ZA200509229B - Method and carrier complexes for delivering molecules to cells - Google Patents
Method and carrier complexes for delivering molecules to cells Download PDFInfo
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- ZA200509229B ZA200509229B ZA200509229A ZA200509229A ZA200509229B ZA 200509229 B ZA200509229 B ZA 200509229B ZA 200509229 A ZA200509229 A ZA 200509229A ZA 200509229 A ZA200509229 A ZA 200509229A ZA 200509229 B ZA200509229 B ZA 200509229B
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US (6) | US7704954B2 (fr) |
EP (7) | EP1625149B1 (fr) |
JP (6) | JP4879020B2 (fr) |
KR (1) | KR101161823B1 (fr) |
CN (2) | CN100506841C (fr) |
AU (1) | AU2004252419B2 (fr) |
BR (1) | BRPI0409911A (fr) |
CA (1) | CA2524258C (fr) |
DK (4) | DK1625149T3 (fr) |
ES (3) | ES2520816T3 (fr) |
HK (6) | HK1089450A1 (fr) |
MX (1) | MXPA05011773A (fr) |
NZ (1) | NZ543410A (fr) |
PL (2) | PL2604286T3 (fr) |
PT (2) | PT2604285E (fr) |
SI (1) | SI2604285T1 (fr) |
WO (1) | WO2005001023A2 (fr) |
ZA (1) | ZA200509229B (fr) |
Families Citing this family (59)
Publication number | Priority date | Publication date | Assignee | Title |
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KR20030062788A (ko) * | 2002-01-19 | 2003-07-28 | 포휴먼텍(주) | 생체분자 전달 펩타이드 mph1-btm 및 이것을포함하는 생명공학제품 |
EP3659618A1 (fr) | 2003-02-04 | 2020-06-03 | Cornell Research Foundation, Inc. | Utilisations d'un peptide aromatique cationique |
PT2604285E (pt) * | 2003-05-01 | 2014-11-12 | Cornell Res Foundation Inc | Método e complexos transportadores para entregar moléculas às células |
CA2971928C (fr) * | 2004-01-23 | 2019-01-08 | Cornell Research Foundation, Inc. | Methodes de reduction de lesions par oxydation |
US7534819B2 (en) * | 2005-06-10 | 2009-05-19 | University Of Washington | Compositions and methods for intracellular delivery of biotinylated cargo |
EP3725324A1 (fr) | 2005-09-16 | 2020-10-21 | Cornell Research Foundation, Inc. | Peptide aromatique-cationique destiné à être utilisé dans un procédé de réduction de l'expression cd36 |
US7723299B2 (en) * | 2005-11-04 | 2010-05-25 | Forhumantech. Co., Ltd. | Methods for treating rheumatoid arthritis using a CTLA-4 fusion protein |
JP2009544688A (ja) * | 2006-07-24 | 2009-12-17 | フォーヒューマンテック カンパニー リミテッド | 虚血性疾患の緩和及び治療のための医薬組成物並びにそれを伝達するための方法 |
KR20090045940A (ko) * | 2006-08-29 | 2009-05-08 | 포휴먼텍(주) | 세포자멸사의 억제를 위한 약학 조성물, 및 이를 전달하는 방법 |
CA2939778C (fr) | 2007-01-31 | 2019-01-29 | Dana-Farber Cancer Institute, Inc. | Peptides p53 stabilises et utilisations de ceux-ci |
EP3159352B1 (fr) | 2007-03-28 | 2023-08-02 | President and Fellows of Harvard College | Polypeptides piqués |
US7981446B2 (en) * | 2007-11-26 | 2011-07-19 | Forhumantech. Co., Ltd. | Pharmaceutical compositions and methods for delivering nucleic acids into cells |
ES2458870T3 (es) | 2008-02-07 | 2014-05-07 | Cornell University | Procedimientos para prevenir o tratar la resistencia a la insulina |
DK2262520T3 (en) | 2008-02-26 | 2017-08-07 | Univ Cornell | COMPOSITIONS FOR PREVENTION AND TREATMENT OF Kidney Injury |
CN102482336B (zh) * | 2008-09-22 | 2015-05-06 | 爱勒让治疗公司 | 拟肽大环化合物 |
JP2012509902A (ja) | 2008-11-24 | 2012-04-26 | エルロン・セラピューティクス・インコーポレイテッド | 改善された特性を有するペプチド模倣大環状分子 |
DE102008061044A1 (de) * | 2008-12-11 | 2010-06-17 | Henkel Ag & Co. Kgaa | Zusammensetzung mit antioxidativ wirksamen Peptiden |
EP3199173B1 (fr) | 2009-03-20 | 2019-04-24 | The General Hospital Corporation d/b/a Massachusetts General Hospital | D-arg-2'6'-dimethyltyrosine-lys-phe-nh2 pour la prévention et le traitement des brûlures |
US20110039766A1 (en) * | 2009-08-12 | 2011-02-17 | Szeto Hazel H | Methods for preventing or treating metabolic syndrome |
DK2470191T3 (da) | 2009-08-24 | 2014-07-07 | Stealth Peptides Int Inc | Fremgangsmåder og præparater til forebyggelse eller behandling af oftalmiske tilstande |
CN102711785A (zh) | 2009-10-05 | 2012-10-03 | 康奈尔大学 | 预防或治疗心力衰竭的方法 |
US20110245182A1 (en) * | 2010-04-06 | 2011-10-06 | Perricone Nicholas V | Topical Uses of Szeto-Schiller Peptides |
US20110245183A1 (en) * | 2010-04-06 | 2011-10-06 | Perricone Nicholas V | Topical Uses of Szeto-Schiller Peptides |
EP2942354A1 (fr) * | 2010-05-03 | 2015-11-11 | Stealth Peptides International, Inc. | Peptides aromatiques-cationiques et utilisations de ceux-ci |
CN102010461B (zh) * | 2010-10-11 | 2014-02-12 | 华南理工大学 | 一种alpha螺旋状阳离子多肽分子及其制法和应用 |
GB201018125D0 (en) * | 2010-10-26 | 2010-12-08 | Marealis As | Peptide |
CN107219358A (zh) * | 2011-03-24 | 2017-09-29 | 康奈尔大学 | 芳香族阳离子肽及其用途 |
CA2839408A1 (fr) * | 2011-06-14 | 2012-12-20 | Stealth Peptides International, Inc. | Peptides aromatiques-cationiques et leurs utilisations |
JP6025311B2 (ja) | 2011-08-01 | 2016-11-16 | キヤノン株式会社 | 眼科診断支援装置および方法 |
CN106913860A (zh) | 2011-09-29 | 2017-07-04 | 梅约医学教育与研究基金会 | 芳族阳离子肽和使用它们的方法 |
EP2768516A4 (fr) * | 2011-10-17 | 2015-08-19 | Univ Cornell | Peptides aromatiques-cationiques et leurs utilisations |
WO2013059525A1 (fr) | 2011-10-18 | 2013-04-25 | Aileron Therapeutics, Inc. | Macrocycles peptidomimétiques |
EP3656394A1 (fr) | 2011-12-09 | 2020-05-27 | Stealth Peptides International, Inc. | Peptides aromatiques-cationiques et leurs utilisations |
CA2862038C (fr) | 2012-02-15 | 2021-05-25 | Aileron Therapeutics, Inc. | Macrocycles peptidomimetiques |
CN104144695A (zh) | 2012-02-15 | 2014-11-12 | 爱勒让治疗公司 | 三唑交联的和硫醚交联的拟肽大环化合物 |
CN104334181A (zh) * | 2012-04-12 | 2015-02-04 | 康肽德生物医药技术有限公司 | 芳香族阳离子肽及其用途 |
EP3132800A1 (fr) * | 2012-08-02 | 2017-02-22 | Stealth Peptides International, Inc. | Procédés pour le traitement de l'athérosclérose |
WO2014138429A2 (fr) | 2013-03-06 | 2014-09-12 | Aileron Therapeutics, Inc. | Macrocycles peptidomimétiques et leur utilisation dans la régulation de hif1alpha |
EP2989120A4 (fr) | 2013-04-25 | 2017-04-19 | Carmel-Haifa University Economic Corp. | Peptides anti-inflammatoires synthétiques et leur utilisation |
WO2015134096A1 (fr) * | 2014-03-03 | 2015-09-11 | Stealth Peptides International, Inc. | Peptides aromatiques-cationiques d'intérêt pharmaceutique |
CA2950410A1 (fr) * | 2014-05-28 | 2015-12-03 | D. Travis Wilson | Compositions therapeutiques comprenant de petites molecules therapeutiques et leurs utilisations |
EP3501532A3 (fr) | 2014-05-28 | 2019-07-17 | Stealth BioTherapeutics Corp | Compositions thérapeutiques comprenant de la frataxine, de la lactoferrine et des enzymes mitochondriales génératrices d'énergie et leurs utilisations |
PL3160984T3 (pl) | 2014-06-25 | 2021-10-25 | Flamma S.P.A. | Sposób wytwarzania d-arginylo-2,6-dimetylo-l-tyrozylo-l-lizylol- fenyloalaninoamidu |
WO2016001042A1 (fr) | 2014-06-30 | 2016-01-07 | Flamma S.P.A. | Procédé de préparation de d-arginyl-2,6-dimethyl-l-tyrosyl-l-lysyl-l-phenylalaninamide |
WO2016004093A2 (fr) * | 2014-07-01 | 2016-01-07 | Stealth Biotherapeutics Corp | Compositions thérapeutiques comprenant des inhibiteurs de la galectine-3 et utilisations de celles-ci |
CA2961258A1 (fr) | 2014-09-24 | 2016-03-31 | Aileron Therapeutics, Inc. | Macrocycles peptidomimetiques et leurs utilisations |
US20160228491A1 (en) * | 2015-02-09 | 2016-08-11 | Stealth Biotherapeutics Corp | Therapeutic compositions including phenazine-3-one and phenothiazine-3-one derivatives and uses thereof |
CA2979847A1 (fr) | 2015-03-20 | 2016-09-29 | Aileron Therapeutics, Inc. | Macrocycles peptidomimetiques et leurs utilisations |
WO2016209261A1 (fr) * | 2015-06-26 | 2016-12-29 | Stealth Biotherapeutics Corp | Compositions thérapeutiques comprenant des conjugués de gramicidine s peptidyl ou des acides gras à substitution imidazole, variants associés, et utilisations de ces compositions |
US10023613B2 (en) | 2015-09-10 | 2018-07-17 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles as modulators of MCL-1 |
US10987434B2 (en) | 2015-10-21 | 2021-04-27 | The Regents Of The University Of Michigan | Detection and treatment of caries and microcavities with nanoparticles |
US20200308220A1 (en) * | 2015-11-30 | 2020-10-01 | Peter Schiller | Aromatic-cationic peptides conjugated to antioxidants and their use in treating complex regional pain syndrome |
JP7218897B2 (ja) | 2016-11-16 | 2023-02-07 | ルカ・サイエンス株式会社 | 心不全の治療及び/又は予防に用いるための心筋幹細胞の製造方法 |
JP7173870B2 (ja) * | 2016-12-28 | 2022-11-16 | 中外製薬株式会社 | 化合物の膜透過性を改善するための自己乳化型製剤 |
CN107230021B (zh) * | 2017-06-08 | 2020-05-26 | 桂林理工大学 | 筛选供水管网泄漏区域的方法 |
AU2019293857A1 (en) * | 2018-06-29 | 2020-12-10 | Glykos Finland Oy | Conjugates |
CN114901258A (zh) | 2019-12-27 | 2022-08-12 | 卢卡科学株式会社 | 分离的具有较小尺寸的线粒体和包裹分离的线粒体的基于脂质膜的囊泡 |
WO2021216499A1 (fr) * | 2020-04-23 | 2021-10-28 | North Carolina State University | Conjugués peptide-microarn pénétrant dans des cellules pour l'administration intracellulaire de cellules |
CN116390723A (zh) | 2020-09-09 | 2023-07-04 | 社会利益网络公司 | 用于将生物素递送至线粒体的方法和组合物 |
Family Cites Families (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2967069D1 (en) * | 1978-01-16 | 1984-08-02 | Univ Boston | Effecting cellular uptake of molecules |
US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
DE68926269T2 (de) * | 1988-06-30 | 1996-08-14 | Astra Ab | Dermorphin-Analoge, deren Herstellungsverfahren, pharmazeutische Zusammensetzungen und Methode zur therapeutischen Behandlung unter Verwendung der Analoge |
US5602100A (en) * | 1988-06-30 | 1997-02-11 | Astra Ab | Dermorphin analogs having pharmacological activity |
US5652122A (en) * | 1989-12-21 | 1997-07-29 | Frankel; Alan | Nucleic acids encoding and methods of making tat-derived transport polypeptides |
US5169934A (en) * | 1990-05-14 | 1992-12-08 | Anergen, Inc. | Intracellularly cleavable compounds |
US5714327A (en) | 1990-07-19 | 1998-02-03 | Kreatech Diagnostics | Platinum-containing compounds, methods for their preparation and applications thereof |
NL9001639A (nl) | 1990-07-19 | 1992-02-17 | Amc Amsterdam | Pt-houdende verbinding, werkwijze voor de bereiding ervan, alsmede toepassing van dergelijke verbindingen. |
US5554728A (en) * | 1991-07-23 | 1996-09-10 | Nexstar Pharmaceuticals, Inc. | Lipid conjugates of therapeutic peptides and protease inhibitors |
US5858784A (en) | 1991-12-17 | 1999-01-12 | The Regents Of The University Of California | Expression of cloned genes in the lung by aerosol- and liposome-based delivery |
US5716644A (en) | 1992-06-11 | 1998-02-10 | Alkermes, Inc. | Composition for sustained release of non-aggregated erythropoietin |
US5674534A (en) | 1992-06-11 | 1997-10-07 | Alkermes, Inc. | Composition for sustained release of non-aggregated erythropoietin |
US5747026A (en) * | 1993-10-15 | 1998-05-05 | University Of Alabama At Birmingham Research Foundation | Antioxidants |
IS4261A (is) | 1994-02-21 | 1995-08-22 | Astra Aktiebolag | Nýir peptíð-ópíóíðar til meðhöndlunar á verkjum og notkun þeirra |
ATE255450T1 (de) * | 1995-06-09 | 2003-12-15 | Hisamitsu Pharmaceutical Co | Matrix für iontophorese |
US5849761A (en) * | 1995-09-12 | 1998-12-15 | Regents Of The University Of California | Peripherally active anti-hyperalgesic opiates |
US5885958A (en) * | 1997-03-25 | 1999-03-23 | Administrators Of The Tulane Educational Fund | Mu-opiate receptor peptides |
US5989463A (en) | 1997-09-24 | 1999-11-23 | Alkermes Controlled Therapeutics, Inc. | Methods for fabricating polymer-based controlled release devices |
WO1999029721A1 (fr) * | 1997-12-10 | 1999-06-17 | Washington University | Systeme anti-pathogene et procedes d'utilisation |
CA2329709A1 (fr) * | 1998-04-24 | 1999-11-04 | Mitokor | Composes et methodes de traitement de maladies liees aux mitochondries |
US7138103B2 (en) * | 1998-06-22 | 2006-11-21 | Immunomedics, Inc. | Use of bi-specific antibodies for pre-targeting diagnosis and therapy |
US6703381B1 (en) * | 1998-08-14 | 2004-03-09 | Nobex Corporation | Methods for delivery therapeutic compounds across the blood-brain barrier |
US6245740B1 (en) | 1998-12-23 | 2001-06-12 | Amgen Inc. | Polyol:oil suspensions for the sustained release of proteins |
SE9900961D0 (sv) | 1999-03-16 | 1999-03-16 | Astra Ab | Novel compounds |
US6669951B2 (en) * | 1999-08-24 | 2003-12-30 | Cellgate, Inc. | Compositions and methods for enhancing drug delivery across and into epithelial tissues |
WO2001025486A1 (fr) * | 1999-10-04 | 2001-04-12 | University Of Medicine And Dentistry Of New Jersey | Methodes d'identification de composes liant un arn |
US6759520B1 (en) * | 1999-10-28 | 2004-07-06 | The New England Medical Center Hospitals, Inc. | Chimeric analgesic peptides |
US20050192215A1 (en) * | 2000-01-21 | 2005-09-01 | Malabika Ghosh | Methods and materials relating to novel polypeptides and polynucleotides |
GB0005703D0 (en) * | 2000-03-09 | 2000-05-03 | Alpharma As | Compounds |
US7498297B2 (en) * | 2000-07-18 | 2009-03-03 | Cornell Research Foundation | Medicinal uses of mu-opioid receptor agonists |
US6900178B2 (en) * | 2000-09-12 | 2005-05-31 | University Of Kentucky Research Foundation | Protection against ischemia and reperfusion injury |
GB0026924D0 (en) * | 2000-11-03 | 2000-12-20 | Univ Cambridge Tech | Antibacterial agents |
ATE437647T1 (de) * | 2001-02-16 | 2009-08-15 | Cellgate Inc | Transporter mit beabstandeten arginin-teilchen |
DE10121982B4 (de) * | 2001-05-05 | 2008-01-24 | Lts Lohmann Therapie-Systeme Ag | Nanopartikel aus Protein mit gekoppeltem Apolipoprotein E zur Überwindung der Blut-Hirn-Schranke und Verfahren zu ihrer Herstellung |
US20070015146A1 (en) | 2001-05-22 | 2007-01-18 | Gene Logic, Inc. | Molecular nephrotoxicology modeling |
US7030082B2 (en) * | 2001-09-07 | 2006-04-18 | Nobex Corporation | Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith |
EP3659618A1 (fr) * | 2003-02-04 | 2020-06-03 | Cornell Research Foundation, Inc. | Utilisations d'un peptide aromatique cationique |
PT2604285E (pt) | 2003-05-01 | 2014-11-12 | Cornell Res Foundation Inc | Método e complexos transportadores para entregar moléculas às células |
US7232824B2 (en) * | 2003-09-30 | 2007-06-19 | Scios, Inc. | Quinazoline derivatives as medicaments |
CA2971928C (fr) | 2004-01-23 | 2019-01-08 | Cornell Research Foundation, Inc. | Methodes de reduction de lesions par oxydation |
US20050272101A1 (en) | 2004-06-07 | 2005-12-08 | Prasad Devarajan | Method for the early detection of renal injury |
EP3725324A1 (fr) | 2005-09-16 | 2020-10-21 | Cornell Research Foundation, Inc. | Peptide aromatique-cationique destiné à être utilisé dans un procédé de réduction de l'expression cd36 |
US20070259377A1 (en) | 2005-10-11 | 2007-11-08 | Mickey Urdea | Diabetes-associated markers and methods of use thereof |
US20080027082A1 (en) | 2006-06-19 | 2008-01-31 | Berthold Hocher | Use of adenosine a1 antagonists in radiocontrast media induced nephropathy |
ES2458870T3 (es) | 2008-02-07 | 2014-05-07 | Cornell University | Procedimientos para prevenir o tratar la resistencia a la insulina |
DK2262520T3 (en) | 2008-02-26 | 2017-08-07 | Univ Cornell | COMPOSITIONS FOR PREVENTION AND TREATMENT OF Kidney Injury |
WO2020005756A1 (fr) | 2018-06-29 | 2020-01-02 | Reald Spark, Llc | Stabilisation pour dispositif d'affichage de confidentialité |
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