ZA200409694B - Novel tissue factor targeted thrombomodulin fusionproteins as anticoagulants. - Google Patents
Novel tissue factor targeted thrombomodulin fusionproteins as anticoagulants. Download PDFInfo
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- ZA200409694B ZA200409694B ZA200409694A ZA200409694A ZA200409694B ZA 200409694 B ZA200409694 B ZA 200409694B ZA 200409694 A ZA200409694 A ZA 200409694A ZA 200409694 A ZA200409694 A ZA 200409694A ZA 200409694 B ZA200409694 B ZA 200409694B
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| EP2325316B8 (en) | 1999-06-02 | 2017-04-19 | Chugai Seiyaku Kabushiki Kaisha | Novel hemopoietin receptor protein, NR10 |
| EP1221482B1 (en) * | 1999-09-27 | 2005-12-28 | Chugai Seiyaku Kabushiki Kaisha | Hemopoietin receptor protein, nr12 |
| CA2425208C (en) | 2000-09-26 | 2013-04-09 | Duke University | Rna aptamers and methods for identifying the same |
| AU2003225256B2 (en) * | 2002-05-01 | 2009-06-04 | Bayer Schering Pharma Aktiengesellschaft | Novel tissue factor targeted thrombomodulin fusion proteins as anticoagulants |
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| AU2003256299A1 (en) | 2002-07-01 | 2004-01-19 | Human Genome Sciences, Inc. | Antibodies that specifically bind to reg iv |
| US7425328B2 (en) | 2003-04-22 | 2008-09-16 | Purdue Pharma L.P. | Tissue factor antibodies and uses thereof |
| US7833978B2 (en) * | 2004-02-20 | 2010-11-16 | Emory University | Thrombomodulin derivatives and conjugates |
| SG152262A1 (en) | 2004-04-22 | 2009-05-29 | Regado Biosciences Inc | Improved modulators of coagulation factors |
| CN101189334B (zh) | 2005-06-03 | 2013-11-06 | 持田制药株式会社 | 抗cd14抗体融合蛋白质 |
| US20090130104A1 (en) * | 2005-10-05 | 2009-05-21 | The Trustees Of The University Of Pennsylvania | Fusion proteins for inhibition and dissolution of coagulation |
| ES2353084T3 (es) * | 2006-04-07 | 2011-02-25 | Novo Nordisk Health Care Ag | Complejo covalente de factor vii y factor tisular. |
| PE20080333A1 (es) | 2006-06-08 | 2008-06-15 | Chugai Pharmaceutical Co Ltd | Agentes para prevenir o tratar enfermedades inflamatorias |
| JP5579385B2 (ja) * | 2006-10-06 | 2014-08-27 | 旭化成ファーマ株式会社 | 播種性血管内血液凝固症候群の治療及び／又は改善剤 |
| US9649499B2 (en) * | 2007-03-28 | 2017-05-16 | Medtronic ATS Medical, Inc. | Method for inhibiting platelet interaction with biomaterial surfaces |
| EP2195343A2 (en) * | 2007-09-20 | 2010-06-16 | Bracco Imaging S.p.A | Method for the preparation of new oligoclonal antibodies |
| RU2596397C2 (ru) | 2007-12-05 | 2016-09-10 | Чугаи Сейяку Кабусики Кайся | Терапевтическое средство от зуда |
| US8333973B2 (en) * | 2008-01-02 | 2012-12-18 | The Trustees Of The University Of Pennsylvania | Targeting recombinant therapeutics to circulating red blood cells |
| UA112050C2 (uk) * | 2008-08-04 | 2016-07-25 | БАЄР ХЕЛСКЕР ЛЛСі | Терапевтична композиція, що містить моноклональне антитіло проти інгібітора шляху тканинного фактора (tfpi) |
| US20110144311A1 (en) * | 2008-08-14 | 2011-06-16 | Rebecca Chmielowski | Methods for purifying antibodies using protein a affinity chromatography |
| WO2010045518A1 (en) * | 2008-10-16 | 2010-04-22 | The Trustees Of The University Of Pennsylvania | Compositions containing thrombomodulin domains and uses thereof |
| US20120165244A1 (en) * | 2008-10-30 | 2012-06-28 | Hua-Lin Wu | Methods for binding lewis y antigen |
| UA109633C2 (uk) | 2008-12-09 | 2015-09-25 | Антитіло людини проти тканинного фактора | |
| EP2230251A1 (en) * | 2009-03-19 | 2010-09-22 | Bracco Imaging S.p.A | Antibodies specifically active in the coronary plaque and method for their identification |
| CA2771328A1 (en) * | 2009-08-28 | 2011-03-03 | Bayer Healthcare Llc | Cofactors for thrombin activation of factor vii and uses thereof |
| GB201007356D0 (en) | 2010-04-30 | 2010-06-16 | Leverton Licence Holdings Ltd | Conjugated factor VIIa |
| US9644197B2 (en) | 2010-06-04 | 2017-05-09 | Sk Chemicals Co., Ltd. | Fusion protein having factor VII activity |
| ES2647388T3 (es) | 2010-06-15 | 2017-12-21 | Genmab A/S | Conjugados farmacológicos de anticuerpos humanos contra factor tisular |
| BR112013002739A2 (pt) * | 2010-08-05 | 2019-09-24 | Council Scient Ind Res | constructos de proteínas de fusão que possuem propriedades trombolíticas e anticoagulantes |
| RU2445365C1 (ru) * | 2010-11-03 | 2012-03-20 | Общество с ограниченной ответственностью "Инновационный Центр "Новые Технологии и Материалы" (ООО "ИЦ Новтехмат") | Штамм гибридных культивируемых клеток mus musculus - продуцент моноклональных антител, специфичных к протеину с человека (варианты) |
| RU2749512C2 (ru) | 2015-04-14 | 2021-06-11 | Чугаи Сейяку Кабусики Кайся | Фармацевтическая композиция для профилактики и/или лечения атопического дерматита, включающая антагонист ил-31 в качестве активного ингредиента |
| US10954502B2 (en) * | 2015-04-28 | 2021-03-23 | Saint Louis University | Thrombin-thrombomodulin fusion proteins as protein C activators |
| WO2017189943A1 (en) * | 2016-04-28 | 2017-11-02 | Saint Louis University | Thrombin-thrombomodulin fusion proteins as a powerful anticoagulant |
| AR110079A1 (es) * | 2016-11-16 | 2019-02-20 | Bayer Healthcare Llc | Factor viii direccionado a los glóbulos rojos y método para su uso |
| BR102017005783A2 (pt) * | 2017-03-21 | 2018-10-02 | Fund Butantan | processo de obtenção de esculptina e seus fragmentos, esculptina recombinante e seus usos |
| EP3861127A1 (en) * | 2018-10-04 | 2021-08-11 | Thrombosis and Coagulation AB | Method for the determination of protein s levels |
| CA3156713A1 (en) | 2019-11-20 | 2021-05-27 | Daisuke Kameoka | Antibody-containing preparation |
| CN114686444B (zh) * | 2020-12-31 | 2024-05-31 | 广州万孚生物技术股份有限公司 | 杂交瘤细胞、抗血栓调节蛋白单克隆抗体及其制备方法和应用 |
| CN114686443B (zh) * | 2020-12-31 | 2023-11-03 | 广州万孚生物技术股份有限公司 | 杂交瘤细胞、抗血栓调节蛋白单克隆抗体及其制备方法和应用 |
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| ZA862768B (en) * | 1985-04-17 | 1986-12-30 | Zymogenetics Inc | Expression of factor vii and ix activities in mammalian cells |
| US5589173A (en) | 1986-11-04 | 1996-12-31 | Genentech, Inc. | Method and therapeutic compositions for the treatment of myocardial infarction |
| US5437864A (en) * | 1987-03-31 | 1995-08-01 | The Scripps Research Institute | Method of inhibiting blood coagulation in extracorporeal circulation by inhibiting human tissue factor |
| US5223427A (en) * | 1987-03-31 | 1993-06-29 | The Scripps Research Institute | Hybridomas producing monoclonal antibodies reactive with human tissue-factor glycoprotein heavy chain |
| US4912207A (en) | 1987-05-06 | 1990-03-27 | Washington University | DNA clone of human thrombomodulin and portions thereof |
| DK299087D0 (da) | 1987-06-12 | 1987-06-12 | Novo Industri As | Proteins and derivatives thereof |
| US5298599A (en) * | 1988-12-30 | 1994-03-29 | Oklahoma Medical Research Foundation | Expression and purification of recombinant soluble tissue factor |
| KR920701459A (ko) * | 1989-02-17 | 1992-08-11 | 코돈 | 트롬보모듈린의 가용성 유사체 |
| US6063763A (en) | 1989-04-28 | 2000-05-16 | Schering Aktiengesellschaft | Protease-resistant thrombomodulin analogs |
| US5256770A (en) | 1990-04-09 | 1993-10-26 | Schering Ag | Oxidation resistant thrombomodulin analogs |
| US5466668A (en) | 1989-04-28 | 1995-11-14 | Schering Aktiengesellschaft | Superior thrombomodulin analogs for pharmaceutical use |
| KR930008093B1 (ko) | 1990-08-03 | 1993-08-25 | 아사히가세이고오교 가부시끼가이샤 | 신규 폴리펩티드 및 이를 유효성분으로 하는 의약조성물 |
| US5506134A (en) | 1990-10-22 | 1996-04-09 | Corvas International, Inc. | Hypridoma and monoclonal antibody which inhibits blood coagulation tissue factor/factor VIIa complex |
| US5843442A (en) * | 1990-10-22 | 1998-12-01 | Corvas International, Inc. | Blood coagulation protein antagonists and uses therefor |
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| TWI338009B (en) * | 2001-10-29 | 2011-03-01 | Genentech Inc | Antibodies for inhibiting blood coagulation and methods of use thereof |
| EP1978108A3 (en) | 2002-01-08 | 2009-01-07 | Siemens Healthcare Diagnostics GmbH | Single nucleotide polymorphisms predicting cardiovascular disease and medication efficacy |
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- 2004-11-30 ZA ZA200409692A patent/ZA200409692B/xx unknown
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2006
- 2006-01-06 HK HK06100300.9A patent/HK1080372A1/zh unknown
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2007
- 2007-06-21 US US11/766,160 patent/US7622122B2/en not_active Expired - Fee Related
- 2007-06-21 US US11/766,155 patent/US7622457B2/en not_active Expired - Fee Related
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