JP2012509273A - 核酸送達系のための放出可能融合性脂質 - Google Patents
核酸送達系のための放出可能融合性脂質 Download PDFInfo
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- JP2012509273A JP2012509273A JP2011536585A JP2011536585A JP2012509273A JP 2012509273 A JP2012509273 A JP 2012509273A JP 2011536585 A JP2011536585 A JP 2011536585A JP 2011536585 A JP2011536585 A JP 2011536585A JP 2012509273 A JP2012509273 A JP 2012509273A
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012509272A (ja) * | 2008-11-17 | 2012-04-19 | エンゾン ファーマシューティカルズ，インコーポレーテッド | 核酸送達系のための放出性カチオン脂質 |
| JP2019535808A (ja) * | 2016-10-17 | 2019-12-12 | 南京▲緑▼叶制▲薬▼有限公司 | ｂｃｌ−２を抑制するアンチセンスオリゴヌクレオチドの脂質ナノ粒子及びその調製方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3539572A1 (en) | 2005-08-24 | 2019-09-18 | ImmunoGen, Inc. | Process for preparing maytansinoid antibody conjugates |
| US20100233270A1 (en) | 2009-01-08 | 2010-09-16 | Northwestern University | Delivery of Oligonucleotide-Functionalized Nanoparticles |
| EP2437790B1 (en) | 2009-06-03 | 2019-02-20 | Immunogen, Inc. | Conjugation methods |
| CA2800401C (en) * | 2010-06-03 | 2020-09-15 | Alnylam Pharmaceuticals, Inc. | Biodegradable lipids for the delivery of active agents |
| DK3135301T3 (en) | 2010-06-22 | 2018-06-25 | Onxeo | OPTIMIZED IN VIVO DELIVERY SYSTEM WITH ENDOSOMOLYTIC SUBSTANCES FOR NUCLEIC ACID CONJUGATES |
| TR201902180T4 (tr) | 2011-03-29 | 2019-03-21 | Immunogen Inc | Tek adimli bi̇r i̇şlem i̇le maytansi̇noi̇d anti̇kor konjugatlarinin hazirlanmasi |
| EP2527440A1 (en) | 2011-05-27 | 2012-11-28 | Institut Curie | Cancer treatment by combining DNA molecules mimicking double strand breaks with hyperthermia |
| ES3065854T3 (en) | 2011-12-07 | 2026-05-08 | Alnylam Pharmaceuticals Inc | Biodegradable lipids for the delivery of active agents |
| JP2015501844A (ja) | 2011-12-16 | 2015-01-19 | 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． | 修飾ヌクレオシド、ヌクレオチドおよび核酸組成物 |
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| WO2014205126A1 (en) | 2013-06-19 | 2014-12-24 | The Regents Of The University Of California | Chemical structures for localized delivery of therapeutic agents |
| JP6527516B2 (ja) | 2013-12-03 | 2019-06-05 | ノースウェスタン ユニバーシティ | リポソーム粒子、前述のものを作製する方法及びその使用 |
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| TWI665192B (zh) | 2014-05-28 | 2019-07-11 | Bayer Cropscience Aktiengesellschaft | 製備二氫異唑衍生物之方法 |
| EP3164113B1 (en) | 2014-06-04 | 2019-03-27 | Exicure, Inc. | Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications |
| WO2016028940A1 (en) | 2014-08-19 | 2016-02-25 | Northwestern University | Protein/oligonucleotide core-shell nanoparticle therapeutics |
| US11213593B2 (en) | 2014-11-21 | 2022-01-04 | Northwestern University | Sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates |
| JP6823067B2 (ja) | 2015-09-10 | 2021-01-27 | タンボ・インコーポレイテッド | 生体直交型組成物 |
| US11364304B2 (en) | 2016-08-25 | 2022-06-21 | Northwestern University | Crosslinked micellar spherical nucleic acids |
| CN107951861B (zh) * | 2016-10-17 | 2020-12-01 | 南京绿叶制药有限公司 | 一种脂质纳米粒膜材料组合物 |
| US10383952B2 (en) * | 2016-12-21 | 2019-08-20 | Arcturus Therapeutics, Inc. | Ionizable cationic lipid for RNA delivery |
| ES2983582T3 (es) | 2017-04-07 | 2024-10-23 | Tambo Inc | Composiciones bioortogonales |
| WO2018209270A1 (en) | 2017-05-11 | 2018-11-15 | Northwestern University | Adoptive cell therapy using spherical nucleic acids (snas) |
| JP2020526558A (ja) | 2017-07-13 | 2020-08-31 | ノースウェスタン ユニバーシティ | オリゴヌクレオチド官能化金属有機構造体ナノ粒子を調製するための一般的かつ直接的な方法 |
| WO2019090359A1 (en) * | 2017-11-06 | 2019-05-09 | Nitto Denko Corporation | Fusogenic compounds for delivery of biologically active molecules |
| US12319711B2 (en) | 2019-09-20 | 2025-06-03 | Northwestern University | Spherical nucleic acids with tailored and active protein coronae |
| US12378560B2 (en) | 2019-10-29 | 2025-08-05 | Northwestern University | Sequence multiplicity within spherical nucleic acids |
| US12589162B2 (en) | 2020-08-07 | 2026-03-31 | Tambo, Inc. | Trans-cyclooctene prodrug of monomethyl auristatin E |
| LU103379B1 (en) * | 2024-09-09 | 2026-03-09 | Re3B Therapeutics Ug I G | Serum-Protein Coated Fusogenic Lipid Particles For Targeted Drug Delivery |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000510820A (ja) * | 1996-03-06 | 2000-08-22 | ジー．ディー．サール アンド カンパニー | 酸化窒素シンターゼインヒビターとして有用なヒドロキシアミジノ誘導体 |
| US20040192778A1 (en) * | 2003-03-26 | 2004-09-30 | Anwar Jardien | Reduction of hair growth |
| WO2005060603A2 (en) * | 2003-12-10 | 2005-07-07 | Nitromed, Inc. | Nitric oxide releasing pyruvate compounds, compositions and methods of use |
| WO2008022309A2 (en) * | 2006-08-18 | 2008-02-21 | F. Hoffmann-La Roche Ag | Polyconjugates for in vivo delivery of polynucleotides |
| JP2008530215A (ja) * | 2005-02-14 | 2008-08-07 | サーナ・セラピューティクス・インコーポレイテッド | 生物学的に活性な分子をデリバリーするための脂質ナノ粒子系組成物および方法 |
| JP2008530021A (ja) * | 2005-02-08 | 2008-08-07 | アイディー バイオメディカル コーポレイション オブ ケベック シー．オー．ビー． アズ グラクソスミスクライン バイオロジカルズ ノース アメリカ | 医薬組成物 |
| JP2008533016A (ja) * | 2005-03-07 | 2008-08-21 | アイディー バイオメディカル コーポレイション オブ ケベック シー．オー．ビー． アズ グラクソスミスクライン バイオロジカルズ ノース アメリカ | 薬学的リポソーム組成物 |
| US20080255234A1 (en) * | 2007-04-11 | 2008-10-16 | Zinpro Corporation | Rumen protected lysine |
| JP2010528985A (ja) * | 2007-05-04 | 2010-08-26 | エムディーアールエヌエー，インコーポレイテッド | アミノ酸脂質およびその使用 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998051278A2 (en) * | 1997-05-14 | 1998-11-19 | Inex Pharmaceuticals Corporation | High efficiency encapsulation of charged therapeutic agents in lipid vesicles |
| US6794499B2 (en) * | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| US6841537B1 (en) * | 1998-04-22 | 2005-01-11 | Protiva Biotherapeutics Inc. | Combination therapy using nucleic acids and conventional drugs |
| US6169078B1 (en) * | 1998-05-12 | 2001-01-02 | University Of Florida | Materials and methods for the intracellular delivery of substances |
| US20030077829A1 (en) * | 2001-04-30 | 2003-04-24 | Protiva Biotherapeutics Inc.. | Lipid-based formulations |
| US20070042983A1 (en) * | 2001-05-18 | 2007-02-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA) |
| US20050222064A1 (en) * | 2002-02-20 | 2005-10-06 | Sirna Therapeutics, Inc. | Polycationic compositions for cellular delivery of polynucleotides |
| CN1882693B (zh) * | 2003-09-15 | 2012-08-15 | 普洛体维生物治疗公司 | 聚乙二醇修饰的脂质化合物及其应用 |
| WO2006007712A1 (en) * | 2004-07-19 | 2006-01-26 | Protiva Biotherapeutics, Inc. | Methods comprising polyethylene glycol-lipid conjugates for delivery of therapeutic agents |
| US7404969B2 (en) * | 2005-02-14 | 2008-07-29 | Sirna Therapeutics, Inc. | Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules |
| CA2638807A1 (en) * | 2006-02-01 | 2007-08-09 | The Burnham Institute For Medical Research | Lymphatic zip codes in tumors and pre-malignant lesions |
| US20070293449A1 (en) * | 2006-06-20 | 2007-12-20 | Nastech Pharmaceutical Company Inc. | Compositions and methods for delivery of double-stranded rna |
-
2009
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- 2009-11-17 TW TW098138943A patent/TW201021852A/zh unknown
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- 2009-11-17 JP JP2011536585A patent/JP2012509273A/ja not_active Ceased
- 2009-11-17 CA CA2742846A patent/CA2742846A1/en not_active Abandoned
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000510820A (ja) * | 1996-03-06 | 2000-08-22 | ジー．ディー．サール アンド カンパニー | 酸化窒素シンターゼインヒビターとして有用なヒドロキシアミジノ誘導体 |
| US20040192778A1 (en) * | 2003-03-26 | 2004-09-30 | Anwar Jardien | Reduction of hair growth |
| WO2005060603A2 (en) * | 2003-12-10 | 2005-07-07 | Nitromed, Inc. | Nitric oxide releasing pyruvate compounds, compositions and methods of use |
| JP2008530021A (ja) * | 2005-02-08 | 2008-08-07 | アイディー バイオメディカル コーポレイション オブ ケベック シー．オー．ビー． アズ グラクソスミスクライン バイオロジカルズ ノース アメリカ | 医薬組成物 |
| JP2008530215A (ja) * | 2005-02-14 | 2008-08-07 | サーナ・セラピューティクス・インコーポレイテッド | 生物学的に活性な分子をデリバリーするための脂質ナノ粒子系組成物および方法 |
| JP2008533016A (ja) * | 2005-03-07 | 2008-08-21 | アイディー バイオメディカル コーポレイション オブ ケベック シー．オー．ビー． アズ グラクソスミスクライン バイオロジカルズ ノース アメリカ | 薬学的リポソーム組成物 |
| WO2008022309A2 (en) * | 2006-08-18 | 2008-02-21 | F. Hoffmann-La Roche Ag | Polyconjugates for in vivo delivery of polynucleotides |
| US20080255234A1 (en) * | 2007-04-11 | 2008-10-16 | Zinpro Corporation | Rumen protected lysine |
| JP2010528985A (ja) * | 2007-05-04 | 2010-08-26 | エムディーアールエヌエー，インコーポレイテッド | アミノ酸脂質およびその使用 |
Non-Patent Citations (9)
| Title |
|---|
| AKAGAWA,M. AND SUYAMA,K.: "Mechanism of formation of elastin crosslinks", CONNECTIVE TISSUE RESEARCH, vol. 41(2), JPN6014013218, 2000, pages 131 - 141, ISSN: 0002780951 * |
| BOUTAUD,O. ET AL.: "Characterization of the Lysyl Adducts Formed from Prostaglandin H2 via the Levuglandin Pathway", BIOCHEMISTRY, vol. 38(29), JPN6014013213, 1999, pages 9389 - 9396, ISSN: 0002780947 * |
| FRIEDMAN,P. ET AL.: "Correlation of antiphospholipid antibody recognition with the structure of synthetic oxidized phosph", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 277(9), JPN6014013212, 2002, pages 7010 - 7020, ISSN: 0002780946 * |
| GARAVELLI,M. ET AL.: "The C5H6NH2+ Protonated Schiff Base: An ab Initio Minimal Model for Retinal Photoisomerization", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 119(29), JPN6014013215, 1997, pages 6891 - 6901, ISSN: 0002780948 * |
| HUGHES,R.C. AND FEENEY,J.: "Ricin-resistant mutants of baby-hamster-kidney cells deficient in α-mannosidase-II-catalyzed proces", EUROPEAN JOURNAL OF BIOCHEMISTRY, vol. 158(2), JPN6014013216, 1986, pages 227 - 37, ISSN: 0002780949 * |
| LIU,Z. ET AL.: "Mass Spectroscopic Characterization of Protein Modification by 4-Hydroxy-2-(E)-nonenal and 4-Oxo-2-(", CHEMICAL RESEARCH IN TOXICOLOGY, vol. 16(7), JPN6014013210, 2003, pages 901 - 911, ISSN: 0002780945 * |
| RUCKLIDGE,G.J. ET AL.: "Preparation and analysis of the products of non-enzymic protein glycosylation and their relationship", BIOCHIMICA ET BIOPHYSICA ACTA, PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, vol. 747(1-2), JPN6014013217, 1983, pages 165 - 70, ISSN: 0002780950 * |
| ZAGOL-IKAPITTE,I. ET AL.: "Characterization of bis(levuglandinyl) urea derivatives as products of reaction between prostaglandi", BIOCHEMISTRY, vol. 43(18), JPN6014013209, 2004, pages 5503 - 5510, ISSN: 0002780944 * |
| ZHUKOV,Y.N. ET AL.: "Interaction of aspartyl adenylate phosphonate analogs with asparagine synthetases from different sou", BIOACTIVE MOLECULES, vol. 3(Biophosphates Their Analogues, JPN6014013219, 1987, pages 321 - 6, ISSN: 0002780952 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012509272A (ja) * | 2008-11-17 | 2012-04-19 | エンゾン ファーマシューティカルズ，インコーポレーテッド | 核酸送達系のための放出性カチオン脂質 |
| JP2019535808A (ja) * | 2016-10-17 | 2019-12-12 | 南京▲緑▼叶制▲薬▼有限公司 | ｂｃｌ−２を抑制するアンチセンスオリゴヌクレオチドの脂質ナノ粒子及びその調製方法 |
Also Published As
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| US20110223257A1 (en) | 2011-09-15 |
| WO2010057160A9 (en) | 2011-05-05 |
| WO2010057160A1 (en) | 2010-05-20 |
| CA2742846A1 (en) | 2010-05-20 |
| CN102215820A (zh) | 2011-10-12 |
| EP2355799A4 (en) | 2012-09-05 |
| EP2355799A1 (en) | 2011-08-17 |
| TW201021852A (en) | 2010-06-16 |
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