Infold Polypeptide Agents for Broad-Spectrum Influenza Neutralization
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Solution Overview
Problem
Current influenza vaccines and therapeutics are limited by their specificity to seasonal strains, and the rapid mutation of influenza viruses, such as H1N1 and H5N1, leads to emerging drug resistance and reduced effectiveness, necessitating the development of broad-spectrum anti-influenza agents that can neutralize multiple strains independently of subtype or clade.
Innovation Solution
The development of polypeptide agents, termed 'infold agents,' which bind to specific regions of the hemagglutinin (HA) polypeptide, including the membrane proximal epitope region (MPER), and HA receptors, particularly sialylated glycans, with high affinity and specificity, competing with HA for receptor binding to inhibit viral infection across various strains.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If seasonal flu vaccines target specific viral strains, then vaccine effectiveness against predicted strains is improved, but the vaccine becomes ineffective against mutated or unexpected strains
Solution Approach 1:
The patent applies universality by designing infold agents that can bind to multiple influenza virus strains simultaneously. The engineered polypeptides are configured to recognize conserved epitopes across different flu strains, enabling a single agent to provide broad-spectrum protection against seasonal and pandemic strains alike, thereby resolving the contradiction between targeting specificity and strain coverage
2Reliability
If antiviral drugs like Tamiflu are used to treat influenza, then treatment effectiveness against sensitive strains is improved, but drug resistance emerges reducing effectiveness
Solution Approach 1:
The patent applies copying by creating engineered polypeptide agents that mimic the binding function of natural antibodies. These infold agents are designed to replicate the protective function of immune responses without being subject to the same resistance mechanisms that affect antiviral drugs, providing an alternative therapeutic approach that bypasses drug resistance issues
3Adaptability or versatility
If infold agents bind to multiple targets including HA polypeptide and receptors, then broad-spectrum neutralization is achieved, but agent complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the influenza virus into distinct target components: the HA polypeptide and the HA receptors. The infold agents are designed to bind to specific segments (epitopes) on these targets, allowing modular recognition of multiple viral components. This segmented approach enables broad-spectrum neutralization through coordinated binding to different viral elements without requiring the agent itself to be overly complex
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
Infold agents effectively neutralize influenza viruses by binding to HA polypeptides and receptors, demonstrating broad-spectrum efficacy across different strains, including those resistant to traditional antivirals, and delaying the onset of disease, as shown in in vitro and in vivo studies.
Implementation Method 1
Infold agents bind to the MPER region independent of HA glycosylation
Implementation Method 2
Infold agents interact with one or more amino acid residues in the HA polypeptide, and/or with one or more glycans bound to the HA polypeptide
Implementation Method 3
Infold agents bind sialylated glycans on HA receptors. Infold agents bind with high affinity and/or specificity to umbrella-topology glycans
Implementation Method 4
Infold agents compete with hemagglutinin for binding to an HA receptor
Data Source
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AI summary
The present invention provides novel agents for broad spectrum influenza neutralization. The present invention provides agents for inhibiting influenza infection by bind to the influenza virus and/or hemagglutinin (HA) polypeptides and/or HA receptors, and reagents and methods relating thereto. The present invention provides a system for analyzing interactions between infolds and the interaction partners that bind to them.