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Publication Number
US-12742182-B2
Publication Date
2026-09-22
Expiration Date
Abstract
Provided herein is a novel immunologically-active alphavirus replicon vector which comprises a nucleic acid encoding alphavirus nonstructural proteins nsp1-4 and a cytokine protein(s)/polypeptide(s), which is useful for the treatment of a cancer and/or an inflammatory disease.
Core Innovation
The disclosure describes an alphavirus replicon vector encoding VEEV non-structural proteins nsp1–nsp4 and a cytokine, including IL-12 constructs with optional transmembrane domains and fusion elements. The vector or composition is delivered in an alphavirus particle or lipid nanoparticle. It provides cancer or inflammatory-disease treatment and immunization, including in combination with checkpoint inhibitors such as anti-PD-1.
The disclosure describes localized cytokine expression as an approach intended to limit systemic toxicity. It reports reduced tumor growth in mouse tumor models with IL-12 replicons, both alone and in combination with anti-PD-1, alongside changes in tumor-infiltrating lymphocytes. The background section itself is not included in the supplied text; therefore, the problem statement is not explicitly described in patent.
Claims Coverage
The supplied claims identify one independent claim, which covers an alphavirus replicon vector. Its claim elements are summarized in one inventive feature.
Alphavirus replicon vector encoding VEEV non-structural proteins and a cytokine
The claim covers an alphavirus replicon vector comprising a polynucleotide that encodes VEEV non-structural proteins nsp1, nsp2, nsp3, and nsp4, and a polypeptide comprising a cytokine with the specified amino acid sequence.
The independent claim centers on a vector encoding VEEV non-structural proteins and a cytokine. Dependent claims refine the encoded proteins, vector architecture, cytokine features, delivery composition, checkpoint-inhibitor combination, and treatment or immunization uses.
Stated Advantages
Localized cytokine expression is presented as an approach intended to limit systemic toxicity.
IL-12 replicons reduced tumor growth in the reported mouse tumor models, alone and in combination with anti-PD-1.
The reported tumor-infiltrating lymphocytes showed increased M1 relative to M2 macrophages and reduced regulatory T cells.
Documented Applications
Treatment of cancer or inflammatory disease, and immunization against cancer or inflammatory disease.
Use with checkpoint inhibitors, including anti-PD-1, for cancer treatment.
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