ES2856055T3 - Glicopolisialilación de proteínas diferentes de las proteínas de coagulación de la sangre - Google Patents
Glicopolisialilación de proteínas diferentes de las proteínas de coagulación de la sangre Download PDFInfo
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- ES2856055T3 ES2856055T3 ES16168473T ES16168473T ES2856055T3 ES 2856055 T3 ES2856055 T3 ES 2856055T3 ES 16168473 T ES16168473 T ES 16168473T ES 16168473 T ES16168473 T ES 16168473T ES 2856055 T3 ES2856055 T3 ES 2856055T3
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- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1075—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of amino acids or peptide residues
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- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
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Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106110311A (zh) * | 2009-07-27 | 2016-11-16 | 百深公司 | 凝血蛋白缀合物 |
| CN109293780B (zh) * | 2018-09-04 | 2021-05-07 | 厦门宏谱福生物科技有限公司 | 一种人组织因子凝血复合物及其制备方法 |
| CN109541115B (zh) * | 2018-11-28 | 2021-04-20 | 西北大学 | 唾液酸化糖链同分异构体的高分辨顺序分离和准确定量分析方法 |
| US11845989B2 (en) | 2019-01-23 | 2023-12-19 | Regeneron Pharmaceuticals, Inc. | Treatment of ophthalmic conditions with angiopoietin-like 7 (ANGPTL7) inhibitors |
| JP2022523301A (ja) | 2019-01-23 | 2022-04-22 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | アンジオポエチン様7(angptl7)阻害剤による眼疾患の治療 |
| WO2020163269A1 (en) * | 2019-02-04 | 2020-08-13 | Xenetic Biosciences, Inc. | Methods of using glycopolysialylated therapeutic proteins |
| US12605461B2 (en) | 2019-07-03 | 2026-04-21 | Molly Sandra Shoichet | Hydrogel compositions and uses thereof |
| WO2022182768A1 (en) | 2021-02-26 | 2022-09-01 | Regeneron Pharmaceuticals, Inc. | Treatment of inflammation with glucocorticoids and angiopoietin-like 7 (angptl7) inhibitors |
| WO2023119230A1 (en) | 2021-12-22 | 2023-06-29 | L'oreal | Coagulation pathway and nicotinamide-adenine dinucleotide pathway modulating compositions and methods of their use |
| FI20245266A1 (en) * | 2024-03-05 | 2025-09-06 | Glucomodicum Oy | Hydrogel conjugated with glucose oxidase |
Family Cites Families (165)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA647314A (en) | 1962-08-21 | J. Lewis Richard | Tire tool | |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| 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 |
| US4970300A (en) | 1985-02-01 | 1990-11-13 | New York University | Modified factor VIII |
| 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 |
| US4847325A (en) * | 1988-01-20 | 1989-07-11 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
| US5153265A (en) | 1988-01-20 | 1992-10-06 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
| US4966999A (en) | 1988-06-07 | 1990-10-30 | Cytogen Corporation | Radiohalogenated compounds for site specific labeling |
| US5122614A (en) | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| SE465222C5 (sv) | 1989-12-15 | 1998-02-10 | Pharmacia & Upjohn Ab | Ett rekombinant, humant faktor VIII-derivat och förfarande för dess framställning |
| SE466754B (sv) | 1990-09-13 | 1992-03-30 | Berol Nobel Ab | Saett att kovalent binda biopolymerer till hydrofila ytor |
| US5492821A (en) | 1990-11-14 | 1996-02-20 | Cargill, Inc. | Stabilized polyacrylic saccharide protein conjugates |
| WO1992016555A1 (en) | 1991-03-18 | 1992-10-01 | Enzon, Inc. | Hydrazine containing conjugates of polypeptides and glycopolypeptides with polymers |
| GB9112212D0 (en) * | 1991-06-06 | 1991-07-24 | Gregoriadis Gregory | Pharmaceutical compositions |
| US5846951A (en) | 1991-06-06 | 1998-12-08 | The School Of Pharmacy, University Of London | Pharmaceutical compositions |
| US6037452A (en) | 1992-04-10 | 2000-03-14 | Alpha Therapeutic Corporation | Poly(alkylene oxide)-Factor VIII or Factor IX conjugate |
| WO1994005332A2 (en) | 1992-09-01 | 1994-03-17 | Berlex Laboratories, Inc. | Glycolation of glycosylated macromolecules |
| DE69329795T2 (de) | 1992-10-02 | 2001-07-05 | Genetics Institute, Inc. | Zusammensetzung, welche den koagulationsfaktor viii beinhaltet; verfahren zu deren herstellung und die benutzung eines oberflächenaktiven stoffes als stabilisator |
| NO934477L (no) | 1992-12-09 | 1994-06-10 | Ortho Pharma Corp | PEG hydrazon- og PEG oksim-bindingdannende reagenser og proteinderivater derav |
| NZ250375A (en) | 1992-12-09 | 1995-07-26 | Ortho Pharma Corp | Peg hydrazone and peg oxime linkage forming reagents and protein derivatives |
| US5298643A (en) | 1992-12-22 | 1994-03-29 | Enzon, Inc. | Aryl imidate activated polyalkylene oxides |
| AU6029594A (en) | 1993-01-15 | 1994-08-15 | Enzon, Inc. | Factor viii - polymeric conjugates |
| 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 |
| SE504074C2 (sv) | 1993-07-05 | 1996-11-04 | Pharmacia Ab | Proteinberedning för subkutan, intramuskulär eller intradermal administrering |
| WO1996041813A2 (en) | 1994-11-09 | 1996-12-27 | Offord Robin E | Functionalized polymers for site-specific attachment |
| AU6255096A (en) | 1995-06-07 | 1996-12-30 | Mount Sinai School Of Medicine Of The City University Of New York, The | Pegylated modified proteins |
| WO1996040662A2 (en) | 1995-06-07 | 1996-12-19 | Cellpro, Incorporated | Aminooxy-containing linker compounds and their application in conjugates |
| SE9503380D0 (sv) | 1995-09-29 | 1995-09-29 | Pharmacia Ab | Protein derivatives |
| EP1731174A3 (en) * | 1996-08-02 | 2007-01-17 | Ortho-McNeil Pharmaceutical, Inc. | Polypeptides having a covalently bound N-terminal polyethylene glycol via hydrazone or oxime bond |
| EP0981548A4 (en) | 1997-04-30 | 2005-11-23 | Enzon Inc | GLYCOSYLATABLE SINGLE CHAIN ANTIGEN-BINDING PROTEINS, MANUFACTURE AND USE THEREOF |
| US6183738B1 (en) | 1997-05-12 | 2001-02-06 | Phoenix Pharamacologics, Inc. | Modified arginine deiminase |
| US20020160948A1 (en) | 1998-07-21 | 2002-10-31 | Aprile Pilon | Recombinant human uteroglobin in treatment of inflammatory and fibrotic conditions |
| EP1717248A1 (en) | 1997-06-04 | 2006-11-02 | Oxford Biomedica (UK) Limited | Tumor targeted vector |
| WO1999003496A1 (en) | 1997-07-21 | 1999-01-28 | The University Of North Carolina At Chapel Hill | Factor ix antihemophilic factor with increased clotting activity |
| WO2001082943A2 (en) | 2000-05-03 | 2001-11-08 | Novo Nordisk A/S | Subcutaneous administration of coagulation factor vii |
| ES2252876T5 (es) | 1997-12-03 | 2014-04-03 | Roche Diagnostics Gmbh | Proceso para preparar polipéptidos con glicolización adecuada |
| US5985263A (en) | 1997-12-19 | 1999-11-16 | Enzon, Inc. | Substantially pure histidine-linked protein polymer conjugates |
| DE19829289C2 (de) | 1998-06-30 | 2001-12-06 | Siemens Ag | Verfahren zur Berechnung der Koeffizienten eines nichtrekursiven digitalen Filters |
| US6552167B1 (en) | 1998-08-28 | 2003-04-22 | Gryphon Therapeutics, Inc. | Polyamide chains of precise length |
| DK1656952T3 (da) | 1998-10-16 | 2014-01-20 | Biogen Idec Inc | Polyalkylenglycolkonjugater af interferon beta-1A og anvendelser deraf |
| DE19852729A1 (de) | 1998-11-16 | 2000-05-18 | Werner Reutter | Rekombinante Glycoproteine, Verfahren zu ihrer Herstellung, sie enthaltende Arzneimittel und ihre Verwendung |
| EP2921180B1 (en) | 1999-02-22 | 2019-08-14 | University of Connecticut | Albumin-free factor VIII formulations |
| KR20020022691A (ko) * | 1999-06-08 | 2002-03-27 | 와이즈먼 앤드루 | 아미노옥시기를 포함하는 원자가 플랫폼 분자 |
| US6697436B1 (en) | 1999-07-13 | 2004-02-24 | Pmc-Sierra, Inc. | Transmission antenna array system with predistortion |
| US6531122B1 (en) | 1999-08-27 | 2003-03-11 | Maxygen Aps | Interferon-β variants and conjugates |
| CN1309423C (zh) | 1999-11-12 | 2007-04-11 | 马克西根控股公司 | 干扰素γ偶联物 |
| 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) |
| DE60138364D1 (de) * | 2000-02-11 | 2009-05-28 | Bayer Healthcare Llc | Gerinnungsfaktor vii oder viia konjugate |
| US6586398B1 (en) | 2000-04-07 | 2003-07-01 | Amgen, Inc. | Chemically modified novel erythropoietin stimulating protein compositions and methods |
| DE60143292D1 (de) | 2000-05-03 | 2010-12-02 | Novo Nordisk Healthcare Ag | Varianten des menschlichen Koagulationsfaktors VII |
| AU2001258536A1 (en) | 2000-05-16 | 2001-11-26 | Lipoxen Technologies Limited | Derivatisation of proteins in aqueous solution |
| CN1434726A (zh) | 2000-06-08 | 2003-08-06 | 拉卓拉药物公司 | 包含高分子量聚环氧乙烷的多价平台分子 |
| US6423826B1 (en) | 2000-06-30 | 2002-07-23 | Regents Of The University Of Minnesota | High molecular weight derivatives of vitamin K-dependent polypeptides |
| US7118737B2 (en) | 2000-09-08 | 2006-10-10 | Amylin Pharmaceuticals, Inc. | Polymer-modified synthetic proteins |
| AU8755001A (en) | 2000-09-13 | 2002-03-26 | Novo Nordisk As | Human coagulation factor vii variants |
| EP1325127B1 (en) | 2000-10-02 | 2009-03-11 | Novo Nordisk Health Care AG | Method for the production of vitamin k-dependent proteins |
| US7001994B2 (en) * | 2001-01-18 | 2006-02-21 | Genzyme Corporation | Methods for introducing mannose 6-phosphate and other oligosaccharides onto glycoproteins |
| MXPA03008590A (es) | 2001-03-22 | 2003-12-08 | Novo Nordisk Healthcare Ag | Derivados del factor vii de coagulacion. |
| WO2003004615A2 (en) | 2001-07-05 | 2003-01-16 | Incyte Genomics, Inc. | Secreted proteins |
| US6913915B2 (en) | 2001-08-02 | 2005-07-05 | Phoenix Pharmacologics, Inc. | PEG-modified uricase |
| US7214660B2 (en) | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
| EP2042196B1 (en) | 2001-10-10 | 2016-07-13 | ratiopharm GmbH | Remodelling and glycoconjugation of Granulocyte Colony Stimulating Factor (G-CSF) |
| US7795210B2 (en) | 2001-10-10 | 2010-09-14 | Novo Nordisk A/S | Protein remodeling methods and proteins/peptides produced by the methods |
| US7265084B2 (en) | 2001-10-10 | 2007-09-04 | Neose Technologies, Inc. | Glycopegylation methods and proteins/peptides produced by the methods |
| US7265085B2 (en) | 2001-10-10 | 2007-09-04 | Neose Technologies, Inc. | Glycoconjugation methods and proteins/peptides produced by the methods |
| US7157277B2 (en) | 2001-11-28 | 2007-01-02 | Neose Technologies, Inc. | Factor VIII remodeling and glycoconjugation of Factor VIII |
| AU2002352524B2 (en) | 2001-11-07 | 2007-10-04 | Nektar Therapeutics | Branched polymers and their conjugates |
| JP2005510229A (ja) | 2001-11-28 | 2005-04-21 | ネオーズ テクノロジーズ, インコーポレイテッド | アミダーゼを用いる糖タンパク質のリモデリング |
| JP2005535280A (ja) | 2001-11-28 | 2005-11-24 | ネオーズ テクノロジーズ, インコーポレイテッド | エンドグリカナーゼを用いる糖タンパク質のリモデリング |
| RU2362807C2 (ru) | 2002-06-21 | 2009-07-27 | Ново Нордиск Хелт Кэр Аг | Конъюгат полипептида фактора vii, способ его получения, его применение и содержащая его фармацевтическая композиция |
| DE10228657A1 (de) | 2002-06-27 | 2004-01-15 | Celanese Ventures Gmbh | Protonenleitende Membran und deren Verwendung |
| US7122189B2 (en) | 2002-08-13 | 2006-10-17 | Enzon, Inc. | Releasable polymeric conjugates based on aliphatic biodegradable linkers |
| US7087229B2 (en) | 2003-05-30 | 2006-08-08 | Enzon Pharmaceuticals, Inc. | Releasable polymeric conjugates based on aliphatic biodegradable linkers |
| EP1681303B1 (en) | 2002-09-11 | 2013-09-04 | Fresenius Kabi Deutschland GmbH | HASylated polypeptides, especially HASylated erythropoietin |
| EP1400533A1 (en) * | 2002-09-11 | 2004-03-24 | Fresenius Kabi Deutschland GmbH | HASylated polypeptides, especially HASylated erythropoietin |
| BR0314106A (pt) * | 2002-09-11 | 2005-07-19 | Fresenius Kabi De Gmbh | Polipeptìdeos hasilados, especialmente eritropoietina hasilada |
| US20040062748A1 (en) | 2002-09-30 | 2004-04-01 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
| EP1578841B2 (en) | 2002-12-31 | 2016-10-12 | Nektar Therapeutics AL, Corporation | Maleamic acid polymer derivatives and their bioconjugates |
| WO2004060965A2 (en) | 2002-12-31 | 2004-07-22 | Nektar Therapeutics Al, Corporation | Hydrolytically stable maleimide-terminated polymers |
| WO2004075923A2 (en) | 2003-02-26 | 2004-09-10 | Nektar Therapeutics Al, Corporation | Polymer-factor viii moiety conjugates |
| KR20060003862A (ko) * | 2003-03-14 | 2006-01-11 | 네오스 테크놀로지스, 인크. | 수용성분기폴리머 및 그 접합체 |
| CA2521784C (en) | 2003-04-08 | 2012-03-27 | Yeda Research And Development Co. Ltd. | Reversible pegylated drugs |
| DE10330674B4 (de) | 2003-07-08 | 2007-01-11 | Eppendorf Ag | Zellbehandlungskammer |
| WO2005014655A2 (en) * | 2003-08-08 | 2005-02-17 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyalkyl starch and a protein |
| JP2007501870A (ja) * | 2003-08-08 | 2007-02-01 | 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 | ヒドロキシアルキルデンプンとg−csfの複合体 |
| EP1654004A2 (en) | 2003-08-08 | 2006-05-10 | Novo Nordisk A/S | Synthesis and application of new structural well defined branched polymers as conjugating agents for peptides |
| EP1653991A2 (en) | 2003-08-08 | 2006-05-10 | Fresenius Kabi Deutschland GmbH | Conjugates of a polymer and a protein linked by an oxime linking group |
| CN1863549A (zh) * | 2003-08-08 | 2006-11-15 | 费森尤斯卡比德国有限公司 | 通过肟连接基团进行连接的聚合物和蛋白质的缀合物 |
| WO2005016974A1 (en) | 2003-08-12 | 2005-02-24 | Lipoxen Technologies Limited | Sialic acid derivatives for protein derivatisation and conjugation |
| JP2007501888A (ja) * | 2003-08-12 | 2007-02-01 | リポクセン テクノロジーズ リミテッド | ポリシアル酸誘導体 |
| 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 |
| KR101237884B1 (ko) | 2003-12-03 | 2013-02-27 | 바이오제너릭스 에이지 | 글리코 peg화 과립구 콜로니 자극인자 |
| AU2004296860B2 (en) | 2003-12-03 | 2010-04-22 | Novo Nordisk A/S | Glycopegylated factor IX |
| WO2005056608A1 (en) * | 2003-12-04 | 2005-06-23 | University Of Utah Research Foundation | Modified macromolecules and methods of making and using thereof |
| US7338933B2 (en) | 2004-01-08 | 2008-03-04 | Neose Technologies, Inc. | O-linked glycosylation of peptides |
| WO2005072778A2 (en) * | 2004-01-29 | 2005-08-11 | Biosynexus, Inc. | Use of amino-oxy functional groups in the preparation of vaccines conjugates |
| GB0412291D0 (en) | 2004-06-02 | 2004-07-07 | Enersys Ltd | A battery |
| RU2276123C2 (ru) | 2004-07-06 | 2006-05-10 | Центральный научно-исследовательский институт геологии нерудных полезных ископаемых (ЦНИИгеолнеруд) | Способ получения комплексного минерального удобрения |
| WO2006020372A2 (en) | 2004-07-23 | 2006-02-23 | Neose Technologies, Inc. | Enzymatic modification of glycopeptides |
| JP2008507990A (ja) | 2004-08-02 | 2008-03-21 | ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト | Fviiの抱合体 |
| US8652334B2 (en) * | 2004-08-12 | 2014-02-18 | Lipoxen Technologies Limited | Fractionation of charged polysaccharide |
| CN101039965A (zh) * | 2004-08-12 | 2007-09-19 | 利普生技术有限公司 | 唾液酸衍生物 |
| WO2006016168A2 (en) * | 2004-08-12 | 2006-02-16 | Lipoxen Technologies Limited | Sialic acid derivatives |
| WO2006031811A2 (en) | 2004-09-10 | 2006-03-23 | Neose Technologies, Inc. | Glycopegylated interferon alpha |
| KR101468345B1 (ko) | 2004-11-12 | 2014-12-03 | 바이엘 헬스케어 엘엘씨 | Fviii의 부위 지향 변형 |
| CA2591852A1 (en) | 2004-12-27 | 2006-07-06 | Baxter International Inc. | Polymer-von willebrand factor-conjugates |
| JP2008526864A (ja) | 2005-01-06 | 2008-07-24 | ネオス テクノロジーズ インコーポレイテッド | 糖断片を用いる糖結合 |
| CN101160326B (zh) * | 2005-02-23 | 2013-04-10 | 利普生技术有限公司 | 用于蛋白质衍生和缀合的活化的唾液酸衍生物 |
| EP1877099B1 (en) * | 2005-04-06 | 2012-09-19 | Genzyme Corporation | Therapeutic conjugates comprising a lysosomal enzyme, polysialic acid and a targeting moiety |
| EP1891231A4 (en) | 2005-05-25 | 2011-06-22 | Novo Nordisk As | GLYCOPEGYLATED FACTOR IX |
| BRPI0611872B8 (pt) | 2005-06-16 | 2021-05-25 | Nektar Therapeutics | reagente polimérico, conjugado, método para preparação de um conjugado e composição farmacêutica |
| EP1893632B1 (en) | 2005-06-17 | 2015-08-12 | Novo Nordisk Health Care AG | Selective reduction and derivatization of engineered factor vii proteins comprising at least one non-native cysteine |
| WO2007007606A1 (ja) | 2005-07-11 | 2007-01-18 | Sharp Kabushiki Kaisha | 可変抵抗素子 |
| US20070105755A1 (en) | 2005-10-26 | 2007-05-10 | Neose Technologies, Inc. | One pot desialylation and glycopegylation of therapeutic peptides |
| WO2007022784A2 (en) | 2005-08-26 | 2007-03-01 | Maxygen Holdings Ltd. | Liquid factor vii composition |
| BRPI0620316A2 (pt) | 2005-12-21 | 2011-11-08 | Wyeth Corp | formulações de proteìnas com viscosidades reduzida e seus usos |
| CA2647314A1 (en) | 2006-03-31 | 2007-11-08 | Baxter International Inc. | Pegylated factor viii |
| US7645860B2 (en) * | 2006-03-31 | 2010-01-12 | Baxter Healthcare S.A. | Factor VIII polymer conjugates |
| EP2089052A4 (en) | 2006-05-24 | 2011-02-16 | Peg Biosciences | POLYETHYLENE GLYCOL-BASED LINK COMPOUNDS AND BIOLOGICALLY ACTIVE CONJUGATES BASED ON SAID COMPOUNDS |
| US7939632B2 (en) | 2006-06-14 | 2011-05-10 | Csl Behring Gmbh | Proteolytically cleavable fusion proteins with high molar specific activity |
| WO2008035373A2 (en) | 2006-07-13 | 2008-03-27 | Serum Institute Of India Ltd | Highly pure polysialic acid and process for preperation thereof |
| WO2008012528A1 (en) * | 2006-07-25 | 2008-01-31 | Lipoxen Technologies Limited | N-terminal polysialylation |
| WO2008025856A2 (en) * | 2006-09-01 | 2008-03-06 | Novo Nordisk Health Care Ag | Modified glycoproteins |
| US8969532B2 (en) | 2006-10-03 | 2015-03-03 | Novo Nordisk A/S | Methods for the purification of polypeptide conjugates comprising polyalkylene oxide using hydrophobic interaction chromatography |
| CA2670618C (en) * | 2006-12-15 | 2016-10-04 | Baxter International Inc. | Factor viia- (poly) sialic acid conjugate having prolonged in vivo half-life |
| EP2099475B1 (en) | 2007-01-03 | 2016-08-24 | Novo Nordisk Health Care AG | Subcutaneous administration of coagulation factor viia-related polypeptides |
| SI2457920T1 (en) * | 2007-01-18 | 2018-02-28 | Genzyme Corporation | Oligosaccharides containing the amino acid group and their conjugates |
| WO2008119815A1 (en) | 2007-04-02 | 2008-10-09 | Novo Nordisk A/S | Subcutaneous administration of coagulation factor ix |
| JP5622569B2 (ja) * | 2007-06-26 | 2014-11-12 | バクスター・インターナショナル・インコーポレイテッドBaxter International Incorp0Rated | 加水分解性ポリマーfmoc−リンカー |
| EP2173759A4 (en) | 2007-07-03 | 2014-01-29 | Childrens Hosp & Res Ct Oak | OLIGOSIAL INSERTS, PROCESS FOR THEIR PREPARATION AND ITS IMMUNOLOGICAL USE |
| KR20100090684A (ko) | 2007-10-09 | 2010-08-16 | 폴리테릭스 리미티드 | 신규한 접합 단백질 및 펩티드 |
| MX2010005317A (es) * | 2007-11-20 | 2010-06-02 | Ambrx Inc | Polipeptidos de insulina modificados y sus usos. |
| CA2711503A1 (en) | 2008-01-08 | 2009-07-16 | Biogenerix Ag | Glycoconjugation of polypeptides using oligosaccharyltransferases |
| KR101582841B1 (ko) | 2008-02-27 | 2016-01-11 | 노보 노르디스크 에이/에스 | 콘쥬게이트된 인자 viii 분자 |
| WO2009130602A2 (en) | 2008-04-24 | 2009-10-29 | Celtic Pharma Peg Ltd. | Factor ix conjugates with extended half-lives |
| CN102065899A (zh) | 2008-05-23 | 2011-05-18 | 诺沃-诺迪斯克保健股份有限公司 | 含有高浓度的芳香族防腐剂的peg-官能化的丝氨酸蛋白酶的制剂 |
| WO2009141433A1 (en) | 2008-05-23 | 2009-11-26 | Novo Nordisk Health Care Ag | Low viscosity compositions comprising a pegylated gla-domain containing protein |
| CA2726942A1 (en) | 2008-06-04 | 2009-12-10 | Bayer Healthcare Llc | Fviii muteins for treatment of von willebrand disease |
| EP2374481B1 (en) | 2008-07-21 | 2015-11-04 | Polytherics Limited | Novel reagents and method for conjugating biological molecules |
| KR101929641B1 (ko) * | 2008-10-17 | 2018-12-14 | 박스알타 인코퍼레이티드 | 낮은 수준의 수용성 중합체를 포함하는 개질된 혈액 인자 |
| CA2740793A1 (en) | 2008-11-03 | 2010-06-03 | Haiyan Jiang | Method for the treatment of hemophilia |
| WO2010083536A1 (en) | 2009-01-19 | 2010-07-22 | Bayer Healthcare Llc | Protein conjugate having an endopeptidase-cleavable bioprotective moiety |
| EP2398822B1 (en) | 2009-02-19 | 2013-01-02 | Novo Nordisk A/S | Modification of factor viii |
| US9005598B2 (en) | 2009-03-04 | 2015-04-14 | Polytherics Limited | Conjugated proteins and peptides |
| US20100330033A1 (en) | 2009-04-16 | 2010-12-30 | Nian Wu | Protein-carrier conjugates |
| GB0908393D0 (en) | 2009-05-15 | 2009-06-24 | Almac Sciences Scotland Ltd | Labelling method |
| KR101912335B1 (ko) * | 2009-07-27 | 2018-10-26 | 리폭센 테크놀로지즈 리미티드 | 비혈액 응고 단백질의 글리코폴리시알화 |
| CN106110311A (zh) * | 2009-07-27 | 2016-11-16 | 百深公司 | 凝血蛋白缀合物 |
| CN102497884A (zh) * | 2009-07-27 | 2012-06-13 | 巴克斯特国际公司 | 凝血蛋白缀合物 |
| EP2461821A4 (en) | 2009-07-31 | 2013-07-03 | Bayer Healthcare Llc | MODIFIED POLYPEPTIDES OF FACTOR IX AND USES THEREOF |
| DE102009028526A1 (de) | 2009-08-13 | 2011-02-24 | Leibniz-Institut Für Polymerforschung Dresden E.V. | Verfahren zur Modifikation und Funktionalisierung von Sacchariden |
| EP2480578A4 (en) | 2009-09-25 | 2013-04-17 | Vybion Inc | MODIFICATION OF POLYPEPTIDE |
| WO2011064247A1 (en) | 2009-11-24 | 2011-06-03 | Novo Nordisk Health Care Ag | Method of purifying pegylated proteins |
| US20130040888A1 (en) | 2010-02-16 | 2013-02-14 | Novo Nordisk A/S | Factor VIII Molecules With Reduced VWF Binding |
| GB201007357D0 (en) | 2010-04-30 | 2010-06-16 | Leverton Licence Holdings Ltd | Conjugated factor VIII |
| GB201007356D0 (en) | 2010-04-30 | 2010-06-16 | Leverton Licence Holdings Ltd | Conjugated factor VIIa |
| WO2012068134A1 (en) | 2010-11-15 | 2012-05-24 | Biogen Idec Inc. | Enrichment and concentration of select product isoforms by overloaded bind and elute chromatography |
| CN103796670A (zh) | 2011-07-08 | 2014-05-14 | 比奥根艾迪克依蒙菲利亚公司 | 因子viii嵌合和杂合多肽及其使用方法 |
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| JP2021042244A (ja) | 2021-03-18 |
| US20160361430A1 (en) | 2016-12-15 |
| CN106110311A (zh) | 2016-11-16 |
| JP2015227385A (ja) | 2015-12-17 |
| HUE028056T2 (en) | 2016-11-28 |
| JP2020037701A (ja) | 2020-03-12 |
| PT2459224T (pt) | 2016-09-05 |
| RU2016121611A3 (https=) | 2019-12-10 |
| US10772968B2 (en) | 2020-09-15 |
| US10350301B2 (en) | 2019-07-16 |
| JP2018024882A (ja) | 2018-02-15 |
| EP3093029A1 (en) | 2016-11-16 |
| PL2459224T3 (pl) | 2017-08-31 |
| RU2014123260A (ru) | 2015-12-20 |
| JP7071093B2 (ja) | 2022-05-18 |
| RU2016121611A (ru) | 2018-11-29 |
| JP2016113626A (ja) | 2016-06-23 |
| RU2662807C2 (ru) | 2018-07-31 |
| JP6208269B2 (ja) | 2017-10-04 |
| EP3093029A8 (en) | 2016-12-28 |
| CN104530182A (zh) | 2015-04-22 |
| US11040109B2 (en) | 2021-06-22 |
| SG10201401194VA (en) | 2014-07-30 |
| NZ623810A (en) | 2015-10-30 |
| US20180200380A1 (en) | 2018-07-19 |
| JP2018035192A (ja) | 2018-03-08 |
| RU2744370C2 (ru) | 2021-03-05 |
| US20190314516A1 (en) | 2019-10-17 |
| JP2022058911A (ja) | 2022-04-12 |
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