Extracellular Drug Conjugates With Non-Cleavable Linkers

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

There is a need for new extracellular-targeted drug conjugates (EDC) that can selectively target diseased cells to minimize off-target toxic effects and effectively treat diseases such as cancer and inflammatory lung diseases, while also providing tools for evaluating protein-protein interactions between Na,K-ATPase and cell signaling pathway proteins.

Innovation Solution

The development of EDCs comprising a targeting moiety, a non-cleavable linker, and a therapeutic or diagnostic agent, where the targeting moiety binds to extracellular targets like CD38 associated with Na,K-ATPase, ensuring selective delivery of the agent through a stable linker that remains intact during binding, thereby minimizing off-target effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If drugs are delivered to specific targets using targeting moieties, then selective targeting is improved, but off-target toxic effects may occur due to instability of the drug-conjugate linkage

Engineering Contradiction:

Improveselective targetingVSAvoidoff-target toxic effects

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent employs a non-cleavable linker that forms a stable, permanent bond between the targeting moiety and the drug, eliminating the need for temporary or degradable linkages. This stable linkage prevents premature drug release and ensures the drug is only activated at the target site, thereby reducing off-target toxic effects while maintaining selective targeting.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent creates a composite structure combining the targeting moiety, non-cleavable linker, and drug into a unified extracellular-targeted drug conjugate. This composite design ensures the drug remains stably attached to the targeting moiety during circulation and only becomes active when bound to the target, improving both selective targeting and reducing off-target effects.

Inventive Principle:

Principle #40Composite materials

2Reliability

If a stable linker is used to maintain agent proximity to target, then therapeutic efficacy is improved, but device complexity increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidconjugate structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and eliminates the need for complex, degradable linkers by using a simple non-cleavable linkage. This simplification reduces the overall complexity of the conjugate structure while maintaining the stability required for reliable therapeutic efficacy. The non-cleavable linker provides sufficient functionality without requiring additional complex features.

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS10675352B2Extracellular targeted drug conjugates

Publication Date: 2020.06.09 CENTROSE LLC

AI summary

Extracellular drug conjugates (EDCs) targeting CD38 are useful in the treatment of diseases such as cancer and immune disorders, including asthma.