# US 12,758,623 B2 · Anti-GUCY2C vaccine compositions and methods of using them

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- Number: US 12,758,623 B2
- Document ID: US12758623B2
- Status: Granted
- Kind: B2
- Application number: 17/775,561
- Filed: 2020-11-09
- Published: 2025-10-09
- Granted: 2026-10-13
- Earliest claimed: 2019-11-07
- Assignees: Thomas Jefferson Univerity
- Applicants: Thomas Jefferson University
- Inventors: Adam E Snook; Scott A. Waldman; Trevor R Baybutt; John C Flickinger
- Web page: https://patentgrep.com/patent/US12758623B2

## CPC

- A61K 39/001154: {Enzymes}
- 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 35/74: Bacteria (therapeutic use of a bacterial protein A61K38/00)
- A61P 35/00: Antineoplastic agents
- C12N 1/20: Bacteria; Culture media therefor
- C12N 15/74: Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
- C12N 15/86: Viral vectors
- A61K 2039/523: {expressing foreign proteins}
- A61K 2039/5252: {inactivated (killed)}
- A61K 2039/5256: {expressing foreign proteins}
- C12N 2710/10021: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2710/10022: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2710/10034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12R 2001/01: Bacteria or Actinomycetales {; using bacteria or Actinomycetales}
- C12Y 406/01002: Guanylate cyclase (4.6.1.2)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12R: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12Y: ENZYMES

## Abstract

Compositions comprising a modified adenovirus AD5.F35 which includes coding sequence of soluble GUCY2C extracellular domain sequences are disclosed. Compositions comprising a Listeria monocytogenes vector which includes coding sequence of soluble GUCY2C extracellular domain sequences are disclosed. Methods of treating individuals diagnosed with cancer/tumors expressing GUCY2C methods of preventing micro-metastasis are disclosed.

## Claims

### Claim 1

A recombinant Ad5.F35 adenovirus comprising:
a) an adenoviral Ad5.F35 vector which is replication defective and further comprising:
b) a gene expression cassette comprising:
i) a heterologous promoter operatively linked to,
ii) a nucleic acid encoding a soluble human GUCY2C domain as set forth in SEQ ID NO: 5 fused in frame to,
iii) a nucleic acid encoding a universal CD4+ helper epitope PADRE.

### Claim 2 (depends on 1)

The recombinant Ad5.F35 adenovirus of claim 1 wherein the PADRE is encoded by SEQ ID NO: 7.

### Claim 3 (depends on 1)

A recombinant Ad5.F35 adenovirus of claim 1 comprising:
a) an adenoviral Ad5.F35 vector which is replication defective and further comprising:
b) a gene expression cassette comprising:
i) a heterologous promoter operatively linked to,
ii) a nucleic acid encoding a soluble human GUCY2C domain fused in frame to,
iii) a nucleic acid encoding a universal CD4+ helper epitope,
wherein the gene expression cassette comprises SEQ ID NO:9.

### Claim 4 (depends on 3)

An injectable pharmaceutical composition comprising an adenovirus of claim 3 and a pharmaceutically acceptable carrier or diluent.

### Claim 5

A method of treating a human patient diagnosed with cancer, wherein cells of said cancer express GUCY2C, the method comprising the steps of
a) administering to the patient an effective amount of an injectable pharmaceutical composition comprising
i) a replication defective recombinant Ad5.F35 adenovirus comprising:
an adenoviral Ad5.F35 vector further comprising:
a gene expression cassette comprising:
a heterologous promoter operatively linked to,
a nucleic acid encoding a soluble human GUCY2C domain that comprises SEQ ID NO: 5 fused in frame to,
a nucleic acid encoding a universal CD4+ helper epitope;
and
b) subsequently administering to the patient an effective amount of an injectable pharmaceutical composition comprising
i) a recombinant Listeria monocytogenes comprising:
a gene expression cassette comprising
a heterologous promoter operatively linked to
a nucleic acid encoding a soluble human GUCY2C domain.

### Claim 6 (depends on 5)

The method of claim 5 wherein:
the nucleic acid encoding the universal CD4+ helper epitope of the gene expression cassette of the recombinant Ad5.F35 adenovirus comprises a nucleic acid encoding the universal CD4+ helper epitope PADRE.

### Claim 7 (depends on 6)

The method of claim 6 wherein:
the nucleic acid encoding universal CD4+ helper epitope PADRE of the gene expression cassette of the recombinant Ad5.F35 adenovirus comprises SEQ ID NO: 7.

### Claim 8

A method of treating a human patient diagnosed with cancer, wherein cells of said cancer express GUCY2C, the method comprising the steps of
a) administering to the patient an effective amount of an injectable pharmaceutical composition comprising
i) a replication defective recombinant Ad5.F35 adenovirus comprising:
an adenoviral Ad5.F35 vector further comprising:
a gene expression cassette comprising:
a heterologous promoter operatively linked to,
a nucleic acid encoding a soluble human GUCY2C domain fused in frame to,
a nucleic acid encoding a universal CD4+helper epitope,
wherein the gene expression cassette of the recombinant Ad5.F35 adenovirus comprises SEQ ID NO:9;
and
b) subsequently administering to the patient an effective amount of an injectable pharmaceutical composition comprising
i) a recombinant Listeria monocytogenes comprising:
a gene expression cassette comprising
a heterologous promoter operatively linked to
a nucleic acid encoding a soluble human GUCY2C domain.

### Claim 9 (depends on 8)

The method of claim 8 wherein the recombinant Listeria monocytogenes comprises a nucleic acid encoding a soluble human GUCY2C domain fused to a Listeria monocytogenes protein ActA.

### Claim 10 (depends on 5)

The method of claim 5 wherein the recombinant Listeria monocytogenes comprises a nucleic acid encoding a soluble human GUCY2C domain fused to Listeria monocytogenes protein ActA.

### Claim 11 (depends on 5)

The method of claim 5 wherein-prior to administering to the patient the injectable pharmaceutical composition that comprises the recombinant Ad5.F35 adenovirus, a sample of cancer tissue is analyzed to determine whether the cancer tissue expresses GUCY2C.

### Claim 12 (depends on 5)

The method of claim 5 wherein the cancer expressing GUCY2C is esophageal, gastric, pancreatic, or colorectal.

### Claim 13 (depends on 5)

The method of claim 5 wherein the cancer is metastatic.

### Claim 14 (depends on 8)

The method of claim 8 wherein-prior to administering to the patient the injectable pharmaceutical composition that comprises the recombinant Ad5.F35 adenovirus, a sample of cancer tissue is analyzed to determine whether the cancer tissue expresses GUCY2C.

### Claim 15 (depends on 8)

The method of claim 8 wherein the cancer expressing GUCY2C is esophageal, gastric, pancreatic, or colorectal.

### Claim 16 (depends on 8)

The method of claim 8 wherein the cancer is metastatic.