# US 8,541,566 B2 · Promoter inducible by reactive oxygen species and vector comprising the same

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- Number: US 8,541,566 B2
- Document ID: US8541566B2
- Status: Granted
- Kind: B2
- Application number: 12/597,891
- Filed: 2008-04-25
- Published: 2010-11-25
- Granted: 2013-09-24
- Earliest claimed: 2007-04-27
- Assignees: Inis Biotech LLC; Fundacion Instituto Leloir; Comision Nacional De Energia Atomica (Cnea); Consejo Nacional De Investigaciones Cientificas Y Tecnicas (Conicet)
- Applicants: Lucia Policastro; Hebe Duran; Osvaldo Podhajcer
- Inventors: Lucia Policastro; Hebe Duran; Osvaldo Podhajcer
- Web page: https://patentgrep.com/patent/US8541566B2

## CPC

- A61K 48/0058: {Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct}
- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 38/45: Transferases (2)
- A61K 41/0057: {Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent}
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 35/00: Antineoplastic agents
- C12N 15/85: for animal cells
- C12N 2830/002: inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor
- C12N 2830/15: chimeric enhancer/promoter combination
- 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)

## Abstract

The invention provides promoters inducible by reactive oxygen species (ROS), capable of driving the expression of a gene of interest, particularly in a tumor cell. More particularly, it refers to promoters inducible by reactive oxygen species, that may be used to drive the expression of a gene of interest, such as a therapeutic gene, or a reporter gene for use in image diagnosis. The promoters comprise at least a fragment of a promoter sequence responsive to said reactive oxygen species, and corresponding to a gene highly expressed in cancer cells, wherein the fragment of the promoter sequence responsive to reactive oxygen species (ROS) is selected from the group of: the VE element of the VEGF promoter, the E6 element of the promoter of the EGR-1 gene, the MMP-1 element and a chimeric promoter containing an E6 element and a VE element. It also provides vectors carrying a human therapeutic or non therapeutic gene of interest, operably linked to said promoter sequence and compositions comprising the same.

## Claims

### Claim 1

A promoter inducible by reactive oxygen species (ROS), the promoter consisting of a chimeric promoter containing an E6 element consisting of the nucleotide sequence of SEQ ID NO: 2 spaced from a VE element consisting of the nucleotide sequence of SEQ ID NO: 1 by a spacing sequence.

### Claim 2 (depends on 1)

The promoter according to claim 1, wherein the spacing sequence is between 6 and 200 base pairs.

### Claim 3 (depends on 2)

The promoter according to claim 2, wherein the spacing sequence is selected from the group of 6 base pairs, 20 base pairs and 40 base pairs.

### Claim 4 (depends on 2)

The promoter according to claim 2, wherein the chimeric promoter is 5′E6(40)VE3′ consisting of the nucleotide sequence of SEQ ID NO:12.

### Claim 5

A vector comprising a promoter inducible by reactive oxygen species (ROS), the vector consisting of a chimeric promoter containing an E6 element consisting of the nucleotide sequence of SEQ ID NO: 2 spaced from a VE element consisting of the nucleotide sequence of SEQ ID NO: 1 by a spacing sequence.

### Claim 6 (depends on 5)

The vector according to claim 5, wherein the spacing sequence is between 6 and 200 base pairs.

### Claim 7 (depends on 6)

The vector according to claim 6, wherein the spacing sequence is selected from the group of 6 base pairs, 20 base pairs and 40 base pairs.

### Claim 8 (depends on 6)

The vector according to claim 6, wherein the chimeric promoter is 5′E6(40)VE3′ consisting of the nucleotide sequence of SEQ ID NO: 12.

### Claim 9 (depends on 8)

The vector according to claim 8, further comprising a therapeutic human gene operatively linked to said promoter sequence.

### Claim 10 (depends on 5)

The vector according to claim 5, further comprising a gene of interest, operatively linked to said promoter sequence.

### Claim 11 (depends on 10)

The vector according to claim 10, wherein the gene of interest is a therapeutic human gene.

### Claim 12 (depends on 11)

The vector according to claim 11, wherein the therapeutic human gene is a suicidal gene.

### Claim 13 (depends on 10)

The vector according to claim 10, wherein the gene encodes a protein detectable in vivo.

### Claim 14 (depends on 5)

The vector according to claim 5, wherein the vector is selected from a viral and a non-viral vector.

### Claim 15 (depends on 5)

A pharmaceutical composition comprising a vector according to claim 5 in a pharmaceutically acceptable carrier.

### Claim 16 (depends on 15)

The composition according to claim 15, further comprising a chemotherapeutical drug.

### Claim 17 (depends on 15)

The pharmaceutical composition according to claim 15, wherein the carrier is a cell.