Anti-PD-L1 Antibodies with Specific HVR Sequences
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Solution Overview
Problem
Current therapeutic compositions targeting the PD-1/PD-L1 pathway are limited in effectively inhibiting tumor growth and immune suppression in cancer treatments.
Innovation Solution
Development of isolated anti-PD-L1 antibodies with specific heavy and light chain variable regions, including HVR sequences, to inhibit PD-L1 signaling, comprising sequences such as GFSLTSYDIS, VIWTGVGTN, and DPYYYGMDY for heavy chains, and RASQDISIWLS, KASNLHT, and LQSQSFPRT for light chains, which can be used in monoclonal, chimeric, or humanized forms to block PD-L1 interactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapeutic compositions targeting PD-1/PD-L1 pathway are used, then some inhibition of tumor growth is achieved, but the inhibition is insufficient and immune suppression persists
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure to achieve higher affinity binding to PD-L1. The engineered antibodies contain specific amino acid substitutions in the variable regions (e.g., heavy chain CDR3 with GMDY motif) that enhance binding parameters, thereby improving therapeutic effectiveness and reducing immune suppression more effectively than prior compositions.
2Measurement precision
If anti-PD-L1 antibodies are developed with specific HVR sequences, then binding affinity to PD-L1 is improved, but antibody structure complexity increases
Solution Approach 1:
The patent applies local quality by introducing specific amino acid modifications only in the hypervariable regions (CDRs) of the antibody, particularly in the heavy chain CDR3 loop. This localized modification approach enhances PD-L1 binding affinity without requiring changes to the entire antibody structure, thus improving binding precision while limiting structural complexity increases to only the essential binding regions.
3Measurement precision
If monoclonal anti-PD-L1 antibodies are produced with specific variable regions, then specificity for PD-L1 is enhanced, but manufacturing complexity increases
Solution Approach 1:
The patent applies copying by using recombinant DNA technology to produce identical copies of the engineered antibody genes in host cells. The specific variable region sequences (including the HVR-H3 with DPYYYGMDY motif) are cloned and expressed in large quantities through cell culture, enabling standardized production of high-specificity antibodies without complex manual purification or assembly processes.
Data Source
AI summary
Aspects of the invention include isolated anti-PD-L1 antibodies, as well as compositions containing such antibodies, and methods of using the same in the treatment of diseases or conditions that are mediated by PD-L1 signaling.