Equine IgG Fc Mutations for Stronger FcRn Binding
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Solution Overview
Problem
There is a need for improved equine IgG Fc region mutations to enhance various characteristics, such as affinity to FcRn, which is crucial for prolonging the half-life and efficacy of therapeutic antibodies in veterinary medicine.
Innovation Solution
Substituting specific amino acid residues at positions 252, 286, 311, 312, 426, 428, 434, or 436 in the equine IgG constant domain with alternative amino acids to modify the interaction with FcRn, thereby enhancing affinity and other functional properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If amino acid substitutions are introduced in the equine IgG constant domain, then affinity to FcRn is improved, but structural complexity increases
Solution Approach 1:
The patent applies parameter changes by substituting specific amino acid residues at defined positions (252, 286, 311, 312, 426, 428, 434, or 436) in the equine IgG constant domain. These targeted substitutions modify the Fc region structure to enhance FcRn binding affinity while maintaining overall structural integrity, resolving the contradiction between improved reliability and increased complexity.
2Duration of action of stationary object
If amino acid substitutions are introduced in the equine IgG constant domain, then half-life is prolonged, but manufacturing complexity increases
Solution Approach 1:
The patent employs parameter changes through site-directed mutagenesis of specific amino acid positions in the constant domain. These controlled substitutions optimize the pH-dependent interaction with FcRn to extend half-life, while the specificity of the approach (targeting only certain positions) helps manage manufacturing complexity by providing clear design guidelines for production.
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 amino acid substitutions in the equine IgG constant domain lead to improved affinity to FcRn, potentially increasing the half-life and efficacy of therapeutic antibodies.
Implementation Method 1
Through a recycling mechanism, the neonatal Fc receptor (FcRn) prolongs the half-life of an IgG in a pH-dependent interaction with its fragment crystallizable (Fc) region.
Data Source
AI summary
The invention relates generally to equine antibody mutants and uses thereof. Specifically, the invention relates to mutations in the constant region of equine antibody for improving various characteristics.