Anti-TSLP Monoclonal Antibodies for Isoform-Specific Binding
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Solution Overview
Problem
Existing antibodies targeting TSLP have limitations in binding affinity and specificity, particularly in distinguishing between long and short isoforms, which can lead to suboptimal clinical outcomes in treating Th2-related diseases like asthma and atopic dermatitis.
Innovation Solution
Development of monoclonal antibodies, including humanized and chimeric variants, with specific VH and VL CDR sequences that enhance binding affinity to TSLP and block TSLP-TSLPR/IL7R interaction, offering improved therapeutic potential for diseases such as asthma, ulcerative colitis, and psoriasis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing antibodies targeting TSLP are used, then treatment for Th2-related diseases can be provided, but binding affinity and specificity are limited, particularly in distinguishing between long and short isoforms
Solution Approach 1:
The patent applies local quality by engineering specific CDR regions (complementarity determining regions) of the antibody to have enhanced binding properties. The variable regions are designed with specific amino acid sequences that provide both high affinity and isoform-discriminating specificity, while other regions of the antibody maintain standard structures. This localized optimization of the binding interface resolves the contradiction between affinity and specificity.
Solution Approach 2:
The patent employs parameter changes by modifying the amino acid sequences in the CDR regions of the antibody to achieve optimal binding characteristics. Specific substitutions, additions, or deletions in the variable regions alter the binding parameters to simultaneously increase affinity and enable discrimination between TSLP isoforms, thereby resolving the technical contradiction.
2Reliability
If monoclonal antibodies with enhanced binding affinity are developed, then therapeutic potential is improved, but development complexity and time increase
Solution Approach 1:
The patent applies preliminary action by pre-designing antibodies with optimized CDR sequences based on structural and functional analysis of TSLP binding. Rather than extensively screening random antibodies, the invention uses rational design approaches to predict and engineer sequences that will achieve the desired affinity and specificity, thereby reducing development time and complexity while maintaining high therapeutic potential.
Data Source
AI summary
Disclosed is an isolated monoclonal antibody that specifically binds human TSLP, or the antigen-binding portion thereof. A nucleic acid molecule encoding the antibody, an expression vector, a host cell and a method for expressing the antibody are also provided. The present disclosure further provides a bispecific molecule, an immunoconjugate, a CAR-immune cell, an oncolytic virus and a pharmaceutical composition comprising the antibody, as well as a treatment method using an anti-TSLP antibody of the disclosure.