CD31 Peptides Inhibit Platelet Activation

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Solution Overview

Problem

Current therapies for thrombotic and inflammatory disorders, such as atherothrombosis and autoimmune diseases, are inadequate in addressing the inappropriate activation of blood leukocytes and platelets, leading to destructive inflammatory responses and thrombotic occlusions, with a need for better understanding of CD31's biological function to provide more efficient treatments.

Innovation Solution

Development of specific 8-amino acid peptides corresponding to the membrane juxta-proximal part of CD31, which are soluble, stable, and capable of inhibiting platelet and leukocyte activation by engaging CD31 signaling pathways, even in cells that have lost surface CD31, thereby preventing disease progression and aneurysm formation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapies are used for thrombotic and inflammatory disorders, then treatment is provided, but they are inadequate in addressing inappropriate activation of blood leukocytes and platelets

Engineering Contradiction:
Improveeffectiveness of therapyVSAvoidability to address inappropriate activation
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent extracts the specific functional domain (amino acids 579-601) from the complete CD31 protein to create a peptide that specifically targets the signaling pathway involved in inappropriate activation of leukocytes and platelets, providing more precise and effective therapy

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the molecular parameter from a large protein (CD31) to a smaller peptide (amino acids 579-601), which alters the pharmacokinetic properties and enables better penetration and targeting of the specific activation pathways while maintaining therapeutic effectiveness

Inventive Principle:
Principle #35Parameter changes

2Reliability

If CD31 signaling pathways are engaged to inhibit platelet and leukocyte activation, then disease progression is prevented, but understanding of CD31's biological function is required

Engineering Contradiction:
Improveprevention of disease progressionVSAvoidcomplexity of understanding biological function
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent isolates the critical signaling domain (amino acids 579-601) from the complex CD31 protein structure, creating a simplified peptide that engages the same protective signaling pathway without requiring complete understanding of all CD31 biological functions

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses the CD31 peptide as an intermediary molecule that bridges the gap between incomplete understanding of CD31 biology and the need to activate protective signaling, allowing therapeutic effect without full mechanistic knowledge

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If peptides are developed to inhibit T-cell proliferation and platelet activation, then thrombotic and inflammatory disorders are treated, but solubility and stability must be achieved

Engineering Contradiction:
Improvetherapeutic effectVSAvoidsolubility and stability of peptide
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent changes the physical-chemical parameters of the peptide by selecting a specific sequence (amino acids 579-601) that inherently provides both therapeutic activity and improved solubility-stability profile compared to other potential peptide sequences

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP2861241B1Improved CD31 peptides
Publication Date: 2021.04.28 INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
  • EP2861241B1 patent drawingFigure 1
  • EP2861241B1 patent drawingFigure 1
  • EP2861241B1 patent drawingFigure 2

AI summary

The present invention provides peptides corresponding to fragments of CD31 that inhibit platelet and leukocyte activation, and to their use in the treatment of thrombotic disease.These peptides find use as therapeutic agents in the treatment of inflammatory diseases and thrombotic diseases such as atherothrombosis, in particular when immobilised onto solid supports.