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Investigating the Degradation Behaviors of a Therapeutic Monoclonal Antibody Associated with pH and Buffer Species.

Abstract This study aimed in understanding the degradation behaviors of an IgG 1 subtype therapeutic monoclonal antibody A (mAb-A) associated with pH and buffer species. The information obtained in this study can augment conventional, stability-based screening paradigms by providing the direction necessary for efficient experimental design. Differential scanning calorimetry (DSC) was used for studying conformational stability. Dynamic light scattering (DLS) was utilized to generate B 22*, a modified second virial coefficient for the character of protein-protein interaction. Size-exclusion chromatography (SEC) and hydrophobic interaction chromatography (HIC) were employed to separate degradation products. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for determining the molecular size and liquid chromatography mass spectrometry (LC-MS) were used for identifying the sequence of the separated fragments. The results showed that both pH and buffer species played the roles in controlling the degradation behaviors of mAb-A, but the pH was more significant. In particular, pH 4.5 induced additional thermal transition peaks occurring at a low temperature compared with pH 6.5. A continual temperature-stress study illustrated that the additional thermal transition peaks related to the least stable structure and a greater fragmentation. Although mAb-A showed the comparable conformational structures and an identical amount of aggregates at time zero between the different types of buffer species at pH 6.5, the aggregation formation rate showed a buffer species-dependent discrepancy over a temperature-stress period. It was found that the levels of aggregations associated with the magnitudes of protein-protein interaction forces.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title aaps pharmscitech
Publication Year Start
%A Zheng, Songyan; Qiu, Difei; Adams, Monica; Li, Jinjiang; Mantri, Rao V.; Gandhi, Rajesh
%T Investigating the Degradation Behaviors of a Therapeutic Monoclonal Antibody Associated with pH and Buffer Species.
%J AAPS PharmSciTech
%D 09/2015
%M ENG
%B This study aimed in understanding the degradation behaviors of an IgG 1 subtype therapeutic monoclonal antibody A (mAb-A) associated with pH and buffer species. The information obtained in this study can augment conventional, stability-based screening paradigms by providing the direction necessary for efficient experimental design. Differential scanning calorimetry (DSC) was used for studying conformational stability. Dynamic light scattering (DLS) was utilized to generate B 22*, a modified second virial coefficient for the character of protein-protein interaction. Size-exclusion chromatography (SEC) and hydrophobic interaction chromatography (HIC) were employed to separate degradation products. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for determining the molecular size and liquid chromatography mass spectrometry (LC-MS) were used for identifying the sequence of the separated fragments. The results showed that both pH and buffer species played the roles in controlling the degradation behaviors of mAb-A, but the pH was more significant. In particular, pH 4.5 induced additional thermal transition peaks occurring at a low temperature compared with pH 6.5. A continual temperature-stress study illustrated that the additional thermal transition peaks related to the least stable structure and a greater fragmentation. Although mAb-A showed the comparable conformational structures and an identical amount of aggregates at time zero between the different types of buffer species at pH 6.5, the aggregation formation rate showed a buffer species-dependent discrepancy over a temperature-stress period. It was found that the levels of aggregations associated with the magnitudes of protein-protein interaction forces.
%Y 10.1208/s12249-015-0403-0
%W PHY
%G AUTHOR
%R 2015..............Z

@Article{Zheng2015,
author="Zheng, Songyan
and Qiu, Difei
and Adams, Monica
and Li, Jinjiang
and Mantri, Rao V.
and Gandhi, Rajesh",
title="Investigating the Degradation Behaviors of a Therapeutic Monoclonal Antibody Associated with pH and Buffer Species.",
journal="AAPS PharmSciTech",
year="2015",
month="Sep",
day="04",
abstract="This study aimed in understanding the degradation behaviors of an IgG 1 subtype therapeutic monoclonal antibody A (mAb-A) associated with pH and buffer species. The information obtained in this study can augment conventional, stability-based screening paradigms by providing the direction necessary for efficient experimental design. Differential scanning calorimetry (DSC) was used for studying conformational stability. Dynamic light scattering (DLS) was utilized to generate B 22*, a modified second virial coefficient for the character of protein-protein interaction. Size-exclusion chromatography (SEC) and hydrophobic interaction chromatography (HIC) were employed to separate degradation products. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for determining the molecular size and liquid chromatography mass spectrometry (LC-MS) were used for identifying the sequence of the separated fragments. The results showed that both pH and buffer species played the roles in controlling the degradation behaviors of mAb-A, but the pH was more significant. In particular, pH 4.5 induced additional thermal transition peaks occurring at a low temperature compared with pH 6.5. A continual temperature-stress study illustrated that the additional thermal transition peaks related to the least stable structure and a greater fragmentation. Although mAb-A showed the comparable conformational structures and an identical amount of aggregates at time zero between the different types of buffer species at pH 6.5, the aggregation formation rate showed a buffer species-dependent discrepancy over a temperature-stress period. It was found that the levels of aggregations associated with the magnitudes of protein-protein interaction forces.",
issn="1530-9932",
doi="10.1208/s12249-015-0403-0",
url="http://www.ncbi.nlm.nih.gov/pubmed/26340951",
language="ENG"
}

%0 Journal Article
%T Investigating the Degradation Behaviors of a Therapeutic Monoclonal Antibody Associated with pH and Buffer Species.
%A Zheng, Songyan
%A Qiu, Difei
%A Adams, Monica
%A Li, Jinjiang
%A Mantri, Rao V.
%A Gandhi, Rajesh
%J AAPS PharmSciTech
%D 2015
%8 Sep 04
%@ 1530-9932
%G ENG
%F Zheng2015
%X This study aimed in understanding the degradation behaviors of an IgG 1 subtype therapeutic monoclonal antibody A (mAb-A) associated with pH and buffer species. The information obtained in this study can augment conventional, stability-based screening paradigms by providing the direction necessary for efficient experimental design. Differential scanning calorimetry (DSC) was used for studying conformational stability. Dynamic light scattering (DLS) was utilized to generate B 22*, a modified second virial coefficient for the character of protein-protein interaction. Size-exclusion chromatography (SEC) and hydrophobic interaction chromatography (HIC) were employed to separate degradation products. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for determining the molecular size and liquid chromatography mass spectrometry (LC-MS) were used for identifying the sequence of the separated fragments. The results showed that both pH and buffer species played the roles in controlling the degradation behaviors of mAb-A, but the pH was more significant. In particular, pH 4.5 induced additional thermal transition peaks occurring at a low temperature compared with pH 6.5. A continual temperature-stress study illustrated that the additional thermal transition peaks related to the least stable structure and a greater fragmentation. Although mAb-A showed the comparable conformational structures and an identical amount of aggregates at time zero between the different types of buffer species at pH 6.5, the aggregation formation rate showed a buffer species-dependent discrepancy over a temperature-stress period. It was found that the levels of aggregations associated with the magnitudes of protein-protein interaction forces.
%U http://dx.doi.org/10.1208/s12249-015-0403-0
%U http://www.ncbi.nlm.nih.gov/pubmed/26340951

PT Journal
AU Zheng, S
   Qiu, D
   Adams, M
   Li, J
   Mantri, RV
   Gandhi, R
TI Investigating the Degradation Behaviors of a Therapeutic Monoclonal Antibody Associated with pH and Buffer Species.
SO AAPS PharmSciTech
PD Sep
PY 2015
DI 10.1208/s12249-015-0403-0
LA ENG
AB This study aimed in understanding the degradation behaviors of an IgG 1 subtype therapeutic monoclonal antibody A (mAb-A) associated with pH and buffer species. The information obtained in this study can augment conventional, stability-based screening paradigms by providing the direction necessary for efficient experimental design. Differential scanning calorimetry (DSC) was used for studying conformational stability. Dynamic light scattering (DLS) was utilized to generate B 22*, a modified second virial coefficient for the character of protein-protein interaction. Size-exclusion chromatography (SEC) and hydrophobic interaction chromatography (HIC) were employed to separate degradation products. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for determining the molecular size and liquid chromatography mass spectrometry (LC-MS) were used for identifying the sequence of the separated fragments. The results showed that both pH and buffer species played the roles in controlling the degradation behaviors of mAb-A, but the pH was more significant. In particular, pH 4.5 induced additional thermal transition peaks occurring at a low temperature compared with pH 6.5. A continual temperature-stress study illustrated that the additional thermal transition peaks related to the least stable structure and a greater fragmentation. Although mAb-A showed the comparable conformational structures and an identical amount of aggregates at time zero between the different types of buffer species at pH 6.5, the aggregation formation rate showed a buffer species-dependent discrepancy over a temperature-stress period. It was found that the levels of aggregations associated with the magnitudes of protein-protein interaction forces.
ER

PMID- 26340951
OWN - NLM
STAT- Publisher
DA  - 20150905
LR  - 20150906
IS  - 1530-9932 (Electronic)
IS  - 1530-9932 (Linking)
DP  - 2015 Sep 4
TI  - Investigating the Degradation Behaviors of a Therapeutic Monoclonal Antibody
      Associated with pH and Buffer Species.
AB  - This study aimed in understanding the degradation behaviors of an IgG 1 subtype
      therapeutic monoclonal antibody A (mAb-A) associated with pH and buffer species. 
      The information obtained in this study can augment conventional, stability-based 
      screening paradigms by providing the direction necessary for efficient
      experimental design. Differential scanning calorimetry (DSC) was used for
      studying conformational stability. Dynamic light scattering (DLS) was utilized to
      generate B 22*, a modified second virial coefficient for the character of
      protein-protein interaction. Size-exclusion chromatography (SEC) and hydrophobic 
      interaction chromatography (HIC) were employed to separate degradation products. 
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for
      determining the molecular size and liquid chromatography mass spectrometry
      (LC-MS) were used for identifying the sequence of the separated fragments. The
      results showed that both pH and buffer species played the roles in controlling
      the degradation behaviors of mAb-A, but the pH was more significant. In
      particular, pH 4.5 induced additional thermal transition peaks occurring at a low
      temperature compared with pH 6.5. A continual temperature-stress study
      illustrated that the additional thermal transition peaks related to the least
      stable structure and a greater fragmentation. Although mAb-A showed the
      comparable conformational structures and an identical amount of aggregates at
      time zero between the different types of buffer species at pH 6.5, the
      aggregation formation rate showed a buffer species-dependent discrepancy over a
      temperature-stress period. It was found that the levels of aggregations
      associated with the magnitudes of protein-protein interaction forces.
FAU - Zheng, Songyan
AU  - Zheng S
AD  - Drug Product Science and Technology, Bristol-Myers Squibb, One Squibb Drive, New 
      Brunswick, New Jersey, 08903, USA, [email protected]
FAU - Qiu, Difei
AU  - Qiu D
FAU - Adams, Monica
AU  - Adams M
FAU - Li, Jinjiang
AU  - Li J
FAU - Mantri, Rao V
AU  - Mantri RV
FAU - Gandhi, Rajesh
AU  - Gandhi R
LA  - ENG
PT  - JOURNAL ARTICLE
DEP - 20150904
TA  - AAPS PharmSciTech
JT  - AAPS PharmSciTech
JID - 100960111
EDAT- 2015/09/06 06:00
MHDA- 2015/09/06 06:00
CRDT- 2015/09/06 06:00
PHST- 2015/04/15 [received]
PHST- 2015/08/21 [accepted]
PHST- 2015/09/04 [aheadofprint]
AID - 10.1208/s12249-015-0403-0 [doi]
PST - aheadofprint
SO  - AAPS PharmSciTech. 2015 Sep 4.
TY  - JOUR
AU  - Zheng, Songyan
AU  - Qiu, Difei
AU  - Adams, Monica
AU  - Li, Jinjiang
AU  - Mantri, Rao V.
AU  - Gandhi, Rajesh
PY  - 2015/Sep/04
TI  - Investigating the Degradation Behaviors of a Therapeutic Monoclonal Antibody Associated with pH and Buffer Species.
JO  - AAPS PharmSciTech
N2  - This study aimed in understanding the degradation behaviors of an IgG 1 subtype therapeutic monoclonal antibody A (mAb-A) associated with pH and buffer species. The information obtained in this study can augment conventional, stability-based screening paradigms by providing the direction necessary for efficient experimental design. Differential scanning calorimetry (DSC) was used for studying conformational stability. Dynamic light scattering (DLS) was utilized to generate B 22*, a modified second virial coefficient for the character of protein-protein interaction. Size-exclusion chromatography (SEC) and hydrophobic interaction chromatography (HIC) were employed to separate degradation products. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for determining the molecular size and liquid chromatography mass spectrometry (LC-MS) were used for identifying the sequence of the separated fragments. The results showed that both pH and buffer species played the roles in controlling the degradation behaviors of mAb-A, but the pH was more significant. In particular, pH 4.5 induced additional thermal transition peaks occurring at a low temperature compared with pH 6.5. A continual temperature-stress study illustrated that the additional thermal transition peaks related to the least stable structure and a greater fragmentation. Although mAb-A showed the comparable conformational structures and an identical amount of aggregates at time zero between the different types of buffer species at pH 6.5, the aggregation formation rate showed a buffer species-dependent discrepancy over a temperature-stress period. It was found that the levels of aggregations associated with the magnitudes of protein-protein interaction forces.
SN  - 1530-9932
UR  - http://dx.doi.org/10.1208/s12249-015-0403-0
UR  - http://www.ncbi.nlm.nih.gov/pubmed/26340951
ID  - Zheng2015
ER  - 
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