Application of mRNA for use as a therapeutic against tumour diseases
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-039/00
A61K-038/19
출원번호
US-0325850
(2014-07-08)
등록번호
US-9155788
(2015-10-13)
우선권정보
DE-101 62 480 (2001-12-19)
발명자
/ 주소
Hoerr, Ingmar
Von Der Mulbe, Florian
Pascolo, Steve
출원인 / 주소
CureVac GmbH
대리인 / 주소
Parker Highlander PLLC
인용정보
피인용 횟수 :
19인용 특허 :
42
초록▼
The present invention relates to a pharmaceutical composition comprising at least one mRNA comprising at least one coding region for at least one antigen from a tumor, in combination with an aqueous solvent and preferably a cytokine, e.g. GM-CSF, and a process for the preparation of the pharmaceutic
The present invention relates to a pharmaceutical composition comprising at least one mRNA comprising at least one coding region for at least one antigen from a tumor, in combination with an aqueous solvent and preferably a cytokine, e.g. GM-CSF, and a process for the preparation of the pharmaceutical composition. The pharmaceutical composition according to the invention is used in particular for therapy and/or prophylaxis against cancer.
대표청구항▼
1. A method of stimulating an antitumour immune response in a subject comprising administering an effective amount of a cell-free composition comprising a mRNA encoding a MUC-1 tumour antigen to a subject having a tumour, thereby stimulating a T-cell mediated cytotoxic antitumor immune response in t
1. A method of stimulating an antitumour immune response in a subject comprising administering an effective amount of a cell-free composition comprising a mRNA encoding a MUC-1 tumour antigen to a subject having a tumour, thereby stimulating a T-cell mediated cytotoxic antitumor immune response in the subject. 2. The method of claim 1, wherein the composition comprises at least one RNase inhibitor. 3. The method of claim 1, wherein the mRNA is complexed with at least one cationic or polycationic agent. 4. The method of claim 3, wherein the cationic or polycationic agent is chosen from the group consisting of protamine, poly-L-lysine, poly-L-arginine and histones. 5. The method of claim 4, wherein the mRNA is complexed with protamine. 6. The method of claim 1, administering one or more adjuvant(s) to the subject. 7. The method of claim 6, wherein the adjuvant is chosen from the Group consisting of lipopolysaccharide, TNF-α, CD40 ligand, GP96, oligonucleotides With aCpG motif, aluminium hydroxide, Freund's adjuvant, lipopeptides and cytokines. 8. The method of claim 7, wherein the cytokine is GM-CSF. 9. The method of claim 1, wherein the wherein the mRNA encoding MUC-1 is modified compared with the wild-type mRNA encoding MUC-1 such that it has no destabilizing sequence element. 10. The method of claim 1, wherein the wherein the mRNA comprises a 5′ cap structure, at least one IRES and/or a poly(A+) tail of at least about 25 nucleotides. 11. The method of claim 1, wherein the wherein the mRNA comprises at least one 5′-stabilizing sequence and/or at least one 3′-stabilizing sequence. 12. The method of claim 11, wherein the 5′- and/or the 3′-stabilizing sequence(s) is/are chosen from the group consisting of untranslated sequences (UTR) of the β-globin gene and a stabilizing sequence of the general formula (C/U)CCANxCCC(U/A)PyxUC(C/U)CC. 13. The method of claim 1, wherein the wherein the mRNA comprises least one analogue of naturally occurring nucleotide selected from the group consisting of phosphorothioates, phosphoroamidates, peptide nucleotides, methylphosphonates, 7-deazaguanosine, 5-methylcytosine and inosine. 14. The method of claim 1, further comprising administering one or more additional mRNA(s) encoding additional tumour antigen(s) to the subject. 15. The method of claim 14, further comprising administering mRNA encoding a PSA tumour antigen and mRNA encoding a PSM tumour antigen. 16. The method of claim 14, further comprising administering mRNA encoding a MAGE tumour antigen and mRNA encoding a NY-ESO-1 tumour antigen. 17. The method of claim 1, wherein the mRNA is administered by injection of an aqueous solution comprising the mRNA. 18. The method of claim 17, wherein the mRNA is administered intradermally. 19. The method of claim 1, wherein the mRNA is administered two or more times. 20. The method of claim 1, wherein the subject has been determined to have a MUC-1 positive tumour.
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