Fully Human Anti-CD3ε Antibodies Reducing Immunogenicity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for fully human monoclonal antibodies and antigen-binding sequences for T-cell retargeting therapies that specifically bind to CD3 epsilon (CD3ε) to effectively recruit T cells to tumor cells and induce tumor-specific activation of T cell cytotoxicity, while minimizing immunogenicity and maintaining native human IgG structure.
Innovation Solution
Development of monoclonal antibodies and antigen-binding fragments that are fully human, chimeric, or humanized, specifically binding to CD3ε, with varying affinities, and capable of forming bispecific antibodies that target CD3ε and tumor-associated antigens, maintaining a native human IgG structure to reduce immunogenicity and enhance therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-human monoclonal antibodies are used for T-cell retargeting, then T cell recruitment and cytotoxicity activation are achieved, but immunogenicity increases and native human IgG structure is lost
Solution Approach 1:
The patent applies parameter changes by modifying the antibody's species origin parameter from non-human to human. The anti-CD3ε antibody is engineered as a fully human monoclonal antibody, changing its immunogenicity parameter while maintaining its binding function to CD3ε on T cells, thereby reducing immunogenicity while preserving T cell recruitment and cytotoxicity activation capabilities
Solution Approach 2:
The patent uses copying by creating a human version of the antibody that replicates the functional properties of non-human anti-CD3ε antibodies. The humanized or fully human antibody copies the antigen-binding capability and T cell retargeting function while adopting human sequence characteristics to reduce immunogenicity
2Object-affected harmful factors
If humanized or fully human antibodies are developed, then immunogenicity is reduced and native human IgG structure is maintained, but development complexity and manufacturing challenges increase
Solution Approach 1:
The patent applies segmentation by dividing the antibody development process into distinct stages: identifying non-human anti-CD3ε antibodies with desired functionality, selecting candidates for humanization, performing humanization through sequence modification, and validating the humanized antibody. This segmented approach manages complexity by breaking down the challenging task of developing fully human antibodies into manageable steps
Solution Approach 2:
The patent uses intermediary approaches by employing humanized antibodies as an intermediate solution between fully non-human and fully human antibodies. The humanization process creates an intermediate form that retains sufficient non-human sequence for functional activity while incorporating human sequences to reduce immunogenicity, serving as a bridge in the development pathway
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 antibodies effectively modulate or inhibit CD3ε functions, facilitating T-cell retargeting and tumor-specific cytotoxicity, with reduced potential for immunogenicity and improved drug-like properties, enhancing the effectiveness of T-cell retargeting therapies.
Implementation Method 1
anti-CD3ε antibodies and antigen binding fragments that bind CD3 epsilon (CD3ε)... specifically bind to CD3ε... capable of forming bispecific antibodies that target CD3ε and tumor-associated antigens
Data Source
AI summary
The disclosure relates to monoclonal antibodies and antigen binding fragments, variants, multimeric versions, or bispecifics thereof that specifically bind CD3 epsilon (CD3ε), as well as methods of making and using these anti-CD3ε antibodies and antigen binding fragments thereof in a variety of therapeutic, diagnostic and prophylactic indications.