AU2013286177B2 - Use of long-acting GLP-1 peptides - Google Patents
Use of long-acting GLP-1 peptides Download PDFInfo
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- AU2013286177B2 AU2013286177B2 AU2013286177A AU2013286177A AU2013286177B2 AU 2013286177 B2 AU2013286177 B2 AU 2013286177B2 AU 2013286177 A AU2013286177 A AU 2013286177A AU 2013286177 A AU2013286177 A AU 2013286177A AU 2013286177 B2 AU2013286177 B2 AU 2013286177B2
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- glp
- agonist
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- glu
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- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/26—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- Immunology (AREA)
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- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Obesity (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Child & Adolescent Psychology (AREA)
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Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
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| DK2696687T3 (en) | 2011-04-12 | 2017-02-06 | Novo Nordisk As | Double-acylated GLP-1 derivatives |
| PL2827885T3 (pl) | 2012-03-22 | 2019-01-31 | Novo Nordisk A/S | Kompozycje peptydów GLP-1 i ich otrzymywanie |
| WO2013189988A1 (en) | 2012-06-20 | 2013-12-27 | Novo Nordisk A/S | Tablet formulation comprising a peptide and a delivery agent |
| ES3041720T3 (en) | 2012-07-01 | 2025-11-14 | Novo Nordisk As | Use of long-acting glp-1 peptides |
| KR20210086717A (ko) | 2013-05-02 | 2021-07-08 | 노보 노르디스크 에이/에스 | Glp-1 화합물의 경구 투여 |
| US10543843B2 (en) * | 2014-10-16 | 2020-01-28 | Yanmar Co., Ltd. | Work vehicle |
| GB201621987D0 (en) * | 2016-12-22 | 2017-02-08 | Archer Virgil L See Archer Sheri A Arecor Ltd | Novel composition |
| DE102017106216A1 (de) * | 2017-03-22 | 2018-09-27 | Amw Gmbh | Extrudierte Depotform zur anhaltenden Wirkstofffreisetzung |
| MX2020001525A (es) | 2017-08-24 | 2020-03-20 | Novo Nordisk As | Composiciones de peptido similar al glucagon tipo 1 (glp-1) y sus usos. |
| IL322969A (en) | 2017-10-12 | 2025-10-01 | Novo Nordisk As | Semaglutide in medical therapy |
| GB201720187D0 (en) * | 2017-12-04 | 2018-01-17 | Imperial Innovations Ltd | Novel Compounds |
| CN111683676B (zh) | 2018-02-02 | 2024-06-18 | 诺和诺德股份有限公司 | 包含glp-1激动剂、n-(8-(2-羟基苯甲酰基)氨基)辛酸的盐和润滑剂的固体组合物 |
| 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 |
| US20210162013A1 (en) * | 2018-08-03 | 2021-06-03 | Brown University | Compositions and methods for improving the bioavailability of glp1 and analogues thereof |
| AU2020229349A1 (en) * | 2019-02-26 | 2021-10-14 | Twist Bioscience Corporation | Variant nucleic acid libraries for GLP1 receptor |
| MX2022004779A (es) * | 2019-11-06 | 2022-06-14 | Novo Nordisk As | Agonistas del receptor del péptido 1 similar al glucagón (glp-1) en demencia. |
| CN119060161A (zh) * | 2019-12-30 | 2024-12-03 | 甘李药业股份有限公司 | 长效glp-1化合物 |
| IL294520A (en) | 2020-02-18 | 2022-09-01 | Novo Nordisk As | Pharmaceutical formulations |
| CN112768087A (zh) * | 2020-12-23 | 2021-05-07 | 吉林大学 | 利用孟德尔随机化方法验证索马鲁肽口服制剂预防二型糖尿病的用途 |
| EP4359074A4 (en) * | 2021-06-24 | 2025-06-04 | Gila Therapeutics, Inc. | METHODS AND KITS FOR INDUCTING SATOURAGE AND TREATMENT OF METABOLIC DISEASES |
| US11865213B2 (en) * | 2021-07-05 | 2024-01-09 | Mapi Pharma Ltd. | Semaglutide depot systems and use thereof |
| AU2022349020A1 (en) | 2021-09-27 | 2024-05-09 | Terns Pharmaceuticals, Inc. | Benzimidazole carboxylic acids as glp-1r agonists |
| AU2022375634A1 (en) | 2021-10-25 | 2024-06-06 | Terns Pharmaceuticals, Inc. | Compounds as glp-1r agonists |
| IL312672A (en) | 2021-11-10 | 2024-07-01 | I2O Therapeutics Inc | Ionic liquid compositions |
| CN115850438B (zh) * | 2021-12-28 | 2023-05-12 | 北京惠之衡生物科技有限公司 | 一种长效glp-1衍生物 |
| JP2025508812A (ja) | 2022-02-23 | 2025-04-10 | ターンズ・ファーマシューティカルズ・インコーポレイテッド | Ｇｌｐ－１ｒアゴニストとしての化合物 |
| US20230374096A1 (en) * | 2022-05-19 | 2023-11-23 | Vault Bioventures, Inc. | Obesity treatment and prevention methods |
| KR20250141711A (ko) | 2022-12-30 | 2025-09-29 | 알지파마 에이에스 | 경구 투여되는 폴리펩타이드 치료제의 전신 생체이용률을 증가시키는 조성물 및 방법 |
| KR20250166323A (ko) | 2023-04-07 | 2025-11-27 | 테른스 파마슈티칼스, 인크. | 간 장애 또는 심장대사 질환의 치료에 사용하기 위한 thr베타 효현제 및 glp-1r 효현제를 포함하는 조합 |
| WO2025024455A1 (en) | 2023-07-24 | 2025-01-30 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for delivery of therapeutic peptides |
| WO2025165146A1 (ko) * | 2024-01-29 | 2025-08-07 | 주식회사 티온랩테라퓨틱스 | 세마글루타이드 또는 티르제파타이드의 개선된 의료 요법 제공을 위한 비만 및 당뇨 치료용으로써, 소수성 이온 페어링 겔레이션을 통한 초기 방출이 제어된 데포 조성물 및 이의 제조방법 |
| CN118845644B (zh) * | 2024-09-27 | 2025-01-17 | 杭州信海医药科技有限公司 | 一种司美格鲁肽注射液的制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010092163A2 (en) * | 2009-02-13 | 2010-08-19 | Boehringer Ingelheim International Gmbh | Antidiabetic medications |
| WO2011138421A1 (en) * | 2010-05-05 | 2011-11-10 | Boehringer Ingelheim International Gmbh | Combination therapy |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK39892D0 (da) | 1992-03-25 | 1992-03-25 | Bernard Thorens | Peptid |
| CZ300837B6 (cs) | 1996-08-30 | 2009-08-26 | Novo Nordisk A/S | Deriváty GLP-1(7-37) nebo jeho analogy, farmaceutický prostredek je obsahující a jejich použití |
| WO2003002136A2 (en) | 2001-06-28 | 2003-01-09 | Novo Nordisk A/S | Stable formulation of modified glp-1 |
| TW200526254A (en) | 2003-09-19 | 2005-08-16 | Novo Nordisk As | Novel GLP-1 derivatives |
| 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 |
| CN106137952B (zh) | 2004-11-12 | 2020-11-17 | 诺和诺德公司 | 促胰岛素肽的稳定制剂 |
| TWI362392B (en) | 2005-03-18 | 2012-04-21 | Novo Nordisk As | Acylated glp-1 compounds |
| BRPI0709964A2 (pt) | 2006-04-14 | 2011-08-02 | Mannkind Corp | formulações farmacêuticas contendo peptìdeo glucagon do tipo 1 (glp-1) |
| CA2677852A1 (en) | 2007-03-20 | 2008-09-25 | Nippon Kayaku Kabushiki Kaisha | Method to monitor drug efficacy in diabetic patients using an assay for 1,5-anhydro-d-glucitol |
| EP2514406A1 (en) | 2007-06-01 | 2012-10-24 | Novo Nordisk A/S | Spontaneously dispersible preconcentrates including a peptide drug in a solid or semisolid carrier |
| JP5476304B2 (ja) | 2007-09-05 | 2014-04-23 | ノボ・ノルデイスク・エー／エス | グルカゴン様ペプチド−１誘導体及びそれらの医薬用途 |
| EP2190873B1 (en) | 2007-09-05 | 2015-07-22 | Novo Nordisk A/S | Truncated glp-1 derivatives and their therapeutical use |
| US20100317057A1 (en) | 2007-12-28 | 2010-12-16 | Novo Nordisk A/S | Semi-recombinant preparation of glp-1 analogues |
| JP2012511586A (ja) | 2008-12-10 | 2012-05-24 | 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 | 医薬組成物 |
| WO2011080103A1 (en) * | 2009-12-16 | 2011-07-07 | Novo Nordisk A/S | Double-acylated glp-1 derivatives |
| WO2012016419A1 (zh) | 2010-08-06 | 2012-02-09 | 浙江贝达药业有限公司 | Glp-1衍生物及其应用 |
| RS60321B1 (sr) | 2010-12-16 | 2020-07-31 | Novo Nordisk As | Čvrste kompozicije koje sadrže glp-1 agonist i so n-(8-(2- hidroksibenzoil)amino)kaprilne kiseline |
| US20130035281A1 (en) * | 2011-02-09 | 2013-02-07 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
| 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 |
| WO2012136790A1 (en) | 2011-04-07 | 2012-10-11 | Glaxo Group Limited | Compositions comprising fusion proteins or conjugates with an improved half -life |
| CN102229668A (zh) | 2011-06-03 | 2011-11-02 | 浙江贝达药业有限公司 | 一种glp-1衍生物及其应用 |
| CN103906528A (zh) * | 2011-06-24 | 2014-07-02 | 安米林药品有限责任公司 | 用glp-1受体激动剂的缓释制剂治疗糖尿病的方法 |
| ES3041720T3 (en) | 2012-07-01 | 2025-11-14 | Novo Nordisk As | Use of long-acting glp-1 peptides |
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2013
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- 2013-06-21 BR BR112014032938A patent/BR112014032938A2/pt not_active Application Discontinuation
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- 2013-06-21 RU RU2015101826A patent/RU2657573C2/ru active
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2014
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2017
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2018
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010092163A2 (en) * | 2009-02-13 | 2010-08-19 | Boehringer Ingelheim International Gmbh | Antidiabetic medications |
| WO2011138421A1 (en) * | 2010-05-05 | 2011-11-10 | Boehringer Ingelheim International Gmbh | Combination therapy |
Non-Patent Citations (2)
| Title |
|---|
| Clinical Trial NCT00696657, entitled "A Randomised Controlled Clinical Trial in Type 2 Diabetes Comparing Semaglutide to Placebo and Liraglutide," pp. 1-5 (3/11/2015) at URL clinicaltrials.gov/archive/NCT00696657/2011_03_25 * |
| S. MADSBAD ET AL, "An overview of once-weekly glucagon-like peptide-1 receptor agonists-available efficacy and safety data and perspectives for the future", DIABETES, OBESITY AND METABOLISM, (20110324), vol. 13, no. 5, pages 394 - 407 * |
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