Evidence map›Paper›PMID 40607534›Full record

ArticlemAbs2025

Characterization of free light chain impurity in a bispecific antibody.

Monica Sadek, Neelima Mantha, Steffen Lippold, Delia Li, Kyle Spitler, Ran Li, Phillip Spinosa, Bob Liu, Steven Luu, Nicholas Woon and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in mAbs, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

15 authors.

Monica SadekAnalytical Development, Genentech Inc., South San Francisco, CA, USA.ORCID 0000-0001-9691-009X
Neelima ManthaPharmaceutical Development, Genentech Inc., South San Francisco, CA, USA.
Steffen LippoldAnalytical Development, Genentech Inc., South San Francisco, CA, USA.
Delia LiAnalytical Development, Genentech Inc., South San Francisco, CA, USA.
Kyle SpitlerAnalytical Development, Genentech Inc., South San Francisco, CA, USA.
Ran LiTranslational Pharmacokinetics and Pharmacodynamics, Development Sciences, Genentech Inc., South San Francisco, CA, USA.
Phillip SpinosaTranslational Pharmacokinetics and Pharmacodynamics, Development Sciences, Genentech Inc., South San Francisco, CA, USA.
Bob LiuBioAnalytical Sciences, Development Sciences, Genentech Inc., South San Francisco, CA, USA.
Steven LuuPharmaceutical Development, Genentech Inc., South San Francisco, CA, USA.
Nicholas WoonAnalytical Development, Genentech Inc., South San Francisco, CA, USA.
Yeying ZhangAnalytical Development, Genentech Inc., South San Francisco, CA, USA.
Jia GuoAnalytical Development, Genentech Inc., South San Francisco, CA, USA.
Renee YangAnalytical Operations, Genentech Inc., South San Francisco, CA, USA.
Jonathan ZarzarPharmaceutical Development, Genentech Inc., South San Francisco, CA, USA.
Yi YangAnalytical Development, Genentech Inc., South San Francisco, CA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bispecific antibodies (bsAbs) target two distinct binding sites, which enable novel mechanisms of action for the treatment of disease. Due to this structural complexity, bsAbs exhibit greater heterogeneity as compared to monospecific antibodies and may require nonstandard purification strategies to remove undesired product-related impurities. However, the implementation of unique manufacturing processes may result in the observation of new impurities. When new impurities are identified, comprehensive characterization of these species is needed to understand the potential impact to the safety and efficacy of the product. In this study, the assessment of a unique purification mode, protein L affinity chromatography, for purification of a bsAb resulted in high levels of free light chain (LC) in the final product. It was discovered that the free LC formed oligomers of various sizes upon accelerated stress in a concentration-, time-, and temperature-dependent manner. This is the first time free LC oligomer has been reported as a product-related impurity. Characterization of the free LC and free LC oligomer species was performed using a variety of chromatographic, electrophoretic, and mass spectrometry tools to gain insight on the formation and behavior of these impurities in the product. These studies informed an impact assessment of the observed free LC and free LC oligomer species on safety, immunogenicity, pharmacokinetics, and bioactivity.

Indexed as

Antibodies, BispecificDrug ContaminationImmunoglobulin Light ChainsAnimalsChromatography, AffinityHumansAntibodies, BispecificImmunoglobulin Light ChainsbiotherapeuticsFree light chainoligomerproduct-related impuritiessafetystability

Identifiers

PMID40607534
PMCPMC12233890

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Registered trials

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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.