Recombinant virus with codon-pair deoptimized region and uses thereof for the treatment of cancer
Inventors
Coleman, John Robert • Mueller, Steffen • Yang, Chen • Wang, Ying • Stauft, Charles
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Assignees
MemberCodagenixCodagenixCodagenix is a clinical-stage synthetic biology company specializing in the design and development of live-attenuated vaccines and viral therapeutics for infectious diseases, cancer, and animal health. Utilizing a proprietary platform that combines codon deoptimization and synthetic biology, Codagenix rapidly engineers viral genomes to create stable, broadly immunogenic, and scalable solutions. Its pipeline includes vaccines targeting dengue, RSV, influenza, COVID-19, yellow fever, Zika, and foot-and-mouth disease, as well as virotherapeutics for cancer and animal health. The company partners with academic institutions, global health organizations, and federal agencies to address critical global health challenges.
Codagenix is a clinical-stage synthetic biology company specializing in the design and development of live-attenuated vaccines and viral therapeutics for infectious diseases, cancer, and animal health. Utilizing a proprietary platform that combines codon deoptimization and synthetic biology, Codagenix rapidly engineers viral genomes to create stable, broadly immunogenic, and scalable solutions. Its pipeline includes vaccines targeting dengue, RSV, influenza, COVID-19, yellow fever, Zika, and foot-and-mouth disease, as well as virotherapeutics for cancer and animal health. The company partners with academic institutions, global health organizations, and federal agencies to address critical global health challenges.
Publication Number
US-12178869-B2
Publication Date
2024-12-31
Expiration Date
Abstract
The present invention is the use of designed recombinant viruses for the treatment of various forms of malignant tumors. The recombinant viruses of the invention are those in which one or more regions of the wild type virus was exchanged with a synthetic recoded sequence that reduces the codon pair score relative to human codon pair bias, or that increase the number for CpG di-nucleotides, or that increases the number of UpA di-nucleotides. The method of the present invention is particularly useful for the treatment of malignant tumors in various organs, such as: breast, skin, colon, bronchial passage, epithelial lining of the gastrointestinal, upper respiratory and genito-urinary tracts, liver, prostate and the brain. Astounding remissions in experimental animals have been demonstrated for the treatment of malignant glioblastoma multiforme, as well as for the treatment of breast cancer and melanoma as well.
Core Innovation
The invention relates to treating a malignant tumor by administering a modified virus sequence directly derived from a wild-type virus. The modified virus includes a codon-pair deoptimized region obtained by substituting at least one genomic region of the wild-type virus with a region encoding the same protein sequence, and the modified virus has a codon pair bias that is less than the codon pair bias of the wild-type virus sequence.
The modified virus may be further modified by substituting genomic regions with regions with increased CpG di-nucleotide instances and/or increased UpA di-nucleotide instances, while encoding the same protein sequence. The modified virus is a modified influenza virus derived from an influenza A virus and comprises SEQ ID NO:5 or SEQ ID NO:6.
The disclosed treatment includes a prime dose and one or more boost doses of the modified virus sequence. The treatment is directed to malignant tumors, including glioblastoma, breast cancer, melanoma, and other listed cancer types, and includes outcome refinements such as reducing the likelihood of recurrence and stimulating an inflammatory and/or pro-inflammatory immune response or an anti-tumor immune response.
Claims Coverage
The document includes two independent methods of treating a malignant tumor. The claim set uses codon-pair deoptimization with reduced codon pair bias and optional CpG and/or UpA di-nucleotide increases while encoding the same protein sequence; a second independent claim adds a prime dose and boost dose regimen.
Codon-pair deoptimized modified influenza virus for malignant tumor treatment
Administering a modified virus directly derived from a wild-type influenza A virus by substituting at least one genomic region with a codon-pair deoptimized region encoding the same protein, where the codon pair bias of the modified virus sequence is less than the codon pair bias of the wild-type virus sequence and the modified virus comprises SEQ ID NO:5 or SEQ ID NO:6.
Optional CpG and/or UpA di-nucleotide increased modifications with same protein encoding
Optionally substituting at least one genomic region with a region with increased CpG di-nucleotide encoding the same protein sequence and/or a region with increased UpA di-nucleotide encoding the same protein sequence.
Prime dose and boost dose administration of codon-pair deoptimized modified influenza virus
Administering a prime dose of a modified influenza virus sequence and one or more boost doses of the same modified virus sequence, where the modified virus is directly derived from a wild-type influenza A virus by substituting at least one genomic region with a codon-pair deoptimized region encoding the same protein sequence to produce the modified virus sequence with reduced codon pair bias and the modified virus comprises SEQ ID NO:5 or SEQ ID NO:6.
Across the independent claims, the core claimed inventive concept is administration of a modified influenza virus derived from an influenza A wild-type virus in which genomic regions are substituted to create a codon-pair deoptimized region with reduced codon pair bias, optionally combined with CpG and/or UpA di-nucleotide increases while encoding the same proteins. The second independent claim further requires a prime dose followed by one or more boost doses using the same modified virus sequence.
Stated Advantages
Reducing the likelihood that the malignant tumor will recur.
Stimulating an inflammatory and/or pro-inflammatory immune response in the tumor and/or stimulating an anti-tumor immune response.
Documented Applications
Treating malignant tumors, including solid tumors.
Treating malignant tumors selected from glioblastoma, adenocarcinoma, melanoma, lung carcinoma, neuroblastoma, breast cancer, bladder cancer, colon cancer, prostate cancer, or liver cancer.
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