Evidence map›Paper›PMID 25484048›Full record

ArticlemAbs2014

Remediating agitation-induced antibody aggregation by eradicating exposed hydrophobic motifs.

Rutilio H Clark, Ramil F Latypov, Cyr De Imus, Jane Carter, Zien Wilson, Kathy Manchulenko, Michael E Brown, Randal R Ketchem

Abstract read
In one paragraph

Article in mAbs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
  2. Article
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  5. Review
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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

8 authors.

Rutilio H Clarka Department of Therapeutic Discovery; Amgen Inc. ; Thousand Oaks , CA USA.
Ramil F Latypov
Cyr De Imus
Jane Carter
Zien Wilson
Kathy Manchulenko
Michael E Brown
Randal R Ketchem

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Therapeutic antibodies must encompass drug product suitable attributes to be commercially marketed. An undesirable antibody characteristic is the propensity to aggregate. Although there are computational algorithms that predict the propensity of a protein to aggregate from sequence information alone, few consider the relevance of the native structure. The Spatial Aggregation Propensity (SAP) algorithm developed by Chennamsetty et. al. incorporates structural and sequence information to identify motifs that contribute to protein aggregation. We have utilized the algorithm to design variants of a highly aggregation prone IgG2. All variants were tested in a variety of high-throughput, small-scale assays to assess the utility of the method described herein. Many variants exhibited improved aggregation stability whether induced by agitation or thermal stress while still retaining bioactivity.

Indexed as

Protein AggregatesProtein MultimerizationAlgorithmsAmino Acid MotifsAntibodies, MonoclonalAntibody AffinityCells, CulturedComputational BiologyHEK293 CellsHumansHydrophobic and Hydrophilic InteractionsImmunoglobulin GInterferon-gammaKiller Cells, NaturalModels, MolecularProtein BindingAntibodies, MonoclonalImmunoglobulin GInterferon-gammaProtein AggregatesaggregationagitationantibodyCDR, complementary-determining regionscomputationalengineeringFab, fragment antigen-bindingFv, variable fragmentIgG, immunoglobulin Gin silicomAb, monoclonal antibodymodelingRAP, relative aggregation propensitySAP, spatial aggregation propensitystabilitythermal

Identifiers

PMID25484048
PMCPMC4622659

What OpenQuestion holds

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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.