Fully Human Monoclonal Antibodies via Antigen-Specific B Cell Co-Culture

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Solution Overview

Problem

Existing methods for producing monoclonal antibodies, such as those using bacteriophages, transgenic animals, or B cell transformation, face inefficiencies, low yield, and immunogenicity issues, and the use of CpG or ssRNA for activation can lead to unwanted antibody production and lower affinity.

Innovation Solution

A process mimicking in vivo mechanisms to produce fully human monoclonal antibodies by isolating peripheral blood mononuclear cells, generating dendritic and CD4+/CD19+ cells, co-culturing them with antigens, and inducing plasma cell formation and IgG class switching, using cytokine cocktails to simulate an inflammatory environment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If CpG or ssRNA is used for cell activation to mount a pronounced immune response, then antibody production is enhanced, but unwanted antibodies against CpG/ODNs/ssRNAs are produced and affinity is reduced

Engineering Contradiction:

Improveantibody productionVSAvoidantibody affinity and purity

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent extracts and removes the problematic CpG/ODN/ssRNA adjuvants from the activation process, replacing them with antigen-specific activation methods that do not induce unwanted antibody production while maintaining desired antibody affinity and purity

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces dendritic cells as intermediary antigen-presenting cells that mediate specific activation of B cells through antigen recognition, replacing the direct but problematic activation by CpG/ODN/ssRNA with a more controlled and specific activation pathway

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If transgenic animals are used to produce human antibodies, then human antibody sequences are obtained, but limited germline repertoire, low protein expression, and residual immunogenicity remain

Engineering Contradiction:

Improvehuman antibody sequence diversityVSAvoidprotein expression and immunogenicity

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent employs human B cells that naturally produce human antibodies through their own germline repertoire, eliminating the need for transgenic animal systems and avoiding associated limitations in diversity, expression levels, and immunogenicity

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

Instead of inserting human antibody genes into animal genomes (transgenic approach), the patent inverts the approach by directly using human B cells that already possess the full human antibody repertoire, thereby obtaining authentic human antibodies without transgenic manipulation

Inventive Principle:

Principle #13The other way round (Inversion)

3Productivity

If B cells are transformed by Epstein-Barr virus to produce monoclonal antibodies, then antibody production is achieved, but transformation efficiency is low and yield is reduced

Engineering Contradiction:

Improvemonoclonal antibody yieldVSAvoidtransformation efficiency

Core Design Contradiction:

ProductivityVSEase of manufacture

Solution Approach 1:

The patent extracts and eliminates the Epstein-Barr virus transformation step from the monoclonal antibody production process, replacing it with alternative methods such as hybridoma technology or direct cloning that achieve higher transformation efficiency and antibody yield without viral manipulation

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs temporary or transient expression systems and short-term cell culture approaches that do not require permanent viral transformation, thereby simplifying the manufacturing process and improving efficiency while maintaining monoclonal antibody production

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

4Adaptability or versatility

If phage display technology is used for antibody library selection, then monoclonal antibody clones can be selected, but the process is complicated, time-consuming, and may not recover all antigen-specific mAbs

Engineering Contradiction:

Improveantibody library coverageVSAvoidselection process duration

Core Design Contradiction:

Adaptability or versatilityVSLoss of time

Solution Approach 1:

The patent replaces the complex mechanical and procedural steps of phage display (library preparation, ligation, in vitro selection) with more streamlined methods such as direct B cell sorting by flow cytometry or recombinant DNA cloning, thereby reducing time loss and improving recovery of all antigen-specific monoclonal antibodies

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS12600786B2C-met and TMX2 antibodies

Publication Date: 2026.04.14 R G C C HLDG AG

AI summary

The present invention provides: a novel method for the production of truly fully human monoclonal antibodies against specific antigens of our choice using isolated human blood cells. These antigens may include but are not limited to peptide sequences found in c-met and TMX2 proteins; an antibody specific for c-met protein produced with said method; an antibody specific for TMX2 protein produced with said method; and a new means and method for the diagnosis, prevention and/or cancer treatment by means of the aforementioned antibodies.