Anti-SARS-CoV-2 NTD Antibodies for Broad Variant Neutralization

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

The emergence of SARS-COV-2 variants of concern has led to increased transmissibility and reduced efficacy of existing therapeutics and vaccines due to mutations on the spike protein, necessitating the development of broadly neutralizing anti-SARS-COV-2 antibodies.

Innovation Solution

Development of anti-SARS-COV-2 antibodies or antigen-binding fragments that target specific epitopes on the spike protein, including the N-terminal domain and supersite b-hairpin, β8-strand, N4-loop, and N-linked glycans, with variable regions exhibiting at least 75% identity to specific sequences, capable of neutralizing multiple SARS-COV-2 strains.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing therapeutics and vaccines target the spike protein of SARS-COV-2, then they provide treatment and prevention capability, but variants of concern with mutations on the spike protein reduce their efficacy

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidvariant coverage
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent develops antibodies that target multiple epitopes on the spike protein (including the N-terminal domain and supersite b-hairpin), enabling a single therapeutic agent to neutralize multiple SARS-COV-2 variants of concern simultaneously, thus achieving universal protection against diverse viral strains

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention focuses on targeting specific conserved regions of the spike protein (such as the N-terminal domain and supersite b-hairpin) that remain relatively unchanged across variants, rather than targeting variable regions. This localized targeting approach ensures maintained efficacy against emerging variants while preserving the antibody's neutralizing function

Inventive Principle:
Principle #3Local quality

2Reliability

If antibodies target specific epitopes on the spike protein to achieve broad neutralization, then neutralization capability improves, but antibody design and production complexity increases

Engineering Contradiction:
Improveneutralization capabilityVSAvoidantibody structure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent identifies and targets distinct epitopic segments on the spike protein (N-terminal domain, supersite b-hairpin, β8-strand, N4-loop) separately, designing antibodies that bind to these discrete regions. This segmentation allows for modular antibody design where each antibody targets a specific epitope, simplifying the overall design process while achieving broad neutralization through combinatorial effects

Inventive Principle:
Principle #1Segmentation

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

The antibodies demonstrate broad neutralization capability against various SARS-COV-2 strains, including variants of concern, and can be used for treatment and prevention of infection, with applications in diagnostic assays and therapeutic compositions.

Implementation Method 1

anti-SARS-COV-2 antibodies or antigen-binding fragments that bind specifically to a SARS-COV-2 antigen... binds specifically to a SARS-COV-2 antigen... targeting the n-terminal domain of the spike protein

Methodology Applied
Scientific EffectAntigen-antibody binding:

Implementation Method 2

capable of neutralizing a plurality of SARS-COV-2 strains... broadly neutralizing anti-SARS-COV-2 antibodies for treating or preventing SARS-COV-2 infection

Methodology Applied
Scientific EffectViral neutralization:

Data Source

PatentUS20250333485A1Broadly neutralizing Anti-SARS-COV-2 antibodies targeting the n-terminal domain of the spike protein and methods of use thereof
Publication Date: 2025.10.30 THE ROCKEFELLER UNIV
  • US20250333485A1 patent drawing
  • US20250333485A1 patent drawing
  • US20250333485A1 patent drawing

AI summary

This disclosure provides anti-SARS-COV-2 antibodies or antigen-binding fragments thereof targeting the N-terminal domain (NTD) of the spike(S) protein. The disclosed anti-SARS-COV-2 antibodies or antigen-binding fragments thereof have broadly neutralizing activities against several SARS-COV-2 variants of concern. The disclosed anti-SARS-COV-2 antibodies represent a therapeutic strategy in protecting from SARS-COV-2 infections.