Hepatitis B core antigen fusion proteins

US7270821B2 · kind B2 · utility

Assignee

• University of Leeds Innovations Limited · GB

Inventors

• Annick Gehin · Leeds, GB
• Robert Owen Gilbert · Ithaca, US
• David Stuart · Felton, GB
• David Rowlands · Leeds, GB

Key dates

• Filing date: Apr 9, 2001
• Grant date: Sep 18, 2007
• Expiry date: Aug 30, 2021

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02A50/30
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The hepatitis B virus (HBV) capsid is made up of a single species of protein called the core antigen (HBcAg) which self-assembles into particles. The particles are highly immunogenic and are able to present heterologous epitopes to the immune system when the epitopes are inserted into a surface-exposed region of the particles called the “e1 loop”. The structural building blocks of the particles are tightly associated dimers of HBcAg in which the adjacent e1 loops are closely juxtaposed. It is proposed that sequences inserted into the e1 loop are conformationally restrained in the assembled particles when presented in monomeric core protein. The invention seeks to solve this problem by covalently linking core proteins as tandem copies (e.g., as dimers) so that insertions can be made independently in each copy. This is particularly useful for insertion of large sequences into the e1 loop because it allows such sequences to be inserted into just one copy of the core protein per tandem repeat, thereby reducing potential conformational clashes in assembly. Alternatively, a different sequence may be inserted into each e1 loop of a tandem repeat, thus increasing the flexibility of HBcAg p…