JP5399244B2 - 選択可能な特性を持つdpp−iv耐性gipハイブリッドポリペプチド - Google Patents
選択可能な特性を持つdpp−iv耐性gipハイブリッドポリペプチド Download PDFInfo
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- JP5399244B2 JP5399244B2 JP2009524707A JP2009524707A JP5399244B2 JP 5399244 B2 JP5399244 B2 JP 5399244B2 JP 2009524707 A JP2009524707 A JP 2009524707A JP 2009524707 A JP2009524707 A JP 2009524707A JP 5399244 B2 JP5399244 B2 JP 5399244B2
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Classifications
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- Health & Medical Sciences (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US50708106A | 2006-08-17 | 2006-08-17 | |
| US11/507,081 | 2006-08-17 | ||
| PCT/US2007/018415 WO2008021560A2 (en) | 2006-08-17 | 2007-08-17 | Dpp-iv resistant gip hybrid polypeptides with selectable properties |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| JP2013220531A Division JP2014058528A (ja) | 2006-08-17 | 2013-10-23 | 選択可能な特性を持つdpp−iv耐性gipハイブリッドポリペプチド |
Publications (3)
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| JP2010500996A JP2010500996A (ja) | 2010-01-14 |
| JP2010500996A5 JP2010500996A5 (https=) | 2011-07-21 |
| JP5399244B2 true JP5399244B2 (ja) | 2014-01-29 |
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| JP2009524707A Expired - Fee Related JP5399244B2 (ja) | 2006-08-17 | 2007-08-17 | 選択可能な特性を持つdpp−iv耐性gipハイブリッドポリペプチド |
| JP2013220531A Pending JP2014058528A (ja) | 2006-08-17 | 2013-10-23 | 選択可能な特性を持つdpp−iv耐性gipハイブリッドポリペプチド |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
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| JP2013220531A Pending JP2014058528A (ja) | 2006-08-17 | 2013-10-23 | 選択可能な特性を持つdpp−iv耐性gipハイブリッドポリペプチド |
Country Status (5)
| Country | Link |
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| EP (1) | EP2057188B1 (https=) |
| JP (2) | JP5399244B2 (https=) |
| AU (1) | AU2007284365A1 (https=) |
| CA (1) | CA2660835A1 (https=) |
| WO (1) | WO2008021560A2 (https=) |
Families Citing this family (86)
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| KR20070115947A (ko) | 2005-02-11 | 2007-12-06 | 아밀린 파마슈티칼스, 인크. | 선택가능한 특성들을 가지는 gip 유사체 및 하이브리드폴리펩타이드 |
| US8263545B2 (en) | 2005-02-11 | 2012-09-11 | Amylin Pharmaceuticals, Inc. | GIP analog and hybrid polypeptides with selectable properties |
| CA2913805A1 (en) | 2005-11-07 | 2007-05-18 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting physiological solubility and stability |
| CA2677932A1 (en) | 2007-02-15 | 2008-08-21 | Indiana University Research And Technology Corporation | Glucagon/glp-1 receptor co-agonists |
| AP2009005091A0 (en) | 2007-07-06 | 2009-12-31 | Theratechnologies Inc | Bifunctional fusion proteins of the alpha-melanocyte stimulating hormone (ALPHA-MSH) and atrial natriuretic protein (ANP) and uses in hypertension andacute kidney injury |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| MX2010004298A (es) | 2007-10-30 | 2010-05-03 | Univ Indiana Res & Tech Corp | Compuestos que exhiben actividad antagonista de glucagon y agonista de glp-1. |
| ES2509883T3 (es) | 2007-10-30 | 2014-10-20 | Indiana University Research And Technology Corporation | Antagonistas de glucagón |
| EP2249853A4 (en) | 2008-01-30 | 2012-12-26 | Univ Indiana Res & Tech Corp | ESTER BASED PEPTIDE PRODRUGS |
| CN102105159B (zh) * | 2008-06-17 | 2015-07-08 | 印第安纳大学研究及科技有限公司 | 基于gip的混合激动剂用于治疗代谢紊乱和肥胖症 |
| WO2010016940A2 (en) * | 2008-08-07 | 2010-02-11 | Ipsen Pharma S.A.S. | Analogues of glucose-dependent insulinotropic polypeptide |
| KR20110043687A (ko) * | 2008-08-07 | 2011-04-27 | 입센 파마 에스.에이.에스 | 포도당 의존적인 인슐린 분비 자극성 폴리펩타이드의 절단형 유사체 |
| AU2009280021B2 (en) * | 2008-08-07 | 2012-10-04 | Ipsen Pharma S.A.S. | Analogues of glucose-dependent insulinotropic polypeptide (GIP) modified at N-terminal |
| ES2574835T3 (es) * | 2008-08-07 | 2016-06-22 | Ipsen Pharma S.A.S. | Análogos del polipéptido insulinotrópico dependiente de glucosa |
| RS59913B1 (sr) | 2008-10-17 | 2020-03-31 | Sanofi Aventis Deutschland | Kombinacija insulina i glp-1-agonista |
| JP5789515B2 (ja) | 2008-12-19 | 2015-10-07 | 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 | インスリン類似体 |
| PE20120332A1 (es) * | 2008-12-19 | 2012-04-14 | Univ Indiana Res & Tech Corp | Profarmacos de peptido de la superfamilia de glucagon basado en amida |
| AU2009335715B2 (en) | 2008-12-19 | 2016-09-15 | Indiana University Research And Technology Corporation | Amide-based insulin prodrugs |
| EP2443146B1 (en) | 2009-06-16 | 2016-10-05 | Indiana University Research And Technology Corporation | Gip receptor-active glucagon compounds |
| MY180661A (en) | 2009-11-13 | 2020-12-04 | Sanofi Aventis Deutschland | Pharmaceutical composition comprising a glp-1 agonist, an insulin and methionine |
| PT3345593T (pt) | 2009-11-13 | 2023-11-27 | Sanofi Aventis Deutschland | Composição farmacêutica compreendendo despro36exendina- 4(1-39)-lys6-nh2 e metionina |
| KR20120123443A (ko) | 2010-01-27 | 2012-11-08 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 대사 장애 및 비만 치료용 글루카곤 길항제-gip 항진제 콘쥬게이트 |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| DE102010015123A1 (de) | 2010-04-16 | 2011-10-20 | Sanofi-Aventis Deutschland Gmbh | Benzylamidische Diphenylazetidinone, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
| JP6050746B2 (ja) | 2010-05-13 | 2016-12-21 | 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 | Gタンパク質共役受容体活性を示すグルカゴンスーパーファミリーのペプチド |
| MX2012013001A (es) | 2010-05-13 | 2013-02-26 | Univ Indiana Res & Tech Corp | Peptidos de la superfamilia de glucagon que presentan actividad del receptor nuclear de hormonas. |
| JP5969469B2 (ja) | 2010-06-16 | 2016-08-17 | 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 | インスリン受容体に対して高い活性を示す単鎖インスリンアゴニスト |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| EP2585102B1 (en) | 2010-06-24 | 2015-05-06 | Indiana University Research and Technology Corporation | Amide-based insulin prodrugs |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| PL2611458T3 (pl) | 2010-08-30 | 2017-02-28 | Sanofi-Aventis Deutschland Gmbh | Zastosowanie AVE0010 do produkcji leku do leczenia cukrzycy typu 2 |
| US9023986B2 (en) | 2010-10-25 | 2015-05-05 | Hoffmann-La Roche Inc. | Glucose-dependent insulinotropic peptide analogs |
| US8507428B2 (en) | 2010-12-22 | 2013-08-13 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting GIP receptor activity |
| US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin |
| PT2707017E (pt) * | 2011-05-13 | 2016-01-12 | Sanofi Aventis Deutschland | Lixisenatida e metformina para tratamento da diabetes tipo 2 |
| RS56173B1 (sr) | 2011-06-22 | 2017-11-30 | Univ Indiana Res & Tech Corp | Koagonisti receptora za glukagon/glp-1 receptora |
| KR20140043793A (ko) | 2011-06-22 | 2014-04-10 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 글루카곤/glp-1 수용체 공동-작용물질 |
| TWI559929B (en) | 2011-09-01 | 2016-12-01 | Sanofi Aventis Deutschland | Pharmaceutical composition for use in the treatment of a neurodegenerative disease |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| JP6324315B2 (ja) | 2011-11-17 | 2018-05-16 | 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 | グルココルチコイド受容体の活性を示すグルカゴンスーパーファミリーのペプチド |
| BR112014015156A2 (pt) | 2011-12-20 | 2020-10-27 | Indiana University Research And Technology Corporation | análogos de insulina à base de ctp, seus métodos de produção e uso no tratamento de hiperglicemia, bem como sequência de ácido nucleico e célula hospedeira |
| CN104583232B (zh) | 2012-06-21 | 2018-04-13 | 印第安纳大学研究及科技有限公司 | 展现gip受体活性的胰高血糖素类似物 |
| EP3395358B1 (en) | 2012-09-26 | 2019-11-06 | Indiana University Research and Technology Corporation | Insulin analog dimers |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| WO2014064811A1 (ja) * | 2012-10-25 | 2014-05-01 | 国立大学法人 東京医科歯科大学 | 肺高血圧症治療剤 |
| AU2013366692B2 (en) | 2012-12-21 | 2017-11-23 | Sanofi | Dual GLP1/GIP or trigonal GLP1/GIP/Glucagon agonists |
| JP6538645B2 (ja) | 2013-03-14 | 2019-07-03 | 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 | インスリン‐インクレチン複合物 |
| SI3004155T1 (sl) | 2013-05-28 | 2022-02-28 | Takeda Pharmaceutical Company Limited | Peptidna spojina |
| EP3080154B1 (en) | 2013-12-13 | 2018-02-07 | Sanofi | Dual glp-1/gip receptor agonists |
| WO2015086728A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
| EP3080152A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Non-acylated exendin-4 peptide analogues |
| WO2015086733A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
| WO2015095719A1 (en) * | 2013-12-20 | 2015-06-25 | The Regents Of The University Of California | Anti-obesity compounds derived from neuromedin u |
| TW201625670A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自exendin-4之雙重glp-1/升糖素受體促效劑 |
| TW201625668A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 作為胜肽性雙重glp-1/昇糖素受體激動劑之艾塞那肽-4衍生物 |
| TW201625669A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自艾塞那肽-4(Exendin-4)之肽類雙重GLP-1/升糖素受體促效劑 |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| CN108271356A (zh) | 2014-09-24 | 2018-07-10 | 印第安纳大学研究及科技有限公司 | 肠降血糖素-胰岛素缀合物 |
| JP6701208B2 (ja) | 2014-09-24 | 2020-05-27 | インディアナ ユニヴァーシティ リサーチ アンド テクノロジー コーポレイション | 脂質化アミド系インスリンプロドラッグ |
| EP3229828B1 (en) | 2014-12-12 | 2023-04-05 | Sanofi-Aventis Deutschland GmbH | Insulin glargine/lixisenatide fixed ratio formulation |
| TWI748945B (zh) | 2015-03-13 | 2021-12-11 | 德商賽諾菲阿凡提斯德意志有限公司 | 第2型糖尿病病患治療 |
| TW201705975A (zh) | 2015-03-18 | 2017-02-16 | 賽諾菲阿凡提斯德意志有限公司 | 第2型糖尿病病患之治療 |
| AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
| TW201706291A (zh) | 2015-07-10 | 2017-02-16 | 賽諾菲公司 | 作為選擇性肽雙重glp-1/升糖素受體促效劑之新毒蜥外泌肽(exendin-4)衍生物 |
| UA127495C2 (uk) | 2015-12-23 | 2023-09-13 | Амджен Інк. | Виділений антигензв'язуючий білок, який специфічно зв'язується з поліпептидом рецептора шлункового інгібіторного пептиду (gipr) людини, та фармацевтична композиція, яка його містить |
| JP6995042B2 (ja) | 2016-05-24 | 2022-02-04 | 武田薬品工業株式会社 | ペプチド化合物 |
| IL313587A (en) | 2017-01-17 | 2024-08-01 | Amgen Inc | Method of treating or ameliorating metabolic disorders using glp-1 receptor agonists conjugated to antagonists for gastric inhibitory peptide receptor (gipr) |
| JOP20190211A1 (ar) | 2017-03-31 | 2019-09-15 | Takeda Pharmaceuticals Co | ببتيد منشط لمستقبل gip |
| KR102743887B1 (ko) * | 2017-05-31 | 2024-12-19 | 유니버시티 오브 코펜하겐 | 장기-작용성 gip 펩타이드 유사체 |
| EA201992502A1 (ru) | 2017-06-20 | 2020-04-22 | Эмджен Инк. | Способ лечения или уменьшения интенсивности метаболических нарушений с применением белков, связывающих рецептор гастроингибиторного пептида (gipr), в комбинации с агонистами glp-1 |
| EP3642238A1 (en) | 2017-06-21 | 2020-04-29 | Amgen Inc. | Method of treating or ameliorating metabolic disorders using antagonistic binding proteins for gastric inhibitory peptide receptor (gipr)/glp-1 receptor agonist fusion proteins |
| MX2020009950A (es) * | 2018-03-23 | 2021-04-28 | Carmot Therapeutics Inc | Moduladores de receptores acoplados a proteina g. |
| TWI847981B (zh) * | 2018-04-25 | 2024-07-11 | 比利時商健生藥品公司 | 類升糖素肽1 (glp-1)融合肽偶合環狀酪酪肽接合物及其用途 |
| US11780900B2 (en) | 2018-04-25 | 2023-10-10 | Janssen Sciences Ireland Unlimited Company | Glucagon like peptide 1 (GLP-1) fusion peptide coupled cyclic peptide tyrosine tyrosine conjugates and uses thereof |
| CN110151973A (zh) * | 2019-04-25 | 2019-08-23 | 上海交通大学医学院附属瑞金医院 | 一种生物活性多肽pacap的应用 |
| US20250346647A2 (en) * | 2019-12-03 | 2025-11-13 | Antag Therapeutics Aps | Optimized GIP Peptide Analogues |
| CN115916812A (zh) * | 2020-03-25 | 2023-04-04 | 武田药品工业株式会社 | Gip受体激动剂肽化合物及其用途 |
| KR20220092446A (ko) * | 2020-12-24 | 2022-07-01 | 한미약품 주식회사 | 단장증후군의 예방 또는 치료를 위한 인슐린 분비 펩타이드 및 glp-2의 병용 요법 |
| US12281149B2 (en) | 2021-05-13 | 2025-04-22 | Carmot Therapeutics, Inc. | Modulators of G-protein coupled receptors |
| EP4687947A1 (en) * | 2023-04-05 | 2026-02-11 | Antag Therapeutics ApS | Gip activity modulators and orthostatic intolerance |
| CN121177454A (zh) * | 2025-09-05 | 2025-12-23 | 南通大学 | Gip受体激动剂在促进毛发再生中的应用 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0404124D0 (en) * | 2004-02-25 | 2004-03-31 | Univ Ulster | Antagonists of GIP |
| NZ579621A (en) * | 2004-02-11 | 2011-03-31 | Amylin Pharmaceuticals Inc | Hybrid polypeptides with selectable properties |
| WO2007022123A2 (en) * | 2005-08-11 | 2007-02-22 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides with selectable properties |
| KR20070115947A (ko) * | 2005-02-11 | 2007-12-06 | 아밀린 파마슈티칼스, 인크. | 선택가능한 특성들을 가지는 gip 유사체 및 하이브리드폴리펩타이드 |
-
2007
- 2007-08-17 WO PCT/US2007/018415 patent/WO2008021560A2/en not_active Ceased
- 2007-08-17 EP EP07837095.4A patent/EP2057188B1/en not_active Not-in-force
- 2007-08-17 AU AU2007284365A patent/AU2007284365A1/en not_active Abandoned
- 2007-08-17 CA CA002660835A patent/CA2660835A1/en not_active Abandoned
- 2007-08-17 JP JP2009524707A patent/JP5399244B2/ja not_active Expired - Fee Related
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2013
- 2013-10-23 JP JP2013220531A patent/JP2014058528A/ja active Pending
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|---|---|
| JP2014058528A (ja) | 2014-04-03 |
| JP2010500996A (ja) | 2010-01-14 |
| WO2008021560A3 (en) | 2008-07-10 |
| WO2008021560A2 (en) | 2008-02-21 |
| EP2057188A2 (en) | 2009-05-13 |
| AU2007284365A1 (en) | 2008-02-21 |
| AU2007284365A2 (en) | 2009-07-16 |
| EP2057188B1 (en) | 2013-07-31 |
| CA2660835A1 (en) | 2008-02-21 |
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