JP2014509837A - 抗cd38抗体 - Google Patents
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- JP2014509837A JP2014509837A JP2013547710A JP2013547710A JP2014509837A JP 2014509837 A JP2014509837 A JP 2014509837A JP 2013547710 A JP2013547710 A JP 2013547710A JP 2013547710 A JP2013547710 A JP 2013547710A JP 2014509837 A JP2014509837 A JP 2014509837A
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Abstract
【選択図】図11
Description
本願は、2010年12月30に出願されたUSSN61/428,699;2011年3月31日に出願されたUSSN61/470,382;2011年3月31日に出願されたUSSN61/470,406;及び2011年5月11日に出願されたUSSN61/485,104の35U.S.C.§119(e)下での利益を主張し、これらの出願は全て、その全体が参照によって本明細書に援用される。
本明細書では、CD38に結合するための試薬及び方法、並びにCD38特異的抗体を含むCD38特異的結合剤を用いた、CD38関連疾患の治療方法及びCD38の検出方法を提供する。
概説
CD38の細胞外ドメインは、ADPリボシルシクラーゼ活性とADPリボシルヒドロラーゼ活性の両方を有する、二機能(bifunctional)酵素活性を有することが示されている。従って、CD38は、NAD+のcADPRへの変換を触媒でき(シクラーゼ)、さらにそれをADPリボースに加水分解できる(ヒドロラーゼ)。cADPRは、細胞増殖、分化及びアポトーシスに重要なセカンドメッセンジャーアクティビティーであるカルシウムの細胞内ストアからの動員に機能する。
従って、本発明は、ヒトCD38タンパク質に特異的に結合する(及び、以下に記載のとおり、追加として、好ましくは、霊長類CD38タンパク質に特異的に結合する)単離された抗CD38抗体を提供する。当分野で既知のとおり、CD38タンパク質は多数の種で見られる。本発明で特に有用なものは、ヒトCD38タンパク質と霊長類CD38タンパク質、特に、臨床試験で使用される霊長類、例えば、カニクイザル(マカカ・ファシキュラリス(Macaca fascicularis)、カニクイザル(Crab eating macaque)、本明細書では「サイノ」(cyno)と称する場合もある)などのCD38タンパク質の両方に結合する抗体である。「ヒトCD38」又は「ヒトCD38抗原」とは、配列番号1、又はエピトープなどの機能性断片(本明細書で定義するとおり)のタンパク質を意味する。一般に、CD38は、短い細胞質内テイル、膜貫通ドメイン及び細胞外ドメインを有し、特定の実施態様において、本発明の抗体は、CD38タンパク質の細胞外部分と結合する。本明細書において「カニクイザルCD38」とは、ヒトCD38と92%同一である配列番号2を意味する。
本発明は、抗CD38抗体、通常は本明細書に記載のとおり、治療及び/又は診断抗体を提供する。本発明での使用が発見される抗体は、本明細書に記載のとおり、多数のフォーマットをとることができ、これには、従来の抗体、並びに抗体誘導体、断片及び模倣物(mimetics)(以下に記載)が挙げられる。原則として、本発明は、本明細書で定義するとおり6個のCDRのセット(以下に記載のとおり、少数のアミノ酸の変化を含む)を含む抗体構造を提供する。
いくつかの実施態様において、抗体は異なる種由来の混合物であってよく、例えば、キメラ抗体及び/又はヒト化抗体などであってよい。すなわち、本発明において、CDRセットは、本明細書において配列により具体的に記載されるもの以外のフレームワーク及び定常領域とともに使用されてよい。
本発明は、さらに変異抗体も提供する。すなわち、本発明の抗体は多数の修飾がなされてよく、これには、CDRにおけるアミノ酸修飾(親和性成熟)、Fc領域におけるアミノ酸修飾、グリコシル化変異体、他のタイプの共有結合修飾などが挙げられるが、これらに限定されない。
別のタイプの共有結合修飾は、グリコシル化での変更である。別の実施態様において、本明細書で開示する抗体は、1つ以上の改変糖型(engineered glycoform)を含むよう修飾され得る。本明細書で使用される場合、「改変糖型」とは抗体と共有結合した炭水化物組成物を意味し、ここで、前記炭水化物組成物は、化学的に親抗体のものとは異なる。改変糖型は、エフェクター機能の増強又は低下を含む(これらに限定されない)種々の目的のために有用であり得る。改変糖型の好ましい形態は、アフコシル化(afucosylation)であり、これは、おそらくFcγRIIIaレセプターへの強固(tighter)な結合を介して、ADCC機能の増加と関連することを示している。これに関連して、「アフコシル化」とは、宿主細胞で製造される抗体の大多数が、実質的にフコースを欠いていることを意味し、例えば、作製された抗体の90〜95〜98%が、抗体の炭水化物部分(通常、Fc領域のN297で結合される)の成分として相当量(appreciable)のフコースを有さないことを意味する。機能的に定義すると、アフコシル化抗体は、通常、FcγRIIIaレセプターに対して、少なくとも50%以上の親和性を示す。
本発明は、それぞれ特定のCDRセット(上記で概説するように、いくつかのアミノ酸置換を含む)を有する多数の抗体を提供する。上記で概説するように、抗体は、6つのCDRのセット、可変領域、又は全長の重鎖及び軽鎖(定常領域を含む)により定義され得る。さらに、上記で概説するように、アミノ酸置換がなされてもよい。一般に、CDR内の変化との関連で、アミノ酸修飾は、CDRの長さが比較的短いことに起因して、なされ得るアミノ酸修飾の数に関して通常記載される。これは、可変、定常又は全長配列に導入され得るアミノ酸修飾の数の議論にも適用できる一方、変化の数に加えて、「%同一性」に関してこれらの変化を定義することも適切である。従って、本明細書に記載されるように、本発明内に含まれる抗体は、本明細書に列挙した配列番号と80、85、90、95、98又は99%同一である。
開示する抗体は、リガンド−レセプター相互作用のブロック、又はレセプターコンポーネント相互作用の阻害での使用が見出され得る。本発明の抗CD38は、「遮断(blocking)」又は「中和」するものであってよい。「中和抗体」は、CD38への結合により、CD38の生物活性、例えば、リガンドと相互作用する能力、酵素活性、シグナリング能力、及び特に活性化リンパ球を生じさせる能力を阻害する抗体を意味することが意図される。CD38の生物活性の阻害は、当分野で既知の複数の標準的in vitro又はin vivoアッセイの1つ以上により評価され得る(以下の実施例を参照されたい)。
本発明は、開示する抗CD38抗体の製造方法をさらに提供する。これらの方法は、本発明の抗体をコードする、1つ以上の単離された核酸を含む宿主細胞を培養する工程を含む。当業者に理解されるように、これは、抗体の特性に応じて、様々な方法で実施され得る。いくつかの実施態様において、本発明の抗体が全長の従来の抗体である場合、例えば、重鎖可変領域及び軽鎖可変領域である場合には、例えば、抗体が製造され、単離可能な条件下で実施される。
本発明の抗体が作製された場合には、CD38関連疾患の診断及びその治療を含む様々な適用での使用が見出される。
一つの側面において、本発明は、炎症性疾患及び免疫疾患と関連する病態を診断及び治療する方法を提供し、特に、活性化リンパ球と関連する疾患の診断及び治療方法を提供する。本明細書に示すように、CD38は、未成熟な造血細胞で発現し、成熟細胞で下方制御され、活性化リンパ球及び形質細胞において高レベルで再発現する。例えば、CD38の高発現は、活性化B細胞、形質細胞、活性化CD4+T細胞、活性化CD8+T細胞、NK細胞、NKT細胞、成熟樹状細胞(DC)及び活性化単球で見られる。
B−CLLは、長年にわたり、持続的な形で骨髄及び末梢血に蓄積する反応不顕性の単クローン性B系細胞の進行性の増加により特徴付けられる難病である。CD38の発現は、B−CLLに対する独立した予後不良因子と考えられる。Hamblin et al.,Blood 99:1023−9(2002)。
多発性骨髄腫は、骨髄における形質細胞の新生増殖により特徴付けられるB細胞系の悪性障害である。現在治療レジメンは、中等度の奏効率を示す。しかし、全体の生存率は横ばいでしかなく、平均生存期間はおよそ3年である。従って、多発性骨髄腫の治療に対して、未だ満たされていない重大な医学的ニーズが存在する。いくつかの実施態様において、開示する抗CD38抗体を用いた多発性骨髄腫の治療方法を提供する。
いくつかの実施態様において、開示抗体を用いた単クローン性免疫グロブリン血症の治療方法を提供する。他の実施態様において、開示抗体を用いたくすぶり型多発性骨髄腫の治療方法を提供する。
本発明に従って使用される抗体の製剤は、任意選択で医薬上許容される担体、賦形剤又は安定化剤とともに、所望の純度を有する抗体を混合することにより保存のために凍結乾燥製剤又は水溶性の形態で調製される(Remington’s Pharmaceutical Sciences 16th edition,Osol,A.Ed.[1980])。許容される担体、賦形剤又は安定化剤は、実施される用量及び濃度において、レシピエントに対して非毒性であり、リン酸、クエン酸及び他の有機酸などのバッファー;アスコルビン酸及びメチオニンを含む抗酸化剤;保存料(オクタデシルジメチルベンジルアンモニウムクロリド;ヘキサメトニウムクロリド;ベンザルコニウムクロリド、ベンゼトニウムクロリド;フェノール、ブチル又はベンジルアルコール:アルキルパベン(メチル又はプロピルパラベンなど);カテコール;レゾルシノール;シクロヘキサノール;3−ペンタノール;及びm−クレゾールなど);低分子量(約10残基未満)ポリペプチド;タンパク質(血清アルブミン、ゼラチン又は免疫グロブリンなど);親水性ポリマー(ポリビニルピロリドンなど);アミノ酸(グリシン、グルタミン、アスパラギン、ヒスチジン、アルギニン又はリシンなど);単糖、二糖及び他の炭水化物(グルコース、マンノース又はデキストリンを含む);キレート化剤(EDTAなど);糖類(スクロース、マンニトール、トレハロース又はソルビトールなど);塩形成カウンターイオン(ナトリウムなど);金属錯体(例えば、Zn−タンパク質錯体);及び/又は非イオン性界面活性剤(TWEEN(商標)、PLURONICS(商標)又はポリエチレングリコール(PEG)など)が挙げられる。
本発明の抗体及び化学療法剤は、既知の方法に従って対象に投与され、例えば、ボーラスとして又は一定期間にわたる持続注入による静脈内投与、筋肉内、腹腔内、脳髄腔内(intracerobrospinal)、皮下、関節内、滑液内、クモ膜下腔内、経口、局所又は吸入による経路により患者に投与される。抗体の静脈内又は皮下投与が好ましい。
本発明の方法において、治療は、疾患又は病態に対する正の治療応答(positive therapeutic response)を提供するために使用される。「正の治療応答」とは、疾患若しくは病態の改善、及び/又は疾患若しくは病態と関連する症状の改善を意図する。例えば、正の治療応答は、疾患における以下の改善の1つ以上を意味し得る:(1)新生細胞数の減少;(2)新生細胞死の増加;(3)新生細胞生存の阻害;(5)腫瘍増殖の阻害(すなわち、ある程度遅らせる、好ましくは停止);(6)患者生存率の増加;及び(7)疾患又は病態と関連する1つ以上の症状のある程度の緩和。
提供する抗CD38抗体は、CD38と関連する腫瘍又は自己免疫疾患病態のin vitro又はin vivoイメージングでの使用も見出される。いくつかの実施態様において、本明細書の記載の抗体は、診断及び治療のために使用され、又は診断のみに使用される。抗CD38抗体を診断と治療の両方に使用する場合には、いくつかの実施態様は、診断抗体が治療抗体との結合に競合しないように、2つの異なるエピトープに対する2つの異なる抗CD38抗体に依拠するが、とはいえ、いくつかの場合では同一の抗体を両方の目的のために使用できる。例えば、いくつかの例において、Ab19抗体を診断的(通常、以下に記載のように標識される)に使用し、一方でAb79を治療的に使用するか、逆もまた同様である。従って、本発明に含まれる組成物は、診断抗体と治療抗体を含むものであり、いくつかの実施態様においては、診断抗体は本明細書に記載のように標識される。さらに、治療抗体と診断抗体の組成物は、本明細書で概説するように、他の薬物と同時投与されてもよい。
他の実施態様において、上述の障害の治療に有用な物質を含む製品を提供する。当該製品は、容器とラベルを含む。適した容器としては、例えば、ボトル、バイアル、シリンジ及び試験管などが挙げられる。容器は、ガラスやプラスチックなど様々な物質から成型されてよい。容器は、病態の治療に有効な組成物を保持し、滅菌アクセスポート(例えば、容器は、皮下注射針による穿刺可能なストッパーを有する注入可能な溶液バッグ又はバイアルであってよい)を有してよい。組成物中の活性剤は抗体である。容器上に又は容器に付随するラベルは、組成物が、選択する病態の治療に使用されることを示す。製品はさらに、リン酸緩衝生理食塩水、リンガー溶液、デキストロース溶液などの医薬上許容されるバッファーを含む第二の容器を含んでよい。製品は、商業上及びユーザーの点から見て好ましい他の物質をさらに含んでよく、これには、他のバッファー、希釈剤、フィルター、ニードル、シリンジ及び使用方法を記載した添付文書が挙げられる。
ヒトCD38(huCD38)を発現するベクターを構築するために、huCD38をコードするポリヌクレオチドをOrigene Technologies Trueclone(登録商標)humanから得たcDNAから単離した。G418(Geneticin)耐性トランスフェクタントの選択を可能にするネオマイシン耐性(neoR)遺伝子を含む安定な発現ベクター(XOMA,Inc.)に単離したhuCD38をクローニングした。選択されたトランスフェクタントに存在するhuCD38遺伝子をシーケンシングして、任意の配列エラーを同定した。GenbankアクセッションNM_001775から外れた配列エラーをPCR部位特異的変異導入により訂正した。最終的なベクターDNAを5’シーケンシングにより確認した。
huCD38、muCD38及びcyCD38を発現するCHO細胞を開発するために、CHO細胞を直鎖化DNAでトランスフェクトした。選択下で一週間置いた後、フローサイトメトリーにより細胞をソーティングし、最も高いhuCD38、muCD38又はcyCD38発現細胞(最大15%)を96ウェルプレートに播種して、単一コロニーを生じさせた。残りの細胞も選択下で播種し、バックアップコロニーを生じさせた。播種してからおよそ12〜14日後に単一コロニーを同定し、96ディープウェルプレートに移した。第二継代後、FACS分析によりクローンをスクリーニングした。トップの産生クローンを継代し、振とうフラスコに広げた。マイコプラズマAVA試験及びスケールアップのために、トップの2クローンを凍結及び/又は培養した。
標的特異抗体のファージディスプレイライブラリーからの選択は、Marksらにより記載される方法(2004,Methods Mol.Biol.248:161−76)に従って実施した。簡単に述べると、ファージディスプレイライブラリーを室温で1時間、100pmolのビオチン化CD38とともにインキュベートし、次いで100μLのストレプトアジビンビーズ懸濁液(DYNABEADS(登録商標)M−280 Streptavidin,Invitrogen)を用いて、形成した複合体を捕捉した。洗浄バッファー(PBS中5%ミルク)でビーズを洗浄することにより非特異的なファージを除去した。結合したファージを0.5mLの100nMトリエチルアミン(TEA)で溶出し、等量の1M TRIS−CI(pH7.4)を添加することによりすぐに中和した。溶出したファージプールを用いて、対数増殖期のTG1 E.coliに感染させ、Marksらの上記文献に記載のように、ファージミドをレスキューした。選択を計3ラウンド繰り返した。
約150のクローンをヒトIgG1抗体として再フォーマットし、以下に記載するとおり、アッセイのパネルを用いて、5つ(Ab19、Ab43、Ab72、Ab79及びAb110)を十分に評価した。In vitro及びin vivoアッセイの両方におけるIgG再フォーマットクローンのパフォーマンスを2つの抗体、BMTK4−1(ベンチマーク1、BM−1又はBMTK−1とも称する)(配列番号24及び25;重鎖及び軽鎖可変領域)及びBMTK4−2(ベンチマーク2、BM−2又はBMTK−2とも称する)(配列番号26及び27;重鎖及び軽鎖可変領域)と比較した。これらのアミノ酸配列は、それぞれ、既知の抗CD38抗体ダラツムマブ(HuMax−CD38とも称され、国際公開No.06/099875に開示される)及びSAR650984(国際公開No.08/047242に開示される)に由来した。呼吸系発疹ウイルスを認識する臨床的に認可された抗体であるパリビズマブ(SYNAGIS(登録商標))(Medlmmune)をCD38結合に対するネガティブコントロールとした。
Alexa Fluor(登録商標)488色素で標識されたAb79を正常ヒト結腸直腸組織、前立腺及びリンパ凍結切片に適用した。Alexa Fluor(登録商標)488色素で標識されたパリビズマブ(Synagis(登録商標))をネガティブ染色コントロールとした。得られた免疫蛍光像を図4に示す。正常ヒト結腸直腸組織、前立腺及びリンパ節において、Ab79について観察された染色パターンは、市販のポリクローナル抗CD38抗体で見られたものと同一であった(データ示さず)。
多発性骨髄腫患者由来の骨髄サンプルに対するAb79結合は、CD138+細胞の濃縮(enrichment)後か、或いはCD138+CD45−/lo細胞のゲーティングによるかのいずかによりフローサイトメトリーにより分析した(図7A)。Ab79は、6つの多発性骨髄腫サンプルのうち4つにおいて、>95%の細胞で発現が見られた。Ab79の結合パターンは、臨床検査室で使用された抗CD38抗体のものと、概して類似しているようであった。さらに、Ab79は、慢性リンパ性白血病罹患者由来の細胞と結合した(図7B)。
カニクイザル交差反応性クローンを、補体依存性細胞傷害(CDC)を誘導する能力について試験した。MOLP−8細胞を、50μLの完全培地(10%胎児ウシ血清を添加したRPMI)中、黒色の96ウェル平底組織培養プレートにウェル当たり10,000細胞の密度で播種した。50μLの2×抗CD38抗体、コントロールIgG抗体又は培地のみのものを各ウェルに添加し、室温で10分間インキュベートしておいた。細胞株に応じて量を変更した(2〜15μL)精製ウサギ補体(cat#CL3441 Cedarlane Laboratories,Canada)を、コントロールウェル以外の各ウェルに添加した。37℃で1時間インキュベートした後、プレートを室温にし、ウェル当たり100μLのセルタイターCytoTox Glo(商標)試薬(Promega G7571/G7573)を添加し、プレートを5〜7分間振とうさせ、発光をEnVision(登録商標)(Perkin Elmer)発光プレートリーダーで読み取った。試験条件:細胞のみ;細胞+補体;細胞+IgGコントロール+補体;細胞+抗体+補体。CDC%は、下記式を用いて計算した:
100−(RLUT/RLUC)×100
[式中、RLUTは、試験サンプルの相対発光単位(relative luminescence unit)であり、RLUCは、補体のみのサンプルの相対発光単位である]。統計分析はPRISMソフトウェアを用いて実施した。抗体濃度に対するCDC%をプロットすることにより決定されたEC50値を表1に示す。
抗体依存性細胞介在性細胞傷害(ADCC)は、標的細胞としてDaudi、MOLP−8及びRPMI−8226細胞株を用いて評価した。Stanford Blood Center(Palo Alto,CA)から得られた軟膜又はLRSから、Ficoll−Plaque(商標)分離によりエフェクター細胞としてPBMCを単離した。PBS中2%FBSを用いて試料を1:3希釈した。35mLの希釈試料の下に15mLのFicoll−Plaque(商標)(GE Healthcare)を徐々に層状にし、1800rpm(ブレーキオフ)で25分間遠心分離した。PBMCを含む濁った中間層を集め、PBS中2%FBSで3回洗浄し、10%DMSO/FBS中、アリコート当たり50×106細胞/mLのアリコートを凍結した。必要な場合には、凍結したPBMCアリコートを融解し、2×106/mLで、10%FBS/RMPI+5ng/mL 組換えヒトIL2(R&D systems #202−IL)中、一晩培養した。
(RLUT/RLUE/T)/(RLUL/RLUE/T)×100
[式中、RLUTは、試験サンプルの相対発光単位であり、RLUE/Tは、標的細胞及びエフェクター細胞のみを含むサンプルの相対発光単位であり、RLULは、TritonX−100で溶解した細胞についての相対発光単位である。]統計分析は、PRISMソフトウェアを用いて実施した。抗体濃度に対する特異的溶解%をプロットすることにより決定されたEC50値を表1に示す。
CD38を発現するMOLP−8細胞は、およそ200万細胞/mLの生存細胞濃度で、1%FBSバッファーに懸濁した。試験すべきmAbは、1×PBS中、2つの96ウェルプレート上、ウェルにわたって段階希釈(2倍)した。各滴定(titration)の最後のウェルは、バッファーのみを含んだ。最終体積が300〜L/ウェルとなり、各ウェルがおよそ100,000細胞含むように各ウェルに追加のPBS及び細胞懸濁液を追加した。mAbを下記に列挙し、滴定で使用した、対応する最終的なmAb結合部位濃度(2×分子濃度)範囲も示す:
ベンチマーク1、[mAb]結合部位=50.8nM〜49.7pM
ベンチマーク2、[mAb]結合部位=49.5nM〜48.3pM
Ab43、[mAb]結合部位=49.3nM〜48.2pM
Ab110、[mAb]結合部位=204nM〜49.9pM
Ab79、[mAb]結合部位=103nM〜25.3pM
Ab72、[mAb]結合部位=103nM〜25.2pM
Ab19、[mAb]結合部位=100nM〜12.2pM
プレートをプレートシェーカーに4℃で5時間置き、その後、プレートを1×PBSで4℃、3回洗浄した。次いで、200μLの99nM Cy5ヤギ抗ヒトIgG Fc特異ポリクローナル抗体(Jackson ImmunoResearch Laboratories,#109−175−008)を各ウェルに添加し、プレートを4℃で30分間振とうさせた。プレートを再度1×PBSで4℃、2回洗浄し、次いで、FACSCanto(商標)II HTSフローサイトメーターを用いて、独特のmAb結合部位濃度を含む各ウェルについて、5000イベントの平均蛍光強度(MFI)を記録した。抗体結合部位濃度の関数としての平均蛍光強度のプロットは、KDを見積もるための下記式を用いて、Scientist 3.0ソフトウェアで非線形フィッティングした:
F=p[(KD+LT+n(M))−{(KD+LT+n(M))2−4n(M)(LT)}1/2]/2+B
[式中、F(平均蛍光強度)、LT(トータルのmAb結合部位濃度)、p(mAbに結合する任意の蛍光単位に関する比例定数)、M(細胞内モル濃度;300μL中、100,000細胞に基づいて0.553fM)、n(細胞当たりのレセプター数)、B(バックグラウンドシグナル)、及びKD=平衡解離定数。]。
可溶性CD38エクトドメイン(ECD)に対するIgG抗体の親和性は、22℃、Biacore(商標)A100上で、表面プラズモン共鳴(SPR)分析により決定した。ヤギ抗ヒトIgGポリクローナル抗体(Caltag H10500)を、チップの4つ全てのフローセル内のスポット1、2、4及び5への標準的なアミンカップリングを用いて、CM5バイオセンサーチップに固定化した。各スポット上の固定化レベルは、5865RU〜6899RUの範囲であった。ヒトCD38はR&D Systems(Cat#2404−AC,Lot#PEH020812A)から得た。CD38のストック濃度は、Paceら((1995)“How to measure and predict molar absorption coefficient of a protein” Protein Science 4(11):2411−23 and Pace and Grimsley(2004)“Spectrophotometric determination of protein concentration”,in Current Protocols in Protein Science,Chapter 3: Unit 3.1)に詳述される方法を用いて決定した(各参考文献の教示は参照により本明細書に援用される)。
免疫蛍光技術を用いて、抗CD38抗体のMOLP−8細胞への内在化を評価した。MOLP−8細胞を集め、Alexa Fluor(登録商標)488に直接結合させた各抗CD38抗体1μgを用いて、RPMI−1640中、5×106細胞を4℃、10分間染色した。1%BSA含有PBSで細胞を洗浄し、1×106細胞を4℃又は37℃で3時間又は6時間インキュベートした。2μgのウサギ抗Alexa Fluor(登録商標)488抗体(Invitrogen)を用いて、4℃、30分間、表面染色をクエンチした。細胞を洗浄し、1%PFAを含むPBSで固定し、Microtest 96ウェルプレート(BD Biosciences)に移し、FACSCanto(商標)II(BD Biosciences)フローサイトメーターを用いたフローサイトメトリーにより評価するか、ImageXpress(登録商標)Micro(Molecular Devices)を20倍の倍率で用いて画像化するかのいずれか行った。
Biacore(登録商標)A100機器を用いて、2つのベンチマーク抗体とAb19及びAb79をビニングした。最初に、NHS/EDCカップリング化学を用いて、CM5チップ上に高密度及び低密度で抗体を固定化した。エピトープビニング実験の各サイクルについて、CD38をこれらの表面上に最初に注入した。次いで、ELISAフォーマットにおけるサンドイッチアッセイと類似して、独特の抗体(固定化抗体のセットから得られたもの)をCD38/抗体複合体を含む表面上に注入した。各サイクルの最後にリン酸パルスを用いて表面を再生した。BSA添加HBS−P(10 mM 10 HEPES pH 7.4、150 mM NaCI、0.005%)P−20を用いて、22℃でデータを集めた。得られたセンサーグラムをBiacore(登録商標) A100 Evaluationソフトウェアパッケージの「Epitope Mapping」モジュールとScrubber for A100データセットのトライアルバージョンを用いて処理した。再現データを使用して、表3に示すとおり、2つの別々の実験から上記4つのmAbに対する二元4×4マトリックスを作製した。
ヒトリンパ腫の播種性Daudi−ルシフェラーゼモデルについて、Ab19及びAb79のin vivo有効性を試験した。Taconic Laboratoriesから得た6〜8週齢のメスCB.17 SCIDマウスに1×106個のDaudi−Luc腫瘍細胞を静脈注射した。研究7日目に、パリビズマブ、Ab79、Ab19、ベンチマーク1及びベンチマーク2をマウス腹腔内に注射した。IVIS Xenogen system(Caliper Life Sciences)を用いて、21日目から毎週、生物発光イメージングを実施し、全身腫瘍組織量をモニタリングした。イメージングのために、イメージジングの10分前にルシフェラーゼ基質(150mg/kg)を動物にIP注射し、次いでイソフルラン下で動物を麻酔し、イメージングした。結果を図8及び9に示す。
CD38は、活性化後のPBMC細胞において劇的に上方制御されることが示された。正常ドナー由来の静止PMBCでは、20%未満の静止細胞がCD38を発現し、レセプター数は、細胞当たりおよそ10,000〜20,000と計算される。正常ドナー由来に対して、活性化PMBCは、60〜75%の細胞がCD38を発現しており、レセプター数は細胞当たり110,000〜160,000と示された。
カニクイザルへAb79を投与すると、リンパ球、B及びT細胞並びにNK細胞の有意な減少が示される。抗体を図6に示す容量で30分間のIV注射を介して投与し、24時間でデータを集めた。同様のデータを4日目、7日目、11日目及び18日目でも示された(sown)。
しかしながら、pK/pDデータは、投与後の動物の回復を示す。図7に示すように、リンパ球数は、単回のIV30分注入投与後(たとえ最も高用量であっても)、数日後にコントロール数と同程度まで回復し、これは、リンパ球前駆細胞の問題ではないことを示している。
3つの異なるモデルを使用する。
HuScidマウスモデルを、偽移植片対宿主モデル(pseudo−gravt−v−hostモデル)、抗破傷風応答(anti−tetanus response)、IgG枯渇、及び全生存に対するモデルとした。CB17/HuSCIDマウスにASGM1を注入してNK細胞を枯渇させ、次いで、一日後にヒトPBMCを注入した。ヒトIgランダム化のために集めた血清を用いて、生着(engraftment)は7〜10日間で進行することが可能であった。一日後、マウスにAb79を10mg/kg、その後TTdを注入し、4日後に第2の投与を、その3日後に第3の投与を行い、ヒトIg計測及び抗破傷風検出のために、その3日後に血清を集めた(最初の投与から計10日)。単一のマウスドナーから得られた結果を図8に示す。図8では、処理時の全てのIgアイソタイプの有意な減少を示す。図9は、各レシピエントグループに対する平均Igレベルの結果を示しており、各データポイントはグループごとの平均値を表す(n=5〜n=10)。図10は、Ab79処理時の抗破傷風応答の有意な低下を示す。最後に、図11は、Ab79処理を用いた場合の、全体の有意な生存率を示す。
Ab79は、げっ歯類CD38と交差反応しないので、代替抗体(surrogate antibody)を開発した。事前準備として、ヒトCD38に対する市販抗体及びマウスCD38に対する市販抗体を用いて、ヒト及びマウス間の細胞タイプ中でのCD38発現レベルの有意な差を示し(図12を参照されたい)、その病気の生態が異なることを示す。従って、サルモデルにおいて、サルCD38と交差反応する抗体を用いることは、かなり有利な結果を生じ得る。
脾臓、血液及び骨髄(データ示さず)、並びに末梢血(図13を参照されたい)から集めたCD38+細胞の同様の枯渇を示す、代替抗体を開発した。さらに、マウス代替抗体を10mg/kgで単回投与してから1、2又は3日後に集めた脾臓、血液及び骨髄における、枯渇の反応速度を図14に示す。血中B細胞の急速な枯渇が24時間以内に示され、脾臓及び骨髄では、よりゆっくりとした枯渇が示された。
血液からは、以下の中間の読み出し(interim readout)(例えば、2週間ごと)を用いて、MRL/lprモデルにおける代替マウス抗CD38を試験する:抗dsDNA自己抗体、CBC、FACS(T/B細胞枯渇について)、尿におけるタンパク質アルブミン及び皮膚炎。最終的な読み出しとして以下が挙げられるが、これらに限定されない:血液からは、抗dsDNA自己抗体、CBC、FACS(T/B細胞枯渇について)、脾臓、リンパ節及び骨髄からは、臓器重量、免疫細胞数、FACS(T/B細胞枯渇について)、腎臓からは、臓器重量、組織病理(H&E and PAS)、IC沈着、炎症細胞、及び皮膚炎症(組織病理)。
マウス代替抗体を用いてマウスCIAモデルを使用し、7つのマウスグループにて、前予防的、予防的及び治療的有効性の両方を評価した。全てのマウスを0日目にCII/CFAで免疫し、21日目にCII/CFAでブーストし、通常、21日目から42日目に疾患の進行が生じた(研究終了)。0日目(前予防)から開始して、グループ1(10匹のマウス)に1週間に2回、10mg/kgの代替抗体をIP注射した。グループ2(n=10)でも同様に投与したが、21日目から開始した。グループ3(n=10)では、疾患発症時(25〜28日目)に同様に注射した。グループ4(n=10)は、0日目に、hIgG1(例えば、アイソタイプ)を用いたが同一レベルで投与した。グループ5(n=10)では、hIgG1を同一レベルで投与したが21日目から開始した、グループ6(n=10)では、21日目に、0.5mg/Lのデキサメタゾン水を投与し、グループ7(n=5)は処置しなかった。
各グループについてn=3を用いて、カニクイザルCIA研究を実施し、グループ1はナイーブ動物であり、ビヒクルのみである。グループ2は、Ab79を3mg/kg又は10mg/kg、q1w(予防的処置はコラーゲン免疫後7日目に開始する)で単回投与する。グループ3は、治療的処置のために、疾患発症時、21日目又は28日目から開始して、3mg/kg又は10mg/kg q1wのAb79である。グループ4は、疾患発症時にも、デキサメタゾンで0.1mg/kg q1dで処置する。
配列番号1(CD38ホモ・サピエンス;NP_001766.2)
MANCEFSPVSGDKPCCRLSRRAQLCLGVSILVLILVVVLAVVVPRWRQQWSGPGTTKRFPETVLARCVKYTEIHPEMRHVDCQSVWDAFKGAFISKHPCNITEEDYQPLMKLGTQTVPCNKILLWSRIKDLAHQFTQVQRDMFTLEDTLLGYLADDLTWCGEFNTSKINYQSCPDWRKDCSNNPVSVFWKTVSRRFAEAACDVVHVMLNGSRSKIFDKNSTFGSVEVHNLQPEKVQTLEAWVIHGGREDSRDLCQDPTIKELESIISKRNIQFSCKNIYRPDKFLQCVKNPEDSSCTSEI
MANCEFSPVSGDKPCCRLSRRAQVCLGVCLLVLLILVVVVAVVLPRWRQQWSGSGTTSRFPETVLARCVKYTEVHPEMRHVDCQSVWDAFKGAFISKYPCNITEEDYQPLVKLGTQTVPCNKTLLWSRIKDLAHQFTQVQRDMFTLEDMLLGYLADDLTWCGEFNTFEINYQSCPDWRKDCSNNPVSVFWKTVSRRFAETACGVVHVMLNGSRSKIFDKNSTFGSVEVHNLQPEKVQALEAWVIHGGREDSRDLCQDPTIKELESIISKRNIRFFCKNIYRPDKFLQCVKNPEDSSCLSGI
GFTFDDYG
ISWNGGKT
ARGSLFHDSSGFYFGH
SSNIGDNY
RDS
QSYDSSLSGS
EVQLLESGGGLVQPGGSLRLSCAASGFTFDDYGMSWVRQAPGKGLEWVSDISWNGGKTHYVDSVKGQFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGSLFHDSSGFYFGHWGQGTLVTVSSASTKGPSVFPLA
QSVLTQPPSASGTPGQRVTISCSGSSSNIGDNYVSWYQQLPGTAPKLLIYRDSQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSLSGSVFGGGTKLTVLGQPKANPTVTLFPPSSEEL
EVQLLESGGGLVQPGGSLRLSCAASGFTFNNYDMTWVRQAPGKGLEWVAVISYDGSDKDYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVYYYGFSGPSMDVWGQGTLVTVSSASTKGPSVFPLA
QSVLTQPPSASGTPGQRVTISCSGSNSNIGSNTVNWYQQLPGTAPKLLIYSDSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSLSGSRVFGGGTKLTVLGQPKANPTVTLFPPSSEEL
GFTFNNYG
ISYDGSDK
ARVYYYGFSGPSMDV
NSNIGSNT
SDS
QSYDSSLSGSR
EVQLLESGGGLVQPGGSLRLSCAASGFTFNNYDMTWVRQAPGKGLEWVAVISYDGSDKDYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVYYYGFSGPSMDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
QSVLTQPPSASGTPGQRVTISCSGSNSNIGSNTVNWYQQLPGTAPKLLIYSDSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSLSGSRVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
EVQLLESGGGLVQPGGSLRLSCAASGFTFDDYGMSWVRQAPGKGLEWVSDISWNGGKTHYVDSVKGQFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGSLFHDSSGFYFGHWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
QSVLTQPPSASGTPGQRVTISCSGSSSNIGDNYVSWYQQLPGTAPKLLIYRDSQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSLSGSVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
MAAQGCAASRLLQLLLQLLLLLLLLAAGGARARWRGEGTSAHLRDIFLGRCAEYRALLSPEQRNKNCTAIWEAFKVALDKDPCSVLPSDYDLFINLSRHSIPRDKSLFWENSHLLVNSFADNTRRFMPLSDVLYGRVADFLSWCRQKNDSGLDYQSCPTS EDCENNPVDSFWKRASIQYSKDSSGVIHVMLNGSEPTGAYPIKGFFADYEIPNLQKEKITRIEIWVMHEIGGPNVESCGEGSMKVLEKRLKDMGFQYSCINDYRPVKLLQCVDHSTHPDCALKSAAAATQRKAPSLYTEQRAGLIIPLFLVLASRTQL
EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSAISGSGGGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKILWFGEPVFDYWGQGTLVTVSS
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKVEIKR
QVQLVQSGAEVAKPGTSVKLSCKASGYTFTDYWMQWVKQRPGQGLEWIGTIYPGDGDTGYAQKFQGKATLTADKSSKTVYMHLSSLASEDSAVYYCARGDYYGSNSLDYWGQGTSVTVSS
DIVMTQSHLSMSTSLGDPVSITCKASQDVSTVVAWYQQKPGQSPRRLIYSASYRYIGVPDRFTGSGAGTDFTFTISSVQAEDLAVYYCQQHYSPPYTFGGGTKLEIKR
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVSRINSDGSSTSYADSMKGQFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGGYYYYAMDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
QSVLTQPPSASGTPGQRVTISCSGGSSNIGYKTVNWYQQLPGTAPKLLIYDNNKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLNGLVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYGMNWVRQAPGKGLEWVSGISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDSNYDFWSGYYYGMDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
QSVLTQPPSASGTPGQRVTISCSGSSSNIGSKTVSWYQQLPGTAPKLLIYDNNKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCSSYAARSTNIIFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVSIIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRATWGGATHDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCATWDDSLNGVLFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
EVQLLESGGGLVQPGGSLRLSCAASGFTFNNYDMTWVRQAPGKGLEWVAVISYDGSDKDYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVYYYGFSGPSMDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
QSVLTQPPSASGTPGQRVTISCSGSNSNIGSNTVNWYQQLPGTAPKLLIYSDSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSLSGSRVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
Claims (20)
- ヒトCD38(配列番号1)及びカニクイザルCD38(配列番号2)に特異的に結合する単離された抗体であって、
a)以下を含む重鎖可変領域:
i)配列番号3を含む第1のCDR;
ii)配列番号4を含む第2のCDR;
iii)配列番号5を含む第3のCDR;及び
b)以下を含む軽鎖可変領域:
i)配列番号6を含む第1のCDR;
ii)配列番号7を含む第2のCDR;
iii)配列番号8を含む第3のCDR;
を含む、抗体。 - 前記重鎖可変領域が配列番号9を含む、請求項1記載の単離された抗体。
- 前記軽鎖可変領域が配列番号10を含む、請求項1記載の単離された抗体。
- 前記重鎖可変領域が配列番号9を含み、前記軽鎖可変領域が配列番号10を含む、請求項1記載の単離された抗体。
- 重鎖が配列番号21を含み、軽鎖が配列番号22を含む、請求項1記載の単離された抗体。
- ヒトCD38(配列番号1)及びカニクイザルCD38(配列番号2)に特異的に結合する単離された抗体であって、
a)以下を含む重鎖可変領域:
i)配列番号13を含む第1のCDR;
ii)配列番号14を含む第2のCDR;
iii)配列番号15を含む第3のCDR;及び
b)以下を含む軽鎖可変領域:
i)配列番号16を含む第1のCDR;
ii)配列番号17を含む第2のCDR;
iii)配列番号18を含む第3のCDR;
を含む、抗体。 - 前記重鎖可変領域が配列番号11を含む、請求項6記載の単離された抗体。
- 前記軽鎖可変領域が配列番号12を含む、請求項6記載の単離された抗体。
- 前記重鎖可変領域が配列番号19を含み、前記軽鎖可変領域が配列番号20を含む、請求項6記載の単離された抗体。
- 重鎖が配列番号34を含み、軽鎖が配列番号35を含む、請求項6記載の単離された抗体。
- さらにFcドメインを含む、請求項1又は6記載の単離された抗体。
- 前記Fcドメインがヒトである、請求項11記載の単離された抗体。
- 前記Fcドメインが変異Fcドメインである、請求項7記載の単離された抗体。
- 請求項2又は7記載の重鎖をコードする、単離された核酸。
- 請求項3又は8記載の軽鎖をコードする、単離された核酸。
- 請求項14又は15記載の単離された核酸を含む、宿主細胞。
- 請求項1又は6記載の抗体の製造方法であって、前記抗体が製造される条件下で請求項16記載の宿主細胞を培養する工程を含む、方法。
- ヒトCD38タンパク質(配列番号1)及びカニクイザルCD38(配列番号2)の生物活性を阻害する方法であって、配列番号1及び配列番号2の少なくともK121、F135、Q139、D141、E239、W241、C275、K276、F284、P291及びE292と相互作用する抗体と前記タンパク質を接触させることによる、方法。
- ヒトCD38(配列番号1)及びカニクイザルCD38(配列番号2)に特異的に結合する単離された抗体であって、
a)以下を含む重鎖可変領域:
i)配列番号3を含む第1のCDR;
ii)配列番号4を含む第2のCDR;
iii)配列番号5を含む第3のCDR;及び
b)以下を含む軽鎖可変領域:
i)配列番号6を含む第1のCDR;
ii)配列番号7を含む第2のCDR;
iii)配列番号8を含む第3のCDR;
を含む抗体を、それを必要とする患者に投与することを含む、自己免疫疾患の治療方法。 - 前記自己免疫疾患が、関節リウマチ、全身性エリテマトーデス、炎症性腸疾患、潰瘍性大腸炎及び移植片対宿主病からなる群から選択される、請求項19記載の方法。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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US10800851B2 (en) | 2014-02-28 | 2020-10-13 | Janssen Biotech, Inc. | Combination therapies with anti-CD38 antibodies |
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US11618787B2 (en) | 2017-10-31 | 2023-04-04 | Janssen Biotech, Inc. | Methods of treating high risk multiple myeloma |
Families Citing this family (163)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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US9732154B2 (en) * | 2014-02-28 | 2017-08-15 | Janssen Biotech, Inc. | Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia |
EP3593812A3 (en) | 2014-03-15 | 2020-05-27 | Novartis AG | Treatment of cancer using chimeric antigen receptor |
UA119352C2 (uk) | 2014-05-01 | 2019-06-10 | Тева Фармасьютикалз Острейліа Пті Лтд | Комбінація леналідоміду або помалідоміду і конструкції анти-cd38 антитіло-атенуйований інтерферон альфа-2b та спосіб лікування суб'єкта, який має cd38-експресуючу пухлину |
AU2015289644A1 (en) | 2014-07-15 | 2017-02-02 | Juno Therapeutics, Inc. | Engineered cells for adoptive cell therapy |
JP2017528433A (ja) | 2014-07-21 | 2017-09-28 | ノバルティス アーゲー | 低い免疫増強用量のmTOR阻害剤とCARの組み合わせ |
CN107106656A (zh) | 2014-10-29 | 2017-08-29 | 梯瓦制药澳大利亚股份有限公司 | 干扰素α2b变体 |
US11773166B2 (en) | 2014-11-04 | 2023-10-03 | Ichnos Sciences SA | CD3/CD38 T cell retargeting hetero-dimeric immunoglobulins and methods of their production |
US11161907B2 (en) | 2015-02-02 | 2021-11-02 | Novartis Ag | Car-expressing cells against multiple tumor antigens and uses thereof |
MA41555A (fr) * | 2015-02-17 | 2017-12-26 | Millennium Pharm Inc | Polythérapie pour le traitement du cancer |
CN113527495A (zh) * | 2015-04-08 | 2021-10-22 | 索伦托药业有限公司 | 与cd38结合的抗体治疗剂 |
WO2016172583A1 (en) | 2015-04-23 | 2016-10-27 | Novartis Ag | Treatment of cancer using chimeric antigen receptor and protein kinase a blocker |
US20180258143A1 (en) | 2015-05-30 | 2018-09-13 | Molecular Templates, Inc. | De-Immunized, Shiga Toxin A Subunit Scaffolds and Cell-Targeting Molecules Comprising the Same |
MA42270A (fr) | 2015-06-24 | 2018-05-02 | Janssen Biotech Inc | Modulation immunitaire et traitement de tumeurs solides avec des anticorps se liant spécifiquement à cd38 |
MY193677A (en) | 2015-07-06 | 2022-10-25 | UCB Biopharma SRL | Tau-binding antibodies |
MA42895A (fr) | 2015-07-15 | 2018-05-23 | Juno Therapeutics Inc | Cellules modifiées pour thérapie cellulaire adoptive |
US11667691B2 (en) | 2015-08-07 | 2023-06-06 | Novartis Ag | Treatment of cancer using chimeric CD3 receptor proteins |
EP3355937A4 (en) | 2015-09-28 | 2019-04-17 | Regents of the University of Minnesota | CHIMERIC ANTIGEN RECEPTOR (CAR) T CELLS AS THERAPEUTIC INTERVENTIONS AT AUTO AND ALLO IMMUNITY |
CN109311966B (zh) | 2015-10-25 | 2023-03-10 | 赛诺菲 | 用于预防或治疗hiv感染的三特异性和/或三价结合蛋白 |
TWI724048B (zh) | 2015-11-03 | 2021-04-11 | 美商健生生物科技公司 | 抗cd38抗體之皮下調配物及其用途 |
WO2017091786A1 (en) | 2015-11-23 | 2017-06-01 | Novartis Ag | Optimized lentiviral transfer vectors and uses thereof |
MX2018008106A (es) | 2015-12-30 | 2019-03-14 | Novartis Ag | Terapias con celulas inmunoefectoras de una eficacia mejorada. |
CN105546709B (zh) * | 2016-02-04 | 2019-01-04 | 山东格瑞德集团有限公司 | 孔板送风布风系统 |
EP3423498A1 (en) | 2016-03-04 | 2019-01-09 | MorphoSys AG | Clinical assessment of m-protein response in multiple myeloma |
WO2017165683A1 (en) | 2016-03-23 | 2017-09-28 | Novartis Ag | Cell secreted minibodies and uses thereof |
RS64771B1 (sr) | 2016-04-13 | 2023-11-30 | Sanofi Sa | Trispecifični i/ili trovalentni vezujući proteini |
KR20180134378A (ko) * | 2016-04-13 | 2018-12-18 | 사노피 | 3특이성 및/또는 3가 결합 단백질 |
CN117717604A (zh) | 2016-07-19 | 2024-03-19 | 梯瓦制药澳大利亚股份有限公司 | 抗cd47联合治疗 |
WO2018015498A1 (en) | 2016-07-20 | 2018-01-25 | Hybrigenics Sa | Combinations of inecalcitol with an anti-cd38 agent and their uses for treating cancer |
MX2019004621A (es) | 2016-11-02 | 2019-11-28 | Engmab Sarl | Anticuerpo biespecifico contra bcma y cd3 y un farmaco inmunologico para uso combinado en el tratamiento del mieloma multiple. |
US20210333279A1 (en) * | 2016-11-04 | 2021-10-28 | Aarhus Universitet | Identification and treatment of tumors characterized by an overexpression of the neonatal fc receptor |
WO2018111340A1 (en) | 2016-12-16 | 2018-06-21 | Novartis Ag | Methods for determining potency and proliferative function of chimeric antigen receptor (car)-t cells |
EP4043485A1 (en) | 2017-01-26 | 2022-08-17 | Novartis AG | Cd28 compositions and methods for chimeric antigen receptor therapy |
US20190375815A1 (en) | 2017-01-31 | 2019-12-12 | Novartis Ag | Treatment of cancer using chimeric t cell receptor proteins having multiple specificities |
EP3589647A1 (en) | 2017-02-28 | 2020-01-08 | Novartis AG | Shp inhibitor compositions and uses for chimeric antigen receptor therapy |
JP7037198B2 (ja) * | 2017-03-01 | 2022-03-16 | 株式会社膠原病研究所 | 自己免疫疾患の予防および/または治療剤、並びに、ワクチン |
CA3057808A1 (en) | 2017-03-24 | 2018-09-27 | Zenyaku Kogyo Co., Ltd. | Anti-igm/b cell surface antigen bispecific antibody |
WO2018183376A1 (en) * | 2017-03-28 | 2018-10-04 | Rigel Pharmaceuticals, Inc. | Acvr2a-specific antibody and method of use thereof |
KR20200006972A (ko) | 2017-04-14 | 2020-01-21 | 톨나인, 인크. | 면역조절 폴리뉴클레오티드, 이의 항체 접합체, 및 이의 사용 방법 |
AU2018280868A1 (en) * | 2017-06-08 | 2020-01-02 | Black Belt Therapeutics Limited | CD38 modulating antibody |
JP7237950B2 (ja) * | 2017-06-08 | 2023-03-13 | ブラック ベルト セラピューティクス リミテッド | Cd38調節抗体 |
WO2018229715A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Compositions comprising anti-cd32b antibodies and methods of use thereof |
EP3828264A1 (en) | 2017-06-20 | 2021-06-02 | Institut Curie | Immune cells defective for suv39h1 |
KR20200017519A (ko) * | 2017-06-20 | 2020-02-18 | 소렌토 쎄라퓨틱스, 인코포레이티드 | Cd38 항체 약물 접합체 |
EP3434692A1 (en) * | 2017-07-24 | 2019-01-30 | Encefa | Compounds which specifically binds to cd38 for use in the treatment of neurodegenerative diseases |
AU2018316521A1 (en) * | 2017-08-16 | 2020-02-13 | Black Belt Therapeutics Limited | CD38 modulating antibody |
US11236173B2 (en) | 2017-08-16 | 2022-02-01 | Black Belt Therapeutics Limited | CD38 antibody |
US11542338B2 (en) | 2017-08-16 | 2023-01-03 | Black Belt Therapeutics Limited | CD38 modulating antibody |
WO2019035938A1 (en) | 2017-08-16 | 2019-02-21 | Elstar Therapeutics, Inc. | MULTISPECIFIC MOLECULES BINDING TO BCMA AND USES THEREOF |
MX2020002802A (es) | 2017-09-13 | 2020-10-12 | Teneobio Inc | Anticuerpos de cadena pesada que se unen a ectoenzimas. |
US20210040205A1 (en) | 2017-10-25 | 2021-02-11 | Novartis Ag | Antibodies targeting cd32b and methods of use thereof |
BR112020007710A2 (pt) | 2017-10-25 | 2020-10-20 | Novartis Ag | métodos para produzir células que expressam receptor de antígeno quimérico |
US20210179709A1 (en) | 2017-10-31 | 2021-06-17 | Novartis Ag | Anti-car compositions and methods |
US20210132042A1 (en) | 2017-11-01 | 2021-05-06 | Juno Therapeutics, Inc. | Methods of assessing or monitoring a response to a cell therapy |
MA49911A (fr) | 2017-11-01 | 2020-06-24 | Juno Therapeutics Inc | Anticorps et récepteurs antigéniques chimériques spécifiques de l'antigene de maturation des lymphocytes b |
SG11202003688PA (en) | 2017-11-01 | 2020-05-28 | Juno Therapeutics Inc | Process for generating therapeutic compositions of engineered cells |
JP7258899B2 (ja) | 2017-11-01 | 2023-04-17 | ジュノー セラピューティクス インコーポレイテッド | T細胞組成物を作製するための方法 |
WO2019089848A1 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Methods associated with tumor burden for assessing response to a cell therapy |
CA3082010A1 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Chimeric antigen receptors specific for b-cell maturation antigen (bcma) |
AU2018362014A1 (en) | 2017-11-03 | 2020-05-28 | Sorrento Therapeutics, Inc. | CD38-directed chimeric antigen receptor constructs |
CN111918876B (zh) * | 2017-11-30 | 2024-02-02 | 豪夫迈·罗氏有限公司 | 抗pd-l1抗体及使用其检测pd-l1的方法 |
ES2949855T3 (es) * | 2017-12-05 | 2023-10-03 | Medical Res Infrastructure & Health Services Fund Tel Aviv Medical Ct | Linfocitos T que comprenden receptores antigénicos quiméricos anti-CD38 y ant-CD138 y los usos de los mismos |
MA51114A (fr) | 2017-12-08 | 2020-10-14 | Juno Therapeutics Inc | Procédé de production d'une compositions de lymphocytes t modifiés |
CN112203680A (zh) | 2017-12-08 | 2021-01-08 | 朱诺治疗学股份有限公司 | 用于细胞疗法的表型标记和相关方法 |
US20210207080A1 (en) | 2017-12-08 | 2021-07-08 | Juno Therapeutics, Inc. | Serum-free media formulation for culturing cells and methods of use thereof |
CN110144008B (zh) * | 2018-02-12 | 2021-03-19 | 杭州尚健生物技术有限公司 | Cd38蛋白抗体及其应用 |
CN108318689A (zh) * | 2018-04-09 | 2018-07-24 | 北京大学深圳研究生院 | 一种多发性骨髓瘤的诊断方法 |
US20210047405A1 (en) | 2018-04-27 | 2021-02-18 | Novartis Ag | Car t cell therapies with enhanced efficacy |
WO2019213282A1 (en) | 2018-05-01 | 2019-11-07 | Novartis Ag | Biomarkers for evaluating car-t cells to predict clinical outcome |
EP3801769A1 (en) | 2018-05-25 | 2021-04-14 | Novartis AG | Combination therapy with chimeric antigen receptor (car) therapies |
EP3802825A1 (en) | 2018-06-08 | 2021-04-14 | Intellia Therapeutics, Inc. | Compositions and methods for immunooncology |
CN108752475B (zh) * | 2018-06-14 | 2021-07-30 | 北京智仁美博生物科技有限公司 | 抗人cd38抗体及其用途 |
AR116109A1 (es) | 2018-07-10 | 2021-03-31 | Novartis Ag | Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos |
TW202019518A (zh) | 2018-07-13 | 2020-06-01 | 丹麥商珍美寶股份有限公司 | Cd38抗體之變體及其用途 |
MA53123A (fr) | 2018-07-13 | 2021-05-19 | Genmab As | Thérapie à médiation par trogocytose utilisant des anticorps cd38 |
CA3108698A1 (en) | 2018-08-09 | 2020-02-13 | Juno Therapeutics, Inc. | Methods for assessing integrated nucleic acids |
US20220275100A1 (en) * | 2018-09-11 | 2022-09-01 | Jiangsu Hengrui Medicine Co., Ltd. | Anti-cd38 antibody, antigen-binding fragment thereof, and pharmaceutical use |
CN109053892B (zh) * | 2018-09-19 | 2021-03-26 | 苏州思坦维生物技术股份有限公司 | 特异结合人及猴cd38抗原的单克隆抗体及其制备方法与应用 |
TW202035458A (zh) | 2018-10-09 | 2020-10-01 | 法商賽諾菲公司 | 三特異性抗cd38、抗cd28和抗cd3結合蛋白和用於治療病毒感染的使用方法 |
KR20210086651A (ko) | 2018-10-26 | 2021-07-08 | 테네오바이오, 인코포레이티드 | Cd38에 결합하는 중쇄 항체 |
US20210393690A1 (en) | 2018-11-01 | 2021-12-23 | Juno Therapeutics, Inc. | Methods for treatment using chimeric antigen receptors specific for b-cell maturation antigen |
CN113614108A (zh) | 2018-11-01 | 2021-11-05 | 朱诺治疗学股份有限公司 | G蛋白偶合受体c类5族成员d(gprc5d)特异性嵌合抗原受体 |
SG11202104012QA (en) | 2018-12-14 | 2021-05-28 | Morphosys Ag | Antibody formulations |
MX2021007392A (es) | 2018-12-20 | 2021-08-24 | Novartis Ag | Regimen de dosificacion y combinacion farmaceutica que comprende derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona. |
EP3914610A1 (en) | 2019-01-23 | 2021-12-01 | Millennium Pharmaceuticals, Inc. | Cd38-binding proteins comprising de-immunized shiga toxin a subunit effectors |
WO2020154540A1 (en) * | 2019-01-23 | 2020-07-30 | Millennium Pharmaceuticals, Inc. | Anti-cd38 antibodies |
MX2021009763A (es) | 2019-02-15 | 2021-09-08 | Novartis Ag | Derivados de 3-(1-oxo-5-(piperidin-4-il)isoindolin-2-il)piperidina -2,6-diona y usos de los mismos. |
EP3924055B1 (en) | 2019-02-15 | 2024-04-03 | Novartis AG | Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
CN113574071A (zh) | 2019-03-15 | 2021-10-29 | 莫佛塞斯公司 | 用于治疗自身抗体介导的自身免疫疾病的抗-cd38抗体及其药物组合物 |
WO2020194242A1 (en) * | 2019-03-28 | 2020-10-01 | Janssen Biotech, Inc. | Clinically proven subcutaneous pharmaceutical compositions comprising anti-cd38 antibodies and their uses in combination with pomalidomide and dexamethasone |
WO2020194244A1 (en) * | 2019-03-28 | 2020-10-01 | Janssen Biotech, Inc. | Clinically proven subcutaneous pharmaceutical compositions comprising anti-cd38 antibodies and their uses in combination with bortezomib and dexamethasone |
US20200308284A1 (en) * | 2019-03-28 | 2020-10-01 | Janssen Biotech, Inc. | Clinically Proven Subcutaneous Pharmaceutical Compositions Comprising Anti-CD38 Antibodies and Their Uses in Combination with Lenalidomide and Dexamethasone |
US20200330593A1 (en) * | 2019-03-28 | 2020-10-22 | Janssen Biotech, Inc. | Clinically Proven Subcutaneous Pharmaceutical Compositions Comprising Anti-CD38 Antibodies and Their Uses in Combination with Bortezomib, Mephalan and Prednisone |
JP2022527084A (ja) * | 2019-03-29 | 2022-05-30 | ソレント・セラピューティクス・インコーポレイテッド | Cd38に結合する操作されたバリアント抗体 |
US11613576B2 (en) | 2019-04-09 | 2023-03-28 | Sanofi | Trispecific binding proteins, methods, and uses thereof |
SG11202111012QA (en) * | 2019-04-09 | 2021-11-29 | Sanofi Sa | Trispecific binding proteins, methods, and uses thereof |
AU2020265749A1 (en) | 2019-05-01 | 2022-01-06 | Juno Therapeutics, Inc. | Cells expressing a chimeric receptor from a modified CD247 locus, related polynucleotides and methods |
SG11202111360YA (en) | 2019-05-01 | 2021-11-29 | Juno Therapeutics Inc | Cells expressing a recombinant receptor from a modified tgfbr2 locus, related polynucleotides and methods |
US20220241413A1 (en) | 2019-06-10 | 2022-08-04 | Takeda Pharmaceutical Company Limited | Combination therapies using cd-38 antibodies |
JP2022538836A (ja) | 2019-06-27 | 2022-09-06 | クリスパー セラピューティクス アクチェンゲゼルシャフト | がんを治療するためのキメラ抗原受容体t細胞及びnk細胞阻害剤の使用 |
CA3142632A1 (en) * | 2019-07-03 | 2021-01-07 | Crystal Bioscience Inc. | Anti-cd38 antibody and methods of use thereof |
AU2020318781A1 (en) | 2019-07-23 | 2022-02-10 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Immune cells defective for SUV39H1 |
CN112538114A (zh) * | 2019-09-20 | 2021-03-23 | 上海普铭生物科技有限公司 | 抗人cd38抗体及其应用 |
EP4054714A4 (en) * | 2019-11-07 | 2023-12-06 | Ohio State Innovation Foundation | METHODS AND COMPOSITIONS FOR SELECTIVE INTRACELLULAR DELIVERY OF CD38 INHIBITORS |
CA3158579A1 (en) | 2019-12-18 | 2021-06-24 | Pranjali DALVI | Heavy chain antibodies binding to cd38 |
AU2020406350A1 (en) | 2019-12-20 | 2022-08-11 | Novartis Ag | Uses of anti-TGF-beta antibodies and checkpoint inhibitors for the treatment of proliferative diseases |
MX2022008050A (es) | 2020-01-16 | 2022-07-27 | Genmab As | Formulaciones de anticuerpos anti cumulo de diferenciacion 38 (cd38) y usos de las mismas. |
JP2023515566A (ja) | 2020-02-28 | 2023-04-13 | タラック セラピューティクス,インク. | トランスグルタミナーゼ媒介コンジュゲーション |
BR112022018987A2 (pt) | 2020-03-26 | 2022-11-01 | Seagen Inc | Métodos de tratamento de mieloma múltiplo |
IL297147A (en) | 2020-04-10 | 2022-12-01 | Juno Therapeutics Inc | Methods and Uses Related to Transgenic Cell Therapy with a Chimeric Antigen Receptor Directed to a B-Cell Maturation Antigen |
EP4121112A4 (en) | 2020-05-08 | 2023-11-15 | The University Of Southern California | SITE-SPECIFIC ANTIBODY-DRUG CONJUGATES BY ADP-RIBOSYL CYCLASES |
US20230178239A1 (en) | 2020-05-13 | 2023-06-08 | Juno Therapeutics, Inc. | Methods of identifying features associated with clinical response and uses thereof |
JP2023529211A (ja) | 2020-06-11 | 2023-07-07 | ノバルティス アーゲー | Zbtb32阻害剤及びその使用 |
JP2023531676A (ja) | 2020-06-23 | 2023-07-25 | ノバルティス アーゲー | 3-(1-オキソイソインドリン-2-イル)ピぺリジン-2,6-ジオン誘導体を含む投与レジメン |
US20220023344A1 (en) | 2020-06-26 | 2022-01-27 | Crispr Therapeutics Ag | Allogeneic cell therapy of acute lymphoblastic leukemia using genetically engineered t cells targeting cd19 |
KR20230042283A (ko) | 2020-06-26 | 2023-03-28 | 주노 테라퓨틱스 게엠베하 | 재조합 수용체를 조건부로 발현하는 조작된 t 세포, 관련된 폴리뉴클레오티드 및 방법 |
EP4188395A1 (en) | 2020-07-30 | 2023-06-07 | Institut Curie | Immune cells defective for socs1 |
CN116134027A (zh) | 2020-08-03 | 2023-05-16 | 诺华股份有限公司 | 杂芳基取代的3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途 |
KR20230090367A (ko) | 2020-11-04 | 2023-06-21 | 주노 쎄러퓨티크스 인코퍼레이티드 | 변형된 불변 cd3 이뮤노글로불린 슈퍼패밀리 쇄 유전자좌로부터 키메라 수용체를 발현하는 세포 및 관련 폴리뉴클레오티드 및 방법 |
JP2024508207A (ja) | 2020-12-02 | 2024-02-26 | ブイアイビー ブイゼットダブリュ | がんに対する組み合わせ治療におけるltbrアゴニスト |
US20220202859A1 (en) | 2020-12-23 | 2022-06-30 | Crispr Therapeutics Ag | Cancer treatment using cd38 inhibitor and/or lenalidomide and t-cells expressing a chimeric antigen receptor |
JP2024509853A (ja) | 2021-03-03 | 2024-03-05 | ジュノー セラピューティクス インコーポレイテッド | T細胞療法およびdgk阻害剤の組合せ |
CA3212343A1 (en) | 2021-03-17 | 2022-09-22 | Kazunori YOSHIKIYO | Gene encoding a chimeric receptor for an anti-acetylcholine receptor autoantibody |
TW202304979A (zh) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | 抗TGFβ抗體及其他治療劑用於治療增殖性疾病之用途 |
AR125468A1 (es) | 2021-04-27 | 2023-07-19 | Novartis Ag | Sistema de producción de vectores virales |
JP2024517863A (ja) | 2021-05-06 | 2024-04-23 | ジュノ・セラピューティクス・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 細胞を刺激し、形質導入する方法 |
EP4337763A1 (en) | 2021-05-10 | 2024-03-20 | Institut Curie | Methods for the treatment of cancer, inflammatory diseases and autoimmune diseases |
WO2022238963A2 (en) | 2021-05-12 | 2022-11-17 | Crispr Therapeutics Ag | Genetically engineered immune cells targeting cd70 for use in treating solid tumors |
AR125851A1 (es) | 2021-05-12 | 2023-08-16 | Crispr Therapeutics Ag | Células inmunes modificadas genéticamente que se focalizan en cd70 para su uso en el tratamiento de neoplasias malignas hematopoyéticas |
WO2022242892A1 (en) * | 2021-05-17 | 2022-11-24 | Université de Liège | Anti-cd38 single-domain antibodies in disease monitoring and treatment |
WO2022248602A1 (en) | 2021-05-25 | 2022-12-01 | Institut Curie | Myeloid cells overexpressing bcl2 |
WO2022271987A1 (en) | 2021-06-23 | 2022-12-29 | TeneoFour, Inc. | Anti-cd38 antibodies and epitopes of same |
IL310372A (en) | 2021-07-28 | 2024-03-01 | Genentech Inc | IL15/IL15R alpha heterodimeric FC-fused proteins for the treatment of blood cancer |
WO2023017392A1 (en) | 2021-08-13 | 2023-02-16 | 3M Innovative Properties Company | Antistatic fabric article |
CN113896802A (zh) * | 2021-10-09 | 2022-01-07 | 宜明昂科生物医药技术(上海)有限公司 | 靶向cd47和cd38的重组融合蛋白及其制备和用途 |
WO2023126458A1 (en) | 2021-12-28 | 2023-07-06 | Mnemo Therapeutics | Immune cells with inactivated suv39h1 and modified tcr |
WO2023147515A1 (en) | 2022-01-28 | 2023-08-03 | Juno Therapeutics, Inc. | Methods of manufacturing cellular compositions |
TW202342520A (zh) | 2022-02-18 | 2023-11-01 | 美商樂天醫藥生技股份有限公司 | 抗計畫性死亡配體1(pd—l1)抗體分子、編碼多核苷酸及使用方法 |
WO2023187024A1 (en) | 2022-03-31 | 2023-10-05 | Institut Curie | Modified rela protein for inducing interferon expression and engineered immune cells with improved interferon expression |
WO2023213969A1 (en) | 2022-05-05 | 2023-11-09 | Juno Therapeutics Gmbh | Viral-binding protein and related reagents, articles, and methods of use |
WO2023214325A1 (en) | 2022-05-05 | 2023-11-09 | Novartis Ag | Pyrazolopyrimidine derivatives and uses thereof as tet2 inhibitors |
WO2023220655A1 (en) | 2022-05-11 | 2023-11-16 | Celgene Corporation | Methods to overcome drug resistance by re-sensitizing cancer cells to treatment with a prior therapy via treatment with a t cell therapy |
WO2023230581A1 (en) | 2022-05-25 | 2023-11-30 | Celgene Corporation | Methods of manufacturing t cell therapies |
WO2023230548A1 (en) | 2022-05-25 | 2023-11-30 | Celgene Corporation | Method for predicting response to a t cell therapy |
WO2024054944A1 (en) | 2022-09-08 | 2024-03-14 | Juno Therapeutics, Inc. | Combination of a t cell therapy and continuous or intermittent dgk inhibitor dosing |
WO2024054775A1 (en) * | 2022-09-09 | 2024-03-14 | Takeda Pharmaceutical Company Limited | Subcutaneous dosing of anti-cd38 antibodies for treating patients with moderate to severe systemic lupus erythematosus |
WO2024079010A1 (en) | 2022-10-10 | 2024-04-18 | F. Hoffmann-La Roche Ag | Combination therapy of a gprc5d tcb and cd38 antibodies |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001509817A (ja) * | 1997-04-07 | 2001-07-24 | ジェネンテク・インコーポレイテッド | 抗vegf抗体 |
WO2006125640A2 (en) * | 2005-05-24 | 2006-11-30 | Morphosys Ag | Generation and profiling of fully human hucal gold®-derived therapeutic antibodies specific for human cd38 |
WO2009077993A2 (en) * | 2007-12-17 | 2009-06-25 | Pfizer Limited | Treatment of interstitial cystitis |
WO2010021874A2 (en) * | 2008-08-20 | 2010-02-25 | Centocor Ortho Biotech Inc. | Engineered anti-il-13 antibodies, compositions, methods and uses |
WO2012092616A1 (en) * | 2010-12-30 | 2012-07-05 | Takeda Pharmaceutical Company Limited | Conjugated anti-cd38 antibodies |
Family Cites Families (130)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
US3691016A (en) | 1970-04-17 | 1972-09-12 | Monsanto Co | Process for the preparation of insoluble enzymes |
CA1023287A (en) | 1972-12-08 | 1977-12-27 | Boehringer Mannheim G.M.B.H. | Process for the preparation of carrier-bound proteins |
US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
US4195128A (en) | 1976-05-03 | 1980-03-25 | Bayer Aktiengesellschaft | Polymeric carrier bound ligands |
US4330440A (en) | 1977-02-08 | 1982-05-18 | Development Finance Corporation Of New Zealand | Activated matrix and method of activation |
CA1093991A (en) | 1977-02-17 | 1981-01-20 | Hideo Hirohara | Enzyme immobilization with pullulan gel |
US4169888A (en) | 1977-10-17 | 1979-10-02 | The Upjohn Company | Composition of matter and process |
US4229537A (en) | 1978-02-09 | 1980-10-21 | New York University | Preparation of trichloro-s-triazine activated supports for coupling ligands |
US4307016A (en) | 1978-03-24 | 1981-12-22 | Takeda Chemical Industries, Ltd. | Demethyl maytansinoids |
US4256746A (en) | 1978-11-14 | 1981-03-17 | Takeda Chemical Industries | Dechloromaytansinoids, their pharmaceutical compositions and method of use |
JPS55102583A (en) | 1979-01-31 | 1980-08-05 | Takeda Chem Ind Ltd | 20-acyloxy-20-demethylmaytansinoid compound |
JPS55162791A (en) | 1979-06-05 | 1980-12-18 | Takeda Chem Ind Ltd | Antibiotic c-15003pnd and its preparation |
JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
JPS5645483A (en) | 1979-09-19 | 1981-04-25 | Takeda Chem Ind Ltd | C-15003phm and its preparation |
EP0028683A1 (en) | 1979-09-21 | 1981-05-20 | Takeda Chemical Industries, Ltd. | Antibiotic C-15003 PHO and production thereof |
JPS5645485A (en) | 1979-09-21 | 1981-04-25 | Takeda Chem Ind Ltd | Production of c-15003pnd |
WO1982001188A1 (en) | 1980-10-08 | 1982-04-15 | Takeda Chemical Industries Ltd | 4,5-deoxymaytansinoide compounds and process for preparing same |
US4450254A (en) | 1980-11-03 | 1984-05-22 | Standard Oil Company | Impact improvement of high nitrile resins |
US4315929A (en) | 1981-01-27 | 1982-02-16 | The United States Of America As Represented By The Secretary Of Agriculture | Method of controlling the European corn borer with trewiasine |
US4313946A (en) | 1981-01-27 | 1982-02-02 | The United States Of America As Represented By The Secretary Of Agriculture | Chemotherapeutically active maytansinoids from Trewia nudiflora |
JPS57192389A (en) | 1981-05-20 | 1982-11-26 | Takeda Chem Ind Ltd | Novel maytansinoid |
US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
US4970198A (en) | 1985-10-17 | 1990-11-13 | American Cyanamid Company | Antitumor antibiotics (LL-E33288 complex) |
EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
US5776093A (en) | 1985-07-05 | 1998-07-07 | Immunomedics, Inc. | Method for imaging and treating organs and tissues |
US5057313A (en) | 1986-02-25 | 1991-10-15 | The Center For Molecular Medicine And Immunology | Diagnostic and therapeutic antibody conjugates |
EP0272253A4 (en) | 1986-03-07 | 1990-02-05 | Massachusetts Inst Technology | METHOD FOR IMPROVING GLYCOPROTE INSTABILITY. |
WO1987006265A1 (en) | 1986-04-17 | 1987-10-22 | Kyowa Hakko Kogyo Co., Ltd. | Novel compounds dc-88a and dc-89a1 and process for their preparation |
US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
US4880935A (en) | 1986-07-11 | 1989-11-14 | Icrf (Patents) Limited | Heterobifunctional linking agents derived from N-succinimido-dithio-alpha methyl-methylene-benzoates |
US5770701A (en) | 1987-10-30 | 1998-06-23 | American Cyanamid Company | Process for preparing targeted forms of methyltrithio antitumor agents |
US5606040A (en) | 1987-10-30 | 1997-02-25 | American Cyanamid Company | Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group |
US5053394A (en) | 1988-09-21 | 1991-10-01 | American Cyanamid Company | Targeted forms of methyltrithio antitumor agents |
FI102355B1 (fi) | 1988-02-11 | 1998-11-30 | Bristol Myers Squibb Co | Menetelmä yhdistävän välikappaleen omaavien antrasykliini-immunokonjugaattien valmistamiseksi |
US5084468A (en) | 1988-08-11 | 1992-01-28 | Kyowa Hakko Kogyo Co., Ltd. | Dc-88a derivatives |
JP2598116B2 (ja) | 1988-12-28 | 1997-04-09 | 協和醗酵工業株式会社 | 新規物質dc113 |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5187186A (en) | 1989-07-03 | 1993-02-16 | Kyowa Hakko Kogyo Co., Ltd. | Pyrroloindole derivatives |
JP2510335B2 (ja) | 1989-07-03 | 1996-06-26 | 協和醗酵工業株式会社 | Dc―88a誘導体 |
US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
CA2026147C (en) | 1989-10-25 | 2006-02-07 | Ravi J. Chari | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
JPH05507080A (ja) | 1990-05-03 | 1993-10-14 | スクリップス クリニック アンド リサーチ ファウンデーション | カリキアマイシン及びエスペラマイシンオリゴサッカライドの形成用中間体 |
LU91067I2 (fr) | 1991-06-14 | 2004-04-02 | Genentech Inc | Trastuzumab et ses variantes et dérivés immuno chimiques y compris les immotoxines |
WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
US5264586A (en) | 1991-07-17 | 1993-11-23 | The Scripps Research Institute | Analogs of calicheamicin gamma1I, method of making and using the same |
US5622929A (en) | 1992-01-23 | 1997-04-22 | Bristol-Myers Squibb Company | Thioether conjugates |
ES2149768T3 (es) | 1992-03-25 | 2000-11-16 | Immunogen Inc | Conjugados de agentes enlazantes de celulas derivados de cc-1065. |
ZA932522B (en) | 1992-04-10 | 1993-12-20 | Res Dev Foundation | Immunotoxins directed against c-erbB-2(HER/neu) related surface antigens |
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 |
AU690528B2 (en) | 1992-12-04 | 1998-04-30 | Medical Research Council | Multivalent and multispecific binding proteins, their manufacture and use |
US5780588A (en) | 1993-01-26 | 1998-07-14 | Arizona Board Of Regents | Elucidation and synthesis of selected pentapeptides |
AU6123894A (en) * | 1993-01-29 | 1994-08-15 | Board Of Trustees Of The Leland Stanford Junior University | Modulation of physiological responses of lymphocytes by cd38 or antibodies thereto |
US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
US5767237A (en) | 1993-10-01 | 1998-06-16 | Teikoku Hormone Mfg. Co., Ltd. | Peptide derivatives |
ATE271557T1 (de) | 1994-04-22 | 2004-08-15 | Kyowa Hakko Kogyo Kk | Dc-89 derivat |
JPH07309761A (ja) | 1994-05-20 | 1995-11-28 | Kyowa Hakko Kogyo Co Ltd | デュオカルマイシン誘導体の安定化法 |
US5773001A (en) | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
US5550246A (en) | 1994-09-07 | 1996-08-27 | The Scripps Research Institute | Calicheamicin mimics |
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 |
US6086875A (en) | 1995-01-17 | 2000-07-11 | The Brigham And Women's Hospital, Inc. | Receptor specific transepithelial transport of immunogens |
US5714586A (en) | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
US5712374A (en) | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
EP0871490B1 (en) | 1995-12-22 | 2003-03-19 | Bristol-Myers Squibb Company | Branched hydrazone linkers |
ES2340112T3 (es) | 1998-04-20 | 2010-05-28 | Glycart Biotechnology Ag | Ingenieria de glicosilacion de anticuerpos para la mejora de la citotoxicidad celular dependiente de anticuerpos. |
US7112661B1 (en) | 1998-10-30 | 2006-09-26 | The Research Foundation Of State University Of New York | Variable heavy chain and variable light chain regions of antibodies to human platelet glycoprotein Ib alpha |
US7425541B2 (en) | 1998-12-11 | 2008-09-16 | Medarex, Inc. | Enzyme-cleavable prodrug compounds |
US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
EP1176195B1 (en) | 1999-04-09 | 2013-05-22 | Kyowa Hakko Kirin Co., Ltd. | Method for controlling the activity of immunologically functional molecule |
US6939545B2 (en) | 1999-04-28 | 2005-09-06 | Genetics Institute, Llc | Composition and method for treating inflammatory disorders |
CA2385528C (en) | 1999-10-01 | 2013-12-10 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
US7303749B1 (en) | 1999-10-01 | 2007-12-04 | Immunogen Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
JP4668498B2 (ja) | 1999-10-19 | 2011-04-13 | 協和発酵キリン株式会社 | ポリペプチドの製造方法 |
US6333410B1 (en) | 2000-08-18 | 2001-12-25 | Immunogen, Inc. | Process for the preparation and purification of thiol-containing maytansinoids |
PL218428B1 (pl) | 2000-10-06 | 2014-12-31 | Kyowa Hakko Kogyo Kk | Komórka, sposoby wytwarzania przeciwciał, leki zawierające przeciwciała, komórka CHO i przeciwciało klasy IgG |
AU2001294175A1 (en) | 2000-10-06 | 2002-04-22 | Kyowa Hakko Kogyo Co. Ltd. | Method of purifying antibody |
IT1320715B1 (it) | 2000-10-19 | 2003-12-10 | Cselt Centro Studi Lab Telecom | Modulo generatore di circuiti per la decodifica di codiciconvoluzionali, metodo per la generazione di tale tipo di circuito e |
EP2341060B1 (en) | 2000-12-12 | 2019-02-20 | MedImmune, LLC | Molecules with extended half-lives, compositions and uses thereof |
EP1243276A1 (en) | 2001-03-23 | 2002-09-25 | Franciscus Marinus Hendrikus De Groot | Elongated and multiple spacers containing activatible prodrugs |
CA2658221C (en) * | 2001-04-27 | 2012-11-27 | Kyowa Hakko Kirin Co., Ltd. | Anti-cd40 monoclonal antibody |
US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
CN1463270A (zh) | 2001-05-31 | 2003-12-24 | 梅达莱克斯公司 | 细胞毒素、其有用的前体药物、连接基团和稳定剂 |
US6441163B1 (en) | 2001-05-31 | 2002-08-27 | Immunogen, Inc. | Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents |
CN1671416B (zh) | 2001-07-12 | 2013-01-02 | 杰斐逊·富特 | 超人源化抗体 |
ES2271321T3 (es) | 2001-08-03 | 2007-04-16 | Tyco Healthcare Group Lp | Marcador para ser usado con un aparato de marcacion de tejido. |
US7317091B2 (en) | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
US8188231B2 (en) | 2002-09-27 | 2012-05-29 | Xencor, Inc. | Optimized FC variants |
ES2544527T3 (es) | 2002-07-31 | 2015-09-01 | Seattle Genetics, Inc. | Conjugados de fármacos y su uso para tratar el cáncer, una enfermedad autoinmune o una enfermedad infecciosa |
EP1391213A1 (en) | 2002-08-21 | 2004-02-25 | Boehringer Ingelheim International GmbH | Compositions and methods for treating cancer using maytansinoid CD44 antibody immunoconjugates and chemotherapeutic agents |
US20060235208A1 (en) | 2002-09-27 | 2006-10-19 | Xencor, Inc. | Fc variants with optimized properties |
DE10246870B3 (de) | 2002-10-08 | 2004-04-29 | Renk Aktiengesellschaft | Elektro-Hydrodynamische Überlagerungslenkung |
CN100526460C (zh) * | 2002-11-08 | 2009-08-12 | 麒麟医药株式会社 | 朊病毒蛋白活性降低的转基因有蹄类动物及其用途 |
AU2003282624A1 (en) | 2002-11-14 | 2004-06-03 | Syntarga B.V. | Prodrugs built as multiple self-elimination-release spacers |
US8084582B2 (en) | 2003-03-03 | 2011-12-27 | Xencor, Inc. | Optimized anti-CD20 monoclonal antibodies having Fc variants |
US7610156B2 (en) | 2003-03-31 | 2009-10-27 | Xencor, Inc. | Methods for rational pegylation of proteins |
US7276497B2 (en) | 2003-05-20 | 2007-10-02 | Immunogen Inc. | Cytotoxic agents comprising new maytansinoids |
CN101186613B (zh) | 2003-05-20 | 2014-09-17 | 伊缪诺金公司 | 含有新的美登素类的改进的细胞毒剂 |
ZA200603619B (en) | 2003-11-06 | 2008-10-29 | Seattle Genetics Inc | Monomethylvaline compounds capable of conjugation to ligands |
JP5064037B2 (ja) | 2004-02-23 | 2012-10-31 | ジェネンテック, インコーポレイテッド | 複素環式自壊的リンカーおよび結合体 |
EP1725586B1 (en) | 2004-03-02 | 2015-01-14 | Seattle Genetics, Inc. | Partially loaded antibodies and methods of their conjugation |
NZ550934A (en) | 2004-05-19 | 2010-05-28 | Medarex Inc | Chemical linkers and conjugates thereof |
US7691962B2 (en) | 2004-05-19 | 2010-04-06 | Medarex, Inc. | Chemical linkers and conjugates thereof |
NZ580115A (en) | 2004-09-23 | 2010-10-29 | Genentech Inc | Cysteine engineered antibody light chains and conjugates |
EP2551282A3 (en) | 2005-03-23 | 2013-02-13 | Genmab A/S | Antibodies against CD38 for treatment of multiple myeloma |
US7714016B2 (en) | 2005-04-08 | 2010-05-11 | Medarex, Inc. | Cytotoxic compounds and conjugates with cleavable substrates |
CN101203241B (zh) | 2005-04-19 | 2012-02-22 | 西雅图基因公司 | 人源化抗-cd70结合物和其应用 |
LT1912671T (lt) | 2005-07-18 | 2017-12-11 | Seattle Genetics, Inc. | Vaisto konjugatai, turintys gliukoronido linkerį |
JP2009509918A (ja) | 2005-08-05 | 2009-03-12 | シンタルガ・ビーブイ | トリアゾール含有放出可能なリンカー、これらの共役体、および製造方法 |
CA2624189A1 (en) | 2005-10-03 | 2007-04-12 | Xencor, Inc. | Fc variants with optimized fc receptor binding properties |
US8088896B2 (en) | 2005-10-12 | 2012-01-03 | Morphosys Ag | Generation and profiling of fully human gold-derived therapeutic antibodies specific for human CD38 |
KR20080068084A (ko) | 2005-10-26 | 2008-07-22 | 메다렉스, 인코포레이티드 | 씨씨-1065 유사체를 제조하기 위한 방법 및 화합물 |
WO2007059404A2 (en) | 2005-11-10 | 2007-05-24 | Medarex, Inc. | Duocarmycin derivatives as novel cytotoxic compounds and conjugates |
US8940784B2 (en) | 2006-02-02 | 2015-01-27 | Syntarga B.V. | Water-soluble CC-1065 analogs and their conjugates |
WO2008007648A1 (fr) | 2006-07-10 | 2008-01-17 | Institute For Antibodies Co., Ltd. | Procédé de classification d'antigène, procédé d'identification d'antigène, procédé d'obtention d' un ensemble d'antigènes ou d'anticorps, procédés de construction d'un panel d'anticorps, anticorps et ens |
DK2081595T3 (da) * | 2006-09-26 | 2019-07-15 | Genmab As | Anti-cd38 plus corticosteroid plus et ikke-corticosteroid kemoterapeutikum til behandling af tumorer |
EP1914242A1 (en) * | 2006-10-19 | 2008-04-23 | Sanofi-Aventis | Novel anti-CD38 antibodies for the treatment of cancer |
AU2007357156B2 (en) | 2007-08-01 | 2013-01-10 | Syntarga B.V. | Substituted CC-1065 analogs and their conjugates |
US20090076249A1 (en) * | 2007-09-19 | 2009-03-19 | Michel De Weers | Antibodies against CD38 for treatment of multiple myeloma |
CN102317283A (zh) | 2008-11-03 | 2012-01-11 | 辛塔佳股份有限公司 | 新型cc-1065类似物及其缀合物 |
EP2191840A1 (en) | 2008-11-28 | 2010-06-02 | Sanofi-Aventis | Antitumor combinations containing antibodies recognizing specifically CD38 and melphalan |
EP2191841A1 (en) | 2008-11-28 | 2010-06-02 | Sanofi-Aventis | Antitumor combinations containing antibodies recognizing specifically CD38 and vincristine |
EP2191843A1 (en) | 2008-11-28 | 2010-06-02 | Sanofi-Aventis | Antitumor combinations containing antibodies recognizing specifically CD38 and cyclophosphamide |
EP2191842A1 (en) | 2008-11-28 | 2010-06-02 | Sanofi-Aventis | Antitumor combinations containing antibodies recognizing specifically CD38 and cytarabine |
WO2010109924A1 (ja) | 2009-03-25 | 2010-09-30 | 国立大学法人東北大学 | Lh型二重特異性抗体 |
US10817851B2 (en) | 2009-12-23 | 2020-10-27 | Aristocrat Technologies Australia Pty Limited | System and method for cashless gaming |
UA112170C2 (uk) | 2010-12-10 | 2016-08-10 | Санофі | Протипухлинна комбінація, що містить антитіло, яке специфічно розпізнає cd38, і бортезоміб |
US11392902B2 (en) | 2017-06-06 | 2022-07-19 | United Parcel Service Of America, Inc. | Systems, methods, apparatuses and computer program products for providing notification of items for pickup and delivery |
WO2020014526A2 (en) * | 2018-07-11 | 2020-01-16 | Anthony Manning | Compositions and methods related to engineered fc-antigen binding domain constructs targeted to cd38 |
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001509817A (ja) * | 1997-04-07 | 2001-07-24 | ジェネンテク・インコーポレイテッド | 抗vegf抗体 |
WO2006125640A2 (en) * | 2005-05-24 | 2006-11-30 | Morphosys Ag | Generation and profiling of fully human hucal gold®-derived therapeutic antibodies specific for human cd38 |
WO2009077993A2 (en) * | 2007-12-17 | 2009-06-25 | Pfizer Limited | Treatment of interstitial cystitis |
WO2010021874A2 (en) * | 2008-08-20 | 2010-02-25 | Centocor Ortho Biotech Inc. | Engineered anti-il-13 antibodies, compositions, methods and uses |
WO2012092616A1 (en) * | 2010-12-30 | 2012-07-05 | Takeda Pharmaceutical Company Limited | Conjugated anti-cd38 antibodies |
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