Viral vectors for cancer therapy
Inventors
Krishnan, Suma • PARRY, Trevor • PREVITE, Dana Michelle • DUERMEYER, Mary Jane
Assignees
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Publication Number
US-11779660-B2
Publication Date
2023-10-10
Expiration Date
Abstract
The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding an immunomodulatory polypeptide (e.g., a pro-inflammatory cytokine such as a human IL-2 or IL-12 polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of cancer, such as lung cancer); and articles of manufacture or kits thereof.
Core Innovation
The invention relates to pharmaceutical compositions comprising a herpes simplex virus comprising a recombinant herpes simplex virus genome. The recombinant herpes simplex virus genome comprises a polynucleotide encoding an Interleukin (IL)-2 polypeptide and a polynucleotide encoding an IL-12 polypeptide, together with a pharmaceutically acceptable excipient.
The recombinant herpes simplex virus genome does not comprise a polynucleotide encoding a Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) polypeptide. The genome comprises an inactivating mutation in an Infected Cell Polypeptide (ICP) 22 herpes simplex virus gene, and additional inactivating mutations in one or more herpes simplex virus genes selected from ICP0, ICP4, ICP27, ICP47, thymidine kinase (tk), UL41, and UL55 are also described.
The recombinant herpes simplex virus approach is framed across HSV-1/HSV-2 and includes replication defective and replication competent populations. The description further relates the recombinant virus to target tissues such as the human airway/respiratory tract and to reducing cytotoxicity and reducing impact on target cell proliferation relative to wild-type HSV.
Claims Coverage
The independent claims are clm-00001 and clm-00017. Across these two independent claims, there are 4 core inventive features: recombinant HSV genomes encoding IL-2 and IL-12, exclusion of GM-CSF, an ICP22 inactivating mutation, and population-level limitations including replication phenotype and pharmaceutically acceptable excipient.
Recombinant HSV genome encoding IL-2 and IL-12
A pharmaceutical composition comprising a herpes simplex virus comprising a recombinant herpes simplex virus genome, wherein the recombinant herpes simplex virus genome comprises a polynucleotide encoding an Interleukin (IL)-2 polypeptide and a polynucleotide encoding an IL-12 polypeptide.
Exclusion of GM-CSF polynucleotide
The recombinant herpes simplex virus genome does not comprise a polynucleotide encoding a Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) polypeptide.
ICP22 inactivating mutation
The recombinant herpes simplex virus genome comprises an inactivating mutation in an Infected Cell Polypeptide (ICP) 22 herpes simplex virus gene.
Replication-defective or replication-competent population
A pharmaceutical composition consisting essentially of a population of herpes simplex viruses, wherein the population of herpes simplex viruses is either all replication defective or all replication competent, and wherein the population comprises recombinant herpes simplex virus genomes comprising a polynucleotide encoding an IL-2 polypeptide and a polynucleotide encoding an IL-12 polypeptide; and a pharmaceutically acceptable excipient.
Collectively, the independent claims cover herpes simplex virus-based pharmaceutical compositions with recombinant genomes encoding IL-2 and IL-12, combined with an inactivating mutation in ICP22; one claim additionally excludes GM-CSF, and the other defines the population as either all replication defective or all replication competent.
Stated Advantages
Reduced cytotoxicity compared with a corresponding wild-type herpes simplex virus population.
Reduced impact on target cell proliferation.
Documented Applications
Human airway/respiratory tract targeting context, including target cells such as respiratory tract/airway epithelial cells and the lung, within a cancer/respiratory delivery context.
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