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US 12,383,589 B2Granted
Synthetic oncolytic LNP-replicon RNA and uses for cancer immunotherapy
AssigneesMassachusetts Institute of Technology, Ohio State Innovation Foundation
InventorsDarrell J. Irvine, Karl Dane Wittrup, Ron Weiss, Yingzhong Li, Noor Momin, Yizhou Dong
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Abstract
The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipid and a self-amplifying replicon RNA comprising a sequence that encodes an immunomodulatory molecule.
Claims19
A method for treating cancer in a subject in need thereof, comprising:
- administering to the subject an effective amount of a synthetic oncolytic virus, comprising:
- (i) a lipid nanoparticle comprising N1,N3,N5-tris(3-(didodecylamino)propyl)benzene-1,3,5-tricarboxamide (TT3);
- and
- (ii) a self-amplifying replicon ribonucleic acid (RNA) comprising a sequence that encodes an interleukin (IL)-12 molecule, wherein the IL-12 molecule is expressed by the self-amplifying replicon RNA.
1 more element
A method for treating cancer in a subject in need thereof, comprising:
- administering to the subject a pharmaceutical composition comprising a synthetic oncolytic virus and a pharmaceutically acceptable carrier;
- wherein the synthetic oncolytic virus comprises:
- (i) a lipid nanoparticle comprising TT3, 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and cholesterol;
- wherein the lipid nanoparticle is capable of triggering immunogenic cell death;
- and
- (ii) a self-amplifying replicon ribonucleic acid (RNA) comprising a sequence that encodes an interleukin (IL)-12 molecule;
- wherein the self-amplifying replicon RNA comprises the nucleotide sequence set forth in SEQ ID NO:
- 1, and wherein the IL-12 molecule is expressed by the self-amplifying replicon RNA;
- and
- wherein the pharmaceutical composition further comprises 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 (C14-PEG2000).
7 more elements
Dependencies are inferred from the claim text.