CLDN18.2 Antagonist Combination for Low PD-L1 Tumor Response

Solution Overview

Problem

Existing combination therapies targeting Claudin 18.2 (CLDN18.2) and PD-1/PD-L1 axis inhibitors face challenges in achieving satisfactory therapeutic efficacy for CLDN18.2-expressing cancers.

Innovation Solution

Administering a therapeutically effective amount of a CLDN18.2 antagonist in combination with a PD-1/PD-L1 axis inhibitor, optionally with a chemotherapeutic agent, to subjects with CLDN18.2 expression in diseased tissues, particularly when PD-L1 expression is low or absent, to sensitize or increase responsiveness to treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If combination therapy of CLDN18.2 antagonist and PD-1/PD-L1 axis inhibitor is administered, then therapeutic efficacy is improved, but treatment complexity increases

Engineering Contradiction:

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines two different therapeutic mechanisms into a single treatment regimen: CLDN18.2-targeted antibody therapy and PD-1/PD-L1 immune checkpoint inhibition. This merging of targeted therapy and immunotherapy approaches creates a synergistic effect that improves therapeutic efficacy while managing treatment complexity through coordinated administration protocols

Inventive Principle:

Principle #5Merging (Combining)

2Reliability

If combination therapy is used to enhance responsiveness in resistant cases, then treatment effectiveness increases, but side effects may increase

Engineering Contradiction:

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by targeting CLDN18.2 specifically in tumor cells while leaving normal cells unaffected. The CLDN18.2 antibody binds selectively to the claudin-18.2 protein expressed on cancer cell surfaces, delivering localized therapeutic action at the tumor site while minimizing systemic side effects through targeted delivery

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20250326834A1Combination therapy of claudin 18.2 antagonist and PD-1/PD-l1 axis inhibitor

Publication Date: 2025.10.23

AI summary

Provided are combination therapies of a CLDN 18.2 antagonist and a PD-1/PD-L1 axis inhibitor for subjects having expression of CLDN 18.2 and having low or no expression of PD-L1 in a disease tissue (e.g., tumor tissue) obtained from the subject.