JP2008522617A - 線維芽細胞成長因子２１の突然変異タンパク質 - Google Patents
線維芽細胞成長因子２１の突然変異タンパク質 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
- C07K14/475—Growth factors; Growth regulators
- C07K14/50—Fibroblast growth factor [FGF]
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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
- 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
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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
- A61P3/06—Antihyperlipidemics
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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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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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
- 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
- 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)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Obesity (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Genetics & Genomics (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Emergency Medicine (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Child & Adolescent Psychology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63588204P | 2004-12-14 | 2004-12-14 | |
| PCT/US2005/044116 WO2006065582A2 (en) | 2004-12-14 | 2005-12-07 | Muteins of fibroblast growth factor 21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008522617A true JP2008522617A (ja) | 2008-07-03 |
| JP2008522617A5 JP2008522617A5 (https=) | 2009-01-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007545564A Withdrawn JP2008522617A (ja) | 2004-12-14 | 2005-12-07 | 線維芽細胞成長因子２１の突然変異タンパク質 |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US7655627B2 (https=) |
| EP (1) | EP1831371A2 (https=) |
| JP (1) | JP2008522617A (https=) |
| WO (1) | WO2006065582A2 (https=) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012504965A (ja) * | 2008-10-10 | 2012-03-01 | アムジエン・インコーポレーテツド | Ｆｇｆ２１変異体およびその使用 |
| JP2012525847A (ja) * | 2009-05-05 | 2012-10-25 | アムジエン・インコーポレーテツド | Ｆｇｆ２１変異体およびその使用 |
Families Citing this family (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7459540B1 (en) | 1999-09-07 | 2008-12-02 | Amgen Inc. | Fibroblast growth factor-like polypeptides |
| US8981061B2 (en) | 2001-03-20 | 2015-03-17 | Novo Nordisk A/S | Receptor TREM (triggering receptor expressed on myeloid cells) and uses thereof |
| GB0426146D0 (en) | 2004-11-29 | 2004-12-29 | Bioxell Spa | Therapeutic peptides and method |
| CA2682147C (en) | 2007-03-30 | 2017-08-08 | Ambrx, Inc. | Modified fgf-21 polypeptides and their uses |
| BRPI0812384A2 (pt) * | 2007-05-22 | 2014-12-02 | Novartis Ag | Métodos de tratamento, diagnóstico e detecção de distúrbios associados a fgf21 |
| EP2296690B1 (en) | 2008-06-04 | 2016-11-30 | Amgen, Inc | Fgf21 mutants and uses thereof |
| AU2013211503C1 (en) * | 2008-10-10 | 2016-09-29 | Amgen Inc. | FGF21 mutants and uses thereof |
| BRPI1007313A2 (pt) | 2009-01-23 | 2016-02-10 | Novo Nordisk As | derivados de fgf21 com ligante de albumina a-b-c-d-e e seu uso. |
| HRP20240135T1 (hr) | 2009-05-05 | 2024-04-12 | Amgen Inc. | Fgf21 mutanti i njihove upotrebe |
| WO2011154349A2 (en) | 2010-06-08 | 2011-12-15 | Novo Nordisk A/S | Fgf21 analogues and derivatives |
| US8324160B2 (en) | 2009-06-17 | 2012-12-04 | Amgen Inc. | Chimeric polypeptides and uses thereof |
| WO2011006072A2 (en) * | 2009-07-10 | 2011-01-13 | Northwestern University | Cardioprotective role of hepatic cells and hepatocyte secretory factors in myocardial ischemia |
| EP2679234A3 (en) | 2009-12-02 | 2014-04-23 | Amgen Inc. | Binding proteins that bind to human FGFR1C, human beta-klotho and both human FGFR1C and human beta-klotho |
| UA109888C2 (uk) * | 2009-12-07 | 2015-10-26 | ІЗОЛЬОВАНЕ АНТИТІЛО АБО ЙОГО ФРАГМЕНТ, ЩО ЗВ'ЯЗУЄТЬСЯ З β-КЛОТО, РЕЦЕПТОРАМИ FGF І ЇХНІМИ КОМПЛЕКСАМИ | |
| EP2460527A1 (en) | 2010-01-21 | 2012-06-06 | Sanofi | Pharmaceutical composition for treating a metabolic syndrome |
| CA2796055A1 (en) | 2010-04-15 | 2011-10-20 | Amgen Inc. | Human fgf receptor and .beta.-klotho binding proteins |
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| EP2595647A1 (en) | 2010-07-20 | 2013-05-29 | Novo Nordisk A/S | N-terminal modified fgf21 compounds |
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| US8754044B2 (en) | 2011-05-03 | 2014-06-17 | Northwestern University | Neuroprotection by hepatic cells and hepatocyte secretory factors |
| SI2710035T1 (sl) | 2011-05-16 | 2017-07-31 | F. Hoffmann-La Roche Ag | Agonisti FGFR1 in tehnike njihove uporabe |
| WO2013006486A2 (en) | 2011-07-01 | 2013-01-10 | Ngm Biopharmaceuticals, Inc. | Compositions, uses and methods for treatment of metabolic disorders and diseases |
| EP2548570A1 (en) | 2011-07-19 | 2013-01-23 | Sanofi | Pharmaceutical composition for treating a metabolic syndrome |
| JP6165168B2 (ja) | 2011-12-22 | 2017-07-19 | ファイザー・インク | 抗糖尿病化合物 |
| SMT201700488T1 (it) | 2012-02-15 | 2017-11-15 | Novo Nordisk As | Anticorpi che legano e bloccano il recettore d'innesco espresso sulle cellule mieloidi-1 (trem-1) |
| US9550830B2 (en) | 2012-02-15 | 2017-01-24 | Novo Nordisk A/S | Antibodies that bind and block triggering receptor expressed on myeloid cells-1 (TREM-1) |
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| EP3774902A1 (en) | 2018-04-02 | 2021-02-17 | Bristol-Myers Squibb Company | Anti-trem-1 antibodies and uses thereof |
| CA3104686A1 (en) | 2018-07-03 | 2020-01-09 | Bristol-Myers Squibb Company | Fgf-21 formulations |
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| IL294534A (en) | 2020-01-08 | 2022-09-01 | Bristol Myers Squibb Co | Fgf-21 conjugate formulations |
| US11981718B2 (en) | 2020-05-27 | 2024-05-14 | Ampsource Biopharma Shanghai Inc. | Dual-function protein for lipid and blood glucose regulation |
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Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7459540B1 (en) | 1999-09-07 | 2008-12-02 | Amgen Inc. | Fibroblast growth factor-like polypeptides |
| US6716626B1 (en) | 1999-11-18 | 2004-04-06 | Chiron Corporation | Human FGF-21 nucleic acids |
| WO2003011213A2 (en) * | 2001-07-30 | 2003-02-13 | Eli Lilly And Company | Method for treating diabetes and obesity |
| AU2003270424A1 (en) | 2002-09-09 | 2004-03-29 | Curagen Corporation | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
| CN1890371A (zh) * | 2003-12-10 | 2007-01-03 | 伊莱利利公司 | 成纤维细胞生长因子的21突变蛋白 |
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2005
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- 2005-12-07 EP EP05853126A patent/EP1831371A2/en not_active Withdrawn
- 2005-12-07 WO PCT/US2005/044116 patent/WO2006065582A2/en not_active Ceased
- 2005-12-07 JP JP2007545564A patent/JP2008522617A/ja not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012504965A (ja) * | 2008-10-10 | 2012-03-01 | アムジエン・インコーポレーテツド | Ｆｇｆ２１変異体およびその使用 |
| JP2012525847A (ja) * | 2009-05-05 | 2012-10-25 | アムジエン・インコーポレーテツド | Ｆｇｆ２１変異体およびその使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2006065582A2 (en) | 2006-06-22 |
| EP1831371A2 (en) | 2007-09-12 |
| WO2006065582A3 (en) | 2006-09-14 |
| US7655627B2 (en) | 2010-02-02 |
| US20070293430A1 (en) | 2007-12-20 |
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