Biotechnology and Bioprocess Engineering 2024; 29(6): 1081-1094  
Development, physico-chemical characterization, and in vivo stability of a novel aglycosylated monoclonal antibody targeting FAM19A5
Won Kyum Kim 1,2 · Jae Young Seong 2,3 · Gyun Min Lee 1
1 Department of Biological Sciences, KAIST, Daejeon 34141, Korea
2 Neuracle Science Co. Ltd, Seoul 02841, Korea
3 Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul 02841, Korea
Correspondence to: ✉ Won Kyum Kim
wonkyum.kim@kaist.ac.kr ; wonkyum.kim@neuracles.com
Received: May 12, 2024; Revised: August 20, 2024; Accepted: September 2, 2024; Published online: October 7, 2024.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Introducing aglycosylation into therapeutic monoclonal antibodies (mAbs) can prevent side effects associated with fragment crystallizable (Fc)-mediated effector functions. This modification induces structural changes in the heavy chain constant domain 2-constant domain 3 within Fc regions, which decreases antibody stability at acidic pH and high temperature. In this study, NS101, a novel aglycosylated mAb targeting family with sequence similarity 19, A5 (FAM19A5) for neurological diseases was evaluated with respect to its developability and in vivo stability as therapeutics. When recombinant CHO cells producing NS101 were cultivated using a fed-batch mode in a 500 L bioreactor, cell growth and mAb production profiles were consistent across three consecutive runs. NS101, thus produced, features an additional intra-disulfide bond in the heavy chain complementarity-determining region 3, contributing strong and sophisticated binding to the cryptic epitope. The melting temperature (Tm) of NS101 was lower than that of commercial glycosylated therapeutic mAbs, but NS101 showed better stability at 4 °C for 36 months. The binding affinity of NS101 to FAM19A5 and neonatal Fc receptor were comparable to those of glycosylated NS101. In addition, in three human cohort groups receiving 6, 12, and 24 mg/kg of NS101, the mean half-life was 22 days, and NS101 exhibited in vivo stability, considering that the half-lives of commercialized therapeutic mAbs and endogenous IgGs are 2–4 weeks and 21 days, respectively. Taken together, the results obtained here demonstrate that NS101, a novel aglycosylated mAb, has potential as a therapeutic agent for neurological diseases.
Keywords: NS101 · FAM19A5 · Aglycosylation · Monoclonal antibody therapeutics · Half-life

This Article


Cited By Articles
  • CrossRef (0)

Services
Social Network Service
Search for

Archives