PD-1 Binding Antibodies With Optimized CDR Sequences
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Solution Overview
Problem
Current therapies targeting PD-1 for cancer and infectious diseases have limited efficacy due to insufficient PD-1-binding agents with high affinity and effectiveness.
Innovation Solution
Development of isolated immunoglobulin heavy and light chain polypeptides with specific complementarity determining region (CDR) amino acid sequences that bind to PD-1, potentially combined with other negative regulators like LAG-3 and TIM-3, to enhance immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current PD-1 therapies are used, then treatment is provided for cancer and infectious diseases, but efficacy is limited due to insufficient binding affinity
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequences of the antibody CDR regions (specifically CDR1, CDR2, and CDR3 of the heavy chain and light chain) to optimize binding affinity to PD-1. The specification describes multiple embodiments with varying amino acid substitutions to achieve enhanced binding characteristics while maintaining therapeutic efficacy.
2Reliability
If PD-1 binding agents are developed with higher affinity, then neutralization of PD-1 activity is improved, but complexity of antibody design increases
Solution Approach 1:
The patent applies local quality by focusing modifications specifically on the CDR regions (complementarity determining regions) of the antibody rather than the entire antibody structure. This allows enhancement of binding affinity through targeted amino acid changes in the antigen-binding sites while maintaining the overall antibody framework and reducing design complexity.
Solution Approach 2:
The patent segments the antibody into distinct variable regions (VH and VL) with specific CDR regions that can be independently optimized. The specification provides separate sequence definitions for heavy chain CDR1-3 and light chain CDR1-3, allowing modular design and optimization of each binding interface separately.
Data Source
AI summary
The invention relates to an isolated immunoglobulin heavy chain polypeptide and an isolated immunoglobulin light chain polypeptide that bind to a programmed death-1 (PD-1) protein. The invention provides a PD-1-binding agent that comprises the aforementioned immunoglobulin heavy chain polypeptide and immunoglobulin light chain polypeptide. The invention also provides related vectors, compositions, and methods of using the PD-1-binding agent to treat a cancer or an infectious disease.