Interferon-beta with enhanced bioavailability

With the indication of multiple sclerosis, interferon-beta (IFN-beta) possesses an increasing market value of over two billion US Dollars. The hydrophobicity of the human interferon-beta molecule however is unwanted both in terms of technical and pharmaceutical aspects. The resultant strong tendency of aggregation for example forces a high technical expenditure for the preparation of the protein in a pure state and affects yield, formulation, stability and bioavailability.

Therefore, at Fraunhofer IGB we have genetically engineered an IFN-beta variant with 9 hydrophobic amino acids substituted by a hydrophilic one which is better soluble (Figure 1) and possesses a higher bioavailability (Figure 3). The following amino acids were substituted by serine: Leu5, Phe8, Cys17, Leu47, Phe50, Leu106, Phe111, Leu116, and Leu120.

In the context of a worldwide valid and exclusive agreement the Vakzine project Management GmbH (VPM) undertakes the development of the patented protein variant expressed in mammalian cells pre-clinically and clinically up to the phase II. No later than after the successful completion of a phase II survey, if applicable even before, VPM strives for out licensing the protein variant on one of the great pharma enterprises.
VPM is a company founded due to an initiative of the Federal Ministry of Education and Research (BMBF) and the German Society for Biotechnological Research (GBF), Braunschweig, for commercializing and development of vaccines. The novel interferon-beta variant is registered as Soluferon®.
Recently, the formulation, the physical / chemical properties and the bioavailability have been examined on behalf of VPM at the Fraunhofer IGB. In addition, production processes were carried out (Figure 2), whereas the GMP-development of the test medication is realized in cooperation of VPM and Probiogen AG, Berlin.

The goal of this study (non-GLP conditions) was the determination of the pharmacokinetics of Soluferon® versus conventional interferon-beta in the blood plasma of rabbits. The new Soluferon® and the conventional interferon-beta were injected to the respective experimental animals subcutaneously for one time.
After application (see Table 1) blood tests were taken for plasma extraction (1-2 ml) at the following times: 0 h (before application), 1 h, 2 h, 3 h, 4 h, 5 h, 7 h, 9 h, 11 h, 12 h, 24 h, 48 h. The blood tests were centrifugated with 5000g for 10 minutes with 10 °C and then stored with -20 °C. The biological activity of Soluferon® in the 288 rabbit plasma samples was determined by means of the antiviral assay (AVA), usual for interferon-beta.

The determination of the antiviral effect in the blood plasma shows a higher biological activity of Soluferon® (Figure 3). The bioavailability was determined by calculating the area under the curve (AUC) using the trapezoidal rule for the groups 1-4 (see Table 1). Soluferon® possesses a bioavailability significantly higher by the factor 6 in comparison to conventional interferon-beta.