ES2977537T3 - Inhibidores peptídicos orales del receptor de interleucina-23 y su uso para tratar enfermedades inflamatorias intestinales - Google Patents
Inhibidores peptídicos orales del receptor de interleucina-23 y su uso para tratar enfermedades inflamatorias intestinales Download PDFInfo
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| USRE49026E1 (en) | 2011-06-14 | 2022-04-12 | Medical Diagnostic Laboratories, Llc | Polypeptides that bound to IL-23 receptor and inhibit binding of IL-23 and cell signaling thereof |
| RS62633B1 (sr) | 2013-03-15 | 2021-12-31 | Protagonist Therapeutics Inc | Analozi hepcidina i njihove primene |
| SI3143037T1 (sl) | 2014-05-16 | 2021-11-30 | Protagonist Therapeutics, Inc. | Antagonisti integrin alpha4beta7 tioeterskih peptidov |
| CN107206254B (zh) | 2014-07-17 | 2021-08-24 | 领导医疗有限公司 | 白细胞介素-23受体的口服肽抑制剂以及其治疗炎症性肠病的用途 |
| WO2016054445A1 (en) | 2014-10-01 | 2016-04-07 | Protagonist Therapeutics, Inc. | Novel cyclic monomer and dimer peptides having integrin antagonist activity |
| WO2016054411A1 (en) | 2014-10-01 | 2016-04-07 | Protagonist Therapeutics, Inc. | NOVEL α4β7 PEPTIDE MONOMER AND DIMER ANTAGONISTS |
| EA035733B9 (ru) * | 2015-07-15 | 2021-01-14 | Протагонист Терепьютикс, Инк. | Пептидные ингибиторы рецептора интерлейкина-23 и их применение для лечения воспалительных заболеваний |
| US10787490B2 (en) | 2015-07-15 | 2020-09-29 | Protaganist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| CA3009834A1 (en) | 2015-12-30 | 2017-07-06 | Protagonist Therapeutics, Inc. | Analogues of hepcidin mimetics with improved in vivo half lives |
| WO2017165676A1 (en) | 2016-03-23 | 2017-09-28 | Protagonist Therapeutics, Inc. | METHODS FOR SYNTHESIZING α4β7 PEPTIDE ANTAGONISTS |
| US20190270786A1 (en) * | 2016-07-27 | 2019-09-05 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 and their use to treat inflammatory diseases |
| 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 |
| CA3097812A1 (en) * | 2018-04-25 | 2019-10-31 | Janssen Pharmaceutica Nv | Thioether cyclic peptide amylin receptor modulators |
| JP2021523138A (ja) | 2018-05-11 | 2021-09-02 | ヤンセン バイオテツク，インコーポレーテツド | Ｉｌ−２３抗体を使用してうつを治療する方法 |
| WO2019246271A1 (en) | 2018-06-20 | 2019-12-26 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an il-12/il-23 inhibitor |
| US20230033021A1 (en) | 2018-06-20 | 2023-02-02 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an integrin inhibitor |
| WO2019246273A1 (en) | 2018-06-20 | 2019-12-26 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with a jak or other kinase inhibitor |
| EP3810095A1 (en) | 2018-06-20 | 2021-04-28 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with a tnf inhibitor |
| WO2019246312A1 (en) | 2018-06-20 | 2019-12-26 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an immunomodulator |
| EP3820883A4 (en) * | 2018-07-12 | 2022-04-20 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| CN111040020B (zh) * | 2018-12-28 | 2022-04-12 | 中国人民解放军军事科学院军事医学研究院 | 一种烯烃硫醚类订书肽及其制备方法与应用 |
| CN110015978B (zh) * | 2019-04-29 | 2021-03-19 | 康化（上海）新药研发有限公司 | O-[2-[[叔丁氧羰基]氨基]乙基]-n-[芴甲氧羰基]-l-酪氨酸的合成方法 |
| CN116082455A (zh) * | 2019-07-10 | 2023-05-09 | 领导医疗有限公司 | 白细胞介素-23受体的肽抑制剂及其用于治疗炎症性疾病的用途 |
| 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 |
| CN110790763A (zh) * | 2019-11-24 | 2020-02-14 | 烟台大学 | 吡啶并二嘧啶及吡啶并二吡唑衍生物的制备方法 |
| EP4090669A4 (en) * | 2020-01-15 | 2024-11-20 | Janssen Biotech, Inc. | PEPTIDE INHIBITORS OF THE INTERLEUKIN-23 RECEPTOR AND THEIR USE IN TREATING INFLAMMATORY DISEASES |
| SI4090670T1 (sl) | 2020-01-15 | 2025-08-29 | Janssen Biotech, Inc. | Peptidni zaviralci receptorja interlevkina-23 in njihova uporaba za zdravljenje vnetnih bolezni |
| US20230129095A1 (en) * | 2020-01-15 | 2023-04-27 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| TWI904146B (zh) * | 2020-03-31 | 2025-11-11 | 美商卡默森屈有限公司 | 使用ｃｃｒ９抑制劑及抗ｉｌ-２３阻斷抗體治療發炎性腸道疾病的組成物及方法 |
| KR20230030649A (ko) * | 2020-06-29 | 2023-03-06 | 유니버시티 오브 워싱턴 | 인간 il23 수용체에 결합하는 폴리펩타이드 |
| IL316550A (en) * | 2020-11-20 | 2024-12-01 | Janssen Pharmaceutica Nv | Compositions of interleukin-23 receptor peptide inhibitors |
| JP2023145581A (ja) * | 2020-11-20 | 2023-10-11 | ヤンセン ファーマシューティカ エヌ．ベー． | インターロイキン－２３受容体のペプチド阻害剤の組成物 |
| EP4314014A4 (en) * | 2021-04-01 | 2025-03-05 | Protagonist Therapeutics, Inc. | HEPCIDIN MIMETICS CONJUGATES |
| JP2024525780A (ja) * | 2021-07-14 | 2024-07-12 | ヤンセン バイオテツク，インコーポレーテツド | インターロイキン－２３受容体のペプチド阻害剤 |
| IL310061A (en) | 2021-07-14 | 2024-03-01 | Janssen Biotech Inc | Peptide inhibitors linked to fatty residues of the interleukin-23 receptor |
| CN117980320A (zh) * | 2021-07-14 | 2024-05-03 | 詹森生物科技公司 | 白介素-23受体的二环肽抑制剂 |
| IL313185A (en) | 2021-12-01 | 2024-07-01 | Zealand Pharma As | Peptide inhibitors of the interleukin-23 receptor |
| KR20230112549A (ko) | 2022-01-20 | 2023-07-27 | 한국과학기술연구원 | 로세부리아 속 또는 비피도박테리움 속 유래 세포외소포체를 포함하는, 염증성 질환의 예방, 개선, 또는 치료용 조성물 |
| AR129203A1 (es) * | 2022-05-04 | 2024-07-31 | Janux Therapeutics Inc | Anticuerpos multiespecíficos activados por tumores para dirigirse a cd28 y pd-l1, y métodos para usarlos |
| CA3260606A1 (en) | 2022-06-30 | 2024-01-04 | Sanofi | NEW PEPTIDES FOR USE AS SELECTIVE IL-23 RECEPTOR ANTAGONISTS |
| EP4628499A1 (en) * | 2022-11-30 | 2025-10-08 | Shanghai Hansoh Biomedical Co., Ltd. | Polypeptide inhibitor, and preparation method therefor and use thereof |
| KR20260007614A (ko) * | 2023-05-04 | 2026-01-14 | 시젱 하이스코 파마수티칼 씨오., 엘티디. | 인터루킨-23 수용체의 펩타이드 억제제의 제조 및 이의 용도 |
| EP4471049A1 (en) | 2023-06-01 | 2024-12-04 | Zealand Pharma A/S | Peptide inhibitors of interleukin-23 receptor |
| EP4471048A1 (en) | 2023-06-01 | 2024-12-04 | Zealand Pharma A/S | Peptide inhibitors of interleukin-23 receptor |
| WO2025051912A1 (en) | 2023-09-08 | 2025-03-13 | Sanofi | New peptides as selective il-23 receptor inhibitors |
| WO2025051920A1 (en) | 2023-09-08 | 2025-03-13 | Sanofi | New peptides as selective il-23 receptor inhibitors |
| WO2026013260A1 (en) | 2024-07-12 | 2026-01-15 | Zealand Pharma A/S | Peptide inhibitors of interleukin-23 receptor |
Family Cites Families (153)
| 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 |
| DK0578728T3 (da) | 1991-04-05 | 1999-04-12 | Genentech Inc | Inhibitorer for aggregering af blodplader, hvilke inhibitorer har høj specificitet for GP IIbIIIa |
| US5569741A (en) | 1992-07-27 | 1996-10-29 | Biomeasure, Inc. | Cyclic octapeptide neuromedin B receptor antagonists |
| CZ168194A3 (en) | 1992-11-12 | 1994-12-15 | Biomeasure | 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 |
| IL128332A0 (en) | 1996-08-30 | 2000-01-31 | Novo Nordisk As | GLP-1 derivatives |
| 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 |
| CA2206028C (en) | 1997-06-04 | 2006-10-03 | Frantisek Ziak | Fitness-balance board |
| 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 |
| EP1033983A1 (en) | 1997-11-24 | 2000-09-13 | 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 |
| EP1100473A2 (en) | 1998-07-28 | 2001-05-23 | InnerDyne, Inc. | Absorbable brachytherapy and chemotherapy delivery devices and methods |
| US20020142374A1 (en) | 1998-08-17 | 2002-10-03 | Michael Gallo | 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 |
| PL351326A1 (en) | 1999-03-17 | 2003-04-07 | Novo Nordisk As | Method for acylating peptides and novel acylating agents |
| IL145748A0 (en) | 1999-04-12 | 2002-07-25 | 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 |
| CA2436326C (en) | 2001-01-09 | 2012-08-14 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Combination therapy using receptor tyrosine kinase inhibitors and angiogenesis inhibitors |
| DE10107707A1 (de) | 2001-02-19 | 2002-08-29 | Wilex Biotechnology Gmbh | Antagonisten für alpha¶4¶beta¶7¶-Integrin |
| 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 |
| WO2004011650A2 (en) | 2002-07-24 | 2004-02-05 | 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 |
| CA2522680A1 (en) | 2003-04-15 | 2004-10-28 | Xenon Pharmaceuticals Inc. | Juvenile hemochromatosis gene (hfe2a), expression products and uses thereof |
| PL1680443T3 (pl) | 2003-11-05 | 2014-02-28 | Dana Farber Cancer Inst Inc | Stabilizowane alfa-helikalne peptydy i ich zastosowanie |
| WO2005064345A2 (en) | 2003-12-19 | 2005-07-14 | Applera Corporation | Methods and systems for protein and peptide evidence assembly |
| SI2177537T1 (sl) | 2004-01-09 | 2012-01-31 | Pfizer | Protitielesa proti MAdCAM |
| US8536140B2 (en) | 2004-03-12 | 2013-09-17 | Mti Meta Tech Inc. | Methods for treating inflammatory bowel disease |
| NZ551934A (en) | 2004-06-24 | 2009-09-25 | Inst Medical W & E Hall | Conjugates comprising a targeting moiety and a peptide that mimics the apoptosis-inducing BH3-only proteins |
| EP1799705A4 (en) | 2004-09-23 | 2008-11-05 | Univ 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 |
| ES2818028T3 (es) | 2004-12-20 | 2021-04-09 | Antibodyshop As | Determinación de lipocalina asociada a gelatinasa de neutrófilos (NGAL) como marcador diagnóstico para trastornos renales |
| US20100183617A1 (en) | 2005-02-23 | 2010-07-22 | University Of Virginia Patent Foundation | Compositions and methods for regulating sas1r |
| US7534764B2 (en) | 2005-06-29 | 2009-05-19 | The Regents Of The University Of California | Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin |
| JP2009509535A (ja) | 2005-09-27 | 2009-03-12 | アムニクス， インコーポレイテッド | タンパク様薬剤およびその使用 |
| TW200744634A (en) * | 2006-02-21 | 2007-12-16 | Wyeth Corp | Methods of using antibodies against human IL-22 |
| WO2007120883A2 (en) | 2006-04-12 | 2007-10-25 | Isis Pharmaceuticals, Inc. | Compositions and their uses directed to hepcidin |
| EP2767595B1 (en) | 2006-05-22 | 2018-09-19 | Clinical Genomics Pty Ltd | Detection method for characterising the anatomical origin of a cell |
| GB0610395D0 (en) | 2006-05-25 | 2006-07-05 | Ge Healthcare Ltd | Novel imaging agents |
| EP2044118A2 (en) * | 2006-06-13 | 2009-04-08 | 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 |
| CA2657338C (en) | 2006-07-21 | 2013-10-22 | Cristalia Produtos Quimicos Farmaceuticos Ltda. | Anti-inflammatory and antiallergic cyclic peptides |
| 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 |
| EP2109480B1 (en) | 2006-12-07 | 2017-06-28 | The Government of the United States of America as Represented by the Secretary of the Department of Health and Human Services | Use of antagonists of the interaction between hiv gp120 and alpha4beta7 integrin |
| MX2009008104A (es) | 2007-02-02 | 2009-08-07 | Amgen Inc | Hepcidina, antagonistas de hepcidina y metodos de uso. |
| JP6017754B2 (ja) | 2007-02-15 | 2016-11-02 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションＩｎｄｉａｎａ Ｕｎｉｖｅｒｓｉｔｙ Ｒｅｓｅａｒｃｈ Ａｎｄ Ｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐｏｒａｔｉｏｎ | グルカゴン／ｇｌｐ−１受容体コアゴニスト |
| PL2059534T3 (pl) * | 2007-02-23 | 2012-09-28 | Merck Sharp & Dohme | Przeciwciała Anty-IL-23p19 wytworzone metodą inżynierii genetycznej |
| US20080260820A1 (en) | 2007-04-19 | 2008-10-23 | Gilles Borrelly | Oral dosage formulations of protease-resistant polypeptides |
| CA2683145C (en) | 2007-04-27 | 2018-06-12 | Katherine E. Lewis | Antagonists to il-17a, il-17f, and il-23p19 and methods of use |
| US8313950B2 (en) | 2007-05-21 | 2012-11-20 | The Ohio State University Research Foundation | Hepcidins as biomarkers for impending lupus nephritis flare |
| WO2009002947A2 (en) | 2007-06-22 | 2008-12-31 | Affymax, Inc. | Compounds and peptides that bind the trail receptor |
| WO2009007849A2 (en) | 2007-07-06 | 2009-01-15 | Valorisation Hsj, Societe En Commandite | Il-23 receptor antagonists and uses thereof |
| 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 |
| CN102459311B (zh) | 2009-04-08 | 2015-08-19 | 武田药品工业株式会社 | 神经调节肽u衍生物 |
| 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 |
| US20130236977A1 (en) | 2010-05-24 | 2013-09-12 | 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. |
| CA2808091C (en) | 2010-08-11 | 2019-05-21 | 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 |
| 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 |
| CA2839408A1 (en) | 2011-06-14 | 2012-12-20 | Stealth Peptides International, Inc. | Aromatic-cationic peptides and uses of same |
| 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 |
| HK1199892A1 (en) | 2011-12-09 | 2015-07-24 | The Regents Of The University Of California | Modified mini-hepcidin peptides and methods of using thereof |
| 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 |
| AU2014216091A1 (en) | 2013-02-15 | 2015-09-03 | Srx Cardio, Llc | Proprotein convertase subtilisin/kexin type 9 allosteric binding ligands to modulate serum low density lipoprotein |
| RS62633B1 (sr) | 2013-03-15 | 2021-12-31 | Protagonist Therapeutics Inc | Analozi hepcidina i njihove primene |
| US20140294901A1 (en) | 2013-04-02 | 2014-10-02 | Protagonist Therapeutics, Inc. | Novel a4b7 peptide dimer antagonists |
| US20140294902A1 (en) | 2013-04-02 | 2014-10-02 | Protagonist Therapeutics, Inc. | Novel a4b7 peptide antagonists |
| CA2916136C (en) | 2013-06-24 | 2022-10-18 | Canbas Co., Ltd. | Peptides and peptidomimetics in combination uses and treatments for cancer patient subpopulations |
| WO2014210056A1 (en) | 2013-06-27 | 2014-12-31 | Stealth Peptides International, Inc. | Peptide therapeutics and methods for using same |
| AU2014331812B2 (en) | 2013-10-09 | 2019-01-17 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for downregulation of pro-inflammatory cytokines |
| WO2015112700A1 (en) | 2014-01-22 | 2015-07-30 | Wisconsin Alumni Research Foundation | Alpha/beta-peptide mimics of z-domain peptides |
| JP2017519810A (ja) | 2014-04-07 | 2017-07-20 | ラ ホヤ ファーマシューティカル カンパニーＬａ Ｊｏｌｌａ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｃｏｍｐａｎｙ | ヘプシジン模倣ペプチドおよびその使用 |
| SI3143037T1 (sl) | 2014-05-16 | 2021-11-30 | Protagonist Therapeutics, Inc. | Antagonisti integrin alpha4beta7 tioeterskih peptidov |
| WO2015183963A2 (en) | 2014-05-28 | 2015-12-03 | Stealth Peptides International, Inc. | Therapeutic compositions including redox-active parabenzoquinones and uses thereof |
| AU2015279571A1 (en) | 2014-06-27 | 2017-02-02 | 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 |
| CN107206254B (zh) | 2014-07-17 | 2021-08-24 | 领导医疗有限公司 | 白细胞介素-23受体的口服肽抑制剂以及其治疗炎症性肠病的用途 |
| WO2016054411A1 (en) | 2014-10-01 | 2016-04-07 | Protagonist Therapeutics, Inc. | NOVEL α4β7 PEPTIDE MONOMER AND DIMER ANTAGONISTS |
| WO2016054445A1 (en) | 2014-10-01 | 2016-04-07 | Protagonist Therapeutics, Inc. | Novel cyclic monomer and dimer peptides having integrin antagonist activity |
| EP3240799B1 (en) | 2014-12-29 | 2021-03-31 | 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 |
| EA035733B9 (ru) | 2015-07-15 | 2021-01-14 | Протагонист Терепьютикс, Инк. | Пептидные ингибиторы рецептора интерлейкина-23 и их применение для лечения воспалительных заболеваний |
| CA3009834A1 (en) | 2015-12-30 | 2017-07-06 | Protagonist Therapeutics, Inc. | Analogues of hepcidin mimetics with improved in vivo half lives |
| WO2017165676A1 (en) | 2016-03-23 | 2017-09-28 | Protagonist Therapeutics, Inc. | METHODS FOR SYNTHESIZING α4β7 PEPTIDE ANTAGONISTS |
| US20190264197A1 (en) | 2016-07-27 | 2019-08-29 | Protagonist Therapeutics, Inc. | Disulfide-rich peptide libraries and methods of use thereof |
| US20190270786A1 (en) | 2016-07-27 | 2019-09-05 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 and their use to treat inflammatory diseases |
| 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 |
| 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 |
| WO2019246273A1 (en) * | 2018-06-20 | 2019-12-26 | Progenity, 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 |
| EP3820883A4 (en) | 2018-07-12 | 2022-04-20 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| EP3953376A4 (en) | 2019-03-28 | 2023-07-12 | Protagonist Therapeutics, Inc. | METHODS OF SYNTHESIS OF BETA HOMOAMINO ACIDS |
| CN116082455A (zh) | 2019-07-10 | 2023-05-09 | 领导医疗有限公司 | 白细胞介素-23受体的肽抑制剂及其用于治疗炎症性疾病的用途 |
| 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 |
| MX2022002633A (es) | 2019-09-03 | 2022-06-02 | Protagonist Therapeutics Inc | Mimeticos de hepcidina conjugada. |
| KR20220125268A (ko) | 2020-01-10 | 2022-09-14 | 프로타고니스트 테라퓨틱스, 인코포레이티드 | α4β7 인테그린 길항제를 사용한 염증성 장 질환의 치료 방법 |
| EP4090669A4 (en) | 2020-01-15 | 2024-11-20 | Janssen Biotech, Inc. | PEPTIDE INHIBITORS OF THE INTERLEUKIN-23 RECEPTOR AND THEIR USE IN TREATING INFLAMMATORY DISEASES |
| US20230129095A1 (en) | 2020-01-15 | 2023-04-27 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| SI4090670T1 (sl) | 2020-01-15 | 2025-08-29 | Janssen Biotech, Inc. | Peptidni zaviralci receptorja interlevkina-23 in njihova uporaba za zdravljenje vnetnih bolezni |
| US20230295259A1 (en) | 2020-07-28 | 2023-09-21 | Protagonist Therapeutics, Inc. | Conjugated Hepcidin Mimetics |
| IL316550A (en) | 2020-11-20 | 2024-12-01 | Janssen Pharmaceutica Nv | Compositions of interleukin-23 receptor peptide inhibitors |
| EP4314014A4 (en) | 2021-04-01 | 2025-03-05 | Protagonist Therapeutics, Inc. | HEPCIDIN MIMETICS CONJUGATES |
| WO2022212698A1 (en) | 2021-04-01 | 2022-10-06 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| AU2022249095A1 (en) | 2021-04-01 | 2023-10-12 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| US20240293511A1 (en) | 2021-06-14 | 2024-09-05 | Protagonist Therapeutics, Inc. | Hepcidin mimetics for treatment of hereditary hemochromatosis |
| IL310061A (en) | 2021-07-14 | 2024-03-01 | Janssen Biotech Inc | Peptide inhibitors linked to fatty residues of the interleukin-23 receptor |
| CN117980320A (zh) | 2021-07-14 | 2024-05-03 | 詹森生物科技公司 | 白介素-23受体的二环肽抑制剂 |
| JP2024525780A (ja) | 2021-07-14 | 2024-07-12 | ヤンセン バイオテツク，インコーポレーテツド | インターロイキン－２３受容体のペプチド阻害剤 |
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2015
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