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US 2019/0134181 A1Published application
Immunomodulating composition for treatment
AssigneeAdmedus Vaccines Pty Ltd.
InventorsJulie DUTTON, Ian FRAZER
Life of this patent
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Abstract
Disclosed are therapeutic compositions and methods for inducing an immune response to human papillomavirus (HPV). More particularly, disclosed is a method for inducing an immune response in a subject by introducing and expressing a nucleic acid molecule encoding an immunogenic HPV antigen.
Claims27
A construct system for the treatment of human papillomavirus (HPV) infection in a subject, wherein the system comprises a first nucleic acid construct and a second nucleic acid construct,
- wherein the first construct comprises a first synthetic coding sequence that encodes a first polypeptide sequence comprising an HPV E6 amino acid sequence conjugated to a HPV E7 amino acid sequence, wherein the HPV E6 and E7 amino acid sequences are both distinguished from a wild-type HPV E6 and E7 coding sequences, respectively, by the replacement of selected codons in the wild-type HPV E6 or E7 coding sequence with synonymous codons, wherein an individual synonymous codon has a preference for producing a greater immune response than a corresponding selected codon, wherein the codon replacements are selected from TABLE 1, wherein at least about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%, of the codons for the first synthetic coding sequence are synonymous codons according to TABLE 1, and wherein the first synthetic coding sequence is operably connected to a regulatory nucleic acid sequence;
- and
- wherein the second construct comprises a second synthetic coding sequence that encodes a first polypeptide sequence comprising an HPV E6 amino acid sequence conjugated to a HPV E7 amino acid sequence, wherein the HPV E6 and E7 amino acid sequences are both distinguished from a wild-type HPV E6 and E7 coding sequences, respectively, by the replacement of selected codons in the wild-type HPV E6 or E7 coding sequence with synonymous codons, wherein an individual synonymous codon has a preference for producing a greater immune response than a corresponding selected codon, wherein the codon replacements are selected from TABLE 1, and wherein at least about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%, of the codons for the first synthetic coding sequence are synonymous codons according to TABLE 1, and wherein the first synthetic coding sequence is operably connected to a regulatory nucleic acid sequence;
- and to a nucleic acid sequence that encodes a ubiquitin molecule;
- and
- wherein TABLE 1 is as follows:
- TABLE 1
- Synonymous
- First Codon
- Codon
- AlaGCG
- AlaGCT
- AlaGCG
- AlaGCC
- AlaGCA
- AlaGCT
- AlaGCA
- AlaGCC
- AlaGCC
- AlaGCT
- ArgCGG
- ArgCGA
- ArgCGG
- ArgCGC
- ArgCGG
- ArgCGT
- ArgCGG
- ArgAGA
- ArgAGG
- ArgCGA
- ArgAGG
- ArgCGC
- ArgAGG
- ArgCGT
- ArgAGG
- ArgAGA
- AsnAAT
- AsnAAC
- AspGAT
- AspGAC
- CysTGT
- CysTGC
- GluGAG
- GluGAA
- GlyGGC
- GlyGGA
- GlyGGT
- GlyGGA
- GlyGGG
- GlyGGA
- IleATA
- IleATC
- IleATA
- IleATT
- IleATT
- IleATC
- LeuTTA
- LeuCTG
- LeuTTA
- LeuCTC
- LeuTTA
- LeuCTA
- LeuTTA
- LeuCTT
- LeuTTA
- LeuTTG
- LeuTTG
- LeuCTG
- LeuTTG
- LeuCTC
- LeuTTG
- LeuCTA
- LeuTTG
- LeuCTT
- LeuCTT
- LeuCTG
- LeuCTT
- LeuCTC
- LeuCTA
- LeuCTG
- LeuCTA
- LeuCTC
- PheTTC
- PheTTT
- ProCCG
- ProCCC
- ProCCG
- ProCCT
- ProCCA
- ProCCC
- ProCCA
- ProCCT
- ProCCT
- ProCCC
- SerAGT
- SerTCG
- SerAGT
- SerTCT
- SerAGT
- SerTCA
- SerAGT
- SerTCC
- SerAGC
- SerTCG
- SerAGC
- SerTCT
- SerAGC
- SerTCA
- SerAGC
- SerTCC
- SerTCC
- SerTCG
- SerTCA
- SerTCG
- SerTCT
- SerTCG
- ThrACT
- ThrACG
- ThrACT
- ThrACC
- ThrACT
- ThrACA
- ThrACA
- ThrACG
- ThrACA
- ThrACC
- ThrACC
- ThrACG
- TyrTAT
- TyrTAC
- ValGTA
- ValGTG
- ValGTA
- ValGTC
- ValGTA
- ValGTT
- ValGTT
- ValGTG
- ValGTT
- ValGTC
137 more elements
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Dependencies are inferred from the claim text.