Bispecific Antibody Assembly via Cell Surface Segmentation
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Solution Overview
Problem
Current bispecific antibodies targeting c-Met and Her3 face challenges such as instability, difficulty in production, and inefficacy in clinical tests, leading to resistance and side effects, limiting their therapeutic effectiveness in cancer treatment.
Innovation Solution
Development of a bispecific antibody that specifically binds to c-Met and Her3, utilizing a novel amino acid sequence for the complementarity determining regions (CDRs) of the anti-Her3 antibody, enhancing stability and therapeutic efficacy by inhibiting both c-Met and Her3 activities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If early bispecific antibodies in IgG form are produced, then therapeutic effects on cancers can be increased by recognizing two antigens simultaneously, but it becomes very difficult to separate and purify desired bispecific antibodies due to random combination between light chains and heavy chains
Solution Approach 1:
The patent divides the bispecific antibody into two separate antibody fragments (first antibody fragment targeting c-Met, second antibody fragment targeting Her3) that are produced independently and then combined through cell surface expression. This segmentation avoids the random combination problem of traditional IgG form bispecific antibodies, enabling precise control over which fragments pair together.
Solution Approach 2:
The patent uses a cell surface as an intermediary platform to produce and assemble the bispecific antibody. By expressing both antibody fragments on the surface of the same cell, the system ensures correct pairing without requiring complex purification steps, thus resolving the manufacturing difficulty while maintaining therapeutic effectiveness.
2Ease of manufacture
If bispecific antibodies with non-IgG forms are developed, then production difficulty is reduced, but their stability in protein folding and pharmacokinetics is not verified
Solution Approach 1:
The patent employs a self-assembly mechanism where the two antibody fragments automatically form a stable bispecific complex through their natural binding properties when co-expressed on cell surfaces. This self-service approach ensures proper folding and stable structure without requiring additional verification steps, while maintaining ease of production.
3Reliability
If conventional anti-EGFR family or anti-c-Met therapy is used, then initial treatment can be effective, but resistance develops when Her3 is activated to exert signal transduction
Solution Approach 1:
The patent creates a bispecific antibody that simultaneously targets two different antigens (c-Met and Her3) with a single molecular entity. This multi-functionality allows the antibody to block both c-Met signaling and Her3-mediated resistance pathways, extending therapeutic effectiveness beyond what single-target therapies can achieve.
Solution Approach 2:
By incorporating Her3 targeting capability into the bispecific antibody from the design stage, the patent prevents Her3 activation before it can induce resistance. This preliminary anti-action blocks the resistance mechanism proactively, extending the duration of therapeutic effect rather than waiting for resistance to develop.
Data Source
AI summary
Provided is an anti-Her3 antibody or antigen-binding fragment thereof, an anti-c-Met/anti-Her3 bispecific antibody including the same, and a method of preventing and/or treating a cancer using the same.