Hapten Polymerization for Antibody Production

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Solution Overview

Problem

Current methods for producing anti-hapten antibodies are inefficient due to the need for carrier proteins and complex chemical modifications, resulting in low hapten density and costly purification processes.

Innovation Solution

Direct polymerization of small, non-immunogenic haptens into immunogenic antigens using cross-linking reagents like dialdehyde, polyaldehyde, or 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide, achieving molecular weights greater than 4,000 Da, eliminating the need for carrier proteins and simplifying the process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If haptens are conjugated onto carrier proteins to elicit antibody production, then antibody production is stimulated, but the procedure becomes complex requiring appropriate carriers and chemical cross-linkers

Engineering Contradiction:
Improveantibody productionVSAvoidprocedure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention extracts and eliminates the carrier protein component from the traditional hapten-carrier conjugate system. By directly polymerizing haptens into immunogenic polymers without carriers, the procedure complexity is reduced while maintaining the ability to stimulate antibody production.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention merges the hapten molecules directly into polymer structures through cross-linking reactions. This combines the antigenic function of haptens with the immunogenic properties of polymers in a single integrated system, eliminating the need for separate carrier proteins.

Inventive Principle:
Principle #5Merging (Combining)

2Reliability

If haptens are conjugated onto carrier proteins, then antibody production is stimulated, but well-trained laboratory personnel are required for intricate chemical modifications

Engineering Contradiction:
Improveantibody productionVSAvoidoperation difficulty
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The polymerization process uses cross-linking reagents that automatically form covalent bonds between hapten molecules under controlled conditions. The system self-assembles into immunogenic polymers without requiring manual intervention for complex chemical modifications, making the procedure easier to perform.

Inventive Principle:
Principle #25Self-service

3Reliability

If haptens are conjugated onto carrier proteins, then antibody production is stimulated, but the proportion of anti-hapten antibodies to anti-carrier antibodies is too small to be effective

Engineering Contradiction:
Improveantibody productionVSAvoidanti-hapten antibody proportion
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The invention removes the carrier protein from the conjugate system, thereby eliminating the source of anti-carrier antibodies. This ensures that the immune response is directed exclusively against the hapten molecules, maximizing the proportion of anti-hapten antibodies in the serum.

Inventive Principle:
Principle #2Taking out (Extraction)

4Reliability

If haptens are conjugated onto carrier proteins, then antibody production is stimulated, but purification of anti-hapten antibodies becomes difficult and costly

Engineering Contradiction:
Improveantibody productionVSAvoidpurification ease
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

By eliminating the carrier protein component, the invention removes the need for complex purification steps required to separate anti-hapten antibodies from anti-carrier antibodies. The polymer-based immunogen system allows for simpler purification protocols, reducing both difficulty and cost.

Inventive Principle:
Principle #2Taking out (Extraction)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This method effectively stimulates the immune system to produce anti-hapten antibodies, with a detection limit as low as 1.8 ppb, simplifying the production and purification of anti-hapten antibodies.

Implementation Method 1

adding a cross-linking reagent into the hapten-containing solution to polymerize the haptens to obtain an immunogen with molecular weight greater than 4,000 Da

Methodology Applied
Scientific EffectChemical Bonding: Chemical Bonding

Implementation Method 2

the amine group and the carboxylic group are cross-linked to each other through a dehydration reaction

Methodology Applied
Scientific EffectDehydration reaction: Hydrolysis

Data Source

PatentUS8829150B2Methods for polymering haptens into immunogens
Publication Date: 2014.09.09 NATIONAL TAIWAN NORMAL UNIVERSITY
  • US8829150B2 patent drawing
  • US8829150B2 patent drawing
  • US8829150B2 patent drawing

AI summary

The present invention discloses methods for polymerizing non-immunogenic haptens into immunogens, which then can be used to stimulate anti-hapten antibody production in animals. Specifically, haptens with amine and/or carboxylic groups are polymerized into macromolecules by using cross-linking reagents, and the derived haptenic polymers are used to immunize animals for the production of anti-hapten antibodies.