Evidence map›Paper›PMID 25512516›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

In silico selection of therapeutic antibodies for development: viscosity, clearance, and chemical stability.

Vikas K Sharma, Thomas W Patapoff, Bruce Kabakoff, Satyan Pai, Eric Hilario, Boyan Zhang, Charlene Li, Oleg Borisov, Robert F Kelley, Ilya Chorny and 3 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 141 papers.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed
8.9field-weighted citation impact, top 2% of its field
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

141 citing papers in PubMed, 254 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Vikas K SharmaEarly Stage Pharmaceutical Development Department.
Thomas W PatapoffEarly Stage Pharmaceutical Development Department.
Bruce KabakoffEarly Stage Pharmaceutical Development Department.
Satyan PaiEarly Stage Pharmaceutical Development Department.
Eric HilarioEarly Stage Pharmaceutical Development Department.
Boyan ZhangProtein Analytical Chemistry, and.
Charlene LiProtein Analytical Chemistry, and.
Oleg BorisovProtein Analytical Chemistry, and.
Robert F KelleyDrug Delivery, Genentech Inc., South San Francisco, CA 94080;
Ilya ChornySimprota Corp., San Francisco, CA 94158; and.
Joe Z ZhouSimprota Corp., San Francisco, CA 94158; and.
Ken A DillLaufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794 dill@laufercenter.org swartz.trevor@gene.com.
Trevor E SwartzEarly Stage Pharmaceutical Development Department, dill@laufercenter.org swartz.trevor@gene.com.
Stony Brook University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

For mAbs to be viable therapeutics, they must be formulated to have low viscosity, be chemically stable, and have normal in vivo clearance rates. We explored these properties by observing correlations of up to 60 different antibodies of the IgG1 isotype. Unexpectedly, we observe significant correlations with simple physical properties obtainable from antibody sequences and by molecular dynamics simulations of individual antibody molecules. mAbs viscosities increase strongly with hydrophobicity and charge dipole distribution and decrease with net charge. Fast clearance correlates with high hydrophobicities of certain complementarity determining regions and with high positive or high negative net charge. Chemical degradation from tryptophan oxidation correlates with the average solvent exposure time of tryptophan residues. Aspartic acid isomerization rates can be predicted from solvent exposure and flexibility as determined by molecular dynamics simulations. These studies should aid in more rapid screening and selection of mAb candidates during early discovery.

Indexed as

AnimalsAntibodies, MonoclonalCHO CellsCricetinaeCricetulusHumansImmunoglobulin GProtein StabilityRecombinant ProteinsViscosityAntibodies, MonoclonalImmunoglobulin GRecombinant Proteinsdegradationmonoclonal antibodiespharmacokineticspredictionviscosity

Identifiers

PMID25512516
PMCPMC4284567
OpenAlexW1971021060

What OpenQuestion holds

Textmetadata
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.