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FORNY20-FORNY2020

KVAL: Design of long-acting SARS-COV-2 neutralizing antibodies

Alternative title: Design av langtidsvirkende SARS-COV-2 nøytraliserende antistoffer

Awarded: NOK 0.50 mill.

Elderly and immunocompromised patients may not raise protective vaccine-induced immunity against the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As such, there is an urgent need for specific treatment that prevents development of severe coronavirus disease 19 (COVID-19). Generation of monoclonal antibodies that can specifically target the virus followed by blocking of infection and elimination from the body is an attractive strategy for both therapy and preventing treatment, which is supported by recent emerging clinical data. However, antibody treatment is expensive and unfortunately not necessarily available for those that are in need at a global scale. As such, we have in partnership with the international non-profit organizations isolated fully-human monoclonal antibodies that effectively block all relevant SARS-CoV-2 strains of concern. The antibodies bind to independent and conserved binding sites on the spike protein, and as such, can therefore be given as a cocktail. However, the uptake and availability of such monoclonal antibodies have been extremely limited due to high doses required and intravenous formulations. In this project, we have tested a unique antibody technology, patented and developed by us, to investigate whether the technology can be used to extend the plasma half-life and improve the distribution of IgG1 monoclonal antibodies directed against SARS-CoV-2. The results show that the monoclonal antibodies combined with the technology can be produced as efficiently as the parental antibodies. Furthermore, we show that the technology provides significantly extended duration of action in a humanized mouse model under optimal conditions that are predictive of pharmacokinetics in a human setting. The encouraging data now motivates verification of the technology in non-human primates.

Resultatene viser at en unik antistoff-teknologi kombinert med to uavhengige anti-SARS-CoV2 IgG-antistoffer gir betydelig forlenget halveringstid i en optimal humanisert dyremodell. Teknologien påvirker verken produksjon av antistoffene eller evne til å nøytralisere SARS-CoV-2 negativt. Prosjektet har derved lykkes med å vise at en egenutviklet antistoff-teknologi kan benyttes til å forlenge virkningstiden til monoklonale antistoffer, noe som er svært gunstig ved profylaktisk behandling av infeksjonssykdommer. Dataene generert vil være viktige i den videre kommersialiseringsfasen hvor vi nå kan vise til konkrete eksempler i fra den aller beste musemodellen tilgjengelig for dette formålet. Målet videre er å vise konseptet i ikke-humane aper samtidig som vi aktivt vil arbeide for at teknologien kommer til anvendelse.

Funding scheme:

FORNY20-FORNY2020