Human Anti-CD20 Antibody Design for Low Immunogenicity
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Solution Overview
Problem
Existing monoclonal antibodies targeting CD20 antigen, such as Rituximab, induce significant immune responses in humans, limiting their clinical use due to the formation of human anti-mouse antibodies (HAMA) and human anti-chimeric antibodies (HACA), necessitating the development of antibodies with minimal antigenicity for chronic treatment.
Innovation Solution
A monoclonal antibody, BCD-132, is developed with a human IgG1 isotype and specific amino acid sequences (SEQ ID NO: 1 and SEQ ID NO: 3 for heavy and light chains) that selectively binds to CD20, minimizing antigenicity and enhancing therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If murine or chimeric monoclonal antibodies are used to target CD20, then therapeutic efficacy against B cell lymphomas is achieved, but human anti-mouse antibodies (HAMA) or human anti-chimeric antibodies (HACA) are formed, limiting chronic treatment
Solution Approach 1:
The patent applies parameter changes by completely transforming the antibody's species origin from murine/chimeric to fully human. This fundamental parameter change in the antibody's molecular composition eliminates the immunogenicity issue while preserving therapeutic efficacy against CD20-expressing B cell lymphomas
Solution Approach 2:
The patent creates a humanized version of the therapeutic antibody by copying the functional structure of effective murine antibodies but replacing the immunogenic murine protein sequences with human protein sequences. This allows the antibody to maintain its therapeutic mechanism while being invisible to the human immune system
2Productivity
If existing anti-CD20 antibodies are used for treatment, then B cell depletion is achieved, but significant antigenicity limits long-term use
Solution Approach 1:
The patent changes the fundamental parameter of antibody species origin from non-human to fully human, which simultaneously maintains B cell depletion efficiency while eliminating antigenicity. This allows chronic treatment without immune response interference
Data Source
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AI summary
The present invention relates to biotechnology and provides a monoclonal antibody that specifically binds to CD20. The invention also relates to DNA encoding said antibody, the corresponding expression vectors and methods of production thereof, as well as methods of treatment using said antibody.