Evidence map›Paper›PMID 31769731›Full record

ArticlemAbs

Heparin chromatography as an

Thomas E Kraft, Wolfgang F Richter, Thomas Emrich, Alexander Knaupp, Michaela Schuster, Andreas Wolfert, Hubert Kettenberger

Open access · goldAbstract 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 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.8field-weighted citation impact, top 5% 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

44 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. DOTAD: A Database of Therapeutic Antibody Developability.Interdisciplinary sciences, computational life sciences · 2024
    Article
  11. Article
  12. Review
  13. Article
  14. Nonspecificity fingerprints for clinical-stage antibodies in solution.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  15. Article
  16. Article
  17. Surface patches induce nonspecific binding and phase separation of antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  18. Article
  19. SUMO: In Silico Sequence Assessment Using Multiple Optimization Parameters.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  20. Review
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

7 authors at 1 institution in 2 countries.

Thomas E KraftRoche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany.ORCID 0000-0002-5528-3197
Wolfgang F RichterRoche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
Thomas EmrichRoche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany.ORCID 0000-0003-1179-4697
Alexander KnauppRoche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany.
Michaela SchusterRoche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany.ORCID 0000-0003-2817-8364
Andreas WolfertRoche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany.ORCID 0000-0003-3605-0010
Hubert KettenbergerRoche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany.
Roche (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The pharmacokinetic (PK) properties of therapeutic antibodies directly affect efficacy, dose and dose intervals, application route and tissue penetration. In indications where health-care providers and patients can choose between several efficacious and safe therapeutic options, convenience (determined by dosing interval or route of application), which is mainly driven by PK properties, can affect drug selection. Therapeutic antibodies can have greatly different PK even if they have identical Fc domains and show no target-mediated drug disposition. Biophysical properties like surface charge or hydrophobicity, and binding to surrogates for high abundant off-targets (e.g., baculovirus particles, Chinese hamster ovary cell membrane proteins) were proposed to be responsible for these differences. Here, we used heparin chromatography to separate a polyclonal mix of endogenous human IgGs (IVIG) into fractions that differ in their PK properties. Heparin was chosen as a surrogate for highly negatively charged glycocalyx components on endothelial cells, which are among the main contributors to nonspecific clearance. By directly correlating heparin retention time with clearance, we identified heparin chromatography as a tool to assess differences in unspecific cell-surface interaction and the likelihood for increased pinocytotic uptake and degradation. Building on these results, we combined predictors for FcRn-mediated recycling and cell-surface interaction. The combination of heparin and FcRn chromatography allow identification of antibodies with abnormal PK by mimicking the major root causes for fast, non-target-mediated, clearance of therapeutic, Fc-containing proteins.

Indexed as

AnimalsCHO CellsChromatographyCricetulusEndothelial CellsHeparinHistocompatibility Antigens Class IHumansImmunoglobulins, IntravenousMetabolic Clearance RatePinocytosisProtein BindingProteolysisReceptors, FcFc receptor, neonatalHeparinHistocompatibility Antigens Class IImmunoglobulins, IntravenousReceptors, FcclearanceFcRnheparinneonatal Fc receptorPharmacokineticspinocytosisprediction

Identifiers

PMID31769731
PMCPMC6927760
OpenAlexW2990616783

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.