# US 9,296,784 B2 · Mesothelin vaccines and model systems

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- Number: US 9,296,784 B2
- Document ID: US9296784B2
- Status: Granted
- Kind: B2
- Application number: 14/042,812
- Filed: 2013-10-01
- Published: 2014-02-20
- Granted: 2016-03-29
- Earliest claimed: 2002-07-12
- Assignees: The Johns Hopkins University
- Applicants: The Johns Hopkins University
- Inventors: Elizabeth Jaffee; Ralph Hruban
- Web page: https://patentgrep.com/patent/US9296784B2

## CPC

- A61K 39/0208: {Specific bacteria not otherwise provided for}
- A61K 39/001168: {Mesothelin [MSLN]}
- A61P 35/00: Antineoplastic agents
- A61P 37/04: Immunostimulants
- C07K 7/06: having 5 to 11 amino acids
- C07K 16/30: from tumour cells
- C12N 15/74: Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
- C12N 15/8509: {for producing genetically modified animals, e.g. transgenic}
- A01K 2267/0331: Animal model for proliferative diseases
- A61K 2039/505: {comprising antibodies}
- A61K 2039/5154: {Antigen presenting cells [APCs], e.g. dendritic cells or macrophages}
- A61K 2039/52: {Bacterial cells; Fungal cells; Protozoal cells}
- A61K 2039/522: {avirulent or attenuated}
- A61K 2039/523: {expressing foreign proteins}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/55511: {Organic adjuvants}
- A61K 2039/55522: {Cytokines; Lymphokines; Interferons}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- A61K 2039/6031: {Proteins}
- C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE}
- C12N 2710/16522: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2740/13043: viral genome or elements thereof as genetic vector
- 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)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.

## Claims

### Claim 1

A method of treating a patient with a cancer that overexpresses mesothelin relative to normal tissue from which the cancer is derived, said method comprising:
administering to the patient a composition comprising a polypeptide consisting of 9 to 25 contiguous amino acid residues of mesothelin, said polypeptide comprising VLPLTVAEV (SEQ ID NO: 2), under conditions in which a T-cell response to mesothelin is induced, wherein the composition does not comprise whole tumor cells.

### Claim 2 (depends on 1)

The method of claim 1 wherein the patient has undergone surgery to remove the cancer.

### Claim 3 (depends on 1)

The method of claim 1 wherein the cancer that overexpresses mesothelin is pancreatic cancer.

### Claim 4 (depends on 3)

The method of claim 3 wherein the patient has undergone surgery to remove the pancreatic cancer.

### Claim 5 (depends on 1)

The method of claim 1 wherein mesothelin-specific CD8+ T cells are induced in the patient.

### Claim 6 (depends on 1)

The method of claim 1 wherein the composition is acellular.

### Claim 7 (depends on 1)

The method of claim 1 wherein the composition comprises Listeria monocytogenes bacteria, and the bacteria express the polypeptide.

### Claim 8 (depends on 1)

The method of claim 1 wherein the composition is administered in sufficient amount to keep the patient tumor-free after removal of the tumor.

### Claim 9 (depends on 1)

The method of claim 1 wherein the composition comprises dendritic cells.

### Claim 10 (depends on 1)

The method of claim 1 wherein the tumor is selected from the group consisting of: ovarian cancer, pancreatic cancer, mesothelioma, and squamous cell carcinomas of the esophagus, lung, and cervix.

### Claim 11 (depends on 1)

The method of claim 1 wherein the polypeptide is fused to another polypeptide or a carrier protein.

### Claim 12 (depends on 11)

The method of claim 11 wherein the polypeptide is fused to a carrier protein and the carrier protein is selected from the group consisting of CD40 ligand, OX-40 ligand, CTLA-4 antagonist, and GM-CSF.

### Claim 13 (depends on 1)

The method of claim 1 wherein the polypeptide is less than 15 amino acid residues.

### Claim 14 (depends on 1)

The method of claim 1 wherein the polypeptide is less than 14 amino acid residues.

### Claim 15 (depends on 1)

The method of claim 1 wherein the polypeptide is less than 13 amino acid residues.

### Claim 16 (depends on 1)

The method of claim 1 wherein the polypeptide is less than 12 amino acid residues.

### Claim 17 (depends on 1)

The method of claim 1 wherein the polypeptide is less than 11 amino acid residues.

### Claim 18 (depends on 1)

The method of claim 1 further comprising the step of measuring induction of a T cell response.

### Claim 19 (depends on 1)

The method of claim 1 further comprising the step of measuring induction of mesothelin-specific CD8+ T cells.

### Claim 20 (depends on 1)

The method of claim 1 further comprising the step of measuring induction of a DTH response.

### Claim 21 (depends on 1)

The method of claim 1 further comprising the step of administering a carrier for stimulating a CD8+ T cell or CD4+ T cell immune response, wherein the carrier is selected from the group consisting of: (a) a bacterial cell that is transformed to express the polypeptide, (b) an antigen presenting cell on whose surface the polypeptide is bound, and (c) a protein selected from the group consisting of CD40, CD40 ligand, OX-40, OX-40 ligand, CTLA-4 antagonist, and GM-CSF.
