HRP960213A2 - RECOMBINANT OBESE (Ob) PROTEINS - Google Patents
RECOMBINANT OBESE (Ob) PROTEINS Download PDFInfo
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- HRP960213A2 HRP960213A2 HR08/484,629A HRP960213A HRP960213A2 HR P960213 A2 HRP960213 A2 HR P960213A2 HR P960213 A HRP960213 A HR P960213A HR P960213 A2 HRP960213 A2 HR P960213A2
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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
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- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- C07—ORGANIC CHEMISTRY
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- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43577795A | 1995-05-05 | 1995-05-05 | |
| US48462995A | 1995-06-07 | 1995-06-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP960213A2 true HRP960213A2 (en) | 1997-10-31 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR08/484,629A HRP960213A2 (en) | 1995-05-05 | 1996-05-02 | RECOMBINANT OBESE (Ob) PROTEINS |
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| US (1) | US6025325A (cs) |
| EP (1) | EP0741187A2 (cs) |
| JP (1) | JP3244627B2 (cs) |
| KR (1) | KR100219970B1 (cs) |
| CN (1) | CN1157290A (cs) |
| AR (1) | AR003087A1 (cs) |
| AU (1) | AU688210B2 (cs) |
| BG (1) | BG62975B1 (cs) |
| BR (1) | BR9602166A (cs) |
| CA (1) | CA2175298A1 (cs) |
| CZ (1) | CZ129796A3 (cs) |
| DE (1) | DE741187T1 (cs) |
| ES (1) | ES2093593T1 (cs) |
| GR (1) | GR960300075T1 (cs) |
| HR (1) | HRP960213A2 (cs) |
| HU (1) | HU220093B (cs) |
| IL (1) | IL118059A0 (cs) |
| IS (1) | IS4343A (cs) |
| MA (1) | MA23856A1 (cs) |
| MY (1) | MY132189A (cs) |
| NO (1) | NO961796L (cs) |
| NZ (1) | NZ286466A (cs) |
| OA (1) | OA10362A (cs) |
| PE (1) | PE50897A1 (cs) |
| PL (1) | PL186568B1 (cs) |
| RO (1) | RO117177B1 (cs) |
| RU (1) | RU96109211A (cs) |
| SG (1) | SG49337A1 (cs) |
| SK (1) | SK56996A3 (cs) |
| SV (1) | SV1996000030A (cs) |
| TN (1) | TNSN96066A1 (cs) |
| TR (1) | TR199600357A2 (cs) |
| TW (1) | TW464655B (cs) |
| UY (1) | UY24219A1 (cs) |
| YU (1) | YU26596A (cs) |
Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE238417T1 (de) | 1991-11-04 | 2003-05-15 | Inst Genetics Llc | Rekombinante knochenmorphogenetische protein heterodimere, zusammensetzungen und verfahren zur verwendung |
| US6479055B1 (en) * | 1993-06-07 | 2002-11-12 | Trimeris, Inc. | Methods for inhibition of membrane fusion-associated events, including respiratory syncytial virus transmission |
| US6471956B1 (en) | 1994-08-17 | 2002-10-29 | The Rockefeller University | Ob polypeptides, modified forms and compositions thereto |
| US6429290B1 (en) | 1994-08-17 | 2002-08-06 | The Rockefeller University | OB polypeptides, modified forms and derivatives |
| 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 |
| US6048837A (en) * | 1994-08-17 | 2000-04-11 | The Rockefeller University | OB polypeptides as modulators of body weight |
| US6350730B1 (en) | 1994-08-17 | 2002-02-26 | The Rockefeller University | OB polypeptides and modified forms as modulators of body weight |
| US6124448A (en) * | 1994-08-17 | 2000-09-26 | The Rockfeller University | Nucleic acid primers and probes for the mammalian OB gene |
| US6001968A (en) * | 1994-08-17 | 1999-12-14 | The Rockefeller University | OB polypeptides, modified forms and compositions |
| US20030040467A1 (en) * | 1998-06-15 | 2003-02-27 | Mary Ann Pelleymounter | Ig/ob fusions and uses thereof. |
| US6936439B2 (en) * | 1995-11-22 | 2005-08-30 | Amgen Inc. | OB fusion protein compositions and methods |
| RU2178307C2 (ru) * | 1995-12-27 | 2002-01-20 | Джинентех Инк. | Производные ов-протеина |
| AU769250B2 (en) * | 1995-12-27 | 2004-01-22 | Genentech Inc. | OB protein derivatives having prolonged half-life |
| US6620413B1 (en) | 1995-12-27 | 2003-09-16 | Genentech, Inc. | OB protein-polymer chimeras |
| US20050019325A1 (en) | 1996-01-08 | 2005-01-27 | Carter Paul J. | WSX receptor agonist antibodies |
| US6541604B1 (en) * | 1996-01-08 | 2003-04-01 | Genentech, Inc. | Leptin receptor having a WSX motif |
| US7074397B1 (en) * | 1996-01-08 | 2006-07-11 | Genentech, Inc. | Method for enhancing proliferation or differentiation of a cell using ob protein |
| WO1997026916A1 (en) * | 1996-01-25 | 1997-07-31 | Eli Lilly And Company | Obesity protein analog compounds and formulations thereof |
| US7067472B1 (en) * | 1996-06-04 | 2006-06-27 | The Scripps Research Institute | Diagnostic and therapeutic methods related to regulating energy mobilization with OB protein and OB antibodies |
| US6001816A (en) * | 1996-06-20 | 1999-12-14 | Merck & Co., Inc. | Gene therapy for leptin deficiency |
| US20060205660A1 (en) * | 1996-06-20 | 2006-09-14 | Sauvage Frederic D | OB protein-immunoglobulin chimeras |
| US20030036629A1 (en) * | 1997-12-12 | 2003-02-20 | Barry Foster | Novel tgf-beta protein purification methods |
| US6656906B1 (en) | 1998-05-20 | 2003-12-02 | Trimeris, Inc. | Hybrid polypeptides with enhanced pharmacokinetic properties |
| US6420339B1 (en) * | 1998-10-14 | 2002-07-16 | Amgen Inc. | Site-directed dual pegylation of proteins for improved bioactivity and biocompatibility |
| US7169889B1 (en) * | 1999-06-19 | 2007-01-30 | Biocon Limited | Insulin prodrugs hydrolyzable in vivo to yield peglylated insulin |
| CZ299516B6 (cs) * | 1999-07-02 | 2008-08-20 | F. Hoffmann-La Roche Ag | Konjugát erythropoetinového glykoproteinu, zpusobjeho výroby a použití a farmaceutická kompozice sjeho obsahem |
| PE20010288A1 (es) | 1999-07-02 | 2001-03-07 | Hoffmann La Roche | Derivados de eritropoyetina |
| US7446183B2 (en) | 2000-06-16 | 2008-11-04 | Asterion Limited | Fusion protein comprising growth hormone and growth hormone receptor |
| KR20030005204A (ko) * | 2000-12-25 | 2003-01-17 | 가부시키가이샤 시세이도 | 교감신경 활성화 향료 조성물 |
| US6867183B2 (en) * | 2001-02-15 | 2005-03-15 | Nobex Corporation | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
| US7060675B2 (en) * | 2001-02-15 | 2006-06-13 | Nobex Corporation | Methods of treating diabetes mellitus |
| EP1234583A1 (en) * | 2001-02-23 | 2002-08-28 | F. Hoffmann-La Roche Ag | PEG-conjugates of HGF-NK4 |
| US7713932B2 (en) * | 2001-06-04 | 2010-05-11 | Biocon Limited | Calcitonin drug-oligomer conjugates, and uses thereof |
| US6828297B2 (en) * | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US6828305B2 (en) * | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of growth hormone drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US6835802B2 (en) | 2001-06-04 | 2004-12-28 | Nobex Corporation | Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties |
| US6713452B2 (en) | 2001-06-04 | 2004-03-30 | Nobex Corporation | Mixtures of calcitonin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US7196059B2 (en) * | 2001-09-07 | 2007-03-27 | Biocon Limited | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
| US7312192B2 (en) * | 2001-09-07 | 2007-12-25 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| US7030082B2 (en) * | 2001-09-07 | 2006-04-18 | Nobex Corporation | Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith |
| US7166571B2 (en) * | 2001-09-07 | 2007-01-23 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| US6913903B2 (en) * | 2001-09-07 | 2005-07-05 | Nobex Corporation | Methods of synthesizing insulin polypeptide-oligomer conjugates, and proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| US6770625B2 (en) | 2001-09-07 | 2004-08-03 | Nobex Corporation | Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith |
| WO2003034996A2 (en) | 2001-10-22 | 2003-05-01 | Amgen, Inc. | Use of leptin for treating human lipoatrophy and method of determining predisposition to said treatment |
| WO2003092614A2 (en) * | 2002-05-02 | 2003-11-13 | Hickle Randall S | Lipid removal from the body |
| RU2363478C2 (ru) | 2003-09-12 | 2009-08-10 | Вайет | Инъецируемые стержни из фосфата кальция для доставки остеогенных белков |
| CA2580313C (en) | 2004-07-19 | 2016-03-15 | Biocon Limited | Insulin-oligomer conjugates, formulations and uses thereof |
| 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 |
| BRPI0818004B8 (pt) * | 2007-10-16 | 2021-05-25 | Biocon Ltd | composição farmacêutica sólida administrável por via oral e o processo da mesma. |
| EP2326339A4 (en) * | 2008-05-21 | 2012-06-20 | Neurotez Inc | METHOD FOR TREATING PROGRESSIVE COGNITIVE DISORDER IN CONNECTION WITH NEUROFIBRILLARY TANGLES |
| WO2010118384A2 (en) | 2009-04-10 | 2010-10-14 | Amylin Pharmaceuticals, Inc. | Amylin agonist compounds for estrogen-deficient mammals |
| WO2012050925A2 (en) | 2010-09-28 | 2012-04-19 | Amylin Pharmaceuticals, Inc. | Highly soluble leptins |
| KR20130141648A (ko) | 2011-01-26 | 2013-12-26 | 노보 노르디스크 에이/에스 | 렙틴 유도체 |
| WO2021113434A1 (en) * | 2019-12-03 | 2021-06-10 | Rodan & Fields, Llc | Peptides and compositions for inhibiting hair growth |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4199337A (en) * | 1978-10-06 | 1980-04-22 | International Telephone And Telegraph Corporation | Method of fabricating high strength optical preforms |
| US4666836A (en) * | 1981-01-02 | 1987-05-19 | The Research Foundation Of State University Of New York | Novel cloning vehicles for polypeptide expression in microbial hosts |
| US4609546A (en) * | 1982-06-24 | 1986-09-02 | Japan Chemical Research Co., Ltd. | Long-acting composition |
| US4643969A (en) * | 1983-07-25 | 1987-02-17 | The Research Foundation Of State University Of New York | Novel cloning vehicles for polypeptide expression in microbial hosts |
| US4757013A (en) * | 1983-07-25 | 1988-07-12 | The Research Foundation Of State University Of New York | Cloning vehicles for polypeptide expression in microbial hosts |
| DE3572982D1 (en) * | 1984-03-06 | 1989-10-19 | Takeda Chemical Industries Ltd | Chemically modified lymphokine and production thereof |
| US5595732A (en) * | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
| US5643575A (en) * | 1993-10-27 | 1997-07-01 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| AU3329895A (en) * | 1994-08-17 | 1996-03-07 | Rockefeller University, The | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
| 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 |
| US5861485A (en) * | 1994-08-23 | 1999-01-19 | Millennium Pharmaceuticals, Inc. | Polypeptides involved in body weight disorders, including obesity |
| US5932462A (en) * | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| US5827734A (en) * | 1995-01-20 | 1998-10-27 | University Of Washington | Materials and methods for determining ob protein in a biological sample |
| US5554727A (en) * | 1995-01-31 | 1996-09-10 | Eli Lilly And Company | Anti-obesity proteins |
| US5563243A (en) * | 1995-01-31 | 1996-10-08 | Eli Lilly And Company | Anti-obesity proteins |
| US5594104A (en) * | 1995-01-31 | 1997-01-14 | Eli Lilly And Company | Anti-obesity proteins |
| US5563245A (en) * | 1995-01-31 | 1996-10-08 | Eli Lilly And Company | Anti-obesity proteins |
| US5563244A (en) * | 1995-01-31 | 1996-10-08 | Eli Lilly And Company | Anti-obesity proteins |
| US5569743A (en) * | 1995-01-31 | 1996-10-29 | Eli Lilly And Company | Anti-obesity proteins |
| US5567803A (en) * | 1995-01-31 | 1996-10-22 | Eli Lilly And Company | Anti-obesity proteins |
| US5580954A (en) * | 1995-01-31 | 1996-12-03 | Eli Lilly And Company | Anti-obesity proteins |
| US5567678A (en) * | 1995-01-31 | 1996-10-22 | Eli Lilly And Company | Anti-obesity proteins |
| CA2211664A1 (en) * | 1995-01-31 | 1996-08-08 | Eli Lilly And Company | Anti-obesity proteins |
| US5574133A (en) * | 1995-01-31 | 1996-11-12 | Eli Lilly And Company | Anti-obesity proteins |
| US5569744A (en) * | 1995-01-31 | 1996-10-29 | Eli Lilly And Company | Anti-obesity proteins |
| US5559208A (en) * | 1995-01-31 | 1996-09-24 | Eli Lilly And Company | Anti-obesity proteins |
| WO1996031526A1 (en) * | 1995-04-06 | 1996-10-10 | Amylin Pharmaceuticals, Inc. | Anti-obesity agents |
| WO1996040912A1 (en) * | 1995-06-07 | 1996-12-19 | Amgen Inc. | Ob protein compositions and method |
| WO1997020933A2 (en) * | 1995-12-06 | 1997-06-12 | Schering Corporation | MUTATIONAL VARIANTS OF MAMMALIAN Ob GENE PROTEINS |
| RU2178307C2 (ru) * | 1995-12-27 | 2002-01-20 | Джинентех Инк. | Производные ов-протеина |
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