Bak Binding Antibodies Inducing Conformational Change
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Solution Overview
Problem
Current technologies lack antibodies capable of activating Bak protein, which is crucial for inducing apoptosis and treating conditions like cancer, as no antibody has been reported to activate Bak effectively.
Innovation Solution
Development of Bak binding antibodies or fragments with specific antigen binding domains that change the conformation of Bak from a non-activated to an activated state, utilizing sequences such as those described in SEQ ID NOs: 7 and 8 for the heavy and light chain variable regions, respectively.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibodies are used to target Bak, then Bak binding may occur, but Bak activation and conformational change do not occur
Solution Approach 1:
The patent applies parameter changes by modifying the antibody's antigen-binding site structure through specific CDR sequence design. The engineered antibody possesses unique CDR3 sequences that enable it to bind to Bak and induce conformational changes, transforming the antibody from a simple binding molecule to an activation-inducing molecule. This structural parameter change in the antibody allows it to reliably activate Bak and trigger apoptosis.
2Adaptability or versatility
If no antibody is designed to activate Bak, then conventional antibody functions are maintained, but Bak activation capability is lost
Solution Approach 1:
The patent achieves multi-functionality by designing an antibody that simultaneously performs binding and activation functions. The engineered antibody not only binds to Bak with high specificity but also induces conformational changes that activate Bak and trigger apoptosis. This dual functionality is accomplished through optimized CDR sequences that enable the antibody to interact with multiple epitopes on Bak, transforming a single-function binding molecule into a multi-functional therapeutic agent.
3Reliability
If antibody structure is modified to activate Bak, then Bak activation capability is improved, but antibody design complexity increases
Solution Approach 1:
The patent applies segmentation by focusing modifications on specific CDR regions (CDR1, CDR2, and CDR3) of the antibody variable domain. Rather than redesigning the entire antibody structure, the invention segments the modification effort into targeted CDR sequence optimizations. This approach enables precise control over Bak interaction and activation while maintaining the overall antibody framework, thereby reducing design complexity compared to comprehensive structural redesign.
Data Source
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AI summary
The present disclosure provides Bak binding proteins that change the conformation of Bak and uses thereof.