EA035527B1 - Производные глюкагона с улучшенной стабильностью - Google Patents
Производные глюкагона с улучшенной стабильностью Download PDFInfo
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- EA035527B1 EA035527B1 EA201791333A EA201791333A EA035527B1 EA 035527 B1 EA035527 B1 EA 035527B1 EA 201791333 A EA201791333 A EA 201791333A EA 201791333 A EA201791333 A EA 201791333A EA 035527 B1 EA035527 B1 EA 035527B1
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- Eurasian Patent Office
- Prior art keywords
- cysteine
- glucagon
- seq
- receptor agonist
- pharmaceutical composition
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
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- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Organic Chemistry (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Hematology (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
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- Molecular Biology (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Child & Adolescent Psychology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
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| KR20140193800 | 2014-12-30 | ||
| PCT/KR2015/014422 WO2016108586A1 (ko) | 2014-12-30 | 2015-12-30 | 안정성이 증가된 글루카곤 유도체 |
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| CN107636009B (zh) * | 2014-12-30 | 2021-04-16 | 韩美药品株式会社 | 具有改善的稳定性的胰高血糖素衍生物 |
| TWI713541B (zh) | 2015-06-30 | 2020-12-21 | 南韓商韓美藥品股份有限公司 | 升糖素衍生物及包含該衍生物之長效接合物之組成物 |
| TWI622596B (zh) | 2015-10-26 | 2018-05-01 | 美國禮來大藥廠 | 升糖素受體促效劑 |
| HUE059737T2 (hu) | 2015-12-31 | 2022-12-28 | Hanmi Pharm Ind Co Ltd | Glükagon, GLP-1 és GIP receptor aktiváló tripla aktivátor |
| PE20190355A1 (es) * | 2016-06-29 | 2019-03-07 | Hanmi Pharm Ind Co Ltd | Derivado de glucagon, conjugado del mismo, composicion que comprende el mismo y uso terapeutico del mismo |
| BR112019016077A2 (pt) | 2017-02-03 | 2020-03-31 | Hanmi Pharm. Co., Ltd. | Conjugado da fórmula 1, método para preparar o conjugado, preparação de atuação longa, preparação para prevenir ou tratar diabetes e método para tratar diabetes |
| BR112020012346A2 (pt) * | 2017-12-22 | 2020-11-24 | Hanmi Pharm. Co., Ltd. | proteína de fusão enzimática terapêutica tendo uma nova estrutura e uso da mesma |
| KR20200134213A (ko) * | 2018-01-23 | 2020-12-01 | 엑스에리스 파머수티클스, 인크. | 소 용량의 안정한 글루카곤을 사용한 베리아트릭 후 저혈당증의 치료 |
| BR112021011557A2 (pt) | 2018-12-21 | 2021-09-14 | Hanmi Pharm. Co., Ltd. | Formulação complexa e composição farmacêutica incluindo insulina e glucagon |
| CN109836486B (zh) * | 2019-01-30 | 2020-09-08 | 北京双因生物科技有限公司 | 成纤维生长因子21变体、其融合蛋白及其用途 |
| US20230192800A1 (en) | 2020-05-22 | 2023-06-22 | Hanmi Pharm. Co., Ltd. | Liquid formulation of long-acting conjugate of glucagon derivative |
| JP2023534949A (ja) | 2020-07-15 | 2023-08-15 | ハンミ ファーマシューティカル カンパニー リミテッド | グルカゴン誘導体又はその結合体の肝臓疾患に対する治療的用途 |
| KR20220140443A (ko) | 2021-04-09 | 2022-10-18 | 한미약품 주식회사 | 글루카곤 유도체를 포함하는 만성 신장 질환 예방 또는 치료용 약학 조성물 |
| KR20230095666A (ko) | 2021-12-22 | 2023-06-29 | 한미약품 주식회사 | 간 표적 물질 및 이의 용도 |
| CN115490760B (zh) * | 2022-07-04 | 2023-04-14 | 北京惠之衡生物科技有限公司 | 一种glp-1受体和gcg受体共激动多肽衍生物 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011117415A1 (en) * | 2010-03-26 | 2011-09-29 | Novo Nordisk A/S | Novel glucagon analogues |
| US8507428B2 (en) * | 2010-12-22 | 2013-08-13 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting GIP receptor activity |
| 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 |
| WO2014170496A1 (en) * | 2013-04-18 | 2014-10-23 | Novo Nordisk A/S | Stable, protracted glp-1/glucagon receptor co-agonists for medical use |
Family Cites Families (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5408037A (en) | 1991-01-17 | 1995-04-18 | Zymogenetics, Inc. | Methods for detecting glucagon antagonists |
| GB9423277D0 (en) | 1994-11-18 | 1995-01-11 | Univ Nottingham | Pulsed laser deposition of coatings |
| US6096871A (en) | 1995-04-14 | 2000-08-01 | Genentech, Inc. | Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life |
| WO1997034631A1 (en) | 1996-03-18 | 1997-09-25 | Board Of Regents, The University Of Texas System | Immunoglobin-like domains with increased half lives |
| US6677136B2 (en) | 2000-05-03 | 2004-01-13 | Amgen Inc. | Glucagon antagonists |
| AU2002317599B2 (en) | 2001-07-31 | 2008-04-03 | 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 |
| JP2006520818A (ja) | 2003-03-19 | 2006-09-14 | イーライ リリー アンド カンパニー | ポリエチレングリコール結合ｇｌｐ−１化合物 |
| RU2356909C2 (ru) | 2003-11-13 | 2009-05-27 | Ханми Фарм. Инд. Ко., Лтд. | Белковый комплекс, полученный с использованием фрагмента иммуноглобулина, и способ получения такого комплекса |
| US8263084B2 (en) | 2003-11-13 | 2012-09-11 | Hanmi Science Co., Ltd | Pharmaceutical composition for treating obesity-related disease comprising insulinotropic peptide conjugate |
| EP2573111A1 (en) | 2006-04-20 | 2013-03-27 | Amgen Inc. | GLP-1 compounds |
| RU2477286C2 (ru) | 2007-01-05 | 2013-03-10 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | АНАЛОГИ ГЛЮКАГОНА, ОБЛАДАЮЩИЕ ПОВЫШЕННОЙ РАСТВОРИМОСТЬЮ В БУФЕРАХ С ФИЗИОЛОГИЧЕСКИМ ЗНАЧЕНИЕМ pH |
| JP2008169195A (ja) | 2007-01-05 | 2008-07-24 | Hanmi Pharmaceutical Co Ltd | キャリア物質を用いたインスリン分泌ペプチド薬物結合体 |
| US20090098130A1 (en) | 2007-01-05 | 2009-04-16 | Bradshaw Curt W | Glucagon-like protein-1 receptor (glp-1r) agonist compounds |
| MX2009008241A (es) | 2007-02-15 | 2009-10-08 | Univ Indiana Res & Tech Corp | Co-agonistas de receptor de glucagon/glp-1. |
| DK2158214T3 (da) | 2007-06-15 | 2011-12-05 | Zealand Pharma As | Glukagonanaloger |
| BRPI0813139A8 (pt) | 2007-06-19 | 2019-01-29 | Glytech Inc | peptídeo glp-1 com adição de cadeia oligossacarídea |
| CA2713348C (en) | 2008-01-30 | 2018-10-09 | Indiana University Research And Technology Corporation | Ester-based peptide prodrugs |
| WO2009155257A1 (en) * | 2008-06-17 | 2009-12-23 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting enhanced solubility and stability physiological ph buffers |
| WO2010011439A2 (en) | 2008-06-17 | 2010-01-28 | Indiana University Research And Technology Corporation | Gip-based mixed agonists for treatment of metabolic disorders and obesity |
| WO2010096052A1 (en) | 2009-02-19 | 2010-08-26 | Merck Sharp & Dohme Corp. | Oxyntomodulin analogs |
| US9150632B2 (en) | 2009-06-16 | 2015-10-06 | Indiana University Research And Technology Corporation | GIP receptor-active glucagon compounds |
| HUE026255T2 (en) | 2009-07-13 | 2016-06-28 | Zealand Pharma As | Acylated glucagon analogues |
| GB0917072D0 (en) | 2009-09-29 | 2009-11-11 | Univ Ulster | Peptide analogues of glucagon for diabetes therapy |
| US8703701B2 (en) | 2009-12-18 | 2014-04-22 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
| MX342409B (es) * | 2010-01-20 | 2016-09-28 | Zealand Pharma As | Tratamiento de enfermedades cardiacas. |
| US9145451B2 (en) | 2010-05-13 | 2015-09-29 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhbiting G protein coupled receptor activity |
| KR101382593B1 (ko) | 2010-07-21 | 2014-04-10 | 한미사이언스 주식회사 | 신규한 지속형 글루카곤 결합체 및 이를 포함하는 비만 예방 및 치료용 약학적 조성물 |
| WO2012150503A2 (en) | 2011-05-03 | 2012-11-08 | Zealand Pharma A/S | Glu-glp-1 dual agonist signaling-selective compounds |
| US10471127B2 (en) | 2011-05-18 | 2019-11-12 | Mederis Diabetes, Llc | Peptide pharmaceuticals for insulin resistance |
| SI2718318T1 (sl) * | 2011-06-10 | 2018-11-30 | Hanmi Science Co., Ltd. | Novi derivati oksintomodulina in le-te obsegajoča farmacevtska sestava za zdravljenje debelosti |
| ES2710356T3 (es) * | 2011-06-17 | 2019-04-24 | Hanmi Science Co Ltd | Conjugado que comprende oxintomodulina y un fragmento de inmunoglobulina, y uso del mismo |
| US9944687B2 (en) | 2011-07-04 | 2018-04-17 | Imperial Innovations Limited | Compounds and their effects on feeding behaviour |
| EP2780031B1 (en) * | 2011-11-17 | 2018-03-07 | Indiana University Research and Technology Corporation | Glucagon superfamily peptides exhibiting glucocorticoid receptor activity |
| KR20150039748A (ko) | 2012-06-21 | 2015-04-13 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | Gip 수용체 활성을 나타내는 글루카곤의 유사체들 |
| EP2864351B1 (en) | 2012-06-21 | 2016-08-10 | Indiana University Research and Technology Corporation | Glucagon analogs exhibiting gip receptor activity |
| AR094821A1 (es) | 2012-07-25 | 2015-09-02 | Hanmi Pharm Ind Co Ltd | Formulación líquida de un conjugado de péptido insulinotrópico de acción prolongada |
| KR101968344B1 (ko) | 2012-07-25 | 2019-04-12 | 한미약품 주식회사 | 옥신토모듈린 유도체를 포함하는 고지혈증 치료용 조성물 |
| WO2014049610A2 (en) | 2012-09-26 | 2014-04-03 | Cadila Healthcare Limited | Peptides as gip, glp-1 and glucagon receptors triple-agonist |
| KR101993393B1 (ko) * | 2012-11-06 | 2019-10-01 | 한미약품 주식회사 | 옥신토모듈린 유도체를 포함하는 당뇨병 또는 비만성 당뇨병 치료용 조성물 |
| TWI652071B (zh) | 2012-11-06 | 2019-03-01 | 韓美藥品股份有限公司 | 包含調酸素及免疫球蛋白片段之蛋白質接合物的液態製劑 |
| BR112015011478B1 (pt) | 2012-11-20 | 2022-10-25 | Mederis Diabetes, Llc | Produtos de peptídeo, seus usos e composição farmacêutica |
| DK3444281T3 (da) | 2012-11-20 | 2022-02-07 | Eumederis Pharmaceuticals Inc | Forbedrede peptidlægemidler |
| CA2895875A1 (en) | 2012-12-21 | 2014-06-26 | Sanofi | Exendin-4 derivatives |
| EP3033355A1 (en) | 2013-08-16 | 2016-06-22 | Medimmune Limited | Gip and glp-1 receptor dual-agonists for the treatment of diabetes |
| WO2015086733A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
| AR100695A1 (es) | 2014-05-30 | 2016-10-26 | Hanmi Pharm Ind Co Ltd | Composición para el tratamiento de diabetes mellitus que comprende insulina y un agonista dual glp-1 / glucagón |
| TWI802396B (zh) | 2014-09-16 | 2023-05-11 | 南韓商韓美藥品股份有限公司 | 長效glp-1/高血糖素受體雙促效劑治療非酒精性脂肝疾病之用途 |
| EP3206710B1 (en) | 2014-09-24 | 2020-05-06 | Indiana University Research & Technology Corporation | Incretin-insulin conjugates |
| KR102418477B1 (ko) * | 2014-12-30 | 2022-07-08 | 한미약품 주식회사 | 글루카곤 유도체 |
| CN107636009B (zh) | 2014-12-30 | 2021-04-16 | 韩美药品株式会社 | 具有改善的稳定性的胰高血糖素衍生物 |
| TWI713541B (zh) | 2015-06-30 | 2020-12-21 | 南韓商韓美藥品股份有限公司 | 升糖素衍生物及包含該衍生物之長效接合物之組成物 |
| TW201718629A (zh) * | 2015-09-25 | 2017-06-01 | 韓美藥品股份有限公司 | 包含多個生理多肽及免疫球蛋白Ｆｃ區之蛋白質接合物 |
| HUE059737T2 (hu) | 2015-12-31 | 2022-12-28 | Hanmi Pharm Ind Co Ltd | Glükagon, GLP-1 és GIP receptor aktiváló tripla aktivátor |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| WO2011117415A1 (en) * | 2010-03-26 | 2011-09-29 | Novo Nordisk A/S | Novel glucagon analogues |
| US8507428B2 (en) * | 2010-12-22 | 2013-08-13 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting GIP receptor activity |
| WO2014170496A1 (en) * | 2013-04-18 | 2014-10-23 | Novo Nordisk A/S | Stable, protracted glp-1/glucagon receptor co-agonists for medical use |
Non-Patent Citations (1)
| Title |
|---|
| CHABENNE et al., "A Glucagon Analog Chemically stabilized for Immediate Treatment of Life Threatening Hypoglycemia" Molecular Metabolism, Vol. 3, pp. 293-300 (January 2014). See the entire document * |
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