Combination Therapy for Hepatitis B Using Phosphorothioated Nucleic Acid Polymers
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for hepatitis B virus (HBV) and HBV/HDV co-infection fail to elicit a durable immunological control, as they do not effectively reduce HBsAg levels, which sequester antibodies and inhibit immune detection, and do not adequately address the stable reservoir of HBV genetic information in infected cells, leading to chronic infection.
Innovation Solution
A combination therapy using a pharmaceutically acceptable phosphorothioated nucleic acid polymer formulation to remove HBsAg from the blood and a nucleoside/nucleotide analog HBV polymerase inhibitor to block the replenishment of the viral reservoir, thereby enhancing immune function and reducing cccDNA copy numbers in infected hepatocytes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If HBV polymerase inhibitors are used to reduce viral production, then infectious virion production is reduced, but HBsAg levels are not effectively reduced and immune control is not achieved
Solution Approach 1:
The patent combines two distinct therapeutic mechanisms: HBV polymerase inhibition (to reduce virion production) and anti-HBsAg antibody administration (to clear HBsAg from blood). This combination therapy merges the benefits of both approaches to achieve both viral production reduction and immune control, resolving the contradiction where monotherapy fails to achieve durable immune control.
Solution Approach 2:
The patent introduces anti-HBsAg antibodies as an intermediary substance that mediates the clearance of HBsAg from the blood. These antibodies act as a bridge between the immune system and the viral antigen, enabling immune control by neutralizing the immunoinhibitory effects of HBsAg that polymerase inhibitors alone cannot address.
2Quantity of substance
If current antiviral treatments are administered, then viral production is suppressed, but treatment duration is prolonged and durable control is not achieved
Solution Approach 1:
By merging polymerase inhibitor therapy with anti-HBsAg antibody administration, the patent achieves both viral production suppression and HBsAg clearance simultaneously. This combination accelerates the overall therapeutic response, allowing for shorter treatment durations while maintaining durable viral suppression that neither monotherapy can achieve alone.
3Reliability
If HBsAg remains in the blood, then antibody sequestration occurs and immune detection is inhibited, but removing HBsAg is essential for immune control
Solution Approach 1:
The patent uses anti-HBsAg antibodies as intermediaries that bind to and neutralize HBsAg in the blood. This intermediary approach prevents HBsAg from sequestering other antibodies and inhibiting immune detection, thereby restoring immune function while simultaneously clearing the harmful antigen from the system.
Solution Approach 2:
The patent converts the harmful immunoinhibitory effects of HBsAg into a benefit by administering exogenous anti-HBsAg antibodies. These therapeutic antibodies not only neutralize the harmful HBsAg but also prevent its ability to sequester endogenous antibodies, transforming the pathological state into a therapeutic opportunity for restoring immune control.
Data Source
Figure 1
Figure 2A~2B
Figure 3A~3B
AI summary
It is disclosed a method for treating hepatitis B virus infection or hepatitis B virus / hepatitis delta virus co-infection, the method comprising administering to a subject in need of such treatment a first pharmaceutically acceptable agent that comprises at least one phosphorothioated nucleic acid polymer and a second pharmaceutically acceptable agent that comprises at least one nucleoside / nucleotide analog HBV polymerase inhibitor.