Development of a new technology to convert a normal antibody into corresponding catalytic antibody

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H02282
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Oita University
• Principal Investigator: HIFUMI EMI 大分大学, 全学研究推進機構, 教授 (90254606)
• Co-Investigator(Kenkyū-buntansha): 加藤 龍一 大学共同利用機関法人高エネルギー加速器研究機構, 物質構造科学研究所, 准教授 (50240833)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 抗体医薬 / 抗体酵素 / 構造多様性 / アルゴリズム / 銅イオン / プロリン / 超可変領域 / 変異体

Outline of Final Research Achievements

In recent years, it has been recognized that one antibody has various kinds of structures. Namely, an antibody has the structural diversity, which has important meaning regarding how to produce the bio products such as antibody drugs possessing a uniform structure. In the first half of the research, we addressed the structural diversity problem of antibodies and solved this problem by using copper ions appropriately. This review article is read by a lot of scientists and engineers in the world.
Then, in the latter half of the research period, we focused on how to make antibodies having an enzymatic action. As a result, we found the epoch-making algorism, in which the antibody light chain can be converted to the catalytic antibody by deleting Pro95 (Kabat numbering) in the hypervariable region (CDR)-3 of the antibody light chain. We also established that this can be applied as a universal technology, and we were able to achieve the goal planned initially, completely.

Free Research Field

生物工学, 抗体工学, 酵素科学, 生体関連化学, バイオテクノロジー

Academic Significance and Societal Importance of the Research Achievements

タンパク質製剤に代表されるバイオ医薬品にはジェネリック医薬品は無く、バイオシミラー医薬品という。これはタンパク質では細かい構造までを含めると全く同じ製品が作れないからである。本研究で成し得た抗体の多様性構造の均一化は、特に産業上役に立つ成果である。
次いで、1975年以降、膨大な数で作製されてきたモノクローナル抗体の何割かに酵素作用を付与する画期的な手法を発見した。これは、新規な予防薬・医薬品に大きな間口を開くことになり、科学的にも産業的も大きな意義を持つ。