JP6084215B2 - ポリエチレングリコールまたはその誘導体でｐｅｇ化されたエキセンジン−４類似体、その調製法、および活性成分としてこれを含有する、糖尿病を予防または処置するための薬学的組成物 - Google Patents
ポリエチレングリコールまたはその誘導体でｐｅｇ化されたエキセンジン−４類似体、その調製法、および活性成分としてこれを含有する、糖尿病を予防または処置するための薬学的組成物 Download PDFInfo
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- JP6084215B2 JP6084215B2 JP2014518803A JP2014518803A JP6084215B2 JP 6084215 B2 JP6084215 B2 JP 6084215B2 JP 2014518803 A JP2014518803 A JP 2014518803A JP 2014518803 A JP2014518803 A JP 2014518803A JP 6084215 B2 JP6084215 B2 JP 6084215B2
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| KR10-2011-0062858 | 2011-06-28 | ||
| KR1020110062858A KR101357117B1 (ko) | 2011-06-28 | 2011-06-28 | 폴리에틸렌글라이콜 또는 이의 유도체로 페길화된 엑센딘-4 유사체, 이의 제조방법 및 이를 유효성분으로 함유하는 당뇨병 예방 또는 치료용 약학적 조성물 |
| PCT/KR2012/005137 WO2013002580A2 (ko) | 2011-06-28 | 2012-06-28 | 폴리에틸렌글라이콜 또는 이의 유도체로 페길화된 엑센딘-4 유사체, 이의 제조방법 및 이를 유효성분으로 함유하는 당뇨병 예방 또는 치료용 약학적 조성물 |
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| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| HRP20181300T1 (hr) | 2012-12-21 | 2018-10-05 | Sanofi | Derivati eksendina-4 kao dvostruki glp1/gip- ili trostruki glp1/gip/glukagon agonisti |
| CN105934257B (zh) | 2013-12-06 | 2020-10-09 | 韩捷 | 用于含氮和羟基的药物的生物可逆引入基团 |
| TW201609796A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 非醯化之艾塞那肽－４（ｅｘｅｎｄｉｎ－４）胜肽類似物 |
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| EP3080154B1 (en) | 2013-12-13 | 2018-02-07 | Sanofi | Dual glp-1/gip receptor agonists |
| EP3080149A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Dual glp-1/glucagon receptor agonists |
| 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 |
| 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 |
| 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 |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| CN105985425B (zh) * | 2014-12-11 | 2019-12-17 | 浙江海昶生物医药技术有限公司 | 一种聚乙二醇修饰的exendin类似物及其制备方法和应用 |
| AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
| AR105284A1 (es) | 2015-07-10 | 2017-09-20 | Sanofi Sa | Derivados de exendina-4 como agonistas peptídicos duales específicos de los receptores de glp-1 / glucagón |
| WO2017024182A1 (en) | 2015-08-04 | 2017-02-09 | Duke University | Genetically encoded intrinsically disordered stealth polymers for delivery and methods of using same |
| US11752213B2 (en) | 2015-12-21 | 2023-09-12 | Duke University | Surfaces having reduced non-specific binding and antigenicity |
| ES2968038T3 (es) | 2015-12-23 | 2024-05-06 | Univ Johns Hopkins | Agonista GLP-1R de acción prolongada como terapia de afecciones neurológicas y neurodegenerativas |
| CN113546159B (zh) * | 2015-12-29 | 2023-09-08 | 派格生物医药(苏州)股份有限公司 | 包含glp-1受体激动剂和胰高血糖素受体激动剂的组合物及其用途 |
| US11467156B2 (en) | 2016-06-01 | 2022-10-11 | Duke University | Nonfouling biosensors |
| WO2018057847A1 (en) | 2016-09-23 | 2018-03-29 | Duke University | Unstructured non-repetitive polypeptides having lcst behavior |
| US11648200B2 (en) | 2017-01-12 | 2023-05-16 | Duke University | Genetically encoded lipid-polypeptide hybrid biomaterials that exhibit temperature triggered hierarchical self-assembly |
| WO2018213320A1 (en) | 2017-05-15 | 2018-11-22 | Duke University | Recombinant production of hybrid lipid-biopolymer materials that self-assemble and encapsulate agents |
| WO2019147954A1 (en) | 2018-01-26 | 2019-08-01 | Duke University | Albumin binding peptide-drug (aibiped) conjugates and methods of making and using same |
| WO2019213150A1 (en) | 2018-04-30 | 2019-11-07 | Duke University | Stimuli-responsive peg-like polymer-based drug delivery platform |
| KR20200135618A (ko) * | 2019-05-23 | 2020-12-03 | ㈜ 디앤디파마텍 | 폴리펩티드를 포함하는 비알코올성 지방간 질환의 예방 또는 치료용 약학 조성물 |
| US11649275B2 (en) | 2018-08-02 | 2023-05-16 | Duke University | Dual agonist fusion proteins |
| US11512314B2 (en) | 2019-07-12 | 2022-11-29 | Duke University | Amphiphilic polynucleotides |
| KR102193211B1 (ko) * | 2019-11-27 | 2020-12-18 | (주)디앤디파마텍 | 비오틴 모이어티가 결합된 폴리펩티드 및 이를 포함하는 경구 투여용 약학적 조성물 |
| US20240181013A1 (en) * | 2021-04-01 | 2024-06-06 | Duke University | Poegma copolymer conjugates and methods of treating diseases |
| US20240374691A1 (en) | 2021-08-25 | 2024-11-14 | Neuraly, Inc. | Glp-1r agonists for use in a treatment of neurologial impairment associated with viral infection |
| KR20240155737A (ko) | 2023-04-20 | 2024-10-29 | 전북대학교산학협력단 | 폴리에틸렌글리콜을 이용한 분자 전달 방법 |
| WO2024229006A1 (en) * | 2023-05-01 | 2024-11-07 | Neuraly, Inc. | Glucagon-like peptide-1 receptor agonist variants and methods thereof |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2343072T3 (es) * | 1999-01-14 | 2010-07-22 | Amylin Pharmaceuticals, Inc. | Exendina para la supresion del glucagon. |
| CN1191273C (zh) * | 1999-05-17 | 2005-03-02 | 康久化学公司 | 长效促胰岛肽 |
| EP1539210A4 (en) * | 2002-09-06 | 2006-06-07 | Bayer Pharmaceuticals Corp | GLP-1 RECEPTOR MODIFIED AGONISTS AND THEIR PHARMACOLOGICAL METHODS OF USE |
| CA2529819A1 (en) * | 2003-06-30 | 2004-09-23 | Domantis Limited | Pegylated single domain antibodies |
| JP2008516621A (ja) * | 2004-10-18 | 2008-05-22 | ノボ ノルディスク アクティーゼルスカブ | 成長ホルモン結合体 |
| WO2007075534A2 (en) * | 2005-12-16 | 2007-07-05 | Nektar Therapeutics Al, Corporation | Polymer conjugates of glp-1 |
| KR100890989B1 (ko) * | 2006-06-01 | 2009-03-31 | 이강춘 | 폴리에틸렌글리콜 또는 이의 유도체로 단일 수식된 엑센딘,이의 제조방법 및 이의 용도 |
| US8420598B2 (en) * | 2007-04-20 | 2013-04-16 | B & L Delipharm Corp. | Mono modified exendin with polyethylene glycol or its derivatives and uses thereof |
| CN101870728A (zh) * | 2009-04-23 | 2010-10-27 | 派格生物医药(苏州)有限公司 | 新型Exendin变体及其缀合物 |
| KR101112578B1 (ko) * | 2009-07-16 | 2012-02-16 | 성균관대학교산학협력단 | 엑센딘의 비강투여용 약제학적 조성물 및 이의 제조방법 |
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|---|---|
| WO2013002580A2 (ko) | 2013-01-03 |
| KR101357117B1 (ko) | 2014-02-06 |
| JP2014520798A (ja) | 2014-08-25 |
| CN103338790B (zh) | 2018-01-23 |
| EP2727605B1 (en) | 2018-04-04 |
| ES2674581T3 (es) | 2018-07-02 |
| WO2013002580A3 (ko) | 2013-04-11 |
| CN103338790A (zh) | 2013-10-02 |
| EP2727605A4 (en) | 2014-12-24 |
| CA2839410C (en) | 2019-05-14 |
| CA2839410A1 (en) | 2013-01-03 |
| DK2727605T3 (en) | 2018-06-25 |
| AU2012276478A1 (en) | 2014-01-23 |
| US10406230B2 (en) | 2019-09-10 |
| US20130217622A1 (en) | 2013-08-22 |
| KR20130008665A (ko) | 2013-01-23 |
| EP2727605A2 (en) | 2014-05-07 |
| US20170189545A1 (en) | 2017-07-06 |
| AU2012276478B2 (en) | 2016-02-25 |
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