Peptide Mimotopes for CLDN18.2 Antibody Detection

Solution Overview

Problem

The development of IMAB362, a monoclonal antibody targeting CLDN18.2 for cancer treatment, faces challenges in detecting and quantifying antibody levels post-administration due to the difficulty in handling and producing transmembrane proteins, which are typically overcome by using anti-idiotypic antibodies but are time-consuming and expensive.

Innovation Solution

Development of peptide-based mimotopes that mimic CLDN18.2 antigenic determinants, utilizing a combined screening and affinity maturation approach via phage display followed by peptide-microarray-based characterization to optimize binding properties, enabling specific and strong binding with the drug candidate IMAB362 for detection in human and murine serum.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If anti-idiotypic antibodies are used to detect IMAB362 antibody levels, then detection specificity is improved, but development time and cost increase

Engineering Contradiction:

Improvedetection specificityVSAvoiddevelopment time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent uses peptide mimotopes as simplified copies of the CLDN18.2 antigen structure. These peptides replicate the key antigenic determinants without requiring full transmembrane protein production, enabling specific antibody detection while dramatically reducing complexity and development time

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The peptide mimotopes serve as inexpensive, easily synthesized alternatives to expensive and difficult-to-produce anti-idiotypic antibodies. The peptides can be rapidly produced through chemical synthesis rather than complex biological systems, reducing both cost and development timeline

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

2Measurement precision

If anti-idiotypic antibodies are used to detect IMAB362 antibody levels, then detection specificity is improved, but production cost increases

Engineering Contradiction:

Improvedetection specificityVSAvoidproduction cost

Core Design Contradiction:

Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent uses peptide mimotopes as simplified copies of the CLDN18.2 antigen structure. These peptides replicate the key antigenic determinants without requiring full transmembrane protein production, enabling specific antibody detection while dramatically reducing complexity and development time

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The peptide mimotopes serve as inexpensive, easily synthesized alternatives to expensive and difficult-to-produce anti-idiotypic antibodies. The peptides can be rapidly produced through chemical synthesis rather than complex biological systems, reducing both cost and development timeline

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Reliability

If transmembrane proteins are used for detection assays, then antigen specificity is maintained, but handling and production difficulty increase

Engineering Contradiction:

Improveantigen specificityVSAvoidhandling difficulty

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent extracts only the essential antigenic determinant regions from the full CLDN18.2 transmembrane protein and incorporates them into simplified peptide mimotopes. This extraction maintains the key binding epitopes while removing the difficult-to-handle transmembrane portions

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses peptide mimotopes as simplified copies of the CLDN18.2 antigen structure. These peptides replicate the key antigenic determinants without requiring full transmembrane protein production, enabling specific antibody detection while dramatically reducing complexity and development time

Inventive Principle:

Principle #26Copying

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The peptide mimotopes provide a cost-effective and reproducible means for detecting antibodies against CLDN18.2, facilitating diagnostic and purification procedures, and are suitable for use in ELISA and other biochemical formats, enhancing the characterization of ADME and PK properties of IMAB362.

Implementation Method 1

These molecules compete with CLDN18.2 for binding to a CLDN18.2 binding domain, e.g. a CLDN18.2 binding domain of an antibody

Methodology Applied

Scientific EffectAntigen-antibody binding:

Implementation Method 2

utilizing a combined screening and affinity maturation approach via phage display

Methodology Applied

Scientific EffectPhage display:

Data Source

PatentUS10858415B2Peptide mimotopes of claudin 18.2 and uses thereof

Publication Date: 2020.12.08 JPT PEPTIDE TECH

AI summary

The present invention provides molecules that mimic antigenic determinants of the integral transmembrane protein claudin 18.2 (CLDN18.2). These molecules compete with CLDN18.2 for binding to a CLDN18.2 binding domain, e.g. a CLDN18.2 binding domain of an antibody, and are capable of detecting antibodies against CLDN18.2. The mimotopes of the invention may be used to generate or inhibit immune responses in animals and preferably humans. Furthermore, they can be used for purposes of detecting agents comprising a CLDN18.2 binding domain in biological samples as well as for purifying agents comprising a CLDN18.2 binding domain.