Human Polyclonal Antibody Production Using Transchromosomal Ungulates
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Solution Overview
Problem
Current immunoglobulin products, such as human IVIG, monoclonal antibodies, and animal-derived pAbs, face limitations including high reactogenicity, reduced half-life and potency, and challenges in timely production during outbreaks, necessitating a rapid method for producing human polyclonal antibodies with high neutralizing activity and a safe profile.
Innovation Solution
A method involving injecting a non-human animal with a pathogen-derived DNA vaccine in multiple locations and an adjuvant at a different location, followed by plasma collection and purification to produce human polyclonal antibodies, using transchromosomal ungulates with human artificial chromosomes for enhanced antibody production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If animal-derived polyclonal antibodies are used to produce antibodies quickly, then productivity is improved, but reactogenicity increases causing severe allergic reactions
Solution Approach 1:
The patent segments the antibody production process by using transchromosomal animals that contain human artificial chromosomes with human immunoglobulin genes. This allows the animal's immune system to produce human antibodies rather than animal antibodies, eliminating reactogenicity while maintaining the rapid production capabilities of animal-derived polyclonal antibodies.
Solution Approach 2:
The transchromosomal animal serves as an intermediary system between human antibody production requirements and animal production capabilities. The animal contains human immunoglobulin genes integrated into its genome, enabling it to function as a living bioreactor that produces human antibodies rapidly while avoiding the harmful effects of animal-derived antibodies in human recipients.
2Manufacturing precision
If monoclonal antibodies are used to target specific epitopes, then manufacturing precision is improved, but adaptability decreases due to rapid mutational escape
Solution Approach 1:
The patent merges the advantages of monoclonal and polyclonal antibodies by producing a polyclonal antibody preparation where all antibodies are of the same human isotype and have standardized Fc regions (monoclonal-like uniformity), while maintaining diversity in antigen-binding regions targeting multiple epitopes (polyclonal-like breadth). This is achieved through immunizing transchromosomal animals with pathogen antigens, generating a repertoire of human antibodies that collectively target multiple epitopes while avoiding rapid mutational escape.
3Object-affected harmful factors
If human polyclonal antibodies are produced from convalescent donors, then safety is improved by avoiding reactogenicity, but productivity decreases due to requirement for large plasma volumes
Solution Approach 1:
The patent fundamentally changes the production parameter from human plasma collection to animal plasma collection. Transchromosomal animals can be immunized and produce large volumes of plasma containing human antibodies, eliminating the plasma volume limitation of human donors while maintaining the safety profile of human-derived antibodies through the transchromosomal system that produces only human immunoglobulins.
Data Source
AI summary
Disclosed herein is a method for producing human antibodies against a pathogen comprising injecting a non-human animal with a pathogen-derived DNA vaccine in at least two locations of the animal; injecting the animal with an adjuvant in a location of the animal different from the location of the DNA vaccine location; collecting plasma from the animal after the injections; and purifying polyclonal antibody from the plasma.