Interferons (IFNs) are a subclass of cytokines that exhibit both antiviral and antiproliferative activity, and is widely used in clinical treatment of hepatitis, inflammation and cancer. On the basis of biochemical and immunological properties, the naturally-occurring human interferons are grouped into three classes: interferon α (leukocyte), interferon β (fibroblast) and interferon γ (immune).
U.S. Pat. Nos. 4,695,623, 4,897,471 and 5,541,293 disclose human interferon polypeptides having amino acid sequences which include common or predominant amino acids found at each position among naturally-occurring alpha interferon subtype polypeptides and are referred to as consensus interferons (IFN-con). The IFN-con amino acid sequences disclosed are designated IFN-con1, IFN-con2, and IFNcon3. The preparation of manufactured genes encoding IFN-con and the expression of said genes in E. coli are also disclosed. In vitro studies comparing the relative antiviral, antiproliferative, and natural killer cell activities of recombinant IFN-con with either leukocyte or other recombinant type-one interferons demonstrate that IFN-con displays significantly higher activity when compared on a mass basis; Ozes et al., J Interferon Research, 12:55-59, 1992. U.S. FDA approved consensus Interferon developed by Amgen in 1997 (INFERGEN™)
There are two trends in developing interferon product: to develop highly-active interferon and long-acting interferon. Consensus interferon INFERGEN™ is representative of highly-active interferon. The activity of consensus interferon obtained by comparing more than ten kinds of natural interferon and designing artificial sequence is greatly higher than that of natural interferon (5-10 times). “Pegasys” and “PEG-Intron” developed by Roche Company and Schering-Plough Corporation respectively are long-acting interferon and their annual sales exceed $1 billions, thus they are “blockbuster” biological-technical drugs. The two drugs extend the half-life of interferon by PEG-modification, while the activity of product is largely dependent on the initial activity of the modified interferon. Therefore, the development of highly-active interferon is an important factor for further optimizing the efficacy of medicament.
INFERGEN™ is produced with Escherichia coli system, followed by a in vitro folding process (the inclusion body is processed by denaturant, and then is re-natured to make the active structure of denatured protein wholly resumed). However, studies revealed that although the activity of consensus interferon is significantly increased, the change of sequence hampers the folding in vitro.
Thus there is a need for improvement of consensus interferon.