Evasin-4 Protein Antagonist for CC-Chemokine Binding

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Solution Overview

Problem

Current therapies lack effective CC-chemokine antagonists, particularly for CCL5 and CCL11, which are crucial in inflammatory and immune responses, and there is a lack of characterized tick proteins acting as CC-chemokine binding proteins or antagonists.

Innovation Solution

A novel protein, evasin-4, derived from the saliva of Rhipicephalus sanguineus ticks, is identified and expressed, which binds CC-chemokines, inhibiting their activity, and its derivatives or mimetics can be used therapeutically as antagonists or for vaccination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapies are used, then treatment of inflammatory and immune diseases is attempted, but effective CC-chemokine antagonists are lacking

Engineering Contradiction:
Improveeffectiveness of CC-chemokine antagonismVSAvoidavailability of targeted chemokine inhibitors
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces evasin-4 as an intermediary protein that binds to CC-chemokines (CCL5 and CCL11) to block their interaction with receptors. This mediator approach provides specific chemokine antagonism without requiring direct receptor modification, resolving the lack of effective antagonists while maintaining therapeutic versatility

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates recombinant copies of evasin-4 and its derivatives to produce therapeutic antagonists. By copying and modifying the natural tick protein sequence, the invention generates multiple variants with optimized binding properties, addressing both effectiveness and availability of targeted inhibitors

Inventive Principle:
Principle #26Copying

2Productivity

If tick proteins are screened randomly, then some binding proteins may be identified, but most sequences remain uncharacterized biochemically or functionally

Engineering Contradiction:
Improvenumber of sequences identifiedVSAvoidfunctional characterization accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent performs preliminary biochemical and functional characterization of evasin-4 through recombinant expression, binding assays, and activity tests before therapeutic development. This preliminary action transforms random sequence identification into precisely characterized functional proteins, resolving the contradiction between productivity and measurement precision

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent systematically varies parameters including protein expression levels, purification conditions, and binding assay conditions to optimize characterization of evasin-4. By changing these parameters, the invention achieves precise functional characterization while maintaining high productivity in protein production and analysis

Inventive Principle:
Principle #35Parameter changes

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

Evasin-4 effectively binds and inhibits CC-chemokines, offering potential therapeutic applications in regulating immune and inflammatory responses, and providing a means to control tick-borne pathogens.

Implementation Method 1

it has been found that the saliva of Rhipicephalus sanguineus (common brown dog tick) contains a novel protein termed herein evasin-4, which binds CC-chemokines and inhibits their activity

Methodology Applied
Scientific EffectProtein binding: Absorption (physical)

Data Source

PatentEP1984392B1Novel CC-chemokine antagonists
Publication Date: 2012.08.08 MERCK SERONO SA
  • EP1984392B1 patent drawingFigure 1
  • EP1984392B1 patent drawingFigure 2A~2B
  • EP1984392B1 patent drawingFigure 3

AI summary

A novel CC-chemokine binding protein is isolated from the saliva of Rhipicephalus sanguineus