Quality control monitoring of therapeutic antibodies on the basis of artificial proteins specific for the higher-order structure of antibody domains
| Project/Area Number |
18K04860
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 27040:Biofunction and bioprocess engineering-related
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| Research Institution | National Institute of Advanced Industrial Science and Technology |
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Principal Investigator |
Watanabe Hideki 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (90422089)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 抗体医薬品 / 品質分析 / バイオセンサー / 人工タンパク質 / 進化分子工学 / ファージディスプレイ |
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| Outline of Final Research Achievements |
Analysis of the higher-order structure of therapeutic antibodies (mAbs) is indispensable for ensuring their efficacy and safety because their therapeutic efficacies, e.g., specificity for antigens and effector functions, are governed by their higher-order structures of mAbs. In this study, biosensing-based quality control monitoring of mAbs was developed by using artificial protein that can recognize higher-order structural changes of mAbs. Specific artificial proteins were generated by using phage display. The generated artificial protein distinguishes between the denatured Fab and Fc regions, showing the domain-specific recognition of denatured mAbs. This specificity could provide more detailed structural information regarding which part of mAbs is structurally collapsed. This biosensing will be able to contribute to the manufacture of high-quality therapeutic mAbs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の学術的特色として、開発した人工タンパク質の分子認識能は、従来は非特異的な疎水性相互作用が支配的とみなされていた変性タンパク質の結合様式に「変性構造の特異的な認識」という新たな視点・知見を提供した。本研究成果によって、抗体の変性領域の特定がドメイン単位で可能となり、高感度・高スループット性を特徴とするバイオセンシング技術の分析分解能が質的に向上し、抗体医薬品の品質分析技術に適した高感度・高分解能・高スループット性を満たす高次構造分析技術が実現する。抗体医薬品の開発競争が激化する中、本技術は高品質な抗体医薬品製造への貢献として、技術的・経済的にも大きな波及効果が見込まれる。
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Report
(3 results)
Research Products
(6 results)
