Anti-CD73 Antibody Variable Region Optimization
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Solution Overview
Problem
Current anti-CD73 antibodies have limitations such as poor inhibitory effects on soluble CD73 enzymatic activity at high concentrations and incomplete blocking of CD73 enzymatic activity, necessitating the development of more effective antibodies with different sequences to target CD73 and modulate the tumor microenvironment.
Innovation Solution
Development of novel antibodies or antigen-binding fragments with specific heavy and light chain variable regions, including complementarity determining regions (CDRs), that bind to CD73 with high affinity, completely block enzymatic activity, and reverse T cell inhibition, as described by specific amino acid sequences and identities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-CD73 antibodies are used, then they can bind to CD73, but they show poor inhibitory effect on soluble CD73 enzymatic activity at high antibody concentrations (hook effect)
Solution Approach 1:
The patent develops novel anti-CD73 antibodies with optimized amino acid sequences in the variable regions (VH and VL), specifically modifying CDR sequences to enhance binding affinity and inhibit the hook effect. The sequence optimizations include specific substitutions in HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 regions to improve inhibitory efficacy across different antibody concentrations.
2Reliability
If existing anti-CD73 antibodies are used, then they can target CD73, but they cannot completely block the enzymatic activity of CD73
Solution Approach 1:
The patent employs sequence optimization of the antibody variable regions to achieve complete blocking of CD73 enzymatic activity. The optimized sequences enhance the antibody's ability to bind to both membrane-bound and soluble CD73, preventing AMP to adenosine conversion and fully inhibiting enzymatic function.
3Reliability
If novel antibodies with optimized sequences are developed, then they can completely block CD73 enzymatic activity, but the development complexity increases
Solution Approach 1:
The patent systematically optimizes specific amino acid positions in the antibody variable regions based on structural and functional analysis of CD73 binding. This targeted approach to sequence modification achieves complete enzymatic blocking while managing development complexity through focused mutations rather than comprehensive redesign.
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 novel antibodies effectively inhibit CD73 enzymatic activity on both membrane-bound and soluble forms, reverse T cell proliferation and activity inhibition, and demonstrate excellent anti-tumor effects while ensuring safety.
Implementation Method 1
The present invention provides a novel antibody or antigen-binding fragment thereof that binds to the CD73 molecule
Data Source
AI summary
The present invention relates to novel antibodies or antigen-binding fragments thereof that specifically bind to CD73 and compositions comprising the antibodies or antigen-binding fragments thereof. The present invention also relates to a nucleic acid encoding the antibody or antigen-binding fragment thereof of the present invention, a vector comprising the polynucleotide, a host cell comprising the nucleic acid or the vector, an immunoconjugate and pharmaceutical composition comprising the antibody or antigen-binding fragment thereof. Furthermore, the present invention relates to the uses of these antibodies or antigen-binding fragments thereof in the immunotherapy, prevention and/or diagnosis of diseases.