JP6594856B2 - 医療用の安定な遷延性ｇｌｐ−１／グルカゴン受容体コアゴニスト - Google Patents
医療用の安定な遷延性ｇｌｐ−１／グルカゴン受容体コアゴニスト Download PDFInfo
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- JP6594856B2 JP6594856B2 JP2016508190A JP2016508190A JP6594856B2 JP 6594856 B2 JP6594856 B2 JP 6594856B2 JP 2016508190 A JP2016508190 A JP 2016508190A JP 2016508190 A JP2016508190 A JP 2016508190A JP 6594856 B2 JP6594856 B2 JP 6594856B2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/605—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K38/28—Insulins
-
- 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
-
- 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
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Endocrinology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (7)
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| US61/814,969 | 2013-04-23 | ||
| EP13196656 | 2013-12-11 | ||
| EP13196656.6 | 2013-12-11 | ||
| PCT/EP2014/058084 WO2014170496A1 (en) | 2013-04-18 | 2014-04-22 | Stable, protracted glp-1/glucagon receptor co-agonists for medical use |
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| JP2016526012A JP2016526012A (ja) | 2016-09-01 |
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| JP (1) | JP6594856B2 (enExample) |
| KR (1) | KR20160021758A (enExample) |
| CN (1) | CN105307672B (enExample) |
| AU (1) | AU2014255608B2 (enExample) |
| BR (1) | BR112015025464A2 (enExample) |
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| SI (1) | SI2986313T1 (enExample) |
| WO (1) | WO2014170496A1 (enExample) |
| ZA (1) | ZA201507010B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2019167361A (ja) * | 2013-04-18 | 2019-10-03 | ノヴォ ノルディスク アー／エス | 医療用の安定な遷延性ｇｌｐ−１／グルカゴン受容体コアゴニスト |
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| TWI596110B (zh) | 2011-09-23 | 2017-08-21 | 諾佛 儂迪克股份有限公司 | 新穎升糖素類似物 |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| WO2014096149A1 (en) | 2012-12-21 | 2014-06-26 | Sanofi | Exendin-4 Derivatives |
| EP2986313B1 (en) | 2013-04-18 | 2019-06-12 | Novo Nordisk A/S | Stable, protracted glp-1/glucagon receptor co-agonists for medical use |
| 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 |
| TW201609795A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 作為雙重ｇｌｐ－１／ｇｉｐ受體促效劑的艾塞那肽－４（ｅｘｅｎｄｉｎ－４）胜肽類似物 |
| WO2015086730A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Non-acylated exendin-4 peptide analogues |
| 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 |
| 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 |
| PL3155017T3 (pl) * | 2014-05-28 | 2024-06-17 | Mederis Diabetes, Llc | Ulepszone farmaceutyki peptydowe dla insulinooporności |
| US10570184B2 (en) | 2014-06-04 | 2020-02-25 | Novo Nordisk A/S | GLP-1/glucagon receptor co-agonists for medical use |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| KR102418477B1 (ko) * | 2014-12-30 | 2022-07-08 | 한미약품 주식회사 | 글루카곤 유도체 |
| SG11201705376SA (en) * | 2014-12-30 | 2017-08-30 | Hanmi Pharm Ind Co Ltd | Glucagon derivative having improved stability |
| AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
| WO2016198628A1 (en) | 2015-06-12 | 2016-12-15 | Sanofi | Non-acylated 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 |
| TN2017000555A1 (en) | 2015-06-30 | 2019-04-12 | Hanmi Pharm Ind Co Ltd | Glucagon derivative and a composition comprising a long acting conjugate of the same |
| 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 |
| KR20170080521A (ko) | 2015-12-31 | 2017-07-10 | 한미약품 주식회사 | 글루카곤, glp-1 및 gip 수용체 모두에 활성을 갖는 삼중 활성체 |
| US10822385B2 (en) * | 2016-01-13 | 2020-11-03 | Novo Nordisk A/S | EGF(A) analogues with fatty acid substituents |
| FR3050112B1 (fr) | 2016-04-15 | 2020-09-04 | Soc Civ Immobiliere Gecinq | Utilisation de l'acide fenofibrique dans le traitement des maladies hepatiques |
| JP7208020B2 (ja) | 2016-06-29 | 2023-01-18 | ハンミ ファーマシューティカル カンパニー リミテッド | グルカゴン誘導体、その結合体、及びそれを含む組成物、並びにその治療的用途 |
| BR112020001286A2 (pt) | 2017-07-19 | 2020-07-28 | Novo Nordisk A/S | composto, e, método de tratamento da diabetes, sobrepeso e/ou doenças cardiovasculares |
| GB201720187D0 (en) | 2017-12-04 | 2018-01-17 | Imperial Innovations Ltd | Novel Compounds |
| EP3735295B1 (en) | 2018-01-03 | 2024-08-21 | Mederis Diabetes, LLC | Improved peptide pharmaceuticals for treatment of nash and other disorders |
| MX2020011427A (es) | 2018-05-04 | 2020-12-07 | Novo Nordisk As | Derivados del polipeptido insulinotropico dependiente de la glucosa (gip) y usos de estos. |
| US20200268835A1 (en) | 2019-02-27 | 2020-08-27 | Novo Nordisk A/S | Compounds For Use in NASH |
| GB201908424D0 (en) | 2019-06-12 | 2019-07-24 | Imp College Innovations Ltd | Novel compounds |
| KR20220143923A (ko) * | 2020-02-21 | 2022-10-25 | 스핏파이어 파마, 엘엘씨 | Glp-1r 및 gcgr 효능제, 제형 및 사용 방법 |
| CN117202924A (zh) | 2020-12-07 | 2023-12-08 | 斯皮特弗尔制药有限责任公司 | 使用glp-1r和gcgr平衡激动剂降低血糖和/或体重的治疗方案和方法 |
| CN116710462A (zh) | 2021-01-20 | 2023-09-05 | 维京治疗公司 | 用于治疗代谢病症和肝病的组合物和方法 |
| IL311411A (en) | 2021-09-15 | 2024-05-01 | Viking Therapeutics Inc | Preparations and methods for the treatment of metabolic and liver disorders |
| TW202346323A (zh) * | 2022-02-07 | 2023-12-01 | 英商梅迪繆思有限公司 | 具有改善的生物穩定性的ｇｌｐ—１及升糖素雙重激動肽 |
Family Cites Families (119)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4356170A (en) | 1981-05-27 | 1982-10-26 | Canadian Patents & Development Ltd. | Immunogenic polysaccharide-protein conjugates |
| ZA90533B (en) | 1989-02-01 | 1990-10-31 | Shionogi & Co | A method for the production of glucagon |
| US5408037A (en) | 1991-01-17 | 1995-04-18 | Zymogenetics, Inc. | Methods for detecting glucagon antagonists |
| US5424286A (en) | 1993-05-24 | 1995-06-13 | Eng; John | Exendin-3 and exendin-4 polypeptides, and pharmaceutical compositions comprising same |
| US5480867A (en) | 1993-12-29 | 1996-01-02 | The Rockefeller University | Glucagon analogs with serine replacements |
| US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| US5869602A (en) | 1995-03-17 | 1999-02-09 | Novo Nordisk A/S | Peptide derivatives |
| DE69626660T2 (de) | 1995-09-08 | 2003-08-21 | Novo Nordisk A/S, Bagsvaerd | 2-alkylpyrrolidine |
| IL125071A0 (en) | 1996-01-17 | 1999-01-26 | Novo Nordisk As | Fused 1,2,4-thiadiazine and fused 1,4-thiazine derivatives their preparation and use |
| WO1997041120A1 (en) | 1996-07-26 | 1997-11-06 | Dr. Reddy's Research Foundation | Thiazolidinedione compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions thereof |
| DE122009000079I2 (de) | 1996-08-30 | 2011-06-16 | Novo Nordisk As Novo Alle | Glp-1 derivate |
| CN1190434C (zh) | 1996-12-31 | 2005-02-23 | 雷迪实验室有限公司 | 新的杂环化合物、其制备方法和含有它们的药物组合物及其在治疗糖尿病和相关疾病中的应用 |
| EP0981526B1 (en) | 1997-05-02 | 2004-02-25 | Dr. Reddy's Laboratories Ltd. | Novel antidiabetic compounds having hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
| US6613942B1 (en) | 1997-07-01 | 2003-09-02 | Novo Nordisk A/S | Glucagon antagonists/inverse agonists |
| JP2003514508A (ja) | 1997-07-01 | 2003-04-15 | ノボ ノルディスク アクティーゼルスカブ | グルカゴン拮抗剤／逆作用剤 |
| IL133604A0 (en) | 1997-07-16 | 2001-04-30 | Novo Nordisk As | Fused 1, 2, 4-thiadiazine derivatives, their preparation and use |
| US6440961B1 (en) | 1997-10-27 | 2002-08-27 | Dr. Reddy's Research Foundation | Tricyclic compounds and their use in medicine: process for their preparation and pharmaceutical compositions containing them |
| WO1999019313A1 (en) | 1997-10-27 | 1999-04-22 | Dr. Reddy's Research Foundation | Novel tricyclic compounds and their use in medicine; process for their preparation and pharmaceutical compositions containing them |
| WO1998045292A1 (en) | 1997-12-02 | 1998-10-15 | Dr. Reddy's Research Foundation | Thiazolidinedione and oxazolidinedione derivatives having antidiabetic, hypolipidaemic and antihypertensive properties |
| AU6325699A (en) | 1998-10-21 | 2000-05-08 | Dr. Reddy's Research Foundation | New compounds, their preparation and use |
| JP2002527507A (ja) | 1998-10-21 | 2002-08-27 | ノボ ノルディスク アクティーゼルスカブ | 新規化合物類、それらの調製及び使用 |
| AU6325599A (en) | 1998-10-21 | 2000-05-08 | Dr. Reddy's Research Foundation | New compounds, their preparation and use |
| EP1123269A1 (en) | 1998-10-21 | 2001-08-16 | Novo Nordisk A/S | New compounds, their preparation and use |
| EP1123267A1 (en) | 1998-10-21 | 2001-08-16 | Novo Nordisk A/S | New compounds, their preparation and use |
| EP1123297A1 (en) | 1998-10-21 | 2001-08-16 | Novo Nordisk A/S | New compounds, their preparation and use |
| CN1137125C (zh) | 1998-12-18 | 2004-02-04 | 诺沃挪第克公司 | 稠合的1,2,4-噻二嗪衍生物、其制备方法和用途 |
| WO2000041121A1 (en) | 1999-01-07 | 2000-07-13 | Ccrewards.Com | Method and arrangement for issuance and management of digital coupons and sales offers |
| AU3033500A (en) | 1999-01-15 | 2000-08-01 | Agouron Pharmaceuticals, Inc. | Non-peptide glp-1 agonists |
| WO2000042023A1 (en) | 1999-01-18 | 2000-07-20 | Novo Nordisk A/S | Substituted imidazoles, their preparation and use |
| JP2002542245A (ja) | 1999-04-16 | 2002-12-10 | ノボ ノルディスク アクティーゼルスカブ | 置換イミダゾール、それらの製造および使用 |
| AU2953699A (en) | 1999-04-16 | 2000-11-02 | Dr. Reddy's Research Foundation | Novel polymorphic forms of an antidiabetic agent: process for their preparation and a pharmaceutical composition containing them |
| AU4465200A (en) | 1999-04-16 | 2000-11-02 | Dr. Reddy's Research Foundation | Novel polymorphic forms of an antidiabetic agent: process for their preparation and a pharmaceutical composition containing them |
| MXPA01010472A (es) | 1999-04-16 | 2002-05-06 | Reddy Research Foundation | Formas polimorficas novedosas de un agente contra la diabetes; procedimiento para su preparacion y composiciones farmaceuticas que las contienen. |
| AU3958000A (en) | 1999-04-20 | 2000-11-02 | Novo Nordisk A/S | New compounds, their preparation and use |
| WO2000063209A1 (en) | 1999-04-20 | 2000-10-26 | Novo Nordisk A/S | New compounds, their preparation and use |
| WO2000063196A1 (en) | 1999-04-20 | 2000-10-26 | Novo Nordisk A/S | New compounds, their preparation and use |
| WO2000063190A1 (en) | 1999-04-20 | 2000-10-26 | Novo Nordisk A/S | New compounds, their preparation and use |
| AU3957600A (en) | 1999-04-26 | 2000-11-10 | Boehringer Ingelheim International Gmbh | Piperidyl-imidazole derivatives, their preparations and therapeutic uses |
| JP4115671B2 (ja) | 1999-05-17 | 2008-07-09 | 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 | 長期間持続するインシュリン向性ペプチド |
| DK1105409T3 (da) | 1999-05-17 | 2006-07-03 | Conjuchem Inc | Beskyttelse af endogene terapeutiske peptider fra peptidaseaktivitet ved konjugering med blodkomponenter |
| EA008837B1 (ru) | 2000-06-16 | 2007-08-31 | Эли Лилли Энд Компани | Аналоги глюкагоноподобного пептида и их применение |
| DK1305301T3 (da) | 2000-07-20 | 2005-10-17 | Hoffmann La Roche | Alpha-acyl- og alpha-heteroatomsubstituerede benzenacetamidglucokinase-aktivatorer |
| GB0121709D0 (en) | 2001-09-07 | 2001-10-31 | Imp College Innovations Ltd | Food inhibition agent |
| US7157277B2 (en) | 2001-11-28 | 2007-01-02 | Neose Technologies, Inc. | Factor VIII remodeling and glycoconjugation of Factor VIII |
| EP2305311A3 (en) | 2001-10-10 | 2011-07-20 | BioGeneriX AG | Glycoconjugation of peptides |
| WO2003062290A1 (en) | 2002-01-16 | 2003-07-31 | Biocompatibles Uk Limited | Polymer conjugates |
| US6953787B2 (en) | 2002-04-12 | 2005-10-11 | Arena Pharmaceuticals, Inc. | 5HT2C receptor modulators |
| JP2006514990A (ja) | 2002-12-27 | 2006-05-18 | ディオベックス， インコーポレイテッド | インスリン誘発性低血糖の予防および制御のための組成物および方法 |
| GB0300571D0 (en) | 2003-01-10 | 2003-02-12 | Imp College Innovations Ltd | Modification of feeding behaviour |
| EP1503283A1 (en) | 2003-08-01 | 2005-02-02 | Hewlett-Packard Development Company, L.P. | Data processing system and method |
| JP4463814B2 (ja) | 2003-08-05 | 2010-05-19 | ノボ ノルディスク アクティーゼルスカブ | 新規のインスリン誘導体 |
| US7807824B2 (en) | 2003-08-12 | 2010-10-05 | Lipoxen Technologies Limited | Sialic acid derivatives for protein derivatisation and conjugation |
| EP2932981B1 (en) | 2003-09-19 | 2021-06-16 | Novo Nordisk A/S | Albumin-binding derivatives of GLP-1 |
| CN100444898C (zh) | 2003-09-19 | 2008-12-24 | 诺沃挪第克公司 | 治疗肽的清蛋白结合型衍生物 |
| RU2401276C2 (ru) | 2003-09-19 | 2010-10-10 | Ново Нордиск А/С | Производные глюкагон-подобного пептида-1 (glp-1) |
| PT2371856T (pt) | 2004-11-12 | 2022-08-12 | Bayer Healthcare Llc | Modificação de fviii direcionada a sítio |
| CN103626884B (zh) | 2005-02-23 | 2016-05-18 | 利普生技术有限公司 | 用于蛋白质衍生和缀合的活化的唾液酸衍生物 |
| TWI362392B (en) | 2005-03-18 | 2012-04-21 | Novo Nordisk As | Acylated glp-1 compounds |
| WO2006097536A2 (en) | 2005-03-18 | 2006-09-21 | Novo Nordisk A/S | Dimeric peptide agonists of the glp-1 receptor |
| JP2008534559A (ja) | 2005-04-01 | 2008-08-28 | ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト | 血液凝固ｆｖｉｉｉ類似体 |
| DK1891105T3 (da) | 2005-06-13 | 2012-07-16 | Imp Innovations Ltd | Hidtil ukendte forbindelser og deres påvirkninger på spiseadfærd |
| RU2007145085A (ru) | 2005-06-15 | 2009-07-20 | Ново Нордиск Хелс Кеа Аг (Ch) | Опосредованное трансглютаминазой коньюгирование гормона роста |
| US20070105755A1 (en) | 2005-10-26 | 2007-05-10 | Neose Technologies, Inc. | One pot desialylation and glycopegylation of therapeutic peptides |
| CN101534846B (zh) | 2005-11-07 | 2014-11-05 | 印第安纳大学研究及科技有限公司 | 显示生理学溶解性和稳定性的胰高血糖素类似物 |
| CA2638779C (en) | 2006-01-31 | 2017-01-03 | National Research Council Of Canada | Production of polysialic acid containing glyconjugates using a self-priming polysialyltransferase |
| EP2471810A1 (en) | 2006-02-22 | 2012-07-04 | Merck Sharp & Dohme Corporation | Oxyntomodulin derivatives |
| US7645860B2 (en) | 2006-03-31 | 2010-01-12 | Baxter Healthcare S.A. | Factor VIII polymer conjugates |
| EP2010222A1 (en) | 2006-03-31 | 2009-01-07 | Baxter International Inc. | Pegylated factor viii |
| WO2008011633A2 (en) | 2006-07-21 | 2008-01-24 | Neose Technologies, Inc. | Glycosylation of peptides via o-linked glycosylation sequences |
| 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 |
| JP5876208B2 (ja) | 2006-12-15 | 2016-03-02 | バクスター・インターナショナル・インコーポレイテッドＢａｘｔｅｒ Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｉｎｃｏｒｐ０Ｒａｔｅｄ | 延長されたｉｎｖｉｖｏ半減期を有する第ＶＩＩａ因子−（ポリ）シアル酸結合体 |
| JP5890085B2 (ja) | 2007-01-05 | 2016-03-22 | 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 | 生理学的ｐＨの緩衝液中で向上した溶解度を示すグルカゴン類縁体 |
| KR20090119876A (ko) | 2007-02-15 | 2009-11-20 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 글루카곤/ｇｌｐ-1 수용체 공동-항진물질 |
| EP2162535A4 (en) | 2007-06-04 | 2011-02-23 | Novo Nordisk As | O-linked glycosylation using N-acetylglucosamine transferases |
| EP2158214B1 (en) | 2007-06-15 | 2011-08-17 | Zealand Pharma A/S | Glucagon analogues |
| EP2155865B1 (en) | 2007-06-15 | 2014-09-17 | National Research Council Of Canada | Engineered versions of polysialyltransferases with enhanced enzymatic properties |
| JP5606314B2 (ja) | 2007-09-05 | 2014-10-15 | ノボ・ノルデイスク・エー／エス | Ａ−ｂ−ｃ−ｄ−で誘導体化されたペプチドとその治療用途 |
| ES2672770T3 (es) * | 2007-09-05 | 2018-06-18 | Novo Nordisk A/S | Derivados del péptido-1 similar al glucagón y su uso farmacéutico |
| AU2008303948A1 (en) * | 2007-09-11 | 2009-04-02 | Mondobiotech Laboratories Ag | Use of the peptide Asn-Asp-Asp-Cys-Glu- Leu-Cys-Val-Asn-Val-Ala-Cys-Thr-Gly-Cys-Leu alone or in combination with the peptide Thr-Thr-Ser-Gln-Val- Arg-Pro-Arg as a therapeutic agent |
| KR20100095441A (ko) | 2007-11-09 | 2010-08-30 | 백스터 인터내셔널 인코포레이티드 | 변형된 재조합 인자 ⅷ 및 폰 빌레브란트 인자 및 사용 방법 |
| US20100317057A1 (en) | 2007-12-28 | 2010-12-16 | Novo Nordisk A/S | Semi-recombinant preparation of glp-1 analogues |
| CN102037004A (zh) | 2008-01-08 | 2011-04-27 | 生物种属学股份公司 | 使用寡糖基转移酶的多肽的糖缀合 |
| AU2009210570B2 (en) | 2008-01-30 | 2014-11-20 | Indiana University Research And Technology Corporation | Ester-based insulin prodrugs |
| CN101965200B (zh) | 2008-02-27 | 2013-06-19 | 诺沃-诺迪斯克有限公司 | 缀合的因子ⅷ分子 |
| CL2009001425A1 (es) | 2008-06-17 | 2010-04-30 | Univ Indiana Res & Tech Corp | Analogos de glucagon con un aminoacido aromatico grande que carece de cadena lateral de imidazol que le confiere actividad agonista del receptor gip; composiciones farmaceutica; kit que los contiene y uso para reducir el aumento de peso, tratar la diabetes o inducir paralisis del tracto intestinal. |
| NZ589847A (en) | 2008-06-17 | 2013-01-25 | Univ Indiana Res & Tech Corp | Glucagon/glp-1 receptor co-agonists |
| EP2307037A4 (en) * | 2008-06-17 | 2011-08-03 | Univ Indiana Res & Tech Corp | GLUCAGON ANALOGUE WITH IMPROVED SOLUBILITY AND STABILITY IN PHYSIOLOGICAL PH BUFFERS |
| EP2987805A3 (en) * | 2008-08-07 | 2016-04-13 | Ipsen Pharma S.A.S. | Analogues of glucose-dependent insulinotropic polypeptide |
| MX2011004085A (es) | 2008-10-17 | 2011-09-27 | Baxter International | Factores sanguineos modificados que comprenden un bajo grado de polimero soluble en agua. |
| JP5635529B2 (ja) | 2008-12-15 | 2014-12-03 | ジーランド ファーマ アクティーゼルスカブ | グルカゴン類似体 |
| DK2370462T3 (da) | 2008-12-15 | 2014-09-08 | Zealand Pharma As | Glucagon-analoger |
| PL2370460T3 (pl) | 2008-12-15 | 2014-09-30 | Zealand Pharma As | Analogi glukagonu |
| CA2747155A1 (en) | 2008-12-15 | 2010-06-24 | Zealand Pharma A/S | Glucagon analogues |
| CN102333788A (zh) | 2009-02-19 | 2012-01-25 | 诺沃—诺迪斯克有限公司 | 因子viii的修饰 |
| US9150632B2 (en) | 2009-06-16 | 2015-10-06 | Indiana University Research And Technology Corporation | GIP receptor-active glucagon compounds |
| CA2767792A1 (en) | 2009-07-13 | 2011-01-20 | Zealand Pharma A/S | Acylated glucagon analogues |
| GB0917072D0 (en) | 2009-09-29 | 2009-11-11 | Univ Ulster | Peptide analogues of glucagon for diabetes therapy |
| WO2011075393A2 (en) | 2009-12-18 | 2011-06-23 | Indiana University Research And Technology Corporation | Glucagon/glp-1 receptor co-agonists |
| CN102892425A (zh) | 2010-01-20 | 2013-01-23 | 西兰制药公司 | 心脏病症的治疗 |
| CN102918056B (zh) | 2010-03-26 | 2016-08-10 | 诺沃—诺迪斯克有限公司 | 新的胰高血糖素类似物 |
| 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 |
| JP2013523620A (ja) | 2010-03-26 | 2013-06-17 | ノヴォ ノルディスク アー／エス | 新規のグルカゴンアナログ |
| AR081975A1 (es) | 2010-06-23 | 2012-10-31 | Zealand Pharma As | Analogos de glucagon |
| US9169310B2 (en) | 2010-06-24 | 2015-10-27 | Zealand Pharma A/S | Glucagon analogues |
| 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 |
| BR112013015389A2 (pt) * | 2010-12-22 | 2016-11-22 | Univ Indiana Res & Tech Corp | análogo de glucagon exibindo atividade de receptor gip |
| AR084558A1 (es) * | 2010-12-22 | 2013-05-22 | Marcadia Biotech | Metodos para tratar trastornos metabolicos y obesidad con peptidos basados en glucagon activos para el receptor de peptido insulinotropico dependiente de glucosa (gip)/peptido-1 similar al glucagon (glp-1) |
| BR112013018269A2 (pt) | 2011-01-20 | 2017-06-06 | Zealand Pharma As | combinação de análogos acilados do glucagon com análogos da insulina |
| MX2013011175A (es) | 2011-03-28 | 2013-11-01 | Novo Nordisk As | Analogos de glucagon novedosos. |
| WO2012138941A1 (en) | 2011-04-05 | 2012-10-11 | Longevity Biotech, Inc. | Compositions comprising glucagon analogs and methods of making and using the same |
| WO2012150503A2 (en) | 2011-05-03 | 2012-11-08 | Zealand Pharma A/S | Glu-glp-1 dual agonist signaling-selective compounds |
| RU2602801C2 (ru) | 2011-05-18 | 2016-11-20 | МЕДЕРИС ДАЙАБИТИЗ, ЭлЭлСи | Пептидные лекарственные препараты с повышенной эффективностью против инсулинорезистентности |
| JP6148228B2 (ja) | 2011-05-18 | 2017-06-14 | ユーメデリス ファーマシューティカルズ，インク． | 改善されたペプチド製剤 |
| PE20240686A1 (es) | 2011-06-10 | 2024-04-10 | Hanmi Science Co Ltd | Peptidos derivados de oxintomodulina con actividad sobre el receptor de glucagon y el receptor de peptido similar a glucagon de tipo 1 (glp-1) |
| PE20140724A1 (es) | 2011-06-22 | 2014-07-10 | Univ Indiana Res & Tech Corp | Coagonistas del receptor de glucagon/glp-1 |
| KR20140043793A (ko) * | 2011-06-22 | 2014-04-10 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 글루카곤/glp-1 수용체 공동-작용물질 |
| TWI596110B (zh) * | 2011-09-23 | 2017-08-21 | 諾佛 儂迪克股份有限公司 | 新穎升糖素類似物 |
| EP2986313B1 (en) | 2013-04-18 | 2019-06-12 | Novo Nordisk A/S | Stable, protracted glp-1/glucagon receptor co-agonists for medical use |
| WO2015086733A1 (en) * | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
-
2014
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019167361A (ja) * | 2013-04-18 | 2019-10-03 | ノヴォ ノルディスク アー／エス | 医療用の安定な遷延性ｇｌｐ−１／グルカゴン受容体コアゴニスト |
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| CA2909581A1 (en) | 2014-10-23 |
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| US20180044394A1 (en) | 2018-02-15 |
| KR20160021758A (ko) | 2016-02-26 |
| MY174727A (en) | 2020-05-11 |
| CN105307672A (zh) | 2016-02-03 |
| SI2986313T1 (sl) | 2019-09-30 |
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| CN105307672B (zh) | 2021-01-05 |
| RU2683039C2 (ru) | 2019-03-26 |
| AU2014255608B2 (en) | 2018-01-25 |
| BR112015025464A2 (pt) | 2017-10-10 |
| RS59124B1 (sr) | 2019-09-30 |
| US20150374794A1 (en) | 2015-12-31 |
| ZA201507010B (en) | 2017-08-30 |
| EP2986313A1 (en) | 2016-02-24 |
| MX362275B (es) | 2019-01-10 |
| JP2016526012A (ja) | 2016-09-01 |
| MX2015014408A (es) | 2017-07-28 |
| EP2986313B1 (en) | 2019-06-12 |
| US20160355562A1 (en) | 2016-12-08 |
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