Synthetic chimeric vaccinia virus
Inventors
Evans, David • Noyce, Ryan • Lederman, Seth
Assignees
Tonix Pharma Holdings Ltd • Tonix Pharma Ltd Ireland • Tonix Pharmaceuticals Holding Corp
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Publication Number
US-12529036-B2
Publication Date
2026-01-20
Expiration Date
Abstract
The invention relates in various aspects to a synthetic chimeric vaccinia virus or compositions comprising such viruses, and the development and use of systems and methods for producing such synthetic chimeric vaccinia viruses. The synthetic chimeric vaccinia viruses are well suited, among others, as virus vaccines or to generate an oncolytic response and pharmaceutical formulations.
Core Innovation
The invention is a synthetic chimeric vaccinia virus replicated and reactivated from DNA derived from chemically synthesized DNA. Its genome includes modifications that eliminate, add, or repair unique restriction sites relative to a wild-type vaccinia virus genome, and chemically synthesized left and right terminal hairpin loops, with one or both loops heterologous to the wild-type genome and having different tandem-repeat regions or a different number of repeats.
The disclosure also encompasses producing the synthetic chimeric vaccinia virus from chemically synthesized DNA fragments and terminal hairpins, utilizing a helper-virus system, and recovering virus particles [procedural detail omitted for safety]. In-vitro growth is reported as comparable to wild-type virus, with applications identified in vaccines, immune-response induction, cancer treatment, and heterologous gene expression.
Claims Coverage
The independent claims cover two inventive features: a synthetic chimeric vaccinia virus with specified genome and terminal hairpin characteristics, and a method of producing that virus from chemically synthesized DNA.
Synthetic chimeric vaccinia virus with modified restriction sites and terminal hairpins
The virus is replicated and reactivated from DNA derived from chemically synthesized DNA. The genome includes modifications that eliminate, add, or repair unique restriction sites relative to a wild-type vaccinia virus genome, and left and right terminal hairpin loops derived from chemically synthesized DNA, wherein one or both loops are heterologous to the wild-type genome and have different tandem-repeat regions or a different number of repeats.
Production of a synthetic chimeric vaccinia virus from chemically synthesized DNA
The method produces the synthetic chimeric vaccinia virus from chemically synthesized DNA fragments with restriction-site modifications and synthesized terminal hairpin loops that differ from wild type in their tandem-repeat regions or number of repeats. The process utilizes a helper-virus system and recovers the synthetic chimeric vaccinia virus from a mixture of virus particles [procedural detail omitted for safety].
The independent claims cover the synthetic chimeric vaccinia virus genome and terminal-hairpin features, as well as a method for producing and recovering the virus from chemically synthesized DNA.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Vaccine and immune-response applications against orthopoxviruses, including triggering or boosting an immune response, or immunizing a human subject against vaccinia virus, variola virus, or monkeypox virus.
Treatment of variola virus infection.
Oncolytic applications, including treatment of cancer.
Heterologous-gene-expression applications.
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