Multi-Arm Linker Conjugates for High Drug-to-Antibody Ratio

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Solution Overview

Problem

Current antibody-drug conjugates (ADCs) face limitations in achieving a high drug-to-antibody ratio (DAR) due to the conventional linker-drug combinations, which can result in reduced efficacy and increased toxicity.

Innovation Solution

The development of a linker modified with one or more arms to conjugate additional drugs, increasing the DAR, and the incorporation of hydrophilic spacers or chains to enhance the water solubility of the linker-drug combination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional linker-drug combinations are used to conjugate drugs to antibodies, then the conjugation process is simple, but the drug-to-antibody ratio (DAR) is limited and therapeutic efficacy is reduced

Engineering Contradiction:

Improvedrug-to-antibody ratioVSAvoidlinker structure complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The linker is divided into multiple arms (first arm, second arm, third arm) that can independently conjugate different drugs to the antibody. Each arm functions as a separate conjugation unit, enabling the attachment of multiple drug molecules (e.g., first drug, second drug, third drug) to the same antibody molecule, thereby increasing the drug-to-antibody ratio without requiring a completely new conjugation approach

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention transitions from conventional single-linker conjugation to a multi-arm linker structure that operates in a dimensional expansion of the conjugation architecture. By introducing multiple arms radiating from a central core, the system achieves higher drug loading capacity (DAR) by utilizing spatial arrangement and structural complexity rather than simply increasing the length or number of sequential linkers

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

2Productivity

If multiple drugs are conjugated to increase the drug load, then the therapeutic activity is enhanced, but the water solubility of the linker-drug combination decreases

Engineering Contradiction:

Improvetherapeutic activityVSAvoidwater solubility

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

Different arms of the linker are designed with different local chemical properties to balance hydrophobicity and hydrophilicity. For example, some arms may contain hydrophobic regions for drug conjugation while other arms incorporate hydrophilic spacers or chains that enhance water solubility. This localized differentiation allows the overall structure to achieve both high drug loading and improved solubility

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

Hydrophilic spacers and hydrophilic chains are introduced as intermediary elements between the hydrophobic drug molecules and the aqueous environment. These intermediaries act as solubility enhancers that bridge the gap between the lipophilic drug cargo and the hydrophilic cellular environment, maintaining water solubility even when multiple drugs are conjugated to the linker

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20250114473A1Compound for conjugation, conjugate and pharmaceutical composition comprising the same

Publication Date: 2025.04.10 FORMOSA LAB

AI summary

Disclosure is a compound with one or more arm(s) for drug conjugation and a conjugate including the compound so as to provide high drug-to-moiety ratio and conjugate more drugs to the conjugate.