BPIFB4 Protein Variant for eNOS Activation in Endothelial Dysfunction

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Solution Overview

Problem

Existing therapies fail to effectively address endothelial dysfunction caused by impaired eNOS and NO-mediated vasodilation, which is associated with various pathological conditions such as hypertension, atherosclerosis, and neurodegenerative diseases.

Innovation Solution

A variant of the BPIFB4 protein, specifically with Valine at position 229, Threonine at position 281, Phenylalanine at position 488, and Threonine at position 494, enhances eNOS activation and NO production, offering therapeutic potential for endothelial dysfunction and related conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing therapies are used to treat endothelial dysfunction, then treatment is provided, but they fail to effectively address the underlying impairment of eNOS and NO-mediated vasodilation

Engineering Contradiction:

Improveeffectiveness of therapyVSAvoidability to address impaired eNOS and NO-mediated vasodilation

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention uses amino acid substitution to change the molecular parameters of the BPIFB4 protein, specifically replacing certain amino acids with others (e.g., substituting aspartic acid with asparagine) to create a variant with enhanced ability to activate eNOS and promote NO production, thereby effectively addressing endothelial dysfunction

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The BPIFB4 protein variant acts as an intermediary molecule that mediates between the administered substance and the eNOS enzyme, enhancing eNOS activation and NO production without directly being eNOS itself, thus providing a indirect but effective treatment mechanism for endothelial dysfunction

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If BPIFB4 protein variant is administered, then eNOS activation and NO production are enhanced, but the complexity of identifying and producing the specific variant increases

Engineering Contradiction:

ImproveeNOS activation and NO production enhancementVSAvoidcomplexity of variant identification and production

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The invention simplifies the production complexity by defining specific amino acid substitution parameters (e.g., aspartic acid to asparagine at particular positions) that can be systematically implemented in protein expression systems, making the production of the therapeutic variant more straightforward and scalable

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12486308B2Variant of a BPIFB4 protein

Publication Date: 2025.12.02 LGV1 SRL

AI summary

The present invention relates to a variant of BPIFB4 protein (Bactericidal/Permeability Increasing protein family B, member 4) and to a polynucleotide or a vector encoding said variant of BPIFB4 protein and to their use for the treatment of pathologies involving impairment of nitric oxide signalling.