STING Agonist Antibody-Drug Conjugates for Targeted Immune Activation

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Solution Overview

Problem

Existing treatments for diseases such as cancer and infectious diseases face challenges due to the inhibition of the STING activation process, leading to reduced efficacy and specificity, and there is a need for targeted therapies that can modulate the STING pathway effectively.

Innovation Solution

Development of antibody-drug conjugates (ADCs) that conjugate a STING agonist with a protein-based recognition-molecule (PBRM) through a linker, allowing targeted delivery and activation of the STING pathway, enhancing immune response and therapeutic impact.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If antibody-drug conjugates are used to target STING pathway, then treatment specificity is improved, but device complexity increases

Engineering Contradiction:

Improvetreatment specificityVSAvoidconjugate structure complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The ADC is divided into three distinct functional segments: a protein-based recognition molecule (antibody) for targeted binding, a linker component for stable attachment and controlled release, and a STING agonist drug moiety for immune activation. This segmentation allows each component to be optimized independently while maintaining overall therapeutic specificity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The linker acts as an intermediary component that bridges the antibody and STING agonist, providing stable conjugation in circulation while enabling controlled drug release at the target site. This intermediary structure resolves the complexity by creating a modular interface between the targeting and therapeutic functions.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If STING agonist is administered systemically, then immune response coverage is improved, but harmful factors increase

Engineering Contradiction:

Improveimmune response coverageVSAvoidsystemic toxicity

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The ADC exhibits local quality by concentrating the STING agonist payload specifically at the target site through antibody-mediated binding. The antibody component directs the drug to specific cells or tissues expressing the target antigen, creating high local drug concentration where immune activation is needed while maintaining low systemic levels to minimize toxicity.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The harmful systemic effects are extracted from the therapeutic action by separating the drug delivery function from the immune activation function. The antibody carrier extracts the toxicity problem from the STING agonist by providing targeted delivery, allowing the agonist to exert its immune-stimulating effect only where the antibody binds, rather than systemically throughout the body.

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS12440576B2Antibody drug conjugates comprising sting agonists

Publication Date: 2025.10.14 MERSANA THERAPEUTICS INC

AI summary

The present disclosure provides scaffolds and antibody-drug conjugates (ADCs) comprising a stimulator of interferon genes (STING). The present disclosure also provides uses of the ADCs in treatment, e.g., treatment of cancer.