ES2509883T3 - Antagonistas de glucagón - Google Patents
Antagonistas de glucagón Download PDFInfo
- Publication number
- ES2509883T3 ES2509883T3 ES08845852.6T ES08845852T ES2509883T3 ES 2509883 T3 ES2509883 T3 ES 2509883T3 ES 08845852 T ES08845852 T ES 08845852T ES 2509883 T3 ES2509883 T3 ES 2509883T3
- Authority
- ES
- Spain
- Prior art keywords
- glucagon
- kda peg
- seq
- pla6
- antagonism
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
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
- 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
- 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)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Toxicology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Antagonista de glucagón que comprende la secuencia de la SEQ ID NO: 42, o un derivado de la SEQ ID NO: 42 que difiere de la SEQ ID NO: 42 por sustituciones de aminoácidos en una a tres posiciones de aminoácidos seleccionadas entre las posiciones 5, 6, 8, 9, 12, 13 y 14 de la SEQ ID NO: 42, en la que el NH2 N-terminal del antagonista de glucagón "o derivado" está sustituido por un grupo hidroxilo, de manera que la Phe en la posición 1 del antagonista de glucagón es ácido fenil láctico (PLA), y sales farmacéuticamente del mismo.
Description
E08845852
02-10-2014
selectivamente sin la restauración del agonismo del glucagón. Los análogos Phe6 nativos sorprendentemente demuestran una restauración del agonismo cuando se pegilan. Sin embargo, esta restauración del agonismo no se observa en los análogos peptídicos PLA6. Se examinaron varios sitios de pegilación específicos, incluyendo las posiciones de aminoácido 8, 11 y 24 (en relación con el péptido de glucagón nativo). La pegilación en la posición 24 del análogo PLA6 muestra el antagonismo de glucagón más potente y selectivo.
Tabla 12: Análogos de glucagón truncados en N-terminal PEGilados y sus actividades de antagonismo del glucagón
- Péptido
- IC50 (nM) (unión al receptor) IC50 (nM) (cAMP, inhibición de glucagón 0,2 mM)
- [C8 (20 kDa PEG), E9]Glucagón (aa6-29)-NH2
- > 1000 sin antagonismo
- [PLA6, C8 (20 kDa PEG), E9]Glucagón (aa6-29)-NH2
- 303 ± 14 236
- [E9, C11 (20 kDa PEG)]Glucagón (aa6-29)-NH2
- > 1000 sin antagonismo
- [PLA6, E9, C11 (20 kDa PEG)]Glucagón (aa6-29)-NH2
- 776 ± 161 664
- [E9, C24 (20 kDa PEG)]Glucagón (aa6-29)-NH2
- > 1000 sin antagonismo
- [PLA6, E9, C24 (20 kDa PEG)]Glucagón (aa6-29)-NH2
- 90 ± 7 126
- [MCA6, E9, C24 (20 kDa PEG)]Glucagón (aa6-29)-NH2
- 208 ± 57 sin antagonismo
- [C5 (1,2 kDa PEG), E9]Glucagón (aa5-29)-NH2
- 1081 ± 268 2281
- [C5 (5 kDa PEG), E9]Glucagón (aa5-29)-NH2
- 634 ± 174 1608
- [C5 (20 kDa PEG), E9]Glucagón (aa5-29)-NH2
- 331 ± 74 976
- [d-Cys5 (20 kDa PEG), E9]Glucagón (aa5-29)-NH2
- > 10000 14764
- [K5(CH2CH2S-20 kDa PEG), E9]Glucagón (aa5-29)-NH2
- > 10000 sin antagonismo
- 3,4 kDaPEG-dímero [C5, E9]Glucagón (aa5-29)-NH2
- 435 ± 256 1343
- [PLA6, C8 (1,2 kDa PEG),E9] Glucagón (aa6-29)-NH2
- 220 ± 36 sin antagonismo
- [PLA6, C8 (5 kDa PEG),E9] Glucagón (aa6-29)-NH2
- 948 ± 297 216
- [PLA6, C8 (20 kDa PEG),E9] Glucagón (aa6-29)-NH2
- 303 ± 14 92
- [PLA6, E9, C24 (1,2 kDa PEG)] Glucagón (aa6-29)-NH2
- 4,7 ± 0,4 18
- [PLA6, E9, C24 (20 kDa PEG)] Glucagón (aa6-29)-NH2
- 90 ± 7 126
- [MCA6, E9, C24 (20 kDa PEG)] Glucagón (aa6-29)-NH2
- 208 ± 57 sin antagonismo
- [Phe6, E9, C24 (20 kDa PEG)] Glucagón (aa6-29)-NH2
- > 10000 sin antagonismo
[0279] Los antagonistas de glucagón descritos en este documento se acilan de la siguiente manera: Los péptidos acilados y/o PEGilados se preparan de la siguiente manera. Los péptidos se sintetizan en una resina de soporte sólido utilizando un sintetizador de péptidos CS Bio 4886 o un sintetizador de péptidos Applied Biosystems
15 430A. Se utiliza química de neutralización in situ tal como se describe por Schnolzer et al., Int. J. Peptide Protein Res.
40: 180-193 (1992). Para los péptidos acilados, el residuo de aminoácido diana a acilar (por ejemplo, la posición diez) se sustituye por un resduo de N ε-Fmoc lisina. El tratamiento del péptido protegido N-terminalmente con BOC completado con piperidina al 20% en DMF durante 30 minutos elimina los grupos FMOC/formilo. El acoplamiento al residuo de Lys con el ε-amino libre se logra mediante el acoplamiento de un exceso molar de diez veces de un aminoácido espaciador
20 protegido con FMOC (por ejemplo, FMOC-(N-BOC)-triptófano-OH) o la cadena de acilo (por ejemplo, C17-COOH) y el reactivo de acoplamiento PyBOP o DEPBT en DMF/DIEA. La eliminación posterior del grupo Fmoc del aminoácido espaciador va seguida por la repetición del acoplamiento con una cadena de acilo. El tratamiento final con 100% de TFA da lugar a la eliminación de cualquier grupo protectore de la cadena lateral y el grupo BOC N-terminal. Las resinas de
49
Claims (1)
-
imagen1 imagen2
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US98378307P | 2007-10-30 | 2007-10-30 | |
US983783P | 2007-10-30 | ||
PCT/US2008/080973 WO2009058662A2 (en) | 2007-10-30 | 2008-10-23 | Glucagon antagonists |
Publications (1)
Publication Number | Publication Date |
---|---|
ES2509883T3 true ES2509883T3 (es) | 2014-10-20 |
Family
ID=40591715
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES08845852.6T Active ES2509883T3 (es) | 2007-10-30 | 2008-10-23 | Antagonistas de glucagón |
Country Status (13)
Country | Link |
---|---|
US (1) | US8981047B2 (es) |
EP (1) | EP2217701B9 (es) |
JP (1) | JP5669582B2 (es) |
AR (1) | AR069110A1 (es) |
AU (1) | AU2008318986B2 (es) |
CA (1) | CA2707861A1 (es) |
CL (1) | CL2008003222A1 (es) |
ES (1) | ES2509883T3 (es) |
HK (1) | HK1143994A1 (es) |
MX (1) | MX2010004297A (es) |
PE (1) | PE20091393A1 (es) |
TW (1) | TW200920404A (es) |
WO (1) | WO2009058662A2 (es) |
Families Citing this family (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1959986B1 (en) | 2005-11-07 | 2014-07-23 | Indiana University Research and Technology Corporation | Glucagon analogs exhibiting physiological solubility and stability |
SG177953A1 (en) | 2007-01-05 | 2012-02-28 | Univ Indiana Res & Tech Corp | Glucagon analogs exhibiting enhanced solubility in physiological ph buffers |
BRPI0807728A2 (pt) | 2007-02-15 | 2012-04-17 | Univ Indiana Res & Tech Corp | co-agonistas de receptor glucagon/glp-1 |
ES2509883T3 (es) | 2007-10-30 | 2014-10-20 | Indiana University Research And Technology Corporation | Antagonistas de glucagón |
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 |
AU2009260302B2 (en) | 2008-06-17 | 2014-10-23 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
CN102088989B (zh) | 2008-06-17 | 2014-11-26 | 印第安纳大学研究及科技有限公司 | 在生理pH缓冲液中具有增强的溶解性和稳定性的胰高血糖素类似物 |
JP6108659B2 (ja) | 2008-06-17 | 2017-04-05 | 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 | 代謝疾患および肥満の治療のためのgipに基づいた混合アゴニスト |
PE20120332A1 (es) | 2008-12-19 | 2012-04-14 | Univ Indiana Res & Tech Corp | Profarmacos de peptido de la superfamilia de glucagon basado en amida |
MX2011013625A (es) | 2009-06-16 | 2012-01-20 | Univ Indiana Res & Tech Corp | Compuestos glucagon activo de receptor de gip. |
GB0917072D0 (en) * | 2009-09-29 | 2009-11-11 | Univ Ulster | Peptide analogues of glucagon for diabetes therapy |
WO2011058193A1 (en) | 2009-11-16 | 2011-05-19 | Mellitech | [1,5]-diazocin derivatives |
US8703701B2 (en) | 2009-12-18 | 2014-04-22 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
CA2788304A1 (en) | 2010-01-27 | 2011-08-04 | Indiana University Research And Technology Corporation | Glucagon antagonist - gip agonist conjugates and compositions for the treatment of metabolic disorders and obesity |
WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
US20130053310A1 (en) * | 2010-03-26 | 2013-02-28 | Novo Nordisk A/S | Novel glucagon analogues |
WO2011143208A1 (en) | 2010-05-13 | 2011-11-17 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhibiting g protein-coupled receptor activity |
EP2569000B1 (en) | 2010-05-13 | 2017-09-27 | Indiana University Research and Technology Corporation | Glucagon superfamily peptides exhibiting nuclear hormone receptor activity |
US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
MX2012014576A (es) | 2010-06-24 | 2013-02-21 | Univ Indiana Res & Tech Corp | Profarmacos de peptido de la superfamilia de glucagon basado en amida. |
TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
KR101382593B1 (ko) | 2010-07-21 | 2014-04-10 | 한미사이언스 주식회사 | 신규한 지속형 글루카곤 결합체 및 이를 포함하는 비만 예방 및 치료용 약학적 조성물 |
ES2533601T3 (es) | 2010-11-03 | 2015-04-13 | Arecor Limited | Nueva composición que comprende glucagón |
WO2012088116A2 (en) | 2010-12-22 | 2012-06-28 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting gip receptor activity |
EP2694095B1 (en) | 2011-04-05 | 2018-03-07 | Longevity Biotech, Inc. | Compositions comprising glucagon analogs and methods of making and using the same |
JP6184404B2 (ja) | 2011-06-22 | 2017-08-23 | 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レセプターコアゴニスト |
EP2723367B1 (en) | 2011-06-22 | 2017-05-03 | Indiana University Research and Technology Corporation | Glucagon/glp-1 receptor co-agonists |
WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
US8859491B2 (en) | 2011-11-17 | 2014-10-14 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhibiting glucocorticoid receptor activity |
CN104185639B (zh) | 2012-03-01 | 2018-06-19 | 诺和诺德股份有限公司 | Glp-1前体药物 |
JP6311708B2 (ja) | 2012-06-21 | 2018-04-18 | 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 | Gip受容体活性を示すグルカゴンアナローグ |
WO2014041375A1 (en) * | 2012-09-17 | 2014-03-20 | Imperial Innovations Limited | Peptide analogues of glucagon and glp1 |
UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
CN104870009B (zh) | 2012-12-21 | 2021-05-18 | 赛诺菲 | 官能化的毒蜥外泌肽-4衍生物 |
WO2015081891A1 (en) | 2013-12-06 | 2015-06-11 | Baikang (Suzhou) Co., Ltd | Bioreversable promoieties for nitrogen-containing and hydroxyl-containing drugs |
EP3080149A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Dual glp-1/glucagon receptor agonists |
EP3080152A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Non-acylated exendin-4 peptide analogues |
EP3080154B1 (en) | 2013-12-13 | 2018-02-07 | 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 |
MX2016010599A (es) | 2014-02-18 | 2016-11-18 | Novo Nordisk As | Analogos de glucagon estables y uso para el tratamiento de hipoglucemia. |
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 |
US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
MD20170055A2 (ro) | 2014-10-24 | 2017-09-30 | Merck Sharp & Dohme Corp | Co-agonişti ai receptorilor glucagonului şi GLP-1 |
AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
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 |
GB201611077D0 (en) | 2016-06-24 | 2016-08-10 | Arecor Ltd | Novel composition |
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 |
JP2021505597A (ja) * | 2017-12-07 | 2021-02-18 | アドシア | ヒトグルカゴンおよびコポリアミノ酸を含む注射水溶液の形態の組成物 |
Family Cites Families (108)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
AU642403B2 (en) | 1989-02-17 | 1993-10-21 | Coselco Mimotopes Pty Ltd | Method for the use and synthesis of peptides |
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 |
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 |
JP2001503963A (ja) | 1996-02-06 | 2001-03-27 | イーライ・リリー・アンド・カンパニー | 糖尿病治療 |
AU724326B2 (en) | 1996-09-09 | 2000-09-14 | 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 |
AU5518798A (en) | 1996-12-03 | 1998-06-29 | Trustees Of Boston University | Specific antagonists for glucose-dependent insulinotropic polypeptide (gip) |
WO1999046283A1 (en) | 1998-03-09 | 1999-09-16 | Zealand Pharmaceuticals A/S | Pharmacologically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
US20030236190A1 (en) | 1998-09-02 | 2003-12-25 | Renuka Pillutla | Isulin and IGF-1 receptor agonists and antagonists |
DE69926007T2 (de) | 1998-10-07 | 2005-12-29 | Medical College Of Georgia Research Institute, Inc. | Glukose-abhängiges, insulinotropisches peptid für die verwendung als osteotropes hormon |
WO2000042026A1 (en) | 1999-01-15 | 2000-07-20 | Novo Nordisk A/S | Non-peptide glp-1 agonists |
WO2000058360A2 (en) | 1999-03-29 | 2000-10-05 | Uutech Limited | Analogs of gastric inhibitory peptide and their use for treatment of diabetes |
GB0404124D0 (en) | 2004-02-25 | 2004-03-31 | Univ Ulster | Antagonists of GIP |
US6458493B2 (en) * | 1999-06-04 | 2002-10-01 | International Business Machines Corporation | Method to control nested to isolated line printing |
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 |
AU2001269833A1 (en) | 2000-06-14 | 2001-12-24 | Cytovax Biotechnologies, Inc. | Use of coiled-coil structural scaffold to generate structure-specific peptides |
ATE424413T1 (de) | 2000-06-16 | 2009-03-15 | Lilly Co Eli | Analoge des glucagon-ähnlichen peptids-1 |
WO2002010195A2 (en) | 2000-08-02 | 2002-02-07 | Theratechnologies Inc. | Modified peptides with increased potency |
US20020045572A1 (en) | 2000-08-15 | 2002-04-18 | Cpd, Llc | Method of treating the syndrome of type 2 diabetes 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 |
US6262062B1 (en) | 2000-08-15 | 2001-07-17 | Cpd, Llc | Method of treating the syndrome of coronary heart disease risk factors in humans |
US6846831B2 (en) | 2000-08-15 | 2005-01-25 | Cpd, Llc | Method of treating the syndrome of lipodystrophy |
ES2367891T3 (es) | 2000-09-29 | 2011-11-10 | Schering Corporation | Interleucina-10 pegilada. |
WO2002048192A2 (en) | 2000-12-13 | 2002-06-20 | Eli Lilly And Company | Amidated glucagon-like peptide-1 |
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 |
JP2005509409A (ja) | 2001-08-08 | 2005-04-14 | ジェンザイム・コーポレーション | 糖尿病および他の血糖疾患の治療方法 |
CA2452044A1 (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 |
PL377687A1 (pl) | 2001-10-18 | 2006-02-06 | Bristol-Myers Squibb Company | Środki naśladujące ludzki peptyd glukagonopodobny typu 1 i ich zastosowanie w leczeniu cukrzycy i stanów związanych z cukrzycą |
JP2005508360A (ja) | 2001-10-19 | 2005-03-31 | イーライ・リリー・アンド・カンパニー | Glp−1およびインスリンの二相混合物 |
WO2003059378A2 (en) | 2001-12-29 | 2003-07-24 | Novo Nordisk A/S | Combined use of a glp-1 compound and another drug for treating dyslipidemia |
US20030232761A1 (en) | 2002-03-28 | 2003-12-18 | Hinke Simon A. | Novel analogues of glucose-dependent insulinotropic polypeptide |
AU2003239478A1 (en) | 2002-06-04 | 2003-12-22 | Eli Lilly And Company | Modified glucagon-like peptide-1 analogs |
AU2003237933A1 (en) | 2002-06-11 | 2003-12-22 | Cellartis Ab | Use of compounds having gip activity for the treatment of disorders associated with abnormal loss of cells and/or for the treatment of obesity |
WO2003105760A2 (en) | 2002-06-15 | 2003-12-24 | Enteromed, Inc. | Prevention and treatment of nonalcoholic fatty liver disease (nafld) by antagonism of the receptor to glucose-dependent insulinotropic polypeptide (gip) |
WO2004022004A2 (en) | 2002-09-06 | 2004-03-18 | Bayer Pharmaceuticals Corporation | Modified glp-1 receptor 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 |
WO2004067548A2 (en) | 2003-01-31 | 2004-08-12 | Theratechnologies Inc. | Chemically modified metabolites of regulatory peptides and methods of producing and using same |
EP1626981A4 (en) | 2003-03-04 | 2006-11-22 | Biorexis Pharmaceutical Corp | PROTEINS PROTECTED AGAINST DIPEPTIDYLPEPTIDASE |
MXPA05009940A (es) | 2003-03-19 | 2005-12-05 | Lilly Co Eli | Compuestos de glp-1 de enlace de glicol polietilenico. |
JP4698579B2 (ja) | 2003-04-08 | 2011-06-08 | イエダ リサーチ アンド デベロップメント カンパニー リミテッド | 可逆的peg化薬物 |
GB0310593D0 (en) * | 2003-05-08 | 2003-06-11 | Leuven K U Res & Dev | Peptidic prodrugs |
CN102174102A (zh) | 2003-05-15 | 2011-09-07 | 塔夫茨大学信托人 | 肽和多肽药物的稳定类似物 |
CA2527743A1 (en) | 2003-06-03 | 2004-12-09 | Novo Nordisk A/S | Stabilized pharmaceutical peptide compositions |
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 |
AU2004251145C1 (en) | 2003-06-12 | 2011-04-14 | Eli Lilly And Company | GLP-1 analog fusion proteins |
US20050124550A1 (en) | 2003-06-18 | 2005-06-09 | Peri Krishna G. | Compounds that modulate the glucagon response and uses thereof |
TW200526254A (en) | 2003-09-19 | 2005-08-16 | Novo Nordisk As | Novel GLP-1 derivatives |
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 |
ATE461217T1 (de) * | 2003-12-18 | 2010-04-15 | Novo Nordisk As | Glp-1-verbindungen |
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 |
US20090286723A1 (en) | 2005-02-11 | 2009-11-19 | Amylin Pharmaceuticals, Inc. | Hybrid Polypeptides with Selectable Properties |
EP2390264A1 (en) | 2005-02-11 | 2011-11-30 | Amylin Pharmaceuticals Inc. | GIP analog and hybrid polypeptides with selectable propperties |
JP2008533104A (ja) | 2005-03-18 | 2008-08-21 | ノボ ノルディスク アクティーゼルスカブ | Glp−1受容体の二量体ペプチドアゴニスト |
WO2006121904A1 (en) | 2005-05-06 | 2006-11-16 | Bayer Pharmaceuticals Corporation | Glucose-dependent insulinotropic polypeptide (gip) receptor agonists and their pharmacological methods of use |
PT1881850E (pt) | 2005-05-13 | 2010-11-26 | Lilly Co Eli | Compostos peguilados de glp-1 |
ATE553124T1 (de) | 2005-06-13 | 2012-04-15 | Imp Innovations Ltd | Oxyntomodulinanaloga und ihre wirkungen auf das fressverhalten |
US20090170762A1 (en) | 2005-09-08 | 2009-07-02 | Uutech Limited | Treatment of Diabetes Related Obesity |
AU2006289259A1 (en) | 2005-09-08 | 2007-03-15 | Uutech Limited | Analogs of gastric inhibitory polypeptide as a treatment for age related decreased pancreatic beta cell function |
EP1959986B1 (en) * | 2005-11-07 | 2014-07-23 | Indiana University Research and Technology Corporation | Glucagon analogs exhibiting physiological solubility and stability |
EP2471810A1 (en) | 2006-02-22 | 2012-07-04 | Merck Sharp & Dohme Corporation | Oxyntomodulin derivatives |
US20090054305A1 (en) | 2006-03-15 | 2009-02-26 | Novo Nordisk A/S | Mixtures of Amylin and Insulin |
WO2007109354A2 (en) | 2006-03-21 | 2007-09-27 | Amylin Pharmaceuticals, Inc. | Peptide-peptidase inhibitor conjugates and methods of using same |
WO2008022015A2 (en) | 2006-08-11 | 2008-02-21 | Trustees Of Tufts College | Retro-inverso incretin analogues, and methods of use thereof |
CA2660835A1 (en) | 2006-08-17 | 2008-02-21 | Amylin Pharmaceuticals, Inc. | Dpp-iv resistant gip hybrid polypeptides with selectable propperties |
EP2057189B1 (en) | 2006-08-25 | 2013-03-06 | Novo Nordisk A/S | Acylated exendin-4 compounds |
US8617531B2 (en) | 2006-12-14 | 2013-12-31 | Bolder Biotechnology, Inc. | Methods of making proteins and peptides containing a single free cysteine |
SG177953A1 (en) | 2007-01-05 | 2012-02-28 | Univ Indiana Res & Tech Corp | Glucagon analogs exhibiting enhanced solubility in physiological ph buffers |
BRPI0807728A2 (pt) * | 2007-02-15 | 2012-04-17 | Univ Indiana Res & Tech Corp | co-agonistas de receptor glucagon/glp-1 |
EP2190873B1 (en) | 2007-09-05 | 2015-07-22 | Novo Nordisk A/S | Truncated glp-1 derivatives and their therapeutical use |
ES2672770T3 (es) | 2007-09-05 | 2018-06-18 | Novo Nordisk A/S | Derivados del péptido-1 similar al glucagón y su uso farmacéutico |
US20100256056A1 (en) | 2007-09-07 | 2010-10-07 | Zheng Xin Dong | Analogues of exendin-4 and exendin-3 |
EP2036923A1 (en) | 2007-09-11 | 2009-03-18 | Novo Nordisk A/S | Improved derivates of amylin |
EP2036539A1 (en) | 2007-09-11 | 2009-03-18 | Novo Nordisk A/S | Stable formulations of amylin and its analogues |
EP2200635A1 (en) | 2007-09-11 | 2010-06-30 | Novo Nordisk A/S | Mixture comprising an amylin peptide and a protracted insulin |
ES2509883T3 (es) | 2007-10-30 | 2014-10-20 | Indiana University Research And Technology Corporation | Antagonistas de glucagón |
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 |
US8261025B2 (en) | 2007-11-12 | 2012-09-04 | International Business Machines Corporation | Software pipelining on a network on chip |
CA2713348C (en) | 2008-01-30 | 2018-10-09 | Indiana University Research And Technology Corporation | Ester-based peptide prodrugs |
CN101980725B (zh) | 2008-02-01 | 2013-06-12 | 阿森迪斯药物股份有限公司 | 包含可自裂解的连接体的前药 |
AU2009260302B2 (en) | 2008-06-17 | 2014-10-23 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
JP6108659B2 (ja) | 2008-06-17 | 2017-04-05 | 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 | 代謝疾患および肥満の治療のためのgipに基づいた混合アゴニスト |
CN102088989B (zh) | 2008-06-17 | 2014-11-26 | 印第安纳大学研究及科技有限公司 | 在生理pH缓冲液中具有增强的溶解性和稳定性的胰高血糖素类似物 |
EP2376098A4 (en) | 2008-12-19 | 2014-06-11 | Univ Indiana Res & Tech Corp | DIPEPTIDE-LINKED MEDICAL AGENTS |
PE20120332A1 (es) | 2008-12-19 | 2012-04-14 | Univ Indiana Res & Tech Corp | Profarmacos de peptido de la superfamilia de glucagon basado en amida |
WO2010096052A1 (en) | 2009-02-19 | 2010-08-26 | Merck Sharp & Dohme Corp. | Oxyntomodulin analogs |
MX2011013625A (es) | 2009-06-16 | 2012-01-20 | Univ Indiana Res & Tech Corp | Compuestos glucagon activo de receptor de gip. |
US8703701B2 (en) | 2009-12-18 | 2014-04-22 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
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 |
AR079345A1 (es) | 2009-12-22 | 2012-01-18 | Lilly Co Eli | Analogo peptidico de oxintomodulina |
CA2788304A1 (en) | 2010-01-27 | 2011-08-04 | 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 |
EP2569000B1 (en) | 2010-05-13 | 2017-09-27 | Indiana University Research and Technology Corporation | Glucagon superfamily peptides exhibiting nuclear hormone receptor activity |
WO2011143208A1 (en) | 2010-05-13 | 2011-11-17 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhibiting g protein-coupled receptor activity |
MX2012014576A (es) | 2010-06-24 | 2013-02-21 | Univ Indiana Res & Tech Corp | Profarmacos de peptido de la superfamilia de glucagon basado en amida. |
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 |
-
2008
- 2008-10-23 ES ES08845852.6T patent/ES2509883T3/es active Active
- 2008-10-23 US US12/739,342 patent/US8981047B2/en not_active Expired - Fee Related
- 2008-10-23 AU AU2008318986A patent/AU2008318986B2/en not_active Ceased
- 2008-10-23 CA CA2707861A patent/CA2707861A1/en not_active Abandoned
- 2008-10-23 WO PCT/US2008/080973 patent/WO2009058662A2/en active Application Filing
- 2008-10-23 EP EP08845852.6A patent/EP2217701B9/en active Active
- 2008-10-23 MX MX2010004297A patent/MX2010004297A/es active IP Right Grant
- 2008-10-23 JP JP2010532154A patent/JP5669582B2/ja not_active Expired - Fee Related
- 2008-10-29 AR ARP080104739A patent/AR069110A1/es unknown
- 2008-10-29 CL CL2008003222A patent/CL2008003222A1/es unknown
- 2008-10-30 TW TW097141806A patent/TW200920404A/zh unknown
- 2008-10-30 PE PE2008001856A patent/PE20091393A1/es not_active Application Discontinuation
-
2010
- 2010-11-12 HK HK10110565.2A patent/HK1143994A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
TW200920404A (en) | 2009-05-16 |
US20120122783A1 (en) | 2012-05-17 |
EP2217701B9 (en) | 2015-02-18 |
AR069110A1 (es) | 2009-12-30 |
AU2008318986A1 (en) | 2009-05-07 |
PE20091393A1 (es) | 2009-09-11 |
HK1143994A1 (en) | 2011-01-21 |
AU2008318986B2 (en) | 2014-12-04 |
JP5669582B2 (ja) | 2015-02-12 |
EP2217701B1 (en) | 2014-07-02 |
US8981047B2 (en) | 2015-03-17 |
EP2217701A2 (en) | 2010-08-18 |
WO2009058662A3 (en) | 2010-01-07 |
JP2011502155A (ja) | 2011-01-20 |
WO2009058662A2 (en) | 2009-05-07 |
CL2008003222A1 (es) | 2009-02-27 |
MX2010004297A (es) | 2010-05-03 |
EP2217701A4 (en) | 2011-06-15 |
CA2707861A1 (en) | 2009-05-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ES2509883T3 (es) | Antagonistas de glucagón | |
JP2013518115A5 (es) | ||
AR065349A1 (es) | Coagonistas del receptor de glucagon/glp-1 | |
ES2558330T3 (es) | Péptido WT1 restringido por HLA-A*3303 y composición farmacéutica que comprende el mismo | |
ES2558842T3 (es) | Agonistas mixtos a base de GIP para el tratamiento de trastornos metabólicos y obesidad | |
ES2351661T3 (es) | Péptido-2 análogo al glucagón. | |
ES2277676T3 (es) | Antagonistas de los peptidos glp-2 intestinotroficos. | |
NO20092774L (no) | HLA-A*1101-begrenset WT1-peptid og farmasoytisk preparat som omfatter dette | |
ES2651946T3 (es) | Utilización de péptidos CD31 en el tratamiento de trastornos trombóticos y autoinmunes | |
PE20120021A1 (es) | Mutantes fgf21 | |
BRPI0508935A (pt) | agonistas de receptor seletivo y4 para intervenções terapêuticas | |
EA201100038A1 (ru) | Коагонисты глюкагонового рецептора/glp-1-рецептора | |
WO2005089789A3 (en) | Y2 selective receptor agonists for therapeutic interventions | |
RU2012101274A (ru) | Соединения глюкагона, активные в отношении рецептора gip | |
PE20091405A1 (es) | Metodos y composiciones que utilizan polipeptidos de fusion de klotho-fgf | |
NZ628987A (en) | Extended recombinant polypeptides and compositions comprising same | |
RS54215B1 (en) | COMPOSITIONS AND PROCEDURES FOR DIAGNOSIS AND TREATMENT OF CANCER | |
RU2011134596A (ru) | Аналоги оксинтомодулина | |
RU2014101697A (ru) | Коагонисты рецепторов глюкагона/glp-1 | |
PE20091067A1 (es) | Variantes de peptidos natriureticos de tipo c | |
RU2015101697A (ru) | Аналоги глюкагона, обладающие активностью рецептора gip | |
AR071874A1 (es) | Proteinas de dominio de armazon basadas en fibronectina multivalentes | |
WO2001058493A8 (en) | Conjugates of follicle stimulating hormones | |
ES2545457T3 (es) | Vacunas de péptidos para cánceres que expresan los polipéptidos DEPDC1 | |
RU2017119773A (ru) | Пептидные антагонисты пептидных гормонов из семейства кальцитонина (cgrp) и их применение |