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    A CONCENTRATE OF THE ANTIHEMOPHILIC FACTOR VIII AND A PROCESS FOR PRODUCING IT
    1.
    发明授权
    A CONCENTRATE OF THE ANTIHEMOPHILIC FACTOR VIII AND A PROCESS FOR PRODUCING IT 失效
    抗血友病因子VIII浓缩物和它的制造工艺。

    公开(公告)号：EP0148843B2

    公开(公告)日：1994-05-04

    申请号：EP84901337.0

    申请日：1984-03-20

    申请人： NOVO NORDISK A/S

    发明人： RASMUSSEN, Mirella, Ezban ,  NORDFANG, Ole

    IPC分类号： A61K37/02 ,  A61K37/04 ,  A61K35/16 ,  C07K15/00

    CPC分类号： A61L2/0023 ,  A61K31/14 ,  A61K38/00 ,  A61L2/04 ,  C07K14/755 ,  Y10S530/83

    摘要： PCT No. PCT/DK84/00019 Sec. 371 Date Oct. 30, 1984 Sec. 102(e) Date Oct. 30, 1984 PCT Filed Mar. 20, 1984 PCT Pub. No. WO84/03628 PCT Pub. Date Sep. 27, 1984.Production of a high purity concentrate of the antihemophilic Factor VIII (AHF) by precipitation of an aqueous solution of cryoprecipitate from blood plasma in a first step with such an amount of polyethylene glycol (PEG), preferably about 4% by weight, as will precipitate a substantial amount of the present fibrinogen, subjecting the fibrinogen-free solution to a second precipitation step with preferably about 12% by weight of PEG in the presence of a salting-in agent, such as an amino acid, in particular lysine or arginine, or a carbohydrate, and then recovering the precipitate with a concentrated content of the present Factor VIII. The obtained Factor VIII concentrate with a very low content of immunoglobulins and other plasma proteins has a solubility in an aqueous injection medium of 45 to 500 units/ml and a high specific activity of up to 50 units/mg protein.

    A PROCESS FOR PRODUCING A COAGULATION ACTIVE COMPLEX OF FACTOR VIII FRAGMENTS
    8.
    发明授权
    A PROCESS FOR PRODUCING A COAGULATION ACTIVE COMPLEX OF FACTOR VIII FRAGMENTS 失效
    VERFAHREN ZUR HERSTELLUNG EINES KOAGULATIONSAKTIVEN KOMPLEXES VOM FAKTOR VIII-FRAGMENT。

    公开(公告)号：EP0272304B1

    公开(公告)日：1994-01-26

    申请号：EP87904383.4

    申请日：1987-06-24

    申请人： NOVO NORDISK A/S

    发明人： NORDFANG, Ole ,  RASMUSSEN, Mirella, Ezban

    IPC分类号： C07K15/06

    CPC分类号： C07K14/755

    摘要： A coagulation active complex of Factor VIII fragments is produced by causing a coagulation inactive FVIII heavy chain to react with a coagulation inactive FVIII light chain in the presence of a complex forming agent. Thus, FVIII-HC and FVIII-LC are converted to coagulation active FVIII complex in the presence of metal ions, such as Mn2+, Ca2+ or Co2+ or a component of the prothrombin complex or a substance having reactivity to compounds containing the group -SH and/or -S-S.

    摘要翻译： 通过在复合成形剂存在下使凝血活性FVIII重链与无凝血活性FVIII轻链反应来产生因子VIII片段的凝血活性复合物。 因此，在金属离子如Mn 2+，Ca 2+或Co 2+或凝血酶原复合物的组分存在下，将FVIII-HC和FVIII-LC转化为凝血活性FVIII复合物，或 对含有-SH和/或-SS基团的化合物具有反应性的物质。

    A PREPARATION FOR THE TREATMENT OF HEMOPHILIA A INHIBITOR PATIENTS AND A PROCESS FOR PRODUCING SUCH A PREPARATION
    10.
    发明授权
    A PREPARATION FOR THE TREATMENT OF HEMOPHILIA A INHIBITOR PATIENTS AND A PROCESS FOR PRODUCING SUCH A PREPARATION 失效
    用于治疗抑郁症患者的制剂和用于制备这种制剂的方法

    公开(公告)号：EP0201574B1

    公开(公告)日：1991-11-27

    申请号：EP85905784.6

    申请日：1985-11-05

    申请人： NOVO NORDISK A/S

    发明人： NORDFANG, Ole ,  RASMUSSEN, Mirella, Ezban

    IPC分类号： A61K37/02 ,  A61K37/04 ,  A61K35/16 ,  C07K15/06

    CPC分类号： C07K14/755 ,  A61K38/00 ,  Y10S514/834

    摘要： A preparation for the treatment of hemophilia A inhibitor patients contains a protein or peptide having a specific Factor VIII:CAg activity of at least 0.5, preferably at least 1 VIII:CAg unit per mg protein, the ratio between the VIII:CAg activity and the VIII:C procoagulant activity being greater than 5:1, preferably greater than 10:1. A fragment of Factor VIII:C, which displays a doublet of a molecular weight of 80/77 kD in electrophoresis, is reactive hemophilia A inhibitor antibodies and has VIII:CAg activity. This fragment and more low-molecular fragments of Factor VIII:C are capable of neutralizing the coagulation inhibiting effect of all tested antibodies. Such fragments can therefore be used as active component in preparations for providing immunotolerance towards Factor VIII:C in high-dose treatment of inhibitor patients. The peptides are moreover useful as an immunosorbent in specific extracorporeal adsorption treatment of inhibitor patients. The inhibitor reactive peptides can e.g. be recovered from plasma fractions by affinity chromatography, hydrophobic interaction chromatography or cation exchange or they may by produced biosynthetically and recovered in a similar manner.