Compositions 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-11135201-B2
Publication Date
2021-10-05
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. Such methods and compositions are particularly useful for treatment of malignancies.
Core Innovation
The invention relates to a composition to improve the efficacy and/or reduce the side effects of suboptimally administered drug therapy. The composition comprises a therapeutically effective quantity of bisantrene or a derivative or analog of bisantrene, together with additional therapeutic components selected to act together in a combinatorial regime. The therapeutic agent is characterized by increased therapeutic efficacy or reduced side effects as compared with the therapeutic agent as administered individually and not in the composition.
The composition further includes an additional therapeutic agent, a therapeutic agent subject to chemosensitization, and a therapeutic agent subject to chemopotentiation. It also includes a second therapeutic agent that forms a multiple drug system, an agent that enhances the activity of the therapeutic agent, at least one survivin modulator or inhibitor, and at least one multidrug resistance reversal agent.
The composition additionally requires at least one directed antibody conjugate and at least one adjuvant, and includes an additional therapeutic agent suitable for use with the therapeutic agent in a combinatorial regime, with quantities chosen to provide effective activity of both agents. The composition further includes a cyclodextrin or a polylactide, and the derivative or analog of bisantrene is selected from a group of named bisantrene analogs.
Claims Coverage
The provided material includes one independent claim covering a bisantrene-based composition that combines multi-agent therapeutic components, survivin and multidrug resistance-related components, a directed antibody conjugate, an adjuvant, and a cyclodextrin or polylactide component, with a combinatorial regime quantity selection concept.
Bisantrene-based efficacy and side-effect improvement composition
A composition to improve the efficacy and/or reduce the side effects of suboptimally administered drug therapy comprising a therapeutically effective quantity of bisantrene or a derivative or analog of bisantrene, where the therapeutic agent possesses increased therapeutic efficacy or reduced side effects as compared with the therapeutic agent as administered individually and not in the composition.
Chemosensitization and chemopotentiation components
The composition further comprises a therapeutic agent subject to chemosensitization and a therapeutic agent subject to chemopotentiation.
Multiple drug system and activity enhancement
The composition further comprises a second therapeutic agent that forms a multiple drug system and an agent that enhances the activity of the therapeutic agent.
Survivin modulation/inhibition and multidrug resistance reversal
The composition further comprises at least one survivin modulator or inhibitor and at least one multidrug resistance reversal agent.
Directed antibody conjugate and adjuvant
The composition further comprises at least one directed antibody conjugate and at least one adjuvant.
Combinatorial regime with chosen quantities for effective activity of both agents
The composition further comprises an additional therapeutic agent suitable for use with the therapeutic agent in a combinatorial regime, wherein the quantities of the therapeutic agent and the additional therapeutic agent are chosen to provide effective activity of both the therapeutic agent and the additional therapeutic agent.
Cyclodextrin or polylactide formulation component
The composition further comprises a cyclodextrin or a polylactide.
Selected bisantrene derivative/analog set
The derivative or analog of bisantrene is selected from the group consisting of the enumerated bisantrene analogs.
Overall claim coverage centers on a single independent composition claim requiring bisantrene or specified derivatives/analogs plus defined combination-regimen components, survivin and multidrug resistance reversal agents, a directed antibody conjugate, an adjuvant, and a cyclodextrin or polylactide component, with the stated comparative outcome of increased efficacy or reduced side effects versus individual administration.
Stated Advantages
Improves efficacy of suboptimally administered drug therapy.
Reduces side effects of suboptimally administered drug therapy.
Provides increased therapeutic efficacy or reduced side effects compared with the therapeutic agent as administered individually and not in the composition.
Documented Applications
Adoptive immunotherapy via bisantrene-activated macrophages producing tumor-cytostatic effects.
Telomerase inhibition and telomere dysfunction effects associated with γH2AX foci and senescence-associated β-galactosidase.
Survivin (BIRC5) promoter inhibition and downregulation leading to apoptosis.
Use as part of a combinatorial drug-combination framework in which the therapeutic agent is selected to improve efficacy or reduce side effects relative to individual administration.
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