# US 2026/0240971 A1 · Compositions for treatment of diffuse intrinsic pontine glioma

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- Number: US 2026/0240971 A1
- Document ID: US20260240971A1
- Status: Published application
- Kind: A1
- Application number: 19/434,197
- Filed: 2025-12-29
- Published: 2026-08-20
- Earliest claimed: 2019-05-02
- Assignees: University of Florida Research Foundation, Inc.
- Applicants: University of Florida Research Foundation, Incorporated
- Inventors: Elias Sayour; James Andrew McGuiness; Hector Ruben Mendez-Gomez; Duane A. Mitchell
- Web page: https://patentgrep.com/patent/US20260240971A1

## CPC

- A61K 39/001114: {CD74, Ii, MHC class II invariant chain or MHC class II gamma chain}
- A61K 39/0011: {Cancer antigens}
- A61P 35/00: Antineoplastic agents
- C07K 14/47: from mammals
- C07K 14/70539: {MHC-molecules, e.g. HLA-molecules}
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- A61K 2039/80: {Vaccine for a specifically defined cancer}
- C07K 2319/00: Fusion polypeptide
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

Provided herein are compositions comprising a liposome comprising RNA molecules and a cationic lipid, wherein the RNA molecules encode at least one MHC Class II epitope of a mutant Histone 3 (H3) protein comprising a K27M mutation and optionally at least one MHC Class I epitope of the mutant H3 protein. In exemplary embodiments, the RNA molecules comprise a sequence of SEQ ID NO: 12 or 14. Methods of increasing central memory T cells, increasing an immune response, or treating a diffuse midline glioma (DMG), in a subject are provided herein. In exemplary embodiments, the methods comprise administering to the subject the compositions provided herein.

## Claims

### Claim at position 1

1-59. (canceled)

### Claim 60

A composition comprising a liposome comprising ribonucleic acid (RNA) molecules and a cationic lipid, wherein the RNA molecules encode at least one MHC Class II epitope (i) comprising at least 30 amino acids of a mutant Histone 3 (H3) protein comprising a K27M mutation and (ii) comprising an amino acid sequence of SEQ ID NO: 24, wherein the liposome has a zeta potential of about 30 mV to about 60 mV.

### Claim 61 (depends on 60)

The composition of claim 60, wherein the RNA molecules encode at least 2 MHC Class II epitope of the mutant H3 protein.

### Claim 62 (depends on 60)

The composition of claim 60, wherein the RNA molecules encode a peptide that binds to at least one or more human MHC Class II molecules.

### Claim 63 (depends on 60)

The composition of claim 60, wherein the liposome comprises RNA molecules that encode at least one MHC Class I epitope of the mutant H3 protein.

### Claim 64 (depends on 60)

The composition of claim 60, wherein the RNA molecules encode a peptide that binds to at least one or more human MHC Class I molecules.

### Claim 65 (depends on 60)

The composition of claim 60, wherein the cationic liposome is 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP).

### Claim 66 (depends on 60)

The composition of claim 60, wherein the composition comprises a plurality of liposomes, each liposome of which is about 50 nm to about 250 nm in diameter.

### Claim 67 (depends on 60)

The composition of claim 60, wherein the RNA molecules are complexed with the cationic lipid via electrostatic interactions.

### Claim 68 (depends on 60)

The composition of claim 60, wherein the RNA molecules comprise a 5′-cap.

### Claim 69 (depends on 60)

The composition of claim 60, wherein the RNA molecules further encode a lysosome-associated membrane protein (LAMP).

### Claim 70

A method of generating a liposome comprising ribonucleic acid (RNA) molecules and a cationic lipid, wherein the RNA molecules encode at least one MHC application Ser. No. 19/434,197 Class II epitope comprising at least 30 amino acids of a mutant Histone 3 (H3) protein comprising a K27M mutation and comprising an amino acid sequence of SEQ ID NO: 24, said method comprising (i) in vitro transcribing a nucleic acid comprising a nucleotide sequence encoding the RNA molecules, (ii) chemically adding a 5′-cap to the in vitro transcribed RNA molecules, and (iii) mixing the RNA molecules comprising the 5′-cap with a cationic lipid, wherein the liposome has a zeta potential of about 30 mV to about 60 mV.

### Claim 71 (depends on 70)

A liposome generated by the method of claim 70.

### Claim 72 (depends on 60)

A composition comprising the liposome of claim 60.

### Claim 73 (depends on 60)

A method of increasing in a subject the number of central memory T cells having antigen specificity for an epitope of a mutant Histone 3 (H3) protein comprising a K27M mutation, said method comprising administering to the subject a composition of claim 60 in an amount effective to increase the central memory T cells in the subject.

### Claim 74 (depends on 60)

A method of enhancing in a subject an immune response against a diffuse midline glioma (DMG) expressing a mutant Histone 3 (H3) protein comprising a K27M mutation, said method comprising administering to the subject a composition of claim 60 in an amount effective to increase an immune response against the DMG in the subject.

### Claim 75 (depends on 60)

A method of treating a subject with a diffuse midline glioma (DMG) expressing a mutant Histone 3 (H3) protein comprising a K27M mutation, said method comprising administering to the subject a composition of claim 60, in an amount effective to treat the DMG in the subject.