Fused-Tricyclic CDN Antibody Conjugates for Targeted Systemic Delivery
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Solution Overview
Problem
Existing STING agonists face challenges in systemic administration due to rapid degradation in the bloodstream and limited applicability to distant-metastasized tumors, necessitating the development of novel cyclic dinucleotide derivatives with potent STING agonist activity and antibody-drug conjugates for targeted delivery to tumor sites.
Innovation Solution
Development of novel CDN derivatives with a fused tricyclic substituent and antibody-drug conjugates that systemically administer STING agonists to targeted cells and organs, enhancing anti-tumor activity by activating immune cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If cyclic dinucleotide derivatives are administered systemically, then they can reach distant-metastasized tumors, but they undergo rapid degradation in the bloodstream
Solution Approach 1:
The patent uses antibodies as intermediary carriers to deliver cyclic dinucleotide derivatives to target tumors. The antibody-drug conjugate system allows the CDN derivative to be transported through the bloodstream without direct exposure, protecting it from degradation while enabling systemic distribution and targeted delivery to distant-metastasized tumors.
Solution Approach 2:
The invention creates composite antibody-drug conjugates by combining cyclic dinucleotide derivatives with antibodies through chemical linkers. This composite structure integrates the stability and targeting capability of antibodies with the STING agonist activity of CDN derivatives, resolving the contradiction between systemic delivery and bloodstream stability.
2Reliability
If conventional STING agonists are used, then they can activate immune cells, but they have limited applicability to distant-metastasized tumors
Solution Approach 1:
The antibody component acts as a mediator that guides the CDN derivative to distant-metastasized tumors through antigen recognition. This allows the STING agonist activity to be preserved while extending the therapeutic reach to metastatic sites that are inaccessible to conventional systemic administration.
Solution Approach 2:
The antibody-drug conjugate system provides multi-functionality: the antibody enables targeted delivery to various tumor types expressing the target antigen, while the CDN derivative maintains its STING agonist activity. This universal platform can be applied to different metastatic tumor models by selecting appropriate antibodies.
3Reliability
If cyclic dinucleotide derivatives are directly administered, then they can activate the cGAS-STING pathway, but they cannot be effectively delivered to targeted cells
Solution Approach 1:
The antibody serves as a delivery intermediary that specifically binds to target cells through antigen recognition, carrying the CDN derivative to the intended destination. This targeted delivery mechanism ensures that the cGAS-STING pathway is activated primarily in tumor cells rather than systemically, improving therapeutic efficiency.
Solution Approach 2:
The invention segments the therapeutic system into distinct functional components: the antibody for targeted delivery, the linker for stable conjugation, and the CDN derivative for STING activation. This segmentation allows each component to be optimized for its specific function while working together as an integrated targeted therapy.
Data Source
AI summary
Desired is development of novel CDN derivatives having STING agonist activity; and a therapeutic agents and/or therapeutic methods using the novel CDN derivatives for diseases associated with STING agonist activity. Further desired is development of a therapeutic agents and/or therapeutic methods capable of delivering the novel CDN derivatives specifically to targeted cells and organs for diseases associated with STING agonist activity. The present invention provides novel CDN derivatives having potent STING agonist activity, and antibody-CDN derivative conjugates including the novel CDN derivatives.