MFAP4 Antibodies Block Integrin Receptor Binding

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Solution Overview

Problem

Current therapeutic strategies for vascular proliferative diseases, such as restenosis after percutaneous coronary interventions, lack effective medicaments to inhibit vascular smooth muscle cell proliferation and migration, and there is a need for treatments that can prevent or treat cardiovascular and vascular eye disorders like AMD and DR.

Innovation Solution

Development of antibodies that specifically block the integrin interacting motif in human microfibrillar-associated protein 4 (MFAP4), which are used to inhibit the interaction between MFAP4 and integrin receptors, thereby preventing or treating cardiovascular proliferative diseases, allergic asthma, and vascular eye disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If percutaneous coronary intervention (PCI) is performed to treat ischemic heart diseases, then the invasiveness is reduced and patient recovery is improved, but restenosis occurs in 30-45% of patients within several months after surgery

Engineering Contradiction:
Improveinvasiveness of treatmentVSAvoidrestenosis prevention
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent uses antibodies as intermediary molecules that specifically bind to MFAP4, blocking its interaction with integrin receptors on vascular smooth muscle cells. This intermediary approach prevents the signaling pathway that leads to restenosis without requiring surgical intervention, thus maintaining the low invasiveness of PCI while improving restenosis prevention efficacy.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent extracts and targets the specific molecular mechanism (MFAP4-integrin interaction) that drives restenosis after PCI. By isolating this key pathogenic pathway and blocking it with antibodies, the treatment addresses the root cause of restenosis while preserving the benefits of minimally invasive PCI procedures.

Inventive Principle:
Principle #2Taking out (Extraction)

2Reliability

If vascular smooth muscle cell proliferation and migration are inhibited to prevent restenosis, then restenosis and neointima formation are reduced, but vascular remodeling processes are affected

Engineering Contradiction:
Improverestenosis preventionVSAvoidvascular remodeling
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies local quality by specifically targeting the MFAP4-integrin interaction pathway in vascular smooth muscle cells, rather than broadly inhibiting all cellular proliferation and migration processes. This localized approach prevents restenosis while preserving other essential vascular remodeling functions that do not depend on this specific pathway.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The antibodies serve as intermediaries that selectively block the MFAP4-integrin signaling pathway, allowing precise modulation of vascular smooth muscle cell behavior. This intermediary mechanism enables differentiation between pathological proliferation (restenosis) and physiological remodeling processes.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If MFAP4 interaction with integrin receptors is blocked to prevent vascular smooth muscle cell activation, then proliferation and migration are reduced, but the mechanism of action needs to be highly specific to avoid off-target effects

Engineering Contradiction:
Improvevascular smooth muscle cell activation controlVSAvoidantibody specificity requirement
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the complex integrin family into specific subtypes (αvβ3 and αvβ5) and develops antibodies that target MFAP4's interaction with these particular receptors. This segmentation approach allows selective inhibition of pathological pathways while preserving other integrin-mediated functions that are essential for normal vascular physiology.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The antibodies act as highly specific intermediaries that bridge MFAP4 and block its binding to integrin receptors with precise molecular recognition. This intermediary mechanism ensures high specificity through antibody-antigen binding, avoiding off-target effects while effectively controlling vascular smooth muscle cell activation.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 antibodies effectively delay and regulate the activation, proliferation, and migration of vascular smooth muscle cells, reducing neointima formation and inflammatory infiltration, thus addressing the challenges of restenosis and vascular remodeling.

Implementation Method 1

antibodies, in particular monoclonal, that bind human Microfibrillar-associated protein 4 (MFAP4)

Methodology Applied
Scientific EffectAntigen-antibody binding:

Implementation Method 2

specifically blocks the integrin interacting motif in human microfibrillar-associated protein 4 (MFAP4)

Methodology Applied
Scientific EffectBlocking interaction:

Data Source

PatentEP2948472B1MFAP4 binding antibodies blocking the interaction between MFAP4 and integrin receptors
Publication Date: 2019.05.22 SYDDANSK UNIV
  • EP2948472B1 patent drawingFigure 1
  • EP2948472B1 patent drawingFigure 2A~2G
  • EP2948472B1 patent drawingFigure 3A~3F

AI summary

Microfibrillar-associated protein 4 (MFAP4) binding antibodies are provided to prevent or to inhibit the proliferation of vascular smooth muscle cells and neointima formation in blood vessels. Furthermore, there are provided antibodies that effectively inhibit remodelling of vessels and prevent progression of arteriosclerosis as well as restenosis of vessels. The provided antibodies block the interaction between MFAP4 and integrin receptors.