Human Monoclonal Antibody Production via EBV Immortalization

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Solution Overview

Problem

The development of human monoclonal antibodies for therapeutic and diagnostic purposes is hindered by the need to 'humanize' antibodies produced in mice, rats, and rabbits, which can cause serum sickness in humans and is time- and expense-intensive, limiting their application.

Innovation Solution

A method involving the immortalization of human B-cells using Epstein-Barr virus (EBV) and cytokine/growth factor cocktails to induce IgM-to-IgG isotype class-switching, allowing for the production of human monoclonal antibodies specific to predetermined antigens, including infectious agents and cancer-related molecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If monoclonal antibodies are produced in mice, rats, and rabbits, then antibody production capability is achieved, but serum sickness occurs in human patients and humanization is required

Engineering Contradiction:

Improvetherapeutic safetyVSAvoidhumanization process complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

Instead of producing antibodies in non-human animals and then humanizing them, the invention inverts the approach by directly producing human monoclonal antibodies in human B-cells through EBV immortalization and cytokine-induced class switching, eliminating the need for humanization processes

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The invention creates a human B-cell system that copies the natural antibody production mechanism, using EBV-transformed human B-cells that can be stimulated to produce human monoclonal antibodies through class switching, rather than relying on non-human animal systems

Inventive Principle:

Principle #26Copying

2Reliability

If humanization of antibodies is performed, then serum sickness is avoided, but time and expense increase significantly

Engineering Contradiction:

Improvetherapeutic safetyVSAvoiddevelopment time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The invention performs preliminary action by directly establishing human B-cell lines capable of producing human antibodies from the outset, rather than performing humanization as a subsequent step after antibody production in non-human animals

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention inverts the conventional sequence by producing human antibodies directly in human cells through EBV immortalization and cytokine treatment, eliminating the time-consuming humanization process entirely

Inventive Principle:

Principle #13The other way round (Inversion)

3Reliability

If humanization of antibodies is performed, then serum sickness is avoided, but development cost increases

Engineering Contradiction:

Improvetherapeutic safetyVSAvoidmanufacturing cost

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The invention copies the human antibody production system using EBV-immortalized human B-cells that can be stimulated to undergo class switching and produce human monoclonal antibodies, replacing the expensive humanization process

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The invention uses transient cytokine treatments and EBV immortalization to create human antibody-producing cell lines without requiring expensive and complex humanization procedures, achieving cost-effective production

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Data Source

PatentUS8715743B2Human monoclonal antibodies and methods for producing the same

Publication Date: 2014.05.06 MUSC FOUNDATION FOR RESEARCH DEVELOPMENT(US)

AI summary

The present invention provides for methods of producing human monoclonal antibodies against a wide variety of antigens including bacterial and viral antigens, as well as tumor antigens, and various autoantigens. Also provided are the antibodies themselves, nucleic acids encoding such antibodies, cells producing such antibodies, and methods of using such antibodies for diagnostic assays and passive immunity against disease states such as infection and cancer.