PMID- 31344474
OWN - NLM
STAT- MEDLINE
DCOM- 20200706
LR  - 20200706
IS  - 1096-0279 (Electronic)
IS  - 1046-5928 (Linking)
VI  - 164
DP  - 2019 Dec
TI  - Monitoring removal of hole-hole homodimer by analytical hydrophobic interaction 
      chromatography in purifying a bispecific antibody.
PG  - 105457
LID - S1046-5928(19)30335-3 [pii]
LID - 10.1016/j.pep.2019.105457 [doi]
AB  - Despite the use of knobs-into-holes (KiH) strategy to promote heterodimerization 
      in recombinant production of bispecific antibody (bsAb), homodimer (especially 
      the hole-hole homodimer) can still be generated in small amount. This by-product 
      needs to be removed by downstream process. However, as homodimer and the target 
      bsAb are usually very close in size, these two species may not be readily 
      differentiated using size-exclusion chromatography-high performance liquid 
      chromatography (SEC-HPLC). Thus, method other than SEC-HPLC needs to be developed 
      to monitor removal of this by-product. Here, through a case study we demonstrate 
      that analytical hydrophobic interaction chromatography (HIC) is a powerful tool 
      for quantitatively monitoring removal of hole-hole homodimer in bsAb 
      purification.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Chen, Tao
AU  - Chen T
AD  - Technology and Process Development (TPD), WuXi Biologics, 288 Fute Zhong Road, 
      Waigaoqiao Free Trade Zone, Shanghai, 200131, China.
FAU - Han, Jinyu
AU  - Han J
AD  - Technology and Process Development (TPD), WuXi Biologics, 288 Fute Zhong Road, 
      Waigaoqiao Free Trade Zone, Shanghai, 200131, China.
FAU - Guo, Gaili
AU  - Guo G
AD  - Technology and Process Development (TPD), WuXi Biologics, 288 Fute Zhong Road, 
      Waigaoqiao Free Trade Zone, Shanghai, 200131, China.
FAU - Wang, Qing
AU  - Wang Q
AD  - Technology and Process Development (TPD), WuXi Biologics, 288 Fute Zhong Road, 
      Waigaoqiao Free Trade Zone, Shanghai, 200131, China.
FAU - Wang, Ying
AU  - Wang Y
AD  - Technology and Process Development (TPD), WuXi Biologics, 288 Fute Zhong Road, 
      Waigaoqiao Free Trade Zone, Shanghai, 200131, China.
FAU - Li, Yifeng
AU  - Li Y
AD  - Technology and Process Development (TPD), WuXi Biologics, 288 Fute Zhong Road, 
      Waigaoqiao Free Trade Zone, Shanghai, 200131, China. Electronic address: 
      li_yifeng@wuxiapptec.com.
LA  - eng
PT  - Journal Article
DEP - 20190723
PL  - United States
TA  - Protein Expr Purif
JT  - Protein expression and purification
JID - 9101496
RN  - 0 (Antibodies, Bispecific)
SB  - IM
MH  - Animals
MH  - Antibodies, Bispecific/chemistry/*isolation & purification
MH  - CHO Cells
MH  - Chromatography, Gel/methods
MH  - Chromatography, High Pressure Liquid/methods
MH  - Cricetulus
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Protein Conformation
MH  - Protein Multimerization
OTO - NOTNLM
OT  - Analytical hydrophobic interaction chromatography (HIC)
OT  - Bispecific antibody (bsAb)
OT  - Glycosylation
OT  - Half-antibody
OT  - Hole-hole homodimer
OT  - Size-exclusion chromatography-high performance liquid chromatography (SEC-HPLC)
EDAT- 2019/07/26 06:00
MHDA- 2020/07/07 06:00
CRDT- 2019/07/26 06:00
PHST- 2019/06/24 00:00 [received]
PHST- 2019/07/17 00:00 [revised]
PHST- 2019/07/22 00:00 [accepted]
PHST- 2019/07/26 06:00 [pubmed]
PHST- 2020/07/07 06:00 [medline]
PHST- 2019/07/26 06:00 [entrez]
AID - S1046-5928(19)30335-3 [pii]
AID - 10.1016/j.pep.2019.105457 [doi]
PST - ppublish
SO  - Protein Expr Purif. 2019 Dec;164:105457. doi: 10.1016/j.pep.2019.105457. Epub 
      2019 Jul 23.