Characterization and Monitoring of a Novel Light-heavy-light Chain Mispair in a Therapeutic Bispecific Antibody.

Bispecific antibodies Correct pairing of cognate heavy chains Disulfide bond mapping Engineered cysteines Heterodimerization of heavy chains Knob-into-hole (KiH) Mispair light chains

Journal

Journal of pharmaceutical sciences
ISSN: 1520-6017
Titre abrégé: J Pharm Sci
Pays: United States
ID NLM: 2985195R

Informations de publication

Date de publication:
08 2021
Historique:
received: 16 02 2021
revised: 15 04 2021
accepted: 15 04 2021
pubmed: 25 4 2021
medline: 5 8 2021
entrez: 24 4 2021
Statut: ppublish

Résumé

Site-specific cysteine engineering, along with other genetic mutations, is broadly implemented in bispecific antibodies (bsAb). Thus far, homodimer, half hole antibody, one-light chain mispaired and light chain swapped variants have been reported as chain-pairing variants for the asymmetric IgG-like bispecific antibodies. Here we report a novel mispair in which the C

Identifiants

pubmed: 33894207
pii: S0022-3549(21)00232-X
doi: 10.1016/j.xphs.2021.04.010
pii:
doi:

Substances chimiques

Antibodies, Bispecific 0
Immunoglobulin G 0
Cysteine K848JZ4886

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2904-2915

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Mingyan Cao (M)

Analytical Sciences, Biopharmaceutical Development, Biopharmaceuticals R&D, AstraZeneca, One Medimmune Way, Gaithersburg, MD 20878, United States. Electronic address: mingyan.cao@astrazeneca.com.

Conner Parthemore (C)

Analytical Sciences, Biopharmaceutical Development, Biopharmaceuticals R&D, AstraZeneca, One Medimmune Way, Gaithersburg, MD 20878, United States.

Yang Jiao (Y)

Analytical Sciences, Biopharmaceutical Development, Biopharmaceuticals R&D, AstraZeneca, One Medimmune Way, Gaithersburg, MD 20878, United States.

Samuel Korman (S)

Analytical Sciences, Biopharmaceutical Development, Biopharmaceuticals R&D, AstraZeneca, One Medimmune Way, Gaithersburg, MD 20878, United States.

Matthew Aspelund (M)

Purification Process Sciences, Biopharmaceutical Development, Biopharmaceuticals R&D, AstraZeneca, One Medimmune Way, Gaithersburg, MD 20878, United States.

Alan Hunter (A)

Purification Process Sciences, Biopharmaceutical Development, Biopharmaceuticals R&D, AstraZeneca, One Medimmune Way, Gaithersburg, MD 20878, United States.

Greg Kilby (G)

Analytical Sciences, Biopharmaceutical Development, Biopharmaceuticals R&D, AstraZeneca, One Medimmune Way, Gaithersburg, MD 20878, United States.

Xiaoyu Chen (X)

Analytical Sciences, Biopharmaceutical Development, Biopharmaceuticals R&D, AstraZeneca, One Medimmune Way, Gaithersburg, MD 20878, United States. Electronic address: xiaoyu.chen@astrazeneca.com.

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Classifications MeSH