US 11,376,269 B2 · Pharmaceutical compositions for the treatment of chemoresistant acute myeloid leukemia (AML)

Abstract

The present invention relates to pharmaceutical compositions for use in the treatment of chemoresistant acute myeloid leukemia (AML). The inventors have established a powerful preclinical model to screen in vivo responses to conventional genotoxics and to mimic the chemoresistance and minimal residual disease as observed in AML patients after chemotherapy. The inventors showed that cytarabine-resistance mechanism involves the CD39-dependent crosstalk between energetic niche and AML mitochondrial functions through CD39-P2Y13-cAMP-PKA signaling axis. In particular, the present invention relates to an inhibitor of the CD39-P2Y13-cAMP-PKA signaling axis for use in a method of treating chemoresistant acute myeloid leukemia (AML) in a patient in need thereof comprising administering to the patient a therapeutically effective amount of said inhibitor.

Claims2

Dependent claims

A method of treating chemoresistant acute myeloid leukemia (AML) in a patient in need thereof, wherein residual chemoresistant AML cells of the patient exhibit increased expression of CD39 compared to primary AML cells, comprising, administering to the patient a therapeutically effective amount of cytarabine and an inhibitor of the CD39-P2Y13-cAMP-PKA signaling axis,

wherein the therapeutically effective amount is sufficient to decrease the generation of adenosine by CD39 and prevent immunosuppression,
wherein the inhibitor of the CD39-P2Y13-cAMP-PKA signaling axis is not suramin;
and
wherein the inhibitor of the CD39-P2Y13-cAMP-PKA signaling axis is a CD39 inhibitor, an antibody having specificity for CD39, or an inhibitor of CD39 expression.

1 more element

Dependencies are inferred from the claim text.

Facts

Application

16/099,209Filed 5 May 2017

Priority

EP 163055316 May 2016

Published

US 2019/0209594 A111 Jul 2019

Granted

5 Jul 2022

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

A61K 31/704
Attached to a carbocyclic compound, e.g. phloridzin: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin,…
A61K 31/00
Medicinal preparations containing organic active ingredients
A61K 31/663
Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon: compounds having two or more phosphorus acid groups or esters…
A61K 31/7068
Containing condensed or non-condensed pyrimidines: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid

Pharmaceutical compositions for the treatment of chemoresistant acute myeloid leukemia (AML)

Life of this patent

Pharmaceutical compositions for the treatment of chemoresistant acute myeloid leukemia (AML)

Life of this patent

Abstract

Claims2