Immunomodulatory therapeutic MRNA compositions encoding activating oncogene mutation peptides
AssigneeModernaTX, Inc.
InventorsEric Yi-Chun Huang, Sze-Wah Tse, Jared Iacovelli, Kristine McKinney, Nicholas Valiante
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Abstract
The disclosure features immunomodulatory therapeutic compositions of an mRNA encoding an activating oncogene mutation peptide and an mRNA encoding a polypeptide that enhances immune responses to the activating oncogene mutation peptide, for example an mRNA encoding an immune potentiator. The disclosure also features methods of using the same, for example, to stimulate anti-cancer immune responses.
Claims44
An immunomodulatory therapeutic composition comprising an mRNA formulated in a lipid nanoparticle (LNP), wherein:
- the mRNA comprises an open reading frame encoding a concatemer of four KRAS activating oncogene mutation peptides, each of the KRAS activating oncogene mutation peptides having an amino acid sequence independently selected from the group consisting of SEQ ID NOs:
- 121, 36, 39, 122, 37, 40, 123, 38, 41, 124, 125, and 72.
An immunomodulatory therapeutic composition, comprising:
- an mRNA comprising an open reading frame encoding a concatemer of 3-10 KRAS activating oncogene mutation peptides, wherein each peptide is about 10-30 amino acids in length, and wherein each peptide comprises a mutation independently selected from the group consisting of G12D, G12V, G12C, G12S, G12A, G12R and G13D mutations in human KRAS of SEQ ID NO:
- 166.
An immunomodulatory therapeutic composition, comprising:
- an mRNA comprising an open reading frame encoding a concatemer of four KRAS activating oncogene mutation peptides, wherein each peptide is about 10-30 amino acids in length, wherein each peptide comprises a mutation independently selected from the group consisting of G12D, G12V, G12C, and G13D mutations in human KRAS of SEQ ID NO:
- 166, and wherein the peptides are linked directly to one another without a linker.
An immunomodulatory therapeutic composition comprising an mRNA formulated in a lipid nanoparticle (LNP), wherein:
- the mRNA comprises an open reading frame encoding a concatemer of four KRAS activating oncogene mutation peptides, the concatemer comprising amino acid sequence SEQ ID NO:
- 137;
- the LNP comprises a molar ratio of about 20-60% Compound 25:
- about 5-25% DSPC:
- about 25-55% cholesterol:
- about 0.1-15% PEG-DMG;
- and
- wherein one or more uridine nucleosides in the mRNA are N1-methylpseudouridine.
An immunomodulatory therapeutic composition comprising an mRNA formulated in a lipid nanoparticle (LNP), wherein:
- the mRNA comprises an open reading frame encoding a concatemer of four KRAS activating oncogene mutation peptides, each of the KRAS activating oncogene mutation peptides having an amino acid sequence independently selected from the group consisting of SEQ ID NOs:
- 39, 40, 41, and 72.
Dependencies are inferred from the claim text.