# US 9,155,788 B2 · Application of mRNA for use as a therapeutic against tumour diseases

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- Number: US 9,155,788 B2
- Document ID: US9155788B2
- Status: Granted
- Kind: B2
- Application number: 14/325,850
- Filed: 2014-07-08
- Published: 2015-01-29
- Granted: 2015-10-13
- Earliest claimed: 2001-12-19
- Assignees: CureVac AG
- Applicants: Curevac GmbH
- Inventors: Ingmar Hoerr; Florian Von Der Mulbe; Steve Pascolo
- Web page: https://patentgrep.com/patent/US9155788B2

## 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 antitumour immune response in a subject comprising administering an effective amount of a cell-free composition comprising a mRNA encoding a MUC-1 tumour antigen to a subject having a tumour, thereby stimulating a T-cell mediated cytotoxic antitumor immune response in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the composition comprises at least one RNase inhibitor.

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 3)

The method of claim 3, wherein the cationic or polycationic agent is chosen from the group consisting of protamine, poly-L-lysine, poly-L-arginine and histones.

### Claim 5 (depends on 4)

The method of claim 4, wherein the mRNA is complexed with protamine.

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 6)

The method of claim 6, wherein the adjuvant is chosen from the Group consisting of lipopolysaccharide, TNF-α, CD40 ligand, GP96, oligonucleotides With aCpG motif, aluminium hydroxide, Freund's adjuvant, lipopeptides and cytokines.

### Claim 8 (depends on 7)

The method of claim 7, wherein the cytokine is GM-CSF.

### Claim 9 (depends on 1)

The method of claim 1, wherein the wherein the mRNA encoding MUC-1 is modified compared with the wild-type mRNA encoding MUC-1 such that it has no destabilizing sequence element.

### Claim 10 (depends on 1)

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

### Claim 11 (depends on 1)

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

### Claim 12 (depends on 11)

The method of claim 11, 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 13 (depends on 1)

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

### Claim 14 (depends on 1)

The method of claim 1, further comprising administering one or more additional mRNA(s) encoding additional tumour antigen(s) to the subject.

### Claim 15 (depends on 14)

The method of claim 14, further comprising administering mRNA encoding a PSA tumour antigen and mRNA encoding a PSM tumour antigen.

### Claim 16 (depends on 14)

The method of claim 14, further comprising administering mRNA encoding a MAGE tumour antigen and mRNA encoding a NY-ESO-1 tumour antigen.

### Claim 17 (depends on 1)

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

### Claim 18 (depends on 17)

The method of claim 17, wherein the mRNA is administered intradermally.

### Claim 19 (depends on 1)

The method of claim 1, wherein the mRNA is administered two or more times.

### Claim 20 (depends on 1)

The method of claim 1, wherein the subject has been determined to have a MUC-1 positive tumour.