Reversible BTK Inhibitor and Checkpoint Inhibitor Combination
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Solution Overview
Problem
Current cancer treatments using irreversible BTK inhibitors and cancer immunotherapies are limited by resistance and insufficient efficacy, particularly in solid cancers, and there is a lack of reported combinations with reversible BTK inhibitors and immune checkpoint inhibitors for enhanced antitumor effects.
Innovation Solution
A pharmaceutical composition combining a reversible BTK inhibitor, such as an oxoisoquinoline or triazine derivative, with an immune checkpoint inhibitor, including anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies, to enhance anticancer action by synergistic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If irreversible BTK inhibitor (ibrutinib) is used for cancer treatment, then antitumor effect is achieved, but resistance develops during treatment
Solution Approach 1:
The patent changes the key parameter of BTK inhibition from irreversible to reversible binding mechanism. By using reversible BTK inhibitors instead of irreversible inhibitors like ibrutinib, the drug maintains effective inhibition while allowing for dynamic adjustment and avoiding the development of resistance that occurs with irreversible binding. This parameter change in the binding mechanism directly addresses the resistance problem while maintaining antitumor efficacy.
2Reliability
If immune checkpoint inhibitor is used for cancer treatment, then antitumor immunity is enhanced, but efficacy is limited to a subset of patients
Solution Approach 1:
The patent merges two different mechanisms of action: reversible BTK inhibition and immune checkpoint inhibition. By combining these two agents, the therapy simultaneously targets both the tumor's signaling pathways (via BTK inhibition) and the immune system's regulatory checkpoints. This combination expands the adaptable patient population by addressing multiple resistance mechanisms and enhancing overall antitumor immunity across diverse cancer types.
3Reliability
If BTK inhibitor is combined with cancer immunotherapy, then synergistic antitumor effect is achieved, but treatment complexity increases
Solution Approach 1:
The patent optimizes the parameter of drug reversibility by selecting reversible BTK inhibitors with appropriate binding kinetics. This parameter change allows for manageable dosing schedules and reduced accumulation effects, thereby simplifying the treatment regimen while maintaining the synergistic antitumor effect when combined with immune checkpoint inhibitors.
Data Source
AI summary
Provided is a novel cancer treatment means in which a reversible BTK inhibitor and immunity checkpoint inhibitor are combined. For example, provided is a pharmaceutical composition for treating cancer wherein BTK inhibitor (I-A) and anti PD-1 antibody are combined.