SG181430A1 - Oxyntomodulin peptide analogue - Google Patents
Oxyntomodulin peptide analogue Download PDFInfo
- Publication number
- SG181430A1 SG181430A1 SG2012036844A SG2012036844A SG181430A1 SG 181430 A1 SG181430 A1 SG 181430A1 SG 2012036844 A SG2012036844 A SG 2012036844A SG 2012036844 A SG2012036844 A SG 2012036844A SG 181430 A1 SG181430 A1 SG 181430A1
- Authority
- SG
- Singapore
- Prior art keywords
- peptide analogue
- cys
- asn
- oxyntomodulin peptide
- oxm
- Prior art date
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- 229940124597 therapeutic agent Drugs 0.000 description 1
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- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
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Classifications
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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
-
- 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
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
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- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Zoology (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Obesity (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Child & Adolescent Psychology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
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| US28888809P | 2009-12-22 | 2009-12-22 | |
| US35257610P | 2010-06-08 | 2010-06-08 | |
| PCT/US2010/060390 WO2011087672A1 (en) | 2009-12-22 | 2010-12-15 | Oxyntomodulin peptide analogue |
Publications (1)
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| SG181430A1 true SG181430A1 (en) | 2012-07-30 |
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| SG2012036844A SG181430A1 (en) | 2009-12-22 | 2010-12-15 | Oxyntomodulin peptide analogue |
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Families Citing this family (80)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7731947B2 (en) | 2003-11-17 | 2010-06-08 | Intarcia Therapeutics, Inc. | Composition and dosage form comprising an interferon particle formulation and suspending vehicle |
| US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
| WO2006083761A2 (en) | 2005-02-03 | 2006-08-10 | Alza Corporation | Solvent/polymer solutions as suspension vehicles |
| 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 |
| US20150038413A1 (en) | 2006-02-03 | 2015-02-05 | Opko Biologics Ltd. | Long-acting polypeptides and methods of producing and administering same |
| US9458444B2 (en) | 2006-02-03 | 2016-10-04 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
| US10351615B2 (en) | 2006-02-03 | 2019-07-16 | Opko Biologics Ltd. | Methods of treatment with long-acting growth hormone |
| US10221228B2 (en) | 2006-02-03 | 2019-03-05 | Opko Biologics Ltd. | Long-acting polypeptides and methods of producing and administering same |
| US8048849B2 (en) | 2006-02-03 | 2011-11-01 | Modigene, Inc. | Long-acting polypeptides and methods of producing same |
| US8946155B2 (en) | 2006-02-03 | 2015-02-03 | Opko Biologics Ltd. | Long-acting polypeptides and methods of producing and administering same |
| US9249407B2 (en) | 2006-02-03 | 2016-02-02 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
| US20140113860A1 (en) | 2006-02-03 | 2014-04-24 | Prolor Biotech Ltd. | Long-acting polypeptides and methods of producing and administering same |
| DK2020990T3 (da) | 2006-05-30 | 2010-12-13 | Intarcia Therapeutics Inc | Strømningsmodulator med en indre kanal til et todelt osmotisk fremføringssystem |
| AU2007284759B2 (en) | 2006-08-09 | 2010-10-28 | Intarcia Therapeutics, Inc. | Osmotic delivery systems and piston assemblies |
| BRPI0807728A2 (pt) | 2007-02-15 | 2012-04-17 | Univ Indiana Res & Tech Corp | co-agonistas de receptor glucagon/glp-1 |
| RU2440097C2 (ru) | 2007-04-23 | 2012-01-20 | Интарсия Терапьютикс, Инк. | Способ лечения диабета ii типа и ожирения, осмотическое устройство для доставки и способ его изготовления |
| EP2217701B9 (en) | 2007-10-30 | 2015-02-18 | Indiana University Research and Technology Corporation | Glucagon antagonists |
| ES2558155T3 (es) | 2007-10-30 | 2016-02-02 | Indiana University Research And Technology Corporation | Compuestos que muestran actividad antagonista de glucacón y agonista de GLP-1 |
| US8343140B2 (en) | 2008-02-13 | 2013-01-01 | Intarcia Therapeutics, Inc. | Devices, formulations, and methods for delivery of multiple beneficial agents |
| SG192405A1 (en) | 2008-06-17 | 2013-08-30 | Univ Indiana Res & Tech Corp | Gip-based mixed agonists for treatment of metabolic disorders and obesity |
| EP2376097A4 (en) | 2008-12-19 | 2012-10-03 | Univ Indiana Res & Tech Corp | PEPTIDE PRODRUGS OF AMIDE-BASED GLUCAGON SUPERFAMILY |
| RU2012101274A (ru) | 2009-06-16 | 2013-07-27 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Соединения глюкагона, активные в отношении рецептора gip |
| US12203113B2 (en) | 2009-07-09 | 2025-01-21 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
| US9663778B2 (en) | 2009-07-09 | 2017-05-30 | OPKO Biologies Ltd. | Long-acting coagulation factors and methods of producing same |
| WO2011037623A1 (en) | 2009-09-28 | 2011-03-31 | Intarcia Therapeutics, Inc. | Rapid establishment and/or termination of substantial steady-state drug delivery |
| MX2012008603A (es) | 2010-01-27 | 2013-01-25 | Univ Indiana Res & Tech Corp | Conjugados de antagonista de glucagon-agonista de gip y composiciones para el tratamiento de desordenes metabolicos y obesidad. |
| WO2011143209A1 (en) | 2010-05-13 | 2011-11-17 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhibiting nuclear hormone receptor activity |
| CA2797089A1 (en) | 2010-05-13 | 2011-11-17 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhibiting g protein-coupled receptor activity |
| NZ612297A (en) | 2010-12-22 | 2015-10-30 | Univ Indiana Res & Tech Corp | Glucagon analogs exhibiting gip receptor activity |
| US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
| US10166295B2 (en) | 2011-06-02 | 2019-01-01 | Opko Biologics Ltd. | Pegylated OXM variants |
| SG10201604564XA (en) | 2011-06-10 | 2016-07-28 | Hanmi Science Co Ltd | Novel oxyntomodulin derivatives and pharmaceutical composition for treating obesity comprising the same |
| HRP20190265T1 (hr) | 2011-06-17 | 2019-04-05 | Hanmi Science Co., Ltd. | Konjugat koji sadrži oksintomodulin i fragment imunoglobulina i njegova uporaba |
| US9156902B2 (en) | 2011-06-22 | 2015-10-13 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
| BR112013032717A2 (pt) | 2011-06-22 | 2017-01-24 | Univ Indiana Res & Tech Corp | coagonistas do receptor de glucagon/glp-1 |
| WO2013074910A1 (en) | 2011-11-17 | 2013-05-23 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhibiting glucocorticoid receptor activity |
| PE20142405A1 (es) | 2012-04-19 | 2015-01-25 | Opko Biolog Ltd | Variantes de oxintomodulina de accion prolongada y metodos de produccion de las mismas |
| EP2854838B1 (en) | 2012-06-04 | 2018-10-17 | OPKO Biologics Ltd. | Pegylated oxm variants |
| CA2877358A1 (en) | 2012-06-21 | 2013-12-27 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting gip receptor activity |
| KR101968344B1 (ko) | 2012-07-25 | 2019-04-12 | 한미약품 주식회사 | 옥신토모듈린 유도체를 포함하는 고지혈증 치료용 조성물 |
| AR092873A1 (es) | 2012-09-26 | 2015-05-06 | Cadila Healthcare Ltd | Peptidos como agonistas triples de los receptores de gip, glp-1 y glugagon |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| TWI816739B (zh) | 2012-11-06 | 2023-10-01 | 南韓商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 |
| EP2922867B1 (en) | 2012-11-20 | 2021-07-21 | OPKO Biologics Ltd. | Method of increasing the hydrodynamic volume of polypeptides by attaching to gonadotrophin carboxy terminal peptides |
| HRP20181300T1 (hr) | 2012-12-21 | 2018-10-05 | Sanofi | Derivati eksendina-4 kao dvostruki glp1/gip- ili trostruki glp1/gip/glukagon agonisti |
| US20150158926A1 (en) | 2013-10-21 | 2015-06-11 | Opko Biologics, Ltd. | Long-acting polypeptides and methods of producing and administering same |
| EP3080154B1 (en) | 2013-12-13 | 2018-02-07 | Sanofi | Dual glp-1/gip receptor agonists |
| WO2015086728A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
| TW201609796A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 非醯化之艾塞那肽－４（ｅｘｅｎｄｉｎ－４）胜肽類似物 |
| EP3080149A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Dual glp-1/glucagon receptor agonists |
| 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 |
| 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 |
| 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 |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| 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 |
| US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
| PH12017501089B1 (en) | 2014-12-10 | 2022-06-22 | Opko Biologics Ltd | Methods of producing long acting ctp-modified growth hormone polypeptides |
| KR102418477B1 (ko) | 2014-12-30 | 2022-07-08 | 한미약품 주식회사 | 글루카곤 유도체 |
| ES2968262T3 (es) | 2015-06-03 | 2024-05-08 | I2O Therapeutics Inc | Sistemas de colocación de implantes |
| 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 |
| AU2016280867B2 (en) | 2015-06-19 | 2020-02-27 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
| AR104932A1 (es) | 2015-06-22 | 2017-08-23 | Lilly Co Eli | Compuestos co-agonistas del glucagón y péptido-1 similar al glugacón (glp-1) |
| 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 |
| TWI622596B (zh) | 2015-10-26 | 2018-05-01 | 美國禮來大藥廠 | 升糖素受體促效劑 |
| CA3024479A1 (en) | 2016-05-16 | 2017-11-23 | Intarcia Therapeutics, Inc. | Glucagon-receptor selective polypeptides and methods of use thereof |
| USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
| USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
| WO2017212494A1 (en) | 2016-06-09 | 2017-12-14 | Opko Biologics Ltd. | Long-acting oxyntomodulin formulation and methods of producing and administering same |
| KR102618424B1 (ko) | 2016-07-11 | 2023-12-26 | 옵코 바이오로직스 리미티드 | 지속성 응고 인자 vii 및 그 제조 방법 |
| TW201832783A (zh) | 2016-12-02 | 2018-09-16 | 法商賽諾菲公司 | 包含ｇｌｐ－１／胰高血糖素雙重激動劑、連接子和透明質酸的接合物 |
| JP7286542B2 (ja) | 2017-01-03 | 2023-06-05 | インターシア セラピューティクス，インコーポレイティド | Ｇｌｐ－１受容体アゴニストの持続的投与及び薬物の同時投与を含む方法 |
| CN108299553B (zh) * | 2017-01-13 | 2021-07-16 | 博瑞生物医药（苏州）股份有限公司 | 胃泌酸调节素修饰物 |
| KR101990075B1 (ko) * | 2018-07-19 | 2019-06-18 | ㈜ 디앤디파마텍 | 폴리펩티드를 포함하는 비만 예방 또는 치료용 약학 조성물 |
| KR20200135618A (ko) * | 2019-05-23 | 2020-12-03 | ㈜ 디앤디파마텍 | 폴리펩티드를 포함하는 비알코올성 지방간 질환의 예방 또는 치료용 약학 조성물 |
| US12338270B2 (en) | 2018-07-19 | 2025-06-24 | D&D Pharmatech Inc. | Pharmaceutical composition comprising polypeptide |
| US12441776B2 (en) * | 2018-11-30 | 2025-10-14 | Eirgen Pharma Ltd. | Oxyntomodulin peptide analog formulations |
| WO2025169190A2 (en) | 2024-02-06 | 2025-08-14 | Opko Biologics Ltd. | Modified oxyntomodulin and methods of use thereof |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5445090A (en) | 1991-07-25 | 1995-08-29 | Mim Industries, Inc. | Interchangeable clamp for use in a sewing machine |
| US5446090A (en) | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
| WO1996014336A1 (en) * | 1994-11-07 | 1996-05-17 | Kyowa Hakko Kogyo Co., Ltd. | Novel oxyntomodulin |
| US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| US6214966B1 (en) | 1996-09-26 | 2001-04-10 | Shearwater Corporation | Soluble, degradable poly(ethylene glycol) derivatives for controllable release of bound molecules into solution |
| US6448369B1 (en) | 1997-11-06 | 2002-09-10 | Shearwater Corporation | Heterobifunctional poly(ethylene glycol) derivatives and methods for their preparation |
| CA2323048C (en) | 1998-03-12 | 2006-10-10 | Shearwater Polymers, Inc. | Poly(ethylene glycol) derivatives with proximal reactive groups |
| KR100653153B1 (ko) | 1999-12-22 | 2006-12-01 | 넥타르 테라퓨틱스 에이엘, 코포레이션 | 수용성 중합체의 입체장애 유도체 |
| US6413507B1 (en) | 1999-12-23 | 2002-07-02 | Shearwater Corporation | Hydrolytically degradable carbamate derivatives of poly (ethylene glycol) |
| US6436386B1 (en) | 2000-11-14 | 2002-08-20 | Shearwater Corporation | Hydroxyapatite-targeting poly (ethylene glycol) and related polymers |
| GB0121709D0 (en) | 2001-09-07 | 2001-10-31 | Imp College Innovations Ltd | Food inhibition agent |
| GB0300571D0 (en) | 2003-01-10 | 2003-02-12 | Imp College Innovations Ltd | Modification of feeding behaviour |
| EA009366B1 (ru) | 2003-03-19 | 2007-12-28 | Эли Лилли Энд Компани | Связанные с полиэтиленгликолем соединения гпп-1 |
| DK1881850T3 (da) | 2005-05-13 | 2011-01-03 | Lilly Co Eli | GLP-1-PEGylerede forbindelser |
| SI1891105T1 (sl) | 2005-06-13 | 2012-07-31 | Imp Innovations Ltd | Analogi oksintomodulina in njihovi učinki na prehranjevalno vedenje |
| GB0511986D0 (en) * | 2005-06-13 | 2005-07-20 | Imp College Innovations Ltd | Novel compounds and their effects on feeding behaviour |
| 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 |
| US7928058B2 (en) * | 2006-02-22 | 2011-04-19 | Merck Sharp & Dohme Corp. | Pharmaceutical composition comprising oxyntomodulin derivatives and a method for reducing body weight using the composition |
| 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 |
| BRPI0807728A2 (pt) | 2007-02-15 | 2012-04-17 | Univ Indiana Res & Tech Corp | co-agonistas de receptor glucagon/glp-1 |
| WO2008152403A1 (en) | 2007-06-15 | 2008-12-18 | Zealand Pharma A/S | Glucagon analogues |
| ES2532116T3 (es) * | 2007-09-05 | 2015-03-24 | Novo Nordisk A/S | Péptidos derivados con A-B-C-D y sus usos terapéuticos |
| WO2010096052A1 (en) | 2009-02-19 | 2010-08-26 | Merck Sharp & Dohme Corp. | Oxyntomodulin analogs |
| AR079344A1 (es) * | 2009-12-22 | 2012-01-18 | Lilly Co Eli | Analogo peptidico de oxintomodulina, composicion farmaceutica que lo comprende y uso para preparar un medicamento util para tratar diabetes no insulinodependiente y/u obesidad |
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