Single-Domain CLDN18.2 Binder for Isoform-Selective Targeting

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Solution Overview

Problem

Existing technologies face challenges in developing antibodies that specifically target CLDN18.2 without recognizing CLDN18.1 due to their high sequence similarity, limiting therapeutic options for conditions associated with CLDN18.2.

Innovation Solution

Development of a single domain antibody (sdAb) that specifically binds to the extracellular domain 1 (ECD1) of human CLDN18.2, with specific CDR sequences and modifications to ensure selective recognition, and can be expressed in various host cells for therapeutic applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antibodies are used to target CLDN18.2, then therapeutic coverage is provided, but specificity against CLDN18.2 without recognizing CLDN18.1 is difficult to achieve due to high sequence similarity

Engineering Contradiction:

ImprovespecificityVSAvoidcomplexity of achieving specificity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the antibody structure into a single variable domain (VH or VL) rather than using the conventional full antibody structure with both heavy and light chains. This segmentation allows the antibody to focus its binding capability on a single antigenic determinant, improving specificity for CLDN18.2 while reducing cross-reactivity with CLDN18.1

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent optimizes the local quality of the complementarity determining regions (CDRs), particularly CDR3, to achieve high specificity. The CDR3 region is engineered with specific amino acid sequences that are optimized to recognize unique epitopes on CLDN18.2, allowing the antibody to distinguish between CLDN18.2 and the highly similar CLDN18.1

Inventive Principle:

Principle #3Local quality

2Length of moving object

If single domain antibodies are used, then molecular weight is reduced improving tissue penetration, but binding affinity and stability may be compromised

Engineering Contradiction:

Improvemolecular weightVSAvoidbinding affinity and stability

Core Design Contradiction:

Length of moving objectVSReliability

Solution Approach 1:

The patent applies parameter changes by optimizing the amino acid sequences in the CDR regions, particularly CDR3, to enhance binding affinity. Specific amino acid substitutions, additions, or deletions are introduced to improve the interaction between the single domain antibody and the CLDN18.2 antigen, compensating for the reduced molecular weight

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite structure by combining the single variable domain with engineered CDR regions that have optimized sequences. This composite approach integrates the benefits of small size with enhanced binding capabilities through carefully designed amino acid sequences in the CDR regions

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS12595302B2CLDN18.2 binding molecule

Publication Date: 2026.04.07 SANYOU BIOPHARMACEUTICALS CO LTD

AI summary

Disclosed is a novel CLDN18.2 binding molecule. Also disclosed are a nucleic acid molecule encoding the CLDN18.2 binding molecule, an expression vector and a host cell for expressing the CLDN18.2 binding molecule. Further disclosed are a method for producing the CLDN18.2 binding molecule and use thereof.