Snare Molecules for Pathogen Capture via Erythrocyte Binding

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Solution Overview

Problem

Current methods for removing pathogens from the circulatory system are limited by their reliance on complement activation, rapid clearance of heteropolymeric antibodies, and serotype specificity, which restricts their effectiveness in capturing continuously emerging viruses and allows for antigen mutation evasion.

Innovation Solution

Development of 'snare' molecules that attach a receptor for pathogenic agents to non-target cells like erythrocytes, allowing these cells to compete with target cells for binding and reduce pathogenicity without complement activation, using antibodies or GPI anchors for attachment and chemical crosslinking for receptor binding.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If heteropolymeric antibodies (HPs) are used to capture pathogens, then pathogen binding efficiency is improved, but circulation half-life is reduced due to rapid clearance via Fc regions

Engineering Contradiction:

Improvepathogen binding efficiencyVSAvoidcirculation half-life

Core Design Contradiction:

ProductivityVSDuration of action of moving object

Solution Approach 1:

The invention extracts the Fc region from the antibody structure, using only the Fab region to bind pathogens. This removes the target for Fc-mediated clearance while preserving antigen-binding capability, thereby extending circulation half-life without sacrificing pathogen capture efficiency

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention changes the molecular structure parameter by using Fab fragments instead of complete antibodies, and further modifies it by PEGylation to reduce renal clearance. These parameter changes transform the pharmacokinetic profile to achieve both high binding efficiency and prolonged circulation

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If monoclonal antibodies specific to pathogenic antigens are used, then binding specificity is improved, but adaptability to antigen mutations is reduced

Engineering Contradiction:

Improvebinding specificityVSAvoidresistance to antigen mutation

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The invention makes the pathogen-binding component universal by using the naturally occurring cellular receptor instead of a monoclonal antibody. This receptor binds conserved essential epitopes that are critical for pathogen function, providing broad-spectrum coverage across different strains and serotypes while maintaining high binding specificity

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

Instead of using an antibody that binds to a variable pathogen antigen, the invention inverts the approach by using the pathogen's own receptor-binding protein to bind to the host cellular receptor. This reverses the specificity relationship, making the system adaptable to antigen mutations while maintaining precise binding through receptor conservation

Inventive Principle:

Principle #13The other way round (Inversion)

3Productivity

If complement-dependent clearance mechanisms are used, then pathogen removal efficiency is improved, but applicability to non-C3b receptor targets is reduced

Engineering Contradiction:

Improvepathogen removal efficiencyVSAvoidapplicability to non-C3b receptor targets

Core Design Contradiction:

ProductivityVSAdaptability or versatility

Solution Approach 1:

The invention introduces non-target cells (such as erythrocytes or albumin) as intermediaries that carry the cellular receptor on their surface. These intermediaries serve as mobile platforms to deliver the receptor to various locations in the circulatory system, enabling clearance of pathogens that do not naturally bind to C3b receptors while maintaining efficient removal through reticuloendothelial system recognition

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 snare molecules efficiently capture pathogens, including viruses, by exploiting the reticuloendothelial system for clearance and maintaining effectiveness against various serotypes and antigenic shifts, providing prolonged circulation and broad-spectrum protection.

Implementation Method 1

an attachment moiety that facilitates attachment or expression of a receptor (e.g., a receptor for a toxic or pathogenic agent) by a cell which is not normally a target for the agent

Methodology Applied

Scientific EffectAntibody binding:

Implementation Method 2

using antibodies or GPI anchors for attachment

Methodology Applied

Scientific EffectGPI anchor attachment:

Implementation Method 3

a binding moiety which is a receptor for the pathogenic or toxic agent

Methodology Applied

Scientific EffectReceptor binding:

Implementation Method 4

The snare molecules efficiently capture pathogens, including viruses, by exploiting the reticuloendothelial system for clearance

Methodology Applied

Scientific EffectReticuloendothelial system clearance:

Implementation Method 5

chemical crosslinking for receptor binding

Methodology Applied

Scientific EffectChemical crosslinking:

Data Source

PatentUS9493538B2Snares for pathogenic or infectious agents and uses related thereto

Publication Date: 2016.11.15 UNIV OF MASSACHUSETTS

AI summary

The present invention provides a snare molecules comprising an attachment moiety (which facilitates attachment of a receptor to a cell) and a receptor for a toxic pathogenic or infectious agent, e.g., a virus. Methods of producing such snare molecules and their therapeutic and/or prophylactic uses are also provided by the present invention.