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-9974774-B2
Publication Date
2018-05-22
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 by identifying at least one factor or parameter associated with the efficacy and/or occurrence of side effects, and by modifying that factor or parameter. The identified factor or parameter is associated with the specific disease or condition being treated, the stage of the disease or condition being treated, selection of an appropriate patient for treatment, and selection of an appropriate phenotype of the patient or the disease or condition being treated.
The drug therapy comprises administration of bisantrene. The disease or condition being treated is cancer selected from refractory breast cancer, breast cancer characterized by overexpressed Her-2-neu, triple-negative breast cancer, acute myelocytic leukemia, and acute leukemias of childhood.
In dependent coverage, the improvement is further specified by indication for use, disease stage, and patient selection. Patient selection criteria include susceptibility to thrombocytopenia or neutropenia, gastrointestinal toxicity intolerance, gene expression status, immune screening, DNA methylation screening, recurrent disease duration of initial response, p53 mutation status, metabolic-enzyme level, and lack of extensive prior treatment.
Claims Coverage
The claims cover one independent method for improving efficacy and/or reducing side effects of suboptimally administered drug therapy by identifying and modifying a factor or parameter associated with efficacy and/or side effects, with the factor or parameter tied to disease/condition, disease stage, patient selection, and/or patient or disease phenotype. The method comprises administration of bisantrene for specified cancer indications, and dependent claims narrow the refinement through indication for use, disease stage, and detailed patient-selection criteria.
Identify a factor or parameter linked to efficacy, side effects, and disease context
Identifying at least one factor or parameter associated with the efficacy and/or occurrence of side effects of the drug therapy, wherein the factor or parameter is additionally associated with the specific disease or condition being treated, the stage of the disease or condition being treated, selection of an appropriate patient for treatment, and selection of an appropriate phenotype of the patient or the disease or condition being treated.
Modify the factor or parameter to improve efficacy and/or reduce side effects
Modifying the factor or parameter to improve the efficacy and/or reduce the side effects of the drug therapy.
Administer bisantrene for selected cancer indications
The drug therapy comprises administration of bisantrene, wherein the disease or condition being treated is cancer selected from refractory breast cancer, breast cancer characterized by overexpressed Her-2-neu, triple-negative breast cancer, acute myelocytic leukemia, and acute leukemias of childhood.
Refine therapy by indication for use, disease stage, and patient selection
The method is refined using an indication for use and/or a disease stage and/or patient selection as additional associated bases for improving the therapy.
Patient selection using specified biomarker and screening criteria
Patient selection is carried out using criteria including susceptibility to thrombocytopenia or neutropenia, GI-toxicity intolerance, gene over-expression or under-expression, immune screening, DNA methylation screening, recurrent disease duration of initial response, p53 mutation status, metabolic-enzyme level, and lack of extensive prior treatment.
Overall, the claim coverage focuses on refining suboptimally administered bisantrene therapy by selecting and altering a factor or parameter associated with both efficacy and side effects, with the factor or parameter tied to disease context, disease stage, patient selection, and patient or disease phenotype. Dependent claims further narrow the method through indication for use, disease stage, and detailed patient-selection criteria.
Stated Advantages
Improve the efficacy of suboptimally administered drug therapy.
Reduce the side effects of suboptimally administered drug therapy.
Documented Applications
Treatment of cancer using drug therapy comprising administration of bisantrene for refractory breast cancer, breast cancer characterized by overexpressed Her-2-neu, triple-negative breast cancer, acute myelocytic leukemia, and acute leukemias of childhood.
Use of disease-stage refinement including angiogenesis inhibition to prevent or limit metastatic spread, recurrent leukemia, or recurrent breast cancer.
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