Humanized Orthopoxvirus Antibody Compositions for Passive Immunity
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Solution Overview
Problem
Current treatments and vaccines for orthopoxvirus infections, such as vaccinia virus, monkeypox virus, and variola virus, are limited in their effectiveness and can cause adverse events like progressive vaccinia and eczema vaccinatum, necessitating improved methods for passive immunity and treatment.
Innovation Solution
Development of humanized antibodies that bind to specific epitopes on intracellular mature and extracellular enveloped virion forms of orthopoxviruses, combined in compositions to provide comprehensive passive immunity against orthopoxvirus infections, including adverse events from smallpox vaccines.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments and vaccines for orthopoxvirus infections are used, then immunity is provided, but adverse events like progressive vaccinia and eczema vaccinatum occur
Solution Approach 1:
The patent applies parameter changes by humanizing the antibody structure (changing from murine to human sequences) and modifying the Fc region to alter immunogenicity and effector function parameters, thereby reducing adverse events while maintaining protective immunity
Solution Approach 2:
The patent creates a humanized copy of the murine antibody 7D11, preserving the antigen-binding capability while replacing the immunogenic murine framework with human sequences, thus maintaining effectiveness while reducing harmful immune responses
2Object-affected harmful factors
If humanized antibodies are developed to reduce immunogenicity, then adverse events are reduced, but serum half-life may be shortened
Solution Approach 1:
The patent modifies the Fc region parameters (isotype, glycosylation, amino acid substitutions) to extend serum half-life while maintaining the humanized structure that reduces immunogenicity
Solution Approach 2:
The patent creates a composite antibody structure combining humanized variable regions with modified Fc regions, integrating the benefits of reduced immunogenicity with extended half-life properties
3Adaptability or versatility
If antibodies bind to multiple epitopes on virion forms, then comprehensive protection is provided, but antibody complexity increases
Solution Approach 1:
The patent designs antibodies with broad reactivity against multiple orthopoxvirus species and forms (IMV and EEV) through conserved epitope targeting, achieving universal protection without requiring separate antibodies for each virus type
Solution Approach 2:
The patent segments the protection strategy into two complementary antibodies (7D11 for IMV, 8A for EEV) that together provide comprehensive coverage, dividing the complex task into manageable functional units
Data Source
AI summary
Provided herein are antibodies and functional fragments thereof for treating or preventing viral diseases, for example pox viral diseases, for example smallpox and monkey pox. Any antibody or functional fragment thereof described herein can be an engineered antibody or engineered antibody fragment. Also, provided herein are compositions and pharmaceutical compositions containing one or more antibodies or functional fragments thereof. Further provided herein are kits containing one or more antibodies or functional fragments thereof, and methods, dosing schedules, dosage amounts, and routes of administration of antibodie(s) and functional fragment(s) thereof. Finally are provided methods of making antibodies and functional fragments thereof.