Evidence map›Paper›PMID 33397191›Full record

ArticlemAbs

Rational selection of building blocks for the assembly of bispecific antibodies.

Danyang Gong, Timothy P Riley, Krzysztof P Bzymek, Ana R Correia, Danqing Li, Christopher Spahr, John H Robinson, Ryan B Case, Zhulun Wang, Fernando Garces

Abstract 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 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.

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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

10 authors.

Danyang GongDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc ., Thousand Oaks, CA USA.ORCID 0000-0002-5663-1640
Timothy P RileyDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc ., Thousand Oaks, CA USA.
Krzysztof P BzymekDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc ., Thousand Oaks, CA USA.
Ana R CorreiaDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc ., Thousand Oaks, CA USA.
Danqing LiDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc ., Thousand Oaks, CA USA.
Christopher SpahrDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc ., Thousand Oaks, CA USA.ORCID 0000-0002-4093-9376
John H RobinsonDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc ., Thousand Oaks, CA USA.
Ryan B CaseDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc ., San Francisco, CA USA.
Zhulun WangDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc ., San Francisco, CA USA.
Fernando GarcesDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc ., Thousand Oaks, CA USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bispecific antibodies, engineered to recognize two targets simultaneously, demonstrate exceptional clinical potential for the therapeutic intervention of complex diseases. However, these molecules are often composed of multiple polypeptide chains of differing sequences. To meet industrial scale productivity, enforcing the correct quaternary assembly of these chains is critical. Here, we describe Chain Selectivity Assessment (CSA), a high-throughput method to rationally select parental monoclonal antibodies (mAbs) to make bispecific antibodies requiring correct heavy/light chain pairing. By deploying CSA, we have successfully identified mAbs that exhibit a native preference toward cognate chain pairing that enables the production of hetero-IgGs without additional engineering. Furthermore, CSA also identified rare light chains (LCs) that permit positive binding of the non-cognate arm in the common LC hetero-IgGs, also without engineering. This rational selection of parental mAbs with favorable developability characteristics is critical to the successful development of bispecific molecules with optimal manufacturability properties.

Indexed as

Antibodies, BispecificAntibodies, MonoclonalAntibody AffinityChromatography, GelChromatography, Ion ExchangeChromatography, LiquidElectrophoresis, CapillaryElectrophoresis, Polyacrylamide GelHEK293 CellsHumansImmunoglobulin GImmunoglobulin Heavy ChainsImmunoglobulin Light ChainsMass SpectrometryProtein EngineeringAntibodies, BispecificAntibodies, MonoclonalImmunoglobulin GImmunoglobulin Heavy ChainsImmunoglobulin Light ChainsBispecificsbuilding blockscognate and non-cognate pairingcommon light chainhetero-IgG

Identifiers

PMID33397191
PMCPMC7808324

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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.