Blood Coagulation FVIII Analogues

摘要

The invention is related to a FVIII analogue which has a circulation time in the blood stream before activation of at least about two times of that of native FVIII and a week after injection to a patient retains at least about 5% of the FVIII activity compared to the initial activity peak value reached after injection. The claimed FVIII analogues comprise a targeted disruption of one or more of the clearance sites in the FVIII molecule by introduction of at least one N-glycosylation site or by introduction of at least one Cys residue within or spatially close to the clearance site in the A2 domain or a combination thereof. The inserted cysteine residues may be further modified by conjugation with a chemical group increasing the molecular weight of the FVIII analogue.