Hydrophilic Antibody-Drug Conjugate Linker for Aggregation Control
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Solution Overview
Problem
Existing antibody-drug conjugates face challenges with hydrophobic linkers that can cause aggregation and reduce antibody affinity, and drug-resistant tumor cells limit their efficacy, necessitating the development of hydrophilic linkers for stable and effective drug delivery.
Innovation Solution
A novel linker structure represented by formula A, featuring hydrophilic groups and specific functional moieties, is used to create a stable and effective antibody-drug conjugate, allowing for higher drug loads and targeted drug release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If hydrophobic linkers are used to deliver cytotoxic drugs, then drug delivery capability is improved, but conjugate aggregation increases and antibody affinity decreases
Solution Approach 1:
The patent changes the chemical parameter of the linker from hydrophobic to hydrophilic character. This fundamental parameter change allows the linker to maintain solubility and prevent aggregation while still delivering hydrophobic cytotoxic drugs, thereby resolving the contradiction between drug load and conjugate stability
Solution Approach 2:
The patent creates a composite linker structure combining hydrophilic segments (such as PEG chains) with drug-carrying capabilities. This composite approach allows the linker to simultaneously provide solubility enhancement to prevent aggregation and maintain the ability to deliver hydrophobic drugs, resolving the contradiction between preventing aggregation and maintaining drug delivery
2Quantity of substance
If hydrophobic linkers are used to deliver cytotoxic drugs, then drug delivery capability is improved, but antibody affinity is reduced
Solution Approach 1:
The patent changes the hydrophobicity parameter of the linker to hydrophilic, which prevents the linker from interfering with antibody-antigen binding interactions. This parameter change ensures that high drug loads can be achieved without compromising antibody affinity, resolving the contradiction between drug load and antibody affinity
Solution Approach 2:
The hydrophilic linker acts as an intermediary that separates the hydrophobic drug from the antibody, preventing direct hydrophobic interactions between the drug and antibody that would reduce affinity. The linker mediates the connection while maintaining both antibody functionality and drug delivery capability
3Quantity of substance
If drug load is increased, then therapeutic effectiveness is improved, but hydrophobic aggregation increases and reduces efficacy
Solution Approach 1:
The patent changes the solvent interaction parameter of the linker to hydrophilic character, which allows high drug loads to be achieved without the linker itself contributing to hydrophobic aggregation. The hydrophilic nature of the linker counteracts the hydrophobic tendency of high drug loads, preventing aggregation and maintaining efficacy
Data Source
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AI summary
The present invention relates to a linker for an antibody-drug conjugate and a use thereof. Specifically, a linker represented by formula I is provided. An antibody-drug conjugate prepared by means of the linker are more stable and more effective, and can be effectively used for treating various diseases such as tumors. Further provided are an antibody-drug conjugate prepared using the linker and a use of the antibody-drug conjugate in treating tumors or other diseases.