JP2021529754A - 自己免疫疾患の処置における使用のための抗cd40抗体 - Google Patents
自己免疫疾患の処置における使用のための抗cd40抗体 Download PDFInfo
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Abstract
Description
本発明は、一般的には、診断及び治療用途のためのヒト化抗CD40抗体に関する。より具体的には、ヒト化抗CD40抗体及びCD40を発現する細胞により特徴付けられる種々の疾患又は障害の処置のための使用方法が開示される。ヒト化抗CD40抗体を含む医薬組成物及びキットも開示される。
CD40は、48kDaのI型内在性膜糖タンパク質であり、腫瘍壊死因子(TNF)レセプタースーパーファミリーのメンバーである。CD40は、正常及び腫瘍性B細胞、指状突起細胞、癌腫、上皮細胞(例えば、ケラチノサイト)、線維芽細胞(例えば、滑膜細胞)及び血小板を含む各種の細胞型において発現される。CD40は、単球、マクロファージ、一部の内皮細胞及び濾胞樹状細胞にも存在する。CD40は、B細胞の個体発生の初期に発現され、CD10及びCD19の出現に続いてB細胞前駆体に現れ、CD21、CD23、CD24の発現及び表面免疫グロブリンM(sIgM)の出現に先立って現れる(Uckun et al., 1990, Blood 15:2449)。CD40は、扁桃及び骨髄由来形質細胞でも検出されている(Pellat-Decounynck et al., 1994, Blood 84:2597)。
本発明は、ヒト化モノクローナル抗体であって、前記抗体が1nM未満のアンタゴニスト活性IC50を有して、ヒトCD40に特異的に結合し、B細胞増殖に100μg/mlまで受容体活性化作用を有さず、ここで、前記抗体が非ヒト霊長類において少なくとも10日のin vivo半減期を有することをさらに特徴とする、ヒト化モノクローナル抗体を提供する。
現在では、CD40媒介性シグナル伝達は、各種のターゲット疾患に関与していると認識されている。これらの障害への介在が治療上有益であるであろうことを示す各種の前臨床データが利用可能であるにもかかわらず、自己免疫疾患の処置に使用することができるアンタゴニスト抗CD40抗体の必要性が依然として存在する。本発明は、好ましい実施態様では、CD40を認識するヒト化抗体に関する。また、これらの抗体は、US第8,591,900号及びWO第2011/123489号にも開示されている。これらの文献それぞれの内容は、参照により本明細書に組み入れられる。具体的な実施態様では、これらのヒト化抗体の配列は、特定のリードマウス抗体の配列に基づいて特定されている。
本明細書において、ヒト化抗CD40抗体並びに本発明の1つ以上のヒト化抗CD40抗体を含む組成物及び製品が記載され、開示される。また、本発明の抗体は、US第8,591,900号及びWO第2011/123489号にも開示されている。これらの文献それぞれの内容は、参照により本明細書に組み入れられる。また、ヒト化抗CD40抗体の抗原結合フラグメントを含む結合剤も記載されている。ヒト化抗CD40抗体及び結合剤は、細胞の増殖を停止させ、CD40を発現する細胞の除去を引き起こし又は何等かの方法で、ターゲット細胞に対する細胞傷害性又は細胞増殖抑制効果を誘引しもしくは引き起こすことができる。ヒト化抗CD40抗体及び結合剤は、CD40表面抗原を発現する細胞の増殖を特徴とする各種の疾患又は障害の処置に使用することができる。ヒト化抗CD40抗体及びCD40結合剤はそれぞれ、CD40エピトープを特異的に認識する少なくとも一部(すなわち、抗原結合フラグメント)を含む。
ヒト化抗CD40抗体及び薬剤は、ヒト化抗CD40抗体又はその抗原結合フラグメントの修飾を含むことができる。例えば、ガンの処置における抗体の有効性を増強するために、エフェクター機能に関して抗体を修飾することが望ましい場合がある。このような修飾の1つは、Fc領域へのシステイン残基の導入であり、それにより、この領域における鎖間ジスルフィド結合形成が可能となる。このようにして生成されたホモ二量体抗体は、内在化能力が改善しかつ/又は補体媒介性細胞殺傷及び/もしくは抗体依存性細胞傷害(ADCC)を向上させることができる。例えば、Caron et al., 1992, J. Exp Med. 176:1191-1195;及びShopes, 1992, J. Immunol. 148:2918-2922を参照のこと。また、増強された抗腫瘍活性を有するホモ二量体抗体は、Wolff et al., 1993, Cancer Research 53: 2560-2565に記載されるように、ヘテロ二官能性架橋剤を使用しても調製することができる。代替的には、抗体は、二重Fc領域を含有するように操作することができ、これにより、抗体の補体溶解及びADCC能力が増強される。Stevenson et al., 1989, Anti-Cancer Drug Design 3: 219-230を参照のこと。
抗CD40抗体のアミノ酸配列変異体は、抗CD40抗体DNAに適切なヌクレオチド変化を導入することにより又はペプチド合成により調製することができる。このような変異体は、例えば、本明細書における実施例の抗CD40抗体のアミノ酸配列内の残基からの欠失及び/又は同配列への挿入及び/又は同残基の置換を含む。最終構築物に到達するために、欠失、挿入及び置換の任意の組み合わせを行う。ただし、最終構築物が所望の特徴を有するという条件である。また、アミノ酸変化は、ヒト化又は変異体抗CD40抗体の翻訳後プロセスを変化させる(例えば、グリコシル化部位の数又は位置を変化させる)ことができる。
(1)疎水性:ノルロイシン、met、ala、val、leu、ile;
(2)中性親水性:cys、ser、thr;
(3)酸性:asp、glu;
(4)塩基性:asn、gin、his、lys、arg;
(5)鎖配向に影響を及ぼす残基: gly、pro;及び
(6)芳香族:trp、tyr、phe
他の実施態様は、ヒト化抗CD40抗体をコードする配列を含む、単離されたポリヌクレオチド、該ポリヌクレオチドを含むベクター及びホスト細胞並びにヒト化抗体の製造のためのリコンビナント技術を包含する。単離されたポリヌクレオチドは、例えば、全長モノクローナル抗体、Fab、Fab’、F(ab’)2及びFvフラグメント、ディアボディ、線状抗体、一本鎖抗体分子並びに抗体フラグメントから形成される多重特異性抗体を含む、任意の所望の形態の抗CD40抗体をコードすることができる。
本明細書で記載された抗体は、親和性精製剤として有用である。この方法では、該抗体は、当技術分野で周知の方法を使用して、固相、例えば、プロテインA樹脂に固定化される。固定化された抗体は、精製されるCD40タンパク質(又はそのフラグメント)を含有するサンプルと接触し、その後、支持体を、固定化された抗体に結合しているCD40タンパク質を除くサンプル中の実質的に全ての物質を除去するであろう適切な溶媒により洗浄する。最後に、支持体を、抗体からCD40タンパク質を放出するであろう別の適切な溶媒により洗浄する。
ヒト化抗CD40抗体は、診断キット、すなわち、診断アッセイを行うための説明書と共に、所定量の試薬のパッケージされた組み合わせにおいて使用することができる。抗体が、酵素によりラベルされている場合、該キットは、酵素により必要とされる基質及び補因子、例えば、検出可能な発色団又はフルオロフォアを提供する基質前駆体を含むことができる。加えて、他の添加剤、例えば、安定剤、バッファー(例えば、ブロックバッファー又は溶解バッファー)等を含ませることができる。種々の試薬の相対量は、アッセイの感度を実質的に最適化する試薬の溶液中の濃度を提供するために、広く変化させることができる。試薬は、溶解時に適切な濃度を有する試薬溶液を提供するであろう賦形剤を含む、通常は凍結乾燥された乾燥粉末として提供することができる。
別の実施態様では、本明細書で開示されたヒト化抗CD40抗体は、本明細書で記載されたCD40の発現に関連する種々の障害の処置に有用である。
抗CD40抗体又は薬剤は、CD40発現ガン又はCD40の発現、例えば、免疫細胞(例えば、リンパ球又は樹状細胞)の不適切な活性化により特徴付けられる免疫学的障害を治療し又は予防するのに有用である。CD40のこのような発現は、例えば、細胞表面でのCD40タンパク質レベルの向上及び/又は発現されたCD40の抗原性の変化に起因する場合がある。免疫学的障害の治療又は予防は、本明細書で記載された方法に従って、このような治療又は予防を必要とする対象に、有効量の抗CD40抗体又は薬剤を投与することにより、該抗体が(i)CD40を発現し、疾患状態に関連する活性化免疫細胞に結合し、(ii)活性化免疫細胞に対して細胞傷害性、細胞増殖抑制性又は免疫サプレッション効果を発揮することにより達成される。
1)B細胞分化及び抗体アイソタイプスイッチングを阻害する
2)T細胞及びマクロファージにおけるサイトカイン及びケモカインの産生並びに接着分子のアップレギュレーションを阻害する
3)樹状細胞の活性化を阻害する
4)炎症誘発性サイトカイン、ケモカイン、マトリックスメタロプロテイナーゼ、プロスタグランジンの産生を阻害し、非免疫細胞(例えば、上皮細胞、内皮細胞及び間葉細胞)における接着分子をダウンレギュレーションする
CD40結合剤(例えば、抗CD40抗体)を含む組成物は、免疫学的障害又はCD40発現ガンを有するか又は有するリスクがある対象に投与することができる。本発明は、さらに、CD40発現ガン又は免疫学的障害の予防又は治療のための医薬の製造における、CD40結合剤(例えば、抗CD40抗体)の使用を提供する。本明細書で使用する場合、「対象」という用語は、CD40結合剤を投与することができる任意のほ乳類患者を意味し、例えば、ヒト及び非ヒトほ乳類、例えば、霊長類、げっ歯類及びイヌを含む。本明細書で記載された方法を使用する処置に特に意図される対象は、ヒトを含む。該抗体又は薬剤は、免疫学的障害又はCD40発現ガンの予防又は治療において、単独で又は他の組成物と組み合わせて投与することができる。
別の態様では、上記された障害の処置に有用な物質を含有する製品が含まれる。該製品は、容器及びラベルを含む。適切な容器は、例えば、ボトル、バイアル、シリンジ及び試験管を含む。容器は、各種の材料、例えば、ガラス又はプラスチックで形成することができる。容器は、状態を処置するのに有効な組成物を保持し、無菌アクセスポートを有することができる。例えば、容器は、皮下注射針により穿孔可能なストッパーを有する静脈内溶液バッグ又はバイアルであることができる。該組成物中の活性剤は、ヒト化抗CD40抗体である。容器上又は容器に付随するラベルは、該組成物が選択された状態を処置するのに使用されることを示す。該製品は、薬学的に許容し得るバッファー、例えば、リン酸緩衝生理食塩水、リンゲル液及びデキストロース溶液を含む第2の容器をさらに含むことができる。該製品は、さらに、商業的及びユーザーの観点から望ましい他の材料(他のバッファー、希釈剤、フィルター、針、シリンジ及び使用説明を伴う添付文書を含む)を含むことができる。
実施例1:ヒト化抗CD40抗体の産生
マウス抗体20E2及び2H11を本明細書で上記された表1及び2に示す。20E2及び2H11クローンのヒト化は完了している。ヒト及びマウスの残基を任意の所定の位置で、ヒト又はマウスのいずれかの残基が存在することができるように変化させたライブラリを作製した。このようなライブラリをヒト生殖系列とマウス抗体との間で異なるアミノ酸について作製した。親マウス抗体の機能を保持するクローンのみを選択した。
A)ヒトIgG1−KO(ノックアウト)/カッパフォーマット(Fc領域にLeu234Ala、Leu235Alaの二重突然変異を有し、エフェクター機能、例えば、FcγR結合及び補体結合が低下している)
B)ヒトIgG4−DM(二重突然変異体)/カッパフォーマット(ヒンジ領域にSer228Pro突然変異を有し、IgG4半分子及びLeu235Glu突然変異の発生を低減し、さらに、FcγR結合が低下している)
−CCFの外観(濁度)
−CCFのろ過特性
−rプロテインAの収率
−溶出及び中和時の濁度
−可溶性凝集体(SEC)
−純度/夾雑パターン(SDS)
−電荷パターン(IEF)
抗体A、抗体B及び抗体Cを、公表されている配列に基づいて産生された抗体4D11(Kirin/Astellas)及びPG−102(PanGenetics)と共に特徴決定した。抗体A、抗体B、抗体C及び4D11についてのデータを以下に示す。PG−102は、アゴニスト活性を示し、B細胞増殖の阻害のみが不完全であった(図示せず)。表2.2に、得られたデータをまとめる。データのより詳細な説明は表2.2に従う。
ヒト化抗体の細胞CD40への特異的結合を、ヒトCD40でトランスフェクションされたHEK293細胞を使用するフローサイトメトリーにより分析した。抗体A、抗体B、及び抗体Cの濃度依存的結合が観察された。該抗体は、同様の結合プロファイルを示した。本発明の抗体及びKirinの抗体4D11のEC50値は全て、約1nMの同じ範囲にある。同範囲は、トランスフェクションされた細胞においてCD40が高レベルであるため、アッセイの感度限界で最も可能性がある。また、ヒト化抗体のヒトRamos細胞の細胞CD40への特異的結合からも、濃度依存性結合が示された。該抗体は、わずかに異なる結合プロファイル及び0.21〜1.22nM EC50値を示した。CD40陰性細胞、例えば、トランスフェクションされていないHEK293細胞又はT細胞系統HSB−2への結合は検出されなかったため、CD40への選択的結合が確認された(データを示さず)。
ヒト化抗体の活性をIL−2及びIL−4の存在下で、末梢血由来のヒトB細胞をリコンビナントCD40Lにより刺激するB細胞増殖アッセイにおいて試験した。抗体A、抗体B及び抗体Cは、B細胞の増殖の強力な阻害を示した。BIの抗体及びKirinの抗体4D11の阻害曲線及びIC50値との比較から、4D11抗体が複数のドナーにわたって試験された場合、より高い効力を有することが示される。CD40Lの非存在下でアゴニスト活性について試験した場合、抗体B、抗体A及び抗体Cの抗体は、4D11抗体と同様に、10μg/m l(67nM)までの濃度で、バックグラウンドレベルを超えるB細胞増殖を誘引しなかった。
A.カニクイザルへの抗体A及び抗体Bの1又は10mg/kgでの単回IV投与
抗体A及び抗体Bそれぞれを、1及び10mg/kg IVで、オスのカニクイザル(N=3)/投与に投与した。血液サンプルを0〜504時間(3週間)で収集し、血清を回収し、サンプルを分析まで−20℃で保存した。サンプルを上記されたサンドイッチELISAにより分析した。両IV投与後のサルにおける両抗体の血清濃度−時間プロファイル及び薬物動態パラメーターを以下に示された表2.7.1(抗体A)及び表2.7.2(抗体B)にまとめる。両抗体とも、用量依存的薬物動態を示した。このことから、低用量では、クリアランスは、主にターゲット媒介性処分に一致して生じ、一方、高用量では、該抗体は、主に異化により除去されることが示唆された。同様の用量依存的薬物動態プロファイルが、膜関連ターゲット(例えば、CD19、CD20、EGFR、CD146及びHER2)をターゲットとする他のMAbについて観察されている。抗体Aについてのクリアランスは、1及び10mg/kg用量についてそれぞれ、0.8及び0.1mL/h/kgであった。抗体Bについてのクリアランスは、1及び10mg/kg用量についてそれぞれ、0.7及び0.1mL/hr/kgであった。同様に、抗体A半減期は、1及び10mg/kg用量についてそれぞれ、1日及び13日であり、抗体B半減期は、同じ各用量について2日及び13日であった。抗体Bは、抗体Aの同じ投与量に対して、より低い用量で半減期がわずかに長かったが、この差は、慢性投与時のより持続的な曝露にはつながらないと予想されるであろう。両化合物についてのAUCは、両化合物についての分布の上比例(supraproportional)及び体積(Vss)であり、血漿体積(約40mL/kg)のものに近似した。このことは、大型の極性タンパク質治療剤について典型的に見られる限定された組織分布を示す。全体として、2つの抗体間の薬物動態パラメーターに明らかな差は存在しない。
上記されたPK研究の一環として、抗CD40抗体の薬力学的効果を分析した。この目的のために、全血サンプルをリコンビナントCD40Lと共に一晩インキュベーションし、B細胞でのCD86発現の増加をフローサイトメトリーにより決定した。サンプルを0日目(処置前)、投与後2、7及び14日目に分析した。CD86発現の増加は比較的小さい(約5〜20%)が、用量依存的効果が観察された。10mg/kg 抗体A及び抗体Bを投与された動物の群において、CD86誘引は、2、7及び14日目に完全に阻害され、この用量での持続的曝露と一致した。1mg/kgを投与された動物は、2日目に完全な阻害を示し、7日目に部分的な阻害を示し、14日目には阻害を示さなかった。薬力学的効果の経時的な消失は、低い投与群において抗体のクリアランスがより速いことと相関する。
CD40は、ヒト血小板において構成的に発現している(Henn, et al., 2001及びInwald, et al., 2003)が、CD40Lは、活性化血小板の細胞表面に迅速かつ一過性に発現している(Henn, et al., 2001)。FcγR結合性を有さない抗CD40抗体は、血小板に対する効果を有するとは予想されないであろうが、これが事実であることを直接実証することが重要である。フローサイトメトリー研究を行い、抗CD40リード候補のヒト及びカニクイザル血小板への結合を実証した。
ヒト化抗体である抗体Aの効力を、移植片対宿主応答を生じさせるために、ヒトPBMCを免疫不全NSGマウスに注射した抗体産生モデルにおいて評価した。ヒトIgM(hIgM)及びIgG(hIgG)の顕著な産生を生着後2週間から検出することができる。抗体Aを5及び1mg/kgの用量で処置すると、生着後2週目及び3週目において、hIgG及びhIgM応答が顕著に阻害された。対照抗体(4D11)を5mg/kg単回投与で評価し、該応答の消失も示された。第2の研究では、全ての抗体である抗体A、抗体B及び抗体Cを1mg/kgの単回用量で試験し、2週目にIgM及びIgG応答の完全な阻害が示された。
レセプターのアップレギュレーション:レセプターのCD40L誘引アップレギュレーションは、フローサイトメトリーにより測定することができる。ヒト全血を可溶性CD40Lの最適化された濃度により刺激することができ、CD20+レセプター+細胞の完全な割合をフローサイトメトリーにより測定することができる。CD20陽性細胞におけるCD86発現の割合の変化を、抗体A及びBを評価するカニクイザルpk研究と並行して測定した。データから、抗体の曝露と一致する時点でのCD86アップレギュレーションの阻害が示される。
一部の例では、本発明の抗体の抗腫瘍特性を決定するのが望ましい場合がある。このような決定は、SCIDマウスリンパ腫異種移植モデルにおいてヒト化抗CD40抗体の抗腫瘍活性をアッセイすることにより行うことができる。このようなSCIDモデルは腫瘍を提示するためにガン細胞を注射することができ、例えば、薬剤処置を開始する13日前に、5×106百万個 腫瘍細胞をSCIDマウス(10匹/群)に皮下注射することができる。本発明のマウス抗CD40抗体又は比較(例えば、対照又は他のヒト化抗体)を週3回(4mg/kg/投与)腹腔内に与える。8又は5回投与した。腫瘍の発生及び成長をマウスにおいてモニターし、腫瘍容積を選択された研究期間、例えば、14日間の研究期間中に毎週測定することができる。好ましくは、結果から、本発明の抗体により処置されたマウスと比較して、対照マウスにおける腫瘍の増殖の2、3、4、5、6、7、8、9、10倍以上の増加を示すであろう。好ましくは、処置期間にわたって、本発明の抗体で処置されたマウスにおける腫瘍増殖は無視できるであろう。このようなデータは、試験されるヒト化抗体がこのBリンパ腫異種移植モデルにおける腫瘍増殖をサプレッションするのに有効であることを裏付けることができる。
腫瘍を有するマウス、例えば、上記されたマウスの生存に対するヒト化抗CD40抗体の効力をSCIDマウスリンパ腫異種移植モデルにおいてアッセイすることができる。SCIDマウス(10匹/群)に、抗体処置の3日前に1×106百万個 腫瘍細胞を静脈内接種させた。ついで、マウスを本発明のマウスもしくはヒト化抗CD40抗体又はIg対照により処置し、週2回(4mg/kg/投与)腹腔内に投与する。合計5回投与する。ついで、ガンを有する対象の生存延長における抗体の効力のレベルを決定するために、死亡率についてマウスケージを毎日調べることができる。
この無作為化プラセボ対照二重盲検研究の目的は、健常な対象において、80、120、180又は240mg 本発明の抗体を週1回SC投与する4週間反復投与の安全性、許容性、薬物動態(PK)及び薬力学(PD)を決定することであった。
研究設計
この第1相研究について、参加施設及びニュージーランド保健当局の独立倫理委員会の承認を受け、参加対象全員からインフォームド・コンセントを得た。該研究は、Boehringer Ingelheimの後援で行われ、Auckland, New Zealandにある1か所の試験施設において、Auckland Clinical Studies Ltdにより行われた。
ボディマスインデックスが18.5〜29.9kg/m2の18〜60歳の適格な対象を登録した。女性参加者は、閉経後、不妊手術を受けた、性交渉を禁じている、精管切除された性交渉のパートナーを有する又は研究薬剤投与前30日以上かつ研究終了後30日までは受けている避妊法を行っている、研究前及び研究期間中に妊娠検査が陰性である必要があった。
本発明の抗体の血漿濃度を、30ng/mlの定量下限を有する有効なサンドイッチ酵素結合免疫吸着アッセイ(ELISA)を使用して分析した。96ウェルマイクロタイタープレートを、最初に、本発明の抗体に対する抗体で被覆し、ブロッキングし、洗浄した。ついで、このプレートを、研究サンプル、キャリブレーター又は品質管理サンプルと共にインキュベーションし、再度洗浄した。本発明の抗体の結合を、本発明の抗体に対するビオチン化抗体、続けて、西洋ワサビペルオキシダーゼとコンジュゲートさせたストレプトアビジン、最後に、ペルオキシダーゼ基質であるテトラメチルベンジジンにより検出された。プレートを比色法で読み取り、データを5パラメーターロジスティックフィットにより分析した。定量範囲は、30〜800ng/mLであった。十分な正確さ及び精度を3つの濃度−低濃度(50又は100ng/mL)、中濃度(126又は200ng/mL)及び高濃度(500又は590ng/mL)での品質管理サンプルによるルーチンな分析中に評価した。ELISAの再現性を、93% サンプルが許容基準(平均値から30%以下の差)に合格した、重複したサンプルの再分析により試験した。
本発明の抗体についての血漿濃度−時間データを、WinNonlin(商標)(バージョン5.02、Gary, NC, USA)を使用する非コンパートメントアプローチにより分析した。決定されたパラメーターは、標準的なWinNonlin(商標)手法を使用する、Cmax、Cmaxを達成するための時間(tmax)、最終排除定数(λz)及び終末t1/2を含んだ。最後の(4回目の)投与後の均一な投与間隔τにわたる濃度−時間曲線下面積(AUC0−τ)を、WinNonlin(商標)の線形アップログダウンアルゴリズムを使用して計算した。蓄積比(RA、Cmaxに基づくCmax;RA、AUC0−τに基づくAUC)を初回投与後の値に対する4回目投与後の値の比として計算した。
薬力学評価には、本発明の抗体によるCD40 ROの評価と、前述の有効なFACSアッセイを使用して全血中のCD54のmegaCD40L誘引アップレギュレーションにより測定されたB細胞活性化の阻害とを含ませた。本発明の抗体の用量とCD40 RO及びCD54アップレギュレーションの阻害との間の関係は、標準的なS字状Emaxモデルを使用して以前に調査され、Albach et al. Eur J Clin Pharmacol. 2018;74(2):161-169に報告されている。
本発明の抗体の安全性及び一般的な許容性を、処置−出現有害イベント(AE)、身体検査、バイタルサイン(血圧及び脈拍)、12誘導心電図(ECG)及び臨床検査(血液学、臨床化学及び尿検査)をモニターすることにより評価した。
正式なサンプル数の決定は行っておらず、PK及び安全性の分析には、投与群あたりに8名の対象で十分であると考えられた。安全性、PK及びPDについて、研究結果を、記述統計量を使用して分析した。安全性集団には、治験薬(本発明の抗体又はプラセボ)が投与された全ての対象を含ませた。PK集団及びPD集団には、治験薬が投与され、PK分析及びPD分析それぞれのための評価可能なデータが得られた全ての対象を含ませた。4回目投与後のAUC0−τ及びCmaxの用量比例性を、パワーモデルを使用して評価した。傾きの95%信頼区間(CI)を計算した。完全な用量比例性は、1の傾きパラメータ(β)により定義された。濃度データのグラフ表示を含む記述分析を行って、定常状態が達成されたかどうかを評価した。
対象
合計40名の健常な対象を無作為化し、本研究において処置した。対象に、プラセボ(n=8)、80mg 本発明の抗体(n=8)、120mg 本発明の抗体(n=8)、180mg 本発明の抗体(n=8)又は240mg 本発明の抗体(n=8)を4週間にわたって週1回の反復SC処置を受けさせた。40名全ての対象が予定観察期間を完了し、早期中止例はなかった。対象の大半は、男性(83%)及び白人(73%)であり、平均(標準偏差[SD])年齢は、30(10.8)であり、平均(SD)ボディマスインデックスは、25(3.1)kg/m2であった。処置群間に関連性のある人口統計学的差異は存在しなかった。
幾何平均(gMean)である、 初回SC投与(1日目)及び最後のSC投与(4日目)投与後の本発明の抗体について選択されたPKパラメーターを表9.2に示す。初回投与後、tmaxの中央値は、週1回の投与ごとに向上したが、tmaxは、4回目の投与後(tmax,4)に明確な用量相関性を何ら示さなかった。投与用量について正規化された最大血漿濃度及びAUC(それぞれ、Cmax,norm,4及びAUCτ,norm,4)は、本発明の抗体の80mg投与群についてより低く、3つのより高い投与群について同様であった。このことから、80mgから120mgへの曝露の比例的増加より大きいが、120mgを超える用量については用量比例動態に近いことが示唆された。Cmax又はAUCに基づく幾何平均蓄積比(それぞれ、RA,Cmax,4及びRA,AUC,4)を決定して、4回の反復投与後の本発明の抗体の蓄積を評価した。80mgでの4回の週1回のSC投与後、RA,Cmax,4及びRA,AUC,4値は、単回投与後よりそれぞれ8.3倍及び11.6倍高かった。このことは、本発明の抗体の蓄積を示した。gMean蓄積は、3つの高用についてより低かった(範囲:RA,Cmax,4について3.7及びRA,AUC,4について4.9〜5.8)。本発明の抗体の終末t1/2は、156〜199時間(6〜8日)の範囲であった。トラフ濃度の目視検査から、定常状態には、いずれの用量でも達しないことが示唆された。全ての投与群についての血漿中トラフ濃度が、その後の投与毎に上昇し続けた(図2)。
本発明の抗体の投与により、用量依存性CD40 RO及びCD54アップレギュレーションの阻害がもたらされた(図3)。
AEの全体的な頻度及び強度は、本発明の抗体処置群において類似していた(全ての本発明の抗体投与[78%]及びプラセボ群[88%])。重篤なAE、重度のAE又は投与中止もしくは死亡に至ったAEは報告されなかった。対象数は少なかったが、本発明の抗体投与、処置関連AE又はAEの頻度及び強度の間に何らの関係もないようであった。感染が、本発明の抗体を受けた8名の対象(25%)及びプラセボを受けた5名の対象(63%)において報告された。血栓塞栓性イベントはなかった。最も頻繁に報告された処置関連AEは、頭痛であり、本発明の抗体を受けた4名(13%)及びプラセボを受けた2名(25%)において報告された。全てのAEは、軽度又は中等度であり、全て回復した。
この研究の目的は、健常な対象において、本発明の抗体(80〜240mg/週)の4週間の上昇SC投与の効果を調査することであった。PKパラメーターの評価から、本発明の抗体の120〜240mgSC投与は動力学がほぼ比例することが示されたが、本発明の抗体の単回IV投与後に、以前の研究で観察されたように、ターゲット媒介性薬剤クリアランスによる80〜120mgのSC用量は動力学が超比例することが示された。その効果は、CD40レセプターの広い分布により増強され(特に、その短いt1/2を有する血小板)、アンタゴニスト抗CD40抗体による他の研究で以前に報告されている。Cmax(初回及び最後の投与後)及びAUC0−τ(最後の投与後)について、本発明の抗体のSC用量範囲120〜240mgにわたって、ほぼ比例した用量−暴露関係が観察された。ここで、両パラメーターについての傾きβ=1.2であった。このことは、おそらく、CD40 ROがこれらの用量で飽和に近いことを示している。80mg及び120mg 本発明の抗体の初回SC投与後に達成された血漿曝露は、健常なボランティアにおける以前の単一上昇用量研究で観察されたものと同様であった。ここで、gMean AUC値120μg・h/mL及び888μg・h/mLがそれぞれ、80mg及び120mg 本発明の抗体の単一SC投与により得られた。本発明の抗体の蓄積が、単回投与(初回投与)の投与と比較して、反復投与後の全ての用量レベルで観察された。一方、120〜240mg 用量では、より低い蓄積が観察され、比較的一定のgMean RA,Cmax値3.7〜4及びgMean RA,AUC値4.9〜6が得られた。投与されたいずれの用量についても、4週間以内に定常状態に達しなかった。モデリングから、120mg 本発明の抗体を週1回投与する場合、定常状態に達するのに12週間かかることが示された(論文準備中)。約12週間以内に定常状態に達するという予測は、120mg 本発明の抗体を週1回12週間SCでの関節リウマチ患者の処置により確認されている。このことは、PK定常状態が約10〜12週間以内に達することが示している26。したがって、これにより、今後の臨床研究で定常状態をより迅速に達成するための負荷用量の使用が支持される。曝露パラメーターであるAUC及びCmaxについて、個体間変動は80mg 投与でより高く(gCV:56.4〜59.1%)、120mg及び180mg 投与で中等度であり(gCV:35.4〜37.4%)、240mg 投与でより低かった(gCV:21.9〜22.4%)。本発明の抗体は、SC注射部位からゆっくり吸収され、tmaxの中央値は、初回投与後に用量と共に増加した。4回目の投与後に、tmax,4との用量関係はなかった。本発明の抗体の反復投与後、推定終末t1/2は、6〜8日の範囲にあり、用量間に明らかな差はなかった。
健常な対象における4週間にわたる本発明の抗体の週1回の反復上昇SC投与後に、PKは、80mg〜120mgの用量についてのターゲット媒性介クリアランスのために、超比例的に増加したが、>120mg 用量についてはほぼ比例した。本発明の抗体の用量依存的蓄積により、今後の臨床研究においてより早く定常状態を達成するための負荷用量の使用が支持される。本発明の抗体は、CD40L誘引CD54アップレギュレーションの持続的な阻害を伴って、CD40−CD40L経路を遮断する可能性が高いことを示した。このため、更なる研究が、より長い投与間隔が自己免疫疾患、例えば、関節リウマチ、全身性エリテマトーデス又はループス腎炎に罹患している患者において臨床的に効率的であることができるかどうかを評価する必要があるであろう。80〜240mgの範囲にわたる本発明の抗体の反復上昇SC投与は、一般的には十分に許容され、急性免疫反応の関連する徴候は観察されなかった。
Claims (7)
- 対象における自己免疫疾患を処置する方法であって、
負荷用量を含む治療上有効量の抗CD40抗体を対象に投与することを含む、
方法。 - 抗CD40抗体が、
a)配列番号:9〜配列番号:11からなる群より選択される重鎖CDR1配列、配列番号:12〜配列番号:15からなる群より選択される重鎖CDR2配列及び配列番号:16〜配列番号:17からなる群より選択される重鎖CDR3配列と、
b)配列番号:18〜配列番号:21からなる群より選択される配列を有する軽鎖CDR1配列、配列番号:22〜配列番号:23の軽鎖CDR2配列及び配列番号:24〜配列番号:25からなる群より選択される軽鎖CDR3配列を含む、請求項1記載の方法。 - 前記抗体が、配列番号:10の重鎖CDR1配列、配列番号:13の重鎖CDR2配列及び配列番号:16の重鎖CDR3配列を含み、ここで、前記抗体が、配列番号:19の軽鎖CDR1配列、配列番号:22の軽鎖CDR2配列及び配列番号:24の軽鎖CDR3配列を含む、請求項1記載の方法。
- 抗CD40抗体が、配列番号:9の重鎖CDR1配列、配列番号:14の重鎖CDR2配列及び配列番号:16の重鎖CDR3配列を含み、ここで、前記抗体が、配列番号:20の軽鎖CDR1配列、配列番号:22の軽鎖CDR2配列及び配列番号:24の軽鎖CDR3配列を含む、請求項1記載の方法。
- 抗CD40抗体が、配列番号:11の重鎖CDR1配列、配列番号:15の重鎖CDR2配列及び配列番号:17の重鎖CDR3配列を含み、前記抗体が、配列番号:21の軽鎖CDR1配列、配列番号:23の軽鎖CDR2配列及び配列番号:25の軽鎖CDR3配列を含む、請求項1記載の方法。
- 抗CD40抗体が、
配列番号:44の重鎖可変領域及び配列番号:43の軽鎖可変領域、
配列番号:53の重鎖可変領域及び配列番号:52の軽鎖可変領域又は
配列番号:58の重鎖可変領域及び配列番号:56の軽鎖可変領域を含む、請求項1記載の方法。 - 抗CD40抗体が、
配列番号:30の重鎖及び配列番号:26の軽鎖、
配列番号:35の重鎖及び配列番号:31の軽鎖又は
配列番号:40の重鎖及び配列番号:36の軽鎖を含む、請求項1記載の方法。
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US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
US4275149A (en) | 1978-11-24 | 1981-06-23 | Syva Company | Macromolecular environment control in specific receptor assays |
US4318980A (en) | 1978-04-10 | 1982-03-09 | Miles Laboratories, Inc. | Heterogenous specific binding assay employing a cycling reactant as label |
JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
WO1981001145A1 (en) | 1979-10-18 | 1981-04-30 | Univ Illinois | Hydrolytic enzyme-activatible pro-drugs |
US4419446A (en) | 1980-12-31 | 1983-12-06 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant DNA process utilizing a papilloma virus DNA as a vector |
US4485045A (en) | 1981-07-06 | 1984-11-27 | Research Corporation | Synthetic phosphatidyl cholines useful in forming liposomes |
NZ201705A (en) | 1981-08-31 | 1986-03-14 | Genentech Inc | Recombinant dna method for production of hepatitis b surface antigen in yeast |
US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
US4601978A (en) | 1982-11-24 | 1986-07-22 | The Regents Of The University Of California | Mammalian metallothionein promoter system |
US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
US4486414A (en) | 1983-03-21 | 1984-12-04 | Arizona Board Of Reagents | Dolastatins A and B cell growth inhibitory substances |
DD266710A3 (de) | 1983-06-06 | 1989-04-12 | Ve Forschungszentrum Biotechnologie | Verfahren zur biotechnischen Herstellung van alkalischer Phosphatase |
US4544545A (en) | 1983-06-20 | 1985-10-01 | Trustees University Of Massachusetts | Liposomes containing modified cholesterol for organ targeting |
US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
US4965199A (en) | 1984-04-20 | 1990-10-23 | Genentech, Inc. | Preparation of functional human factor VIII in mammalian cells using methotrexate based selection |
US4879231A (en) | 1984-10-30 | 1989-11-07 | Phillips Petroleum Company | Transformation of yeasts of the genus pichia |
US4737456A (en) | 1985-05-09 | 1988-04-12 | Syntex (U.S.A.) Inc. | Reducing interference in ligand-receptor binding assays |
EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
GB8610600D0 (en) | 1986-04-30 | 1986-06-04 | Novo Industri As | Transformation of trichoderma |
US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
GB8705477D0 (en) | 1987-03-09 | 1987-04-15 | Carlton Med Prod | Drug delivery systems |
US4816444A (en) | 1987-07-10 | 1989-03-28 | Arizona Board Of Regents, Arizona State University | Cell growth inhibitory substance |
US4975278A (en) | 1988-02-26 | 1990-12-04 | Bristol-Myers Company | Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells |
US5076973A (en) | 1988-10-24 | 1991-12-31 | Arizona Board Of Regents | Synthesis of dolastatin 3 |
US4978744A (en) | 1989-01-27 | 1990-12-18 | Arizona Board Of Regents | Synthesis of dolastatin 10 |
FR2646437B1 (fr) | 1989-04-28 | 1991-08-30 | Transgene Sa | Nouvelles sequences d'adn, leur application en tant que sequence codant pour un peptide signal pour la secretion de proteines matures par des levures recombinantes, cassettes d'expression, levures transformees et procede de preparation de proteines correspondant |
US4879278A (en) | 1989-05-16 | 1989-11-07 | Arizona Board Of Regents | Isolation and structural elucidation of the cytostatic linear depsipeptide dolastatin 15 |
US4986988A (en) | 1989-05-18 | 1991-01-22 | Arizona Board Of Regents | Isolation and structural elucidation of the cytostatic linear depsipeptides dolastatin 13 and dehydrodolastatin 13 |
EP0402226A1 (en) | 1989-06-06 | 1990-12-12 | Institut National De La Recherche Agronomique | Transformation vectors for yeast yarrowia |
US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
US5138036A (en) | 1989-11-13 | 1992-08-11 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Isolation and structural elucidation of the cytostatic cyclodepsipeptide dolastatin 14 |
US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
JP4124480B2 (ja) | 1991-06-14 | 2008-07-23 | ジェネンテック・インコーポレーテッド | 免疫グロブリン変異体 |
US5874082A (en) * | 1992-07-09 | 1999-02-23 | Chiron Corporation | Humanized anti-CD40 monoclonal antibodies and fragments capable of blocking B cell proliferation |
DE69315847T2 (de) | 1992-08-21 | 1998-06-25 | Genentech Inc | Verfahren zur behandlung einer durch lfa-1 vermittelten störung |
RO118524B1 (ro) | 1992-11-13 | 2003-06-30 | Idec Pharmaceuticals Corp San | Metoda pentru tratarea unei tulburari legata de celulele b |
US6034065A (en) | 1992-12-03 | 2000-03-07 | Arizona Board Of Regents | Elucidation and synthesis of antineoplastic tetrapeptide phenethylamides of dolastatin 10 |
US5635483A (en) | 1992-12-03 | 1997-06-03 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Tumor inhibiting tetrapeptide bearing modified phenethyl amides |
US5410024A (en) | 1993-01-21 | 1995-04-25 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Human cancer inhibitory pentapeptide amides |
US5780588A (en) | 1993-01-26 | 1998-07-14 | Arizona Board Of Regents | Elucidation and synthesis of selected pentapeptides |
US5504191A (en) | 1994-08-01 | 1996-04-02 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Human cancer inhibitory pentapeptide methyl esters |
US5530097A (en) | 1994-08-01 | 1996-06-25 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Human cancer inhibitory peptide amides |
US5521284A (en) | 1994-08-01 | 1996-05-28 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Human cancer inhibitory pentapeptide amides and esters |
US5554725A (en) | 1994-09-14 | 1996-09-10 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Synthesis of dolastatin 15 |
US5599902A (en) | 1994-11-10 | 1997-02-04 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Cancer inhibitory peptides |
US5663149A (en) | 1994-12-13 | 1997-09-02 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Human cancer inhibitory pentapeptide heterocyclic and halophenyl amides |
US6096871A (en) | 1995-04-14 | 2000-08-01 | Genentech, Inc. | Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life |
US6130237A (en) | 1996-09-12 | 2000-10-10 | Cancer Research Campaign Technology Limited | Condensed N-aclyindoles as antitumor agents |
US6037454A (en) | 1996-11-27 | 2000-03-14 | Genentech, Inc. | Humanized anti-CD11a antibodies |
US6239104B1 (en) | 1997-02-25 | 2001-05-29 | Arizona Board Of Regents | Isolation and structural elucidation of the cytostatic linear and cyclo-depsipeptides dolastatin 16, dolastatin 17, and dolastatin 18 |
US5888809A (en) | 1997-05-01 | 1999-03-30 | Icos Corporation | Hamster EF-1α transcriptional regulatory DNA |
US6323315B1 (en) | 1999-09-10 | 2001-11-27 | Basf Aktiengesellschaft | Dolastatin peptides |
WO2001024823A1 (en) * | 1999-10-04 | 2001-04-12 | Chiron Corporation | Cd40 antagonist for treating psoriasis |
US7256257B2 (en) | 2001-04-30 | 2007-08-14 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
WO2003029296A1 (en) * | 2001-10-02 | 2003-04-10 | Chiron Corporation | Human anti-cd40 antibodies |
KR101192496B1 (ko) | 2003-11-06 | 2012-10-18 | 시애틀 지네틱스, 인크. | 리간드에 접합될 수 있는 모노메틸발린 화합물 |
WO2006125117A2 (en) * | 2005-05-18 | 2006-11-23 | Novartis Ag | Methods for diagnosis and treatment of diseases having an autoimmune and/or inflammatory component |
BR112018001907A2 (pt) * | 2015-09-01 | 2018-09-25 | Boehringer Ingelheim Int | uso de anticorpos anti-cd40 para o tratamento de nefrite lúpica |
EP4213939A1 (en) * | 2020-09-21 | 2023-07-26 | Boehringer Ingelheim International GmbH | Use of anti-cd40 antibodies for treatment of inflammatory conditions |
-
2019
- 2019-06-28 KR KR1020217003107A patent/KR20210027436A/ko unknown
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- 2019-06-28 US US17/252,175 patent/US20210261678A1/en not_active Abandoned
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- 2019-06-28 EP EP19740274.6A patent/EP3813950A1/en active Pending
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013523130A (ja) * | 2010-03-31 | 2013-06-17 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 抗cd40抗体 |
Non-Patent Citations (1)
Title |
---|
EUR. J. CLIN. PHARMACOL., vol. 74, [2], JPN6023019449, February 2018 (2018-02-01), pages 161 - 169, ISSN: 0005058842 * |
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CN112334195A (zh) | 2021-02-05 |
EA202190094A1 (ru) | 2021-04-21 |
MX2020013885A (es) | 2021-03-09 |
PH12020552235A1 (en) | 2021-06-28 |
BR112020024078A2 (pt) | 2021-02-17 |
KR20210027436A (ko) | 2021-03-10 |
US20210261678A1 (en) | 2021-08-26 |
EP3813950A1 (en) | 2021-05-05 |
CA3101469A1 (en) | 2020-01-02 |
AU2019291890A1 (en) | 2020-12-17 |
CL2020003348A1 (es) | 2021-07-19 |
WO2020006347A1 (en) | 2020-01-02 |
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