# US 9,750,823 B2 · Use of a truncated CCN1 promoter for cancer diagnostics, therapeutics and theranostics

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- Number: US 9,750,823 B2
- Document ID: US9750823B2
- Status: Granted
- Kind: B2
- Application number: 14/895,247
- Filed: 2014-06-04
- Published: 2016-04-14
- Granted: 2017-09-05
- Earliest claimed: 2013-06-04
- Applicants: Virginia Commonwealth University
- Inventors: Paul B. Fisher; Swadesh K. Das; Rupesh Dash; Devanand Sarkar; Siddik Sarkar; Jolene Windle
- Web page: https://patentgrep.com/patent/US9750823B2

## CPC

- A61K 48/0058: {Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct}
- A01K 67/0275: Genetically modified vertebrates, e.g. transgenic
- A61K 35/761: Adenovirus
- A61K 49/0008: {Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure}
- A61K 49/005: {characterised by the carrier molecule carrying the fluorescent agent}
- C12N 15/86: Viral vectors
- A01K 2207/12: Animals modified by administration of exogenous cells
- A01K 2217/052: inducing gain of function
- A01K 2217/206: Animal model comprising tissue-specific expression system, e.g. tissue specific expression of transgene, of Cre recombinase
- A01K 2227/105: Murine
- A01K 2267/0331: Animal model for proliferative diseases
- A01K 2267/0393: Animal model comprising a reporter system for screening tests
- C12N 2015/8536: {Animal models for genetic diseases}
- C12N 2015/8572: {Animal models for proliferative diseases, e.g. comprising an oncogene}
- C12N 2710/10332: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- C12N 2830/008: cell type or tissue specific enhancer/promoter combination
- C12N 2830/34: being a transcription initiation element
- 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)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Recombinant vectors in which expression of one or more elements (e.g. genes required for viral replication, detectable imaging agents, therapeutic agents, etc.) is driven by a truncated CCN 1 cancer selective promoter (tCCN1-Prom) are provided, as are cells and transgenic animals that contain such vectors. The vectors are used in cancer therapy and/or diagnostics, and the transgenic mice are used to monitor cancer progression, e.g. in screening assays.

## Claims

### Claim 1

A recombinant vector comprising a truncated connective tissue growth factor/cysteine rich protein/nephroblastoma overexpressed gene-1 (CCN1) cancer selective promoter comprising the nucleotide sequence as set forth in SEQ ID NO: 1.

### Claim 2 (depends on 1)

The recombinant vector of claim 1, wherein said truncated CCN1 cancer selective promoter is operably linked to at least one gene of interest.

### Claim 3 (depends on 1)

The recombinant vector of claim 1, wherein said recombinant vector is a viral vector.

### Claim 4 (depends on 3)

The recombinant vector of claim 3, wherein said viral vector is selected from the group consisting of: an adenoviral vector, a lentiviral vector, a herpes simplex virus vector, a measles virus vector, and a vaccinia virus vector.

### Claim 5 (depends on 2)

The recombinant vector of claim 2, wherein said at least one gene of interest encodes one or more of an anticancer agent, an imaging agent, and a gene that is required for viral replication.

### Claim 6 (depends on 1)

A mammalian cell comprising the recombinant vector according to claim 1.

### Claim 7 (depends on 6)

The cell of claim 6, wherein said mammalian cell is a cancer cell.

### Claim 8 (depends on 5)

A method of treating cancer in a patient in need thereof, comprising administering to said patient a composition comprising the recombinant vector of claim 5, wherein said at least one gene of interest comprises a gene encoding an anticancer agent, wherein said anticancer agent is expressed in the subject at a level effective to exert an anticancer effect, and wherein said cancer is bladder cancer, brain cancer, breast carcinoma, cervical carcinoma, colorectal cancer, endometrial carcinoma, esophageal carcinoma, gastric cancer, gestational trophoblastic disease, hematopoietic cell cancer, hepatocarcinoma, lung cancer, melanoma, neuroblastoma, osteosarcoma, ovarian carcinoma, pancreatic cancer, prostate cancer, renal cancer, retinoblastoma, uterine sarcoma, vaginal carcinoma, or vulvar carcinoma.

### Claim 9 (depends on 8)

The method of claim 8, wherein the gene encoding the anticancer agent is a melanoma differentiation-associated 7/interleukin 24 (mda-7/IL-24) gene.

### Claim 10 (depends on 8)

The method of claim 8, wherein the vector is a viral vector and comprises a gene required for viral replication operably linked to a cancer-specific or cancer-selective promoter.

### Claim 11 (depends on 5)

A method of imaging cancer in a patient in need thereof, comprising administering to said patient a composition comprising the recombinant vector of claim 5, wherein said at least one gene of interest comprises a gene encoding an imaging agent, and detecting a signal from the imaging agent.

### Claim 12 (depends on 11)

The method of claim 11, wherein the vector is a non-viral vector.

### Claim 13 (depends on 11)

The method of claim 11, wherein the vector is a viral vector and further comprises a gene required for viral replication operably linked to a cancer-specific or cancer-selective promoter.

### Claim 14 (depends on 5)

The recombinant vector of claim 5, wherein the vector is a viral vector, and wherein the vector, in addition to the truncated CCN1 cancer selective promoter comprising SEQ ID NO: 1, further comprises one or more cancer-specific or cancer-selective promoters operably linked to a gene encoding one or more of an anticancer agent, an imaging agent, and a gene required for viral replication.

### Claim 15 (depends on 14)

The vector of claim 14, wherein the CCN1 cancer selective promoter is operably linked to gene encoding an anticancer agent.

### Claim 16 (depends on 14)

The vector of claim 14, wherein the CCN1 cancer selective promoter is operably linked to a gene encoding an imaging agent.

### Claim 17 (depends on 14)

The vector of claim 14, wherein the CCN1 cancer selective promoter is operably linked to a gene required for viral replication.

### Claim 18 (depends on 14)

The vector of claim 14, wherein at least one of the one or more cancer-specific or cancer-selective promoters is a progression elevated gene-1 promoter (PEG-Prom).

### Claim 19 (depends on 5)

A nanoparticle comprising the vector of claim 5.