Anti-TLR9 Agents: CDR Engineering for Specificity
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Solution Overview
Problem
Existing anti-TLR9 agents lack sufficient target specificity and signal-to-noise ratios, which hampers their effectiveness in therapeutic and diagnostic applications.
Innovation Solution
Development of monoclonal antibodies and their antigen-binding fragments that exhibit superior target specificity and signal-to-noise ratios for TLR9, utilizing specific amino acid sequences in their complementarity determining regions (CDRs) to enhance binding affinity and selectivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing anti-TLR9 agents are used, then therapeutic and diagnostic applications can be pursued, but target specificity and signal-to-noise ratios are insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequences in the complementarity determining regions (CDRs) of the antibody variable domains. Specifically, the heavy chain CDRs (CDRH1, CDRH2, CDRH3) and light chain CDRs (CDRL1, CDRL2, CDRL3) are engineered with specific amino acid substitutions to optimize binding affinity and specificity for TLR9, thereby improving target specificity and signal-to-noise ratio
Solution Approach 2:
The patent applies local quality by making specific amino acid modifications only in the CDR regions of the antibody variable domains while maintaining the overall antibody structure. The heavy chain variable domain contains CDRH1 (amino acid sequence NX1X2MX3), CDRH2 (amino acid sequence SISSX1X2SYIX3YX4X5X6VKG), and CDRH3 (amino acid sequence X1X2X3X4X5X6X7X8X9X10), while the light chain variable domain contains CDRL1 (amino acid sequence X1ASEDIYNX2LA), CDRL2 (amino acid sequence X1X2X3X4LX5X6), and CDRL3 (amino acid sequence X1QX2X3X4X5X6X7T). These localized modifications enhance binding to TLR9 without altering the overall antibody architecture
Data Source
AI summary
Compositions and methods for making and using anti-TLR9 agents, for example, monoclonal antibodies, TLR9-binding antibody fragments, and derivatives are described, as are kits, nucleic acids encoding such molecules, diagnostic reagents and kits that include anti-TLR9 agents, and methods of making and using the same.