-16 |
| ES2212305T3 (es) | 2004-07-16 |
| AU7983798A (en) | 1999-01-04 |
| EP1017365A1 (en) | 2000-07-12 |
| ATE255882T1 (de) | 2003-12-15 |
| EP1017365B1 (en) | 2003-12-10 |
| CA2294579C (en) | 2007-10-09 |
| HK1025906A1 (en) | 2000-12-01 |
| DE69820465D1 (de) | 2004-01-22 |
| DK1017365T3 (da) | 2004-03-29 |
| CA2294579A1 (en) | 1998-12-30 |
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