Cyclic Dinucleotide STING Agonists for HBV Immune Activation
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Solution Overview
Problem
Current treatments for chronic hepatitis B virus (HBV) infection are limited, with existing therapies offering low cure rates, drug resistance, and tolerability issues, failing to achieve complete suppression of virus production, and there is a need for therapeutic agents that can enhance immune response and reduce viral burden.
Innovation Solution
Development of novel compounds acting as STING (Stimulator of Interferon Genes) agonists, specifically cyclic dinucleotide derivatives, which activate the STING pathway to enhance innate and adaptive immunity, potentially used in combination with other immunotherapies for treating HBV and various cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies are used for chronic HBV infection, then treatment can be provided, but cure rates are low and drug resistance occurs
Solution Approach 1:
The patent employs parameter changes by modifying the chemical structure of cyclic dinucleotide compounds to create novel derivatives with improved biological activity. The general formula (I) allows systematic variation of substituents (R, R1B, R1C, R2B, R2C, B1, W, X, Y, Z) to optimize STING agonist potency and overcome drug resistance while maintaining reliability in treating HBV infection.
2Productivity
If existing therapies are used for chronic HBV infection, then treatment can be provided, but complete suppression of virus production is not achieved
Solution Approach 1:
The patent uses cyclic dinucleotide compounds as intermediaries that activate the STING pathway, which serves as a mediator between viral detection and immune response activation. This intermediary mechanism enables complete suppression of HBV production by triggering a robust innate and adaptive immune response through Type I interferon and pro-inflammatory cytokine production.
3Reliability
If STING pathway is activated to enhance immune response, then antiviral and antitumor activity is improved, but treatment complexity increases
Solution Approach 1:
The patent achieves universality by developing cyclic dinucleotide compounds that can activate the STING pathway for multiple therapeutic applications including antiviral therapy for HBV and antitumor activity against various cancers. This multi-functional approach allows a single compound class to address diverse diseases through the common STING signaling pathway, simplifying treatment strategies despite the complexity of immune modulation.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These compounds stimulate a robust immune response, activating type I interferons and pro-inflammatory cytokines, leading to potential long-lasting immunity against HBV and antitumor activity, offering improved treatment options for HBV and cancer therapies.
Implementation Method 1
Activation of the STING pathway results in production of Type I interferons (mainly IFN-α and IFN-β) induced through the IRF3 (interferon regulatory factor 3) pathway
Implementation Method 2
TBK1 also activates the nuclear factor kappa-light-chain-enhancer of activated B cells pathway which leads to production of pro-inflammatory cytokines (IL-1α, IL-1β, IL-2, IL-6, TNF-α, etc.)
Data Source
AI summary
Disclosed are compounds, compositions and methods for treating of diseases, syndromes, or disorders that are affected by the modulation of STING. Such compounds are represented by Formula (I) as follows:wherein R, R1B, R1C, R2B, R2C, B1, W, X, Y, Z are defined herein.