Evidence map›Paper›PMID 24463572›Full record

ArticleNature biotechnology2014

Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface.

Steven M Lewis, Xiufeng Wu, Anna Pustilnik, Arlene Sereno, Flora Huang, Heather L Rick, Gurkan Guntas, Andrew Leaver-Fay, Eric M Smith, Carolyn Ho and 7 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biotechnology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
161citing papers in PubMed, 1 pooled it
–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

161 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Generation of Bispecific Antibodies Using FAST-Ig™.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
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  16. T-Cell Engagers In Multiple Myeloma: A Clinical Review.Blood and lymphatic cancer : targets and therapy · 2025
    Review
  17. Review
  18. Review
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Steven M Lewis1] Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [2].
Xiufeng Wu1] Eli Lilly Biotechnology Center, San Diego, California, USA. [2].
Anna PustilnikEli Lilly Biotechnology Center, San Diego, California, USA.
Arlene SerenoEli Lilly Biotechnology Center, San Diego, California, USA.
Flora HuangEli Lilly Biotechnology Center, San Diego, California, USA.
Heather L RickDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Gurkan GuntasDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Andrew Leaver-FayDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Eric M SmithEli Lilly Biotechnology Center, San Diego, California, USA.
Carolyn HoEli Lilly Biotechnology Center, San Diego, California, USA.
Christophe Hansen-EstruchEli Lilly Biotechnology Center, San Diego, California, USA.
Aaron K ChamberlainEli Lilly Biotechnology Center, San Diego, California, USA.
Stephanie M TruhlarEli Lilly Biotechnology Center, San Diego, California, USA.
Elaine M ConnerDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Shane AtwellEli Lilly Biotechnology Center, San Diego, California, USA.
Brian Kuhlman1] Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Stephen J DemarestEli Lilly Biotechnology Center, San Diego, California, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Robust generation of IgG bispecific antibodies has been a long-standing challenge. Existing methods require extensive engineering of each individual antibody, discovery of common light chains, or complex and laborious biochemical processing. Here we combine computational and rational design approaches with experimental structural validation to generate antibody heavy and light chains with orthogonal Fab interfaces. Parental monoclonal antibodies incorporating these interfaces, when simultaneously co-expressed, assemble into bispecific IgG with improved heavy chain-light chain pairing. Bispecific IgGs generated with this approach exhibit pharmacokinetic and other desirable properties of native IgG, but bind target antigens monovalently. As such, these bispecific reagents may be useful in many biotechnological applications.

Indexed as

AnimalsAntibodies, BispecificBiotechnologyHumansImmunoglobulin Fab FragmentsImmunoglobulin GMaleMiceModels, BiologicalModels, MolecularProtein BindingProtein ConformationProtein EngineeringAntibodies, BispecificImmunoglobulin Fab FragmentsImmunoglobulin G

Identifiers

PMID24463572

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.