# US 8,771,942 B2 · SCDs as modifiers of the p53 pathway and methods of use

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- Number: US 8,771,942 B2
- Document ID: US8771942B2
- Status: Granted
- Kind: B2
- Application number: 12/714,257
- Filed: 2010-02-26
- Published: 2010-06-24
- Granted: 2014-07-08
- Earliest claimed: 2002-03-01
- Assignees: Exelixis, Inc.
- Applicants: Marcia Belvin; Helen Francis-Lang; Lori Friedman; Gregory D. Plowman; Timothy S. Heuer
- Inventors: Marcia Belvin; Helen Francis-Lang; Lori Friedman; Gregory D. Plowman; Timothy S. Heuer
- Web page: https://patentgrep.com/patent/US8771942B2

## CPC

- G01N 33/5011: {for testing antineoplastic activity}
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12Q 1/485: {involving kinase}
- C12Q 1/527: involving lyase
- G01N 33/5017: {for testing neoplastic activity}
- G01N 33/573: for enzymes or isoenzymes
- G01N 33/575: for cancer
- G01N 33/57515: of the breast
- G01N 33/5752: of the lungs
- G01N 33/57535: of the large intestine, e.g. colon, rectum or anus
- G01N 33/57545: of the ovaries
- G01N 33/57575: {involving oncogenic proteins}
- G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites}
- G01N 33/57595: {involving intracellular compounds}
- G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels}
- G01N 2333/82: Translation products from oncogenes
- G01N 2333/90212: acting on a sulfur group of donors (1.8)
- G01N 2333/912: transferring phosphorus containing groups, e.g. kinases (2.7)
- G01N 2333/988: Lyases (4.), e.g. aldolases, heparinase, enolases, fumarase
- G01N 2500/00: Screening for compounds of potential therapeutic value
- G01N 2500/10: involving cells
- 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
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

Human SCD genes are identified as modulators of the p53 pathway, and thus are therapeutic targets for disorders associated with defective p53 function. Methods for identifying modulators of p53, comprising screening for agents that modulate the activity of SCD are provided.

## Claims

### Claim 1

A method of identifying a candidate p53 pathway enhancing agent, said method comprising the steps of:
(a) providing a first assay system comprising cultured cells that express a stearoyl-CoA desaturase (SCD) nucleic acid encoding the SCD polypeptide of SEQ ID NO: 11;
(b) contacting the first assay system with a candidate test agent;
(c) measuring the expression of said SCD nucleic acid in the first assay system in the presence and absence of said candidate test agent;
(d) identifying the test agent as a candidate p53 pathway enhancing agent by detecting a decrease in the expression of SCD nucleic acid in the presence of said test agent;
(e) providing a second assay system comprising cultured cells expressing said SCD polypeptide, wherein the second assay system is capable of detecting an enhancement in the p53 pathway and wherein the assay of the second assay system is selected from the group consisting of an apoptosis assay, a cell proliferation assay, an angiogenesis assay, and a hypoxic induction assay;
(f) contacting the second assay system with the test agent of (b); and
(g) confirming the test agent as a p53 pathway enhancing agent by detecting an enhancement in the second assay system.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cultured cells of the first assay system additionally have defective p53 function.

### Claim 3 (depends on 1)

The method of claim 1, wherein the candidate test agent is a nucleic acid modulator against said SCD nucleic acid.

### Claim 4 (depends on 3)

The method of claim 3, wherein the nucleic acid modulator is an antisense oligomer.

### Claim 5 (depends on 4)

The method of claim 4, wherein the nucleic acid modulator is a PMO.

### Claim 6 (depends on 3)

The method of claim 3, wherein the nucleic acid modulator is an siRNA.