ES2521490T3 - Conjugado de factor VIIa - ácido (poli)siálico con una vida media in vivo prolongada. - Google Patents
Conjugado de factor VIIa - ácido (poli)siálico con una vida media in vivo prolongada. Download PDFInfo
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- ES2521490T3 ES2521490T3 ES07865679.0T ES07865679T ES2521490T3 ES 2521490 T3 ES2521490 T3 ES 2521490T3 ES 07865679 T ES07865679 T ES 07865679T ES 2521490 T3 ES2521490 T3 ES 2521490T3
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- fviia
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87521706P | 2006-12-15 | 2006-12-15 | |
| US875217P | 2006-12-15 | ||
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Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2008012600A (es) | 2006-03-31 | 2008-12-12 | Baxter Int | Factor viii pegilado. |
| US7982010B2 (en) | 2006-03-31 | 2011-07-19 | Baxter International Inc. | Factor VIII polymer conjugates |
| US7985839B2 (en) | 2006-03-31 | 2011-07-26 | Baxter International Inc. | Factor VIII polymer conjugates |
| US7645860B2 (en) * | 2006-03-31 | 2010-01-12 | Baxter Healthcare S.A. | Factor VIII polymer conjugates |
| BRPI0720282B8 (pt) * | 2006-12-15 | 2021-05-25 | Baxalta GmbH | construção proteica, composição farmacêutica, e, kit |
| CA3090908A1 (en) * | 2007-04-26 | 2008-11-06 | Aptevo Biotherapeutics Llc | Recombinant vitamin k dependent proteins with high sialic acid content and methods of preparing same |
| BRPI0813772A2 (pt) | 2007-06-26 | 2014-12-30 | Baxter Int | Composto, processo para a preparação de um composto, e, conjugado |
| LT2349342T (lt) * | 2008-10-17 | 2018-10-10 | Baxalta GmbH | Modifikuoti kraujo faktoriai, apimantys nedidelį vandenyje tirpaus polimero kiekį |
| EP2398822B1 (en) | 2009-02-19 | 2013-01-02 | Novo Nordisk A/S | Modification of factor viii |
| US12203113B2 (en) | 2009-07-09 | 2025-01-21 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
| CN104530182A (zh) | 2009-07-27 | 2015-04-22 | 利普森技术有限公司 | 非凝血蛋白的糖基多唾液酸化 |
| HRP20160916T1 (hr) | 2009-07-27 | 2016-11-18 | Baxalta GmbH | Konjugati proteina za koagulaciju krvi |
| US8809501B2 (en) | 2009-07-27 | 2014-08-19 | Baxter International Inc. | Nucleophilic catalysts for oxime linkage |
| US9795683B2 (en) | 2009-07-27 | 2017-10-24 | Lipoxen Technologies Limited | Glycopolysialylation of non-blood coagulation proteins |
| US8642737B2 (en) | 2010-07-26 | 2014-02-04 | Baxter International Inc. | Nucleophilic catalysts for oxime linkage |
| WO2011060242A2 (en) | 2009-11-13 | 2011-05-19 | Talecris Biotherapeutics, Inc. | Von willebrand factor (vwf)-containing preparations, and methods, kits, and uses related thereto |
| US20130040888A1 (en) | 2010-02-16 | 2013-02-14 | Novo Nordisk A/S | Factor VIII Molecules With Reduced VWF Binding |
| GB201007356D0 (en) | 2010-04-30 | 2010-06-16 | Leverton Licence Holdings Ltd | Conjugated factor VIIa |
| ES2731626T3 (es) | 2010-07-30 | 2019-11-18 | Baxalta Inc | Catalizadores nucleofílicos para enlace oxima |
| SG191298A1 (en) | 2010-12-22 | 2013-07-31 | Baxter Int | Materials and methods for conjugating a water soluble fatty acid derivative to a protein |
| CA2849673A1 (en) | 2011-09-23 | 2013-03-28 | Novo Nordisk A/S | Novel glucagon analogues |
| WO2013156488A2 (en) | 2012-04-16 | 2013-10-24 | Leverton Licence Holdings Limited | Optimised subcutaneous therapeutic agents |
| AU2013204754C1 (en) | 2012-05-16 | 2018-10-11 | Takeda Pharmaceutical Company Limited | Nucleophilic Catalysts for Oxime Linkage |
| CN104661685A (zh) * | 2012-10-15 | 2015-05-27 | 诺和诺德保健Ag（股份有限公司） | 因子vii缀合物 |
| CA3185756A1 (en) * | 2012-12-24 | 2014-07-03 | Coagulant Therapeutics Corporation | Short-acting factor vii polypeptides |
| PL2986313T3 (pl) | 2013-04-18 | 2019-12-31 | Novo Nordisk A/S | Stabilni, dłużej działający współagoniści receptora glp-1/glukagonu do zastosowań medycznych |
| AU2014336252A1 (en) | 2013-10-15 | 2016-04-07 | Novo Nordisk Health Care Ag | Coagulation factor VII polypeptides |
| US20150158926A1 (en) | 2013-10-21 | 2015-06-11 | Opko Biologics, Ltd. | Long-acting polypeptides and methods of producing and administering same |
| AR099340A1 (es) * | 2014-02-12 | 2016-07-13 | Novo Nordisk As | Conjugados del factor de coagulación ix |
| SG11201608006QA (en) * | 2014-04-11 | 2016-10-28 | Csl Ltd | Half-life extended factor fviia protein for prevention and treatment of bleeding and dosing regimens therefor |
| JP2017525656A (ja) | 2014-06-04 | 2017-09-07 | ノヴォ ノルディスク アー／エス | 医療用のｇｌｐ−１／グルカゴン受容体コアゴニスト |
| SG11201704706RA (en) | 2014-12-10 | 2017-07-28 | Opko Biologics Ltd | Methods of producing long acting ctp-modified growth hormone polypeptides |
| JP2015155469A (ja) * | 2015-06-01 | 2015-08-27 | 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 | 第ｆｖｉｉｉ因子ポリマー結合体 |
| WO2018011799A1 (en) * | 2016-07-11 | 2018-01-18 | Opko Biologics Ltd. | Long-acting coagulation factor vii and methods of producing same |
| JP2018115170A (ja) * | 2018-03-02 | 2018-07-26 | バクスアルタ ゲーエムベーハー | 第ｆｖｉｉｉ因子ポリマー結合体 |
| KR20210151780A (ko) * | 2019-02-04 | 2021-12-14 | 제네틱 바이오사이언시스, 인코포레이티드 | 글리코폴리시알화된 치료 단백질 사용 방법 |
Family Cites Families (135)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3487890A (en) | 1967-04-14 | 1970-01-06 | Boyles Bros Drilling Co | Core drilling system |
| US3847890A (en) | 1971-11-01 | 1974-11-12 | A Green | Acidic monosaccharide-substituted proteins |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| 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 |
| GR860984B (en) | 1985-04-17 | 1986-08-18 | Zymogenetics Inc | Expression of factor vii and ix activities in mammalian cells |
| 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 |
| 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 |
| AU1676992A (en) | 1991-03-18 | 1992-10-21 | 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 |
| CA2124690C (en) | 1992-10-02 | 2007-09-11 | Thomas Osterberg | Composition comprising coagulation factor viii formulation, process for its preparation and use of a surfactant as stabilizer |
| 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 |
| FR2700268B1 (fr) | 1993-01-13 | 1995-03-31 | Lvmh Rech | Composition cosmétique ou pharmaceutique, notamment dermatologique, contenant un extrait de Vismia. |
| AU6029594A (en) | 1993-01-15 | 1994-08-15 | Enzon, Inc. | Factor viii - polymeric conjugates |
| AU7097094A (en) | 1993-06-01 | 1994-12-20 | 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 |
| CA2204726A1 (en) | 1994-11-09 | 1996-12-27 | Robin E. Offord | Functionalized polymers for site-specific attachment |
| WO1996040731A1 (en) | 1995-06-07 | 1996-12-19 | Mount Sinai School Of Medicine Of The City University Of New York | Pegylated modified proteins |
| SE9503380D0 (sv) | 1995-09-29 | 1995-09-29 | Pharmacia Ab | Protein derivatives |
| US5763401A (en) | 1996-07-12 | 1998-06-09 | Bayer Corporation | Stabilized albumin-free recombinant factor VIII preparation having a low sugar content |
| DE69800640T2 (de) | 1997-01-29 | 2001-07-05 | Polymasc Pharmaceuticals Plc, London | Pegylationsverfahren |
| JP2002505574A (ja) | 1997-04-30 | 2002-02-19 | エンゾン，インコーポレイテッド | ポリアルキレンオキシド修飾された単鎖ポリペプチド |
| US6183738B1 (en) | 1997-05-12 | 2001-02-06 | Phoenix Pharamacologics, Inc. | Modified arginine deiminase |
| US6673575B1 (en) | 1997-12-03 | 2004-01-06 | Roche Diagnostics Gmbh | Method for preparing polypeptides with appropriate glycosilation |
| US5985263A (en) | 1997-12-19 | 1999-11-16 | Enzon, Inc. | Substantially pure histidine-linked protein polymer conjugates |
| EP1079805B1 (en) | 1998-04-27 | 2004-11-24 | Opperbas Holding B.V. | Pharmaceutical composition comprising factor viii and neutral liposomes |
| DE69914611T2 (de) | 1998-08-28 | 2004-12-23 | Gryphon Therapeutics, Inc., South San Francisco | Verfahren zur herstellung von polyamidketten von genauer länge und deren konjugate mit proteinen |
| HU229888B1 (en) | 1998-10-16 | 2014-11-28 | Biogen Idec Ma Inc Cambridge | Polymer conjugates of interferon betha-1a and uses |
| DE19852729A1 (de) | 1998-11-16 | 2000-05-18 | Werner Reutter | Rekombinante Glycoproteine, Verfahren zu ihrer Herstellung, sie enthaltende Arzneimittel und ihre Verwendung |
| DK2130554T3 (da) | 1999-02-22 | 2012-12-03 | Univ Connecticut | Albuminfrie faktor VIII-præparater |
| US6531122B1 (en) | 1999-08-27 | 2003-03-11 | Maxygen Aps | Interferon-β variants and conjugates |
| US7230081B1 (en) | 1999-11-12 | 2007-06-12 | Maxygen Holdings, Ltd. | Interferon gamma conjugates |
| JP2003521930A (ja) | 2000-02-11 | 2003-07-22 | マキシゲン・エイピーエス | 第ＶＩＩ因子または第ＶＩＩａ因子様分子 |
| US6586398B1 (en) | 2000-04-07 | 2003-07-01 | Amgen, Inc. | Chemically modified novel erythropoietin stimulating protein compositions and methods |
| ES2449224T3 (es) | 2000-05-03 | 2014-03-18 | Novo Nordisk Health Care Ag | Administración subcutánea del Factor de coagulación VII |
| DE60143292D1 (de) | 2000-05-03 | 2010-12-02 | Novo Nordisk Healthcare Ag | Varianten des menschlichen Koagulationsfaktors VII |
| CA2414076A1 (en) | 2000-06-08 | 2001-12-13 | La Jolla Pharmaceutical Company | Multivalent platform molecules comprising high molecular weight polyethylene oxide |
| 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 |
| PL204888B1 (pl) | 2000-09-13 | 2010-02-26 | Novo Nordisk Healthcare Ag | Wariant polipeptydu czynnika VII, konstrukcja kwasu nukleinowego, rekombinowana komórka gospodarza, zwierzę transgeniczne, sposób wytwarzania wariantu polipeptydu czynnika VII, kompozycja farmaceutyczna i zastosowanie wariantu polipeptydu czynnika VII |
| EP1325113B1 (en) * | 2000-10-02 | 2010-04-21 | Novo Nordisk Health Care AG | Factor vii glycoforms |
| DE60137525D1 (de) | 2000-10-16 | 2009-03-12 | Chugai Pharmaceutical Co Ltd | Peg-modifiziertes erythropoietin |
| WO2002077218A1 (en) | 2001-03-22 | 2002-10-03 | Novo Nordisk Health Care Ag | Coagulation factor vii derivatives |
| US6913915B2 (en) | 2001-08-02 | 2005-07-05 | Phoenix Pharmacologics, Inc. | PEG-modified uricase |
| US7795210B2 (en) | 2001-10-10 | 2010-09-14 | Novo Nordisk A/S | Protein remodeling methods and proteins/peptides produced by the methods |
| US8008252B2 (en) * | 2001-10-10 | 2011-08-30 | Novo Nordisk A/S | Factor VII: remodeling and glycoconjugation of Factor VII |
| ES2411007T3 (es) | 2001-10-10 | 2013-07-04 | Novo Nordisk A/S | Remodelación y glicoconjugación de péptidos |
| US7214660B2 (en) | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
| JP4758608B2 (ja) | 2001-11-07 | 2011-08-31 | ネクター セラピューティックス | 分枝ポリマーおよびそれらの結合体 |
| DE60228492D1 (de) | 2001-11-28 | 2008-10-02 | Neose Technologies Inc | Remodellierung von glycoproteinen unter verwendung von endoglycanasen |
| US7368108B2 (en) | 2001-11-28 | 2008-05-06 | Neose Technologies, Inc. | Glycopeptide remodeling using amidases |
| PT1517710E (pt) * | 2002-06-21 | 2011-07-08 | Novo Nordisk Healthcare Ag | Glicoformas do factor vii peguilado |
| MXPA04012496A (es) * | 2002-06-21 | 2005-09-12 | Novo Nordisk Healthcare Ag | Glicoformos del factor vii pegilados. |
| US7087229B2 (en) | 2003-05-30 | 2006-08-08 | Enzon Pharmaceuticals, Inc. | Releasable polymeric conjugates based on aliphatic biodegradable linkers |
| US7122189B2 (en) | 2002-08-13 | 2006-10-17 | Enzon, Inc. | Releasable polymeric conjugates based on aliphatic biodegradable linkers |
| KR101045401B1 (ko) | 2002-09-11 | 2011-06-30 | 프레제니우스 카비 도이치란트 게엠베하 | 하이드록시알킬 전분 유도체 |
| US20040062748A1 (en) | 2002-09-30 | 2004-04-01 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
| WO2004060965A2 (en) | 2002-12-31 | 2004-07-22 | Nektar Therapeutics Al, Corporation | Hydrolytically stable maleimide-terminated polymers |
| ATE399185T1 (de) | 2002-12-31 | 2008-07-15 | Nektar Therapeutics Al Corp | Maleinsäureamid polymerderivate und ihre biokonjugate |
| EP2572732A1 (en) | 2003-02-26 | 2013-03-27 | Nektar Therapeutics | Polymer-factor VIII moiety conjugates |
| EP1613261A4 (en) * | 2003-04-09 | 2011-01-26 | Novo Nordisk As | INTRA-CELLULAR FORMATION OF PEPTIDE CONJUGATES |
| EP1653996A2 (en) | 2003-08-08 | 2006-05-10 | Novo Nordisk Health Care AG | Use of galactose oxidase for selective chemical conjugation of protractor molecules to proteins of therapeutic interest |
| 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 |
| ES2294535T3 (es) | 2003-08-12 | 2008-04-01 | Lipoxen Technologies Limited | Derivados del acido polisialico. |
| WO2005016974A1 (en) | 2003-08-12 | 2005-02-24 | Lipoxen Technologies Limited | Sialic acid derivatives for protein derivatisation and conjugation |
| EP1673453A2 (en) | 2003-10-07 | 2006-06-28 | Novo Nordisk Health Care AG | Hybrid molecules having factor vii/viia activity |
| WO2005055950A2 (en) | 2003-12-03 | 2005-06-23 | Neose Technologies, Inc. | Glycopegylated factor ix |
| CA2552892C (en) | 2004-01-08 | 2014-08-05 | Neose Technologies, Inc. | O-linked glycosylation of peptides |
| KR100651220B1 (ko) | 2004-06-29 | 2006-11-29 | 씨제이 주식회사 | Ｌ-메씨오닌 생산 균주 및 상기 균주를 이용한ｌ-메씨오닌의 생산방법 |
| WO2006006168A2 (en) | 2004-07-14 | 2006-01-19 | Mali Arel | Feeding bottles |
| WO2006020372A2 (en) | 2004-07-23 | 2006-02-23 | Neose Technologies, Inc. | Enzymatic modification of glycopeptides |
| WO2006013202A2 (en) | 2004-08-02 | 2006-02-09 | Novo Nordisk Health Care Ag | Conjugation of fvii |
| EP1776389B1 (en) | 2004-08-12 | 2016-06-29 | Lipoxen Technologies Limited | Sialic acid derivatives |
| KR101483917B1 (ko) | 2004-11-12 | 2015-01-16 | 바이엘 헬스케어 엘엘씨 | Ｆｖｉｉｉ의 부위 지향 변형 |
| PL1835938T3 (pl) * | 2004-12-27 | 2014-01-31 | Baxalta Inc | Koniugaty polimer-czynnik von Willebrandta |
| US20100009902A1 (en) | 2005-01-06 | 2010-01-14 | Neose Technologies, Inc. | Glycoconjugation Using Saccharyl Fragments |
| US8217154B2 (en) * | 2005-02-23 | 2012-07-10 | Lipoxen Technologies Limited | Activated sialic acid derivatives for protein derivatisation and conjugation |
| CN101137396A (zh) * | 2005-03-11 | 2008-03-05 | 弗雷泽纽斯卡比德国有限公司 | 由无活性初始材料制备生物活性糖蛋白 |
| JP5216580B2 (ja) | 2005-05-25 | 2013-06-19 | ノヴォ ノルディスク アー／エス | グリコペグ化第ｉｘ因子 |
| ES2553160T3 (es) | 2005-06-17 | 2015-12-04 | Novo Nordisk Health Care Ag | Reducción y derivatización selectivas de proteínas Factor VII transformadas por ingeniería que comprenden al menos una cisteína no nativa |
| WO2007022784A2 (en) | 2005-08-26 | 2007-03-01 | Maxygen Holdings Ltd. | Liquid factor vii composition |
| JP5405122B2 (ja) | 2005-12-21 | 2014-02-05 | ワイス・エルエルシー | 低粘度のタンパク質製剤およびその用途 |
| US7982010B2 (en) | 2006-03-31 | 2011-07-19 | Baxter International Inc. | Factor VIII polymer conjugates |
| MX2008012600A (es) | 2006-03-31 | 2008-12-12 | Baxter Int | Factor viii pegilado. |
| US7645860B2 (en) | 2006-03-31 | 2010-01-12 | Baxter Healthcare S.A. | Factor VIII polymer conjugates |
| US7985839B2 (en) | 2006-03-31 | 2011-07-26 | Baxter International Inc. | Factor VIII polymer conjugates |
| US20090285780A1 (en) | 2006-05-24 | 2009-11-19 | Chyi Lee | Peg linker compounds and biologically active conjugates thereof |
| JP2007319283A (ja) * | 2006-05-31 | 2007-12-13 | Nippon Sherwood Medical Industries Ltd | 医療用バッグ |
| US7939632B2 (en) | 2006-06-14 | 2011-05-10 | Csl Behring Gmbh | Proteolytically cleavable fusion proteins with high molar specific activity |
| PL2049692T3 (pl) | 2006-07-13 | 2016-08-31 | Serum Inst India Ltd | Sposób wytwarzania poli(kwasu sialowego) o wysokiej czystości |
| KR101400105B1 (ko) | 2006-07-25 | 2014-06-19 | 리폭센 테크놀로지즈 리미티드 | Ｎ-말단 폴리시알화 |
| EP2054521A4 (en) | 2006-10-03 | 2012-12-19 | Novo Nordisk As | PROCESS FOR CLEANING POLYPEPTIDE CONJUGATES |
| BRPI0720282B8 (pt) | 2006-12-15 | 2021-05-25 | Baxalta GmbH | construção proteica, composição farmacêutica, e, kit |
| JP5558106B2 (ja) | 2007-01-03 | 2014-07-23 | ノボ ノルディスク ヘルス ケア アーゲー | 凝固第ｖｉｉ因子関連ポリペプチドの皮下投与 |
| WO2008119815A1 (en) | 2007-04-02 | 2008-10-09 | Novo Nordisk A/S | Subcutaneous administration of coagulation factor ix |
| BRPI0813772A2 (pt) | 2007-06-26 | 2014-12-30 | Baxter Int | Composto, processo para a preparação de um composto, e, conjugado |
| EP2173759A4 (en) | 2007-07-03 | 2014-01-29 | Childrens Hosp & Res Ct Oak | OLIGOSIAL INSERTS, PROCESS FOR THEIR PREPARATION AND ITS IMMUNOLOGICAL USE |
| WO2009047500A1 (en) | 2007-10-09 | 2009-04-16 | Polytherics Limited | Novel conjugated proteins and peptides |
| CN102037004A (zh) | 2008-01-08 | 2011-04-27 | 生物种属学股份公司 | 使用寡糖基转移酶的多肽的糖缀合 |
| RU2573587C2 (ru) | 2008-02-27 | 2016-01-20 | Ново Нордиск А/С | Конъюгированные молекулы фактора viii |
| CN102046205A (zh) | 2008-04-24 | 2011-05-04 | 凯尔特药物Peg有限公司 | 具有延长的半衰期的因子ix缀合物 |
| WO2009141433A1 (en) | 2008-05-23 | 2009-11-26 | Novo Nordisk Health Care Ag | Low viscosity compositions comprising a pegylated gla-domain containing protein |
| US20110104142A1 (en) | 2008-05-23 | 2011-05-05 | Novo Nordisk Health Care Ag | Formulations of peg-functionalised serine proteases with high concentrations of an aromatic preservative |
| MX2010013219A (es) | 2008-06-04 | 2011-04-11 | Bayer Healthcare Llc | Muteínas de fviii para el tratamiento de la enfermedad de von willebrand. |
| EP2326349B1 (en) | 2008-07-21 | 2015-02-25 | Polytherics Limited | Novel reagents and method for conjugating biological molecules |
| EP2352515A4 (en) | 2008-11-03 | 2012-04-25 | Bayer Healthcare Llc | METHOD FOR TREATING HEMOPHILIA |
| EP2387413A4 (en) | 2009-01-19 | 2015-12-23 | Bayer Healthcare Llc | PROTEIN CONJUGATE WITH AN ENDOPEPTIDASE-SPLICABLE BIOPROTEKTIVES PART |
| EP2398822B1 (en) | 2009-02-19 | 2013-01-02 | Novo Nordisk A/S | Modification of factor viii |
| WO2010100430A1 (en) | 2009-03-04 | 2010-09-10 | Polytherics Limited | Conjugated proteins and peptides |
| WO2010120365A2 (en) | 2009-04-16 | 2010-10-21 | Wu Nian | Protein-carrier conjugates |
| GB0908393D0 (en) | 2009-05-15 | 2009-06-24 | Almac Sciences Scotland Ltd | Labelling method |
| HRP20160916T1 (hr) | 2009-07-27 | 2016-11-18 | Baxalta GmbH | Konjugati proteina za koagulaciju krvi |
| US9795683B2 (en) | 2009-07-27 | 2017-10-24 | Lipoxen Technologies Limited | Glycopolysialylation of non-blood coagulation proteins |
| AU2010278721A1 (en) | 2009-07-31 | 2012-02-16 | Bayer Healthcare Llc | Modified factor IX polypeptides 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 |
| WO2011037896A2 (en) | 2009-09-25 | 2011-03-31 | Vybion, Inc. | Polypeptide modification |
| JP5827955B2 (ja) | 2009-11-24 | 2015-12-02 | ノヴォ・ノルディスク・ヘルス・ケア・アーゲー | Ｐｅｇ化タンパク質の精製方法 |
| US20130040888A1 (en) | 2010-02-16 | 2013-02-14 | Novo Nordisk A/S | Factor VIII Molecules With Reduced VWF Binding |
| GB201007356D0 (en) | 2010-04-30 | 2010-06-16 | Leverton Licence Holdings Ltd | Conjugated factor VIIa |
| GB201007357D0 (en) | 2010-04-30 | 2010-06-16 | Leverton Licence Holdings Ltd | Conjugated factor VIII |
| WO2012068134A1 (en) | 2010-11-15 | 2012-05-24 | Biogen Idec Inc. | Enrichment and concentration of select product isoforms by overloaded bind and elute chromatography |
| EP2729161B1 (en) | 2011-07-08 | 2018-12-19 | Bioverativ Therapeutics Inc. | Factor viii chimeric and hybrid polypeptides, and methods of use thereof |
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