Humanized TIRC7 Antibodies With CDR Mutations for Immune Modulation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is an unmet need for therapeutic antibodies that specifically target T-cell mediated, B-cell mediated, and monocyte mediated immune responses, particularly for autoimmune diseases such as multiple sclerosis and type 1 diabetes, as current treatments do not effectively address these immune-related disorders.
Innovation Solution
Development of humanized antigen binding proteins (ABPs) with improved affinity for TIRC7, comprising specific CDR regions and framework sequences, capable of modulating immune responses by inhibiting TIRC7 expression, thereby reducing inflammation and proliferation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for autoimmune diseases, then general immune suppression is achieved, but specificity for T-cell mediated immune responses is insufficient
Solution Approach 1:
The patent applies local quality by designing antibodies with specific CDR regions (CDRH1: GYTFITYV, CDRH2: INPYNDGT, CDRH3: AEFITKTVGGSNWYLDV) that are optimized to bind specifically to TIRC7 on T-cells, while other regions use human consensus framework sequences. This localized optimization provides high specificity for T-cell mediated immune responses without affecting other immune cell types, resolving the contradiction between general effectiveness and specific adaptability.
2Strength
If antibody affinity for TIRC7 is increased through mutation, then binding strength is improved, but complexity of antibody structure increases
Solution Approach 1:
The patent increases binding affinity by introducing specific mutations only in the CDR regions (such as AEFITKTVGGSNWYLDV in CDRH3), while maintaining the standard human consensus framework sequences in the non-binding regions. This localized mutation strategy enhances TIRC7 binding strength without unnecessarily complicating the overall antibody structure, as the framework regions remain simple and well-characterized.
Solution Approach 2:
The patent optimizes binding affinity by carefully selecting and mutating specific amino acid residues in the CDR regions to match the physicochemical properties required for high-affinity TIRC7 binding. These parameter changes (amino acid substitutions, deletions, or insertions) are made only where necessary to improve binding, keeping the overall structural complexity manageable while achieving enhanced strength of interaction.
3Object-affected harmful factors
If humanized antibody framework sequences are used, then immunogenicity is reduced, but binding affinity may be compromised
Solution Approach 1:
The patent resolves this contradiction by using human consensus framework sequences in the non-binding regions to minimize immunogenicity, while concentrating all affinity-enhancing mutations exclusively in the CDR regions. This spatial separation ensures that the humanized framework provides low immunogenicity while the mutated CDRs provide high binding affinity, achieving both goals simultaneously without compromise.
Data Source
AI summary
The present disclosure provides human T-cell immune response cDNA 7 (TIRC7) antibodies, having improved TIRC7 binding affinity, and/or activity. The TIRC7 antibodies of the invention are generated by mutation of a parent TIRC7 antibody reports most of the humanized candidates, position 43 was Q (Gln, amide). But in the best humanized VH (cAb1466-VH) mutation of position 43 was Q (Gln, amide) to K (Lys, basic) appears to important for successful affinity/stability over the next best humanized VH.