JP2022545761A - 抗cd47抗体およびその使用 - Google Patents
抗cd47抗体およびその使用 Download PDFInfo
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Abstract
Description
「a」または「an」の実体という用語は、その実体の1つまたは複数を指すことに留意されたい。例えば、「抗体(an antibody)」とは、1つまたは複数の抗体を表すものと理解される。したがって、「a」(または「an」)、「1つまたは複数」および「少なくとも1つ」という用語は、本明細書では互換的に使用することができる。
抗CD47抗体
第1表.CDR領域の配列
第2表.アミノ酸類似性マトリックス
二官能性分子
腫瘍抗原標的分子として、CD47に特異的な抗体または抗原結合断片を、免疫細胞に特異的な第2の抗原結合断片と組み合わせて二重特異性抗体を生成することができる。
抗体をコードするポリヌクレオチドおよび抗体を調製する方法
治療
併用療法
診断方法
組成物
実施例
例1:ヒトCD47に対するマウスモノクローナル抗体の生成
第4表.G08およびH06の変数配列
例3:G08およびH06クローンのヒト化設計
第6表G08およびH06のCDR配列(太字/斜体はバックミューテーションを示している)
第7表.ヒト化CD47抗体の設計
例5:RBC凝集アッセイにおけるRBC保存特性
例6:Biacore(登録商標)によるヒト化抗体のフルキネティックアフィニティー
第8表.ヒト化抗体のアフィニティーランキング
第9表.Biacore(登録商標)によるアフィニティー
例8:Raji-Lucリンパ腫マウスモデルでの薬効実験
Claims (26)
- 抗体またはその断片であって、前記抗体またはその断片は、ヒトCD47(CD分類47)タンパク質に特異性を有し、かつ
(a)配列番号1のアミノ酸配列を含むVH CDR1、または配列番号1からの単一の置換、欠失もしくは挿入を有する配列番号1のバリアント;
(b)配列番号2もしくは配列番号7のアミノ酸配列を含むVH CDR2、または配列番号2もしくは配列番号7の4位、7位、12位もしくは15位に単一の置換、欠失もしくは挿入を有する配列番号2もしくは配列番号7のバリアント;
(c)配列番号3もしくは配列番号8のアミノ酸配列を含むVH CDR3、または配列番号3もしくは配列番号8の1位もしくは2位に単一の置換、欠失もしくは挿入を有する配列番号3もしくは配列番号8のバリアント;
(d)配列番号4もしくは配列番号9のアミノ酸配列を含むVL CDR1、または配列番号4もしくは配列番号9の1位もしくは6位に単一の置換、欠失もしくは挿入を有する配列番号4もしくは配列番号9のバリアント;
(e)配列番号5のアミノ酸配列を含むVL CDR2、または配列番号5からの単一の置換、欠失もしくは挿入を有する配列番号5のバリアント;および
(f)配列番号6もしくは配列番号10のアミノ酸配列を含むVL CDR3、または配列番号6もしくは配列番号10の5位に単一の置換、欠失もしくは挿入を有する配列番号6もしくは配列番号10のバリアントを
を含む、抗体またはその断片。 - 配列番号1のVH CDR1、配列番号2のVH CDR2、配列番号3のVH CDR3、配列番号4のVL CDR1、配列番号5のVL CDR2、および配列番号6のVL CDR3を含む、請求項1に記載の抗体またはその断片。
- 配列番号11および15~16からなる群から選択されるアミノ酸配列、または配列番号11および15~16からなる群から選択されるアミノ酸配列に対して少なくとも90%の配列同一性を有するペプチドを含む重鎖可変領域を含む、請求項2に記載の抗体またはその断片。
- 配列番号12および17からなる群から選択されるアミノ酸配列、または配列番号12および17からなる群から選択されるアミノ酸配列に対して少なくとも90%の配列同一性を有するペプチドを含む軽鎖可変領域を含む、請求項2または3に記載の抗体またはその断片。
- 配列番号15もしくは16の前記アミノ酸配列、または配列番号15もしくは16の前記アミノ酸配列に対して少なくとも90%の配列同一性を有するペプチドを含む重鎖可変領域と、配列番号17の前記アミノ酸配列、または配列番号17の前記アミノ酸配列に対して少なくとも90%の配列同一性を有するペプチドを含む軽鎖可変領域とを含む、請求項4に記載の抗体またはその断片。
- 配列番号1のVH CDR1、配列番号7のVH CDR2、配列番号8のVH CDR3、配列番号9のVL CDR1、配列番号5のVL CDR2、および配列番号10のVL CDR3を含む、請求項1に記載の抗体またはその断片。
- 配列番号13および18~19からなる群から選択されるアミノ酸配列、または配列番号13および18~19からなる群から選択されるアミノ酸配列に対して少なくとも90%の配列同一性を有するペプチドを含む重鎖可変領域を含む、請求項6に記載の抗体またはその断片。
- 配列番号14および20からなる群から選択されるアミノ酸配列、または配列番号14および20からなる群から選択されるアミノ酸配列に対して少なくとも90%の配列同一性を有するペプチドを含む軽鎖可変領域を含む、請求項6または7に記載の抗体またはその断片。
- 配列番号18もしくは19の前記アミノ酸配列、または配列番号18もしくは19の前記アミノ酸配列に対して少なくとも90%の配列同一性を有するペプチドを含む重鎖可変領域と、配列番号20の前記アミノ酸配列、または配列番号20の前記アミノ酸配列に対して少なくとも90%の配列同一性を有するペプチドを含む軽鎖可変領域とを含む、請求項8に記載の抗体またはその断片。
- 前記抗体またはその断片がヒト化抗体である、請求項1から9のいずれか一項に記載の抗体またはその断片。
- 請求項1から10のいずれか一項に記載の断片と、第2の特異性を有する第2の抗原結合断片とを含む、二重特異性抗体。
- 前記第2の特異性が免疫細胞上の分子に対するものである、請求項11に記載の二重特異性抗体。
- 前記分子が、PD-L1、PD-1、CTLA-4、LAG-3、CD28、CD122、4-1BB、TIM3、OX-40、OX40L、CD40、CD40L、LIGHT、ICOS、ICOSL、GITR、GITRL、TIGIT、CD27、VISTA、B7H3、B7H4、HEVM、BTLA、KIR、およびこれらの任意の組み合わせからなる群から選択される、請求項12に記載の二重特異性抗体。
- 前記断片および前記第2の抗原結合断片が、それぞれ独立して、Fab断片、単鎖可変断片(scFv)またはシングルドメイン抗体から選択される、請求項11から13のいずれか一項に記載の二重特異性抗体。
- 請求項1から10のいずれか一項に記載の抗体またはその断片、もしくは請求項11から14のいずれか一項に記載の二重特異性抗体と、薬学的に許容され得る担体とを含む、組成物。
- 請求項1から10のいずれか一項に記載の抗体またはその断片、もしくは請求項11から14のいずれか一項に記載の二重特異性抗体をコードする1つまたは複数のポリヌクレオチド。
- 請求項1から10のいずれか一項に記載の抗体またはその断片、もしくは請求項11から14のいずれか一項に記載の二重特異性抗体をコードする1つまたは複数のポリヌクレオチドを含む、単離された細胞。
- 癌の治療を必要とする患者の癌を治療するための、請求項1から10のいずれか一項に記載の抗体またはその断片、請求項11から14のいずれか一項に記載の二重特異性抗体、または請求項15に記載の組成物。
- 前記癌が固形腫瘍である、請求項18に記載の抗体またはその断片、二重特異性抗体、または組成物。
- 前記癌が血液悪性腫瘍である、請求項18に記載の抗体またはその断片、二重特異性抗体、または組成物。
- 前記癌が、膀胱癌、肝臓癌、結腸癌、直腸癌、子宮内膜癌、白血病、リンパ腫、膵臓癌、小細胞肺癌、非小細胞肺癌、乳癌、尿道癌、頭頸部癌、胃腸癌、胃癌、食道癌、卵巣癌、腎癌、黒色腫、前立腺癌、甲状腺癌、およびこれらの任意の組み合わせからなる群から選択される、請求項18に記載の抗体またはその断片、二重特異性抗体、または組成物。
- 第2の癌治療薬をさらに含む、請求項18から21のいずれか一項に記載の抗体またはその断片、二重特異性抗体、または組成物。
- 自己免疫疾患または炎症性疾患の治療を必要とする患者の自己免疫または炎症性疾患を治療するための、請求項1から10のいずれか一項に記載の抗体またはその断片、請求項11から14のいずれか一項に記載の二重特異性抗体、または請求項15に記載の組成物。
- 前記自己免疫疾患または炎症性疾患が、パーキンソン病、関節炎、関節リウマチ、多発性硬化症、乾癬、乾癬性関節炎、クローン病、炎症性腸疾患、潰瘍性大腸炎、狼瘡、全身性エリテマトーデス、若年性関節リウマチ、若年性特発性関節炎、グレーブス病、橋本甲状腺炎、アジソン病、セリアック病、皮膚筋炎、多発性硬化症、重症筋無力症、悪性貧血、シェーグレン症候群、I型糖尿病、血管炎、ぶどう膜炎、アテローム性動脈硬化症および強直性脊椎炎からなる群から選択される、請求項23に記載の抗体またはその断片、二重特異性抗体、または組成物。
- 前記自己免疫疾患または炎症性疾患がアテローム性動脈硬化症である、請求項23に記載の抗体またはその断片、二重特異性抗体、または組成物。
- サンプル中のCD47の発現を検出する方法であって、請求項1から10のいずれか一項に記載の抗体またはその断片、もしくは請求項11から14のいずれか一項に記載の二重特異性抗体を、前記抗体またはその断片がCD47に結合する条件で前記サンプルと接触させることと、前記サンプル中のCD47の発現を示す結合を検出することとを含む、方法。
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