JP6480865B2 - 新規なα４β７ペプチド二量体拮抗薬 - Google Patents
新規なα４β７ペプチド二量体拮抗薬 Download PDFInfo
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- JP6480865B2 JP6480865B2 JP2015536909A JP2015536909A JP6480865B2 JP 6480865 B2 JP6480865 B2 JP 6480865B2 JP 2015536909 A JP2015536909 A JP 2015536909A JP 2015536909 A JP2015536909 A JP 2015536909A JP 6480865 B2 JP6480865 B2 JP 6480865B2
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- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9273093B2 (en) | 2012-10-11 | 2016-03-01 | Protagonist Therapeutics, Inc. | α4β7 peptide dimer antagonists |
| EP2970505A4 (en) | 2013-03-14 | 2016-10-19 | California Inst Biomedical Res | SPECIFIC ANTIBODIES AND USES THEREOF |
| SG10201707622XA (en) | 2013-03-15 | 2017-11-29 | Protagonist Therapeutics Inc | Hepcidin analogues and uses therof |
| US20140294901A1 (en) * | 2013-04-02 | 2014-10-02 | Protagonist Therapeutics, Inc. | Novel a4b7 peptide dimer antagonists |
| JP6822839B2 (ja) | 2013-09-13 | 2021-01-27 | ザ・スクリップス・リサーチ・インスティテュート | 修飾された治療剤、及びその組成物 |
| CA2933701C (en) | 2013-12-18 | 2022-05-31 | The California Institute For Biomedical Research | Modified therapeutic agents, stapled peptide lipid conjugates, and compositions thereof |
| HRP20211448T1 (hr) * | 2014-05-16 | 2021-12-24 | Protagonist Therapeutics, Inc. | Alfa4beta7 integrin tioeter peptidni antagonisti |
| CN113563423A (zh) | 2014-07-17 | 2021-10-29 | 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 |
| AU2015328002A1 (en) * | 2014-10-01 | 2017-04-27 | Protagonist Therapeutics, Inc. | Novel alpha4beta7 peptide monomer and dimer antagonists |
| CN107921098A (zh) * | 2015-06-17 | 2018-04-17 | 加州生物医学研究所 | 修饰的治疗剂及其组合物 |
| US10787490B2 (en) | 2015-07-15 | 2020-09-29 | Protaganist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| WO2017041001A2 (en) | 2015-09-04 | 2017-03-09 | The California Institute For Biomedical Research | Insulin immunoglobulin fusion proteins |
| WO2017069627A1 (en) | 2015-10-23 | 2017-04-27 | Universiteit Twente | Integrin binding peptides and uses thereof |
| EP3377471A4 (en) | 2015-11-11 | 2019-11-20 | Encycle Therapeutics, Inc. | FRAGMENT SYNTHESIS OF CYCLIC PEPTIDES |
| US11161891B2 (en) | 2015-12-09 | 2021-11-02 | The Scripps Research Institute | Relaxin immunoglobulin fusion proteins and methods of use |
| CA3009834A1 (en) | 2015-12-30 | 2017-07-06 | Protagonist Therapeutics, Inc. | Analogues of hepcidin mimetics with improved in vivo half lives |
| EP3411069B1 (en) | 2016-02-04 | 2024-07-10 | The Scripps Research Institute | Humanized anti-cd3 antibodies, conjugates and uses thereof |
| CN109195618A (zh) * | 2016-03-23 | 2019-01-11 | 领导医疗有限公司 | 用于合成α4β7肽拮抗剂的方法 |
| EP3538542B1 (en) | 2016-11-11 | 2021-08-04 | Zealand Pharma A/S | Cyclic peptides multimers targeting alpha 4beta 7 integrin |
| WO2018205008A1 (en) | 2017-05-10 | 2018-11-15 | Encycle Therapeutics, Inc. | HOMODETIC CYCLIC PEPTIDES TARGETING α4β7 1NTEGRIN |
| WO2019051494A1 (en) | 2017-09-11 | 2019-03-14 | Protagonist Therapeutics, Inc. | OPIOID AGONIST PEPTIDES AND USES THEREOF |
| EP3749345A4 (en) | 2018-02-08 | 2022-04-06 | Protagonist Therapeutics, Inc. | CONJUGATED HEPCIDIN MIMETICS |
| CN113631569A (zh) * | 2019-03-28 | 2021-11-09 | 领导医疗有限公司 | 用于合成β-高氨基酸的方法 |
| MX2022000397A (es) | 2019-07-10 | 2022-04-25 | Protagonist Therapeutics Inc | Inhibidores peptídicos del receptor de interleucina-23 y su uso para tratar enfermedades inflamatorias. |
| AU2021205415A1 (en) * | 2020-01-10 | 2022-07-21 | Protagonist Therapeutics, Inc. | Methods for treating inflammatory bowel diseases with α4β7 integrin antagonists |
| EP4613761A2 (en) | 2020-01-15 | 2025-09-10 | Janssen Biotech, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| WO2021146454A1 (en) | 2020-01-15 | 2021-07-22 | Janssen Biotech, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| PE20240631A1 (es) | 2020-11-20 | 2024-03-26 | Janssen Pharmaceutica Nv | Composiciones de inhibidores peptidicos del receptor de interleucina-23 |
| JP2024522196A (ja) | 2021-06-09 | 2024-06-11 | ザ スクリプス リサーチ インスティテュート | 長時間作用型デュアルｇｉｐ／ｇｌｐ－１ペプチドコンジュゲートおよび使用方法 |
| EP4370146A4 (en) | 2021-07-14 | 2025-05-21 | Janssen Biotech, Inc. | Lipidated peptide inhibitors of the interleukin-23 receptor |
Family Cites Families (48)
| 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 |
| DK0578728T3 (da) * | 1991-04-05 | 1999-04-12 | Genentech Inc | Inhibitorer for aggregering af blodplader, hvilke inhibitorer har høj specificitet for GP IIbIIIa |
| 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 |
| AU8399998A (en) * | 1997-07-11 | 1999-02-08 | Innerdyne, 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 |
| US6271252B1 (en) | 1997-11-24 | 2001-08-07 | Merck & Co., Inc. | Cyclic amino acid derivatives as cell adhesion inhibitors |
| WO2000006243A2 (en) * | 1998-07-28 | 2000-02-10 | Innerdyne, Inc. | Absorbable brachytherapy and chemotherapy delivery devices and methods |
| AUPP616598A0 (en) | 1998-09-25 | 1998-10-15 | University Of Queensland, The | Auxiliary for amide bond formation |
| AUPP616498A0 (en) | 1998-09-25 | 1998-10-15 | University Of Queensland, The | Synthesis of cyclic peptides |
| AUPP660698A0 (en) | 1998-10-21 | 1998-11-12 | University Of Queensland, The | A method of protein engineering |
| CN1350534A (zh) | 1999-04-12 | 2002-05-22 | 阿文蒂斯药物有限公司 | 作为整联蛋白拮抗剂的取代双环杂芳基化合物 |
| WO2001068586A2 (en) | 2000-03-14 | 2001-09-20 | Novartis Ag | α4β1 AND α4β7 INTEGRIN 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 |
| AU2003301059A1 (en) | 2002-12-18 | 2004-07-22 | Wyeth | Methods for screening, treating and diagnosing inflammatory bowel disease and compositions thereof |
| WO2004058804A1 (en) | 2002-12-24 | 2004-07-15 | Walter And Eliza Hall Institute Of Medical Research | Peptides and therapeutic uses thereof |
| CA2830063C (en) | 2003-11-05 | 2017-10-31 | Dana-Farber Cancer Institute, Inc. | Stabilized alpha helical peptides and uses thereof |
| EP1695255B1 (en) | 2003-12-19 | 2016-09-07 | Applied Biosystems, LLC | Methods and systems for protein and peptide evidence assembly |
| MX350383B (es) | 2004-01-09 | 2017-09-04 | Pfizer | Anticuerpos contra madcam. |
| US8536140B2 (en) | 2004-03-12 | 2013-09-17 | Mti Meta Tech Inc. | Methods for treating inflammatory bowel disease |
| AU2005256155A1 (en) | 2004-06-24 | 2006-01-05 | The Walter And Eliza Hall Institute Of Medical Research | Conjugates and therapeutic uses thereof |
| WO2006062685A2 (en) | 2004-11-11 | 2006-06-15 | Affymax, Inc. | Novel peptides that bind to the erythropoietin receptor |
| US20080300180A1 (en) | 2004-11-30 | 2008-12-04 | Gastrotech Pharma A/S | Growth Hormone Secretagogue Receptor 1A Ligands |
| CA2655372A1 (en) | 2006-06-13 | 2007-12-21 | Zymogenetics, Inc. | Il-17 and il-23 antagonists and methods of using the same |
| 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 |
| US20080260820A1 (en) | 2007-04-19 | 2008-10-23 | Gilles Borrelly | Oral dosage formulations of protease-resistant polypeptides |
| EP2392597B1 (en) | 2007-04-27 | 2014-04-02 | ZymoGenetics, Inc. | Antagonists to IL-17A, IL-17F, and IL-23P19 and methods of use |
| US20090131317A1 (en) * | 2007-06-22 | 2009-05-21 | Affymax, Inc. | Compounds and peptides that bind the trail receptor |
| US20100190710A1 (en) | 2007-07-06 | 2010-07-29 | Valorisation Hsj, Societe En Commandite | Il-23 receptor antagonists and uses thereof |
| 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 |
| 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 |
| US10416172B2 (en) | 2010-03-31 | 2019-09-17 | Medical Diagnostic Laboratories, Llc | Recombinant soluble truncated IL-23 receptor (IL-23R) capable of inhibiting IL-23R-mediated cell signaling |
| WO2012101599A2 (en) | 2011-01-27 | 2012-08-02 | 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 |
| CA2855122A1 (en) | 2011-12-09 | 2013-06-13 | The Regents Of The University Of California | Modified mini-hepcidin peptides and methods of using thereof |
| US20150157692A1 (en) | 2012-05-23 | 2015-06-11 | The University Of Chicago | Methods of treating obesity |
| US9273093B2 (en) | 2012-10-11 | 2016-03-01 | Protagonist Therapeutics, Inc. | α4β7 peptide dimer antagonists |
| CN105378159A (zh) | 2013-02-15 | 2016-03-02 | Srx心脏有限责任公司 | 调节血清低密度脂蛋白（LDL）水平的前蛋白转化酶枯草杆菌蛋白酶/Kexin 9 型（PCSK9）变构结合配体 |
| 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 |
| DK3013351T3 (da) | 2013-06-24 | 2020-01-27 | Canbas Co Ltd | Peptider og peptidmimetika i kombinationanvendelser og behandlinger til cancerpatient-subpopulationer |
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