BSP Removal for Vascular Calcification in CKD

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Solution Overview

Problem

Current treatments for chronic kidney disease (CKD) do not effectively address the progression of extracellular tissue and vascular calcification, atherosclerosis, and the associated cardiovascular risks, despite efforts to manage biochemical parameters.

Innovation Solution

A method involving the administration of a receptor molecule, such as a human monoclonal antibody, that recognizes and binds to bone-sialoprotein (BSP) in the blood or plasma to inhibit calcification processes, potentially using plasmapheresis or direct administration to reduce circulating BSP levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional therapeutic approaches (phosphate-binding agents, calcimimetics, dialysis) are used to manage biochemical parameters, then serum phosphate and calcium levels are controlled, but vascular and tissue calcification progresses

Engineering Contradiction:

Improveserum phosphate and calcium levelsVSAvoidvascular and tissue calcification

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes bone sialoprotein (BSP) from the blood of CKD patients using plasmapheresis or immunoadsorption techniques. This directly eliminates the harmful substance (BSP) that drives vascular calcification, rather than merely controlling mineral levels. The harmful factor (BSP) is separated and removed from the bloodstream, addressing the root cause of calcification progression.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses an intermediary substance (antibodies against BSP or BSP-binding materials) to capture and remove BSP from the blood. These intermediaries specifically bind to BSP, facilitating its removal through plasmapheresis or immunoadsorption columns. This mediator approach allows selective elimination of the harmful protein without affecting other blood components.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If no specific intervention is applied, then current standard of care is maintained, but cardiovascular mortality remains high in CKD patients

Engineering Contradiction:

Improvestandard of careVSAvoidcardiovascular mortality

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies preliminary action by removing BSP from the blood before it can cause extensive vascular calcification and cardiovascular events. By proactively eliminating the harmful protein through plasmapheresis or immunoadsorption, the treatment prevents the progression of calcification and reduces future cardiovascular risk, rather than treating established disease.

Inventive Principle:

Principle #10Preliminary action

3Quantity of substance

If phosphate-binding agents and calcium supplements are administered, then dietary phosphate is controlled, but vascular calcification is not prevented

Engineering Contradiction:

Improvedietary phosphate intakeVSAvoidvascular calcification

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful effect of accumulated BSP into a beneficial treatment target. By identifying BSP as the key driver of vascular calcification, the invention transforms the previously unaddressed harmful factor into a specific therapeutic target. Plasmapheresis and immunoadsorption convert the harmful circulating BSP into removable waste products, eliminating its calcification-promoting effects.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

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 approach demonstrates significant reduction in vascular and tissue calcification, improved kidney function, and decreased cardiovascular risks, as evidenced by reduced calcification, fibrosis, and improved survival rates in animal models with CKD.

Implementation Method 1

administration of a receptor molecule, such as a human monoclonal antibody, that recognizes and binds to bone-sialoprotein (BSP) in the blood or plasma

Methodology Applied

Scientific EffectAntibody-antigen binding: Absorption (physical)

Implementation Method 2

potentially using plasmapheresis or direct administration to reduce circulating BSP levels

Methodology Applied

Scientific EffectPlasmapheresis: Centrifugal Separation

Data Source

PatentUS10947301B2Method of treating extracellular tissue and vascular calcification and arteriosclerosis

Publication Date: 2021.03.16 IMMUNDIAGNOSTIK AG

AI summary

A novel therapy concept based on a removal of circulating BSP (bone sialoprotein) from the plasma of patients with chronic kidney disease (CKD) or highly at risk of developing arterial and vascular calcifications. The method comprises method of treatment of extracellular tissue and vascular calcifications, atherosclerosis, arteriosclerosis, and arterial calcification. The beneficial effects of this therapy have been proven by the observed correspondence between levels of circulating free BSP levels and mortality of CKD patients as well as in animal models.