Evidence map›Paper›PMID 39322793›Full record

ArticlePharmaceutical research2024

Identification and Activity Study of an Impurity Band Observed in the nrSDS-PAGE of Aflibercept.

Meng Li, Weiyu Li, Xin Wang, Gang Wu, Jialiang Du, Gangling Xu, Maoqin Duan, Xiaojuan Yu, Chunbo Cui, Chunyu Liu and 3 more

Abstract read
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In one paragraph

Article in Pharmaceutical research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Meng Li *NHC Key Laboratory of Research On Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, P.R. China, 102629.
Weiyu Li *NHC Key Laboratory of Research On Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, P.R. China, 102629.
Xin WangFujian Institute for Food and Drug Quality Control, Fuzhou, China.
Gang WuNHC Key Laboratory of Research On Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, P.R. China, 102629.
Jialiang DuNHC Key Laboratory of Research On Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, P.R. China, 102629.
Gangling XuNHC Key Laboratory of Research On Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, P.R. China, 102629.
Maoqin DuanNHC Key Laboratory of Research On Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, P.R. China, 102629.
Xiaojuan YuNHC Key Laboratory of Research On Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, P.R. China, 102629.
Chunbo CuiNHC Key Laboratory of Research On Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, P.R. China, 102629.
Chunyu LiuNHC Key Laboratory of Research On Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, P.R. China, 102629.
Zhihao FuNHC Key Laboratory of Research On Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, P.R. China, 102629.
Chuanfei YuNHC Key Laboratory of Research On Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, P.R. China, 102629. yucf@nifdc.org.cn.
Lan WangNHC Key Laboratory of Research On Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, P.R. China, 102629. wanglan@nifdc.org.cn.

Funding

National Key Research and Development Program 2021YFF0600804-C02-05
6 · The paper itself

Abstract

backgroundAflibercept is a biopharmaceutical targeting vascular endothelial growth factor (VEGF) that has shown promise in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) in adults. Quality control studies of aflibercept employing non-reduced SDS-PAGE (nrSDS-PAGE) have shown that a significant variant band (IM1) is consistently present below the main band. Considering the quality control strategy of biopharmaceuticals, structural elucidation and functional studies are required.

methodsIn this study, the variant bands in nrSDS-PAGE were collected through electroelution and identified by peptide mass fingerprinting based on liquid chromatography-tandem MS (LC-MS/MS). This variant was expressed using knob-into-hole (KIH) design transient transfection for the detection of ligand affinity, binding activity and biological activity.

resultsThe variant band was formed by C-terminal truncation at position N99 of one chain in the aflibercept homodimer. Then, this variant was successfully expressed using KIH design transient transfection. The ligand affinity of the IM1 truncated variant was reduced by 18-fold, and neither binding activity nor biological activity were detected.

conclusionsThe efficacy of aflibercept is influenced by the loss of biological activity of the variant. Therefore, this study supports the development of a quality control strategy for aflibercept.

Indexed as

Electrophoresis, Polyacrylamide GelReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsAngiogenesis InhibitorsChromatography, LiquidDrug ContaminationHumansMacular DegenerationMacular EdemaPeptide MappingTandem Mass SpectrometryVascular Endothelial Growth Factor AafliberceptAngiogenesis InhibitorsReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsVascular Endothelial Growth Factor AElectroelutionHeterogeneityLC–MSN-glycosylationSDS-PAGESize variants

Identifiers

PMID39322793

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