TW200306202A - Extended glucagon-like peptide-1 analogs - Google Patents
Extended glucagon-like peptide-1 analogs Download PDFInfo
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- TW200306202A TW200306202A TW092100093A TW92100093A TW200306202A TW 200306202 A TW200306202 A TW 200306202A TW 092100093 A TW092100093 A TW 092100093A TW 92100093 A TW92100093 A TW 92100093A TW 200306202 A TW200306202 A TW 200306202A
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- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| US34647402P | 2002-01-08 | 2002-01-08 | |
| US40509702P | 2002-08-21 | 2002-08-21 |
Publications (1)
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| TW200306202A true TW200306202A (en) | 2003-11-16 |
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Family Applications (1)
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| TW092100093A TW200306202A (en) | 2002-01-08 | 2003-01-03 | Extended glucagon-like peptide-1 analogs |
Country Status (11)
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| US (1) | US7482321B2 (https=) |
| EP (1) | EP1585959A4 (https=) |
| JP (1) | JP4282485B2 (https=) |
| AR (1) | AR038102A1 (https=) |
| AU (1) | AU2003200839B2 (https=) |
| BR (1) | BR0306706A (https=) |
| CA (1) | CA2468700A1 (https=) |
| MX (1) | MXPA04006679A (https=) |
| PE (1) | PE20030820A1 (https=) |
| TW (1) | TW200306202A (https=) |
| WO (1) | WO2003058203A2 (https=) |
Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1605897B1 (en) | 2003-03-19 | 2012-07-25 | Eli Lilly And Company | Polyethelene glycol link glp-1 compounds |
| ATE498404T1 (de) | 2003-12-09 | 2011-03-15 | Novo Nordisk As | Regulierung der nahrungspräferenz mit glp-1- agonisten |
| US7538185B2 (en) | 2004-01-08 | 2009-05-26 | Theratechnologies Inc. | Glucagon-like peptide-1 analogs with long duration of action |
| JP2008501765A (ja) * | 2004-06-11 | 2008-01-24 | ノボ ノルディスク アクティーゼルスカブ | Ｇｌｐ−１アゴニストを用いた薬剤誘発性肥満の中和 |
| EP1781695A1 (en) * | 2004-08-18 | 2007-05-09 | Eli Lilly And Company | Selective vpac2 receptor peptide agonists |
| CA2603630C (en) | 2005-01-14 | 2015-06-09 | Wuxi Grandchamp Pharmaceutical Technology Co., Ltd. | Modified exendins and uses thereof |
| JP5755398B2 (ja) | 2005-03-18 | 2015-07-29 | ノヴォ ノルディスク アー／エス | 伸長されたｇｌｐ−１化合物 |
| TWI372629B (en) | 2005-03-18 | 2012-09-21 | Novo Nordisk As | Acylated glp-1 compounds |
| BRPI0612471A2 (pt) * | 2005-05-05 | 2016-09-06 | Cadila Healthcare Ltd | novos compostos como agonistas glp-1 |
| PT1881850E (pt) * | 2005-05-13 | 2010-11-26 | Lilly Co Eli | Compostos peguilados de glp-1 |
| US20080194482A1 (en) * | 2005-08-11 | 2008-08-14 | Jorge Alsina-Fernandez | Selective Apac2 Receptor Peptide Agonists |
| PL1767545T3 (pl) | 2005-09-22 | 2010-04-30 | Biocompatibles Uk Ltd | Polipeptydy fuzyjne GLP-1 (glukagonopodobny peptyd-1) o zwiększonej odporności na peptydazy |
| BRPI0617740A2 (pt) | 2005-10-26 | 2011-08-02 | Lilly Co Eli | agonistas seletivos peptìdicos do receptor vpac2, composição farmacêutica e uso dos referidos agonistas |
| ES2586236T3 (es) * | 2005-11-04 | 2016-10-13 | Glaxosmithkline Llc | Procedimientos para administrar agentes hipoglucémicos |
| EP2570133B1 (en) | 2005-11-07 | 2016-03-23 | Indiana University Research and Technology Corporation | Glucagon analogs exhibiting physiological solubility and stability |
| 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 |
| CA2638733A1 (en) * | 2006-02-28 | 2007-09-07 | Eli Lilly And Company | Selective vpac2 receptor peptide agonists |
| JP2009532422A (ja) * | 2006-04-03 | 2009-09-10 | ノボ・ノルデイスク・エー／エス | Ｇｌｐ−１ペプチドアゴニスト |
| ES2495741T3 (es) | 2006-04-20 | 2014-09-17 | Amgen, Inc | Compuestos de GLP-1 |
| ATE444741T1 (de) | 2006-05-10 | 2009-10-15 | Biocompatibles Uk Ltd | Glp-1 peptide enthaltende kugelförmige mikrokapseln, deren produktion und deren verwendung |
| TWI430806B (zh) | 2006-09-13 | 2014-03-21 | Smithkline Beecham Corp | 用於投與長效降血糖藥劑之方法 |
| AU2008216265B2 (en) | 2007-02-15 | 2014-04-03 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
| EP1972349A1 (en) * | 2007-03-21 | 2008-09-24 | Biocompatibles UK Limited | GLP-1 fusion peptides conjugated to polymer(s), their production and use |
| EP1975176A1 (en) * | 2007-03-27 | 2008-10-01 | Biocompatibles UK Limited | Novel glp-1 fusion peptides, their production and use |
| CA2693504A1 (en) | 2007-08-03 | 2009-02-12 | Eli Lilly And Company | Treatment for obesity |
| US8980830B2 (en) | 2007-10-30 | 2015-03-17 | Indiana University Research And Technology Corporation | Peptide compounds exhibiting glucagon antagonist and GLP-1 agonist activity |
| 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 |
| WO2010054326A2 (en) | 2008-11-07 | 2010-05-14 | The General Hospital Corporation | C-terminal fragments of glucagon-like peptide-1 (glp-1) |
| US8748377B2 (en) | 2008-12-10 | 2014-06-10 | Glaxosmithkline Llc | Pharmaceutical compositions |
| CN102325539A (zh) | 2008-12-19 | 2012-01-18 | 印第安纳大学研究及科技有限公司 | 基于酰胺的胰高血糖素超家族肽前药 |
| WO2010148089A1 (en) | 2009-06-16 | 2010-12-23 | Indiana University Research And Technology Corporation | Gip receptor-active glucagon compounds |
| 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 |
| JP2013525491A (ja) | 2010-05-04 | 2013-06-20 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | 心血管障害を治療または予防し心血管保護を提供する方法 |
| CA2797095A1 (en) | 2010-05-13 | 2011-11-17 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhibiting nuclear hormone receptor activity |
| WO2011143208A1 (en) | 2010-05-13 | 2011-11-17 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhibiting g protein-coupled receptor activity |
| RU2580317C2 (ru) | 2010-06-24 | 2016-04-10 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Пептидные пролекарства, принадлежащие к суперсемейству амид-содержащих глюкагонов |
| WO2012054861A1 (en) | 2010-10-22 | 2012-04-26 | Nektar Therapeutics | Glp-1 polymer conjugates having a releasable linkage |
| WO2012054822A1 (en) | 2010-10-22 | 2012-04-26 | Nektar Therapeutics | Pharmacologically active polymer-glp-1 conjugates |
| US9040481B2 (en) | 2010-11-02 | 2015-05-26 | The General Hospital Corporation | Methods for treating steatotic disease |
| JP2013543898A (ja) | 2010-11-24 | 2013-12-09 | デュレクト コーポレイション | 生体分解性薬物送達組成物 |
| US8507428B2 (en) | 2010-12-22 | 2013-08-13 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting GIP receptor activity |
| BR112013032717A2 (pt) | 2011-06-22 | 2017-01-24 | Univ Indiana Res & Tech Corp | coagonistas do receptor de glucagon/glp-1 |
| RS56173B1 (sr) | 2011-06-22 | 2017-11-30 | Univ Indiana Res & Tech Corp | Koagonisti receptora za glukagon/glp-1 receptora |
| WO2013006692A2 (en) | 2011-07-06 | 2013-01-10 | The General Hospital Corporation | Methods of treatment using a pentapeptide derived from the c-terminus of glucagon-like peptide 1 (glp-1) |
| 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 |
| RU2014117678A (ru) | 2011-11-17 | 2015-12-27 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Пептиды глюкагонового суперсемейства, обладающие глюкокортикоидной рецепторной активностью |
| US20140294977A1 (en) | 2011-11-23 | 2014-10-02 | Durect Corporation | Radiation-Sterilized Biodegradable Drug Delivery Composition |
| CA2877358A1 (en) | 2012-06-21 | 2013-12-27 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting gip receptor activity |
| KR20160021183A (ko) * | 2013-06-20 | 2016-02-24 | 노보 노르디스크 에이/에스 | Glp-1 유도체 및 그것의 용도 |
| 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 |
| JP6564369B2 (ja) | 2013-12-09 | 2019-08-21 | デュレクト コーポレイション | 薬学的活性剤複合体、ポリマー複合体、ならびにこれらを伴う組成物及び方法 |
| JP6730278B2 (ja) | 2014-11-27 | 2020-07-29 | ノヴォ ノルディスク アー／エス | Ｇｌｐ−１誘導体及びその使用 |
| WO2016097108A1 (en) | 2014-12-17 | 2016-06-23 | Novo Nordisk A/S | Glp-1 derivatives and uses thereof |
| RS63523B1 (sr) | 2018-04-05 | 2022-09-30 | Sun Pharmaceutical Ind Ltd | Novi glp-1 analozi |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL128332A0 (en) * | 1996-08-30 | 2000-01-31 | Novo Nordisk As | GLP-1 derivatives |
| JP2002512175A (ja) * | 1998-02-27 | 2002-04-23 | ノボ ノルディスク アクティーゼルスカブ | Ｇｌｐ−１類似体の誘導体類 |
| EP1062240B1 (en) | 1998-02-27 | 2010-04-28 | Novo Nordisk A/S | N-terminally modified glp-1 derivatives |
| AU5027299A (en) | 1998-07-31 | 2000-02-28 | Novo Nordisk A/S | Use of glp-1 and analogues for preventing type ii diabetes |
| BR0116024A (pt) * | 2000-12-07 | 2005-12-13 | Lilly Co Eli | Proteìna de fusão heteróloga e uso da mesma |
| EP1411968B1 (en) | 2001-07-31 | 2008-09-17 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Glp-1 exendin-4 peptide analogs and uses thereof |
| CA2452044A1 (en) * | 2001-08-28 | 2003-03-13 | Eli Lilly And Company | Pre-mixes of glp-1 and basal insulin |
| WO2003035099A1 (en) * | 2001-10-19 | 2003-05-01 | Eli Lilly And Company | Biphasic mixtures of glp-1 and insulin |
-
2003
- 2003-01-03 MX MXPA04006679A patent/MXPA04006679A/es unknown
- 2003-01-03 US US10/499,111 patent/US7482321B2/en not_active Expired - Fee Related
- 2003-01-03 CA CA002468700A patent/CA2468700A1/en not_active Abandoned
- 2003-01-03 TW TW092100093A patent/TW200306202A/zh unknown
- 2003-01-03 JP JP2003558463A patent/JP4282485B2/ja not_active Expired - Fee Related
- 2003-01-03 AR ARP030100014A patent/AR038102A1/es unknown
- 2003-01-03 EP EP03700026A patent/EP1585959A4/en not_active Withdrawn
- 2003-01-03 BR BRPI0306706-8A patent/BR0306706A/pt not_active IP Right Cessation
- 2003-01-03 WO PCT/US2003/000001 patent/WO2003058203A2/en not_active Ceased
- 2003-01-03 AU AU2003200839A patent/AU2003200839B2/en not_active Ceased
- 2003-01-06 PE PE2003000021A patent/PE20030820A1/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| BR0306706A (pt) | 2007-03-27 |
| WO2003058203A3 (en) | 2007-02-01 |
| EP1585959A2 (en) | 2005-10-19 |
| CA2468700A1 (en) | 2003-07-17 |
| JP2005528337A (ja) | 2005-09-22 |
| WO2003058203A2 (en) | 2003-07-17 |
| AR038102A1 (es) | 2004-12-29 |
| US7482321B2 (en) | 2009-01-27 |
| AU2003200839A1 (en) | 2003-07-24 |
| EP1585959A4 (en) | 2007-11-14 |
| PE20030820A1 (es) | 2003-10-04 |
| MXPA04006679A (es) | 2004-11-10 |
| JP4282485B2 (ja) | 2009-06-24 |
| US20060014241A1 (en) | 2006-01-19 |
| AU2003200839B2 (en) | 2008-12-11 |
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