Dimeric SMAC Mimetics Reversing HIV Latency

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Solution Overview

Problem

Current HIV treatments, such as HAART, are complex and can lead to drug resistance, incomplete suppression of viral replication, and residual inflammation, with latent HIV reservoirs remaining in individuals, necessitating new therapies to achieve viral remission or cure.

Innovation Solution

Development of dimeric SMAC mimetics that activate the non-canonical NF-kB pathway to reverse HIV latency, deplete HIV-infected cells, and potentially cure HIV infection by inducing HIV RNA expression in resting CD4+ T cells, even under antiretroviral therapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If HAART therapy is used to suppress HIV replication, then patient survival and quality of life are improved, but drug resistance emerges and viral reservoirs remain latent

Engineering Contradiction:

Improvepatient survivalVSAvoiddrug resistance

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful latent viral reservoirs into a benefit by using SMAC mimetics to reactivate latent HIV from reservoirs. This reactivation allows the immune system and antiretroviral drugs to eliminate the previously hidden viral populations, turning the reservoirs from a source of resistance into targets for complete viral clearance

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent applies preliminary action by using SMAC mimetics to reactivate latent HIV before administering antiretroviral therapy. By reactivating the latent virus first, the treatment ensures that all viral forms (both latent and active) are present and susceptible to drug action, preventing future resistance development

Inventive Principle:

Principle #10Preliminary action

2Reliability

If HAART therapy is used to suppress HIV replication, then viral replication is suppressed, but residual inflammation and non-AIDS morbidities increase

Engineering Contradiction:

Improveviral suppressionVSAvoidsystemic inflammation

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and eliminates the source of chronic inflammation by targeting and clearing latent HIV reservoirs. By removing the persistent viral antigen load from reservoirs, the underlying cause of immune activation and inflammation is eliminated, allowing the immune system to return to a healthier state

Inventive Principle:

Principle #2Taking out (Extraction)

3Reliability

If complex HAART regimens are administered daily, then viral replication is suppressed, but treatment complexity and non-adherence increase

Engineering Contradiction:

Improveviral suppressionVSAvoidtreatment complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent achieves continuous viral suppression with simplified therapy by using SMAC mimetics to reactivate latent virus, making the entire viral population (latent and active) susceptible to standard antiretroviral drugs. This allows for continuous elimination of virus without requiring complex intermittent dosing schedules

Inventive Principle:

Principle #20Continuity of useful action

Data Source

PatentUS11873310B2Compounds useful in HIV therapy

Publication Date: 2024.01.16 VIIV HEALTHCARE CO

AI summary

The invention relates to compounds of Formula (I), (Ia), (Ib), (II) or (III), salts thereof, pharmaceutical compositions thereof, as well as therapeutic methods of treatment and prevention.