Multispecific Antigen-Binding Polypeptides for SARS-CoV-2 VOCs
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Solution Overview
Problem
Current therapeutic antibodies are ineffective against SARS-CoV-2 variants of concern (VOCs) due to resistance, increased pathogenicity, and evasion of current vaccines, and are difficult to manufacture and administer, particularly in immunocompromised individuals.
Innovation Solution
Development of antigen binding polypeptides with specific structures and amino acid sequences that target SARS-CoV-2 proteins, including various combinations of immunoglobulin light and heavy chain variable and constant regions, designed to enhance broad VOC reactivity and ease of manufacture.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapeutic antibodies are used to target SARS-CoV-2, then they can provide immune response, but they become ineffective against variants of concern due to resistance and evasion
Solution Approach 1:
The patent describes multispecific antibodies that can bind to multiple SARS-CoV-2 variants simultaneously, providing broad-spectrum coverage. The antibody constructs include variable regions from different parental antibodies that recognize conserved epitopes across variants, enabling a single therapeutic agent to neutralize multiple variant strains effectively
Solution Approach 2:
The invention employs composite antibody structures formed by combining variable and constant regions from different parental antibodies. These chimeric constructs integrate binding specificities from multiple sources, creating a composite therapeutic molecule that overcomes variant resistance while maintaining neutralization capacity
2Ease of manufacture
If traditional therapeutic antibodies are manufactured, then they can provide treatment, but they are difficult to manufacture and administer
Solution Approach 1:
The patent describes antibody constructs with modular architectures comprising separate variable and constant regions that can be independently optimized. The multispecific formats allow segmentation of binding functions while maintaining manufacturability through standardized constant regions and well-established expression systems
Solution Approach 2:
The invention utilizes engineered amino acid sequences and modified constant regions to optimize manufacturing properties. The antibody constructs incorporate stabilizing mutations and optimized half-life characteristics that facilitate production while preserving therapeutic efficacy and enabling flexible administration routes
Data Source
AI summary
Disclosed are antigen binding polypeptides and antigen binding polypeptide complexes (e.g., antibodies and antigen binding fragments thereof) having certain structural features. Also disclosed are polynucleotides and vectors encoding such polypeptides and polypeptide complexes; host cells, pharmaceutical compositions and kits containing such polypeptides and polypeptide complexes; and methods of using such polypeptides and polypeptide complexes.