Humanized Anti-VEGF Antibody Consensus CDR Design

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Solution Overview

Problem

There is a continuous need for new therapeutic antibodies, particularly those that can effectively target specific antigens such as VEGF, as existing antibodies may not fully address the requirements for efficacy and specificity in treating conditions like cancer and cardiovascular diseases.

Innovation Solution

Development of monoclonal antibodies with CDR regions defined by consensus sequences derived from analysis of related antibodies, ensuring high specificity and binding affinity, and potential humanization to reduce immunogenicity, allowing for targeted therapy against VEGF.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If monoclonal antibodies are developed to target VEGF with high specificity, then binding affinity and therapeutic efficacy are improved, but the risk of immune response and immunogenicity increases

Engineering Contradiction:
Improvebinding affinityVSAvoidimmune response
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by humanizing the antibody structure - changing the species origin of the antibody constant regions from non-human (mouse or rabbit) to human, while maintaining the variable regions that provide VEGF binding specificity. This parameter change (species origin of constant regions) reduces immunogenicity and immune response while preserving binding affinity through the maintained variable regions.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If new therapeutic antibodies are continuously developed, then therapeutic efficacy and disease coverage are improved, but development time and resource investment increase

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoiddevelopment time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent applies universality by creating a humanized antibody platform that can target multiple diseases and conditions through the same humanized antibody framework. The humanized anti-VEGF antibody can treat cancer, cardiovascular diseases, and other VEGF-related conditions, providing multi-functional therapeutic value and reducing the need for separate development programs for each indication.

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

Solution Approach 2:

The patent applies preliminary action by conducting comprehensive sequence alignment and consensus sequence determination among multiple related antibodies before finalizing the humanized antibody design. This preliminary analysis of variable regions and CDRs from multiple sources (mouse and rabbit antibodies) establishes an optimized blueprint that guides subsequent humanization and production, streamlining the development process.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If consensus sequences are used to define CDR regions, then antibody specificity and binding affinity are improved, but the complexity of antibody design and characterization increases

Engineering Contradiction:
ImprovespecificityVSAvoidantibody design complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies merging by combining the variable regions from multiple different antibodies (mouse and rabbit anti-VEGF antibodies) to create a consensus sequence that defines the CDR regions. This merging of sequences from multiple sources consolidates the binding specificity information into a unified design framework, improving specificity while providing a systematic approach to design.

Inventive Principle:
Principle #5Merging (Combining)

Data Source

PatentEP2259795B1Anti-VEGF antibody
Publication Date: 2016.04.06 EPITOMICS INC
  • EP2259795B1 patent drawingFigure 1
  • EP2259795B1 patent drawingFigure 1
  • EP2259795B1 patent drawingFigure 1

AI summary

An antibody is provided. In certain cases, the antibody comprises: a) a heavy chain variable domain that comprises CDR regions that are substantially identical to the heavy chain CDR regions of a selected antibody and b) a light chain variable domain that comprises CDR regions that are substantially identical to the light chain CDR regions of the selected antibody, where the antibody binds a selected target.