Fully Human Antibody R66 Reducing Immunogenicity
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Solution Overview
Problem
Current anti-RSV monoclonal antibodies, such as Palivizumab, are humanized and may elicit immunological responses in humans due to non-human sequences, and they primarily target glycoprotein F, which has limited neutralization and fusion inhibition capabilities, with conserved amino acid sequences among RSV strains.
Innovation Solution
Development of a fully human monoclonal antibody, R66, with specific heavy and light chain CDR sequences that provide high affinity and specificity for RSV, reducing immunogenicity and targeting the RSV antigen F effectively.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If a humanized antibody is used to reduce immunogenicity, then the antibody can be administered to human patients, but residual murine sequences still elicit human anti-murine responses
Solution Approach 1:
The patent applies parameter changes by transitioning from humanized antibodies containing murine sequences to fully human antibodies. This is achieved by constructing a human antibody library using phage display technology and selecting high-affinity fully human antibodies that bind to RSV glycoprotein F, thereby eliminating murine sequences and the associated human anti-murine response while maintaining therapeutic efficacy
2Reliability
If existing monoclonal antibodies target glycoprotein F, then they can prevent viral spread, but they have limited neutralization and fusion inhibition capabilities
Solution Approach 1:
The patent applies local quality by designing antibodies with optimized complementarity-determining regions (CDRs) that specifically target epitopes on RSV glycoprotein F. The selected fully human antibodies possess enhanced local binding characteristics at the antigen-binding site, enabling improved neutralization and fusion inhibition capabilities while maintaining prevention of viral spread
3Object-affected harmful factors
If fully human antibodies are obtained by conventional methods, then they avoid immunogenicity issues, but they produce antibodies with low affinities or depend on specific human donors
Solution Approach 1:
The patent applies universality by creating a phage display library containing diverse human antibody variants that can be screened for high affinity. This universal platform allows selection of multiple high-affinity fully human antibodies against RSV without depending on specific human donors, thereby achieving both low immunogenicity and high binding affinity through in vitro selection of optimal clones
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 fully human monoclonal antibody R66 demonstrates higher affinity and reduced side effects, offering improved therapeutic and diagnostic performance by specifically binding to RSV antigen F, potentially overcoming limitations of existing antibodies.
Implementation Method 1
The fully human monoclonal antibody R66 demonstrates higher affinity and reduced side effects, offering improved therapeutic and diagnostic performance by specifically binding to RSV antigen F
Data Source
AI summary
Disclosed are an antibody (preferably a fully human antibody R66) against respiratory syncytical virus RSV, encoding nucleic acids thereof, a vetor and a host cell comprising the same, and a preparation method thereof. Disclosed are also a use of the antibody (preferably a fully human antibody R66) against RSV in the prevention and treatment of RSV-related diseases, and a use of the same in detecting TSV. The above antibody against RSV is preferably a fully human monoclonal antibody. Compared with other animal-derived (e.g., murine) anti-RSV antidodies, the immunogenicity caused by species differences is greatly reduced. With good specificity and affinity, if used for clinic, it will greatly reduce side effects.