Humanized GPRC5D Antibody CDR Engineering for High-Affinity, Specific Binding

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Solution Overview

Problem

Current monoclonal antibodies targeting human GPRC5D lack high affinity and specificity, limiting their effectiveness in diagnostic and therapeutic applications for multiple myeloma and other tumor diseases.

Innovation Solution

Development of recombinant humanized monoclonal antibodies with specific CDR sequences that exhibit high affinity and specificity for human GPRC5D, enabling applications in CAR-T immunotherapy, bispecific antibodies, and antibody-drug conjugates for cancer treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current monoclonal antibodies are used to target human GPRC5D, then they can be applied in diagnostic and therapeutic settings, but they lack high affinity and specificity which limits their effectiveness

Engineering Contradiction:
ImproveeffectivenessVSAvoidaffinity and specificity
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent applies parameter changes by optimizing the amino acid sequences of the antibody's CDR regions (VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, VL-CDR3) to achieve high affinity and specificity for human GPRC5D. The invention provides specific sequence variants with improved binding characteristics, directly addressing the affinity and specificity deficiency of current antibodies while maintaining their diagnostic and therapeutic effectiveness

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If recombinant humanized monoclonal antibodies with specific CDR sequences are developed, then high affinity and specificity for human GPRC5D is achieved, but the complexity of antibody construction and validation increases

Engineering Contradiction:
Improveaffinity and specificityVSAvoidantibody construction complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the antibody into distinct functional modules with specific CDR sequences (VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, VL-CDR3). Each CDR region is independently optimized and can be combined in systematic ways to create multiple antibody variants, making the complex design process more manageable and modular

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent creates universal CDR sequence templates that can be applied across multiple antibody constructs for different applications (CAR-T, bispecific antibodies, ADCs). The standardized CDR sequences serve as building blocks that can be universally utilized to generate high-affinity antibodies against GPRC5D, reducing overall development complexity through reuse

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentEP4582449A1Recombinant humanized monoclonal antibody targeting human GPRC5d and application thereof
Publication Date: 2025.07.09 SUZHOU DIMA BIOTECHNOLOGY CO LTD
  • EP4582449A1 patent drawingFigure 1~2
  • EP4582449A1 patent drawingFigure 3a~3b
  • EP4582449A1 patent drawingFigure 4a~4b

AI summary

The present invention relates to a specific recombinant humanized monoclonal antibody targeting human GPRC5D and an application thereof, can be used in ELISA and flow detection methods, and can be used for diagnosis and treatment targeting GPRC5D protein. The monoclonal antibody comprises a heavy chain variable region and a light chain variable region, and the amino acid sequence and nucleotide sequence of the monoclonal antibody can be used alone or in double-stranded combination. In addition, the sequences of the specific recombinant humanized monoclonal antibody targeting human GPRC5D can be constructed into biological materials or preparations such as monoclonal antibodies, antibody conjugates, bispecific antibodies, CAR-immune cells, etc., and can be used for the diagnosis and treatment of GPRC5D-related diseases.