Interferon-beta with enhanced bioavailability

Indications and market value

Surface of the interferon-beta molecules variant IFN-beta Ser 17 and the new interferon-beta variant Soluferon®.
Figure 1: Surface of the interferon-beta molecules variant IFN-beta Ser 17 (left) and the new interferon-beta variant Soluferon® (right). The new interferon-beta is better soluble due to more hydrophilic regions (red).

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.

Pre-clinical and clinical development

Production of the new interferon-beta variant in the 10-liter fermenter.
Production of the new interferon-beta variant in the 10-liter fermenter.

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.

Design of Soluferon® pharmacokinetics study

Applikationsschema der Pharmakokinetik-Studie im Tierversuch.
Table 1: Application scheme of the pharmacokinetics study in animal experiments. IU: international units, BW: body weight.

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.

Result: Enhanced bioavailability

Figure 4: Pharmacokinetics of the new interferon-beta variant (red) in comparison to conventional interferon-beta (blue) in animal experiments (rabbits). Shown is the biological activity in the blood plasma after a single subcutaneous application. Time-related average plasma concentration of antiviral activity of group 1 (interferon-beta, 33 μg/animal) vs group 3 (Soluferon®, 33μg/animal). IU: international units BW: body weight

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.


Soluferon® has great potential as new drug on the world market, expected to have smaller side effects and an increased effectiveness. The new interferon-beta variant gives cause for hope to all multiple sclerosis patients and can possibly also be used for treatment of other illnesses, for example virus infections or cancer.