JP2015520163A5 - - Google Patents
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- JP2015520163A5 JP2015520163A5 JP2015512831A JP2015512831A JP2015520163A5 JP 2015520163 A5 JP2015520163 A5 JP 2015520163A5 JP 2015512831 A JP2015512831 A JP 2015512831A JP 2015512831 A JP2015512831 A JP 2015512831A JP 2015520163 A5 JP2015520163 A5 JP 2015520163A5
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- Prior art keywords
- growth factor
- soluble polymer
- factor
- protein
- water
- Prior art date
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| IL266361B2 (en) * | 2016-11-14 | 2024-02-01 | Novartis Ag | Methods and preparations for the treatment of cartilage damage and arthritis |
| JP7002036B2 (ja) * | 2016-11-17 | 2022-01-20 | パナソニックIpマネジメント株式会社 | 膜電極接合体および固体酸化物形燃料電池 |
| US11786586B2 (en) | 2016-12-23 | 2023-10-17 | Aoa Dx | Carbohydrate structures and uses thereof |
| CN108503901B (zh) * | 2018-04-17 | 2020-07-07 | 哈尔滨工业大学 | 一种抗菌普鲁兰多糖/壳聚糖复合食品包装膜的制备方法 |
| SG11202107497XA (en) | 2019-01-23 | 2021-08-30 | Regeneron Pharma | Treatment of ophthalmic conditions with angiopoietin-like 7 (angptl7) inhibitors |
| US11845989B2 (en) | 2019-01-23 | 2023-12-19 | Regeneron Pharmaceuticals, Inc. | Treatment of ophthalmic conditions with angiopoietin-like 7 (ANGPTL7) inhibitors |
| EP4298219A1 (en) | 2021-02-26 | 2024-01-03 | Regeneron Pharmaceuticals, Inc. | Treatment of inflammation with glucocorticoids and angiopoietin-like 7 (angptl7) inhibitors |
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Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS54113492A (en) | 1978-02-24 | 1979-09-05 | Sanyo Chem Ind Ltd | Preparation of glucoprotein derivative |
| US4356170A (en) | 1981-05-27 | 1982-10-26 | Canadian Patents & Development Ltd. | Immunogenic polysaccharide-protein conjugates |
| US4757006A (en) | 1983-10-28 | 1988-07-12 | Genetics Institute, Inc. | Human factor VIII:C gene and recombinant methods for production |
| US5250421A (en) | 1986-01-03 | 1993-10-05 | Genetics Institute, Inc. | Method for producing factor VIII:C-type proteins |
| US5198349A (en) | 1986-01-03 | 1993-03-30 | Genetics Institute, Inc. | Method for producing factor VIII:C and analogs |
| JPH0387173A (ja) | 1987-09-10 | 1991-04-11 | Teijin Ltd | ヒト活性化天然型ファクター8cの製造方法及びそれに用いる形質転換体 |
| US5846951A (en) | 1991-06-06 | 1998-12-08 | The School Of Pharmacy, University Of London | Pharmaceutical compositions |
| NZ256921A (en) | 1992-10-02 | 1996-05-28 | Pharmacia Ab | Formulations of coagulation factor viii and a non-ionic surfactant and their preparation |
| NZ250375A (en) * | 1992-12-09 | 1995-07-26 | Ortho Pharma Corp | Peg hydrazone and peg oxime linkage forming reagents and protein derivatives |
| WO1994028024A1 (en) * | 1993-06-01 | 1994-12-08 | Enzon, Inc. | Carbohydrate-modified polymer conjugates with erythropoietic activity |
| US5621039A (en) | 1993-06-08 | 1997-04-15 | Hallahan; Terrence W. | Factor IX- polymeric conjugates |
| WO1996040662A2 (en) | 1995-06-07 | 1996-12-19 | Cellpro, Incorporated | Aminooxy-containing linker compounds and their application in conjugates |
| WO1999003496A1 (en) | 1997-07-21 | 1999-01-28 | The University Of North Carolina At Chapel Hill | Factor ix antihemophilic factor with increased clotting activity |
| US7074878B1 (en) | 1999-12-10 | 2006-07-11 | Harris J Milton | Hydrolytically degradable polymers and hydrogels made therefrom |
| US6413507B1 (en) | 1999-12-23 | 2002-07-02 | Shearwater Corporation | Hydrolytically degradable carbamate derivatives of poly (ethylene glycol) |
| ES2256234T3 (es) | 2000-05-16 | 2006-07-16 | Lipoxen Technologies Limited | Derivatizacion de proteinas en solucion acuosa. |
| US7265084B2 (en) | 2001-10-10 | 2007-09-04 | Neose Technologies, Inc. | Glycopegylation methods and proteins/peptides produced by the methods |
| KR100948532B1 (ko) | 2001-11-07 | 2010-03-23 | 넥타르 테라퓨틱스 | 분지형 중합체 및 그의 공액체 |
| CA2496317C (en) | 2002-09-11 | 2014-02-18 | Fresenius Kabi Deutschland Gmbh | Method of producing hydroxyalkyl starch derivatives |
| EP1681303B1 (en) | 2002-09-11 | 2013-09-04 | Fresenius Kabi Deutschland GmbH | HASylated polypeptides, especially HASylated erythropoietin |
| ES2512499T3 (es) | 2003-04-08 | 2014-10-24 | Yeda Research And Development Co., Ltd. | Fármacos pegilados reversibles |
| US20070026485A1 (en) | 2003-04-09 | 2007-02-01 | Neose Technologies, Inc. | Glycopegylation methods and proteins/peptides produced by the methods |
| US20080206182A1 (en) * | 2003-08-08 | 2008-08-28 | Fresenius Kabi Deutschland Gmbh | Conjugates of a Polymer and a Protein Linked by an Oxime Group |
| EP1654290B1 (en) | 2003-08-12 | 2019-03-13 | Lipoxen Technologies Limited | Sialic acid derivatives for protein derivatisation and conjugation |
| US8633157B2 (en) | 2003-11-24 | 2014-01-21 | Novo Nordisk A/S | Glycopegylated erythropoietin |
| US20060040856A1 (en) | 2003-12-03 | 2006-02-23 | Neose Technologies, Inc. | Glycopegylated factor IX |
| NZ547554A (en) | 2003-12-03 | 2009-09-25 | Biogenerix Ag | Glycopegylated granulocyte colony stimulating factor |
| ES2593318T3 (es) | 2004-08-12 | 2016-12-07 | Lipoxen Technologies Limited | Derivados de ácido siálico |
| US8268967B2 (en) | 2004-09-10 | 2012-09-18 | Novo Nordisk A/S | Glycopegylated interferon α |
| DK1835938T3 (da) | 2004-12-27 | 2013-11-04 | Baxter Int | Polymer-von Willebrand-faktor-konjugater |
| CN101242858B (zh) | 2005-06-16 | 2012-12-19 | 尼克塔治疗公司 | 具有可降解键的轭合物以及用于制备这种轭合物的聚合物试剂 |
| US7645860B2 (en) | 2006-03-31 | 2010-01-12 | Baxter Healthcare S.A. | Factor VIII polymer conjugates |
| EP2059527B1 (en) | 2006-09-01 | 2014-12-03 | Novo Nordisk Health Care AG | Modified glycoproteins |
| BRPI0720282B8 (pt) | 2006-12-15 | 2021-05-25 | Baxalta GmbH | construção proteica, composição farmacêutica, e, kit |
| GB0908393D0 (en) * | 2009-05-15 | 2009-06-24 | Almac Sciences Scotland Ltd | Labelling method |
| AU2010281453C1 (en) * | 2009-07-27 | 2019-08-15 | Takeda Pharmaceutical Company Limited | Blood coagulation protein conjugates |
| EP3081233B1 (en) * | 2009-07-27 | 2020-12-23 | Baxalta GmbH | Glycopolysialylation of proteins other than blood coagulation proteins |
| DK2598172T3 (da) * | 2010-07-30 | 2019-07-01 | Baxalta GmbH | Nukleofile katalysatorer til oximforbindelse |
| KR101560541B1 (ko) * | 2012-04-13 | 2015-10-19 | 아우토리브 디벨롭먼트 아베 | 에어백 모듈과 스티어링 휠의 조립체 |
| AU2013204754C1 (en) * | 2012-05-16 | 2018-10-11 | Takeda Pharmaceutical Company Limited | Nucleophilic Catalysts for Oxime Linkage |
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