Evidence map›Paper›PMID 23924797›Full record

ArticlemAbs

Improving biophysical properties of a bispecific antibody scaffold to aid developability: quality by molecular design.

Thomas Spreter Von Kreudenstein, Eric Escobar-Carbrera, Paula I Lario, Igor D'Angelo, Karine Brault, John Kelly, Yves Durocher, Jason Baardsnes, R Jeremy Woods, Michael Hongwei Xie and 6 more

Abstract read
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

77 citing papers in PubMed.

  1. Review
  2. Targeted extracellular degradation of LRP8 promotes ferroptosis in cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Engineered protein G variants for multifunctional antibody-based assemblies.Protein science : a publication of the Protein Society · 2025
    Article
  14. Article
  15. Article
  16. Bispecific antibody drug conjugates: Making 1+1>2.Acta pharmaceutica Sinica. B · 2024
    Review
  17. Article
  18. Article
  19. Review
  20. Review

17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Thomas Spreter Von KreudensteinZymeworks Inc.; Vancouver, BC Canada.
Eric Escobar-Carbrera
Paula I Lario
Igor D'Angelo
Karine Brault
John Kelly
Yves Durocher
Jason Baardsnes
R Jeremy Woods
Michael Hongwei Xie
Pierre-Alain Girod
Michael D L Suits
Martin J Boulanger
David K Y Poon
Gordon Y K Ng
Surjit B Dixit

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

While the concept of Quality-by-Design is addressed at the upstream and downstream process development stages, we questioned whether there are advantages to addressing the issues of biologics quality early in the design of the molecule based on fundamental biophysical characterization, and thereby reduce complexities in the product development stages. Although limited number of bispecific therapeutics are in clinic, these developments have been plagued with difficulty in producing materials of sufficient quality and quantity for both preclinical and clinical studies. The engineered heterodimeric Fc is an industry-wide favorite scaffold for the design of bispecific protein therapeutics because of its structural, and potentially pharmacokinetic, similarity to the natural antibody. Development of molecules based on this concept, however, is challenged by the presence of potential homodimer contamination and stability loss relative to the natural Fc. We engineered a heterodimeric Fc with high heterodimeric specificity that also retains natural Fc-like biophysical properties, and demonstrate here that use of engineered Fc domains that mirror the natural system translates into an efficient and robust upstream stable cell line selection process as a first step toward a more developable therapeutic.

Indexed as

AnimalsAntibodiesAntibodies, BispecificAntibody SpecificityCHO CellsChromatography, LiquidCricetinaeCricetulusDrug DesignHumansHydrogen-Ion ConcentrationHydrophobic and Hydrophilic InteractionsImmunoglobulin Fc FragmentsMass SpectrometryModels, MolecularMutationAntibodiesAntibodies, BispecificImmunoglobulin Fc Fragmentsantibody engineeringantibody stabilitybiophysical characterization of antibodybispecific antibodyFc engineeringheterodimeric antibodyLC-MS of antibodyquality by design

Identifiers

PMID23924797
PMCPMC3851217

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.