Humanized Antibody CDR Engineering for SARS-CoV-2 Neutralization
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Solution Overview
Problem
Current strategies are inadequate in effectively controlling and treating diseases associated with SARS-CoV-2, particularly in reducing its infectivity and binding to human ACE2 receptors.
Innovation Solution
Development of isolated or purified antibodies, such as nanobodies, with specific complementarity determining regions (CDRs) that bind to SARS-CoV-2, including the spike protein or receptor-binding domain, competing with ACE2 for binding, thereby reducing viral infectivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current strategies are used to control SARS-CoV-2, then treatment approaches are limited, but effectiveness in reducing infectivity and binding to ACE2 is inadequate
Solution Approach 1:
The patent changes the molecular parameters of the antibody by engineering specific complementarity determining regions (CDRs) with optimized amino acid sequences. This results in antibodies with enhanced binding affinity to the SARS-CoV-2 spike protein and improved ability to block ACE2 binding, directly addressing the inadequacy of current treatment effectiveness
Solution Approach 2:
The patent creates composite antibody structures by combining humanized antibody frameworks with engineered CDR sequences derived from different sources. This composite approach produces antibodies that maintain human compatibility while achieving superior neutralization activity, expanding the versatility of treatment options
2Object-affected harmful factors
If antibodies with high binding affinity to SARS-CoV-2 are developed, then viral infectivity is reduced, but specific antibody structure complexity increases
Solution Approach 1:
The patent segments the antibody structure into distinct functional regions: humanized framework regions for stability and compatibility, and engineered CDR regions (CDR1, CDR2, CDR3) for specific viral binding. This segmentation allows independent optimization of each region's function while maintaining overall structural integrity and reducing unnecessary complexity
Solution Approach 2:
The patent applies local quality by making specific amino acid substitutions only in the CDR regions where they are needed for enhanced binding affinity, while keeping the framework regions simple and humanized. This localized engineering achieves high binding affinity without requiring complex changes throughout the entire antibody structure
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 antibodies effectively inhibit SARS-CoV-2 infectivity and binding to human ACE2, providing a potential therapeutic or prophylactic solution for COVID-19 by using specific CDRs that enhance binding affinity and reduce viral progression.
Implementation Method 1
an isolated or purified antibody or fragment thereof, including a first binding domain, wherein the first binding domain includes: a first complementarity determining region including a polypeptide sequence having at least 90% sequence identity to any one of SEQ ID NOs: 150-155; a second complementarity determining region including a polypeptide sequence having at least 90% sequence identity to any one of SEQ ID NOs: 160-167; and/or a third complementarity determining region including a polypeptide sequence having at least 90% sequence identity to any one of SEQ ID NOs: 170-175
Implementation Method 2
the first binding domain binds to a spike protein of a coronavirus or a receptor-binding domain of a coronavirus... the antibody or fragment thereof further includes a second binding domain that binds to a coronavirus or a portion thereof... competing (e.g., with SARS-CoV-2) for binding with angiotensin converting enzyme 2 (ACE2)
Data Source
AI summary
The present disclosure relates to an isolated or purified antibody, or a fragment thereof, having a binding domain that binds to a coronavirus (e.g., SARS-COV-2) or a portion thereof. In other embodiments, the antibody includes a binding domain that competes with binding to angiotensin converting enzyme 2 (ACE2) or a portion thereof. Methods of using such antibodies are also described herein, such as methods of treating or delaying the progression of a disease associated with a coronavirus.