# US 2015/0147339 A1 · Biomarkers for psma targeted therapy for prostate cancer

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- Number: US 2015/0147339 A1
- Document ID: US20150147339A1
- Status: Published application
- Kind: A1
- Application number: 14/542,316
- Filed: 2014-11-14
- Published: 2015-05-28
- Earliest claimed: 2013-11-15
- Assignees: PSMA Development Company, LLC
- Applicants: Psma Development Company, LLC
- Inventors: WILLIAM C. OLSON; VINCENT DIPIPPO
- Web page: https://patentgrep.com/patent/US20150147339A1

## CPC

- G01N 33/57555: of the prostate
- 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}
- G16B 20/00: ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
- G16B 25/10: Gene or protein expression profiling; Expression-ratio estimation or normalisation
- G16B 99/00: Subject matter not provided for in other groups of this subclass
- G16H 50/30: for calculating health indices; for individual health risk assessment
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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)
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA

## Abstract

Provided herein are a number of methods, assays and diagnostic tests based on one or more biomarkers as well as related kits and compositions that can be used to identify subjects or patients that would likely benefit from a treatment (or continued treatment), such as a PSMA targeted therapy. Also provided are methods for treating the identified subjects or patients.

## Claims

### Claim 1

A companion diagnostic test comprising:
a. obtaining one or more biological samples from a subject undergoing a treatment or considered for a treatment;
b. assaying a panel of biomarkers;
c. generating a score with an algorithm based on the assay results of said panel of biomarkers; and
d. determining the likely responsiveness of said subject to said treatment based on the score.

### Claim 2 (depends on 1)

The companion diagnostic test of claim 1, wherein at least one of the biological samples is obtained at baseline or prior to treatment.

### Claim 3

(canceled)

### Claim 4 (depends on 1)

The companion diagnostic test of claim 1, wherein the panel of biomarkers comprises serum neuroendocrine markers.

### Claim 5

(canceled)

### Claim 6 (depends on 1)

The companion diagnostic test of claim 1, wherein the algorithm comprises:
(a) CgA subject assay value≦3×(Upper Limit of Normal (ULN) and
NSE subject assay value≦1.5 ULN, equals low neuroendocrine levels;
(b) CgA subject assay value≦3×5 nmole/L and
NSE subject assay value≦1.5×12.5 ng/mL, equals low neuroendocrine levels;
(c) CgA subject assay value>3×ULN and
NSE subject assay value>1.5 ULN, equals high neuroendocrine levels; or
(d) CgA subject assay value>3×5 nmole/L and
NSE subject assay value>1.5×12.5 ng/mL, equals high neuroendocrine levels.

### Claim at position 7

7-9. (canceled)

### Claim 10 (depends on 1)

The companion diagnostic test of claim 1, wherein the panel of biomarkers further comprises a Prostate Serum Antigen (PSA) assay.

### Claim 11 (depends on 10)

The companion diagnostic test of claim 10, wherein the PSA algorithm comprises:
PSA value>100 ng/mL, equals high PSA; or
PSA value<100 ng/mL, equals low PSA.

### Claim 12

(canceled)

### Claim 13 (depends on 1)

The companion diagnostic test of claim 1, wherein the algorithm comprises:
CgA subject assay value≦3×ULN and
NSE subject assay value≦1.5 ULN, equals low neuroendocrine levels; and
PSA value>100 ng/mL.

### Claim 14 (depends on 1)

The companion diagnostic test of claim 1, wherein the panel of biomarkers further comprises prostate-specific membrane antigen (PSMA) intensity, wherein the intensity of PSMA is determined with an immunohistochemical (IHC) procedure and determining an H-score.

### Claim 15 (depends on 14)

The companion diagnostic test of claim 14, wherein the H-score is calculated according to the following formula:
H-score=(% cells showing 3+staining intensity)×3+(% cells showing 2+staining intensity)×2+(% cells showing 1+staining intensity).

### Claim 16 (depends on 15)

The companion diagnostic test of claim 15, where the algorithm comprises:
H-score is ≧200.

### Claim 17 (depends on 16)

The companion diagnostic test of claim 16, wherein an H-score ≧200 equals high PSMA intensity.

### Claim 18

(canceled)

### Claim 19 (depends on 1)

The companion diagnostic test of claim 1, wherein the algorithm comprises:
CgA subject assay value≦3×ULN and
NSE subject assay value≦1.5 ULN, equals low neuroendocrine levels;
PSA value>100 ng/mL; and
H-score is ≧200.

### Claim 20 (depends on 1)

The companion diagnostic test of claim 1, wherein the panel of biomarkers further comprises Circulating Tumor Cells (CTCs) assay.

### Claim at position 19

21-23. (canceled)

### Claim 24 (depends on 1)

The companion diagnostic test of claim 1, wherein the panel of biomarkers further comprises an assay of cell surface PSMA density.

### Claim 25 (depends on 24)

The companion diagnostic test of claim 24, wherein the algorithm comprises:
cell surface PSMA density>100,000 molecules of PSMA/PSMA+ CTC, equals high cell surface PSMA density; or
cell surface PSMA density>3+ average cell fluorescence intensity on a scale of zero to 4+ fluorescence intensity, equals high cell surface PSMA density, and the neuroendocrine level is low.

### Claim 26

(canceled)

### Claim 27 (depends on 24, 25, 26)

The companion diagnostic test of claim 24 any one of claims 24-26, wherein the cell surface PSMA density is measured by mean fluorescence intensity (MFI).

### Claim 28

(canceled)

### Claim 29 (depends on 27)

The companion diagnostic test of claim 27, wherein the algorithm comprises:
MFI>24, equals high cell surface PSMA density, and the neuroendocrine level is low.

### Claim 30 (depends on 1)

The companion diagnostic test of claim 1, wherein a score at baseline of
(a) low neuroendocrine levels, and
high PSA,
is indicative of likely responsiveness to treatment; or
(b) low neuroendocrine levels,
high PSA, and
high PSMA intensity or high cell surface PSMA density on PSMA+ CTC or tumor tissue,
is indicative of likely responsiveness to treatment.

### Claim at position 27

31-60. (canceled)

### Claim 61

A method of treating metastatic prostate cancer comprising:
a) performing a biomarker test on a patient at baseline; and
b) providing a treatment to the patient according to the results of the biomarker test.

### Claim at position 29

62-96. (canceled)

### Claim 97

A biomarker assay for identifying a subject likely to respond to a PSMA targeted therapy comprising: determining the average cell surface PSMA density on PSMA+ CTCs.

### Claim at position 31

98-130. (canceled)

### Claim 131

A biomarker assay for identifying a subject likely to respond to a PSMA targeted therapy comprising: measuring one or more serum neuroendocrine markers in a sample from a subject.

### Claim at position 33

132-142. (canceled)

### Claim 143

A diagnostic kit for selecting a prostate cancer patient for treatment by a PSMA ligand-anticancer agent conjugate, wherein the diagnostic kit comprises;
assay reagents to measure serum levels of neuroendocrine enzymes and instructions for selecting;
reagents for use in an biomarker assay to determine the PSMA density on PSMA+ CTCs in a biological sample obtained from the patient, and instructions for selecting; or
reagents for use in an IHC assay to determine the H-score of a biological sample obtained from the patient, and instructions for selecting.

### Claim at position 35

144-161. (canceled)