RU2580317C2 - Пептидные пролекарства, принадлежащие к суперсемейству амид-содержащих глюкагонов - Google Patents
Пептидные пролекарства, принадлежащие к суперсемейству амид-содержащих глюкагонов Download PDFInfo
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- RU2580317C2 RU2580317C2 RU2013103093/04A RU2013103093A RU2580317C2 RU 2580317 C2 RU2580317 C2 RU 2580317C2 RU 2013103093/04 A RU2013103093/04 A RU 2013103093/04A RU 2013103093 A RU2013103093 A RU 2013103093A RU 2580317 C2 RU2580317 C2 RU 2580317C2
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- 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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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
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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
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- A—HUMAN NECESSITIES
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- 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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- A—HUMAN NECESSITIES
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P5/00—Drugs for disorders of the endocrine system
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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| PCT/US2011/040330 WO2011163012A2 (en) | 2010-06-24 | 2011-06-14 | Amide based glucagon superfamily peptide prodrugs |
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Families Citing this family (76)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2572952T3 (es) | 2005-11-07 | 2016-06-03 | Indiana University Research And Technology Corporation | Análogos de glucagón que muestran solubilidad y estabilidad fisiológicas |
| MX2009008241A (es) | 2007-02-15 | 2009-10-08 | Univ Indiana Res & Tech Corp | Co-agonistas de receptor de glucagon/glp-1. |
| CA2682174C (en) | 2007-03-28 | 2021-04-06 | President And Fellows Of Harvard College | Stitched polypeptides |
| US8980830B2 (en) | 2007-10-30 | 2015-03-17 | Indiana University Research And Technology Corporation | Peptide compounds exhibiting glucagon antagonist and GLP-1 agonist activity |
| ES2509883T3 (es) | 2007-10-30 | 2014-10-20 | Indiana University Research And Technology Corporation | Antagonistas de glucagón |
| CA2713348C (en) | 2008-01-30 | 2018-10-09 | Indiana University Research And Technology Corporation | Ester-based peptide prodrugs |
| AR072160A1 (es) | 2008-06-17 | 2010-08-11 | Univ Indiana Res & Tech Corp | Co-agonistas del receptor de glucagon/glp-1 |
| 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 |
| WO2010080609A1 (en) | 2008-12-19 | 2010-07-15 | Indiana University Research And Technology Corporation | Amide-based insulin prodrugs |
| CA2747490C (en) | 2008-12-19 | 2017-02-14 | Indiana University Research And Technology Corporation | Insulin analogs |
| AU2009327418A1 (en) | 2008-12-19 | 2010-06-24 | Indiana University Research And Technology Corporation | Amide based glucagon superfamily peptide prodrugs |
| US9150632B2 (en) | 2009-06-16 | 2015-10-06 | Indiana University Research And Technology Corporation | GIP receptor-active glucagon compounds |
| US8551946B2 (en) * | 2010-01-27 | 2013-10-08 | Indiana University Research And Technology Corporation | Glucagon antagonist-GIP agonist conjugates and compositions for the treatment of metabolic disorders and obesity |
| JP6121323B2 (ja) | 2010-05-13 | 2017-05-10 | 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 | 核内ホルモン受容体の活性を示すグルカゴンスーパーファミリーのペプチド |
| US9145451B2 (en) | 2010-05-13 | 2015-09-29 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhbiting G protein coupled receptor activity |
| AU2011268327B2 (en) | 2010-06-16 | 2016-02-25 | Indiana University Research And Technology Corporation | Single chain insulin agonists exhibiting high activity at the insulin receptor |
| CA2803164C (en) | 2010-06-24 | 2018-08-21 | Indiana University Research And Technology Corporation | Amide-based insulin prodrugs |
| WO2012021875A1 (en) | 2010-08-13 | 2012-02-16 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles with triazole linkers |
| PE20140186A1 (es) | 2010-12-22 | 2014-02-13 | Univ Indiana Res & Tech Corp | Analogos de glucagon que presentan actividad de receptor de gip |
| 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 |
| CN103748109A (zh) | 2011-06-22 | 2014-04-23 | 印第安纳大学研究及科技有限公司 | 胰高血糖素/glp-1受体共同激动剂 |
| JP6179864B2 (ja) | 2011-06-22 | 2017-08-16 | インディアナ ユニヴァーシティ リサーチ アンド テクノロジー コーポレイション | グルカゴン／ｇｌｐ−１レセプタコ−アゴニスト |
| CN108929375A (zh) | 2011-10-18 | 2018-12-04 | 爱勒让治疗公司 | 拟肽大环化合物 |
| EP2780031B1 (en) | 2011-11-17 | 2018-03-07 | Indiana University Research and Technology Corporation | Glucagon superfamily peptides exhibiting glucocorticoid receptor activity |
| US9573987B2 (en) | 2011-12-20 | 2017-02-21 | Indiana University Research And Technology Corporation | CTP-based insulin analogs for treatment of diabetes |
| CN112500466B (zh) | 2012-02-15 | 2022-05-03 | 艾瑞朗医疗公司 | 拟肽大环化合物 |
| CA2864120A1 (en) | 2012-02-15 | 2013-08-22 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| US9452225B2 (en) * | 2012-03-01 | 2016-09-27 | Novo Nordisk A/S | GLP-1 prodrugs |
| EP2824184B1 (en) | 2012-03-04 | 2017-09-27 | Bonac Corporation | micro-RNA INHIBITOR |
| EP2864351B1 (en) | 2012-06-21 | 2016-08-10 | Indiana University Research and Technology Corporation | Glucagon analogs exhibiting gip receptor activity |
| KR20150039748A (ko) * | 2012-06-21 | 2015-04-13 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | Gip 수용체 활성을 나타내는 글루카곤의 유사체들 |
| KR101968344B1 (ko) | 2012-07-25 | 2019-04-12 | 한미약품 주식회사 | 옥신토모듈린 유도체를 포함하는 고지혈증 치료용 조성물 |
| CA2886228A1 (en) | 2012-09-26 | 2014-04-03 | Indiana University Research And Technology Corporation | Insulin analog dimers |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| CN104812384B (zh) | 2012-11-01 | 2020-09-18 | 爱勒让治疗公司 | 二取代的氨基酸及其制备和使用方法 |
| 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 |
| KR101993393B1 (ko) | 2012-11-06 | 2019-10-01 | 한미약품 주식회사 | 옥신토모듈린 유도체를 포함하는 당뇨병 또는 비만성 당뇨병 치료용 조성물 |
| CA2895875A1 (en) | 2012-12-21 | 2014-06-26 | Sanofi | Exendin-4 derivatives |
| WO2014158900A1 (en) | 2013-03-14 | 2014-10-02 | Indiana University Research And Technology Corporation | Insulin-incretin conjugates |
| EP2986314A4 (en) * | 2013-03-15 | 2016-04-13 | Univ Indiana Res & Tech Corp | PRODRUGS WITH EXTENDED EFFECT |
| US9907856B2 (en) | 2013-07-08 | 2018-03-06 | The Regents Of The University Of California | Carboxymethylcellulose-peptide conjugates and methods for using the same |
| WO2015035419A1 (en) * | 2013-09-09 | 2015-03-12 | Hoffmann-La Roche Inc. | Dosages of gip/glp-1 co-agonist peptides for human administration |
| AU2014359894B2 (en) | 2013-12-06 | 2020-09-17 | Baikang (Suzhou) Co., Ltd | Bioreversable promoieties for nitrogen-containing and hydroxyl-containing drugs |
| WO2015086733A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
| WO2015086730A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Non-acylated exendin-4 peptide analogues |
| EP3080154B1 (en) | 2013-12-13 | 2018-02-07 | Sanofi | Dual glp-1/gip receptor agonists |
| EP3080150B1 (en) | 2013-12-13 | 2018-08-01 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
| AR098616A1 (es) | 2013-12-18 | 2016-06-01 | Lilly Co Eli | Péptido para el tratamiento de hipoglicemia severa |
| 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 |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| GB2528436A (en) | 2014-07-15 | 2016-01-27 | Lancaster Univ Business Entpr Ltd | Treatment of neurological diseases |
| 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 |
| EP3197478A4 (en) | 2014-09-24 | 2018-05-30 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| ES2947409T3 (es) | 2014-09-24 | 2023-08-08 | Univ Indiana Res & Tech Corp | Profármacos de insulina a base de amida lipídica |
| EP3206710B1 (en) | 2014-09-24 | 2020-05-06 | Indiana University Research & Technology Corporation | Incretin-insulin conjugates |
| MA55068A (fr) | 2014-10-24 | 2022-01-05 | Merck Sharp & Dohme | Co-agonistes des récepteurs du glucagon et du glp-1 |
| KR102418477B1 (ko) | 2014-12-30 | 2022-07-08 | 한미약품 주식회사 | 글루카곤 유도체 |
| SG11201707750YA (en) | 2015-03-20 | 2017-10-30 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and uses thereof |
| AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
| AR105284A1 (es) | 2015-07-10 | 2017-09-20 | Sanofi Sa | Derivados de exendina-4 como agonistas peptídicos duales específicos de los receptores de glp-1 / glucagón |
| WO2018009778A1 (en) * | 2016-07-07 | 2018-01-11 | Baylor College Of Medicine | Combination of glp-1 and glp-2 for treating or preventing metabolic diseases, disorders and syndromes |
| WO2018229252A1 (en) | 2017-06-16 | 2018-12-20 | Zealand Pharma A/S | Dosage regimes for the administration of glucagon-like-peptide-2 (glp-2) analogues |
| CN116143939A (zh) * | 2017-11-24 | 2023-05-23 | 浙江道尔生物科技有限公司 | 一种治疗代谢疾病的多重活性蛋白 |
| WO2020061244A2 (en) * | 2018-09-19 | 2020-03-26 | Georgia Tech Research Corporation | Self-titrating bacterial protease-activated prodrug |
| WO2021083306A1 (zh) * | 2019-10-31 | 2021-05-06 | 东莞市东阳光生物药研发有限公司 | Glp-1/gcg双受体激动剂多肽 |
| CN115697414A (zh) * | 2020-06-03 | 2023-02-03 | 哥本哈根大学 | Glp1r激动剂nmdar拮抗剂缀合物 |
| KR102446310B1 (ko) | 2020-07-22 | 2022-09-23 | 노보 노르디스크 에이/에스 | 경구 전달에 적합한 glp-1 및 gip 수용체에서의 공-작용제 |
| EP4240420A1 (en) | 2020-11-06 | 2023-09-13 | Novo Nordisk A/S | Glp-1 prodrugs and uses hereof |
| WO2023012263A1 (en) | 2021-08-04 | 2023-02-09 | Novo Nordisk A/S | Solid oral peptide formulations |
| 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 |
| WO2023217744A1 (en) | 2022-05-10 | 2023-11-16 | Novo Nordisk A/S | Prodrugs of glp-1 polypeptide and uses thereof |
| CN114636773B (zh) * | 2022-05-23 | 2022-08-23 | 广东国标医药科技有限公司 | 一种药用辅料中聚乙二醇单甲醚2000的含量测定方法 |
| WO2024110614A1 (en) | 2022-11-25 | 2024-05-30 | Novo Nordisk A/S | Oral administration of peptide therapeutics, such as glp-1 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009095479A2 (en) * | 2008-02-01 | 2009-08-06 | Ascendis Pharma As | Prodrug comprising a self-cleavable linker |
| WO2009099763A1 (en) * | 2008-01-30 | 2009-08-13 | Indiana University Research And Technology Corporation | Ester-based peptide prodrugs |
| RU2011129784A (ru) * | 2008-12-19 | 2013-01-27 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Основанные на амидах пролекарства пептидов глюкагонового надсемейства |
Family Cites Families (117)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US171920A (en) | 1876-01-11 | Improvement in hat and coat hooks | ||
| US3740385A (en) | 1970-05-07 | 1973-06-19 | M Ondetti | N-terminal derivatives of secretin |
| US4275152A (en) | 1977-02-03 | 1981-06-23 | Eastman Kodak Company | Hydrolysis of protein-bound cholesterol esters |
| PT83613B (en) | 1985-10-28 | 1988-11-21 | Lilly Co Eli | Process for the selective chemical removal of a protein amino-terminal residue |
| WO1987005330A1 (en) | 1986-03-07 | 1987-09-11 | Michel Louis Eugene Bergh | Method for enhancing glycoprotein stability |
| US4741897A (en) | 1986-07-08 | 1988-05-03 | Baxter Travenol | Thyroxine analogs and reagents for thyroid hormone assays |
| US5539084A (en) | 1989-02-17 | 1996-07-23 | Coselco Mimotopes Pty. Ltd. | Method for the use and synthesis of peptides |
| CA2073856C (en) | 1990-01-24 | 2002-12-03 | Douglas I. Buckley | Glp-1 analogs useful for diabetes treatment |
| CA2024855C (en) | 1990-09-07 | 1997-12-09 | Boehringer Ingelheim (Canada) Ltd./ Boehringer Ingelheim (Canada) Ltee | Process and intermediates for producing glucagon |
| JPH04145099A (ja) | 1990-10-05 | 1992-05-19 | Sanwa Kagaku Kenkyusho Co Ltd | Ｇｉｐ様活性を有するポリペプチド誘導体及びその用途 |
| US5510459A (en) | 1991-01-17 | 1996-04-23 | Zymogenetics, Inc. | Glucagon antagonists |
| US5359030A (en) | 1993-05-10 | 1994-10-25 | Protein Delivery, Inc. | Conjugation-stabilized polypeptide compositions, therapeutic delivery and diagnostic formulations comprising same, and method of making and using the same |
| US5480867A (en) | 1993-12-29 | 1996-01-02 | The Rockefeller University | Glucagon analogs with serine replacements |
| US5512549A (en) | 1994-10-18 | 1996-04-30 | Eli Lilly And Company | Glucagon-like insulinotropic peptide analogs, compositions, and methods of use |
| US5691309A (en) | 1995-01-31 | 1997-11-25 | Eli Lilly And Company | Anti-obesity proteins |
| US5869602A (en) | 1995-03-17 | 1999-02-09 | Novo Nordisk A/S | Peptide derivatives |
| DE19530865A1 (de) | 1995-08-22 | 1997-02-27 | Michael Dr Med Nauck | Wirkstoff sowie Mittel zur parenteralen Ernährung |
| WO1997013500A2 (en) | 1995-10-12 | 1997-04-17 | Supergen, Inc. | LIPOSOME FORMULATIONS OF 5β STEROIDS |
| US6180767B1 (en) | 1996-01-11 | 2001-01-30 | Thomas Jefferson University | Peptide nucleic acid conjugates |
| WO1997029180A1 (en) | 1996-02-06 | 1997-08-14 | Eli Lilly And Company | Diabetes therapy |
| WO1998011126A1 (en) | 1996-09-09 | 1998-03-19 | Zealand Pharmaceuticals A/S | Peptide prodrugs containing an alpha-hydroxyacid linker |
| UA65549C2 (uk) | 1996-11-05 | 2004-04-15 | Елі Ліллі Енд Компані | Спосіб регулювання ожиріння шляхом периферійного введення аналогів та похідних glp-1 (варіанти) та фармацевтична композиція |
| WO1998024464A1 (en) | 1996-12-03 | 1998-06-11 | Trustees Of Boston University | Specific antagonists for glucose-dependent insulinotropic polypeptide (gip) |
| IL138214A0 (en) | 1998-03-09 | 2001-10-31 | Zealand Pharmaceuticals As | Pharmacolgically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
| DE19828113A1 (de) | 1998-06-24 | 2000-01-05 | Probiodrug Ges Fuer Arzneim | Prodrugs von Inhibitoren der Dipeptidyl Peptidase IV |
| US20030236190A1 (en) | 1998-09-02 | 2003-12-25 | Renuka Pillutla | Isulin and IGF-1 receptor agonists and antagonists |
| EP1119625B1 (en) | 1998-10-07 | 2005-06-29 | Medical College Of Georgia Research Institute, Inc. | Glucose-dependent insulinotropic peptide for use as an osteotropic hormone |
| DE69938669D1 (de) * | 1998-12-07 | 2008-06-19 | Sod Conseils Rech Applic | Analoge des glucagon ähnlichen peptides-1 (glp-1) |
| AU3033500A (en) | 1999-01-15 | 2000-08-01 | Agouron Pharmaceuticals, Inc. | Non-peptide glp-1 agonists |
| DE60012721T4 (de) | 1999-03-29 | 2010-09-09 | Uutech Ltd., Coleraine | Analoge des magensaft inhibierenden peptides und ihre verwendung für die behandlung von diabetes |
| US7601691B2 (en) | 1999-05-17 | 2009-10-13 | Conjuchem Biotechnologies Inc. | Anti-obesity agents |
| AUPQ661800A0 (en) | 2000-03-31 | 2000-05-04 | Metabolic Pharmaceuticals Limited | Insulin-potentiating compounds |
| AU2001257278A1 (en) | 2000-04-27 | 2001-11-07 | Bionebraska, Inc. | Gastric inhibitory polypeptide diagnostic test for detecting susceptibility to type-2 diabetes, impaired glucose tolerance, or impaired fasting glucose |
| US6677136B2 (en) | 2000-05-03 | 2004-01-13 | Amgen Inc. | Glucagon antagonists |
| CA2410604A1 (en) | 2000-06-14 | 2001-12-20 | Cytovax Biotechnologies, Inc. | Use of coiled-coil structural scaffold to generate structure-specific peptides |
| KR100847615B1 (ko) | 2000-06-16 | 2008-07-21 | 일라이 릴리 앤드 캄파니 | 글루카곤-유사 펩티드-1 유사체 |
| US20030204063A1 (en) | 2000-08-02 | 2003-10-30 | Denis Gravel | Modified biological peptides with increased potency |
| GB2382346B (en) | 2000-08-04 | 2004-08-11 | Dmi Biosciences Inc | Method of synthesizing diketopiperazines |
| US20020045572A1 (en) | 2000-08-15 | 2002-04-18 | Cpd, Llc | Method of treating the syndrome of type 2 diabetes in humans |
| US6262062B1 (en) | 2000-08-15 | 2001-07-17 | Cpd, Llc | Method of treating the syndrome of coronary heart disease risk factors in humans |
| US6528520B2 (en) | 2000-08-15 | 2003-03-04 | Cpd, Llc | Method of treating the syndrome of coronary heart disease risk factors in humans |
| ATE516820T1 (de) | 2000-09-29 | 2011-08-15 | Schering Corp | Pegyliertes interleukin 10 |
| AU2002228608A1 (en) | 2000-12-13 | 2002-06-24 | Eli Lilly And Company | Amidated glucagon-like peptide-1 |
| EP1243276A1 (en) | 2001-03-23 | 2002-09-25 | Franciscus Marinus Hendrikus De Groot | Elongated and multiple spacers containing activatible prodrugs |
| IL158418A0 (en) | 2001-04-19 | 2004-05-12 | Scripps Research Inst | In vivo incorporation of unnatural amino acids |
| 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 |
| AU2002327430A1 (en) | 2001-08-08 | 2003-02-24 | Genzyme Corporation | Methods for treating diabetes and other blood sugar disorders |
| BR0212080A (pt) | 2001-08-23 | 2006-04-04 | Lilly Co Eli | composto de glp-1, método de estimulação de receptor de glp-1 em um indivìduo necessitando de tal estimulação, e, uso de um composto de glp-1 |
| WO2003020201A2 (en) | 2001-08-28 | 2003-03-13 | Eli Lilly And Company | Pre-mixes of glp-1 and basal insulin |
| GB0121709D0 (en) | 2001-09-07 | 2001-10-31 | Imp College Innovations Ltd | Food inhibition agent |
| US7041646B2 (en) | 2001-10-05 | 2006-05-09 | Bayer Pharmaceuticals Corporation | Methods of treating type 2 diabetes with peptides acting as both GLP-1 receptor agonists and glucagon receptor antagonists |
| AR036711A1 (es) | 2001-10-05 | 2004-09-29 | Bayer Corp | Peptidos que actuan como agonistas del receptor del glp-1 y como antagonistas del receptor del glucagon y sus metodos de uso farmacologico |
| US7238671B2 (en) * | 2001-10-18 | 2007-07-03 | Bristol-Myers Squibb Company | Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions |
| US7238670B2 (en) | 2001-10-18 | 2007-07-03 | Bristol-Myers Squibb Company | Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions |
| MXPA04003569A (es) | 2001-10-19 | 2004-07-23 | Lilly Co Eli | Mezclas bifasicas de glp-1 e insulina. |
| BR0215029A (pt) | 2001-12-20 | 2005-12-20 | Lilly Co Eli | Molécula de insulina, uso da mesma, composição, uso desta, microcristal, processo para prepará-lo, uso deste, e, métodos para preparar uma molécula de insulina, para tratar hiperglicemia, e para tratar diabetes mellitus |
| AU2002351752A1 (en) | 2001-12-29 | 2003-07-30 | Novo Nordisk A/S | Combined use of a glp-1 compound and another drug for treating dyslipidemia |
| MXPA04006679A (es) | 2002-01-08 | 2004-11-10 | Lilly Co Eli | Analogos extendidos de peptido-1 de tipo glucagon. |
| US20030232761A1 (en) | 2002-03-28 | 2003-12-18 | Hinke Simon A. | Novel analogues of glucose-dependent insulinotropic polypeptide |
| US20060252916A1 (en) | 2002-06-04 | 2006-11-09 | Eli Lilly And Company | Modified glucagon-like peptide-1 analogs |
| FR2842209B1 (fr) | 2002-07-09 | 2007-11-23 | Nouvelle protease aspartique dite saspase et son utilisation dans le domaine cosmetique et therapeutique | |
| EP1539210A4 (en) | 2002-09-06 | 2006-06-07 | Bayer Pharmaceuticals Corp | GLP-1 RECEPTOR MODIFIED AGONISTS AND THEIR PHARMACOLOGICAL METHODS OF USE |
| US7192922B2 (en) | 2002-11-19 | 2007-03-20 | Allegheny-Singer Research Institute | Method of treating left ventricular dysfunction |
| ES2897506T3 (es) | 2003-01-09 | 2022-03-01 | Macrogenics Inc | Identificación y modificación de anticuerpos con regiones Fc variantes y métodos de utilización de los mismos |
| WO2004067548A2 (en) | 2003-01-31 | 2004-08-12 | Theratechnologies Inc. | Chemically modified metabolites of regulatory peptides and methods of producing and using same |
| 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 |
| CA2521784C (en) | 2003-04-08 | 2012-03-27 | Yeda Research And Development Co. Ltd. | Reversible pegylated drugs |
| TWI353991B (en) | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
| 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 |
| EP1633390B1 (en) | 2003-06-03 | 2012-01-18 | Novo Nordisk A/S | Stabilized pharmaceutical glp-1 peptide compositions |
| UA87458C2 (ru) | 2003-06-12 | 2009-07-27 | Елі Ліллі Енд Компані | Гибридные белки-аналоги glp-1 |
| US20050124550A1 (en) | 2003-06-18 | 2005-06-09 | Peri Krishna G. | Compounds that modulate the glucagon response and uses thereof |
| AU2004273573B2 (en) | 2003-09-19 | 2010-04-22 | Novo Nordisk A/S | Albumin-binding derivatives of therapeutic peptides |
| US20050187147A1 (en) | 2003-09-22 | 2005-08-25 | Newman Michael J. | Compositions and methods for increasing drug efficiency |
| US7364875B2 (en) | 2003-10-30 | 2008-04-29 | Cresent Innovations, Inc. | Method for producing medical and commercial grade poly-gamma-glutamic acid of high molecular weight |
| WO2005058954A1 (en) | 2003-12-18 | 2005-06-30 | Novo Nordisk A/S | Novel glp-1 compounds |
| US20060286129A1 (en) | 2003-12-19 | 2006-12-21 | Emisphere Technologies, Inc. | Oral GLP-1 formulations |
| US20080318837A1 (en) | 2003-12-26 | 2008-12-25 | Nastech Pharmaceutical Company Inc. | Pharmaceutical Formation For Increased Epithelial Permeability of Glucose-Regulating Peptide |
| SG158158A1 (en) | 2004-12-22 | 2010-01-29 | Centocor Inc | Glp-1 agonists, compositions, methods and uses |
| US20090286723A1 (en) | 2005-02-11 | 2009-11-19 | Amylin Pharmaceuticals, Inc. | Hybrid Polypeptides with Selectable Properties |
| BRPI0606992A2 (pt) | 2005-02-11 | 2009-07-28 | Amylin Pharmaceuticals Inc | análogo e polipeptìdeos hìbridos de gip com propriedades selecionáveis |
| EP1863537A2 (en) | 2005-03-18 | 2007-12-12 | Novo Nordisk A/S | Dimeric peptide agonists of the glp-1 receptor |
| ATE482724T1 (de) | 2005-05-13 | 2010-10-15 | Lilly Co Eli | Pegylierte glp-1-verbindungen |
| EP1891105B1 (en) | 2005-06-13 | 2012-04-11 | Imperial Innovations Limited | Oxyntomodulin analogues and their effects on feeding behaviour |
| KR20080052649A (ko) | 2005-09-08 | 2008-06-11 | 트러스티즈 오브 터프츠 칼리지 | 안정화된 ｇｌｐ―1 유사체 |
| US7846445B2 (en) | 2005-09-27 | 2010-12-07 | Amunix Operating, Inc. | Methods for production of unstructured recombinant polymers and uses thereof |
| ES2572952T3 (es) | 2005-11-07 | 2016-06-03 | Indiana University Research And Technology Corporation | Análogos de glucagón que muestran solubilidad y estabilidad fisiológicas |
| AU2007221366B2 (en) | 2006-02-22 | 2012-08-23 | Msd Italia S.R.L. | Oxyntomodulin derivatives |
| EP1996224B1 (en) | 2006-03-15 | 2012-11-07 | Novo Nordisk A/S | Mixtures of amylin and insulin |
| 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 |
| EP2573111A1 (en) | 2006-04-20 | 2013-03-27 | Amgen Inc. | GLP-1 compounds |
| US20090318353A1 (en) | 2006-08-25 | 2009-12-24 | Novo Nordisk A/S | Acylated Exendin-4 Compounds |
| CN104193815A (zh) | 2006-09-08 | 2014-12-10 | Ambrx公司 | 经修饰的人类血浆多肽或Fc骨架和其用途 |
| 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 |
| MX2009008241A (es) | 2007-02-15 | 2009-10-08 | Univ Indiana Res & Tech Corp | Co-agonistas de receptor de glucagon/glp-1. |
| US8933197B2 (en) | 2007-08-15 | 2015-01-13 | Amunix Operating Inc. | Compositions comprising modified biologically active polypeptides |
| US20100292133A1 (en) | 2007-09-05 | 2010-11-18 | Novo Nordisk A/S | Truncated glp-1 derivaties and their therapeutical use |
| WO2009030738A1 (en) | 2007-09-05 | 2009-03-12 | Novo Nordisk A/S | Glucagon-like peptide-1 derivatives and their pharmaceutical use |
| EP2650006A1 (en) | 2007-09-07 | 2013-10-16 | Ipsen Pharma S.A.S. | Analogues of exendin-4 and exendin-3 |
| GB0717399D0 (en) * | 2007-09-07 | 2007-10-17 | Uutech Ltd | Use of GLP-1 analogues for the treatment of disorders associated with dysfunctional synaptic transmission |
| EP2036539A1 (en) | 2007-09-11 | 2009-03-18 | Novo Nordisk A/S | Stable formulations of amylin and its analogues |
| EP2036923A1 (en) | 2007-09-11 | 2009-03-18 | Novo Nordisk A/S | Improved derivates of amylin |
| WO2009034117A1 (en) | 2007-09-11 | 2009-03-19 | Novo Nordisk A/S | Mixture comprising an amylin peptide and a protracted insulin |
| US8980830B2 (en) | 2007-10-30 | 2015-03-17 | Indiana University Research And Technology Corporation | Peptide compounds exhibiting glucagon antagonist and GLP-1 agonist activity |
| ES2509883T3 (es) | 2007-10-30 | 2014-10-20 | Indiana University Research And Technology Corporation | Antagonistas de glucagón |
| 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 |
| WO2009155257A1 (en) | 2008-06-17 | 2009-12-23 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting enhanced solubility and stability physiological ph buffers |
| AR072160A1 (es) | 2008-06-17 | 2010-08-11 | Univ Indiana Res & Tech Corp | Co-agonistas del receptor de glucagon/glp-1 |
| KR20110114568A (ko) | 2008-12-19 | 2011-10-19 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 디펩티드 링크된 약효 물질 |
| 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 |
| US8703701B2 (en) | 2009-12-18 | 2014-04-22 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
| US8551946B2 (en) | 2010-01-27 | 2013-10-08 | Indiana University Research And Technology Corporation | Glucagon antagonist-GIP agonist conjugates and compositions for the treatment of metabolic disorders and obesity |
| 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 |
| US9145451B2 (en) | 2010-05-13 | 2015-09-29 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhbiting G protein coupled receptor activity |
| JP6121323B2 (ja) | 2010-05-13 | 2017-05-10 | 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 | 核内ホルモン受容体の活性を示すグルカゴンスーパーファミリーのペプチド |
| 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 |
-
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- 2011-06-14 CN CN201180031415XA patent/CN103179979A/zh active Pending
- 2011-06-14 KR KR1020127033177A patent/KR20130102470A/ko not_active Withdrawn
- 2011-06-14 WO PCT/US2011/040330 patent/WO2011163012A2/en not_active Ceased
- 2011-06-14 EP EP11798640.6A patent/EP2588126A4/en not_active Withdrawn
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009099763A1 (en) * | 2008-01-30 | 2009-08-13 | Indiana University Research And Technology Corporation | Ester-based peptide prodrugs |
| WO2009095479A2 (en) * | 2008-02-01 | 2009-08-06 | Ascendis Pharma As | Prodrug comprising a self-cleavable linker |
| RU2011129784A (ru) * | 2008-12-19 | 2013-01-27 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Основанные на амидах пролекарства пептидов глюкагонового надсемейства |
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| EP2588126A2 (en) | 2013-05-08 |
| US20130123462A1 (en) | 2013-05-16 |
| RU2013103093A (ru) | 2014-07-27 |
| TW201209062A (en) | 2012-03-01 |
| MX2012014576A (es) | 2013-02-21 |
| WO2011163012A2 (en) | 2011-12-29 |
| AR081471A1 (es) | 2012-09-05 |
| KR20130102470A (ko) | 2013-09-17 |
| CA2796894A1 (en) | 2011-12-29 |
| CN103179979A (zh) | 2013-06-26 |
| JP2013540102A (ja) | 2013-10-31 |
| US8778872B2 (en) | 2014-07-15 |
| WO2011163012A3 (en) | 2013-07-11 |
| EP2588126A4 (en) | 2015-07-08 |
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