ES2641325T3 - Antagonistas peptídicos de la familia calcitonina CGRP de hormonas peptídicas y su uso - Google Patents
Antagonistas peptídicos de la familia calcitonina CGRP de hormonas peptídicas y su uso Download PDFInfo
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Classifications
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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
- C07K14/57527—Calcitonin gene related peptide
-
- 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
- A61K38/225—Calcitonin gene related peptide
-
- 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
- A61K38/23—Calcitonins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
- A61P5/22—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of calcitonin
-
- 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
- C07K14/585—Calcitonins
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261591236P | 2012-01-26 | 2012-01-26 | |
| US201261591236P | 2012-01-26 | ||
| PCT/US2013/023260 WO2013112912A1 (en) | 2012-01-26 | 2013-01-25 | Peptide antagonists of the calcitonin cgrp family of peptide hormones and their use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2641325T3 true ES2641325T3 (es) | 2017-11-08 |
Family
ID=47682066
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13703494.8T Active ES2641325T3 (es) | 2012-01-26 | 2013-01-25 | Antagonistas peptídicos de la familia calcitonina CGRP de hormonas peptídicas y su uso |
| ES17175988T Active ES2819825T3 (es) | 2012-01-26 | 2013-01-25 | Antagonistas peptídicos de la familia calcitonina CGRP de hormonas peptídicas y su uso |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17175988T Active ES2819825T3 (es) | 2012-01-26 | 2013-01-25 | Antagonistas peptídicos de la familia calcitonina CGRP de hormonas peptídicas y su uso |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US9193776B2 (enExample) |
| EP (2) | EP3272769B1 (enExample) |
| JP (3) | JP6025871B2 (enExample) |
| KR (2) | KR101855242B1 (enExample) |
| CN (2) | CN108997490A (enExample) |
| AU (2) | AU2013211929B2 (enExample) |
| CA (1) | CA2861392C (enExample) |
| DK (1) | DK2807187T3 (enExample) |
| ES (2) | ES2641325T3 (enExample) |
| IL (2) | IL233655A (enExample) |
| MX (1) | MX347229B (enExample) |
| NO (1) | NO2864579T3 (enExample) |
| RU (2) | RU2624016C2 (enExample) |
| WO (1) | WO2013112912A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX347229B (es) * | 2012-01-26 | 2017-04-19 | Christopher J Soares | Antagonistas de péptido de la familia cgrp de calcitonina de hormonas de péptido y su uso. |
| JP6538682B2 (ja) * | 2013-07-30 | 2019-07-03 | ソアレス クリストファー ジェイ. | Cgrpアゴニストペプチド |
| JO3669B1 (ar) | 2015-01-06 | 2020-08-27 | Ferring Bv | بيبتيدات مضَادَّة لببتيد المرتبط بجين الكالسيتونين |
| CN116063580A (zh) * | 2016-01-04 | 2023-05-05 | 艾得佩索拉公司 | 肽类似物 |
| JP7123932B2 (ja) * | 2016-09-02 | 2022-08-23 | クリストファー ジェイ. ソアレス | 神経保護及び神経疾患におけるcgrp受容体アンタゴニストの使用 |
| CA2967616A1 (en) * | 2016-09-19 | 2018-03-19 | The Governors Of The University Of Alberta | Brain penetrant amylin receptor based peptides for alzheimer's disease |
| US20200353088A1 (en) * | 2017-11-06 | 2020-11-12 | Auckland Uniservices Limited | Peptide conjugate cgrp receptor antagonists and methods of preparation and uses thereof |
| JP7214102B2 (ja) * | 2019-01-18 | 2023-01-30 | 株式会社大一商会 | 遊技機 |
| JP7214100B2 (ja) * | 2019-01-18 | 2023-01-30 | 株式会社大一商会 | 遊技機 |
| JP7214104B2 (ja) * | 2019-01-18 | 2023-01-30 | 株式会社大一商会 | 遊技機 |
| CN116456981A (zh) * | 2020-11-19 | 2023-07-18 | 辉瑞爱尔兰制药公司 | 用于改善的grp抑制剂递送的组合物 |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3645090A (en) | 1969-06-19 | 1972-02-29 | Citizen Watch Co Ltd | Day-date quick-adjuster for calender timepiece |
| US3940475A (en) | 1970-06-11 | 1976-02-24 | Biological Developments, Inc. | Radioimmune method of assaying quantitatively for a hapten |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| NO812612L (no) | 1980-08-06 | 1982-02-08 | Ferring Pharma Ltd | Enzym-inhibitorer. |
| US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| CH657779A5 (de) | 1982-10-05 | 1986-09-30 | Sandoz Ag | Galenische zusammensetzungen enthaltend calcitonin. |
| IT1164225B (it) | 1983-05-13 | 1987-04-08 | Anic Spa | Analoghi retro-invertiti del pentapeptide potenziante la bradichina bpp5a e metodi per la loro preparazione |
| US4530838A (en) | 1983-07-08 | 1985-07-23 | The Salk Institute For Biological Studies | Synthetic calcitonin-gene-related peptides for lowering blood pressure or gastric acid secretion in mammals |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
| JPS62129297A (ja) * | 1985-08-09 | 1987-06-11 | Toyo Jozo Co Ltd | カルシトニン遺伝子関連ペプチド誘導体 |
| JPS62231168A (ja) | 1986-03-21 | 1987-10-09 | ハイブリテツク・インコ−ポレイテツド | アナライト−レセプタ−分析用内部標準を設けるための改良法 |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| US6552170B1 (en) | 1990-04-06 | 2003-04-22 | Amgen Inc. | PEGylation reagents and compounds formed therewith |
| US5206161A (en) | 1991-02-01 | 1993-04-27 | Genentech, Inc. | Human plasma carboxypeptidase B |
| ES2181691T5 (es) | 1992-06-11 | 2007-10-01 | Alkermes Controlled Therapeutics, Inc. | Sistema de distribucion de proteina eritropoyetina. |
| US5354934A (en) | 1993-02-04 | 1994-10-11 | Amgen Inc. | Pulmonary administration of erythropoietin |
| AU6524794A (en) | 1993-03-24 | 1994-10-11 | Amylin Pharmaceuticals, Inc. | Cloned receptors and methods for screening |
| US5698401A (en) | 1995-11-14 | 1997-12-16 | Abbott Laboratories | Use of nuclear magnetic resonance to identify ligands to target biomolecules |
| US5910482A (en) * | 1996-03-19 | 1999-06-08 | Board Of Regents, The University Of Texas System | Treatment or prevention of preeclampsia, eclampsia with calcitonin gene related peptide, CGRP analog, progestational agent, nitric oxide source, and cyclooxygenase inhibitor |
| WO1997041223A1 (en) | 1996-04-15 | 1997-11-06 | The University Of Miami | Molecular clone of cgrp receptor component protein and uses thereof |
| US20050054557A1 (en) | 2002-05-09 | 2005-03-10 | Goldberg Michael M. | Compositions for delivering parathyroid hormone and calcitonin |
| WO2004084859A2 (en) | 2003-03-21 | 2004-10-07 | Nastech Pharmaceutical Company Inc. | Nasal calcitonin formulations containing chlorobutanol |
| US20060286129A1 (en) | 2003-12-19 | 2006-12-21 | Emisphere Technologies, Inc. | Oral GLP-1 formulations |
| ATE471340T1 (de) | 2004-02-11 | 2010-07-15 | Amylin Pharmaceuticals Inc | Peptide der amylin familie, verfahren zu deren herstellung und verwendung |
| JP4926069B2 (ja) | 2004-11-01 | 2012-05-09 | アミリン・ファーマシューティカルズ,インコーポレイテッド | 肥満ならびに肥満関連疾患および障害の治療方法 |
| US8263545B2 (en) * | 2005-02-11 | 2012-09-11 | Amylin Pharmaceuticals, Inc. | GIP analog and hybrid polypeptides with selectable properties |
| EA011653B1 (ru) * | 2005-02-11 | 2009-04-28 | Амилин Фармасьютикалз, Инк. | Аналоги и гибридные полипептиды gip с избираемыми свойствами |
| CN101208098A (zh) * | 2005-03-31 | 2008-06-25 | 安米林药品公司 | 用于治疗精神病和精神障碍的胰淀素和胰淀素激动剂 |
| AU2006230420B2 (en) * | 2005-03-31 | 2011-11-24 | Amylin Pharmaceuticals, Llc | Compositions and methods for the control, prevention, and treatment of obesity and eating disorders |
| EP1954313A1 (en) * | 2005-11-01 | 2008-08-13 | Amylin Pharmaceuticals, Inc. | Treatment of obesity and related disorders |
| WO2007055743A2 (en) * | 2005-11-01 | 2007-05-18 | Amylin Pharmaceuticals, Inc. | Treatment of obesity and related disorders |
| EP3045182B1 (en) * | 2005-11-14 | 2018-03-07 | Teva Pharmaceuticals International GmbH | Antagonist antibodies directed against calcitonin gene-related peptide for treating cluster headache |
| CN101939022A (zh) | 2007-11-14 | 2011-01-05 | 安米林药品公司 | 治疗肥胖以及肥胖相关疾病和病症的方法 |
| US8748375B2 (en) | 2009-03-17 | 2014-06-10 | Amylin Pharmaceuticals, Llc | Methods for affecting body composition using amylin agonists |
| WO2013059336A1 (en) | 2011-10-18 | 2013-04-25 | Amylin Pharmaceuticals, Llc | Amylin-calcitonin chimeric peptides conjugated to duration enchancing moieties |
| MX347229B (es) | 2012-01-26 | 2017-04-19 | Christopher J Soares | Antagonistas de péptido de la familia cgrp de calcitonina de hormonas de péptido y su uso. |
| EP2820016B1 (en) | 2012-02-27 | 2017-08-02 | Bristol-Myers Squibb Company | N- (5s, 6s, 9r) - 5 -amino- 6 - (2, 3 - difluorophenyl) -6, 7, 8, 9 - tetrahydro - 5h - cyclohepta [b]pyridin-9 -yl- 4 - (2 - oxo-2, 3 - dihydro - 1h- imidazo [4, 5 -b]pyridin - 1 - yl) piperidine - 1 - carboxylate, hemisulfate salt |
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