JPWO2022097061A5 - - Google Patents
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- JPWO2022097061A5 JPWO2022097061A5 JP2023526881A JP2023526881A JPWO2022097061A5 JP WO2022097061 A5 JPWO2022097061 A5 JP WO2022097061A5 JP 2023526881 A JP2023526881 A JP 2023526881A JP 2023526881 A JP2023526881 A JP 2023526881A JP WO2022097061 A5 JPWO2022097061 A5 JP WO2022097061A5
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- 108010046304 B-Cell Activation Factor Receptor Proteins 0.000 claims description 17
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Description
１０．参照による援用
本出願に引用される全ての刊行物、特許、特許出願及び他の文献は、各個別の刊行物、特許、特許出願又は他の文献があらゆる目的から参照により援用されることが個別に指示されたものと見なすのと同程度に、本明細書によってあらゆる目的から全体として参照により援用される。本明細書に援用される参考文献の１つ以上の教示と本開示との間に何らかの矛盾があった場合、本明細書の教示が意図される。
以下に、本願の当初の特許請求の範囲に記載された発明を付記する。
［１］ （ａ）抗ＣＤ１９剤；及び
（ｂ）Ｂ細胞標的化剤
を含む組み合わせ。
［２］ 前記抗ＣＤ１９剤は、ＣＤ１９結合分子である、［１］に記載の組み合わせ。
［３］ 前記ＣＤ１９結合分子は、
（ａ）配列番号１、配列番号２及び配列番号３のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号１４、配列番号１５及び配列番号１６のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３；
（ｂ）配列番号４、配列番号５及び配列番号６のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号１７、配列番号１８及び配列番号１９のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３；
（ｃ）配列番号７、配列番号８及び配列番号９のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号２０、配列番号２１及び配列番号２２のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３；又は
（ｄ）配列番号１０、配列番号１１及び配列番号１２のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号２３、配列番号２４及び配列番号２５のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３
を含む、［２］に記載の組み合わせ。
［４］ 前記ＣＤ１９結合分子は、配列番号１３のアミノ酸配列を有するＶＨ及び／又は配列番号２６のアミノ酸配列を有するＶＬを含む、［３］に記載の組み合わせ。
［５］ 前記ＣＤ１９結合分子は、
（ａ）配列番号２７、配列番号２８及び配列番号２９のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号４０、配列番号４１及び配列番号４２のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３；
（ｂ）配列番号３０、配列番号３１及び配列番号３２のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号４３、配列番号４４及び配列番号４５のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３；
（ｃ）配列番号３３、配列番号３４及び配列番号３５のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号４６、配列番号４７及び配列番号４８のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３；又は
（ｄ）配列番号３６、配列番号３７及び配列番号３８のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号４９、配列番号５０及び配列番号５１のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３
を含む、［２］に記載の組み合わせ。
［６］ 前記ＣＤ１９結合分子は、配列番号３９のアミノ酸配列を有するＶＨ及び／又は配列番号５２のアミノ酸配列を有するＶＬを含む、［５］に記載の組み合わせ。
［７］ 前記ＣＤ１９結合分子は、抗体、抗体フラグメント、ｓｃＦｖ、ｄｓＦｖ、Ｆｖ、Ｆａｂ、ｓｃＦａｂ、（Ｆａｂ’）２又は単一ドメイン抗体（ＳＤＡＢ）を含む、［２］～［６］のいずれかに記載の組み合わせ。
［８］ 前記ＣＤ１９結合分子は、抗体又はその抗原結合ドメインを含む、［７］に記載の組み合わせ。
［９］ 前記ＣＤ１９結合分子は、単一特異性結合分子である、［２］～［８］のいずれかに記載の組み合わせ。
［１０］ 前記ＣＤ１９結合分子は、多重特異性結合分子（ＭＢＭ）である、［２］～［８］のいずれかに記載の組み合わせ。
［１１］ 前記ＣＤ１９結合分子は、
（ａ）ＣＤ１９に特異的に結合する抗原結合モジュール１（ＡＢＭ１）；及び
（ｂ）異なる標的分子に特異的に結合する抗原結合モジュール２（ＡＢＭ２）
を含む、［１０］に記載の組み合わせ。
［１２］ ＡＢＭ２は、ヒトＴ細胞受容体（ＴＣＲ）複合体の構成要素に特異的に結合する、［１１］に記載の組み合わせ。
［１３］ 前記ＴＣＲ複合体の前記構成要素は、ＣＤ３である、［１２］に記載の組み合わせ。
［１４］ ＡＢＭ２は、ＣＤ３ｈｉのＣＤＲ配列を含む、［１３］に記載の組み合わせ。
［１５］ ＡＢＭ２は、表９Ａに記載されるＣＤ３ｈｉの重鎖及び軽鎖可変配列を含む、［１３］に記載の組み合わせ。
［１６］ 前記ＣＤ１９結合分子は、二重特異性結合分子（ＢＢＭ）である、［１０］～［１５］のいずれかに記載の組み合わせ。
［１７］ 前記ＣＤ１９結合分子は、ＣＤ１９以外の標的分子に特異的に結合する抗原結合モジュール３（ＡＢＭ３）を含む三重特異性結合分子（ＴＢＭ）である、［１１］～［１５］のいずれかに記載の組み合わせ。
［１８］ ＡＢＭ２は、ヒトＴ細胞受容体（ＴＣＲ）複合体の構成要素に特異的に結合し、及びＡＢＭ３は、（ｉ）ヒトＣＤ２、又は（ｉｉ）腫瘍関連抗原（ＴＡＡ）に特異的に結合する、［１７］に記載の組み合わせ。
［１９］ 三価である、［１７］又は［１８］に記載の組み合わせ。
［２０］ ＡＢＭ３は、ヒトＣＤ２に特異的に結合する、［１７］～［１９］のいずれかに記載の組み合わせ。
［２１］ ＡＢＭ３は、ＣＤ５８部分である、［２０］に記載の組み合わせ。
［２２］ 前記ＣＤ５８部分は、表１２に記載されるＣＤ５８－６のアミノ酸配列を含む、［２１］に記載の組み合わせ。
［２３］ 前記ＣＤ１９結合分子は、Ｆｃヘテロ二量体を一緒に形成する第１の変異体Ｆｃ領域及び第２の変異体Ｆｃ領域を含む、［１０］～［２２］のいずれかに記載の組み合わせ。
［２４］ 前記ＣＤ１９結合分子は、
（ａ）ＣＤ１９に特異的に結合し、且つ配列番号４、配列番号５及び配列番号６のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号１７、配列番号１８及び配列番号１９のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３を含む抗原結合モジュール１（ＡＢＭ１）；
（ｂ）ヒトＴ細胞受容体（ＴＣＲ）複合体の構成要素に特異的に結合する抗原結合モジュール２（ＡＢＭ２）；及び
（ｃ）ヒトＣＤ２に特異的に結合する抗原結合モジュール３（ＡＢＭ３）
を含む三重特異性結合分子（ＴＢＭ）である、［２］に記載の組み合わせ。
［２５］ 前記ＣＤ１９結合分子は、三価である、［２４］に記載の組み合わせ。
［２６］ ＡＢＭ１は、Ｆａｂである、［２４］又は［２５］に記載の組み合わせ。
［２７］ ＡＢＭ１は、配列番号１３のアミノ酸配列を有するＶＨ及び配列番号２６のアミノ酸配列を有するＶＬを含む、［２４］～［２６］のいずれかに記載の組み合わせ。
［２８］ 前記ＴＣＲ複合体の前記構成要素は、ＣＤ３である、［２４］～［２７］のいずれかに記載の組み合わせ。
［２９］ ＡＢＭ２は、抗ＣＤ３抗体又はその抗原結合ドメインである、［２８］に記載の組み合わせ。
［３０］ ＡＢＭ２は、ＣＤ３ｈｉのＣＤＲ配列を含む、［２９］に記載の組み合わせ。
［３１］ ＡＢＭ２は、表９Ａに記載されるＣＤ３ｈｉの重鎖及び軽鎖可変配列を含む、［２９］又は［３０］に記載の組み合わせ。
［３２］ 前記抗ＣＤ３抗体又はその抗原結合ドメインは、ｓｃＦｖの形態である、［２９］～［３１］のいずれかに記載の組み合わせ。
［３３］ ＡＢＭ２は、表９ＡにおいてＣＤ３ｈｉとして指定されるｓｃＦｖのアミノ酸配列を含む、［３２］に記載の組み合わせ。
［３４］ ＡＢＭ３は、ＣＤ５８部分である、［２４］～［３３］のいずれかに記載の組み合わせ。
［３５］ ＡＢＭ３は、表１２に記載されるＣＤ５８－６のアミノ酸配列を含む、［２４］～［３４］のいずれかに記載の組み合わせ。
［３６］ Ｆｃドメインを含む、［２４］～［３５］のいずれかに記載の組み合わせ。
［３７］ Ｆｃヘテロ二量体を一緒に形成する第１の変異体Ｆｃ領域及び第２の変異体Ｆｃ領域を含む、［２４］～［３５］のいずれかに記載の組み合わせ。
［３８］ 前記第１の変異体Ｆｃ領域は、変異体ヒトＩｇＧ１ Ｆｃ領域であり、及び前記第２の変異体Ｆｃ領域は、変異体ヒトＩｇＧ１ Ｆｃ領域であり、前記第１及び第２の変異体Ｆｃ領域は、Ｌ２３４Ａ、Ｌ２３５Ａ及びＧ２３７Ａ（「ＬＡＬＡＧＡ」）置換、Ｌ２３４Ａ、Ｌ２３５Ａ、Ｓ２６７Ｋ及びＰ３２９Ａ（「ＬＡＬＡＳＫＰＡ」）置換、Ｄ２６５Ａ、Ｐ３２９Ａ及びＳ２６７Ｋ（「ＤＡＰＡＳＫ」）置換、Ｇ２３７Ａ、Ｄ２６５Ａ及びＰ３２９Ａ（「ＧＡＤＡＰＡ」）置換、Ｇ２３７Ａ、Ｄ２６５Ａ、Ｐ３２９Ａ及びＳ２６７Ｋ（「ＧＡＤＡＰＡＳＫ」）置換、Ｌ２３４Ａ、Ｌ２３５Ａ及びＰ３２９Ｇ（「ＬＡＬＡＰＧ」）置換又はＬ２３４Ａ、Ｌ２３５Ａ及びＰ３２９Ａ（「ＬＡＬＡＰＡ」）置換を含み、アミノ酸残基は、ＥＵ番号付け方式に従って番号付けされている、［３７］に記載の組み合わせ。
［３９］ 前記ＣＤ１９結合分子は、
（ａ）ＣＤ１９に特異的に結合し、且つ（ｉ）配列番号４、配列番号５及び配列番号６のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号１７、配列番号１８及び配列番号１９のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３；又は（ｉｉ）配列番号３０、配列番号３１及び配列番号３２のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号４３、配列番号４４及び配列番号４５のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３を含むＦａｂである抗原結合モジュール１（ＡＢＭ１）；
（ｂ）ＣＤ３に特異的に結合し、且つ表９ＡにおいてＣＤ３ｈｉとして指定されるｓｃＦｖのアミノ酸配列を含む抗原結合モジュール２（ＡＢＭ２）；
（ｃ）ヒトＣＤ２に特異的に結合し、且つ表１２に記載されるＣＤ５８－６のアミノ酸配列を含む抗原結合モジュール３（ＡＢＭ３）；及び
（ｄ）Ｆｃドメイン
を含む三重特異性結合分子（ＴＢＭ）である、［２］に記載の組み合わせ。
［４０］ 前記ＣＤ１９結合分子は、
（ａ）第１の半抗体重鎖であって、そのアミノ酸配列は、配列番号６３のアミノ酸配列及びＦｃ配列を含む、第１の半抗体重鎖；
（ｂ）第１の半抗体軽鎖であって、そのアミノ酸配列は、配列番号６４のアミノ酸配列を含む、第１の半抗体軽鎖；
（ｃ）第２の半抗体であって、そのアミノ酸配列は、配列番号６５のアミノ酸配列及びＦｃ配列を含む、第２の半抗体
を含む、［２］に記載の組み合わせ。
［４１］ 前記ＣＤ１９結合分子は、
（ａ）第１のポリペプチドであって、そのアミノ酸配列は、配列番号７４のアミノ酸配列を含む、第１のポリペプチド；
（ｂ）第２のポリペプチドであって、そのアミノ酸配列は、配列番号６４のアミノ酸配列を含む、第２のポリペプチド；及び
（ｃ）第３のポリペプチドであって、そのアミノ酸配列は、配列番号７５又は配列番号８６のアミノ酸配列を含む、第３のポリペプチド
を含む、［２］に記載の組み合わせ。
［４２］ 前記ＣＤ１９結合分子は、
（ａ）第１のポリペプチドであって、そのアミノ酸配列は、配列番号７６のアミノ酸配列を含む、第１のポリペプチド；
（ｂ）第２のポリペプチドであって、そのアミノ酸配列は、配列番号６４のアミノ酸配列を含む、第２のポリペプチド；及び
（ｃ）第３のポリペプチドであって、そのアミノ酸配列は、配列番号７５又は配列番号８６のアミノ酸配列を含む、第３のポリペプチド
を含む、［２］に記載の組み合わせ。
［４３］ 前記ＣＤ１９結合分子は、
（ａ）第１のポリペプチドであって、そのアミノ酸配列は、配列番号７４のアミノ酸配列を含む、第１のポリペプチド；
（ｂ）第２のポリペプチドであって、そのアミノ酸配列は、配列番号６４のアミノ酸配列を含む、第２のポリペプチド；及び
（ｃ）第３のポリペプチドであって、そのアミノ酸配列は、配列番号８６のアミノ酸配列を含む、第３のポリペプチド
を含む、［２］に記載の組み合わせ。
［４４］ 前記ＣＤ１９結合分子は、
（ａ）第１のポリペプチドであって、そのアミノ酸配列は、配列番号１１２０のアミノ酸配列を含む、第１のポリペプチド；
（ｂ）第２のポリペプチドであって、そのアミノ酸配列は、配列番号１１２２のアミノ酸配列を含む、第２のポリペプチド；及び
（ｃ）第３のポリペプチドであって、そのアミノ酸配列は、配列番号１１１０のアミノ酸配列を含む、第３のポリペプチド
を含む、［２］に記載の組み合わせ。
［４５］ 前記ＣＤ１９結合分子は、
（ａ）第１のポリペプチドであって、そのアミノ酸配列は、配列番号１１２７のアミノ酸配列を含む、第１のポリペプチド；
（ｂ）第２のポリペプチドであって、そのアミノ酸配列は、配列番号１１２９のアミノ酸配列を含む、第２のポリペプチド；及び
（ｃ）第３のポリペプチドであって、そのアミノ酸配列は、配列番号１１１０のアミノ酸配列を含む、第３のポリペプチド
を含む、［２］に記載の組み合わせ。
［４６］ 前記ＣＤ１９結合分子は、
（ａ）第１のポリペプチドであって、そのアミノ酸配列は、配列番号１１２４のアミノ酸配列を含む、第１のポリペプチド；
（ｂ）第２のポリペプチドであって、そのアミノ酸配列は、配列番号１１２６のアミノ酸配列を含む、第２のポリペプチド；及び
（ｃ）第３のポリペプチドであって、そのアミノ酸配列は、配列番号１１１０のアミノ酸配列を含む、第３のポリペプチド
を含む、［２］に記載の組み合わせ。
［４７］ 前記ＣＤ１９結合分子は、
（ａ）第１のポリペプチドであって、そのアミノ酸配列は、配列番号１１３４のアミノ酸配列を含む、第１のポリペプチド；
（ｂ）第２のポリペプチドであって、そのアミノ酸配列は、配列番号１１３５のアミノ酸配列を含む、第２のポリペプチド；及び
（ｃ）第３のポリペプチドであって、そのアミノ酸配列は、配列番号１１１０のアミノ酸配列を含む、第３のポリペプチド
を含む、［２］に記載の組み合わせ。
［４８］ 前記ＣＤ１９結合分子は、
（ａ）第１のポリペプチドであって、そのアミノ酸配列は、配列番号１１３６のアミノ酸配列を含む、第１のポリペプチド；
（ｂ）第２のポリペプチドであって、そのアミノ酸配列は、配列番号１１３７のアミノ酸配列を含む、第２のポリペプチド；及び
（ｃ）第３のポリペプチドであって、そのアミノ酸配列は、配列番号１１１０のアミノ酸配列を含む、第３のポリペプチド
を含む、［２］に記載の組み合わせ。
［４９］ 前記ＣＤ１９結合分子は、
（ａ）第１のポリペプチドであって、そのアミノ酸配列は、配列番号１１３８のアミノ酸配列を含む、第１のポリペプチド；
（ｂ）第２のポリペプチドであって、そのアミノ酸配列は、配列番号１１３９のアミノ酸配列を含む、第２のポリペプチド；及び
（ｃ）第３のポリペプチドであって、そのアミノ酸配列は、配列番号１１１０のアミノ酸配列を含む、第３のポリペプチド
を含む、［２］に記載の組み合わせ。
［５０］ 前記ＣＤ１９結合分子は、
（ａ）第１のポリペプチドであって、そのアミノ酸配列は、配列番号１１４０のアミノ酸配列を含む、第１のポリペプチド；
（ｂ）第２のポリペプチドであって、そのアミノ酸配列は、配列番号１１４１のアミノ酸配列を含む、第２のポリペプチド；及び
（ｃ）第３のポリペプチドであって、そのアミノ酸配列は、配列番号１１１０のアミノ酸配列を含む、第３のポリペプチド
を含む、［２］に記載の組み合わせ。
［５１］ 前記ＣＤ１９結合分子は、
（ａ）第１のポリペプチドであって、そのアミノ酸配列は、配列番号１１３１のアミノ酸配列を含む、第１のポリペプチド；
（ｂ）第２のポリペプチドであって、そのアミノ酸配列は、配列番号１１３２のアミノ酸配列を含む、第２のポリペプチド；及び
（ｃ）第３のポリペプチドであって、そのアミノ酸配列は、配列番号１１３３のアミノ酸配列を含む、第３のポリペプチド
を含む、［２］に記載の組み合わせ。
［５２］ 前記ＣＤ１９結合分子は、ブリナツモマブ、コルツキシマブラブタンシン、ＭＯＲ２０８、ＭＥＤＩ－５５１、デニンツズマブマホドチン、ＤＩ－Ｂ４、タプリツモマブパプトクス、ＸｍＡｂ５８７１、ＡＦＭ１１、ＭＤＸ－１３４２、ＡＦＭ１１、ロンカスツキシマブテシリン又はＧＢＲ４０１である、［２］に記載の組み合わせ。
［５３］ 前記抗ＣＤ１９剤は、ＣＤ１９に結合するキメラ抗原受容体（「ＣＡＲ」）分子を発現する細胞の集団（「ＣＡＲ組成物」）である、［１］に記載の組み合わせ。
［５４］ 前記ＣＡＲ組成物は、チサゲンレクロイセル、アキシカブタゲンシロロイセル、リソカブタゲンマラロイセル又はブレクスカブタゲンオートロイセルである、［５３］に記載の組み合わせ。
［５５］ 前記ＣＡＲ組成物は、チサゲンレクロイセルである、［５４］に記載の組み合わせ。
［５６］ 前記Ｂ細胞標的化剤は、Ｂ細胞枯渇剤である、［１］～［５５］のいずれかに記載の組み合わせ。
［５７］ 前記Ｂ細胞標的化剤は、ＢＡＦＦ受容体（ＢＡＦＦＲ）結合分子である、［１］～［５６］のいずれかに記載の組み合わせ。
［５８］ 前記ＢＡＦＦＲ結合分子は、抗体又はその抗原結合ドメインである、［５７］に記載の組み合わせ。
［５９］ 前記ＢＡＦＦＲ結合分子は、表１８に記載されるイアナルマブのアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２、ＣＤＲ－Ｈ３並びに表１８に記載されるイアナルマブのアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３を含む、［５７］又は［５８］に記載の組み合わせ。
［６０］ 前記ＢＡＦＦＲ結合分子は、重鎖可変領域（ＶＨ）及び軽鎖可変領域（ＶＬ）であって、表１８に記載されるイアナルマブのＶＨ及びＶＬ配列を有する重鎖可変領域（ＶＨ）及び軽鎖可変領域（ＶＬ）を含む、［５９］に記載の組み合わせ。
［６１］ 前記ＢＡＦＦＲ結合分子は、イアナルマブである、［６０］に記載の組み合わせ。
［６２］ 前記Ｂ細胞標的化剤は、ＣＤ２０結合分子である、［１］～［５６］のいずれかに記載の組み合わせ。
［６３］ 前記ＣＤ２０結合分子は、リツキシマブ、オファツムマブ、オクレリズマブ、ベルツズマブ又はオビヌツズマブである、［６２］に記載の組み合わせ。
［６４］ 前記Ｂ細胞標的化剤は、ＣＤ２２結合分子である、［１］～［５６］のいずれかに記載の組み合わせ。
［６５］ 前記ＣＤ２２結合分子は、エプラツズマブ、イノツズマブ又はイノツズマブオゾガマイシンである、［６４］に記載の組み合わせ。
［６６］ 前記Ｂ細胞標的化剤は、ＢＡＦＦ結合分子である、［１］～［５６］のいずれかに記載の組み合わせ。
［６７］ 前記ＢＡＦＦ結合分子は、ベリムマブ、チブリズマブ、ＢＲ３－Ｆｃ、ブリシビモド又はアタシセプトである、［６６］に記載の組み合わせ。
［６８］ １つ以上の追加の薬剤を更に含む、［１］～［６７］のいずれかに記載の組み合わせ。
［６９］ 前記１つ以上の追加の薬剤は、コルチコステロイドを含む、［６８］に記載の組み合わせ。
［７０］ 前記コルチコステロイドは、デキサメタゾンである、［６９］に記載の組み合わせ。
［７１］ 前記１つ以上の追加の薬剤は、免疫調節イミド薬（ＩＭｉＤ）を含む、［６８］～［７０］のいずれかに記載の組み合わせ。
［７２］ 前記免疫調節イミド薬（ＩＭｉＤ）は、レナリドミド、サリドマイド、ポマリドミド又はイベルドミドである、［７１］に記載の組み合わせ。
［７３］ 前記免疫調節イミド薬（ＩＭｉＤ）は、レナリドミドである、［７２］に記載の組み合わせ。
［７４］ 前記抗ＣＤ１９剤及びＢ細胞標的化剤は、別個の分子である、［１］～［７３］のいずれかに記載の組み合わせ。
［７５］ 前記抗ＣＤ１９剤及びＢ細胞標的化剤は、別個の医薬組成物中で製剤化される、［１］～［７４］のいずれかに記載の組み合わせ。
［７６］ Ｂ細胞悪性腫瘍を有する対象を治療する方法で使用するための、［１］～［７５］のいずれかに記載の組み合わせ。
［７７］ Ｂ細胞悪性腫瘍を有する対象を治療する方法であって、［１］～［７４］のいずれかに記載の組み合わせを前記対象に投与することを含む方法。
［７８］ 前記方法は、前記抗ＣＤ１９剤の前記対象への初回投与前に、前記Ｂ細胞標的化剤を前記対象に１回以上投与することを含む、［７６］に記載の使用のための組み合わせ又は［７７］に記載の方法。
［７９］ 前記方法は、前記抗ＣＤ１９剤の前記対象への初回投与前に、前記Ｂ細胞標的化剤を前記対象に単回投与することを含む、［７６］～［７８］のいずれかに記載の使用のための組み合わせ又は方法。
［８０］ 前記方法は、前記抗ＣＤ１９剤の前記対象への初回投与前に、前記Ｂ細胞標的化剤を前記対象に２回以上投与することを含む、［７６］～［７８］のいずれかに記載の使用のための組み合わせ又は方法。
［８１］ 前記方法は、前記Ｂ細胞標的化剤及び前記抗ＣＤ１９剤を前記対象に同時に投与することを含む、［７６］に記載の使用のための組み合わせ又は［７７］に記載の方法。
［８２］ 前記Ｂ細胞悪性腫瘍は、細胞表面ＣＤ１９を発現するＢ細胞悪性腫瘍である、［７６］～［８１］のいずれかに記載の使用のための組み合わせ又は方法。
［８３］ 前記疾患又は障害は、非ホジキンリンパ腫である、［７６］～［８１］のいずれかに記載の使用のための組み合わせ又は方法。
［８４］ 前記疾患又は障害は、びまん性大細胞型Ｂ細胞リンパ腫（ＤＬＢＣＬ）である、［７６］～［８１］のいずれかに記載の使用のための組み合わせ又は方法。
［８５］ 前記疾患又は障害は、再発性及び／又は難治性ＤＬＢＣＬである、［７６］～［８１］のいずれかに記載の使用のための組み合わせ又は方法。
［８６］ 前記疾患又は障害は、急性リンパ芽球性白血病（ＡＬＬ）である、［７６］～［８１］のいずれかに記載の使用のための組み合わせ又は方法。
［８７］ 前記疾患又は障害は、マントル細胞リンパ腫（ＭＣＬ）である、［７６］～［８１］のいずれかに記載の使用のための組み合わせ又は方法。
［８８］ 前記疾患又は障害は、バーキットリンパ腫である、［７６］～［８１］のいずれかに記載の使用のための組み合わせ又は方法。
［８９］ 前記対象は、少なくとも１回の以前の標準治療に失敗している、［８２］～［８８］のいずれかに記載の使用のための組み合わせ又は方法。
［９０］ 前記対象は、最大で５回の以前の標準治療に失敗している、［８９］に記載の使用のための組み合わせ又は方法。
［９１］ 前記対象は、１回の以前の標準治療に失敗している、［８９］又は［９０］に記載の使用のための組み合わせ又は方法。
［９２］ 前記対象は、２回の以前の標準治療に失敗している、［８９］又は［９０］に記載の使用のための組み合わせ又は方法。
［９３］ 前記対象は、３回の以前の標準治療に失敗している、［８９］又は［９０］に記載の使用のための組み合わせ又は方法。
［９４］ 前記対象は、４回の以前の標準治療に失敗している、［８９］又は［９０］に記載の使用のための組み合わせ又は方法。
［９５］ 前記対象は、５回の以前の標準治療に失敗している、［８９］又は［９０］に記載の使用のための組み合わせ又は方法。
［９６］ 前記少なくとも１回の以前の標準治療は、抗ＣＤ２０療法を含む．［８９］～［９５］のいずれかに記載の使用のための組み合わせ又は方法。
［９７］ 前記抗ＣＤ２０療法は、リツキシマブである、［９６］に記載の使用のための組み合わせ又は方法。
［９８］ 前記対象は、１つ以上の他の承認された療法に対して不耐性又は不適格である、［８９］～［９７］のいずれかに記載の使用のための組み合わせ又は方法。
［９９］ 前記１つ以上の他の承認された療法は、自家幹細胞移植（ＡＳＣＴ）を含む、［９８］に記載の使用のための組み合わせ又は方法。
［１００］ 前記対象は、ＣＡＲ組成物に対して非応答者である、［８９］～［９９］のいずれかに記載の使用のための組み合わせ又は方法。
［１０１］ 前記ＣＡＲ組成物は、抗ＣＤ１９ ＣＡＲ組成物である、［１００］に記載の使用のための組み合わせ又は方法。
［１０２］ 前記ＣＡＲ組成物は、ＣＴＬ０１９、チサゲンレクロイセル、アキシカブタゲンシロロイセル、ブレクスカブタゲンオートロイセル又はリソカブタゲンマラロイセルを含む、［１００］又は［１０１］に記載の使用のための組み合わせ又は方法。
［１０３］ 前記抗ＣＤ１９剤は、キメラ抗原受容体を含まず、且つ／又はＣＡＲ組成物ではない、［１００］～［１０２］のいずれかに記載の使用のための組み合わせ又は方法。
［１０４］ 抗ＣＤ１９結合ドメイン、膜貫通ドメイン及び細胞内シグナル伝達ドメインを含む、ＣＤ１９に結合するキメラ抗原受容体（「ＣＡＲ」）分子であって、前記抗ＣＤ１９結合ドメインは、配列番号１、配列番号２及び配列番号３のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号１４、配列番号１５及び配列番号１６のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３を含む、キメラ抗原受容体（「ＣＡＲ」）分子。
［１０５］ 抗ＣＤ１９結合ドメイン、膜貫通ドメイン及び細胞内シグナル伝達ドメインを含む、ＣＤ１９に結合するキメラ抗原受容体（「ＣＡＲ」）分子であって、前記抗ＣＤ１９結合ドメインは、配列番号４、配列番号５及び配列番号６のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号１７、配列番号１８及び配列番号１９のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３を含む、キメラ抗原受容体（「ＣＡＲ」）分子。
［１０６］ 抗ＣＤ１９結合ドメイン、膜貫通ドメイン及び細胞内シグナル伝達ドメインを含む、ＣＤ１９に結合するキメラ抗原受容体（「ＣＡＲ」）分子であって、前記抗ＣＤ１９結合ドメインは、配列番号７、配列番号８及び配列番号９のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号２０、配列番号２１及び配列番号２２のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３を含む、キメラ抗原受容体（「ＣＡＲ」）分子。
［１０７］ 抗ＣＤ１９結合ドメイン、膜貫通ドメイン及び細胞内シグナル伝達ドメインを含む、ＣＤ１９に結合するキメラ抗原受容体（「ＣＡＲ」）分子であって、前記抗ＣＤ１９結合ドメインは、配列番号１０、配列番号１１及び配列番号１２のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号２３、配列番号２４及び配列番号２５のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３を含む、キメラ抗原受容体（「ＣＡＲ」）分子。
［１０８］ 前記抗ＣＤ１９結合ドメインは、配列番号１３のアミノ酸配列を有するＶＨ及び／又は配列番号２６のアミノ酸配列を有するＶＬを含む、［１０４］～［１０７］のいずれかに記載のＣＡＲ分子。
［１０９］ 抗ＣＤ１９結合ドメイン、膜貫通ドメイン及び細胞内シグナル伝達ドメインを含む、ＣＤ１９に結合するキメラ抗原受容体（「ＣＡＲ」）分子であって、前記抗ＣＤ１９結合ドメインは、配列番号２７、配列番号２８及び配列番号２９のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号４０、配列番号４１及び配列番号４２のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３を含む、キメラ抗原受容体（「ＣＡＲ」）分子。
［１１０］ 抗ＣＤ１９結合ドメイン、膜貫通ドメイン及び細胞内シグナル伝達ドメインを含む、ＣＤ１９に結合するキメラ抗原受容体（「ＣＡＲ」）分子であって、前記抗ＣＤ１９結合ドメインは、配列番号３０、配列番号３１及び配列番号３２のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号４３、配列番号４４及び配列番号４５のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３を含む、キメラ抗原受容体（「ＣＡＲ」）分子。
［１１１］ 抗ＣＤ１９結合ドメイン、膜貫通ドメイン及び細胞内シグナル伝達ドメインを含む、ＣＤ１９に結合するキメラ抗原受容体（「ＣＡＲ」）分子であって、前記抗ＣＤ１９結合ドメインは、配列番号３３、配列番号３４及び配列番号３５のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号４６、配列番号４７及び配列番号４８のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３を含む、キメラ抗原受容体（「ＣＡＲ」）分子。
［１１２］ 抗ＣＤ１９結合ドメイン、膜貫通ドメイン及び細胞内シグナル伝達ドメインを含む、ＣＤ１９に結合するキメラ抗原受容体（「ＣＡＲ」）分子であって、前記抗ＣＤ１９結合ドメインは、配列番号３６、配列番号３７及び配列番号３８のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びに配列番号４９、配列番号５０及び配列番号５１のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３を含む、キメラ抗原受容体（「ＣＡＲ」）分子。
［１１３］ 前記抗ＣＤ１９結合ドメインは、配列番号３９のアミノ酸配列を有するＶＨ及び／又は配列番号５２のアミノ酸配列を有するＶＬを含む、［１０９］～［１１２］のいずれかに記載のＣＡＲ分子。
［１１４］ 前記ＢＡＦＦＲ結合分子は、イアナルマブのＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２及びＣＤＲ－Ｈ３並びにイアナルマブのＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３を含む、［５７］又は［５８］に記載の組み合わせ。
［１１５］ 前記ＢＡＦＦＲ結合分子は、重鎖可変領域（ＶＨ）及び軽鎖可変領域（ＶＬ）であって、イアナルマブのＶＨ及びＶＬ配列を有する重鎖可変領域（ＶＨ）及び軽鎖可変領域（ＶＬ）を含む、［５７］又は［１１４］に記載の組み合わせ。
［１１６］ 前記ＢＡＦＦＲ結合分子は、イアナルマブである、［５７］又は［１１４］若しくは［１１５］のいずれかに記載の組み合わせ。
［１１７］ 前記ＢＡＦＦＲ結合分子は、それぞれ配列番号５３、配列番号５４、配列番号５５のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２、ＣＤＲ－Ｈ３並びにそれぞれ配列番号５６、配列番号５７、配列番号５８のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２及びＣＤＲ－Ｌ３を含む、［５７］に記載の組み合わせ。
［１１８］ 前記ＢＡＦＦＲ結合分子は、重鎖可変領域（ＶＨ）及び軽鎖可変領域（ＶＬ）であって、配列番号５９のＶＨ配列及び配列番号６０のＶＬ配列を有する重鎖可変領域（ＶＨ）及び軽鎖可変領域（ＶＬ）を含む、［５７］又は［１１７］に記載の組み合わせ。
［１１９］ 前記ＢＡＦＦＲ結合分子は、配列番号６１の重鎖配列及び配列番号６２の軽鎖配列を含む、［５７］又は［１１７］若しくは［１１８］のいずれかに記載の組み合わせ。
［１２０］ 前記方法は、前記抗ＣＤ１９剤を前記対象に投与する前に前記Ｂ細胞標的化剤を投与することを含む、［７６］に記載の使用のための組み合わせ又は［７７］に記載の方法。
10. INCORPORATION BY REFERENCE All publications, patents, patent applications, and other documents cited in this application are hereby incorporated by reference in their entirety for all purposes to the same extent as if each individual publication, patent, patent application, or other document was individually indicated to be incorporated by reference for all purposes. In the event of any conflict between the teachings of one or more of the references incorporated herein and this disclosure, the teachings of this specification are intended.
The invention as originally claimed in the present application is set forth below.
[1] (a) an anti-CD19 agent; and
(b) B cell targeting agent
Combinations including:
[2] The combination according to [1], wherein the anti-CD19 agent is a CD19 binding molecule.
[3] The CD19-binding molecule comprises:
(a) CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NO:14, SEQ ID NO:15, and SEQ ID NO:16;
(b) CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NO:17, SEQ ID NO:18, and SEQ ID NO:19;
(c) CDR-H1, CDR-H2 and CDR-H3 having the amino acid sequences of SEQ ID NO:7, SEQ ID NO:8 and SEQ ID NO:9, and CDR-L1, CDR-L2 and CDR-L3 having the amino acid sequences of SEQ ID NO:20, SEQ ID NO:21 and SEQ ID NO:22; or
(d) CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NOs: 10, 11, and 12, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NOs: 23, 24, and 25.
The combination according to [2],
[4] The combination according to [3], wherein the CD19 binding molecule comprises a VH having the amino acid sequence of SEQ ID NO: 13 and/or a VL having the amino acid sequence of SEQ ID NO: 26.
[5] The CD19-binding molecule comprises:
(a) CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NOs: 27, 28, and 29, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NOs: 40, 41, and 42;
(b) CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NOs: 30, 31, and 32, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NOs: 43, 44, and 45;
(c) CDR-H1, CDR-H2 and CDR-H3 having the amino acid sequences of SEQ ID NO: 33, SEQ ID NO: 34 and SEQ ID NO: 35, and CDR-L1, CDR-L2 and CDR-L3 having the amino acid sequences of SEQ ID NO: 46, SEQ ID NO: 47 and SEQ ID NO: 48; or
(d) CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NOs: 36, 37, and 38, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NOs: 49, 50, and 51.
The combination according to [2],
[6] The combination according to [5], wherein the CD19 binding molecule comprises a VH having the amino acid sequence of SEQ ID NO: 39 and/or a VL having the amino acid sequence of SEQ ID NO: 52.
[7] The combination according to any of [2] to [6], wherein the CD19 binding molecule comprises an antibody, an antibody fragment, scFv, dsFv, Fv, Fab, scFab, (Fab')2, or a single domain antibody (SDAB).
[8] The combination according to [7], wherein the CD19 binding molecule comprises an antibody or an antigen-binding domain thereof.
[9] The combination according to any of [2] to [8], wherein the CD19 binding molecule is a monospecific binding molecule.
[10] The combination according to any of [2] to [8], wherein the CD19 binding molecule is a multispecific binding molecule (MBM).
[11] The CD19-binding molecule comprises:
(a) an antigen binding module 1 (ABM1) that specifically binds to CD19; and
(b) an antigen binding module 2 (ABM2) that specifically binds to a different target molecule;
The combination according to [10],
[12] The combination according to [11], wherein ABM2 specifically binds to a component of the human T cell receptor (TCR) complex.
[13] The combination according to [12], wherein the component of the TCR complex is CD3.
[14] The combination according to [13], wherein ABM2 comprises a CDR sequence of CD3hi.
[15] The combination according to [13], wherein ABM2 comprises heavy and light chain variable sequences of CD3hi as set forth in Table 9A.
[16] The combination according to any of [10] to [15], wherein the CD19-binding molecule is a bispecific binding molecule (BBM).
[17] The combination according to any of [11] to [15], wherein the CD19-binding molecule is a trispecific binding molecule (TBM) comprising an antigen-binding module 3 (ABM3) that specifically binds to a target molecule other than CD19.
[18] The combination of [17], wherein ABM2 specifically binds to a component of the human T cell receptor (TCR) complex, and ABM3 specifically binds to (i) human CD2, or (ii) a tumor-associated antigen (TAA).
[19] The combination according to [17] or [18], which is trivalent.
[20] The combination according to any one of [17] to [19], wherein ABM3 specifically binds to human CD2.
[21] The combination according to [20], wherein ABM3 is a CD58 moiety.
[22] The combination according to [21], wherein the CD58 portion comprises an amino acid sequence of CD58-6 as set forth in Table 12.
[23] The combination of any of [10] to [22], wherein the CD19 binding molecule comprises a first variant Fc region and a second variant Fc region that together form an Fc heterodimer.
[24] The CD19-binding molecule comprises:
(a) an antigen-binding module 1 (ABM1) which specifically binds to CD19 and comprises CDR-H1, CDR-H2 and CDR-H3 having the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, and CDR-L1, CDR-L2 and CDR-L3 having the amino acid sequences of SEQ ID NO:17, SEQ ID NO:18 and SEQ ID NO:19;
(b) an antigen binding module 2 (ABM2) that specifically binds to a component of the human T cell receptor (TCR) complex; and
(c) antigen-binding module 3 (ABM3) that specifically binds to human CD2
The combination according to [2], wherein the trispecific binding molecule (TBM) comprises:
[25] The combination according to [24], wherein the CD19 binding molecule is trivalent.
[26] The combination according to [24] or [25], wherein ABM1 is Fab.
[27] The combination according to any one of [24] to [26], wherein ABM1 comprises a VH having the amino acid sequence of SEQ ID NO: 13 and a VL having the amino acid sequence of SEQ ID NO: 26.
[28] The combination according to any one of [24] to [27], wherein the component of the TCR complex is CD3.
[29] The combination according to [28], wherein ABM2 is an anti-CD3 antibody or an antigen-binding domain thereof.
[30] The combination according to [29], wherein ABM2 comprises a CDR sequence of CD3hi.
[31] The combination according to [29] or [30], wherein ABM2 comprises heavy and light chain variable sequences of CD3hi as set forth in Table 9A.
[32] The combination according to any of [29] to [31], wherein the anti-CD3 antibody or antigen-binding domain thereof is in the form of an scFv.
[33] The combination according to [32], wherein ABM2 comprises the amino acid sequence of an scFv designated as CD3hi in Table 9A.
[34] The combination according to any one of [24] to [33], wherein ABM3 is a CD58 moiety.
[35] The combination according to any one of [24] to [34], wherein ABM3 comprises an amino acid sequence of CD58-6 shown in Table 12.
[36] The combination according to any one of [24] to [35], which comprises an Fc domain.
[37] The combination of any one of [24] to [35], comprising a first mutant Fc region and a second mutant Fc region that together form an Fc heterodimer.
[38] The first variant Fc Region is a variant human IgGl Fc Region, and the second variant Fc Region is a variant human IgGl Fc Region, wherein the first and second variant Fc Regions comprise L234A, L235A, and G237A ("LALAGA") substitutions, L234A, L235A, S267K, and P329A ("LALASKPA") substitutions, D265A, P329A, and S267K ("DAPASK") substitutions, G237A, D265A, and P329A ("GADAPA") substitutions, or "), G237A, D265A, P329A and S267K ("GADAPASK") substitutions, L234A, L235A and P329G ("LALAPG") substitutions or L234A, L235A and P329A ("LALAPA") substitutions, wherein the amino acid residues are numbered according to the EU numbering system.
[39] The CD19-binding molecule comprises:
(a) an antigen binding module 1 (ABM1) which specifically binds to CD19 and is a Fab comprising: (i) CDR-H1, CDR-H2 and CDR-H3 having the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, and CDR-L1, CDR-L2 and CDR-L3 having the amino acid sequences of SEQ ID NO:17, SEQ ID NO:18 and SEQ ID NO:19; or (ii) CDR-H1, CDR-H2 and CDR-H3 having the amino acid sequences of SEQ ID NO:30, SEQ ID NO:31 and SEQ ID NO:32, and CDR-L1, CDR-L2 and CDR-L3 having the amino acid sequences of SEQ ID NO:43, SEQ ID NO:44 and SEQ ID NO:45;
(b) an antigen binding module 2 (ABM2) that specifically binds CD3 and comprises the amino acid sequence of an scFv designated as CD3hi in Table 9A;
(c) an antigen binding module 3 (ABM3) that specifically binds human CD2 and comprises the amino acid sequence of CD58-6 as set forth in Table 12; and
(d) an Fc domain
The combination according to [2], wherein the trispecific binding molecule (TBM) comprises:
[40] The CD19-binding molecule comprises:
(a) a first half antibody heavy chain, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:63 and an Fc sequence;
(b) a first half antibody light chain, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:64;
(c) a second half antibody, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:65 and an Fc sequence.
The combination according to [2],
[41] The CD19-binding molecule comprises:
(a) a first polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:74;
(b) a second polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:64; and
(c) a third polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:75 or SEQ ID NO:86.
The combination according to [2],
[42] The CD19-binding molecule comprises:
(a) a first polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:76;
(b) a second polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:64; and
(c) a third polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:75 or SEQ ID NO:86.
The combination according to [2],
[43] The CD19-binding molecule comprises:
(a) a first polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:74;
(b) a second polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:64; and
(c) a third polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:86.
The combination according to [2],
[44] The CD19-binding molecule comprises:
(a) a first polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1120;
(b) a second polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1122; and
(c) a third polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1110.
The combination according to [2],
[45] The CD19-binding molecule comprises:
(a) a first polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1127;
(b) a second polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1129; and
(c) a third polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1110.
The combination according to [2],
[46] The CD19-binding molecule comprises:
(a) a first polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1124;
(b) a second polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1126; and
(c) a third polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1110.
The combination according to [2],
[47] The CD19-binding molecule comprises:
(a) a first polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1134;
(b) a second polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1135; and
(c) a third polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1110.
The combination according to [2],
[48] The CD19-binding molecule comprises:
(a) a first polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1136;
(b) a second polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1137; and
(c) a third polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1110.
The combination according to [2],
[49] The CD19-binding molecule comprises:
(a) a first polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1138;
(b) a second polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1139; and
(c) a third polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1110.
The combination according to [2],
[50] The CD19-binding molecule comprises:
(a) a first polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1140;
(b) a second polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1141; and
(c) a third polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1110.
The combination according to [2],
[51] The CD19-binding molecule comprises:
(a) a first polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1131;
(b) a second polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1132; and
(c) a third polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1133.
The combination according to [2],
[52] The combination of [2], wherein the CD19 binding molecule is blinatumomab, cortuximab ravtansine, MOR208, MEDI-551, denintuzumab mafodotin, DI-B4, taplitumomab paptox, XmAb5871, AFM11, MDX-1342, AFM11, loncastuximab tesirine, or GBR401.
[53] The combination of [1], wherein the anti-CD19 agent is a population of cells expressing a chimeric antigen receptor ("CAR") molecule that binds to CD19 (the "CAR composition").
[54] The combination according to [53], wherein the CAR composition is tisagenlecleucel, axicabtagene ciloleucel, lysocabtagene malareucel, or brexcabtagene autoleucel.
[55] The combination of [54], wherein the CAR composition is tisagenlecleucel.
[56] The combination of any of [1] to [55], wherein the B cell targeting agent is a B cell depleting agent.
[57] The combination of any of [1] to [56], wherein the B cell targeting agent is a BAFF receptor (BAFFR) binding molecule.
[58] The combination according to [57], wherein the BAFFR-binding molecule is an antibody or an antigen-binding domain thereof.
[59] The combination of [57] or [58], wherein the BAFFR binding molecule comprises CDR-H1, CDR-H2, CDR-H3 having the amino acid sequence of ianalumab as set forth in Table 18, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequence of ianalumab as set forth in Table 18.
[60] The combination of [59], wherein the BAFFR binding molecule comprises a heavy chain variable region (VH) and a light chain variable region (VL) having the VH and VL sequences of ianalumab as set forth in Table 18.
[61] The combination according to [60], wherein the BAFFR binding molecule is ianalumab.
[62] The combination of any of [1] to [56], wherein the B cell targeting agent is a CD20 binding molecule.
[63] The combination according to [62], wherein the CD20 binding molecule is rituximab, ofatumumab, ocrelizumab, veltuzumab or obinutuzumab.
[64] The combination of any of [1] to [56], wherein the B cell targeting agent is a CD22 binding molecule.
[65] The combination according to [64], wherein the CD22 binding molecule is epratuzumab, inotuzumab, or inotuzumab ozogamicin.
[66] The combination of any of [1] to [56], wherein the B cell targeting agent is a BAFF-binding molecule.
[67] The combination according to [66], wherein the BAFF-binding molecule is belimumab, tibulizumab, BR3-Fc, blisibimod, or atacicept.
[68] The combination of any one of [1] to [67], further comprising one or more additional drugs.
[69] The combination of [68], wherein the one or more additional drugs comprises a corticosteroid.
[70] The combination of [69], wherein the corticosteroid is dexamethasone.
[71] The combination of any of [68] to [70], wherein the one or more additional agents comprises an immunomodulatory imid drug (IMiD).
[72] The combination of [71], wherein the immunomodulatory imid drug (IMiD) is lenalidomide, thalidomide, pomalidomide or iverdimide.
[73] The combination of [72], wherein the immunomodulatory imid drug (IMiD) is lenalidomide.
[74] The combination of any of [1] to [73], wherein the anti-CD19 agent and the B cell targeting agent are separate molecules.
[75] The combination of any of [1] to [74], wherein the anti-CD19 agent and the B cell targeting agent are formulated in separate pharmaceutical compositions.
[76] The combination according to any one of [1] to [75] for use in a method for treating a subject having a B cell malignancy.
[77] A method of treating a subject having a B-cell malignancy, comprising administering to the subject a combination according to any one of [1] to [74].
[78] The combination for use of [76] or the method of [77], wherein the method comprises administering the B cell targeting agent to the subject one or more times prior to a first administration of the anti-CD19 agent to the subject.
[79] The combination or method for use of any of [76] to [78], wherein the method comprises administering a single dose of the B cell targeting agent to the subject prior to a first administration of the anti-CD19 agent to the subject.
[80] The combination or method for use of any of [76] to [78], wherein the method comprises administering the B cell targeting agent to the subject two or more times prior to a first administration of the anti-CD19 agent to the subject.
[81] The combination for use of [76] or the method of [77], wherein the method comprises administering the B cell targeting agent and the anti-CD19 agent simultaneously to the subject.
[82] The combination or method for use according to any of [76] to [81], wherein the B cell malignancy is a B cell malignancy that expresses cell surface CD19.
[83] The combination or method for use according to any of [76] to [81], wherein the disease or disorder is non-Hodgkin's lymphoma.
[84] The combination or method for use according to any of [76] to [81], wherein the disease or disorder is diffuse large B-cell lymphoma (DLBCL).
[85] The combination or method for use according to any of [76] to [81], wherein the disease or disorder is relapsed and/or refractory DLBCL.
[86] The combination or method for use according to any of [76] to [81], wherein the disease or disorder is acute lymphoblastic leukemia (ALL).
[87] The combination or method for use according to any of [76] to [81], wherein the disease or disorder is mantle cell lymphoma (MCL).
[88] The combination or method for use according to any of [76] to [81], wherein the disease or disorder is Burkitt's lymphoma.
[89] The combination or method for use according to any of [82] to [88], wherein the subject has failed at least one previous standard of care treatment.
[90] The combination or method for use of [89], wherein the subject has failed up to five previous standard therapies.
[91] The combination or method for use of [89] or [90], wherein the subject has failed one previous standard of care.
[92] The combination or method for use of [89] or [90], wherein the subject has failed two previous standard therapies.
[93] The combination or method for use of [89] or [90], wherein the subject has failed three previous standard therapies.
[94] The combination or method for use of [89] or [90], wherein the subject has failed four previous standard therapies.
[95] The combination or method for use of [89] or [90], wherein the subject has failed five previous standard therapies.
[96] The combination or method for use according to any one of [89] to [95], wherein the at least one previous standard therapy comprises an anti-CD20 therapy.
[97] The combination or method for use of [96], wherein the anti-CD20 therapy is rituximab.
[98] The combination or method for use according to any of [89] to [97], wherein the subject is intolerant or ineligible for one or more other approved therapies.
[99] The combination or method for use of [98], wherein the one or more other approved therapies includes autologous stem cell transplantation (ASCT).
[100] The combination or method for use according to any of [89] to [99], wherein the subject is a non-responder to a CAR composition.
[101] The combination or method for use according to [100], wherein the CAR composition is an anti-CD19 CAR composition.
[102] The combination or method for use according to [100] or [101], wherein the CAR composition comprises CTL019, tisagenlecleucel, axicabtagene ciloleucel, brexcabtagene autoleucel, or lysocabtagene malareucel.
[103] The combination or method for use according to any of [100] to [102], wherein the anti-CD19 agent does not comprise a chimeric antigen receptor and/or is not a CAR composition.
[104] A chimeric antigen receptor ("CAR") molecule that binds to CD19, comprising an anti-CD19 binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the anti-CD19 binding domain comprises CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NO:14, SEQ ID NO:15, and SEQ ID NO:16.
[105] A chimeric antigen receptor ("CAR") molecule that binds to CD19, comprising an anti-CD19 binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the anti-CD19 binding domain comprises CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NOs:4, 5, and 6, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NOs:17, 18, and 19.
[106] A chimeric antigen receptor ("CAR") molecule that binds to CD19, comprising an anti-CD19 binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the anti-CD19 binding domain comprises CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NOs:7, 8, and 9, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NOs:20, 21, and 22.
[107] A chimeric antigen receptor ("CAR") molecule that binds to CD19, comprising an anti-CD19 binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the anti-CD19 binding domain comprises CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NO:23, SEQ ID NO:24, and SEQ ID NO:25.
[108] The CAR molecule according to any of [104] to [107], wherein the anti-CD19 binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 13 and/or a VL having the amino acid sequence of SEQ ID NO: 26.
[109] A chimeric antigen receptor ("CAR") molecule that binds to CD19, comprising an anti-CD19 binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the anti-CD19 binding domain comprises CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NOs:27, 28, and 29, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NOs:40, 41, and 42.
[110] A chimeric antigen receptor ("CAR") molecule that binds to CD19, comprising an anti-CD19 binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the anti-CD19 binding domain comprises CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NOs:30, 31, and 32, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NOs:43, 44, and 45.
[111] A chimeric antigen receptor ("CAR") molecule that binds to CD19, comprising an anti-CD19 binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the anti-CD19 binding domain comprises CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NOs:33, 34, and 35, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NOs:46, 47, and 48.
[112] A chimeric antigen receptor ("CAR") molecule that binds to CD19, comprising an anti-CD19 binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the anti-CD19 binding domain comprises CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NOs:36, 37, and 38, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NOs:49, 50, and 51.
[113] The CAR molecule according to any of [109] to [112], wherein the anti-CD19 binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 39 and/or a VL having the amino acid sequence of SEQ ID NO: 52.
[114] The combination of [57] or [58], wherein the BAFFR binding molecule comprises CDR-H1, CDR-H2, and CDR-H3 of ianalumab, and CDR-L1, CDR-L2, and CDR-L3 of ianalumab.
[115] The combination of [57] or [114], wherein the BAFFR binding molecule comprises a heavy chain variable region (VH) and a light chain variable region (VL) having the VH and VL sequences of ianalumab.
[116] The combination of any one of [57], [114], or [115], wherein the BAFFR binding molecule is ianalumab.
[117] The combination according to [57], wherein the BAFFR binding molecule comprises CDR-H1, CDR-H2, and CDR-H3 having the amino acid sequences of SEQ ID NO:53, SEQ ID NO:54, and SEQ ID NO:55, respectively, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NO:56, SEQ ID NO:57, and SEQ ID NO:58, respectively.
[118] The combination of [57] or [117], wherein the BAFFR binding molecule comprises a heavy chain variable region (VH) and a light chain variable region (VL), the heavy chain variable region (VH) having the VH sequence of SEQ ID NO:59 and the light chain variable region (VL) having the VL sequence of SEQ ID NO:60.
[119] The combination of any of [57], [117], or [118], wherein the BAFFR binding molecule comprises a heavy chain sequence of SEQ ID NO: 61 and a light chain sequence of SEQ ID NO: 62.
[120] The combination for use of [76] or the method of [77], wherein the method comprises administering the B cell targeting agent prior to administering the anti-CD19 agent to the subject.
Claims (20)
（ｂ）ＢＡＦＦ受容体結合分子と
を含む組合せ物であって、
前記ＣＤ１９結合分子は、
（i）ＣＤ１９に特異的に結合し、且つ（ｉ）配列番号１３のアミノ酸配列を有するＶＨおよび配列番号２６のアミノ酸配列を有するＶＬを含むＦａｂである抗原結合モジュール１（ＡＢＭ１）；
（ii）ＣＤ３に特異的に結合し、且つ配列番号１２８１のｓｃＦｖのアミノ酸配列を含む抗原結合モジュール２（ＡＢＭ２）；
（iii）ヒトＣＤ２に特異的に結合し、且つ配列番号１３１５のアミノ酸配列を含む抗原結合モジュール３（ＡＢＭ３）；及び
（iv）Ｆｃドメイン
を含む三重特異性結合分子（ＴＢＭ）であり、
前記ＢＡＦＦ受容体結合分子は、抗体又はその抗原結合ドメインであり、それぞれが配列番号５３、５４および５５のアミノ酸配列を有するＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２、ＣＤＲ－Ｈ３ならびにそれぞれが配列番号５６、５７および５８のアミノ酸配列を有するＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２およびＣＤＲ－Ｌ３のＣＤＲ配列を含む、
組合せ物。 (a) a CD19 binding molecule; and
(b) a BAFF receptor-binding molecule;
A combination comprising:
The CD19 binding molecule comprises:
(i) an antigen binding module 1 (ABM1) that specifically binds to CD19 and is a Fab comprising a VH having the amino acid sequence of SEQ ID NO: 13 and a VL having the amino acid sequence of SEQ ID NO: 26;
(ii) an antigen-binding module 2 (ABM2) that specifically binds to CD3 and comprises the amino acid sequence of the scFv of SEQ ID NO: 1281;
(iii) an antigen binding module 3 (ABM3) that specifically binds to human CD2 and comprises the amino acid sequence of SEQ ID NO: 1315; and
(iv) Fc domain
and a trispecific binding molecule (TBM) comprising:
The BAFF receptor binding molecule is an antibody or an antigen-binding domain thereof, and comprises CDR sequences of CDR-H1, CDR-H2, CDR-H3 having the amino acid sequences of SEQ ID NOs: 53, 54, and 55, respectively, and CDR-L1, CDR-L2, and CDR-L3 having the amino acid sequences of SEQ ID NOs: 56, 57, and 58, respectively;
Combination .
（ａ）修飾Ｔ３６６Ｗを含む第１のＣＨ３ドメイン；及び(a) a first CH3 domain comprising the modification T366W; and
（ｂ）第１のＣＨ３ドメインとヘテロ二量体を形成し、且つ修飾Ｔ３６６Ｓ、Ｌ３６８Ａ及びＹ４０７Ｖを含む第２のＣＨ３ドメイン(b) a second CH3 domain that forms a heterodimer with the first CH3 domain and includes the modifications T366S, L368A and Y407V.
を含むヒトＩｇＧ１ Ｆｃドメインである、請求項２に記載の組合せ物。The combination according to claim 2, wherein the Fc domain is a human IgG1 Fc domain comprising:
（ａ）修飾Ｓ３５４Ｃを含む第１のＣＨ３ドメイン；及び(a) a first CH3 domain comprising the modification S354C; and
（ｂ）修飾Ｙ３４９Ｃを含む第２のＣＨ３ドメイン(b) a second CH3 domain comprising the modification Y349C.
を含むヒトＩｇＧ１ Ｆｃドメインである、請求項２または３に記載の組合せ物。The combination according to claim 2 or 3, wherein the Fc domain is a human IgG1 Fc domain comprising:
前記第１の半抗体におけるＦｃ領域および前記第２の半抗体におけるＦｃ領域は、Ｆｃヘテロ二量体を形成している、the Fc region of the first half antibody and the Fc region of the second half antibody form an Fc heterodimer;
請求項２～４のいずれか一項に記載の組合せ物。A combination according to any one of claims 2 to 4.
（ａ）第１の半抗体重鎖であって、そのアミノ酸配列は、配列番号６３のアミノ酸配列及びＦｃ配列を含む、第１の半抗体重鎖；
（ｂ）第１の半抗体軽鎖であって、そのアミノ酸配列は、配列番号６４のアミノ酸配列を含む、第１の半抗体軽鎖；
（ｃ）第２の半抗体であって、そのアミノ酸配列は、配列番号６５のアミノ酸配列及びＦｃ配列を含む、第２の半抗体
を含む、請求項５に記載の組合せ物。 The CD19 binding molecule comprises:
(a) a first half antibody heavy chain, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:63 and an Fc sequence;
(b) a first half antibody light chain, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:64;
(c) a second half antibody, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 65 and an Fc sequence.
（ａ）第１のポリペプチドであって、そのアミノ酸配列は、配列番号７４のアミノ酸配列を含む、第１のポリペプチド；
（ｂ）第２のポリペプチドであって、そのアミノ酸配列は、配列番号６４のアミノ酸配列を含む、第２のポリペプチド；及び
（ｃ）第３のポリペプチドであって、そのアミノ酸配列は、配列番号７５又は配列番号８６のアミノ酸配列を含む、第３のポリペプチド
を含む、請求項５に記載の組合せ物。 The CD19 binding molecule comprises:
(a) a first polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:74;
The combination of claim 5, comprising: (b) a second polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 64 ; and (c) a third polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:75 or SEQ ID NO: 86 .
（ａ）第１のポリペプチドであって、そのアミノ酸配列は、配列番号１１２７のアミノ酸配列を含む、第１のポリペプチド；
（ｂ）第２のポリペプチドであって、そのアミノ酸配列は、配列番号１１２９のアミノ酸配列を含む、第２のポリペプチド；及び
（ｃ）第３のポリペプチドであって、そのアミノ酸配列は、配列番号１１１０のアミノ酸配列を含む、第３のポリペプチド
を含む、請求項５に記載の組合せ物。 The CD19 binding molecule comprises:
(a) a first polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO: 1127;
The combination of claim 5, comprising: (b) a second polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:1129; and (c) a third polypeptide, the amino acid sequence of which comprises the amino acid sequence of SEQ ID NO:1110.
15. The combination for use according to claim 14 , wherein the method comprises administering the B cell targeting agent prior to administering the anti-CD19 agent to the subject.
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| US202063110490P | 2020-11-06 | 2020-11-06 | |
| US202063110501P | 2020-11-06 | 2020-11-06 | |
| US63/110,501 | 2020-11-06 | ||
| US63/110,490 | 2020-11-06 | ||
| US202063114371P | 2020-11-16 | 2020-11-16 | |
| US202063114370P | 2020-11-16 | 2020-11-16 | |
| US63/114,370 | 2020-11-16 | ||
| US63/114,371 | 2020-11-16 | ||
| US202163147501P | 2021-02-09 | 2021-02-09 | |
| US202163147488P | 2021-02-09 | 2021-02-09 | |
| US63/147,501 | 2021-02-09 | ||
| US63/147,488 | 2021-02-09 | ||
| PCT/IB2021/060216 WO2022097061A1 (en) | 2020-11-06 | 2021-11-04 | Anti-cd19 agent and b cell targeting agent combination therapy for treating b cell malignancies |
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| EP4126241A1 (en) * | 2020-03-27 | 2023-02-08 | Novartis AG | Bispecific combination therapy for treating proliferative diseases and autoimmune disorders |
| EP4565620A1 (en) * | 2022-08-05 | 2025-06-11 | Shanghai Kaijin Biotechnology , Ltd | Multi-specific polypeptide complexes |
| CN120457212A (en) * | 2022-11-04 | 2025-08-08 | 优莫佳生物制药股份有限公司 | Lentiviral particles displaying fusion molecules and uses thereof |
| WO2025067496A1 (en) * | 2023-09-28 | 2025-04-03 | 南京驯鹿生物技术股份有限公司 | Fully-human antibody and car-t cell targeting baff-r and use thereof |
| KR20250117586A (en) * | 2024-01-26 | 2025-08-05 | 에스지메디칼 주식회사 | Combination therapy of bispecific antibody and car-t |
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