Anti-MET Single-Domain Antibody Constructs for NSCLC

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Solution Overview

Problem

Current therapies targeting MET in non-small cell lung cancer (NSCLC) have shown limited therapeutic benefit due to resistance and inefficacy, highlighting the need for more effective antibody-based treatments.

Innovation Solution

Development of isolated anti-MET constructs comprising a single-domain antibody (sdAb) moiety specifically recognizing MET, which can be used for imaging and therapeutic applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional monoclonal antibodies are used to target MET, then the therapy shows initial effectiveness, but resistance inevitably arises and therapeutic benefit is limited

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidduration of therapeutic response

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent changes the fundamental parameter of antibody structure by using camelid VHH domains instead of conventional monoclonal antibodies. This structural parameter change results in different binding characteristics and mechanisms of action that overcome resistance developed against conventional antibodies, thereby improving both therapeutic effectiveness and duration of response.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a simplified copy of the antibody binding function using only the VHH domain (variable heavy chain domain) without the full monoclonal antibody structure. This copied binding function maintains specificity for MET while avoiding the limitations of conventional antibodies, including resistance development.

Inventive Principle:

Principle #26Copying

2Measurement precision

If larger conventional antibodies are used, then they can bind to MET, but their size limits access to cryptic epitopes and reduces molecular dexterity

Engineering Contradiction:

Improvebinding specificityVSAvoidantibody size

Core Design Contradiction:

Measurement precisionVSLength of moving object

Solution Approach 1:

The patent extracts only the essential antigen-binding component (VHH domain) from the full monoclonal antibody structure. This extracted binding domain is sufficient for specific MET recognition but is much smaller in size, enabling access to cryptic epitopes and providing superior molecular dexterity while maintaining binding specificity.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent segments the antibody function into separate components, using only the VHH domain for antigen binding rather than the complete monoclonal antibody structure. This segmentation allows the binding function to operate independently with enhanced accessibility and flexibility.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20250152759A1Single-domain antibodies and variants thereof against met

Publication Date: 2025.05.15 WISCONSIN ALUMNI RES FOUND

AI summary

The present application provides constructs comprising a single-domain antibody (sdAb) moiety that specifically recognizes mesenchymal epithelial transition factor receptor (MET). Also provided are methods of making and using these constructs.