Modified Binding Molecules for Low-Background ADA Assays

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Solution Overview

Problem

Biologic therapies face challenges due to high background noise in anti-drug antibody (ADA) assays caused by pre-existing drug non-specific binding interactions in human serum or plasma samples, obscuring true treatment-emergent ADA detection.

Innovation Solution

Engineering binding molecules, such as monoclonal antibodies with specific C-terminal heavy chain sequences and antigen-binding portions, to minimize or mitigate pre-existing background reactivity, using assays with modified capture and detection agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If standard binding molecules are used in ADA assays, then the assay can detect antibodies, but high background noise from pre-existing drug non-specific binding interactions obscures true treatment-emergent ADA detection

Engineering Contradiction:

ImproveADA detection accuracyVSAvoidbackground noise

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes the C-terminal heavy chain sequence from the binding molecule to eliminate the source of pre-existing background reactivity. By using binding molecules lacking this specific sequence or containing modified sequences, the assay removes the harmful non-specific binding component while preserving the ability to detect true ADA

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies local quality by specifically modifying only the C-terminal heavy chain region of the binding molecule while leaving other functional regions intact. This localized modification targets the source of background noise without compromising the overall binding functionality needed for ADA detection

Inventive Principle:

Principle #3Local quality

2Object-affected harmful factors

If binding molecules with modified C-terminal heavy chain sequences are engineered, then background reactivity is reduced, but the molecular structure becomes more complex

Engineering Contradiction:

Improvebackground reactivityVSAvoidmolecular structure complexity

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent discards the problematic C-terminal heavy chain sequence from the binding molecule structure. By removing this specific segment that causes pre-existing reactivity, the molecule is simplified rather than complicated, as the discarded portion is the source of harm rather than a necessary functional element

Inventive Principle:

Principle #34Discarding and recovering

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

Reduces high background signal in ADA analysis, enhancing the signal-to-noise ratio and enabling effective detection of immunogenicity of biologic therapies.

Implementation Method 1

a binding molecule, comprising a C-terminal heavy chain sequence LSPG, or an antigen-binding portion thereof, wherein said binding molecule mitigates interaction with pre-existing serum proteins

Methodology Applied

Scientific EffectAntigen-antibody binding:

Data Source

PatentUS12523659B2Modifying binding molecules to minimize pre-existing interactions

Publication Date: 2026.01.13 REGENERON PHARMACEUTICALS INC

AI summary

The present disclosure is directed towards modifying binding molecules in order to minimize pre-existing binding interactions, including binding molecules engineered to minimize or mitigate background reactivity in a sample matrix caused by drug non-specific binding interactions.