Phage Peptide Library Screening for Precise Antibody Detection

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Solution Overview

Problem

Traditional phage display systems lack sensitivity and accuracy in detecting antigenic variations of viral peptides, particularly in identifying autoantibody targets, due to skewed representation of differentially expressed cDNAs and low expression of clones in the correct reading frame.

Innovation Solution

A phage library is developed that uniformly expresses peptide libraries, such as the substantially complete human peptidome, combined with high-throughput DNA sequencing, allowing for precise and accurate detection of antiviral antibody responses and identification of cross-reactive autoimmune epitopes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional phage display systems are used to detect viral peptides, then the system can identify antibody targets, but the sensitivity and accuracy are insufficient due to skewed representation of differentially expressed cDNAs and low expression of clones in the correct reading frame

Engineering Contradiction:

Improvedetection sensitivity and accuracyVSAvoidrepresentation accuracy of cDNAs

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent changes the fundamental parameter of peptide expression by transitioning from cDNA-based phage display to a synthetic peptide library system. This eliminates the skewed representation inherent in cDNA libraries and ensures uniform expression of all peptides in the correct reading frame, thereby improving both detection sensitivity and reliability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent extracts the problematic cDNA library component from the detection system and replaces it with a synthetic peptide library. This removal eliminates the source of skewed representation and low expression rates, allowing for more reliable and sensitive antibody detection

Inventive Principle:

Principle #2Taking out (Extraction)

2Adaptability or versatility

If fragmented cDNA libraries are expressed in traditional phage display systems, then antibody targets can be identified, but the system suffers from highly skewed representation of differentially expressed cDNAs and only a small fraction of clones express coding sequences in the correct reading frame

Engineering Contradiction:

Improveability to identify antibody targetsVSAvoidexpression efficiency of correct reading frame clones

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent fundamentally changes the expression parameter by using synthetic peptides with optimized sequences rather than fragmented cDNAs. This ensures that all peptides are expressed in the correct reading frame with high efficiency, while maintaining the ability to identify antibody targets across diverse viral pathogens

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent segments the viral proteomes into comprehensive peptide libraries that cover all possible antibody targets. This segmentation approach, combined with synthetic expression, ensures complete coverage of antigenic epitopes while maintaining high expression efficiency for all clones

Inventive Principle:

Principle #1Segmentation

3Adaptability or versatility

If full-length folded proteins are used for antigen detection, then normally inaccessible epitopes can be targeted, but the detection sensitivity decreases compared to shorter peptides

Engineering Contradiction:

Improveability to target inaccessible epitopesVSAvoiddetection sensitivity

Core Design Contradiction:

Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent segments full-length proteins into comprehensive overlapping peptide libraries that collectively cover all epitopes including normally inaccessible regions. This segmentation maintains the ability to target all epitopes while using shorter peptide lengths that exhibit higher detection sensitivity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent adds the dimension of peptide length variation by incorporating peptides of different lengths (15-20 amino acids, 21-30 amino acids, and longer) into the library. This multi-dimensional approach ensures coverage of all epitope types while optimizing for the detection sensitivity characteristics of shorter peptides

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

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

Enables simultaneous detection of antiviral antibody responses to virtually all known human-infecting viruses, with improved speed and precision, facilitating diagnostic and clinical applications.

Implementation Method 1

contacting a reaction sample comprising a display library with a biological sample comprising antibodies, wherein the display library comprises a plurality of peptides derived from a plurality of pathogens

Methodology Applied

Scientific EffectPhage display:

Data Source

PatentUS12601088B2Detection of an antibody against a pathogen

Publication Date: 2026.04.14 THE BRIGHAM & WOMEN S HOSPITAL INC

AI summary

Provided herein are methods of detecting an antibody directed against a pathogen and uses thereof.