preparation on the basis of factor viii for the treatment of haemofili a inhibitorpatienter and procedure for the manufacture of such a preparation

摘要

PCT No. PCT/DK85/00105 Sec. 371 Date Jun. 20, 1986 Sec. 102(e) Date Jun. 20, 1986 PCT Filed Nov. 5, 1985 PCT Pub. No. WO86/02838 PCT Pub. Date May 22, 1986.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 VI-II: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 be biosynthetically and recovered in a similar manner.