Artificial Interferons - Interferon alpha 2 mutants with improved anti Hepatitis B virus activity

Ref.-Nr. 5850

Keywords: modified interferon IFNα2 with amino acids originating from IFNα14, antiviral therapy against chronic Hepatitis B infection

Interferons (IFNs) are used to treat certain chronic viral diseases, such as hepatitis B virus (HBV) infection. However, conventional interferon (IFNα2) inactivates HBV and prevents progressing liver damage in only about 25% of the treated patients with chronic hepatitis B. We found that the IFN subtype IFNα14 has much higher antiviral activity against HBV than IFNα2.

The invention comprises IFNα2 mutants achieved by designing an IFNα2 with amino acids from IFNα14, which significantly improved their antiviral activity against chronic HBV. As IFNα14 is not suitable for use as a drug, unlike IFNα2, and considering that the IFNα2 mutant is almost as effective as IFNα14, it appears that the IFNα2 mutant could be a viable option for clinical application.

Vorteile

  • Higher antiviral efficacy than conventional IFN2 therapy
  • High biocompatibility
  • IFNα2 as drug backbone is clinically well-established
  • Applies to a broad range of viruses

Kommerzielle Anwendung

On behalf of the University of Duisburg-Essen, PROvendis offers an exclusive licence for IFNα2 variants against chronic HBV.

 

Aktueller Stand

Assessment against HBVResults IFNα2 mutant

1. Antiviral (AV) activity

(HbsAg: Hepatitis B surface antigen ELISA; HBV DNA: qRT-PCR)

In vitro: IFNα2 mutant shows 28x higher AV activity compared to IFNα2 in differentiated hepatic cell lines (dHepaRG),

IFNα2 mutant shows 4x higher AV activity compared to IFNα2 in primary human hepatocytes (PHH)

In vivo: Data from transgenic mice expected in December 2023

2. Side effects in vivo

(Temperature curve, induction of cytokine storm)

No detectable side effects from IFNα2 mutant in transgenic mice (shortterm treatment)

3. Immune signaling

(Activation of non-classical downstream signaling pathways – Reporter cell assays)

IFNa2 mutant activated additional signaling pathways apart from the classical JAK-STAT signaling pathway of type I IFNs.

Technologie-Reifegrad

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Nachweis der Funktionstüchtigkeit

Relevante Veröffentlichungen

WO 2021/214054 A1

An invention of the University of Duisburg-Essen.

Dr. Jürgen Walkenhorst

jw@provendis.info
+49 208 9410537