Recombinant EV71 Neutralizing Antibodies for Neurological Complication Prevention

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Solution Overview

Problem

Current treatments for enterovirus 71 (EV71) infections, particularly in children, are inadequate as they often result in severe neurological complications and death due to insufficient production of neutralizing antibodies, with no effective agent available to inhibit viral propagation or clear virus particles.

Innovation Solution

Development of recombinant human monoclonal antibodies specific to EV71 using a yeast two-hybrid system and antibody affinity maturation techniques, which are expressed as single-chain antibodies to target and neutralize the virus, potentially combined with therapeutic or diagnostic agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments are used for EV71 infections, then symptomatic relief is provided, but severe neurological complications and death occur due to insufficient neutralizing antibody production

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidsevere neurological complications
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent develops recombinant human monoclonal antibodies that can be administered prophylactically or therapeutically to provide neutralizing antibodies before the patient's own immune system can produce sufficient antibodies. This preliminary action prevents the development of severe neurological complications rather than treating them after onset.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The recombinant monoclonal antibodies serve as an intermediary substance that mediates the neutralization of EV71 virus particles. These engineered antibodies act as a bridge between the administered treatment and the viral target, providing the neutralizing function that the patient's immune system fails to produce in time.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If no effective agent is available to inhibit viral propagation, then the natural course of infection proceeds, but viral particles persist and cause severe complications

Engineering Contradiction:
Improveviral clearance rateVSAvoidinfection outcome
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent extracts and isolates the neutralizing function from the complex immune response by producing recombinant monoclonal antibodies that specifically target EV71. These purified antibodies can be administered to directly neutralize viral particles and inhibit propagation without requiring the patient's immune system to mount an effective response.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the parameter of antibody availability by introducing exogenously produced recombinant monoclonal antibodies into the system. This alters the concentration and specificity of neutralizing antibodies present during infection, ensuring sufficient levels are available to clear viral particles before severe complications develop.

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If symptomatic treatment is provided without neutralizing antibodies, then fever and malaise are managed, but viral propagation continues unchecked

Engineering Contradiction:
Improvetreatment simplicityVSAvoidviral propagation
Core Design Contradiction:
Ease of operationVSObject-generated harmful factors

Solution Approach 1:

The patent merges symptomatic management with antiviral neutralization by combining recombinant monoclonal antibodies with supportive care protocols. This integrated approach simultaneously addresses viral propagation through antibody-mediated neutralization and manages symptoms through conventional measures, providing comprehensive treatment rather than separate interventions.

Inventive Principle:
Principle #5Merging (Combining)

Data Source

PatentUS7482006B2Recombinant enterovirus 71 neutralizing antibodies and applications thereof
Publication Date: 2009.01.27 DEV CENT FOR BIOTECHNOLOGY
  • US7482006B2 patent drawing
  • US7482006B2 patent drawing
  • US7482006B2 patent drawing

AI summary

Provided is an antibody against enterovirus 71 comprising the amino acid sequence shown in SEQ ID NOS: 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26 or functionally active homologues thereof. Also provided are methods for obtaining the antibody comprising (a) selecting a yeast expressing such an antibody from a yeast library, (b) culturing the yeast under conditions that the antibody is expressed, and (c) recovering the antibody from the culture. Also provided is a process for producing the antibody comprising (a) culturing a host cell under conditions that the antibody is expressed, (b) recovering the antibody from the culture, wherein the host cells are transformed or transfected for expressing the antibody against enterovirus 71. Also provided are pharmaceutical compositions comprising an antibody against enterovirus 71 and a pharmaceutically acceptable carrier or diluent, wherein the antibody has an anti-virus agent or detectable label attached thereto.