Macrocyclic Compounds for Blocking PD-L1/PD-1 and PD-L1/CD80 Interactions
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Solution Overview
Problem
The interaction between PD-L1 and PD-1 or CD80 leads to immune suppression and T cell exhaustion, which is a challenge in treating diseases like cancer and infectious diseases, as it inhibits effective immune responses.
Innovation Solution
Macrocyclic compounds that inhibit the interaction of PD-L1 with PD-1 and CD80, enhancing immune responses by blocking these interactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PD-L1 interacts with PD-1 or CD80, then immune suppression occurs and T cell exhaustion increases, but effective immune responses are inhibited
Solution Approach 1:
The patent employs monoclonal antibodies as intermediary substances that specifically bind to PD-L1, blocking its interaction with PD-1 and CD80. These antibodies act as mediators that prevent the harmful binding without directly modifying the target proteins, thereby restoring immune response effectiveness while eliminating immune suppression.
Solution Approach 2:
The invention extracts and isolates the harmful interaction mechanism by identifying and targeting the specific PD-L1/PD-1 and PD-L1/CD80 binding interface. Through taking out this specific interaction pathway using targeted antibodies, the patent eliminates the harmful effect of immune suppression while preserving other necessary immune functions.
2Reliability
If monoclonal antibodies block PD-L1 interactions, then T cell activation is restored and augmented, but the complexity of therapy increases
Solution Approach 1:
The patent utilizes parameter changes in antibody design, including variable region sequences, affinity constants, and epitope targeting, to optimize T cell activation while managing therapy complexity. By carefully adjusting these parameters, the invention achieves effective immune restoration with standardized monoclonal antibody therapies.
Solution Approach 2:
The monoclonal antibodies described in the patent exhibit multi-functionality by simultaneously blocking both PD-L1/PD-1 and PD-L1/CD80 interactions through a single agent. This universal approach simplifies therapy compared to using multiple separate antibodies for each interaction, thereby restoring T cell activation without proportionally increasing therapeutic complexity.
3Productivity
If PD-1/PD-L1 pathway is blocked, then immune response to tumors is enhanced, but the mechanism of action becomes more complex
Solution Approach 1:
The patent segments the complex PD-L1 interaction network by developing antibodies that specifically target distinct epitopes on PD-L1. This segmentation allows for enhanced antitumor immune response through focused blockade of key interaction sites, while the modular antibody design actually simplifies the overall mechanism compared to targeting multiple different proteins.
Solution Approach 2:
The invention merges the blockade of two separate interaction pathways (PD-L1/PD-1 and PD-L1/CD80) into a single therapeutic mechanism using monoclonal antibodies against PD-L1. This combining approach enhances antitumor immunity by simultaneously addressing multiple suppression pathways while simplifying the therapeutic regimen to a single agent rather than multiple therapies.
Data Source
AI summary
In accordance with the present disclosure, macrocyclic compounds have been discovered that bind to PD-L1 and are capable of inhibiting the interaction of PD-L1 with PD-1 and CD80. These macrocyclic compounds exhibit in vitro immunomodulatory efficacy thus making them therapeutic candidates for the treatment of various diseases including cancer and infectious diseases.