# US 12,473,554 B2 · MRNA treatment nanoparticles

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- Number: US 12,473,554 B2
- Document ID: US12473554B2
- Status: Granted
- Kind: B2
- Application number: 18/520,449
- Filed: 2023-11-27
- Published: 2024-05-16
- Granted: 2025-11-18
- Earliest claimed: 2020-04-22
- Assignees: Nutcracker Therapeutics, Inc.
- Applicants: Nutcracker Therapeutics, Inc.
- Inventors: Samuel Deutsch; Daniel Frimannsson; Nicole Fay; Colin McKinlay; Ole Haabeth
- Web page: https://patentgrep.com/patent/US12473554B2

## CPC

- B01L 3/502761: {specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules}
- C12N 15/117: Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
- A61K 9/145: {with organic compounds}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 39/12: Viral antigens
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/14: for RNA viruses
- A61P 35/00: Antineoplastic agents
- B01L 3/50273: {characterised by the means or forces applied to move the fluids}
- C07K 16/2818: {against CD28 or CD152}
- C12N 15/88: using microencapsulation, e.g. using {amphiphile} liposome vesicle
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/54: {characterised by the route of administration}
- A61K 2039/55522: {Cytokines; Lymphokines; Interferons}
- A61K 2039/55538: {IL-12}
- A61K 2039/892: {Reproductive system [uterus, ovaries, cervix, testes]}
- B01L 2300/0681: Filter
- B01L 2300/0819: Microarrays; Biochips
- B01L 2300/0887: Laminated structure
- B01L 2300/123: Flexible; Elastomeric
- B01L 2400/0481: squeezing of channels or chambers
- B01L 2400/0487: fluid pressure, pneumatics
- B01L 2400/0655: pinch valves
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Provided herein are examples of mRNA treatment nanoparticles and methods of using them to treat a patient. An mRNA treatment nanoparticle may include one or more mRNAs encoding a tumor-specific antigen and an immunomodulatory agent; and a delivery vehicle molecule encapsulating the one or more mRNAs.

## Claims

### Claim 1

A method comprising administering a therapeutic mRNA composition to a subject in need thereof, wherein the therapeutic mRNA composition comprises:
a first mRNA scaffold comprising a first mRNA coding region encoding HPV16 E6 E7;
a second mRNA scaffold comprising a second mRNA coding region encoding interleukin-12, wherein the second mRNA coding region has a nucleic acid sequence identical to SEQ ID NO:5; and
a third mRNA scaffold comprising a third mRNA coding region encoding tumor necrosis factor superfamily member 14 (TNFSF14) wherein the third mRNA coding region has a nucleic acid sequence identical to SEQ ID NO:11, and
wherein the first mRNA scaffold, the second mRNA scaffold and, the third mRNA scaffold are encapsulated in a delivery vehicle, wherein the delivery vehicle is selected from the group consisting of lipid nanoparticles, polymer-based nanoparticles, cationic lipids, ionizable lipids, amino-lipidated peptoids, amphipathic molecules/nanoparticles, and tertiary amino lipidated cationic peptoids.

### Claim 2 (depends on 1)

The method of claim 1, wherein the first mRNA scaffold and the second mRNA scaffold are encapsulated in a single delivery vehicle.

### Claim 3 (depends on 1)

The method of claim 1, wherein the first mRNA scaffold, the second mRNA scaffold, and the third mRNA scaffold are encapsulated in a single delivery vehicle.

### Claim 4 (depends on 1)

The method of claim 1, wherein the interleukin-12 has an amino acid sequence identical to SEQ ID NO:6.

### Claim 5 (depends on 1)

The method of claim 1, wherein the TNFSF14 has an amino acid sequence identical to SEQ ID NO:12.

### Claim 6 (depends on 1)

The method of claim 1, wherein the TNFSF14 is wild type TNFSF14.

### Claim 7 (depends on 1)

The method of claim 1, wherein the therapeutic mRNA composition further comprises an immunostimulator.

### Claim 8 (depends on 7)

The method of claim 7, wherein the immunostimulator comprises CpG oligodeoxynucleotides.

### Claim 9 (depends on 1)

The method of claim 1, wherein the therapeutic mRNA composition is administered via injection.

### Claim 10 (depends on 9)

The method of claim 9, wherein the therapeutic mRNA composition is administered via intratumoral injection.

### Claim 11 (depends on 10)

The method of claim 10, wherein the intratumoral injection is repeated at least one or more times with a wait between injections, wherein the wait is between about 1 and about 14 days.

### Claim 12 (depends on 1)

The method of claim 1, wherein the subject is known to have cervical cancer or pre-cancerous cervical indications.