JP2021502416A - ヒトがんの治療のためのモノクローナル抗体neo−201 - Google Patents
ヒトがんの治療のためのモノクローナル抗体neo−201 Download PDFInfo
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- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
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Abstract
Description
本明細書は、2017年11月30日に提出された米国仮出願第62/592,778号、及び2017年11月3日に提出された米国仮出願第62/581,380号の利益を主張し、これらのそれぞれは、参照によりその全体が本明細書に組み込まれる。
この出願は、本開示の一部として、その全体が本明細書に参照により組み込まれる、32563バイトのサイズを有し、2018年11月2日に作成された「43282o4402.txt」という名前のファイルに列挙されている生物学的配列を含む。
抗体依存性細胞傷害(ADCC)、時間0から無限大までの血漿中濃度時間曲線下面積(AUCinf)、時間0から無限大までの血漿中濃度−時間曲線下の線量正規化面積(AUCinf/D)、ベースライン(BL)、補体依存性細胞毒性(CDC)、クリアランス(CL)、観察された最大血漿中濃度(Cmax)、用量正規化測定最大血漿濃度(Cmax/D)、エストロゲン受容体(ER)、半減期(HL)、免疫組織化学(IHC)、ナチュラルキラー(NK)、非小細胞肺癌(NSCLC)、末梢血単核細胞(PBMC)、プロゲステロン受容体(PR)、腫瘍関連抗原(TAA)、観察された最大血漿濃度時間(Tmax)、分布容積(Vz)。
以下のリストの各文書を含む、本明細書で引用される各文書は、参照によりその全体が本明細書に組み込まれる。
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Claims (47)
- 有効量のNEO−201抗体を、それを必要とする患者に投与することを含む、がん腫細胞を死滅させる方法。
- 有効量のNEO−201抗体を、それを必要とする患者に投与することを含む、がん腫を治療する方法。
- 有効量のNEO−201抗体を、それを必要とする患者に投与することを含む、がん腫の再発を予防する方法。
- 有効量のNEO−201抗体を、それを必要とする患者に投与することを含む、がん腫を有する患者の腫瘍量を減少させる方法。
- 前記抗体は、補体媒介性細胞毒性(CDC)を媒介し、それにより前記患者のがん腫細胞を死滅させる、先行請求項のいずれか1項に記載の方法。
- 前記患者は、前記投与前または前記投与時にナチュラルキラー(「NK」)が枯渇している、先行請求項のいずれか1項に記載の方法。
- 前記患者は、前記投与前または前記投与時に重度のNK枯渇である、先行請求項のいずれか1項に記載の方法。
- 前記投与前または前記投与時に、前記患者がNK枯渇しているかを決定することをさらに含む、請求項6に記載の方法。
- 前記投与前または前記投与時に、前記患者が重度にNK枯渇しているかを決定することをさらに含む、請求項6に記載の方法。
- 前記患者は、任意によりCNKD(例えば、CNKD1、CNKD2)、またはFNKD(例えば、FNKD1)を含むNK細胞欠損症(NKD)を有する、先行請求項のいずれか1項に記載の方法。
- 前記患者は、別の治療法の結果としてNKが枯渇しているか、または重度にNKが枯渇している、先行請求項のいずれか1項に記載の方法。
- 前記患者はがん治療を受けている、先行請求項のいずれか1項に記載の方法。
- 前記患者は化学療法または放射線療法を受けている、先行請求項のいずれか1項に記載の方法。
- 前記化学療法は、1つ以上のプロテアソーム阻害剤(例えば、ボルテゾミブ、MG132)、ヒストンデアセチラーゼ阻害剤(例えば、バルプロ酸、トリコスタチンA、スベロイルアニリド−ヒドロキサム酸(SAH)、酪酸ナトリウム)、遺伝毒性剤(例えば、ドキソルビシン、メルファラン、シスプラチン、Ara−C、アフィジコリン、マイトマイシン、メトトレキサート、エトポシド)、GSK阻害剤(例えば、LiCl、BIO、SB21)、BET阻害剤(例えば、JQ1)、HSP90阻害剤(例えば、ラディシコラ(radicicola))、17−AAG)、微小管集合阻害剤(例えば、ビンクリスチン、サイトカラシンD、ノコダゾール、ドセタキセル)、及び/または免疫調節薬(例えば、レナリドマイド)を投与することを含む、請求項13に記載の方法。
- 前記投与前または前記投与時に、NK細胞は、前記個体における末梢血単核細胞(PBMC)の5%未満を構成する、先行請求項のいずれか1項に記載の方法。
- 前記投与前または前記投与時に、NK細胞は、前記個体における末梢血単核細胞(PBMC)の3%未満を構成する、先行請求項のいずれか1項に記載の方法。
- 前記投与前または前記投与時に、前記患者の70%未満のPBMC NK細胞がCD56dimCD16+NK細胞である、先行請求項のいずれか1項に記載の方法。
- 前記投与前または前記投与時に、前記患者の50%未満のPBMC NK細胞がCD56dimCD16+NK細胞である、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体は、配列番号28及び配列番号29に含まれるCDR配列の少なくとも1つ、2つ、3つ、4つ、5つ、または6つすべてを含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体は、配列番号38に対して少なくとも90%の同一性を有する可変重鎖配列を含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体は、配列番号39に対して少なくとも90%の同一性を有する可変軽鎖配列を含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体は、配列番号38に対して少なくとも90%の同一性を有する可変重鎖配列、及び配列番号39に対して少なくとも90%の同一性を有する可変軽鎖配列を含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体は、配列番号38の可変重鎖配列及び配列番号39の可変軽鎖配列を含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体は、配列番号28のアミノ酸20〜470に対して少なくとも90%の同一性を有する重鎖配列、及び配列番号29のアミノ酸20〜233に対して少なくとも90%の同一性を有する軽鎖配列を含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体は、配列番号28及び配列番号29に含まれる6つすべての前記CDR配列を含む、請求項22または23に記載の方法。
- 前記NEO−201抗体は、配列番号28の前記重鎖可変領域配列及び配列番号29の前記軽鎖可変領域配列を含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体は、配列番号28のアミノ酸20〜470を含む重鎖配列、及び配列番号29のアミノ酸20〜233を含む軽鎖配列を含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体は、ヒトIgG1の定常ドメインを含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体はヒト化されている、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体は、別の部分にコンジュゲートされている、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体は、別の細胞毒性部分、標識、放射性部分、または親和性タグにコンジュゲートされている、先行請求項のいずれか1項に記載の方法。
- 前記がん腫の細胞の死滅を増強するかまたは刺激するための有効量のサイトカインアゴニストを前記患者に投与することをさらに含む、先行請求項のいずれか1項に記載の方法。
- 前記サイトカインアゴニストは、インターロイキン−2(IL−2)、インターロイキン21(IL−21)、ALT−803、IL−15阻害剤、チェックポイント阻害剤、抗PD1、抗PDL1、抗CTLA−4、抗−41BB、抗OX40、抗Tim−3、またはそれらの組み合わせである、請求項31に記載の方法。
- 前記がん腫の細胞の死滅を増強するかまたは刺激するための有効量の補体調節タンパク質(CRP)アンタゴニストを前記患者に投与することをさらに含む、先行請求項のいずれか1項に記載の方法。
- 前記CRPアンタゴニストは、CD46、CD55、またはCD59のうちの1つ以上に拮抗する、請求項33に記載の方法。
- 前記CRPアンタゴニストは、抗体またはその抗原結合断片を含む、請求項33または34に記載の方法。
- 前記サイトカインアゴニストは、IL−15アゴニストまたはIL−15スーパーアゴニストを含む、請求項31に記載の方法。
- 前記サイトカインアゴニストが、IL−15受容体α/IgG1 Fc融合タンパク質に結合したIL−15変異体(IL−15N72D)からなる複合体を含む、請求項31に記載の方法。
- 前記サイトカインアゴニストがALT−803を含む、請求項37に記載の方法。
- 前記NEO−201抗体の前記有効投与量が、前記サイトカインアゴニストを含まない前記NEO−201抗体単独での治療と比較して低減される、請求項31〜38のいずれか1項に記載の方法。
- 前記がんは、結腸癌である、先行請求項のいずれか1項に記載の方法。
- 前記がんは、膵癌である、先行請求項のいずれか1項に記載の方法。
- 前記がんは、卵巣癌である、先行請求項のいずれか1項に記載の方法。
- 前記がんは、胃癌である、先行請求項のいずれか1項に記載の方法。
- 前記がんは、肺癌である、先行請求項のいずれか1項に記載の方法。
- 前記がんは、乳癌である、先行請求項のいずれか1項に記載の方法。
- 前記がんは、子宮癌である、先行請求項のいずれか1項に記載の方法。
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