Modified Fc Domain Binding Agents for Coronavirus Treatment
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Solution Overview
Problem
Current therapies for coronavirus infections, including SARS-CoV-2, lack effectiveness in treating and preventing the infection, with existing anti-viral drugs showing insufficient evidence for efficient treatment and a need for improved therapies to address inflammation and immune response.
Innovation Solution
Development of binding agents comprising a binding domain that targets viral proteins and a modified Fc domain with reduced pro-inflammatory activity, specifically designed to neutralize viruses and modulate immune complex function by reducing binding to activating receptors and increasing binding to inhibitory receptors, thereby reducing inflammation and enhancing anti-inflammatory immune complex formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a wild-type Fc domain is used in binding agents, then the binding agent can effectively neutralize the virus, but the binding agent exhibits high pro-inflammatory activity due to strong binding to activating Fc receptors
Solution Approach 1:
The patent modifies the Fc domain by changing amino acid parameters at specific positions (e.g., position 234 from Leu to Ala, position 235 from Leu to Ala) to alter its binding characteristics. This parameter change reduces binding affinity to activating Fc receptors (FcγRI, FcγRIIa, FcγRIII) while maintaining virus neutralization capability, thereby reducing pro-inflammatory activity.
Solution Approach 2:
The patent applies local modification to the Fc domain region, specifically targeting the Fc portion of the antibody while maintaining the binding domain's integrity. By locally modifying the Fc domain's amino acid sequence at specific positions, the patent achieves reduced pro-inflammatory activity without compromising the overall virus neutralization function.
2Reliability
If a wild-type Fc domain is used in binding agents, then the binding agent can neutralize the virus, but the binding agent binds strongly to activating Fc receptors leading to enhanced inflammation
Solution Approach 1:
The patent changes the amino acid parameters at specific positions in the Fc domain (e.g., Leu234Ala, Leu235Ala) to reduce binding affinity to activating Fc receptors. This parameter modification decreases the binding agent's ability to activate inflammatory pathways while preserving its virus neutralization function.
3Productivity
If existing anti-viral drugs are used for coronavirus infection, then treatment can be attempted, but the drugs show insufficient evidence for efficient treatment
Solution Approach 1:
The patent extracts and modifies the Fc domain component of binding agents to create a therapeutic with optimized properties. By separating and modifying the Fc domain independently from the binding domain, the patent creates a binding agent that combines effective virus neutralization with reduced pro-inflammatory activity, addressing the limitations of existing anti-viral drugs.
Data Source
AI summary
Provided herein are methods of treating a virus infection, such as a coronavirus infection, by delivering to a subject in need a binding agent, wherein the binding agent comprising (i) at least one binding domain that binds to a viral protein expressed on the surface of a virus, and (ii) a modified Fc domain that exhibits either (a) reduced binding to an Fc activating receptor or (b) increased binding to an Fc inhibitory receptor compared to a wild-type Fc domain. The binding agent may be delivered as a polynucleotide (e.g. mRNA) or as a protein, and may be contained in a vehicle for delivery, such as a viral or non-viral vector. The present disclosure also relates to the polynucleotides, proteins, and vehicles (e.g. viral and non-viral vector) and composition thereof, including for use in the methods.