Early determination of potential critical quality attributes of therapeutic antibodies in developability studies through surface plasmon resonance-based relative binding activity assessment
Precise measurement of the binding activity changes of therapeutic antibodies is important to determine the potential critical quality attributes (CQAs) in developability assessment at the early stage of antibody development. Here, we report a surface plasmon resonance (SPR)-based relative binding a...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2024.2374607 |
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| author | Shuai Wang Yanqiu Wang Zhenzhen Li Ye Hong Zhaohui Wang Jiteng Fan Qiong Wang Yuanjie Ge Xiaofeng Zhao Guangcun Cheng Changyan Chen Yadan Wu Yayuan Fu |
| author_facet | Shuai Wang Yanqiu Wang Zhenzhen Li Ye Hong Zhaohui Wang Jiteng Fan Qiong Wang Yuanjie Ge Xiaofeng Zhao Guangcun Cheng Changyan Chen Yadan Wu Yayuan Fu |
| author_sort | Shuai Wang |
| collection | DOAJ |
| description | Precise measurement of the binding activity changes of therapeutic antibodies is important to determine the potential critical quality attributes (CQAs) in developability assessment at the early stage of antibody development. Here, we report a surface plasmon resonance (SPR)-based relative binding activity method, which incorporates both binding affinity and binding response and allows us to determine relative binding activity of antibodies with high accuracy and precision. We applied the SPR-based relative binding activity method in multiple forced degradation studies of antibody developability assessment. The current developability assessment strategy provided comprehensive, precise characterization of antibody binding activity in the stability studies, enabling us to perform correlation analysis and establish the structure–function relationship between relative binding activity and quality attributes. The impact of a given quality attribute on binding activity could be confidently determined without isolating antibody variants. We identified several potential CQAs, including Asp isomerization, Asn deamidation, and fragmentation. Some potential CQAs affected binding affinity of antibody and resulted in a reduction of binding activity. Certain potential CQAs impaired antibody binding to antigen and led to a loss of binding activity. A few potential CQAs could influence both binding affinity and binding response and cause a substantial decrease in antibody binding activity. Specifically, we identified low abundance Asn33 deamidation in the light chain complementarity-determining region as a potential CQA, in which all the stressed antibody samples showed Asn33 deamidation abundances ranging from 4.2% to 27.5% and a mild binding affinity change from 1.76 nM to 2.16 nM. |
| format | Article |
| id | doaj-art-19cb036bf9994ae38eb022d448f32c83 |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-19cb036bf9994ae38eb022d448f32c832025-01-31T04:19:38ZengTaylor & Francis GroupmAbs1942-08621942-08702024-12-0116110.1080/19420862.2024.2374607Early determination of potential critical quality attributes of therapeutic antibodies in developability studies through surface plasmon resonance-based relative binding activity assessmentShuai Wang0Yanqiu Wang1Zhenzhen Li2Ye Hong3Zhaohui Wang4Jiteng Fan5Qiong Wang6Yuanjie Ge7Xiaofeng Zhao8Guangcun Cheng9Changyan Chen10Yadan Wu11Yayuan Fu12State Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, ChinaState Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, ChinaState Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, ChinaState Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, ChinaState Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, ChinaState Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, ChinaState Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, ChinaState Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, ChinaState Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, ChinaState Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, ChinaState Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, ChinaState Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, ChinaState Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, ChinaPrecise measurement of the binding activity changes of therapeutic antibodies is important to determine the potential critical quality attributes (CQAs) in developability assessment at the early stage of antibody development. Here, we report a surface plasmon resonance (SPR)-based relative binding activity method, which incorporates both binding affinity and binding response and allows us to determine relative binding activity of antibodies with high accuracy and precision. We applied the SPR-based relative binding activity method in multiple forced degradation studies of antibody developability assessment. The current developability assessment strategy provided comprehensive, precise characterization of antibody binding activity in the stability studies, enabling us to perform correlation analysis and establish the structure–function relationship between relative binding activity and quality attributes. The impact of a given quality attribute on binding activity could be confidently determined without isolating antibody variants. We identified several potential CQAs, including Asp isomerization, Asn deamidation, and fragmentation. Some potential CQAs affected binding affinity of antibody and resulted in a reduction of binding activity. Certain potential CQAs impaired antibody binding to antigen and led to a loss of binding activity. A few potential CQAs could influence both binding affinity and binding response and cause a substantial decrease in antibody binding activity. Specifically, we identified low abundance Asn33 deamidation in the light chain complementarity-determining region as a potential CQA, in which all the stressed antibody samples showed Asn33 deamidation abundances ranging from 4.2% to 27.5% and a mild binding affinity change from 1.76 nM to 2.16 nM.https://www.tandfonline.com/doi/10.1080/19420862.2024.2374607Antibody developmentcritical quality attributedevelopability assessmentforced degradationrelative binding activitysurface plasmon resonance |
| spellingShingle | Shuai Wang Yanqiu Wang Zhenzhen Li Ye Hong Zhaohui Wang Jiteng Fan Qiong Wang Yuanjie Ge Xiaofeng Zhao Guangcun Cheng Changyan Chen Yadan Wu Yayuan Fu Early determination of potential critical quality attributes of therapeutic antibodies in developability studies through surface plasmon resonance-based relative binding activity assessment mAbs Antibody development critical quality attribute developability assessment forced degradation relative binding activity surface plasmon resonance |
| title | Early determination of potential critical quality attributes of therapeutic antibodies in developability studies through surface plasmon resonance-based relative binding activity assessment |
| title_full | Early determination of potential critical quality attributes of therapeutic antibodies in developability studies through surface plasmon resonance-based relative binding activity assessment |
| title_fullStr | Early determination of potential critical quality attributes of therapeutic antibodies in developability studies through surface plasmon resonance-based relative binding activity assessment |
| title_full_unstemmed | Early determination of potential critical quality attributes of therapeutic antibodies in developability studies through surface plasmon resonance-based relative binding activity assessment |
| title_short | Early determination of potential critical quality attributes of therapeutic antibodies in developability studies through surface plasmon resonance-based relative binding activity assessment |
| title_sort | early determination of potential critical quality attributes of therapeutic antibodies in developability studies through surface plasmon resonance based relative binding activity assessment |
| topic | Antibody development critical quality attribute developability assessment forced degradation relative binding activity surface plasmon resonance |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2024.2374607 |
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