# US 9,434,994 B2 · Methods for prediction of clinical outcome to epidermal growth factor receptor inhibitors by non-small cell lung cancer patients

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- Number: US 9,434,994 B2
- Document ID: US9434994B2
- Status: Granted
- Kind: B2
- Application number: 13/542,529
- Filed: 2012-07-05
- Published: 2013-01-03
- Granted: 2016-09-06
- Earliest claimed: 2004-05-27
- Assignees: The Regents of the University of Colorado, a body corporate
- Applicants: Marileila Varella Garcia; Paul A. Bunn, Jr.; Federico Cappuzzo; Wilbur A. Franklin; Fred R. Hirsch
- Inventors: Marileila Varella Garcia; Paul A. Bunn, Jr.; Federico Cappuzzo; Wilbur A. Franklin; Fred R. Hirsch
- Web page: https://patentgrep.com/patent/US9434994B2

## CPC

- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/112: Disease subtyping, staging or classification
- C12Q 2600/118: Prognosis of disease development
- C12Q 2600/156: Polymorphic or mutational markers
- C12Q 2600/158: Expression markers
- 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

Disclosed are methods to obtain an expression score to evaluate gene expression in a tissue specimen obtained from a person having or suspected of having cancer.

## Claims

### Claim 1

A method to select a non-small cell lung cancer patient (NSCLC) patient as being predicted to respond to therapeutic administration of an EGFR inhibitor comprising:
a) determining by immunohistochemistry an EGFR fraction score, wherein the EGFR fraction score corresponds to the percentage of cells in a tumor tissue specimen received from a NSCLC patient that stain positive for EGFR protein expressed as a number between 0 and 100 corresponding to the percentage of cells in the sample of tumor cells staining positive for the EGFR protein between 0% and 100%;
b) determining an EGFR intensity score that corresponds to the staining intensity of the EGFR protein in the specimen of tumor cells expressed as a number of at least 1 and not greater than 4 corresponding to the intensity of the staining of the EGFR protein in the sample of tumor cells;
c) calculating an EGFR expression score that is the product of the EGFR fraction score and the EGFR intensity score expressed as an integer between 0 and 400 corresponding to the numerical product of the EGFR fraction score, expressed as a number between 0 and 100, and the EGFR intensity score, expressed as a number of at least one 1 and not greater than 4;
d) determining by immunohistochemistry a P-AKT fraction score, wherein the P-AKT fraction score corresponds to the percentage of cells in a tumor tissue specimen received from a NSCLC patient that stain positive for phosphorylated AKT protein expressed as a number between 0 and 100 corresponding to the percentage of cells in the sample of tumor cells staining positive for the phosphorylated AKT protein between 0% and 100%;
e) determining a P-AKT intensity score that corresponds to the staining intensity of the phosphorylated AKT protein in the specimen of tumor cells expressed as a number of at least 1 and not greater than 4 corresponding to the intensity of the staining of the phosphorylated AKT protein in the sample of tumor cells;
f) calculating a P-AKT expression score that is the product of the P-AKT fraction score and the P-AKT intensity score expressed as an integer between 0 and 400 corresponding to the numerical product of the P-AKT fraction score, expressed as a number between 0 and 100, and the P-AKT intensity score, expressed as a number of at least one 1 and not greater than 4;
g) selecting the NSCLC patient as being predicted to respond to therapeutic administration of an EGFR inhibitor, if the EGFR expression score and the P-AKT expression score are each equal to or greater than 200; or
h) selecting the NSCLC patient as being predicted to not respond to therapeutic administration of an EGFR inhibitor, if the EGFR expression score is equal to or greater than 200 and the P-AKT expression score is less than 200.