公开(公告)号：EP1969127B2

公开(公告)日：2017-07-12

申请号：EP06848864.2

申请日：2006-12-21

申请人： CNJ HOLDINGS, INC ,  University of North Carolina at Chapel Hill

发明人： DROHAN, William, N. ,  GRIFFITH, Michael, J. ,  TAYLOR, John, R. ,  STAFFORD, Darrel, W.

IPC分类号： C12N15/57 ,  C12P21/02

CPC分类号： C12P21/00 ,  C12N9/0006 ,  C12N9/6424 ,  C12N9/6429 ,  C12N9/6437 ,  C12N9/644 ,  C12N9/647 ,  C12N9/88 ,  C12Y101/04001 ,  C12Y304/21005 ,  C12Y304/21021 ,  C12Y304/21022 ,  C12Y401/0109

摘要： The invention relates to commercially viable methods for producing biologically active vitamin K dependent proteins, particularly Factor IX. Factor IX is produced at a level of at least about 15mg/L and is at least 25% biologically active. The method relies upon co-expression of one or more of paired basic amino acid converting encyme (PACE), vitamin K dependent epoxide reductase (VKOR) and vitamin K dependent ³-glutamyl carboxylase (VKGC) at a preferred ratio so that the vitamin K dependent protein is efficiently produced and processed by a recombinant cell.

摘要翻译： 本发明涉及用于生产生物活性维生素K依赖性蛋白质，特别是因子IX的商业上可行的方法。 因子IX以至少约15mg / L的水平产生并且具有至少25％的生物活性。 该方法依赖于以优选的比例共同表达配对的碱性氨基酸转换en（PACE），维生素K依赖性环氧化物还原酶（VKOR）和维生素K依赖性3-谷氨酰羧化酶（VKGC）中的一种或多种，​​使得维生素K 通过重组细胞有效地产生和加工蛋白质依赖性蛋白质。

公开(公告)号：EP2361932B1

公开(公告)日：2016-05-04

申请号：EP10182890.3

申请日：2004-05-06

申请人： Biogen Hemophilia Inc.

发明人： Peters, Robert T. ,  Mezo, Adam R ,  Rivera, Daniel S ,  Bitonti, Alan J ,  Stattel, James M ,  Low, Susan C

IPC分类号： C07K14/505 ,  C07K14/555 ,  C07K14/56 ,  C07K14/565 ,  C07K14/745 ,  C07K14/475 ,  C07K16/00 ,  C12N9/64 ,  C12N9/96 ,  A61K47/48

CPC分类号： C07K14/755 ,  A61K38/00 ,  A61K47/60 ,  A61K47/642 ,  A61K47/68 ,  A61K47/6803 ,  A61K47/6811 ,  A61K47/6813 ,  A61K47/6835 ,  C07K14/475 ,  C07K14/505 ,  C07K14/555 ,  C07K14/56 ,  C07K14/565 ,  C07K14/59 ,  C07K14/61 ,  C07K14/70503 ,  C07K14/745 ,  C07K16/00 ,  C07K2317/52 ,  C07K2319/00 ,  C07K2319/30 ,  C12N9/6437 ,  C12N9/644 ,  C12N9/647 ,  C12N9/96 ,  C12Y304/21021 ,  C12Y304/21022

摘要： A chimeric protein is synthesized by a) recombinantly expressing a fusion protein comprising at least a portion of an immunoglobulin constant region and a splicing protein capable of forming a C terminus thioester on the portion of an immunoglobulin constant region; b) adding a thiol cofactor to the fusion protein of a); and c) adding at least one biologically active molecule having an N terminal cysteine.

公开(公告)号：EP2357196B1

公开(公告)日：2016-05-04

申请号：EP10182902.6

申请日：2004-05-06

申请人： Biogen Hemophilia Inc.

发明人： Peters, Robert T. ,  Mezo, Adam R ,  Rivera, Daniel S ,  Bitoni, Alan J ,  Stattel, James M ,  Low, Susan C

IPC分类号： C07K14/505 ,  A61K47/48 ,  C07K14/555 ,  C07K14/56 ,  C07K14/565 ,  C07K14/745 ,  C07K14/475 ,  C07K16/00 ,  C12N9/64 ,  C12N9/96

CPC分类号： C07K14/755 ,  A61K38/00 ,  A61K47/60 ,  A61K47/642 ,  A61K47/68 ,  A61K47/6803 ,  A61K47/6811 ,  A61K47/6813 ,  A61K47/6835 ,  C07K14/475 ,  C07K14/505 ,  C07K14/555 ,  C07K14/56 ,  C07K14/565 ,  C07K14/59 ,  C07K14/61 ,  C07K14/70503 ,  C07K14/745 ,  C07K16/00 ,  C07K2317/52 ,  C07K2319/00 ,  C07K2319/30 ,  C12N9/6437 ,  C12N9/644 ,  C12N9/647 ,  C12N9/96 ,  C12Y304/21021 ,  C12Y304/21022

摘要： A chimeric protein is synthesized by a) recombinantly expressing a fusion protein comprising at least a portion of an immunoglobulin constant region and a splicing protein capable of forming a C terminus thioester on the portion of an immunoglobulin constant region; b) adding a thiol cofactor to the fusion protein of a); and c) adding at least one biologically active molecule having an N terminal cysteine.

公开(公告)号：EP2753706A4

公开(公告)日：2015-08-12

申请号：EP12830128

申请日：2012-08-31

申请人： MEDIMMUNE LLC

发明人： HUNTER ALAN ,  WANG XIANGYANG ,  PABST TIMOTHY ,  WENDELER MICHAELA ,  WANG JIHONG ,  CAREY KENDALL ,  STROUSE ROBERT ,  VARGHESE JOHNSON

IPC分类号： C12P21/02

CPC分类号： C12N9/6429 ,  C07K14/745 ,  C12N9/647

摘要： The present application relates to methods for purifying recombinant coagulation factor proteins, including for example, prothrombin (Factor II). In embodiments, the methods provide purified prothrombin that exhibit increased bioactivity and reduced levels of thrombin, thereby increasing the safety of the prothrombin. Also provided are purified recombinant coagulation factor proteins.

公开(公告)号：EP1991255B1

公开(公告)日：2015-06-17

申请号：EP07722853.4

申请日：2007-02-19

申请人： CSL Behring GmbH

发明人： SCHULTE, Stefan ,  HAUSER, Hans-Peter ,  KALINA, Uwe ,  WEIMER, Thomas

IPC分类号： C12N9/64 ,  A61K38/01 ,  A61K38/36

CPC分类号： C12N9/647 ,  A61K38/012 ,  A61K38/36 ,  C12N9/6432 ,  C12Y304/21006

公开(公告)号：EP2292748B1

公开(公告)日：2014-12-17

申请号：EP10185166.5

申请日：2004-10-12

申请人： Medlmmune Limited

发明人： Fenge, Christel ,  Lovgren, Ann ,  Thelin, Anders

IPC分类号： C12N9/64 ,  C12N9/74 ,  C12P21/02

CPC分类号： C12N9/647 ,  A61K38/00 ,  C12N9/6429 ,  C12P21/02 ,  C12Y304/21005

公开(公告)号：EP2526115A1

公开(公告)日：2012-11-28

申请号：EP11700547.0

申请日：2011-01-18

申请人： Novo Nordisk Health Care AG

发明人： BJELKE, Jais, Rose

IPC分类号： C07K1/22 ,  C07K14/745

CPC分类号： C12N9/647 ,  C07K14/745 ,  C12N9/644 ,  C12Y304/21022

摘要： The present invention relates to the purification of vitamin K-dependent blood coagulation factors, such as Factor IX (FIX). In particular, the invention provides a method for purifying Factor IX having a desired content of gamma-carboxyglutamic acid from a sample comprising a mixture of species of said Factor IX having different contents of gamma-carboxyglutamic acid, said method comprising the steps of: (a) loading said Factor IX sample onto an immunoaffinity chromatography material coupled to a binding moiety for gamma-carboxyglutamic acid; (b) eluting said Factor IX; and (c) selecting a fraction obtained from said elution wherein the polypeptides in the fraction have the desired content of gamma-carboxyglutamic acids; characterized in that the total concentration of Factor IX within said sample exceeds the binding ability of the immunoaffinity chromatography material.

公开(公告)号：EP2300497B1

公开(公告)日：2012-08-08

申请号：EP09769279.2

申请日：2009-06-24

申请人： Octapharma AG

发明人： BORGVALL, Carin ,  ERICSSON, Ulrika ,  GILLJAM, Gustav ,  JERNBERG, Mats ,  WINGE, Stefan

IPC分类号： C07K14/755

CPC分类号： C07K14/755 ,  A61K38/37 ,  B01D15/3847 ,  C12N9/647 ,  B01D15/3809

摘要： A process of purifying or enriching coagulation FVIII employing chromatography comprising the steps of providing a fraction containing FVIII in an aqueous solution having a high ionic strength; contacting the fraction containing FVIII with a multimodal resin; optionally washing the multimodal resin having FVIII adsorbed with an aqueous washing buffer; eluting FVIII containing fractions by an aqueous elution buffer comprising at least one amino acid which is positively charged at pH 6 to 8; and optionally collecting FVIII containing fractions in purified or enriched form.

公开(公告)号：EP2392655A3

公开(公告)日：2012-02-29

申请号：EP10177342.2

申请日：2004-09-09

申请人： Novo Nordisk Health Care AG

发明人： Østergaard, Henrik ,  Bjørn, Søren E. ,  Persson, Egon

IPC分类号： C12N9/64

CPC分类号： C07K14/745 ,  A61K38/00 ,  C12N9/6437 ,  C12N9/647 ,  C12Y304/21021

摘要： The present invention relates to novel coagulation Factor VII polypeptides, polynucleotide constructs encoding such polypeptides, as well as vectors and host cells comprising and expressing the polynucleotide, pharmaceutical compositions, uses and methods of treatment.

公开(公告)号：EP2292748A1

公开(公告)日：2011-03-09

申请号：EP10185166.5

申请日：2004-10-12

申请人： AstraZeneca AB

发明人： Fenge, Christel ,  Lovgren, Ann ,  Thelin, Anders

IPC分类号： C12N9/64 ,  C12N9/74 ,  C12P21/02

CPC分类号： C12N9/647 ,  A61K38/00 ,  C12N9/6429 ,  C12P21/02 ,  C12Y304/21005

摘要： The present invention relates to methods and tools for producing large quantities of gamma-carboxylated protein comprising: (i) culturing a cell adapted to express a protein which requires gamma-carboxylation and γ-glutamyl carboxylase in a ratio of at least 10:1, under conditions suitable for expression of both proteins, and (ii) isolating gamma-carboxylated protein

摘要翻译： 本发明涉及用于生产大量γ-羧化蛋白质的方法和工具，其包括：（i）培养适于表达需要γ-羧化的蛋白质的细胞和至少10:1的比例的3-谷氨酰羧化酶， 在适合表达两种蛋白质的条件下，和（ii）分离γ-羧化蛋白质