IP Library Granted Patent US 8,263,354
Granted Patent B2
US 8,263,354 · App. 12/815,321 · Granted Sep 11, 2012

Methods for assessing cancer for increased sensitivity to 10-propargyl-10-deazaaminopterin

Assignee: Sloan-Kettering Institute for Cancer Research
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Quick Facts
Patent No.
US 8,263,354
App. No.
12/815,321
Granted
Sep 11, 2012
Kind
B2
Abstract

Sensitivity of a patient's cancer to treatment with 10-propargyl-10-deazaaminopterin is assessed and patients are selected for treatment of cancer with 10-propargyl-10-deazaaminopterin, by determining the amount of a selected polypeptide expressed by the cancer and comparing the amount with the amount of the selected polypeptide expressed by a reference cancer. The polypeptide includes a member of a folate pathway polypeptide within a cell and may include at least one of reduced folate carrier-1 enzyme (RFC-1), dihydrofolate reductase (DHFR), folylpoly-gamma-glutamate synthetase (FPGS), thymidylate synthase (TS), γ-glutamyl hydrolase (GGH), and glycinamide ribonucleotide formyltransferase (GARFT).

Claims (18)

1. A method of selecting a patient for treatment of a cancer with 10-propargyl-10-deazaaminopterin, the method comprising the steps of:

(a) obtaining a sample of the patient's cancer tissue;

(b) determining the expression level of a polypeptide comprising a member of a folate pathway polypeptide within a cell comprising least one of reduced folate carrier-1 enzyme (RFC-1), dihydrofolate reductase (DHFR), folylpoly-gamma-glutamate synthetase (FPGS), thymidylate synthase (TS), γ-glutamyl hydrolase (GGH), and glycinamide ribonucleotide formyltransferase (GARFT) in the sample;

(c) comparing the determined expression level in the sample with a reference expression level for the polypeptide comprising a member of a folate pathway polypeptide within a cell; and

(d) selecting the patient for treatment 10-propargyl-10-deazaaminopterin where the comparison of the expression level in the sample of the polypeptide comprising a member of a folate pathway polypeptide within a cell and the corresponding reference expression level indicate sensitivity of patient's cancer tissue to 10-propargyl-10-deazaaminopterin.

2. The method of claim 1 , wherein the patient's cancer is a solid tumor or a lymphoma.

3. The method of claim 2 , wherein the solid tumor is selected from the group consisting of NSCLC, head and neck cancer, prostate cancer, and breast cancer.

4. A method for assessing sensitivity of a patient's cancer to treatment with 10-propargyl-10-deazaaminopterin comprising the steps of:

(a) obtaining a sample of the patient's cancer tissue;

(b) determining the expression level of at least one member of a folate pathway polypeptide within a cell comprising least one of reduced folate carrier-1 enzyme (RFC-1), dihydrofolate reductase (DHFR), folylpoly-gamma-glutamate synthetase (FPGS), thymidylate synthase (TS), -glutamyl hydrolase (GGH), and glycinamide ribonucleotide formyltransferase (GARFT) expressed in the sample;

(c) comparing the determined expression level in the sample with a reference expression level for the polypeptide comprising a member of a folate pathway polypeptide within a cell of a reference cancer to determine whether the expression level for the polypeptide comprising a member of a folate pathway polypeptide within a cell in the sample is indicative of an expression level that predicts sensitivity to 10-propargyl-10-deazaaminopterin; and

(d) generating a report of the predicted sensitivity of the sample to 10-propargyl-10-deazaaminopterin.

5. The method of claim 4 , wherein the reference cancer is a solid tumor or a lymphoma.

6. The method of claim 5 , wherein the solid tumor is selected from the group consisting of NSCLC, head and neck cancer, prostate cancer, and breast cancer.

7. A method for assessing sensitivity of a cancer to treatment with 10-propargyl-10-deazaaminopterin comprising the steps of

(a) obtaining a sample of the lymphoma;

(b) determining the amount of a member of a folate pathway polypeptide within a cell comprising least one of reduced folate carrier-1 enzyme (RFC-1), dihydrofolate reductase (DHFR), folylpoly-gamma-glutamate synthetase (FPGS), thymidylate synthase (TS), γ-glutamyl hydrolase (GGH), and glycinamide ribonucleotide formyltransferase (GARFT) expressed by the sample wherein higher levels of expressed polypeptide comprising a member of a folate pathway polypeptide within a cell are indicative of sensitivity to 10-propargyl-10-deazaaminopterin; and

(c) generating a report of the predicted sensitivity of the sample to 10-propargyl-10-deazaaminopterin.

Assignments (3)
CONFIRMATORY LICENSE Recorded Dec 30, 2015
From: SLOAN-KETTERING INST CAN RESEARCH
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 037398/0759 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 2, 2011
From: O'CONNOR, OWEN A.
To: SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH
Reel/Frame 026851/0316 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 20, 2011
From: SIROTNAK, FRANCIS
To: SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH
Reel/Frame 025666/0720 →
Continuity (5)
Continuation In Part 12637254 · Dec 14, 2009
Continuation 11953031 · Dec 8, 2007
Continuation In Part 11568254
Provisional Application 60521593 · May 30, 2004
Related Publication 20110111436A1 · May 12, 2011