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US 11,717,548 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.
Claims22
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 RNA comprising a sequence that encodes an interleukin (IL)-12 molecule;
- and
- wherein the IL-12 molecule is expressed by the self-amplifying replicon RNA.
2 more elements
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;
- and
- (ii) a self-amplifying replicon RNA comprising a sequence that encodes an interleukin (IL)-12 molecule;
- wherein the self-amplifying replicon RNA comprises a nucleotide sequence that has at least 90% sequence identity to the sequence set forth in SEQ ID NO:
- 1;
- wherein the lipid nanoparticle is capable of triggering immunogenic cell death;
- wherein the IL-12 molecule is expressed by the self-amplifying replicon RNA;
- and
- wherein the pharmaceutical composition further comprises C14-PEG2000.
7 more elements
Dependencies are inferred from the claim text.