# US 10,441,645 B2 · MSLN targeting DNA vaccine for cancer immunotherapy

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- Number: US 10,441,645 B2
- Document ID: US10441645B2
- Status: Granted
- Kind: B2
- Application number: 15/785,743
- Filed: 2017-10-17
- Published: 2018-03-08
- Granted: 2019-10-15
- Earliest claimed: 2013-12-18
- Assignees: Vaximm AG
- Applicants: Vaximm GmbH
- Inventors: Marco Springer; Heinz Lubenau
- Web page: https://patentgrep.com/patent/US10441645B2

## CPC

- A61P 35/00: Antineoplastic agents
- C12N 1/20: Bacteria; Culture media therefor
- A61K 39/001168: {Mesothelin [MSLN]}
- C12N 1/205: Bacterial isolates
- C12N 1/36: Adaptation or attenuation of cells
- A61K 2039/522: {avirulent or attenuated}
- A61K 2039/523: {expressing foreign proteins}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/542: {oral/gastrointestinal}
- C12R 2001/42: Salmonella
- 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
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- C12R: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention relates to an attenuated mutant strain of Salmonella comprising a recombinant DNA molecule encoding Mesothelin. In particular, the present invention relates to the use of said attenuated mutant strain of Salmonella in cancer immunotherapy.

## Claims

### Claim 1

A method for treating or vaccinating a patient against a cancer comprising administering to the patient an attenuated mutant strain of Salmonella comprising at least one copy of a recombinant DNA molecule comprising an expression cassette encoding Mesothelin (MSLN), wherein the MSLN is human MSLN, the attenuated mutant strain of Salmonella is Salmonella typhi Ty21a, and wherein the expression cassette is a eukaryotic expression cassette.

### Claim 2 (depends on 1)

The method of claim 1, wherein the recombinant DNA molecule further comprises the kanamycin antibiotic resistance gene, the pMB1 ori, and wherein the eukaryotic expression cassette encoding human MSLN is under the control of a CMV promoter, wherein the human MSLN has the nucleic acid sequence as found in SEQ ID NO:2.

### Claim 3 (depends on 1)

The method of claim 1, wherein the method further comprises administration of one or more further strain(s) of Salmonella comprising at least one copy of a recombinant DNA molecule comprising an expression cassette encoding a tumor antigen and/or a tumor stroma antigen, and wherein the one or more further strain(s) of Salmonella is/are Salmonella typhi Ty21a comprising a eukaryotic expression cassette.

### Claim 4 (depends on 3)

The method of claim 3, wherein the one or more further strain(s) of Salmonella typhi Ty21a of claim 3, is co-administered with the attenuated mutant strain of Salmonella typhi Ty21a.

### Claim 5 (depends on 1)

The method of claim 1, wherein the method further comprises administering chemotherapy, radiotherapy or a checkpoint inhibitory antibody to the patient.

### Claim 6 (depends on 1)

The method of claim 1, wherein the attenuated mutant strain of Salmonella typhi Ty21a is administered orally.

### Claim 7 (depends on 1)

The method of claim 1, wherein the cancer is selected from mesotheliomas, ovarian and pancreatic cancers, squamous cell carcinomas of the cervix, head and neck, vulva, lung and esophagus, lung adenocarcinomas, endometrial carcinomas, biphasic synovial sarcomas, desmoplastic small round cell tumors, and gastric adenocarcinomas.

### Claim 8 (depends on 1)

The method of claim 1, wherein the single dose comprises from about 105 to about 1011, particularly from about 106 to about 1010, more particularly from about 106 to about 109, more particularly from about 106 to about 108, most particularly from about 106 to about 10′ colony forming units (CFU) of said attenuated mutant strain of Salmonella typhi Ty21a.

### Claim 9 (depends on 1)

The method of claim 1 further comprising the step of assessing the MSLN expression pattern and/or the pre-immune response against MSLN of the patient, and wherein the treatment is individualized cancer immunotherapy treatment.

### Claim 10 (depends on 1)

The method of claim 1, wherein MSLN has the amino acid sequence of SEQ ID NO:1 or is at least 80% identical to SEQ ID NO:1.

### Claim 11 (depends on 3)

The method of claim 3, wherein said one or more further strain(s) of Salmonella typhi Ty21a comprise(s) a strain of Salmonella typhi Ty21 encoding human VEGFR-2.

### Claim 12 (depends on 5)

The method of claim 5, wherein the attenuated mutant strain of Salmonella typhi Ty21a is administered before or during the chemotherapy or the radiotherapy treatment, or before or during administration of the checkpoint inhibitory antibody or before and during the chemotherapy or the radiotherapy treatment or administration of the checkpoint inhibitory antibody.