US 2026/0216307 A1 · MULTIEPITOPE VACCINE CASSETTES

Abstract

Disclosed herein are compositions that include antigen-encoding nucleic acid sequences having multiple iterations of KRAS neoepitope-encoding sequences and/or lacking immunodominant epitopes. Also disclosed are nucleotides, cells, and methods associated with the compositions including their use as vaccines.

Claims27

Dependent claims

-20. (canceled)

A composition for delivery of an antigen expression system, comprising:

the antigen expression system, wherein the antigen expression system comprises one or more vectors,
the one or more vectors comprising:
(a) a vector backbone, wherein the backbone comprises:
(i) at least one promoter nucleotide sequence, and
(ii) optionally, at least one polyadenylation (poly(A)) sequence;
and
(b) a cassette, wherein the cassette comprises:
(i) at least one antigen-encoding nucleic acid sequence, comprising:
(I) an epitope-encoding nucleic acid sequence encoding a KRAS-associated MHC class I neoepitope, and
wherein each of the epitope-encoding nucleic acid sequences comprises;
(A) optionally, a 5′ linker sequence, and
(B) optionally, a 3′ linker sequence;
(ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence;
and
(iii) optionally, at least one MHC class II epitope-encoding nucleic acid sequence;
(iv) optionally, at least one nucleic acid sequence encoding a GPGPG amino acid linker sequence (SEQ ID NO:56);
and
(v) optionally, at least one second poly(A) sequence, wherein the second poly(A) sequence is a native poly(A) sequence or an exogenous poly(A) sequence to the vector backbone,
wherein if the second promoter nucleotide sequence is absent, the antigen-encoding nucleic acid sequence is operably linked to the at least one promoter nucleotide sequence, and
wherein the at least one antigen-encoding nucleic acid sequence comprises at least two iterations of the epitope-encoding nucleic acid sequence encoding the KRAS-associated MHC class I neoepitope,
wherein at least one of the at least two KRAS-associated MHC class I neoepitopes is characterized by each of the following characteristics:
(i) the KRAS-associated MHC class I neoepitope is expressed in a tumor cell of a subject according to exome, transcriptome, or whole genome nucleotide sequencing data obtained from the subject;
(ii) the KRAS-associated MHC class I neoepitope comprises at least one alteration that makes the KRAS-associated MHC class I neoepitope distinct from a corresponding wild-type peptide expressed in a normal cell of the subject according to the exome, transcriptome, or whole genome sequencing data obtained from the subject;
and
(iii) the KRAS-associated MHC class I neoepitope is predicted to presented by an MHC allele on the surface of the tumor cell of the subject according to a presentation model trained on peptide-KRAS binding data.

22 more elements

A method for treating a subject with cancer, the method comprising administering to the subject an immunotherapy comprising an antigen-based vaccine to the subject, wherein the antigen-based vaccine comprises an antigen expression system, comprising:

the antigen expression system,
wherein the antigen expression system comprises one or more vectors,
the one or more vectors comprising:
(a) a vector backbone, wherein the backbone comprises:
(i) at least one promoter nucleotide sequence, and
(ii) optionally, at least one polyadenylation (poly(A)) sequence;
and
(b) a cassette, wherein the cassette comprises:
(i) at least one antigen-encoding nucleic acid sequence, comprising:
(I) an epitope-encoding nucleic acid sequence encoding a KRAS-associated MHC class I neoepitope, and
wherein each of the epitope-encoding nucleic acid sequences comprises;
(A) optionally, a 5′ linker sequence, and
(B) optionally, a 3′ linker sequence;
(ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence;
and
(iii) optionally, at least one MHC class II epitope-encoding nucleic acid sequence;
(iv) optionally, at least one nucleic acid sequence encoding a GPGPG amino acid linker sequence (SEQ ID NO:56);
and
(v) optionally, at least one second poly(A) sequence, wherein the second poly(A) sequence is a native poly(A) sequence or an exogenous poly(A) sequence to the vector backbone,
wherein if the second promoter nucleotide sequence is absent, the antigen-encoding nucleic acid sequence is operably linked to the at least one promoter nucleotide sequence, and wherein the at least one antigen-encoding nucleic acid sequence comprises at least two iterations of the epitope-encoding nucleic acid sequence encoding the KRAS-associated MHC class I neoepitope,
wherein at least one of the at least two KRAS-associated MHC class I neoepitopes is characterized by each of the following characteristics:
(i) the KRAS-associated MHC class I neoepitope is expressed in a tumor cell of a subject according to exome, transcriptome, or whole genome nucleotide sequencing data obtained from the subject;
(ii) the KRAS-associated MHC class I neoepitope comprises at least one alteration that makes the KRAS-associated MHC class I neoepitope distinct from a corresponding wild-type peptide expressed in a normal cell of the subject according to the exome, transcriptome, or whole genome sequencing data obtained from the subject;
and
(iii) the KRAS-associated MHC class I neoepitope is predicted to presented by an MHC allele on the surface of the tumor cell of the subject according to a presentation model trained on peptide-KRAS binding data.

22 more elements

Dependencies are inferred from the claim text.

Facts

Application

19/325,188Filed 10 Sep 2025

Priority

6 Aug 2020

Published

30 Jul 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification14 codes

A61K 39/001111
Receptors, cell surface antigens or cell surface determinants: immunoglobulin superfamily
A61K 39/0011
Vertebrate antigens: cancer antigens
A61K 40/4253
Enzymes: gTPases, e.g. Ras or Rho
A61P 35/00
Antineoplastic agents

Family

Application63/062,268Us provisional application · filed 6 Aug 2020

Application17/727,610Division · filed 22 Apr 2022

Application18/458,062Division · filed 29 Aug 2023

Application19/325,188Division

Application17/727,610Continuation

US 11,771,747 B2Related patent

US 2022/0265797 A1Published application

US 2024/0285739 A1Published application

US 2026/0216307 A1This patent

From the US filing history. Foreign family members aren’t listed.

Abstract

Claims27

Dependent claims

-20. (canceled)

A composition for delivery of an antigen expression system, comprising:

the antigen expression system, wherein the antigen expression system comprises one or more vectors,
the one or more vectors comprising:
(a) a vector backbone, wherein the backbone comprises:
(i) at least one promoter nucleotide sequence, and
(ii) optionally, at least one polyadenylation (poly(A)) sequence;
and
(b) a cassette, wherein the cassette comprises:
(i) at least one antigen-encoding nucleic acid sequence, comprising:
(I) an epitope-encoding nucleic acid sequence encoding a KRAS-associated MHC class I neoepitope, and
wherein each of the epitope-encoding nucleic acid sequences comprises;
(A) optionally, a 5′ linker sequence, and
(B) optionally, a 3′ linker sequence;
(ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence;
and
(iii) optionally, at least one MHC class II epitope-encoding nucleic acid sequence;
(iv) optionally, at least one nucleic acid sequence encoding a GPGPG amino acid linker sequence (SEQ ID NO:56);
and
(v) optionally, at least one second poly(A) sequence, wherein the second poly(A) sequence is a native poly(A) sequence or an exogenous poly(A) sequence to the vector backbone,
wherein if the second promoter nucleotide sequence is absent, the antigen-encoding nucleic acid sequence is operably linked to the at least one promoter nucleotide sequence, and
wherein the at least one antigen-encoding nucleic acid sequence comprises at least two iterations of the epitope-encoding nucleic acid sequence encoding the KRAS-associated MHC class I neoepitope,
wherein at least one of the at least two KRAS-associated MHC class I neoepitopes is characterized by each of the following characteristics:
(i) the KRAS-associated MHC class I neoepitope is expressed in a tumor cell of a subject according to exome, transcriptome, or whole genome nucleotide sequencing data obtained from the subject;
(ii) the KRAS-associated MHC class I neoepitope comprises at least one alteration that makes the KRAS-associated MHC class I neoepitope distinct from a corresponding wild-type peptide expressed in a normal cell of the subject according to the exome, transcriptome, or whole genome sequencing data obtained from the subject;
and
(iii) the KRAS-associated MHC class I neoepitope is predicted to presented by an MHC allele on the surface of the tumor cell of the subject according to a presentation model trained on peptide-KRAS binding data.

22 more elements

the antigen expression system,
wherein the antigen expression system comprises one or more vectors,
the one or more vectors comprising:
(a) a vector backbone, wherein the backbone comprises:
(i) at least one promoter nucleotide sequence, and
(ii) optionally, at least one polyadenylation (poly(A)) sequence;
and
(b) a cassette, wherein the cassette comprises:
(i) at least one antigen-encoding nucleic acid sequence, comprising:
(I) an epitope-encoding nucleic acid sequence encoding a KRAS-associated MHC class I neoepitope, and
wherein each of the epitope-encoding nucleic acid sequences comprises;
(A) optionally, a 5′ linker sequence, and
(B) optionally, a 3′ linker sequence;
(ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence;
and
(iii) optionally, at least one MHC class II epitope-encoding nucleic acid sequence;
(iv) optionally, at least one nucleic acid sequence encoding a GPGPG amino acid linker sequence (SEQ ID NO:56);
and
(v) optionally, at least one second poly(A) sequence, wherein the second poly(A) sequence is a native poly(A) sequence or an exogenous poly(A) sequence to the vector backbone,
wherein if the second promoter nucleotide sequence is absent, the antigen-encoding nucleic acid sequence is operably linked to the at least one promoter nucleotide sequence, and wherein the at least one antigen-encoding nucleic acid sequence comprises at least two iterations of the epitope-encoding nucleic acid sequence encoding the KRAS-associated MHC class I neoepitope,
wherein at least one of the at least two KRAS-associated MHC class I neoepitopes is characterized by each of the following characteristics:
(i) the KRAS-associated MHC class I neoepitope is expressed in a tumor cell of a subject according to exome, transcriptome, or whole genome nucleotide sequencing data obtained from the subject;
(ii) the KRAS-associated MHC class I neoepitope comprises at least one alteration that makes the KRAS-associated MHC class I neoepitope distinct from a corresponding wild-type peptide expressed in a normal cell of the subject according to the exome, transcriptome, or whole genome sequencing data obtained from the subject;
and
(iii) the KRAS-associated MHC class I neoepitope is predicted to presented by an MHC allele on the surface of the tumor cell of the subject according to a presentation model trained on peptide-KRAS binding data.

22 more elements

Dependencies are inferred from the claim text.

Multiepitope vaccine cassettes

Life of this patent

Abstract

Claims27

Multiepitope vaccine cassettes

Life of this patent

Abstract

Claims27