EA028665B1 - Соединения - двойные агонисты gip-glp-1 и способы - Google Patents
Соединения - двойные агонисты gip-glp-1 и способы Download PDFInfo
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- EA028665B1 EA028665B1 EA201491918A EA201491918A EA028665B1 EA 028665 B1 EA028665 B1 EA 028665B1 EA 201491918 A EA201491918 A EA 201491918A EA 201491918 A EA201491918 A EA 201491918A EA 028665 B1 EA028665 B1 EA 028665B1
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- C07K14/575—Hormones
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Families Citing this family (83)
| Publication number | Priority date | Publication date | Assignee | Title |
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| AP3329A (en) | 2009-07-13 | 2015-06-30 | Zealand Pharma As | Acylated glucagon analogues |
| NZ702333A (en) | 2012-05-03 | 2017-06-30 | Zealand Pharma As | Gip-glp-1 dual agonist compounds and methods |
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| TWI608013B (zh) | 2012-09-17 | 2017-12-11 | 西蘭製藥公司 | 升糖素類似物 |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| WO2014096179A1 (en) * | 2012-12-19 | 2014-06-26 | Novo Nordisk A/S | Novel glp-1 receptor agonists with cholesterol efflux activity |
| JP2016506401A (ja) | 2012-12-21 | 2016-03-03 | サノフイ | 二重ｇｌｐ１／ｇｉｐまたは三方ｇｌｐ１／ｇｉｐ／グルカゴンアゴニストとしてのエキセンジン−４誘導体 |
| AR096440A1 (es) | 2013-05-28 | 2015-12-30 | Takeda Pharmaceuticals Co | Compuesto peptídico agonista del receptor del péptido similar al glucagón tipo i (glp-1) y del péptido insulinotrópico dependiente de glucosa (gip) |
| LT3057984T (lt) | 2013-10-17 | 2018-12-27 | Zealand Pharma A/S | Acilinti gliukagono analogai |
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| KR102310392B1 (ko) * | 2013-11-06 | 2021-10-13 | 질랜드 파마 에이/에스 | 글루카곤-ｇｌｐ-1-ｇｉｐ 삼원 효능제 화합물 |
| AU2014345569B2 (en) * | 2013-11-06 | 2020-08-13 | Zealand Pharma A/S | GIP-GLP-1 dual agonist compounds and methods |
| CN112043835B (zh) | 2013-12-06 | 2022-10-21 | 韩捷 | 用于含氮和羟基的药物的生物可逆引入基团 |
| RU2716985C2 (ru) | 2014-10-29 | 2020-03-17 | Зилэнд Фарма А/С | Соединения-агонисты gip и способы |
| JO3575B1 (ar) * | 2015-01-09 | 2020-07-05 | Lilly Co Eli | مركبات مساعد مشترك من gip وglp-1 |
| JP6989385B2 (ja) | 2015-04-16 | 2022-01-05 | ジーランド ファーマ アクティーゼルスカブ | アシル化グルカゴン類似体 |
| JP2018529749A (ja) | 2015-10-07 | 2018-10-11 | シプルメット・ゲーエムベーハー | ペプチド薬物を経口送達するための医薬製剤 |
| TWI622596B (zh) | 2015-10-26 | 2018-05-01 | 美國禮來大藥廠 | 升糖素受體促效劑 |
| EP3467106B1 (en) * | 2016-05-24 | 2025-07-09 | Takeda Pharmaceutical Company Limited | Peptide compound |
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| GB201620611D0 (en) | 2016-12-05 | 2017-01-18 | Univ Of Lancaster | Treatment of neurological diseases |
| US11285180B2 (en) | 2016-12-06 | 2022-03-29 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods of enhancing the potency of incretin-based drugs in subjects in need thereof |
| JOP20190211A1 (ar) | 2017-03-31 | 2019-09-15 | Takeda Pharmaceuticals Co | ببتيد منشط لمستقبل gip |
| WO2019140030A1 (en) | 2018-01-12 | 2019-07-18 | Eli Lilly And Company | Combination therapy |
| US10577905B2 (en) | 2018-02-12 | 2020-03-03 | Eagle Technology, Llc | Hydrocarbon resource recovery system and RF antenna assembly with latching inner conductor and related methods |
| WO2019193204A1 (en) | 2018-04-06 | 2019-10-10 | Cyprumed Gmbh | Pharmaceutical compositions for the transmucosal delivery of therapeutic peptides and proteins |
| RU2020136305A (ru) | 2018-05-04 | 2022-05-05 | Ново Нордиск А/С | Производные gip и пути их применения |
| TWI705820B (zh) | 2018-06-22 | 2020-10-01 | 美商美國禮來大藥廠 | Gip/glp1促效劑組合物 |
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| KR20210024583A (ko) | 2018-07-23 | 2021-03-05 | 일라이 릴리 앤드 캄파니 | 요법을 위한 gip/glp1 공효능제 사용 방법 |
| AU2019309798A1 (en) | 2018-07-23 | 2021-02-11 | Eli Lilly And Company | Method of using a GIP/GLP1 co-agonist for diabetes |
| JP2022503793A (ja) * | 2018-09-24 | 2022-01-12 | 武田薬品工業株式会社 | Ｇｉｐ受容体アゴニストペプチド化合物及びその使用 |
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| WO2020207477A1 (zh) * | 2019-04-11 | 2020-10-15 | 江苏豪森药业集团有限公司 | Glp-1和gip受体双重激动剂化合物及其应用 |
| AR119471A1 (es) | 2019-08-01 | 2021-12-22 | Lilly Co Eli | Compuestos agonistas de gipr |
| EP4017866A1 (en) | 2019-08-19 | 2022-06-29 | Eli Lilly and Company | Methods of making incretin analogs |
| WO2021066600A1 (ko) | 2019-10-04 | 2021-04-08 | 한미약품 주식회사 | 글루카곤, 및 glp-1 수용체 및 gip 수용체 이중 작용제를 포함하는 조성물 및 이의 치료학적 용도 |
| CN110684082B (zh) | 2019-10-08 | 2021-12-10 | 江苏诺泰澳赛诺生物制药股份有限公司 | Gip和glp-1双激动多肽化合物及药学上可接受的盐与用途 |
| MX2022005661A (es) | 2019-11-11 | 2022-09-07 | Boehringer Ingelheim Int | Agonistas del receptor npy2. |
| WO2021093883A1 (zh) * | 2019-11-15 | 2021-05-20 | 江苏豪森药业集团有限公司 | 双受体重激动剂化合物及其药物组合物 |
| CN114761420B (zh) * | 2019-12-03 | 2026-04-28 | 安泰博医药 | 优化的gip肽类似物 |
| CN119039417B (zh) * | 2020-01-17 | 2026-03-06 | 联邦生物科技(珠海横琴)有限公司 | 多肽化合物及其应用 |
| IL294955A (en) * | 2020-01-23 | 2022-09-01 | Lilly Co Eli | Cobalt-agonist gip/glp1 compounds |
| TW202140058A (zh) | 2020-01-30 | 2021-11-01 | 美商美國禮來大藥廠 | 提派肽（ｔｉｒｚｅｐａｔｉｄｅ）之治療用途 |
| JP2023519446A (ja) * | 2020-03-25 | 2023-05-10 | 武田薬品工業株式会社 | Ｇｉｐ受容体アゴニストペプチド化合物のｑｄ投薬及びその使用 |
| TW202216746A (zh) * | 2020-06-22 | 2022-05-01 | 印度商太陽製藥工業有限公司 | 長效型ｇｌｐ－１／ｇｉｐ雙重促效劑 |
| CA3184723A1 (en) | 2020-07-22 | 2022-01-27 | Patrick J. KNERR | Glp-1 and gip receptor co-agonists |
| AU2021312323A1 (en) | 2020-07-22 | 2023-02-02 | Novo Nordisk A/S | Co-agonists at GLP-1 and GIP receptors suitable for oral delivery |
| UA130066C2 (uk) | 2020-08-07 | 2025-10-29 | Бьорінгер Інгельхайм Інтернаціональ Гмбх | Розчинні агоністи рецепторів npy2 |
| WO2022049310A1 (en) | 2020-09-07 | 2022-03-10 | Cyprumed Gmbh | Improved pharmaceutical formulations of glp-1 receptor agonists |
| BR112023003668A2 (pt) | 2020-10-17 | 2023-04-25 | Sun Pharmaceutical Ind Ltd | Agonistas duplos de glp-1/gip |
| WO2022117056A1 (zh) * | 2020-12-02 | 2022-06-09 | 南京明德新药研发有限公司 | 含内酰胺修饰的多肽类化合物 |
| CN114617956B (zh) * | 2020-12-10 | 2023-10-03 | 江苏中新医药有限公司 | 一种高效降糖的蛋白质药物 |
| KR20230126712A (ko) * | 2020-12-23 | 2023-08-30 | 제지앙 도어 바이오로직스 코., 엘티디. | 지속형 글루카곤 유도체 |
| WO2022159395A1 (en) | 2021-01-20 | 2022-07-28 | Viking Therapeutics, Inc. | Compositions and methods for the treatment of metabolic and liver disorders |
| KR20240004943A (ko) | 2021-05-07 | 2024-01-11 | 일라이 릴리 앤드 캄파니 | 침식성 정제 |
| CN117015551B (zh) * | 2021-05-28 | 2024-05-28 | 广东众生睿创生物科技有限公司 | 多肽的制备及其应用 |
| EP4345105A4 (en) | 2021-06-01 | 2025-04-23 | Nanjing Zhihe Medicine Technology Co., Ltd | Polypeptide derivative with dual targeted activation of GLP-1R and GIPR, manufacturing process therefor and use thereof |
| CN115850437A (zh) * | 2021-09-02 | 2023-03-28 | 广东东阳光药业有限公司 | Glp-1/gip双靶多肽、融合蛋白及其应用 |
| IL311411A (en) | 2021-09-15 | 2024-05-01 | Viking Therapeutics Inc | Preparations and methods for the treatment of metabolic and liver disorders |
| AU2022386489A1 (en) * | 2021-11-12 | 2024-05-23 | Jiangsu Hengrui Pharmaceuticals Co., Ltd. | Pharmaceutical composition of glp-1 receptor and gip receptor dual agonist, and use thereof |
| TW202330584A (zh) | 2022-01-20 | 2023-08-01 | 丹麥商諾佛 儂迪克股份有限公司 | 前藥及其用途 |
| CN116947978A (zh) * | 2022-04-19 | 2023-10-27 | 北京惠之衡生物科技有限公司 | 一种glp-1和gip受体共激动多肽衍生物及其盐和制剂 |
| IL318349A (en) | 2022-07-13 | 2025-03-01 | Hangzhou Zhongmeihuadong Pharmaceutical Co Ltd | Glp-1/gip dual agonist, preparation method and use thereof |
| CA3261877A1 (en) * | 2022-07-15 | 2024-01-18 | Pep2Tango Therapeutics Inc. | COMPOSITIONS COMPRISING MULTI-AGONIST PEPTIDES, MANUFACTURING PROCESSES AND METHODS OF USE |
| CA3262093A1 (en) * | 2022-07-20 | 2024-01-25 | Viking Therapeutics, Inc. | Pharmaceutical Formulations and Methods for the Treatment of Metabolic and Liver Disorders |
| CA3266547A1 (en) | 2022-08-29 | 2024-03-07 | Eli Lilly And Company | COMPOSITIONS FOR ORAL ADMINISTRATION |
| WO2024059674A1 (en) | 2022-09-15 | 2024-03-21 | Eli Lilly And Company | Gip and glp-1 dual agonist compounds |
| CN118255864A (zh) * | 2022-12-26 | 2024-06-28 | 杭州中美华东制药有限公司 | Gip受体激动剂及其用途 |
| JP2026502943A (ja) | 2022-12-30 | 2026-01-27 | アルギファルマ エーエス | 経口投与されるポリペプチド治療剤の全身バイオアベイラビリティを高める組成物および方法 |
| IL322205A (en) | 2023-01-31 | 2025-09-01 | Lilly Co Eli | GIP/GLP1/GCG trireceptor agonists and their uses |
| WO2024165571A2 (en) | 2023-02-06 | 2024-08-15 | E-Therapeutics Plc | Inhibitors of expression and/or function |
| WO2024209050A1 (en) | 2023-04-05 | 2024-10-10 | Antag Therapeutics Aps | Gip activity modulators and orthostatic intolerance |
| KR20240167410A (ko) | 2023-05-19 | 2024-11-26 | 주식회사 아울바이오 | 티르제파타이드를 포함하는 미립구, 이의 제조방법, 및 이를 포함하는 약학적 조성물 |
| WO2024252366A1 (en) | 2023-06-09 | 2024-12-12 | Sun Pharmaceutical Industries Limited | Glp-1/gip dual, glp-1/gcg dual and glp-1/gip/gcg triple receptor agonists |
| KR20260032481A (ko) | 2023-06-30 | 2026-03-09 | 질랜드 파마 에이/에스 | 병용 요법 |
| CN116693652B (zh) * | 2023-08-02 | 2024-01-05 | 北京惠之衡生物科技有限公司 | 一种glp-1/gip受体双重激动剂衍生物及其制备方法和应用 |
| CN117646017A (zh) * | 2023-11-02 | 2024-03-05 | 中国人民解放军海军军医大学 | Gip/glp-1双激动剂多肽编码基因、及其重组乳酸菌和应用 |
| WO2025114501A1 (en) | 2023-11-30 | 2025-06-05 | Novo Nordisk A/S | Tri-agonists of the glp-1, gip, and amylin receptors |
| WO2025125576A2 (en) | 2023-12-15 | 2025-06-19 | E-Therapeutics Plc | Inhibitors of expression and/or function |
| EP4686757A1 (en) | 2024-07-31 | 2026-02-04 | e-therapeutics PLC | Inhibitors of expression and/or function |
| WO2025133348A1 (en) | 2023-12-22 | 2025-06-26 | E-Therapeutics Plc | Inhibitors of expression and/or function |
| WO2025196502A1 (en) | 2024-03-20 | 2025-09-25 | North Carolina Agricultural & Technical State University | Choline kinase inhibitors as a therapeutic treatment for obesity |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010016940A2 (en) * | 2008-08-07 | 2010-02-11 | Ipsen Pharma S.A.S. | Analogues of glucose-dependent insulinotropic polypeptide |
Family Cites Families (81)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ202757A (en) | 1981-12-23 | 1985-11-08 | Novo Industri As | Peptides and medicaments |
| JP3149958B2 (ja) | 1996-08-30 | 2001-03-26 | ノボ ノルディスク アクティーゼルスカブ | Ｇｌｐ―１誘導体 |
| EP0932614A1 (en) | 1996-09-09 | 1999-08-04 | Zealand Pharmaceuticals A/S | Peptide prodrugs containing an alpha-hydroxyacid linker |
| CZ295838B6 (cs) | 1996-09-09 | 2005-11-16 | Zealand Pharma A/S | Způsob výroby peptidů |
| JP2003522721A (ja) | 1997-11-14 | 2003-07-29 | アミリン・ファーマシューティカルズ，インコーポレイテッド | 新規なエキセンジンアゴニスト化合物 |
| AU757658B2 (en) | 1998-03-09 | 2003-02-27 | Zealand Pharma A/S | Pharmacologically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
| WO2000034331A2 (en) | 1998-12-07 | 2000-06-15 | Societe De Conseils De Recherches Et D'applications Scientifiques Sas | Analogues of glp-1 |
| 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 |
| EP1076066A1 (en) | 1999-07-12 | 2001-02-14 | Zealand Pharmaceuticals A/S | Peptides for lowering blood glucose levels |
| GB0121709D0 (en) | 2001-09-07 | 2001-10-31 | Imp College Innovations Ltd | Food inhibition agent |
| AU2002346491A1 (en) | 2001-12-19 | 2003-07-09 | Eli Lilly And Company | Crystalline compositions for controlling blood glucose |
| CZ2004710A3 (cs) | 2001-12-20 | 2005-02-16 | Eli Lilly And Company | Inzulínová sloučenina s protrahovaným účinkem |
| GB0300571D0 (en) | 2003-01-10 | 2003-02-12 | Imp College Innovations Ltd | Modification of feeding behaviour |
| US20060217290A1 (en) | 2003-04-29 | 2006-09-28 | Kohn Wayne D | Insulin analogs having protracted time action |
| EP2494983B1 (en) | 2004-11-12 | 2019-04-24 | Novo Nordisk A/S | Stable formulations of glp-1 |
| CN101155828A (zh) * | 2005-02-11 | 2008-04-02 | 安米林药品公司 | Gip类似物和具有可选择性质的杂合多肽 |
| TWI372629B (en) | 2005-03-18 | 2012-09-21 | Novo Nordisk As | Acylated glp-1 compounds |
| JP2008539735A (ja) * | 2005-05-06 | 2008-11-20 | バイエル・フアーマシユーチカルズ・コーポレーシヨン | グルカゴン様ペプチド１（ｇｌｐ−１）受容体アンタゴニストおよびそれらの薬理学的使用方法 |
| CA2612063A1 (en) | 2005-06-13 | 2006-12-21 | Imperial Innovations Limited | Oxyntomodulin analogues and their effects on feeding behaviour |
| US20090202497A1 (en) | 2005-08-23 | 2009-08-13 | The General Hospital Corporation | Use of glp-1, glp-1 derivatives or glp-1 fragments for skin regeneration, stimulation of hair growth, or treatment of diabetes |
| CA2628241C (en) | 2005-11-07 | 2016-02-02 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting physiological solubility and stability |
| WO2007081824A2 (en) | 2006-01-06 | 2007-07-19 | Case Western Reserve University | Fibrillation resistant proteins |
| EP2471810A1 (en) | 2006-02-22 | 2012-07-04 | Merck Sharp & Dohme Corporation | Oxyntomodulin derivatives |
| EP2004238A2 (en) * | 2006-03-21 | 2008-12-24 | Amylin Pharmaceuticals, Inc. | Peptide-peptidase inhibitor conjugates and methods of using same |
| EA020324B1 (ru) | 2006-07-18 | 2014-10-30 | Санофи-Авентис | АНТИТЕЛА К РЕЦЕПТОРУ ЭФРИНА EphA2 И ИХ ПРИМЕНЕНИЕ |
| ITMI20061607A1 (it) | 2006-08-09 | 2008-02-10 | Maria Vincenza Carriero | Peptidi con attivita farmacologica |
| EP2057189B1 (en) * | 2006-08-25 | 2013-03-06 | Novo Nordisk A/S | Acylated exendin-4 compounds |
| WO2008043033A2 (en) | 2006-10-04 | 2008-04-10 | Case Western Reserve University | Fibrillation-resistant insulin and insulin analogues |
| TWI428346B (zh) | 2006-12-13 | 2014-03-01 | Imp Innovations Ltd | 新穎化合物及其等對進食行為影響 |
| MX2009008241A (es) | 2007-02-15 | 2009-10-08 | Univ Indiana Res & Tech Corp | Co-agonistas de receptor de glucagon/glp-1. |
| EP2025684A1 (en) | 2007-08-15 | 2009-02-18 | Zealand Pharma A/S | Glucagon analogues |
| JP5385266B2 (ja) | 2007-06-15 | 2014-01-08 | ジーランド ファーマ アクティーゼルスカブ | グルカゴン類似体 |
| ES2632504T3 (es) | 2007-11-20 | 2017-09-13 | Ambrx, Inc. | Polipéptidos de insulina modificados y sus usos |
| DE102008003568A1 (de) | 2008-01-09 | 2009-07-16 | Sanofi-Aventis Deutschland Gmbh | Neue Insulinderivate mit extrem verzögertem Zeit-/ Wirkungsprofil |
| BRPI0907119A2 (pt) | 2008-01-09 | 2015-07-14 | Sanofi Aventis Deutschland | Derivados de insulina tendo um perfil de ação de tempo extremamente retardado |
| DE102008003566A1 (de) | 2008-01-09 | 2009-07-16 | Sanofi-Aventis Deutschland Gmbh | Neue Insulinderivate mit extrem verzögertem Zeit-/ Wirkungsprofil |
| AU2009203809B2 (en) | 2008-01-09 | 2013-07-25 | Sanofi-Aventis Deutschland Gmbh | Novel insulin derivatives having an extremely delayed time-action profile |
| US8993516B2 (en) | 2008-04-14 | 2015-03-31 | Case Western Reserve University | Meal-time insulin analogues of enhanced stability |
| WO2009132129A2 (en) | 2008-04-22 | 2009-10-29 | Case Western Reserve University | Isoform-specific insulin analogues |
| TWI451876B (zh) | 2008-06-13 | 2014-09-11 | Lilly Co Eli | 聚乙二醇化之離脯胰島素化合物 |
| TWI541023B (zh) | 2008-06-17 | 2016-07-11 | 印第安納大學科技研究公司 | 在生理ｐｈ緩衝液中呈現增強之溶解度及穩定性之升糖激素類似物 |
| TWI474835B (zh) * | 2008-06-17 | 2015-03-01 | Univ Indiana Res & Tech Corp | 用於治療代謝病症及肥胖症之基於ｇｉｐ之混合激動劑 |
| EP2300037B1 (en) | 2008-06-17 | 2016-03-30 | Indiana University Research and Technology Corporation | Glucagon/glp-1 receptor co-agonists |
| PL219335B1 (pl) | 2008-07-04 | 2015-04-30 | Inst Biotechnologii I Antybiotyków | Pochodna insuliny lub jej farmaceutycznie dopuszczalna sól, jej zastosowanie oraz zawierająca ją kompozycja farmaceutyczna |
| ES2552636T3 (es) | 2008-07-31 | 2015-12-01 | Case Western Reserve University | Insulina estabilizada por halógenos |
| JP5591243B2 (ja) | 2008-09-12 | 2014-09-17 | ノボ・ノルデイスク・エー／エス | ペプチド又はタンパク質のアシル化の方法 |
| MX2011006314A (es) | 2008-12-15 | 2011-09-22 | Zealand Pharma As | Analogos de glucagon. |
| AU2008365557A1 (en) | 2008-12-15 | 2011-07-21 | Zealand Pharma A/S | Glucagon analogues |
| EA020537B1 (ru) | 2008-12-15 | 2014-11-28 | Зилэнд Фарма А/С | Аналоги глюкагона |
| PL2370462T3 (pl) | 2008-12-15 | 2015-01-30 | Zealand Pharma As | Analogi glukagonu |
| CN102245624B (zh) | 2008-12-19 | 2016-08-10 | 印第安纳大学研究及科技有限公司 | 基于酰胺的胰岛素前药 |
| 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 |
| WO2010107487A2 (en) | 2009-03-18 | 2010-09-23 | Wu Nian | Lipid-drug conjugates for drug delivery |
| CN101519446A (zh) | 2009-03-31 | 2009-09-02 | 上海一就生物医药有限公司 | 一种重组人胰岛素及其类似物的制备方法 |
| WO2010148089A1 (en) | 2009-06-16 | 2010-12-23 | Indiana University Research And Technology Corporation | Gip receptor-active glucagon compounds |
| AP3329A (en) | 2009-07-13 | 2015-06-30 | Zealand Pharma As | Acylated glucagon analogues |
| CA2784757A1 (en) | 2009-12-16 | 2011-07-07 | Novo Nordisk A/S | Double-acylated glp-1 derivatives |
| EA026384B1 (ru) | 2010-01-20 | 2017-04-28 | Зилэнд Фарма А/С | Лечение заболеваний сердца |
| EP2528618A4 (en) | 2010-01-27 | 2015-05-27 | Univ Indiana Res & Tech Corp | GLUCAGON ANTAGONISTE AND GIP AGONISTS CONJUGATES AND COMPOSITIONS FOR THE TREATMENT OF METABOLISM DISEASES AND ADIPOSITAS |
| JP2013523620A (ja) | 2010-03-26 | 2013-06-17 | ノヴォ ノルディスク アー／エス | 新規のグルカゴンアナログ |
| AR080592A1 (es) | 2010-03-26 | 2012-04-18 | Lilly Co Eli | Peptido con actividad para el gip-r y glp-1-r, formulacion famaceutica que lo comprende, su uso para preparar un medicamento util para el tratamiento de diabetes mellitus y para inducir la perdida de peso |
| CN102186881B (zh) | 2010-04-27 | 2015-04-08 | 贝达药业股份有限公司 | 胰高血糖素样肽-1衍生物及其应用 |
| UY33462A (es) | 2010-06-23 | 2012-01-31 | Zealand Pharma As | Analogos de glucagon |
| KR20130086343A (ko) | 2010-06-24 | 2013-08-01 | 질랜드 파마 에이/에스 | 글루카곤 유사체 |
| US9708383B2 (en) | 2010-11-09 | 2017-07-18 | Novo Nordisk A/S | Double-acylated GLP-1 derivatives |
| SG192038A1 (en) | 2011-01-20 | 2013-08-30 | Zealand Pharma As | Combination of acylated glucagon analogues with insulin analogues |
| RU2013145013A (ru) | 2011-03-28 | 2015-05-10 | Ново Нордиск А/С | Новые аналоги глюкагона |
| DK2696687T3 (en) | 2011-04-12 | 2017-02-06 | Novo Nordisk As | Double-acylated GLP-1 derivatives |
| WO2012150503A2 (en) | 2011-05-03 | 2012-11-08 | Zealand Pharma A/S | Glu-glp-1 dual agonist signaling-selective compounds |
| US9453062B2 (en) * | 2011-06-10 | 2016-09-27 | Beijing Hanmi Pharmaceutical Co., Ltd. | Glucose dependent insulinotropic polypeptide analogs, pharmaceutical compositions and use thereof |
| MY167234A (en) | 2011-09-23 | 2018-08-14 | Novo Nordisk As | Novel glucagon analogues |
| KR20140114845A (ko) | 2011-12-23 | 2014-09-29 | 질랜드 파마 에이/에스 | 글루카곤 유사체 |
| NZ702333A (en) | 2012-05-03 | 2017-06-30 | Zealand Pharma As | Gip-glp-1 dual agonist compounds and methods |
| MX356957B (es) | 2012-07-23 | 2018-06-20 | Zealand Pharma As | Analogos del glucagon. |
| TWI608013B (zh) | 2012-09-17 | 2017-12-11 | 西蘭製藥公司 | 升糖素類似物 |
| LT3057984T (lt) | 2013-10-17 | 2018-12-27 | Zealand Pharma A/S | Acilinti gliukagono analogai |
| US9988429B2 (en) | 2013-10-17 | 2018-06-05 | Zealand Pharma A/S | Glucagon analogues |
| AU2014345569B2 (en) | 2013-11-06 | 2020-08-13 | Zealand Pharma A/S | GIP-GLP-1 dual agonist compounds and methods |
| CA2939763A1 (en) | 2014-02-18 | 2015-08-27 | Novo Nordisk A/S | Stable glucagon analogues and use for treatment of hypoglycaemia |
| JP6989385B2 (ja) | 2015-04-16 | 2022-01-05 | ジーランド ファーマ アクティーゼルスカブ | アシル化グルカゴン類似体 |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010016940A2 (en) * | 2008-08-07 | 2010-02-11 | Ipsen Pharma S.A.S. | Analogues of glucose-dependent insulinotropic polypeptide |
Non-Patent Citations (6)
| Title |
|---|
| ALPESHKUMAR K. MALDE, SUDHA S. SRIVASTAVA, EVANS C. COUTINHO: "Understanding interactions of gastric inhibitory polypeptide (GIP) with its G-protein coupled receptor through NMR and molecular modeling", JOURNAL OF PEPTIDE SCIENCE, JOHN WILEY & SONS, vol. 13, no. 5, 1 May 2007 (2007-05-01), pages 287 - 300, XP055077705, ISSN: 10752617, DOI: 10.1002/psc.839 * |
| GREEN B D, ET AL.: "STRUCTURALLY MODIFIED ANALOGUES OF GLUCAGON-LIKE PEPTIDE-1 (GLP-1) AND GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE (GIP) AS FUTURE ANTIDIABETIC AGENTS", CURRENT PHARMACEUTICAL DESIGN, BENTHAM SCIENCE PUBLISHERS, NL, vol. 10, no. 29, 1 January 2004 (2004-01-01), NL, pages 3651 - 3662, XP009068381, ISSN: 1381-6128, DOI: 10.2174/1381612043382774 * |
| IRWIN NIGEL ET AL: "Antidiabetic potential of two novel fatty acid derivatised, N-terminally modified analogues of glucose-dependent insulinotropic polypeptide (GIP): N-AcGIP(LysPAL(16)) and N-AcGIP(LysPAL(37))", BIOLOGICAL CHEMISTRY, WALTER DE GRUYTER GMBH & CO., BERLIN, DE, vol. 386, no. 7, 1 July 2005 (2005-07-01), BERLIN, DE, pages 679 - 687, XP002428433, ISSN: 1431-6730, DOI: 10.1515/BC.2005.079 * |
| RUNGE STEFFEN; SCHIMMER SUSANN; OSCHMANN JAN; SCHIODT CHRISTINE BRUUN; KNUDSEN SANNE M¦LLER; JEPPESEN CLAUS BEKKER; MADSEN KJELD; : "Differential structural properties of GLP-1 and exendin-4 determine their relative affinity for the GLP-1 receptor N-terminal extracellular domain", BIOCHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 46, no. 19, 15 May 2007 (2007-05-15), US, pages 5830 - 5840, XP009095139, ISSN: 0006-2960, DOI: 10.1021/bi062309m * |
| SUSANNE MANHART, SIMON A. HINKE, CHRISTOPHER H. S. MCINTOSH, RAYMOND A. PEDERSON, HANS-ULRICH DEMUTH: "Structure-function analysis of a series of novel GIP analogues containing different helical length linkers.", BIOCHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 42, no. 10, 18 March 2003 (2003-03-18), US, pages 3081 - 3088, XP002661510, ISSN: 0006-2960, DOI: 10.1021/BI026868E * |
| VICTOR A. GAULT, BARRY D. KERR, PATRICK HARRIOTT, PETER R. FLATT: "Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity", CLINICAL SCIENCE, MEDICAL RESEARCH SOCIETY., vol. 84, no. 3, 1 August 2011 (2011-08-01), pages 331 - 117, XP055077821, ISSN: 01435221, DOI: 10.1042/CS20110006 * |
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| AU2013255751B2 (en) | 2017-10-05 |
| HK1208232A1 (en) | 2016-02-26 |
| IN2014MN02304A (online.php) | 2015-08-07 |
| SG11201407137PA (en) | 2014-11-27 |
| MX2014013318A (es) | 2015-09-28 |
| JP2015517459A (ja) | 2015-06-22 |
| EP2844669B1 (en) | 2018-08-01 |
| IL235463A0 (en) | 2014-12-31 |
| US20190135886A1 (en) | 2019-05-09 |
| US10100097B2 (en) | 2018-10-16 |
| JP6228187B2 (ja) | 2017-11-08 |
| BR112014027348B1 (pt) | 2022-12-20 |
| TW201348252A (zh) | 2013-12-01 |
| EP2844669A1 (en) | 2015-03-11 |
| CN104470948A (zh) | 2015-03-25 |
| CN104470948B (zh) | 2018-06-15 |
| WO2013164483A1 (en) | 2013-11-07 |
| KR20150003910A (ko) | 2015-01-09 |
| TWI689515B (zh) | 2020-04-01 |
| US20150299281A1 (en) | 2015-10-22 |
| EA201491918A1 (ru) | 2015-07-30 |
| BR112014027348A2 (pt) | 2017-06-27 |
| AU2013255751A1 (en) | 2014-12-18 |
| CA2872314C (en) | 2021-08-31 |
| PH12014502452A1 (en) | 2015-02-02 |
| TR201815338T4 (tr) | 2018-11-21 |
| NZ702333A (en) | 2017-06-30 |
| CA2872314A1 (en) | 2013-11-07 |
| KR102184241B1 (ko) | 2020-12-01 |
| MX356641B (es) | 2018-06-07 |
| AR090937A1 (es) | 2014-12-17 |
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