# US 7,745,405 B2 · Peptides selectively lethal to malignant and transformed mammalian cells

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- Number: US 7,745,405 B2
- Document ID: US7745405B2
- Status: Granted
- Kind: B2
- Application number: 11/977,521
- Filed: 2007-10-25
- Published: 2008-03-27
- Granted: 2010-06-29
- Earliest claimed: 2000-04-05
- Assignees: The Research Foundation of State University of New York
- Inventors: Matthew R. Pincus
- Web page: https://patentgrep.com/patent/US7745405B2

## CPC

- C07K 14/4746: {p53}
- A61K 38/04: Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof ({enzyme inhibitors A61K38/005;} gastrins {A61K38/2207}, somatostatins A61K38/31, melanotropins A61K38/34 {; protease inhibitors A61K38/55})
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/1709: {from mammals}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 2039/5254: {avirulent or attenuated}
- A61K 2039/5256: {expressing foreign proteins}
- C07K 2319/03: containing a transmembrane segment
- C12N 2799/022: where the vector is derived from an adenovirus
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- 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)
- 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 present invention provides peptides corresponding to all or a portion of amino acid residues 12-26 of human p53 protein. When fused to a membrane-penetrating leader sequence, the peptides are either lethal to malignant or transformed cells or else cause reversion to the untransformed morphological phenotype. The subject peptides are thus useful in treating neoplastic disease in an animal, preferably a human. Also provided are pharmaceutical compositions comprising the subject peptides admixed with a pharmaceutical acceptable carrier. Methods of treating neoplastic disease in a patient by administering a subject peptide are also provided.

## Claims

### Claim 1

A composition comprising a peptide, the peptide consisting of the amino acid sequence: PPLSQETFSDLWKLL (SEQ ID NO:1) fused to a membrane-penetrating leader sequence.

### Claim 2

A composition comprising a peptide, the peptide consisting of the amino acid sequence: PPLSQETFS (SEQ ID NO:2) fused to a membrane penetrating leader sequence.

### Claim 3

A composition comprising a peptide, the peptide consisting of the amino acid sequence: ETFSDLWKLL (SEQ ED NO:3) fused to a membrane penetrating leader sequence.

### Claim 4

A composition comprising at least one peptide consisting of the amino acid sequence: PPLSQETFSDLWKLL (SEQ ID NO:1), PPLSQETFS (SEQ ID NO:2), or ETFSDLWKLL (SEQ ID NO:3), said peptide fused to a membrane penetrating leader sequence.

### Claim 5 (depends on 1, 2, 3, 4)

The composition of any one of claims 1-4 wherein the membrane-penetrating leader sequence comprises the amino acid sequence: KKWKMRRNQFWVKVQRG (SEQ ID NO:4).

### Claim 6 (depends on 1, 2, 3, 4)

The composition according to any one of claims 1-4 which is a pharmaceutical composition, wherein the peptide is admixed with a pharmaceutically acceptable carrier.

### Claim 7 (depends on 5)

The composition according to claim 5 which is a pharmaceutical composition, wherein the peptide is admixed with a pharmaceutically acceptable carrier.

### Claim 8

A method of treating neoplastic disease in a subject, said method comprising administering to the subject, a therapeutically effective amount of a composition comprising at least one peptide consisting of the amino acid sequence: PPLSQETFSDLWKLL (SEQ ID NO:1), PPLSQETFS (SEQ ID NO:2), or ETFSDLWKLL (SEQ ID NO:3), said peptide fused to a membrane penetrating leader sequence.

### Claim 9 (depends on 1, 2, 3, 4)

A method of treating neoplastic disease in a subject, said method comprising administering to the subject, a therapeutically effective amount of the composition of any one of claims 1-4.

### Claim 10 (depends on 8)

The method of claim 8 wherein the composition is a pharmaceutical composition comprising the peptide admixed with a pharmaceutically acceptable carrier.

### Claim 11 (depends on 8)

The method of claim 8 wherein the membrane-penetrating leader sequence comprises the amino acid sequence: KKWKMRRNQFWVKVQRG (SEQ ID NO:4).

### Claim 12 (depends on 9)

The method of claim 9 wherein the composition is a pharmaceutical composition comprising the peptide admixed with a pharmaceutically acceptable carrier.

### Claim 13 (depends on 9)

The method of claim 9 wherein the membrane-penetrating leader sequence comprises the amino acid sequence: KKWKMRRNQFWVKVQRG (SEQ ID NO:4).