Broadly Neutralizing Antibodies Targeting the S2 Stem Helix

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Solution Overview

Problem

Existing vaccines and antibodies targeting the receptor binding domain (RBD) of the spike protein are susceptible to mutations in SARS-CoV-2 variants and other betacoronaviruses, leading to neutralization escape and a need for antibodies that target more conserved regions of the spike protein to provide broad neutralization against various coronavirus variants.

Innovation Solution

Development of antibodies or antigen-binding fragments that specifically bind to the S2 stem helix of betacoronaviruses, utilizing heavy and light chain CDR sequences as exemplified in the patent, which are designed to neutralize a wide range of coronavirus variants, including SARS-CoV-2 and other betacoronaviruses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibodies target the RBD of the spike protein, then neutralization potency is improved, but susceptibility to viral mutations and neutralization escape increases

Engineering Contradiction:

Improveneutralization potencyVSAvoidresistance to viral variants

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The antibody target site is segmented from the variable RBD region to the more conserved S2 stem helix region, separating the targeting function from the mutable RBD while maintaining neutralization capability through alternative epitope recognition

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Instead of targeting the immunodominant but mutable RBD region, the invention inverts the approach by targeting the S2 stem helix region which is less immunogenic but more conserved across variants, thereby achieving broad neutralization despite viral mutations

Inventive Principle:

Principle #13The other way round (Inversion)

2Adaptability or versatility

If antibodies target conserved regions of the spike protein, then breadth of neutralization is improved, but neutralization potency against specific variants may be reduced

Engineering Contradiction:

Improvebreadth of neutralizationVSAvoidneutralization potency

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The invention merges targeting of highly conserved epitopes on the S2 stem helix with engineered high-affinity binding, combining the advantages of broad coverage from conserved region targeting with potent neutralization through optimized antibody affinity and avidity effects

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS20260035438A1Human broadly neutralizing antibodies against betacoronaviruses

Publication Date: 2026.02.05 THE SCRIPPS RES INST

AI summary

The invention provides novel broadly neutralizing antibodies and related antibody compositions against betacoronaviruses, e.g., SARS-CoV-2. Also provided in the invention are polynucleotides and vectors encoding such antibodies, as well as pharmaceutical compositions containing the antibodies or polynucleotides. Therapeutic uses of the antibodies or pharmaceutical compositions in preventing or treating betacoronaviral infections (e.g., SARS-CoV-2 infection) are also encompassed by the invention.