US2020392585A1PendingUtilityA1
Context dependent diagnostics test for guiding cancer treatment
Assignee: EUTROPICS PHARMACEUTICALS INCPriority: Jan 12, 2015Filed: Jun 25, 2020Published: Dec 17, 2020
Est. expiryJan 12, 2035(~8.5 yrs left)· nominal 20-yr term from priority
G16B 40/20G16B 40/10C12Q 2600/106C12Q 1/6886C12Q 2600/158C12Q 2600/156C12Q 2600/118G16B 40/00A61K 31/453A61P 35/02G16H 50/50
59
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The present disclosure provides diagnostic methods that are relevant to various cancers and which comprise improvements on a BH3 profiling diagnostic method. The methods are relevant for selecting a cancer treatment for a patient, comprising measurement of response to agents that perturb the MCL1 and BFL1 proteins in their function to sequester pro-apoptotic proteins using BH3 profiling of patient cancer cells and inclusion of one or more clinical features of the patient into a predictive algorithm to classify each patient's likelihood of clinical response to one or more cancer treatments that perturb the function of MCL1.
Claims
exact text as granted — not AI-modified1 - 66 . (canceled)
67 . A method for selecting a patient having a hematologic cancer for treatment, comprising:
a) permeabilizing an aliquot of cells obtained from a bone marrow aspirate of the patient; b) contacting the aliquot of permeabilized bone marrow aspirate cells with a BIM peptide, c) measuring BIM peptide-induced mitochondrial outer membrane permeabilization (MOMP) in the aliquot of bone marrow aspirate cells, to determine a percent priming for the BIM peptide, d) selecting the patient as suitable for therapy if the BIM percent priming is greater than about 40%, and e) administering a therapy comprising a hypomethylating agent to the selected patient of step (d).
68 . The method of claim 67 , wherein the hematologic cancer is selected from acute myelogenous leukemia (AML), multiple myeloma, follicular lymphoma, acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin's lymphoma.
69 . The method of claim 67 , wherein the patient is a FMS-like tyrosine kinase 3 (FLT3) negative patient.
70 . The method of claim 67 , wherein the hypomethylating agent is selected from azacitidine, decitabine, guadecitabine, and FdCyd.
71 . The method of claim 67 , wherein the method further comprises predicting a clinical response in the patient.
72 . The method of claim 71 , wherein the clinical response is at least about 1, about 2, about 3, or about 5 year progression/event-free survival.
73 . The method of claim 67 , wherein the patient is evaluated for a risk factor selected from age, cytogenetic risk classification, FMS-like tyrosine kinase-3 (FLT-3) mutation status, nucleophosmin 1 (NPM1) mutation status, MDS/Marrow Disorder History, prior chemotherapy history, Bone Marrow (BM) Blast %, and White Blood Cell (WBC) Count at Diagnosis.
74 . The method of claim 67 , wherein the BIM peptide is at a concentration of 0.1 μM in the BIM peptide-induced MOMP aliquot.
75 . The method of claim 67 , wherein the priming is defined by the following equation:
%
Priming
=
(
1
-
(
BIMAUC
-
C
C
C
P
A
U
C
)
(
D
M
S
O
A
U
C
-
C
C
C
P
A
U
C
)
)
×
100
,
wherein:
the BIM AUC comprises either an area under a curve or a signal intensity of the BIM peptide,
the CCCP (Carbonyl cyanide m-chlorophenyl hydrazone) AUC comprises either an area under a curve or a signal intensity of a baseline positive control, and
the DMSO AUC comprises either an area under a curve or a signal intensity of a baseline negative control.
76 . The method of claim 75 , wherein the area under the curve for BIM AUC, CCCP AUC, and DMSO AUC are each established by homogenous time-resolved fluorescence (HTRF).
77 . The method of claim 75 , wherein the signal intensity for BIM AUC, CCCP AUC, and BIM AUC are each a single time point measurement that occurs over a window from between about 0 to about 300 min to about 0 to about 30 min.
78 . The method of claim 75 , wherein the area under the curve for BIM AUC, CCCP AUC, and DMSO AUC are each established by fluorescence activated cell sorting (FACS).
79 . The method of claim 75 , wherein the signal intensity for BIM AUC, CCCP AUC, and DMSO AUC are each a single time point measurement that occurs between about 5 min and about 300 min.
80 . The method of claim 67 , wherein the MOMP is measured using JC-1 staining.
81 . The method of claim 75 , wherein the MOMP is measured using JC-1 staining.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.