BR0213402A - Métodos para identificar uma célula de mamìfero capaz de produzir uma molécula proteinácea, para selecionar uma célula de mamìfero capaz de produzir uma molécula proteinácea, para se obter uma célula de mamìfero a partir de uma população heterogênea de células, e para produzir uma molécula proteinácea, composição farmaceuticamente aceitável, eritropoietina recombinantemente produzida, usos de uma célula de mamìfero, da eritropoietina recombinantemente produzida, e de uma composição de moléculas semelhantes à eritropoietina, preparação farmacêutica, método para o tratamento preventivo e/ou terapêutico de um distúrbio, composição de moléculas semelhates à eritropoietina, métodos para produzir, em uma célula de mamìfero, moléculas proteináceas, para produzir uma fração enriquecida em uma molécula proteinácea, e para fracionar uma mistura que contém moléculas proteináceas, fração, e, usos de uma fração ou composição, e de eritropoietina recombinantemente produzìvel em uma célula de mamìfero - Google Patents
Métodos para identificar uma célula de mamìfero capaz de produzir uma molécula proteinácea, para selecionar uma célula de mamìfero capaz de produzir uma molécula proteinácea, para se obter uma célula de mamìfero a partir de uma população heterogênea de células, e para produzir uma molécula proteinácea, composição farmaceuticamente aceitável, eritropoietina recombinantemente produzida, usos de uma célula de mamìfero, da eritropoietina recombinantemente produzida, e de uma composição de moléculas semelhantes à eritropoietina, preparação farmacêutica, método para o tratamento preventivo e/ou terapêutico de um distúrbio, composição de moléculas semelhates à eritropoietina, métodos para produzir, em uma célula de mamìfero, moléculas proteináceas, para produzir uma fração enriquecida em uma molécula proteinácea, e para fracionar uma mistura que contém moléculas proteináceas, fração, e, usos de uma fração ou composição, e de eritropoietina recombinantemente produzìvel em uma célula de mamìferoInfo
- Publication number
- BR0213402A BR0213402A BR0213402-0A BR0213402A BR0213402A BR 0213402 A BR0213402 A BR 0213402A BR 0213402 A BR0213402 A BR 0213402A BR 0213402 A BR0213402 A BR 0213402A
- Authority
- BR
- Brazil
- Prior art keywords
- mammalian cell
- erythropoietin
- producing
- molecule
- proteinaceous
- Prior art date
Links
- 210000004962 mammalian cell Anatomy 0.000 title abstract 11
- 102000003951 Erythropoietin Human genes 0.000 title abstract 7
- 108090000394 Erythropoietin Proteins 0.000 title abstract 7
- 229940105423 erythropoietin Drugs 0.000 title abstract 7
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 title abstract 7
- 238000000034 method Methods 0.000 title abstract 6
- 239000000203 mixture Substances 0.000 title 5
- 210000004027 cell Anatomy 0.000 title 1
- 239000000825 pharmaceutical preparation Substances 0.000 title 1
- 230000003449 preventive effect Effects 0.000 title 1
- 230000001225 therapeutic effect Effects 0.000 title 1
- 230000004481 post-translational protein modification Effects 0.000 abstract 5
- 230000013595 glycosylation Effects 0.000 abstract 2
- 238000006206 glycosylation reaction Methods 0.000 abstract 2
- 102000004169 proteins and genes Human genes 0.000 abstract 2
- 108090000623 proteins and genes Proteins 0.000 abstract 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 abstract 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 230000001537 neural effect Effects 0.000 abstract 1
- 229920001542 oligosaccharide Polymers 0.000 abstract 1
- 150000002482 oligosaccharides Chemical class 0.000 abstract 1
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
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
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- 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
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- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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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
- C07K14/505—Erythropoietin [EPO]
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/005—Glycopeptides, glycoproteins
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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
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10341—Use of virus, viral particle or viral elements as a vector
- C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Virology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
Abstract
"MéTODOS PARA IDENTIFICAR UMA CéLULA DE MAMìFERO CAPAZ DE PRODUZIR UMA MOLéCULA PROTEINáCEA, PARA SELECIONAR UMA CéLULA DE MAMìFERO CAPAZ DE PRODUZIR UMA MOLéCULA PROTEINáCEA, PARA SE OBTER UMA CéLULA DE MAMìFERO A PARTIR DE UMA POPULAçãO HETEROGêNEA DE CéLULAS, E PARA PRODUZIR UMA MOLéCULA PROTEINáCEA, COMPOSIçãO FARMACEUTICAMENTE ACEITáVEL, ERITROPOIETINA RECOMBINANTEMENTE PRODUZIDA, USOS DE UMA CéLULA DE MAMìFERO, DA ERITROPOIETINA RECOMBINANTEMENTE PRODUZIDA, E DE UMA COMPOSIçãO DE MOLéCULAS SEMELHANTES A ERITROPOIETINA, PREPARAçãO FARMACêUTICA, MéTODO PARA O TRATAMENTO PREVENTIVO E/OU TERAPêUTICO DE UM DISTúRBIO COMPOSIçãO DE MOLéCULAS SEMELHANTES à ERITROPOIETINA, MéTODOS PARA PRODUZIR, EM UMA CéLULA DE MAMìFERO, MOLéCULAS PROTEINáCEAS, PARA PRODUZIR UMA FRAçãO ENRIQUECIDA EM UMA MOLéCULA PROTEINáCEA, E PARA FRACIONAR UMA MISTURA QUE CONTEM MOLéCULAS PROTEINáCEAS, FRAçãO, E, USOS DE UMA FRAçãO OU COMPOSIçãO, E DE ERITROPOIETINA RECOMBINANTEMENTE PRODUZìVEL EM UMA CéLULA DE MAMìFERO". A presente invenção provê métodos para identificar, selecionar e obter células de mamíferos que sejam capazes de produzir moléculas proteináceas que compreendem modificações pós-translacionais predeterminadas, em que referidas modificações pós-translacionais são realizadas pela célula de mamífero em que a molécula proteinácea é expressa. Preferivelmente, referidas modificações pós-translacionais prederminadas compreendem glicosilação. A invenção ainda provê métodos para se obter e produzir moléculas proteináceas com o uso de células de mamíferos obteníveis por um método da presente invenção. Preferivelmente, referidas moléculas proteináceas compreendem eritropoietina (EPO), uma vez que o efeito da EPO (recombinante) depende intensamente do padrão de glicosilação dos oligossacarídeos presentes na proteína. As células de mamíferos que foram obtidas à base de sua capacidade de produzir proteínas e/ou modificações pós-translacionais, que são indicativos para uma modificação pós-translacional predeterminada, o que é desejável, são também providas. Preferivelmente, referidas células de mamíferos possuem características neurais e propriedades tais, que quantidades significativas de proteinas recombinantes podem ser produzidas, as quais abriguem propriedades do tipo <39>neural ou cerebral<39>.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/NL2001/000792 WO2003050286A1 (en) | 2001-10-29 | 2001-10-29 | Methods and means for producing proteins with predetermined post-translational modifications |
| PCT/NL2002/000257 WO2003089468A1 (en) | 2002-04-19 | 2002-04-19 | Methods and means for producing proteins with predetermined post-translational modifications |
| PCT/NL2002/000686 WO2003038100A1 (en) | 2001-10-29 | 2002-10-29 | Methods and means for producing proteins with predetermined post-translational modifications |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR0213402A true BR0213402A (pt) | 2004-10-13 |
Family
ID=26642018
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR0213402-0A BR0213402A (pt) | 2001-10-29 | 2002-10-29 | Métodos para identificar uma célula de mamìfero capaz de produzir uma molécula proteinácea, para selecionar uma célula de mamìfero capaz de produzir uma molécula proteinácea, para se obter uma célula de mamìfero a partir de uma população heterogênea de células, e para produzir uma molécula proteinácea, composição farmaceuticamente aceitável, eritropoietina recombinantemente produzida, usos de uma célula de mamìfero, da eritropoietina recombinantemente produzida, e de uma composição de moléculas semelhantes à eritropoietina, preparação farmacêutica, método para o tratamento preventivo e/ou terapêutico de um distúrbio, composição de moléculas semelhates à eritropoietina, métodos para produzir, em uma célula de mamìfero, moléculas proteináceas, para produzir uma fração enriquecida em uma molécula proteinácea, e para fracionar uma mistura que contém moléculas proteináceas, fração, e, usos de uma fração ou composição, e de eritropoietina recombinantemente produzìvel em uma célula de mamìfero |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US7304031B2 (pt) |
| EP (2) | EP2292770B1 (pt) |
| JP (1) | JP4583029B2 (pt) |
| CN (1) | CN100347306C (pt) |
| AT (1) | ATE542904T1 (pt) |
| AU (1) | AU2002335585B2 (pt) |
| BR (1) | BR0213402A (pt) |
| CA (2) | CA2756610C (pt) |
| DK (1) | DK1440157T3 (pt) |
| EA (2) | EA012340B1 (pt) |
| ES (1) | ES2381104T3 (pt) |
| IL (3) | IL161674A (pt) |
| NO (1) | NO20042209L (pt) |
| WO (1) | WO2003038100A1 (pt) |
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| EA201791275A1 (ru) | 2014-12-10 | 2017-12-29 | Опко Байолоджикс Лтд. | Способы получения ctp-модифицированных полипептидов длительного действия |
| IL301728A (en) | 2015-06-19 | 2023-05-01 | Opko Biologics Ltd | Long-term coagulation factors and methods for their preparation |
| HUE064463T2 (hu) | 2016-07-11 | 2024-03-28 | Opko Biologics Ltd | Hosszantartó hatású VII. koagulációs faktor és az elõállítására vonatkozó eljárások |
| CN109415426B (zh) * | 2016-07-12 | 2022-03-11 | 赫克萨尔股份公司 | 具有降低的唾液酸残基的乙酰化率的糖蛋白 |
| WO2018182529A1 (en) * | 2017-03-29 | 2018-10-04 | Agency For Science, Technology And Research | Anti oligosaccharide antibody |
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| CN111514279B (zh) * | 2020-06-16 | 2023-07-18 | 温州医科大学附属第二医院（温州医科大学附属育英儿童医院） | 神经营养因子3在制备治疗男性性腺功能减退症的药物中的应用 |
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| AU646822B2 (en) | 1989-10-13 | 1994-03-10 | Kirin-Amgen Inc. | Erythropoietin isoforms |
| US5789247A (en) * | 1994-04-01 | 1998-08-04 | Ballay; Annick | Expression in non-tumoral human lymphoblastoid lines with an integrative vector |
| US6783980B2 (en) * | 1995-06-15 | 2004-08-31 | Crucell Holland B.V. | Packaging systems for human recombinant adenovirus to be used in gene therapy |
| KR100470180B1 (ko) | 1995-06-15 | 2005-02-04 | 크루셀 홀란드 비.브이. | 유전자 요법에 사용할 수 있는 인간의 재조합아데노바이러스 패키징 시스템 |
| WO1998044141A2 (en) * | 1997-03-27 | 1998-10-08 | The University Of British Columbia | Insect expression vectors |
| CA2221819A1 (en) | 1997-03-27 | 1998-09-27 | Thomas A. Gigliatti | Insect expression vectors |
| US6929946B1 (en) * | 1998-11-20 | 2005-08-16 | Crucell Holland B.V. | Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells |
| CA2383940A1 (en) | 1999-04-13 | 2000-10-19 | The Kenneth S. Warren Laboratories, Inc. | Modulation of excitable tissue function by peripherally administered erythropoietin |
| CN100457914C (zh) * | 1999-04-15 | 2009-02-04 | 荷兰克鲁塞尔公司 | 用编码腺病毒e1蛋白的序列在人体细胞中生产重组蛋白 |
| US7297680B2 (en) * | 1999-04-15 | 2007-11-20 | Crucell Holland B.V. | Compositions of erythropoietin isoforms comprising Lewis-X structures and high sialic acid content |
| US20050164386A1 (en) * | 1999-04-15 | 2005-07-28 | Uytdehaag Alphonsus G. | Overexpression of enzymes involved in post-translational protein modifications in human cells |
| US6855544B1 (en) * | 1999-04-15 | 2005-02-15 | Crucell Holland B.V. | Recombinant protein production in a human cell |
| US6913922B1 (en) * | 1999-05-18 | 2005-07-05 | Crucell Holland B.V. | Serotype of adenovirus and uses thereof |
| FI109811B (fi) * | 2000-09-26 | 2002-10-15 | Medicel Oy | Menetelmä GDP-L-fukoosin valmistamiseksi ja menetelmässä käytettäviä välineitä |
| DE10056136A1 (de) | 2000-11-07 | 2002-05-16 | Nemod New Modalities | Verwendung von Schwangerschaftsproteinen, Liposomen, nativen Muzin-Fragmenten und Mimikry-Verbindungen zur Behandlung und Prophylaxe von entzündlichen Erkrankungen, zur Verhinderung der Metastasierung und zur Prophylaxe von Tumorerkrankungen |
| US7473767B2 (en) | 2001-07-03 | 2009-01-06 | The Institute For Systems Biology | Methods for detection and quantification of analytes in complex mixtures |
| EP2042196B1 (en) * | 2001-10-10 | 2016-07-13 | ratiopharm GmbH | Remodelling and glycoconjugation of Granulocyte Colony Stimulating Factor (G-CSF) |
| CN100347306C (zh) * | 2001-10-29 | 2007-11-07 | 克鲁塞尔荷兰公司 | 生产具有预定的翻译后修饰的蛋白质的方法和手段 |
| EP2314629B2 (en) * | 2002-07-18 | 2022-11-16 | Merus N.V. | Recombinant production of mixtures of antibodies |
| WO2005090390A1 (en) * | 2004-03-17 | 2005-09-29 | Crucell Holland B.V. | Novel assay for the separation and quantification of hemagglutinin antigens |
| US7183371B2 (en) * | 2004-11-01 | 2007-02-27 | General Electric Company | Method for making polycarbonate |
| US20080139608A1 (en) * | 2006-12-06 | 2008-06-12 | Universiteit Leiden | 2,6,8, Trisubstituted 1-deazapurines and their different uses |
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- 2002-10-29 JP JP2003540365A patent/JP4583029B2/ja not_active Expired - Fee Related
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| EP2292770A3 (en) | 2012-12-19 |
| IL201674A (en) | 2013-10-31 |
| US7785833B2 (en) | 2010-08-31 |
| EP2292770B1 (en) | 2014-11-26 |
| US7696157B2 (en) | 2010-04-13 |
| US20050164917A1 (en) | 2005-07-28 |
| CA2756610C (en) | 2015-08-25 |
| EP1440157B1 (en) | 2012-01-25 |
| EA008220B1 (ru) | 2007-04-27 |
| ES2381104T3 (es) | 2012-05-23 |
| EA200400605A1 (ru) | 2004-08-26 |
| EP2292770A2 (en) | 2011-03-09 |
| CN100347306C (zh) | 2007-11-07 |
| CA2465007A1 (en) | 2003-05-08 |
| US7304031B2 (en) | 2007-12-04 |
| CN1578838A (zh) | 2005-02-09 |
| EA012340B1 (ru) | 2009-10-30 |
| CA2756610A1 (en) | 2003-05-08 |
| DK1440157T3 (da) | 2012-05-07 |
| JP2005507426A (ja) | 2005-03-17 |
| US20080032922A1 (en) | 2008-02-07 |
| EA200602163A1 (ru) | 2007-04-27 |
| US20070117742A1 (en) | 2007-05-24 |
| IL201673A (en) | 2013-10-31 |
| NO20042209L (no) | 2004-07-28 |
| AU2002335585B2 (en) | 2007-08-16 |
| IL161674A (en) | 2014-06-30 |
| CA2465007C (en) | 2012-01-17 |
| JP4583029B2 (ja) | 2010-11-17 |
| WO2003038100A1 (en) | 2003-05-08 |
| EP1440157A1 (en) | 2004-07-28 |
| ATE542904T1 (de) | 2012-02-15 |
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