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Publication Number
US-10098943-B2
Publication Date
2018-10-16
Expiration Date
Abstract
Provided is a virus like particle comprising one or more flavivirus structural proteins, and a composition or vaccine comprising thereof, its use in the prevention or treatment of flavivirus infection. The flavivirus structural protein contains at least one amino acid alteration in the envelope region. Examples of flavivirus contains dengue virus.
Core Innovation
The invention provides a virus like particle comprising a flavivirus envelope protein having an amino acid substitution at position 108 of SEQ ID NO: 20, or at a position determined as corresponding to position 108 of SEQ ID NO: 20 by alignment. The disclosure further describes envelope-region amino acid alterations including substitutions at defined positions identified through corresponding alignments relative to SEQ ID NO: 20.
The virus like particles are described in the context of flavivirus structural proteins, including prM protein and an envelope protein, where the envelope region contains one or more alterations. The provided variants include a dengue virus-like particle (DEN1 VLP) example with envelope-region substitutions including K203N and F108A, and additional described position-based substitutions such as K246M via corresponding alignment.
Beyond the particles themselves, the disclosure describes encoding nucleic acids and vectors to express the flavivirus structural proteins, including nucleic acid molecules encoding the virus like particle components and expression vectors. It further describes pharmaceutical or vaccine compositions comprising the virus like particle and/or encoded antigen, including adjuvants, and methods for inducing antibody and neutralizing antibody in mammals, as well as therapeutic or preventive methods against flavivirus infection disease, including dengue.
Claims Coverage
One independent claim is identified. It contains a core inventive feature centered on a flavivirus envelope protein substitution at position 108 of SEQ ID NO: 20 (or an alignment-corresponding position), with dependent claims further defining additional position-specific envelope substitutions and narrowing to specified flavivirus species and production/usage aspects.
Virus like particle with envelope substitution at position 108
A virus like particle comprising a flavivirus envelope protein, wherein said envelope protein comprises an amino acid substitution at position 108 of SEQ ID NO: 20, or at a position determined as corresponding to position 108 of SEQ ID NO: 20 by alignment.
Position 108 phenylalanine to alanine substitution
A virus-like particle of claim 1 is defined such that it contains a substitution at position 108 (or the position corresponding to 108) where phenylalanine is replaced by alanine.
Position 203 envelope substitution
A virus like particle whose envelope protein includes an amino acid substitution at position 203 of SEQ ID NO: 20 (or a corresponding position determined by alignment).
Position 246 lysine to methionine substitution
A virus-like particle according to claim 13 is defined such that the substitution at position 246 (or its corresponding position) changes lysine to methionine.
Specified flavivirus species for the virus like particle
The virus like particle according to claim 1, wherein the flavivirus is West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, or Japanese encephalitis virus.
Production by culturing transfected cells and recovering virus like particles
The claim covers producing virus-like particles by culturing transfected cells with a polynucleotide encoding the virus-like particle envelope protein and recovering the virus-like particles from the cell culture.
Across the independent claim and its refinements, the central claimed inventive aspect is an envelope protein with an amino acid substitution at position 108 of SEQ ID NO: 20 (or an alignment-corresponding position). Dependent refinements add additional envelope substitutions at defined positions (including position 203 and/or position 246), restrict the flavivirus species to listed examples, and include production by culturing transfected cells and recovering the virus like particles.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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