CA2238307A1 - Ob protein derivatives having prolonged half-life - Google Patents
Ob protein derivatives having prolonged half-life Download PDFInfo
- Publication number
- CA2238307A1 CA2238307A1 CA002238307A CA2238307A CA2238307A1 CA 2238307 A1 CA2238307 A1 CA 2238307A1 CA 002238307 A CA002238307 A CA 002238307A CA 2238307 A CA2238307 A CA 2238307A CA 2238307 A1 CA2238307 A1 CA 2238307A1
- Authority
- CA
- Canada
- Prior art keywords
- protein
- derivative
- native
- immunoglobulin
- polypeptide
- 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.)
- Abandoned
Links
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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
- C07K14/5759—Products of obesity genes, e.g. leptin, obese (OB), tub, fat
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Child & Adolescent Psychology (AREA)
- Genetics & Genomics (AREA)
- Emergency Medicine (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Toxicology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US57949495A | 1995-12-27 | 1995-12-27 | |
| US08/579494 | 1995-12-27 | ||
| US66718496A | 1996-06-20 | 1996-06-20 | |
| US08/667184 | 1996-06-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2238307A1 true CA2238307A1 (en) | 1997-07-10 |
Family
ID=27077779
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002238307A Abandoned CA2238307A1 (en) | 1995-12-27 | 1996-12-19 | Ob protein derivatives having prolonged half-life |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP0870026B1 (OSRAM) |
| JP (1) | JP4037905B2 (OSRAM) |
| CN (1) | CN1154726C (OSRAM) |
| AT (1) | ATE267255T1 (OSRAM) |
| AU (1) | AU1520097A (OSRAM) |
| BR (1) | BR9612359A (OSRAM) |
| CA (1) | CA2238307A1 (OSRAM) |
| CZ (1) | CZ9802013A3 (OSRAM) |
| DE (1) | DE69632546T2 (OSRAM) |
| IL (1) | IL124831A0 (OSRAM) |
| MX (1) | MX9804687A (OSRAM) |
| NZ (1) | NZ326592A (OSRAM) |
| RU (1) | RU2178307C2 (OSRAM) |
| WO (1) | WO1997024440A1 (OSRAM) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7112659B2 (en) | 1995-11-22 | 2006-09-26 | Amgen, Inc. | OB fusion protein compositions and methods |
| US7208577B2 (en) | 1995-11-22 | 2007-04-24 | Amgen, Inc. | Methods of increasing lean tissue mass using OB protein compositions |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6001968A (en) * | 1994-08-17 | 1999-12-14 | The Rockefeller University | OB polypeptides, modified forms and compositions |
| DE741187T1 (de) * | 1995-05-05 | 1997-04-30 | Hoffmann La Roche | Rekombinante Obesitäts-(OB)-Proteine |
| NZ527007A (en) * | 1995-11-22 | 2005-01-28 | Amgen Inc | Methods of increasing lean tissue mass using OB protein compositions |
| US6025324A (en) * | 1996-05-15 | 2000-02-15 | Hoffmann-La Roche Inc. | Pegylated obese (ob) protein compositions |
| AU770897B2 (en) * | 1996-12-20 | 2004-03-04 | Amgen, Inc. | OB fusion protein compositions and methods |
| ATE351910T1 (de) * | 1996-12-20 | 2007-02-15 | Amgen Inc | Ob-fusionsprotein enthaltende zusammensetzungen und verfahren |
| ES2183351T3 (es) * | 1997-04-17 | 2003-03-16 | Amgen Inc | Composicones que comprenden conjugados de proteina ob humana activa estable con una cadena fc de inmunoglobulinas y metodos. |
| AU2002300605B8 (en) * | 1997-04-17 | 2006-02-09 | Amgen Inc. | Compositions Comprising Conjugates of Stable, Active, Human OB Protein with Antibody FC Chain and Methods |
| US6017876A (en) * | 1997-08-15 | 2000-01-25 | Amgen Inc. | Chemical modification of granulocyte-colony stimulating factor (G-CSF) bioactivity |
| PT1037927E (pt) | 1997-12-08 | 2004-10-29 | Emd Lexigen Res Ct Corp | Proteinas de fusao heterodimericas uteis para imunoterapia de abordagem selectiva e estimulacao imunologica geral |
| US6878811B1 (en) | 1998-04-23 | 2005-04-12 | Ajinomoto Co., Inc. | Substance with antithrombotic activity and method for detecting glycokallidin |
| US6492138B1 (en) | 1998-05-21 | 2002-12-10 | Amgen Canada Inc. | Polynucleotides encoding a novel SHC-binding protein |
| US6420339B1 (en) * | 1998-10-14 | 2002-07-16 | Amgen Inc. | Site-directed dual pegylation of proteins for improved bioactivity and biocompatibility |
| US7067110B1 (en) | 1999-07-21 | 2006-06-27 | Emd Lexigen Research Center Corp. | Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
| DE60025832T2 (de) | 1999-08-09 | 2006-08-31 | Emd Lexigen Research Center Corp., Billerica | Mehrere zytokin-antikörper komplexen |
| AU2154401A (en) | 1999-11-12 | 2001-05-30 | Merck Patent Gmbh | Erythropoietin forms with improved properties |
| HUP0204475A2 (en) | 2000-02-11 | 2003-04-28 | Merck Patent Gmbh | Enhancing the circulating half-life of antibody-based fusion proteins |
| EP1294401B1 (en) | 2000-06-29 | 2007-08-01 | EMD Lexigen Research Center Corp. | Enhancement of antibody-cytokine fusion protein mediated immune responses by combined treatment with immunocytokine uptake enhancing agents |
| US7635680B2 (en) | 2001-02-21 | 2009-12-22 | Alavita Pharmaceuticals, Inc. | Attenuation of reperfusion injury |
| US7645739B2 (en) | 2001-02-21 | 2010-01-12 | Alavita Pharmaceuticals, Inc. | Modified annexin compositions and methods of using same |
| ATE359807T1 (de) * | 2001-02-21 | 2007-05-15 | Surromed Inc | Modifizierte annexin-proteine und verhinderung und behandlung von thrombose |
| US7635676B2 (en) | 2001-02-21 | 2009-12-22 | Alavita Pharmaccuticals, Inc. | Modified annexin proteins and methods for their use in organ transplantation |
| RU2003129528A (ru) | 2001-03-07 | 2005-04-10 | Мерк Патент ГмбХ (DE) | Способ экспрессии белков, содержащих в качестве компонента гибридный изотип антитела |
| WO2002079415A2 (en) | 2001-03-30 | 2002-10-10 | Lexigen Pharmaceuticals Corp. | Reducing the immunogenicity of fusion proteins |
| DE60239454D1 (de) | 2001-05-03 | 2011-04-28 | Merck Patent Gmbh | Rekombinanter, tumorspezifischer antikörper und dessen verwendung |
| EP1454138B1 (en) | 2001-12-04 | 2012-01-18 | Merck Patent GmbH | Immunocytokines with modulated selectivity |
| CA2510180C (en) | 2002-12-17 | 2012-09-11 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Humanized antibody (h14.18) of the mouse 14.18 antibody binding to gd2 and its fusion with il-2 |
| US7314859B2 (en) | 2002-12-27 | 2008-01-01 | Diobex, Inc. | Compositions and methods for the prevention and control of insulin-induced hypoglycemia |
| US7655618B2 (en) | 2002-12-27 | 2010-02-02 | Diobex, Inc. | Compositions and methods for the prevention and control of insulin-induced hypoglycemia |
| US20050176108A1 (en) * | 2003-03-13 | 2005-08-11 | Young-Min Kim | Physiologically active polypeptide conjugate having prolonged in vivo half-life |
| DK1682583T3 (da) * | 2003-11-13 | 2012-05-07 | Hanmi Holdings Co Ltd | Proteinkompleksdannelse under anvendelse af immunoglobulinfragment samt fremgangsmåde til fremstilling deraf |
| CN100467488C (zh) | 2003-12-30 | 2009-03-11 | 默克专利有限公司 | Il-7融合蛋白 |
| RU2370276C2 (ru) | 2003-12-31 | 2009-10-20 | Мерк Патент Гмбх | Fc-ЭРИТРОПОЭТИН СЛИТЫЙ БЕЛОК С УЛУЧШЕННОЙ ФАРМАКОКИНЕТИКОЙ |
| WO2005066348A2 (en) | 2004-01-05 | 2005-07-21 | Emd Lexigen Research Center Corp. | Interleukin-12 targeted to oncofoetal fibronectin |
| KR100639397B1 (ko) * | 2004-03-18 | 2006-10-26 | (주)에스제이바이오메드 | 항비만용 면역원성 하이브리드 폴리펩타이드 및 이를포함하는 항비만 백신 조성물 |
| US7589179B2 (en) | 2004-12-09 | 2009-09-15 | Merck Patent Gmbh | IL-7 variants with reduced immunogenicity |
| US8227408B2 (en) | 2005-09-07 | 2012-07-24 | Neurotez, Inc. | Leptin as an anti-amyloidogenic biologic and methods for delaying the onset and reducing Alzheimer's disease-like pathology |
| US8716220B2 (en) | 2005-09-07 | 2014-05-06 | Nikolaos Tezapsidis | Leptin compositions and methods for treating progressive cognitive function disorders resulting from accumulation of neurofibrillary tangles and amyloid beta |
| US8642543B2 (en) | 2005-09-07 | 2014-02-04 | Neurotez, Inc. | Methods for treating progressive cognitive disorders related to neurofibrillary tangles |
| EP1972349A1 (en) * | 2007-03-21 | 2008-09-24 | Biocompatibles UK Limited | GLP-1 fusion peptides conjugated to polymer(s), their production and use |
| JP5781501B2 (ja) | 2009-04-22 | 2015-09-24 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ | 改変されたＦｃＲｎ結合部位を有する抗体融合タンパク質 |
| CN104147596A (zh) * | 2013-05-14 | 2014-11-19 | 李荣秀 | 生物药非共价结合聚合物延长治疗浓度的方法及用途 |
| CN104524568B (zh) * | 2015-01-08 | 2018-04-20 | 中国人民解放军第二军医大学 | 一种治疗肥胖症的药物组合物及其应用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6309853B1 (en) * | 1994-08-17 | 2001-10-30 | The Rockfeller University | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
| DE741187T1 (de) * | 1995-05-05 | 1997-04-30 | Hoffmann La Roche | Rekombinante Obesitäts-(OB)-Proteine |
| GB9511935D0 (en) * | 1995-06-13 | 1995-08-09 | Smithkline Beecham Plc | Novel compound |
-
1996
- 1996-12-19 WO PCT/US1996/020718 patent/WO1997024440A1/en not_active Ceased
- 1996-12-19 IL IL12483196A patent/IL124831A0/xx unknown
- 1996-12-19 CZ CZ982013A patent/CZ9802013A3/cs unknown
- 1996-12-19 EP EP96945295A patent/EP0870026B1/en not_active Expired - Lifetime
- 1996-12-19 RU RU98113706/14A patent/RU2178307C2/ru active
- 1996-12-19 DE DE69632546T patent/DE69632546T2/de not_active Expired - Lifetime
- 1996-12-19 AT AT96945295T patent/ATE267255T1/de active
- 1996-12-19 AU AU15200/97A patent/AU1520097A/en not_active Abandoned
- 1996-12-19 CA CA002238307A patent/CA2238307A1/en not_active Abandoned
- 1996-12-19 CN CNB961992654A patent/CN1154726C/zh not_active Expired - Lifetime
- 1996-12-19 NZ NZ326592A patent/NZ326592A/en not_active IP Right Cessation
- 1996-12-19 BR BR9612359A patent/BR9612359A/pt not_active Application Discontinuation
- 1996-12-19 JP JP52455197A patent/JP4037905B2/ja not_active Expired - Lifetime
-
1998
- 1998-06-11 MX MX9804687A patent/MX9804687A/es active IP Right Grant
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7112659B2 (en) | 1995-11-22 | 2006-09-26 | Amgen, Inc. | OB fusion protein compositions and methods |
| US7208577B2 (en) | 1995-11-22 | 2007-04-24 | Amgen, Inc. | Methods of increasing lean tissue mass using OB protein compositions |
| US7718400B2 (en) | 1995-11-22 | 2010-05-18 | Amylin Pharmaceuticals, Inc. | Methods of increasing lean tissue mass using OB protein compositions |
| US8080254B2 (en) | 1995-11-22 | 2011-12-20 | Amgen, Inc. | OB fusion protein compositions and methods |
Also Published As
| Publication number | Publication date |
|---|---|
| AU1520097A (en) | 1997-07-28 |
| EP0870026B1 (en) | 2004-05-19 |
| CN1205738A (zh) | 1999-01-20 |
| JP4037905B2 (ja) | 2008-01-23 |
| ATE267255T1 (de) | 2004-06-15 |
| IL124831A0 (en) | 1999-01-26 |
| DE69632546D1 (de) | 2004-06-24 |
| RU2178307C2 (ru) | 2002-01-20 |
| MX9804687A (es) | 1998-10-31 |
| EP0870026A1 (en) | 1998-10-14 |
| CN1154726C (zh) | 2004-06-23 |
| WO1997024440A1 (en) | 1997-07-10 |
| DE69632546T2 (de) | 2005-06-30 |
| CZ9802013A3 (cs) | 1998-09-16 |
| BR9612359A (pt) | 1999-07-13 |
| NZ326592A (en) | 2001-05-25 |
| JP2000504210A (ja) | 2000-04-11 |
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| EEER | Examination request | ||
| FZDE | Discontinued |