US 10,596,248 B2Granted

Immunomodulating composition for treatment

AssigneeJingang Medicine (Australia) Pty Ltd

InventorsJulie Dutton, Ian Frazer

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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.

Claims19

Dependent claims

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, and wherein the first synthetic coding sequence comprises the polynucleotide sequence set forth in SEQ ID NO:
7 and 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 encoded by a HPV E6 and E7 coding sequence, respectively, that are both distinguished from a wild-type HPV E6 and E7 coding sequence, 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
Wild-type 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.

138 more elements

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 encoded by a HPV E6 and E7 coding sequence, respectively, that are both distinguished from a wild-type HPV E6 and E7 coding sequence, 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, and wherein the second synthetic coding sequence comprises the polynucleotide sequence set forth in SEQ ID NO:
8 and 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
Wild-type
Synonymous
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.

138 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/060,410Filed 9 Dec 2016
Priority: AU 20159050999 Dec 2015
Published: US 2019/0134181 A19 May 2019
Granted: 24 Mar 2020
Term ends: Not estimatedThe source records don’t support an estimate.

Classification14 codes

A61K 39/12
Medicinal preparations containing antigens or antibodies: viral antigens
A61P 31/20
Antivirals: for DNA viruses
C07K 14/005
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof: from viruses
C07K 14/025
DNA viruses: papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus

Family

US 2019/0134181 A1Pre-grant publication · published 9 May 2019
US 10,596,248 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

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, and wherein the first synthetic coding sequence comprises the polynucleotide sequence set forth in SEQ ID NO:
7 and 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 encoded by a HPV E6 and E7 coding sequence, respectively, that are both distinguished from a wild-type HPV E6 and E7 coding sequence, 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
Wild-type 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.

138 more elements

Facts

Application

16/060,410Filed 9 Dec 2016

Priority

AU 20159050999 Dec 2015

Published

US 2019/0134181 A19 May 2019

Granted

24 Mar 2020

Term ends

Not estimatedThe source records don’t support an estimate.

Classification14 codes

A61K 39/12
Medicinal preparations containing antigens or antibodies: viral antigens
A61P 31/20
Antivirals: for DNA viruses
C07K 14/005
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof: from viruses
C07K 14/025
DNA viruses: papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus