[특허]Expression system for modulating an immune response

Expression system for modulating an immune response 원문보기

IPC분류정보
국가/구분	United States(US) Patent 등록
국제특허분류(IPC7판)	C40B-050/06 A61K-039/00 A61K-039/245 C07K-014/005 C12N-015/85 A61K-039/12
출원번호	US-0090932 (2011-04-20)
등록번호	US-9795658 (2017-10-24)
발명자 / 주소	Frazer, Ian Hector Dutton, Julie Louise
출원인 / 주소	Admedus Vaccines Pty Ltd
대리인 / 주소	Cooley LLP
인용정보	피인용 횟수 : 0 인용 특허 : 56

초록 ▼

The present invention discloses methods and compositions for modulating the quality of an immune response to a target antigen in a mammal, which response results from the expression of a polynucleotide that encodes at least a portion of the target antigen, wherein the quality is modulated by replacing at least one codon of the polynucleotide with a synonymous codon that has a higher or lower preference of usage by the mammal to confer the immune response than the codon it replaces.

대표청구항 ▼

1. A method for constructing a nucleic acid construct, comprising: (1) providing a synthetic polynucleotide from which a polypeptide is producible to confer a stronger or enhanced immune response to a target antigen in a mammal than that conferred by a parent polynucleotide that encodes the same polypeptide under the same conditions, wherein the synthetic polynucleotide is constructed by replacing at least 5% of codons in the parent polynucleotide with synonymous codons, wherein individual codon replacements are carried out by: (a) selecting a first codon of the parent polynucleotide for replacement with a synonymous codon, wherein the synonymous codon is selected on the basis that it exhibits a preference for producing a greater cellular or humoral immune response than the first codon in a comparison of codon preferences for producing the cellular or humoral immune response; and (b) replacing the first codon with the synonymous codon to construct the synthetic polynucleotide; and (2) operably connecting to the synthetic polynucleotide a nucleic acid sequence that encodes a protein-destabilizing element that increases processing and presentation of the polypeptide through the class I major histocompatibility (MHC) pathway wherein the first and synonymous codons are selected from TABLE 3: TABLE 3First CodonSynonymous CodonAlaGCGAlaGCTAlaGCAAlaGCTAlaGCCAlaGCTArgCGGArgCGAArgCGGArgCGTArgCGGArgAGAArgAGGArgCGAArgAGGArgCGTArgAGGArgAGAGluGAGGluGAAGlyGGCGlyGGAGlyGGTGlyGGAGlyGGGGlyGGALeuTTALeuCTALeuTTALeuCTTLeuTTALeuTTGLeuTTGLeuCTALeuTTGLeuCTTPheTTCPheTTTProCCGProCCTProCCAProCCTSerAGTSerTCGSerAGTSerTCTSerAGTSerTCASerAGCSerTCGSerAGCSerTCTSerAGCSerTCASerAGCSerTCCSerTCCSerTCGSerTCASerTCGSerTCTSerTCGThrACTThrACGThrACTThrACAThrACAThrACGThrACCThrACGValGTAValGTT. 2. The method according to claim 1, wherein the protein-destabilizing element is selected from the group consisting of a destabilizing amino acid at the amino-terminus of the polypeptide, a PEST sequence and an ubiquitin. 3. The method according to claim 1, wherein the synthetic polynucleotide confers a greater cellular or humoral immune response than the parent polynucleotide under the same conditions and wherein the first and synonymous codons are selected from TABLE 3, and wherein the target antigen is a herpes simplex virus antigen. 4. The method according to claim 3, wherein the herpes simplex virus antigen is a glycoprotein D. 5. The method according to claim 3, wherein the herpes simplex virus antigen is gD2. 6. The method according to claim 1, wherein the protein-destabilizing element is an ubiquitin. 7. The method according to claim 1, wherein the synthetic polynucleotide confers a greater cellular or humoral immune response than the parent polynucleotide under the same conditions and wherein the first and synonymous codons are selected from TABLE 3, and wherein the target antigen is a herpes simplex virus antigen and the protein-destabilizing element is an ubiquitin. 8. The method according to claim 7, wherein the herpes simplex virus antigen is a glycoprotein D. 9. The method according to claim 7, wherein the herpes simplex virus antigen is gD2. 10. The method according to claim 3, further comprising selecting a second codon of the parent polynucleotide for replacement with a synonymous codon, wherein the synonymous codon is selected on the basis that it exhibits a preference for producing a greater cellular or humoral immune response than the first codon in a comparison of codon preferences for producing the cellular or humoral immune response; and (b) replacing the second codon with the synonymous codon, wherein the first and synonymous codons are selected from TABLE 4: TABLE 4SecondSynonymousSecondSynonymousSecondSynonymousCodonCodonCodonCodonCodonCodonAlaGCGAlaGCTIleATAIleATCSerAGTSerTCGAlaGCGAlaGCCIleATAIleATTSerAGTSerTCTAlaGCAAlaGCTIleATTIleATCSerAGTSerTCAAlaGCAAlaGCCSerAGTSerTCCAlaGCCAlaGCTLeuTTALeuCTGSerAGCSerTCGLeuTTALeuCTCSerAGCSerTCTArgCGGArgCGALeuTTALeuCTASerAGCSerTCAArgCGGArgCGCLeuTTALeuCTTSerAGCSerTCCArgCGGArgCGTLeuTTALeuTTGSerTCCSerTCGArgCGGArgAGALeuTTGLeuCTGSerTCASerTCGArgAGGArgCGALeuTTGLeuCTCSerTCTSerTCGArgAGGArgCGCLeuTTGLeuCTAArgAGGArgCGTLeuTTGLeuCTTThrACTThrACGArgAGGArgAGALeuCTTLeuCTGThrACTThrACCLeuCTTLeuCTCThrACTThrACAAsnAATAsnAACLeuCTALeuCTGThrACAThrACGLeuCTALeuCTCThrACAThrACCAspGATAspGACThrACCThrACGPheuTTCPheTTTCysTGTCysTGCTyrTATTyrTACProCCGProCCCGluGAGGluGAAProCCGProCCTValGTAValGTGProCCAProCCCValGTAValGTCGlyGGCGlyGGAProCCAProCCTValGTAValGTTGlyGGTGlyGGAProCCTProCCCValGTTValGTGGlyGGGGlyGGAValGTTValGTC.

이 특허에 인용된 특허 (56)

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A62	인명구조; 소방(사다리 E06C)
A62B	인명구조용의 기구, 장치 또는 방법(특히 의료용에 사용되는 밸브 A61M 39/00; 특히 물에서 쓰이는 인명구조 장치 또는 방법 B63C 9/00; 잠수장비 B63C 11/00; 특히 항공기에 쓰는 것, 예. 낙하산, 투출좌석 B64D; 특히 광산에서 쓰이는 구조장치 E21F 11/00)
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Expression system for modulating an immune response 원문보기

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Expression system for modulating an immune response 원문보기

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