BR112014027348B1 - Compostos agonistas duplos gip-glp-1 e métodos - Google Patents
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| AP3329A (en) | 2009-07-13 | 2015-06-30 | Zealand Pharma As | Acylated glucagon analogues |
| JP6228187B2 (ja) | 2012-05-03 | 2017-11-08 | ジーランド ファーマ アクティーゼルスカブ | Ｇｉｐ−ｇｌｐ−１デュアルアゴニスト化合物及び方法 |
| AU2013295035B2 (en) | 2012-07-23 | 2017-08-03 | Zealand Pharma A/S | Glucagon analogues |
| 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 |
| JP2016503046A (ja) * | 2012-12-19 | 2016-02-01 | ノヴォ ノルディスク アー／エス | コレステロール流出活性を有する新規ｇｌｐ−１受容体アゴニスト |
| HK1211232A1 (en) | 2012-12-21 | 2016-05-20 | Sanofi | Exendin-4 derivatives as dual glp1/gip or trigonal glp1/gip/glucagon agonists |
| LT3004155T (lt) | 2013-05-28 | 2021-12-27 | Takeda Pharmaceutical Company Limited | Peptidų junginys |
| US9988429B2 (en) | 2013-10-17 | 2018-06-05 | Zealand Pharma A/S | Glucagon analogues |
| WO2015055801A1 (en) | 2013-10-17 | 2015-04-23 | Zealand Pharma A/S | Acylated glucagon analogues |
| AU2014345570B2 (en) | 2013-11-06 | 2019-01-24 | Zealand Pharma A/S | Glucagon-GLP-1-GIP triple agonist compounds |
| MX2016005556A (es) * | 2013-11-06 | 2016-07-15 | Zealand Pharma As | Compuestos agonistas duales de gip-glp-1 y procedimientos. |
| 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 |
| US10253078B2 (en) | 2014-10-29 | 2019-04-09 | Zealand Pharma A/S | GIP agonist compounds and methods |
| JO3575B1 (ar) * | 2015-01-09 | 2020-07-05 | Lilly Co Eli | مركبات مساعد مشترك من gip وglp-1 |
| US10336802B2 (en) | 2015-04-16 | 2019-07-02 | Zealand Pharma A/S | Acylated glucagon analogue |
| EP3359181A1 (en) | 2015-10-07 | 2018-08-15 | Cyprumed GmbH | Pharmaceutical formulations for the oral delivery of peptide drugs |
| TWI622596B (zh) | 2015-10-26 | 2018-05-01 | 美國禮來大藥廠 | 升糖素受體促效劑 |
| WO2017204219A1 (ja) * | 2016-05-24 | 2017-11-30 | 武田薬品工業株式会社 | ペプチド化合物 |
| WO2018065634A1 (en) | 2016-10-07 | 2018-04-12 | Cyprumed Gmbh | Pharmaceutical compositions for the nasal delivery of peptide or protein drugs |
| 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 |
| EP3773475A1 (en) | 2018-04-06 | 2021-02-17 | Cyprumed GmbH | Pharmaceutical compositions for the transmucosal delivery of therapeutic peptides and proteins |
| KR102379958B1 (ko) * | 2018-05-04 | 2022-04-01 | 노보 노르디스크 에이/에스 | Gip 유도체 및 이의 용도 |
| 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 |
| CN120754229A (zh) | 2018-07-23 | 2025-10-10 | 伊莱利利公司 | 使用gip/glp1共激动剂用于治疗的方法 |
| EP3826662B9 (en) | 2018-07-23 | 2025-02-19 | Eli Lilly and Company | Method of using a gip/glp1 co-agonist for diabetes |
| CN112469731B (zh) * | 2018-07-23 | 2024-11-29 | 伊莱利利公司 | Gip/glp1共激动剂化合物 |
| 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 |
| AU2020206388B2 (en) * | 2019-01-07 | 2022-12-01 | Vitalixir (Beijing) Co., Ltd | Novel polypeptide and therapeutic uses thereof |
| MX2021012277A (es) * | 2019-04-11 | 2021-11-12 | Jiangsu Hansoh Pharmaceutical Group Co Ltd | Agonista multireceptor y uso medico del mismo. |
| TWI764209B (zh) | 2019-08-01 | 2022-05-11 | 美商美國禮來大藥廠 | Gipr促效劑化合物 |
| MX2022002115A (es) | 2019-08-19 | 2022-03-17 | Lilly Co Eli | Metodos para preparar analogos de incretina. |
| 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 |
| EP4058047A1 (en) | 2019-11-11 | 2022-09-21 | Boehringer Ingelheim International GmbH | Npy2 receptor agonists |
| CN113383014B (zh) * | 2019-11-15 | 2024-06-18 | 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 |
| CA3157387A1 (en) * | 2019-12-03 | 2021-06-10 | Mette Marie Rosenkilde | Optimized gip peptide analogues |
| 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 |
| WO2021150673A1 (en) | 2020-01-23 | 2021-07-29 | Eli Lilly And Company | Gip/glp1 co-agonist compounds |
| TW202228762A (zh) | 2020-01-30 | 2022-08-01 | 美商美國禮來大藥廠 | 提派肽(tirzepatide)之治療用途 |
| AR121650A1 (es) * | 2020-03-25 | 2022-06-22 | Takeda Pharmaceuticals Co | Dosificación qd de compuestos peptídicos agonistas del receptor de gip y sus usos |
| 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 |
| MX2023000303A (es) | 2020-07-22 | 2023-02-09 | Novo Nordisk As | Coagonistas de los receptores del peptido 1 similar al glucagon (glp-1) y del polipeptido insulinotropico dependiente de glucosa (gip) adecuados para el suministro oral. |
| BR112023000229A2 (pt) | 2020-07-22 | 2023-01-31 | Novo Nordisk As | Composto, composição farmacêutica, e, peptídeo |
| 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 |
| CN116171164A (zh) | 2020-10-17 | 2023-05-26 | 太阳医药工业有限公司 | Glp-1/gip双重激动剂 |
| EP4257597A4 (en) * | 2020-12-02 | 2025-04-02 | Dongbao Purple Star (Hangzhou) Biopharmaceutical Co., Ltd. | LACTAM-MODIFIED POLYPEPTIDE COMPOUNDS |
| 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 |
| WO2022133797A1 (zh) * | 2020-12-23 | 2022-06-30 | 浙江道尔生物科技有限公司 | 一种长效胰高血糖素衍生物 |
| WO2022159395A1 (en) | 2021-01-20 | 2022-07-28 | Viking Therapeutics, Inc. | Compositions and methods for the treatment of metabolic and liver disorders |
| CN117642153A (zh) | 2021-05-07 | 2024-03-01 | 伊莱利利公司 | 易蚀片剂 |
| CN118307645A (zh) * | 2021-05-28 | 2024-07-09 | 广东众生睿创生物科技有限公司 | 多肽的制备及其应用 |
| WO2022253202A1 (zh) | 2021-06-01 | 2022-12-08 | 南京知和医药科技有限公司 | 一种glp-1r和gipr双重靶向激动作用的多肽衍生物及其制备方法和用途 |
| US20250223331A1 (en) * | 2021-09-02 | 2025-07-10 | Sunshine Lake Pharma Co., Ltd. | Glp-1/gip dual-targeted polypeptide and fusion protein and applications thereof |
| MX2024003236A (es) | 2021-09-15 | 2024-06-19 | Viking Therapeutics Inc | Composiciones y metodos para el tratamiento de trastornos metabolicos y hepaticos. |
| CA3237796A1 (en) * | 2021-11-12 | 2023-05-19 | Zhenbin Li | 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 |
| UY40349A (es) | 2022-07-13 | 2024-01-31 | Hangzhou Zhongmeihuadong Pharmaceutical Co Ltd | Agonista dual de glp-1/gip, método de preparación y uso del mismo |
| JP2025523903A (ja) * | 2022-07-15 | 2025-07-25 | ペプトゥータンゴ・セラピューティクス・インコーポレイテッド | マルチアゴニストペプチドを含む組成物並びに製造及び使用方法 |
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| JP2025531200A (ja) | 2022-09-15 | 2025-09-19 | イーライ リリー アンド カンパニー | Ｇｉｐ及びｇｌｐ－１二重アゴニスト化合物 |
| 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 |
| PE20252287A1 (es) | 2023-01-31 | 2025-09-18 | Lilly Co Eli | Agonistas del trirreceptor gip/glp1/gcg y usos de estos |
| 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 |
| EP4714434A1 (en) | 2023-05-19 | 2026-03-25 | Aulbio Co., Ltd. | Microsphere comprising thyrazepatide, method for preparing same, and pharmaceutical composition comprising same |
| EP4724471A1 (en) | 2023-06-09 | 2026-04-15 | Sun Pharmaceutical Industries Limited | Glp-1/gip dual, glp-1/gcg dual and glp-1/gip/gcg triple receptor agonists |
| AU2024306538A1 (en) | 2023-06-30 | 2025-12-04 | Zealand Pharma A/S | Combination therapy |
| 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 |
| JP7755031B2 (ja) | 2023-11-30 | 2025-10-15 | ノヴォ ノルディスク アー／エス | Ｇｌｐ－１、ｇｉｐ、およびアミリン受容体の三重作動薬 |
| WO2025125576A2 (en) | 2023-12-15 | 2025-06-19 | 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 |
| EP4686757A1 (en) | 2024-07-31 | 2026-02-04 | 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 |
Family Cites Families (82)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ202757A (en) | 1981-12-23 | 1985-11-08 | Novo Industri As | Peptides and medicaments |
| IL128332A0 (en) | 1996-08-30 | 2000-01-31 | Novo Nordisk As | GLP-1 derivatives |
| CZ295838B6 (cs) | 1996-09-09 | 2005-11-16 | Zealand Pharma A/S | Způsob výroby peptidů |
| WO1998011126A1 (en) | 1996-09-09 | 1998-03-19 | Zealand Pharmaceuticals A/S | Peptide prodrugs containing an alpha-hydroxyacid linker |
| WO1999025727A2 (en) | 1997-11-14 | 1999-05-27 | Amylin Pharmaceuticals, Inc. | Novel exendin agonist compounds |
| JP4394279B2 (ja) | 1998-03-09 | 2010-01-06 | ジーランド ファーマ アクティーゼルスカブ | 酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体 |
| DE69922043T2 (de) | 1998-12-07 | 2005-11-24 | Société de Conseils de Recherches et d'Applications Scientifiques S.A.S. | Glp-1 analoge |
| US6451987B1 (en) | 1999-03-15 | 2002-09-17 | Novo Nordisk A/S | Ion exchange chromatography of proteins and peptides |
| EP1956000B1 (en) | 1999-03-17 | 2016-10-05 | Novo Nordisk A/S | Acylating agents useful for acylating peptides |
| 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 |
| PL374949A1 (en) | 2001-12-20 | 2005-11-14 | Eli Lilly And Company | Insulin molecule having protracted time action |
| 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 |
| RU2413530C9 (ru) | 2004-11-12 | 2021-05-18 | Ново Нордиск А/С | Стабильные препараты инсулинотропных пептидов |
| 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 |
| EP1883419A4 (en) * | 2005-05-06 | 2010-08-04 | Bayer Pharmaceuticals Corp | GLUCAGON-LIKE PEPTIDE-1 (GLP-1) RECEPTOR AGONISTS AND THEIR PHARMACOLOGICAL USES |
| RU2485135C2 (ru) | 2005-06-13 | 2013-06-20 | Импиэриэл Инноувейшнс Лимитид | Соединения оксинтомодулина (варианты), фармацевтическая композиция на их основе, способы лечения и профилактики ожирения и сопутствующих заболеваний (варианты) и лекарственное средство (варианты) |
| WO2007024899A2 (en) | 2005-08-23 | 2007-03-01 | 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 |
| EP2570133B1 (en) | 2005-11-07 | 2016-03-23 | 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 |
| CN101389648B (zh) | 2006-02-22 | 2013-07-17 | 默沙东公司 | 肽胃泌酸调节素衍生物 |
| WO2007109354A2 (en) * | 2006-03-21 | 2007-09-27 | Amylin Pharmaceuticals, Inc. | Peptide-peptidase inhibitor conjugates and methods of using same |
| ES2673822T3 (es) | 2006-07-18 | 2018-06-25 | Sanofi | Anticuerpo antagonista contra EphA2 para el tratamiento de cáncer |
| ITMI20061607A1 (it) | 2006-08-09 | 2008-02-10 | Maria Vincenza Carriero | Peptidi con attivita farmacologica |
| US20090318353A1 (en) * | 2006-08-25 | 2009-12-24 | Novo Nordisk A/S | Acylated Exendin-4 Compounds |
| EP2074140B8 (en) | 2006-10-04 | 2015-10-28 | 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 |
| AU2008216265B2 (en) | 2007-02-15 | 2014-04-03 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
| 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 |
| EP2025684A1 (en) | 2007-08-15 | 2009-02-18 | Zealand Pharma A/S | Glucagon analogues |
| MX2010005317A (es) | 2007-11-20 | 2010-06-02 | Ambrx Inc | Polipeptidos de insulina modificados y sus usos. |
| DE102008003566A1 (de) | 2008-01-09 | 2009-07-16 | Sanofi-Aventis Deutschland Gmbh | Neue Insulinderivate mit extrem verzögertem Zeit-/ Wirkungsprofil |
| CN102007143B (zh) | 2008-01-09 | 2015-08-26 | 塞诺菲-安万特德国有限公司 | 具有超延迟时效特征的新型胰岛素衍生物 |
| EP2229406B1 (de) | 2008-01-09 | 2015-04-22 | Sanofi-Aventis Deutschland GmbH | Neue insulinderivate mit extrem verzögertem zeit- / wirkungsprofil |
| DE102008003568A1 (de) | 2008-01-09 | 2009-07-16 | Sanofi-Aventis Deutschland Gmbh | Neue Insulinderivate mit extrem verzögertem Zeit-/ Wirkungsprofil |
| US8993516B2 (en) | 2008-04-14 | 2015-03-31 | Case Western Reserve University | Meal-time insulin analogues of enhanced stability |
| RU2010147076A (ru) | 2008-04-22 | 2012-05-27 | Кейз Вестерн Ризев Юнивесити (Us) | Аналоги инсулина специфичные к изоформам |
| 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 |
| EP2300037B1 (en) | 2008-06-17 | 2016-03-30 | Indiana University Research and Technology Corporation | Glucagon/glp-1 receptor co-agonists |
| WO2009155257A1 (en) | 2008-06-17 | 2009-12-23 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting enhanced solubility and stability physiological ph buffers |
| DK2300035T3 (en) | 2008-06-17 | 2015-11-16 | Univ Indiana Res & Tech Corp | Mixed GIP-based agonists for the treatment of metabolic diseases and obesity |
| 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 |
| CA2732439A1 (en) | 2008-07-31 | 2010-02-04 | Case Western Reserve University | Halogen-stabilized insulin |
| KR101417873B1 (ko) * | 2008-08-07 | 2014-07-09 | 입센 파마 에스.에이.에스 | 포도당 의존적인 인슐린 분비 자극성 폴리펩타이드의 유사체 |
| US8637647B2 (en) | 2008-09-12 | 2014-01-28 | Novo Nordisk A/S | Method of acylating a peptide or protein |
| WO2010070255A1 (en) | 2008-12-15 | 2010-06-24 | Zealand Pharma A/S | Glucagon analogues |
| US8685919B2 (en) | 2008-12-15 | 2014-04-01 | Zealand Pharma A/S | Glucagon analogues |
| KR20110126592A (ko) | 2008-12-15 | 2011-11-23 | 질랜드 파마 에이/에스 | 글루카곤 유사체 |
| JP5635531B2 (ja) | 2008-12-15 | 2014-12-03 | 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 |
| WO2010080609A1 (en) | 2008-12-19 | 2010-07-15 | Indiana University Research And Technology Corporation | Amide-based insulin prodrugs |
| WO2010080606A1 (en) | 2008-12-19 | 2010-07-15 | Indiana University Research And Technology Corporation | Insulin analogs |
| 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 |
| EP2512518A1 (en) | 2009-12-16 | 2012-10-24 | Novo Nordisk A/S | Glp-1 receptor agonist compounds with a modified n-terminus |
| BR112012018104A2 (pt) | 2010-01-20 | 2017-10-17 | Zeland Pharma As | tratamento de doenças cardíacas |
| 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 |
| EP2552952A1 (en) | 2010-03-26 | 2013-02-06 | Novo Nordisk A/S | Novel glucagon analogues |
| 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 |
| BR112012027545B1 (pt) | 2010-04-27 | 2020-09-24 | Betta Pharmaceuticals Co., Ltd. | Composto, composição farmacêutica, uso da composição farmacêutica e uso de um composto |
| UY33462A (es) | 2010-06-23 | 2012-01-31 | Zealand Pharma As | Analogos de glucagon |
| PH12012502472A1 (en) | 2010-06-24 | 2013-03-25 | Zealand Pharma As | Glucagon analogues |
| EP2637698B1 (en) | 2010-11-09 | 2022-04-20 | Novo Nordisk A/S | Double-acylated glp-1 derivatives |
| KR20140043709A (ko) | 2011-01-20 | 2014-04-10 | 질랜드 파마 에이/에스 | 아실화 글루카곤 유사체와 인슐린 유사체의 조합 |
| JP2014510739A (ja) | 2011-03-28 | 2014-05-01 | ノヴォ ノルディスク アー／エス | 新規のグルカゴン類似体 |
| RU2602601C2 (ru) | 2011-04-12 | 2016-11-20 | Ново Нордиск А/С | Дважды ацилированные производные glp-1 |
| WO2012150503A2 (en) | 2011-05-03 | 2012-11-08 | Zealand Pharma A/S | Glu-glp-1 dual agonist signaling-selective compounds |
| WO2012167744A1 (en) * | 2011-06-10 | 2012-12-13 | Beijing Hanmi Pharmaceutical Co., Ltd. | Glucose dependent insulinotropic polypeptide analogs, pharmaceutical compositions and use thereof |
| RU2610175C2 (ru) | 2011-09-23 | 2017-02-08 | Ново Нордиск А/С | Новые аналоги глюкагона |
| WO2013092703A2 (en) | 2011-12-23 | 2013-06-27 | Zealand Pharma A/S | Glucagon analogues |
| JP6228187B2 (ja) | 2012-05-03 | 2017-11-08 | ジーランド ファーマ アクティーゼルスカブ | Ｇｉｐ−ｇｌｐ−１デュアルアゴニスト化合物及び方法 |
| AU2013295035B2 (en) | 2012-07-23 | 2017-08-03 | Zealand Pharma A/S | Glucagon analogues |
| TWI608013B (zh) | 2012-09-17 | 2017-12-11 | 西蘭製藥公司 | 升糖素類似物 |
| WO2015055801A1 (en) | 2013-10-17 | 2015-04-23 | Zealand Pharma A/S | Acylated glucagon analogues |
| US9988429B2 (en) | 2013-10-17 | 2018-06-05 | Zealand Pharma A/S | Glucagon analogues |
| MX2016005556A (es) | 2013-11-06 | 2016-07-15 | Zealand Pharma As | Compuestos agonistas duales de gip-glp-1 y procedimientos. |
| WO2015124612A1 (en) | 2014-02-18 | 2015-08-27 | Novo Nordisk A/S | Stable glucagon analogues and use for treatment of hypoglycaemia |
| US10336802B2 (en) | 2015-04-16 | 2019-07-02 | Zealand Pharma A/S | Acylated glucagon analogue |
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| BR112014027348A2 (pt) | 2017-06-27 |
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| WO2013164483A1 (en) | 2013-11-07 |
| TW201348252A (zh) | 2013-12-01 |
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