Dactinomycin compositions and methods for the treatment of myelodysplastic syndrome and acute myeloid leukemia
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Publication Number
US-10973773-B2
Publication Date
2021-04-13
Expiration Date
Abstract
The disclosure provides compositions comprising dactinomycin, formulated for delivery by nanoparticle, and methods for treating a myelodysplastic syndrome (MDS) or cancer, for example, NPM1-mutated acute myeloid leukemia (AML), by administration of the compositions of the disclosure.
Core Innovation
The invention relates to anti-cancer treatment using dactinomycin encapsulated in nanoparticles. A therapeutically effective amount of dactinomycin is provided as nanoparticle-encapsulated dactinomycin, and the nanoparticles comprise PLA-mPEG, where the PLA-mPEG comprises about 25% mPEG by weight and has a molecular weight of about 30,000 Da.
The nanoparticles have an average size of about 100 nm to about 200 nm. The therapeutically effective amount of dactinomycin is configured to result in a Cmax of about 1 ng/ml to about 20 ng/ml, and the formulation approach is aimed at controlling dactinomycin exposure using nanoparticle encapsulation.
The disclosed compositions can optionally include a surfactant and can include a defined dactinomycin content by weight. The disclosed use can also include optional combination regimens in which at least one additional specified chemotherapeutic drug class is included with molar-ratio relationships relative to dactinomycin.
Claims Coverage
The claims cover nanoparticle-encapsulated dactinomycin compositions defined by PLA-mPEG composition, nanoparticle size, and a target Cmax range. Dependent claims further refine the formulation by adding optional formulation components, specifying dactinomycin weight-percent, and defining optional combination regimens with specified chemotherapeutic drug classes and molar-ratio constraints. In total, the claims recite five inventive features.
Pla-mpeg nanoparticle encapsulation of dactinomycin with target cmax
A composition comprising a therapeutically effective amount of dactinomycin encapsulated in nanoparticles comprising PLA-mPEG, wherein the PLA-mPEG comprises about 25% mPEG by weight, the molecular weight of the PLA-mPEG is about 30,000 Da, and the nanoparticles have an average size of about 100 nm to about 200 nm, wherein the therapeutically effective amount results in a Cmax of about 1 ng/ml to about 20 ng/ml.
Optional surfactant addition to PLA-mPEG nanoparticle-encapsulated dactinomycin
The composition further comprises a surfactant in the nanoparticle-encapsulated dactinomycin composition.
Polyvinyl alcohol surfactant in PLA-mPEG nanoparticle-encapsulated dactinomycin
The surfactant is polyvinyl alcohol.
Defined dactinomycin weight-percent range in the composition
The composition further comprises about 5% by weight to about 15% by weight dactinomycin.
Optional combination therapy with specified chemotherapeutic drug class molar ratios
The composition further comprises a therapeutically effective amount of at least one additional specified chemotherapeutic drug class, with the molar ratio of the selected drug class to dactinomycin being 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, <1:1, or any ratio in between.
The claims primarily cover nanoparticle-encapsulated dactinomycin using PLA-mPEG with specified composition and nanoparticle size, configured to achieve a specified Cmax exposure range, and further define optional surfactant inclusion, dactinomycin weight-percent, and combination regimens with specified chemotherapeutic drug classes and molar ratios.
Stated Advantages
Documented Applications
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