MABEL INC;株式会社メイベル;NARA MEDICAL UNIV;公立大学法人奈良県立医科大学
发明人:
MORI TOSHIO,森 俊雄,SUGIURA SHIGEKI,杉浦 重樹,TAKAGI YUMI,▲高▼木 由美
申请号：
JP2018028157
公开号：
JP2019142804A
申请日:
2018.02.20
申请国别(地区):
JP
年份:
2019
代理人:
摘要：
To provide monoclonal antibodies and an antigen-binding fragment thereof which specifically bind to adenosine-type cyclopurine (Cyclo-dA) on DNA, which have no need to destructively extract a DNA sample from a tissue sample or completely decompose to mononucleotide, and can be used simply with higher sensitivity than known antibodies.SOLUTION: Provided is an antibody or antigen-binding fragment thereof that specifically binds to adenosine-type cyclopurine, in which a heavy chain variable (VH) region and a light chain variable (VL) region comprising three complementarity determining regions (CDRs) respectively are comprised, the amino acid sequence of CDR1 in the VH region is Gly-Tyr-Ser-Ile-Thr-Ser-Gly-Tyr-Ser (SEQ ID NO: 1), and the amino acid sequence of CDR2 in the VH region is Ile-His-Tyr-Ser-Gly -Arg-Thr (SEQ ID NO: 2), the amino acid sequence of CDR3 in the VH region is Ala-Thr-Tyr-Asp-Tyr-Asp-Gly-Tyr-Tyr-Val-Met-Asp-Tyr (SEQ ID NO: 3), the amino acid sequence of CDR1 in the VL region is Gln-Ser-Ile-Val-Asn-Ser-Asn-Gly-Asn-Thr-Tyr (SEQ ID NO: 4), the amino acid sequence of CDR2 in the VL region is Lys-Val-Ser (SEQ ID NO: 5), and the amino acid sequence of CDR3 in the VL region is Phe-Gln-Gly-Ser-His-Val-Pro-Arg-Thr (SEQ ID NO: 6), or the antibody or antigen-binding fragment comprising 1-3 conservative amino acid substitutions in one or more amino acid sequences selected from the group consisting of SEQ ID NOs: 1, 3, 4, and 6, and function-conservative variants thereof.SELECTED DRAWING: None【課題】組織サンプルから破壊的にＤＮＡサンプルを抽出したり、モノヌクレオチドまで完全に分解することが必須ではなく、かつ、公知の抗体よりも感度が高く簡便に使用することができる、ＤＮＡ上のアデノシン型サイクロプリン（Ｃｙｃｌｏ－ｄＡ）に特異的に結合するモノクローナル抗体ならびにその抗原結合断片を提供すること。【解決手段】それぞれ３つの相補性決定領域（ＣＤＲ）を含む重鎖可変（ＶＨ）領域および軽鎖可変（ＶＬ）領域を含み、ＶＨ領域のＣＤＲ１のアミノ酸配列がＧｌｙ－Ｔｙｒ－Ｓｅｒ－Ｉｌｅ－Ｔｈｒ－Ｓｅｒ－Ｇｌｙ－Ｔｙｒ－Ｓｅｒ（配列番号１）であり、ＶＨ領域のＣＤＲ２のアミノ酸配列がＩｌｅ－Ｈｉｓ－Ｔｙｒ－Ｓｅｒ－Ｇｌｙ－Ａｒｇ－Ｔｈｒ（配列番号２）であり、ＶＨ領域のＣＤＲ３のアミノ酸配列がＡｌａ－Ｔｈｒ－Ｔｙｒ－Ａｓｐ－Ｔｙｒ－Ａｓｐ－Ｇｌｙ－Ｔｙｒ－Ｔｙｒ－Ｖａｌ－Ｍｅｔ－Ａｓｐ－Ｔｙｒ（配列番号３）であり、ＶＬ領域のＣＤＲ１のアミノ酸配列がＧｌｎ－Ｓｅｒ－Ｉｌｅ－Ｖａｌ－Ａｓｎ－Ｓｅｒ－Ａｓｎ－Ｇｌｙ－Ａｓｎ－Ｔｈｒ－Ｔｙｒ（配列番号４）であり、Ｖ
