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Kafe 바로가기국가/구분 | United States(US) Patent 등록 |
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국제특허분류(IPC7판) |
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출원번호 | US-0043927 (2013-10-02) |
등록번호 | US-9597380 (2017-03-21) |
발명자 / 주소 |
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출원인 / 주소 |
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대리인 / 주소 |
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인용정보 | 피인용 횟수 : 2 인용 특허 : 399 |
The invention relates to compositions and methods for the manufacture and optimization of modified mRNA molecules via optimization of their terminal architecture.
1. A method of reducing a protein antigen-mediated immune response in a subject, comprising administering to the subject a composition comprising a chemically modified mRNA and a pharmaceutically acceptable carrier, wherein the chemically modified mRNA comprises (a) a 5′ untranslated region (5′ UTR)
1. A method of reducing a protein antigen-mediated immune response in a subject, comprising administering to the subject a composition comprising a chemically modified mRNA and a pharmaceutically acceptable carrier, wherein the chemically modified mRNA comprises (a) a 5′ untranslated region (5′ UTR);(b) a region of linked nucleosides encoding said protein antigen;(c) a 3′ untranslated region (3′ UTR) comprising at least one miR-142-3p microRNA binding site; and(d) a 3′ tailing region of linked nucleosides, wherein the chemically modified mRNA comprises fully modified 1-methyl pseudouridine nucleosides, and optionally comprises fully modified 5′ methyl-cytidine nucleosides, thereby reducing the protein antigen-mediated immune response in the subject. 2. The method of claim 1, wherein the first region of linked nucleosides is codon optimized. 3. The method of claim 1, wherein the chemically modified mRNA comprises fully modified 1-methyl pseudouridine nucleosides without fully modified 5′ methyl-cytidine nucleosides. 4. The method of claim 1, wherein the chemically modified mRNA comprises fully modified 1-methyl pseudouridine nucleosides and fully modified 5′ methyl-cytidine nucleosides. 5. The method of claim 1, wherein the miR-142-3p microRNA binding site comprises the sequence set forth in SEQ ID NO: 1404. 6. The method of claim 1, wherein the 3′ tailing region of linked nucleosides comprises a poly A tail of at least 100, at least 120, or at least 140 nucleosides. 7. The method of claim 1, wherein the chemically modified mRNA further comprises a 5′ cap structure. 8. The method of claim 7, wherein the 5′ cap structure comprises Cap1. 9. The method of claim 1, wherein the protein antigen is a therapeutic protein, cytokine, growth factor, antibody or fusion protein. 10. The method of claim 1, wherein the chemically modified mRNA is formulated with a liposome, lipoplex, or lipid nanoparticle. 11. The method of claim 10, wherein the chemically modified mRNA is formulated with a lipid nanoparticle. 12. The method of claim 11, wherein the lipid nanoparticle comprises a cationic or ionizable lipid. 13. The method of claim 12, wherein the cationic lipid is selected from the group consisting of DLin-MC3-DMA, DLin-DMA, C12-200 and DLin-KC2-DMA.
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