Anti-TIM-3 Antibody Engineering for High-Affinity Neutralization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for additional antagonists of TIM-3 that bind with high affinity and effectively neutralize TIM-3 activity, as current immunotherapies for tumors based on preclinical studies are under investigation.
Innovation Solution
Development of novel antibodies that bind to TIM-3 with high affinity and neutralize its activity, including specific immunoglobulin heavy and light chain polypeptides with defined sequences and modifications, such as IgG4 polypeptides with hinge region mutations, and potential glycosylation and disulfide bonds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing TIM-3 antagonists are used, then some binding activity is achieved, but affinity is insufficient and neutralization effectiveness is limited
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure through hinge region mutations (e.g., IgG4 hinge mutations) and glycosylation modifications to enhance binding affinity and neutralization effectiveness. These structural parameter changes enable the antibody to achieve higher affinity binding to TIM-3 while maintaining or improving neutralization capability, directly resolving the contradiction between binding affinity and neutralization effectiveness.
2Ease of manufacture
If antibody structure is simplified, then manufacturing is easier, but binding affinity and functional activity are reduced
Solution Approach 1:
The patent applies local quality by introducing specific modifications only in critical regions of the antibody structure, such as the hinge region and glycosylation sites, while maintaining the overall simplicity of the antibody design. This localized modification approach enhances binding affinity and functional activity without requiring complex structural changes throughout the entire antibody molecule, thus balancing manufacturing ease with functional effectiveness.
Data Source
AI summary
Provided herein are anti-T Cell Immunoglobulin and Mucin Protein-3 (TIM-3) antibodies having particular immunoglobulin heavy chain polypeptide and immunoglobulin light chain polypeptide sequences and methods of using the anti-TIM-3 antibodies to treat a disorder or disease that is responsive to TIM-3 inhibition, such as cancer, an infectious disease, or an autoimmune disease.