# US 9,040,662 B2 · Methods and compositions comprising a C-terminal Bax peptide

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- Number: US 9,040,662 B2
- Document ID: US9040662B2
- Status: Granted
- Kind: B2
- Application number: 14/240,801
- Filed: 2012-08-24
- Published: 2014-09-11
- Granted: 2015-05-26
- Earliest claimed: 2011-08-25
- Assignees: University of Central Florida Research Foundation, Inc.
- Applicants: Annette Khaled; Rebecca Boohaker; Michael Lee; Jesus Perez Figueroa
- Inventors: Annette Khaled; Rebecca Boohaker; Michael Lee; Jesus Perez Figueroa
- Web page: https://patentgrep.com/patent/US9040662B2

## CPC

- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A01N 43/38: condensed with carbocyclic rings
- A61K 9/513: {Organic macromolecular compounds; Dendrimers}
- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- A61K 38/1761: {Apoptosis related proteins, e.g. Apoptotic protease-activating factor-1 (APAF-1), Bax, Bax-inhibitory protein(s)(BI; bax-I), Myeloid cell leukemia associated protein (MCL-1), Inhibitor of apoptosis [IAP] or Bcl-2}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- A61K 9/5153: {Polyesters, e.g. poly(lactide-co-glycolide)}
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

In an aspect, the invention relates to compositions and methods for permeabilizing membranes of cells. In an aspect, the invention relates to compositions and methods for killing cells. In an aspect, the invention relates to compositions and methods of permeabilizing the membranes of cancer cells or microbial cells.

## Claims

### Claim 1

A method of permeabilizing membranes of cells, comprising, administering to the cell an effective amount of a) a C-terminal B cell lymphoma-2 (Bcl-2)-associated X protein (Bax) peptide (CT20p peptide), wherein the CT20p peptide comprises SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4, or a combination of two or more of SEQ ID NOs: 1-4, or b) a composition comprising a CT20p peptide, wherein the composition comprises SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4, or a combination of two or more of SEQ ID NOs: 1-4.

### Claim 2 (depends on 1)

The method of claim 1, further comprising repeating the administration of the CT20p peptide or the composition comprising the CT20p peptide.

### Claim 3 (depends on 1)

The method of claim 1, comprising administering the CT20p peptide or CT20p peptide composition directly into a tumor cell.

### Claim 4 (depends on 1)

The method of claim 1, further comprising inducing cell death.

### Claim 5 (depends on 4)

The method of claim 4, wherein the cell death occurs independently of endogenous Bax activity, or endogenous caspase activity, or both.

### Claim 6 (depends on 4)

The method of claim 4, wherein the cell death is resistant to B cell lymphoma-2 (Bcl-2) over-expression.

### Claim 7 (depends on 1)

The method of claim 1, wherein the CT20p peptide is encapsulated in polymeric nanoparticles.

### Claim 8 (depends on 7)

The method of claim 7, wherein the nanoparticles are aminated.

### Claim 9 (depends on 7)

The method of claim 7, wherein the nanoparticles are carboxylated.

### Claim 10 (depends on 1)

The method of claim 1, further comprising administering to the cell one or more therapeutic agents.

### Claim 11 (depends on 1)

The method of claim 1, wherein the cell is a cancer cell.

### Claim 12 (depends on 11)

The method of claim 11, wherein the cancer cell is a breast cancer cell, colorectal cancer cell, or lung cancer cell, or wherein the cancer cell is a drug resistant cancer cell.

### Claim 13 (depends on 1)

The method of claim 1, wherein the membrane is a mitochondrial membrane.

### Claim 14

A composition for permeabilizing membranes in cells, comprising, a CT20p peptide, wherein the CT20p peptide comprises SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4, or a combination of two or more of SEQ ID NOs: 1-4.

### Claim 15 (depends on 14)

The composition of claim 14, wherein the CT20p peptide is encapsulated in polymeric nanoparticles.

### Claim 16 (depends on 15)

The composition of claim 15, wherein the nanoparticles are aminated.

### Claim 17 (depends on 15)

The composition of claim 15, wherein the nanoparticles are carboxylated.

### Claim 18 (depends on 14)

The composition of claim 14, further comprising one or more therapeutic agents.
