Repeated administration of natural ancrod to patients suffering from thrombotic diseases results in a stimulation of the immune system, which counteracts the pharmacological activity of the enzyme, limiting its clinical applicability. It has been suggested that the immunogenicity of ancrod may be due to the presence of its nonmammalian-type glycans. However, recombinant production of the enzyme appears to have overcome the problem . Ancrod has been produced by recombinant methods in different expression systems including E. coli and mouse fibroblast cells, in glycosylated and nonglycosylated forms. The recombinant protein has been purified from culture media by affinity and ionexchange chromatography with a purity level greater than 97%. The recombinant protein is considered more effective for therapy than the natural protein owing to its reduced immunogenicity and reduced hemorrhagic complications on its administration [85,86]. Viprinex is a commercial preparation of ancrod, which is licensed to Neurobiologic Technologies Inc. This product has recently completed phase-II clinical trials in the United States and is due to start phase-III trials in 2005. The preparation has been targeted for use in the treatment of acute ischemic stroke within 3 h of symptom onset, for which the only currently approved drug is tPA [87,88].
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