Bacteriophage g3p Protein Amyloid Binding and Disaggregation

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Solution Overview

Problem

Current therapeutic approaches for amyloid-related diseases, such as Alzheimer's and neurodegenerative tauopathies, are inadequate in effectively preventing or reversing amyloid formation and aggregation, and existing methods lack a reliable mechanism for amyloid binding and disaggregation.

Innovation Solution

The use of filamentous bacteriophage g3p protein, amyloid-binding fragments, and mutants/variants that directly bind amyloid fibers, facilitating their disaggregation and preventing aggregation, offering a novel therapeutic and diagnostic approach for amyloid-related diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional therapeutic approaches are used for amyloid-related diseases, then treatment is provided, but they are inadequate in effectively preventing or reversing amyloid formation and aggregation

Engineering Contradiction:
Improveeffectiveness of therapyVSAvoidamyloid formation and aggregation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent employs filamentous bacteriophage as an intermediary substance that mediates the binding and disaggregation of amyloid aggregates. The bacteriophage particles act as a bridge between the therapeutic goal and the amyloid pathology, utilizing their natural binding properties to achieve therapeutic effect without directly modifying the amyloid structure through harsh chemical or physical means.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention utilizes parameter changes in the bacteriophage-amyloid interaction, specifically the binding affinity and disaggregation efficiency under different physiological conditions. By optimizing parameters such as pH, temperature, and ionic strength, the bacteriophage can effectively bind to and disaggregate amyloid aggregates while maintaining stability in the physiological environment.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If existing methods are used, then some treatment is provided, but they lack a reliable mechanism for amyloid binding and disaggregation

Engineering Contradiction:
Improvemechanism reliabilityVSAvoidamyloid aggregates
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The bacteriophage serves as a reliable intermediary mechanism that provides a well-defined molecular interface for amyloid binding. The specific interaction between bacteriophage surface proteins and amyloid fibrils creates a predictable and controllable disaggregation mechanism, overcoming the lack of reliable binding mechanisms in existing therapies.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention replaces mechanical or physical disruption methods with a biochemical mechanism based on specific molecular recognition and binding. Instead of using harsh physical forces to break apart amyloid aggregates, the bacteriophage utilizes its natural binding properties to gently and specifically interact with and disaggregate the aggregates through biochemical interactions.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Object-generated harmful factors

If filamentous bacteriophage are used to bind and disaggregate amyloid, then amyloid load is reduced, but the complexity of the therapeutic composition increases

Engineering Contradiction:
Improveamyloid loadVSAvoidtherapeutic composition complexity
Core Design Contradiction:
Object-generated harmful factorsVSDevice complexity

Solution Approach 1:

The invention extracts and utilizes the specific amyloid-binding capability of filamentous bacteriophage, separating this functional property from the complete viral particle. By focusing on the essential binding and disaggregation function, the therapy achieves effectiveness while minimizing unnecessary complexity associated with the full viral structure.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The bacteriophage exhibits local quality in its interaction with amyloid, where specific regions or surface proteins on the bacteriophage are responsible for amyloid binding and disaggregation. This localized functionality allows for targeted therapy without requiring the entire bacteriophage structure to be involved, simplifying the therapeutic approach while maintaining effectiveness.

Inventive Principle:
Principle #3Local quality

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

These compositions effectively reduce amyloid load, inhibit aggregation, and provide a diagnostic tool for amyloid-related diseases, demonstrating potential in treating and diagnosing conditions like Alzheimer's and other neurodegenerative disorders.

Implementation Method 1

g3p and fragments and mutants and variants of g3p that bind amyloid

Methodology Applied
Scientific EffectAmyloid binding: Adsorption

Data Source

PatentEP2785364B1Use of p3 of bacteriophage as amyloid binding agents
Publication Date: 2019.01.09 PROCLARA BIOSCIENCES INC
  • EP2785364B1 patent drawingFigure 1
  • EP2785364B1 patent drawingFigure 2A
  • EP2785364B1 patent drawingFigure 2B

AI summary

The invention relates to agents and to pharmaceutical compositions for reducing the formation of amyloid and/or for promoting the disaggregation of amyloid proteins. The compositions may also be used to detect amyloid.