Fc-Modified Antibodies for Extended Half-Life and Stability
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Solution Overview
Problem
Current monoclonal antibody therapies for diseases like COVID-19 face challenges due to high production costs, short stability, and the need for repeated administrations, limiting their use, especially in developing regions, and existing nucleic acid-based delivery methods have suboptimal stability and half-life.
Innovation Solution
Development of recombinant nucleic acid molecules encoding antibodies with modified Fc domains for extended half-life, increased stability, altered complement binding, and modified Fc-FcγR interactions, which are used to create synthetic antibodies that can be administered to induce an immune response and treat diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If traditional monoclonal antibody therapies are used, then therapeutic efficacy is achieved, but production cost is high and half-life is short
Solution Approach 1:
The patent applies parameter changes by modifying the Fc domain of antibodies through specific amino acid substitutions (e.g., M252Y, S254T, T256E, L234F, L235E, P331S, E430G, S239D, I332E, G236A, A330L, G236R, L328R, L235Q, or K322Q) to extend half-life and improve stability. These parameter changes in the antibody structure directly address the contradiction by achieving longer duration of action without proportionally increasing production cost
Solution Approach 2:
The patent creates composite antibody structures by combining modified Fc domains with variable regions, resulting in chimeric or humanized antibodies with enhanced properties. The Fc-modified antibodies represent composite structures that integrate different functional elements to achieve both extended half-life and maintained efficacy at reasonable production costs
2Duration of action of moving object
If traditional monoclonal antibody therapies are used, then therapeutic effect is achieved, but frequency of administration is high
Solution Approach 1:
By changing the parameters of the Fc domain through amino acid modifications, the patent extends the half-life of antibodies to several weeks or months, thereby reducing the frequency of administrations from frequent (e.g., weekly or monthly) to less frequent (e.g., every few months), saving significant time for patients
3Stability of the object's composition
If Fc domain modifications are made to extend half-life, then stability is improved, but complexity of antibody structure increases
Solution Approach 1:
The patent makes targeted parameter changes by introducing specific amino acid substitutions at defined positions in the Fc domain, rather than making widespread modifications. This focused approach improves stability while minimizing structural complexity increases, as only 1-20 specific residues are modified out of hundreds in the full antibody structure
Data Source
AI summary
Disclosed herein are nucleic acid encoded Fc-modified antibodies and methods of use of the same for the treatment of diseases and disorders.