Anti-GPRC5D Antibody CDR Design for High-Affinity Binding

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Solution Overview

Problem

There is an urgent need for a novel anti-GPRC5D antibody to target the overexpression of GPRC5D in patients with multiple myeloma, which is associated with poor disease outcomes.

Innovation Solution

Development of an anti-GPRC5D antibody or its antigen binding fragment, comprising specific heavy and light chain complementarity determining regions, with sequences as shown in SEQ ID NOs, and potential modifications, for targeted therapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a novel anti-GPRC5D antibody is developed to target overexpressed GPRC5D in multiple myeloma, then therapeutic efficacy is improved, but the complexity of antibody development and characterization increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidantibody development complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the antibody structure into defined complementarity determining regions (CDRs) with specific sequence identities, allowing systematic development and characterization of anti-GPRC5D antibodies through modular CDR design rather than developing entire antibody molecules de novo

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent establishes specific parameter thresholds for CDR sequence identity (at least 80%, 90%, 95%, or 99% identity to reference sequences) to define novel anti-GPRC5D antibodies, providing clear criteria for antibody characterization and reducing development uncertainty

Inventive Principle:

Principle #35Parameter changes

2Reliability

If the antibody binds to GPRC5D with high affinity for therapeutic application, then treatment effectiveness is improved, but the precision requirements for antibody design and manufacturing increase

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidantibody design precision

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent focuses quality control on specific local regions (the CDRs) of the antibody molecule by defining sequence identity requirements for these particular segments, rather than requiring uniform precision across the entire antibody structure, thereby achieving high binding affinity through targeted design

Inventive Principle:

Principle #3Local quality

3Measurement precision

If the antibody is designed with specific CDR sequences for high GPRC5D specificity, then binding affinity is improved, but the complexity of sequence verification and quality control increases

Engineering Contradiction:

Improvebinding affinityVSAvoidquality control complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent creates universal reference CDR sequences that can serve as templates for multiple antibody variants, allowing a single set of reference sequences to define multiple novel antibodies with different degrees of novelty (80%, 90%, 95%, or 99% identity), thereby simplifying quality control through a unified reference framework

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentEP4640708A1Novel Anti-GPRC5d antibody

Publication Date: 2025.10.29 CHIMAGEN BIOSCIENCES LTD

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AI summary

The present invention provides an anti-GPRC5D antibody or an antigen-binding fragment thereof, an isolated polynucleotide encoding same, a pharmaceutical composition comprising same, and a use thereof.