Combination therapy for MDS

Patent metadata

Field	Value
Publication number	US-9855273-B2
Application number	US-201615288402-A
Country	US
Kind code	B2
Filing date	Oct 7, 2016
Priority date	May 22, 2013
Publication date	Jan 2, 2018
Grant date	Jan 2, 2018

Abstract

Disclosed are compositions and methods for the treatment of disorders such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The disclosed methods include administering to an individual in need of such treatment a composition that may include an IRAK1/4 inhibitor. In other aspects, the method may include administration of a BLC2 inhibitor.

First claim

What is claimed:

1. A method of treating acute myeloid leukemia in an individual comprising the step of administering to said individual a composition comprising an IRAK1/4 inhibitor.

2. The method of claim 1 wherein said IRAK1/4 inhibitor is selected from N-acyl-2-aminobenzimidazoles, imidazo[1,2-a]pyridino-pyrimidine, imidazo[1,2-a]pyridino-pyridine, benzimidazolo-pyridine, N-(2-morpholinylethyl)-2-(3-nitrobenzoylamido)-benzimidazole,

(IRAK1/4), or combinations thereof.

3. The method of claim 1 wherein said IRAK1/4 inhibitor comprises an RNAi sufficient to inhibit IRAK1 expression.

4. The method of claim 1 , further comprising the step of administering to said individual an apoptotic modulator.

5. The method of claim 1 , further comprising the step of administering to said individual an apoptotic modulator, wherein said apoptotic modulator comprises a BCL2 inhibitor.

6. The method of claim 1 , comprising the step of administering to said individual an apoptotic modulator, wherein said apoptotic modulator comprises a BCL2 inhibitor selected from

and
combinations thereof.

7. The method of claim 1 wherein said administering step is selected from orally, rectally, nasally, topically, parenterally, subcutaneously, intramuscularly, intravenously, transdermally, or a combination thereof.

8. The method of claim 1 wherein said administration decreases the incidence of marrow failure, immune dysfunction, transformation to overt leukemia, or combinations thereof in said individual, as compared to an individual not receiving said composition.

9. The method of claim 1 wherein said method decreases a marker of viability of MDS cells.

10. The method of claim 1 , wherein said treatment decreases a marker of viability of MDS and/or AML cells, wherein marker is selected from survival over time, proliferation, growth, migration, formation of colonies, chromatic assembly, DNA binding, RNA metabolism, cell migration, cell adhesion, inflammation, or a combination thereof.

Assignees

• Children'S Hospital Medical Center

Inventors

• Starczynowski Daniel
• Rhyasen Garrett W

Classifications

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• A61K31/635

  having a heterocyclic ring, e.g. sulfadiazine · CPC title

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title