# US 8,273,705 B2 · Conversion of apoptotic proteins

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- Number: US 8,273,705 B2
- Document ID: US8273705B2
- Status: Granted
- Kind: B2
- Application number: 12/364,415
- Filed: 2009-02-02
- Published: 2009-08-27
- Granted: 2012-09-25
- Earliest claimed: 2002-12-12
- Assignees: The Burnham Institute
- Inventors: John C. Reed; Xiao-kun Zhang; Bin Guo; Bingzhen Lin; Siva Kumar Kolluri
- Web page: https://patentgrep.com/patent/US8273705B2

## CPC

- G01N 33/5091: {for testing the pathological state of an organism}
- A61K 38/1709: {from mammals}
- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61P 35/00: Antineoplastic agents
- C07K 16/2857: {against nuclear receptors, e.g. retinoic acid receptor [RAR], RXR, orphan receptor}
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- G01N 33/5011: {for testing antineoplastic activity}
- G01N 33/502: {for testing non-proliferative effects}
- G01N 33/5079: {Mitochondria}
- G01N 2510/00: Detection of programmed cell death, i.e. apoptosis
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- 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
- 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)

## Abstract

Compounds that modulate the function of anti-apoptotic proteins such as Bcl-2 and Bcl-XL are identified. These compounds have the ability to convert the activity of Bcl-2-family member proteins from anti-apoptotic to pro-apoptotic. Methods for inducing apoptosis are described, together with methods for identifying molecules that induce apoptosis through interaction with Bcl-2-family members.

## Claims

### Claim 1

A method of inducing apoptosis in a cancer cell, comprising contacting said cell with a compound capable of inducing a conformational change in Bcl-2, so as to convert said Bcl-2 into a pro-apoptotic form, without cleaving said Bcl-2, wherein said compound is a peptide compound, and wherein said peptide compound comprises a Bcl-2 binding fragment of the human TR3 receptor of SEQ ID NO: 3 having Bcl-2 binding activity.

### Claim 2 (depends on 1)

The method of claim 1, wherein said fragment comprises the 69 amino acids between amino acids 467 and 536 of the human TR3 receptor of SEQ ID NO: 3.

### Claim 3 (depends on 1)

The method of claim 1, wherein the compound comprises at least one D-amino acid.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1)

The method of claim 1, wherein said compound binds to the N-terminal portion of Bcl-2.

### Claim 8 (depends on 7)

The method of claim 7, wherein said compound binds to amino acids 1-80 of the N terminal portion of Bcl-2.