CA2895156A1 - Dual glp1/gip or trigonal glp1/gip/glucagon agonists - Google Patents
Dual glp1/gip or trigonal glp1/gip/glucagon agonists Download PDFInfo
- Publication number
- CA2895156A1 CA2895156A1 CA2895156A CA2895156A CA2895156A1 CA 2895156 A1 CA2895156 A1 CA 2895156A1 CA 2895156 A CA2895156 A CA 2895156A CA 2895156 A CA2895156 A CA 2895156A CA 2895156 A1 CA2895156 A1 CA 2895156A1
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- Prior art keywords
- carboxy
- butyryl
- ethoxy
- amino acid
- acid residue
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12306647 | 2012-12-21 | ||
| EP12306647.4 | 2012-12-21 | ||
| PCT/EP2013/077313 WO2014096150A1 (en) | 2012-12-21 | 2013-12-19 | Dual glp1/gip or trigonal glp1/gip/glucagon agonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2895156A1 true CA2895156A1 (en) | 2014-06-26 |
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Country Status (38)
Families Citing this family (96)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9255154B2 (en) | 2012-05-08 | 2016-02-09 | Alderbio Holdings, Llc | Anti-PCSK9 antibodies and use thereof |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| PE20151433A1 (es) | 2012-12-21 | 2015-10-16 | Alios Biopharma Inc | Nucleosidos sustituidos, nucleotidos y analogos de los mismos |
| RS57531B1 (sr) | 2012-12-21 | 2018-10-31 | Sanofi Sa | Derivati eksendina-4 kao dualni glp1/gip- ili trigonalni glp1/gip/glukagon agonisti |
| UA111305C2 (uk) | 2012-12-21 | 2016-04-11 | Пфайзер Інк. | Конденсовані лактами арилу та гетероарилу |
| CA2908581C (en) | 2013-05-28 | 2021-07-13 | Takeda Pharmaceutical Company Limited | Peptide compound |
| CA2929107C (en) * | 2013-11-06 | 2023-09-26 | Zealand Pharma A/S | Glucagon-glp-1-gip triple agonist compounds |
| AU2014345569B2 (en) | 2013-11-06 | 2020-08-13 | Zealand Pharma A/S | GIP-GLP-1 dual agonist compounds and methods |
| EP3080150B1 (en) | 2013-12-13 | 2018-08-01 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
| WO2015086733A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
| WO2015086729A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/gip receptor agonists |
| 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 |
| 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 |
| 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 |
| KR101877187B1 (ko) | 2014-06-17 | 2018-07-10 | 화이자 인코포레이티드 | 치환된 다이하이드로이소퀴놀린온 화합물 |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| MX381640B (es) | 2014-10-29 | 2025-03-04 | Zealand Pharma As | Metodos y compuestos agonistas de gip. |
| PE20171154A1 (es) | 2014-12-30 | 2017-08-16 | Hanmi Pharm Ind Co Ltd | Derivados de glucagon con estabilidad mejorada |
| JOP20200119A1 (ar) | 2015-01-09 | 2017-06-16 | Lilly Co Eli | مركبات مساعد مشترك من gip وglp-1 |
| US10993993B2 (en) | 2015-05-28 | 2021-05-04 | Immunoforge Co., Ltd. | Pharmaceutical composition for treating muscle atrophy or sarcopenia including glucagon-like peptide (GLP-1) or GLP-1 receptor agonist |
| KR101661332B1 (ko) * | 2015-05-28 | 2016-09-29 | (의료)길의료재단 | 글루카곤 유사 펩타이드-1 수용체 항진제를 포함하는 근감소증 치료용 약학 조성물 |
| AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
| WO2016198624A1 (en) * | 2015-06-12 | 2016-12-15 | Sanofi | Exendin-4 derivatives as trigonal glp-1/glucagon/gip receptor agonists |
| KR102005456B1 (ko) | 2015-06-30 | 2019-07-30 | 한미약품 주식회사 | 신규 글루카곤 유도체 및 이의 지속형 결합체를 포함하는 조성물 |
| 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 |
| TWI622596B (zh) | 2015-10-26 | 2018-05-01 | 美國禮來大藥廠 | 升糖素受體促效劑 |
| MX2018007323A (es) | 2015-12-14 | 2019-01-10 | Sanofi Sa | Agonistas selectivos del receptor de glucagon que comprenden una porcion quelante para propositos de imagenologia. |
| JP7026044B2 (ja) | 2015-12-23 | 2022-02-25 | ザ・ジョンズ・ホプキンス・ユニバーシティー | 神経性状態および神経変性状態の治療としての長時間作用型ＧＬＰ－１ｒアゴニスト |
| CN113456820B (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 |
| MX2018008128A (es) * | 2015-12-31 | 2018-12-06 | Hanmi Pharm Ind Co Ltd | Conjugado persistente de triple activador que activa el receptor de glucagon, glp-1 y gip. |
| US10676517B2 (en) * | 2016-03-10 | 2020-06-09 | Medimmune Limited | Glucagon and GLP-1 co-agonists for the treatment of obesity |
| US10501516B2 (en) | 2016-05-24 | 2019-12-10 | Takeda Pharmaceutical Company Limited | Peptide compound |
| MX2019000019A (es) | 2016-06-29 | 2019-05-06 | Hanmi Pharm Ind Co Ltd | Derivado de glucagon, conjugado del mismo, composicion que comprende el mismo y uso terapeutico del mismo. |
| TW201821434A (zh) * | 2016-10-10 | 2018-06-16 | 法商賽諾菲公司 | 製備包含親脂性修飾的離胺酸側鏈的肽的方法 |
| EP3526242A1 (en) * | 2016-10-12 | 2019-08-21 | University of Copenhagen | Peptide dual agonists of gipr and glp2r |
| TW201833132A (zh) * | 2016-12-02 | 2018-09-16 | 法商賽諾菲公司 | 作為肽類ｇｌｐ１／升糖素／ｇｉｐ三重受體激動劑之新穎化合物 |
| TW201832783A (zh) | 2016-12-02 | 2018-09-16 | 法商賽諾菲公司 | 包含ｇｌｐ－１／胰高血糖素雙重激動劑、連接子和透明質酸的接合物 |
| AR110301A1 (es) * | 2016-12-02 | 2019-03-13 | Sanofi Sa | Compuestos como agonistas peptídicos de receptores de glp1 / glucagón / gip |
| US10392366B2 (en) | 2017-02-21 | 2019-08-27 | Sanofi | Azetidine compounds as GPR119 modulators for the treatment of diabetes, obesity, dyslipidemia and related disorders |
| JOP20180028A1 (ar) | 2017-03-31 | 2019-01-30 | Takeda Pharmaceuticals Co | مركب ببتيد |
| AU2018303625A1 (en) * | 2017-07-19 | 2020-02-06 | Novo Nordisk A/S | Bifunctional compounds |
| KR102686854B1 (ko) * | 2017-08-09 | 2024-07-18 | 사노피 | 지방간 질환 및 지방간염의 치료에서의 glp-1/글루카곤 수용체 작용제 |
| CN115304666B (zh) * | 2017-11-24 | 2025-09-19 | 浙江道尔生物科技有限公司 | 一种治疗代谢疾病的胰高血糖素类似物 |
| GB201720187D0 (en) | 2017-12-04 | 2018-01-17 | Imperial Innovations Ltd | Novel Compounds |
| HUE067499T2 (hu) | 2018-04-05 | 2024-10-28 | Sun Pharmaceutical Ind Ltd | Új GLP-1 analógok |
| CA3096493A1 (en) | 2018-04-10 | 2019-10-17 | Sanofi-Aventis Deutschland Gmbh | Method for cleavage of solid phase-bound peptides from the solid phase |
| JP7332620B2 (ja) | 2018-04-10 | 2023-08-23 | サノフィ－アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | キャップ付加を伴うリキシセナチドの合成 |
| TWI829687B (zh) | 2018-05-07 | 2024-01-21 | 丹麥商諾佛 儂迪克股份有限公司 | 包含glp-1促效劑與n-(8-(2-羥基苯甲醯基)胺基)辛酸之鹽的固體組成物 |
| TW202015735A (zh) | 2018-05-30 | 2020-05-01 | 法商賽諾菲公司 | 包含ｇｌｐ－１／升糖素／ｇｉｐ三重受體促效劑、連接子及透明質酸之接合物 |
| TW202535916A (zh) * | 2018-11-01 | 2025-09-16 | 美商美國禮來大藥廠 | 蛋白質酪胺酸-酪胺酸類似物及其使用方法 |
| KR102119188B1 (ko) * | 2018-11-13 | 2020-06-08 | 이뮤노포지 주식회사 | 글루카곤 유사 펩타이드-1(glp-1), glp-1 유래 펩타이드, 또는 glp-1 분해 억제제를 포함하는 근감소증 또는 근위축증 치료용 약학 조성물 |
| US20220153853A1 (en) | 2018-12-21 | 2022-05-19 | Jiangsu Hengrui Medicine Co., Ltd. | Bispecific protein |
| US20220088148A1 (en) * | 2018-12-21 | 2022-03-24 | Hanmi Pharm, Co., Ltd. | A pharmaceutical composition comprising insulin and trigonal glucagon/glp-1/gip receptor agonist |
| EP3909975A4 (en) * | 2019-01-07 | 2022-11-09 | Vitalixir (Beijing) Co., Ltd | NOVEL POLYPEPTIDE AND THERAPEUTIC USES THEREOF |
| BR112021020071A2 (pt) * | 2019-04-11 | 2021-12-14 | Jiangsu Hansoh Pharmaceutical Group Co Ltd | Compostos agonistas duplos do receptor de glp-1 e gip e uso dos mesmos |
| WO2020214013A1 (ko) * | 2019-04-19 | 2020-10-22 | 한미약품 주식회사 | 글루카곤, glp-1 및 gip 수용체 모두에 활성을 갖는 삼중 활성체 또는 이의 결합체의 고지혈증에 대한 치료적 용도 |
| WO2020214012A1 (ko) * | 2019-04-19 | 2020-10-22 | 한미약품 주식회사 | 글루카곤, glp-1 및 gip 수용체 모두에 활성을 갖는 삼중 활성체 또는 이의 결합체를 포함하는 고지혈증 예방 또는 치료용 약학적 조성물 및 예방 또는 치료 방법 |
| GB201908424D0 (en) * | 2019-06-12 | 2019-07-24 | Imp College Innovations Ltd | Novel compounds |
| BR112022002962A2 (pt) | 2019-08-16 | 2022-07-05 | Applied Molecular Transport Inc | Composições, formulações e produção e purificação de interleucina |
| CN111040022B (zh) * | 2019-12-23 | 2021-12-14 | 万新医药科技(苏州)有限公司 | 针对胰高血糖素样肽-1受体、胰高血糖素受体、以及抑胃肽受体的三重激动剂 |
| CN115298207A (zh) * | 2020-01-23 | 2022-11-04 | 伊莱利利公司 | Gip/glp1共激动剂化合物 |
| CA3174635A1 (en) | 2020-03-06 | 2021-09-10 | Sanofi | Peptides as selective gip receptor agonists |
| JP7736315B2 (ja) | 2020-03-31 | 2025-09-09 | アンタロス メディカル アクティエボラーグ | イメージング及び治療目的のキレート部分を含む選択的ｇｉｐ受容体アゴニスト |
| CA3174423A1 (en) * | 2020-04-20 | 2021-10-28 | Hanmi Pharm. Co., Ltd. | Composition for prevention or treatment of hyperlipidemia comprising trigonal glucagon/glp-1/gip receptor agonist or conjugate thereof and method using the same |
| CN114222755B (zh) * | 2020-05-29 | 2024-06-11 | 北京拓界生物医药科技有限公司 | Glp-1和gip受体双重激动剂化合物及其应用 |
| WO2022007809A1 (zh) * | 2020-07-06 | 2022-01-13 | 鸿绪生物医药科技（北京）有限公司 | 新型多肽制剂及其治疗用途 |
| CA3185229A1 (en) * | 2020-07-06 | 2022-01-13 | Jie Han | Novel polypeptide and therapeutic use thereof |
| TW202214679A (zh) | 2020-07-22 | 2022-04-16 | 丹麥商諾佛 儂迪克股份有限公司 | Glp-1及gip受體共促效劑 |
| IL299701A (en) | 2020-07-22 | 2023-03-01 | Novo Nordisk As | GLP-1 and GIP receptor co-agonists suitable for oral administration |
| CA3190959A1 (en) * | 2020-08-12 | 2022-02-17 | Txp Pharma Ag | Exendin-4 peptide analogues |
| WO2022090447A1 (en) | 2020-10-30 | 2022-05-05 | Novo Nordisk A/S | Glp-1, gip and glucagon receptor triple agonists |
| 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 |
| KR20230160369A (ko) * | 2021-03-25 | 2023-11-23 | 브라이트제네 바이오-메디컬 테크놀로지 코., 엘티디. | Gip 및 glp-1의 이중 수용체 작용제, 약물 조성물 및 용도 |
| US12215133B2 (en) | 2021-03-25 | 2025-02-04 | Brightgene Bio-Medical Technology Co., Ltd. | GIP and GLP-1 dual receptor agonist, pharmaceutical composition, and use |
| KR20240013798A (ko) | 2021-05-26 | 2024-01-30 | 더 유나이티드 바이오-테크놀로지 (헝친) 컴퍼니 리미티드 | 다중 작용제 및 이의 사용 |
| MX2023015068A (es) * | 2021-06-18 | 2024-01-17 | Beijing Tuo Jie Biopharmaceutical Co Ltd | Analogo de glucagon y uso medico del mismo. |
| CN115572326B (zh) * | 2021-06-21 | 2025-01-10 | 广东东阳光药业股份有限公司 | Glp-1、gcg和gip受体的三重激动剂 |
| TW202313667A (zh) * | 2021-07-30 | 2023-04-01 | 大陸商南京明德新藥研發有限公司 | 含內醯胺橋的多肽化合物 |
| EP4399224A1 (en) | 2021-09-06 | 2024-07-17 | Sanofi | New peptides as potent and selective gip receptor agonists |
| US20250115654A1 (en) * | 2021-11-12 | 2025-04-10 | Fujian Shengdi Pharmaceutical Co., Ltd. | Pharmaceutical composition of glp-1 receptor and gip receptor dual agonist, and use thereof |
| AU2022401780A1 (en) * | 2021-12-01 | 2024-07-04 | Jiangsu Hengrui Pharmaceuticals Co., Ltd. | Pharmaceutical composition of glp-1 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 |
| CN115960258B (zh) * | 2022-09-30 | 2024-01-12 | 广西医科大学附属肿瘤医院 | 一类GLP-1/glucagon/Y2受体三重激动剂及其应用 |
| WO2024165571A2 (en) | 2023-02-06 | 2024-08-15 | E-Therapeutics Plc | Inhibitors of expression and/or function |
| GB202302686D0 (en) * | 2023-02-24 | 2023-04-12 | Imperial College Innovations Ltd | Novel compounds |
| WO2025016303A1 (zh) * | 2023-07-14 | 2025-01-23 | 北京拓界生物医药科技有限公司 | Glp-1、gip和gcg受体三激动剂及其应用 |
| CN120329412A (zh) * | 2023-11-06 | 2025-07-18 | 成都奥达生物科技有限公司 | 一种三激动剂化合物 |
| 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 |
| WO2025162423A1 (zh) * | 2024-02-02 | 2025-08-07 | 杭州先为达生物科技股份有限公司 | 针对glp-1r、gipr和gcgr的三激动剂 |
| WO2025176999A2 (en) * | 2024-02-23 | 2025-08-28 | Ip2Ipo Innovations Limited | Novel compounds |
| WO2025196502A1 (en) | 2024-03-20 | 2025-09-25 | North Carolina Agricultural & Technical State University | Choline kinase inhibitors as a therapeutic treatment for obesity |
| WO2025219590A1 (en) | 2024-04-19 | 2025-10-23 | Actimed Therapeutics Ltd | Beta-blockers for preserving muscle mass, bone density, and cardiac function in weight loss treatments |
| CN119390784A (zh) * | 2024-07-11 | 2025-02-07 | 中国药科大学 | 一种双激动多肽化合物及其医药用途 |
| US12303604B1 (en) | 2024-10-16 | 2025-05-20 | Currax Pharmaceuticals Llc | Pharmaceutical formulations comprising naltrexone and/or bupropion |
Family Cites Families (437)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU225496B1 (en) | 1993-04-07 | 2007-01-29 | Scios Inc | Pharmaceutical compositions of prolonged delivery, containing peptides |
| US6284727B1 (en) | 1993-04-07 | 2001-09-04 | Scios, Inc. | Prolonged delivery of peptides |
| US5424286A (en) | 1993-05-24 | 1995-06-13 | Eng; John | Exendin-3 and exendin-4 polypeptides, and pharmaceutical compositions comprising same |
| US5641757A (en) | 1994-12-21 | 1997-06-24 | Ortho Pharmaceutical Corporation | Stable 2-chloro-2'-deoxyadenosine formulations |
| WO1998005351A1 (en) | 1996-08-08 | 1998-02-12 | Amylin Pharmaceuticals, Inc. | Methods for regulating gastrointestinal motility |
| DE69737479T4 (de) | 1996-08-30 | 2010-05-06 | Novo Nordisk A/S | Glp-1 derivate |
| US6458924B2 (en) | 1996-08-30 | 2002-10-01 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
| CA2277112C (en) | 1997-01-07 | 2008-08-26 | Amylin Pharmaceuticals, Inc. | Use of exendins and agonists thereof for the reduction of food intake |
| US7312196B2 (en) | 1997-01-08 | 2007-12-25 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides |
| US6410511B2 (en) | 1997-01-08 | 2002-06-25 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides |
| US6723530B1 (en) | 1997-02-05 | 2004-04-20 | Amylin Pharmaceuticals, Inc. | Polynucleotides encoding proexendin, and methods and uses thereof |
| US7157555B1 (en) | 1997-08-08 | 2007-01-02 | Amylin Pharmaceuticals, Inc. | Exendin agonist compounds |
| DK1019077T4 (da) | 1997-08-08 | 2011-03-07 | Amylin Pharmaceuticals Inc | Hidtil ukendte exendinagonistforbindelser |
| JP2001523688A (ja) | 1997-11-14 | 2001-11-27 | 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 | 新規エキセンジン・アゴニスト化合物 |
| US7220721B1 (en) | 1997-11-14 | 2007-05-22 | Amylin Pharmaceuticals, Inc. | Exendin agonist peptides |
| WO1999025727A2 (en) | 1997-11-14 | 1999-05-27 | Amylin Pharmaceuticals, Inc. | Novel exendin agonist compounds |
| US7223725B1 (en) | 1997-11-14 | 2007-05-29 | Amylin Pharmaceuticals, Inc. | Exendin agonist compounds |
| AU760609B2 (en) | 1998-01-09 | 2003-05-15 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides |
| US6703359B1 (en) | 1998-02-13 | 2004-03-09 | Amylin Pharmaceuticals, Inc. | Inotropic and diuretic effects of exendin and GLP-1 |
| EP1056775B1 (en) | 1998-02-27 | 2010-04-28 | Novo Nordisk A/S | Glp-1 derivatives of glp-1 and exendin with protracted profile of action |
| CA2321026A1 (en) | 1998-03-09 | 1999-09-16 | Zealand Pharmaceuticals A/S | Pharmacologically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
| WO1999047160A1 (en) | 1998-03-13 | 1999-09-23 | Novo Nordisk A/S | Stabilized aqueous peptide solutions |
| US6998387B1 (en) | 1998-03-19 | 2006-02-14 | Amylin Pharmaceuticals, Inc. | Human appetite control by glucagon-like peptide receptor binding compounds |
| NZ527473A (en) | 1998-06-12 | 2005-02-25 | Amylin Pharmaceuticals Inc | Glucagon-like peptide-1 improves beta-cell response to glucose in subjects with impaired glucose tolerance |
| ES2553108T3 (es) | 1998-08-10 | 2015-12-04 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Diferenciación de células no productoras de insulina en células productoras de insulina mediante GLP-1 o exendina-4 y utilizaciones de las mismas |
| CA2343268A1 (en) | 1998-09-17 | 2000-03-23 | Eli Lilly And Company | Protein formulations |
| US6429197B1 (en) | 1998-10-08 | 2002-08-06 | Bionebraska, Inc. | Metabolic intervention with GLP-1 or its biologically active analogues to improve the function of the ischemic and reperfused brain |
| US6284725B1 (en) | 1998-10-08 | 2001-09-04 | Bionebraska, Inc. | Metabolic intervention with GLP-1 to improve the function of ischemic and reperfused tissue |
| US7259136B2 (en) | 1999-04-30 | 2007-08-21 | Amylin Pharmaceuticals, Inc. | Compositions and methods for treating peripheral vascular disease |
| DE69928006T2 (de) | 1998-12-22 | 2006-07-13 | Eli Lilly And Co., Indianapolis | Lagerstabile flüssige zusammensetzungen von glucagon-ähnlichem peptid-1 |
| EP1143989B1 (en) | 1999-01-14 | 2006-12-13 | Amylin Pharmaceuticals, Inc. | Exendins for glucagon suppression |
| US7399489B2 (en) | 1999-01-14 | 2008-07-15 | Amylin Pharmaceuticals, Inc. | Exendin analog formulations |
| US20030087820A1 (en) | 1999-01-14 | 2003-05-08 | Young Andrew A. | Novel exendin agonist formulations and methods of administration thereof |
| EP1609478A1 (en) | 1999-01-14 | 2005-12-28 | Amylin Pharmaceuticals, Inc. | Exendin agonist peptide formulations |
| EP1956000B1 (en) | 1999-03-17 | 2016-10-05 | Novo Nordisk A/S | Acylating agents useful for acylating peptides |
| US6451974B1 (en) | 1999-03-17 | 2002-09-17 | Novo Nordisk A/S | Method of acylating peptides and novel acylating agents |
| US6924264B1 (en) | 1999-04-30 | 2005-08-02 | Amylin Pharmaceuticals, Inc. | Modified exendins and exendin agonists |
| CN1372570A (zh) | 1999-04-30 | 2002-10-02 | 安米林药品公司 | 修饰的exendin和exendin激动剂 |
| CA2363712C (en) | 1999-05-17 | 2011-05-10 | Conjuchem Inc. | Long lasting insulinotropic peptides |
| US6514500B1 (en) | 1999-10-15 | 2003-02-04 | Conjuchem, Inc. | Long lasting synthetic glucagon like peptide {GLP-!} |
| US6849714B1 (en) | 1999-05-17 | 2005-02-01 | Conjuchem, Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| US6887470B1 (en) | 1999-09-10 | 2005-05-03 | Conjuchem, Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| US6482799B1 (en) | 1999-05-25 | 2002-11-19 | The Regents Of The University Of California | Self-preserving multipurpose ophthalmic solutions incorporating a polypeptide antimicrobial |
| US6506724B1 (en) | 1999-06-01 | 2003-01-14 | Amylin Pharmaceuticals, Inc. | Use of exendins and agonists thereof for the treatment of gestational diabetes mellitus |
| US6344180B1 (en) | 1999-06-15 | 2002-02-05 | Bionebraska, Inc. | GLP-1 as a diagnostic test to determine β-cell function and the presence of the condition of IGT and type II diabetes |
| US6528486B1 (en) | 1999-07-12 | 2003-03-04 | Zealand Pharma A/S | Peptide agonists of GLP-1 activity |
| US6972319B1 (en) | 1999-09-28 | 2005-12-06 | Bayer Pharmaceuticals Corporation | Pituitary adenylate cyclase activating peptide (PACAP)receptor 3 (R3) agonists and their pharmacological methods of use |
| GB9930882D0 (en) | 1999-12-30 | 2000-02-23 | Nps Allelix Corp | GLP-2 formulations |
| CA2396157A1 (en) | 2000-01-10 | 2001-07-19 | Amylin Pharmaceuticals, Inc. | Use of exendins and agonists thereof for modulation of triglyceride levels and treatment of dyslipidemia |
| MXPA02009031A (es) | 2000-03-14 | 2004-08-19 | Amylin Pharmaceuticals Inc | Efectos del peptido-1(7-36) tipo glucagon en la motilidad antro-piloro.duodenal. |
| CA2380423A1 (en) | 2000-05-17 | 2001-11-22 | Bionebraska, Inc. | Peptide pharmaceutical formulations |
| EP1282436B1 (en) | 2000-05-19 | 2008-06-11 | Amylin Pharmaceuticals, Inc. | Treatment of acute coronary syndrome with glp-1 |
| EP1317412A1 (en) | 2000-08-18 | 2003-06-11 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US7507714B2 (en) | 2000-09-27 | 2009-03-24 | Bayer Corporation | Pituitary adenylate cyclase activating peptide (PACAP) receptor 3 (R3) agonists and their pharmacological methods of use |
| ES2347137T3 (es) | 2000-10-20 | 2010-10-26 | Amylin Pharmaceuticals, Inc. | Tratamiento de miocardio hibernante y cardiomiopatia diabetica con un peptido gpl-1. |
| DK1355942T3 (da) | 2000-12-07 | 2008-11-17 | Lilly Co Eli | GLP-1-fusionsproteiner |
| MXPA03005135A (es) | 2000-12-13 | 2003-12-04 | Lilly Co Eli | Regimen de tratamiento cronico usando peptidos insulinotropicos similares al glucagon. |
| GB2371227A (en) | 2001-01-10 | 2002-07-24 | Grandis Biotech Gmbh | Crystallisation - resistant aqueous growth hormone formulations |
| US6573237B2 (en) | 2001-03-16 | 2003-06-03 | Eli Lilly And Company | Protein formulations |
| CN1162446C (zh) | 2001-05-10 | 2004-08-18 | 上海华谊生物技术有限公司 | 促胰岛素分泌肽衍生物 |
| AU2002308706A1 (en) | 2001-06-01 | 2002-12-16 | Eli Lilly And Company | Glp-1 formulations with protracted time action |
| DE60224284T2 (de) | 2001-06-28 | 2008-12-18 | Novo Nordisk A/S | Stabile formulierung von modifiziertem glp-1 |
| EP1485707B1 (en) | 2001-07-16 | 2009-01-14 | caprotec bioanalytics GmbH | Capture compounds, collections thereof and methods for analyzing the proteome and complex compositions |
| EP2022505B1 (en) | 2001-07-31 | 2011-12-14 | The Government of the United States of America, as represented by the Secretary of the Department of Health and Human Services | GLP-1, exendin-4, peptide analogs and uses thereof |
| US7238663B2 (en) | 2001-08-28 | 2007-07-03 | Eli Lilly And Company | Pre-mixes of GLP-1 and basal insulin |
| EP1448222A4 (en) | 2001-10-19 | 2006-05-17 | Lilly Co Eli | BIPHASIC MIXTURES OF GLP-1 AND INSULIN |
| EP2261250B1 (en) | 2001-12-21 | 2015-07-01 | Human Genome Sciences, Inc. | GCSF-Albumin fusion proteins |
| AU2002364587A1 (en) | 2001-12-21 | 2003-07-30 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7105489B2 (en) | 2002-01-22 | 2006-09-12 | Amylin Pharmaceuticals, Inc. | Methods and compositions for treating polycystic ovary syndrome |
| JP4417113B2 (ja) | 2002-02-20 | 2010-02-17 | エミスフェアー・テクノロジーズ・インク | Ｇｌｐ−１分子の投与方法 |
| ES2311094T3 (es) | 2002-02-27 | 2009-02-01 | Immunex Corporation | Composicion estabilizada de tnfr-fc que comprende arginina. |
| DK1502102T3 (da) | 2002-03-11 | 2009-05-04 | Caprotec Bioanalytics Gmbh | Forbindelser og fremgangsmåder til analysering af proteomet |
| US7141240B2 (en) | 2002-03-12 | 2006-11-28 | Cedars-Sinai Medical Center | Glucose-dependent insulin-secreting cells transfected with a nucleotide sequence encoding GLP-1 |
| WO2003084563A1 (en) | 2002-04-04 | 2003-10-16 | Novo Nordisk A/S | Glp-1 agonist and cardiovascular complications |
| JP2005530732A (ja) | 2002-04-10 | 2005-10-13 | イーライ・リリー・アンド・カンパニー | 胃不全麻痺の治療 |
| US6861236B2 (en) | 2002-05-24 | 2005-03-01 | Applied Nanosystems B.V. | Export and modification of (poly)peptides in the lantibiotic way |
| AU2003232172A1 (en) | 2002-06-14 | 2003-12-31 | Novo Nordisk A/S | Combined use of a modulator of cd3 and a glp-1 compound |
| US20040037826A1 (en) | 2002-06-14 | 2004-02-26 | Michelsen Birgitte Koch | Combined use of a modulator of CD3 and a GLP-1 compound |
| DE10227232A1 (de) | 2002-06-18 | 2004-01-15 | Aventis Pharma Deutschland Gmbh | Saure Insulinzubereitungen mit verbesserter Stabilität |
| ES2327328T3 (es) | 2002-07-04 | 2009-10-28 | Zealand Pharma A/S | Glp-1 y procedimientos para el tratamiento de la diabetes. |
| US20070065469A1 (en) | 2002-07-09 | 2007-03-22 | Michael Betz | Liquid formulations with high concentration of human growth hormone (high) comprising glycine |
| US20060165733A1 (en) | 2002-07-09 | 2006-07-27 | Michael Betz | Liquid formulations with high concentration of hunan growth hormone (hgh) comprising phenol |
| US20040038865A1 (en) | 2002-08-01 | 2004-02-26 | Mannkind Corporation | Cell transport compositions and uses thereof |
| US20080260838A1 (en) | 2003-08-01 | 2008-10-23 | Mannkind Corporation | Glucagon-like peptide 1 (glp-1) pharmaceutical formulations |
| WO2004012672A2 (en) | 2002-08-01 | 2004-02-12 | Mannkind Corporation | Cell transport compositions and uses thereof |
| HRP20050157B1 (en) | 2002-08-21 | 2013-01-31 | Boehringer Ingelheim Pharma | 8-[3-amino-piperidin-1-yl]-xanthines,the production thereof and the use of the same as medicaments |
| US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| US7544657B2 (en) | 2002-10-02 | 2009-06-09 | Zealand Pharma A/S | Stabilized Exendin-4 compounds |
| US6969702B2 (en) | 2002-11-20 | 2005-11-29 | Neuronova Ab | Compounds and methods for increasing neurogenesis |
| US20050209142A1 (en) | 2002-11-20 | 2005-09-22 | Goran Bertilsson | Compounds and methods for increasing neurogenesis |
| SI1583541T1 (sl) | 2002-11-20 | 2011-08-31 | Neuronova Ab | Spojine in postopki za povečanje nevrogeneze |
| US20040209803A1 (en) | 2002-12-19 | 2004-10-21 | Alain Baron | Compositions for the treatment and prevention of nephropathy |
| AU2003297356A1 (en) | 2002-12-17 | 2004-07-14 | Amylin Pharmaceuticals, Inc. | Prevention and treatment of cardiac arrhythmias |
| US7790681B2 (en) | 2002-12-17 | 2010-09-07 | Amylin Pharmaceuticals, Inc. | Treatment of cardiac arrhythmias with GLP-1 receptor ligands |
| GB0300571D0 (en) | 2003-01-10 | 2003-02-12 | Imp College Innovations Ltd | Modification of feeding behaviour |
| ES2512499T3 (es) | 2003-04-08 | 2014-10-24 | Yeda Research And Development Co., Ltd. | Fármacos pegilados reversibles |
| WO2004089985A1 (en) | 2003-04-11 | 2004-10-21 | Novo Nordisk A/S | Stable pharmaceutical compositions |
| AU2004240630B2 (en) | 2003-05-15 | 2010-10-07 | Trustees Of Tufts College | Stable analogs of peptide and polypeptide therapeutics |
| KR101128320B1 (ko) | 2003-05-23 | 2012-04-12 | 넥타르 테라퓨틱스 | 아미도카르보네이트 연결기를 갖는 ｐｅｇ 유도체 |
| US7947261B2 (en) | 2003-05-23 | 2011-05-24 | Nektar Therapeutics | Conjugates formed from polymer derivatives having particular atom arrangements |
| US8008255B2 (en) | 2003-05-30 | 2011-08-30 | Amylin Pharmaceuticals, Inc. | Methods and compositions for enhanced transmucosal delivery of peptides and proteins |
| ATE529126T1 (de) | 2003-06-03 | 2011-11-15 | Novo Nordisk As | Stabilisierte pharmazeutische peptid zusammensetzungen |
| CA2527743A1 (en) | 2003-06-03 | 2004-12-09 | Novo Nordisk A/S | Stabilized pharmaceutical peptide compositions |
| JP2007524592A (ja) | 2003-06-03 | 2007-08-30 | ノボ・ノルデイスク・エー／エス | 安定化された薬学的ペプチド組成物 |
| JP4936884B2 (ja) | 2003-06-03 | 2012-05-23 | ノボ・ノルデイスク・エー／エス | 安定化された薬学的ペプチド組成物 |
| US8921311B2 (en) | 2003-08-01 | 2014-12-30 | Mannkind Corporation | Method for treating hyperglycemia |
| EP2264065B1 (en) | 2003-08-05 | 2017-03-08 | Novo Nordisk A/S | Novel insulin derivatives |
| WO2005019261A1 (en) | 2003-08-21 | 2005-03-03 | Novo Nordisk A/S | Separation of polypeptides comprising a racemized amino acid |
| US20060247167A1 (en) | 2003-09-01 | 2006-11-02 | Novo Nordisk A/S | Stable formulations of peptides |
| EP1663295A2 (en) | 2003-09-01 | 2006-06-07 | Novo Nordisk A/S | Stable formulations of peptides |
| JP2007537981A (ja) | 2003-09-19 | 2007-12-27 | ノボ ノルディスク アクティーゼルスカブ | 新規の血漿タンパク質親和性タグ |
| US20060287221A1 (en) | 2003-11-13 | 2006-12-21 | Novo Nordisk A/S | Soluble pharmaceutical compositions for parenteral administration comprising a GLP-1 peptide and an insulin peptide of short time action for treatment of diabetes and bulimia |
| ES2373660T3 (es) | 2003-11-13 | 2012-02-07 | Novo Nordisk A/S | Composición farmacéutica que comprende un análogo insulinotrópico de glp-1 (7-37), insulina asp(b28) y un tensioactivo. |
| US20050281879A1 (en) | 2003-11-14 | 2005-12-22 | Guohua Chen | Excipients in drug delivery vehicles |
| US20050106214A1 (en) | 2003-11-14 | 2005-05-19 | Guohua Chen | Excipients in drug delivery vehicles |
| CN1882356B (zh) | 2003-11-20 | 2015-02-25 | 诺沃挪第克公司 | 对于生产和用于注射装置中是最佳的含有丙二醇的肽制剂 |
| WO2005081619A2 (en) | 2003-11-20 | 2005-09-09 | Neuronova Ab | Compounds and methods for increasing neurogenesis |
| EP1692168B1 (en) | 2003-12-03 | 2011-07-20 | Novo Nordisk A/S | Single-chain insulin |
| JP2007513965A (ja) | 2003-12-10 | 2007-05-31 | ネクター セラピューティクス アラバマ，コーポレイション | ポリマー・活性剤複合体の二つの集団を含む組成物 |
| US20050143303A1 (en) | 2003-12-26 | 2005-06-30 | Nastech Pharmaceutical Company Inc. | Intranasal administration of glucose-regulating peptides |
| US20060210614A1 (en) | 2003-12-26 | 2006-09-21 | Nastech Pharmaceutical Company Inc. | Method of treatment of a metabolic disease using intranasal administration of exendin peptide |
| CN1938334A (zh) * | 2004-01-30 | 2007-03-28 | 瓦拉塔药品公司 | Glp－1激动剂和胃泌素化合物的联合使用 |
| EP1718665B1 (en) | 2004-02-11 | 2013-04-10 | Amylin Pharmaceuticals, LLC | Hybrid polypeptides with selectable properties |
| JP2008500281A (ja) | 2004-02-11 | 2008-01-10 | 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 | アミリンファミリーペプチドおよびそれらを作成し使用するための方法 |
| US8076288B2 (en) | 2004-02-11 | 2011-12-13 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides having glucose lowering activity |
| EP2335715A3 (en) | 2004-02-11 | 2013-12-18 | Amylin Pharmaceuticals, LLC | Pancreatic polypeptide family motifs and polypeptides comprising the same |
| US7399744B2 (en) | 2004-03-04 | 2008-07-15 | Amylin Pharmaceuticals, Inc. | Methods for affecting body composition |
| CN1968700A (zh) | 2004-04-15 | 2007-05-23 | 阿尔克姆斯有限公司 | 聚合物基的持续释放装置 |
| US7456254B2 (en) | 2004-04-15 | 2008-11-25 | Alkermes, Inc. | Polymer-based sustained release device |
| US20060110423A1 (en) | 2004-04-15 | 2006-05-25 | Wright Steven G | Polymer-based sustained release device |
| US20090069226A1 (en) | 2004-05-28 | 2009-03-12 | Amylin Pharmaceuticals, Inc. | Transmucosal delivery of peptides and proteins |
| WO2005117584A2 (en) | 2004-05-28 | 2005-12-15 | Amylin Pharmaceuticals, Inc | Improved transmucosal delivery of peptides and proteins |
| EP1758575A1 (en) | 2004-06-11 | 2007-03-07 | Novo Nordisk A/S | Counteracting drug-induced obesity using glp-1 agonists |
| US20070021346A1 (en) | 2005-05-26 | 2007-01-25 | Ewing William R | N-terminally modified GLP-1 receptor modulators |
| US7875700B2 (en) | 2004-07-19 | 2011-01-25 | Biocon Limited | Cation complexes of insulin compound conjugates, formulation and uses thereof |
| US7638299B2 (en) | 2004-07-21 | 2009-12-29 | Ambrx, Inc. | Biosynthetic polypeptides utilizing non-naturally encoded amino acids |
| BRPI0514115A (pt) | 2004-08-03 | 2008-05-27 | Biorexis Technology Inc | terapia de combinação empregando-se proteìnas de fusão de transferrina compreendendo glp-1 |
| US20070204633A1 (en) | 2004-08-16 | 2007-09-06 | Whisson Maxwell E | Apparatus and Method for Cooling of Air |
| JP4965446B2 (ja) | 2004-08-31 | 2012-07-04 | ノヴォ ノルディスク アー／エス | ペプチド、ポリペプチド及びタンパク質の安定化のためのトリス（ヒドロキシメチル）アミノメタンの使用 |
| DE102004043153B4 (de) | 2004-09-03 | 2013-11-21 | Philipps-Universität Marburg | Erfindung betreffend GLP-1 und Exendin |
| EP1790665B1 (en) | 2004-09-07 | 2014-11-05 | Chugai Seiyaku Kabushiki Kaisha | Process for producing water-soluble modified hyaluronic acid |
| EP1791554A2 (en) | 2004-09-17 | 2007-06-06 | Novo Nordisk A/S | Pharmaceutical compositions containing insulin and insulinotropic peptide |
| KR101506925B1 (ko) | 2004-10-01 | 2015-03-30 | 램스코르 인코포레이티드 | 편리하게 이식가능한 서방형 약물 조성물 |
| WO2006037811A2 (en) | 2004-10-07 | 2006-04-13 | Novo Nordisk A/S | Protracted exendin-4 compounds |
| US7595294B2 (en) | 2004-10-08 | 2009-09-29 | Transition Therapeutics, Inc. | Vasoactive intestinal polypeptide pharmaceuticals |
| JP4944034B2 (ja) | 2004-10-13 | 2012-05-30 | アイシス ファーマシューティカルズ， インコーポレーテッド | Ｐｔｐ１ｂ発現のアンチセンス調節 |
| US7442682B2 (en) | 2004-10-19 | 2008-10-28 | Nitto Denko Corporation | Transepithelial delivery of peptides with incretin hormone activities |
| CN101056650A (zh) | 2004-11-12 | 2007-10-17 | 诺和诺德公司 | 促胰岛素肽的稳定制剂 |
| ES2575984T3 (es) | 2004-11-12 | 2016-07-04 | Novo Nordisk A/S | Formulaciones estables de péptidos que contienen un análogo de GLP-1 acilado y una insulina basal |
| WO2006051110A2 (en) | 2004-11-12 | 2006-05-18 | Novo Nordisk A/S | Stable formulations of insulinoptropic peptides |
| SG157423A1 (en) | 2004-12-02 | 2009-12-29 | Domantis Ltd | Bispecific domain antibodies targeting serum albumin and glp-1 or pyy |
| AU2005316524B2 (en) | 2004-12-13 | 2012-01-12 | Amylin Pharmaceuticals, Llc | Pancreatic Polypeptide Family motifs, polypeptides and methods comprising the same |
| EP1827501B2 (en) | 2004-12-21 | 2013-11-20 | Nektar Therapeutics | Stabilized polymeric thiol reagents |
| CN101044162B (zh) | 2004-12-22 | 2010-10-27 | 伊莱利利公司 | Glp-1类似物融合蛋白质制剂 |
| US20070021336A1 (en) | 2004-12-24 | 2007-01-25 | Christen Anderson | Use of GLP-1 and agonists thereof to prevent cardiac myocyte apoptosis |
| US8716221B2 (en) | 2005-01-14 | 2014-05-06 | Wuxi Grandchamp Pharmaceutical Technology Co., Ltd. | Modified exendins and uses thereof |
| EP1845105A4 (en) | 2005-01-14 | 2009-02-18 | Wuxi Grandchamp Pharmaceutical | MODIFIED EXENDINES AND CORRESPONDING USES |
| WO2006082588A2 (en) | 2005-02-07 | 2006-08-10 | Pharmalight Inc. | Method and device for ophthalmic administration of active pharmaceutical ingredients |
| US8263545B2 (en) | 2005-02-11 | 2012-09-11 | Amylin Pharmaceuticals, Inc. | GIP analog and hybrid polypeptides with selectable properties |
| EP1853627A2 (en) | 2005-02-11 | 2007-11-14 | Amylin Pharmaceuticals, Inc. | Gip analog and hybrid polypeptides with selectable properties |
| WO2006097535A2 (en) | 2005-03-18 | 2006-09-21 | Novo Nordisk A/S | Peptide agonists of the glucagon family with secretin like activity |
| EP1888103B1 (en) | 2005-04-11 | 2012-03-21 | Amylin Pharmaceuticals, Inc. | Use of glp-1, exendin and agonists thereof to delay or prevent cardiac remodeling |
| WO2006114396A1 (en) | 2005-04-24 | 2006-11-02 | Novo Nordisk A/S | Injection device |
| EP1888118B1 (en) | 2005-05-25 | 2016-08-17 | Novo Nordisk A/S | Polypeptide formulations stabilized with ethylenediamine |
| ES2399645T3 (es) | 2005-06-06 | 2013-04-02 | Camurus Ab | Formulaciones de análogos de GLP-1 |
| WO2006134340A2 (en) | 2005-06-13 | 2006-12-21 | Imperial Innovations Limited | Oxyntomodulin analogues and their effects on feeding behaviour |
| GB0511986D0 (en) | 2005-06-13 | 2005-07-20 | Imp College Innovations Ltd | Novel compounds and their effects on feeding behaviour |
| CN101242858B (zh) | 2005-06-16 | 2012-12-19 | 尼克塔治疗公司 | 具有可降解键的轭合物以及用于制备这种轭合物的聚合物试剂 |
| EP2099495A2 (en) | 2005-08-04 | 2009-09-16 | Nektar Therapeutics AL, Corporation | Conjugates of a g-csf moiety and a polymer |
| WO2007016764A1 (en) | 2005-08-06 | 2007-02-15 | Qinghua Wang | Composition and method for prevention and treatment of type i diabetes |
| EP1922336B1 (en) | 2005-08-11 | 2012-11-21 | Amylin Pharmaceuticals, LLC | Hybrid polypeptides with selectable properties |
| PT3524261T (pt) | 2005-08-19 | 2024-01-12 | Amylin Pharmaceuticals Llc | Exendina para o tratamento da diabetes e redução do peso corporal |
| IN2014DN09128A (enExample) | 2005-09-14 | 2015-07-10 | Mannkind Corp | |
| BRPI0616195A2 (pt) | 2005-09-20 | 2011-06-14 | Novartis Ag | uso de um inibidor de dpp-iv para reduzir eventos hipoglicÊmicos |
| WO2007047834A2 (en) | 2005-10-18 | 2007-04-26 | Biocon Limited | Oral peptide conjugates for metabolic diseases |
| US7687608B2 (en) | 2005-10-19 | 2010-03-30 | Smartcells, Inc. | Methods for reducing the mitogenicity of lectin compositions |
| US8338368B2 (en) | 2005-11-07 | 2012-12-25 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting physiological solubility and stability |
| WO2007053946A1 (en) | 2005-11-09 | 2007-05-18 | Conjuchem Biotechnologies Inc. | Method of treating diabetes and/or obesity with reduced nausea side effects using an insulinotropic peptide conjugated to albumin |
| EP1965828A2 (en) | 2005-12-02 | 2008-09-10 | Nastech Pharmaceutical Company Inc. | Pharmaceutical formulation for increased epithelial permeability of glucose-regulating peptide |
| EP1968607B1 (en) | 2005-12-02 | 2014-01-15 | Nabil Habib Lab | Treatment of cancer and other diseases |
| BRPI0620571A2 (pt) | 2005-12-08 | 2011-11-22 | Nastech Pharm Co | formulação farmacêutica aquosa, forma de dosagem de exendina, solução aquosa, uso de uma formulação farmacêutica, e uso de uma formulação farmacêutica aquosa |
| JP5096363B2 (ja) | 2005-12-16 | 2012-12-12 | ネクター セラピューティックス | Ｇｌｐ−１のポリマ複合体 |
| US8841255B2 (en) | 2005-12-20 | 2014-09-23 | Duke University | Therapeutic agents comprising fusions of vasoactive intestinal peptide and elastic peptides |
| US20130172274A1 (en) | 2005-12-20 | 2013-07-04 | Duke University | Methods and compositions for delivering active agents with enhanced pharmacological properties |
| US8178495B2 (en) | 2008-06-27 | 2012-05-15 | Duke University | Therapeutic agents comprising a GLP-1 receptor agonist and elastin-like peptide |
| US8334257B2 (en) | 2005-12-20 | 2012-12-18 | Duke University | Methods and compositions for delivering active agents with enhanced pharmacological properties |
| JP5242415B2 (ja) | 2006-01-18 | 2013-07-24 | フォアシーエイサー ファーマシューティカルズ インコーポレイテッド | 高い安定性を持つ薬理組成物 |
| WO2007092772A2 (en) | 2006-02-03 | 2007-08-16 | Medimmune, Inc. | Protein formulations |
| US7704953B2 (en) | 2006-02-17 | 2010-04-27 | Mdrna, Inc. | Phage displayed cell binding peptides |
| JP5412273B2 (ja) | 2006-03-21 | 2014-02-12 | アミリン・ファーマシューティカルズ，リミテッド・ライアビリティ・カンパニー | ペプチド−ぺプチダーゼ阻害剤及びその使用 |
| RU2419452C2 (ru) | 2006-04-13 | 2011-05-27 | Ипсен Фарма С.А.С. | ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ hGLP-1, ЭКСЕНДИНА-4 И ИХ АНАЛОГОВ |
| KR20150042304A (ko) | 2006-04-14 | 2015-04-20 | 맨카인드 코포레이션 | 글루카곤 유사 펩타이드 1 （ｇｌｐ-1） 약제학적 제제 |
| PE20080251A1 (es) | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
| WO2007133778A2 (en) | 2006-05-12 | 2007-11-22 | Amylin Pharmaceuticals, Inc. | Methods to restore glycemic control |
| EA200870575A1 (ru) | 2006-05-26 | 2009-08-28 | Амилин Фармасьютикалз, Инк. | Композиции и способы лечения застойной сердечной недостаточности |
| WO2007139589A1 (en) | 2006-05-26 | 2007-12-06 | Bristol-Myers Squibb Company | Sustained release glp-1 receptor modulators |
| PT2038423E (pt) | 2006-06-21 | 2013-03-27 | Biocon Ltd | Método de produção de um polipéptido biologicamente activo possuindo actividade insulinotrópica |
| SI2494959T1 (sl) | 2006-07-05 | 2015-04-30 | Foamix Pharmaceuticals Ltd. | Penilno sredstvo dikarboksilne kisline in njega farmacevtski sestavki |
| AU2007278994B2 (en) | 2006-07-24 | 2013-08-15 | Biorexis Pharmaceutical Corporation | Exendin fusion proteins |
| US7928186B2 (en) | 2006-08-02 | 2011-04-19 | Phoenix Pharmaceuticals, Inc. | Cell permeable bioactive peptide conjugates |
| US20090325860A1 (en) | 2006-08-04 | 2009-12-31 | Nastech Pharmaceutical Company Inc. | Compositions for intranasal delivery of human insulin and uses thereof |
| KR101200728B1 (ko) | 2006-08-09 | 2012-11-13 | 인타르시아 세라퓨틱스 인코포레이티드 | 삼투성 전달 시스템 및 피스톤 조립체 |
| WO2008021560A2 (en) | 2006-08-17 | 2008-02-21 | Amylin Pharmaceuticals, Inc. | Dpp-iv resistant gip hybrid polypeptides with selectable properties |
| US8497240B2 (en) | 2006-08-17 | 2013-07-30 | Amylin Pharmaceuticals, Llc | DPP-IV resistant GIP hybrid polypeptides with selectable properties |
| EP2057189B1 (en) * | 2006-08-25 | 2013-03-06 | Novo Nordisk A/S | Acylated exendin-4 compounds |
| CN102827284B (zh) | 2006-11-14 | 2015-07-29 | 上海仁会生物制药股份有限公司 | 带有聚乙二醇基团的Exendin或其类似物及其制剂和用途 |
| EP2124883A2 (en) | 2006-12-12 | 2009-12-02 | Amylin Pharmaceuticals, Inc. | Pharmaceutical formulations and methods for making the same |
| 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 |
| RU2432361C2 (ru) | 2007-01-05 | 2011-10-27 | КовЭкс Текнолоджиз Айэлэнд Лимитед | Соединения агонисты рецептора глюкагоноподобного белка-1 (glp-1r) |
| EP2124974B1 (en) | 2007-01-05 | 2017-03-15 | Indiana University Research and Technology Corporation | Glucagon analogs exhibiting enhanced solubility in physiological ph buffers |
| US20090098130A1 (en) * | 2007-01-05 | 2009-04-16 | Bradshaw Curt W | Glucagon-like protein-1 receptor (glp-1r) agonist compounds |
| CN101663317A (zh) * | 2007-01-05 | 2010-03-03 | CovX科技爱尔兰有限公司 | 胰高血糖素样蛋白-1受体glp-1r激动剂化合物 |
| WO2008098212A2 (en) | 2007-02-08 | 2008-08-14 | Diobex, Inc. | Extended release formulations of glucagon and other peptides and proteins |
| US8454971B2 (en) | 2007-02-15 | 2013-06-04 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
| WO2008130066A1 (en) | 2007-04-20 | 2008-10-30 | Kang Choon Lee | Mono modified exendin with polyethylene glycol or its derivatives and uses thereof |
| RU2440097C2 (ru) | 2007-04-23 | 2012-01-20 | Интарсия Терапьютикс, Инк. | Способ лечения диабета ii типа и ожирения, осмотическое устройство для доставки и способ его изготовления |
| US8236760B2 (en) | 2007-04-27 | 2012-08-07 | Cedars-Sinsai Medical Center | Use of GLP-1 receptor agonists for the treatment of short bowel syndrome |
| US7829664B2 (en) | 2007-06-01 | 2010-11-09 | Boehringer Ingelheim International Gmbh | Modified nucleotide sequence encoding glucagon-like peptide-1 (GLP-1), nucleic acid construct comprising same for production of glucagon-like peptide-1 (GLP-1), human cells comprising said construct and insulin-producing constructs, and methods of use thereof |
| EP2164519A2 (en) | 2007-06-08 | 2010-03-24 | Ascendis Pharma AS | Long-acting polymeric prodrugs of exendin |
| US7994122B2 (en) | 2007-06-15 | 2011-08-09 | Zealand Pharma A/S | Glucagon analogues |
| EP2175834B8 (en) | 2007-07-10 | 2012-08-22 | Eli Lilly And Company | Glp-1-fc fusion protein formulation |
| CA2693504A1 (en) | 2007-08-03 | 2009-02-12 | Eli Lilly And Company | Treatment for obesity |
| CN101366692A (zh) | 2007-08-15 | 2009-02-18 | 江苏豪森药业股份有限公司 | 一种稳定的艾塞那肽制剂 |
| NZ599756A (en) | 2007-08-30 | 2013-09-27 | Curedm Group Holdings Llc | Compositions and methods of using proislet peptides and analogs thereof |
| WO2009030771A1 (en) | 2007-09-05 | 2009-03-12 | Novo Nordisk A/S | Peptides derivatized with a-b-c-d- and their therapeutical use |
| US20100256056A1 (en) | 2007-09-07 | 2010-10-07 | Zheng Xin Dong | Analogues of exendin-4 and exendin-3 |
| US8785396B2 (en) | 2007-10-24 | 2014-07-22 | Mannkind Corporation | Method and composition for treating migraines |
| HUE025485T2 (en) | 2007-10-24 | 2016-02-29 | Mannkind Corp | Respiratory dry powder formulation containing GLP-1 for use in the treatment of hyperglycemia and diabetes by pulmonary administration |
| AU2008316636B2 (en) | 2007-10-24 | 2014-02-06 | Mannkind Corporation | Delivery of active agents |
| ES2558155T3 (es) | 2007-10-30 | 2016-02-02 | Indiana University Research And Technology Corporation | Compuestos que muestran actividad antagonista de glucacón y agonista de GLP-1 |
| MX2010004297A (es) | 2007-10-30 | 2010-05-03 | Univ Indiana Res & Tech Corp | Antagonistas de glucagon. |
| CN107412742B (zh) | 2007-11-16 | 2022-03-15 | 诺沃—诺迪斯克有限公司 | 包含glp-1肽或毒蜥外泌肽-4和基础胰岛素肽的药物组合物 |
| WO2009067268A1 (en) | 2007-11-23 | 2009-05-28 | Michael Rothkopf | Methods of enhancing diabetes resolution |
| CN101444618B (zh) | 2007-11-26 | 2012-06-13 | 杭州九源基因工程有限公司 | 含有艾塞那肽的药物制剂 |
| JP2011506442A (ja) | 2007-12-11 | 2011-03-03 | コンジュケム バイオテクノロジーズ インコーポレイテッド | インスリン分泌性ペプチド結合体の製剤 |
| BRPI0907371A2 (pt) | 2008-01-09 | 2015-11-24 | Sanofi Aventis Deutschland | derivados de insulina com um perfil de tempo-ação muito retardado |
| EP2249853A4 (en) | 2008-01-30 | 2012-12-26 | Univ Indiana Res & Tech Corp | ESTER BASED PEPTIDE PRODRUGS |
| RS58948B1 (sr) | 2008-02-01 | 2019-08-30 | Ascendis Pharma As | Prolek koji sadrži linker koji se može sam odcepiti |
| MY161108A (en) | 2008-02-06 | 2017-04-14 | Biocon Ltd | Fermentation medias and processes thereof |
| WO2009114959A1 (zh) | 2008-03-20 | 2009-09-24 | 中国人民解放军军事医学科学院毒物药物研究所 | 可注射用缓释药物制剂及其制备方法 |
| WO2009125423A2 (en) | 2008-04-07 | 2009-10-15 | National Institute Of Immunology | Compositions useful for the treatment of diabetes and other chronic disorder |
| TW200950799A (en) | 2008-05-07 | 2009-12-16 | Merrion Res Iii Ltd | Compositions of GnRH related compounds and processes of preparation |
| ES2552646T3 (es) | 2008-05-21 | 2015-12-01 | Amylin Pharmaceuticals, Inc. | Exendinas para disminuir el colesterol y los triglicéridos |
| WO2009143014A1 (en) | 2008-05-23 | 2009-11-26 | Amylin Pharmaceuticals, Inc. | Glp-1 receptor agonist bioassays |
| US9358352B2 (en) | 2008-06-13 | 2016-06-07 | Mannkind Corporation | Dry powder drug delivery system and methods |
| US8485180B2 (en) | 2008-06-13 | 2013-07-16 | Mannkind Corporation | Dry powder drug delivery system |
| CN109568740B (zh) | 2008-06-13 | 2022-05-27 | 曼金德公司 | 干粉吸入器和用于药物输送的系统 |
| JP5775450B2 (ja) | 2008-06-17 | 2015-09-09 | 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 | グルカゴン／ｇｌｐ−１受容体コアゴニスト |
| KR20110039230A (ko) | 2008-06-17 | 2011-04-15 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 생리학적 ｐＨ 완충액에서 강화된 용해도 및 안정성을 나타내는 글루카곤 유사체 |
| CN102083854A (zh) | 2008-06-17 | 2011-06-01 | 大塚化学株式会社 | 附加了糖链的glp-1肽 |
| 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 |
| EP2303247A4 (en) | 2008-07-21 | 2012-08-01 | Syneron Medical Ltd | TRANSDERMALES SYSTEM FOR THE EXTENDED RELEASE OF INCRETINS AND INCRETIN MIMETIC PEPTIDES |
| WO2010013012A2 (en) | 2008-08-01 | 2010-02-04 | Lund University Bioscience Ab | Novel polypeptides and uses thereof |
| CN101670096B (zh) | 2008-09-11 | 2013-01-16 | 杭州九源基因工程有限公司 | 含有艾塞那肽的药物制剂 |
| RS59913B1 (sr) | 2008-10-17 | 2020-03-31 | Sanofi Aventis Deutschland | Kombinacija insulina i glp-1-agonista |
| ES2620610T3 (es) | 2008-12-10 | 2017-06-29 | Glaxosmithkline Llc | Composiciones farmacéuticas de albiglutide |
| EP2370462B1 (en) | 2008-12-15 | 2014-07-16 | Zealand Pharma A/S | Glucagon analogues |
| CN102282166B (zh) | 2008-12-15 | 2015-04-01 | 西兰制药公司 | 胰高血糖素类似物 |
| MX2011006314A (es) | 2008-12-15 | 2011-09-22 | Zealand Pharma As | Analogos de glucagon. |
| MA32970B1 (fr) | 2008-12-15 | 2012-01-02 | Zealand Pharma As | Analogues du glucagon |
| RU2550696C2 (ru) | 2008-12-19 | 2015-05-10 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Основанные на амидах пролекарства пептидов глюкагонового надсемейства |
| CN101538323B (zh) | 2009-01-13 | 2012-05-09 | 深圳翰宇药业股份有限公司 | 一种纯化艾塞那肽的方法 |
| DE102009006602A1 (de) | 2009-01-29 | 2010-08-05 | Bayer Schering Pharma Aktiengesellschaft | Alkylamino-substituierte Dicyanopyridine und deren Aminosäureester-Prodrugs |
| WO2010096052A1 (en) | 2009-02-19 | 2010-08-26 | Merck Sharp & Dohme Corp. | Oxyntomodulin analogs |
| KR101733816B1 (ko) | 2009-03-04 | 2017-05-08 | 맨카인드 코포레이션 | 개선된 건조 분말 약물 전달 시스템 |
| WO2010100241A1 (en) | 2009-03-05 | 2010-09-10 | Sanofi-Aventis Deutschland Gmbh | Drug delivery device with retractable needle |
| US8642544B2 (en) | 2009-04-01 | 2014-02-04 | Amylin Pharmaceuticals, Llc | N-terminus conformationally constrained GLP-1 receptor agonist compounds |
| WO2010118034A2 (en) | 2009-04-06 | 2010-10-14 | Board Of Regents, The University Of Texas System | Cyclic peptide analogues for non-invasive imaging of pancreatic beta-cells |
| RU2503688C2 (ru) | 2009-04-22 | 2014-01-10 | Алтеоген, Инк | Слитый белок или пептид с увеличенным временем полужизни in vivo, поддерживаемый за счет замедленного высвобождения in vivo, и способ увеличения времени полужизни in vivo с его применением |
| 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 |
| CN101559041B (zh) | 2009-05-19 | 2014-01-15 | 中国科学院过程工程研究所 | 粒径均一的多肽药物缓释微球或微囊制剂及制备方法 |
| DK3189868T3 (da) | 2009-05-20 | 2025-01-13 | Sanofi Aventis Deutschland | Prop til lægemiddelholdige patroner i lægemiddelfremføringsanordninger omfattende et elektronisk kodningselement |
| WO2010133675A1 (en) | 2009-05-20 | 2010-11-25 | Sanofi-Aventis Deutschland Gmbh | A bung for drug containing cartridges in drug delivery devices |
| US20120231022A1 (en) | 2009-05-28 | 2012-09-13 | Amylin Pharmaceuticals, Inc. | Glp-1 receptor agonist compounds for sleep enhancement |
| EP2440235A1 (en) | 2009-06-11 | 2012-04-18 | Novo Nordisk A/S | Glp-1 and fgf21 combinations for treatment of diabetes type 2 |
| EP2443146B1 (en) | 2009-06-16 | 2016-10-05 | Indiana University Research And Technology Corporation | Gip receptor-active glucagon compounds |
| RU2012103240A (ru) | 2009-07-02 | 2013-08-10 | Ангиокем Инк. | Мультимерные пептидные конъюгаты и их применение |
| AP3329A (en) | 2009-07-13 | 2015-06-30 | Zealand Pharma As | Acylated glucagon analogues |
| CN101601646B (zh) | 2009-07-22 | 2011-03-23 | 南京凯瑞尔纳米生物技术有限公司 | 治疗糖尿病的鼻腔滴剂及其制备方法 |
| WO2011011675A1 (en) | 2009-07-23 | 2011-01-27 | Zelos Therapeutics, Inc. | Pharmaceutically acceptable formulations/compositions for peptidyl drugs |
| KR20120089843A (ko) | 2009-07-31 | 2012-08-14 | 사노피-아벤티스 도이칠란트 게엠베하 | 인슐린 링커 접합체를 포함한 프로드럭 |
| WO2011017835A1 (en) | 2009-08-11 | 2011-02-17 | Nanjing University | Preparation method of protein or peptide nanoparticles for in vivo drug delivery by unfolding and refolding |
| CN101993485B (zh) | 2009-08-20 | 2013-04-17 | 重庆富进生物医药有限公司 | 促胰岛素分泌肽类似物同源二聚体及其用途 |
| US20120148586A1 (en) | 2009-08-27 | 2012-06-14 | Joyce Ching Tsu Chou | Glucagon-like protein-1 receptor (glp-1r) agonists for treating autoimmune disorders |
| CN104147611A (zh) | 2009-09-30 | 2014-11-19 | 葛兰素集团有限公司 | 具有延长的半衰期的药物融合体和缀合物 |
| WO2011049713A2 (en) | 2009-10-22 | 2011-04-28 | Biodel Inc. | Stabilized glucagon solutions |
| US20110097386A1 (en) | 2009-10-22 | 2011-04-28 | Biodel, Inc. | Stabilized glucagon solutions |
| US9610329B2 (en) | 2009-10-22 | 2017-04-04 | Albireo Pharma, Inc. | Stabilized glucagon solutions |
| JPWO2011052523A1 (ja) | 2009-10-30 | 2013-03-21 | 株式会社糖鎖工学研究所 | 抗原性ｇｌｐ−１アナログの糖鎖付加体 |
| EP2496583B1 (en) | 2009-11-02 | 2014-12-10 | Pfizer Inc | Dioxa-bicyclo[3.2.1]octane-2,3,4-triol derivatives |
| US20120294855A1 (en) | 2009-11-03 | 2012-11-22 | Eli Lilly & Company | Glp-1 receptor agonist compounds for obstructive sleep apnea |
| ES2534191T3 (es) | 2009-11-13 | 2015-04-20 | Sanofi-Aventis Deutschland Gmbh | Composición farmacéutica que comprende un agonista de GLP-1, una insulina y metionina |
| CA2780043C (en) | 2009-11-13 | 2019-01-29 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical composition comprising a glp-1 agonist and methionine |
| CN102753170A (zh) | 2009-12-15 | 2012-10-24 | 新陈代谢解决方案开发公司 | 治疗糖尿病及其它代谢性疾病的ppar节制的噻唑烷二酮和组合 |
| JP5634526B2 (ja) | 2009-12-15 | 2014-12-03 | メタボリック ソリューションズ ディベロップメント カンパニー， エルエルシー | 代謝性疾患を処置するためのｐｐａｒ温存チアゾリジンジオン塩 |
| JP2013514371A (ja) | 2009-12-15 | 2013-04-25 | メタボリック ソリューションズ ディベロップメント カンパニー， エルエルシー | 肥満および他の代謝性疾患の処置のためのＰＰＡＲγ温存チアゾリジンジオンならびに組み合わせ物 |
| DK2512470T3 (en) | 2009-12-15 | 2017-02-27 | Octeta Therapeutics Llc | PPAR SAVING THIAZOLIDE INDIA AND COMBINATIONS TO TREAT NEURODEGENERATIVE DISEASES |
| CN102791731B (zh) | 2009-12-16 | 2016-04-20 | 诺沃—诺迪斯克有限公司 | Glp-1类似物和衍生物 |
| US8703701B2 (en) | 2009-12-18 | 2014-04-22 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
| CN102933200B (zh) | 2009-12-18 | 2015-11-25 | 莱迪杜德制药公司 | 包含磷脂的单相凝胶组合物 |
| CN101798588B (zh) * | 2009-12-21 | 2015-09-09 | 上海仁会生物制药股份有限公司 | Glp-1受体激动剂生物学活性测定方法 |
| AR079345A1 (es) | 2009-12-22 | 2012-01-18 | Lilly Co Eli | Analogo peptidico de oxintomodulina |
| AR079344A1 (es) | 2009-12-22 | 2012-01-18 | Lilly Co Eli | Analogo peptidico de oxintomodulina, composicion farmaceutica que lo comprende y uso para preparar un medicamento util para tratar diabetes no insulinodependiente y/u obesidad |
| PH12012501494A1 (en) | 2010-01-20 | 2012-10-22 | Zealand Pharma As | Treatment of cardiac conditions |
| IN2012DN06437A (enExample) | 2010-01-27 | 2015-10-09 | Univ Indiana Res & Tech Corp | |
| KR101772855B1 (ko) | 2010-02-01 | 2017-08-31 | 사노피-아벤티스 도이칠란트 게엠베하 | 카트리지 홀더, 약물 전달 장치 및 카트리지를 카트리지 홀더에 고정시키기 위한 방법 |
| WO2011109784A1 (en) | 2010-03-05 | 2011-09-09 | Conjuchem, Llc | Formulation of insulinotropic peptide conjugates |
| WO2011119857A2 (en) | 2010-03-24 | 2011-09-29 | Shifamed, Llc | Intravascular tissue disruption |
| 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 |
| WO2011117415A1 (en) | 2010-03-26 | 2011-09-29 | Novo Nordisk A/S | Novel glucagon analogues |
| CN103079587B (zh) | 2010-05-13 | 2016-05-11 | 印第安纳大学研究及科技有限公司 | 呈现核激素受体活性的胰高血糖素超家族肽 |
| KR20130111923A (ko) | 2010-05-13 | 2013-10-11 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | G-단백결합 수용체 활성을 나타내는 글루카곤 슈퍼패밀리 펩티드 |
| AU2011202239C1 (en) | 2010-05-19 | 2017-03-16 | Sanofi | Long-acting formulations of insulins |
| WO2011144751A1 (en) | 2010-05-20 | 2011-11-24 | Glaxo Group Limited | Improved anti-serum albumin binding variants |
| WO2011156407A2 (en) | 2010-06-09 | 2011-12-15 | Amylin Pharmaceuticals, Inc. | Glp-1 receptor agonists to treat pancre-atitis |
| CN101891823B (zh) | 2010-06-11 | 2012-10-03 | 北京东方百泰生物科技有限公司 | 一种Exendin-4及其类似物融合蛋白 |
| US8636711B2 (en) | 2010-06-14 | 2014-01-28 | Legacy Emanuel Hospital & Health Center | Stabilized glucagon solutions and uses therefor |
| UY33462A (es) | 2010-06-23 | 2012-01-31 | Zealand Pharma As | Analogos de glucagon |
| US9234023B2 (en) | 2010-06-24 | 2016-01-12 | Biousian Biosystems, Inc. | Glucagon-like peptide-1 glycopeptides |
| RU2580317C2 (ru) | 2010-06-24 | 2016-04-10 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Пептидные пролекарства, принадлежащие к суперсемейству амид-содержащих глюкагонов |
| WO2011163473A1 (en) | 2010-06-25 | 2011-12-29 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting enhanced solubility and stability in physiological ph buffers |
| US20130137645A1 (en) | 2010-07-19 | 2013-05-30 | Mary S. Rosendahl | Modified peptides and proteins |
| WO2012012460A1 (en) | 2010-07-19 | 2012-01-26 | Xeris Pharmaceuticals, Inc. | Stable glucagon formulations for the treatment of hypoglycemia |
| JP2013535471A (ja) | 2010-07-28 | 2013-09-12 | アミリン・ファーマシューティカルズ，リミテッド・ライアビリティ・カンパニー | 安定化した領域を有するｇｌｐ−１受容体アゴニスト化合物 |
| CN102397558B (zh) | 2010-09-09 | 2013-08-14 | 中国人民解放军军事医学科学院毒物药物研究所 | Exendin-4类似物的定位聚乙二醇化修饰物及其用途 |
| EP2438930A1 (en) | 2010-09-17 | 2012-04-11 | Sanofi-Aventis Deutschland GmbH | Prodrugs comprising an exendin linker conjugate |
| CA2812951A1 (en) | 2010-09-28 | 2012-04-19 | Amylin Pharmaceuticals, Llc | Engineered polypeptides having enhanced duration of action |
| JP5894174B2 (ja) | 2010-11-03 | 2016-03-23 | アレコー リミテッド | グルカゴンを含む新規組成物 |
| JP6092113B2 (ja) | 2010-11-09 | 2017-03-08 | マンカインド コーポレイション | セロトニン受容体アゴニストおよびジケトピペラジンを含む偏頭痛治療のための組成物 |
| EP2460552A1 (en) | 2010-12-06 | 2012-06-06 | Sanofi-Aventis Deutschland GmbH | Drug delivery device with locking arrangement for dose button |
| CN102552883B (zh) | 2010-12-09 | 2014-02-19 | 天津药物研究院 | 一种多肽复合物、药物组合物、其制备方法和应用 |
| PT2651398T (pt) | 2010-12-16 | 2018-03-09 | Novo Nordisk As | Composições sólidas compreendendo um agonista de glp-1 e um sal de ácido n-(8-(2-hidroxibenzoil)amino) caprílico |
| EA201390941A1 (ru) | 2010-12-22 | 2013-12-30 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Аналоги глюкагона, проявляющие активность на рецепторе gip |
| US9161953B2 (en) | 2010-12-22 | 2015-10-20 | Amylin Pharmaceuticals, Llc | GLP-1 receptor agonists for islet cell transplantation |
| CN102532301B (zh) | 2010-12-31 | 2014-09-03 | 上海医药工业研究院 | 一类新型的Exendin-4类似物及其制备方法 |
| US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
| CN102100906A (zh) | 2011-02-18 | 2011-06-22 | 深圳翰宇药业股份有限公司 | 一种艾塞那肽的药用制剂及其制备方法 |
| MX342675B (es) | 2011-03-10 | 2016-10-07 | Xeris Pharmaceuticals Inc | Formulaciones estables para inyeccion parenteral de farmacos de peptido. |
| CN102718858B (zh) | 2011-03-29 | 2014-07-02 | 天津药物研究院 | 胰高血糖素样肽-1类似物单体、二聚体及其制备方法与应用 |
| CN106928341B (zh) | 2011-03-30 | 2021-06-01 | 上海仁会生物制药股份有限公司 | 定点单取代聚乙二醇化Exendin类似物及其制备方法 |
| DK2694095T3 (en) | 2011-04-05 | 2018-05-28 | Longevity Biotech Inc | COMPOSITIONS COMPREHENSIVE GLUCAGON ANALOGS AND METHODS FOR PREPARING AND USING THE SAME |
| EP2696897A2 (en) | 2011-04-11 | 2014-02-19 | Yeda Research and Development Co. Ltd. | Albumin binding probes and drug conjugates thereof |
| WO2012150503A2 (en) | 2011-05-03 | 2012-11-08 | Zealand Pharma A/S | Glu-glp-1 dual agonist signaling-selective compounds |
| CN102766204B (zh) | 2011-05-05 | 2014-10-15 | 天津药物研究院 | 胰高血糖素样肽-1突变体多肽及其制备方法和其应用 |
| CA3134906A1 (en) | 2011-05-18 | 2012-11-22 | Mederis Diabetes, Llc | Improved peptide pharmaceuticals for insulin resistance |
| WO2012162547A2 (en) | 2011-05-25 | 2012-11-29 | Amylin Pharmaceuticals, Inc. | Long duration dual hormone conjugates |
| UA113626C2 (xx) | 2011-06-02 | 2017-02-27 | Композиція для лікування діабету, що містить кон'югат інсуліну тривалої дії та кон'югат інсулінотропного пептиду тривалої дії | |
| KR102002783B1 (ko) | 2011-06-10 | 2019-07-24 | 베이징 한미 파마슈티컬 컴퍼니 리미티드 | 포도당 의존성 인슐리노트로핀 폴리펩타이드 유사물질, 이의 약학적 조성물 및 응용 |
| PE20140765A1 (es) | 2011-06-10 | 2014-06-14 | Hanmi Science Co Ltd | Derivados de oxintomodulina novedosos y composicion farmaceutica para tratar la obesidad que comprende los mismos |
| UA125895C2 (uk) | 2011-06-17 | 2022-07-06 | Ханмі Сайенс Ко., Лтд. | КОН'ЮГАТ, ЩО МІСТИТЬ ПОХІДНУ ОКСИНТОМОДУЛІНУ ТА Fc-ДІЛЯНКУ ІМУНОГЛОБУЛІНУ, ТА ЙОГО ЗАСТОСУВАННЯ |
| KR101874401B1 (ko) | 2011-06-17 | 2018-07-04 | 할로자임, 아이엔씨 | 히알루로난 분해 효소의 안정한 제형 |
| EA031230B1 (ru) | 2011-06-22 | 2018-12-28 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Агонисты глюкагонового рецептора/glp-1-рецептора |
| BR112013032717A2 (pt) | 2011-06-22 | 2017-01-24 | Univ Indiana Res & Tech Corp | coagonistas do receptor de glucagon/glp-1 |
| US20140220134A1 (en) | 2011-06-24 | 2014-08-07 | Astrazeneca Pharamceuticals LP | Method for treating diabetes with extended release formulation of glp-1 receptor agonists |
| KR101357117B1 (ko) | 2011-06-28 | 2014-02-06 | 비앤엘델리팜 주식회사 | 폴리에틸렌글라이콜 또는 이의 유도체로 페길화된 엑센딘-4 유사체, 이의 제조방법 및 이를 유효성분으로 함유하는 당뇨병 예방 또는 치료용 약학적 조성물 |
| WO2013004983A1 (en) | 2011-07-04 | 2013-01-10 | Imperial Innovations Limited | Novel compounds and their effects on feeding behaviour |
| EP2729481B1 (en) | 2011-07-08 | 2018-10-17 | Amylin Pharmaceuticals, LLC | Engineered polypeptides having enhanced duration of action with reduced immunogenicity |
| BR112014002986A2 (pt) | 2011-08-10 | 2017-06-13 | Adocia | composição sob a forma de uma solução injetável, e formulação de dose única |
| JP6169079B2 (ja) | 2011-08-24 | 2017-07-26 | フェーズバイオ ファーマシューティカルズ，インコーポレイテッド | 徐放のための活性剤の製剤 |
| WO2013029279A1 (zh) | 2011-09-03 | 2013-03-07 | 深圳市健元医药科技有限公司 | 新的glp-ⅰ类似物及其制备方法和用途 |
| CA2849673A1 (en) | 2011-09-23 | 2013-03-28 | Novo Nordisk A/S | Novel glucagon analogues |
| EP2771024B1 (en) | 2011-10-28 | 2018-11-28 | Sanofi-Aventis Deutschland GmbH | Treatment protocol of diabetes type 2 |
| CN102363633B (zh) | 2011-11-16 | 2013-11-20 | 天津拓飞生物科技有限公司 | 胰高血糖素样肽-1突变体多肽及其制备方法、药物组合物和其应用 |
| CN103957927B (zh) | 2011-11-17 | 2016-11-09 | 印第安纳大学研究及科技有限公司 | 呈现糖皮质激素受体活性的胰高血糖素超家族肽 |
| IN2014KN01341A (enExample) | 2011-11-29 | 2015-10-16 | Jurox Pty Ltd | |
| SMT202200355T1 (it) | 2011-12-16 | 2022-11-18 | Modernatx Inc | Composizioni di mrna modificato |
| SG11201402640SA (en) | 2011-12-22 | 2014-10-30 | Pfizer | Anti-diabetic compounds |
| PE20142113A1 (es) | 2011-12-23 | 2014-12-03 | Zealand Pharma As | Analogos de glucagon |
| EP2797585A4 (en) | 2011-12-29 | 2015-10-07 | Latitude Pharmaceuticals Inc | STABILIZED GLUCAGONNANOULULSIONS |
| CN107583039A (zh) | 2012-01-09 | 2018-01-16 | 阿道恰公司 | Ph为7且至少含pi为5.8至8.5之基础胰岛素和取代共聚(氨基酸)的可注射溶液 |
| WO2013148871A1 (en) | 2012-03-28 | 2013-10-03 | Amylin Pharmaceuticals, Llc | Engineered polypeptides |
| US20150133373A1 (en) | 2012-03-28 | 2015-05-14 | Amylin Pharmaceuticals, Llc | Transmucosal delivery of engineered polypeptides |
| EP2834260A4 (en) | 2012-04-02 | 2016-08-10 | Moderna Therapeutics Inc | MODIFIED POLYNUCLEOTIDES FOR THE PREPARATION OF MEMBRANE PROTEINS |
| CN108949772A (zh) | 2012-04-02 | 2018-12-07 | 现代泰克斯公司 | 用于产生与人类疾病相关的生物制剂和蛋白质的修饰多核苷酸 |
| CN102649947A (zh) | 2012-04-20 | 2012-08-29 | 无锡和邦生物科技有限公司 | 一种用于测定glp-1及其功能类似物生物活性的细胞株及其应用 |
| EP2841090A1 (en) | 2012-04-24 | 2015-03-04 | Amylin Pharmaceuticals, LLC | Site-specific enzymatic modification of exendins and analogs thereof |
| US20130289241A1 (en) | 2012-04-26 | 2013-10-31 | Shanghai Ambiopharm, Inc. | Method for preparing exenatide |
| WO2013182217A1 (en) | 2012-04-27 | 2013-12-12 | Sanofi-Aventis Deutschland Gmbh | Quantification of impurities for release testing of peptide products |
| US8901484B2 (en) | 2012-04-27 | 2014-12-02 | Sanofi-Aventis Deutschland Gmbh | Quantification of impurities for release testing of peptide products |
| KR102184241B1 (ko) * | 2012-05-03 | 2020-12-01 | 질랜드 파마 에이/에스 | Ｇｉｐ-ｇｌｐ-1 이원 작용제 화합물 및 방법 |
| WO2013164484A1 (en) | 2012-05-03 | 2013-11-07 | Zealand Pharma A/S | Glucagon-like-peptide-2 (glp-2) analogues |
| EP2664374A1 (en) | 2012-05-15 | 2013-11-20 | F. Hoffmann-La Roche AG | Lysin-glutamic acid dipeptide derivatives |
| CN103421094A (zh) | 2012-05-24 | 2013-12-04 | 上海医药工业研究院 | 一种具有epo类似活性的多肽化合物 |
| US20150174209A1 (en) | 2012-05-25 | 2015-06-25 | Amylin Pharmaceuticals. Llc | Insulin-pramlintide compositions and methods for making and using them |
| IN2014KN02830A (enExample) | 2012-06-14 | 2015-05-08 | Sanofi Sa | |
| AU2013277372B2 (en) | 2012-06-21 | 2018-03-29 | Indiana University Research And Technology Corporation | Analogs of glucagon exhibiting GIP receptor activity |
| EP2864351B1 (en) | 2012-06-21 | 2016-08-10 | Indiana University Research and Technology Corporation | Glucagon analogs exhibiting gip receptor activity |
| CA2878457C (en) | 2012-07-12 | 2021-01-19 | Mannkind Corporation | Dry powder drug delivery systems and methods |
| ES2620111T3 (es) | 2012-07-23 | 2017-06-27 | Zealand Pharma A/S | Análogos de glucagón |
| KR101968344B1 (ko) | 2012-07-25 | 2019-04-12 | 한미약품 주식회사 | 옥신토모듈린 유도체를 포함하는 고지혈증 치료용 조성물 |
| AR094821A1 (es) | 2012-07-25 | 2015-09-02 | Hanmi Pharm Ind Co Ltd | Formulación líquida de un conjugado de péptido insulinotrópico de acción prolongada |
| AR092862A1 (es) | 2012-07-25 | 2015-05-06 | Hanmi Pharm Ind Co Ltd | Formulacion liquida de insulina de accion prolongada y un peptido insulinotropico y metodo de preparacion |
| WO2014027253A1 (en) | 2012-08-14 | 2014-02-20 | Wockhardt Limited | Pharmaceutical microparticulate compositions of polypeptides |
| WO2014027254A1 (en) | 2012-08-14 | 2014-02-20 | Wockhardt Limited | Pharmaceutical microparticulate compositions of polypeptides |
| CN102816244A (zh) | 2012-08-23 | 2012-12-12 | 无锡和邦生物科技有限公司 | 一种Exendin-4肽与人血清白蛋白HSA的融合蛋白及其制备方法 |
| CN102827270A (zh) | 2012-09-13 | 2012-12-19 | 无锡和邦生物科技有限公司 | 一种聚乙二醇化艾塞那肽衍生物及其用途 |
| US9546205B2 (en) | 2012-09-17 | 2017-01-17 | Imperial Innovations Limited | Peptide analogues of glucagon and GLP1 |
| TWI608013B (zh) | 2012-09-17 | 2017-12-11 | 西蘭製藥公司 | 升糖素類似物 |
| WO2014049610A2 (en) | 2012-09-26 | 2014-04-03 | Cadila Healthcare Limited | Peptides as gip, glp-1 and glucagon receptors triple-agonist |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| KR101993393B1 (ko) | 2012-11-06 | 2019-10-01 | 한미약품 주식회사 | 옥신토모듈린 유도체를 포함하는 당뇨병 또는 비만성 당뇨병 치료용 조성물 |
| WO2014073842A1 (en) | 2012-11-06 | 2014-05-15 | Hanmi Pharm. Co., Ltd. | Liquid formulation of protein conjugate comprising the oxyntomodulin and an immunoglobulin fragment |
| KR102365582B1 (ko) | 2012-11-20 | 2022-02-18 | 메더리스 다이어비티즈, 엘엘씨 | 인슐린 저항성에 대한 개선된 펩티드 약제 |
| TWI674270B (zh) | 2012-12-11 | 2019-10-11 | 英商梅迪繆思有限公司 | 用於治療肥胖之升糖素與glp-1共促效劑 |
| RS57531B1 (sr) * | 2012-12-21 | 2018-10-31 | Sanofi Sa | Derivati eksendina-4 kao dualni glp1/gip- ili trigonalni glp1/gip/glukagon agonisti |
| CN103908657A (zh) | 2012-12-31 | 2014-07-09 | 复旦大学附属华山医院 | 胰升糖素样肽-1类似物在制备眼科疾病药物中的用途 |
| EP3238734A1 (en) | 2013-03-14 | 2017-11-01 | Medimmune Limited | Pegylated glucagon and glp-1 co-agonists for the treatment of obesity |
| WO2014158900A1 (en) | 2013-03-14 | 2014-10-02 | Indiana University Research And Technology Corporation | Insulin-incretin conjugates |
| CN105324125A (zh) | 2013-03-15 | 2016-02-10 | 印第安纳大学研究及科技有限公司 | 具有长效的前体药物 |
| WO2014170496A1 (en) | 2013-04-18 | 2014-10-23 | Novo Nordisk A/S | Stable, protracted glp-1/glucagon receptor co-agonists for medical use |
| JP2014227368A (ja) | 2013-05-21 | 2014-12-08 | 国立大学法人帯広畜産大学 | 糖尿病および高血糖状態の処置のためのグルカゴンアナログ |
| CN103304660B (zh) | 2013-07-12 | 2016-08-10 | 上海昂博生物技术有限公司 | 一种利拉鲁肽的合成方法 |
| CN103405753B (zh) | 2013-08-13 | 2016-05-11 | 上海仁会生物制药股份有限公司 | 稳定的促胰岛素分泌肽水针药物组合物 |
| US9896495B2 (en) | 2013-10-17 | 2018-02-20 | Zealand Pharma A/S | Acylated glucagon analogues |
| US9988429B2 (en) | 2013-10-17 | 2018-06-05 | Zealand Pharma A/S | Glucagon analogues |
| CA2929107C (en) | 2013-11-06 | 2023-09-26 | Zealand Pharma A/S | Glucagon-glp-1-gip triple agonist compounds |
| EP3080150B1 (en) | 2013-12-13 | 2018-08-01 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
| WO2015086731A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Exendin-4 peptide analogues as dual glp-1/glucagon receptor agonists |
| WO2015086733A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
| WO2015086729A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/gip receptor agonists |
| 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 |
| TW201609798A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | Ｅｘｅｎｄｉｎ－４胜肽類似物 |
| CN103665148B (zh) | 2013-12-17 | 2016-05-11 | 中国药科大学 | 一种可口服给药的降糖多肽及其制法和用途 |
| CN103980358B (zh) | 2014-01-03 | 2016-08-31 | 杭州阿诺生物医药科技股份有限公司 | 一种制备利拉鲁肽的方法 |
| KR20160104724A (ko) | 2014-01-09 | 2016-09-05 | 사노피 | 인슐린 유사체 및/또는 인슐린 유도체의 안정화된 약제학적 제형 |
| CN105899191B (zh) | 2014-01-09 | 2020-06-16 | 赛诺菲 | 胰岛素类似物和/或胰岛素衍生物的稳定化不含甘油的药物制剂 |
| GB201404002D0 (en) | 2014-03-06 | 2014-04-23 | Imp Innovations Ltd | Novel compounds |
| 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 |
| 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 |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| CN106519015B (zh) | 2014-09-23 | 2020-04-17 | 深圳市图微安创科技开发有限公司 | 胃泌酸调节素类似物 |
| US9988430B2 (en) | 2014-10-10 | 2018-06-05 | Novo Nordisk A/S | Stable GLP-1 based GLP-1/glucagon receptor co-agonists |
| EP3825324A1 (en) | 2014-10-24 | 2021-05-26 | Merck Sharp & Dohme Corp. | Co-agonists of the glucagon and glp-1 receptors |
| WO2016198604A1 (en) | 2015-06-12 | 2016-12-15 | Sanofi | Exendin-4 derivatives as dual glp-1 /glucagon receptor agonists |
| WO2016198624A1 (en) | 2015-06-12 | 2016-12-15 | Sanofi | Exendin-4 derivatives as trigonal glp-1/glucagon/gip receptor agonists |
| 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 |
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2013
- 2013-12-19 RS RS20180942A patent/RS57531B1/sr unknown
- 2013-12-19 AU AU2013360721A patent/AU2013360721A1/en not_active Abandoned
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- 2013-12-19 DK DK13810958.2T patent/DK2934567T3/en active
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- 2013-12-19 KR KR1020157017458A patent/KR20150096684A/ko not_active Withdrawn
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- 2013-12-19 JP JP2015548554A patent/JP6408998B2/ja not_active Expired - Fee Related
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