IL-17-Binding Antibody Amino Acid Modifications
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Solution Overview
Problem
Current IL-17 antibodies have sub-optimum pharmacokinetics, stability, and efficacy in vivo, limiting their therapeutic utility for treating IL-17-mediated diseases.
Innovation Solution
Development of an IL-17-binding agent comprising specific immunoglobulin heavy and light chain polypeptides with modified amino acid sequences that enhance binding affinity, stability, and pharmacokinetics, specifically designed to neutralize IL-17 activity effectively.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If currently available IL-17 antibodies are used, then IL-17 binding function is achieved, but pharmacokinetics, stability and efficacy in vivo are sub-optimum
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequences of the immunoglobulin heavy and light chains to optimize the antibody's pharmacokinetic properties and stability while maintaining IL-17 binding function. Specific amino acid substitutions are made to improve half-life, reduce immunogenicity, and enhance overall therapeutic performance in vivo.
Solution Approach 2:
The patent creates a composite antibody structure by combining modified heavy chain and light chain polypeptides with specific amino acid sequences. This composite design integrates multiple functional improvements including enhanced binding affinity, improved stability, and optimized pharmacokinetics into a single therapeutic agent.
2Measurement precision
If IL-17 antibodies are designed to increase binding affinity, then neutralization of IL-17 activity is improved, but pharmacokinetics and stability may be compromised
Solution Approach 1:
The patent simultaneously optimizes multiple parameters including binding affinity and stability through coordinated amino acid substitutions in both heavy and light chains. The modifications are designed to work together to enhance both binding strength and molecular stability rather than compromising one for the other.
Solution Approach 2:
The patent applies local quality changes by making specific targeted amino acid substitutions at particular positions in the antibody sequences. These localized modifications are strategically chosen to enhance binding affinity at the antigen interface while maintaining or improving overall structural stability through separate stabilizing substitutions elsewhere in the molecule.
Data Source
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AI summary
The invention relates to an isolated IL-17-binding agent which comprises an immunoglobulin heavy chain polypeptide comprising SEQ ID NO: 1 and optionally an immunoglobulin light chain polypeptide comprising SEQ ID NO: 23, except that one or more specific of residues of SEQ ID NO: 1 and SEQ ID NO: 23 are replaced with a different residue. The invention also provides vectors, compositions, and methods of using the IL-17-binding agent to treat an IL-17-mediated disease.