CA2370477C - Recombinant protein production in a human cell using sequences encoding adenovirus e1 protein - Google Patents
Recombinant protein production in a human cell using sequences encoding adenovirus e1 protein Download PDFInfo
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- CA2370477C CA2370477C CA2370477A CA2370477A CA2370477C CA 2370477 C CA2370477 C CA 2370477C CA 2370477 A CA2370477 A CA 2370477A CA 2370477 A CA2370477 A CA 2370477A CA 2370477 C CA2370477 C CA 2370477C
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- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (5)
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| EP99201176 | 1999-04-15 | ||
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| EP99204434.7 | 1999-12-21 | ||
| EP99201176.7 | 1999-12-21 | ||
| PCT/NL2000/000247 WO2000063403A2 (en) | 1999-04-15 | 2000-04-17 | Recombinant protein production in a human cell using sequences encoding adenovirus e1 protein |
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| CA2370477A1 CA2370477A1 (en) | 2000-10-26 |
| CA2370477C true CA2370477C (en) | 2010-06-29 |
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| SI (2) | SI1533380T1 (enExample) |
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Families Citing this family (117)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003089468A1 (en) * | 2002-04-19 | 2003-10-30 | Crucell Holland B.V. | Methods and means for producing proteins with predetermined post-translational modifications |
| WO2003050286A1 (en) * | 2001-10-29 | 2003-06-19 | Crucell Holland B.V. | Methods and means for producing proteins with predetermined post-translational modifications |
| US8236561B2 (en) | 1999-04-15 | 2012-08-07 | Crucell Holland B.V. | Efficient production of IgA in recombinant mammalian cells |
| WO2003048197A1 (en) * | 2001-12-07 | 2003-06-12 | Crucell Holland B.V. | Production and of viruses, viral isolates and vaccines |
| 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 |
| US6855544B1 (en) | 1999-04-15 | 2005-02-15 | Crucell Holland B.V. | Recombinant protein production in a human cell |
| US7604960B2 (en) | 1999-04-15 | 2009-10-20 | Crucell Holland B.V. | Transient protein expression methods |
| US7527961B2 (en) | 1999-11-26 | 2009-05-05 | Crucell Holland B.V. | Production of vaccines |
| US7425437B2 (en) * | 1999-11-26 | 2008-09-16 | Crucell Holland B.V. | Vaccines against West Nile Virus |
| US7521220B2 (en) * | 1999-11-26 | 2009-04-21 | Crucell Holland B.V. | Production of vaccines |
| US7192759B1 (en) | 1999-11-26 | 2007-03-20 | Crucell Holland B.V. | Production of vaccines |
| EP1256803A1 (en) | 2001-05-07 | 2002-11-13 | Crucell Holland B.V. | Methods for the identification of antiviral compounds |
| 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 |
| CN100547069C (zh) * | 2001-12-07 | 2009-10-07 | 克鲁塞尔荷兰公司 | 病毒、病毒分离物和疫苗的生产 |
| US20050048038A1 (en) * | 2001-12-17 | 2005-03-03 | Jones David Halford Ashton | Efficient production of f(ab')2 fragments in mammalian cells |
| KR100454016B1 (ko) * | 2002-01-05 | 2004-10-26 | 한국과학기술원 | 항예정사 유전자로 형질전환되고 ｄｈｆｒ 유전자가결핍된 신규한 ｃｈｏ 세포주, 그의 제조 방법 및 상기형질전환된 ｃｈｏ 숙주 세포를 이용한 목적단백질의 생산방법 |
| ATE359087T1 (de) * | 2002-01-09 | 2007-05-15 | Crucell Holland Bv | Verwendung von erythropoietin zur behandlung oder vorbeugung von herzversagen |
| CN100522999C (zh) | 2002-02-14 | 2009-08-05 | 免疫医疗公司 | 抗cd20抗体及其融合蛋白和使用方法 |
| US8287864B2 (en) | 2002-02-14 | 2012-10-16 | Immunomedics, Inc. | Structural variants of antibodies for improved therapeutic characteristics |
| EP1483294B2 (en) | 2002-03-01 | 2019-10-30 | Immunomedics, Inc. | Internalizing anti-cd74 antibodies and methods of use |
| MXPA04012656A (es) | 2002-06-14 | 2005-08-15 | Immunomedics Inc | Anticuerpo hpam4 monoclonal humanizado. |
| SI1523496T1 (sl) | 2002-07-18 | 2011-11-30 | Merus B V | Rekombinantno proizvajanje zmesi protiteles |
| USRE47770E1 (en) | 2002-07-18 | 2019-12-17 | Merus N.V. | Recombinant production of mixtures of antibodies |
| EP1546203B1 (en) | 2002-08-01 | 2012-06-20 | Immunomedics, Inc. | Alpha-fetoprotein immu31 antibodies and fusion proteins and methods of use thereof |
| US7541440B2 (en) | 2002-09-30 | 2009-06-02 | Immunomedics, Inc. | Chimeric, human and humanized anti-granulocyte antibodies and methods of use |
| US8524477B2 (en) | 2002-10-29 | 2013-09-03 | Crucell Holland B.V. | Methods to obtain recombinant proteins with increased sialylation from cells that express adenovirus E1A protein, and proteins obtained thereby |
| US7534427B2 (en) | 2002-12-31 | 2009-05-19 | Immunomedics, Inc. | Immunotherapy of B cell malignancies and autoimmune diseases using unconjugated antibodies and conjugated antibodies and antibody combinations and fusion proteins |
| CA2520891C (en) | 2003-05-09 | 2014-07-08 | Crucell Holland B.V. | Cultures of e1-immortalized cells and processes for culturing the same to increase product yields therefrom |
| AU2004240782B2 (en) * | 2003-05-23 | 2011-04-21 | Crucell Holland B.V. | Production of recombinant IGM in per.C6 cells |
| EP2395017A3 (en) | 2003-05-30 | 2012-12-19 | Merus B.V. | Design and use of paired variable regions of specific binding molecules |
| US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
| NZ543635A (en) | 2003-06-25 | 2008-05-30 | Crucell Holland Bv | Human C-type lectin: a suitable target molecule for binding molecules, particularly immunoconjugates, in the diagnosis, prevention and/or treatment of myeloid neoplastic diseases such as AML and CML |
| US7109304B2 (en) | 2003-07-31 | 2006-09-19 | Immunomedics, Inc. | Humanized anti-CD19 antibodies |
| EP1508576A1 (en) * | 2003-08-20 | 2005-02-23 | Crucell Holland B.V. | Efficient production of IgA in recombinant mammalian cells |
| CN1863918B (zh) | 2003-10-02 | 2011-03-30 | 克鲁塞尔荷兰公司 | 用于重组腺病毒的包装细胞 |
| WO2005059149A2 (en) * | 2003-12-12 | 2005-06-30 | Chromagenics B.V. | Improved protein production |
| DK1737971T3 (da) | 2004-01-20 | 2017-11-13 | Merus Nv | Blandinger af bindingsproteiner |
| PL1720972T3 (pl) * | 2004-03-05 | 2014-06-30 | Dpx Holdings Bv | Proces hodowli komórek poprzez ciągłą perfuzję i zmienny przepływ styczny |
| CN102139106B (zh) | 2004-05-27 | 2014-10-08 | 克鲁塞尔荷兰公司 | 能中和狂犬病病毒的结合分子及其应用 |
| JP4852046B2 (ja) | 2004-10-12 | 2012-01-11 | クルセル ホランド ベー ヴェー | 癌の治療及び検出に用いる結合分子 |
| AU2005300503B2 (en) | 2004-11-08 | 2010-12-16 | Chromagenics B.V. | Selection of host cells expressing protein at high levels |
| ATE550037T1 (de) | 2004-11-11 | 2012-04-15 | Crucell Holland Bv | Zusammensetzungen gegen das sars-coronavirus und ihre verwendungen |
| CA2591665C (en) | 2004-12-20 | 2015-05-05 | Crucell Holland B.V. | Binding molecules capable of neutralizing west nile virus and uses thereof |
| US8349332B2 (en) | 2005-04-06 | 2013-01-08 | Ibc Pharmaceuticals, Inc. | Multiple signaling pathways induced by hexavalent, monospecific and bispecific antibodies for enhanced toxicity to B-cell lymphomas and other diseases |
| US8475794B2 (en) | 2005-04-06 | 2013-07-02 | Ibc Pharmaceuticals, Inc. | Combination therapy with anti-CD74 antibodies provides enhanced toxicity to malignancies, Autoimmune disease and other diseases |
| WO2006120230A2 (en) | 2005-05-12 | 2006-11-16 | Crucell Holland B.V. | Host cell specific binding molecules capable of neutralizing viruses and uses thereof |
| EP1739179A1 (en) | 2005-06-30 | 2007-01-03 | Octapharma AG | Serum-free stable transfection and production of recombinant human proteins in human cell lines |
| US20080286819A1 (en) * | 2005-11-07 | 2008-11-20 | Ravetch Jeffrey V | Reagents, Methods and Systems for Selecting a Cytotoxic Antibody or Variant Thereof |
| US20080206246A1 (en) * | 2006-04-05 | 2008-08-28 | Ravetch Jeffrey V | Polypeptides with enhanced anti-inflammatory and decreased cytotoxic properties and relating methods |
| US8470318B2 (en) | 2005-11-07 | 2013-06-25 | The Rockefeller University | Polypeptides with enhanced anti-inflammatory and decreased cytotoxic properties and relating methods |
| AR053416A1 (es) | 2005-11-10 | 2007-05-09 | Protech Pharma S A | Combinacion de glicoisoformas para el tratamiento o prevencion de la septicemia, linea celular transgenica productora de glicoformas de eritropoyetina, composicion farmaceutica que comprende a dicha combinacion, procedimientos para obtener la linea celular, procedimiento para producir dicha combinac |
| DE102005054628A1 (de) | 2005-11-16 | 2007-05-24 | Cevec Pharmaceuticals Gmbh | Verfahren zur Herstellung von permanenten humanen Zelllinien |
| US7642078B2 (en) | 2005-12-28 | 2010-01-05 | Crucell Holland B.V. | Methods to obtain recombinant proteins with increased sialylation from cells that express adenovirus E1A protein, and proteins obtained thereby |
| WO2007107578A1 (en) | 2006-03-20 | 2007-09-27 | Chromagenics B.V. | Expression augmenting dna fragments, use thereof, and methods for finding thereof |
| MX2008012843A (es) * | 2006-04-05 | 2009-01-19 | Univ Rockefeller | Polipeptidos con propiedades antiinflamatorias aumentadas y citotoxicas reducidas y metodos relacionados. |
| EP3018142A1 (en) | 2006-06-06 | 2016-05-11 | Crucell Holland B.V. | Human binding molecules having killing activity against staphylococci and uses thereof |
| JP5586952B2 (ja) | 2006-06-06 | 2014-09-10 | クルセル ホランド ベー ヴェー | 腸球菌に対する殺活性を有するヒトの結合分子及びその使用方法 |
| AU2007272054C1 (en) | 2006-07-14 | 2014-08-28 | Dpx Holdings B.V. | Improved process for the culturing of cells |
| MY170607A (en) | 2006-09-07 | 2019-08-20 | Crucell Holland Bv | Human binding molecules capable of neutralizing influenza virus h5n1 and uses thereof |
| PT2059532E (pt) | 2006-09-07 | 2013-03-07 | Crucell Holland Bv | Moléculas de ligação humanas capazes de neutralizar o vírus da gripe h5n1 e seus usos |
| AU2007317755A1 (en) * | 2006-10-27 | 2008-05-15 | The Rockefeller University | Polypeptides with enhanced anti-inflammatory and decreased cytotoxic properties and relating methods |
| JP2010512306A (ja) * | 2006-10-27 | 2010-04-22 | ザ ロックフェラー ユニバーシティー | 抗炎症特性が増強され、細胞毒性特性が減少したポリペプチドおよび関連する方法 |
| US8071332B2 (en) | 2007-08-10 | 2011-12-06 | Toto Ltd. | Recombinant mammal cells, method of producing thereof, and method of producing proteins of interest |
| WO2009074318A2 (en) * | 2007-12-13 | 2009-06-18 | Roche Diagnostics Gmbh | Novel rubella e1 envelope protein variants and their use in the detection of anti-rubella antibodies |
| US20120039939A1 (en) * | 2008-04-11 | 2012-02-16 | The Johns Hopkins University | Compositions and methods for vaccine and virus production |
| EP2279410B1 (en) | 2008-04-22 | 2015-11-11 | The Rockefeller University | Methods of identifying anti-inflammatory compounds |
| DK2307538T3 (da) * | 2008-07-15 | 2016-01-18 | Crucell Holland Bv | Skalérbar fremgangsmåde til dyrkning af per.c6-celler og fremstilling af produkter derfra |
| MX2011000891A (es) | 2008-07-21 | 2011-06-01 | Immunomedics Inc | Variantes estructurales de anticuerpos para caracteristicas terapeuticas mejoradas. |
| WO2010127939A1 (en) | 2009-04-23 | 2010-11-11 | Crucell Holland B.V. | Recombinant human alpha1-antitrypsin |
| US8470327B2 (en) | 2009-05-11 | 2013-06-25 | Crucell Holland B.V. | Human binding molecules capable of neutralizing influenza virus H3N2 and uses thereof |
| US20120270264A1 (en) | 2009-10-01 | 2012-10-25 | Toto Ltd. | Dna construct, and process for production of recombinant cho cell using same |
| DK2505654T4 (da) | 2010-02-08 | 2020-07-27 | Regeneron Pharma | Mus med fælles letkæde |
| US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
| US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
| US8961978B2 (en) | 2011-07-14 | 2015-02-24 | Crucell Holland B.V. | Human binding molecules capable of neutralizing influenza A viruses of phylogenetic group 1 and phylogenetic group 2 and influenza B viruses |
| MY172718A (en) | 2011-08-05 | 2019-12-11 | Regeneron Pharma | Humanized universal light chain mice |
| WO2013093760A2 (en) | 2011-12-19 | 2013-06-27 | Grifols, S.A. | Compositions, methods, and kits for preparing sialylated recombinant proteins |
| CN102827273A (zh) * | 2012-02-16 | 2012-12-19 | 张小莺 | 抗痘苗病毒IgY抗体的制备 |
| ES2664625T3 (es) | 2012-03-08 | 2018-04-20 | Janssen Vaccines & Prevention B.V. | Moléculas de unión humanas que pueden unirse a los virus de la influenza b y neutralizarlos, y sus usos |
| CA2870821C (en) | 2012-04-20 | 2022-06-14 | Merus B.V. | Methods and means for the production of ig-like molecules |
| US9657290B2 (en) | 2012-07-03 | 2017-05-23 | The Board Of Trustees Of The Leland Stanford Junior University | Scalable bio-element analysis |
| WO2014006217A1 (en) | 2012-07-06 | 2014-01-09 | Genmab B.V. | Dimeric protein with triple mutations |
| WO2014048910A1 (en) | 2012-09-27 | 2014-04-03 | Crucell Holland B.V. | Human binding molecules capable of binding to and neutralizing hepatitis b viruses and uses thereof |
| LT2900694T (lt) | 2012-09-27 | 2018-11-12 | Merus N.V. | Bispecifiniai igg antikūnai kaip t ląstelių aktyvatoriai |
| EA035846B1 (ru) | 2013-04-15 | 2020-08-20 | Янссен Вэксинс Энд Превеншн Б.В. | Антитела человека, связывающиеся с g-белком rsv |
| CN105189547B (zh) | 2013-04-15 | 2020-01-17 | 扬森疫苗与预防公司 | 结合到rsv g蛋白的人类抗体 |
| DE112014003136A5 (de) | 2013-07-01 | 2016-04-21 | Charité - Universitätsmedizin Berlin | Immortalisierte humane Chorionzelllinie sowie Verfahren zur Immortalisierung humaner Chorionzellen |
| CN104693308B (zh) * | 2013-12-05 | 2020-08-04 | 同济大学 | 感受胞内pH变化的Smad5蛋白及其应用 |
| EP2883883A1 (en) | 2013-12-16 | 2015-06-17 | Cardio3 Biosciences S.A. | Therapeutic targets and agents useful in treating ischemia reperfusion injury |
| WO2015130172A1 (en) | 2014-02-28 | 2015-09-03 | Merus B.V. | Antibodies that bind egfr and erbb3 |
| JP6967853B2 (ja) | 2014-02-28 | 2021-11-17 | メルス ナムローゼ フェンノートシャップ | ＥｒｂＢ−２およびＥｒｂＢ−３に結合する抗体 |
| BR112016021572A2 (pt) | 2014-03-21 | 2017-10-03 | Regeneron Pharma | Métodos para preparar um animal não humano geneticamente modificado e para produzir proteínas de ligação, hibridoma, ácido nucleico, célula, e, proteína de ligação |
| TWI743024B (zh) | 2014-06-06 | 2021-10-21 | 美商健臻公司 | 灌注培養方法及其用途 |
| CA2975655C (en) | 2015-02-05 | 2023-09-19 | Janssen Vaccines & Prevention B.V. | Binding molecules directed against influenza hemagglutinin and uses thereof |
| WO2016124682A1 (en) | 2015-02-05 | 2016-08-11 | Janssen Vaccines & Prevention B.V. | Human neutralizing antibodies binding to influenza neuraminidase |
| US10370653B2 (en) | 2015-02-22 | 2019-08-06 | The Board Of Trustees Of The Leland Stanford Junior University | Micro-screening apparatus, process, and products |
| CA2979702A1 (en) | 2015-03-19 | 2016-09-22 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
| PL3115376T3 (pl) | 2015-07-10 | 2019-01-31 | Merus N.V. | Ludzkie przeciwciało wiążące cd3 |
| SG11201803359VA (en) | 2015-10-23 | 2018-05-30 | Merus Nv | Binding molecules that inhibit cancer growth |
| WO2017148889A1 (en) | 2016-03-01 | 2017-09-08 | Janssen Vaccines & Prevention B.V. | Human neutralizing antibodies binding to influenza b neuraminidase |
| CN115254210A (zh) | 2016-11-14 | 2022-11-01 | 浩康生物系统公司 | 用于分选目标颗粒的方法和装置 |
| SG11201907927SA (en) | 2017-03-28 | 2019-10-30 | Janssen Vaccines & Prevention Bv | Binding molecules that specifically bind to tau |
| US11780925B2 (en) | 2017-03-31 | 2023-10-10 | Merus N.V. | ErbB-2 and ErbB3 binding bispecific antibodies for use in the treatment of cells that have an NRG1 fusion gene |
| WO2018192974A1 (en) | 2017-04-18 | 2018-10-25 | Université Libre de Bruxelles | Biomarkers and targets for proliferative diseases |
| BR112019024230A2 (pt) | 2017-05-17 | 2020-06-09 | Merus N.V. | combinação de um anticorpo bispecífico erbb-2 / erbb-3 com terapia endócrina para câncer de mama |
| SG11202001050PA (en) | 2017-08-09 | 2020-03-30 | Merus Nv | Antibodies that bind egfr and cmet |
| TW201930351A (zh) | 2017-10-06 | 2019-08-01 | 日商小野藥品工業股份有限公司 | 雙特異性抗體 |
| EA202091350A1 (ru) | 2017-12-04 | 2020-09-02 | Янссен Вэксинс Энд Превеншн Б.В. | Связывающие молекулы, специфично связывающиеся с тау-белком |
| WO2019149798A1 (en) | 2018-02-01 | 2019-08-08 | Janssen Vaccines & Prevention B.V. | Binding molecules that specifically bind to tau |
| TWI849895B (zh) | 2018-02-09 | 2024-07-21 | 日商小野藥品工業股份有限公司 | 雙特異性抗體 |
| EP3768701B1 (en) | 2018-03-23 | 2023-08-02 | Université Libre de Bruxelles | Wnt signaling agonist molecules |
| TW202509079A (zh) | 2019-04-04 | 2025-03-01 | 日商小野藥品工業股份有限公司 | 雙特異性抗體 |
| TWI809286B (zh) | 2019-07-05 | 2023-07-21 | 日商小野藥品工業股份有限公司 | 以pd-1/cd3雙特異性蛋白質所進行之血液性癌症治療 |
| TW202118790A (zh) | 2019-07-30 | 2021-05-16 | 日商小野藥品工業股份有限公司 | 雙特異性抗體 |
| US20220332825A1 (en) | 2019-08-08 | 2022-10-20 | Ono Pharmaceutical Co., Ltd. | Bispecific protein |
| AU2022288080A1 (en) * | 2021-06-11 | 2023-12-07 | Monsanto Technology Llc | Methods and compositions for altering protein accumulation |
| EP4578876A1 (en) | 2022-08-23 | 2025-07-02 | ONO Pharmaceutical Co., Ltd. | Bispecific antibody |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2573436B1 (fr) * | 1984-11-20 | 1989-02-17 | Pasteur Institut | Adn recombinant comportant une sequence nucleotidique codant pour un polypeptide determine sous le controle d'un promoteur d'adenovirus, vecteurs contenant cet adn recombinant, cellules eucaryotes transformees par cet adn recombinant, produits d'excretion de ces cellules transformees et leurs applications, notamment a la constitution de vaccins |
| US4892737A (en) * | 1988-09-22 | 1990-01-09 | University Of Florida | Composition and method for enhancing permeability of topical drugs |
| GB8900483D0 (en) * | 1989-01-10 | 1989-03-08 | Celltech Ltd | Recombinant dna method |
| ATE150486T1 (de) * | 1991-08-01 | 1997-04-15 | Fond Nat Transfusion Sanguine | Expression in nicht-tumorbildenden menschlichen lymphoblasten zellinien mit einem integrierenden vektor |
| FI951138L (fi) * | 1993-07-13 | 1995-04-13 | Rhone Poulenc Rorer Sa | Puuttellisia adenovirusvektoreita ja niiden käyttö geeniterapiassa |
| US5610043A (en) * | 1994-04-28 | 1997-03-11 | The United States Of America As Represented By The Department Of Health And Human Services | Human prostatic cell lines immortalized by adenovirus 12-simian virus 40 (AD12/SV40) hybrid virus |
| DE69638058D1 (de) * | 1995-06-15 | 2009-11-26 | Crucell Holland Bv | Verpackungssysteme für humane rekombinante Adenoviren zur Gentherapie |
-
2000
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- 2000-04-17 EP EP00921175A patent/EP1161548B2/en not_active Expired - Lifetime
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- 2000-04-17 DK DK09174441.7T patent/DK2163640T3/da active
- 2000-04-17 NZ NZ514951A patent/NZ514951A/xx not_active IP Right Cessation
- 2000-04-17 SI SI200030662T patent/SI1161548T2/sl unknown
- 2000-04-17 ES ES09174441T patent/ES2378272T3/es not_active Expired - Lifetime
- 2000-04-17 AT AT00921175T patent/ATE289354T1/de active
- 2000-04-17 MX MXPA01010360A patent/MXPA01010360A/es active IP Right Grant
- 2000-04-17 JP JP2000612481A patent/JP4210036B2/ja not_active Expired - Lifetime
- 2000-04-17 DK DK00921175.6T patent/DK1161548T4/da active
- 2000-04-17 PT PT05100732T patent/PT1533380E/pt unknown
- 2000-04-17 AT AT09174441T patent/ATE536417T1/de active
- 2000-04-17 DE DE60043273T patent/DE60043273D1/de not_active Expired - Lifetime
- 2000-04-17 AT AT05100732T patent/ATE447617T1/de active
- 2000-04-17 PT PT00921175T patent/PT1161548E/pt unknown
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2001
- 2001-10-10 IL IL145849A patent/IL145849A/en not_active IP Right Cessation
- 2001-10-12 NO NO20014977A patent/NO328951B1/no not_active IP Right Cessation
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2010
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