# US 9,433,670 B2 · Application of mRNA for use as a therapeutic against tumour diseases

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- Number: US 9,433,670 B2
- Document ID: US9433670B2
- Status: Granted
- Kind: B2
- Application number: 14/965,551
- Filed: 2015-12-10
- Published: 2016-03-31
- Granted: 2016-09-06
- Earliest claimed: 2001-12-19
- Assignees: CureVac AG
- Applicants: CureVac AG
- Inventors: Ingmar Hoerr; Florian Von Der Mülbe; Steve Pascolo
- Web page: https://patentgrep.com/patent/US9433670B2

## CPC

- A61K 38/193: {Colony stimulating factors [CSF]}
- A61K 9/0021: {Intradermal administration, e.g. through microneedle arrays or needleless injectors}
- A61K 39/001129: {Molecules with a "CD" designation not provided for elsewhere}
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 37/04: Immunostimulants
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/54: {characterised by the route of administration}
- A61K 2039/55522: {Cytokines; Lymphokines; Interferons}
- A61K 2039/572: {cytotoxic response}
- A61K 2039/70: {Multivalent vaccine}
- 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

## Abstract

The present invention relates to a pharmaceutical composition comprising at least one mRNA comprising at least one coding region for at least one antigen from a tumor, in combination with an aqueous solvent and preferably a cytokine, e.g. GM-CSF, and a process for the preparation of the pharmaceutical composition. The pharmaceutical composition according to the invention is used in particular for therapy and/or prophylaxis against cancer.

## Claims

### Claim 1

A method of stimulating an antitumor immune response in a subject comprising administering an effective amount of a cell-free composition comprising mRNA encoding an MAGE antigen to a subject in need thereof, thereby stimulating a T-cell mediated cytotoxic anticancer immune response in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject has a cancer.

### Claim 3 (depends on 2)

The method of claim 2, wherein the cancer is a lung or skin cancer.

### Claim 4 (depends on 1)

The method of claim 1, wherein the composition comprises mRNA encoding at least 2, 3, 4 or 5 different tumor antigens.

### Claim 5 (depends on 1)

The method of claim 1, wherein the method further comprises administering at least 2, 3, 4 or 5 different cell-free compositions comprising mRNA encoding different tumor antigens to the subject.

### Claim 6 (depends on 1)

The method of claim 1, wherein the mRNA is complexed with at least one cationic or polycationic agent.

### Claim 7 (depends on 6)

The method of claim 6, wherein the cationic or polycationic agent is chosen from the group consisting of protamine, poly-L-lysine, poly-L-arginine and histones.

### Claim 8 (depends on 7)

The method of claim 7, wherein the mRNA is complexed with protamine.

### Claim 9 (depends on 1)

The method of claim 1, further comprising administering one or more adjuvant(s) to the subject.

### Claim 10 (depends on 9)

The method of claim 9, wherein the adjuvant is chosen from the group consisting of lipopolysaccharide, TNF-α, CD40 ligand, GP96, oligonucleotides with a CpG motif, aluminum hydroxide, Freund's adjuvant, a lipopeptide and a cytokine.

### Claim 11 (depends on 10)

The method of claim 10, wherein the cytokine is GM-CSF.

### Claim 12 (depends on 1)

The method of claim 1, wherein the mRNA encoding the antigen has a different nucleic acid sequence compared with the wild-type mRNA encoding the antigen.

### Claim 13 (depends on 1)

The method of claim 1, wherein the mRNA comprises a 5′ cap structure, at least one IRES and/or a poly(A+) tail of at least 25 nucleotides.

### Claim 14 (depends on 13)

The method of claim 13, wherein the mRNA comprises a 5′ cap structure and a poly(A+) tail of at least 25 nucleotides.

### Claim 15 (depends on 1)

The method of claim 1, wherein the mRNA comprises at least one 5′-stabilizing sequence and/or at least one 3′-stabilizing sequence.

### Claim 16 (depends on 15)

The method of claim 15, wherein the 5′- and/or the 3′-stabilizing sequence(s) is/are chosen from the group consisting of untranslated sequences (UTR) of the β-globin gene and a stabilizing sequence of the general formula (C/U)CCANxCCC(U/A)PyxUC(C/U)CC.

### Claim 17 (depends on 1)

The method of claim 1, wherein the mRNA comprises at least one analog of naturally occurring nucleotide selected from the group consisting of phosphorothioates, phosphoroamidates, peptide nucleotides, methylphosphates, 7-deazaguanosine, 5-methylcytosine and inosine.

### Claim 18 (depends on 1)

The method of claim 1, wherein the cell-free composition comprising mRNA is administered by injection of an aqueous solution comprising the mRNA.

### Claim 19 (depends on 1)

The method of claim 1, wherein the cell-free composition comprising mRNA is administered intradermally.

### Claim 20 (depends on 1)

The method of claim 1, wherein the cell-free composition comprising mRNA is administered two or more times.