H1N1 HA Polypeptide Variants for Influenza Diagnostics and Therapeutics

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Solution Overview

Problem

The rapid outbreak of the 2009 H1N1 influenza virus posed uncertainties regarding its virulence, transmissibility, and origins, with a higher percentage of infected individuals experiencing gastrointestinal distress and vomiting, necessitating effective treatments, prevention methods, and diagnostic tools to address its unique characteristics.

Innovation Solution

Development of compositions and methods utilizing H1N1 HA variants with enhanced human binding and infectivity for vaccine development, therapeutic applications, and diagnostic systems, including agents that bind specifically to H1N1 HA polypeptides and interfere with binding interactions with glycans, particularly umbrella-topology glycans, to detect and prevent infection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If H1N1 HA variants with enhanced human binding and infectivity are used for vaccine development, then vaccine effectiveness against enhanced variants is improved, but the complexity of identifying and characterizing these variants increases

Engineering Contradiction:
Improvevaccine effectivenessVSAvoidvariant characterization complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs parameter changes by modifying amino acid sequences at specific positions (190, 225, 226) in the HA polypeptide to create variants with enhanced human binding and infectivity. These parameter changes allow systematic exploration of variant characteristics and their impact on vaccine effectiveness.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates copies of the H1N1 HA polypeptide with specific amino acid modifications to generate variants that mimic enhanced human binding properties. These copied and modified variants serve as models for vaccine development and diagnostic standardization.

Inventive Principle:
Principle #26Copying

2Measurement precision

If specific binding agents for H1N1 HA polypeptides are developed for detection, then diagnostic precision is improved, but the difficulty of detecting and measuring variant specificity increases

Engineering Contradiction:
Improveinfection detection precisionVSAvoidvariant specificity detection difficulty
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent introduces specific binding agents as intermediaries that recognize and bind to H1N1 HA polypeptides and their variants. These binding agents serve as mediators between the viral variants and detection systems, enabling precise identification of enhanced human binding variants through their specific binding characteristics.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If agents that interfere with HA-glycan binding interactions are developed, then therapeutic effectiveness is improved, but the complexity of interfering with specific binding interactions increases

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidbinding interference complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent converts the harmful binding interaction between HA polypeptide and glycans into a beneficial therapeutic mechanism by developing agents that specifically interfere with this binding. The interference agents block the viral attachment mechanism, turning the understanding of the binding mechanism into a therapeutic advantage.

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

Solution Approach 2:

The patent employs parameter changes by modifying the binding characteristics of HA polypeptide variants at specific amino acid positions to create enhanced human binding variants, which then serve as targets for therapeutic agents designed to interfere with these specific binding parameters.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS9709567B2Compositions and methods for diagnosing and/or treating influenza infection
Publication Date: 2017.07.18 MASSACHUSETTS INST OF TECH
  • US9709567B2 patent drawing
  • US9709567B2 patent drawing
  • US9709567B2 patent drawing

AI summary

The present invention provides HA polypeptides (e.g., H1 HA polypeptides) that bind to umbrella-topology glycans, and reagents and methods relating thereto. The present invention provides binding agents that bind to HA polypeptides (e.g., H1 HA polypeptides), and reagents and methods relating thereto. The present invention provides interfering agents that inhibit the binding of HA polypeptides (e.g., H1 HA polypeptides) to HA receptors, and reagents and methods relating thereto. The present invention provides compositions and methods for treating, preventing, and/or diagnosing influenza infection utilizing HA polypeptides, HA polypeptide binding agents, HA polypeptide interfering agents, and/or vaccine compositions comprising any of the foregoing.