JPWO2021053559A5 - - Google Patents

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JPWO2021053559A5
JPWO2021053559A5 JP2022516632A JP2022516632A JPWO2021053559A5 JP WO2021053559 A5 JPWO2021053559 A5 JP WO2021053559A5 JP 2022516632 A JP2022516632 A JP 2022516632A JP 2022516632 A JP2022516632 A JP 2022516632A JP WO2021053559 A5 JPWO2021053559 A5 JP WO2021053559A5
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Priority claimed from PCT/IB2020/058648 external-priority patent/WO2021053559A1/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、本開示に対する様々な置換形態、変更形態及び修正形態がなされ得ることを意図する。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、利点及び修正形態は、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均等物を認識又は確認することができる。このような均等物は、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請求項の範囲の再作成は、様々な国の特許法による制限に起因する場合があり、請求項の主題を放棄するものと解釈されるべきではない。

以下の態様を包含し得る。
［１］ 癌の処置を、それを必要とする対象において行う方法であって、治療有効量の、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を前記対象に投与することを含み、前記癌は、ＭＳＳ結腸直腸癌（ＣＲＣ）、胆管癌（肝内若しくは肝外）、膵臓癌、食道癌、食道胃接合部（ＥＧＪ）癌又は胃癌である、方法。
［２］ 癌の処置であって、それを必要とする対象における処置に使用するための、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を含む組成物であって、前記癌は、ＭＳＳ結腸直腸癌（ＣＲＣ）、胆管癌（肝内若しくは肝外）、膵臓癌、食道癌、食道胃接合部（ＥＧＪ）癌又は胃癌である、組成物。
［３］ 癌の処置であって、それを必要とする対象における処置のための医薬の製造における、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を含む組成物の使用であって、前記癌は、ＭＳＳ結腸直腸癌（ＣＲＣ）、胆管癌（肝内若しくは肝外）、膵臓癌、食道癌、食道胃接合部（ＥＧＪ）癌又は胃癌である、使用。
［４］ 癌の処置であって、それを必要とする対象における処置のための、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を含む組成物の使用であって、前記癌は、ＭＳＳ結腸直腸癌（ＣＲＣ）、胆管癌（肝内若しくは肝外）、膵臓癌、食道癌、食道胃接合部（ＥＧＪ）癌又は胃癌である、使用。
［５］ 前記抗体又はその抗原結合断片は、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、上記［１］～４］のいずれか一項に記載の方法、組成物又は使用。
［６］ 前記ＨＣＤＲ１、ＨＣＤＲ２、ＨＣＤＲ３、ＬＣＤＲ１、ＬＣＤＲ２及びＬＣＤＲ３は、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、上記［１］～［５］のいずれか一項に記載の方法、組成物又は使用。
［７］ 前記抗体又はその抗原結合断片は、表１に提供される重鎖可変領域を含む、上記［１］～［６］のいずれか一項に記載の方法、組成物又は使用。
［８］ 前記抗体又はその抗原結合断片は、表１に提供される軽鎖可変領域を含む、上記［１］～［７］のいずれか一項に記載の方法、組成物又は使用。
［９］ 前記抗体又はその抗原結合断片は、以下：
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
の任意の１つから選択される、上記［１］～［４］のいずれか一項に記載の方法、組成物又は使用。
［１０］ 前記抗体又はその抗原結合断片は、以下：
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
の任意の１つから選択される、上記［１］～［４］のいずれか一項に記載の方法、組成物又は使用。
［１１］ 前記抗体又はその抗原結合断片は、以下：
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
の任意の１つから選択される、上記［１］～［４］のいずれか一項に記載の方法、組成物又は使用。
［１２］ 前記抗体又はその抗原結合断片は、
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、上記［１］～［４］のいずれか一項に記載の方法、組成物又は使用。
［１３］ 前記抗体又はその抗原結合断片は、
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、上記［１］～［４］のいずれか一項に記載の方法、組成物又は使用。
［１４］ 前記抗体又はその抗原結合断片は、
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、上記［１］～［４］のいずれか一項に記載の方法、組成物又は使用。
［１５］ 前記抗体又はその抗原結合断片は、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、上記［１］～［４］のいずれか一項に記載の方法、組成物又は使用。
［１６］ 前記抗体又はその抗原結合断片は、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、上記［１］～［４］のいずれか一項に記載の方法、組成物又は使用。
［１７］ 前記抗体又はその抗原結合断片は、ヒトＥＮＴＰＤ２におけるエピトープに結合し、前記エピトープは、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、上記［１］～［１６］のいずれか一項に記載の方法、組成物又は使用。
［１８］ 前記抗体又はその抗原結合断片は、ヒトＥＮＴＰＤ２におけるエピトープに結合し、前記エピトープは、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、上記［１］～［１６］のいずれか一項に記載の方法、組成物又は使用。
［１９］ 前記抗体又はその抗原結合断片は、ヒトＥＮＴＰＤ２タンパク質への結合について、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、上記［１］～［４］のいずれか一項に記載の方法、組成物又は使用。
［２０］ 前記抗体又はその抗原結合断片は、表１に提供される任意の抗体又は抗原結合断片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、重複するエピトープ又は実質的に重複するエピトープに結合する、上記［１］～［４］のいずれか一項に記載の方法、組成物又は使用。
［２１］ 前記抗体又はその抗原結合断片は、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、上記［１］～［２０］のいずれか一項に記載の方法、組成物又は使用。
［２２］ 前記抗体又はその抗原結合断片は、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、上記［１］～［２０］のいずれか一項に記載の方法、組成物又は使用。
［２３］ 前記抗体又はその抗原結合断片は、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、上記［１］～［２０］のいずれか一項に記載の方法、組成物又は使用。
［２４］ 前記抗体又はその抗原結合断片は、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、上記［１］～［２３］のいずれか一項に記載の方法、組成物又は使用。
［２５］ 前記抗体又はその抗原結合断片は、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、上記［１］～［２４］のいずれか一項に記載の方法、組成物又は使用。
［２６］ 前記抗体又はその抗原結合断片は、ＥＮＴＰＤ２へのＡＴＰの結合を妨害するか、又はＥＮＴＰＤ２の触媒ドメイン内にＡＴＰを捕捉する、上記［１］～［２５］のいずれか一項に記載の方法、組成物又は使用。
［２７］ 前記抗体は、ＩｇＧ１、ＩｇＧ２、ＩｇＧ３又はＩｇＧ４アイソタイプを有する、上記［１］～［２６］のいずれか一項に記載の方法、組成物又は使用。
［２８］ 前記抗体又はその抗原結合断片は、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、上記［１］～［２７］のいずれか一項に記載の方法、組成物又は使用。
［２９］ 前記抗体又はその抗原結合断片は、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、上記［１］～［２８］のいずれか一項に記載の方法、組成物又は使用。
［３０］ 前記抗体は、ヒト若しくはヒト化抗体又はその断片である、上記［１］～［２９］のいずれか一項に記載の方法、組成物又は使用。
［３１］ 前記癌は、ＥＮＴＰＤ２＋癌である、上記［１］～［３０］のいずれか一項に記載の方法、組成物又は使用。
［３２］ 前記抗体又はその抗原結合断片は、１時間注入（臨床的に指示される場合、２時間まで）として前記対象に静脈内投与される、上記［１］～［３１］のいずれか一項に記載の方法、組成物又は使用。
［３３］ 前記抗体又はその抗原結合断片は、抗ＣＤ７３ Ａｂ、スパルタリズマブ（ＰＤＲ００１）及びＮＩＲ１７８からなる群から選択される少なくとも１つの追加の治療薬と組み合わせて投与される、上記［１］～［３２］のいずれか一項に記載の方法、組成物又は使用。
［３４］ 前記抗ＣＤ７３ Ａｂは、１時間注入（臨床的に指示される場合、２時間まで）として前記対象に静脈内投与される、上記［３３］に記載の方法、組成物又は使用。
［３５］ スパルタリズマブは、３０分注入（臨床的に指示される場合、２時間まで）として前記対象に静脈内投与される、上記［３３］又は［３４］に記載の方法、組成物又は使用。
［３６］ ＮＩＲ１７８は、前記対象によって経口的に服用される、上記［３３］～［３５］のいずれか一項に記載の方法、組成物又は使用。
［３７］ 前記抗体又はその抗原結合断片は、１０ｍｇ、３０ｍｇ、１００ｍｇ、１５０ｍｇ、３００ｍｇ、６００ｍｇ、１２００ｍｇ又は２４００ｍｇで２週間又は４週間毎に１回、前記対象に投与される、上記［１］～［３６］のいずれか一項に記載の方法、組成物又は使用。
［３８］ 前記抗ＣＤ７３ Ａｂは、２００ｍｇ又は４００ｍｇで２週間毎に１回、前記対象に投与される、上記［３３］～［３７］のいずれか一項に記載の方法、組成物又は使用。
［３９］ スパルタリズマブは、４００ｍｇで４週間毎に１回、前記対象に投与される、上記［３３］～［３８］のいずれか一項に記載の方法、組成物又は使用。
［４０］ ＮＩＲ１７８は、８０ｍｇ又は１６０ｍｇで１日２回（ＢＩＤ）、連続して前記対象に投与される、上記［３３］～［３９］のいずれか一項に記載の方法、組成物又は使用。 Although certain aspects and claims have been disclosed herein in detail, this is done by way of example only and for purposes of illustration only, and the following claims or any corresponding future No limitations are intended as to the scope of the claimed subject matter of this application. In particular, the inventors intend that various substitutions, changes, and modifications may be made to this disclosure without departing from the spirit and scope of this disclosure as defined by the claims. Selection of nucleic acid starting materials, clones or library types of interest is considered to be a routine matter for those skilled in the art having knowledge of the embodiments described herein. Other aspects, advantages, and modifications are believed to be within the scope of the following claims. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be covered by the appended claims. Recasting of the scope of the claims in a later-filed corresponding application may result from limitations under the patent laws of various countries and should not be construed as a waiver of claimed subject matter.

The following aspects may be included.
[1] A method for treating cancer in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of an antibody that specifically binds to human ENTPD2 protein or an antigen-binding fragment thereof. , the cancer is MSS colorectal cancer (CRC), bile duct cancer (intrahepatic or extrahepatic), pancreatic cancer, esophageal cancer, esophagogastric junction (EGJ) cancer or gastric cancer.
[2] A composition comprising an antibody that specifically binds to human ENTPD2 protein or an antigen-binding fragment thereof for use in the treatment of cancer in a subject in need thereof, wherein the cancer is , MSS colorectal cancer (CRC), cholangiocarcinoma (intrahepatic or extrahepatic), pancreatic cancer, esophageal cancer, esophagogastric junction (EGJ) cancer or gastric cancer.
[3] Use of a composition comprising an antibody that specifically binds to human ENTPD2 protein or an antigen-binding fragment thereof in the manufacture of a medicament for the treatment of cancer in a subject in need thereof. , the cancer is MSS colorectal cancer (CRC), cholangiocarcinoma (intrahepatic or extrahepatic), pancreatic cancer, esophageal cancer, esophagogastric junction (EGJ) cancer or gastric cancer.
[4] Use of a composition comprising an antibody that specifically binds to human ENTPD2 protein or an antigen-binding fragment thereof for the treatment of cancer in a subject in need thereof, wherein the cancer is , MSS colorectal cancer (CRC), cholangiocarcinoma (intrahepatic or extrahepatic), pancreatic cancer, esophageal cancer, esophagogastric junction (EGJ) cancer or gastric cancer.
[5] The antibody or antigen-binding fragment thereof includes heavy chain complementarity determining region 1 (HCDR1), heavy chain complementarity determining region 2 (HCDR2), and heavy chain of any antibody or antigen-binding fragment provided in Table 1. [1] to 4 above, comprising complementarity determining region 3 (HCDR3), light chain complementarity determining region 1 (LCDR1), light chain complementarity determining region 2 (LCDR2) and light chain complementarity determining region 3 (LCDR3). ] The method, composition or use according to any one of the above.
[6] The HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are any of the above [1] to [5], selected from the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences provided in Table 1. The method, composition or use according to item 1.
[7] The method, composition or use according to any one of [1] to [6] above, wherein the antibody or antigen-binding fragment thereof comprises the heavy chain variable region provided in Table 1.
[8] The method, composition or use according to any one of [1] to [7] above, wherein the antibody or antigen-binding fragment thereof comprises the light chain variable region provided in Table 1.
[9] The antibody or antigen-binding fragment thereof is as follows:
1) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 1,
HCDR2 sequence comprising SEQ ID NO: 2,
HCDR3 sequence comprising SEQ ID NO: 3,
LCDR1 sequence comprising SEQ ID NO: 14,
LCDR2 sequence comprising SEQ ID NO: 15, and
LCDR3 sequence comprising SEQ ID NO: 16;
2) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 4,
HCDR2 sequence comprising SEQ ID NO: 5,
HCDR3 sequence comprising SEQ ID NO: 3,
LCDR1 sequence comprising SEQ ID NO: 17,
LCDR2 sequence comprising SEQ ID NO: 18, and
LCDR3 sequence comprising SEQ ID NO: 19;
3) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 7,
HCDR2 sequence comprising SEQ ID NO: 8,
HCDR3 sequence comprising SEQ ID NO: 9,
LCDR1 sequence comprising SEQ ID NO: 20,
LCDR2 sequence comprising SEQ ID NO: 18, and
LCDR3 sequence comprising SEQ ID NO: 16;
4) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 37;
HCDR2 sequence comprising SEQ ID NO: 38,
HCDR3 sequence comprising SEQ ID NO: 39,
LCDR1 sequence comprising SEQ ID NO: 50,
LCDR2 sequence comprising SEQ ID NO: 51, and
LCDR3 sequence comprising SEQ ID NO: 52;
5) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 40,
HCDR2 sequence comprising SEQ ID NO: 41,
HCDR3 sequence comprising SEQ ID NO: 39,
LCDR1 sequence comprising SEQ ID NO: 53,
LCDR2 sequence comprising SEQ ID NO: 54, and
LCDR3 sequence comprising SEQ ID NO: 55;
6) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 43,
HCDR2 sequence comprising SEQ ID NO: 44,
HCDR3 sequence comprising SEQ ID NO: 45,
LCDR1 sequence comprising SEQ ID NO: 56,
LCDR2 sequence comprising SEQ ID NO: 54, and
LCDR3 sequence comprising SEQ ID NO: 52;
7) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 37,
HCDR2 sequence comprising SEQ ID NO: 38,
HCDR3 sequence comprising SEQ ID NO: 39,
LCDR1 sequence comprising SEQ ID NO: 61,
LCDR2 sequence comprising SEQ ID NO: 51, and
LCDR3 sequence comprising SEQ ID NO: 52;
8) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 40,
HCDR2 sequence comprising SEQ ID NO: 41,
HCDR3 sequence comprising SEQ ID NO: 39,
LCDR1 sequence comprising SEQ ID NO: 62,
LCDR2 sequence comprising SEQ ID NO: 54, and
LCDR3 sequence comprising SEQ ID NO: 55;
9) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 43,
HCDR2 sequence comprising SEQ ID NO: 44,
HCDR3 sequence comprising SEQ ID NO: 45,
LCDR1 sequence comprising SEQ ID NO: 63,
LCDR2 sequence comprising SEQ ID NO: 54, and
LCDR3 sequence comprising SEQ ID NO: 52;
10) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 37;
HCDR2 sequence comprising SEQ ID NO: 38,
HCDR3 sequence comprising SEQ ID NO: 68,
LCDR1 sequence comprising SEQ ID NO: 50,
LCDR2 sequence comprising SEQ ID NO: 51, and
LCDR3 sequence comprising SEQ ID NO: 52;
11) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 40,
HCDR2 sequence comprising SEQ ID NO: 41,
HCDR3 sequence comprising SEQ ID NO: 68,
LCDR1 sequence comprising SEQ ID NO: 53,
LCDR2 sequence comprising SEQ ID NO: 54, and
LCDR3 sequence comprising SEQ ID NO: 55;
12) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 43,
HCDR2 sequence comprising SEQ ID NO: 44,
HCDR3 sequence comprising SEQ ID NO: 69,
LCDR1 sequence comprising SEQ ID NO: 56,
LCDR2 sequence comprising SEQ ID NO: 54, and
LCDR3 sequence comprising SEQ ID NO: 52;
13) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 82,
HCDR2 sequence comprising SEQ ID NO: 83,
HCDR3 sequence comprising SEQ ID NO: 84,
LCDR1 sequence comprising SEQ ID NO: 95,
LCDR2 sequence comprising SEQ ID NO: 96, and
LCDR3 sequence comprising SEQ ID NO: 97;
14) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 85,
HCDR2 sequence comprising SEQ ID NO: 86,
HCDR3 sequence comprising SEQ ID NO: 84,
LCDR1 sequence comprising SEQ ID NO: 98,
LCDR2 sequence comprising SEQ ID NO: 99, and
LCDR3 sequence comprising SEQ ID NO: 100;
15) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 88,
HCDR2 sequence comprising SEQ ID NO: 89,
HCDR3 sequence comprising SEQ ID NO: 90,
LCDR1 sequence comprising SEQ ID NO: 101,
LCDR2 sequence comprising SEQ ID NO: 99, and
LCDR3 sequence comprising SEQ ID NO: 97;
16) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 106,
HCDR2 sequence comprising SEQ ID NO: 107;
HCDR3 sequence comprising SEQ ID NO: 108,
LCDR1 sequence comprising SEQ ID NO: 119,
LCDR2 sequence comprising SEQ ID NO: 120, and
LCDR3 sequence comprising SEQ ID NO: 121;
17) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 109,
HCDR2 sequence comprising SEQ ID NO: 110,
HCDR3 sequence comprising SEQ ID NO: 108,
LCDR1 sequence comprising SEQ ID NO: 122,
LCDR2 sequence comprising SEQ ID NO: 99, and
LCDR3 sequence comprising SEQ ID NO: 123;
18) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 112,
HCDR2 sequence comprising SEQ ID NO: 113,
HCDR3 sequence comprising SEQ ID NO: 114,
LCDR1 sequence comprising SEQ ID NO: 124,
LCDR2 sequence comprising SEQ ID NO: 99, and
LCDR3 sequence comprising SEQ ID NO: 121;
19) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 106,
HCDR2 sequence comprising SEQ ID NO: 129,
HCDR3 sequence comprising SEQ ID NO: 108,
LCDR1 sequence comprising SEQ ID NO: 119,
LCDR2 sequence comprising SEQ ID NO: 120, and
LCDR3 sequence comprising SEQ ID NO: 121;
20) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 109,
HCDR2 sequence comprising SEQ ID NO: 130,
HCDR3 sequence comprising SEQ ID NO: 108,
LCDR1 sequence comprising SEQ ID NO: 122,
LCDR2 sequence comprising SEQ ID NO: 99, and
LCDR3 sequence comprising SEQ ID NO: 123;
21) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 112,
HCDR2 sequence comprising SEQ ID NO: 131,
HCDR3 sequence comprising SEQ ID NO: 114,
LCDR1 sequence comprising SEQ ID NO: 124,
LCDR2 sequence comprising SEQ ID NO: 99, and
LCDR3 sequence comprising SEQ ID NO: 121;
22) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 136,
HCDR2 sequence comprising SEQ ID NO: 137;
HCDR3 sequence comprising SEQ ID NO: 138,
LCDR1 sequence comprising SEQ ID NO: 149,
LCDR2 sequence comprising SEQ ID NO: 150, and
LCDR3 sequence comprising SEQ ID NO: 151;
23) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 139,
HCDR2 sequence comprising SEQ ID NO: 140,
HCDR3 sequence comprising SEQ ID NO: 138,
LCDR1 sequence comprising SEQ ID NO: 152,
LCDR2 sequence comprising SEQ ID NO: 153, and
LCDR3 sequence comprising SEQ ID NO: 154;
24) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 142,
HCDR2 sequence comprising SEQ ID NO: 143,
HCDR3 sequence comprising SEQ ID NO: 144,
LCDR1 sequence comprising SEQ ID NO: 155,
LCDR2 sequence comprising SEQ ID NO: 153, and
LCDR3 sequence comprising SEQ ID NO: 151;
25) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 160,
HCDR2 sequence comprising SEQ ID NO: 161,
HCDR3 sequence comprising SEQ ID NO: 162,
LCDR1 sequence comprising SEQ ID NO: 173,
LCDR2 sequence comprising SEQ ID NO: 150, and
LCDR3 sequence comprising SEQ ID NO: 174;
26) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 163,
HCDR2 sequence comprising SEQ ID NO: 164,
HCDR3 sequence comprising SEQ ID NO: 162,
LCDR1 sequence comprising SEQ ID NO: 175,
LCDR2 sequence comprising SEQ ID NO: 153, and
LCDR3 sequence comprising SEQ ID NO: 176;
27) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 166,
HCDR2 sequence comprising SEQ ID NO: 167,
HCDR3 sequence comprising SEQ ID NO: 168,
LCDR1 sequence comprising SEQ ID NO: 177,
LCDR2 sequence comprising SEQ ID NO: 153, and
LCDR3 sequence comprising SEQ ID NO: 174;
28) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 37,
HCDR2 sequence comprising SEQ ID NO: 220,
HCDR3 sequence comprising SEQ ID NO: 221,
LCDR1 sequence comprising SEQ ID NO: 61,
LCDR2 sequence comprising SEQ ID NO: 51, and
LCDR3 sequence comprising SEQ ID NO: 52;
29) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 40,
HCDR2 sequence comprising SEQ ID NO: 222,
HCDR3 sequence comprising SEQ ID NO: 221,
LCDR1 sequence comprising SEQ ID NO: 62,
LCDR2 sequence comprising SEQ ID NO: 54, and
LCDR3 sequence comprising SEQ ID NO: 55;
30) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 43,
HCDR2 sequence comprising SEQ ID NO: 223,
HCDR3 sequence comprising SEQ ID NO: 224,
LCDR1 sequence comprising SEQ ID NO: 63,
LCDR2 sequence comprising SEQ ID NO: 54, and
LCDR3 sequence comprising SEQ ID NO: 52;
31) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 37,
HCDR2 sequence comprising SEQ ID NO: 220,
HCDR3 sequence comprising SEQ ID NO: 68,
LCDR1 sequence comprising SEQ ID NO: 61,
LCDR2 sequence comprising SEQ ID NO: 51, and
LCDR3 sequence comprising SEQ ID NO: 52;
32) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 40,
HCDR2 sequence comprising SEQ ID NO: 222,
HCDR3 sequence comprising SEQ ID NO: 68,
LCDR1 sequence comprising SEQ ID NO: 62,
LCDR2 sequence comprising SEQ ID NO: 54, and
LCDR3 sequence comprising SEQ ID NO: 55;
33) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 43,
HCDR2 sequence comprising SEQ ID NO: 223,
HCDR3 sequence comprising SEQ ID NO: 69,
LCDR1 sequence comprising SEQ ID NO: 63,
LCDR2 sequence comprising SEQ ID NO: 54, and
LCDR3 sequence comprising SEQ ID NO: 52;
34) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 1,
HCDR2 sequence comprising SEQ ID NO: 245,
HCDR3 sequence comprising SEQ ID NO: 246,
LCDR1 sequence comprising SEQ ID NO: 254,
LCDR2 sequence comprising SEQ ID NO: 15, and
LCDR3 sequence comprising SEQ ID NO: 255;
35) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 4,
HCDR2 sequence comprising SEQ ID NO: 247,
HCDR3 sequence comprising SEQ ID NO: 246,
LCDR1 sequence comprising SEQ ID NO: 17,
LCDR2 sequence comprising SEQ ID NO: 18, and
LCDR3 sequence comprising SEQ ID NO: 256;
36) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 7,
HCDR2 sequence comprising SEQ ID NO: 248,
HCDR3 sequence comprising SEQ ID NO: 249,
LCDR1 sequence comprising SEQ ID NO: 20,
LCDR2 sequence comprising SEQ ID NO: 18, and
LCDR3 sequence comprising SEQ ID NO: 255;
37) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 1,
HCDR2 sequence comprising SEQ ID NO: 261,
HCDR3 sequence comprising SEQ ID NO: 262,
LCDR1 sequence comprising SEQ ID NO: 254,
LCDR2 sequence comprising SEQ ID NO: 15, and
LCDR3 sequence comprising SEQ ID NO: 16;
38) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 4,
HCDR2 sequence comprising SEQ ID NO: 247,
HCDR3 sequence comprising SEQ ID NO: 262,
LCDR1 sequence comprising SEQ ID NO: 17,
LCDR2 sequence comprising SEQ ID NO: 18, and
LCDR3 sequence comprising SEQ ID NO: 19;
39) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 7,
HCDR2 sequence comprising SEQ ID NO: 248,
HCDR3 sequence comprising SEQ ID NO: 263,
LCDR1 sequence comprising SEQ ID NO: 20,
LCDR2 sequence comprising SEQ ID NO: 18, and
LCDR3 sequence comprising SEQ ID NO: 16;
40) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 272,
HCDR2 sequence comprising SEQ ID NO: 273,
HCDR3 sequence comprising SEQ ID NO: 274,
LCDR1 sequence comprising SEQ ID NO: 254,
LCDR2 sequence comprising SEQ ID NO: 285, and
LCDR3 sequence comprising SEQ ID NO: 16;
41) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 275,
HCDR2 sequence comprising SEQ ID NO: 276,
HCDR3 sequence comprising SEQ ID NO: 274,
LCDR1 sequence comprising SEQ ID NO: 17,
LCDR2 sequence comprising SEQ ID NO: 286, and
LCDR3 sequence comprising SEQ ID NO: 19;
42) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 278,
HCDR2 sequence comprising SEQ ID NO: 279,
HCDR3 sequence comprising SEQ ID NO: 280,
LCDR1 sequence comprising SEQ ID NO: 20,
LCDR2 sequence comprising SEQ ID NO: 286, and
LCDR3 sequence containing SEQ ID NO: 16
The method, composition or use according to any one of [1] to [4] above, selected from any one of the following.
[10] The antibody or antigen-binding fragment thereof is as follows:
1) An antibody comprising a heavy chain variable region (VH) comprising SEQ ID NO: 10 or a sequence at least about 95% identical to it, and a light chain variable region (VL) comprising SEQ ID NO: 21 or a sequence at least about 95% identical to it or an antigen-binding fragment thereof;
2) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 25 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 29 or a sequence at least about 95% identical to it;
3) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 33 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 29 or a sequence at least about 95% identical to it;
4) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 46 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 57 or a sequence at least about 95% identical to it;
5) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 46 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 64 or a sequence at least about 95% identical to it;
6) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 70 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 74 or a sequence at least about 95% identical to it;
7) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 25 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 78 or a sequence at least about 95% identical to it;
8) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 91 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 102 or a sequence at least about 95% identical to it;
9) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 115 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 125 or a sequence at least about 95% identical to it;
10) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 132 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 125 or a sequence at least about 95% identical to it;
11) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 145 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 156 or a sequence at least about 95% identical to it;
12) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 169 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 178 or a sequence at least about 95% identical to it;
13) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 225 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 229 or a sequence at least about 95% identical to it;
14) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 233 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 237 or a sequence at least about 95% identical to it;
15) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 241 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 229 or a sequence at least about 95% identical to it;
16) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 250 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 257 or a sequence at least about 95% identical to it;
17) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 264 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 268 or a sequence at least about 95% identical to it; or
18) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 281 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 287 or a sequence at least about 95% identical to it
The method, composition or use according to any one of [1] to [4] above, selected from any one of the following.
[11] The antibody or antigen-binding fragment thereof is as follows:
1) An antibody comprising a heavy chain comprising SEQ ID NO: 12 or a sequence at least about 95% identical to it, and a light chain comprising SEQ ID NO: 23 or a sequence at least about 95% identical to it;
2) an antibody comprising a heavy chain comprising SEQ ID NO: 27 or a sequence at least about 95% identical to it and a light chain comprising SEQ ID NO: 31 or a sequence at least about 95% identical to it;
3) an antibody comprising a heavy chain comprising SEQ ID NO: 35 or a sequence at least about 95% identical to it and a light chain comprising SEQ ID NO: 31 or a sequence at least about 95% identical to it;
4) an antibody comprising a heavy chain comprising SEQ ID NO: 48 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 59 or a sequence at least about 95% or more identical thereto;
5) an antibody comprising a heavy chain comprising SEQ ID NO: 48 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 66 or a sequence at least about 95% or more identical thereto;
6) an antibody comprising a heavy chain comprising SEQ ID NO: 72 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 76 or a sequence at least about 95% or more identical thereto;
7) an antibody comprising a heavy chain comprising SEQ ID NO: 27 or a sequence at least about 95% identical to it and a light chain comprising SEQ ID NO: 80 or a sequence at least about 95% identical to it;
8) an antibody comprising a heavy chain comprising SEQ ID NO: 93 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 104 or a sequence at least about 95% or more identical thereto;
9) an antibody comprising a heavy chain comprising SEQ ID NO: 117 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 127 or a sequence at least about 95% or more identical thereto;
10) An antibody comprising a heavy chain comprising SEQ ID NO: 134 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 127 or a sequence at least about 95% or more identical thereto;
11) an antibody comprising a heavy chain comprising SEQ ID NO: 147 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 158 or a sequence at least about 95% or more identical thereto;
12) an antibody comprising a heavy chain comprising SEQ ID NO: 171 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 180 or a sequence at least about 95% or more identical thereto;
13) An antibody comprising a heavy chain comprising SEQ ID NO: 227 or a sequence at least about 95% identical to it and a light chain comprising SEQ ID NO: 231 or a sequence at least about 95% identical to it;
14) an antibody comprising a heavy chain comprising SEQ ID NO: 235 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 239 or a sequence at least about 95% or more identical thereto;
15) An antibody comprising a heavy chain comprising SEQ ID NO: 243 or a sequence at least about 95% identical to it and a light chain comprising SEQ ID NO: 231 or a sequence at least about 95% identical to it;
16) An antibody comprising a heavy chain comprising SEQ ID NO: 252 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 259 or a sequence at least about 95% or more identical thereto;
17) an antibody comprising a heavy chain comprising SEQ ID NO: 266 or a sequence at least about 95% identical to it and a light chain comprising SEQ ID NO: 270 or a sequence at least about 95% identical to it; or
18) An antibody comprising a heavy chain comprising SEQ ID NO: 283 or a sequence at least about 95% identical to it and a light chain comprising SEQ ID NO: 289 or a sequence at least about 95% identical to it.
The method, composition or use according to any one of [1] to [4] above, selected from any one of the following.
[12] The antibody or antigen-binding fragment thereof is
HCDR1 sequence comprising SEQ ID NO: 1,
HCDR2 sequence comprising SEQ ID NO: 2,
HCDR3 sequence comprising SEQ ID NO: 3,
LCDR1 sequence comprising SEQ ID NO: 14,
LCDR2 sequence comprising SEQ ID NO: 15, and
LCDR3 sequence containing SEQ ID NO: 16
The method, composition or use according to any one of [1] to [4] above, comprising:
[13] The antibody or antigen-binding fragment thereof is
HCDR1 sequence comprising SEQ ID NO: 4,
HCDR2 sequence comprising SEQ ID NO: 5,
HCDR3 sequence comprising SEQ ID NO: 3,
LCDR1 sequence comprising SEQ ID NO: 17,
LCDR2 sequence comprising SEQ ID NO: 18, and
LCDR3 sequence containing SEQ ID NO: 19
The method, composition or use according to any one of [1] to [4] above, comprising:
[14] The antibody or antigen-binding fragment thereof is
HCDR1 sequence comprising SEQ ID NO: 7,
HCDR2 sequence comprising SEQ ID NO: 8,
HCDR3 sequence comprising SEQ ID NO: 9,
LCDR1 sequence comprising SEQ ID NO: 20,
LCDR2 sequence comprising SEQ ID NO: 18, and
LCDR3 sequence containing SEQ ID NO: 16
The method, composition or use according to any one of [1] to [4] above, comprising:
[15] The antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) comprising SEQ ID NO: 10 or a sequence at least about 95% or more identical thereto, and a heavy chain variable region (VH) comprising SEQ ID NO: 10 or a sequence at least about 95% or more identical thereto. The method, composition or use according to any one of [1] to [4] above, comprising a light chain variable region (VL).
[16] The antibody or antigen-binding fragment thereof comprises a light chain comprising SEQ ID NO: 12 or a sequence at least about 95% identical to SEQ ID NO: 12 or at least about 95% identical to SEQ ID NO: 23 or above [1] - The method, composition or use according to any one of [4].
[17] The antibody or antigen-binding fragment thereof binds to an epitope in human ENTPD2, and the epitope includes the following residues: 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 or Ty The above [1] to [16] containing at least one of r398 ] The method, composition or use according to any one of the above.
[18] The antibody or antigen-binding fragment thereof binds to an epitope in human ENTPD2, and the epitope includes 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 Asp397, the above [1] to [16] any one of A method, composition or use as described in.
[19] Any one of [1] to [4] above, wherein the antibody or antigen-binding fragment thereof competes with any antibody or antigen-binding fragment provided in Table 1 for binding to human ENTPD2 protein. A method, composition or use as described in.
[20] The antibody or antigen-binding fragment thereof binds to the same epitope, substantially the same epitope, an overlapping epitope, or a substantially overlapping epitope as the epitope of any antibody or antigen-binding fragment provided in Table 1. , the method, composition or use according to any one of [1] to [4] above.
[21] The antibody or antigen-binding fragment thereof binds to human ENTPD2 protein with a dissociation constant (K D ) of less than 10 nM, for example, as measured by Biacore, according to any one of [1] to [20] above. Methods, compositions or uses as described.
[22] The antibody or antigen-binding fragment thereof according to any one of [1] to [20] above, binds to human ENTPD2 protein with a dissociation constant (K D ) of less than 5 nM, as measured, for example, by Biacore. Methods, compositions or uses as described.
[23] The antibody or antigen-binding fragment thereof according to any one of [1] to [20] above, binds to human ENTPD2 protein with a dissociation constant (K D ) of less than 3 nM, as measured, for example, by Biacore. Methods, compositions or uses as described.
[24] 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%, [1] to [23] above. ] The method, composition or use according to any one of the above.
[25] The method and composition according to any one of [1] to [24] above, wherein the antibody or antigen-binding fragment thereof inhibits the ability of ENTPD2 to hydrolyze adenosine triphosphate (ATP). thing or use
[26] The antibody or antigen-binding fragment thereof according to any one of [1] to [25] above, wherein the antibody or antigen-binding fragment thereof interferes with the binding of ATP to ENTPD2 or captures ATP within the catalytic domain of ENTPD2. A method, composition or use of.
[27] The method, composition or use according to any one of [1] to [26] above, wherein the antibody has an IgG1, IgG2, IgG3 or IgG4 isotype.
[28] Any of the above [1] to [27], wherein the antibody or antigen-binding fragment thereof comprises an Fc region selected from an IgG1 Fc region, an IgG2 Fc region, an IgG4 Fc region, or an IgG2/IgG4 hybrid Fc region. A method, composition or use according to paragraph 1.
[29] The antibody or antigen-binding fragment thereof comprises a modified Fc region that has reduced antibody-dependent cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) activity compared to the parent antibody. The method, composition or use according to any one of [1] to [28] above.
[30] The method, composition or use according to any one of [1] to [29] above, wherein the antibody is a human or humanized antibody or a fragment thereof.
[31] The method, composition or use according to any one of [1] to [30] above, wherein the cancer is ENTPD2+ cancer.
[32] Any one of [1] to [31] above, wherein said antibody or antigen-binding fragment thereof is administered intravenously to said subject as a 1 hour infusion (up to 2 hours if clinically indicated). Methods, compositions or uses as described in Section.
[33] The antibody or antigen-binding fragment thereof is administered in combination with at least one additional therapeutic agent selected from the group consisting of anti-CD73 Ab, spartalizumab (PDR001), and NIR178, [1] to The method, composition or use according to any one of [32].
[34] The method, composition or use of [33] above, wherein the anti-CD73 Ab is administered intravenously to the subject as a 1 hour infusion (up to 2 hours if clinically indicated).
[35] The method, composition, or method of [33] or [34] above, wherein spartalizumab is administered intravenously to said subject as a 30 minute infusion (up to 2 hours if clinically indicated). use.
[36] The method, composition or use according to any one of [33] to [35] above, wherein NIR178 is taken orally by the subject.
[37] The antibody or antigen-binding fragment thereof is administered to the subject at a dose of 10 mg, 30 mg, 100 mg, 150 mg, 300 mg, 600 mg, 1200 mg or 2400 mg once every two weeks or every four weeks, [1] to The method, composition or use according to any one of [36].
[38] The method, composition or use according to any one of [33] to [37] above, wherein the anti-CD73 Ab is administered to the subject once every two weeks at 200 mg or 400 mg.
[39] The method, composition or use according to any one of [33] to [38] above, wherein spartalizumab is administered to the subject at 400 mg once every four weeks.
[40] The method, composition or use according to any one of [33] to [39] above, wherein NIR178 is continuously administered to the subject twice a day (BID) at 80 mg or 160 mg. .

Claims (38)

癌の処置であって、それを必要とする対象における処置に使用するための、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を含む組成物であって、前記癌は、ＭＳＳ結腸直腸癌（ＣＲＣ）、胆管癌（肝内若しくは肝外）、膵臓癌、食道癌、食道胃接合部（ＥＧＪ）癌又は胃癌である、組成物。 A composition comprising an antibody that specifically binds to human ENTPD2 protein or an antigen-binding fragment thereof for use in the treatment of cancer in a subject in need thereof, wherein the cancer is MSS colon. A composition that is rectal cancer (CRC), cholangiocarcinoma (intrahepatic or extrahepatic), pancreatic cancer, esophageal cancer, esophagogastric junction (EGJ) cancer or gastric cancer. 癌の処置であって、それを必要とする対象における処置のための医薬の製造における、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を含む組成物の使用であって、前記癌は、ＭＳＳ結腸直腸癌（ＣＲＣ）、胆管癌（肝内若しくは肝外）、膵臓癌、食道癌、食道胃接合部（ＥＧＪ）癌又は胃癌である、使用。 Use of a composition comprising an antibody that specifically binds to human ENTPD2 protein or an antigen-binding fragment thereof in the manufacture of a medicament for the treatment of cancer in a subject in need thereof, said cancer The use is MSS colorectal cancer (CRC), cholangiocarcinoma (intrahepatic or extrahepatic), pancreatic cancer, esophageal cancer, esophagogastric junction (EGJ) cancer or gastric cancer. 前記抗体又はその抗原結合断片は、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、請求項１又は２に記載の組成物又は使用。 The antibody or antigen-binding fragment thereof may include heavy chain complementarity-determining region 1 (HCDR1), heavy chain complementarity-determining region 2 (HCDR2), heavy chain complementarity-determining region 2 (HCDR2), or heavy chain complementarity-determining region 2 (HCDR2) of any antibody or antigen-binding fragment provided in Table 1. The set according to claim 1 or 2 , comprising region 3 (HCDR3), light chain complementarity determining region 1 (LCDR1), light chain complementarity determining region 2 (LCDR2) and light chain complementarity determining region 3 (LCDR3). composition or use. 前記ＨＣＤＲ１、ＨＣＤＲ２、ＨＣＤＲ３、ＬＣＤＲ１、ＬＣＤＲ２及びＬＣＤＲ３は、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１～３のいずれか一項に記載の組成物又は使用。 4. According to any one of claims 1 to 3 , said HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are selected from the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences provided in Table 1. Composition or use. 前記抗体又はその抗原結合断片は、表１に提供される重鎖可変領域を含む、請求項１～４のいずれか一項に記載の組成物又は使用。 A composition or use according to any one of claims 1 to 4 , wherein the antibody or antigen-binding fragment thereof comprises the heavy chain variable region provided in Table 1. 前記抗体又はその抗原結合断片は、表１に提供される軽鎖可変領域を含む、請求項１～５のいずれか一項に記載の組成物又は使用。 A composition or use according to any one of claims 1 to 5 , wherein the antibody or antigen-binding fragment thereof comprises the light chain variable region provided in Table 1. 前記抗体又はその抗原結合断片は、以下：
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
の任意の１つから選択される、請求項１又は２に記載の組成物又は使用。 The antibody or antigen-binding fragment thereof:
1) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 1,
HCDR2 sequence comprising SEQ ID NO: 2,
HCDR3 sequence comprising SEQ ID NO: 3,
LCDR1 sequence comprising SEQ ID NO: 14,
LCDR2 sequence comprising SEQ ID NO: 15, and LCDR3 sequence comprising SEQ ID NO: 16;
2) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 4,
HCDR2 sequence comprising SEQ ID NO: 5,
HCDR3 sequence comprising SEQ ID NO: 3,
LCDR1 sequence comprising SEQ ID NO: 17,
LCDR2 sequence comprising SEQ ID NO: 18, and LCDR3 sequence comprising SEQ ID NO: 19;
3) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 7,
HCDR2 sequence comprising SEQ ID NO: 8,
HCDR3 sequence comprising SEQ ID NO: 9,
LCDR1 sequence comprising SEQ ID NO: 20,
LCDR2 sequence comprising SEQ ID NO: 18, and LCDR3 sequence comprising SEQ ID NO: 16;
4) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 37;
HCDR2 sequence comprising SEQ ID NO: 38,
HCDR3 sequence comprising SEQ ID NO: 39,
LCDR1 sequence comprising SEQ ID NO: 50,
LCDR2 sequence comprising SEQ ID NO: 51, and LCDR3 sequence comprising SEQ ID NO: 52;
5) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 40,
HCDR2 sequence comprising SEQ ID NO: 41,
HCDR3 sequence comprising SEQ ID NO: 39,
LCDR1 sequence comprising SEQ ID NO: 53,
LCDR2 sequence comprising SEQ ID NO: 54, and LCDR3 sequence comprising SEQ ID NO: 55;
6) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 43,
HCDR2 sequence comprising SEQ ID NO: 44,
HCDR3 sequence comprising SEQ ID NO: 45,
LCDR1 sequence comprising SEQ ID NO: 56,
LCDR2 sequence comprising SEQ ID NO: 54, and LCDR3 sequence comprising SEQ ID NO: 52;
7) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 37,
HCDR2 sequence comprising SEQ ID NO: 38,
HCDR3 sequence comprising SEQ ID NO: 39,
LCDR1 sequence comprising SEQ ID NO: 61,
LCDR2 sequence comprising SEQ ID NO: 51, and LCDR3 sequence comprising SEQ ID NO: 52;
8) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 40,
HCDR2 sequence comprising SEQ ID NO: 41,
HCDR3 sequence comprising SEQ ID NO: 39,
LCDR1 sequence comprising SEQ ID NO: 62,
LCDR2 sequence comprising SEQ ID NO: 54, and LCDR3 sequence comprising SEQ ID NO: 55;
9) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 43,
HCDR2 sequence comprising SEQ ID NO: 44,
HCDR3 sequence comprising SEQ ID NO: 45,
LCDR1 sequence comprising SEQ ID NO: 63,
LCDR2 sequence comprising SEQ ID NO: 54, and LCDR3 sequence comprising SEQ ID NO: 52;
10) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 37,
HCDR2 sequence comprising SEQ ID NO: 38,
HCDR3 sequence comprising SEQ ID NO: 68,
LCDR1 sequence comprising SEQ ID NO: 50,
LCDR2 sequence comprising SEQ ID NO: 51, and LCDR3 sequence comprising SEQ ID NO: 52;
11) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 40,
HCDR2 sequence comprising SEQ ID NO: 41,
HCDR3 sequence comprising SEQ ID NO: 68,
LCDR1 sequence comprising SEQ ID NO: 53,
LCDR2 sequence comprising SEQ ID NO: 54, and LCDR3 sequence comprising SEQ ID NO: 55;
12) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 43,
HCDR2 sequence comprising SEQ ID NO: 44,
HCDR3 sequence comprising SEQ ID NO: 69,
LCDR1 sequence comprising SEQ ID NO: 56,
LCDR2 sequence comprising SEQ ID NO: 54, and LCDR3 sequence comprising SEQ ID NO: 52;
13) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 82,
HCDR2 sequence comprising SEQ ID NO: 83,
HCDR3 sequence comprising SEQ ID NO: 84,
LCDR1 sequence comprising SEQ ID NO: 95,
LCDR2 sequence comprising SEQ ID NO: 96, and LCDR3 sequence comprising SEQ ID NO: 97;
14) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 85,
HCDR2 sequence comprising SEQ ID NO: 86,
HCDR3 sequence comprising SEQ ID NO: 84,
LCDR1 sequence comprising SEQ ID NO: 98,
LCDR2 sequence comprising SEQ ID NO: 99, and LCDR3 sequence comprising SEQ ID NO: 100;
15) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 88,
HCDR2 sequence comprising SEQ ID NO: 89,
HCDR3 sequence comprising SEQ ID NO: 90,
LCDR1 sequence comprising SEQ ID NO: 101,
LCDR2 sequence comprising SEQ ID NO: 99, and LCDR3 sequence comprising SEQ ID NO: 97;
16) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 106,
HCDR2 sequence comprising SEQ ID NO: 107;
HCDR3 sequence comprising SEQ ID NO: 108,
LCDR1 sequence comprising SEQ ID NO: 119,
LCDR2 sequence comprising SEQ ID NO: 120, and LCDR3 sequence comprising SEQ ID NO: 121;
17) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 109,
HCDR2 sequence comprising SEQ ID NO: 110,
HCDR3 sequence comprising SEQ ID NO: 108,
LCDR1 sequence comprising SEQ ID NO: 122,
LCDR2 sequence comprising SEQ ID NO: 99, and LCDR3 sequence comprising SEQ ID NO: 123;
18) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 112,
HCDR2 sequence comprising SEQ ID NO: 113,
HCDR3 sequence comprising SEQ ID NO: 114,
LCDR1 sequence comprising SEQ ID NO: 124,
LCDR2 sequence comprising SEQ ID NO: 99, and LCDR3 sequence comprising SEQ ID NO: 121;
19) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 106,
HCDR2 sequence comprising SEQ ID NO: 129,
HCDR3 sequence comprising SEQ ID NO: 108,
LCDR1 sequence comprising SEQ ID NO: 119,
LCDR2 sequence comprising SEQ ID NO: 120, and LCDR3 sequence comprising SEQ ID NO: 121;
20) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 109,
HCDR2 sequence comprising SEQ ID NO: 130,
HCDR3 sequence comprising SEQ ID NO: 108,
LCDR1 sequence comprising SEQ ID NO: 122,
LCDR2 sequence comprising SEQ ID NO: 99, and LCDR3 sequence comprising SEQ ID NO: 123;
21) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 112,
HCDR2 sequence comprising SEQ ID NO: 131,
HCDR3 sequence comprising SEQ ID NO: 114,
LCDR1 sequence comprising SEQ ID NO: 124,
LCDR2 sequence comprising SEQ ID NO: 99, and LCDR3 sequence comprising SEQ ID NO: 121;
22) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 136,
HCDR2 sequence comprising SEQ ID NO: 137,
HCDR3 sequence comprising SEQ ID NO: 138,
LCDR1 sequence comprising SEQ ID NO: 149,
LCDR2 sequence comprising SEQ ID NO: 150, and LCDR3 sequence comprising SEQ ID NO: 151;
23) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 139,
HCDR2 sequence comprising SEQ ID NO: 140,
HCDR3 sequence comprising SEQ ID NO: 138,
LCDR1 sequence comprising SEQ ID NO: 152,
LCDR2 sequence comprising SEQ ID NO: 153, and LCDR3 sequence comprising SEQ ID NO: 154;
24) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 142,
HCDR2 sequence comprising SEQ ID NO: 143,
HCDR3 sequence comprising SEQ ID NO: 144,
LCDR1 sequence comprising SEQ ID NO: 155,
LCDR2 sequence comprising SEQ ID NO: 153, and LCDR3 sequence comprising SEQ ID NO: 151;
25) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 160,
HCDR2 sequence comprising SEQ ID NO: 161,
HCDR3 sequence comprising SEQ ID NO: 162,
LCDR1 sequence comprising SEQ ID NO: 173,
LCDR2 sequence comprising SEQ ID NO: 150, and LCDR3 sequence comprising SEQ ID NO: 174;
26) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 163,
HCDR2 sequence comprising SEQ ID NO: 164,
HCDR3 sequence comprising SEQ ID NO: 162,
LCDR1 sequence comprising SEQ ID NO: 175,
LCDR2 sequence comprising SEQ ID NO: 153, and LCDR3 sequence comprising SEQ ID NO: 176;
27) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 166,
HCDR2 sequence comprising SEQ ID NO: 167,
HCDR3 sequence comprising SEQ ID NO: 168,
LCDR1 sequence comprising SEQ ID NO: 177,
LCDR2 sequence comprising SEQ ID NO: 153, and LCDR3 sequence comprising SEQ ID NO: 174;
28) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 37,
HCDR2 sequence comprising SEQ ID NO: 220,
HCDR3 sequence comprising SEQ ID NO: 221,
LCDR1 sequence comprising SEQ ID NO: 61,
LCDR2 sequence comprising SEQ ID NO: 51, and LCDR3 sequence comprising SEQ ID NO: 52;
29) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 40,
HCDR2 sequence comprising SEQ ID NO: 222,
HCDR3 sequence comprising SEQ ID NO: 221,
LCDR1 sequence comprising SEQ ID NO: 62,
LCDR2 sequence comprising SEQ ID NO: 54, and LCDR3 sequence comprising SEQ ID NO: 55;
30) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 43,
HCDR2 sequence comprising SEQ ID NO: 223,
HCDR3 sequence comprising SEQ ID NO: 224,
LCDR1 sequence comprising SEQ ID NO: 63,
LCDR2 sequence comprising SEQ ID NO: 54, and LCDR3 sequence comprising SEQ ID NO: 52;
31) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 37;
HCDR2 sequence comprising SEQ ID NO: 220,
HCDR3 sequence comprising SEQ ID NO: 68,
LCDR1 sequence comprising SEQ ID NO: 61,
LCDR2 sequence comprising SEQ ID NO: 51, and LCDR3 sequence comprising SEQ ID NO: 52;
32) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 40,
HCDR2 sequence comprising SEQ ID NO: 222,
HCDR3 sequence comprising SEQ ID NO: 68,
LCDR1 sequence comprising SEQ ID NO: 62,
LCDR2 sequence comprising SEQ ID NO: 54, and LCDR3 sequence comprising SEQ ID NO: 55;
33) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 43,
HCDR2 sequence comprising SEQ ID NO: 223,
HCDR3 sequence comprising SEQ ID NO: 69,
LCDR1 sequence comprising SEQ ID NO: 63,
LCDR2 sequence comprising SEQ ID NO: 54, and LCDR3 sequence comprising SEQ ID NO: 52;
34) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 1,
HCDR2 sequence comprising SEQ ID NO: 245,
HCDR3 sequence comprising SEQ ID NO: 246,
LCDR1 sequence comprising SEQ ID NO: 254,
LCDR2 sequence comprising SEQ ID NO: 15, and LCDR3 sequence comprising SEQ ID NO: 255;
35) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 4,
HCDR2 sequence comprising SEQ ID NO: 247,
HCDR3 sequence comprising SEQ ID NO: 246,
LCDR1 sequence comprising SEQ ID NO: 17,
LCDR2 sequence comprising SEQ ID NO: 18, and LCDR3 sequence comprising SEQ ID NO: 256;
36) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 7,
HCDR2 sequence comprising SEQ ID NO: 248,
HCDR3 sequence comprising SEQ ID NO: 249,
LCDR1 sequence comprising SEQ ID NO: 20,
LCDR2 sequence comprising SEQ ID NO: 18, and LCDR3 sequence comprising SEQ ID NO: 255;
37) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 1,
HCDR2 sequence comprising SEQ ID NO: 261,
HCDR3 sequence comprising SEQ ID NO: 262,
LCDR1 sequence comprising SEQ ID NO: 254,
LCDR2 sequence comprising SEQ ID NO: 15, and LCDR3 sequence comprising SEQ ID NO: 16;
38) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 4,
HCDR2 sequence comprising SEQ ID NO: 247,
HCDR3 sequence comprising SEQ ID NO: 262,
LCDR1 sequence comprising SEQ ID NO: 17,
LCDR2 sequence comprising SEQ ID NO: 18, and LCDR3 sequence comprising SEQ ID NO: 19;
39) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 7,
HCDR2 sequence comprising SEQ ID NO: 248,
HCDR3 sequence comprising SEQ ID NO: 263,
LCDR1 sequence comprising SEQ ID NO: 20,
LCDR2 sequence comprising SEQ ID NO: 18, and LCDR3 sequence comprising SEQ ID NO: 16;
40) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 272,
HCDR2 sequence comprising SEQ ID NO: 273,
HCDR3 sequence comprising SEQ ID NO: 274,
LCDR1 sequence comprising SEQ ID NO: 254,
LCDR2 sequence comprising SEQ ID NO: 285, and LCDR3 sequence comprising SEQ ID NO: 16;
41) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 275,
HCDR2 sequence comprising SEQ ID NO: 276,
HCDR3 sequence comprising SEQ ID NO: 274,
LCDR1 sequence comprising SEQ ID NO: 17,
LCDR2 sequence comprising SEQ ID NO: 286, and LCDR3 sequence comprising SEQ ID NO: 19;
42) Antibodies or antigen-binding fragments thereof comprising:
HCDR1 sequence comprising SEQ ID NO: 278,
HCDR2 sequence comprising SEQ ID NO: 279,
HCDR3 sequence comprising SEQ ID NO: 280,
LCDR1 sequence comprising SEQ ID NO: 20,
3. A composition or use according to claim 1 or 2 , selected from any one of the following: an LCDR2 sequence comprising SEQ ID NO: 286; and an LCDR3 sequence comprising SEQ ID NO: 16. 前記抗体又はその抗原結合断片は、以下：
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
の任意の１つから選択される、請求項１又は２に記載の組成物又は使用。 The antibody or antigen-binding fragment thereof:
1) An antibody comprising a heavy chain variable region (VH) comprising SEQ ID NO: 10 or a sequence at least about 95% identical to it, and a light chain variable region (VL) comprising SEQ ID NO: 21 or a sequence at least about 95% identical to it or an antigen-binding fragment thereof;
2) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 25 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 29 or a sequence at least about 95% identical to it;
3) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 33 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 29 or a sequence at least about 95% identical to it;
4) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 46 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 57 or a sequence at least about 95% identical to it;
5) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 46 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 64 or a sequence at least about 95% identical to it;
6) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 70 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 74 or a sequence at least about 95% identical to it;
7) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 25 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 78 or a sequence at least about 95% identical to it;
8) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 91 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 102 or a sequence at least about 95% identical to it;
9) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 115 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 125 or a sequence at least about 95% identical to it;
10) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 132 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 125 or a sequence at least about 95% identical to it;
11) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 145 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 156 or a sequence at least about 95% identical to it;
12) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 169 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 178 or a sequence at least about 95% identical to it;
13) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 225 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 229 or a sequence at least about 95% identical to it;
14) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 233 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 237 or a sequence at least about 95% identical to it;
15) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 241 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 229 or a sequence at least about 95% identical to it;
16) An antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 250 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 257 or a sequence at least about 95% identical to it;
17) an antibody or antigen-binding fragment thereof comprising a VH comprising SEQ ID NO: 264 or a sequence at least about 95% identical to it and a VL comprising SEQ ID NO: 268 or a sequence at least about 95% identical to it; or 18) SEQ ID NO: 281 or an antibody or an antigen-binding fragment thereof comprising a VH comprising a sequence at least about 95% identical to SEQ ID NO: 287 or a sequence at least about 95% identical thereto. Composition or use according to item 1 or 2 . 前記抗体又はその抗原結合断片は、以下：
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
の任意の１つから選択される、請求項１又は２に記載の組成物又は使用。 The antibody or antigen-binding fragment thereof:
1) An antibody comprising a heavy chain comprising SEQ ID NO: 12 or a sequence at least about 95% identical to it, and a light chain comprising SEQ ID NO: 23 or a sequence at least about 95% identical to it;
2) an antibody comprising a heavy chain comprising SEQ ID NO: 27 or a sequence at least about 95% identical to it and a light chain comprising SEQ ID NO: 31 or a sequence at least about 95% identical to it;
3) an antibody comprising a heavy chain comprising SEQ ID NO: 35 or a sequence at least about 95% identical to it and a light chain comprising SEQ ID NO: 31 or a sequence at least about 95% identical to it;
4) an antibody comprising a heavy chain comprising SEQ ID NO: 48 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 59 or a sequence at least about 95% or more identical thereto;
5) an antibody comprising a heavy chain comprising SEQ ID NO: 48 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 66 or a sequence at least about 95% or more identical thereto;
6) an antibody comprising a heavy chain comprising SEQ ID NO: 72 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 76 or a sequence at least about 95% or more identical thereto;
7) an antibody comprising a heavy chain comprising SEQ ID NO: 27 or a sequence at least about 95% identical to it and a light chain comprising SEQ ID NO: 80 or a sequence at least about 95% identical to it;
8) an antibody comprising a heavy chain comprising SEQ ID NO: 93 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 104 or a sequence at least about 95% or more identical thereto;
9) an antibody comprising a heavy chain comprising SEQ ID NO: 117 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 127 or a sequence at least about 95% or more identical thereto;
10) An antibody comprising a heavy chain comprising SEQ ID NO: 134 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 127 or a sequence at least about 95% or more identical thereto;
11) an antibody comprising a heavy chain comprising SEQ ID NO: 147 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 158 or a sequence at least about 95% or more identical thereto;
12) an antibody comprising a heavy chain comprising SEQ ID NO: 171 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 180 or a sequence at least about 95% or more identical thereto;
13) An antibody comprising a heavy chain comprising SEQ ID NO: 227 or a sequence at least about 95% identical to it and a light chain comprising SEQ ID NO: 231 or a sequence at least about 95% identical to it;
14) an antibody comprising a heavy chain comprising SEQ ID NO: 235 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 239 or a sequence at least about 95% or more identical thereto;
15) An antibody comprising a heavy chain comprising SEQ ID NO: 243 or a sequence at least about 95% identical to it and a light chain comprising SEQ ID NO: 231 or a sequence at least about 95% identical to it;
16) An antibody comprising a heavy chain comprising SEQ ID NO: 252 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 259 or a sequence at least about 95% or more identical thereto;
17) An antibody comprising a heavy chain comprising SEQ ID NO: 266 or a sequence at least about 95% or more identical thereto and a light chain comprising SEQ ID NO: 270 or a sequence at least about 95% or more identical thereto; or 18) SEQ ID NO: 283 or at least 3. The antibody according to claim 1 or 2 , wherein the antibody comprises a heavy chain comprising a sequence that is about 95% or more identical to SEQ ID NO: 289 or a light chain that has a sequence at least about 95% or more identical thereto. Composition or use. 前記抗体又はその抗原結合断片は、
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又は２に記載の組成物又は使用。 The antibody or antigen-binding fragment thereof is
HCDR1 sequence comprising SEQ ID NO: 1,
HCDR2 sequence comprising SEQ ID NO: 2,
HCDR3 sequence comprising SEQ ID NO: 3,
LCDR1 sequence comprising SEQ ID NO: 14,
3. A composition or use according to claim 1 or 2 , comprising 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は、
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又は２に記載の組成物又は使用。 The antibody or antigen-binding fragment thereof is
HCDR1 sequence comprising SEQ ID NO: 4,
HCDR2 sequence comprising SEQ ID NO: 5,
HCDR3 sequence comprising SEQ ID NO: 3,
LCDR1 sequence comprising SEQ ID NO: 17,
3. A composition or use according to claim 1 or 2 , comprising 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は、
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又は２に記載の組成物又は使用。 The antibody or antigen-binding fragment thereof is
HCDR1 sequence comprising SEQ ID NO: 7,
HCDR2 sequence comprising SEQ ID NO: 8,
HCDR3 sequence comprising SEQ ID NO: 9,
LCDR1 sequence comprising SEQ ID NO: 20,
3. A composition or use according to claim 1 or 2 , comprising 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は、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、請求項１又は２に記載の組成物又は使用。 The antibody or antigen-binding fragment thereof has a heavy chain variable region (VH) comprising SEQ ID NO: 10 or a sequence at least about 95% or more identical thereto, and a light chain variable region (VH) comprising SEQ ID NO: 21 or a sequence at least about 95% or more identical thereto. Composition or use according to claim 1 or 2 , comprising a region (VL). 前記抗体又はその抗原結合断片は、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、請求項１又は２に記載の組成物又は使用。 1 . The antibody or antigen-binding fragment thereof comprises a heavy chain comprising SEQ ID NO: 12 or a sequence at least about 95% or more identical thereto, and a light chain comprising SEQ ID NO: 23 or a sequence at least about 95% or more identical thereto. or the composition or use according to 2 . 前記抗体又はその抗原結合断片は、ヒトＥＮＴＰＤ２におけるエピトープに結合し、前記エピトープは、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１～１４のいずれか一項に記載の組成物又は使用。 The antibody or antigen-binding fragment thereof binds to an epitope in human ENTPD2, which epitope comprises the following residues: His50, Asp76, Pro78, Gly79, Gly80, Tyr85, Asp87, Asn88, Gly91, Gln94, Ser95, Gly98, At least one of Glu101, Gln102, Gln105, Asp106, Arg245, Thr272, Gln273, Leu275, Asp278, Arg298, Ala347, Ala350, Thr351, Arg392, Ala393, Arg394, or Tyr398 Any one of claims 1 to 14 , comprising: A composition or use as described in. 前記抗体又はその抗原結合断片は、ヒトＥＮＴＰＤ２におけるエピトープに結合し、前記エピトープは、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１～１４のいずれか一項に記載の組成物又は使用。 The antibody or antigen-binding fragment thereof binds to an epitope in human ENTPD2, which epitope comprises the following residues: Gly79, Gln250, Leu253, Trp266, Arg268, Gly269, Phe270, Ser271, Thr272, Gln273, Val274, Leu275, ASP278, ARG298, SER300, SER302, GLY303, THR380, TRP380, ALA382, GLY390, ARG392, ARG393, ARG393, ASP397, at least one ASP397. , Composition according to any one of claims 1 to 14 Or use. 前記抗体又はその抗原結合断片は、ヒトＥＮＴＰＤ２タンパク質への結合について、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、請求項１又は２に記載の組成物又は使用。 3. A composition or use according to claim 1 or 2 , wherein the antibody or antigen-binding fragment thereof competes with any antibody or antigen-binding fragment provided in Table 1 for binding to human ENTPD2 protein. 前記抗体又はその抗原結合断片は、表１に提供される任意の抗体又は抗原結合断片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、重複するエピトープ又は実質的に重複するエピトープに結合する、請求項１又は２に記載の組成物又は使用。 12. The antibody or antigen-binding fragment thereof binds to the same epitope, substantially the same epitope, an overlapping epitope, or a substantially overlapping epitope as the epitope of any antibody or antigen-binding fragment provided in Table 1. Composition or use according to item 1 or 2 . 前記抗体又はその抗原結合断片は、例えばＢｉａｃｏｒｅにより測定して、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組成物又は使用。 A composition according to any one of claims 1 to 18 , wherein the antibody or antigen-binding fragment thereof binds to human ENTPD2 protein with a dissociation constant (K D ) of less than 10 nM, for example as determined by Biacore. use. 前記抗体又はその抗原結合断片は、例えばＢｉａｃｏｒｅにより測定して、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組成物又は使用。 19. The composition according to any one of claims 1 to 18 , wherein the antibody or antigen-binding fragment thereof binds to human ENTPD2 protein with a dissociation constant (K D ) of less than 5 nM, for example as determined by Biacore. use. 前記抗体又はその抗原結合断片は、例えばＢｉａｃｏｒｅにより測定して、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組成物又は使用。 19. The composition according to any one of claims 1 to 18 , wherein the antibody or antigen-binding fragment thereof binds to human ENTPD2 protein with a dissociation constant (K D ) of less than 3 nM, for example as determined by Biacore. use. 前記抗体又はその抗原結合断片は、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組成物又は使用。 22. Any one of claims 1-21 , wherein the antibody or antigen-binding fragment thereof inhibits human ENTPD2 enzymatic activity by at least 40%, at least 50%, at least 60%, at least 70%, at least 80% or at least 90%. A composition or use as described in. 前記抗体又はその抗原結合断片は、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組成物又は使用。 23. The composition or use according to any one of claims 1 to 22 , wherein the antibody or 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は、ＥＮＴＰＤ２へのＡＴＰの結合を妨害するか、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組成物又は使用。 24. A composition or use according to any one of claims 1 to 23, wherein the antibody or antigen-binding fragment thereof interferes with the binding of ATP to ENTPD2 or traps ATP within the catalytic domain of ENTPD2. . 前記抗体は、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組成物又は使用。 A composition or use 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は、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組成物又は使用。 26. The combination according to any one of claims 1 to 25 , wherein the antibody or antigen-binding fragment thereof comprises an Fc region selected from an IgG1 Fc region, an IgG2 Fc region, an IgG4 Fc region or an IgG2/IgG4 hybrid Fc region. composition or use. 前記抗体又はその抗原結合断片は、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組成物又は使用。 1 . The antibody or antigen-binding fragment thereof comprises a modified Fc region having reduced antibody-dependent cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) activity compared to the parent antibody. The composition or use according to any one of -26 . 前記抗体は、ヒト若しく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組成物又は使用。 A composition or use according to any one of claims 1 to 27 , wherein the antibody is a human or humanized antibody or a fragment thereof. 前記癌は、ＥＮＴＰＤ２＋癌である、請求項１～２８のいずれか一項に記載の組成物又は使用。 A composition or use according to any one of claims 1 to 28 , wherein the cancer is an ENTPD2+ cancer. 前記抗体又はその抗原結合断片は、１時間注入（臨床的に指示される場合、２時間まで）として前記対象に静脈内投与される、請求項１～２９のいずれか一項に記載の組成物又は使用。 30. The composition of any one of claims 1 to 29 , wherein the antibody or antigen-binding fragment thereof is administered intravenously to the subject as a 1 hour infusion (up to 2 hours if clinically indicated). thing or use 前記抗体又はその抗原結合断片は、抗ＣＤ７３ Ａｂ、スパルタリズマブ（ＰＤＲ００１）及びＮＩＲ１７８からなる群から選択される少なくとも１つの追加の治療薬と組み合わせて投与される、請求項１～３０のいずれか一項に記載の組成物又は使用。 Any of claims 1-30 , wherein the antibody or antigen-binding fragment thereof is administered in combination with at least one additional therapeutic agent selected from the group consisting of anti-CD73 Ab, spartalizumab (PDR001) and NIR178. Composition or use according to paragraph 1. 前記抗ＣＤ７３ Ａｂは、１時間注入（臨床的に指示される場合、２時間まで）として前記対象に静脈内投与される、請求項３１に記載の組成物又は使用。 32. The composition or use of claim 31 , wherein the anti-CD73 Ab is administered intravenously to the subject as a 1 hour infusion (up to 2 hours if clinically indicated). スパルタリズマブは、３０分注入（臨床的に指示される場合、２時間まで）として前記対象に静脈内投与される、請求項３１又は３２に記載の組成物又は使用。 33. The composition or use of claim 31 or 32 , wherein spartalizumab is administered intravenously to the subject as a 30 minute infusion (up to 2 hours if clinically indicated). ＮＩＲ１７８は、前記対象によって経口的に服用される、請求項３１～３３のいずれか一項に記載の組成物又は使用。 A composition or use according to any one of claims 31 to 33 , wherein NIR178 is taken orally by the subject. 前記抗体又はその抗原結合断片は、１０ｍｇ、３０ｍｇ、１００ｍｇ、１５０ｍｇ、３００ｍｇ、６００ｍｇ、１２００ｍｇ又は２４００ｍｇで２週間又は４週間毎に１回、前記対象に投与される、請求項１～３４のいずれか一項に記載の組成物又は使用。 Any of claims 1 to 34 , wherein the antibody or antigen-binding fragment thereof is administered to the subject at 10 mg, 30 mg, 100 mg, 150 mg, 300 mg, 600 mg, 1200 mg or 2400 mg once every two or four weeks. Composition or use according to paragraph 1. 前記抗ＣＤ７３ Ａｂは、２００ｍｇ又は４００ｍｇで２週間毎に１回、前記対象に投与される、請求項３１～３５のいずれか一項に記載の組成物又は使用。 A composition or use according to any one of claims 31 to 35 , wherein the anti-CD73 Ab is administered to the subject at 200 mg or 400 mg once every two weeks. スパルタリズマブは、４００ｍｇで４週間毎に１回、前記対象に投与される、請求項３１～３６のいずれか一項に記載の組成物又は使用。 A composition or use according to any one of claims 31 to 36 , wherein spartalizumab is administered to the subject at 400 mg once every four weeks. ＮＩＲ１７８は、８０ｍｇ又は１６０ｍｇで１日２回（ＢＩＤ）、連続して前記対象に投与される、請求項３１～３７のいずれか一項に記載の組成物又は使用。 38. A composition or use according to any one of claims 31 to 37 , wherein NIR178 is administered to the subject continuously at 80 mg or 160 mg twice a day (BID).
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