Human EGF Domain Protein Neutralizes Gram-Negative Endotoxin

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Solution Overview

Problem

Current treatments for Gram-negative bacteria infections, particularly those causing endotoxemia, are hindered by antibiotic resistance and the inability of early antibiotics to effectively target lipopolysaccharides on bacterial cell walls, leading to high mortality rates and the need for novel therapeutic approaches.

Innovation Solution

Human-originated EGF domain proteins with specific amino acid sequences are used to inhibit Gram-negative bacteria and hydrolyze lipopolysaccharides, offering a new class of medicaments for treating infections and endotoxemia.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibiotics are used to treat Gram-negative bacteria infection, then bactericidal effect is improved, but drug resistance progression occurs

Engineering Contradiction:
Improvebactericidal effectVSAvoiddrug resistance
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent converts the harmful effect of lipopolysaccharide (which causes endotoxemia) into a beneficial target by designing EGF domain proteins that specifically bind to and neutralize lipopolysaccharide on the bacterial cell wall, transforming the pathogenic factor into a therapeutic target

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

Solution Approach 2:

The EGF domain protein acts as an intermediary substance that mediates between the immune system and the bacterial endotoxin, binding to lipopolysaccharide to prevent its harmful effects while facilitating immune recognition and clearance of the bacteria

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If early types of antibiotics are used to treat Gram-negative bacteria, then treatment simplicity is improved, but effectiveness against lipopolysaccharide is worsened

Engineering Contradiction:
Improvetreatment simplicityVSAvoidantibacterial effectiveness
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent changes the fundamental parameter of antibacterial mechanism from traditional cell wall synthesis inhibition or protein synthesis inhibition to direct binding and neutralization of lipopolysaccharide by EGF domain proteins, enabling effective treatment of endotoxemia while maintaining treatment simplicity

Inventive Principle:
Principle #35Parameter changes

3Productivity

If antibiotics are used to kill bacteria, then bacterial elimination is improved, but endotoxin release increases

Engineering Contradiction:
Improvebacterial eliminationVSAvoidendotoxin release
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The EGF domain protein performs preliminary anti-action by binding to and neutralizing lipopolysaccharide on the bacterial cell wall before the bacteria are killed by antibiotics, preventing the release of endotoxin into the bloodstream and subsequent endotoxemia

Inventive Principle:
Principle #9Preliminary anti-action

Solution Approach 2:

The patent applies preliminary action by having the EGF domain protein pre-bind to lipopolysaccharide on intact bacteria, preparing the endotoxin for neutralization before antibiotic-induced bacterial lysis would otherwise release it into the circulation

Inventive Principle:
Principle #10Preliminary action

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 human-originated EGF domain proteins demonstrate inhibitory effects on Gram-negative bacteria, effectively reducing endotoxin levels and providing a novel therapeutic option for treating infections and associated endotoxemia.

Implementation Method 1

The EGF domain protein of human origin has the capability of inhibiting Gram-negative bacteria and hydrolyzing lipopolysaccharides

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Implementation Method 2

the agents such as prostaglandin synthetase inhibitor, levamisole, and tuftsin are also useful in treatment of the Gram-negative bacteria infection

Methodology Applied
Scientific EffectBinding: Adsorption

Data Source

PatentEP3006460B1Human source EGF structural domain protein and application of same
Publication Date: 2020.08.26 CHENGDU SOURCEBIO LIMITED LIABILITY
  • EP3006460B1 patent drawingFigure 1~3
  • EP3006460B1 patent drawingFigure 4~5
  • EP3006460B1 patent drawingFigure 6~8

AI summary

In the invention, the minimum inhibitory concentrations of human-originatcd EGF domain proteins against different Gram-negative bacteria are detected with the in vitro antibacterial activity. It has been shown that the human-originated EGF domain proteins have an obvious inhibitory effect on the Gram-negative bacteria, so as to develop a novel class of medicaments for treating Gram-negative bacteria infection. It has been demonstrated by silver staining that the human-originated EGF domain proteins have the effect on hydrolyzing and eliminating the endotoxin, which facilitates the development of a novel class of medicaments for treating endotoxemia. The amino acid sequences of the human-originated EGF domain proteins are the one described in SEQ ID NO: 1 in the sequence listing, or those having homology of over 50% to the amino acid sequence described in SEQ ID NO: 1.