KR20100110799A - 화학적으로 변형된 제 ９ 인자 - Google Patents
화학적으로 변형된 제 ９ 인자 Download PDFInfo
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- KR20100110799A KR20100110799A KR1020107014071A KR20107014071A KR20100110799A KR 20100110799 A KR20100110799 A KR 20100110799A KR 1020107014071 A KR1020107014071 A KR 1020107014071A KR 20107014071 A KR20107014071 A KR 20107014071A KR 20100110799 A KR20100110799 A KR 20100110799A
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| EP2353588B1 (en) | 2010-01-21 | 2015-04-15 | Agricultural Technology Research Institute | A sustained release preparation of factor IX |
| TWI788044B (zh) | 2013-03-15 | 2022-12-21 | 美商百歐維拉提夫治療公司 | 因子ｉｘ多肽調配物 |
| AR099340A1 (es) * | 2014-02-12 | 2016-07-13 | Novo Nordisk As | Conjugados del factor de coagulación ix |
| US10772942B2 (en) | 2014-03-24 | 2020-09-15 | Bioverativ Therapeutics Inc. | Lyophilized factor IX formulations |
| US20220378840A1 (en) * | 2019-11-29 | 2022-12-01 | Rutgers, The State University Of New Jersey | Compositions, kits and methods for storage of blood products and methods of use thereof |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS538750B2 (enExample) | 1971-08-18 | 1978-03-31 | ||
| AT348548B (de) | 1977-04-08 | 1979-02-26 | Laevosan Gmbh & Co Kg | Verfahren zur herstellung von alsblutplasma- expander geeignerter hydroxyaethylstaerke |
| US5614500A (en) | 1983-03-04 | 1997-03-25 | The Scripps Research Institute | Compositions containing highly purified factor IX proteins prepared by immunoaffinity chromatography |
| DE3313600A1 (de) * | 1983-04-14 | 1984-10-18 | Laevosan-Gesellschaft mbH & Co. KG, Linz | Plasmastreckmittel auf staerkebasis und verfahren zu ihrer herstellung |
| DE19975071I2 (de) | 1989-06-16 | 2000-02-03 | Fresenius Ag | Hydroxyethylstaerke als Plasmaexpander Verfahren zu ihrer Herstellung und Verwendung als kolloidales Plasmaersatzmittel |
| FR2702160B1 (fr) | 1993-03-02 | 1995-06-02 | Biovecteurs As | Vecteurs particulaires synthétiques et procédé de préparation. |
| DE4310974C2 (de) * | 1993-04-03 | 1996-08-01 | Fresenius Ag | Verwendung von Hydroxyethylstärke zur Verbesserung der Mikrozirkulation |
| FR2704145B1 (fr) | 1993-04-21 | 1995-07-21 | Pasteur Institut | Vecteur particulaire et composition pharmaceutique le contenant. |
| US5621039A (en) * | 1993-06-08 | 1997-04-15 | Hallahan; Terrence W. | Factor IX- polymeric conjugates |
| FR2723849B1 (fr) | 1994-08-31 | 1997-04-11 | Biovector Therapeutics Sa | Procede pour augmenter l'immunogenicite, produit obtenu et composition pharmaceutique |
| EP0973544B1 (de) * | 1997-04-08 | 2001-06-27 | Baxter Aktiengesellschaft | Immuntolerante prothrombinkomplex-präparation |
| US7179617B2 (en) * | 2001-10-10 | 2007-02-20 | Neose Technologies, Inc. | Factor IX: remolding and glycoconjugation of Factor IX |
| EP1620118B1 (en) | 2003-04-08 | 2014-06-18 | Yeda Research And Development Co., Ltd. | Reversible pegylated drugs |
| WO2005014655A2 (en) * | 2003-08-08 | 2005-02-17 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyalkyl starch and a protein |
| EP1694315A4 (en) * | 2003-12-03 | 2009-10-28 | Novo Nordisk As | FACTOR IX GLYCOPEGYL |
| US20060040856A1 (en) * | 2003-12-03 | 2006-02-23 | Neose Technologies, Inc. | Glycopegylated factor IX |
| KR101215226B1 (ko) | 2004-03-01 | 2012-12-26 | 베. 브라운 멜중엔 악티엔게젤샤프트 | 하이드록시에틸전분 |
| WO2005092928A1 (en) * | 2004-03-11 | 2005-10-06 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyalkyl starch and a protein, prepared by reductive amination |
| WO2006018204A1 (en) * | 2004-08-17 | 2006-02-23 | Zlb Behring Gmbh | Modified vitamin k dependent polypeptides |
| JP2008532966A (ja) * | 2005-03-11 | 2008-08-21 | フレゼニウス・カビ・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 不活性出発物質からの生理活性糖タンパク質の生成 |
| WO2007101681A1 (en) | 2006-03-07 | 2007-09-13 | Baxter International Inc | Highly phosphorylated and sulfated recombinant factor ix |
| CN101454267B (zh) | 2006-03-29 | 2012-09-26 | 帝斯曼知识产权资产管理有限公司 | 姜黄素的合成 |
| TW200804416A (en) * | 2006-06-19 | 2008-01-16 | Nautilus Technology Llc | Modified coagulation factor IX polypeptides and use thereof for treatment |
| EP2155865B1 (en) * | 2007-06-15 | 2014-09-17 | National Research Council Of Canada | Engineered versions of polysialyltransferases with enhanced enzymatic properties |
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2008
- 2008-12-19 NZ NZ603997A patent/NZ603997A/xx not_active IP Right Cessation
- 2008-12-19 EP EP12008216A patent/EP2568043A1/en not_active Withdrawn
- 2008-12-19 EP EP12008214A patent/EP2568041A1/en not_active Withdrawn
- 2008-12-19 CA CA2709960A patent/CA2709960A1/en not_active Abandoned
- 2008-12-19 NZ NZ598193A patent/NZ598193A/xx not_active IP Right Cessation
- 2008-12-19 CN CN2008801232530A patent/CN101952422A/zh active Pending
- 2008-12-19 RU RU2010131189/10A patent/RU2010131189A/ru not_active Application Discontinuation
- 2008-12-19 EP EP12008215A patent/EP2568042A1/en not_active Withdrawn
- 2008-12-19 EP EP08868384A patent/EP2247723A1/en not_active Withdrawn
- 2008-12-19 US US12/339,619 patent/US20090176708A1/en not_active Abandoned
- 2008-12-19 KR KR1020107014071A patent/KR20100110799A/ko not_active Ceased
- 2008-12-19 NZ NZ585835A patent/NZ585835A/en not_active IP Right Cessation
- 2008-12-19 AU AU2008342260A patent/AU2008342260B2/en not_active Expired - Fee Related
- 2008-12-19 WO PCT/EP2008/010925 patent/WO2009083187A1/en not_active Ceased
- 2008-12-19 JP JP2010540056A patent/JP2011507919A/ja active Pending
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2010
- 2010-05-31 IL IL206095A patent/IL206095A0/en unknown
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| AU2008342260A1 (en) | 2009-07-09 |
| EP2247723A1 (en) | 2010-11-10 |
| CN101952422A (zh) | 2011-01-19 |
| US20090176708A1 (en) | 2009-07-09 |
| NZ598193A (en) | 2012-12-21 |
| CA2709960A1 (en) | 2009-07-09 |
| JP2011507919A (ja) | 2011-03-10 |
| US20120177625A1 (en) | 2012-07-12 |
| AU2008342260B2 (en) | 2013-10-17 |
| NZ585835A (en) | 2012-07-27 |
| NZ603997A (en) | 2013-02-22 |
| EP2568043A1 (en) | 2013-03-13 |
| EP2568042A1 (en) | 2013-03-13 |
| IL206095A0 (en) | 2010-11-30 |
| EP2568041A1 (en) | 2013-03-13 |
| RU2010131189A (ru) | 2012-02-10 |
| WO2009083187A8 (en) | 2009-09-17 |
| WO2009083187A1 (en) | 2009-07-09 |
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