JP2019506403A - がんを処置するためのox40アゴニストおよび4−1bbアゴニストモノクローナル抗体の組み合わせ - Google Patents
がんを処置するためのox40アゴニストおよび4−1bbアゴニストモノクローナル抗体の組み合わせ Download PDFInfo
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Abstract
Description
本発明がより容易に理解され得るように、ある特定の技術用語および科学用語を以下に具体的に定義する。本文献のいずれかの箇所で具体的に定義されない限り、本明細書において使用される全ての他の技術用語および科学用語は、本発明が属する技術分野の当業者によって一般に理解される意味を有する。
本発明の一態様では、本発明は、OX40アゴニストおよび4−1BBアゴニストを含む組み合わせ療法を個体に投与することを含む、個体におけるがんを処置するための方法を提供する。
分子生物学における標準的な方法は、Sambrook,Fritsch、およびManiatis(1982および1989、第2版、2001、第3版)Molecular Cloning、A Laboratory Manual、Cold Spring Harbor Laboratory Press、Cold Spring Harbor、NY;SambrookおよびRussell(2001)Molecular Cloning、第3版、Cold Spring Harbor Laboratory Press、Cold Spring Harbor、NY;Wu(1993)Recombinant DNA、Vol.217、Academic Press、San Diego、CAにおいて記載されている。標準的な方法はまた、細菌細胞におけるクローニングおよびDNA突然変異生成(Vol.1)、哺乳動物細胞および酵母におけるクローニング(Vol.2)、糖複合体およびタンパク質の発現(Vol.3)、ならびにバイオインフォマティクス(Vol.4)について記載している、Ausbelら、(2001)Current Protocols in Molecular Biology、Vols.1〜4、John Wiley and Sons,Inc. New York、NYにおいても見ることができる。
(実施例1)
CT26結腸癌マウスモデルにおける抗OX40(OX86 mIgG1)および抗4−1−BBモノクローナル抗体の組み合わせ活性
抗OX40抗体 mIgG1および抗4−1BB mIgG1抗体の潜在的な組み合わせ効果を、インビボで、マウスCT26結腸癌同系腫瘍モデルにおいて評価した。
B16−F10黒色腫マウスモデルにおける抗OX40(OX86 mIgG1)および抗4−1−BBモノクローナル抗体の組み合わせ活性
実施例1に記載したサロゲートアゴニスト抗OX40および抗4−1BB抗体の組み合わせを、腫瘍におけるT細胞浸潤が比較的少ない、あまり免疫原性でない、B16−F10黒色腫同系モデルにおいても研究した。C57BL/6マウスにB16−F10細胞を接種し、次いで、腫瘍細胞接種後11日目、14日目、17日目、および21日目に、マウスを、アイソタイプ対照抗体、5mg/kgの抗OX40抗体および1mg/kgの抗4−1BB抗体の組み合わせ、または単一の作用物質の各々で処置した。結果は、抗OX40抗体および抗4−1BB抗体の組み合わせが、公開されたデータと一致して、この侵攻性モデルにおいて、確立された腫瘍の成長を阻害しなかったことを示した(Grayら、Eur J Immunol.38(9):2499〜511、2008)。
OX40アゴニストおよび4−1BBアゴニストでの組み合わせ処置
この実施例は、選択された進行したまたは固形の転移性固形腫瘍を有する患者における、抗4−1BB抗体と組み合わされた抗OX40抗体の、安全性、有効性、抗腫瘍活性、薬物動態学、薬力学、およびバイオマーカー調節の1つまたは複数を評価するための、臨床試験研究を説明する。
Claims (44)
- OX40アゴニストおよび4−1BBアゴニストを含む組み合わせ療法を個体に投与することを含む、個体におけるがんを処置するための方法。
- OX40アゴニストが、OX40に特異的に結合するモノクローナル抗体であり、かつ、
配列番号7で示されるアミノ酸配列を含む重鎖可変領域(VH)のVH相補性決定領域1(CDR1)、VH CDR2、およびVH CDR3を含むVH、ならびに、
配列番号8で示されるアミノ酸配列を含む軽鎖可変領域(VL)のVL CDR1、VL CDR2、およびVL CDR3を含むVL
を含む、請求項1に記載の方法。 - 4−1BBアゴニストが、4−1BBに特異的に結合するモノクローナル抗体であり、かつ、
配列番号17で示されるアミノ酸配列を含む重鎖可変領域(VH)のVH CDR1、VH CDR2、およびVH CDR3を含むVH、ならびに、
配列番号18で示されるアミノ酸配列を含む軽鎖可変領域(VL)のVL CDR1、VL CDR2、およびVL CDR3を含むVL
を含む、請求項1または2に記載の方法。 - OX40モノクローナル抗体が、配列番号1で示されるアミノ酸配列を含むVH CDR1、配列番号2で示されるアミノ酸配列を含むVH CDR2、配列番号3で示されるアミノ酸配列を含むVH CDR3、配列番号4で示されるアミノ酸配列を含むVL CDR1、配列番号5で示されるアミノ酸配列を含むVL CDR2、および配列番号6で示されるアミノ酸配列を含むVL CDR3を含み、かつ、
4−1BBモノクローナル抗体が、配列番号11で示されるアミノ酸配列を含むVH CDR1、配列番号12で示されるアミノ酸配列を含むVH CDR2、配列番号13で示されるアミノ酸配列を含むVH CDR3、配列番号14で示されるアミノ酸配列を含むVL CDR1、配列番号15で示されるアミノ酸配列を含むVL CDR2、および配列番号16で示されるアミノ酸配列を含むVL CDR3を含む、
請求項1〜3のいずれか一項に記載の方法。 - OX40モノクローナル抗体が、配列番号9で示されるアミノ酸配列を含む重鎖、および配列番号10で示されるアミノ酸配列を含む軽鎖を含む、請求項1〜4のいずれか一項に記載の方法。
- 4−1BBモノクローナル抗体が、配列番号19で示されるアミノ酸配列を含む重鎖、および配列番号20で示されるアミノ酸配列を含む軽鎖を含む、請求項1〜5のいずれか一項に記載の方法。
- OX40アゴニストおよび4−1BBアゴニストが個別に、同時に、または連続的に投与される、請求項1〜6のいずれか一項に記載の方法。
- OX40アゴニストが、4−1BBアゴニストと時間をあけて投与される、請求項1〜7のいずれか一項に記載の方法。
- OX40アゴニストが2週間ごとに投与され、4−1BBアゴニストが4週間ごとに投与される、請求項1〜8のいずれか一項に記載の方法。
- OX40アゴニストが、0.01mg/kg、0.03mg/kg、0.1mg/kg、0.3mg/kg、1mg/kg、1.5mg/kg、3mg/kg、5mg/kg、および10mg/kgからなる群から選択される用量で2週間ごとに投与され、4−1BBアゴニストが、対象当たり1、5、10、20、30、40、50、60、70、80、90、100、150、200、および500mgからなる群から選択される一定用量で4週間ごとに投与される、請求項1〜9のいずれか一項に記載の方法。
- がんが固形腫瘍である、請求項1〜10のいずれか一項に記載の方法。
- がんが、黒色腫、頭/頚部扁平上皮細胞癌(HNSCC)、肝細胞癌、腎臓細胞癌(RCC)、膀胱がん、子宮頸がん、胃(gastric)がん、または非小細胞肺がん(NSCLC)である、請求項1〜11のいずれか一項に記載の方法。
- 個体におけるがんを処置するための、4−1BBアゴニストと組み合わせて使用するためのOX40アゴニストを含む薬剤。
- OX40アゴニストが、OX40に特異的に結合するモノクローナル抗体であり、かつ、
配列番号7で示されるアミノ酸配列を含む重鎖可変領域(VH)のVH相補性決定領域1(CDR1)、VH CDR2、およびVH CDR3を含むVH、ならびに、
配列番号8で示されるアミノ酸配列を含む軽鎖可変領域(VL)のVL CDR1、VL CDR2、およびVL CDR3を含むVL
を含む、請求項13に記載の薬剤。 - 4−1BBアゴニストが、4−1BBに特異的に結合するモノクローナル抗体であり、かつ、
配列番号17で示されるアミノ酸配列を含む重鎖可変領域(VH)のVH CDR1、VH CDR2、およびVH CDR3を含むVH、ならびに、
配列番号18で示されるアミノ酸配列を含む軽鎖可変領域(VL)のVL CDR1、VL CDR2、およびVL CDR3を含むVL
を含む、請求項13または14に記載の薬剤。 - OX40モノクローナル抗体が、配列番号1で示されるアミノ酸配列を含むVH CDR1、配列番号2で示されるアミノ酸配列を含むVH CDR2、配列番号3で示されるアミノ酸配列を含むVH CDR3、配列番号4で示されるアミノ酸配列を含むVL CDR1、配列番号5で示されるアミノ酸配列を含むVL CDR2、および配列番号6で示されるアミノ酸配列を含むVL CDR3を含み、かつ、
4−1BBモノクローナル抗体が、配列番号11で示されるアミノ酸配列を含むVH CDR1、配列番号12で示されるアミノ酸配列を含むVH CDR2、配列番号13で示されるアミノ酸配列を含むVH CDR3、配列番号14で示されるアミノ酸配列を含むVL CDR1、配列番号15で示されるアミノ酸配列を含むVL CDR2、および配列番号16で示されるアミノ酸配列を含むVL CDR3を含む、
請求項13〜15のいずれか一項に記載の薬剤。 - OX40モノクローナル抗体が、配列番号9で示されるアミノ酸配列を含む重鎖、および配列番号10で示されるアミノ酸配列を含む軽鎖を含む、請求項13〜16のいずれか一項に記載の薬剤。
- 4−1BBモノクローナル抗体が、配列番号19で示されるアミノ酸配列を含む重鎖、および配列番号20で示されるアミノ酸配列を含む軽鎖を含む、請求項13〜17のいずれか一項に記載の薬剤。
- 個体におけるがんを処置するための、OX40アゴニストと組み合わせて使用するための4−1BBアゴニストを含む薬剤。
- 4−1BBアゴニストが、4−1BBに特異的に結合するモノクローナル抗体であり、かつ、
配列番号17で示されるアミノ酸配列を含む重鎖可変領域(VH)のVH CDR1、VH CDR2、およびVH CDR3を含むVH、ならびに、
配列番号18で示されるアミノ酸配列を含む軽鎖可変領域(VL)のVL CDR1、VL CDR2、およびVL CDR3を含むVL
を含む、請求項19に記載の薬剤。 - OX40アゴニストが、OX40に特異的に結合するモノクローナル抗体であり、かつ、
配列番号7で示されるアミノ酸配列を含む重鎖可変領域(VH)のVH相補性決定領域1(CDR1)、VH CDR2、およびVH CDR3を含むVH、ならびに、
配列番号8で示されるアミノ酸配列を含む軽鎖可変領域(VL)のVL CDR1、VL CDR2、およびVL CDR3を含むVL
を含む、請求項19または20に記載の薬剤。 - OX40モノクローナル抗体が、配列番号1で示されるアミノ酸配列を含むVH CDR1、配列番号2で示されるアミノ酸配列を含むVH CDR2、配列番号3で示されるアミノ酸配列を含むVH CDR3、配列番号4で示されるアミノ酸配列を含むVL CDR1、配列番号5で示されるアミノ酸配列を含むVL CDR2、および配列番号6で示されるアミノ酸配列を含むVL CDR3を含み、かつ、
4−1BBモノクローナル抗体が、配列番号11で示されるアミノ酸配列を含むVH CDR1、配列番号12で示されるアミノ酸配列を含むVH CDR2、配列番号13で示されるアミノ酸配列を含むVH CDR3、配列番号14で示されるアミノ酸配列を含むVL CDR1、配列番号15で示されるアミノ酸配列を含むVL CDR2、および配列番号16で示されるアミノ酸配列を含むVL CDR3を含む、
請求項19〜21のいずれか一項に記載の薬剤。 - OX40モノクローナル抗体が、配列番号9で示されるアミノ酸配列を含む重鎖、および配列番号10で示されるアミノ酸配列を含む軽鎖を含む、請求項19〜22のいずれか一項に記載の薬剤。
- 4−1BBモノクローナル抗体が、配列番号19で示されるアミノ酸配列を含む重鎖、および配列番号20で示されるアミノ酸配列を含む軽鎖を含む、請求項19〜23のいずれか一項に記載の薬剤。
- 第1の容器、第2の容器、および添付文書を含むキットであって、第1の容器が、少なくとも1用量の、OX40アゴニストを含む薬剤を含み、第2の容器が、少なくとも1用量の、4−1BBアゴニストを含む薬剤を含み、かつ、添付文書が、薬剤を使用して個体のがんを処置するための指示を含む、キット。
- OX40アゴニストが、OX40に特異的に結合するモノクローナル抗体であり、かつ、
配列番号7で示されるアミノ酸配列を含む重鎖可変領域(VH)のVH相補性決定領域1(CDR1)、VH CDR2、およびVH CDR3を含むVH、ならびに、
配列番号8で示されるアミノ酸配列を含む軽鎖可変領域(VL)のVL CDR1、VL CDR2、およびVL CDR3を含むVL
を含む、請求項25に記載のキット。 - 4−1BBアゴニストが、4−1BBに特異的に結合するモノクローナル抗体であり、かつ、
配列番号17で示されるアミノ酸配列を含む重鎖可変領域(VH)のVH CDR1、VH CDR2、およびVH CDR3を含むVH、ならびに、
配列番号18で示されるアミノ酸配列を含む軽鎖可変領域(VL)のVL CDR1、VL CDR2、およびVL CDR3を含むVL
を含む、請求項25または26に記載のキット。 - OX40モノクローナル抗体が、配列番号1で示されるアミノ酸配列を含むVH CDR1、配列番号2で示されるアミノ酸配列を含むVH CDR2、配列番号3で示されるアミノ酸配列を含むVH CDR3、配列番号4で示されるアミノ酸配列を含むVL CDR1、配列番号5で示されるアミノ酸配列を含むVL CDR2、および配列番号6で示されるアミノ酸配列を含むVL CDR3を含み、かつ、
4−1BBモノクローナル抗体が、配列番号11で示されるアミノ酸配列を含むVH CDR1、配列番号12で示されるアミノ酸配列を含むVH CDR2、配列番号13で示されるアミノ酸配列を含むVH CDR3、配列番号14で示されるアミノ酸配列を含むVL CDR1、配列番号15で示されるアミノ酸配列を含むVL CDR2、および配列番号16で示されるアミノ酸配列を含むVL CDR3を含む、
請求項25〜27のいずれか一項に記載のキット。 - OX40モノクローナル抗体が、配列番号9で示されるアミノ酸配列を含む重鎖、および配列番号10で示されるアミノ酸配列を含む軽鎖を含む、請求項25〜28のいずれか一項に記載のキット。
- 4−1BBモノクローナル抗体が、配列番号19で示されるアミノ酸配列を含む重鎖、および配列番号20で示されるアミノ酸配列を含む軽鎖を含む、請求項25〜29のいずれか一項に記載のキット.
- がんの治療において使用するためのOX40アゴニストを含む組成物であって、OX40アゴニストが、4−1BBアゴニストと組み合わせて個別に、連続的に、または同時に使用するためのものである組成物。
- OX40アゴニストが、OX40に特異的に結合するモノクローナル抗体であり、かつ、
配列番号7で示されるアミノ酸配列を含む重鎖可変領域(VH)のVH相補性決定領域1(CDR1)、VH CDR2、およびVH CDR3を含むVH、ならびに、
配列番号8で示されるアミノ酸配列を含む軽鎖可変領域(VL)のVL CDR1、VL CDR2、およびVL CDR3を含むVL
を含む、請求項31に記載の組成物。 - 4−1BBアゴニストが、4−1BBに特異的に結合するモノクローナル抗体であり、かつ、
配列番号17で示されるアミノ酸配列を含む重鎖可変領域(VH)のVH CDR1、VH CDR2、およびVH CDR3を含むVH、ならびに、
配列番号18で示されるアミノ酸配列を含む軽鎖可変領域(VL)のVL CDR1、VL CDR2、およびVL CDR3を含むVL
を含む、請求項31または32に記載の組成物。 - OX40モノクローナル抗体が、配列番号1で示されるアミノ酸配列を含むVH CDR1、配列番号2で示されるアミノ酸配列を含むVH CDR2、配列番号3で示されるアミノ酸配列を含むVH CDR3、配列番号4で示されるアミノ酸配列を含むVL CDR1、配列番号5で示されるアミノ酸配列を含むVL CDR2、および配列番号6で示されるアミノ酸配列を含むVL CDR3を含み、かつ、
4−1BBモノクローナル抗体が、配列番号11で示されるアミノ酸配列を含むVH CDR1、配列番号12で示されるアミノ酸配列を含むVH CDR2、配列番号13で示されるアミノ酸配列を含むVH CDR3、配列番号14で示されるアミノ酸配列を含むVL CDR1、配列番号15で示されるアミノ酸配列を含むVL CDR2、および配列番号16で示されるアミノ酸配列を含むVL CDR3を含む、
請求項31〜33のいずれか一項に記載の組成物。 - OX40モノクローナル抗体が、配列番号9で示されるアミノ酸配列を含む重鎖、および配列番号10で示されるアミノ酸配列を含む軽鎖を含む、請求項31〜34のいずれか一項に記載の組成物。
- 4−1BBモノクローナル抗体が、配列番号19で示されるアミノ酸配列を含む重鎖、および配列番号20で示されるアミノ酸配列を含む軽鎖を含む、請求項31〜35のいずれか一項に記載の組成物。
- がんの治療において使用するための4−1BBアゴニストを含む組成物であって、4−1BBアゴニストが、OX40アゴニストと組み合わせて個別に、連続的に、または同時に使用するためのものである組成物。
- 4−1BBアゴニストが、4−1BBに特異的に結合するモノクローナル抗体であり、かつ、
配列番号17で示されるアミノ酸配列を含む重鎖可変領域(VH)のVH CDR1、VH CDR2、およびVH CDR3を含むVH、ならびに、
配列番号18で示されるアミノ酸配列を含む軽鎖可変領域(VL)のVL CDR1、VL CDR2、およびVL CDR3を含むVL
を含む、請求項37に記載の組成物。 - OX40アゴニストが、OX40に特異的に結合するモノクローナル抗体であり、かつ、
配列番号7で示されるアミノ酸配列を含む重鎖可変領域(VH)のVH相補性決定領域1(CDR1)、VH CDR2、およびVH CDR3を含むVH、ならびに、
配列番号8で示されるアミノ酸配列を含む軽鎖可変領域(VL)のVL CDR1、VL CDR2、およびVL CDR3を含むVL
を含む、請求項37または38に記載の組成物。 - OX40モノクローナル抗体が、配列番号1で示されるアミノ酸配列を含むVH CDR1、配列番号2で示されるアミノ酸配列を含むVH CDR2、配列番号3で示されるアミノ酸配列を含むVH CDR3、配列番号4で示されるアミノ酸配列を含むVL CDR1、配列番号5で示されるアミノ酸配列を含むVL CDR2、および配列番号6で示されるアミノ酸配列を含むVL CDR3を含み、かつ、
4−1BBモノクローナル抗体が、配列番号11で示されるアミノ酸配列を含むVH CDR1、配列番号12で示されるアミノ酸配列を含むVH CDR2、配列番号13で示されるアミノ酸配列を含むVH CDR3、配列番号14で示されるアミノ酸配列を含むVL CDR1、配列番号15で示されるアミノ酸配列を含むVL CDR2、および配列番号16で示されるアミノ酸配列を含むVL CDR3を含む、
請求項37〜39のいずれか一項に記載の組成物。 - OX40モノクローナル抗体が、配列番号9で示されるアミノ酸配列を含む重鎖、および配列番号10で示されるアミノ酸配列を含む軽鎖を含む、請求項37〜40のいずれか一項に記載の組成物。
- 4−1BBモノクローナル抗体が、配列番号19で示されるアミノ酸配列を含む重鎖、および配列番号20で示されるアミノ酸配列を含む軽鎖を含む、請求項37〜41のいずれか一項に記載の組成物。
- がんが、膀胱がん、乳がん、胃(gastric)がん、腎明細胞がん、子宮頸がん、頭/頚部扁平上皮細胞癌(HNSCC)、肺扁平上皮細胞癌、悪性黒色腫、非小細胞肺がん(NSCLC)、卵巣がん、膵臓がん、前立腺がん、腎臓細胞癌(RCC)、肝細胞癌、小細胞肺がん(SCLC)、トリプルネガティブ乳がん、非ホジキンリンパ腫(NHL)、びまん性大細胞型B細胞リンパ腫(DLBCL)、EBV陽性DLBCL、濾胞リンパ腫、急性リンパ芽球性白血病(ALL)、急性骨髄性白血病(AML)、慢性リンパ性白血病(CLL)、慢性骨髄性白血病(CML)、縦隔原発大細胞型B細胞リンパ腫、マントル細胞リンパ腫(MCL)、小リンパ球性リンパ腫(SLL)、T細胞/組織球豊富型大細胞型B細胞リンパ腫、ホジキンリンパ腫(HL)、多発性骨髄腫(MM)、骨髄細胞白血病−1タンパク質(Mcl−1)、または骨髄異形成症候群(MDS)である、請求項1〜42のいずれか一項に記載の方法、使用するための薬剤、組成物、またはキット。
- OX40アゴニストが、OX40に特異的に結合するモノクローナル抗体であり、かつ、配列番号7で示されるアミノ酸配列を含む重鎖可変領域(VH)、および配列番号8で示されるアミノ酸配列を含む軽鎖可変領域(VL)を含むモノクローナル抗体であり、かつ、4−1BBアゴニストが、4−1BBに特異的に結合し、かつ、配列番号17で示されるアミノ酸を含むVH、および配列番号18で示されるアミノ酸を含む、請求項1〜43のいずれか一項に記載の方法、使用するための薬剤、組成物、またはキット。
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AU2017211540A1 (en) | 2018-07-19 |
MX2018008995A (es) | 2019-01-10 |
AU2017211540B2 (en) | 2020-04-30 |
CN108473587A (zh) | 2018-08-31 |
RU2018127164A3 (ja) | 2020-02-28 |
AU2020210145A1 (en) | 2020-08-13 |
HK1259253A1 (zh) | 2019-11-29 |
EP3408294A1 (en) | 2018-12-05 |
RU2748949C2 (ru) | 2021-06-02 |
US20190031765A1 (en) | 2019-01-31 |
KR20180103150A (ko) | 2018-09-18 |
KR20210013777A (ko) | 2021-02-05 |
RU2018127164A (ru) | 2020-02-28 |
WO2017130076A1 (en) | 2017-08-03 |
BR112018014016A2 (pt) | 2019-02-05 |
CA2955184A1 (en) | 2017-07-25 |
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