Anti-LAG3 Antibody Variable Regions for High-Affinity Ligand Blocking
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Solution Overview
Problem
There is a lack of high-affinity antibodies targeting LAG-3 with good activity to block the interaction of LAG-3 with multiple ligands, as well as better efficacy and pharmacokinetics (PK).
Innovation Solution
Development of novel anti-LAG-3 antibodies with specific amino acid sequences in their heavy and light chain variable regions, capable of binding to LAG3, and optionally including Fc regions, with enhanced affinity and blocking capabilities for LAG3 ligands.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibodies targeting LAG-3 are used, then some blocking activity is achieved, but high affinity and efficacy to block interactions with multiple ligands are insufficient
Solution Approach 1:
The patent applies parameter changes by optimizing the amino acid sequences in the CDR regions of the antibody variable domains. Specific substitutions, additions, or deletions of amino acids in HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are made to enhance binding affinity to LAG-3 while maintaining the ability to block interactions with multiple ligands including MHC class II, FGL1, and LSECtin.
2Reliability
If existing anti-LAG-3 antibodies are developed, then some therapeutic potential is achieved, but pharmacokinetics (PK) properties are not optimized
Solution Approach 1:
The patent optimizes pharmacokinetic properties by modifying the constant regions of the antibody, including the Fc portion. Amino acid substitutions in the Fc region are made to enhance half-life, improve stability, and optimize tissue distribution while maintaining therapeutic efficacy against LAG-3 expressing tumors.
Data Source
AI summary
Provided are anti-LAG3 antibodies or antigen-binding fragments thereof, isolated polynucleotides encoding the same, pharmaceutical compositions comprising the same and the uses thereof.