# US 10,918,740 B2 · RNA containing composition for treatment of tumor diseases

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- Number: US 10,918,740 B2
- Document ID: US10918740B2
- Status: Granted
- Kind: B2
- Application number: 16/039,988
- Filed: 2018-07-19
- Published: 2019-02-21
- Granted: 2021-02-16
- Earliest claimed: 2015-04-22
- Assignees: CureVac AG
- Applicants: CureVac AG
- Inventors: Mariola Fotin-Mleczek; Aleksandra Kowalczyk; Regina Heidenreich; Patrick Baumhof; Jochen Probst; Karl-Josef Kallen
- Web page: https://patentgrep.com/patent/US10918740B2

## CPC

- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)}
- A61K 38/19: Cytokines; Lymphokines; Interferons
- A61K 38/191: {Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta}
- A61K 38/208: {IL-12}
- A61K 39/12: Viral antigens
- A61K 39/145: Orthomyxoviridae, e.g. influenza virus
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 48/0025: {wherein the non-active part clearly interacts with the delivered nucleic acid}
- A61K 48/0041: {the non-active part being polymeric}
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- C07K 16/30: from tumour cells
- C07K 16/34: against blood group antigens
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 15/117: Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/54: {characterised by the route of administration}
- A61K 2039/55511: {Organic adjuvants}
- A61K 2039/55522: {Cytokines; Lymphokines; Interferons}
- A61K 2039/55538: {IL-12}
- A61K 2039/55561: {CpG containing adjuvants; Oligonucleotide containing adjuvants}
- A61K 2039/585: {wherein the target is cancer}
- C07K 2317/75: Agonist effect on antigen
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C12N 2310/17: Immunomodulatory nucleic acids
- C12N 2320/30: Special therapeutic applications
- C12N 2760/16034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- 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
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention relates to RNA containing compositions for use in the treatment or prophylaxis of tumor and/or cancer diseases, to a pharmaceutical composition, to a kit and to uses of the RNA containing compositions for the treatment or prophylaxis of tumor and/or cancer diseases.

## Claims

### Claim 1

A method of treating solid tumor in a patient in need thereof, the method comprising administering intratumorally to the tumor in the patient a pharmaceutically effective amount of a composition comprising an mRNA encoding IL-23 and having at least about 90% identity to wild-type mature human IL-23, wherein the mRNA encoding IL-23 is complexed with one or more lipids, thereby forming liposomes, lipid nanoparticles and/or lipoplexes.

### Claim 2 (depends on 1)

The method of claim 1, further comprising the administration of at least a second anticancer therapy.

### Claim 3 (depends on 2)

The method of claim 2, wherein the second anticancer therapy is a chemotherapy, a hormone therapy, an immunotherapy, a checkpoint modulator therapy, a cytokine therapy, a radiation therapy, and/or a surgery.

### Claim 4 (depends on 3)

The method of claim 3, wherein the checkpoint modulator therapy is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, a LAG3 inhibitor, a TIM3 inhibitor, an OX-40 stimulator, a 4-1BB stimulator, a CD40L stimulator, a CD28 stimulator, and a GITR stimulator.

### Claim 5 (depends on 3)

The method of claim 3, wherein the checkpoint modulator therapy is selected from the group consisting of an agonistic antibody, an antagonistic antibody, a dominant negative receptor, a decoy receptor, and a ligand.

### Claim 6 (depends on 5)

The method of claim 5, wherein the antagonistic antibody is directed against PD-1, PD-L1, or CTLA-4.

### Claim 7 (depends on 5)

The method of claim 5, wherein the decoy receptor is a soluble PD-1 receptor.

### Claim 8 (depends on 5)

The method of claim 5, wherein the checkpoint modulator comprising a mRNA encoding an agonistic antibody, an antagonistic antibody, a dominant negative receptor, a decoy receptor, or a ligand.

### Claim 9 (depends on 1)

The method of claim 1, wherein the G/C content of the coding region of the mRNA is increased compared with the G/C content of the coding region of the wild type mRNA, and wherein the coded amino acid sequence of said G/C-enriched mRNA is not modified compared with the encoded amino acid sequence of the wild type mRNA.

### Claim 10 (depends on 1)

The method of claim 1, wherein the mRNA comprises a 5′-UTR element and/or a 3′-UTR element.

### Claim 11 (depends on 10)

The method of claim 10, wherein the mRNA comprises at least one histone stem-loop.

### Claim 12 (depends on 10)

The method of claim 10, wherein the mRNA comprises a 5′-CAP structure, a poly(A) sequence, and/or a poly(C) sequence.

### Claim 13 (depends on 1)

The method of claim 1, wherein the lipid is a cationic or polycationic lipid.

### Claim 14 (depends on 1)

The method of claim 1, wherein the cancer is prostate cancer, lung cancer, breast cancer, brain cancer, head and neck cancer, thyroid cancer, colon cancer, stomach cancer, liver cancer, pancreas cancer, ovary cancer, skin cancer, urinary cancer, bladder cancer, uterine cancer, lymphoma or cervical cancer.

### Claim 15 (depends on 1)

The method of claim 1, further comprising administering at least a second mRNA encoding a cytokine.

### Claim 16 (depends on 15)

The method of claim 15, comprising administering at least a second mRNA encoding IL-18.

### Claim 17 (depends on 1)

The method of claim 1, wherein the mRNA encoding IL-23 comprises a 5′-CAP structure and a poly(A) sequence, and wherein the composition is administered by injection into tumor tissue.

### Claim 18 (depends on 17)

The method of claim 17, further comprising administering at least a second mRNA encoding IL-18.

### Claim 19 (depends on 2)

The method of claim 2, wherein the second cancer therapy is administering at least a second mRNA encoding OX40L.