Anti-TSLP Receptor Antibody CDR Modifications
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current anti-human TSLP receptor antibodies have limitations in neutralizing activity, which affects their efficacy in treating allergic inflammatory diseases such as asthma and systemic sclerosis, and there is a need for an antibody with enhanced binding and neutralizing capabilities to reduce dosage and medical expenses.
Innovation Solution
Development of an anti-human TSLP receptor antibody with a heavy chain variable region consisting of amino acid sequences 1 to 118 and a light chain variable region consisting of amino acid sequences 1 to 108, along with modifications such as glutamic acid modification to pyroglutamic acid, to enhance binding and neutralizing activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-human TSLP receptor antibodies are used, then binding activity is achieved, but neutralizing activity is insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the antibody's amino acid sequence parameters. Specifically, it identifies critical amino acid residues in the CDR regions and modifies them to enhance neutralizing activity while maintaining binding activity. This resolves the contradiction by changing the molecular parameters of the antibody to achieve superior therapeutic effect.
2Reliability
If higher dosage of antibody is used to compensate for low neutralizing activity, then therapeutic effect is maintained, but medical expenses increase
Solution Approach 1:
The patent modifies the antibody's amino acid composition to enhance its neutralizing potency, thereby reducing the quantity required for effective treatment. The optimized antibody structure achieves higher therapeutic effect at lower dosages, directly addressing the contradiction between therapeutic efficacy and dosage quantity.
3Reliability
If antibody structure is optimized for higher neutralizing activity, then therapeutic efficacy improves, but development complexity increases
Solution Approach 1:
The patent applies local quality by focusing modifications on specific critical amino acid residues within the CDR regions rather than redesigning the entire antibody structure. This targeted approach enhances neutralizing activity while minimizing development complexity, as only specific local regions are optimized based on structural analysis and functional data.
Data Source
Figure 1
Figure 2
Figure 3
AI summary
[Problem] To provide an anti-human TSLP receptor antibody that specifically binds to human TSLP receptor and inhibits an action of human TSLP through human TSLP receptor. [Means for Solution] An anti-human TSLP receptor antibody had been studied by the present inventors, and an anti-human TSLP receptor antibody comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 1 and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 3 was provided. It was revealed that the anti-human TSLP receptor antibody inhibits expression of TARC mRNA induced by TSLP and production of MDC proteins, and suppressed an allergic reaction in a monkey Ascaris antigen sensitization model, and then the present invention was completed.