ADC Payload-Binding Compositions for Off-Target Toxicity Control

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Solution Overview

Problem

Clinical application of antibody-drug conjugates (ADCs) has been limited by substantial off-target toxicity, which restricts tolerable doses below levels needed for tumor eradication, failing to fully realize their therapeutic potential.

Innovation Solution

Administering ADCs with payload-binding agents, such as antibodies or antibody fragments, that specifically target the drug portion of the ADC to reduce off-target toxicity, using various administration routes and regimens.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ADCs are administered at higher doses to achieve tumor eradication, then anti-tumor efficacy is improved, but off-target toxicity increases

Engineering Contradiction:

Improveanti-tumor efficacyVSAvoidoff-target toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a payload-binding agent (PBA) as an intermediary substance that specifically binds to free payload molecules. This PBA acts as a mediator between the toxic payload and the non-target tissues, sequestering the free payload and preventing it from interacting with healthy cells while allowing the ADC to maintain its therapeutic function at higher doses

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If tolerable doses are limited due to off-target toxicity, then safety is improved, but anti-tumor efficacy deteriorates

Engineering Contradiction:

ImprovesafetyVSAvoidanti-tumor efficacy

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The payload-binding agent serves as a protective intermediary that enables dose escalation by neutralizing free payload in circulation. This allows clinicians to administer higher ADC doses that would otherwise be too toxic, thereby restoring anti-tumor efficacy while maintaining an acceptable safety profile through the PBA's protective action

Inventive Principle:

Principle #24Intermediary (Mediator)

3Measurement precision

If ADCs are used for targeted delivery, then specificity is improved, but off-target toxicity still occurs

Engineering Contradiction:

Improvetargeting specificityVSAvoidnon-target toxicity

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful effect of payload leakage into a beneficial one by using the presence of free payload as a target for the PBA. The very payload molecules that escape from the ADC and cause toxicity become the binding targets for the PBA, which then sequesters them and prevents tissue damage, effectively transforming the harmful free payload into a useful binding target

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS12624123B2Compositions and methods for reducing off-target toxicity of antibody drug conjugates

Publication Date: 2026.05.12 THE RES FOUNDATION FOR THE STATE UNIV OF NEW YORK

AI summary

Provided are compositions and methods for reducing off-target toxicity of antibody-drug conjugates (ADCs). The compositions comprise an ADC, and an agent targeted to the drug (payload) that is delivered by or derived from the ADC. The ADC and the agent targeted to the payload may be delivered together or separately in the treatment of various conditions (such as tumors) by ADCs. Examples of agents targeted to payload include antibodies, fragments, or modifications thereof.