Concatemeric peptide epitope RNAs
Inventors
Ciaramella, Giuseppe • Huang, Eric Yi-Chun • Valiante, Nicholas • Zaks, Tal
Assignees
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Publication Number
US-12150980-B2
Publication Date
2024-11-26
Expiration Date
Abstract
The invention relates to concatemeric peptide epitope RNAs, as well as methods and compositions thereof. mRNA vaccines are also provided according to the invention, including cancer vaccines.
Core Innovation
The invention relates to an mRNA cancer vaccine comprising an mRNA with an open reading frame encoding a concatemeric cancer antigen composed of 10-100 peptide epitopes. At least one of the 10-100 peptide epitopes is an MHC class I epitope, and the vaccine includes a lipid nanoparticle for delivery.
The lipid nanoparticle comprises ionizable cationic lipid, non-cationic lipid, sterol, and PEG-modified lipid, with molar percentage ranges for these components. The mRNA is described with standard components including a 5′ cap, 5′ UTR, open reading frame, 3′ UTR, and poly(A) tail, and can include nucleoside chemical modifications.
The concatemeric antigen is arranged as a concatemeric sequence and can include epitope processing features such as cleavage-sensitive sites and linkers. The concept also contemplates epitope length and presentation for MHC-I and MHC-II, recall antigen and neoepitope concatemer antigens, and mRNA sequence concepts such as 5′ cap forms.
Claims Coverage
The independent claims define an mRNA cancer vaccine with a concatemeric cancer antigen comprising 10-100 peptide epitopes and a lipid nanoparticle with defined molar percentage ranges, including a requirement that at least one epitope is an MHC class I epitope. The coverage is grounded on these core inventive features, with dependent claims further refining epitope and mRNA/lipid characteristics.
Concatemeric cancer antigen with 10-100 peptide epitopes
An mRNA comprising an open reading frame encoding a concatemeric cancer antigen comprising 10-100 peptide epitopes.
Lipid nanoparticle with defined molar percentages
The lipid nanoparticle comprises 20-60 mol% ionizable cationic lipid, 5-25 mol% non-cationic lipid, 25-55 mol% sterol, and 0.5-15 mol% PEG-modified lipid.
At least one MHC class I epitope
At least one of the 10-100 peptide epitopes encoded by the mRNA is an MHC class I epitope.
Proportional inclusion of MHC class II epitopes
At least 30% of the 10-100 peptide epitopes encoded by the mRNA are MHC class II epitopes.
Epitope structural features including linker and cleavage sensitivity
The mRNA further encodes peptide epitopes that are directly or linker-connected without a cleavage-sensitive site, including peptide epitopes of 25-35 amino acids containing a centrally located SNP-encoded mutation.
mRNA-encoded cytokine payload
The mRNA cancer vaccine further comprises an mRNA that encodes a cytokine.
Permissible chemical modifications of the mRNA nucleosides
The mRNA contains at least one chemical modification selected from a specified group of nucleoside analogs including pseudouridine, N1-methylpseudouridine, 2-thiouridine, 4′-thiouridine, 5-methylcytosine, and 2′-O-methyl uridine.
Overall claim coverage centers on an mRNA cancer vaccine where a concatemeric cancer antigen of 10-100 peptide epitopes is delivered via a lipid nanoparticle with a defined lipid composition, and the encoded epitope set includes at least one MHC class I epitope.
Stated Advantages
Not explicitly described in patent.
Documented Applications
mRNA cancer vaccine delivery using lipid nanoparticle formulations for RNA/mRNA vaccines.
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