# US 2013/0158111 A1 · Compositions and Methods for Depleting Mutant p53

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- Number: US 2013/0158111 A1
- Document ID: US20130158111A1
- Status: Published application
- Kind: A1
- Application number: 13/721,681
- Filed: 2012-12-20
- Published: 2013-06-20
- Earliest claimed: 2011-12-20
- Assignees: Georgetown University
- Inventors: Fung-Lung Chung; Anthony Di Pasqua
- Web page: https://patentgrep.com/patent/US20130158111A1

## CPC

- A61K 31/26: Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
- A61K 45/00: Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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)

## Abstract

The invention is directed towards methods of treating abnormal tissues in a subject or sensitizing an abnormal tissue to a chemotherapeutic agent. The methods comprise screening at least a portion of an abnormal tissue for at least one mutant form of p53 protein, and administering at least one isothiocyanate (ITC) to the subject or abnormal tissue if the abnormal tissue is positive for the at least one mutant form of p53.

## Claims

### Claim 1

A method of treating an abnormal tissue in a subject, the method comprising
a) screening at least a portion of the abnormal tissue for at least one mutant form of p53 protein, and
b) administering at least one isothiocyanate (ITC) to the subject if the abnormal tissue is positive for the at least one mutant form of p53.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject is a mammal.

### Claim 3 (depends on 1)

The method of claim 1, wherein the abnormal tissue is cancerous.

### Claim 4 (depends on 1)

The method of claim 1, wherein the ITC is sulforophane (SFN), phenylethyl ITC (PEITC), benzyl ITC (BITC).

### Claim 5 (depends on 1)

The method of claim 1, wherein the ITC is conjugated.

### Claim 6 (depends on 5)

The method of claim 5, wherein the conjugate to the ITC is a thiol conjugate.

### Claim 7 (depends on 1)

The method of claim 1, wherein the abnormal tissue is lung tissue, breast tissue, colon tissue and prostate tissue.

### Claim 8 (depends on 1)

The method of claim 1, wherein ITC is administered orally.

### Claim 9 (depends on 1)

The method of claim 1, further comprising co-administering an anti-cancer agent with the ITC.

### Claim 10 (depends on 1)

The method of claim 1, wherein the mutant p53 has a mutation at V143, P151, R175, G245, R248, R249, R273, P274, R280 and R282 of the amino acid sequence of SEQ ID NO:1.

### Claim 11

A method of altering the three-dimensional conformation of a mutant p53 protein, the method comprising administering at least one isothiocyanate (ITC) to the mutant p53 protein to alter the three-dimensional conformation of the mutant p53 protein.

### Claim 12 (depends on 11)

The method of claim 11, wherein the mutant p53 protein is present in a cell or group of cells and the administration of the at least one ITC to the mutant p53 protein comprises administering the ITC to the cell or group of cells.

### Claim 13 (depends on 12)

The method of claim 12, wherein the cell or group of cells is comprised within a subject and the administration of the at least one ITC to the mutant p53 protein comprises administering the ITC to the cell or group of cells comprises administration of the at least one ITC to the mutant p53 protein comprises administering the ITC to the subject.

### Claim 14 (depends on 13)

The method of claim 13, wherein the subject is a mammal.

### Claim 15 (depends on 12)

The method of claim 12, wherein the cell is a cancer cell.

### Claim 16 (depends on 11)

The method of claim 11, wherein the ITC is sulforophane (SFN), phenylethyl ITC (PEITC), benzyl ITC (BITC).

### Claim 17 (depends on 11)

The method of claim 11, wherein the ITC is conjugated.

### Claim 18 (depends on 17)

The method of claim 17, wherein the conjugate to the ITC is a thiol conjugate.

### Claim 19 (depends on 15)

The method of claim 15, wherein the cancel cell is a lung cancer cell, a breast cancer cell, a colon cancer cell or a prostate cancer cell.

### Claim 20 (depends on 14)

The method of claim 14, wherein ITC is administered orally.

### Claim 21 (depends on 14)

The method of claim 14, further comprising co-administering an anti-cancer agent with the ITC.

### Claim 22 (depends on 11)

The method of claim 11, wherein the mutant p53 has a mutation at V143, P151, R175, G245, R248, R249, R273, P274, R280 and R282 of the amino acid sequence of SEQ ID NO:1.