AU2006226045B2 - Charged lipoprotein complexes and their uses - Google Patents
Charged lipoprotein complexes and their uses Download PDFInfo
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- AU2006226045B2 AU2006226045B2 AU2006226045A AU2006226045A AU2006226045B2 AU 2006226045 B2 AU2006226045 B2 AU 2006226045B2 AU 2006226045 A AU2006226045 A AU 2006226045A AU 2006226045 A AU2006226045 A AU 2006226045A AU 2006226045 B2 AU2006226045 B2 AU 2006226045B2
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- apoa
- apolipoprotein
- lipoprotein complex
- charged
- hdl
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8206750B2 (en) | 2005-03-24 | 2012-06-26 | Cerenis Therapeutics Holding S.A. | Charged lipoprotein complexes and their uses |
| WO2006125304A1 (en) * | 2005-05-25 | 2006-11-30 | Liponex, Inc. | Pharmaceutical compositions for treating or preventing coronary artery disease |
| JP5394236B2 (ja) * | 2006-06-01 | 2014-01-22 | インスティトュート デ カーディオロジー デ モントリオール | 弁膜症治療方法及び化合物 |
| US9173890B2 (en) | 2007-09-20 | 2015-11-03 | Abbott Cardiovascular Systems Inc. | Sustained release of Apo A-I mimetic peptides and methods of treatment |
| US7985727B1 (en) | 2007-09-20 | 2011-07-26 | Abbott Cardiovascular Systems Inc. | Apo A-I mimetic peptides and methods of treatment |
| US8101565B2 (en) | 2007-09-20 | 2012-01-24 | Abbott Cardiovascular Systems Inc. | Sustained release of Apo A-I mimetic peptides and methods of treatment |
| US8044021B2 (en) | 2007-09-20 | 2011-10-25 | Abbott Cardiovascular Systems Inc. | Sustained release of apo A-I mimetic peptides and methods of treatment |
| US7985728B1 (en) | 2007-09-20 | 2011-07-26 | Abbott Cardiovascular Systems Inc. | Sustained release of Apo A-I mimetic peptides and methods of treatment |
| WO2010057203A2 (en) | 2008-11-17 | 2010-05-20 | The Board Of Regents Of The University Of Texas System | Hdl particles for delivery of nucleic acids |
| US8378068B2 (en) | 2009-02-16 | 2013-02-19 | Cerenis Therapeutics Holding Sa | Apolipoprotein A-I mimics |
| WO2011006994A1 (en) | 2009-07-16 | 2011-01-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Hdl comprising a therapeutic agent and use in therapy |
| US10894098B2 (en) | 2012-04-09 | 2021-01-19 | Signablok, Inc. | Methods and compositions for targeted imaging |
| US12419839B2 (en) | 2009-10-09 | 2025-09-23 | Signablok, Inc. | Methods and compositions for targeted delivery of protein fragments |
| WO2011044545A2 (en) * | 2009-10-09 | 2011-04-14 | Sigalov Alexander B | Methods and compositions for targeted imaging |
| US20110152112A1 (en) * | 2009-12-23 | 2011-06-23 | Artery Therapeutics, Inc. | Diagnosis and treatment of reverse cholesterol transport deficiency-related diseases |
| WO2012012870A1 (en) * | 2010-07-28 | 2012-02-02 | Institut De Cardiologie De Montreal | Pharmaceutical compositions for the treatment of left ventricular diastolic dysfunction comprising an apolipoprotein peptide/phospholipid complex |
| TW201215394A (en) * | 2010-08-30 | 2012-04-16 | Hoffmann La Roche | Tetranectin-apolipoprotein A-I, lipid particles containing it and its use |
| CN105288589A (zh) | 2011-02-07 | 2016-02-03 | 塞勒尼斯医疗控股公司 | 脂蛋白复合物及其制备和用途 |
| AU2015271986B2 (en) * | 2011-02-07 | 2018-02-22 | Cerenis Therapeutics Holding Sa | Lipoprotein complexes and manufacturing and uses thereof |
| EP2688584A4 (en) * | 2011-03-25 | 2015-05-20 | Univ Columbia | PEGYLATED HUMAN HDL PARTICLES AND METHOD OF PREPARING THEM |
| KR20140054115A (ko) | 2011-08-25 | 2014-05-08 | 에프. 호프만-라 로슈 아게 | 단축 테트라넥틴-아포지단백질 a-i 융합 단백질, 그를 함유하는 지질 입자 및 그의 용도 |
| WO2014160237A2 (en) * | 2013-03-14 | 2014-10-02 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of prognosing preeclampsia |
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| EP2853259A1 (en) * | 2013-09-30 | 2015-04-01 | Université Pierre et Marie Curie (Paris 6) | Reconstituted high density lipoproteins composition and uses thereof |
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| US20170165200A1 (en) * | 2015-11-20 | 2017-06-15 | University Of North Texas Health Science Center | Composition of lipid-based nanoparticles for small molecules and macromolecules |
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| CN110151972A (zh) * | 2018-02-11 | 2019-08-23 | 中国中医科学院中医基础理论研究所 | 基于多肽的重组高密度脂蛋白前体及其制备方法与应用 |
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| DE202019003092U1 (de) * | 2019-07-24 | 2020-01-17 | Ruth-Maria Korth | Test zur Bestimmung von Proteophospholipiden und FIDA-Formeln zur Bestimmung von Schutzfaktoren , die mit Substraten auszugleichen sind |
| AU2021254856A1 (en) | 2020-04-16 | 2022-11-10 | Abionyx Pharma Sa | CER-001 therapy for treating kidney disease |
| WO2021209823A1 (en) | 2020-04-16 | 2021-10-21 | Abionyx Pharma Sa | Methods for treating acute conditions using lipid binding protein- based complexes |
| JP2023543498A (ja) | 2020-10-01 | 2023-10-16 | アビオニクス ファーマ エスエー | 脂質結合タンパク質ベースの複合体を使用した、眼疾患を治療するための方法 |
| US20240215570A1 (en) | 2021-04-15 | 2024-07-04 | Abionyx Pharma Sa | Use of lipid binding protein-based complexes in organ preservation solutions |
| KR102531293B1 (ko) * | 2021-12-06 | 2023-05-16 | (주) 멥스젠 | 신규한 재구축 고밀도 지단백 나노입자 |
| WO2023194797A1 (en) | 2022-04-06 | 2023-10-12 | Abionyx Pharma Sa | Methods for treating eye diseases using lipid binding protein-based complexes |
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| AU2023284357A1 (en) | 2022-06-10 | 2025-01-23 | Abionyx Pharma Sa | Methods for treating acute conditions using lipid binding protein-based complexes |
| IL322074A (en) | 2023-01-13 | 2025-09-01 | Abionyx Pharma Sa | Treatment using a lipid-binding protein molecule |
| WO2025093929A1 (en) | 2023-10-31 | 2025-05-08 | Abionyx Pharma Sa | Lipid binding protein molecule therapy |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003096983A2 (en) * | 2002-05-17 | 2003-11-27 | Esperion Therapeutics, Inc. | Method of treating dyslipidemic disorders |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5052123A (cg-RX-API-DMAC7.html) * | 1973-01-18 | 1975-05-09 | ||
| US4466958A (en) * | 1981-03-18 | 1984-08-21 | Morrison L M | Food supplement |
| JPS59164553A (ja) * | 1983-03-08 | 1984-09-17 | Fuji Photo Film Co Ltd | カラ−写真感光材料 |
| DE3417696A1 (de) * | 1984-05-12 | 1985-11-14 | Robert Bosch Gmbh, 7000 Stuttgart | Vorrichtung zum volumetrischen abmessen und abfuellen von fluessigkeitsmengen |
| US5128318A (en) * | 1987-05-20 | 1992-07-07 | The Rogosin Institute | Reconstituted HDL particles and uses thereof |
| GB8712540D0 (en) | 1987-05-28 | 1987-07-01 | Ucb Sa | Expression of human proapolipoprotein a-i |
| US5231090A (en) * | 1990-07-30 | 1993-07-27 | University Of Miami | Treatment for hypercholesterolemia |
| US5220043A (en) | 1991-03-21 | 1993-06-15 | Ohio University | Synthesis of D-erythro-sphingomyelins |
| SE9103701D0 (sv) | 1991-12-13 | 1991-12-13 | Kabi Pharmacia Ab | Apolipoprotein |
| WO1995008986A1 (en) | 1993-09-27 | 1995-04-06 | Smithkline Beecham Corporation | Camptothecin formulations |
| US5746223A (en) * | 1996-10-11 | 1998-05-05 | Williams; Kevin Jon | Method of forcing the reverse transport of cholesterol from a body part to the liver while avoiding harmful disruptions of hepatic cholesterol homeostasis |
| WO1995025749A2 (en) | 1994-03-22 | 1995-09-28 | Research Corporation Technologies, Inc. | Eating suppressant peptides |
| US5932536A (en) | 1994-06-14 | 1999-08-03 | The Rockefeller University | Compositions for neutralization of lipopolysaccharides |
| US5948756A (en) * | 1995-08-31 | 1999-09-07 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Therapeutic lipoprotein compositions |
| IL120005A (en) * | 1997-01-14 | 2000-08-31 | Ramot University Authority Of | Pharmaceutical compositions for the treatment of the eye |
| US6004925A (en) | 1997-09-29 | 1999-12-21 | J. L. Dasseux | Apolipoprotein A-I agonists and their use to treat dyslipidemic disorders |
| US6046166A (en) | 1997-09-29 | 2000-04-04 | Jean-Louis Dasseux | Apolipoprotein A-I agonists and their use to treat dyslipidemic disorders |
| US6037323A (en) | 1997-09-29 | 2000-03-14 | Jean-Louis Dasseux | Apolipoprotein A-I agonists and their use to treat dyslipidemic disorders |
| US6287590B1 (en) * | 1997-10-02 | 2001-09-11 | Esperion Therapeutics, Inc. | Peptide/lipid complex formation by co-lyophilization |
| US6017882A (en) * | 1997-10-23 | 2000-01-25 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| GB9919713D0 (en) | 1999-08-19 | 1999-10-20 | Queen Mary & Westfield College | New medical use of high density lipoprotein |
| US6514523B1 (en) * | 2000-02-14 | 2003-02-04 | Ottawa Heart Institute Research Corporation | Carrier particles for drug delivery and process for preparation |
| AU2001278336B2 (en) | 2000-07-31 | 2007-01-18 | Ottawa Heart Institute Research Corporation | Charged phospholipid compositions and methods for their use |
| US6664230B1 (en) | 2000-08-24 | 2003-12-16 | The Regents Of The University Of California | Orally administered peptides to ameliorate atherosclerosis |
| US7199102B2 (en) | 2000-08-24 | 2007-04-03 | The Regents Of The University Of California | Orally administered peptides synergize statin activity |
| US7148197B2 (en) | 2000-08-24 | 2006-12-12 | The Regents Of The University Of California | Orally administered small peptides synergize statin activity |
| US7144862B2 (en) | 2000-08-24 | 2006-12-05 | The Regents Of The University Of California | Orally administered peptides to ameliorate atherosclerosis |
| US7217785B2 (en) | 2001-05-09 | 2007-05-15 | The Regents Of The University Of California | Cysteine-containing peptides having antioxidant properties |
| EP1425031B8 (en) | 2001-08-20 | 2008-09-03 | CSL Behring AG | Hdl for the treatment of stroke and other ischemic conditions |
| AUPR798901A0 (en) | 2001-09-28 | 2001-10-25 | Medvet Science Pty. Ltd. | Spheroidal hdl particles with a defined phospholipid composition |
| AU2002362612B2 (en) | 2001-09-28 | 2007-11-15 | Cedars-Sinai Medical Center | Prevention and treatment of restenosis by local administration of drug |
| US7223726B2 (en) | 2002-01-14 | 2007-05-29 | The Regents Of The University Of California | Apolipoprotein A-I mutant proteins having cysteine substitutions and polynucleotides encoding same |
| FR2836043B1 (fr) | 2002-02-15 | 2004-06-04 | Inst Nat Sante Rech Med | Vesicules lipidiques, preparation et utilisations |
| CN1668645A (zh) * | 2002-05-17 | 2005-09-14 | 埃斯佩里安医疗公司 | 治疗缺血再灌注的方法和组合物 |
| MXPA05001091A (es) * | 2002-07-30 | 2005-04-28 | Esperion Therapeutics Inc | Metodos para utilizar proteina apolipoproteina a-i animal no humana. |
| US8206750B2 (en) | 2005-03-24 | 2012-06-26 | Cerenis Therapeutics Holding S.A. | Charged lipoprotein complexes and their uses |
| JP5394236B2 (ja) * | 2006-06-01 | 2014-01-22 | インスティトュート デ カーディオロジー デ モントリオール | 弁膜症治療方法及び化合物 |
| CN105288589A (zh) | 2011-02-07 | 2016-02-03 | 塞勒尼斯医疗控股公司 | 脂蛋白复合物及其制备和用途 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003096983A2 (en) * | 2002-05-17 | 2003-11-27 | Esperion Therapeutics, Inc. | Method of treating dyslipidemic disorders |
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