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Behind the paper · Antibody Therapeutics 2023

How fast can an antibody be re-engineered when the target keeps changing?

Fast enough to chase a moving target in real time. A 2023 Antibody Therapeutics paper documents a single parent clone re-matured in iterative rounds as new escape variants appeared, ending with a panel that neutralised the variants circulating at that time at picomolar affinity. The subject was SARS-CoV-2; the transferable result is the turnaround.
Entzminger KC, Fleming JK, Entzminger PD, Espinosa LY, Samadi A, Hiramoto Y, Okumura SCJ, Maruyama T. Rapid engineering of SARS-CoV-2 therapeutic antibodies to increase breadth of neutralization, including BQ.1.1, CA.3.1, CH.1.1, XBB.1.16, and XBB.1.5. Antib Ther. 2023;6(2):108–118.  PMID 37324547  ·  doi:10.1093/abt/tbad006
Read this as a speed and adaptability result, not a current product claim. The variants named in the paper were those circulating in early 2023. SARS-CoV-2 has continued to evolve since, and we make no claim that these antibodies neutralise variants circulating today. What the paper establishes is the engineering capability and the cycle time.

The problem the paper set out to solve

An antibody against a fast-evolving target has a shelf life. Escape variants appear, neutralisation drops, and the molecule that took two years to develop is obsolete. The conventional response — start a new discovery campaign — is too slow to keep up.

The alternative tested here was to treat the original clone as a starting point rather than a finished product, and to re-mature it repeatedly as the target moved. Engineering was performed in iterative stages, in real time, as variants emerged.

What was done and what came out

  • Started from one parent clone that neutralised the original Wuhan-Hu-1 strain.
  • Re-matured in successive rounds using in vitro affinity maturation by phage display — the same STage-Enhanced Maturation (STEM™) approach used in our commercial affinity work.
  • Produced a panel that neutralised the Omicron-lineage variants circulating in early 2023, confirmed by surrogate virus neutralisation test.
  • Reached picomolar affinity against all variants tested in that panel.

The authors describe the work as validating “a unique general strategy” rather than a single molecule — which is the honest framing. The molecules are dated. The method is not.

Why this transfers beyond one virus

Any programme where the antigen changes under you has the same shape of problem. Viral escape is the obvious case, but so are tumour antigen heterogeneity, cross-species reactivity where the orthologue differs, resistance-driven sequence drift, and any situation where a lead works on one variant of a target and not the next.

In all of those, the useful question is not “can you make an antibody” but “how quickly can you make the next one from the one we already have, without starting over and without losing what already worked”. That is what this paper measures.

Two features of the approach do the work. Iterative rather than single-shot maturation means each round starts from the current best molecule instead of the original. And selection against multiple antigen variants in the same campaign produces breadth deliberately, rather than hoping a clone raised on one variant happens to cover others.

One further note on authorship: unlike most papers in this series, this one has no academic co-authors. It is entirely Abwiz Bio work.

Have a lead that stopped covering your target?

Escape variants, a new orthologue, a resistant subpopulation — tell us what the antibody used to bind and what it needs to bind now. A PhD scientist reads it and replies within two business days. No NDA needed to start.

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Frequently asked questions

Do these antibodies neutralise variants circulating now?

We do not claim that. The panel was characterised against variants circulating in early 2023 and the virus has continued to evolve. The paper is evidence of engineering speed and of a repeatable method, not a current-coverage claim.

Can you broaden an antibody we already own?

That is exactly the pattern here — one parent clone, re-matured against additional variants. It works when the variants share enough of the epitope for a common solution to exist. Send the sequence and the variant set and we will give you a view before you commit.

How is iterative maturation different from one round of affinity maturation?

Each round starts from the current best molecule rather than the original parent, so improvements compound instead of competing. It also lets the selection pressure change between rounds, which is how breadth is built deliberately rather than hoped for.

Is this only for viral targets?

No. The same approach applies wherever a lead must cover several related sequences — cross-species reactivity, tumour antigen variants, or a resistant subpopulation.

Who owns the engineered antibodies?

In commercial engagements the sponsor does, sequences included, with no downstream royalties in standard scope.

Want this run on your target?

Re-maturing a lead as the target moves is a campaign, not a one-off. These are the services that run it.

Every campaign is scoped individually and quoted. Email info@abwizbio.com with your target or lead sequence, or see all 25 publications and the full service menu.

Abwiz Bio Inc. · 9823 Pacific Heights Blvd, Suite J, San Diego, CA 92121, USA · info@abwizbio.com · +1 858-352-6911