Combinatorial methods to improve the therapeutic benefit of bisantrene and analogs and derivatives thereof
Inventors
Garner, William J. • FRANKLIN, Amie • Rothman, John
Assignees
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Publication Number
US-10500192-B2
Publication Date
2019-12-10
Expiration Date
Abstract
The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to bisantrene or derivatives, analogs, or prodrugs thereof.
Core Innovation
The invention relates to improving the efficacy and/or reducing the side effects of suboptimally administered drug therapy. The method identifies at least one factor or parameter associated with the efficacy and/or occurrence of side effects of the drug therapy, and modifies that factor or parameter to improve efficacy and/or reduce side effects. The drug therapy comprises administration of bisantrene or a derivative or analog thereof in a combinatorial regime.
When the combinatorial regime uses a derivative or analog of bisantrene, the derivative or analog is selected from Formula (II) through Formula (XIV), named bisantrene analogs, anthracen-9-ylmethylene-[2-methoxyethoxymethylsulfanyl]-5-pyridin-3-yl-[1,2,4]triazol-4-amine, compounds having the schematic structure B(Q)n, and salt forms of the compounds.
The combinatorial regime is described in the context of cancer therapy, and the drug therapy is administered to treat a form of cancer selected from refractory breast cancer, triple-negative breast cancer, acute myelocytic leukemia, and acute leukemias of childhood. The disclosed partial content further indicates combinatorial and mechanistic context for adjunct factors within cancer therapy, including multidrug resistance reversal agents, survivin inhibition, telomerase/telomere dysfunction, macrophage/innate immunity activation, and enhancement of radiation therapy.
Claims Coverage
The disclosed material includes one independent method claim, with dependent claims that narrow the drug embodiment, the cancer indications, and the combinatorial regime. Across the claims, inventive features center on improving efficacy and/or reducing side effects by identifying and modifying a factor or parameter, where the factor is use of bisantrene or selected bisantrene derivatives/analogs in a combinatorial regime.
Improving efficacy and reducing side effects by modifying an identified factor or parameter
A method to improve the efficacy and/or reduce the side effects of suboptimally administered drug therapy by identifying at least one factor or parameter associated with the efficacy and/or occurrence of side effects, and modifying the factor or parameter to improve the efficacy and/or reduce the side effects.
Combinatorial regime of bisantrene or a derivative or analog thereof as the factor or parameter
The drug therapy comprises administration of bisantrene or a derivative or analog thereof, wherein the factor or parameter is use of bisantrene or a derivative or analog thereof in a combinatorial regime.
Derivative or analog selection from defined bisantrene analog group
When the use in a combinatorial regime is a use of a derivative or analog of bisantrene, the derivative or analog is selected from Formula (II) through Formula (XIV), a named anthracen-9-ylmethylene-[2-methoxyethoxymethylsulfanyl]-5-pyridin-3-yl-[1,2,4]triazol-4-amine, named bisantrene analogs listed in the claims, compounds having the schematic structure B(Q)n, and salt forms of the compounds.
Cancer indication selected from specified cancer forms
The drug therapy is administered to treat a form of cancer selected from refractory breast cancer, triple-negative breast cancer, acute myelocytic leukemia, and acute leukemias of childhood.
Combinatorial regime defined by enumerated combination partner categories
In the combinatorial regime, the combination partner is selected from categories including agents that induce immunoactivity, induce macrophage activation, cytokines, agents inhibiting telomerase, agents inhibiting survivin, agents inducing demethylation, adjuvants, antibodies, innate or adaptive immune stimulators, checkpoint inhibitors, mTOR antagonists, Akt inhibitors, notch inhibitors, HSP inhibitors, phosphatidylinositide 3-kinase inhibitors, kinase inhibitors, cytarabine, and taxane/taxol.
The claims cover a method that improves efficacy and reduces side effects of suboptimally administered drug therapy by identifying and modifying a factor or parameter, where the factor is the use of bisantrene or selected bisantrene derivatives/analogs in a combinatorial regime. The claims further define eligible bisantrene derivatives/analogs, selected cancer indications, and enumerated combination partner categories.
Stated Advantages
Improving the efficacy of suboptimally administered drug therapy.
Reducing the side effects of suboptimally administered drug therapy.
Documented Applications
Treatment of refractory breast cancer, triple-negative breast cancer, acute myelocytic leukemia, and acute leukemias of childhood.
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