sTNFR2 Vaccine for Chronic Inflammation via TNFα Sequestration

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Solution Overview

Problem

Current therapeutic interventions for chronic inflammation, particularly those targeting TNFα, have limitations such as the development of antidrug antibodies, high costs, and contraindications in certain patients, while there are no therapeutic interventions targeting sTNFR2.

Innovation Solution

Development of a vaccine targeting the Δ7 or Δ7,8 splice variants of soluble TNF receptor II (sTNFR2), either as an mRNA vaccine encoding these variants or as a peptide vaccine comprising the amino acid sequence of these variants, to provide a therapeutic option for patients where TNFα inhibitors are not recommended.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If TNFα inhibitors are used to treat chronic inflammation, then inflammation is reduced and symptoms are alleviated, but antidrug antibodies and neutralizing antibodies develop limiting efficacy

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidantidrug antibodies

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts the therapeutic benefit of TNFα inhibition while removing the harmful antibody response by targeting sTNFR2 instead of TNFα directly. The vaccine encodes sTNFR2 protein that binds to TNFα, sequestering it away from its receptors and preventing inflammation without triggering antidrug antibody formation against the cytokine itself.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The sTNFR2 protein acts as an intermediary molecule that binds to TNFα and prevents it from interacting with its receptors. This mediator approach allows indirect TNFα inhibition, achieving anti-inflammatory effects while avoiding direct confrontation with the cytokine that would trigger harmful antibody responses.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If TNFα inhibitors are used to treat chronic inflammation, then inflammation is reduced, but the cost exceeds $75,000 per year making them unattainable in low-income populations

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidcost of therapy

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The vaccine employs a cost-effective mRNA or peptide encoding sTNFR2 that can be produced at lower cost compared to complex monoclonal antibody therapies. The vaccine induces endogenous production of sTNFR2, creating a sustainable, affordable therapeutic approach that eliminates the need for continuous expensive drug administrations.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Reliability

If TNFα inhibitors are used to treat chronic inflammation, then inflammation is reduced, but they are contraindicated in certain patients with chronic infections

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidpatient eligibility

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The sTNFR2 vaccine provides localized, targeted inhibition of TNFα through soluble receptor binding, preserving local immune responses at infection sites while reducing systemic inflammation. This localized action allows treatment of inflammatory conditions in patients with chronic infections by maintaining necessary antimicrobial immunity while blocking harmful inflammatory pathways.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20250064907A1Therapeutic vaccines for treatment of chronic inflammatory diseases

Publication Date: 2025.02.27 ATHEROVAX LLC

AI summary

Described herein are nucleic acid and peptide vaccines comprising sTNFR2 sequences complementary to variants of companion animal TNFR2 genes and methods for treating human or companion animal subjects for chronic inflammatory diseases.