# US 2008/0188412 A1 · Bcl-2 promoted cell death

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- Number: US 2008/0188412 A1
- Document ID: US20080188412A1
- Status: Published application
- Kind: A1
- Application number: 12/002,844
- Filed: 2007-12-18
- Published: 2008-08-07
- Earliest claimed: 2005-12-23
- Inventors: Giulio Taglialatela; Bryce Portier
- Web page: https://patentgrep.com/patent/US20080188412A1

## CPC

- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- G01N 33/566: using specific carrier or receptor proteins as ligand binding reagents {where possible specific carrier or receptor proteins are classified with their target compounds}
- G01N 33/575: for cancer
- G01N 2500/04: Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention is directed towards a method of screening compounds that disrupt Bcl-2/FKBP38 binding and thereby induce apoptosis. The invention is also directed towards a method of promoting apoptotic cell death in Bcl-2 producing cells or tissues by contacting the cells or tissues with a sufficient amount of BH4 peptide or mimetic thereof to inhibit binding of Bcl-2 and FKBP38. Additionally, the invention is directed towards a method of purging malignant, Bcl-2 producing cells from a mixed population of cells, by contacting the mixed population with a sufficient amount of BH4 peptide or a mimetic thereof to disrupt Bcl-2/FKBP38 binding and trigger apoptosis in Bcl-2 producing cells. The mixed population of cells can be in or from an individual.

## Claims

### Claim at position 1

-6. (canceled)

### Claim 7

A method of promoting apoptotic cell death in Bcl-2 producing cells, comprising the step of contacting the cells in vitro with a sufficient amount of a composition comprising BH4 peptide or a homolog thereof to interfere with the binding of Bcl-2 and FKBP38.

### Claim at position 3

8-16. (canceled)

### Claim 17 (depends on 7)

The method of claim 7, wherein the Bcl-2 producing cells are cancer cells.

### Claim 18 (depends on 17)

The method of claim 17, wherein the cancer cells are in an individual.

### Claim 19 (depends on 17)

The method of claim 17, wherein the Bcl-2 producing cells are selected from the group of cells contributing to malignancies selected from the group consisting of leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, precursor B-lymphoblastic and leukemia/lymphoma.

### Claim 20 (depends on 17)

The method of claim 17, wherein the Bcl-2 producing cells are selected from the group of cells contributing to malignancies selected from the group consisting of lymphoma, diffuse large B-cell lymphoma and Hodgkin lymphoma.

### Claim 21 (depends on 17)

The method of claim 17, wherein the Bcl-2 producing cells are selected from the group of cells contributing to malignancies selected from the group consisting of squamous cell carcinoma, liposarcoma, squamous cell carcinoma and melanoma.

### Claim 22 (depends on 17)

The method of claim 17, wherein the Bcl-2 producing cells are selected from the group of cells contributing to malignancies selected from the group consisting of meningioma, breast carcinoma, gliobastoma, ependymoma, gastrointestinal stromal tumors, colon cancer, and hormone-refractory breast cancer.

### Claim 23 (depends on 17)

The method of claim 17, wherein the Bcl-2 producing cells are selected from the group of cells contributing to malignancies selected from the group consisting of prostate, colorectal, lung, gastric and renal neuroblastoma.

### Claim 24 (depends on 17)

The method of claim 17, wherein the Bcl-2 producing cells are selected from the group of cells contributing to malignancies selected from the group consisting of non-Hodgkin's lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, and chronic leukemia.