Evidence map›Paper›PMID 25961854›Full record

ArticlemAbs2015

A novel screening method to assess developability of antibody-like molecules.

Neeraj Kohli, Nidhi Jain, Melissa L Geddie, Maja Razlog, Lihui Xu, Alexey A Lugovskoy

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
5.1field-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

42 citing papers in PubMed, 76 citations in OpenAlex.

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  8. DOTAD: A Database of Therapeutic Antibody Developability.Interdisciplinary sciences, computational life sciences · 2024
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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

6 authors at 1 institution in 1 country.

Neeraj Kohlia Merrimack Pharmaceuticals, Inc. ; Cambridge , MA , USA.
Nidhi Jain
Melissa L Geddie
Maja Razlog
Lihui Xu
Alexey A Lugovskoy
Merrimack Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Monoclonal antibodies and antibody-like molecules represent a fast-growing class of bio-therapeutics that has rapidly transformed patient care in a variety of disease indications. The discovery of antibodies that bind to particular targets with high affinity is now a routine exercise and a variety of in vitro and in vivo techniques are available for this purpose. However, it is still challenging to identify antibodies that, in addition to having the desired biological effect, also express well, remain soluble at different pH levels, remain stable at high concentrations, can withstand high shear stress, and have minimal non-specific interactions. Many promising antibody programs have ultimately failed in development due to the problems associated with one of these factors. Here, we present a simple high-performance liquid chromatography (HPLC)-based screening method to assess these developability factors earlier in discovery process. This method is robust and requires only microgram quantities of proteins. Briefly, we show that for antibodies injected on a commercially available pre-packed Zenix HPLC column, the retention times are inversely related to their colloidal stability with antibodies prone to precipitation or aggregation retained longer on the column with broader peaks. By simply varying the salt content of running buffer, we were also able to estimate the nature of interactions between the antibodies and the column. We believe this approach should generally be applicable to assessment of the developability of other classes of bio-therapeutic molecules, and that the addition of this simple tool early in the discovery process will lead to selection of molecules with improved developability characteristics.

Indexed as

Antibodies, MonoclonalCell LineChromatography, High Pressure LiquidHumansHydrogen-Ion ConcentrationRecombinant ProteinsAntibodies, MonoclonalRecombinant ProteinsAC-SINS, affinity capture self-interaction nanoparticle spectroscopyCIC, cross-interaction chromatographycolloidal stabilitydevelopabilityDSF, differential scanning fluorimetryHTP, high throughputmAb, monoclonal antibodyscFv, single chain variable fragmentSEC, size exclusion chromatographysize exclusion chromatographySMAC, standup monolayer chromatographystandup monolayer absorption chromatographyTm, melting temperatureZenix column

Identifiers

PMID25961854
PMCPMC4622974
OpenAlexW1939141202

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.