Plinabulin Combination Therapy to Reverse Checkpoint Resistance

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Solution Overview

Problem

Cancer cells develop resistance to immune checkpoint inhibitors, rendering existing therapies ineffective for many patients.

Innovation Solution

Administering plinabulin-based combination therapies, including plinabulin and additional chemotherapy agents or immune checkpoint inhibitors, to enhance anti-tumor immunity and overcome resistance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If immune checkpoint inhibitors are used to treat cancer, then anti-tumor immunity is enhanced, but tumors develop resistance rendering the therapy ineffective

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidduration of response

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent combines plinabulin with immune checkpoint inhibitors to create a combination therapy that overcomes resistance. Plinabulin enhances antigen processing and presentation while checkpoint inhibitors block inhibitory signals, creating a synergistic effect that restores therapeutic effectiveness in resistant tumors.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent changes the therapeutic parameter by introducing plinabulin, which modifies the immune microenvironment through enhanced antigen presentation. This parameter change allows the immune system to recognize and attack tumors that have become resistant to checkpoint inhibitor monotherapy.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If plinabulin-based combination therapies are administered, then resistance to immune checkpoint inhibitors is reversed, but treatment complexity increases

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidtreatment regimen complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the treatment approach by using plinabulin to specifically target antigen processing defects while combining it with checkpoint inhibitors that address immune suppression. This segmentation allows each agent to address a specific resistance mechanism, making the complex treatment more manageable and targeted.

Inventive Principle:

Principle #1Segmentation

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Plinabulin promotes antigen processing and presentation, reversing resistance to immune checkpoint inhibitors, reducing tumor mass by 50% to 100%, and effectively treating refractory cancers.

Implementation Method 1

Plinabulin can efficiently promote antigen processing and presentation by dendritic cells to effector cells, such as T-cells

Methodology Applied

Scientific EffectAntigen processing and presentation:

Data Source

PatentUS12377094B2Therapeutic compositions and methods for treating checkpoint inhibitor-resistant tumors using plinabulin-based combination therapies

Publication Date: 2025.08.05 BEYONDSPRING PHARMACEUTICALS INC

AI summary

Disclosed herein are methods of treating, preventing or ameliorating a disease or condition associated with cancer or a tumor. In some embodiments, the method includes administering a compound of Formula (I) to a subject in need thereof wherein the cancer or the tumor is or becomes resistant to one or more immune checkpoint inhibitors.