ES2901704T3 - Análogos de hepcidina y usos de los mismos - Google Patents
Análogos de hepcidina y usos de los mismos Download PDFInfo
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- ES2901704T3 ES2901704T3 ES14763104T ES14763104T ES2901704T3 ES 2901704 T3 ES2901704 T3 ES 2901704T3 ES 14763104 T ES14763104 T ES 14763104T ES 14763104 T ES14763104 T ES 14763104T ES 2901704 T3 ES2901704 T3 ES 2901704T3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Obesity (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361800284P | 2013-03-15 | 2013-03-15 | |
| US201361800048P | 2013-03-15 | 2013-03-15 | |
| PCT/US2014/030352 WO2014145561A2 (en) | 2013-03-15 | 2014-03-17 | Hepcidin analogues and uses therof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2901704T3 true ES2901704T3 (es) | 2022-03-23 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14763104T Active ES2901704T3 (es) | 2013-03-15 | 2014-03-17 | Análogos de hepcidina y usos de los mismos |
Country Status (20)
| Country | Link |
|---|---|
| US (8) | US9822157B2 (enExample) |
| EP (2) | EP4091624A1 (enExample) |
| JP (2) | JP6525471B2 (enExample) |
| KR (1) | KR102236829B1 (enExample) |
| CN (1) | CN105451755B (enExample) |
| AU (2) | AU2014232954B2 (enExample) |
| CA (1) | CA2906830C (enExample) |
| DK (1) | DK2968443T3 (enExample) |
| ES (1) | ES2901704T3 (enExample) |
| HR (1) | HRP20211911T1 (enExample) |
| HU (1) | HUE057168T2 (enExample) |
| IL (1) | IL241043B (enExample) |
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Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2855122A1 (en) | 2011-12-09 | 2013-06-13 | The Regents Of The University Of California | Modified mini-hepcidin peptides and methods of using thereof |
| PT2968443T (pt) | 2013-03-15 | 2021-12-28 | Protagonist Therapeutics Inc | Análogos de hepcidina e seus usos |
| WO2015157283A1 (en) | 2014-04-07 | 2015-10-15 | Merganser Biotech Llc | Hepdicin mimetic peptides and uses thereof |
| SG10201810321PA (en) | 2014-05-16 | 2018-12-28 | Protagonist Therapeutics Inc | α4β7 INTEGRIN THIOETHER PEPTIDE ANTAGONISTS |
| CA2953721A1 (en) * | 2014-06-27 | 2015-12-30 | Protagonist Therapeutics, Inc. | Hepcidin and mini-hepcidin analogues and uses therof |
| ES2977537T3 (es) | 2014-07-17 | 2024-08-26 | Protagonist Therapeutics Inc | Inhibidores peptídicos orales del receptor de interleucina-23 y su uso para tratar enfermedades inflamatorias intestinales |
| SG11201702553RA (en) | 2014-10-01 | 2017-04-27 | Protagonist Therapeutics Inc | NOVEL α4β7 PEPTIDE MONOMER AND DIMER ANTAGONISTS |
| US10301371B2 (en) | 2014-10-01 | 2019-05-28 | Protagonist Therapeutics, Inc. | Cyclic monomer and dimer peptides having integrin antagonist activity |
| US10787490B2 (en) | 2015-07-15 | 2020-09-29 | Protaganist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| WO2017117411A1 (en) | 2015-12-30 | 2017-07-06 | Protagonist Therapeutics, Inc. | Analogues of hepcidin mimetics with improved in vivo half lives |
| US10407468B2 (en) | 2016-03-23 | 2019-09-10 | Protagonist Therapeutics, Inc. | Methods for synthesizing α4β7 peptide antagonists |
| WO2018128828A1 (en) | 2016-12-23 | 2018-07-12 | Bayer Healthcare Llc | Novel hepcidin mimetics and uses thereof |
| JP2020504160A (ja) * | 2017-01-18 | 2020-02-06 | ラ ホヤ ファーマシューティカル カンパニーＬａ Ｊｏｌｌａ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｃｏｍｐａｎｙ | 鉄過剰症を治療するための組成物及び方法 |
| EP4092038A1 (en) | 2017-09-11 | 2022-11-23 | Protagonist Therapeutics, Inc. | Opioid agonist peptides and uses thereof |
| EP4501952A3 (en) * | 2018-02-08 | 2025-04-16 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| EP3894416B1 (en) | 2018-12-13 | 2022-11-09 | Global Blood Therapeutics, Inc. | Ferroportin inhibitors and methods of use |
| US20220105121A1 (en) * | 2019-02-08 | 2022-04-07 | Clear Creek Bio, Inc. | Compositions and methods for inhibiting inosine monophosphate dehydrogenase |
| US20220105120A1 (en) * | 2019-02-08 | 2022-04-07 | Clear Creek Bio, Inc. | Compositions and methods for inhibiting inosine monophosphate dehydrogenase |
| EP3997105A4 (en) | 2019-07-10 | 2023-09-13 | Protagonist Therapeutics, Inc. | PEPTIDE INHIBITORS OF THE INTERLEUKIN-23 RECEPTOR AND THEIR USE TO TREAT INFLAMMATORY DISEASES |
| BR112022003999A2 (pt) | 2019-09-03 | 2022-05-31 | Protagonist Therapeutics Inc | Miméticos de hepcidina conjugados |
| CN115279782A (zh) | 2020-01-15 | 2022-11-01 | 詹森生物科技公司 | 白介素-23受体的肽抑制剂及其用于治疗炎性疾病的用途 |
| IL294680A (en) | 2020-01-15 | 2022-09-01 | Janssen Biotech Inc | Peptide inhibitors of the interleukin-23 receptor and their use for the treatment of inflammatory diseases |
| KR102521421B1 (ko) * | 2020-01-22 | 2023-04-14 | 연세대학교 산학협력단 | 헤테로키랄 펩티드 복합체 및 이의 자가조립 중간체를 포함한 핵자기공명분광 잔류쌍극결합 측정용 조성물 |
| CA3181583A1 (en) | 2020-04-28 | 2021-11-04 | Global Blood Therapeutics, Inc. | Methods of use for pyrimidines as ferroportin inhibitors |
| CA3181577A1 (en) | 2020-04-28 | 2021-11-04 | Global Blood Therapeutics, Inc. | Thieno pyrimidines as ferroportin inhibitors |
| MX2022013518A (es) | 2020-04-28 | 2023-02-01 | Global Blood Therapeutics Inc | Pirimidinas cicloalquiladas como inhibidores de la ferroportina. |
| CN111560051B (zh) * | 2020-05-26 | 2022-11-25 | 大连工业大学 | 一种具有促铁吸收活性的虾源九肽及其应用 |
| AU2021315564A1 (en) * | 2020-07-28 | 2023-02-09 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| IL302996B2 (en) | 2020-11-20 | 2025-04-01 | Janssen Pharmaceutica Nv | Compositions of interleukin-23 receptor peptide inhibitors |
| CA3213688A1 (en) * | 2021-04-01 | 2022-10-06 | Ashok Bhandari | Conjugated hepcidin mimetics |
| KR20240021833A (ko) * | 2021-06-14 | 2024-02-19 | 프로타고니스트 테라퓨틱스, 인코포레이티드 | 유전성 혈색소 침착증의 치료를 위한 헵시딘 모방체 |
| AU2022311814A1 (en) | 2021-07-14 | 2024-02-29 | Janssen Biotech, Inc. | Lipidated peptide inhibitors of interleukin-23 receptor |
| WO2023150618A2 (en) * | 2022-02-02 | 2023-08-10 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| US20250170216A1 (en) * | 2022-02-02 | 2025-05-29 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| US12011489B2 (en) | 2022-03-30 | 2024-06-18 | Christopher Key | Compositions and methods for treating inflammatory disease |
| WO2025207760A1 (en) | 2024-03-27 | 2025-10-02 | Protagonist Therapeutics, Inc. | Formulations of a hepcidin peptide analogue |
Family Cites Families (161)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4684620A (en) | 1984-09-04 | 1987-08-04 | Gibson-Stephens Neuropharmaceuticals, Inc. | Cyclic polypeptides having mu-receptor specificity |
| US4724229A (en) | 1986-09-30 | 1988-02-09 | Smithkline Beckman Corporation | Arg-arg-arg-vasopressin antagonists |
| JPH02306947A (ja) | 1989-05-01 | 1990-12-20 | Monsanto Co | キラルβ―アミノ酸の製造方法 |
| US5192746A (en) | 1990-07-09 | 1993-03-09 | Tanabe Seiyaku Co., Ltd. | Cyclic cell adhesion modulation compounds |
| DE69226077T2 (de) | 1991-04-05 | 1998-12-03 | Genentech, Inc., South San Francisco, Calif. | PLAETTCHENAGGREGATIONSINHIBITOREN MIT HOHER SPEZIFIZITAET ZUM GP IIbIIIa |
| US5569741A (en) | 1992-07-27 | 1996-10-29 | Biomeasure, Inc. | Cyclic octapeptide neuromedin B receptor antagonists |
| WO1994011018A1 (en) | 1992-11-12 | 1994-05-26 | Biomeasure, Inc. | Opioid peptides |
| US5293050A (en) | 1993-03-25 | 1994-03-08 | International Business Machines Corporation | Semiconductor quantum dot light emitting/detecting devices |
| AU673731B2 (en) | 1993-06-03 | 1996-11-21 | Banyu Pharmaceutical Co., Ltd. | Novel endothelin antagonistic peptide |
| GB9516994D0 (en) | 1995-08-18 | 1995-10-18 | Iaf Biochem Int | Solution synthesis of peripheral acting analgestic opioid tetrapeptides |
| US6037324A (en) | 1996-01-04 | 2000-03-14 | Leukosite, Inc. | Inhibitors of MAdCAM-1-mediated interactions and methods of use therefor |
| US5990084A (en) | 1996-04-19 | 1999-11-23 | Novo Nordisk A/S | Compounds with growth hormone releasing properties |
| GB9613112D0 (en) | 1996-06-21 | 1996-08-28 | Zeneca Ltd | Chemical compounds |
| US7122623B2 (en) | 1996-07-12 | 2006-10-17 | Adherex Technologies, Inc. | Compounds and methods for modulating cell adhesion |
| ES2283025T3 (es) | 1996-08-30 | 2007-10-16 | Novo Nordisk A/S | Derivados de glp-1.1. |
| US5942492A (en) | 1996-11-12 | 1999-08-24 | Angstrom Pharmaceuticals, Inc. | Cyclic peptides that bind to urokinase-type plasminogen activator receptor |
| US5993811A (en) | 1997-02-03 | 1999-11-30 | Biology Associates, Llc | Method and compositions for preventing and treating the systemic inflammatory response syndrome including sepsis |
| EP0998309A1 (en) | 1997-07-11 | 2000-05-10 | Innerdyne Medical, Inc. | Methods and systems for preparing and sealing radiation delivery structures |
| US6818617B1 (en) | 1997-08-15 | 2004-11-16 | Temple University- Of The Commonwealth System Of Higher Education | EC-3, an inhibitor of α4β1 and α4β7 integrins |
| CA2309338A1 (en) | 1997-11-24 | 1999-06-03 | Merck & Co., Inc. | Cyclic amino acid derivatives as cell adhesion inhibitors |
| US8038984B2 (en) | 1998-06-20 | 2011-10-18 | Washington University | Membrane-permeant peptide complexes for treatment of sepsis |
| JP2002524108A (ja) | 1998-07-28 | 2002-08-06 | インナーダイン， インコーポレイテッド | 吸収性近接照射療法および化学療法送達デバイスならびに方法 |
| CA2341029A1 (en) | 1998-08-17 | 2000-02-24 | Abgenix, Inc. | Generation of modified molecules with increased serum half-lives |
| US6087334A (en) | 1998-08-21 | 2000-07-11 | Amylin Pharmaceuticals, Inc. | Anti-diabetic peptides |
| AUPP616498A0 (en) | 1998-09-25 | 1998-10-15 | University Of Queensland, The | Synthesis of cyclic peptides |
| AUPP616598A0 (en) | 1998-09-25 | 1998-10-15 | University Of Queensland, The | Auxiliary for amide bond formation |
| AUPP660698A0 (en) | 1998-10-21 | 1998-11-12 | University Of Queensland, The | A method of protein engineering |
| US6451987B1 (en) | 1999-03-15 | 2002-09-17 | Novo Nordisk A/S | Ion exchange chromatography of proteins and peptides |
| HUP0200297A3 (en) | 1999-03-17 | 2002-09-30 | Novo Nordisk As | Method for acylating peptides and the glutaminic acid derivatives as acylating agents |
| NZ514602A (en) | 1999-04-12 | 2003-06-30 | Aventis Pharma Ltd | Substituted bicyclic heteroaryl compounds as integrin antagonists |
| WO2001068586A2 (en) | 2000-03-14 | 2001-09-20 | Novartis Ag | α4β1 AND α4β7 INTEGRIN INHIBITORS |
| US20110131679A2 (en) | 2000-04-19 | 2011-06-02 | Thomas La Rosa | Rice Nucleic Acid Molecules and Other Molecules Associated with Plants and Uses Thereof for Plant Improvement |
| RU2292904C2 (ru) | 2001-01-09 | 2007-02-10 | Мерк Патент Гмбх | Комбинированная терапия, использующая ингибиторы рецептора тирозинкиназы и ингибиторы ангиогенезиса |
| DE10107707A1 (de) | 2001-02-19 | 2002-08-29 | Wilex Biotechnology Gmbh | Antagonisten für alpha¶4¶beta¶7¶-Integrin |
| EP1451211A2 (en) | 2001-03-30 | 2004-09-01 | University of Copenhagen | Compositions and methods for modulating guanylyl cyclase signaling receptor (gc-c) activity and for treating meniere's disease |
| US20040142325A1 (en) | 2001-09-14 | 2004-07-22 | Liat Mintz | Methods and systems for annotating biomolecular sequences |
| AUPS039702A0 (en) | 2002-02-08 | 2002-03-07 | University Of Queensland, The | Common protein surface shapes and uses therefor |
| US20030166138A1 (en) | 2002-02-21 | 2003-09-04 | Todd Kinsella | Cyclic peptides and analogs useful to treat allergies |
| AU2003254585A1 (en) | 2002-07-24 | 2004-02-16 | Intercell Ag | Antigens encoded by alternative reading frame from pathogenic viruses |
| AU2003301059A1 (en) | 2002-12-18 | 2004-07-22 | Wyeth | Methods for screening, treating and diagnosing inflammatory bowel disease and compositions thereof |
| US20070032417A1 (en) | 2002-12-24 | 2007-02-08 | Walter And Eliza Hall Institute Of Medical Research | Peptides and therapeutic uses thereof |
| EP2006298A3 (en) | 2003-04-15 | 2009-04-22 | Xenon Pharmaceuticals Inc. | Juvenile hemochromatosis gene (HFE2A), expression products and uses thereof |
| PT2332968T (pt) | 2003-11-05 | 2016-08-17 | Harvard College | Péptidos alfa-helicoidais adequados para a activação ou inibição da morte celular |
| WO2005064345A2 (en) * | 2003-12-19 | 2005-07-14 | Applera Corporation | Methods and systems for protein and peptide evidence assembly |
| CN1956738B (zh) | 2004-01-09 | 2013-05-29 | 辉瑞大药厂 | MAdCAM抗体 |
| US8536140B2 (en) | 2004-03-12 | 2013-09-17 | Mti Meta Tech Inc. | Methods for treating inflammatory bowel disease |
| WO2006000034A1 (en) | 2004-06-24 | 2006-01-05 | The Walter And Eliza Hall Institute Of Medical Research | Conjugates and therapeutic uses thereof |
| WO2006032104A1 (en) | 2004-09-23 | 2006-03-30 | The University Of Melbourne | Antigenic complex for the diagnosis and treatment of porphyromonas gingivalis infection |
| WO2006062685A2 (en) | 2004-11-11 | 2006-06-15 | Affymax, Inc. | Novel peptides that bind to the erythropoietin receptor |
| JP2008521840A (ja) | 2004-11-30 | 2008-06-26 | ガストロテック・ファルマ・アクティーゼルスカブ | 成長ホルモン分泌促進物質レセプター１ａリガンド |
| CN101163971B (zh) | 2004-12-20 | 2013-03-20 | 免疫体公司 | 测定作为肾病诊断标记物的嗜中性粒细胞明胶酶相关性脂笼蛋白 |
| US20100183617A1 (en) | 2005-02-23 | 2010-07-22 | University Of Virginia Patent Foundation | Compositions and methods for regulating sas1r |
| CA2549477A1 (en) | 2005-06-29 | 2006-12-29 | The Regents Of The University Of California | Competitive regulation of hepcidin mrna by soluble and cell-associated hemojuvelin |
| US20070212703A1 (en) | 2005-09-27 | 2007-09-13 | Stemmer Willem P | Proteinaceous pharmaceuticals and uses thereof |
| EP2371957A1 (en) | 2006-04-12 | 2011-10-05 | Isis Pharmaceuticals, Inc. | Compositions and their uses directed to hepcidin |
| BRPI0713098A2 (pt) | 2006-05-22 | 2012-10-16 | Clinical Genomics Pty Ltd | método para determinar a origem anatÈmica de uma célula ou população celular derivada do intestino grosso de um indivìduo, método de detecção para determinar a origem anatÈmica de uma célula ou população celular derivada do intestino grosso de um indivìduo, sistema de detecção, meio de armazenagem legìvel por computador, arranjo de ácido nucleico, uso de um arranjo, método para determinar o inìcio ou predisposição para o inìcio de uma anormalidade celular ou uma condição destinguida por uma anormalidade celular no intestino grosso, kit de diagnóstico para ensaiar amostras biológicas |
| GB0610395D0 (en) | 2006-05-25 | 2006-07-05 | Ge Healthcare Ltd | Novel imaging agents |
| WO2007147019A2 (en) | 2006-06-13 | 2007-12-21 | Zymogenetics, Inc. | Il-17 and il-23 antagonists and methods of using the same |
| US20080019913A1 (en) | 2006-07-07 | 2008-01-24 | University Of Arizona Office Of Technology Transfer | Enkepahlin analogs with improved bioavailability |
| WO2008045252A2 (en) | 2006-10-04 | 2008-04-17 | The Board Of Trustees Of The Leland Stanford Junior University | Engineered integrin binding peptides |
| US7713937B2 (en) | 2006-11-10 | 2010-05-11 | Cara Therapeutics, Inc. | Synthetic peptide amides and dimeric forms thereof |
| WO2008140602A2 (en) | 2006-12-07 | 2008-11-20 | The Govenment Of The Usa As Represented By The Secretary Of The Dept. Of Health And Human Services | USE OF ANTAGONISTS OF THE INTERACTION BETWEEN HIV GP120 AND α4β7 INTEGRIN |
| PE20090722A1 (es) * | 2007-02-02 | 2009-07-13 | Amgen Inc | Hepcidina, antagonistas de la hepcidina y metodos de uso |
| EA017849B1 (ru) | 2007-02-15 | 2013-03-29 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Соагонисты глюкагоновых/glp-1-рецепторов |
| MX2009009079A (es) | 2007-02-23 | 2009-08-31 | Schering Corp | Anticuerpos anti-il-23p19 de ingenieria. |
| US20080260820A1 (en) | 2007-04-19 | 2008-10-23 | Gilles Borrelly | Oral dosage formulations of protease-resistant polypeptides |
| WO2008134659A2 (en) | 2007-04-27 | 2008-11-06 | Zymogenetics, Inc. | Antagonists to il-17a, il-17f, and il-23p19 and methods of use |
| WO2008144041A1 (en) * | 2007-05-21 | 2008-11-27 | The Ohio State University Research Foundation | Hepcidins as biomarkers for impending lupus nephritis flare |
| US20090131317A1 (en) | 2007-06-22 | 2009-05-21 | Affymax, Inc. | Compounds and peptides that bind the trail receptor |
| CN101990547A (zh) | 2007-07-06 | 2011-03-23 | 瓦勒瑞萨欣Hsj有限合伙公司 | Il-23受体拮抗剂以及其应用 |
| CN101358201A (zh) | 2007-07-31 | 2009-02-04 | 钱忠明 | 重组人铁调素腺病毒、其制备方法及应用 |
| CN101307085B (zh) | 2007-08-01 | 2012-06-13 | 香港理工大学深圳研究院 | 抑制铁调素调节蛋白的siRNA、重组慢病毒及其应用 |
| CA2707840A1 (en) | 2007-08-20 | 2009-02-26 | Allozyne, Inc. | Amino acid substituted molecules |
| GR1006896B (el) * | 2007-08-24 | 2010-07-20 | Ελληνικο Ινστιτουτο Παστερ, | Μεθοδος παραγωγης μιας πεπτιδικης ορμονης |
| WO2009039185A1 (en) | 2007-09-17 | 2009-03-26 | The Trustees Of Columbia University In The City Of New York | Uses of immunologically modified scaffold for tissue prevascularization and cell transplantation |
| US20100280098A1 (en) | 2007-10-05 | 2010-11-04 | Juliano Rudolph L | Receptor targeted oligonucleotides |
| JP2012507723A (ja) | 2008-11-03 | 2012-03-29 | シェーリング コーポレイション | 炎症性腸疾患生物マーカーおよび関連治療方法 |
| CN102245626A (zh) | 2008-12-05 | 2011-11-16 | 加利福尼亚大学董事会 | 微型铁调素肽及其使用方法 |
| DE102009007381A1 (de) | 2009-01-29 | 2010-08-05 | Amp-Therapeutics Gmbh & Co. Kg | Antibiotische Peptide |
| US8999935B2 (en) | 2009-02-11 | 2015-04-07 | New York University | Treatment of osteoporosis in peri- and post-menopausal women with hepcidin |
| WO2010116752A1 (ja) | 2009-04-08 | 2010-10-14 | 武田薬品工業株式会社 | ニューロメジンｕ誘導体 |
| TWI578992B (zh) * | 2009-04-30 | 2017-04-21 | 諾克森製藥股份有限公司 | 與鐵調節激素（ｈｅｐｃｉｄｉｎ）結合之核酸類 |
| US20110142889A1 (en) | 2009-12-16 | 2011-06-16 | Nod Pharmaceuticals, Inc. | Compositions and methods for oral drug delivery |
| CN104725472A (zh) | 2010-01-25 | 2015-06-24 | 康奈尔大学 | 芳香族阳离子肽及其用途 |
| US9523073B2 (en) | 2010-03-31 | 2016-12-20 | Medical Diagnostic Laboratories, Llc | Elisa for a naturally-occurring soluble truncated form of IL-23 receptor |
| JP2011231085A (ja) | 2010-04-30 | 2011-11-17 | Osaka Prefecture Univ | 環状ペプチド |
| WO2011149942A2 (en) * | 2010-05-24 | 2011-12-01 | Children's Medical Center Corporation | Compositions and methods for plasma peptide analysis |
| IT1406051B1 (it) | 2010-08-05 | 2014-02-06 | D M G Italia S R L | Uso di hmgb1 come marcatore biologico di infiammazione intestinale umana, metodo non invasivo per la sua rilevazione in campioni fecali e kit relativo. |
| EP3626253B8 (en) | 2010-08-11 | 2022-04-20 | Ironwood Pharmaceuticals, Inc. | Stable formulations of linaclotide |
| EP2444101A1 (en) | 2010-10-21 | 2012-04-25 | Universitätsklinikum Freiburg | Selective targeting of the CD40L/Mac-1 interaction by small peptide inhibitors and its use for the treatment of inflammation and atherogenesis |
| US9243034B2 (en) | 2011-01-27 | 2016-01-26 | Ramot At Tel-Aviv University Ltd. | Glycogen synthase kinase-3 inhibitors |
| US9169292B2 (en) | 2011-06-14 | 2015-10-27 | Medical Diagnostic Laboratories, Llc | Polypeptides that bound to IL-23 receptor and inhibit binding of IL-23 and cell signaling thereof |
| US8946150B2 (en) | 2011-06-14 | 2015-02-03 | Medical Diagnostic Laboratories, LLC. | Polypeptides that bound to IL-23 receptor and inhibit binding of IL-23 and cell signaling thereof |
| US9605027B2 (en) | 2011-06-14 | 2017-03-28 | Medical Diagnostic Laboratories, Llc | Polypeptides that bound to IL-23 receptor and inhibit binding of IL-23 and cell signaling thereof |
| CN103764159A (zh) | 2011-06-14 | 2014-04-30 | 康肽德生物医药技术有限公司 | 芳香族阳离子肽及其用途 |
| CA2855122A1 (en) | 2011-12-09 | 2013-06-13 | The Regents Of The University Of California | Modified mini-hepcidin peptides and methods of using thereof |
| ES2755104T3 (es) | 2012-05-17 | 2020-04-21 | Ra Pharmaceuticals Inc | Inhibidores peptídicos y peptidomiméticos |
| WO2013177432A1 (en) | 2012-05-23 | 2013-11-28 | The University Of Chicago | Methods of treating obesity |
| US9024044B2 (en) | 2012-06-14 | 2015-05-05 | Ajinomoto Co., Inc. | Heteroarylcarboxylic acid ester derivative |
| US9273093B2 (en) | 2012-10-11 | 2016-03-01 | Protagonist Therapeutics, Inc. | α4β7 peptide dimer antagonists |
| HK1219048A1 (zh) | 2013-02-15 | 2017-03-24 | Srx Cardio, Llc | 前蛋白转化酶枯草杆菌蛋白酶/kexin 9型(pcsk9)变构结合配体来调节低密度脂蛋白(ldl)血清水平 |
| PT2968443T (pt) | 2013-03-15 | 2021-12-28 | Protagonist Therapeutics Inc | Análogos de hepcidina e seus usos |
| US20140294902A1 (en) | 2013-04-02 | 2014-10-02 | Protagonist Therapeutics, Inc. | Novel a4b7 peptide antagonists |
| US20140294901A1 (en) | 2013-04-02 | 2014-10-02 | Protagonist Therapeutics, Inc. | Novel a4b7 peptide dimer antagonists |
| JP6401255B2 (ja) | 2013-06-24 | 2018-10-10 | 株式会社 キャンバス | ペプチド及びペプチド模倣物の併用並びに癌患者亜集団の処置 |
| CA2916492A1 (en) | 2013-06-27 | 2014-12-31 | Stealth Biotherapeutics Corp | Peptide therapeutics and methods for using same |
| EP3065757A4 (en) | 2013-10-09 | 2017-08-23 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for downregulation of pro-inflammatory cytokines |
| US9284362B2 (en) | 2014-01-22 | 2016-03-15 | Wisconsin Alumni Research Foundation | α/β-peptide mimics of Z-domain peptides |
| WO2015157283A1 (en) | 2014-04-07 | 2015-10-15 | Merganser Biotech Llc | Hepdicin mimetic peptides and uses thereof |
| SG10201810321PA (en) | 2014-05-16 | 2018-12-28 | Protagonist Therapeutics Inc | α4β7 INTEGRIN THIOETHER PEPTIDE ANTAGONISTS |
| WO2015183963A2 (en) | 2014-05-28 | 2015-12-03 | Stealth Peptides International, Inc. | Therapeutic compositions including redox-active parabenzoquinones and uses thereof |
| CA2953721A1 (en) | 2014-06-27 | 2015-12-30 | Protagonist Therapeutics, Inc. | Hepcidin and mini-hepcidin analogues and uses therof |
| WO2016004093A2 (en) | 2014-07-01 | 2016-01-07 | Stealth Biotherapeutics Corp | Therapeutic compositions including galectin-3 inhibitors and uses thereof |
| ES2977537T3 (es) | 2014-07-17 | 2024-08-26 | Protagonist Therapeutics Inc | Inhibidores peptídicos orales del receptor de interleucina-23 y su uso para tratar enfermedades inflamatorias intestinales |
| SG11201702553RA (en) | 2014-10-01 | 2017-04-27 | Protagonist Therapeutics Inc | NOVEL α4β7 PEPTIDE MONOMER AND DIMER ANTAGONISTS |
| US10301371B2 (en) | 2014-10-01 | 2019-05-28 | Protagonist Therapeutics, Inc. | Cyclic monomer and dimer peptides having integrin antagonist activity |
| US20170362292A1 (en) | 2014-12-29 | 2017-12-21 | The Regents Of The University Of California | S-Alkylated Hepcidin Peptides and Methods of Making and Using Thereof |
| US20160199437A1 (en) | 2015-01-08 | 2016-07-14 | D. Travis Wilson | Therapeutic compositions including iron chelators and uses thereof |
| WO2016115168A1 (en) | 2015-01-12 | 2016-07-21 | Synthorx, Inc. | Incorporation of unnatural nucleotides and methods thereof |
| 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 |
| WO2016195663A1 (en) | 2015-06-02 | 2016-12-08 | Stealth Peptides International, Inc. | Therapeutic compositions including bpm 31510, variants and analogues thereof, and uses thereof |
| WO2016200364A1 (en) | 2015-06-08 | 2016-12-15 | Stealth Peptides International, Inc. | THERAPEUTIC COMPOSITIONS INCLUDING SkQ COMPOUNDS AND USES THEREOF |
| US10787490B2 (en) | 2015-07-15 | 2020-09-29 | Protaganist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| CN108348580B (zh) | 2015-07-15 | 2022-05-10 | 领导医疗有限公司 | 白细胞介素-23受体的肽抑制剂以及其治疗炎症性疾病的用途 |
| JP6810988B2 (ja) | 2015-10-23 | 2021-01-13 | ヴィフォール （インターナショナル） アクチェンゲゼルシャフトＶｉｆｏｒ （Ｉｎｔｅｒｎａｔｉｏｎａｌ） ＡＧ | 新規なフェロポーチン阻害剤 |
| WO2017117411A1 (en) | 2015-12-30 | 2017-07-06 | Protagonist Therapeutics, Inc. | Analogues of hepcidin mimetics with improved in vivo half lives |
| US10407468B2 (en) | 2016-03-23 | 2019-09-10 | Protagonist Therapeutics, Inc. | Methods for synthesizing α4β7 peptide antagonists |
| WO2018022937A1 (en) | 2016-07-27 | 2018-02-01 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 and their use to treat inflammatory diseases |
| WO2018022917A1 (en) | 2016-07-27 | 2018-02-01 | Protagonist Therapeutics, Inc. | Disulfide-rich peptide libraries and methods of use thereof |
| US20180099023A1 (en) | 2016-09-06 | 2018-04-12 | La Jolla Pharmaceutical Company | Methods of treating iron overload |
| WO2018089693A2 (en) | 2016-11-09 | 2018-05-17 | Protagonist Therapeutics, Inc. | Methods for determining and monitoring gastrointestinal inflammation |
| US11192918B2 (en) | 2016-12-06 | 2021-12-07 | Stichting Voor De Technische Wetenschappen | Multicyclic peptides and methods for their preparation |
| WO2018128828A1 (en) | 2016-12-23 | 2018-07-12 | Bayer Healthcare Llc | Novel hepcidin mimetics and uses thereof |
| WO2018136646A1 (en) | 2017-01-18 | 2018-07-26 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| EP4092038A1 (en) | 2017-09-11 | 2022-11-23 | Protagonist Therapeutics, Inc. | Opioid agonist peptides and uses thereof |
| EP4501952A3 (en) | 2018-02-08 | 2025-04-16 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| US12171764B2 (en) | 2018-06-20 | 2024-12-24 | Biora Therapeutics, Inc. | Treatment of a disease of the gastrointestinal tract with a JAK or other kinase inhibitor |
| JOP20190150A1 (ar) | 2018-06-21 | 2019-12-21 | Merck Sharp & Dohme | مركبات مناهضة لـ pcsk9 |
| WO2020014646A1 (en) | 2018-07-12 | 2020-01-16 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| WO2020198682A1 (en) | 2019-03-28 | 2020-10-01 | Protagonist Therapeutics, Inc. | METHODS FOR SYNTHESIZING β-HOMOAMINO ACIDS |
| TW202116793A (zh) | 2019-07-10 | 2021-05-01 | 美商領導醫療有限公司 | 介白素-23受體之肽抑制劑及其於治療發炎疾病的用途 |
| EP3997105A4 (en) | 2019-07-10 | 2023-09-13 | Protagonist Therapeutics, Inc. | PEPTIDE INHIBITORS OF THE INTERLEUKIN-23 RECEPTOR AND THEIR USE TO TREAT INFLAMMATORY DISEASES |
| BR112022003999A2 (pt) | 2019-09-03 | 2022-05-31 | Protagonist Therapeutics Inc | Miméticos de hepcidina conjugados |
| US20230063321A1 (en) | 2020-01-10 | 2023-03-02 | Suneel Kumar Gupta | Methods for Treating Inflammatory Bowel Diseases with alpha4beta7 Integrin Antagonists |
| CN115279782A (zh) | 2020-01-15 | 2022-11-01 | 詹森生物科技公司 | 白介素-23受体的肽抑制剂及其用于治疗炎性疾病的用途 |
| WO2021146458A1 (en) | 2020-01-15 | 2021-07-22 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| IL294680A (en) | 2020-01-15 | 2022-09-01 | Janssen Biotech Inc | Peptide inhibitors of the interleukin-23 receptor and their use for the treatment of inflammatory diseases |
| AU2021315564A1 (en) | 2020-07-28 | 2023-02-09 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| IL302996B2 (en) | 2020-11-20 | 2025-04-01 | Janssen Pharmaceutica Nv | Compositions of interleukin-23 receptor peptide inhibitors |
| US20240226225A1 (en) | 2021-04-01 | 2024-07-11 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| AU2022249097A1 (en) | 2021-04-01 | 2023-10-12 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| CA3213688A1 (en) | 2021-04-01 | 2022-10-06 | Ashok Bhandari | Conjugated hepcidin mimetics |
| KR20240021833A (ko) | 2021-06-14 | 2024-02-19 | 프로타고니스트 테라퓨틱스, 인코포레이티드 | 유전성 혈색소 침착증의 치료를 위한 헵시딘 모방체 |
| AU2022311814A1 (en) | 2021-07-14 | 2024-02-29 | Janssen Biotech, Inc. | Lipidated peptide inhibitors of interleukin-23 receptor |
| EP4370531A4 (en) | 2021-07-14 | 2025-09-03 | Janssen Biotech Inc | PEPTIDE INHIBITORS OF THE INTERLEUKIN-23 RECEPTOR |
| MX2024000761A (es) | 2021-07-14 | 2024-04-18 | Janssen Biotech Inc | Inhibidores peptidicos biciclicos del receptor de interleucina-23. |
| US20250179196A1 (en) | 2021-07-30 | 2025-06-05 | Janssen Biotech, Inc. | Materials and methods of making or using il-23r binding proteins |
| WO2023150618A2 (en) | 2022-02-02 | 2023-08-10 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| US20250170216A1 (en) | 2022-02-02 | 2025-05-29 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| US20250360187A1 (en) | 2022-06-07 | 2025-11-27 | Protagonist Therapeutics, Inc. | Hepcidin mimetics for treatment of sickle cell disease |
| WO2024011188A1 (en) | 2022-07-07 | 2024-01-11 | Protagonist Therapeutics, Inc. | Combination therapy for treatment of iron overload diseases |
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