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Publication Number
US-9732325-B2
Publication Date
2017-08-15
Expiration Date
Abstract
The present invention relates to a novel Modified Vaccinia Ankara (MVA) virus. The present invention also relates to a method for culturing said MVA virus and to a method for producing said MVA virus. Further, the present invention relates to a pharmaceutical composition comprising said MVA virus and one or more pharmaceutical acceptable excipient(s), diluent(s), and/or carrier(s). Furthermore, the present invention relates to a vaccine comprising said MVA virus. In addition, the present invention relates to said MVA virus for use in medicine.
Core Innovation
The invention relates to a Modified Vaccinia Ankara (MVA) virus comprising a nucleic acid sequence encoding an A3L gene product and/or an A34R gene product, with at least one mutation that results in an amino acid sequence modification in defined regions of the A3L and/or A34R gene product according to SEQ ID reference positions. The mutation regions span amino acid positions 634 to 644 of the A3L gene product, or corresponding positions, and/or amino acid positions 81 to 91 of the A34R gene product, or corresponding positions.
The document further describes hyperattenuated, host-restricted MVA viruses generated or selected in chemically defined suspension culture on avian cell substrates, including CR and CR.pIX and chicken embryo fibroblast (CEF). Core mutations are described in structural proteins including A3L, A9L, and A34R, with amino acid substitutions associated with improved properties including infectious activity and higher extracellular infectious units.
The described MVA variants are positioned for increased industrial production yields and easier purification by isolating cell-free supernatant, as well as improved DNA purity. The patent context also includes genomic sequencing confirmation, functional assays assessing yield and attenuation in mammalian cell lines, and composition concepts for vaccine and pharmaceutical uses for the MVA variants and related nucleic acid constructs.
Claims Coverage
The claims coverage centers on one independent claim defining MVA viruses with defined mutation regions in the A3L and/or A34R gene products, with dependent claims adding inventive features by introducing an additional A9L gene product, narrowing mutation position constraints, and specifying permissible mutation types or particular substitution examples, including defined sequence identity constraints.
MVA with A3L and/or A34R mutation region modifications
A Modified Vaccinia Ankara (MVA) virus comprising a nucleic acid sequence encoding an A3L gene product and/or an A34R gene product, wherein the nucleic acid sequence comprises at least one mutation resulting in an amino acid sequence modification of said gene product(s), with the modification located in a region spanning amino acid positions 634 to 644 of the A3L gene product, or in a region spanning amino acid positions 81 to 91 of the A34R gene product, or corresponding positions.
Overall, the independent-claim-defined inventive core is mutation of defined residue regions in the A3L and/or A34R gene products in an MVA genome, with claim refinements in the dependent claims expanding coverage to include an additional A9L gene product and further constraining which amino-acid positions and substitution outcomes are permitted, including at least one variant definition tied to an A9L sequence identity threshold.
Stated Advantages
Improved infectious activity and higher extracellular infectious units for increased industrial production yields.
Easier purification via cell-free supernatant isolation.
Improved DNA purity.
Documented Applications
Vaccine and pharmaceutical composition uses are outlined for the MVA variants and related nucleic acid constructs.
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