JPWO2019224711A5 - - Google Patents
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- JPWO2019224711A5 JPWO2019224711A5 JP2020564908A JP2020564908A JPWO2019224711A5 JP WO2019224711 A5 JPWO2019224711 A5 JP WO2019224711A5 JP 2020564908 A JP2020564908 A JP 2020564908A JP 2020564908 A JP2020564908 A JP 2020564908A JP WO2019224711 A5 JPWO2019224711 A5 JP WO2019224711A5
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- 108091007172 antigens Proteins 0.000 claims description 82
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- 108020004707 nucleic acids Proteins 0.000 claims description 12
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- 102100016493 CD33 Human genes 0.000 claims description 11
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- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 8
- 201000005510 acute lymphocytic leukemia Diseases 0.000 claims description 8
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Description
当業者は、広い発明概念から逸脱することなく前述の実施形態に変更を行うことができることを理解するであろう。したがって、本発明は、開示された特定の実施形態に制限されず、本説明によって定義されるように本発明の趣旨及び範囲内の修正を包含することを意図するものと理解される。
以下の態様を包含し得る。
［１］ ＣＤ３３のＣ２ドメインに特異的に結合する、単離モノクローナル抗体又はその抗原結合断片。
［２］ 以下のポリペプチド配列を有する、重鎖相補性決定領域１（ＨＣＤＲ１）、ＨＣＤＲ２、ＨＣＤＲ３、軽鎖相補性決定領域１（ＬＣＤＲ１）、ＬＣＤＲ２、及びＬＣＤＲ３を含む、上記［１］に記載の単離モノクローナル抗体又はその抗原結合断片：
ａ．それぞれ、配列番号４４７、４４８、４４９、５６７、５６８、及び５６９、
ｂ．それぞれ、配列番号４４４、４４５、４４６、５６４、５６５、及び５６６、
ｃ．それぞれ、配列番号３５４、３５５、３５６、４７７、４７８、及び４７９、
ｄ．それぞれ、配列番号３７８、３７９、３８０、５０１、５０２、及び５０３、
ｅ．それぞれ、配列番号４１１、４１２、４１３、５３１、５３２、及び５３３、
ｆ．それぞれ、配列番号３４８、３４９、３５０、４７１、４７２、及び４７３、
ｇ．それぞれ、配列番号３６０、３６１、３６２、４８３、４８４、及び４８５、
ｈ．それぞれ、配列番号３６３、３６４、３６５、４８６、４８７、及び４８８、
ｉ．それぞれ、配列番号３６６、３６７、３６８、４８９、４９０、及び４９１、
ｊ．それぞれ、配列番号３６９、３７０、３７１、４９２、４９３、及び４９４、
ｋ．それぞれ、配列番号３８７、３８８、３８９、４９２、４９３、及び４９４、
ｌ．それぞれ、配列番号４０２、４０３、４０４、５２２、５２３、及び５２４、
ｍ．それぞれ、配列番号４０８、４０９、４１０、５２８、５２９、及び５３０、
ｎ．それぞれ、配列番号４２３、４２４、４２５、５４３、５４４、及び５４５、又は
ｏ．それぞれ、配列番号４２６、４２７、４２８、５４６、５４７、及び５４８。
［３］ 配列番号２９２、２９１、２６１、２６９、２８０、２５９、２６３、２６４、２６５、２６６、２７２、２７７、２７９、２８４、若しくは２８５と少なくとも９５％同一のポリペプチド配列を有する重鎖可変領域、又は配列番号３３２、３３１、３０２、３１０、３２０、３００、３０４、３０５、３０６、３０７、３１７、３１９、３２４、若しくは３２５と少なくとも９５％同一のポリペプチド配列を有する軽鎖可変領域を含む、上記［１］又は［２］に記載の単離モノクローナル抗体又はその抗原結合断片。
［４］ 以下を含む、上記［１］～［３］のいずれか一項に記載の単離モノクローナル抗体又はその抗原結合断片：
ａ．配列番号２９２のポリペプチド配列を有する重鎖可変領域及び配列番号３３２のポリペプチド配列を有する軽鎖可変領域、
ｂ．配列番号２９１のポリペプチド配列を有する重鎖可変領域及び配列番号３３１のポリペプチド配列を有する軽鎖可変領域、
ｃ．配列番号２６１のポリペプチド配列を有する重鎖可変領域及び配列番号３０２のポリペプチド配列を有する軽鎖可変領域、
ｄ．配列番号２６９のポリペプチド配列を有する重鎖可変領域及び配列番号３１０のポリペプチド配列を有する軽鎖可変領域、
ｅ．配列番号２８０のポリペプチド配列を有する重鎖可変領域及び配列番号３２２のポリペプチド配列を有する軽鎖可変領域、
ｆ．配列番号２５９のポリペプチド配列を有する重鎖可変領域及び配列番号３００のポリペプチド配列を有する軽鎖可変領域、
ｇ．配列番号２６３のポリペプチド配列を有する重鎖可変領域及び配列番号３０４のポリペプチド配列を有する軽鎖可変領域、
ｈ．配列番号２６４のポリペプチド配列を有する重鎖可変領域及び配列番号３０５のポリペプチド配列を有する軽鎖可変領域、
ｉ．配列番号２６５のポリペプチド配列を有する重鎖可変領域及び配列番号３０６のポリペプチド配列を有する軽鎖可変領域、
ｊ．配列番号２６６のポリペプチド配列を有する重鎖可変領域及び配列番号３０７のポリペプチド配列を有する軽鎖可変領域、
ｋ．配列番号２７２のポリペプチド配列を有する重鎖可変領域及び配列番号３０７のポリペプチド配列を有する軽鎖可変領域、
ｌ．配列番号２７７のポリペプチド配列を有する重鎖可変領域及び配列番号３１７のポリペプチド配列を有する軽鎖可変領域、
ｍ．配列番号２７９のポリペプチド配列を有する重鎖可変領域及び配列番号３１９のポリペプチド配列を有する軽鎖可変領域、
ｎ．配列番号２８４のポリペプチド配列を有する重鎖可変領域及び配列番号３２４のポリペプチド配列を有する軽鎖可変領域、又は
ｏ．配列番号２８５のポリペプチド配列を有する重鎖可変領域及び配列番号３２５のポリペプチド配列を有する軽鎖可変領域。
［５］ 約２ｎＭ未満のＥＣ
５０
でインビトロにおいて抗体依存性細胞性細胞傷害（ＡＤＣＣ）を誘導する、上記［１］～［４］のいずれか一項に記載の単離モノクローナル抗体又はその抗原結合断片。
［６］ ＩｇＧ１低フコース骨格を含む、上記［５］に記載の単離モノクローナル抗体又はその抗原結合断片。
［７］ 約５×１０
－９
Ｍ未満の解離定数（ＫＤ）でＣＤ３３に結合する、上記［１］～［４］のいずれか一項に記載の単離モノクローナル抗体又はその抗原結合断片。
［８］ 約２ｎＭ未満のＥＣ
５０
で、ＣＤ３３に結合し、内部移行を誘導する、上記［１］～［４］のいずれか一項に記載の単離モノクローナル抗体又はその抗原結合断片。
［９］ キメラである、上記［１］～［８］のいずれか一項に記載の単離モノクローナル抗体又はその抗原結合断片。
［１０］ ヒトである又はヒト化されている、上記［１］～［９］のいずれか一項に記載の単離モノクローナル抗体又はその抗原結合断片。
［１１］ 治療剤にコンジュゲートしている、上記［１］～［１０］のいずれか一項に記載の単離モノクローナル抗体又はその抗原結合断片。
［１２］ 上記［１］～［１０］のいずれか一項に記載のモノクローナル抗体又はその抗原結合断片をコードしている、単離核酸。
［１３］ 上記［１２］に記載の単離核酸を含む、ベクター。
［１４］ 上記［１３］に記載のベクターを含む、宿主細胞。
［１５］ 上記［１］～［１０］のいずれか一項に記載の単離モノクローナル抗体又はその抗原結合断片と、医薬上許容できる担体とを含む、医薬組成物。
［１６］ それを必要としている対象における癌を治療する方法であって、上記［１５］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。
［１７］ 前記癌が、血液癌である、上記［１６］に記載の方法。
［１８］ 前記血液癌が、白血病、リンパ腫、又は多発性骨髄腫からなる群から選択される、上記［１７］に記載の方法。
［１９］ 前記血液癌が、急性骨髄性白血病（ＡＭＬ）、骨髄異形成症候群（ＭＤＳ）、急性リンパ性白血病（ＡＬＬ）、びまん性大細胞型Ｂ細胞リンパ腫（ＤＬＢＣＬ）、慢性骨髄性白血病（ＣＭＬ）、又は芽球性形質細胞様樹状細胞腫瘍（ＤＰＤＣＮ）である、上記［１７］に記載の方法。
［２０］ 上記［１］～［１０］のいずれか一項に記載のモノクローナル抗体又はその抗原結合断片を生成する方法であって、前記モノクローナル抗体又は抗原結合断片を生成する条件下で、前記モノクローナル抗体又は抗原結合断片をコードしている核酸を含む細胞を培養することと、前記細胞又は培養物から前記抗体又は抗原結合断片を回収することと、を含む、方法。
［２１］ 上記［１］～［１０］のいずれか一項に記載のモノクローナル抗体又はその抗原結合断片を含む、医薬組成物を作製する方法であって、前記モノクローナル抗体又はその抗原結合断片を医薬上許容できる担体と組み合わせて、医薬組成物を得ることを含む、方法。
［２２］ 抗ＣＤ３３抗体又はその抗原結合断片と、抗ＣＤ３抗体又はその抗原結合断片とを含む、抗ＣＤ３３／抗ＣＤ３二重特異性抗体であって、
前記抗ＣＤ３３抗体又はその抗原結合断片が、以下のポリペプチド配列を有する重鎖相補性決定領域１（ＨＣＤＲ１）、ＨＣＤＲ２、ＨＣＤＲ３、軽鎖相補性決定領域１（ＬＣＤＲ１）、ＬＣＤＲ２、及びＬＣＤＲ３を含み：
ａ．それぞれ、配列番号４４７、４４８、４４９、５６７、５６８、及び５６９、
ｂ．それぞれ、配列番号４４４、４４５、４４６、５６４、５６５、及び５６６、
ｃ．それぞれ、配列番号３５４、３５５、３５６、４７７、４７８、及び４７９、
ｄ．それぞれ、配列番号３７８、３７９、３８０、５０１、５０２、及び５０３、
ｅ．それぞれ、配列番号４１１、４１２、４１３、５３１、５３２、及び５３３、
ｆ．それぞれ、配列番号３４８、３４９、３５０、４７１、４７２、及び４７３、
ｇ．それぞれ、配列番号３６０、３６１、３６２、４８３、４８４、及び４８５、
ｈ．それぞれ、配列番号３６３、３６４、３６５、４８６、４８７、及び４８８、
ｉ．それぞれ、配列番号３６６、３６７、３６８、４８９、４９０、及び４９１、
ｊ．それぞれ、配列番号３６９、３７０、３７１、４９２、４９３、及び４９４、
ｋ．それぞれ、配列番号３８７、３８８、３８９、４９２、４９３、及び４９４、
ｌ．それぞれ、配列番号４０２、４０３、４０４、５２２、５２３、及び５２４、
ｍ．それぞれ、配列番号４０８、４０９、４１０、５２８、５２９、及び５３０、
ｎ．それぞれ、配列番号４２３、４２４、４２５、５４３、５４４、及び５４５、又は
ｏ．それぞれ、配列番号４２６、４２７、４２８、５４６、５４７、及び５４８、
前記抗ＣＤ３抗体又はその抗原結合断片が、以下のポリペプチド配列を有する重鎖相補性決定領域１（ＨＣＤＲ１）、ＨＣＤＲ２、ＨＣＤＲ３、軽鎖相補性決定領域１（ＬＣＤＲ１）、ＬＣＤＲ２、及びＬＣＤＲ３を含む、二重特異性抗体：
１）それぞれ、配列番号３４２、３４３、３４４、４６５、４６６、及び４６７、又は
２）それぞれ、配列番号３４５、３４６、３４７、４６８、４６９、及び４７０。
［２３］ 前記抗ＣＤ３３抗体又はその抗原結合断片が、配列番号２９２、２９１、２６１、２６９、２８０、２５９、２６３、２６４、２６５、２６６、２７２、２７７、２７９、２８４、若しくは２８５と少なくとも９５％同一のポリペプチド配列を有する重鎖可変領域、又は配列番号３３２、３３１、３０２、３１０、３２０、３００、３０４、３０５、３０６、３０７、３１７、３１９、３２４、若しくは３２５と少なくとも９５％同一のポリペプチド配列を有する軽鎖可変領域を含み、前記抗ＣＤ３抗体又はその抗原結合断片が、配列番号２５７若しくは２５８と少なくとも９５％同一のポリペプチド配列を有する重鎖可変領域、又は配列番号２９８若しくは２９９と少なくとも９５％同一のポリペプチド配列を有する軽鎖可変領域を含む、上記［２２］に記載の抗ＣＤ３３／抗ＣＤ３二重特異性抗体又はその抗原結合断片。
［２４］ 以下を含む、上記［２２］又は［２３］に記載の抗ＣＤ３３／抗ＣＤ３二重特異性抗体又はその抗原結合断片：
ａ．配列番号２９２のポリペプチド配列を有する重鎖可変領域、及び配列番号３３２のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｂ．配列番号２９１のポリペプチド配列を有する重鎖可変領域、及び配列番号３３１のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｃ．配列番号２６１のポリペプチド配列を有する重鎖可変領域、及び配列番号３０２のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｄ．配列番号２６９のポリペプチド配列を有する重鎖可変領域、及び配列番号３１０のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｅ．配列番号２８０のポリペプチド配列を有する重鎖可変領域、及び配列番号３２２のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｆ．配列番号２５９のポリペプチド配列を有する重鎖可変領域、及び配列番号３００のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｇ．配列番号２６３のポリペプチド配列を有する重鎖可変領域、及び配列番号３０４のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｈ．配列番号２６４のポリペプチド配列を有する重鎖可変領域、及び配列番号３０５のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｉ．配列番号２６５のポリペプチド配列を有する重鎖可変領域、及び配列番号３０６のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｊ．配列番号２６６のポリペプチド配列を有する重鎖可変領域、及び配列番号３０７のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｋ．配列番号２７２のポリペプチド配列を有する重鎖可変領域、及び配列番号３０７のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｌ．配列番号２７７のポリペプチド配列を有する重鎖可変領域、及び配列番号３１７のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｍ．配列番号２７９のポリペプチド配列を有する重鎖可変領域、及び配列番号３１９のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｎ．配列番号２８４のポリペプチド配列を有する重鎖可変領域、及び配列番号３２４のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｏ．配列番号２８５のポリペプチド配列を有する重鎖可変領域、及び配列番号３２５のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｐ．配列番号２９２のポリペプチド配列を有する重鎖可変領域、及び配列番号３３２のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｑ．配列番号２９１のポリペプチド配列を有する重鎖可変領域、及び配列番号３３１のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｒ．配列番号２６１のポリペプチド配列を有する重鎖可変領域、及び配列番号３０２のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｓ．配列番号２６９のポリペプチド配列を有する重鎖可変領域、及び配列番号３１０のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｔ．配列番号２８０のポリペプチド配列を有する重鎖可変領域、及び配列番号３２２のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｕ．配列番号２５９のポリペプチド配列を有する重鎖可変領域、及び配列番号３００のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｖ．配列番号２６３のポリペプチド配列を有する重鎖可変領域、及び配列番号３０４のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｗ．配列番号２６４のポリペプチド配列を有する重鎖可変領域、及び配列番号３０５のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｘ．配列番号２６５のポリペプチド配列を有する重鎖可変領域、及び配列番号３０６のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｙ．配列番号２６６のポリペプチド配列を有する重鎖可変領域、及び配列番号３０７のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｚ．配列番号２７２のポリペプチド配列を有する重鎖可変領域、及び配列番号３０７のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ａａ．配列番号２７７のポリペプチド配列を有する重鎖可変領域、及び配列番号３１７のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｂｂ．配列番号２７９のポリペプチド配列を有する重鎖可変領域、及び配列番号３１９のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｃｃ．配列番号２８４のポリペプチド配列を有する重鎖可変領域、及び配列番号３２４のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、又は
ｄｄ．配列番号２８５のポリペプチド配列を有する重鎖可変領域、及び配列番号３２５のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域。
［２５］ 前記抗ＣＤ３３抗体又はその抗原結合断片が、ＣＤ３３のＣ２ドメインに特異的に結合する、上記［２２］～［２４］のいずれか一項に記載の抗ＣＤ３３／抗ＣＤ３二重特異性抗体又はその抗原結合断片。
［２６］ 約１ｎＭ未満のＥＣ
５０
値でインビトロにおいてＣＤ３３発現細胞のＴ細胞依存性細胞傷害を誘導する、上記［２２］～［２５］のいずれか一項に記載の抗ＣＤ３３／抗ＣＤ３二重特異性抗体又はその抗原結合断片。
［２７］ キメラである、上記［２２］～［２６］のいずれか一項に記載の抗ＣＤ３３／抗ＣＤ３二重特異性抗体又はその抗原結合断片。
［２８］ ヒトである又はヒト化されている、上記［２２］～［２７］のいずれか一項に記載の抗ＣＤ３３／抗ＣＤ３二重特異性抗体又はその抗原結合断片。
［２９］ 上記［２２］～［２８］のいずれか一項に記載の抗ＣＤ３３／抗ＣＤ３二重特異性抗体又はその抗原結合断片をコードしている、単離核酸。
［３０］ 上記［２９］に記載の単離核酸を含む、ベクター。
［３１］ 上記［３０］に記載のベクターを含む、宿主細胞。
［３２］ 上記［２２］～［２８］のいずれか一項に記載の抗ＣＤ３３／抗ＣＤ３二重特異性抗体又はその抗原結合断片と、医薬上許容できる担体とを含む、医薬組成物。
［３３］ それを必要としている対象における癌を治療する方法であって、上記［３２］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。
［３４］ 前記癌が、血液癌である、上記［３３］に記載の方法。
［３５］ 前記血液癌が、白血病、リンパ腫、又は多発性骨髄腫からなる群から選択される、上記［３４］に記載の方法。
［３６］ 前記血液癌が、急性骨髄性白血病（ＡＭＬ）、骨髄異形成症候群（ＭＤＳ）、急性リンパ性白血病（ＡＬＬ）、びまん性大細胞型Ｂ細胞リンパ腫（ＤＬＢＣＬ）、慢性骨髄性白血病（ＣＭＬ）、又は芽球性形質細胞様樹状細胞腫瘍（ＤＰＤＣＮ）である、上記［３５］に記載の方法。
［３７］ 上記［２２］～［２８］のいずれか一項に記載の抗ＣＤ３３／抗ＣＤ３二重特異性抗体又はその抗原結合断片を生成する方法であって、前記抗ＣＤ３３／抗ＣＤ３二重特異性抗体又は抗原結合断片を生成する条件下で、前記抗ＣＤ３３／抗ＣＤ３二重特異性抗体又は抗原結合断片をコードしている核酸を含む細胞を培養することと、前記細胞又は培養物から前記抗ＣＤ３３／抗ＣＤ３二重特異性抗体又は抗原結合断片を回収することと、を含む、方法。
［３８］ 上記［２２］～［２８］のいずれか一項に記載の抗ＣＤ３３／抗ＣＤ３二重特異性抗体又はその抗原結合断片を含む、医薬組成物を作製する方法であって、前記抗ＣＤ３３／抗ＣＤ３二重特異性抗体又はその抗原結合断片を医薬上許容できる担体と組み合わせて、医薬組成物を得ることを含む、方法。
Those skilled in the art will appreciate that modifications can be made to the aforementioned embodiments without departing from the broader invention concept. Accordingly, it is understood that the invention is not limited to the particular embodiments disclosed and is intended to include modifications within the spirit and scope of the invention as defined by this description.
The following aspects may be included.
[1] An isolated monoclonal antibody or an antigen-binding fragment thereof that specifically binds to the C2 domain of CD33.
[2] The above-mentioned [1], which comprises heavy chain complementarity determining regions 1 (HCDR1), HCDR2, HCDR3, light chain complementarity determining regions 1 (LCDR1), LCDR2, and LCDR3 having the following polypeptide sequences. Isolated monoclonal antibody or antigen-binding fragment thereof:
a. SEQ ID NOs: 447, 448, 449, 567, 568, and 569, respectively,
b. SEQ ID NOs: 444, 445, 446, 564, 565, and 566, respectively,
c. SEQ ID NOs: 354, 355, 356, 477, 478, and 479, respectively,
d. SEQ ID NOs: 378, 379, 380, 501, 502, and 503, respectively,
e. SEQ ID NOs: 411, 412, 413, 513, 532, and 533, respectively,
f. SEQ ID NOs: 348, 349, 350, 471, 472, and 473, respectively.
g. SEQ ID NOs: 360, 361, 362, 483, 484, and 485, respectively.
h. SEQ ID NOs: 363, 364, 365, 486, 487, and 488, respectively,
i. SEQ ID NOs: 366, 376, 368, 489, 490, and 491, respectively,
j. SEQ ID NOs: 369, 370, 371, 492, 493, and 494, respectively.
k. SEQ ID NOs: 387, 388, 389, 492, 493, and 494, respectively.
l. SEQ ID NOs: 402, 403, 404, 522, 523, and 524, respectively,
m. SEQ ID NOs: 408, 409, 410, 528, 259, and 530, respectively,
n. SEQ ID NOs: 423, 424, 425, 543, 544, and 545, respectively, or
o. SEQ ID NOs: 426, 427, 428, 546, 547, and 548, respectively.
[3] A heavy chain variable region having a polypeptide sequence that is at least 95% identical to SEQ ID NO: 292, 291, 261, 269, 280, 259, 263, 264, 265, 266, 272, 277, 279, 284, or 285. , Or a light chain variable region having a polypeptide sequence that is at least 95% identical to SEQ ID NO: 332, 331, 302, 310, 320, 300, 304, 305, 306, 307, 317, 319, 324, or 325. The isolated monoclonal antibody or antigen-binding fragment thereof according to the above [1] or [2].
[4] The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of the above [1] to [3], which comprises the following:
a. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 292 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 332,
b. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 291 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 331,
c. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 261 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 302,
d. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 269 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 310,
e. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 280 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 322,
f. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 259 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 300,
g. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 263 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 304,
h. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 264 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 305,
i. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 265 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 306,
j. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 266 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 307,
k. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 272 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 307,
l. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 277 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 317,
m. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 279 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 319,
n. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 284 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 324, or
o. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 285 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 325.
[5] The isolated monoclonal antibody or antigen binding thereof according to any one of [1] to [4] above, which induces antibody-dependent cellular cytotoxicity (ADCC) in vitro with an EC 50 of less than about 2 nM. piece.
[6] The isolated monoclonal antibody or antigen-binding fragment thereof according to the above [5], which comprises an IgG1 low fucose skeleton.
[7] The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of [1] to [4] above, which binds to CD33 with a dissociation constant (KD) of less than about 5 × 10-9 M.
[8] The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of the above [1] to [4], which binds to CD33 and induces internal migration with an EC50 of less than about 2 nM .
[9] The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of the above [1] to [8], which is a chimera.
[10] The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of the above [1] to [9], which is human or humanized.
[11] The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of the above [1] to [10], which is conjugated to a therapeutic agent.
[12] An isolated nucleic acid encoding the monoclonal antibody according to any one of the above [1] to [10] or an antigen-binding fragment thereof.
[13] A vector containing the isolated nucleic acid according to the above [12].
[14] A host cell containing the vector according to the above [13].
[15] A pharmaceutical composition comprising the isolated monoclonal antibody according to any one of the above [1] to [10] or an antigen-binding fragment thereof, and a pharmaceutically acceptable carrier.
[16] A method for treating cancer in a subject in need thereof, comprising administering to the subject the pharmaceutical composition according to [15] above.
[17] The method according to the above [16], wherein the cancer is a blood cancer.
[18] The method according to [17] above, wherein the blood cancer is selected from the group consisting of leukemia, lymphoma, or multiple myeloma.
[19] The blood cancers include acute myelogenous leukemia (AML), myelogenous dysplasia syndrome (MDS), acute lymphocytic leukemia (ALL), diffuse large cell B-cell lymphoma (DLBCL), and chronic myelogenous leukemia (CML). ), Or the method according to [17] above, which is a blastoid plasma cell-like dendritic cell tumor (DPDCN).
[20] The method for producing a monoclonal antibody or an antigen-binding fragment thereof according to any one of the above [1] to [10], wherein the monoclonal antibody or the antigen-binding fragment is produced. A method comprising culturing a cell comprising a nucleic acid encoding an antibody or antigen binding fragment and recovering the antibody or antigen binding fragment from the cell or culture.
[21] A method for producing a pharmaceutical composition containing the monoclonal antibody according to any one of the above [1] to [10] or an antigen-binding fragment thereof, wherein the monoclonal antibody or the antigen-binding fragment thereof is used as a pharmaceutical. A method comprising obtaining a pharmaceutical composition in combination with an acceptable carrier.
[22] An anti-CD33 / anti-CD3 bispecific antibody comprising an anti-CD33 antibody or an antigen-binding fragment thereof and an anti-CD3 antibody or an antigen-binding fragment thereof.
The anti-CD33 antibody or antigen-binding fragment thereof comprises heavy chain complementarity determining regions 1 (HCDR1), HCDR2, HCDR3, light chain complementarity determining regions 1 (LCDR1), LCDR2, and LCDR3 having the following polypeptide sequences. :
a. SEQ ID NOs: 447, 448, 449, 567, 568, and 569, respectively,
b. SEQ ID NOs: 444, 445, 446, 564, 565, and 566, respectively,
c. SEQ ID NOs: 354, 355, 356, 477, 478, and 479, respectively,
d. SEQ ID NOs: 378, 379, 380, 501, 502, and 503, respectively,
e. SEQ ID NOs: 411, 412, 413, 513, 532, and 533, respectively,
f. SEQ ID NOs: 348, 349, 350, 471, 472, and 473, respectively.
g. SEQ ID NOs: 360, 361, 362, 483, 484, and 485, respectively.
h. SEQ ID NOs: 363, 364, 365, 486, 487, and 488, respectively,
i. SEQ ID NOs: 366, 376, 368, 489, 490, and 491, respectively,
j. SEQ ID NOs: 369, 370, 371, 492, 493, and 494, respectively.
k. SEQ ID NOs: 387, 388, 389, 492, 493, and 494, respectively.
l. SEQ ID NOs: 402, 403, 404, 522, 523, and 524, respectively,
m. SEQ ID NOs: 408, 409, 410, 528, 259, and 530, respectively,
n. SEQ ID NOs: 423, 424, 425, 543, 544, and 545, respectively, or
o. SEQ ID NOs: 426, 427, 428, 546, 547, and 548, respectively,
The anti-CD3 antibody or antigen-binding fragment thereof comprises heavy chain complementarity determining regions 1 (HCDR1), HCDR2, HCDR3, light chain complementarity determining regions 1 (LCDR1), LCDR2, and LCDR3 having the following polypeptide sequences. , Bispecific antibodies:
1) SEQ ID NOs: 342, 343, 344, 465, 466, and 467, respectively, or
2) SEQ ID NOs: 345, 346, 347, 468, 469, and 470, respectively.
[23] The anti-CD33 antibody or antigen-binding fragment thereof is at least 95% with SEQ ID NO: 292, 291, 261, 269, 280, 259, 263, 264, 265, 266, 272, 277, 279, 284, or 285. A poly that is at least 95% identical to a heavy chain variable region having the same polypeptide sequence, or SEQ ID NO: 332, 331, 302, 310, 320, 300, 304, 305, 306, 307, 317, 319, 324, or 325. A heavy chain variable region comprising a light chain variable region having a peptide sequence, wherein the anti-CD3 antibody or antigen-binding fragment thereof has a polypeptide sequence that is at least 95% identical to SEQ ID NO: 257 or 258, or to SEQ ID NO: 298 or 299. The anti-CD33 / anti-CD3 bispecific antibody or antigen-binding fragment thereof according to the above [22], which comprises a light chain variable region having at least 95% of the same polypeptide sequence.
[24] The anti-CD33 / anti-CD3 bispecific antibody or antigen-binding fragment thereof according to the above [22] or [23], which comprises the following:
a. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 292, a light chain variable region having the polypeptide sequence of SEQ ID NO: 332, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
b. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 291 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 331, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
c. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 261 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 302, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
d. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 269, a light chain variable region having the polypeptide sequence of SEQ ID NO: 310, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
e. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 280, a light chain variable region having the polypeptide sequence of SEQ ID NO: 322, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
f. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 259, a light chain variable region having the polypeptide sequence of SEQ ID NO: 300, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
g. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 263, a light chain variable region having the polypeptide sequence of SEQ ID NO: 304, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
h. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 264, a light chain variable region having the polypeptide sequence of SEQ ID NO: 305, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
i. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 265, a light chain variable region having the polypeptide sequence of SEQ ID NO: 306, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
j. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 266, a light chain variable region having the polypeptide sequence of SEQ ID NO: 307, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
k. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 272, a light chain variable region having the polypeptide sequence of SEQ ID NO: 307, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
l. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 277, a light chain variable region having the polypeptide sequence of SEQ ID NO: 317, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
m. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 279, a light chain variable region having the polypeptide sequence of SEQ ID NO: 319, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
n. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 284, a light chain variable region having the polypeptide sequence of SEQ ID NO: 324, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
o. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 285, a light chain variable region having the polypeptide sequence of SEQ ID NO: 325, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
p. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 292, a light chain variable region having the polypeptide sequence of SEQ ID NO: 332, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
q. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 291 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 331, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
r. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 261 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 302, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
s. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 269, a light chain variable region having the polypeptide sequence of SEQ ID NO: 310, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
t. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 280, a light chain variable region having the polypeptide sequence of SEQ ID NO: 322, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
u. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 259, a light chain variable region having the polypeptide sequence of SEQ ID NO: 300, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
v. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 263, a light chain variable region having the polypeptide sequence of SEQ ID NO: 304, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
w. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 264, a light chain variable region having the polypeptide sequence of SEQ ID NO: 305, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
x. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 265, a light chain variable region having the polypeptide sequence of SEQ ID NO: 306, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
y. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 266, a light chain variable region having the polypeptide sequence of SEQ ID NO: 307, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
z. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 272, a light chain variable region having the polypeptide sequence of SEQ ID NO: 307, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
aa. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 277, a light chain variable region having the polypeptide sequence of SEQ ID NO: 317, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
bb. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 279, a light chain variable region having the polypeptide sequence of SEQ ID NO: 319, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
cc. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 284, a light chain variable region having the polypeptide sequence of SEQ ID NO: 324, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence, or
dd. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 285, a light chain variable region having the polypeptide sequence of SEQ ID NO: 325, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. A light chain variable region with a peptide sequence.
[25] The anti-CD33 / anti-CD3 bispecific according to any one of [22] to [24] above, wherein the anti-CD33 antibody or an antigen-binding fragment thereof specifically binds to the C2 domain of CD33. Antibodies or antigen-binding fragments thereof.
[26] The anti-CD33 / anti-CD3 dual according to any one of [22] to [25] above, which induces T cell-dependent cytotoxicity of CD33-expressing cells in vitro with an EC50 value of less than about 1 nM. Specific antibodies or antigen-binding fragments thereof.
[27] The anti-CD33 / anti-CD3 bispecific antibody or antigen-binding fragment thereof according to any one of the above [22] to [26], which is a chimera.
[28] The anti-CD33 / anti-CD3 bispecific antibody or antigen-binding fragment thereof according to any one of the above [22] to [27], which is human or humanized.
[29] An isolated nucleic acid encoding the anti-CD33 / anti-CD3 bispecific antibody or antigen-binding fragment thereof according to any one of [22] to [28] above.
[30] A vector containing the isolated nucleic acid according to the above [29].
[31] A host cell containing the vector according to the above [30].
[32] A pharmaceutical composition comprising the anti-CD33 / anti-CD3 bispecific antibody according to any one of the above [22] to [28] or an antigen-binding fragment thereof, and a pharmaceutically acceptable carrier.
[33] A method for treating cancer in a subject in need thereof, comprising administering to the subject the pharmaceutical composition according to [32] above.
[34] The method according to [33] above, wherein the cancer is a blood cancer.
[35] The method according to [34] above, wherein the hematological carcinoma is selected from the group consisting of leukemia, lymphoma, or multiple myeloma.
[36] The blood cancers include acute myelogenous leukemia (AML), myelogenous dysplasia syndrome (MDS), acute lymphocytic leukemia (ALL), diffuse large cell B-cell lymphoma (DLBCL), and chronic myelogenous leukemia (CML). ), Or the method according to [35] above, which is a blastoid plasma cell-like dendritic cell tumor (DPDCN).
[37] The method for producing an anti-CD33 / anti-CD3 bispecific antibody or an antigen-binding fragment thereof according to any one of the above [22] to [28], wherein the anti-CD33 / anti-CD3 double. Culturing cells containing the nucleic acids encoding the anti-CD33 / anti-CD3 bispecific antibody or antigen-binding fragment under conditions that produce specific antibodies or antigen-binding fragments, and from said cells or cultures. A method comprising recovering the anti-CD33 / anti-CD3 bispecific antibody or antigen binding fragment.
[38] A method for producing a pharmaceutical composition comprising the anti-CD33 / anti-CD3 bispecific antibody according to any one of the above [22] to [28] or an antigen-binding fragment thereof, wherein the anti-CD33 / anti-CD3 bispecific antibody is prepared. A method comprising combining a CD33 / anti-CD3 bispecific antibody or antigen-binding fragment thereof with a pharmaceutically acceptable carrier to obtain a pharmaceutical composition.
Claims (39)
ａ．それぞれ、配列番号４４７、４４８、４４９、５６７、５６８、及び５６９、
ｂ．それぞれ、配列番号４４４、４４５、４４６、５６４、５６５、及び５６６、
ｃ．それぞれ、配列番号３５４、３５５、３５６、４７７、４７８、及び４７９、
ｄ．それぞれ、配列番号３７８、３７９、３８０、５０１、５０２、及び５０３、
ｅ．それぞれ、配列番号４１１、４１２、４１３、５３１、５３２、及び５３３、
ｆ．それぞれ、配列番号３４８、３４９、３５０、４７１、４７２、及び４７３、
ｇ．それぞれ、配列番号３６０、３６１、３６２、４８３、４８４、及び４８５、
ｈ．それぞれ、配列番号３６３、３６４、３６５、４８６、４８７、及び４８８、
ｉ．それぞれ、配列番号３６６、３６７、３６８、４８９、４９０、及び４９１、
ｊ．それぞれ、配列番号３６９、３７０、３７１、４９２、４９３、及び４９４、
ｋ．それぞれ、配列番号３８７、３８８、３８９、４９２、４９３、及び４９４、
ｌ．それぞれ、配列番号４０２、４０３、４０４、５２２、５２３、及び５２４、
ｍ．それぞれ、配列番号４０８、４０９、４１０、５２８、５２９、及び５３０、
ｎ．それぞれ、配列番号４２３、４２４、４２５、５４３、５４４、及び５４５、又は
ｏ．それぞれ、配列番号４２６、４２７、４２８、５４６、５４７、及び５４８。 The isolated monoclonal of claim 1, comprising heavy chain complementarity determining regions 1 (HCDR1), HCDR2, HCDR3, light chain complementarity determining regions 1 (LCDR1), LCDR2, and LCDR3 having the following polypeptide sequences: Antibodies or antigen-binding fragments thereof:
a. SEQ ID NOs: 447, 448, 449, 567, 568, and 569, respectively,
b. SEQ ID NOs: 444, 445, 446, 564, 565, and 566, respectively,
c. SEQ ID NOs: 354, 355, 356, 477, 478, and 479, respectively,
d. SEQ ID NOs: 378, 379, 380, 501, 502, and 503, respectively,
e. SEQ ID NOs: 411, 412, 413, 513, 532, and 533, respectively,
f. SEQ ID NOs: 348, 349, 350, 471, 472, and 473, respectively.
g. SEQ ID NOs: 360, 361, 362, 483, 484, and 485, respectively.
h. SEQ ID NOs: 363, 364, 365, 486, 487, and 488, respectively,
i. SEQ ID NOs: 366, 376, 368, 489, 490, and 491, respectively,
j. SEQ ID NOs: 369, 370, 371, 492, 493, and 494, respectively.
k. SEQ ID NOs: 387, 388, 389, 492, 493, and 494, respectively.
l. SEQ ID NOs: 402, 403, 404, 522, 523, and 524, respectively,
m. SEQ ID NOs: 408, 409, 410, 528, 259, and 530, respectively,
n. SEQ ID NOs: 423, 424, 425, 543, 544, and 545, respectively, or o. SEQ ID NOs: 426, 427, 428, 546, 547, and 548, respectively.
ａ．配列番号２９２のポリペプチド配列を有する重鎖可変領域及び配列番号３３２のポリペプチド配列を有する軽鎖可変領域、
ｂ．配列番号２９１のポリペプチド配列を有する重鎖可変領域及び配列番号３３１のポリペプチド配列を有する軽鎖可変領域、
ｃ．配列番号２６１のポリペプチド配列を有する重鎖可変領域及び配列番号３０２のポリペプチド配列を有する軽鎖可変領域、
ｄ．配列番号２６９のポリペプチド配列を有する重鎖可変領域及び配列番号３１０のポリペプチド配列を有する軽鎖可変領域、
ｅ．配列番号２８０のポリペプチド配列を有する重鎖可変領域及び配列番号３２２のポリペプチド配列を有する軽鎖可変領域、
ｆ．配列番号２５９のポリペプチド配列を有する重鎖可変領域及び配列番号３００のポリペプチド配列を有する軽鎖可変領域、
ｇ．配列番号２６３のポリペプチド配列を有する重鎖可変領域及び配列番号３０４のポリペプチド配列を有する軽鎖可変領域、
ｈ．配列番号２６４のポリペプチド配列を有する重鎖可変領域及び配列番号３０５のポリペプチド配列を有する軽鎖可変領域、
ｉ．配列番号２６５のポリペプチド配列を有する重鎖可変領域及び配列番号３０６のポリペプチド配列を有する軽鎖可変領域、
ｊ．配列番号２６６のポリペプチド配列を有する重鎖可変領域及び配列番号３０７のポリペプチド配列を有する軽鎖可変領域、
ｋ．配列番号２７２のポリペプチド配列を有する重鎖可変領域及び配列番号３０７のポリペプチド配列を有する軽鎖可変領域、
ｌ．配列番号２７７のポリペプチド配列を有する重鎖可変領域及び配列番号３１７のポリペプチド配列を有する軽鎖可変領域、
ｍ．配列番号２７９のポリペプチド配列を有する重鎖可変領域及び配列番号３１９のポリペプチド配列を有する軽鎖可変領域、
ｎ．配列番号２８４のポリペプチド配列を有する重鎖可変領域及び配列番号３２４のポリペプチド配列を有する軽鎖可変領域、又は
ｏ．配列番号２８５のポリペプチド配列を有する重鎖可変領域及び配列番号３２５のポリペプチド配列を有する軽鎖可変領域。 The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of claims 1 to 4 , which comprises the following:
a. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 292 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 332,
b. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 291 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 331,
c. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 261 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 302,
d. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 269 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 310,
e. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 280 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 322,
f. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 259 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 300,
g. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 263 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 304,
h. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 264 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 305,
i. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 265 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 306,
j. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 266 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 307,
k. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 272 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 307,
l. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 277 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 317,
m. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 279 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 319,
n. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 284 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 324, or o. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 285 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 325.
それを必要としている対象における癌を治療する方法で用いるためのものであり、
前記方法が、前記医薬組成物を前記対象に投与することを含む、医薬組成物。 The pharmaceutical composition according to claim 16.
It is intended for use in methods of treating cancer in subjects in need of it.
A pharmaceutical composition , wherein the method comprises administering the pharmaceutical composition to the subject.
前記抗ＣＤ３３抗体又はその抗原結合断片が、以下のポリペプチド配列を有する重鎖相補性決定領域１（ＨＣＤＲ１）、ＨＣＤＲ２、ＨＣＤＲ３、軽鎖相補性決定領域１（ＬＣＤＲ１）、ＬＣＤＲ２、及びＬＣＤＲ３を含み：
ａ．それぞれ、配列番号４４７、４４８、４４９、５６７、５６８、及び５６９、
ｂ．それぞれ、配列番号４４４、４４５、４４６、５６４、５６５、及び５６６、
ｃ．それぞれ、配列番号３５４、３５５、３５６、４７７、４７８、及び４７９、
ｄ．それぞれ、配列番号３７８、３７９、３８０、５０１、５０２、及び５０３、
ｅ．それぞれ、配列番号４１１、４１２、４１３、５３１、５３２、及び５３３、
ｆ．それぞれ、配列番号３４８、３４９、３５０、４７１、４７２、及び４７３、
ｇ．それぞれ、配列番号３６０、３６１、３６２、４８３、４８４、及び４８５、
ｈ．それぞれ、配列番号３６３、３６４、３６５、４８６、４８７、及び４８８、
ｉ．それぞれ、配列番号３６６、３６７、３６８、４８９、４９０、及び４９１、
ｊ．それぞれ、配列番号３６９、３７０、３７１、４９２、４９３、及び４９４、
ｋ．それぞれ、配列番号３８７、３８８、３８９、４９２、４９３、及び４９４、
ｌ．それぞれ、配列番号４０２、４０３、４０４、５２２、５２３、及び５２４、
ｍ．それぞれ、配列番号４０８、４０９、４１０、５２８、５２９、及び５３０、
ｎ．それぞれ、配列番号４２３、４２４、４２５、５４３、５４４、及び５４５、又は
ｏ．それぞれ、配列番号４２６、４２７、４２８、５４６、５４７、及び５４８、
前記抗ＣＤ３抗体又はその抗原結合断片が、以下のポリペプチド配列を有する重鎖相補性決定領域１（ＨＣＤＲ１）、ＨＣＤＲ２、ＨＣＤＲ３、軽鎖相補性決定領域１（ＬＣＤＲ１）、ＬＣＤＲ２、及びＬＣＤＲ３を含む、二重特異性抗体：
１）それぞれ、配列番号３４２、３４３、３４４、４６５、４６６、及び４６７、又は
２）それぞれ、配列番号３４５、３４６、３４７、４６８、４６９、及び４７０。 An anti-CD33 / anti-CD3 bispecific antibody comprising an anti-CD33 antibody or an antigen-binding fragment thereof and an anti-CD3 antibody or an antigen-binding fragment thereof.
The anti-CD33 antibody or antigen-binding fragment thereof comprises heavy chain complementarity determining regions 1 (HCDR1), HCDR2, HCDR3, light chain complementarity determining regions 1 (LCDR1), LCDR2, and LCDR3 having the following polypeptide sequences. :
a. SEQ ID NOs: 447, 448, 449, 567, 568, and 569, respectively,
b. SEQ ID NOs: 444, 445, 446, 564, 565, and 566, respectively,
c. SEQ ID NOs: 354, 355, 356, 477, 478, and 479, respectively,
d. SEQ ID NOs: 378, 379, 380, 501, 502, and 503, respectively,
e. SEQ ID NOs: 411, 412, 413, 513, 532, and 533, respectively,
f. SEQ ID NOs: 348, 349, 350, 471, 472, and 473, respectively.
g. SEQ ID NOs: 360, 361, 362, 483, 484, and 485, respectively.
h. SEQ ID NOs: 363, 364, 365, 486, 487, and 488, respectively,
i. SEQ ID NOs: 366, 376, 368, 489, 490, and 491, respectively,
j. SEQ ID NOs: 369, 370, 371, 492, 493, and 494, respectively.
k. SEQ ID NOs: 387, 388, 389, 492, 493, and 494, respectively.
l. SEQ ID NOs: 402, 403, 404, 522, 523, and 524, respectively,
m. SEQ ID NOs: 408, 409, 410, 528, 259, and 530, respectively,
n. SEQ ID NOs: 423, 424, 425, 543, 544, and 545, respectively, or o. SEQ ID NOs: 426, 427, 428, 546, 547, and 548, respectively,
The anti-CD3 antibody or antigen-binding fragment thereof comprises heavy chain complementarity determining regions 1 (HCDR1), HCDR2, HCDR3, light chain complementarity determining regions 1 (LCDR1), LCDR2, and LCDR3 having the following polypeptide sequences. , Bispecific antibodies:
1) SEQ ID NOs: 342, 343, 344, 465, 466, and 467, respectively, or 2) SEQ ID NOs: 345, 346, 347, 468, 469, and 470, respectively.
ａ．配列番号２９２のポリペプチド配列を有する重鎖可変領域、及び配列番号３３２のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｂ．配列番号２９１のポリペプチド配列を有する重鎖可変領域、及び配列番号３３１のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｃ．配列番号２６１のポリペプチド配列を有する重鎖可変領域、及び配列番号３０２のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｄ．配列番号２６９のポリペプチド配列を有する重鎖可変領域、及び配列番号３１０のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｅ．配列番号２８０のポリペプチド配列を有する重鎖可変領域、及び配列番号３２２のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｆ．配列番号２５９のポリペプチド配列を有する重鎖可変領域、及び配列番号３００のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｇ．配列番号２６３のポリペプチド配列を有する重鎖可変領域、及び配列番号３０４のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｈ．配列番号２６４のポリペプチド配列を有する重鎖可変領域、及び配列番号３０５のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｉ．配列番号２６５のポリペプチド配列を有する重鎖可変領域、及び配列番号３０６のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｊ．配列番号２６６のポリペプチド配列を有する重鎖可変領域、及び配列番号３０７のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｋ．配列番号２７２のポリペプチド配列を有する重鎖可変領域、及び配列番号３０７のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｌ．配列番号２７７のポリペプチド配列を有する重鎖可変領域、及び配列番号３１７のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｍ．配列番号２７９のポリペプチド配列を有する重鎖可変領域、及び配列番号３１９のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｎ．配列番号２８４のポリペプチド配列を有する重鎖可変領域、及び配列番号３２４のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｏ．配列番号２８５のポリペプチド配列を有する重鎖可変領域、及び配列番号３２５のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５７のポリペプチド配列を有する重鎖可変領域、及び配列番号２９８のポリペプチド配列を有する軽鎖可変領域、
ｐ．配列番号２９２のポリペプチド配列を有する重鎖可変領域、及び配列番号３３２のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｑ．配列番号２９１のポリペプチド配列を有する重鎖可変領域、及び配列番号３３１のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｒ．配列番号２６１のポリペプチド配列を有する重鎖可変領域、及び配列番号３０２のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｓ．配列番号２６９のポリペプチド配列を有する重鎖可変領域、及び配列番号３１０のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｔ．配列番号２８０のポリペプチド配列を有する重鎖可変領域、及び配列番号３２２のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｕ．配列番号２５９のポリペプチド配列を有する重鎖可変領域、及び配列番号３００のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｖ．配列番号２６３のポリペプチド配列を有する重鎖可変領域、及び配列番号３０４のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｗ．配列番号２６４のポリペプチド配列を有する重鎖可変領域、及び配列番号３０５のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｘ．配列番号２６５のポリペプチド配列を有する重鎖可変領域、及び配列番号３０６のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｙ．配列番号２６６のポリペプチド配列を有する重鎖可変領域、及び配列番号３０７のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｚ．配列番号２７２のポリペプチド配列を有する重鎖可変領域、及び配列番号３０７のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ａａ．配列番号２７７のポリペプチド配列を有する重鎖可変領域、及び配列番号３１７のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｂｂ．配列番号２７９のポリペプチド配列を有する重鎖可変領域、及び配列番号３１９のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、
ｃｃ．配列番号２８４のポリペプチド配列を有する重鎖可変領域、及び配列番号３２４のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域、又は
ｄｄ．配列番号２８５のポリペプチド配列を有する重鎖可変領域、及び配列番号３２５のポリペプチド配列を有する軽鎖可変領域、及び配列番号２５８のポリペプチド配列を有する重鎖可変領域、及び配列番号２９９のポリペプチド配列を有する軽鎖可変領域。 The anti-CD33 / anti-CD3 bispecific antibody or antigen-binding fragment thereof according to claim 23 or 24 , comprising:
a. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 292, a light chain variable region having the polypeptide sequence of SEQ ID NO: 332, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
b. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 291 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 331, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
c. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 261 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 302, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
d. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 269, a light chain variable region having the polypeptide sequence of SEQ ID NO: 310, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
e. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 280, a light chain variable region having the polypeptide sequence of SEQ ID NO: 322, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
f. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 259, a light chain variable region having the polypeptide sequence of SEQ ID NO: 300, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
g. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 263, a light chain variable region having the polypeptide sequence of SEQ ID NO: 304, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
h. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 264, a light chain variable region having the polypeptide sequence of SEQ ID NO: 305, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
i. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 265, a light chain variable region having the polypeptide sequence of SEQ ID NO: 306, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
j. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 266, a light chain variable region having the polypeptide sequence of SEQ ID NO: 307, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
k. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 272, a light chain variable region having the polypeptide sequence of SEQ ID NO: 307, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
l. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 277, a light chain variable region having the polypeptide sequence of SEQ ID NO: 317, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
m. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 279, a light chain variable region having the polypeptide sequence of SEQ ID NO: 319, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
n. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 284, a light chain variable region having the polypeptide sequence of SEQ ID NO: 324, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
o. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 285, a light chain variable region having the polypeptide sequence of SEQ ID NO: 325, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 257, and a poly of SEQ ID NO: 298. Light chain variable region with peptide sequence,
p. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 292, a light chain variable region having the polypeptide sequence of SEQ ID NO: 332, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
q. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 291 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 331, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
r. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 261 and a light chain variable region having the polypeptide sequence of SEQ ID NO: 302, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
s. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 269, a light chain variable region having the polypeptide sequence of SEQ ID NO: 310, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
t. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 280, a light chain variable region having the polypeptide sequence of SEQ ID NO: 322, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
u. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 259, a light chain variable region having the polypeptide sequence of SEQ ID NO: 300, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
v. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 263, a light chain variable region having the polypeptide sequence of SEQ ID NO: 304, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
w. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 264, a light chain variable region having the polypeptide sequence of SEQ ID NO: 305, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
x. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 265, a light chain variable region having the polypeptide sequence of SEQ ID NO: 306, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
y. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 266, a light chain variable region having the polypeptide sequence of SEQ ID NO: 307, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
z. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 272, a light chain variable region having the polypeptide sequence of SEQ ID NO: 307, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
aa. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 277, a light chain variable region having the polypeptide sequence of SEQ ID NO: 317, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
bb. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 279, a light chain variable region having the polypeptide sequence of SEQ ID NO: 319, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. Light chain variable region with peptide sequence,
cc. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 284, a light chain variable region having the polypeptide sequence of SEQ ID NO: 324, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. A light chain variable region having a peptide sequence, or dd. A heavy chain variable region having the polypeptide sequence of SEQ ID NO: 285, a light chain variable region having the polypeptide sequence of SEQ ID NO: 325, a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 258, and a poly of SEQ ID NO: 299. A light chain variable region with a peptide sequence.
それを必要としている対象における癌を治療する方法で用いるためのものであり、
前記方法は、前記医薬組成物を前記対象に投与することを含む、医薬組成物。 33. The pharmaceutical composition according to claim 33.
It is intended for use in methods of treating cancer in subjects in need of it.
The method comprises administering the pharmaceutical composition to the subject.
A method for producing a pharmaceutical composition comprising the anti-CD33 / anti-CD3 bispecific antibody according to any one of claims 23 to 29 or an antigen-binding fragment thereof, wherein the anti-CD33 / anti-CD3 double. A method comprising combining a specific antibody or antigen binding fragment thereof with a pharmaceutically acceptable carrier to obtain a pharmaceutical composition.
Applications Claiming Priority (5)
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| US201862676123P | 2018-05-24 | 2018-05-24 | |
| US62/676,123 | 2018-05-24 | ||
| US201962825846P | 2019-03-29 | 2019-03-29 | |
| US62/825,846 | 2019-03-29 | ||
| PCT/IB2019/054182 WO2019224711A2 (en) | 2018-05-24 | 2019-05-21 | Anti-cd33 antibodies, anti-cd33/anti-cd3 bispecific antibodies and uses thereof |
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| JP2021524244A JP2021524244A (en) | 2021-09-13 |
| JPWO2019224711A5 true JPWO2019224711A5 (en) | 2022-05-25 |
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| JP2020564908A Pending JP2021524244A (en) | 2018-05-24 | 2019-05-21 | Anti-CD33 antibody, anti-CD33 / anti-CD3 bispecific antibody, and its use |
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Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108289949B (en) | 2015-05-29 | 2022-04-12 | 安普希韦纳治疗公司 | Methods of use of bispecific CD33 and CD3 binding proteins |
| MX2020012587A (en) | 2018-05-24 | 2021-04-28 | Janssen Biotech Inc | Anti-cd3 antibodies and uses thereof. |
| DE102018127845A1 (en) | 2018-11-07 | 2020-05-07 | Grimme Landmaschinenfabrik Gmbh & Co. Kg | Process for regulating the operation of a machine for harvesting root crops |
| JP2022523188A (en) * | 2019-02-22 | 2022-04-21 | メモリアル スローン ケタリング キャンサー センター | CD33 antibody and how to treat cancer with it |
| IL293670A (en) * | 2019-12-09 | 2022-08-01 | Twist Bioscience Corp | Variant nucleic acid libraries for adenosine receptors |
| BR112022018176A2 (en) * | 2020-03-13 | 2022-12-06 | Janssen Biotech Inc | MATERIALS AND METHODS FOR CONNECTION OF SIGLEC-3/CD33 |
| US20210284731A1 (en) * | 2020-03-13 | 2021-09-16 | Janssen Biotech, Inc. | Methods and materials for modulating an immune response |
| US20230190810A1 (en) * | 2020-03-31 | 2023-06-22 | Fred Hutchinson Cancer Center | Anti-cd33 antibodies and uses thereof |
| US11919944B2 (en) | 2020-05-11 | 2024-03-05 | Augmenta Biosciences, Inc. | Antibodies for SARS-CoV-2 and uses thereof |
| JP2023542257A (en) | 2020-09-16 | 2023-10-05 | アムジェン インコーポレイテッド | Method of administering therapeutic doses of bispecific T cell inducing molecules for the treatment of cancer |
| WO2022159620A1 (en) * | 2021-01-21 | 2022-07-28 | Twist Bioscience Corporation | Methods and compositions relating to adenosine receptors |
| EP4294528A2 (en) | 2021-02-16 | 2023-12-27 | JANSSEN Pharmaceutica NV | Trispecific antibody targeting bcma, gprc5d, and cd3 |
| IL306108A (en) | 2021-03-24 | 2023-11-01 | Janssen Biotech Inc | TRISPECIFIC ANTIBODY TARGETING CD79b, CD20, AND CD3 |
| WO2022228471A1 (en) * | 2021-04-27 | 2022-11-03 | 上海驯鹿生物技术有限公司 | Gene-edited hematopoietic stem cell and combined use thereof with car-t cell |
| CN117715935A (en) * | 2021-07-30 | 2024-03-15 | 南京传奇生物科技有限公司 | anti-CD33 antibodies and uses thereof |
| CA3228414A1 (en) * | 2021-09-02 | 2023-03-09 | Anthony DANIYAN | Anti-cd33 antibodies and uses thereof |
| AU2022344595A1 (en) * | 2021-09-13 | 2024-05-02 | Janssen Biotech, Inc | CD33 X Vδ2 MULTISPECIFIC ANTIBODIES FOR THE TREATMENT OF CANCER |
| WO2023081898A1 (en) * | 2021-11-08 | 2023-05-11 | Alector Llc | Soluble cd33 as a biomarker for anti-cd33 efficacy |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020142000A1 (en) | 1999-01-15 | 2002-10-03 | Digan Mary Ellen | Anti-CD3 immunotoxins and therapeutic uses therefor |
| US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
| HUE026914T2 (en) | 2002-11-07 | 2016-08-29 | Immunogen Inc | Anti-cd33 antibodies and method for treatment of acute myeloid leukemia using the same |
| CA2577082A1 (en) | 2004-09-02 | 2006-03-16 | Genentech, Inc. | Heteromultimeric molecules |
| DK3050963T3 (en) | 2005-03-31 | 2019-12-09 | Chugai Pharmaceutical Co Ltd | Process for producing polypeptide by arrangement control |
| DE102005028778A1 (en) | 2005-06-22 | 2006-12-28 | SUNJÜT Deutschland GmbH | Multi-layer foil, useful for lining a flexible container, comprises a barrier layer, a stretch-poor plastic layer, an antistatic plastic layer and a layer containing a safe material for food |
| ES2856451T3 (en) | 2005-10-11 | 2021-09-27 | Amgen Res Munich Gmbh | Compositions comprising specific antibodies for different species, and uses thereof |
| JP2009541275A (en) | 2006-06-22 | 2009-11-26 | ノボ・ノルデイスク・エー／エス | Production of bispecific antibodies |
| EP3461842A1 (en) | 2007-04-03 | 2019-04-03 | Amgen Research (Munich) GmbH | Cross-species-specific binding domain |
| TR201816277T4 (en) | 2007-04-03 | 2018-11-21 | Amgen Res Munich Gmbh | Cross-species-specific binding domain. |
| CA2682626A1 (en) | 2007-04-03 | 2008-10-09 | Micromet Ag | Cross-species-specific bispecific binders |
| AU2009299794B2 (en) | 2008-10-01 | 2015-08-13 | Amgen Research (Munich) Gmbh | Cross-species-specific single domain bispecific single chain antibody |
| RS54900B1 (en) | 2008-10-01 | 2016-10-31 | Amgen Res (Munich) Gmbh | Cross-species-specific psmaxcd3 bispecific single chain antibody |
| US9260522B2 (en) | 2008-10-01 | 2016-02-16 | Amgen Research (Munich) Gmbh | Bispecific single chain antibodies with specificity for high molecular weight target antigens |
| EP2424567B1 (en) | 2009-04-27 | 2018-11-21 | OncoMed Pharmaceuticals, Inc. | Method for making heteromultimeric molecules |
| SG10201800757TA (en) | 2010-04-20 | 2018-02-27 | Genmab As | Heterodimeric antibody fc-containing proteins and methods for production thereof |
| UA112062C2 (en) | 2010-10-04 | 2016-07-25 | Бьорінгер Інгельхайм Інтернаціональ Гмбх | CD33-Binding Agent |
| PL2635607T3 (en) | 2010-11-05 | 2020-05-18 | Zymeworks Inc. | Stable heterodimeric antibody design with mutations in the fc domain |
| CA2854233C (en) | 2011-11-04 | 2020-05-12 | Zymeworks Inc. | Stable heterodimeric antibody design with mutations in the fc domain |
| LT2931030T (en) | 2012-12-14 | 2020-11-10 | Open Monoclonal Technology, Inc. | Polynucleotides encoding rodent antibodies with human idiotypes and animals comprising same |
| AR097648A1 (en) | 2013-09-13 | 2016-04-06 | Amgen Inc | COMBINATION OF EPIGENETIC FACTORS AND BIESPECTIVE COMPOUNDS THAT HAVE LIKE DIANA CD33 AND CD3 IN THE TREATMENT OF MYELOID LEUKEMIA |
| WO2015089344A1 (en) | 2013-12-13 | 2015-06-18 | Genentech, Inc. | Anti-cd33 antibodies and immunoconjugates |
| US9212225B1 (en) | 2014-07-01 | 2015-12-15 | Amphivena Therapeutics, Inc. | Bispecific CD33 and CD3 binding proteins |
| SG11201701599UA (en) * | 2014-09-05 | 2017-03-30 | Janssen Pharmaceutica Nv | Cd123 binding agents and uses thereof |
| CN107922480B (en) * | 2015-06-12 | 2022-09-23 | 艾利妥 | anti-CD 33 antibodies and methods of use thereof |
| EP3307779A2 (en) * | 2015-06-12 | 2018-04-18 | Alector LLC | Anti-cd33 antibodies and methods of use thereof |
| MA47691A (en) | 2017-08-03 | 2020-01-08 | Alector Llc | ANTI-CD33 ANTIBODIES AND PROCESSES FOR USE |
| EA202091976A1 (en) | 2018-02-20 | 2021-07-06 | Драгонфлай Терапьютикс, Инк. | VARIABLE ANTIBODY DOMAINS TARGETING CD33 AND THEIR APPLICATION |
| MX2020012587A (en) * | 2018-05-24 | 2021-04-28 | Janssen Biotech Inc | Anti-cd3 antibodies and uses thereof. |
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