ES2286679T3 - Compuestos, procedimientos y formulaciones para la liberacion oral de un compuesto de peptido de tipo glucagon (glp)-1 o un peptido agonist a del receptor de melanocortina 4 (mc4). - Google Patents
Compuestos, procedimientos y formulaciones para la liberacion oral de un compuesto de peptido de tipo glucagon (glp)-1 o un peptido agonist a del receptor de melanocortina 4 (mc4). Download PDFInfo
- Publication number
- ES2286679T3 ES2286679T3 ES04779447T ES04779447T ES2286679T3 ES 2286679 T3 ES2286679 T3 ES 2286679T3 ES 04779447 T ES04779447 T ES 04779447T ES 04779447 T ES04779447 T ES 04779447T ES 2286679 T3 ES2286679 T3 ES 2286679T3
- Authority
- ES
- Spain
- Prior art keywords
- compound
- peptide
- glp
- alkyl
- formulations
- 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.)
- Expired - Lifetime
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- 239000000203 mixture Substances 0.000 title claims abstract description 39
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 24
- 239000000556 agonist Substances 0.000 title claims description 13
- 238000000034 method Methods 0.000 title abstract description 9
- 102000051325 Glucagon Human genes 0.000 title 1
- 108060003199 Glucagon Proteins 0.000 title 1
- 239000002131 composite material Substances 0.000 title 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49653703P | 2003-08-20 | 2003-08-20 | |
| US496537P | 2003-08-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2286679T3 true ES2286679T3 (es) | 2007-12-01 |
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| ES04779447T Expired - Lifetime ES2286679T3 (es) | 2003-08-20 | 2004-08-18 | Compuestos, procedimientos y formulaciones para la liberacion oral de un compuesto de peptido de tipo glucagon (glp)-1 o un peptido agonist a del receptor de melanocortina 4 (mc4). |
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| EP (1) | EP1658285B1 (enExample) |
| JP (2) | JP4754487B2 (enExample) |
| CN (1) | CN100398536C (enExample) |
| AT (1) | ATE361294T1 (enExample) |
| AU (1) | AU2004267044B8 (enExample) |
| BR (1) | BRPI0413676B8 (enExample) |
| CA (1) | CA2530983C (enExample) |
| DE (1) | DE602004006279T2 (enExample) |
| ES (1) | ES2286679T3 (enExample) |
| MX (1) | MXPA06001916A (enExample) |
| WO (1) | WO2005019212A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2006269321A1 (en) | 2005-07-08 | 2007-01-18 | Ipsen Pharma S.A.S. | Ligands of melanocortin receptors |
| HUE037147T2 (hu) | 2005-07-08 | 2018-08-28 | Ipsen Pharma | Melanokortin-receptor ligandumai |
| WO2008027958A2 (en) * | 2006-08-31 | 2008-03-06 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| CA2689016C (en) * | 2007-05-25 | 2014-08-12 | Ipsen Pharma S.A.S. | Melanocortin receptor ligands modified with hydantoin |
| BRPI0909947A2 (pt) | 2008-06-09 | 2017-06-27 | Palatin Technologies Inc | '' peptídeo cíclico, composição farmacêutica, método de tratamento de uma doença, indicação, condição ou síndrome mediada por receptor de melanocortina em seres humanos ou mamíferos não humanos, e, método de tratamento de condição que reage a alterações da função de receptor de melanocortina em seres humanos ou mamíferos não humanos'' |
| CN102458436B (zh) | 2009-06-08 | 2015-06-03 | 帕拉丁科技公司 | 黑皮质素受体特异性肽 |
| UY32690A (es) | 2009-06-08 | 2011-01-31 | Astrazeneca Ab | Péptidos específicos para receptores de melanocortina |
| EP2440572B1 (en) | 2009-06-08 | 2017-04-05 | Palatin Technologies, Inc. | Lactam-bridged melanocortin receptor-specific peptides |
| BR112012011780A2 (pt) | 2009-11-23 | 2019-09-24 | Palatin Technologies, Inc | peptídeo linear,composição farmacêutica,métodopara tratamento de umadoença,indicação,condição ou sídrome mediadsa por receptor de melanocortina emum mamífero humano ou não humano e método para tratamento de uma condição responsiva ás alterações em função de receptor de melanocortina em um mamifero humano ou não humano |
| MX2012005862A (es) | 2009-11-23 | 2012-09-07 | Palatin Technologies Inc | Peptidos ciclicos especificos del receptor de melanocortina-1. |
| US10357348B2 (en) * | 2013-08-19 | 2019-07-23 | Warren Matthew Leevy | Fluid manifold |
| US20160244860A1 (en) * | 2015-02-20 | 2016-08-25 | Cytec Industries Inc. | Aliphatic-aromatic heterocyclic compounds and uses thereof in metal extractant compositions |
| WO2016168388A2 (en) | 2015-04-14 | 2016-10-20 | Palatin Technologies, Inc. | Therapies for obesity, diabetes and related indications |
| CN105017136A (zh) * | 2015-07-24 | 2015-11-04 | 陈吉美 | 一种2-溴-3-甲氧基吡啶的制备方法 |
| BR112019016241A2 (pt) | 2017-02-08 | 2020-04-07 | Bayer Cropscience Ag | derivados de triazol e seu uso como fungicidas |
| EP3580218A1 (en) | 2017-02-08 | 2019-12-18 | Bayer CropScience Aktiengesellschaft | Novel triazole derivatives |
| CN110267952A (zh) | 2017-02-08 | 2019-09-20 | 拜耳公司 | 三唑硫酮衍生物 |
| AU2018217749A1 (en) | 2017-02-10 | 2019-08-01 | Bayer Aktiengesellschaft | Composition for controlling harmful microorganisms comprising 1 -(phenoxy-pyridinyl)-2-(1,2,4-triazol-1 -yl)-ethanol derivatives |
| WO2020020816A1 (en) | 2018-07-26 | 2020-01-30 | Bayer Aktiengesellschaft | Novel triazole derivatives |
| CN111793038B (zh) * | 2019-04-08 | 2022-08-12 | 新发药业有限公司 | 一种取代噁唑化合物的环保制备方法 |
| WO2025158275A1 (en) | 2024-01-24 | 2025-07-31 | Pfizer Inc. | Combination therapy using glucose-dependent insulinotropic polypeptide receptor antagonist compounds and glp-1 receptor agonist compounds |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2423709A (en) * | 1947-07-08 | X-aryl thiazole | ||
| US595503A (en) * | 1897-12-14 | Cross-clevis | ||
| US3412193A (en) * | 1965-12-13 | 1968-11-19 | American Cyanamid Co | 11-(4-methyl-1-piperazinyl)dibenz[b, f][1, 4]oxazepines or thiazepines for controlling fertility |
| US3578671A (en) * | 1967-11-06 | 1971-05-11 | Wyeth John & Brother Ltd | Oxazoles |
| FR2374910A1 (fr) * | 1976-10-23 | 1978-07-21 | Choay Sa | Preparation a base d'heparine, comprenant des liposomes, procede pour l'obtenir et medicaments contenant de telles preparations |
| AU610083B2 (en) * | 1986-08-18 | 1991-05-16 | Clinical Technologies Associates, Inc. | Delivery systems for pharmacological agents |
| EP0451790A1 (de) * | 1990-04-12 | 1991-10-16 | Hoechst Aktiengesellschaft | 3,5-disubstituierte 2-Isoxazoline und Isoxazole, Verfahren zu deren Herstellung, diese enthaltende Mittel und ihre Verwendung |
| US5541155A (en) * | 1994-04-22 | 1996-07-30 | Emisphere Technologies, Inc. | Acids and acid salts and their use in delivery systems |
| US5693338A (en) * | 1994-09-29 | 1997-12-02 | Emisphere Technologies, Inc. | Diketopiperazine-based delivery systems |
| US5643957A (en) * | 1993-04-22 | 1997-07-01 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US6001347A (en) * | 1995-03-31 | 1999-12-14 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5650386A (en) * | 1995-03-31 | 1997-07-22 | Emisphere Technologies, Inc. | Compositions for oral delivery of active agents |
| BR9604880A (pt) * | 1995-03-31 | 1998-05-19 | Emisphere Tech Inc | Composto composição forma de unidade de dosagem métodos para administração de um agente biologicamente ativo para preparar uma composição para administração de um agente ativo e para preparar um composto e composição farmacológica |
| US5989539A (en) * | 1995-03-31 | 1999-11-23 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5965121A (en) * | 1995-03-31 | 1999-10-12 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5866536A (en) * | 1995-03-31 | 1999-02-02 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5820881A (en) * | 1995-04-28 | 1998-10-13 | Emisphere Technologies, Inc. | Microspheres of diamide-dicarboxylic acids |
| GB9604242D0 (en) * | 1996-02-28 | 1996-05-01 | Glaxo Wellcome Inc | Chemical compounds |
| JP4056589B2 (ja) * | 1996-07-19 | 2008-03-05 | 武田薬品工業株式会社 | 複素環化合物、その製造法および用途 |
| US6211215B1 (en) * | 1996-07-19 | 2001-04-03 | Takeda Chemical Industries, Ltd. | Heterocyclic compounds, their production and use |
| DK1093819T3 (da) * | 1997-02-07 | 2006-09-11 | Emisphere Tech Inc | Forbindelse og præparat til tilförsel af aktive midler |
| US6313088B1 (en) * | 1997-02-07 | 2001-11-06 | Emisphere Technologies, Inc. | 8-[(2-hydroxy-4-methoxy benzoyl) amino]-octanoic acid compositions for delivering active agents |
| CN1338924A (zh) | 1999-01-08 | 2002-03-06 | 艾米斯菲尔技术有限公司 | 聚合物输送剂和输送剂化合物 |
| JP4854855B2 (ja) * | 1999-02-11 | 2012-01-18 | エミスフェアー・テクノロジーズ・インク | オキサジアゾール化合物及び活性剤をデリバリーするための組成物 |
| WO2000050386A1 (en) | 1999-02-26 | 2000-08-31 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| JP4588221B2 (ja) | 1999-04-05 | 2010-11-24 | エミスフェアー・テクノロジーズ・インク | 活性剤を送達するための二ナトリウム塩、一水和物、およびエタノール溶媒和物 |
| SE9902987D0 (sv) * | 1999-08-24 | 1999-08-24 | Astra Pharma Prod | Novel compounds |
| AR035016A1 (es) * | 1999-08-25 | 2004-04-14 | Takeda Chemical Industries Ltd | Composicion de azol promotor de produccion/secrecion de neurotrofina, compuesto prodroga del mismo, composicion farmaceutica que lo comprende y uso del mismo para preparar esta ultima. |
| CZ20021570A3 (cs) | 1999-11-05 | 2002-10-16 | Emisphere Technologies, Inc. | Fenylaminkarboxylové kyseliny a kompozice pro dodávání aktivních činidel |
| ES2298168T3 (es) | 1999-12-16 | 2008-05-16 | Emisphere Technologies, Inc. | Compuestos y composiciones para suministrar agentes activos. |
| EP1246792B1 (en) | 2000-01-13 | 2014-08-13 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| PT1299348E (pt) | 2000-06-29 | 2008-05-12 | Emisphere Tech Inc | Compostos e composições para administração de agentes activos |
| IL154110A0 (en) * | 2000-08-23 | 2003-07-31 | Lilly Co Eli | Oxazolyl-arylpropionic acid derivatives and their use as ppar agonists |
| US6982278B2 (en) * | 2000-08-23 | 2006-01-03 | Eli Lilly And Company | Oxazolyl-aryloxyacetic acid derivatives and their use as ppar agonists |
| AU2002215218A1 (en) * | 2000-11-17 | 2002-05-27 | Takeda Chemical Industries Ltd. | Isoxazole derivatives |
| JP4148672B2 (ja) * | 2000-11-17 | 2008-09-10 | 武田薬品工業株式会社 | イソオキサゾール誘導体 |
| HUP0302526A2 (hu) | 2000-12-21 | 2003-11-28 | Glaxo Group Limited | Makrolid vegyületek, eljárás az előállításukra, alkalmazásuk és ezeket tartalmazó gyógyszerkészítmények |
| JP4248244B2 (ja) * | 2001-02-14 | 2009-04-02 | 明治製菓株式会社 | １２、１３位変換新規１６員環マクロライド誘導体 |
| GB2373186A (en) * | 2001-02-23 | 2002-09-18 | Astrazeneca Ab | Pharmaceutical combinations of a CCR3 antagonist and a compound which is usefulreatment of asthma, allergic disease or inflammation |
| AU2002305720A1 (en) * | 2001-05-30 | 2002-12-09 | Huening, Tracy, T. | Piperazine pentanamide hiv protease inhibitors |
| CN1568187A (zh) * | 2001-08-15 | 2005-01-19 | Icos股份有限公司 | 2h－2,3－二氮杂萘－1－酮和其使用方法 |
| US6969057B2 (en) | 2001-10-30 | 2005-11-29 | Illinois Tool Works Inc. | Method and apparatus for adjusting and positioning air caps |
| AU2002367426A1 (en) * | 2001-12-28 | 2003-07-24 | Takeda Chemical Industries, Ltd. | Neurotrophic factor production/secretion accelerator |
| US20050148497A1 (en) | 2002-02-20 | 2005-07-07 | Khan Mohammed A. | Method for administering glp-1 molecules |
| CA2487315A1 (en) * | 2002-05-24 | 2003-12-04 | Takeda Pharmaceutical Company Limited | 1,2-azole derivatives with hypoglycemic and hypolipidemic activity |
| JP2004277397A (ja) * | 2002-05-24 | 2004-10-07 | Takeda Chem Ind Ltd | １，２−アゾール誘導体 |
| WO2005000339A2 (en) | 2003-06-19 | 2005-01-06 | Eli Lilly And Company | Melanocortin receptor 4(mc4) agonists and their uses |
| WO2005019184A1 (en) * | 2003-08-20 | 2005-03-03 | Eli Lilly And Company | Compounds, methods and formulations for the oral delivery of a glucagon like peptide (glp)-1 compound or an melanocortin 4 receptor (mc4) agonist peptide |
-
2004
- 2004-08-18 ES ES04779447T patent/ES2286679T3/es not_active Expired - Lifetime
- 2004-08-18 JP JP2006523866A patent/JP4754487B2/ja not_active Expired - Fee Related
- 2004-08-18 AT AT04779447T patent/ATE361294T1/de not_active IP Right Cessation
- 2004-08-18 US US10/566,012 patent/US20070293423A1/en not_active Abandoned
- 2004-08-18 CN CNB2004800227912A patent/CN100398536C/zh not_active Expired - Fee Related
- 2004-08-18 EP EP04779447A patent/EP1658285B1/en not_active Expired - Lifetime
- 2004-08-18 DE DE602004006279T patent/DE602004006279T2/de not_active Expired - Lifetime
- 2004-08-18 BR BRPI0413676A patent/BRPI0413676B8/pt not_active IP Right Cessation
- 2004-08-18 CA CA2530983A patent/CA2530983C/en not_active Expired - Fee Related
- 2004-08-18 AU AU2004267044A patent/AU2004267044B8/en not_active Ceased
- 2004-08-18 WO PCT/US2004/024387 patent/WO2005019212A1/en not_active Ceased
- 2004-08-18 MX MXPA06001916A patent/MXPA06001916A/es active IP Right Grant
-
2008
- 2008-11-03 US US12/263,722 patent/US7947841B2/en not_active Expired - Fee Related
-
2011
- 2011-04-14 US US13/087,255 patent/US8546581B2/en not_active Expired - Fee Related
- 2011-05-09 JP JP2011104435A patent/JP2011207886A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| AU2004267044B8 (en) | 2009-12-17 |
| BRPI0413676A (pt) | 2006-10-24 |
| US20110190205A1 (en) | 2011-08-04 |
| CA2530983A1 (en) | 2005-03-03 |
| WO2005019212A1 (en) | 2005-03-03 |
| BRPI0413676B1 (pt) | 2018-07-24 |
| US8546581B2 (en) | 2013-10-01 |
| US20090239798A1 (en) | 2009-09-24 |
| DE602004006279T2 (de) | 2007-12-27 |
| BRPI0413676B8 (pt) | 2021-05-25 |
| US7947841B2 (en) | 2011-05-24 |
| EP1658285B1 (en) | 2007-05-02 |
| JP2011207886A (ja) | 2011-10-20 |
| DE602004006279D1 (de) | 2007-06-14 |
| CN100398536C (zh) | 2008-07-02 |
| ATE361294T1 (de) | 2007-05-15 |
| JP4754487B2 (ja) | 2011-08-24 |
| CN1832944A (zh) | 2006-09-13 |
| JP2007502817A (ja) | 2007-02-15 |
| CA2530983C (en) | 2012-09-25 |
| MXPA06001916A (es) | 2006-05-17 |
| US20070293423A1 (en) | 2007-12-20 |
| EP1658285A1 (en) | 2006-05-24 |
| AU2004267044A1 (en) | 2005-03-03 |
| AU2004267044B2 (en) | 2009-12-03 |
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