JPWO2019229658A5 - - Google Patents

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JPWO2019229658A5
JPWO2019229658A5 JP2020566241A JP2020566241A JPWO2019229658A5 JP WO2019229658 A5 JPWO2019229658 A5 JP WO2019229658A5 JP 2020566241 A JP2020566241 A JP 2020566241A JP 2020566241 A JP2020566241 A JP 2020566241A JP WO2019229658 A5 JPWO2019229658 A5 JP WO2019229658A5
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JP2021525510A (en
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Priority claimed from PCT/IB2019/054422 external-priority patent/WO2019229658A1/en
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特定の態様及び特許請求の範囲が本明細書で詳細に開示されてきたが、これは例示のみを目的として例として行われたものであり、添付の特許請求の範囲、又は任意の対応する将来の出願の特許請求の範囲の主題の範囲に関して限定することを意図するものではない。特に、本発明者らは、特許請求の範囲によって定義される本開示の趣旨及び範囲から逸脱することなく、本開示に対して様々な置換、変更、及び修正を行うことができることを意図している。核酸出発物質、目的のクローン、又はライブラリー型の選択は、本明細書に記載される態様の知識を有する当業者にとって日常的な問題であると考えられる。他の態様、利点、及び修正は、以下の特許請求の範囲内にあると考えられる。当業者は、日常的な実験のみを用いて、本明細書に記載される本発明の特定の態様の多くの等価物を認識するか、又は確認することができる。このような等価物は、添付の特許請求の範囲に包含されるものとする。後に提出される対応する出願におけるクレームの範囲の再作成は、様々な国の特許法による制限に起因する場合があり、クレームの主題を放棄するものと解釈されるべきではない。
本発明は以下の態様を含み得る。
［１］
ヒトＥＮＴＰＤ２タンパク質に特異的に結合する抗体又はその抗原結合断片であって、前記抗体又はその抗原結合断片が、表１に提供される任意の抗体又は抗原結合断片の重鎖相補性決定領域１（ＨＣＤＲ１）、重鎖相補性決定領域２（ＨＣＤＲ２）、重鎖相補性決定領域３（ＨＣＤＲ３）、軽鎖相補性決定領域１（ＬＣＤＲ１）、軽鎖相補性決定領域２（ＬＣＤＲ２）、及び軽鎖相補性決定領域３（ＬＣＤＲ３）を含む、抗体又はその抗原結合断片。
［２］
前記ＨＣＤＲ１、ＨＣＤＲ２、ＨＣＤＲ３、ＬＣＤＲ１、ＬＣＤＲ２、及びＬＣＤＲ３が、表１に提供されるＨＣＤＲ１、ＨＣＤＲ２、ＨＣＤＲ３、ＬＣＤＲ１、ＬＣＤＲ２、及びＬＣＤＲ３配列から選択される、［１］に記載の抗体又はその抗原結合断片。
［３］
前記抗体又はその抗原結合断片が、表１に提供される重鎖可変領域を含む、［１］又は［２］に記載の抗体又はその抗原結合断片。
［４］
前記抗体又はその抗原結合断片が、表１に提供される軽鎖可変領域を含む、［１］～［３］のいずれか一項に記載の抗体又はその抗原結合断片。
［５］
前記抗体又はその抗原結合断片が、以下の任意の１つ：
１）以下を含む抗体又はその抗原結合断片：
配列番号１を含むＨＣＤＲ１配列、
配列番号２を含むＨＣＤＲ２配列、
配列番号３を含むＨＣＤＲ３配列、
配列番号１４を含むＬＣＤＲ１配列、
配列番号１５を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列；
２）以下を含む抗体又はその抗原結合断片：
配列番号４を含むＨＣＤＲ１配列、
配列番号５を含むＨＣＤＲ２配列、
配列番号３を含むＨＣＤＲ３配列、
配列番号１７を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号１９を含むＬＣＤＲ３配列；
３）以下を含む抗体又はその抗原結合断片：
配列番号７を含むＨＣＤＲ１配列、
配列番号８を含むＨＣＤＲ２配列、
配列番号９を含むＨＣＤＲ３配列、
配列番号２０を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列；
４）以下を含む抗体又はその抗原結合断片：
配列番号３７を含むＨＣＤＲ１配列、
配列番号３８を含むＨＣＤＲ２配列、
配列番号３９を含むＨＣＤＲ３配列、
配列番号５０を含むＬＣＤＲ１配列、
配列番号５１を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
５）以下を含む抗体又はその抗原結合断片：
配列番号４０を含むＨＣＤＲ１配列、
配列番号４１を含むＨＣＤＲ２配列、
配列番号３９を含むＨＣＤＲ３配列、
配列番号５３を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５５を含むＬＣＤＲ３配列；
６）以下を含む抗体又はその抗原結合断片：
配列番号４３を含むＨＣＤＲ１配列、
配列番号４４を含むＨＣＤＲ２配列、
配列番号４５を含むＨＣＤＲ３配列、
配列番号５６を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
７）以下を含む抗体又はその抗原結合断片：
配列番号３７を含むＨＣＤＲ１配列、
配列番号３８を含むＨＣＤＲ２配列、
配列番号３９を含むＨＣＤＲ３配列、
配列番号６１を含むＬＣＤＲ１配列、
配列番号５１を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
８）以下を含む抗体又はその抗原結合断片：
配列番号４０を含むＨＣＤＲ１配列、
配列番号４１を含むＨＣＤＲ２配列、
配列番号３９を含むＨＣＤＲ３配列、
配列番号６２を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５５を含むＬＣＤＲ３配列；
９）以下を含む抗体又はその抗原結合断片：
配列番号４３を含むＨＣＤＲ１配列、
配列番号４４を含むＨＣＤＲ２配列、
配列番号４５を含むＨＣＤＲ３配列、
配列番号６３を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
１０）以下を含む抗体又はその抗原結合断片：
配列番号３７を含むＨＣＤＲ１配列、
配列番号３８を含むＨＣＤＲ２配列、
配列番号６８を含むＨＣＤＲ３配列、
配列番号５０を含むＬＣＤＲ１配列、
配列番号５１を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
１１）以下を含む抗体又はその抗原結合断片：
配列番号４０を含むＨＣＤＲ１配列、
配列番号４１を含むＨＣＤＲ２配列、
配列番号６８を含むＨＣＤＲ３配列、
配列番号５３を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５５を含むＬＣＤＲ３配列；
１２）以下を含む抗体又はその抗原結合断片：
配列番号４３を含むＨＣＤＲ１配列、
配列番号４４を含むＨＣＤＲ２配列、
配列番号６９を含むＨＣＤＲ３配列、
配列番号５６を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
１３）以下を含む抗体又はその抗原結合断片：
配列番号８２を含むＨＣＤＲ１配列、
配列番号８３を含むＨＣＤＲ２配列、
配列番号８４を含むＨＣＤＲ３配列、
配列番号９５を含むＬＣＤＲ１配列、
配列番号９６を含むＬＣＤＲ２配列、及び
配列番号９７を含むＬＣＤＲ３配列；
１４）以下を含む抗体又はその抗原結合断片：
配列番号８５を含むＨＣＤＲ１配列、
配列番号８６を含むＨＣＤＲ２配列、
配列番号８４を含むＨＣＤＲ３配列、
配列番号９８を含むＬＣＤＲ１配列、
配列番号９９を含むＬＣＤＲ２配列、及び
配列番号１００を含むＬＣＤＲ３配列；
１５）以下を含む抗体又はその抗原結合断片：
配列番号８８を含むＨＣＤＲ１配列、
配列番号８９を含むＨＣＤＲ２配列、
配列番号９０を含むＨＣＤＲ３配列、
配列番号１０１を含むＬＣＤＲ１配列、
配列番号９９を含むＬＣＤＲ２配列、及び
配列番号９７を含むＬＣＤＲ３配列；
１６）以下を含む抗体又はその抗原結合断片：
配列番号１０６を含むＨＣＤＲ１配列、
配列番号１０７を含むＨＣＤＲ２配列、
配列番号１０８を含むＨＣＤＲ３配列、
配列番号１１９を含むＬＣＤＲ１配列、
配列番号１２０を含むＬＣＤＲ２配列、及び
配列番号１２１を含むＬＣＤＲ３配列；
１７）以下を含む抗体又はその抗原結合断片：
配列番号１０９を含むＨＣＤＲ１配列、
配列番号１１０を含むＨＣＤＲ２配列、
配列番号１０８を含むＨＣＤＲ３配列、
配列番号１２２を含むＬＣＤＲ１配列、
配列番号９９を含むＬＣＤＲ２配列、及び
配列番号１２３を含むＬＣＤＲ３配列；
１８）以下を含む抗体又はその抗原結合断片：
配列番号１１２を含むＨＣＤＲ１配列、
配列番号１１３を含むＨＣＤＲ２配列、
配列番号１１４を含むＨＣＤＲ３配列、
配列番号１２４を含むＬＣＤＲ１配列、
配列番号９９を含むＬＣＤＲ２配列、及び
配列番号１２１を含むＬＣＤＲ３配列；
１９）以下を含む抗体又はその抗原結合断片：
配列番号１０６を含むＨＣＤＲ１配列、
配列番号１２９を含むＨＣＤＲ２配列、
配列番号１０８を含むＨＣＤＲ３配列、
配列番号１１９を含むＬＣＤＲ１配列、
配列番号１２０を含むＬＣＤＲ２配列、及び
配列番号１２１を含むＬＣＤＲ３配列；
２０）以下を含む抗体又はその抗原結合断片：
配列番号１０９を含むＨＣＤＲ１配列、
配列番号１３０を含むＨＣＤＲ２配列、
配列番号１０８を含むＨＣＤＲ３配列、
配列番号１２２を含むＬＣＤＲ１配列、
配列番号９９を含むＬＣＤＲ２配列、及び
配列番号１２３を含むＬＣＤＲ３配列；
２１）以下を含む抗体又はその抗原結合断片：
配列番号１１２を含むＨＣＤＲ１配列、
配列番号１３１を含むＨＣＤＲ２配列、
配列番号１１４を含むＨＣＤＲ３配列、
配列番号１２４を含むＬＣＤＲ１配列、
配列番号９９を含むＬＣＤＲ２配列、及び
配列番号１２１を含むＬＣＤＲ３配列；
２２）以下を含む抗体又はその抗原結合断片：
配列番号１３６を含むＨＣＤＲ１配列、
配列番号１３７を含むＨＣＤＲ２配列、
配列番号１３８を含むＨＣＤＲ３配列、
配列番号１４９を含むＬＣＤＲ１配列、
配列番号１５０を含むＬＣＤＲ２配列、及び
配列番号１５１を含むＬＣＤＲ３配列；
２３）以下を含む抗体又はその抗原結合断片：
配列番号１３９を含むＨＣＤＲ１配列、
配列番号１４０を含むＨＣＤＲ２配列、
配列番号１３８を含むＨＣＤＲ３配列、
配列番号１５２を含むＬＣＤＲ１配列、
配列番号１５３を含むＬＣＤＲ２配列、及び
配列番号１５４を含むＬＣＤＲ３配列；
２４）以下を含む抗体又はその抗原結合断片：
配列番号１４２を含むＨＣＤＲ１配列、
配列番号１４３を含むＨＣＤＲ２配列、
配列番号１４４を含むＨＣＤＲ３配列、
配列番号１５５を含むＬＣＤＲ１配列、
配列番号１５３を含むＬＣＤＲ２配列、及び
配列番号１５１を含むＬＣＤＲ３配列；
２５）以下を含む抗体又はその抗原結合断片：
配列番号１６０を含むＨＣＤＲ１配列、
配列番号１６１を含むＨＣＤＲ２配列、
配列番号１６２を含むＨＣＤＲ３配列、
配列番号１７３を含むＬＣＤＲ１配列、
配列番号１５０を含むＬＣＤＲ２配列、及び
配列番号１７４を含むＬＣＤＲ３配列；
２６）以下を含む抗体又はその抗原結合断片：
配列番号１６３を含むＨＣＤＲ１配列、
配列番号１６４を含むＨＣＤＲ２配列、
配列番号１６２を含むＨＣＤＲ３配列、
配列番号１７５を含むＬＣＤＲ１配列、
配列番号１５３を含むＬＣＤＲ２配列、及び
配列番号１７６を含むＬＣＤＲ３配列；
２７）以下を含む抗体又はその抗原結合断片：
配列番号１６６を含むＨＣＤＲ１配列、
配列番号１６７を含むＨＣＤＲ２配列、
配列番号１６８を含むＨＣＤＲ３配列、
配列番号１７７を含むＬＣＤＲ１配列、
配列番号１５３を含むＬＣＤＲ２配列、及び
配列番号１７４を含むＬＣＤＲ３配列；
２８）以下を含む抗体又はその抗原結合断片：
配列番号３７を含むＨＣＤＲ１配列、
配列番号２２０を含むＨＣＤＲ２配列、
配列番号２２１を含むＨＣＤＲ３配列、
配列番号６１を含むＬＣＤＲ１配列、
配列番号５１を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
２９）以下を含む抗体又はその抗原結合断片：
配列番号４０を含むＨＣＤＲ１配列、
配列番号２２２を含むＨＣＤＲ２配列、
配列番号２２１を含むＨＣＤＲ３配列、
配列番号６２を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５５を含むＬＣＤＲ３配列；
３０）以下を含む抗体又はその抗原結合断片：
配列番号４３を含むＨＣＤＲ１配列、
配列番号２２３を含むＨＣＤＲ２配列、
配列番号２２４を含むＨＣＤＲ３配列、
配列番号６３を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
３１）以下を含む抗体又はその抗原結合断片：
配列番号３７を含むＨＣＤＲ１配列、
配列番号２２０を含むＨＣＤＲ２配列、
配列番号６８を含むＨＣＤＲ３配列、
配列番号６１を含むＬＣＤＲ１配列、
配列番号５１を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
３２）以下を含む抗体又はその抗原結合断片：
配列番号４０を含むＨＣＤＲ１配列、
配列番号２２２を含むＨＣＤＲ２配列、
配列番号６８を含むＨＣＤＲ３配列、
配列番号６２を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５５を含むＬＣＤＲ３配列；
３３）以下を含む抗体又はその抗原結合断片：
配列番号４３を含むＨＣＤＲ１配列、
配列番号２２３を含むＨＣＤＲ２配列、
配列番号６９を含むＨＣＤＲ３配列、
配列番号６３を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
３４）以下を含む抗体又はその抗原結合断片：
配列番号１を含むＨＣＤＲ１配列、
配列番号２４５を含むＨＣＤＲ２配列、
配列番号２４６を含むＨＣＤＲ３配列、
配列番号２５４を含むＬＣＤＲ１配列、
配列番号１５を含むＬＣＤＲ２配列、及び
配列番号２５５を含むＬＣＤＲ３配列；
３５）以下を含む抗体又はその抗原結合断片：
配列番号４を含むＨＣＤＲ１配列、
配列番号２４７を含むＨＣＤＲ２配列、
配列番号２４６を含むＨＣＤＲ３配列、
配列番号１７を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号２５６を含むＬＣＤＲ３配列；
３６）以下を含む抗体又はその抗原結合断片：
配列番号７を含むＨＣＤＲ１配列、
配列番号２４８を含むＨＣＤＲ２配列、
配列番号２４９を含むＨＣＤＲ３配列、
配列番号２０を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号２５５を含むＬＣＤＲ３配列；
３７）以下を含む抗体又はその抗原結合断片：
配列番号１を含むＨＣＤＲ１配列、
配列番号２６１を含むＨＣＤＲ２配列、
配列番号２６２を含むＨＣＤＲ３配列、
配列番号２５４を含むＬＣＤＲ１配列、
配列番号１５を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列；
３８）以下を含む抗体又はその抗原結合断片：
配列番号４を含むＨＣＤＲ１配列、
配列番号２４７を含むＨＣＤＲ２配列、
配列番号２６２を含むＨＣＤＲ３配列、
配列番号１７を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号１９を含むＬＣＤＲ３配列；
３９）以下を含む抗体又はその抗原結合断片：
配列番号７を含むＨＣＤＲ１配列、
配列番号２４８を含むＨＣＤＲ２配列、
配列番号２６３を含むＨＣＤＲ３配列、
配列番号２０を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列；
４０）以下を含む抗体又はその抗原結合断片：
配列番号２７２を含むＨＣＤＲ１配列、
配列番号２７３を含むＨＣＤＲ２配列、
配列番号２７４を含むＨＣＤＲ３配列、
配列番号２５４を含むＬＣＤＲ１配列、
配列番号２８５を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列；
４１）以下を含む抗体又はその抗原結合断片：
配列番号２７５を含むＨＣＤＲ１配列、
配列番号２７６を含むＨＣＤＲ２配列、
配列番号２７４を含むＨＣＤＲ３配列、
配列番号１７を含むＬＣＤＲ１配列、
配列番号２８６を含むＬＣＤＲ２配列、及び
配列番号１９を含むＬＣＤＲ３配列；
４２）以下を含む抗体又はその抗原結合断片：
配列番号２７８を含むＨＣＤＲ１配列、
配列番号２７９を含むＨＣＤＲ２配列、
配列番号２８０を含むＨＣＤＲ３配列、
配列番号２０を含むＬＣＤＲ１配列、
配列番号２８６を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列
から選択される、［１］又は［２］に記載の抗体又はその抗原結合断片。
［６］
前記抗体又はその抗原結合断片が、以下の任意の１つ：
１）配列番号１０又はそれと少なくとも約９５％以上同一の配列を含む重鎖可変領域（ＶＨ）、及び配列番号２１又はそれと少なくとも約９５％以上同一の配列を含む軽鎖可変領域（ＶＬ）を含む抗体又はその抗原結合断片；
２）配列番号２５又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号２９又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
３）配列番号３３又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号２９又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
４）配列番号４６又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号５７又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
５）配列番号４６又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号６４又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
６）配列番号７０又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号７４又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
７）配列番号２５又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号７８又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
８）配列番号９１又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号１０２又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
９）配列番号１１５又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号１２５又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１０）配列番号１３２又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号１２５又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１１）配列番号１４５又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号１５６又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１２）配列番号１６９又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号１７８又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１３）配列番号２２５又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号２２９又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１４）配列番号２３３又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号２３７又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１５）配列番号２４１又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号２２９又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１６）配列番号２５０又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号２５７又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１７）配列番号２６４又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号２６８又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；又は
１８）配列番号２８１又はそれと少なくとも約９５％以上同一の配列を含むＶＨ、及び配列番号２８７又はそれと少なくとも約９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片
から選択される、［１］～［５］のいずれか一項に記載の抗体又はその抗原結合断片。
［７］
抗体又はその抗原結合断片が、以下の任意の１つ：
１）配列番号１２又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号２３又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
２）配列番号２７又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号３１又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
３）配列番号３５又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号３１又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
４）配列番号４８又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号５９又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
５）配列番号４８又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号６６又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
６）配列番号７２又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号７６又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
７）配列番号２７又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号８０又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
８）配列番号９３又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号１０４又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
９）配列番号１１７又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号１２７又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
１０）配列番号１３４又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号１２７又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
１１）配列番号１４７又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号１５８又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
１２）配列番号１７１又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号１８０又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
１３）配列番号２２７又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号２３１又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
１４）配列番号２３５又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号２３９又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
１５）配列番号２４３又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号２３１又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
１６）配列番号２５２又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号２５９又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；
１７）配列番号２６６又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号２７０又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体；又は
１８）配列番号２８３又はそれと少なくとも約９５％以上同一の配列を含む重鎖、及び配列番号２８９又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む抗体
から選択される、［１］～［６］のいずれか一項に記載の抗体又はその抗原結合断片。
［８］
前記抗体又はその抗原結合断片が：
配列番号１を含むＨＣＤＲ１配列、
配列番号２を含むＨＣＤＲ２配列、
配列番号３を含むＨＣＤＲ３配列、
配列番号１４を含むＬＣＤＲ１配列、
配列番号１５を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列
を含む、［１］～［７］のいずれか一項に記載の抗体又はその抗原結合断片。
［９］
前記抗体又はその抗原結合断片が：
配列番号４を含むＨＣＤＲ１配列、
配列番号５を含むＨＣＤＲ２配列、
配列番号３を含むＨＣＤＲ３配列、
配列番号１７を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号１９を含むＬＣＤＲ３配列
を含む、［１］～［７］のいずれか一項に記載の抗体又はその抗原結合断片。
［１０］
前記抗体又はその抗原結合断片が：
配列番号７を含むＨＣＤＲ１配列、
配列番号８を含むＨＣＤＲ２配列、
配列番号９を含むＨＣＤＲ３配列、
配列番号２０を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列
を含む、［１］～［７］のいずれか一項に記載の抗体又はその抗原結合断片。
［１１］
前記抗体又はその抗原結合断片が、配列番号１０又はそれと少なくとも約９５％以上同一の配列を含む重鎖可変領域（ＶＨ）、及び配列番号２１又はそれと少なくとも約９５％以上同一の配列を含む軽鎖可変領域（ＶＬ）を含む、［１］～［７］のいずれか一項に記載の抗体又はその抗原結合断片。
［１２］
前記抗体又はその抗原結合断片が、配列番号１２又はそれと少なくとも約９５％以上同一の配列、及び配列番号２３又はそれと少なくとも約９５％以上同一の配列を含む軽鎖を含む、［１］～［７］のいずれか一項に記載の抗体又はその抗原結合断片。
［１３］
前記抗体又はその抗原結合断片が、ヒトＥＮＴＰＤ２におけるエピトープに結合し、前記エピトープが、以下の残基：Ｈｉｓ５０、Ａｓｐ７６、Ｐｒｏ７８、Ｇｌｙ７９、Ｇｌｙ８０、Ｔｙｒ８５、Ａｓｐ８７、Ａｓｎ８８、Ｇｌｙ９１、Ｇｌｎ９４、Ｓｅｒ９５、Ｇｌｙ９８、Ｇｌｕ１０１、Ｇｌｎ１０２、Ｇｌｎ１０５、Ａｓｐ１０６、Ａｒｇ２４５、Ｔｈｒ２７２、Ｇｌｎ２７３、Ｌｅｕ２７５、Ａｓｐ２７８、Ａｒｇ２９８、Ａｌａ３４７、Ａｌａ３５０、Ｔｈｒ３５１、Ａｒｇ３９２、Ａｌａ３９３、Ａｒｇ３９４、又はＴｙｒ３９８の少なくとも１つを含む、［１］～［１２］のいずれか一項に記載の抗体又はその抗原結合断片。
［１４］
前記抗体又はその抗原結合断片が、ヒトＥＮＴＰＤ２におけるエピトープに結合し、前記エピトープが、以下の残基：Ｇｌｙ７９、Ｇｌｎ２５０、Ｌｅｕ２５３、Ｔｒｐ２６６、Ａｒｇ２６８、Ｇｌｙ２６９、Ｐｈｅ２７０、Ｓｅｒ２７１、Ｔｈｒ２７２、Ｇｌｎ２７３、Ｖａｌ２７４、Ｌｅｕ２７５、Ａｓｐ２７８、Ａｒｇ２９８、Ｓｅｒ３００、Ｓｅｒ３０２、Ｇｌｙ３０３、Ｔｈｒ３８０、Ｔｒｐ３８１、Ａｌａ３８２、Ｇｌｙ３９０、Ｇｌｎ３９１、Ａｒｇ３９２、Ａｌａ３９３、Ａｒｇ３９４、又はＡｓｐ３９７の少なくとも１つを含む、［１］～［１２］のいずれか一項に記載の抗体又はその抗原結合断片。
［１５］
ヒトＥＮＴＰＤ２におけるエピトープに特異的に結合する抗体又はその抗原結合断片であって、前記エピトープが、以下の残基：Ｈｉｓ５０、Ａｓｐ７６、Ｐｒｏ７８、Ｇｌｙ７９、Ｇｌｙ８０、Ｔｙｒ８５、Ａｓｐ８７、Ａｓｎ８８、Ｇｌｙ９１、Ｇｌｎ９４、Ｓｅｒ９５、Ｇｌｙ９８、Ｇｌｕ１０１、Ｇｌｎ１０２、Ｇｌｎ１０５、Ａｓｐ１０６、Ａｒｇ２４５、Ｔｈｒ２７２、Ｇｌｎ２７３、Ｌｅｕ２７５、Ａｓｐ２７８、Ａｒｇ２９８、Ａｌａ３４７、Ａｌａ３５０、Ｔｈｒ３５１、Ａｒｇ３９２、Ａｌａ３９３、Ａｒｇ３９４、又はＴｙｒ３９８の少なくとも１つを含む、抗体又はその抗原結合断片。
［１６］
ヒトＥＮＴＰＤ２におけるエピトープに特異的に結合する抗体又はその抗原結合断片であって、前記エピトープが、以下の残基：Ｇｌｙ７９、Ｇｌｎ２５０、Ｌｅｕ２５３、Ｔｒｐ２６６、Ａｒｇ２６８、Ｇｌｙ２６９、Ｐｈｅ２７０、Ｓｅｒ２７１、Ｔｈｒ２７２、Ｇｌｎ２７３、Ｖａｌ２７４、Ｌｅｕ２７５、Ａｓｐ２７８、Ａｒｇ２９８、Ｓｅｒ３００、Ｓｅｒ３０２、Ｇｌｙ３０３、Ｔｈｒ３８０、Ｔｒｐ３８１、Ａｌａ３８２、Ｇｌｙ３９０、Ｇｌｎ３９１、Ａｒｇ３９２、Ａｌａ３９３、Ａｒｇ３９４、又はＡｓｐ３９７の少なくとも１つを含む、抗体又はその抗原結合断片。
［１７］
ヒトＥＮＴＰＤ２タンパク質に対する結合について、表１に提供される任意の抗体又は抗原結合断片と競合する、抗体又はその抗原結合断片。
［１８］
表１に提供される任意の抗体又は抗原結合断片のいずれかのエピトープと同じエピトープ、実質的に同じエピトープ、それと重複するエピトープ、それと実質的に重複するエピトープに結合する、抗体又はその抗原結合断片。
［１９］
前記抗体又はその抗原結合断片が、例えばＢｉａｃｏｒｅにより測定して、１０ｎＭ未満の解離定数（Ｋ Ｄ ）でヒトＥＮＴＰＤ２タンパク質に結合する、［１］～［１８］のいずれか一項に記載の抗体又はその抗原結合断片。
［２０］
前記抗体又はその抗原結合断片が、例えばＢｉａｃｏｒｅにより測定して、５ｎＭ未満の解離定数（Ｋ Ｄ ）でヒトＥＮＴＰＤ２タンパク質に結合する、［１］～［１８］のいずれか一項に記載の抗体又はその抗原結合断片。
［２１］
前記抗体又はその抗原結合断片が、例えばＢｉａｃｏｒｅにより測定して、３ｎＭ未満の解離定数（Ｋ Ｄ ）でヒトＥＮＴＰＤ２タンパク質に結合する、［１］～［１８］のいずれか一項に記載の抗体又はその抗原結合断片。
［２２］
前記抗体又はその抗原結合断片が、ヒトＥＮＴＰＤ２酵素活性を少なくとも４０％、少なくとも５０％、少なくとも６０％、少なくとも７０％、少なくとも８０％、又は少なくとも９０％阻害する、［１］～［２１］のいずれか一項に記載の抗体又はその抗原結合断片。
［２３］
前記抗体又はその抗原結合断片が、アデノシン三リン酸塩（ＡＴＰ）の加水分解のＥＮＴＰＤ２の能力を阻害する、［１］～［２２］のいずれか一項に記載の抗体又はその抗原結合断片。
［２４］
前記抗体又はその抗原結合断片が、ＥＮＴＰＤ２へのＡＴＰの結合を妨害し、又はＥＮＴＰＤ２の触媒ドメイン内にＡＴＰを捕捉する、［１］～［２３］のいずれか一項に記載の抗体又はその抗原結合断片。
［２５］
前記抗体が、ＩｇＧ１、ＩｇＧ２、ＩｇＧ３又はＩｇＧ４アイソタイプを有する、［１］～［２４］のいずれか一項に記載の抗体又はその抗原結合断片。
［２６］
前記抗体又はその抗原結合断片が、ＩｇＧ１ Ｆｃ領域、ＩｇＧ２ Ｆｃ領域、ＩｇＧ４ Ｆｃ領域、又はＩｇＧ２／ＩｇＧ４ハイブリッドＦｃ領域から選択されるＦｃ領域を含む、［１］～［２５］のいずれか一項に記載の抗体又はその抗原結合断片。
［２７］
前記抗体又はその抗原結合断片が、前記親抗体と比較して低下した抗体依存性細胞傷害（ＡＤＣＣ）又は補体依存性細胞傷害（ＣＤＣ）活性を有する改変されたＦｃ領域を含む、［１］～［２６］のいずれか一項に記載の抗体又はその抗原結合断片。
［２８］
前記抗体又はその抗原結合断片が、ヒト又はヒト化抗体又はその断片である、［１］～［２７］のいずれか一項に記載の抗体又はその抗原結合断片。
［２９］
［１］～［２８］のいずれか一項に記載の抗体又はその抗原結合断片をコードする核酸又は核酸のセット。
［３０］
［２９］に記載の核酸又は核酸のセットを含むベクター。
［３１］
前記ベクターが、ＤＮＡベクター、ＲＮＡベクター、プラスミド、コスミド、又はウイルスベクターから選択される、［３０］に記載のベクター。
［３２］
前記ベクターが、以下のウイルス：レンチウイルス、アデノウイルス、アデノ随伴ウイルス（ＡＡＶ）、単純ヘルペスウイルス（ＨＳＶ）、パルボウイルス、レトロウイルス、ワクシニアウイルス、シンビス（Ｓｉｎｂｉｓ）ウイルス、インフルエンザウイルス、レオウイルス、ニューカッスル病ウイルス（ＮＤＶ）、はしかウイルス、水疱性口内炎ウイルス（ＶＳＶ）、ポリオウイルス、ポックスウイルス、セネカバレー（Ｓｅｎｅｃａ Ｖａｌｌｅｙ）ウイルス、コクサッキーウイルス、エンテロウイルス、粘液腫ウイルス、又はマラバウイルスの任意の１つに基づくウイルスベクターである、［３１］に記載のベクター。
［３３］
前記ベクターがＡＡＶベクターである、［３２］に記載のベクター。
［３４］
前記ベクターがレンチウイルスベクターである、［３１］に記載のベクター。
［３５］
プロモーターをさらに含む、［３０］～［３４］のいずれか一項に記載のベクター。
［３６］
検出可能マーカーをさらに含む、［３０］～［３５］のいずれか一項に記載のベクター。
［３７］
２９に記載の核酸若しくは核酸のセット又は［３０］～［３６］のいずれか一項に記載のベクターを含む細胞。
［３８］
［３７］に記載の細胞を培養し、前記抗体又はその抗原結合断片を培養培地から収集することを含む、抗体又はその抗原結合断片の産生方法。
［３９］
［１］～［２８］のいずれか一項に記載の抗体又はその抗原結合断片、［２９］に記載の核酸又は核酸のセット、［３０］～［３６］のいずれか一項に記載のベクター、又は［３７］に記載の細胞、及び薬学的に許容される担体を含む医薬組成物。
［４０］
医薬としての使用のための、［１］～［２８］のいずれか一項に記載の抗体又はその抗原結合断片、［２９］に記載の核酸又は核酸のセット、［３０］～［３６］のいずれか一項に記載のベクター、［３７］に記載の細胞、又は［３９］に記載の医薬組成物。
［４１］
癌の処置における使用のための、［１］～［２８］のいずれか一項に記載の抗体又はその抗原結合断片、［２９］に記載の核酸、［３０］～［３６］のいずれか一項に記載のベクター、［３７］に記載の細胞、又は［３９］に記載の医薬組成物。
［４２］
癌の処置のための医薬の製造における、［１］～［２８］のいずれか一項に記載の抗体又はその抗原結合断片、［２９］に記載の核酸、［３０］～［３６］のいずれか一項に記載のベクター、［３７］に記載の細胞、又は［３９］に記載の医薬組成物の使用。
［４３］
前記癌が、ＥＮＴＰＤ２＋癌である、［４１］に記載の使用のための抗体、又は［４２］に記載の使用。
［４４］
前記癌が、結腸直腸癌（ＣＲＣ）、胃癌（例えば、胃腺癌、胃癌腫）、食道癌（例えば、食道扁平上皮癌（ＥＳＣＣ））、膵癌、胆管癌、肺癌（例えば、小細胞肺癌）、乳癌（例えば、乳腺癌）、又は卵巣癌である、［４１］に記載の使用のための抗体、又は［４２］に記載の使用。
［４５］
前記抗体又はその抗原結合断片、前記核酸又は核酸のセット、前記ベクター、前記細胞、又は前記医薬組成物が、静脈内、腫瘍内又は皮下経路を介して前記対象に投与される、［４１］に記載の使用のための抗体、又は［４２］に記載の使用。
［４６］
前記抗体分子が、少なくとも１つの追加の治療薬又は手順と組み合わせて投与される、［４１］に記載の使用のための抗体、又は［４２］に記載の使用。
［４７］
前記少なくとも１つの追加の治療薬又は手順が、化学療法、標的化抗癌療法、腫瘍溶解性薬物、細胞毒性剤、免疫ベースの治療法、サイトカイン、外科手技、放射線療法、共刺激分子の活性化因子、阻害分子の阻害剤、ワクチン、又は細胞療法の１つ以上から選択される、［４６］に記載の使用のための抗体、又は［４６］に記載の使用。
［４８］
前記少なくとも１つの追加の治療薬が、ＰＤ－１阻害剤、例えばＰＤ－１抗体である、［４６］に記載の使用のための抗体又は［４６］に記載の使用。
［４９］
前記ＰＤ－１阻害剤が、ＰＤＲ００１、ニボルマブ、ペムブロリズマブ、ピディリズマブ、ＭＥＤＩ０６８０、ＲＥＧＮ２８１０、ＴＳＲ－０４２、ＰＦ－０６８０１５９１、又はＡＭＰ－２２４から選択される、［４８］に記載の使用のための抗体、又は［４８］に記載の使用。
［５０］
前記少なくとも１つの追加の治療薬が、ＰＤ－Ｌ１阻害剤、例えば、ＰＤ－Ｌ１抗体である、［４６］に記載の使用のための抗体、又は［４６］に記載の使用。
［５１］
前記ＰＤ－Ｌ１阻害剤が、ＦＡＺ０５３、アテゾリズマブ、アベルマブ、デュルバルマブ、又はＢＭＳ－９３６５５９から選択される、［５０］に記載の使用のための抗体、又は［５０］に記載の使用。
［５２］
前記少なくとも１つの追加の治療薬が、Ａ２ＡＲアンタゴニストであり、前記Ａ２ＡＲアンタゴニストが：
ｉ．抗ＣＤ７３抗体分子若しくはその抗原結合断片であって、場合により前記抗ＣＤ７３抗体は、以下：
ａ．配列番号２９５のアミノ酸配列を含む重鎖可変領域及び配列番号２９６のアミノ酸配列を含む軽鎖可変領域、又は配列番号２９５又は２９６と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
ｂ．配列番号２９９のアミノ酸配列を含む重鎖可変領域及び配列番号３００のアミノ酸配列を含む軽鎖可変領域、又は配列番号２９９又は３００と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
ｃ．配列番号３０２のアミノ酸配列を含む重鎖可変領域及び配列番号３０３のアミノ酸配列を含む軽鎖可変領域、又は配列番号３０２又は３０３と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
ｄ．配列番号３０４のアミノ酸配列を含む重鎖可変領域及び配列番号３０５のアミノ酸配列を含む軽鎖可変領域、又は配列番号３０４又は３０５と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
ｅ．配列番号３０６のアミノ酸配列を含む重鎖可変領域及び配列番号３０７のアミノ酸配列を含む軽鎖可変領域、又は配列番号３０６又は３０７と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；又は
ｆ．配列番号３０８のアミノ酸配列を含む重鎖可変領域及び配列番号３０９のアミノ酸配列を含む軽鎖可変領域、又は配列番号３０８又は３０９と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
から選択される抗ＣＤ７３抗体分子若しくはその抗原結合断片、
又は
ｉｉ．ＰＢＦ５０９／ＮＩＲ１７８、ＣＰＩ４４４／Ｖ８１４４４、ＡＺＤ４６３５／ＨＴＬ－１０７１、ビパデナント、ＧＢＶ－２０３４、ＡＢ９２８、テオフィリン、イストラデフィリン、トザデナント／ＳＹＮ－１１５、ＫＷ－６３５６、ＳＴ－４２０６、及びプレラデナント／ＳＣＨ ４２０８１４；又は
ｉｉｉ．５－ブロモ－２，６－ジ－（１Ｈ－ピラゾール－１－イル）ピリミジン－４－アミン、又はその薬学的に許容される塩；（Ｓ）－７－（５－メチルフラン－２－イル）－３－（（６－（（（テトラヒドロフラン－３－イル）オキシ）メチル）ピリジン－２－イル）メチル）－３Ｈ－［１，２，３］トリアゾロ［４，５－ｄ］ピリミジン－５－アミン、又はその薬学的に許容される塩；（Ｒ）－７－（５－メチルフラン－２－イル）－３－（（６－（（（テトラヒドロフラン－３－イル）オキシ）メチル）ピリジン－２－イル）メチル）－３Ｈ－［１，２，３］トリアゾロ［４，５－ｄ］ピリミジン－５－アミン、又はそのラセミ体、又はその薬学的に許容される塩；７－（５－メチルフラン－２－イル）－３－（（６－（（（テトラヒドロフラン－３－イル）オキシ）メチル）ピリジン－２－イル）メチル）－３Ｈ－［１，２，３］トリアゾロ［４，５－ｄ］ピリミジン－５－アミン、又はその薬学的に許容される塩；及び６－（２－クロロ－６－メチルピリジン－４－イル）－５－（４－フルオロフェニル）－１，２，４－トリアジン－３－アミン、又はその薬学的に許容される塩
から選択される、［４６］～［５１］のいずれか一項に記載の使用のための抗体、又は［４６］～［５１］のいずれか一項に記載の使用。
［５３］
前記少なくとも１つの追加の治療薬が：
ｉ．ＣＴＬＡ－４阻害剤、場合により前記ＣＴＬＡ－４阻害剤は、イピリムマブ又はトレメリムマブから選択される；
ｉｉ．ＴＩＭ－３阻害剤、場合により前記ＴＩＭ－３阻害剤は、ＭＢＧ４５３、ＴＳＲ－０２２、又はＬＹ３３２１３６７から選択される；
ｉｉｉ．ＬＡＧ－３阻害剤、場合により前記ＬＡＧ－３阻害剤は、ＬＡＧ５２５、ＢＭＳ－９８６０１６、ＴＳＲ－０３３、ＭＫ－４２８０又はＲＥＧＮ３７６７から選択される；
ｉｖ．ＧＩＴＲ作動薬、場合により前記ＧＩＴＲ作動薬は、ＧＷＮ３２３、ＢＭＳ－９８６１５６、ＭＫ－４１６６、ＭＫ－１２４８、ＴＲＸ５１８、ＩＮＣＡＧＮ１８７６、ＡＭＧ ２２８、又はＩＮＢＲＸ－１１０から選択される；
ｖ．抗ＣＤ３多重特異性抗体分子、場合により前記抗ＣＤ３多重特異性抗体分子は、抗ＣＤ３ｘ抗ＣＤ１２３二重特異性抗体分子（例えば、ＸＥＮＰ１４０４５）、又は抗ＣＤ３ｘ抗ＣＤ２０二重特異性抗体分子（例えば、ＸＥＮＰ１３６７６）である；
ｖｉ．サイトカイン分子、場合により前記サイトカイン分子は、ＩＬ－１５受容体α（ＩＬ－１５Ｒａ）の可溶型と複合体化されたＩＬ－１５である；
ｖｉｉ．マクロファージコロニー－刺激因子（Ｍ－ＣＳＦ）阻害剤、場合により前記Ｍ－ＣＳＦ阻害剤は、ＭＣＳ１１０である；
ｖｉｉｉ．ＣＳＦ－１Ｒ阻害剤、場合により前記ＣＳＦ－１Ｒ阻害剤は、ＢＬＺ９４５である；
ｉｘ．インドールアミン２，３－ジオキシゲナーゼ（ＩＤＯ）及び／又はトリプトファン２，３－ジオキシゲナーゼ（ＴＤＯ）の阻害剤；
ｘ．ＴＧＦ－β阻害剤；
ｘｉ．腫瘍溶解性ウイルス；
ｘｉｉ．キメラ抗原受容体（ＣＡＲ）Ｔ細胞療法
から選択される、［４６］に記載の使用のための抗体、又は［４６］に記載の使用。
［５４］
前記少なくとも１つの追加の治療薬は、１）タンパク質キナーゼＣ（ＰＫＣ）阻害剤；２）熱ショックタンパク質９０（ＨＳＰ９０）阻害剤；３）ホスホイノシチド３－キナーゼ（ＰＩ３Ｋ）及び／又はラパマイシンの標的（ｍＴＯＲ）の阻害剤；４）チトクロムＰ４５０の阻害剤（例えば、ＣＹＰ１７阻害剤又は１７α－ヒドロキシラーゼ／Ｃ１７－２０リアーゼ阻害剤）；５）鉄キレート化剤；６）アロマターゼ阻害剤；７）ｐ５３の阻害剤、例えばｐ５３／Ｍｄｍ２相互作用の阻害剤；８）アポトーシス誘発剤；９）血管新生阻害剤；１０）アルドステロンシンターゼ阻害剤；１１）スムーズンド（ＳＭＯ）受容体阻害剤；１２）プロラクチン受容体（ＰＲＬＲ）阻害剤；１３）Ｗｎｔシグナル伝達阻害剤；１４）ＣＤＫ４／６阻害剤；１５）線維芽細胞増殖因子受容体２（ＦＧＦＲ２）／線維芽細胞増殖因子受容体４（ＦＧＦＲ４）阻害剤；１６）マクロファージコロニー刺激因子（Ｍ－ＣＳＦ）阻害剤；１７）ｃ－ＫＩＴ、ヒスタミン放出、Ｆｌｔ３（例えば、ＦＬＫ２／ＳＴＫ１）又はＰＫＣの１つ以上の阻害剤；１８）ＶＥＧＦＲ－２（例えば、ＦＬＫ－１／ＫＤＲ）、ＰＤＧＦＲβ、ｃ－ＫＩＴ又はＲａｆキナーゼＣの１つ以上の阻害剤；１９）ソマトスタチン作動薬及び／又は成長ホルモン放出阻害剤；２０）未分化リンパ腫キナーゼ（ＡＬＫ）阻害剤；２１）インスリン様増殖因子１受容体（ＩＧＦ－１Ｒ）阻害剤；２２）Ｐ－糖タンパク質１阻害剤；２３）血管内皮増殖因子受容体（ＶＥＧＦＲ）阻害剤；２４）ＢＣＲ－ＡＢＬキナーゼ阻害剤；２５）ＦＧＦＲ阻害剤；２６）ＣＹＰ１１Ｂ２の阻害剤；２７）ＨＤＭ２阻害剤、例えば前記ＨＤＭ２－ｐ５３相互作用の阻害剤；２８）チロシンキナーゼの阻害剤；２９）ｃ－ＭＥＴの阻害剤；３０）ＪＡＫの阻害剤；３１）ＤＡＣの阻害剤；３２）１１β－ヒドロキシラーゼの阻害剤；３３）ＩＡＰの阻害剤；３４）ＰＩＭキナーゼの阻害剤；３５）ポーキュパインの阻害剤；３６）ＢＲＡＦ、例えばＢＲＡＦ Ｖ６００Ｅ又は野生型ＢＲＡＦの阻害剤；３７）ＨＥＲ３の阻害剤；３８）ＭＥＫの阻害剤；又は３９）脂質キナーゼの阻害剤；又は表１６に提供される１つ以上の薬剤から選択される、［４６］に記載の使用のための抗体、又は［４６］に記載の使用。
［５５］
処置を必要とする対象における癌の処置方法であって、前記方法は、治療有効量の［１］～［２８］のいずれか一項に記載の抗体又は抗原結合断片、［２９］に記載の核酸、［３０］～［３６］のいずれか一項に記載のベクター、［３７］に記載の細胞、又は［３９］に記載の医薬組成物を前記対象に投与することを含む、方法。
［５６］
前記癌が、ＥＮＴＰＤ２＋癌である、［５５］に記載の方法。
［５７］
前記癌が、結腸直腸癌（ＣＲＣ）、胃癌（例えば、胃腺癌、胃癌腫）、食道癌（例えば、食道扁平上皮癌（ＥＳＣＣ））、膵癌、胆管癌、肺癌（例えば、小細胞肺癌）、乳癌（例えば、乳腺癌）、又は卵巣癌である、［５５］に記載の方法。
［５８］
前記抗体又はその抗原結合断片、前記核酸又は核酸のセット、前記ベクター、前記細胞、又は前記医薬組成物が、静脈内、腫瘍内又は皮下経路を介して前記対象に投与される、［５５］～［５７］のいずれか一項に記載の方法。
［５９］
対象における免疫応答の刺激方法であって、前記方法は、［１］～［２８］のいずれか一項に記載の抗体又は抗原結合断片、［２９］に記載の核酸又は核酸のセット、［３０］～［３６］のいずれか一項に記載のベクター、［３７］に記載の細胞、又は［３９］に記載の医薬組成物を、前記免疫応答を刺激するのに有効な量で前記対象に投与することを含む、方法。
［６０］
少なくとも１つの追加の治療薬又は手順を前記対象に投与することをさらに含む、［５５］～［５９］のいずれか一項に記載の方法。
［６１］
前記１つ以上の追加のの治療薬又は処置は、化学療法、標的化抗癌療法、腫瘍溶解性薬物、細胞傷害性薬剤、免疫に基づく療法、サイトカイン、外科的処置、放射線処置、共刺激分子の活性化剤、阻害分子の阻害剤、ワクチン又は細胞療法の１つ以上から選択される、［６０］に記載の方法。
［６２］
前記少なくとも１つの追加の治療薬が、ＰＤ－１阻害剤、例えばＰＤ－１抗体である、［６０］に記載の方法。
［６３］
前記ＰＤ－１阻害剤が、ＰＤＲ００１、ニボルマブ、ペムブロリズマブ、ピディリズマブ、ＭＥＤＩ０６８０、ＲＥＧＮ２８１０、ＴＳＲ－０４２、ＰＦ－０６８０１５９１、又はＡＭＰ－２２４から選択される、６２に記載の方法。
［６４］
前記少なくとも１つの追加の治療薬が、ＰＤ－Ｌ１阻害剤、例えば、ＰＤ－Ｌ１抗体である、６０に記載の方法。
［６５］
前記ＰＤ－Ｌ１阻害剤が、ＦＡＺ０５３、アテゾリズマブ、アベルマブ、デュルバルマブ、又はＢＭＳ－９３６５５９から選択される、６４に記載の方法。
［６６］
前記少なくとも１つの追加の治療薬が、Ａ２ＡＲアンタゴニストであり、前記Ａ２ＡＲアンタゴニストが：
ｉ．抗ＣＤ７３抗体分子若しくはその抗原結合断片であって、場合により前記抗ＣＤ７３抗体は、以下：
ａ．配列番号２９５のアミノ酸配列を含む重鎖可変領域及び配列番号２９６のアミノ酸配列を含む軽鎖可変領域、又は配列番号２９５又は２９６と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
ｂ．配列番号２９９のアミノ酸配列を含む重鎖可変領域及び配列番号３００のアミノ酸配列を含む軽鎖可変領域、又は配列番号２９９又は３００と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
ｃ．配列番号３０２のアミノ酸配列を含む重鎖可変領域及び配列番号３０３のアミノ酸配列を含む軽鎖可変領域、又は配列番号３０２又は３０３と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
ｄ．配列番号３０４のアミノ酸配列を含む重鎖可変領域及び配列番号３０５のアミノ酸配列を含む軽鎖可変領域、又は配列番号３０４又は３０５と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
ｅ．配列番号３０６のアミノ酸配列を含む重鎖可変領域及び配列番号３０７のアミノ酸配列を含む軽鎖可変領域、又は配列番号３０６又は３０７と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；又は
ｆ．配列番号３０８のアミノ酸配列を含む重鎖可変領域及び配列番号３０９のアミノ酸配列を含む軽鎖可変領域、又は配列番号３０８又は３０９と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
から選択される抗ＣＤ７３抗体分子若しくはその抗原結合断片、
又は
ｉｉ．ＰＢＦ５０９／ＮＩＲ１７８、ＣＰＩ４４４／Ｖ８１４４４、ＡＺＤ４６３５／ＨＴＬ－１０７１、ビパデナント、ＧＢＶ－２０３４、ＡＢ９２８、テオフィリン、イストラデフィリン、トザデナント／ＳＹＮ－１１５、ＫＷ－６３５６、ＳＴ－４２０６、及びプレラデナント／ＳＣＨ ４２０８１４；又は
ｉｉｉ．５－ブロモ－２，６－ジ－（１Ｈ－ピラゾール－１－イル）ピリミジン－４－アミン、又はその薬学的に許容される塩；（Ｓ）－７－（５－メチルフラン－２－イル）－３－（（６－（（（テトラヒドロフラン－３－イル）オキシ）メチル）ピリジン－２－イル）メチル）－３Ｈ－［１，２，３］トリアゾロ［４，５－ｄ］ピリミジン－５－アミン、又はその薬学的に許容される塩；（Ｒ）－７－（５－メチルフラン－２－イル）－３－（（６－（（（テトラヒドロフラン－３－イル）オキシ）メチル）ピリジン－２－イル）メチル）－３Ｈ－［１，２，３］トリアゾロ［４，５－ｄ］ピリミジン－５－アミン、又はそのラセミ体、又はその薬学的に許容される塩；７－（５－メチルフラン－２－イル）－３－（（６－（（（テトラヒドロフラン－３－イル）オキシ）メチル）ピリジン－２－イル）メチル）－３Ｈ－［１，２，３］トリアゾロ［４，５－ｄ］ピリミジン－５－アミン、又はその薬学的に許容される塩；及び６－（２－クロロ－６－メチルピリジン－４－イル）－５－（４－フルオロフェニル）－１，２，４－トリアジン－３－アミン、又はその薬学的に許容される塩
から選択される、［６０］に記載の方法。
［６７］
前記少なくとも１つの追加の治療薬が：
ｉ．ＣＴＬＡ－４阻害剤、場合により前記ＣＴＬＡ－４阻害剤は、イピリムマブ又はトレメリムマブから選択される；
ｉｉ．ＴＩＭ－３阻害剤、場合により前記ＴＩＭ－３阻害剤は、ＭＢＧ４５３、ＴＳＲ－０２２、又はＬＹ３３２１３６７から選択される；
ｉｉｉ．ＬＡＧ－３阻害剤、場合により前記ＬＡＧ－３阻害剤は、ＬＡＧ５２５、ＢＭＳ－９８６０１６、ＴＳＲ－０３３、ＭＫ－４２８０又はＲＥＧＮ３７６７から選択される；
ｉｖ．ＧＩＴＲ作動薬、場合により前記ＧＩＴＲ作動薬は、ＧＷＮ３２３、ＢＭＳ－９８６１５６、ＭＫ－４１６６、ＭＫ－１２４８、ＴＲＸ５１８、ＩＮＣＡＧＮ１８７６、ＡＭＧ ２２８、又はＩＮＢＲＸ－１１０から選択される；
ｖ．抗ＣＤ３多重特異性抗体分子、場合により前記抗ＣＤ３多重特異性抗体分子は、抗ＣＤ３ｘ抗ＣＤ１２３二重特異性抗体分子（例えば、ＸＥＮＰ１４０４５）、又は抗ＣＤ３ｘ抗ＣＤ２０二重特異性抗体分子（例えば、ＸＥＮＰ１３６７６）である；
ｖｉ．サイトカイン分子、場合により前記サイトカイン分子は、ＩＬ－１５受容体α（ＩＬ－１５Ｒａ）の可溶型と複合体化されたＩＬ－１５である；
ｖｉｉ．マクロファージコロニー－刺激因子（Ｍ－ＣＳＦ）阻害剤、場合により前記Ｍ－ＣＳＦ阻害剤は、ＭＣＳ１１０である；
ｖｉｉｉ．ＣＳＦ－１Ｒ阻害剤、場合により前記ＣＳＦ－１Ｒ阻害剤は、ＢＬＺ９４５である；
ｉｘ．インドールアミン２，３－ジオキシゲナーゼ（ＩＤＯ）及び／又はトリプトファン２，３－ジオキシゲナーゼ（ＴＤＯ）の阻害剤；
ｘ．ＴＧＦ－β阻害剤；
ｘｉ．腫瘍溶解性ウイルス；
ｘｉｉ．キメラ抗原受容体（ＣＡＲ）Ｔ細胞療法
から選択される、［６０］に記載の方法。
［６８］
前記少なくとも１つの追加の治療薬は、１）タンパク質キナーゼＣ（ＰＫＣ）阻害剤；２）熱ショックタンパク質９０（ＨＳＰ９０）阻害剤；３）ホスホイノシチド３－キナーゼ（ＰＩ３Ｋ）及び／又はラパマイシンの標的（ｍＴＯＲ）の阻害剤；４）チトクロムＰ４５０の阻害剤（例えば、ＣＹＰ１７阻害剤又は１７α－ヒドロキシラーゼ／Ｃ１７－２０リアーゼ阻害剤）；５）鉄キレート化剤；６）アロマターゼ阻害剤；７）ｐ５３の阻害剤、例えばｐ５３／Ｍｄｍ２相互作用の阻害剤；８）アポトーシス誘発剤；９）血管新生阻害剤；１０）アルドステロンシンターゼ阻害剤；１１）スムーズンド（ＳＭＯ）受容体阻害剤；１２）プロラクチン受容体（ＰＲＬＲ）阻害剤；１３）Ｗｎｔシグナル伝達阻害剤；１４）ＣＤＫ４／６阻害剤；１５）線維芽細胞増殖因子受容体２（ＦＧＦＲ２）／線維芽細胞増殖因子受容体４（ＦＧＦＲ４）阻害剤；１６）マクロファージコロニー刺激因子（Ｍ－ＣＳＦ）阻害剤；１７）ｃ－ＫＩＴ、ヒスタミン放出、Ｆｌｔ３（例えば、ＦＬＫ２／ＳＴＫ１）又はＰＫＣの１つ以上の阻害剤；１８）ＶＥＧＦＲ－２（例えば、ＦＬＫ－１／ＫＤＲ）、ＰＤＧＦＲβ、ｃ－ＫＩＴ又はＲａｆキナーゼＣの１つ以上の阻害剤；１９）ソマトスタチン作動薬及び／又は成長ホルモン放出阻害剤；２０）未分化リンパ腫キナーゼ（ＡＬＫ）阻害剤；２１）インスリン様増殖因子１受容体（ＩＧＦ－１Ｒ）阻害剤；２２）Ｐ－糖タンパク質１阻害剤；２３）血管内皮増殖因子受容体（ＶＥＧＦＲ）阻害剤；２４）ＢＣＲ－ＡＢＬキナーゼ阻害剤；２５）ＦＧＦＲ阻害剤；２６）ＣＹＰ１１Ｂ２の阻害剤；２７）ＨＤＭ２阻害剤、例えば前記ＨＤＭ２－ｐ５３相互作用の阻害剤；２８）チロシンキナーゼの阻害剤；２９）ｃ－ＭＥＴの阻害剤；３０）ＪＡＫの阻害剤；３１）ＤＡＣの阻害剤；３２）１１β－ヒドロキシラーゼの阻害剤；３３）ＩＡＰの阻害剤；３４）ＰＩＭキナーゼの阻害剤；３５）ポーキュパインの阻害剤；３６）ＢＲＡＦ、例えば、ＢＲＡＦ Ｖ６００Ｅ又は野生型ＢＲＡＦの阻害剤；３７）ＨＥＲ３の阻害剤；３８）ＭＥＫの阻害剤；３９）脂質キナーゼの阻害剤；又は表１６に提供される１つ以上の薬剤から選択される、［６０］に記載の方法。
［６９］
［１］～［２４］のいずれか一項に記載の抗体又は抗原結合断片、［２５］に記載の核酸又は核酸のセット、［２６］～［３２］のいずれか一項に記載のベクター、［３３］に記載の細胞、又は［３５］に記載の医薬組成物が、前記少なくとも１つの追加の治療薬と同時に、その前に、又はその後に投与される、［６０］に記載の方法。
［７０］
前記抗体又はその抗原結合断片、前記核酸又は核酸のセット、前記ベクター、前記細胞、又は前記医薬組成物の投与は、以下の効果：
（ａ）前記対象における腫瘍又は病変部位中の増大した数のＣＤ４５＋ＣＤ４－ＣＤ８＋ＣＤ６９＋ＣＤ２５＋細胞；
（ｂ）前記対象における腫瘍又は病変部位中の増大した数のＣＤ４５＋ＣＤ８－ＣＤ４＋ＦＯＸＰ３－ＣＤ６９＋ＣＤ２５＋細胞；
（ｃ）前記対象における低下した血漿ＭＣＰ１又はＩＬ－１βレベル；又は
（ｄ）前記対象における腫瘍又は病変部位中の増大したＭＣＰ１レベル
の１つ以上を有する、［５５］～［６９］のいずれか一項に記載の方法。
［７１］
処置を必要とする対象における癌の処置方法であって、前記方法は、治療有効量の［１］～［２８］のいずれか一項に記載の前記抗体又は抗原結合断片を、ＰＤ－１阻害剤又はＰＤ－Ｌ１阻害剤から選択される第２の治療薬と組み合わせて前記対象に投与することを含む、方法。
［７２］
対象における癌の免疫応答の刺激方法であって、前記方法は、［１］～［２８］のいずれか一項に記載の抗体又は抗原結合断片を、ＰＤ－１阻害剤又はＰＤ－Ｌ１阻害剤から選択される第２の治療薬と組み合わせて前記対象に投与することを含む、方法。
［７３］
対象における癌の処置における使用のための、［１］～［２８］のいずれか一項に記載の抗体又は抗原結合断片を、ＰＤ－１阻害剤又はＰＤ－Ｌ１阻害剤から選択される第２の治療薬と組み合わせて含む組成物。
［７４］
対象における癌の処置における使用のための組成物であって、前記組成物（ｃｏｍｐｏｓｉｓｔｉｏｎ）は、前記［１］～［２８］のいずれか一項に記載の抗体又は抗原結合断片を、ＰＤ－１阻害剤又はＰＤ－Ｌ１阻害剤から選択される第２の治療薬と組み合わせて含む、組成物。
［７５］
前記第２の治療薬がＰＤ－１阻害剤である、［７１］若しくは［７２］に記載の方法、又は［７３］若しくは［７４］に記載の組成物。
［７６］
前記ＰＤ－１阻害剤がＰＤ－１抗体である、［７１］若しくは［７２］に記載の方法、又は［７３］若しくは［７４］に記載の組成物。
［７７］
前記ＰＤ－１阻害剤が、ＰＤＲ００１、ニボルマブ、ペムブロリズマブ、ピディリズマブ、ＭＥＤＩ０６８０、ＲＥＧＮ２８１０、ＴＳＲ－０４２、ＰＦ－０６８０１５９１、又はＡＭＰ－２２４から選択される、［７１］若しくは［７２］に記載の方法、又は［７３］若しくは［７４］に記載の組成物。
［７８］
前記第２の治療薬がＰＤ－Ｌ１阻害剤である、［７１］若しくは［７２］に記載の方法、又は［７３］若しくは［７４］に記載の組成物。
［７９］
前記ＰＤ－Ｌ１阻害剤がＰＤ－Ｌ１抗体である、［７１］若しくは［７２］に記載の方法、又は［７３］若しくは［７４］に記載の組成物。
［８０］
前記ＰＤ－Ｌ１阻害剤が、ＦＡＺ０５３、アテゾリズマブ、アベルマブ、デュルバルマブ、又はＢＭＳ－９３６５５９から選択される、［７１］若しくは［７２］に記載の方法、又は［７３］若しくは［７４］に記載の組成物。
［８１］
前記癌がＥＮＴＰＤ２＋癌である、［７１］に記載の方法又は［７３］若しくは［７４］に記載の組成物。
［８２］
前記癌が、結腸直腸癌（ＣＲＣ）、胃癌（例えば、胃腺癌、胃癌腫）、食道癌（例えば、食道扁平上皮癌（ＥＳＣＣ））、膵癌、胆管癌、肺癌（例えば、小細胞肺癌）、乳癌（例えば、乳腺癌）、又は卵巣癌である、［７１］に記載の方法又は［７３］若しくは［７４］に記載の組成物。 Specific embodiments and claims have been disclosed in detail herein, but this has been done as an example for illustrative purposes only, the appended claims, or any corresponding future. It is not intended to limit the scope of the subject matter of the claims of the application. In particular, the inventors intend to make various substitutions, changes, and amendments to the present disclosure without departing from the spirit and scope of the present disclosure as defined by the claims. There is. The choice of nucleic acid starting material, clone of interest, or library type is considered to be a routine matter for those of skill in the art who have knowledge of the embodiments described herein. Other aspects, advantages, and amendments are considered to be within the scope of the following claims. One of ordinary skill in the art can recognize or confirm many equivalents of the particular aspects of the invention described herein using only routine experimentation. Such equivalents shall be included in the appended claims. The re-creation of the scope of the claims in the corresponding application filed later may be due to the limitations of the patent laws of various countries and should not be construed as abandoning the subject matter of the claims.
The present invention may include the following aspects.
[1]
An antibody that specifically binds to a human ENTPD2 protein or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof is a heavy chain complementarity determining region 1 of any antibody or antigen-binding fragment provided in Table 1. HCDR1), heavy chain complementarity determining regions 2 (HCDR2), heavy chain complementarity determining regions 3 (HCDR3), light chain complementarity determining regions 1 (LCDR1), light chain complementarity determining regions 2 (LCDR2), and light chains. An antibody or antigen-binding fragment thereof comprising complementarity determining regions 3 (LCDR3).
[2]
The antibody or antigen binding thereof according to [1], wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences provided in Table 1. piece.
[3]
The antibody or antigen-binding fragment thereof according to [1] or [2], wherein the antibody or antigen-binding fragment thereof contains a heavy chain variable region provided in Table 1.
[4]
The antibody or antigen-binding fragment thereof according to any one of [1] to [3], wherein the antibody or antigen-binding fragment thereof contains a light chain variable region provided in Table 1.
[5]
The antibody or antigen-binding fragment thereof may be any one of the following:
1) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence containing SEQ ID NO: 1,
HCDR2 sequence, including SEQ ID NO: 2,
HCDR3 sequence, including SEQ ID NO: 3,
LCDR1 sequence, including SEQ ID NO: 14.
An LCDR2 sequence containing SEQ ID NO: 15 and
LCDR3 sequence containing SEQ ID NO: 16;
2) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 4,
HCDR2 sequence, including SEQ ID NO: 5,
HCDR3 sequence, including SEQ ID NO: 3,
LCDR1 sequence, including SEQ ID NO: 17.
An LCDR2 sequence containing SEQ ID NO: 18 and
LCDR3 sequence containing SEQ ID NO: 19;
3) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence containing SEQ ID NO: 7,
HCDR2 sequence containing SEQ ID NO: 8,
HCDR3 sequence, including SEQ ID NO: 9.
LCDR1 sequence, including SEQ ID NO: 20
An LCDR2 sequence containing SEQ ID NO: 18 and
LCDR3 sequence containing SEQ ID NO: 16;
4) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 37,
HCDR2 sequence, including SEQ ID NO: 38,
HCDR3 sequence, including SEQ ID NO: 39,
LCDR1 sequence, including SEQ ID NO: 50,
An LCDR2 sequence containing SEQ ID NO: 51, and
LCDR3 sequence containing SEQ ID NO: 52;
5) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 40,
HCDR2 sequence, including SEQ ID NO: 41,
HCDR3 sequence, including SEQ ID NO: 39,
LCDR1 sequence, including SEQ ID NO: 53,
An LCDR2 sequence containing SEQ ID NO: 54, and
LCDR3 sequence containing SEQ ID NO: 55;
6) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 43,
HCDR2 sequence, including SEQ ID NO: 44,
HCDR3 sequence, including SEQ ID NO: 45,
LCDR1 sequence, including SEQ ID NO: 56,
An LCDR2 sequence containing SEQ ID NO: 54, and
LCDR3 sequence containing SEQ ID NO: 52;
7) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 37,
HCDR2 sequence, including SEQ ID NO: 38,
HCDR3 sequence, including SEQ ID NO: 39,
LCDR1 sequence, including SEQ ID NO: 61,
An LCDR2 sequence containing SEQ ID NO: 51, and
LCDR3 sequence containing SEQ ID NO: 52;
8) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 40,
HCDR2 sequence, including SEQ ID NO: 41,
HCDR3 sequence, including SEQ ID NO: 39,
LCDR1 sequence, including SEQ ID NO: 62,
An LCDR2 sequence containing SEQ ID NO: 54, and
LCDR3 sequence containing SEQ ID NO: 55;
9) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 43,
HCDR2 sequence, including SEQ ID NO: 44,
HCDR3 sequence, including SEQ ID NO: 45,
LCDR1 sequence, including SEQ ID NO: 63,
An LCDR2 sequence containing SEQ ID NO: 54, and
LCDR3 sequence containing SEQ ID NO: 52;
10) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 37,
HCDR2 sequence, including SEQ ID NO: 38,
HCDR3 sequence, including SEQ ID NO: 68,
LCDR1 sequence, including SEQ ID NO: 50,
An LCDR2 sequence containing SEQ ID NO: 51, and
LCDR3 sequence containing SEQ ID NO: 52;
11) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 40,
HCDR2 sequence, including SEQ ID NO: 41,
HCDR3 sequence, including SEQ ID NO: 68,
LCDR1 sequence, including SEQ ID NO: 53,
An LCDR2 sequence containing SEQ ID NO: 54, and
LCDR3 sequence containing SEQ ID NO: 55;
12) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 43,
HCDR2 sequence, including SEQ ID NO: 44,
HCDR3 sequence, including SEQ ID NO: 69,
LCDR1 sequence, including SEQ ID NO: 56,
An LCDR2 sequence containing SEQ ID NO: 54, and
LCDR3 sequence containing SEQ ID NO: 52;
13) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 82,
HCDR2 sequence, including SEQ ID NO: 83,
HCDR3 sequence, including SEQ ID NO: 84,
LCDR1 sequence, including SEQ ID NO: 95,
An LCDR2 sequence containing SEQ ID NO: 96, and
LCDR3 sequence containing SEQ ID NO: 97;
14) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 85,
HCDR2 sequence, including SEQ ID NO: 86,
HCDR3 sequence, including SEQ ID NO: 84,
LCDR1 sequence, including SEQ ID NO: 98,
An LCDR2 sequence containing SEQ ID NO: 99, and
LCDR3 sequence containing SEQ ID NO: 100;
15) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 88,
HCDR2 sequence, including SEQ ID NO: 89,
HCDR3 sequence, including SEQ ID NO: 90,
LCDR1 sequence, including SEQ ID NO: 101,
An LCDR2 sequence containing SEQ ID NO: 99, and
LCDR3 sequence containing SEQ ID NO: 97;
16) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 106,
HCDR2 sequence, including SEQ ID NO: 107,
HCDR3 sequence, including SEQ ID NO: 108,
LCDR1 sequence, including SEQ ID NO: 119,
An LCDR2 sequence containing SEQ ID NO: 120, and
LCDR3 sequence containing SEQ ID NO: 121;
17) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 109,
HCDR2 sequence, including SEQ ID NO: 110,
HCDR3 sequence, including SEQ ID NO: 108,
LCDR1 sequence, including SEQ ID NO: 122,
An LCDR2 sequence containing SEQ ID NO: 99, and
LCDR3 sequence containing SEQ ID NO: 123;
18) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 112,
HCDR2 sequence, including SEQ ID NO: 113,
HCDR3 sequence, including SEQ ID NO: 114,
LCDR1 sequence, including SEQ ID NO: 124,
An LCDR2 sequence containing SEQ ID NO: 99, and
LCDR3 sequence containing SEQ ID NO: 121;
19) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 106,
HCDR2 sequence, including SEQ ID NO: 129,
HCDR3 sequence, including SEQ ID NO: 108,
LCDR1 sequence, including SEQ ID NO: 119,
An LCDR2 sequence containing SEQ ID NO: 120, and
LCDR3 sequence containing SEQ ID NO: 121;
20) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 109,
HCDR2 sequence, including SEQ ID NO: 130,
HCDR3 sequence, including SEQ ID NO: 108,
LCDR1 sequence, including SEQ ID NO: 122,
An LCDR2 sequence containing SEQ ID NO: 99, and
LCDR3 sequence containing SEQ ID NO: 123;
21) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 112,
HCDR2 sequence, including SEQ ID NO: 131,
HCDR3 sequence, including SEQ ID NO: 114,
LCDR1 sequence, including SEQ ID NO: 124,
An LCDR2 sequence containing SEQ ID NO: 99, and
LCDR3 sequence containing SEQ ID NO: 121;
22) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 136,
HCDR2 sequence, including SEQ ID NO: 137,
HCDR3 sequence, including SEQ ID NO: 138,
LCDR1 sequence, including SEQ ID NO: 149,
An LCDR2 sequence containing SEQ ID NO: 150, and
LCDR3 sequence containing SEQ ID NO: 151;
23) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 139,
HCDR2 sequence, including SEQ ID NO: 140,
HCDR3 sequence, including SEQ ID NO: 138,
LCDR1 sequence, including SEQ ID NO: 152,
An LCDR2 sequence containing SEQ ID NO: 153, and
LCDR3 sequence containing SEQ ID NO: 154;
24) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 142,
HCDR2 sequence, including SEQ ID NO: 143,
HCDR3 sequence, including SEQ ID NO: 144,
LCDR1 sequence, including SEQ ID NO: 155,
An LCDR2 sequence containing SEQ ID NO: 153, and
LCDR3 sequence containing SEQ ID NO: 151;
25) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 160,
HCDR2 sequence, including SEQ ID NO: 161.
HCDR3 sequence, including SEQ ID NO: 162,
LCDR1 sequence, including SEQ ID NO: 173,
An LCDR2 sequence containing SEQ ID NO: 150, and
LCDR3 sequence containing SEQ ID NO: 174;
26) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 163,
HCDR2 sequence, including SEQ ID NO: 164,
HCDR3 sequence, including SEQ ID NO: 162,
LCDR1 sequence, including SEQ ID NO: 175,
An LCDR2 sequence containing SEQ ID NO: 153, and
LCDR3 sequence containing SEQ ID NO: 176;
27) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 166,
HCDR2 sequence, including SEQ ID NO: 167,
HCDR3 sequence, including SEQ ID NO: 168,
LCDR1 sequence, including SEQ ID NO: 177,
An LCDR2 sequence containing SEQ ID NO: 153, and
LCDR3 sequence containing SEQ ID NO: 174;
28) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 37,
HCDR2 sequence, including SEQ ID NO: 220,
HCDR3 sequence, including SEQ ID NO: 221
LCDR1 sequence, including SEQ ID NO: 61,
An LCDR2 sequence containing SEQ ID NO: 51, and
LCDR3 sequence containing SEQ ID NO: 52;
29) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 40,
HCDR2 sequence, including SEQ ID NO: 222,
HCDR3 sequence, including SEQ ID NO: 221
LCDR1 sequence, including SEQ ID NO: 62,
An LCDR2 sequence containing SEQ ID NO: 54, and
LCDR3 sequence containing SEQ ID NO: 55;
30) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 43,
HCDR2 sequence, including SEQ ID NO: 223,
HCDR3 sequence, including SEQ ID NO: 224,
LCDR1 sequence, including SEQ ID NO: 63,
An LCDR2 sequence containing SEQ ID NO: 54, and
LCDR3 sequence containing SEQ ID NO: 52;
31) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 37,
HCDR2 sequence, including SEQ ID NO: 220,
HCDR3 sequence, including SEQ ID NO: 68,
LCDR1 sequence, including SEQ ID NO: 61,
An LCDR2 sequence containing SEQ ID NO: 51, and
LCDR3 sequence containing SEQ ID NO: 52;
32) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 40,
HCDR2 sequence, including SEQ ID NO: 222,
HCDR3 sequence, including SEQ ID NO: 68,
LCDR1 sequence, including SEQ ID NO: 62,
An LCDR2 sequence containing SEQ ID NO: 54, and
LCDR3 sequence containing SEQ ID NO: 55;
33) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 43,
HCDR2 sequence, including SEQ ID NO: 223,
HCDR3 sequence, including SEQ ID NO: 69,
LCDR1 sequence, including SEQ ID NO: 63,
An LCDR2 sequence containing SEQ ID NO: 54, and
LCDR3 sequence containing SEQ ID NO: 52;
34) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence containing SEQ ID NO: 1,
HCDR2 sequence, including SEQ ID NO: 245,
HCDR3 sequence, including SEQ ID NO: 246,
LCDR1 sequence, including SEQ ID NO: 254,
An LCDR2 sequence containing SEQ ID NO: 15 and
LCDR3 sequence containing SEQ ID NO: 255;
35) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 4,
HCDR2 sequence, including SEQ ID NO: 247,
HCDR3 sequence, including SEQ ID NO: 246,
LCDR1 sequence, including SEQ ID NO: 17.
An LCDR2 sequence containing SEQ ID NO: 18 and
LCDR3 sequence containing SEQ ID NO: 256;
36) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence containing SEQ ID NO: 7,
HCDR2 sequence, including SEQ ID NO: 248,
HCDR3 sequence, including SEQ ID NO: 249,
LCDR1 sequence, including SEQ ID NO: 20
An LCDR2 sequence containing SEQ ID NO: 18 and
LCDR3 sequence containing SEQ ID NO: 255;
37) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence containing SEQ ID NO: 1,
HCDR2 sequence, including SEQ ID NO: 261.
HCDR3 sequence, including SEQ ID NO: 262,
LCDR1 sequence, including SEQ ID NO: 254,
An LCDR2 sequence containing SEQ ID NO: 15 and
LCDR3 sequence containing SEQ ID NO: 16;
38) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 4,
HCDR2 sequence, including SEQ ID NO: 247,
HCDR3 sequence, including SEQ ID NO: 262,
LCDR1 sequence, including SEQ ID NO: 17.
An LCDR2 sequence containing SEQ ID NO: 18 and
LCDR3 sequence containing SEQ ID NO: 19;
39) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence containing SEQ ID NO: 7,
HCDR2 sequence, including SEQ ID NO: 248,
HCDR3 sequence, including SEQ ID NO: 263,
LCDR1 sequence, including SEQ ID NO: 20
An LCDR2 sequence containing SEQ ID NO: 18 and
LCDR3 sequence containing SEQ ID NO: 16;
40) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 272,
HCDR2 sequence, including SEQ ID NO: 273,
HCDR3 sequence, including SEQ ID NO: 274,
LCDR1 sequence, including SEQ ID NO: 254,
An LCDR2 sequence containing SEQ ID NO: 285, and
LCDR3 sequence containing SEQ ID NO: 16;
41) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 275,
HCDR2 sequence, including SEQ ID NO: 276,
HCDR3 sequence, including SEQ ID NO: 274,
LCDR1 sequence, including SEQ ID NO: 17.
An LCDR2 sequence containing SEQ ID NO: 286, and
LCDR3 sequence containing SEQ ID NO: 19;
42) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 278,
HCDR2 sequence, including SEQ ID NO: 279,
HCDR3 sequence, including SEQ ID NO: 280,
LCDR1 sequence, including SEQ ID NO: 20
An LCDR2 sequence containing SEQ ID NO: 286, and
LCDR3 sequence containing SEQ ID NO: 16
The antibody or antigen-binding fragment thereof according to [1] or [2], which is selected from.
[6]
The antibody or antigen-binding fragment thereof may be any one of the following:
1) Containing a heavy chain variable region (VH) containing SEQ ID NO: 10 or at least about 95% or more identical sequence, and a light chain variable region (VL) containing SEQ ID NO: 21 or at least about 95% or more identical sequence. Antibodies or antigen-binding fragments thereof;
2) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 25 or at least about 95% or more identical sequence, and VL containing SEQ ID NO: 29 or at least about 95% or more identical sequence;
3) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 33 or at least about 95% or more identical sequence, and VL containing SEQ ID NO: 29 or at least about 95% or more identical sequence;
4) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 46 or a VH containing at least about 95% or more the same sequence as SEQ ID NO: 57 or VL containing at least about 95% or more the same sequence with SEQ ID NO: 57;
5) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 46 or at least about 95% or more identical sequence, and VL containing SEQ ID NO: 64 or at least about 95% or more identical sequence;
6) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 70 or at least about 95% or more identical sequence, and VL containing SEQ ID NO: 74 or at least about 95% or more identical sequence;
7) An antibody or antigen-binding fragment thereof containing SEQ ID NO: 25 or VH containing at least about 95% or more the same sequence as SEQ ID NO: 78 or VL containing at least about 95% or more the same sequence with SEQ ID NO: 78;
8) An antibody or antigen-binding fragment thereof containing SEQ ID NO: 91 or VH containing at least about 95% or more the same sequence as SEQ ID NO: 102 or VL containing at least about 95% or more the same sequence with SEQ ID NO: 102;
9) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 115 or VH containing at least about 95% or more identical sequence, and SEQ ID NO: 125 or VL containing at least about 95% or more identical sequence;
10) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 132 or a VH containing at least about 95% or more the same sequence as SEQ ID NO: 125 or VL containing at least about 95% or more the same sequence with SEQ ID NO: 125;
11) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 145 or VH containing at least about 95% or more identical sequence, and SEQ ID NO: 156 or VL containing at least about 95% or more identical sequence;
12) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 169 or VH containing at least about 95% or more identical sequence, and SEQ ID NO: 178 or VL containing at least about 95% or more identical sequence;
13) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 225 or VH containing at least about 95% or more identical sequence, and SEQ ID NO: 229 or VL containing at least about 95% or more identical sequence;
14) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 233 or a VH containing at least about 95% or more identical sequence, and SEQ ID NO: 237 or VL containing at least about 95% or more identical sequence;
15) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 241 or VH containing at least about 95% or more identical sequence, and SEQ ID NO: 229 or VL containing at least about 95% or more identical sequence;
16) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 250 or VH containing at least about 95% or more identical sequence, and SEQ ID NO: 257 or VL containing at least about 95% or more identical sequence;
17) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 264 or VH containing at least about 95% or more identical sequence, and SEQ ID NO: 268 or VL containing at least about 95% or more identical sequence.
18) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 281 or VH containing at least about 95% or more identical sequence, and SEQ ID NO: 287 or VL containing at least about 95% or more identical sequence.
The antibody or antigen-binding fragment thereof according to any one of [1] to [5], which is selected from the above.
[7]
The antibody or antigen-binding fragment thereof is any one of the following:
1) An antibody containing a heavy chain containing SEQ ID NO: 12 or at least about 95% or more identical sequence, and a light chain containing SEQ ID NO: 23 or at least about 95% or more identical sequence;
2) An antibody comprising a heavy chain containing SEQ ID NO: 27 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 31 or at least about 95% or more identical sequence;
3) An antibody comprising a heavy chain containing SEQ ID NO: 35 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 31 or at least about 95% or more identical sequence;
4) An antibody comprising a heavy chain containing SEQ ID NO: 48 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 59 or at least about 95% or more identical sequence;
5) An antibody comprising a heavy chain containing SEQ ID NO: 48 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 66 or at least about 95% or more identical sequence;
6) An antibody comprising a heavy chain containing SEQ ID NO: 72 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 76 or at least about 95% or more identical sequence;
7) An antibody comprising a heavy chain containing SEQ ID NO: 27 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 80 or at least about 95% or more identical sequence;
8) An antibody comprising a heavy chain containing SEQ ID NO: 93 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 104 or at least about 95% or more identical sequence;
9) An antibody comprising a heavy chain containing SEQ ID NO: 117 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 127 or at least about 95% or more identical sequence;
10) An antibody comprising a heavy chain containing SEQ ID NO: 134 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 127 or at least about 95% or more identical sequence;
11) An antibody comprising a heavy chain containing SEQ ID NO: 147 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 158 or at least about 95% or more identical sequence;
12) An antibody comprising a heavy chain containing SEQ ID NO: 171 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 180 or at least about 95% or more identical sequence;
13) An antibody comprising a heavy chain containing SEQ ID NO: 227 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 231 or at least about 95% or more identical sequence;
14) An antibody comprising a heavy chain containing SEQ ID NO: 235 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 239 or at least about 95% or more identical sequence;
15) An antibody comprising a heavy chain containing SEQ ID NO: 243 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 231 or at least about 95% or more identical sequence;
16) An antibody comprising a heavy chain containing SEQ ID NO: 252 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 259 or at least about 95% or more identical sequence;
17) An antibody comprising a heavy chain comprising SEQ ID NO: 266 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 270 or at least about 95% or more identical sequence;
18) An antibody comprising a heavy chain containing SEQ ID NO: 283 or at least about 95% or more identical sequence, and a light chain comprising SEQ ID NO: 289 or at least about 95% or more identical sequence.
The antibody or antigen-binding fragment thereof according to any one of [1] to [6], which is selected from the above.
[8]
The antibody or antigen-binding fragment thereof is:
HCDR1 sequence containing SEQ ID NO: 1,
HCDR2 sequence, including SEQ ID NO: 2,
HCDR3 sequence, including SEQ ID NO: 3,
LCDR1 sequence, including SEQ ID NO: 14.
An LCDR2 sequence containing SEQ ID NO: 15 and
LCDR3 sequence containing SEQ ID NO: 16
The antibody or antigen-binding fragment thereof according to any one of [1] to [7].
[9]
The antibody or antigen-binding fragment thereof is:
HCDR1 sequence, including SEQ ID NO: 4,
HCDR2 sequence, including SEQ ID NO: 5,
HCDR3 sequence, including SEQ ID NO: 3,
LCDR1 sequence, including SEQ ID NO: 17.
An LCDR2 sequence containing SEQ ID NO: 18 and
LCDR3 sequence containing SEQ ID NO: 19
The antibody or antigen-binding fragment thereof according to any one of [1] to [7].
[10]
The antibody or antigen-binding fragment thereof is:
HCDR1 sequence containing SEQ ID NO: 7,
HCDR2 sequence containing SEQ ID NO: 8,
HCDR3 sequence, including SEQ ID NO: 9.
LCDR1 sequence, including SEQ ID NO: 20
An LCDR2 sequence containing SEQ ID NO: 18 and
LCDR3 sequence containing SEQ ID NO: 16
The antibody or antigen-binding fragment thereof according to any one of [1] to [7].
[11]
A heavy chain variable region (VH) in which the antibody or antigen-binding fragment thereof contains at least about 95% or more of the same sequence as SEQ ID NO: 10 or a light chain containing at least about 95% or more of the same sequence as SEQ ID NO: 21 or the same. The antibody or antigen-binding fragment thereof according to any one of [1] to [7], which comprises a variable region (VL).
[12]
[1] to [7], wherein the antibody or an antigen-binding fragment thereof comprises a light chain containing SEQ ID NO: 12 or at least about 95% or more identical sequence, and SEQ ID NO: 23 or at least about 95% or more identical sequence. ] The antibody according to any one of the above items or an antigen-binding fragment thereof.
[13]
The antibody or antigen-binding fragment thereof binds to an epitope in human ENTPD2, and the epitope is the following residues: His50, Asp76, Pro78, Gly79, Gly80, Tyr85, Asp87, Asn88, Gly91, Gln94, Ser95, Gly98, Glu101, Gln102, Gln105, Asp106, Arg245, Thr272, Grn273, Leu275, Asp278, Arg298, Ala347, Ala350, Thr351, Arg392, Ala393, Arg394, or any one of [1] to [1]. The antibody or antigen-binding fragment thereof according to the above item.
[14]
The antibody or antigen-binding fragment thereof binds to an epitope in human ENTPD2, and the epitope is the following residues: Gly79, Gln250, Leu253, Trp266, Arg268, Gly269, Phe270, Ser271, Thr272, Gln273, Val274, Leu275, The item according to any one of [1] to [12], which comprises at least one of Asp278, Arg298, Ser300, Ser302, Gly303, Thr380, Trp381, Ala382, Gly390, Gln391, Arg392, Ala393, Arg394, or Asp397. An antibody or an antigen-binding fragment thereof.
[15]
An antibody or antigen-binding fragment thereof that specifically binds to an epitope in human ENTPD2, wherein the epitope is the following residues: His50, Asp76, Pro78, Gly79, Gly80, Tyr85, Asp87, Asn88, Gly91, Gln94, Ser95. , Gly98, Glu101, Gln102, Gln105, Asp106, Arg245, Thr272, Grn273, Leu275, Asp278, Arg298, Ala347, Ala350, Thr351, Arg392, Ala393, Arg394, or at least one antibody thereof-binding antibody thereof. ..
[16]
An antibody or antigen-binding fragment thereof that specifically binds to an epitope in human ENTPD2, wherein the epitope is the following residues: Gly79, Gln250, Leu253, Trp266, Arg268, Gly269, Phe270, Ser271, Thr272, Gln273, Val274. , Leu275, Asp278, Arg298, Ser300, Ser302, Gly303, Thr380, Trp381, Ala382, Gly390, Gln391, Arg392, Ala393, Arg394, or an antigen-binding fragment thereof.
[17]
An antibody or antigen-binding fragment thereof that competes with any of the antibodies or antigen-binding fragments provided in Table 1 for binding to the human ENTPD2 protein.
[18]
An antibody or antigen-binding fragment thereof that binds to the same epitope, substantially the same epitope, an epitope that overlaps with it, or an epitope that substantially overlaps with any of the epitopes of any of the antibodies or antigen-binding fragments provided in Table 1. ..
[19]
The antibody or antigen-binding fragment thereof has a dissociation constant (K) of less than 10 nM as measured by, for example, Biacore. D ), The antibody or antigen-binding fragment thereof according to any one of [1] to [18], which binds to the human ENTPD2 protein.
[20]
The antibody or antigen-binding fragment thereof has a dissociation constant of less than 5 nM (K) as measured by, for example, Biacore. D ), The antibody or antigen-binding fragment thereof according to any one of [1] to [18], which binds to the human ENTPD2 protein.
[21]
The antibody or antigen-binding fragment thereof has a dissociation constant (K) of less than 3 nM as measured by, for example, Biacore. D ), The antibody or antigen-binding fragment thereof according to any one of [1] to [18], which binds to the human ENTPD2 protein.
[22]
Any of [1] to [21], wherein the antibody or an antigen-binding fragment thereof inhibits human ENTPD2 enzyme activity by at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%. The antibody or antigen-binding fragment thereof according to the above item.
[23]
The antibody or antigen-binding fragment thereof according to any one of [1] to [22], wherein the antibody or an antigen-binding fragment thereof inhibits the ability of ENTPD2 to hydrolyze adenosine triphosphate (ATP).
[24]
The antibody or antigen thereof according to any one of [1] to [23], wherein the antibody or an antigen-binding fragment thereof interferes with the binding of ATP to ENTPD2 or captures ATP in the catalytic domain of ENTPD2. Bonded fragment.
[25]
The antibody or antigen-binding fragment thereof according to any one of [1] to [24], wherein the antibody has an IgG1, IgG2, IgG3 or IgG4 isotype.
[26]
Item 1. The antibody described or an antigen-binding fragment thereof.
[27]
The antibody or antigen-binding fragment thereof comprises a modified Fc region having reduced antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cellular cytotoxicity (CDC) activity as compared to the parent antibody [1]. The antibody or antigen-binding fragment thereof according to any one of [26].
[28]
The antibody or antigen-binding fragment thereof according to any one of [1] to [27], wherein the antibody or an antigen-binding fragment thereof is a human or humanized antibody or a fragment thereof.
[29]
A nucleic acid or a set of nucleic acids encoding the antibody or antigen-binding fragment thereof according to any one of [1] to [28].
[30]
A vector comprising the nucleic acid or set of nucleic acids according to [29].
[31]
The vector according to [30], wherein the vector is selected from a DNA vector, an RNA vector, a plasmid, a cosmid, or a viral vector.
[32]
The vector contains the following viruses: lentivirus, adenovirus, adeno-associated virus (AAV), simple herpesvirus (HSV), parvovirus, retrovirus, vaccinia virus, Sinbis virus, influenza virus, leovirus, newcastle. Virus based on any one of disease virus (NDV), scab virus, bullous stomatitis virus (VSV), poliovirus, poxvirus, Seneca Valley virus, coxsackie virus, enterovirus, mucinoma virus, or malavavirus. The vector according to [31], which is a vector.
[33]
The vector according to [32], wherein the vector is an AAV vector.
[34]
The vector according to [31], wherein the vector is a lentiviral vector.
[35]
The vector according to any one of [30] to [34], further comprising a promoter.
[36]
The vector according to any one of [30] to [35], further comprising a detectable marker.
[37]
A cell comprising the nucleic acid or set of nucleic acids according to 29 or the vector according to any one of [30] to [36].
[38]
[37] A method for producing an antibody or an antigen-binding fragment thereof, which comprises culturing the cell according to [37] and collecting the antibody or an antigen-binding fragment thereof from a culture medium.
[39]
The antibody or antigen-binding fragment thereof according to any one of [1] to [28], the nucleic acid or set of nucleic acids according to [29], and the vector according to any one of [30] to [36]. , Or a pharmaceutical composition comprising the cell according to [37] and a pharmaceutically acceptable carrier.
[40]
The antibody according to any one of [1] to [28] or an antigen-binding fragment thereof, the nucleic acid or the set of nucleic acids according to [29], of [30] to [36] for use as a pharmaceutical. The vector according to any one of the above, the cell according to [37], or the pharmaceutical composition according to [39].
[41]
The antibody according to any one of [1] to [28] or an antigen-binding fragment thereof, the nucleic acid according to [29], or any one of [30] to [36] for use in the treatment of cancer. The vector according to the section, the cell according to [37], or the pharmaceutical composition according to [39].
[42]
The antibody according to any one of [1] to [28] or an antigen-binding fragment thereof, the nucleic acid according to [29], or any of [30] to [36] in the manufacture of a pharmaceutical agent for treating cancer. Use of the vector according to item 1, the cell according to [37], or the pharmaceutical composition according to [39].
[43]
The antibody for use according to [41], or the use according to [42], wherein the cancer is ENTPD2 + cancer.
[44]
The cancers include colorectal cancer (CRC), gastric cancer (eg, gastric adenocarcinoma, gastric cancer), esophageal cancer (eg, esophageal squamous epithelial cancer (ESCC)), pancreatic cancer, bile duct cancer, lung cancer (eg, small cell lung cancer). The antibody for use according to [41], or the use according to [42], which is breast cancer (eg, breast cancer) or ovarian cancer.
[45]
To the subject, said antibody or antigen-binding fragment thereof, said nucleic acid or set of nucleic acids, said vector, said cell, or said pharmaceutical composition is administered to said subject via an intravenous, intratumoral or subcutaneous route. Antibodies for the described use, or the use according to [42].
[46]
The antibody for use according to [41], or the use according to [42], wherein the antibody molecule is administered in combination with at least one additional therapeutic agent or procedure.
[47]
The at least one additional therapeutic agent or procedure is chemotherapy, targeted anti-cancer therapy, tumor-dissolving drug, cytotoxic agent, immune-based therapies, cytokines, surgical procedures, radiotherapy, activation of costimulatory molecules. The antibody for use according to [46], or the use according to [46], selected from one or more of a factor, an inhibitor of an inhibitory molecule, a vaccine, or a cell therapy.
[48]
The antibody for use according to [46] or the use according to [46], wherein the at least one additional therapeutic agent is a PD-1 inhibitor, eg, a PD-1 antibody.
[49]
The antibody for use according to [48], wherein the PD-1 inhibitor is selected from PDR001, nivolumab, pembrolizumab, pidirizumab, MEDI0680, REGN2810, TSR-042, PF-06801591, or AMP-224. Use according to [48].
[50]
The antibody for use according to [46], or the use according to [46], wherein the at least one additional therapeutic agent is a PD-L1 inhibitor, eg, a PD-L1 antibody.
[51]
The antibody for use according to [50], or the use according to [50], wherein the PD-L1 inhibitor is selected from FAZ053, atezolizumab, avelumab, durvalumab, or BMS-936559.
[52]
The at least one additional therapeutic agent is an A2AR antagonist and the A2AR antagonist is:
i. An anti-CD73 antibody molecule or an antigen-binding fragment thereof, wherein the anti-CD73 antibody may be described below.
a. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 295 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 296, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 295 or 296. Anti-CD73 antibody molecule containing sequence;
b. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 299 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 300, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 299 or 300. Anti-CD73 antibody molecule containing sequence;
c. Amino acids that are at least 85%, 90%, 95% or more identical to the heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 302 and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 303, or SEQ ID NO: 302 or 303. Anti-CD73 antibody molecule containing sequence;
d. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 304 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 305, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 304 or 305. Anti-CD73 antibody molecule containing sequence;
e. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 306 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 307, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 306 or 307. Anti-CD73 antibody molecule containing sequence; or
f. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 308 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 309, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 308 or 309. Anti-CD73 antibody molecule containing sequence;
Anti-CD73 antibody molecule or antigen-binding fragment thereof selected from
Or
ii. PBF509 / NIR178, CPI444 / V81444, AZD4635 / HTL-1071, Vipadenant, GBV-2034, AB928, Theophylline, Istradefylline, Tozadenant / SYN-115, KW-6356, ST-4206, and Preladenant / SCH4
iii. 5-bromo-2,6-di- (1H-pyrazole-1-yl) pyrimidin-4-amine, or a pharmaceutically acceptable salt thereof; (S) -7- (5-methylfuran-2-yl) ) -3-((6-(((tetra-3-yl) oxy) methyl) Pyridine-2-yl) Methyl) -3H- [1,2,3] Triazolo [4,5-d] Pyrimidine-5 -Amine, or a pharmaceutically acceptable salt thereof; (R) -7- (5-methylfuran-2-yl) -3-((6-(((tetra-3-yl) oxy) methyl) pyridine) -2-yl) Methyl) -3H- [1,2,3] triazolo [4,5-d] pyrimidin-5-amine, or its lasemi, or pharmaceutically acceptable salt thereof; 7- (5) -Methylfuran-2-yl) -3-((6-(((tetra-3-yl) oxy) methyl) pyridin-2-yl) methyl) -3H- [1,2,3] triazolo [4, 5-d] Pyrimidine-5-amine, or a pharmaceutically acceptable salt thereof; and 6- (2-chloro-6-methylpyridin-4-yl) -5- (4-fluorophenyl) -1,2 , 4-Triazine-3-amine, or a pharmaceutically acceptable salt thereof
The antibody for use according to any one of [46] to [51] selected from, or the use according to any one of [46] to [51].
[53]
The at least one additional therapeutic agent is:
i. The CTLA-4 inhibitor, and optionally the CTLA-4 inhibitor, is selected from ipilimumab or tremelimumab;
ii. The TIM-3 inhibitor, and optionally the TIM-3 inhibitor, is selected from MBG453, TSR-022, or LY3321367;
iii. The LAG-3 inhibitor, and optionally the LAG-3 inhibitor, is selected from LAG525, BMS-986016, TSR-033, MK-4280 or REGN3767;
iv. The GITR agonist, and optionally the GITR agonist, is selected from GWN323, BMS-986156, MK-4166, MK-1248, TRX518, INCAGN1876, AMG228, or INBRX-110;
v. The anti-CD3 multispecific antibody molecule, and optionally the anti-CD3 multispecific antibody molecule, is an anti-CD3x anti-CD123 bispecific antibody molecule (eg, XENP14045) or an anti-CD3x anti-CD20 bispecific antibody molecule (eg, eg). XENP13676);
vi. The cytokine molecule, and optionally the cytokine molecule, is IL-15 complexed with the soluble form of IL-15 receptor α (IL-15Ra);
vii. The macrophage colony-stimulating factor (M-CSF) inhibitor, and optionally the M-CSF inhibitor, is MCS110;
viii. The CSF-1R inhibitor, and optionally the CSF-1R inhibitor, is BLZ945;
ix. Indoleamine 2,3-dioxygenase (IDO) and / or tryptophan 2,3-dioxygenase (TDO) inhibitor;
x. TGF-β inhibitor;
xi. Oncolytic virus;
xii. Chimeric antigen receptor (CAR) T cell therapy
The antibody for use according to [46], or the use according to [46], selected from.
[54]
The at least one additional therapeutic agent is 1) a protein kinase C (PKC) inhibitor; 2) a heat shock protein 90 (HSP90) inhibitor; 3) a phosphoinositide 3-kinase (PI3K) and / or a target for rapamycin (mTOR). ) Inhibitors; 4) Thitochrome P450 inhibitors (eg, CYP17 inhibitors or 17α-hydroxylase / C17-20 lyase inhibitors); 5) Iron chelating agents; 6) Aromatase inhibitors; 7) Inhibition of p53 Agents such as p53 / Mdm2 interaction inhibitors; 8) apoptosis-inducing agents; 9) angiogenesis inhibitors; 10) aldosterone kinase inhibitors; 11) smoothund (SMO) receptor inhibitors; 12) prolactin receptors ( PRLR) inhibitor; 13) Wnt signaling inhibitor; 14) CDK4 / 6 inhibitor; 15) fibroblast proliferative factor receptor 2 (FGFR2) / fibroblast proliferative factor receptor 4 (FGFR4) inhibitor; 16 ) Macrophage colony stimulating factor (M-CSF) inhibitor; 17) c-KIT, histamine release, one or more inhibitors of Flt3 (eg, FLK2 / STK1) or PKC; 18) VEGFR-2 (eg, FLK-). 1 / KDR), PDGFRβ, c-KIT or Raf kinase C one or more inhibitors; 19) somatostatin agonists and / or growth hormone release inhibitors; 20) undifferentiated lymphoma kinase (ALK) inhibitors; 21) Insulin-like growth factor 1 receptor (IGF-1R) inhibitor; 22) P-glycoprotein 1 inhibitor; 23) Vascular endothelial growth factor receptor (VEGFR) inhibitor; 24) BCR-ABL kinase inhibitor; 25) FGFR inhibitor; 26) CYP11B2 inhibitor; 27) HDM2 inhibitor, eg, the HDM2-p53 interaction inhibitor; 28) tyrosine kinase inhibitor; 29) c-MET inhibitor; 30) JAK inhibition Agents; 31) DAC inhibitors; 32) 11β-hydroxylase inhibitors; 33) IAP inhibitors; 34) PIM kinase inhibitors; 35) porcupine inhibitors; 36) BRAF, eg BRAF V600E or wild. Inhibitors of type BRAF; 37) inhibitors of HER3; 38) inhibitors of MEK; or 39) inhibitors of lipid kinases; or selected from one or more agents provided in Table 16, [46]. The antibody for the use described, or the use according to [46].
[55]
A method for treating cancer in a subject in need of treatment, wherein the method is the antibody or antigen binding fragment according to any one of [1] to [28], which is a therapeutically effective amount, according to [29]. A method comprising administering to the subject a nucleic acid, the vector according to any one of [30] to [36], the cells according to [37], or the pharmaceutical composition according to [39].
[56]
The method according to [55], wherein the cancer is ENTPD2 + cancer.
[57]
The cancers include colorectal cancer (CRC), gastric cancer (eg, gastric adenocarcinoma, gastric cancer), esophageal cancer (eg, esophageal squamous epithelial cancer (ESCC)), pancreatic cancer, bile duct cancer, lung cancer (eg, small cell lung cancer). The method according to [55], wherein the method is breast cancer (eg, breast cancer) or ovarian cancer.
[58]
The antibody or antigen-binding fragment thereof, the nucleic acid or a set of nucleic acids, the vector, the cells, or the pharmaceutical composition is administered to the subject via an intravenous, intratumoral or subcutaneous route, [55] to The method according to any one of [57].
[59]
A method for stimulating an immune response in a subject, wherein the method comprises the antibody or antigen binding fragment according to any one of [1] to [28], the nucleic acid or set of nucleic acids according to [29], [30]. ] To [36], the vector according to any one of [36], the cell according to [37], or the pharmaceutical composition according to [39] to the subject in an amount effective for stimulating the immune response. Methods, including administration.
[60]
The method of any one of [55]-[59], further comprising administering to the subject an at least one additional therapeutic agent or procedure.
[61]
The one or more additional therapeutic agents or treatments include chemotherapy, targeted anticancer therapy, tumor lytic drugs, cytotoxic agents, immune-based therapies, cytokines, surgical procedures, radiation treatments, costimulatory molecules. 60. The method according to [60], which is selected from one or more of an activator, an inhibitor of an inhibitory molecule, a vaccine or a cell therapy.
[62]
60. The method of [60], wherein the at least one additional therapeutic agent is a PD-1 inhibitor, eg, a PD-1 antibody.
[63]
62. The method of 62, wherein the PD-1 inhibitor is selected from PDR001, nivolumab, pembrolizumab, pidirizumab, MEDI0680, REGN2810, TSR-042, PF-06801591, or AMP-224.
[64]
60. The method of 60, wherein the at least one additional therapeutic agent is a PD-L1 inhibitor, eg, a PD-L1 antibody.
[65]
64. The method according to 64, wherein the PD-L1 inhibitor is selected from FAZ053, atezolizumab, avelumab, durvalumab, or BMS-936559.
[66]
The at least one additional therapeutic agent is an A2AR antagonist and the A2AR antagonist is:
i. An anti-CD73 antibody molecule or an antigen-binding fragment thereof, wherein the anti-CD73 antibody may be described below.
a. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 295 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 296, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 295 or 296. Anti-CD73 antibody molecule containing sequence;
b. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 299 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 300, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 299 or 300. Anti-CD73 antibody molecule containing sequence;
c. Amino acids that are at least 85%, 90%, 95% or more identical to the heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 302 and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 303, or SEQ ID NO: 302 or 303. Anti-CD73 antibody molecule containing sequence;
d. Heavy chain variable region containing the amino acid sequence of SEQ ID NO: 304 and light chain variable region containing the amino acid sequence of SEQ ID NO: 305, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 304 or 305. Anti-CD73 antibody molecule containing sequence;
e. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 306 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 307, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 306 or 307. Anti-CD73 antibody molecule containing sequence; or
f. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 308 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 309, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 308 or 309. Anti-CD73 antibody molecule containing sequence;
Anti-CD73 antibody molecule or antigen-binding fragment thereof selected from
Or
ii. PBF509 / NIR178, CPI444 / V81444, AZD4635 / HTL-1071, Vipadenant, GBV-2034, AB928, Theophylline, Istradefylline, Tozadenant / SYN-115, KW-6356, ST-4206, and Preladenant / SCH4
iii. 5-bromo-2,6-di- (1H-pyrazole-1-yl) pyrimidin-4-amine, or a pharmaceutically acceptable salt thereof; (S) -7- (5-methylfuran-2-yl) ) -3-((6-(((tetra-3-yl) oxy) methyl) Pyridine-2-yl) Methyl) -3H- [1,2,3] Triazolo [4,5-d] Pyrimidine-5 -Amine, or a pharmaceutically acceptable salt thereof; (R) -7- (5-methylfuran-2-yl) -3-((6-(((tetra-3-yl) oxy) methyl) pyridine) -2-yl) Methyl) -3H- [1,2,3] triazolo [4,5-d] pyrimidin-5-amine, or its lasemi, or pharmaceutically acceptable salt thereof; 7- (5) -Methylfuran-2-yl) -3-((6-(((tetra-3-yl) oxy) methyl) pyridin-2-yl) methyl) -3H- [1,2,3] triazolo [4, 5-d] Pyrimidine-5-amine, or a pharmaceutically acceptable salt thereof; and 6- (2-chloro-6-methylpyridin-4-yl) -5- (4-fluorophenyl) -1,2 , 4-Triazine-3-amine, or a pharmaceutically acceptable salt thereof
The method according to [60], which is selected from.
[67]
The at least one additional therapeutic agent is:
i. The CTLA-4 inhibitor, and optionally the CTLA-4 inhibitor, is selected from ipilimumab or tremelimumab;
ii. The TIM-3 inhibitor, and optionally the TIM-3 inhibitor, is selected from MBG453, TSR-022, or LY3321367;
iii. The LAG-3 inhibitor, and optionally the LAG-3 inhibitor, is selected from LAG525, BMS-986016, TSR-033, MK-4280 or REGN3767;
iv. The GITR agonist, and optionally the GITR agonist, is selected from GWN323, BMS-986156, MK-4166, MK-1248, TRX518, INCAGN1876, AMG228, or INBRX-110;
v. The anti-CD3 multispecific antibody molecule, and optionally the anti-CD3 multispecific antibody molecule, is an anti-CD3x anti-CD123 bispecific antibody molecule (eg, XENP14045) or an anti-CD3x anti-CD20 bispecific antibody molecule (eg, eg). XENP13676);
vi. The cytokine molecule, and optionally the cytokine molecule, is IL-15 complexed with the soluble form of IL-15 receptor α (IL-15Ra);
vii. The macrophage colony-stimulating factor (M-CSF) inhibitor, and optionally the M-CSF inhibitor, is MCS110;
viii. The CSF-1R inhibitor, and optionally the CSF-1R inhibitor, is BLZ945;
ix. Indoleamine 2,3-dioxygenase (IDO) and / or tryptophan 2,3-dioxygenase (TDO) inhibitor;
x. TGF-β inhibitor;
xi. Oncolytic virus;
xii. Chimeric antigen receptor (CAR) T cell therapy
The method according to [60], which is selected from.
[68]
The at least one additional therapeutic agent is 1) a protein kinase C (PKC) inhibitor; 2) a heat shock protein 90 (HSP90) inhibitor; 3) a phosphoinositide 3-kinase (PI3K) and / or a target for rapamycin (mTOR). ) Inhibitors; 4) Thitochrome P450 inhibitors (eg, CYP17 inhibitors or 17α-hydroxylase / C17-20 lyase inhibitors); 5) Iron chelating agents; 6) Aromatase inhibitors; 7) Inhibition of p53 Agents such as p53 / Mdm2 interaction inhibitors; 8) apoptosis-inducing agents; 9) angiogenesis inhibitors; 10) aldosterone kinase inhibitors; 11) smoothund (SMO) receptor inhibitors; 12) prolactin receptors ( PRLR) inhibitor; 13) Wnt signaling inhibitor; 14) CDK4 / 6 inhibitor; 15) fibroblast proliferative factor receptor 2 (FGFR2) / fibroblast proliferative factor receptor 4 (FGFR4) inhibitor; 16 ) Macrophage colony stimulating factor (M-CSF) inhibitor; 17) c-KIT, histamine release, one or more inhibitors of Flt3 (eg, FLK2 / STK1) or PKC; 18) VEGFR-2 (eg, FLK-). 1 / KDR), PDGFRβ, c-KIT or Raf kinase C one or more inhibitors; 19) somatostatin agonists and / or growth hormone release inhibitors; 20) undifferentiated lymphoma kinase (ALK) inhibitors; 21) Insulin-like growth factor 1 receptor (IGF-1R) inhibitor; 22) P-glycoprotein 1 inhibitor; 23) Vascular endothelial growth factor receptor (VEGFR) inhibitor; 24) BCR-ABL kinase inhibitor; 25) FGFR inhibitor; 26) CYP11B2 inhibitor; 27) HDM2 inhibitor, eg, the HDM2-p53 interaction inhibitor; 28) tyrosine kinase inhibitor; 29) c-MET inhibitor; 30) JAK inhibition Agents; 31) DAC inhibitors; 32) 11β-hydroxylase inhibitors; 33) IAP inhibitors; 34) PIM kinase inhibitors; 35) porcupine inhibitors; 36) BRAF, eg BRAF V600E or Inhibitors of wild-type BRAF; 37) inhibitors of HER3; 38) inhibitors of MEK; 39) inhibitors of lipid kinases; or selected from one or more agents provided in Table 16, in [60]. The method described.
[69]
The antibody or antigen-binding fragment according to any one of [1] to [24], the nucleic acid or set of nucleic acids according to [25], and the vector according to any one of [26] to [32]. The method according to [60], wherein the cell according to [33] or the pharmaceutical composition according to [35] is administered at the same time as the at least one additional therapeutic agent, before or after.
[70]
Administration of the antibody or antigen-binding fragment thereof, the nucleic acid or a set of nucleic acids, the vector, the cells, or the pharmaceutical composition has the following effects:
(A) An increased number of CD45 + CD4-CD8 + CD69 + CD25 + cells in the tumor or lesion site in the subject;
(B) An increased number of CD45 + CD8-CD4 + FOXP3-CD69 + CD25 + cells in the tumor or lesion site in the subject;
(C) Decreased plasma MCP1 or IL-1β levels in the subject; or
(D) Increased MCP1 levels in the tumor or lesion site in the subject
The method according to any one of [55] to [69], which comprises one or more of.
[71]
A method for treating cancer in a subject in need of treatment, wherein the method inhibits PD-1 inhibition of the antibody or antigen-binding fragment according to any one of [1] to [28], which is a therapeutically effective amount. A method comprising administering to said subject in combination with a second therapeutic agent selected from agents or PD-L1 inhibitors.
[72]
A method for stimulating an immune response of cancer in a subject, wherein the antibody or antigen-binding fragment according to any one of [1] to [28] is used as a PD-1 inhibitor or PD-L1 inhibitor. A method comprising administering to said subject in combination with a second therapeutic agent selected from.
[73]
The antibody or antigen-binding fragment according to any one of [1] to [28] for use in the treatment of cancer in a subject is selected from a PD-1 inhibitor or a PD-L1 inhibitor. A composition containing in combination with a therapeutic agent for.
[74]
A composition for use in the treatment of cancer in a subject, wherein the composition comprises the antibody or antigen-binding fragment according to any one of the above [1] to [28], PD-1. A composition comprising in combination with a second therapeutic agent selected from an inhibitor or a PD-L1 inhibitor.
[75]
The method according to [71] or [72], or the composition according to [73] or [74], wherein the second therapeutic agent is a PD-1 inhibitor.
[76]
The method according to [71] or [72], or the composition according to [73] or [74], wherein the PD-1 inhibitor is a PD-1 antibody.
[77]
The method according to [71] or [72], wherein the PD-1 inhibitor is selected from PDR001, nivolumab, pembrolizumab, pidirizumab, MEDI0680, REGN2810, TSR-042, PF-06801591, or AMP-224. [73] or the composition according to [74].
[78]
The method according to [71] or [72], or the composition according to [73] or [74], wherein the second therapeutic agent is a PD-L1 inhibitor.
[79]
The method according to [71] or [72], or the composition according to [73] or [74], wherein the PD-L1 inhibitor is a PD-L1 antibody.
[80]
The method according to [71] or [72], or the composition according to [73] or [74], wherein the PD-L1 inhibitor is selected from FAZ053, atezolizumab, avelumab, durvalumab, or BMS-936559. ..
[81]
The method according to [71] or the composition according to [73] or [74], wherein the cancer is ENTPD2 + cancer.
[82]
The cancers include colorectal cancer (CRC), gastric cancer (eg, gastric adenocarcinoma, gastric cancer), esophageal cancer (eg, esophageal squamous epithelial cancer (ESCC)), pancreatic cancer, bile duct cancer, lung cancer (eg, small cell lung cancer). The method according to [71] or the composition according to [73] or [74], which is breast cancer (eg, breast cancer) or ovarian cancer.

Claims (64)

ヒトＥＮＴＰＤ２タンパク質に特異的に結合する抗体又はその抗原結合断片であって、前記抗体又はその抗原結合断片が、表１に提供される任意の抗体又は抗原結合断片の重鎖相補性決定領域１（ＨＣＤＲ１）、重鎖相補性決定領域２（ＨＣＤＲ２）、重鎖相補性決定領域３（ＨＣＤＲ３）、軽鎖相補性決定領域１（ＬＣＤＲ１）、軽鎖相補性決定領域２（ＬＣＤＲ２）、及び軽鎖相補性決定領域３（ＬＣＤＲ３）を含む、抗体又はその抗原結合断片。 An antibody that specifically binds to a human ENTPD2 protein or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof is a heavy chain complementarity determining region 1 of any antibody or antigen-binding fragment provided in Table 1. HCDR1), heavy chain complementarity determining regions 2 (HCDR2), heavy chain complementarity determining regions 3 (HCDR3), light chain complementarity determining regions 1 (LCDR1), light chain complementarity determining regions 2 (LCDR2), and light chains. An antibody or antigen-binding fragment thereof comprising complementarity determining regions 3 (LCDR3). 前記ＨＣＤＲ１、ＨＣＤＲ２、ＨＣＤＲ３、ＬＣＤＲ１、ＬＣＤＲ２、及びＬＣＤＲ３が、表１に提供されるＨＣＤＲ１、ＨＣＤＲ２、ＨＣＤＲ３、ＬＣＤＲ１、ＬＣＤＲ２、及びＬＣＤＲ３配列から選択される、請求項１に記載の抗体又はその抗原結合断片。 The antibody or antigen binding thereof according to claim 1, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences provided in Table 1. piece. 前記抗体又はその抗原結合断片が、表１に提供される重鎖可変領域を含む、請求項１又は請求項２に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region provided in Table 1. 前記抗体又はその抗原結合断片が、表１に提供される軽鎖可変領域を含む、請求項１～３のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, wherein the antibody or antigen-binding fragment thereof comprises a light chain variable region provided in Table 1. 前記抗体又はその抗原結合断片が、以下の任意の１つ：
１）以下を含む抗体又はその抗原結合断片：
配列番号１を含むＨＣＤＲ１配列、
配列番号２を含むＨＣＤＲ２配列、
配列番号３を含むＨＣＤＲ３配列、
配列番号１４を含むＬＣＤＲ１配列、
配列番号１５を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列；
２）以下を含む抗体又はその抗原結合断片：
配列番号４を含むＨＣＤＲ１配列、
配列番号５を含むＨＣＤＲ２配列、
配列番号３を含むＨＣＤＲ３配列、
配列番号１７を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号１９を含むＬＣＤＲ３配列；
３）以下を含む抗体又はその抗原結合断片：
配列番号７を含むＨＣＤＲ１配列、
配列番号８を含むＨＣＤＲ２配列、
配列番号９を含むＨＣＤＲ３配列、
配列番号２０を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列；
４）以下を含む抗体又はその抗原結合断片：
配列番号３７を含むＨＣＤＲ１配列、
配列番号３８を含むＨＣＤＲ２配列、
配列番号３９を含むＨＣＤＲ３配列、
配列番号５０を含むＬＣＤＲ１配列、
配列番号５１を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
５）以下を含む抗体又はその抗原結合断片：
配列番号４０を含むＨＣＤＲ１配列、
配列番号４１を含むＨＣＤＲ２配列、
配列番号３９を含むＨＣＤＲ３配列、
配列番号５３を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５５を含むＬＣＤＲ３配列；
６）以下を含む抗体又はその抗原結合断片：
配列番号４３を含むＨＣＤＲ１配列、
配列番号４４を含むＨＣＤＲ２配列、
配列番号４５を含むＨＣＤＲ３配列、
配列番号５６を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
７）以下を含む抗体又はその抗原結合断片：
配列番号３７を含むＨＣＤＲ１配列、
配列番号３８を含むＨＣＤＲ２配列、
配列番号３９を含むＨＣＤＲ３配列、
配列番号６１を含むＬＣＤＲ１配列、
配列番号５１を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
８）以下を含む抗体又はその抗原結合断片：
配列番号４０を含むＨＣＤＲ１配列、
配列番号４１を含むＨＣＤＲ２配列、
配列番号３９を含むＨＣＤＲ３配列、
配列番号６２を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５５を含むＬＣＤＲ３配列；
９）以下を含む抗体又はその抗原結合断片：
配列番号４３を含むＨＣＤＲ１配列、
配列番号４４を含むＨＣＤＲ２配列、
配列番号４５を含むＨＣＤＲ３配列、
配列番号６３を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
１０）以下を含む抗体又はその抗原結合断片：
配列番号３７を含むＨＣＤＲ１配列、
配列番号３８を含むＨＣＤＲ２配列、
配列番号６８を含むＨＣＤＲ３配列、
配列番号５０を含むＬＣＤＲ１配列、
配列番号５１を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
１１）以下を含む抗体又はその抗原結合断片：
配列番号４０を含むＨＣＤＲ１配列、
配列番号４１を含むＨＣＤＲ２配列、
配列番号６８を含むＨＣＤＲ３配列、
配列番号５３を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５５を含むＬＣＤＲ３配列；
１２）以下を含む抗体又はその抗原結合断片：
配列番号４３を含むＨＣＤＲ１配列、
配列番号４４を含むＨＣＤＲ２配列、
配列番号６９を含むＨＣＤＲ３配列、
配列番号５６を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
１３）以下を含む抗体又はその抗原結合断片：
配列番号８２を含むＨＣＤＲ１配列、
配列番号８３を含むＨＣＤＲ２配列、
配列番号８４を含むＨＣＤＲ３配列、
配列番号９５を含むＬＣＤＲ１配列、
配列番号９６を含むＬＣＤＲ２配列、及び
配列番号９７を含むＬＣＤＲ３配列；
１４）以下を含む抗体又はその抗原結合断片：
配列番号８５を含むＨＣＤＲ１配列、
配列番号８６を含むＨＣＤＲ２配列、
配列番号８４を含むＨＣＤＲ３配列、
配列番号９８を含むＬＣＤＲ１配列、
配列番号９９を含むＬＣＤＲ２配列、及び
配列番号１００を含むＬＣＤＲ３配列；
１５）以下を含む抗体又はその抗原結合断片：
配列番号８８を含むＨＣＤＲ１配列、
配列番号８９を含むＨＣＤＲ２配列、
配列番号９０を含むＨＣＤＲ３配列、
配列番号１０１を含むＬＣＤＲ１配列、
配列番号９９を含むＬＣＤＲ２配列、及び
配列番号９７を含むＬＣＤＲ３配列；
１６）以下を含む抗体又はその抗原結合断片：
配列番号１０６を含むＨＣＤＲ１配列、
配列番号１０７を含むＨＣＤＲ２配列、
配列番号１０８を含むＨＣＤＲ３配列、
配列番号１１９を含むＬＣＤＲ１配列、
配列番号１２０を含むＬＣＤＲ２配列、及び
配列番号１２１を含むＬＣＤＲ３配列；
１７）以下を含む抗体又はその抗原結合断片：
配列番号１０９を含むＨＣＤＲ１配列、
配列番号１１０を含むＨＣＤＲ２配列、
配列番号１０８を含むＨＣＤＲ３配列、
配列番号１２２を含むＬＣＤＲ１配列、
配列番号９９を含むＬＣＤＲ２配列、及び
配列番号１２３を含むＬＣＤＲ３配列；
１８）以下を含む抗体又はその抗原結合断片：
配列番号１１２を含むＨＣＤＲ１配列、
配列番号１１３を含むＨＣＤＲ２配列、
配列番号１１４を含むＨＣＤＲ３配列、
配列番号１２４を含むＬＣＤＲ１配列、
配列番号９９を含むＬＣＤＲ２配列、及び
配列番号１２１を含むＬＣＤＲ３配列；
１９）以下を含む抗体又はその抗原結合断片：
配列番号１０６を含むＨＣＤＲ１配列、
配列番号１２９を含むＨＣＤＲ２配列、
配列番号１０８を含むＨＣＤＲ３配列、
配列番号１１９を含むＬＣＤＲ１配列、
配列番号１２０を含むＬＣＤＲ２配列、及び
配列番号１２１を含むＬＣＤＲ３配列；
２０）以下を含む抗体又はその抗原結合断片：
配列番号１０９を含むＨＣＤＲ１配列、
配列番号１３０を含むＨＣＤＲ２配列、
配列番号１０８を含むＨＣＤＲ３配列、
配列番号１２２を含むＬＣＤＲ１配列、
配列番号９９を含むＬＣＤＲ２配列、及び
配列番号１２３を含むＬＣＤＲ３配列；
２１）以下を含む抗体又はその抗原結合断片：
配列番号１１２を含むＨＣＤＲ１配列、
配列番号１３１を含むＨＣＤＲ２配列、
配列番号１１４を含むＨＣＤＲ３配列、
配列番号１２４を含むＬＣＤＲ１配列、
配列番号９９を含むＬＣＤＲ２配列、及び
配列番号１２１を含むＬＣＤＲ３配列；
２２）以下を含む抗体又はその抗原結合断片：
配列番号１３６を含むＨＣＤＲ１配列、
配列番号１３７を含むＨＣＤＲ２配列、
配列番号１３８を含むＨＣＤＲ３配列、
配列番号１４９を含むＬＣＤＲ１配列、
配列番号１５０を含むＬＣＤＲ２配列、及び
配列番号１５１を含むＬＣＤＲ３配列；
２３）以下を含む抗体又はその抗原結合断片：
配列番号１３９を含むＨＣＤＲ１配列、
配列番号１４０を含むＨＣＤＲ２配列、
配列番号１３８を含むＨＣＤＲ３配列、
配列番号１５２を含むＬＣＤＲ１配列、
配列番号１５３を含むＬＣＤＲ２配列、及び
配列番号１５４を含むＬＣＤＲ３配列；
２４）以下を含む抗体又はその抗原結合断片：
配列番号１４２を含むＨＣＤＲ１配列、
配列番号１４３を含むＨＣＤＲ２配列、
配列番号１４４を含むＨＣＤＲ３配列、
配列番号１５５を含むＬＣＤＲ１配列、
配列番号１５３を含むＬＣＤＲ２配列、及び
配列番号１５１を含むＬＣＤＲ３配列；
２５）以下を含む抗体又はその抗原結合断片：
配列番号１６０を含むＨＣＤＲ１配列、
配列番号１６１を含むＨＣＤＲ２配列、
配列番号１６２を含むＨＣＤＲ３配列、
配列番号１７３を含むＬＣＤＲ１配列、
配列番号１５０を含むＬＣＤＲ２配列、及び
配列番号１７４を含むＬＣＤＲ３配列；
２６）以下を含む抗体又はその抗原結合断片：
配列番号１６３を含むＨＣＤＲ１配列、
配列番号１６４を含むＨＣＤＲ２配列、
配列番号１６２を含むＨＣＤＲ３配列、
配列番号１７５を含むＬＣＤＲ１配列、
配列番号１５３を含むＬＣＤＲ２配列、及び
配列番号１７６を含むＬＣＤＲ３配列；
２７）以下を含む抗体又はその抗原結合断片：
配列番号１６６を含むＨＣＤＲ１配列、
配列番号１６７を含むＨＣＤＲ２配列、
配列番号１６８を含むＨＣＤＲ３配列、
配列番号１７７を含むＬＣＤＲ１配列、
配列番号１５３を含むＬＣＤＲ２配列、及び
配列番号１７４を含むＬＣＤＲ３配列；
２８）以下を含む抗体又はその抗原結合断片：
配列番号３７を含むＨＣＤＲ１配列、
配列番号２２０を含むＨＣＤＲ２配列、
配列番号２２１を含むＨＣＤＲ３配列、
配列番号６１を含むＬＣＤＲ１配列、
配列番号５１を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
２９）以下を含む抗体又はその抗原結合断片：
配列番号４０を含むＨＣＤＲ１配列、
配列番号２２２を含むＨＣＤＲ２配列、
配列番号２２１を含むＨＣＤＲ３配列、
配列番号６２を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５５を含むＬＣＤＲ３配列；
３０）以下を含む抗体又はその抗原結合断片：
配列番号４３を含むＨＣＤＲ１配列、
配列番号２２３を含むＨＣＤＲ２配列、
配列番号２２４を含むＨＣＤＲ３配列、
配列番号６３を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
３１）以下を含む抗体又はその抗原結合断片：
配列番号３７を含むＨＣＤＲ１配列、
配列番号２２０を含むＨＣＤＲ２配列、
配列番号６８を含むＨＣＤＲ３配列、
配列番号６１を含むＬＣＤＲ１配列、
配列番号５１を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
３２）以下を含む抗体又はその抗原結合断片：
配列番号４０を含むＨＣＤＲ１配列、
配列番号２２２を含むＨＣＤＲ２配列、
配列番号６８を含むＨＣＤＲ３配列、
配列番号６２を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５５を含むＬＣＤＲ３配列；
３３）以下を含む抗体又はその抗原結合断片：
配列番号４３を含むＨＣＤＲ１配列、
配列番号２２３を含むＨＣＤＲ２配列、
配列番号６９を含むＨＣＤＲ３配列、
配列番号６３を含むＬＣＤＲ１配列、
配列番号５４を含むＬＣＤＲ２配列、及び
配列番号５２を含むＬＣＤＲ３配列；
３４）以下を含む抗体又はその抗原結合断片：
配列番号１を含むＨＣＤＲ１配列、
配列番号２４５を含むＨＣＤＲ２配列、
配列番号２４６を含むＨＣＤＲ３配列、
配列番号２５４を含むＬＣＤＲ１配列、
配列番号１５を含むＬＣＤＲ２配列、及び
配列番号２５５を含むＬＣＤＲ３配列；
３５）以下を含む抗体又はその抗原結合断片：
配列番号４を含むＨＣＤＲ１配列、
配列番号２４７を含むＨＣＤＲ２配列、
配列番号２４６を含むＨＣＤＲ３配列、
配列番号１７を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号２５６を含むＬＣＤＲ３配列；
３６）以下を含む抗体又はその抗原結合断片：
配列番号７を含むＨＣＤＲ１配列、
配列番号２４８を含むＨＣＤＲ２配列、
配列番号２４９を含むＨＣＤＲ３配列、
配列番号２０を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号２５５を含むＬＣＤＲ３配列；
３７）以下を含む抗体又はその抗原結合断片：
配列番号１を含むＨＣＤＲ１配列、
配列番号２６１を含むＨＣＤＲ２配列、
配列番号２６２を含むＨＣＤＲ３配列、
配列番号２５４を含むＬＣＤＲ１配列、
配列番号１５を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列；
３８）以下を含む抗体又はその抗原結合断片：
配列番号４を含むＨＣＤＲ１配列、
配列番号２４７を含むＨＣＤＲ２配列、
配列番号２６２を含むＨＣＤＲ３配列、
配列番号１７を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号１９を含むＬＣＤＲ３配列；
３９）以下を含む抗体又はその抗原結合断片：
配列番号７を含むＨＣＤＲ１配列、
配列番号２４８を含むＨＣＤＲ２配列、
配列番号２６３を含むＨＣＤＲ３配列、
配列番号２０を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列；
４０）以下を含む抗体又はその抗原結合断片：
配列番号２７２を含むＨＣＤＲ１配列、
配列番号２７３を含むＨＣＤＲ２配列、
配列番号２７４を含むＨＣＤＲ３配列、
配列番号２５４を含むＬＣＤＲ１配列、
配列番号２８５を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列；
４１）以下を含む抗体又はその抗原結合断片：
配列番号２７５を含むＨＣＤＲ１配列、
配列番号２７６を含むＨＣＤＲ２配列、
配列番号２７４を含むＨＣＤＲ３配列、
配列番号１７を含むＬＣＤＲ１配列、
配列番号２８６を含むＬＣＤＲ２配列、及び
配列番号１９を含むＬＣＤＲ３配列；
４２）以下を含む抗体又はその抗原結合断片：
配列番号２７８を含むＨＣＤＲ１配列、
配列番号２７９を含むＨＣＤＲ２配列、
配列番号２８０を含むＨＣＤＲ３配列、
配列番号２０を含むＬＣＤＲ１配列、
配列番号２８６を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列
から選択される、請求項１又は請求項２に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof may be any one of the following:
1) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence containing SEQ ID NO: 1,
HCDR2 sequence, including SEQ ID NO: 2,
HCDR3 sequence, including SEQ ID NO: 3,
LCDR1 sequence, including SEQ ID NO: 14.
An LCDR2 sequence containing SEQ ID NO: 15 and an LCDR3 sequence containing SEQ ID NO: 16;
2) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 4,
HCDR2 sequence, including SEQ ID NO: 5,
HCDR3 sequence, including SEQ ID NO: 3,
LCDR1 sequence, including SEQ ID NO: 17.
An LCDR2 sequence containing SEQ ID NO: 18 and an LCDR3 sequence containing SEQ ID NO: 19;
3) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence containing SEQ ID NO: 7,
HCDR2 sequence containing SEQ ID NO: 8,
HCDR3 sequence, including SEQ ID NO: 9.
LCDR1 sequence, including SEQ ID NO: 20
An LCDR2 sequence containing SEQ ID NO: 18 and an LCDR3 sequence containing SEQ ID NO: 16;
4) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 37,
HCDR2 sequence, including SEQ ID NO: 38,
HCDR3 sequence, including SEQ ID NO: 39,
LCDR1 sequence, including SEQ ID NO: 50,
An LCDR2 sequence containing SEQ ID NO: 51 and an LCDR3 sequence containing SEQ ID NO: 52;
5) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 40,
HCDR2 sequence, including SEQ ID NO: 41,
HCDR3 sequence, including SEQ ID NO: 39,
LCDR1 sequence, including SEQ ID NO: 53,
An LCDR2 sequence containing SEQ ID NO: 54 and an LCDR3 sequence containing SEQ ID NO: 55;
6) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 43,
HCDR2 sequence, including SEQ ID NO: 44,
HCDR3 sequence, including SEQ ID NO: 45,
LCDR1 sequence, including SEQ ID NO: 56,
An LCDR2 sequence containing SEQ ID NO: 54 and an LCDR3 sequence containing SEQ ID NO: 52;
7) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 37,
HCDR2 sequence, including SEQ ID NO: 38,
HCDR3 sequence, including SEQ ID NO: 39,
LCDR1 sequence, including SEQ ID NO: 61,
An LCDR2 sequence containing SEQ ID NO: 51 and an LCDR3 sequence containing SEQ ID NO: 52;
8) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 40,
HCDR2 sequence, including SEQ ID NO: 41,
HCDR3 sequence, including SEQ ID NO: 39,
LCDR1 sequence, including SEQ ID NO: 62,
An LCDR2 sequence containing SEQ ID NO: 54 and an LCDR3 sequence containing SEQ ID NO: 55;
9) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 43,
HCDR2 sequence, including SEQ ID NO: 44,
HCDR3 sequence, including SEQ ID NO: 45,
LCDR1 sequence, including SEQ ID NO: 63,
An LCDR2 sequence containing SEQ ID NO: 54 and an LCDR3 sequence containing SEQ ID NO: 52;
10) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 37,
HCDR2 sequence, including SEQ ID NO: 38,
HCDR3 sequence, including SEQ ID NO: 68,
LCDR1 sequence, including SEQ ID NO: 50,
An LCDR2 sequence containing SEQ ID NO: 51 and an LCDR3 sequence containing SEQ ID NO: 52;
11) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 40,
HCDR2 sequence, including SEQ ID NO: 41,
HCDR3 sequence, including SEQ ID NO: 68,
LCDR1 sequence, including SEQ ID NO: 53,
An LCDR2 sequence containing SEQ ID NO: 54 and an LCDR3 sequence containing SEQ ID NO: 55;
12) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 43,
HCDR2 sequence, including SEQ ID NO: 44,
HCDR3 sequence, including SEQ ID NO: 69,
LCDR1 sequence, including SEQ ID NO: 56,
An LCDR2 sequence containing SEQ ID NO: 54 and an LCDR3 sequence containing SEQ ID NO: 52;
13) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 82,
HCDR2 sequence, including SEQ ID NO: 83,
HCDR3 sequence, including SEQ ID NO: 84,
LCDR1 sequence, including SEQ ID NO: 95,
An LCDR2 sequence containing SEQ ID NO: 96 and an LCDR3 sequence containing SEQ ID NO: 97;
14) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 85,
HCDR2 sequence, including SEQ ID NO: 86,
HCDR3 sequence, including SEQ ID NO: 84,
LCDR1 sequence, including SEQ ID NO: 98,
An LCDR2 sequence containing SEQ ID NO: 99 and an LCDR3 sequence containing SEQ ID NO: 100;
15) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 88,
HCDR2 sequence, including SEQ ID NO: 89,
HCDR3 sequence, including SEQ ID NO: 90,
LCDR1 sequence, including SEQ ID NO: 101,
An LCDR2 sequence containing SEQ ID NO: 99 and an LCDR3 sequence containing SEQ ID NO: 97;
16) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 106,
HCDR2 sequence, including SEQ ID NO: 107,
HCDR3 sequence, including SEQ ID NO: 108,
LCDR1 sequence, including SEQ ID NO: 119,
An LCDR2 sequence containing SEQ ID NO: 120 and an LCDR3 sequence containing SEQ ID NO: 121;
17) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 109,
HCDR2 sequence, including SEQ ID NO: 110,
HCDR3 sequence, including SEQ ID NO: 108,
LCDR1 sequence, including SEQ ID NO: 122,
An LCDR2 sequence containing SEQ ID NO: 99 and an LCDR3 sequence containing SEQ ID NO: 123;
18) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 112,
HCDR2 sequence, including SEQ ID NO: 113,
HCDR3 sequence, including SEQ ID NO: 114,
LCDR1 sequence, including SEQ ID NO: 124,
An LCDR2 sequence containing SEQ ID NO: 99 and an LCDR3 sequence containing SEQ ID NO: 121;
19) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 106,
HCDR2 sequence, including SEQ ID NO: 129,
HCDR3 sequence, including SEQ ID NO: 108,
LCDR1 sequence, including SEQ ID NO: 119,
An LCDR2 sequence containing SEQ ID NO: 120 and an LCDR3 sequence containing SEQ ID NO: 121;
20) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 109,
HCDR2 sequence, including SEQ ID NO: 130,
HCDR3 sequence, including SEQ ID NO: 108,
LCDR1 sequence, including SEQ ID NO: 122,
An LCDR2 sequence containing SEQ ID NO: 99 and an LCDR3 sequence containing SEQ ID NO: 123;
21) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 112,
HCDR2 sequence, including SEQ ID NO: 131,
HCDR3 sequence, including SEQ ID NO: 114,
LCDR1 sequence, including SEQ ID NO: 124,
An LCDR2 sequence containing SEQ ID NO: 99 and an LCDR3 sequence containing SEQ ID NO: 121;
22) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 136,
HCDR2 sequence, including SEQ ID NO: 137,
HCDR3 sequence, including SEQ ID NO: 138,
LCDR1 sequence, including SEQ ID NO: 149,
An LCDR2 sequence containing SEQ ID NO: 150 and an LCDR3 sequence containing SEQ ID NO: 151;
23) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 139,
HCDR2 sequence, including SEQ ID NO: 140,
HCDR3 sequence, including SEQ ID NO: 138,
LCDR1 sequence, including SEQ ID NO: 152,
An LCDR2 sequence containing SEQ ID NO: 153 and an LCDR3 sequence containing SEQ ID NO: 154;
24) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 142,
HCDR2 sequence, including SEQ ID NO: 143,
HCDR3 sequence, including SEQ ID NO: 144,
LCDR1 sequence, including SEQ ID NO: 155,
An LCDR2 sequence containing SEQ ID NO: 153 and an LCDR3 sequence containing SEQ ID NO: 151;
25) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 160,
HCDR2 sequence, including SEQ ID NO: 161.
HCDR3 sequence, including SEQ ID NO: 162,
LCDR1 sequence, including SEQ ID NO: 173,
An LCDR2 sequence containing SEQ ID NO: 150 and an LCDR3 sequence containing SEQ ID NO: 174;
26) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 163,
HCDR2 sequence, including SEQ ID NO: 164,
HCDR3 sequence, including SEQ ID NO: 162,
LCDR1 sequence, including SEQ ID NO: 175,
An LCDR2 sequence containing SEQ ID NO: 153 and an LCDR3 sequence containing SEQ ID NO: 176;
27) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 166,
HCDR2 sequence, including SEQ ID NO: 167,
HCDR3 sequence, including SEQ ID NO: 168,
LCDR1 sequence, including SEQ ID NO: 177,
An LCDR2 sequence containing SEQ ID NO: 153 and an LCDR3 sequence containing SEQ ID NO: 174;
28) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 37,
HCDR2 sequence, including SEQ ID NO: 220,
HCDR3 sequence, including SEQ ID NO: 221
LCDR1 sequence, including SEQ ID NO: 61,
An LCDR2 sequence containing SEQ ID NO: 51 and an LCDR3 sequence containing SEQ ID NO: 52;
29) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 40,
HCDR2 sequence, including SEQ ID NO: 222,
HCDR3 sequence, including SEQ ID NO: 221
LCDR1 sequence, including SEQ ID NO: 62,
An LCDR2 sequence containing SEQ ID NO: 54 and an LCDR3 sequence containing SEQ ID NO: 55;
30) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 43,
HCDR2 sequence, including SEQ ID NO: 223,
HCDR3 sequence, including SEQ ID NO: 224,
LCDR1 sequence, including SEQ ID NO: 63,
An LCDR2 sequence containing SEQ ID NO: 54 and an LCDR3 sequence containing SEQ ID NO: 52;
31) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 37,
HCDR2 sequence, including SEQ ID NO: 220,
HCDR3 sequence, including SEQ ID NO: 68,
LCDR1 sequence, including SEQ ID NO: 61,
An LCDR2 sequence containing SEQ ID NO: 51 and an LCDR3 sequence containing SEQ ID NO: 52;
32) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 40,
HCDR2 sequence, including SEQ ID NO: 222,
HCDR3 sequence, including SEQ ID NO: 68,
LCDR1 sequence, including SEQ ID NO: 62,
An LCDR2 sequence containing SEQ ID NO: 54 and an LCDR3 sequence containing SEQ ID NO: 55;
33) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 43,
HCDR2 sequence, including SEQ ID NO: 223,
HCDR3 sequence, including SEQ ID NO: 69,
LCDR1 sequence, including SEQ ID NO: 63,
An LCDR2 sequence containing SEQ ID NO: 54 and an LCDR3 sequence containing SEQ ID NO: 52;
34) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence containing SEQ ID NO: 1,
HCDR2 sequence, including SEQ ID NO: 245,
HCDR3 sequence, including SEQ ID NO: 246,
LCDR1 sequence, including SEQ ID NO: 254,
An LCDR2 sequence containing SEQ ID NO: 15 and an LCDR3 sequence containing SEQ ID NO: 255;
35) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 4,
HCDR2 sequence, including SEQ ID NO: 247,
HCDR3 sequence, including SEQ ID NO: 246,
LCDR1 sequence, including SEQ ID NO: 17.
An LCDR2 sequence containing SEQ ID NO: 18 and an LCDR3 sequence containing SEQ ID NO: 256;
36) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence containing SEQ ID NO: 7,
HCDR2 sequence, including SEQ ID NO: 248,
HCDR3 sequence, including SEQ ID NO: 249,
LCDR1 sequence, including SEQ ID NO: 20
An LCDR2 sequence containing SEQ ID NO: 18 and an LCDR3 sequence containing SEQ ID NO: 255;
37) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence containing SEQ ID NO: 1,
HCDR2 sequence, including SEQ ID NO: 261.
HCDR3 sequence, including SEQ ID NO: 262,
LCDR1 sequence, including SEQ ID NO: 254,
An LCDR2 sequence containing SEQ ID NO: 15 and an LCDR3 sequence containing SEQ ID NO: 16;
38) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 4,
HCDR2 sequence, including SEQ ID NO: 247,
HCDR3 sequence, including SEQ ID NO: 262,
LCDR1 sequence, including SEQ ID NO: 17.
An LCDR2 sequence containing SEQ ID NO: 18 and an LCDR3 sequence containing SEQ ID NO: 19;
39) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence containing SEQ ID NO: 7,
HCDR2 sequence, including SEQ ID NO: 248,
HCDR3 sequence, including SEQ ID NO: 263,
LCDR1 sequence, including SEQ ID NO: 20
An LCDR2 sequence containing SEQ ID NO: 18 and an LCDR3 sequence containing SEQ ID NO: 16;
40) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 272,
HCDR2 sequence, including SEQ ID NO: 273,
HCDR3 sequence, including SEQ ID NO: 274,
LCDR1 sequence, including SEQ ID NO: 254,
An LCDR2 sequence containing SEQ ID NO: 285 and an LCDR3 sequence containing SEQ ID NO: 16;
41) Antibodies containing the following or antigen-binding fragments thereof:
HCDR1 sequence, including SEQ ID NO: 275,
HCDR2 sequence, including SEQ ID NO: 276,
HCDR3 sequence, including SEQ ID NO: 274,
LCDR1 sequence, including SEQ ID NO: 17.
An LCDR2 sequence containing SEQ ID NO: 286 and an LCDR3 sequence containing SEQ ID NO: 19;
42) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence, including SEQ ID NO: 278,
HCDR2 sequence, including SEQ ID NO: 279,
HCDR3 sequence, including SEQ ID NO: 280,
LCDR1 sequence, including SEQ ID NO: 20
The antibody or antigen-binding fragment thereof according to claim 1 or 2, selected from the LCDR2 sequence comprising SEQ ID NO: 286 and the LCDR3 sequence comprising SEQ ID NO: 16. 前記抗体又はその抗原結合断片が、以下の任意の１つ：
１）配列番号１０又はそれと少なくとも９５％以上同一の配列を含む重鎖可変領域（ＶＨ）、及び配列番号２１又はそれと少なくとも９５％以上同一の配列を含む軽鎖可変領域（ＶＬ）を含む抗体又はその抗原結合断片；
２）配列番号２５又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号２９又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
３）配列番号３３又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号２９又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
４）配列番号４６又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号５７又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
５）配列番号４６又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号６４又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
６）配列番号７０又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号７４又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
７）配列番号２５又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号７８又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
８）配列番号９１又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号１０２又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
９）配列番号１１５又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号１２５又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１０）配列番号１３２又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号１２５又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１１）配列番号１４５又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号１５６又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１２）配列番号１６９又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号１７８又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１３）配列番号２２５又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号２２９又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１４）配列番号２３３又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号２３７又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１５）配列番号２４１又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号２２９又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１６）配列番号２５０又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号２５７又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；
１７）配列番号２６４又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号２６８又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片；又は
１８）配列番号２８１又はそれと少なくとも９５％以上同一の配列を含むＶＨ、及び配列番号２８７又はそれと少なくとも９５％以上同一の配列を含むＶＬを含む抗体又はその抗原結合断片
から選択される、請求項１～５のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof may be any one of the following:
1) Heavy chain variable region (VH) containing SEQ ID NO: 10 or at least 95% identical sequence to it, and light chain variable region (VH) containing SEQ ID NO: 21 or at least 95% identical sequence to it. VL) -containing antibody or antigen-binding fragment thereof;
2) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 25 or at least 95% identical sequence to it, and VL containing SEQ ID NO: 29 or at least 95% identical sequence thereof;
3) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 33 or at least 95% identical sequence to it, and VL containing SEQ ID NO: 29 or at least 95% identical sequence to it;
4) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 46 or at least 95% identical sequence to it, and VL containing SEQ ID NO: 57 or at least 95% identical sequence to it;
5) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 46 or at least 95% identical sequence to it, and VL containing SEQ ID NO: 64 or at least 95% identical sequence to it;
6) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 70 or at least 95% identical sequence to it, and VL containing SEQ ID NO: 74 or at least 95% identical sequence to it;
7) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 25 or at least 95% identical sequence to it, and VL containing SEQ ID NO: 78 or at least 95% identical sequence to it;
8) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 91 or a VH containing at least 95% or more the same sequence as SEQ ID NO: 102 or VL containing at least 95% or more the same sequence with SEQ ID NO: 102;
9) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 115 or at least 95% identical sequence to it, and VL containing SEQ ID NO: 125 or at least 95% identical sequence to it;
10) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 132 or at least 95% identical sequence to it, and VL containing SEQ ID NO: 125 or at least 95% identical sequence to it;
11) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 145 or at least 95% identical sequence to it, and VL containing SEQ ID NO: 156 or at least 95% identical sequence thereof;
12) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 169 or a VH containing at least 95% or more the same sequence as SEQ ID NO: 178 or VL containing at least 95% or more the same sequence with SEQ ID NO: 178;
13) An antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 225 or at least 95% or more identical sequence, and VL containing SEQ ID NO: 229 or at least 95% or more identical sequence;
14) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 233 or a VH containing at least 95% or more identical sequence, and SEQ ID NO: 237 or VL containing at least 95% or more identical sequence;
15) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 241 or VH containing at least 95% identical sequence to it, and SEQ ID NO: 229 or VL containing at least 95% identical sequence thereof;
16) An antibody or antigen-binding fragment thereof comprising VH containing SEQ ID NO: 250 or at least 95% identical sequence to it, and VL containing SEQ ID NO: 257 or at least 95% identical sequence thereof;
17) An antibody or antigen-binding fragment thereof comprising SEQ ID NO: 264 or VH containing at least 95% or more identical sequence, and SEQ ID NO: 268 or VL containing at least 95% or more identical sequence. 18) Select from an antibody or antigen-binding fragment thereof containing VH containing SEQ ID NO: 281 or at least 95% or more identical sequence, and VL containing SEQ ID NO: 287 or at least 95% or more identical sequence. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 5. 抗体又はその抗原結合断片が、以下の任意の１つ：
１）配列番号１２又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号２３又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
２）配列番号２７又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号３１又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
３）配列番号３５又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号３１又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
４）配列番号４８又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号５９又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
５）配列番号４８又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号６６又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
６）配列番号７２又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号７６又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
７）配列番号２７又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号８０又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
８）配列番号９３又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号１０４又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
９）配列番号１１７又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号１２７又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
１０）配列番号１３４又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号１２７又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
１１）配列番号１４７又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号１５８又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
１２）配列番号１７１又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号１８０又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
１３）配列番号２２７又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号２３１又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
１４）配列番号２３５又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号２３９又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
１５）配列番号２４３又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号２３１又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
１６）配列番号２５２又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号２５９又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；
１７）配列番号２６６又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号２７０又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体；又は
１８）配列番号２８３又はそれと少なくとも９５％以上同一の配列を含む重鎖、及び配列番号２８９又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む抗体
から選択される、請求項１～６のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof is any one of the following:
1) An antibody comprising a heavy chain containing SEQ ID NO: 12 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 23 or at least 95% identical sequence to it;
2) An antibody comprising a heavy chain containing SEQ ID NO: 27 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 31 or at least 95% identical sequence to it;
3) An antibody comprising a heavy chain containing SEQ ID NO: 35 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 31 or at least 95% identical sequence to it;
4) An antibody comprising a heavy chain containing SEQ ID NO: 48 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 59 or at least 95% identical sequence to it;
5) An antibody comprising a heavy chain containing SEQ ID NO: 48 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 66 or at least 95% identical sequence to it;
6) An antibody comprising a heavy chain containing SEQ ID NO: 72 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 76 or at least 95% identical sequence to it;
7) An antibody comprising a heavy chain containing SEQ ID NO: 27 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 80 or at least 95% identical sequence to it;
8) An antibody comprising a heavy chain containing SEQ ID NO: 93 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 104 or at least 95% identical sequence to it;
9) An antibody comprising a heavy chain containing SEQ ID NO: 117 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 127 or at least 95% identical sequence to it;
10) An antibody comprising a heavy chain containing SEQ ID NO: 134 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 127 or at least 95% identical sequence to it;
11) An antibody comprising a heavy chain containing SEQ ID NO: 147 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 158 or at least 95% identical sequence to it;
12) An antibody comprising a heavy chain containing SEQ ID NO: 171 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 180 or at least 95% identical sequence to it;
13) An antibody comprising a heavy chain containing SEQ ID NO: 227 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 231 or at least 95% identical sequence to it;
14) An antibody comprising a heavy chain containing SEQ ID NO: 235 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 239 or at least 95% identical sequence to it;
15) An antibody comprising a heavy chain containing SEQ ID NO: 243 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 231 or at least 95% identical sequence to it;
16) An antibody comprising a heavy chain containing SEQ ID NO: 252 or at least 95% identical sequence to it, and a light chain comprising SEQ ID NO: 259 or at least 95% identical sequence to it;
17) An antibody comprising heavy chain comprising SEQ ID NO: 266 or at least 95% identical sequence to it, and light chain comprising SEQ ID NO: 270 or at least 95% identical sequence to it; or 18) SEQ ID NO: 1. Claim 1 selected from an antibody comprising a heavy chain comprising No. 283 or at least 95% identical sequence and a light chain comprising SEQ ID NO: 289 or at least 95% identical sequence. The antibody or antigen-binding fragment thereof according to any one of 6 to 6. 前記抗体又はその抗原結合断片が：
配列番号１を含むＨＣＤＲ１配列、
配列番号２を含むＨＣＤＲ２配列、
配列番号３を含むＨＣＤＲ３配列、
配列番号１４を含むＬＣＤＲ１配列、
配列番号１５を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列
を含む、請求項１～７のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof is:
HCDR1 sequence containing SEQ ID NO: 1,
HCDR2 sequence, including SEQ ID NO: 2,
HCDR3 sequence, including SEQ ID NO: 3,
LCDR1 sequence, including SEQ ID NO: 14.
The antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, which comprises an LCDR2 sequence comprising SEQ ID NO: 15 and an LCDR3 sequence comprising SEQ ID NO: 16. 前記抗体又はその抗原結合断片が：
配列番号４を含むＨＣＤＲ１配列、
配列番号５を含むＨＣＤＲ２配列、
配列番号３を含むＨＣＤＲ３配列、
配列番号１７を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号１９を含むＬＣＤＲ３配列
を含む、請求項１～７のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof is:
HCDR1 sequence, including SEQ ID NO: 4,
HCDR2 sequence, including SEQ ID NO: 5,
HCDR3 sequence, including SEQ ID NO: 3,
LCDR1 sequence, including SEQ ID NO: 17.
The antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, which comprises an LCDR2 sequence comprising SEQ ID NO: 18 and an LCDR3 sequence comprising SEQ ID NO: 19. 前記抗体又はその抗原結合断片が：
配列番号７を含むＨＣＤＲ１配列、
配列番号８を含むＨＣＤＲ２配列、
配列番号９を含むＨＣＤＲ３配列、
配列番号２０を含むＬＣＤＲ１配列、
配列番号１８を含むＬＣＤＲ２配列、及び
配列番号１６を含むＬＣＤＲ３配列
を含む、請求項１～７のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof is:
HCDR1 sequence containing SEQ ID NO: 7,
HCDR2 sequence containing SEQ ID NO: 8,
HCDR3 sequence, including SEQ ID NO: 9.
LCDR1 sequence, including SEQ ID NO: 20
The antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, which comprises an LCDR2 sequence comprising SEQ ID NO: 18 and an LCDR3 sequence comprising SEQ ID NO: 16. 前記抗体又はその抗原結合断片が、配列番号１０又はそれと少なくとも９５％以上同一の配列を含む重鎖可変領域（ＶＨ）、及び配列番号２１又はそれと少なくとも９５％以上同一の配列を含む軽鎖可変領域（ＶＬ）を含む、請求項１～７のいずれか一項に記載の抗体又はその抗原結合断片。 A heavy chain variable region (VH) containing SEQ ID NO: 10 or at least 95% identical to the antibody or antigen-binding fragment thereof, and SEQ ID NO: 21 or at least 95% identical to the sequence. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, which comprises a light chain variable region (VL) comprising. 前記抗体又はその抗原結合断片が、配列番号１２又はそれと少なくとも９５％以上同一の配列、及び配列番号２３又はそれと少なくとも９５％以上同一の配列を含む軽鎖を含む、請求項１～７のいずれか一項に記載の抗体又はその抗原結合断片。 Claimed that the antibody or an antigen-binding fragment thereof comprises a light chain comprising SEQ ID NO: 12 or at least 95% or more identical sequence to SEQ ID NO: 23 or SEQ ID NO: 23 or at least 95% identical sequence. The antibody or antigen-binding fragment thereof according to any one of 1 to 7. 前記抗体又はその抗原結合断片が、ヒトＥＮＴＰＤ２におけるエピトープに結合し、前記エピトープが、以下の残基：Ｈｉｓ５０、Ａｓｐ７６、Ｐｒｏ７８、Ｇｌｙ７９、Ｇｌｙ８０、Ｔｙｒ８５、Ａｓｐ８７、Ａｓｎ８８、Ｇｌｙ９１、Ｇｌｎ９４、Ｓｅｒ９５、Ｇｌｙ９８、Ｇｌｕ１０１、Ｇｌｎ１０２、Ｇｌｎ１０５、Ａｓｐ１０６、Ａｒｇ２４５、Ｔｈｒ２７２、Ｇｌｎ２７３、Ｌｅｕ２７５、Ａｓｐ２７８、Ａｒｇ２９８、Ａｌａ３４７、Ａｌａ３５０、Ｔｈｒ３５１、Ａｒｇ３９２、Ａｌａ３９３、Ａｒｇ３９４、又はＴｙｒ３９８の少なくとも１つを含む、請求項１～１２のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof binds to an epitope in human ENTPD2, and the epitope is the following residues: His50, Asp76, Pro78, Gly79, Gly80, Tyr85, Asp87, Asn88, Gly91, Gln94, Ser95, Gly98, Any one of Glu101, Gln102, Gln105, Asp106, Arg245, Thr272, Grn273, Leu275, Asp278, Arg298, Ala347, Ala350, Thr351, Arg392, Ala393, Arg394, or Tyr398. The antibody or antigen-binding fragment thereof according to the section. 前記抗体又はその抗原結合断片が、ヒトＥＮＴＰＤ２におけるエピトープに結合し、前記エピトープが、以下の残基：Ｇｌｙ７９、Ｇｌｎ２５０、Ｌｅｕ２５３、Ｔｒｐ２６６、Ａｒｇ２６８、Ｇｌｙ２６９、Ｐｈｅ２７０、Ｓｅｒ２７１、Ｔｈｒ２７２、Ｇｌｎ２７３、Ｖａｌ２７４、Ｌｅｕ２７５、Ａｓｐ２７８、Ａｒｇ２９８、Ｓｅｒ３００、Ｓｅｒ３０２、Ｇｌｙ３０３、Ｔｈｒ３８０、Ｔｒｐ３８１、Ａｌａ３８２、Ｇｌｙ３９０、Ｇｌｎ３９１、Ａｒｇ３９２、Ａｌａ３９３、Ａｒｇ３９４、又はＡｓｐ３９７の少なくとも１つを含む、請求項１～１２のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof binds to an epitope in human ENTPD2, and the epitope is the following residues: Gly79, Gln250, Leu253, Trp266, Arg268, Gly269, Phe270, Ser271, Thr272, Gln273, Val274, Leu275, The antibody according to any one of claims 1 to 12, which comprises at least one of Asp278, Arg298, Ser300, Ser302, Gly303, Thr380, Trp381, Ala382, Gly390, Gln391, Arg392, Ala393, Arg394, or Asp397. The antigen-binding fragment. ヒトＥＮＴＰＤ２におけるエピトープに特異的に結合する抗体又はその抗原結合断片であって、前記エピトープが、以下の残基：Ｈｉｓ５０、Ａｓｐ７６、Ｐｒｏ７８、Ｇｌｙ７９、Ｇｌｙ８０、Ｔｙｒ８５、Ａｓｐ８７、Ａｓｎ８８、Ｇｌｙ９１、Ｇｌｎ９４、Ｓｅｒ９５、Ｇｌｙ９８、Ｇｌｕ１０１、Ｇｌｎ１０２、Ｇｌｎ１０５、Ａｓｐ１０６、Ａｒｇ２４５、Ｔｈｒ２７２、Ｇｌｎ２７３、Ｌｅｕ２７５、Ａｓｐ２７８、Ａｒｇ２９８、Ａｌａ３４７、Ａｌａ３５０、Ｔｈｒ３５１、Ａｒｇ３９２、Ａｌａ３９３、Ａｒｇ３９４、又はＴｙｒ３９８の少なくとも１つを含む、抗体又はその抗原結合断片。 An antibody or antigen-binding fragment thereof that specifically binds to an epitope in human ENTPD2, wherein the epitope is the following residues: His50, Asp76, Pro78, Gly79, Gly80, Tyr85, Asp87, Asn88, Gly91, Gln94, Ser95. , Gly98, Glu101, Gln102, Gln105, Asp106, Arg245, Thr272, Grn273, Leu275, Asp278, Arg298, Ala347, Ala350, Thr351, Arg392, Ala393, Arg394, or at least one antibody thereof-binding antibody thereof. .. ヒトＥＮＴＰＤ２におけるエピトープに特異的に結合する抗体又はその抗原結合断片であって、前記エピトープが、以下の残基：Ｇｌｙ７９、Ｇｌｎ２５０、Ｌｅｕ２５３、Ｔｒｐ２６６、Ａｒｇ２６８、Ｇｌｙ２６９、Ｐｈｅ２７０、Ｓｅｒ２７１、Ｔｈｒ２７２、Ｇｌｎ２７３、Ｖａｌ２７４、Ｌｅｕ２７５、Ａｓｐ２７８、Ａｒｇ２９８、Ｓｅｒ３００、Ｓｅｒ３０２、Ｇｌｙ３０３、Ｔｈｒ３８０、Ｔｒｐ３８１、Ａｌａ３８２、Ｇｌｙ３９０、Ｇｌｎ３９１、Ａｒｇ３９２、Ａｌａ３９３、Ａｒｇ３９４、又はＡｓｐ３９７の少なくとも１つを含む、抗体又はその抗原結合断片。 An antibody or antigen-binding fragment thereof that specifically binds to an epitope in human ENTPD2, wherein the epitope is the following residues: Gly79, Gln250, Leu253, Trp266, Arg268, Gly269, Phe270, Ser271, Thr272, Gln273, Val274. , Leu275, Asp278, Arg298, Ser300, Ser302, Gly303, Thr380, Trp381, Ala382, Gly390, Gln391, Arg392, Ala393, Arg394, or an antigen-binding fragment thereof. ヒトＥＮＴＰＤ２タンパク質に対する結合について、表１に提供される任意の抗体又は抗原結合断片と競合する、抗体又はその抗原結合断片。 An antibody or antigen-binding fragment thereof that competes with any of the antibodies or antigen-binding fragments provided in Table 1 for binding to the human ENTPD2 protein. 表１に提供される任意の抗体又は抗原結合断片のいずれかのエピトープと同じエピトープ、実質的に同じエピトープ、それと重複するエピトープ、それと実質的に重複するエピトープに結合する、抗体又はその抗原結合断片。 An antibody or antigen-binding fragment thereof that binds to the same epitope, substantially the same epitope, an epitope that overlaps with it, or an epitope that substantially overlaps with any of the epitopes of any of the antibodies or antigen-binding fragments provided in Table 1. .. 前記抗体又はその抗原結合断片が、１０ｎＭ未満の解離定数（ＫＤ）でヒトＥＮＴＰＤ２タンパク質に結合する、請求項１～１８のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof according to any one of claims 1 to 18, wherein the antibody or an antigen-binding fragment thereof binds to a human ENTPD2 protein with a dissociation constant (KD) of less than 10 nM. 前記抗体又はその抗原結合断片が、５ｎＭ未満の解離定数（ＫＤ）でヒトＥＮＴＰＤ２タンパク質に結合する、請求項１～１８のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof according to any one of claims 1 to 18, wherein the antibody or an antigen-binding fragment thereof binds to a human ENTPD2 protein with a dissociation constant (KD) of less than 5 nM. 前記抗体又はその抗原結合断片が、３ｎＭ未満の解離定数（ＫＤ）でヒトＥＮＴＰＤ２タンパク質に結合する、請求項１～１８のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof according to any one of claims 1 to 18, wherein the antibody or an antigen-binding fragment thereof binds to a human ENTPD2 protein with a dissociation constant (KD) of less than 3 nM. 前記抗体又はその抗原結合断片が、ヒトＥＮＴＰＤ２酵素活性を少なくとも４０％、少なくとも５０％、少なくとも６０％、少なくとも７０％、少なくとも８０％、又は少なくとも９０％阻害する、請求項１～２１のいずれか一項に記載の抗体又はその抗原結合断片。 Any one of claims 1 to 21, wherein the antibody or antigen-binding fragment thereof inhibits human ENTPD2 enzyme activity by at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%. The antibody or antigen-binding fragment thereof according to the section. 前記抗体又はその抗原結合断片が、アデノシン三リン酸塩（ＡＴＰ）の加水分解のＥＮＴＰＤ２の能力を阻害する、請求項１～２２のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof according to any one of claims 1 to 22, wherein the antibody or an antigen-binding fragment thereof inhibits the ability of ENTPD2 to hydrolyze adenosine triphosphate (ATP). 前記抗体又はその抗原結合断片が、ＥＮＴＰＤ２へのＡＴＰの結合を妨害し、又はＥＮＴＰＤ２の触媒ドメイン内にＡＴＰを捕捉する、請求項１～２３のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof according to any one of claims 1 to 23, wherein the antibody or an antigen-binding fragment thereof interferes with the binding of ATP to ENTPD2 or captures ATP in the catalytic domain of ENTPD2. .. 前記抗体が、ＩｇＧ１、ＩｇＧ２、ＩｇＧ３又はＩｇＧ４アイソタイプを有する、請求項１～２４のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof according to any one of claims 1 to 24, wherein the antibody has an IgG1, IgG2, IgG3 or IgG4 isotype. 前記抗体又はその抗原結合断片が、ＩｇＧ１ Ｆｃ領域、ＩｇＧ２ Ｆｃ領域、ＩｇＧ４ Ｆｃ領域、又はＩｇＧ２／ＩｇＧ４ハイブリッドＦｃ領域から選択されるＦｃ領域を含む、請求項１～２５のいずれか一項に記載の抗体又はその抗原結合断片。 13. An antibody or an antigen-binding fragment thereof. 前記抗体又はその抗原結合断片が、前記親抗体と比較して低下した抗体依存性細胞傷害（ＡＤＣＣ）又は補体依存性細胞傷害（ＣＤＣ）活性を有する改変されたＦｃ領域を含む、請求項１～２６のいずれか一項に記載の抗体又はその抗原結合断片。 Claim 1 comprises a modified Fc region in which the antibody or antigen-binding fragment thereof has reduced antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cellular cytotoxicity (CDC) activity as compared to the parent antibody. The antibody or antigen-binding fragment thereof according to any one of Items to 26. 前記抗体又はその抗原結合断片が、ヒト又はヒト化抗体又はその断片である、請求項１～２７のいずれか一項に記載の抗体又はその抗原結合断片。 The antibody or antigen-binding fragment thereof according to any one of claims 1 to 27, wherein the antibody or an antigen-binding fragment thereof is a human or humanized antibody or a fragment thereof. 請求項１～２８のいずれか一項に記載の抗体又はその抗原結合断片をコードする核酸又は核酸のセット。 A nucleic acid or a set of nucleic acids encoding the antibody according to any one of claims 1 to 28 or an antigen-binding fragment thereof. 請求項２９に記載の核酸又は核酸のセットを含むベクター。 A vector comprising the nucleic acid or set of nucleic acids of claim 29. 前記ベクターが、ＤＮＡベクター、ＲＮＡベクター、プラスミド、コスミド、又はウイルスベクターから選択される、請求項３０に記載のベクター。 The vector according to claim 30, wherein the vector is selected from a DNA vector, an RNA vector, a plasmid, a cosmid, or a viral vector. 前記ベクターが、以下のウイルス：レンチウイルス、アデノウイルス、アデノ随伴ウイルス（ＡＡＶ）、単純ヘルペスウイルス（ＨＳＶ）、パルボウイルス、レトロウイルス、ワクシニアウイルス、シンビス（Ｓｉｎｂｉｓ）ウイルス、インフルエンザウイルス、レオウイルス、ニューカッスル病ウイルス（ＮＤＶ）、はしかウイルス、水疱性口内炎ウイルス（ＶＳＶ）、ポリオウイルス、ポックスウイルス、セネカバレー（Ｓｅｎｅｃａ Ｖａｌｌｅｙ）ウイルス、コクサッキーウイルス、エンテロウイルス、粘液腫ウイルス、又はマラバウイルスの任意の１つに基づくウイルスベクターである、請求項３１に記載のベクター。 The vector contains the following viruses: lentivirus, adenovirus, adeno-associated virus (AAV), simple herpesvirus (HSV), parvovirus, retrovirus, vaccinia virus, Sinbis virus, influenza virus, leovirus, newcastle. Virus based on any one of disease virus (NDV), scab virus, bullous stomatitis virus (VSV), poliovirus, poxvirus, Seneca Valley virus, coxsackie virus, enterovirus, mucinoma virus, or malavavirus. The vector according to claim 31, which is a vector. 前記ベクターがＡＡＶベクターである、請求項３２に記載のベクター。 The vector according to claim 32, wherein the vector is an AAV vector. 前記ベクターがレンチウイルスベクターである、請求項３１に記載のベクター。 The vector according to claim 31, wherein the vector is a lentiviral vector. プロモーターをさらに含む、請求項３０～３４のいずれか一項に記載のベクター。 The vector according to any one of claims 30 to 34, further comprising a promoter. 検出可能マーカーをさらに含む、請求項３０～３５のいずれか一項に記載のベクター。 The vector according to any one of claims 30 to 35, further comprising a detectable marker. 請求項２９に記載の核酸若しくは核酸のセット又は請求項３０～３６のいずれか一項に記載のベクターを含む細胞。 A cell comprising the nucleic acid or set of nucleic acids according to claim 29 or the vector according to any one of claims 30-36. 請求項３７に記載の細胞を培養し、前記抗体又はその抗原結合断片を培養培地から収集することを含む、抗体又はその抗原結合断片の産生方法。 A method for producing an antibody or an antigen-binding fragment thereof, which comprises culturing the cell according to claim 37 and collecting the antibody or an antigen-binding fragment thereof from a culture medium. 請求項１～２８のいずれか一項に記載の抗体又はその抗原結合断片、請求項２９に記載の核酸又は核酸のセット、請求項３０～３６のいずれか一項に記載のベクター、又は請求項３７に記載の細胞、及び薬学的に許容される担体を含む医薬組成物。 The antibody or antigen-binding fragment thereof according to any one of claims 1 to 28, the nucleic acid or set of nucleic acids according to claim 29, the vector according to any one of claims 30 to 36, or the vector according to claim. 37. A pharmaceutical composition comprising the cell according to 37 and a pharmaceutically acceptable carrier. 医薬としての使用のための、請求項１～２８のいずれか一項に記載の抗体又はその抗原結合断片、請求項２９に記載の核酸又は核酸のセット、請求項３０～３６のいずれか一項に記載のベクター、請求項３７に記載の細胞、又は請求項３９に記載の医薬組成物。 The antibody or antigen-binding fragment thereof according to any one of claims 1 to 28, the nucleic acid or a set of nucleic acids according to claim 29, or any one of claims 30 to 36 for use as a pharmaceutical. The vector according to claim 37, the cell according to claim 37, or the pharmaceutical composition according to claim 39. 癌の処置における使用のための、請求項１～２８のいずれか一項に記載の抗体又はその抗原結合断片、請求項２９に記載の核酸、請求項３０～３６のいずれか一項に記載のベクター、請求項３７に記載の細胞、又は請求項３９に記載の医薬組成物。 The antibody or antigen-binding fragment thereof according to any one of claims 1 to 28, the nucleic acid according to claim 29, and any one of claims 30 to 36 for use in the treatment of cancer. The vector, the cell of claim 37, or the pharmaceutical composition of claim 39. 癌の処置のための医薬の製造における、請求項１～２８のいずれか一項に記載の抗体又はその抗原結合断片、請求項２９に記載の核酸、請求項３０～３６のいずれか一項に記載のベクター、請求項３７に記載の細胞、又は請求項３９に記載の医薬組成物の使用。 The antibody or antigen-binding fragment thereof according to any one of claims 1 to 28, the nucleic acid according to claim 29, and any one of claims 30 to 36 in the manufacture of a pharmaceutical agent for treating cancer. Use of the vector of claim 37, the cell of claim 37, or the pharmaceutical composition of claim 39. 前記癌が、ＥＮＴＰＤ２＋癌である、請求項４１に記載の使用のための抗体、又は請求項４２に記載の使用。 The antibody for use according to claim 41, or the use according to claim 42, wherein the cancer is ENTPD2 + cancer. 前記癌が、結腸直腸癌（ＣＲＣ）、胃癌、食道癌、膵癌、胆管癌、肺癌、乳癌、又は卵巣癌である、請求項４１に記載の使用のための抗体、又は請求項４２に記載の使用。 42. The antibody for use according to claim 41, wherein the cancer is colorectal cancer (CRC), gastric cancer, esophageal cancer, pancreatic cancer, cholangiocarcinoma, lung cancer, breast cancer, or ovarian cancer. Use as described in. 前記抗体又はその抗原結合断片、前記核酸又は核酸のセット、前記ベクター、前記細胞、又は前記医薬組成物が、静脈内、腫瘍内又は皮下経路を介して前記対象に投与される、請求項４１に記載の使用のための抗体、又は請求項４２に記載の使用。 41. The subject, wherein the antibody or antigen-binding fragment thereof, the nucleic acid or a set of nucleic acids, the vector, the cells, or the pharmaceutical composition is administered to the subject via an intravenous, intratumoral or subcutaneous route. The antibody for the described use, or the use according to claim 42. 前記抗体分子が、少なくとも１つの追加の治療薬又は手順と組み合わせて投与される、請求項４１に記載の使用のための抗体、又は請求項４２に記載の使用。 The antibody for use according to claim 41, or the use according to claim 42, wherein the antibody molecule is administered in combination with at least one additional therapeutic agent or procedure. 前記少なくとも１つの追加の治療薬又は手順が、化学療法、標的化抗癌療法、腫瘍溶解性薬物、細胞毒性剤、免疫ベースの治療法、サイトカイン、外科手技、放射線療法、共刺激分子の活性化因子、阻害分子の阻害剤、ワクチン、又は細胞療法の１つ以上から選択される、請求項４６に記載の使用のための抗体、又は請求項４６に記載の使用。 The at least one additional therapeutic agent or procedure is chemotherapy, targeted anti-cancer therapy, tumor-dissolving drug, cytotoxic agent, immune-based therapies, cytokines, surgical procedures, radiotherapy, activation of costimulatory molecules. The antibody for use according to claim 46, or the use according to claim 46, selected from one or more of a factor, an inhibitor of an inhibitory molecule, a vaccine, or a cell therapy. 前記少なくとも１つの追加の治療薬が、ＰＤ－１阻害剤である、請求項４６に記載の使用のための抗体又は請求項４６に記載の使用。 The antibody for use according to claim 46 or the use according to claim 46, wherein the at least one additional therapeutic agent is a PD-1 inhibitor. 前記ＰＤ－１阻害剤が、ＰＤＲ００１、ニボルマブ、ペムブロリズマブ、ピディリズマブ、ＭＥＤＩ０６８０、ＲＥＧＮ２８１０、ＴＳＲ－０４２、ＰＦ－０６８０１５９１、又はＡＭＰ－２２４から選択される、請求項４８に記載の使用のための抗体、又は請求項４８に記載の使用。 The antibody for use according to claim 48, wherein the PD-1 inhibitor is selected from PDR001, nivolumab, pembrolizumab, pidirizumab, MEDI0680, REGN2810, TSR-042, PF-06801591, or AMP-224. The use according to claim 48. 前記少なくとも１つの追加の治療薬が、ＰＤ－Ｌ１阻害剤である、請求項４６に記載の使用のための抗体、又は請求項４６に記載の使用。 The antibody for use according to claim 46, or the use according to claim 46, wherein the at least one additional therapeutic agent is a PD-L1 inhibitor. 前記ＰＤ－Ｌ１阻害剤が、ＦＡＺ０５３、アテゾリズマブ、アベルマブ、デュルバルマブ、又はＢＭＳ－９３６５５９から選択される、請求項５０に記載の使用のための抗体、又は請求項５０に記載の使用。 The antibody for use according to claim 50, or the use according to claim 50, wherein the PD-L1 inhibitor is selected from FAZ053, atezolizumab, avelumab, durvalumab, or BMS-936559. 前記少なくとも１つの追加の治療薬が、Ａ２ＡＲアンタゴニストであり、前記Ａ２ＡＲアンタゴニストが：
ｉ．抗ＣＤ７３抗体分子若しくはその抗原結合断片であって、場合により前記抗ＣＤ７３抗体は、以下：
ａ．配列番号２９５のアミノ酸配列を含む重鎖可変領域及び配列番号２９６のアミノ酸配列を含む軽鎖可変領域、又は配列番号２９５又は２９６と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
ｂ．配列番号２９９のアミノ酸配列を含む重鎖可変領域及び配列番号３００のアミノ酸配列を含む軽鎖可変領域、又は配列番号２９９又は３００と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
ｃ．配列番号３０２のアミノ酸配列を含む重鎖可変領域及び配列番号３０３のアミノ酸配列を含む軽鎖可変領域、又は配列番号３０２又は３０３と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
ｄ．配列番号３０４のアミノ酸配列を含む重鎖可変領域及び配列番号３０５のアミノ酸配列を含む軽鎖可変領域、又は配列番号３０４又は３０５と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
ｅ．配列番号３０６のアミノ酸配列を含む重鎖可変領域及び配列番号３０７のアミノ酸配列を含む軽鎖可変領域、又は配列番号３０６又は３０７と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；又は
ｆ．配列番号３０８のアミノ酸配列を含む重鎖可変領域及び配列番号３０９のアミノ酸配列を含む軽鎖可変領域、又は配列番号３０８又は３０９と少なくとも８５％、９０％、９５％又はそれを超えて同一のアミノ酸配列を含む抗ＣＤ７３抗体分子；
から選択される抗ＣＤ７３抗体分子若しくはその抗原結合断片、
又は
ｉｉ．ＰＢＦ５０９／ＮＩＲ１７８、ＣＰＩ４４４／Ｖ８１４４４、ＡＺＤ４６３５／ＨＴＬ－１０７１、ビパデナント、ＧＢＶ－２０３４、ＡＢ９２８、テオフィリン、イストラデフィリン、トザデナント／ＳＹＮ－１１５、ＫＷ－６３５６、ＳＴ－４２０６、及びプレラデナント／ＳＣＨ ４２０８１４；又は
ｉｉｉ．５－ブロモ－２，６－ジ－（１Ｈ－ピラゾール－１－イル）ピリミジン－４－アミン、又はその薬学的に許容される塩；（Ｓ）－７－（５－メチルフラン－２－イル）－３－（（６－（（（テトラヒドロフラン－３－イル）オキシ）メチル）ピリジン－２－イル）メチル）－３Ｈ－［１，２，３］トリアゾロ［４，５－ｄ］ピリミジン－５－アミン、又はその薬学的に許容される塩；（Ｒ）－７－（５－メチルフラン－２－イル）－３－（（６－（（（テトラヒドロフラン－３－イル）オキシ）メチル）ピリジン－２－イル）メチル）－３Ｈ－［１，２，３］トリアゾロ［４，５－ｄ］ピリミジン－５－アミン、又はそのラセミ体、又はその薬学的に許容される塩；７－（５－メチルフラン－２－イル）－３－（（６－（（（テトラヒドロフラン－３－イル）オキシ）メチル）ピリジン－２－イル）メチル）－３Ｈ－［１，２，３］トリアゾロ［４，５－ｄ］ピリミジン－５－アミン、又はその薬学的に許容される塩；及び６－（２－クロロ－６－メチルピリジン－４－イル）－５－（４－フルオロフェニル）－１，２，４－トリアジン－３－アミン、又はその薬学的に許容される塩
から選択される、請求項４６～５１のいずれか一項に記載の使用のための抗体、又は請求項４６～５１のいずれか一項に記載の使用。 The at least one additional therapeutic agent is an A2AR antagonist and the A2AR antagonist is:
i. An anti-CD73 antibody molecule or an antigen-binding fragment thereof, wherein the anti-CD73 antibody may be described below.
a. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 295 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 296, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 295 or 296. Anti-CD73 antibody molecule containing sequence;
b. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 299 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 300, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 299 or 300. Anti-CD73 antibody molecule containing sequence;
c. Amino acids that are at least 85%, 90%, 95% or more identical to the heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 302 and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 303, or SEQ ID NO: 302 or 303. Anti-CD73 antibody molecule containing sequence;
d. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 304 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 305, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 304 or 305. Anti-CD73 antibody molecule containing sequence;
e. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 306 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 307, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 306 or 307. An anti-CD73 antibody molecule containing a sequence; or f. A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 308 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 309, or at least 85%, 90%, 95% or more identical amino acids to SEQ ID NO: 308 or 309. Anti-CD73 antibody molecule containing sequence;
Anti-CD73 antibody molecule or antigen-binding fragment thereof selected from
Or ii. PBF509 / NIR178, CPI444 / V81444, AZD4635 / HTL-1071, Vipadenant, GBV-2034, AB928, Theophylline, Istradefylline, Tozadenant / SYN-115, KW-6356, ST-4206, and Preladenant / SCH4 .. 5-bromo-2,6-di- (1H-pyrazole-1-yl) pyrimidin-4-amine, or a pharmaceutically acceptable salt thereof; (S) -7- (5-methylfuran-2-yl) ) -3-((6-(((tetra-3-yl) oxy) methyl) Pyridine-2-yl) Methyl) -3H- [1,2,3] Triazolo [4,5-d] Pyrimidine-5 -Amine, or a pharmaceutically acceptable salt thereof; (R) -7- (5-methylfuran-2-yl) -3-((6-(((tetra-3-yl) oxy) methyl) pyridine) -2-yl) Methyl) -3H- [1,2,3] triazolo [4,5-d] pyrimidin-5-amine, or its lasemi, or pharmaceutically acceptable salt thereof; 7- (5) -Methylfuran-2-yl) -3-((6-(((tetra-3-yl) oxy) methyl) pyridin-2-yl) methyl) -3H- [1,2,3] triazolo [4, 5-d] Pyrimidine-5-amine, or a pharmaceutically acceptable salt thereof; and 6- (2-chloro-6-methylpyridin-4-yl) -5- (4-fluorophenyl) -1,2 , 4-Triazine-3-amine, or an antibody for use according to any one of claims 46-51, selected from pharmaceutically acceptable salts thereof, or any of claims 46-51. Use as described in item 1. 前記少なくとも１つの追加の治療薬が：
ｉ．ＣＴＬＡ－４阻害剤、場合により前記ＣＴＬＡ－４阻害剤は、イピリムマブ又はトレメリムマブから選択される；
ｉｉ．ＴＩＭ－３阻害剤、場合により前記ＴＩＭ－３阻害剤は、ＭＢＧ４５３、ＴＳＲ－０２２、又はＬＹ３３２１３６７から選択される；
ｉｉｉ．ＬＡＧ－３阻害剤、場合により前記ＬＡＧ－３阻害剤は、ＬＡＧ５２５、ＢＭＳ－９８６０１６、ＴＳＲ－０３３、ＭＫ－４２８０又はＲＥＧＮ３７６７から選択される；
ｉｖ．ＧＩＴＲ作動薬、場合により前記ＧＩＴＲ作動薬は、ＧＷＮ３２３、ＢＭＳ－９８６１５６、ＭＫ－４１６６、ＭＫ－１２４８、ＴＲＸ５１８、ＩＮＣＡＧＮ１８７６、ＡＭＧ ２２８、又はＩＮＢＲＸ－１１０から選択される；
ｖ．抗ＣＤ３多重特異性抗体分子、場合により前記抗ＣＤ３多重特異性抗体分子は、抗ＣＤ３ｘ抗ＣＤ１２３二重特異性抗体分子、又は抗ＣＤ３ｘ抗ＣＤ２０二重特異性抗体分子である；
ｖｉ．サイトカイン分子、場合により前記サイトカイン分子は、ＩＬ－１５受容体α（ＩＬ－１５Ｒａ）の可溶型と複合体化されたＩＬ－１５である；
ｖｉｉ．マクロファージコロニー－刺激因子（Ｍ－ＣＳＦ）阻害剤、場合により前記Ｍ－ＣＳＦ阻害剤は、ＭＣＳ１１０である；
ｖｉｉｉ．ＣＳＦ－１Ｒ阻害剤、場合により前記ＣＳＦ－１Ｒ阻害剤は、ＢＬＺ９４５である；
ｉｘ．インドールアミン２，３－ジオキシゲナーゼ（ＩＤＯ）及び／又はトリプトファン２，３－ジオキシゲナーゼ（ＴＤＯ）の阻害剤；
ｘ．ＴＧＦ－β阻害剤；
ｘｉ．腫瘍溶解性ウイルス；
ｘｉｉ．キメラ抗原受容体（ＣＡＲ）Ｔ細胞療法
から選択される、請求項４６に記載の使用のための抗体、又は請求項４６に記載の使用。 The at least one additional therapeutic agent is:
i. The CTLA-4 inhibitor, and optionally the CTLA-4 inhibitor, is selected from ipilimumab or tremelimumab;
ii. The TIM-3 inhibitor, and optionally the TIM-3 inhibitor, is selected from MBG453, TSR-022, or LY3321367;
iii. The LAG-3 inhibitor, and optionally the LAG-3 inhibitor, is selected from LAG525, BMS-986016, TSR-033, MK-4280 or REGN3767;
iv. The GITR agonist, and optionally the GITR agonist, is selected from GWN323, BMS-986156, MK-4166, MK-1248, TRX518, INCAGN1876, AMG228, or INBRX-110;
v. The anti-CD3 multispecific antibody molecule, and optionally the anti-CD3 multispecific antibody molecule, is an anti-CD3x anti-CD123 bispecific antibody molecule, or an anti-CD3x anti-CD20 bispecific antibody molecule ;
vi. The cytokine molecule, and optionally the cytokine molecule, is IL-15 complexed with the soluble form of IL-15 receptor α (IL-15Ra);
vii. The macrophage colony-stimulating factor (M-CSF) inhibitor, and optionally the M-CSF inhibitor, is MCS110;
viii. The CSF-1R inhibitor, and optionally the CSF-1R inhibitor, is BLZ945;
ix. Indoleamine 2,3-dioxygenase (IDO) and / or tryptophan 2,3-dioxygenase (TDO) inhibitor;
x. TGF-β inhibitor;
xi. Oncolytic virus;
xii. The antibody for use according to claim 46, or the use according to claim 46, selected from chimeric antigen receptor (CAR) T cell therapies. 前記少なくとも１つの追加の治療薬は、１）タンパク質キナーゼＣ（ＰＫＣ）阻害剤；２）熱ショックタンパク質９０（ＨＳＰ９０）阻害剤；３）ホスホイノシチド３－キナーゼ（ＰＩ３Ｋ）及び／又はラパマイシンの標的（ｍＴＯＲ）の阻害剤；４）チトクロムＰ４５０の阻害剤；５）鉄キレート化剤；６）アロマターゼ阻害剤；７）ｐ５３の阻害剤；８）アポトーシス誘発剤；９）血管新生阻害剤；１０）アルドステロンシンターゼ阻害剤；１１）スムーズンド（ＳＭＯ）受容体阻害剤；１２）プロラクチン受容体（ＰＲＬＲ）阻害剤；１３）Ｗｎｔシグナル伝達阻害剤；１４）ＣＤＫ４／６阻害剤；１５）線維芽細胞増殖因子受容体２（ＦＧＦＲ２）／線維芽細胞増殖因子受容体４（ＦＧＦＲ４）阻害剤；１６）マクロファージコロニー刺激因子（Ｍ－ＣＳＦ）阻害剤；１７）ｃ－ＫＩＴ、ヒスタミン放出、Ｆｌｔ３又はＰＫＣの１つ以上の阻害剤；１８）ＶＥＧＦＲ－２、ＰＤＧＦＲβ、ｃ－ＫＩＴ又はＲａｆキナーゼＣの１つ以上の阻害剤；１９）ソマトスタチン作動薬及び／又は成長ホルモン放出阻害剤；２０）未分化リンパ腫キナーゼ（ＡＬＫ）阻害剤；２１）インスリン様増殖因子１受容体（ＩＧＦ－１Ｒ）阻害剤；２２）Ｐ－糖タンパク質１阻害剤；２３）血管内皮増殖因子受容体（ＶＥＧＦＲ）阻害剤；２４）ＢＣＲ－ＡＢＬキナーゼ阻害剤；２５）ＦＧＦＲ阻害剤；２６）ＣＹＰ１１Ｂ２の阻害剤；２７）ＨＤＭ２阻害剤；２８）チロシンキナーゼの阻害剤；２９）ｃ－ＭＥＴの阻害剤；３０）ＪＡＫの阻害剤；３１）ＤＡＣの阻害剤；３２）１１β－ヒドロキシラーゼの阻害剤；３３）ＩＡＰの阻害剤；３４）ＰＩＭキナーゼの阻害剤；３５）ポーキュパインの阻害剤；３６）ＢＲＡＦ；３７）ＨＥＲ３の阻害剤；３８）ＭＥＫの阻害剤；又は３９）脂質キナーゼの阻害剤；又は表１６に提供される１つ以上の薬剤から選択される、請求項４６に記載の使用のための抗体、又は請求項４６に記載の使用。 The at least one additional therapeutic agent is 1) a protein kinase C (PKC) inhibitor; 2) a heat shock protein 90 (HSP90) inhibitor; 3) a phosphoinositide 3-kinase (PI3K) and / or a target for rapamycin (mTOR). ) Inhibitors; 4) Thitochrome P450 inhibitors ; 5) Iron kinases; 6) Aromatase inhibitors; 7) p53 inhibitors ; 8) Proliferative inducers; 9) Angiogenesis inhibitors; Inhibitors; 11) Kinase (SMO) receptor inhibitors; 12) Prolactin receptor (PRLR) inhibitors; 13) Wnt signaling inhibitors; 14) CDK4 / 6 inhibitors; 15) Fibroblast proliferation factor acceptance Body 2 (FGFR2) / Fibroblast proliferation factor receptor 4 (FGFR4) inhibitor; 16) Macrophage colony stimulating factor (M-CSF) inhibitor; 17) c-KIT, histamine release, Flt 3 or PKC 1 One or more inhibitors; 18) One or more inhibitors of VEGFR- 2, PDGFRβ, c-KIT or Raf kinase C; 19) Somatostatin agonists and / or growth hormone release inhibitors; 20) Undifferentiated lymphoma kinase ( ALK) Inhibitor; 21) Kinase-like growth factor 1 receptor (IGF-1R) inhibitor; 22) P-glycoprotein 1 inhibitor; 23) Vascular endothelial growth factor receptor (VEGFR) inhibitor; 24) BCR- ABL kinase inhibitor; 25) FGFR inhibitor; 26) CYP11B2 inhibitor; 27) HDM2 inhibitor ; 28) tyrosine kinase inhibitor; 29) c-MET inhibitor; 30) JAK inhibitor; 31) DAC inhibitor; 32) 11β-hydroxylase inhibitor; 33) IAP inhibitor; 34) PIM kinase inhibitor; 35) porcupine inhibitor; 36) BRA F; 37) HER3 inhibitor; 38 ) MEK inhibitor; or 39) lipid kinase inhibitor; or the antibody for use according to claim 46, which is selected from one or more agents provided in Table 16, or the antibody according to claim 46. Use of. 対象における癌の処置における使用のための、請求項１～２８のいずれか一項に記載の抗体又は抗原結合断片を、ＰＤ－１阻害剤又はＰＤ－Ｌ１阻害剤から選択される第２の治療薬と組み合わせて含む組成物。 A second treatment in which the antibody or antigen binding fragment according to any one of claims 1-28 for use in the treatment of cancer in a subject is selected from a PD-1 inhibitor or a PD-L1 inhibitor. A composition containing in combination with a drug. 対象における癌の処置における使用のための組成物であって、前記組成物（ｃｏｍｐｏｓｉｓｔｉｏｎ）は、前記請求項１～２８のいずれか一項に記載の抗体又は抗原結合断片を、ＰＤ－１阻害剤又はＰＤ－Ｌ１阻害剤から選択される第２の治療薬と組み合わせて含む、組成物。 A composition for use in the treatment of cancer in a subject, wherein the composition comprises the antibody or antigen-binding fragment according to any one of claims 1 to 28 as a PD-1 inhibitor. Or a composition comprising in combination with a second therapeutic agent selected from PD-L1 inhibitors. 前記第２の治療薬がＰＤ－１阻害剤である、請求項５５又は５６に記載の組成物。 The composition according to claim 55 or 56 , wherein the second therapeutic agent is a PD-1 inhibitor. 前記ＰＤ－１阻害剤がＰＤ－１抗体である、請求項５５又は５６に記載の組成物。 The composition according to claim 55 or 56 , wherein the PD-1 inhibitor is a PD-1 antibody. 前記ＰＤ－１阻害剤が、ＰＤＲ００１、ニボルマブ、ペムブロリズマブ、ピディリズマブ、ＭＥＤＩ０６８０、ＲＥＧＮ２８１０、ＴＳＲ－０４２、ＰＦ－０６８０１５９１、又はＡＭＰ－２２４から選択される、請求項５５又は５６に記載の組成物。 The composition of claim 55 or 56 , wherein the PD-1 inhibitor is selected from PDR001, nivolumab, pembrolizumab, pidirizumab, MEDI0680, REGN2810, TSR-042, PF-06801591, or AMP-224. 前記第２の治療薬がＰＤ－Ｌ１阻害剤である、請求項５５又は５６に記載の組成物。 The composition according to claim 55 or 56 , wherein the second therapeutic agent is a PD-L1 inhibitor. 前記ＰＤ－Ｌ１阻害剤がＰＤ－Ｌ１抗体である、請求項５５又は５６に記載の組成物。 The composition according to claim 55 or 56 , wherein the PD-L1 inhibitor is a PD-L1 antibody. 前記ＰＤ－Ｌ１阻害剤が、ＦＡＺ０５３、アテゾリズマブ、アベルマブ、デュルバルマブ、又はＢＭＳ－９３６５５９から選択される、請求項５５又は５６に記載の組成物。 The composition according to claim 55 or 56 , wherein the PD-L1 inhibitor is selected from FAZ053, atezolizumab, avelumab, durvalumab, or BMS-936559. 前記癌がＥＮＴＰＤ２＋癌である、請求項５５又は５６に記載の組成物。 The composition according to claim 55 or 56 , wherein the cancer is ENTPD2 + cancer. 前記癌が、結腸直腸癌（ＣＲＣ）、胃癌、食道癌、膵癌、胆管癌、肺癌、乳癌、又は卵巣癌である、請求項５５又は５６に記載の組成物。

The composition according to claim 55 or 56 , wherein the cancer is colorectal cancer (CRC), gastric cancer, esophageal cancer, pancreatic cancer, cholangiocarcinoma, lung cancer, breast cancer, or ovarian cancer.
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