Modified Orthopoxvirus Interferon-Binding Protein for Inflammation Control

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Solution Overview

Problem

Current therapies for excessive Type I interferons, which are critical for immune responses but can cause acute inflammation and organ failure when produced in excess, lack a safe and effective method for neutralization, particularly due to species specificity and the difficulty in broadly targeting all Type I IFN subtypes.

Innovation Solution

A modified Orthopoxvirus Type I interferon-binding protein, devoid of the cell-binding region, is developed to specifically bind and neutralize Type I interferons, providing a therapeutic composition that can be administered to reduce or control harmful inflammatory responses in mammals.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If a modified Orthopoxvirus Type I interferon-binding protein is used to neutralize Type I interferons, then the harmful inflammatory effects are reduced, but the complexity of the therapeutic composition increases

Engineering Contradiction:
Improveinflammatory effectsVSAvoidtherapeutic composition complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent extracts and removes the cell-binding region from the Orthopoxvirus Type I interferon-binding protein, retaining only the interferon-binding domain. This extraction eliminates unnecessary complexity while preserving the neutralizing function against Type I interferons, directly resolving the contradiction between effectiveness and composition complexity.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The protein is segmented into functional domains, with the cell-binding region separated from the interferon-binding region. This segmentation allows the therapeutic composition to focus solely on interferon neutralization without the complicating cell-binding activity, reducing overall complexity while maintaining therapeutic efficacy.

Inventive Principle:
Principle #1Segmentation

2Ease of operation

If the cell-binding region is removed from the interferon-binding protein, then the protein can diffuse systemically and be easily cleared, but the protein's ability to bind to cells is lost

Engineering Contradiction:
Improvesystemic diffusion and clearanceVSAvoidcell-binding function
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The cell-binding region is extracted and removed from the protein structure. This removal enables systemic diffusion and easy clearance from the body, which are desirable properties for a therapeutic agent. The loss of cell-binding function is acceptable because the therapeutic mechanism relies on interferon neutralization in circulation, not on cellular uptake.

Inventive Principle:
Principle #2Taking out (Extraction)

3Reliability

If existing IFN therapies are used to treat excessive Type I interferon, then immune response is boosted, but severe and life-threatening adverse effects occur

Engineering Contradiction:
Improveimmune responseVSAvoidadverse effects
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent uses a viral-derived protein (Orthopoxvirus interferon-binding protein) that naturally binds and neutralizes interferons. By removing the cell-binding region, the harmful cell-targeting activity is eliminated while preserving the beneficial interferon-neutralizing activity. This converts a potentially harmful viral protein into a safe therapeutic agent that reduces interferon-mediated inflammation without causing severe adverse effects.

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

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

The modified protein effectively neutralizes Type I interferons, reducing inflammation and preventing negative side effects, with the ability to diffuse systemically and be easily cleared from the body, allowing for controlled regulation of IFN levels and protection against lethal shock and other inflammatory conditions.

Implementation Method 1

The compositions contain a modified Orthopoxvirus Type I interferon-binding protein (IFN-binding protein), which neutralizes Type I interferons by binding specifically thereto

Methodology Applied
Scientific EffectSpecific binding: Absorption (physical)

Data Source

PatentUS10548946B2Therapeutic compositions for neutralizing type I interferons, and methods of use
Publication Date: 2020.02.04 UNITED STATES OF AMERICA THE AS REPRESENTED BY THE SEC OF THE ARMY
  • US10548946B2 patent drawing
  • US10548946B2 patent drawing
  • US10548946B2 patent drawing

AI summary

The inventions describe here cover therapeutic compositions, and methods of use, for neutralizing Type I interferons in a mammal. The compositions contain a soluble Orthopoxvirus IFN-binding protein that is modified to remove the cell-binding region, and that specifically binds to Type I IFNs, and a pharmaceutically acceptable carrier or excipient. Another variation of the invention entails a novel IFN-binding protein that is modified to remove the cell-binding region and the signal sequence.