HUE033661T2 - Apolipoprotein A-I Mimics - Google Patents
Apolipoprotein A-I Mimics Download PDFInfo
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- HUE033661T2 HUE033661T2 HUE15157397A HUE15157397A HUE033661T2 HU E033661 T2 HUE033661 T2 HU E033661T2 HU E15157397 A HUE15157397 A HU E15157397A HU E15157397 A HUE15157397 A HU E15157397A HU E033661 T2 HUE033661 T2 HU E033661T2
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- leu
- peptide
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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Landscapes
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| US9644038B2 (en) | 2011-12-21 | 2017-05-09 | The Regents Of The University Of California | Apolipoprotein nanodiscs with telodendrimer |
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| BR112016025470A2 (pt) | 2014-05-02 | 2017-08-15 | Cerenis Therapeutics Holding S A | ?hdl terapêutico? |
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| EP3273944B1 (en) | 2015-03-25 | 2024-11-20 | The Regents of The University of Michigan | Compositions and methods for delivery of biomacromolecule agents |
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| WO2017205454A1 (en) * | 2016-05-24 | 2017-11-30 | Bryce Chackerian | Immunogens, compositions, and methods for treating dyslipidemia |
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| WO2019030574A1 (en) * | 2017-08-10 | 2019-02-14 | Cerenis Therapeutics Holding | Cargomers |
| WO2019030575A1 (en) * | 2017-08-10 | 2019-02-14 | Cerenis Therapeutics Holding | APOMÈRES |
| WO2021209808A1 (en) * | 2020-04-16 | 2021-10-21 | Abionyx Pharma Sa | Cer-001 therapy for treating kidney disease |
| CN115427064A (zh) | 2020-04-16 | 2022-12-02 | 阿比奥尼克斯制药公司 | 使用基于脂质结合蛋白的复合物治疗急性病况的方法 |
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| EP4221686A2 (en) | 2020-10-01 | 2023-08-09 | Abionyx Pharma SA | Compositions comprising lipid binding protein-based complexes for use for treating eye diseases |
| EP4259280A4 (en) * | 2020-12-11 | 2025-02-12 | The Regents Of The University Of Michigan | Compositions and methods for preventing, attenuating, and treating medical conditions with shdl nanoparticles |
| JP2024514154A (ja) | 2021-04-15 | 2024-03-28 | アビオニクス ファーマ エスエー | 臓器保存溶液における脂質結合タンパク質ベースの複合体の使用 |
| CN114940711B (zh) * | 2021-10-25 | 2023-05-12 | 中山大学 | 载脂蛋白a-i模拟肽及其应用 |
| AU2023250345A1 (en) | 2022-04-06 | 2024-11-14 | Abionyx Pharma Sa | Methods for treating eye diseases using lipid binding protein-based complexes |
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Family Cites Families (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| CA1173360A (en) * | 1979-06-22 | 1984-08-28 | Jurg Schrank | Pharmaceutical preparations |
| US4215051A (en) | 1979-08-29 | 1980-07-29 | Standard Oil Company (Indiana) | Formation, purification and recovery of phthalic anhydride |
| US4376110A (en) | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
| NO812612L (no) | 1980-08-06 | 1982-02-08 | Ferring Pharma Ltd | Enzym-inhibitorer. |
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4643988A (en) * | 1984-05-15 | 1987-02-17 | Research Corporation | Amphipathic peptides |
| US4880635B1 (en) * | 1984-08-08 | 1996-07-02 | Liposome Company | Dehydrated liposomes |
| JPS61152632A (ja) | 1984-12-26 | 1986-07-11 | Dai Ichi Seiyaku Co Ltd | 抗動脈硬化剤 |
| US4857319A (en) * | 1985-01-11 | 1989-08-15 | The Regents Of The University Of California | Method for preserving liposomes |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US5972890A (en) * | 1988-05-02 | 1999-10-26 | New England Deaconess Hospital Corporation | Synthetic peptides for arterial imaging |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5220043A (en) | 1991-03-21 | 1993-06-15 | Ohio University | Synthesis of D-erythro-sphingomyelins |
| JPH0559081A (ja) | 1991-08-29 | 1993-03-09 | Kirin Brewery Co Ltd | 新規スフインゴ糖脂質、その製造法および使用 |
| WO1993025581A1 (en) | 1992-06-12 | 1993-12-23 | N.V. Innogenetics S.A. | New peptides and proteins, process for their preparation and their use as cholesterol acceptors |
| TW261533B (enExample) | 1992-07-16 | 1995-11-01 | Kirin Brewery | |
| US5674855A (en) | 1992-08-12 | 1997-10-07 | The Rogosin Institute | Methods and compositions useful in prophylaxis and therapy of endotoxin related conditions |
| PT665897E (pt) | 1992-10-01 | 2003-11-28 | Trustees Of Columbia U In The | Bibliotecas quimicas combinatorias complexas codificadas com etiquetas |
| SE9203753D0 (sv) | 1992-12-11 | 1992-12-11 | Kabi Pharmacia Ab | Expression system for producing apolipoprotein ai-m |
| FR2734568B1 (fr) | 1995-05-22 | 1997-06-20 | Rhone Poulenc Rorer Sa | Nouveaux variants de l'apolipoproteine |
| 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 |
| US6518412B1 (en) | 1997-09-29 | 2003-02-11 | Jean-Louis Dasseux | Gene therapy approaches to supply 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 |
| CA2320117A1 (en) | 1998-02-12 | 1999-08-19 | Emory University | Sphingolipid derivatives and their methods of use |
| BR0009520A (pt) | 1999-04-01 | 2002-06-11 | Esperion Therapeutics Inc | Composto, método para sintetizar o mesmo, composição, metódos para o tratramento ou prevenção, em um paciente, de doença cardiovascular, dislipidemia, dislipoproteinemia, distúrbio de metabolismo de glucose, doença de alzheimer, sìndrome x ou sìndrome metabólica, septicemia, distúrbio trombótico, distúrbio associado com receptor ativado por proliferador de peroxissoma, obesidade, pancreatite, hipertensão, doença renal, câncer, inflamação, impotência, para reduzir o teor de gordura de carne de gado bovino, e, para reduzir o teor de colesterol de ovos de aves |
| AU5717301A (en) * | 2000-04-21 | 2001-11-07 | Amgen Inc | Apo-ai/aii peptide derivatives |
| US6664230B1 (en) * | 2000-08-24 | 2003-12-16 | The Regents Of The University Of California | Orally administered peptides to ameliorate atherosclerosis |
| US7144862B2 (en) * | 2000-08-24 | 2006-12-05 | The Regents Of The University Of California | Orally administered peptides to ameliorate atherosclerosis |
| MXPA04002848A (es) * | 2001-09-28 | 2005-06-06 | Esperion Therapeutics Inc | Prevencion y tratamiento de restenosis por administracion local de medicamento. |
| AU2003239489A1 (en) * | 2002-05-17 | 2003-12-02 | Esperion Therapeutics, Inc. | Method of treating dyslipidemic disorders |
| DE10237571A1 (de) | 2002-08-13 | 2004-02-26 | Biotronik Meß- und Therapiegeräte GmbH & Co. Ingenieurbüro Berlin | Endovaskuläres Implantat mit aktiver Beschichtung |
| JP2007536200A (ja) * | 2003-07-17 | 2007-12-13 | ミジェニックス インコーポレイテッド | リポペプチド抗生物質誘導体の組成物およびその使用方法 |
| US7569546B2 (en) * | 2004-07-16 | 2009-08-04 | Trustees Of Tufts College | Apolipoprotein A1 mimetics and uses thereof |
| US8206750B2 (en) | 2005-03-24 | 2012-06-26 | Cerenis Therapeutics Holding S.A. | Charged lipoprotein complexes and their uses |
| EP1885855A4 (en) | 2005-05-05 | 2009-03-04 | Valorisation Hsj Soc En Comman | CYTOKIN RECEPTOR MODULATORS AND USES THEREOF |
| TW200744627A (en) | 2006-02-21 | 2007-12-16 | Pfizer Prod Inc | Methods for the treatment of macular degeneration and related eye conditions |
| ES2402823T3 (es) * | 2006-06-01 | 2013-05-09 | Institut De Cardiologie De Montreal | Compuesto para uso en el tratamiento de estenosis valvular |
| US20080138284A1 (en) * | 2006-09-26 | 2008-06-12 | Lipid Sciences, Inc. | Novel Peptides That Promote Lipid Efflux |
| WO2008094905A2 (en) | 2007-01-29 | 2008-08-07 | Lipid Sciences, Inc. | Encapsulated hdl mimetic peptides |
| US7956035B2 (en) | 2007-03-01 | 2011-06-07 | Csl Limited | Treatment of endothelial dysfunction in diabetic patients |
| WO2008156873A2 (en) | 2007-06-20 | 2008-12-24 | Merck & Co., Inc. | Apoa-1 peptide mimetics |
| US9173890B2 (en) | 2007-09-20 | 2015-11-03 | Abbott Cardiovascular Systems Inc. | Sustained release of Apo A-I mimetic peptides and methods of treatment |
| EP2389189A4 (en) | 2009-01-23 | 2012-12-19 | Inst Cardiologie Montreal | METHOD FOR PREVENTING AND TREATING DIASTOLIC DYSFUNCTION WITH A MIMETAL APOLIPOPROTEIN A1 (APOA1) -PEPTIDE / PHOSPHOLIPID COMPLEX |
| SMT201700203T1 (it) | 2009-02-16 | 2017-05-08 | Cerenis Therapeutics Holding Sa | Mimetici di apolipoproteina a-i |
| US20130197226A1 (en) * | 2010-07-28 | 2013-08-01 | Jean-Claude Tardif | Pharmaceutical compositions for the treatment of left ventricular diastolic dysfunction comprising an apolipoprotein peptide/phospholipid complex |
| US9708354B2 (en) | 2013-03-15 | 2017-07-18 | Cerenis Therapeutics Holding Sa | Methods for the synthesis of sphingomyelins and dihydrosphingomyelins |
| JP6438417B2 (ja) | 2013-03-15 | 2018-12-12 | セレニス セラピューティクス ホールディング エスアー | スフィンゴミエリンおよびジヒドロスフィンゴミエリンの合成のための方法 |
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