JP2013539361A - 改変された等電点を有する抗体 - Google Patents
改変された等電点を有する抗体 Download PDFInfo
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- JP2013539361A JP2013539361A JP2013522017A JP2013522017A JP2013539361A JP 2013539361 A JP2013539361 A JP 2013539361A JP 2013522017 A JP2013522017 A JP 2013522017A JP 2013522017 A JP2013522017 A JP 2013522017A JP 2013539361 A JP2013539361 A JP 2013539361A
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- antibody
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- glutamic acid
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Abstract
【選択図】なし
Description
本発明は、一般に、抗体の1つまたは複数の定常領域ドメインに、アミノ酸置換(「pI変異型」または「pI置換」)を組み込むことにより、(「pI抗体」を形成するために)抗体の等電点(pI)を減少させることに関連する組成物および方法に関する。pI置換は、pIアミノ酸のpIが、定常ドメイン内の特定の位置にある天然アミノ酸のpIよりも低下するように選択される。様々な実施形態において、定常ドメイン変異型は、抗体のpIを減少させ、本明細書で初めて示されるように、in vivo血中半減期を改善する。上で述べた通りであるが、抗体のCDR領域での変異型の生成による、抗体のpIの低下は、血中半減期の増加につながり得ることを示唆している可能性のあるデータは限られている。しかし、本発明の定常ドメインは、可変領域にモジュラな形で追加することができ、よって、血中半減期を増加した抗体の設計を大幅に簡易化するため、本発明は、CDR pIの操作に大きな利益をもたらす。
本発明は、抗体、一般には、治療用抗体のpI変異型の生成に関する。以下で論じるように、「抗体」という用語は、一般的に用いられる。本発明で有用な抗体は、従来的な抗体ならびに、後述する抗体誘導体、フラグメントおよびミメティックも含め、本明細書に記述されるように、数多くの形式を取る。一般に、「抗体」という用語は、CH1、CH2、CH3およびCLを含むが、これらに制限されない定常ドメインを少なくとも1つ含む任意のポリペプチドを包含する。
0B (TRAIL R2 DR5、KILLER、TRICK−2A、TRICK−B)、TNFRSF10C (TRAIL R3 DcR1、LIT、TRID)、TNFRSF10D (TRAIL R4 DcR2、TRUNDD)、TNFRSF11A (RANK ODF R、TRANCE R)、TNFRSF11B(OPG OCIF、TR1)、TNFRSF12(TWEAK R FN14)、TNFRSF13B(TACI)、TNFRSF13C(BAFF R)、TNFRSF14(HVEM ATAR、HveA、LIGHT R、TR2)、TNFRSF16(NGFR p75NTR)、TNFRSF17(BCMA)、TNFRSF18(GITR AITR)、TNFRSF19(TROY TAJ、TRADE)、TNFRSF19L (RELT)、TNFRSF1A(TNF RI CD120a、p55−60)、TNFRSF1B (TNF RII CD120b、p75−80)、TNFRSF26(TNFRH3)、TNFRSF3 (LTbR TNF RIII、TNFC R)、TNFRSF4(OX40 ACT35、TXGP1 R)、TNFRSF5(CD40 p50)、TNFRSF6 (Fas Apo−1、APT1、CD95)、TNFRSF6B(DcR3 M68、TR6)、TNFRSF7(CD27)、TNFRSF8(CD30)、TNFRSF9 (4−1BB CD137、ILA)、TNFRSF21(DR6)、TNFRSF22 (DcTRAIL R2 TNFRH2)、TNFRST23(DcTRAIL R1 TNFRH1)、TNFRSF25 (DR3 Apo−3、LARD、TR−3、TRAMP、WSL−1)、TNFSF10 (TRAIL Apo−2リガンド、TL2)、TNFSF11(TRANCE/RANKリガンドODF、OPGリガンド)、TNFSF12 (TWEAK Apo−3リガンド、DR3リガンド)、TNFSF13(APRIL TALL2)、TNFSF13B(BAFF BLYS、TALL1、THANK、TNFSF20)、TNFSF14(LIGHT HVEMリガンド、LTg)、TNFSF15 (TL1A/VEGI)、TNFSF18(GITRリガンドAITRリガンド、TL6)、TNFSF1A(TNF−aコネクチン、DIF、TNFSF2)、TNFSF1B(TNF−b LTa、TNFSF1)、TNFSF3(LTb TNFC、p33)、TNFSF4(OX40リガンドgp34、TXGP1)、TNFSF5 (CD40リガンドCD154、gp39、HIGM1、IMD3、TRAP)、TNFSF6(FasリガンドApo−1 リガンド、APT1リガンド)、TNFSF7(CD27リガンドCD70)、TNFSF8(CD30リガンドCD153)、TNFSF9 (4−1BBリガンドCD137リガンド)、TP−1、t−PA、Tpo、TRAIL、TRAIL R、TRAIL−R1、TRAIL−R2、TRANCE、トランスフェリン受容体、TRF、Trk、TROP−2、TSG、TSLP、腫瘍関連抗原CA 125、Lewis Y関連炭水化物を発現している腫瘍関連抗原、TWEAK、TXB2、Ung、uPAR、uPAR−1、ウロキナーゼ、VCAM、VCAM−1、VECAD、VE−カドヘリン、VE−カドヘリン−2、VEFGR−1(flt−1)、VEGF、VEGFR、VEGFR−3(flt−4)、VEGI、VIM、ウイルス抗原、VLA、VLA−1、VLA−4、VNRインテグリン、フォン−ウィルブランド病因子、WIF−1、WNT1、WNT2、WNT2B/13、WNT3、WNT3A、WNT4、WNT5A、WNT5B、WNT6、WNT7A、WNT7B、WNT8A、WNT8B、WNT9A、WNT9A、WNT9B、WNT10A、WNT10B、WNT11、WNT16、XCL1、XCL2、XCR1、XCR1、XEDAR、XIAP、XPD、ならびにホルモンおよび成長因子の受容体。
よって開発中の抗細胞間接着分子−1(ICAM−1)(CD54)抗体である、MOR101および MOR102、MorphoSysによって開発中の抗繊維芽細胞成長因子受容体3(FGFR−3)抗体である、MOR201、Protein Design Labsによって開発中の抗CD3抗体である、Nuvion(登録商標) (ビジリズマブ)、Protein Design Labsによって開発中の抗ガンマインターフェロン抗体である、HuZAF(商標)、Protein Design Labsによって開発中の抗α5β1インテグリン、Protein Design Labsによって開発中の抗IL−12、Xomaによって開発中の抗Ep−CAM抗体である、ING−1、Xomaによって開発中の抗ベータ2インテグリン抗体である、MLN01、Seattle Geneticsによって開発されたpI−ADC抗体が含まれる、他の臨床産生物および候補に実質的に類似した、多種多様な抗体で有用になり得、この段落中で上に引用した参照のすべては、参照により本明細書に明白に組み込まれる。
B.キメラ抗体およびヒト化抗体
C.pI変異型
重鎖pI変異型
軽鎖pI変異型
重鎖および軽鎖pI変異型
III. その他のアミノ酸置換
本発明のpI抗体は、pIの低下を示す。一般に、少なくとも0.5log(例えばpH点の半分に対応)の低下が見られ、少なくとも約1、1.5、2、2.5及び3低下すると、本発明で特に使用できる。pIは、当技術分野で周知のように、実験により計算するか又は決定することができる。さらに、pIが5.から5.5から6の範囲であるpI抗体は、血清半減期が良好に延長されると思われる。当業者にとって当然のことながら、及び図30で示されるように、これより低いpIは、ますます多くの突然変異が必要となり、物理学的限界に到達するので、達成するのは困難である。
FcRn修飾
いくつかの実施態様において、本発明のpI変異体は、FcRn結合ドメインにおけるアミノ酸置換と組み合わせることができる。驚くべきことに、本発明は、pI変異体が独立でもよく、場合によってはFc変異体と組み合わせられてもよく、その結果、FcRn受容体に対する結合の増加ならびに半減期延長の両方が起こることを示す。
FcRnに対する結合親和性を向上させ及び/又は血清半減期を延長させるために行われる置換に加えて、Fc領域において、一般にはFcγR受容体に対する結合を変化させるために、その他の置換が行われ得る。
親和性成熟
いくつかの実施態様において、抗体のCDRの1以上において1以上のアミノ酸修飾が行われる。一般に、何れの単一のCDRでも1又は2又は3アミノ酸のみが置換され、一般には、CDRのセット内で4、5、6、7、8 9又は10を超える変化が行われることはない。しかし、何れのCDRにおける置換ゼロ、1、2又は3個の置換の何れの組み合わせも、独立であり得、場合によっては何らかの他の置換と組み合わせられ得ることが認識されるべきである。
いくつかの実施態様において、抗体−薬物複合体(ADC)を形成させるために本発明のpI抗体を薬物と複合体化させる。一般に、ADCは癌への適用において使用され、細胞毒性又は細胞分裂停止剤の局所送達のための抗体−薬物複合体の使用によって、薬物部分の腫瘍への標的送達が可能となり、これにより有効性が高まり、毒性が低下し得る。この技術の概説は、Ducry et al.,Bioconjugate Chem.,21:5−13(2010),Carter et al.,Cancer J.14(3):154(2008)及びSenter,Current Opin.Chem.Biol.13:235−244(2009)(これらは全てその全体において参照により本明細書によって組み込まれる。)で提供される。
いくつかの実施態様において、ADCは、ドラスタチン又はドロスタチンペプチド類似体及び誘導体、アウリスタチンに複合体化されたpI抗体を含む(米国特許第5,635,483号;同第5,780,588号)。ドラスタチン及びアウリスタチンは、微小管ダイナミクス、GTP加水分解及び核及び細胞分裂を妨げ(Woyke et al(2001)Antimicrob.Agents and Chemother.45(12):3580−3584)、抗癌(米国特許第5,663,149号)及び抗真菌活性(Pettit et al(1998)Antimicrob.Agents Chemother.42:2961−2965)を有することが示されている。ドラスタチン又はアウリスタチン薬物部分は、ペプチド薬物部分のN(アミノ)末端又はC(カルボキシル)末端を通じて抗体に連結され得る(WO02/088172)。
他の実施態様において、ADCは、1以上のカリケアマイシン分子に複合体化された本発明の抗体を含む。例えば、マイロターグは、最初の市販ADC薬物であり、ペイロードとしてカリケアマイシンγ1を使用する(その全体において参照により組み込まれる米国特許第4,970,198号を参照のこと)。さらなるカリケアマイシン誘導体は、米国特許第5,264,586号、同第5,384,412号、同第5,550,246号、同第5,739,116号、同第5,773,001号、同第5,767,285号及び同第5,877,296号(全て明確に参照により組み込まれる。)に記載されている。カリケアマイシンファミリーの抗生物質は、ピコモル濃度以下で2本鎖DNA破壊を起こすことができる。カリケアマイシンファミリーの複合体の調製については、米国特許第5,712,374号、同第5,714,586号、同第5,739,116号、同第5,767,285号、同第5,770,701号、同第5,770,710号、同第5,773,001号、同第5,877,296号(全てAmerican Cyanamid Companyに対するもの)を参照のこと。使用され得るカリケアマイシンの構造類似体には、γ1I、α2I、α2I、N−アセチル−γ1I、PSAG及びθI1が含まれるが、限定されない(Hinman et al.,Cancer Research 53:3336−3342(1993),Lode et al.,Cancer Research 58:2925−2928(1998)及びAmerican Cyanamidに対する上述の米国特許)。抗体が複合体化され得る別の抗腫瘍薬は、抗葉酸剤であるQFAである。カリケアマイシン及びQFAの両者は、細胞内作用部位を有し、原形質膜を容易に横断しない。従って、抗体介在性の内在化を通じたこれらの薬剤の細胞取り込みによってそれらの細胞毒性効果が大きく向上する。
CC−1065(参照により組み込まれる4,169,888を参照)及びデュオカルマイシンは、ADCで利用される抗腫瘍抗生物質ファミリーのメンバーである。これらの抗生物質は、アポトーシスをもたらす事象のカスケードを開始させる、副溝のアデニンのN3で配列選択的にDNAをアルキル化することを通じて作用すると思われる。
本発明の抗体と複合体化することができる他の抗腫瘍剤としては、BCNU、ストレプトゾシン、ビンクリスチン及び5−フルオロウラシル、米国特許第5,053,394号、同第5,770,710号に記載の、まとめてLL−E33288複合体として知られる薬剤のファミリーならびにエスペラマイシン(米国特許第5,877,296号)が挙げられる。
一般に、本抗体−薬物複合体化合物は、薬物単位と抗体単位との間にリンカーを含む。いくつかの実施態様において、リンカーは、適切な環境下でリンカーの切断により抗体から薬物単位が放出されるように、細胞内又は細胞外条件下で切断可能である。例えば、ある種のプロテアーゼを分泌する固形腫瘍は、切断可能リンカーの標的となり得;その他の実施態様において、この標的は、利用される細胞内プロテアーゼである。また他の実施態様において、リンカー単位は切断可能ではなく、例えばライソソームにおける抗体分解によって、薬物が放出される。
薬物負荷は、pにより表され、これは分子中の抗体あたりの平均薬物部分数である。薬物負荷(「p」)は、抗体あたり1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20以上の部分(D)であり得るが、平均数は分数又は少数であることが多い。一般に、1から4の薬物負荷は有用であることが多く、1から2も有用である。本発明のADCは、1から20の薬物部分の範囲と複合体化された抗体の集合を含む。複合体化反応からのADCの調製における抗体あたりの平均薬物部分数は、質量分析及びELISAアッセイなどの従来の手段により特徴を調べ得る。
細胞において薬物又は抗体−薬物複合体が細胞分裂停止及び/又は細胞毒性効果を発揮するか否かを判定する方法は公知である。一般に、細胞培養液中で抗体薬物複合体の標的タンパク質を発現する哺乳動物細胞に曝露すること;約6時間から約5日間、細胞を培養すること;及び細胞生存能を測定することによって、抗体薬物複合体の細胞毒性又は細胞分裂停止活性を測定し得る。抗体薬物複合体の、生存性(増殖)、細胞毒性及びアポトーシス(カスパーゼ活性化)の誘導を測定するために、細胞に基づくインビトロアッセイを使用することができる。
別のタイプの共有修飾は、グリコシル化の変更である。別の実施態様において、1以上の改変グリコフォームを含むように本明細書中で開示される抗体を修飾することができる。「改変グリコフォーム」という用語は、本明細書中で使用される場合、抗体に共有結合される炭水化物組成物を意味し、この炭水化物組成物は、親抗体とは化学的に異なる。改変グリコフォームは、エフェクター機能を促進又は低下させることを含むが限定されない様々な目的のために有用であり得る。改変グリコフォームの好ましい形態は、脱フコシル化であり、これは、おそらくはFcγRIIIa受容体へのより密着した結合を通じて、ADCC機能の向上と相関することが示されている。この内容において、「脱フコシル化」は、宿主細胞で産生される抗体の殆どが実質的にフコースを欠くこと、例えば生成抗体の90−95−98%が抗体の炭水化物部分の成分としてあまりフコースがないことを意味する(一般にFc領域のN297で結合)。機能面で定義されるように、脱フコシル化抗体は一般に、FcγRIIIa受容体に対して少なくとも50%以上の親和性を示す。
本発明のpI抗体をコードする核酸が本発明内に含まれる。重及び軽鎖定常ドメインの両方がpI抗体に含まれる場合、一般にこれらは、抗体の四量体構造を生成させるために、標準的宿主細胞(例えばCHO細胞など)内で組み合わせられるそれぞれをコードする核酸を使用して作製される。1つのpI改変定常ドメインのみを作製している場合、1個の核酸のみが使用される。
治療法における本発明のpI抗体の使用は、抗原結合成分に依存し;例えば全長標準治療用抗体の場合、抗体のFvが結合する抗原に依存する。即ち、当業者にとって当然のことながら、分子の半減期の延長というさらなる利益を得ながら特異的な疾患の治療を行うことができる。この結果、投与頻度の減少(患者コンプライアンスがより良好になり得る)、用量低下及び製造コスト低下を含むがこれらに限定されない様々な利益が得られ得る。
ボーラスとしての静脈内投与又は長時間にわたる連続点滴によって、筋肉内、腹腔内、イントラセロブロスピナル(intracerobrospinal)、皮下、関節内、滑液嚢内、髄腔内、経口、局所又は吸入経路によってなど、公知の方法に従って、本発明の抗体及び化学療法剤を対象に投与する。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、疾患又は状態に関して陽性治療反応を提供するために、治療を使用する。「陽性治療反応」は、疾患又は状態の改善、及び/又は疾患又は状態に関連する症状の改善を指す。例えば、陽性治療反応は、疾患の次の改善の1以上を指す:(1)新生物細胞数の減少;(2)新生物細胞死の増加;(3)新生物細胞生存の阻害;(5)腫瘍成長の阻害(即ち、ある程度遅延させること、好ましくは停止させること);(6)患者生存率の向上;及び(7)疾患又は状態に関連する1以上の症状のある程度の緩和。
本発明を説明するために下記で実施例を提供する。これらの実施例は、何らかの特定の適用又は運用理論に本発明を拘束するものではない。本発明において論じられる全定常領域の位置について、付番はKabatのEUインデックスに従うものである(全体的に参照により組み込まれる、Kabat et al.,1991,Sequences of Proteins of Immunological Interest,5th Ed.,United States Public Health Service,National Institutes of Health,Bethesda)。抗体の分野の当業者にとって当然のことながら、この慣例は、免疫グロブリンファミリーにおける保存的位置に対して正規化された参照を可能にする、免疫グロブリン配列の特異的な領域における非連続付番から構成される。従って、EUインデックスにより定義されるような所定の免疫グロブリンの位置はその連続配列に対応する必要はない。
定常ドメインにおいて置換を操作することにより、より低いpIで抗体定常鎖を修飾した。塩基性アミノ酸(K又はR)を酸性アミノ酸(D又はE)に置換することによって、pIを低下させるように改変することができ、その結果、pIが最も大きく低下する。塩基性アミノ酸から中性アミノ酸へ及び中性アミノ酸から酸性アミノ酸への突然変異によってもpIが低下する。アミノ酸pK値のリストは、Bjellqvist et al.,1994,Electrophoresis 15:529−539の表1で見出すことができる。
抗体のpIを低下させるために、IgG1抗体のCH1及びCKドメインにおいて、アミノ酸修飾を操作した。上記の分析に基づき、重鎖CH1に対して選択される置換は、119E、133E、164E、205E、208D及び210Eであり、軽鎖Cκ置換に対する置換は、126E、145E、152D、156E、169E及び202Eであった。これらの変異定常鎖は、それぞれIgG1−CH1−pI(6)及びCK−pI(6)と呼ばれ、それらのアミノ酸配列を図4で提供する。
上述のようなhuFcRnマウスにおいてベバシズマブのIgG1及びIgG2アイソタイプ型のPK試験を行った。4回の個別のPK試験からのIgG1の結果を図14で示す。この4回の試験からの半減期は、3.0、3.9、2.8及び2.9日であり、その結果、平均半減期は3.2日となった。IgG2試験からのPKの結果を図15で示す。IgG2の半減期は5.9日であった。
様々なアプローチを用いて、タンパク質又は抗体のpI低下を遂行することができる。最大塩基性レベルにおいて、pKaが高い残基(リジン、アルギニン及びある程度はヒスチジン)を中性又は陰性残基で置換し、及び/又は中性残基を低pKa残基(アスパラギン酸及びグルタミン酸)で置換する。特定の置換は、構造における位置、機能における役割及び免疫原性を含む様々な因子に依存し得る。
低pIと半減期延長との間の関係の2つの局面を試験するために、一連の新しいpI改変変異体を作製した。最初に、9493IgG1−pI(12)変異体に基づく、調節される一連の変異体を作製することによって電荷のパラメーターを調べた。これらの変異体、10017、10018及び10019は、それらのpI及びベバシズマブIgG1 WTに対する正及び負荷電残基の相違とともに表4に記載する。
上述のように、IgGサブクラス(IgG1、IgG2、IgG3及びIgG4)間のアイソタイプの相違を利用することによってpIを低下させる置換が免疫原性を惹起するリスクを最小化するために、労力を注ぎ得る。この原理に基づいて新しい一連の新規アイソタイプを設計した。繰り返すが、局所配列レベルで免疫認識が起こる、即ち、MHC II及びT−細胞受容体が、一般には9残基長のエピトープ認識するので、配列において近接するアイソタイプ置換によってpIを変化させる置換を遂行した。このようにして、天然のアイソタイプに適合させるためにエピトープを延長させた。従って、このような置換は、他のヒトIgGアイソタイプに存在するエピトープを構成し、従って耐容されることが予想される。
IgG1-pI(7)= K133E/K205E/K210E/K274E/R355E/K392E/K447#
IgG1-pI(11)= K133E/K205E/K210E/K274E/K320E/K322E/K326E/K334E/R355E/K392E/K447#
IgG1/2-pI(7)= K133E/K205E/K210E/Q274E/R355E/K392E/K447#
IgG1/2-pI(11)= K133E/K205E/K210E/Q274E/K320E/K322E/K326E/K334E/R355E/K392E/K447#
CK-pI(4)= K126E/K145E/K169E/K207E
Fv=ベバシズマブにより計算したpI
CK及びCλとの間の相同性は、IgGサブクラス間ほど高くないが(図18で示すように)、存在する配列及び構造相同性はそれでもなお、アイソタイプ低−pI軽鎖定常領域を作製するための置換に対する指標となり得る。図18において、より高いpI(K、R及びH)又はより低いpI(D及びE)に寄与する残基がある位置を太字で強調する。灰色は、等電点を低下させるために好ましくはアスパラギン酸又はグルタミン酸で置換され得るリジン、アルギニン及びヒスチジンを示す。CK及びCλの構造アラインメントを構築し(図35)、いくつかのCK/Cλアイソタイプ変異体を作製するための指標として配列アラインメントとともに使用した。これらのpI−改変変異体を表8で記載し、アミノ酸配列を図28で提供する。
Claims (10)
- 式:A−X119−T−K−G−P−S−V−F−P−L−A−P−X131−S−X133−S−T−S−X137−X138−T−A−A−L−G−C−L−V−K−D−Y−F−P−E−P−V−T−V−S−W−N−S−G−A−L−X164−S−G−V−H−T−F−P−A−V−L−Q−S−S−G−L−Y−S−L−S−S−V−V−T−V−P−S−S−X192−X193−G−T−X196−T−Y−X199−C−N−V−X203−H−X205−P−S−X208−T−X210−V−D−K−X214−V−E−X217−K−X219−C−X221−X222−X223−X224−X225−C−P−P−C−P−A−P−X233−X234−X235−X236−G−P−S−V−F−L−F−P−P−K−P−K−D−T−L−M−I−S−R−T−P−E−V−T−C−V−V−V−D−V−S−H−E−D−P−E−V−X274−F−N−W−Y−V−D−G−V−E−V−H−N−A−K−T−K−P−R−E−E−Q−X296−N−S−T−X300−R−V−V−S−V−L−T−V−X309−H−Q−D−W−L−N−G−K−E−Y−X320−C−X322−V−S−N−X326−X327−L−P−A−P−I−E−X334−T−I−S−K−X339−K−G−Q−P−R−E−P−Q−V−Y−T−L−P−P−S−X355−E−E−M−T−K−N−Q−V−S−L−T−C−L−V−K−G−F−Y−P−S−D−I−A−V−E−W−E−S−X384−G−Q−P−E−N−N−Y−X392−T−T−P−P−X397−L−D−S−D−G−S−F−F−L−Y−S−K−L−T−V−D−K−S−R−W−Q−X419−G−N−V−F−S−C−S−V−X428−H−E−A−L−H−X434−H−Y−T−Q−K−S−L−S−L−S−P−G−X447
を有する、変異重鎖定常ドメインを含む抗体であって、
式中、X119が、S及びEからなる群から選択され;
式中、X131が、S及びCからなる群から選択され;
式中、X133が、K、R、E及びQからなる群から選択され;
式中、X137が、G及びEからなる群から選択され;
式中、X138が、G及びSからなる群から選択され;
式中、X164が、T及びEからなる群から選択され;
式中、X192が、S及びNからなる群から選択され;
式中、X193が、L及びFからなる群から選択され;
式中、X196が、Q及びKからなる群から選択され;
式中、X199が、I及びTからなる群から選択され;
式中、X203が、N及びDからなる群から選択され;
式中、X205が、K、E及びQからなる群から選択され;
式中、X208が、N及びDからなる群から選択され;
式中、X210が、K、E及びQからなる群から選択され;
式中、X214が、K及びTからなる群から選択され;
式中、X217が、P及びRからなる群から選択され;
式中、X219が、S及びCからなる群から選択され;
式中、X220が、C、PLG及びGからなる群から選択され;
式中、X221が、D及び欠失からなる群から選択され;
式中、X222が、K、V及びTからなる群から選択され;
式中、X223が、T及び欠失からなる群から選択され;
式中、X224が、H及びEからなる群から選択され;
式中、X225が、T及び欠失からなる群から選択され;
式中、X233が、E及びPからなる群から選択され;
式中、X234が、L及びVからなる群から選択され;
式中、X235が、L、A及び欠失からなる群から選択され;
式中、X236が、G、A及び欠失からなる群から選択され;
式中、X274が、K、Q及びEからなる群から選択され;
式中、X296が、Y及びFからなる群から選択され;
式中、X300が、Y及びFからなる群から選択され;
式中、X309が、L及びVからなる群から選択され;
式中、X320が、K及びEからなる群から選択され;
式中、X322が、K及びEからなる群から選択され;
式中、X326が、K及びEからなる群から選択され;
式中、X327が、A及びGからなる群から選択され;
式中、X334が、K及びEからなる群から選択され;
式中、X339が、A及びTからなる群から選択され;
式中、X355が、R、Q及びEからなる群から選択され;
式中、X384が、N及びSからなる群から選択され;
式中、X392が、K、N及びEからなる群から選択され;
式中、X397が、V及びMからなる群から選択され;
式中、X419が、Q及びEからなる群から選択され;
式中、X428が、M及びLからなる群から選択され;
式中、X434が、N及びSからなる群から選択され;
式中、X447が、K、DEDE及び欠失からなる群から選択され;
該変異重鎖定常ドメインが、配列番号2と比較した場合に少なくとも6個の突然変異を含み、該変異重鎖定常ドメインが配列番号3ではなく、前記付番がEUインデックスに従う、抗体。 - 前記変異重鎖定常ドメインが、配列番号2と比較した場合に少なくとも10個の突然変異を含む、請求項1に記載の抗体。
- 前記変異重鎖定常ドメインが、配列番号2と比較した場合に少なくとも15個の突然変異を含む、請求項1に記載の抗体。
- 軽鎖定常ドメインをさらに含む、請求項1、2又は3に記載の抗体。
- 前記軽鎖定常ドメインが配列番号112である、請求項4に記載の抗体。
- 前記軽鎖定常ドメインが、式:X108−T−V−A−A−P−S−V−F−I−F−P−P−S−D−E−X124−L−X126−S−G−T−A−S−V−V−C−L−L−N−X138−F−Y−P−R−E−A−X145−V−Q−W−K−V−D−X152−A−L−Q−X156−G−N−S−Q−E−S−V−T−E−Q−D−S−X169−D−S−T−Y−S−L−S−S−T−L−T−L−S−K−A−D−Y−E−K−H−K−V−Y−A−C−E−V−T−H−X199−G−L−X202−S−P−V−T−X207−S−F−N−R−G−E−X214を有する変異軽鎖定常ドメインであり、
式中、X108が、R及びQからなる群から選択され;
式中、X124が、Q及びEからなる群から選択され;
式中、X126が、K、E及びQからなる群から選択され;
式中、X138が、N及びDからなる群から選択され;
式中、X145が、K、E、Q及びTからなる群から選択され;
式中、X152が、N及びDからなる群から選択され;
式中、X156が、S及びEからなる群から選択され;
式中、X169が、K、E及びQからなる群から選択され;
式中、X199が、Q及びEからなる群から選択され;
式中、X202が、S及びEからなる群から選択され;
式中、X207が、K及びEからなる群から選択され;
式中、X214が、C及びCDEDEからなる群から選択され、
該変異軽鎖定常ドメインが、配列番号112と比較した場合に少なくとも2個の突然変異を含む、請求項4に記載の抗体。 - 前期抗体が、
a)重鎖定常ドメインにおいて配列番号52と、軽鎖定常ドメインにおいて配列番号117と、を含む抗体;
b)重鎖定常ドメインにおいて配列番号98と、軽鎖定常ドメインにおいて配列番号152と、を含む抗体;
c)重鎖定常ドメインにおいて配列番号66と、軽鎖定常ドメインにおいて配列番号152と、を含む抗体;及び
d)配列番号191を含む抗体;及び
e)重鎖定常ドメインにおいて配列番号98と、軽鎖定常ドメインにおいて配列番号150と、を含む抗体
からなる群から選択される、請求項7に記載の抗体。 - 請求項1から7に記載の抗体をコードする核酸。
- 請求項8に記載の核酸を含有する宿主細胞。
- 請求項9に記載の宿主細胞を培養し、細胞培養物から抗体を回収することを含む、請求項1から7の何れかに記載の抗体を産生させる方法。
Applications Claiming Priority (11)
Application Number | Priority Date | Filing Date | Title |
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US36896210P | 2010-07-29 | 2010-07-29 | |
US36896910P | 2010-07-29 | 2010-07-29 | |
US61/368,969 | 2010-07-29 | ||
US61/368,962 | 2010-07-29 | ||
US39150910P | 2010-10-08 | 2010-10-08 | |
US39151510P | 2010-10-08 | 2010-10-08 | |
US61/391,515 | 2010-10-08 | ||
US61/391,509 | 2010-10-08 | ||
US201161439263P | 2011-02-03 | 2011-02-03 | |
US61/439,263 | 2011-02-03 | ||
PCT/US2011/046041 WO2012016227A2 (en) | 2010-07-29 | 2011-07-29 | Antibodies with modified isoelectric points |
Publications (3)
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---|---|---|---|---|
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Families Citing this family (114)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
US20090010920A1 (en) | 2003-03-03 | 2009-01-08 | Xencor, Inc. | Fc Variants Having Decreased Affinity for FcyRIIb |
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US11046784B2 (en) | 2006-03-31 | 2021-06-29 | Chugai Seiyaku Kabushiki Kaisha | Methods for controlling blood pharmacokinetics of antibodies |
WO2007114325A1 (ja) | 2006-03-31 | 2007-10-11 | Chugai Seiyaku Kabushiki Kaisha | 二重特異性抗体を精製するための抗体改変方法 |
PH12018501459A1 (en) | 2007-09-26 | 2019-11-11 | Chugai Pharmaceutical Co Ltd | Modified antibody constant region |
MX369784B (es) | 2007-09-26 | 2019-11-21 | Chugai Pharmaceutical Co Ltd | Metodo de modificacion del punto isoelectrico de anticuerpos mediante la sustitucion de aminoacidos en region de determinacion de complementariedad (cdr). |
DK2708559T3 (en) | 2008-04-11 | 2018-06-14 | Chugai Pharmaceutical Co Ltd | Antigen-binding molecule capable of repeatedly binding two or more antigen molecules |
JP5787446B2 (ja) | 2009-03-19 | 2015-09-30 | 中外製薬株式会社 | 抗体定常領域改変体 |
JP5717624B2 (ja) | 2009-03-19 | 2015-05-13 | 中外製薬株式会社 | 抗体定常領域改変体 |
WO2011028952A1 (en) | 2009-09-02 | 2011-03-10 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
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JP5889181B2 (ja) | 2010-03-04 | 2016-03-22 | 中外製薬株式会社 | 抗体定常領域改変体 |
AU2011283694B2 (en) | 2010-07-29 | 2017-04-13 | Xencor, Inc. | Antibodies with modified isoelectric points |
CN108715614A (zh) | 2010-11-30 | 2018-10-30 | 中外制药株式会社 | 与多分子的抗原重复结合的抗原结合分子 |
FR2976811A1 (fr) | 2011-06-22 | 2012-12-28 | Lfb Biotechnologies | Utilisation d'un anticorps anti-cd20 a haute adcc pour le traitement de la maladie de waldenstrom |
WO2013022855A1 (en) * | 2011-08-05 | 2013-02-14 | Xencor, Inc. | Antibodies with modified isoelectric points and immunofiltering |
US10851178B2 (en) | 2011-10-10 | 2020-12-01 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
DK2766392T3 (da) * | 2011-10-10 | 2019-10-07 | Xencor Inc | Fremgangsmåde til oprensning af antistoffer |
GB201203051D0 (en) * | 2012-02-22 | 2012-04-04 | Ucb Pharma Sa | Biological products |
GB201203071D0 (en) * | 2012-02-22 | 2012-04-04 | Ucb Pharma Sa | Biological products |
US9708388B2 (en) | 2012-04-11 | 2017-07-18 | Hoffmann-La Roche Inc. | Antibody light chains |
EP3597747B1 (en) | 2012-08-24 | 2023-03-15 | Chugai Seiyaku Kabushiki Kaisha | Mouse fcgammarii-specific fc antibody |
CA2882272C (en) | 2012-08-24 | 2023-08-29 | Chugai Seiyaku Kabushiki Kaisha | Fc.gamma.riib-specific fc region variant |
EP2943511B1 (en) | 2013-01-14 | 2019-08-07 | Xencor, Inc. | Novel heterodimeric proteins |
US11053316B2 (en) | 2013-01-14 | 2021-07-06 | Xencor, Inc. | Optimized antibody variable regions |
US10131710B2 (en) | 2013-01-14 | 2018-11-20 | Xencor, Inc. | Optimized antibody variable regions |
US9605084B2 (en) | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
US9701759B2 (en) | 2013-01-14 | 2017-07-11 | Xencor, Inc. | Heterodimeric proteins |
US10487155B2 (en) | 2013-01-14 | 2019-11-26 | Xencor, Inc. | Heterodimeric proteins |
US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
EP2945969A1 (en) | 2013-01-15 | 2015-11-25 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
US9353163B2 (en) * | 2013-03-14 | 2016-05-31 | Regeneron Pharmaceuticals, Inc. | Apelin fusion proteins and uses thereof |
WO2014145907A1 (en) | 2013-03-15 | 2014-09-18 | Xencor, Inc. | Targeting t cells with heterodimeric proteins |
US20140294812A1 (en) * | 2013-03-15 | 2014-10-02 | Xencor, Inc. | Fc variants that improve fcrn binding and/or increase antibody half-life |
US10519242B2 (en) | 2013-03-15 | 2019-12-31 | Xencor, Inc. | Targeting regulatory T cells with heterodimeric proteins |
US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
US10106624B2 (en) | 2013-03-15 | 2018-10-23 | Xencor, Inc. | Heterodimeric proteins |
AU2014250434B2 (en) | 2013-04-02 | 2019-08-08 | Chugai Seiyaku Kabushiki Kaisha | Fc region variant |
RU2758952C1 (ru) | 2013-09-27 | 2021-11-03 | Чугаи Сейяку Кабусики Кайся | Способ получения полипептидного гетеромультимера |
EA201691027A1 (ru) | 2013-11-20 | 2016-12-30 | Ридженерон Фармасьютикалз, Инк. | Модуляторы aplnr и их применение |
SG10202008629XA (en) | 2014-03-28 | 2020-10-29 | Xencor Inc | Bispecific antibodies that bind to cd38 and cd3 |
EP3888690A3 (en) | 2014-05-16 | 2021-10-20 | MedImmune, LLC | Molecules with altered neonate fc receptor binding having enhanced therapeutic and diagnostic properties |
SI3166970T1 (sl) * | 2014-07-10 | 2021-09-30 | Bioarctic Ab | Izboljšana A-beta protofibril vezavna protitelesa |
PL3221346T3 (pl) * | 2014-11-21 | 2021-03-08 | Bristol-Myers Squibb Company | Przeciwciała ze zmodyfikowanym regionem stałym łańcucha ciężkiego |
NZ731633A (en) | 2014-11-21 | 2022-01-28 | Bristol Myers Squibb Co | Antibodies against cd73 and uses thereof |
US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
IL252480B2 (en) | 2014-11-26 | 2023-12-01 | Xencor Inc | Heterodimeric antibodies that bind CD3 and tumor antigens |
JP2017536830A (ja) | 2014-11-26 | 2017-12-14 | ゼンコー・インコーポレイテッドXencor、 Inc. | Cd3及びcd38に結合するヘテロ二量体抗体 |
JP6227191B1 (ja) | 2014-12-19 | 2017-11-08 | 中外製薬株式会社 | 抗ミオスタチン抗体、変異Fc領域を含むポリペプチド、および使用方法 |
EP3237449A2 (en) | 2014-12-22 | 2017-11-01 | Xencor, Inc. | Trispecific antibodies |
KR102605798B1 (ko) | 2015-02-05 | 2023-11-23 | 추가이 세이야쿠 가부시키가이샤 | 이온 농도 의존적 항원 결합 도메인을 포함하는 항체, Fc 영역 개변체, IL-8에 결합하는 항체, 및 그들의 사용 |
US10227411B2 (en) | 2015-03-05 | 2019-03-12 | Xencor, Inc. | Modulation of T cells with bispecific antibodies and FC fusions |
WO2016159213A1 (ja) | 2015-04-01 | 2016-10-06 | 中外製薬株式会社 | ポリペプチド異種多量体の製造方法 |
EA201792497A1 (ru) | 2015-06-03 | 2018-05-31 | Бристол-Майерс Сквибб Компани | Антитела к gitr для диагностики злокачественной опухоли |
TWI751300B (zh) | 2015-09-18 | 2022-01-01 | 日商中外製藥股份有限公司 | Il-8 結合抗體及其用途 |
SG10201911226QA (en) * | 2015-09-23 | 2020-01-30 | Genentech Inc | Optimized variants of anti-vegf antibodies |
US11623957B2 (en) | 2015-12-07 | 2023-04-11 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and PSMA |
JP7141336B2 (ja) | 2015-12-25 | 2022-09-22 | 中外製薬株式会社 | 抗ミオスタチン抗体および使用方法 |
KR20180091918A (ko) | 2015-12-28 | 2018-08-16 | 추가이 세이야쿠 가부시키가이샤 | Fc 영역 함유 폴리펩타이드의 정제를 효율화하기 위한 방법 |
IL263542B1 (en) | 2016-06-14 | 2024-06-01 | Xencor Inc | Bispecific antibodies inhibit immunological checkpoint |
KR101822352B1 (ko) | 2016-06-17 | 2018-01-25 | 추가이 세이야쿠 가부시키가이샤 | 항-마이오스타틴 항체 및 사용 방법 |
WO2018005706A1 (en) | 2016-06-28 | 2018-01-04 | Xencor, Inc. | Heterodimeric antibodies that bind somatostatin receptor 2 |
JP6527643B2 (ja) | 2016-08-05 | 2019-06-05 | 中外製薬株式会社 | Il−8関連疾患の治療用又は予防用組成物 |
US10793632B2 (en) | 2016-08-30 | 2020-10-06 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
SG10201607778XA (en) | 2016-09-16 | 2018-04-27 | Chugai Pharmaceutical Co Ltd | Anti-Dengue Virus Antibodies, Polypeptides Containing Variant Fc Regions, And Methods Of Use |
AU2017342559B2 (en) | 2016-10-14 | 2022-03-24 | Xencor, Inc. | Bispecific heterodimeric fusion proteins containing IL-15/IL-15Ralpha Fc-fusion proteins and PD-1 antibody fragments |
KR20200006115A (ko) | 2017-05-16 | 2020-01-17 | 브리스톨-마이어스 스큅 컴퍼니 | 항-gitr 효능제 항체에 의한 암의 치료 |
WO2019006472A1 (en) | 2017-06-30 | 2019-01-03 | Xencor, Inc. | TARGETED HETETRODIMERIC FUSION PROTEINS CONTAINING IL-15 / IL-15RA AND ANTIGEN-BINDING DOMAINS |
US10981992B2 (en) | 2017-11-08 | 2021-04-20 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
CA3082383A1 (en) | 2017-11-08 | 2019-05-16 | Xencor, Inc. | Bispecific and monospecific antibodies using novel anti-pd-1 sequences |
US11319355B2 (en) | 2017-12-19 | 2022-05-03 | Xencor, Inc. | Engineered IL-2 Fc fusion proteins |
SG11202009010RA (en) | 2018-03-15 | 2020-10-29 | Chugai Pharmaceutical Co Ltd | Anti-dengue virus antibodies having cross-reactivity to zika virus and methods of use |
US10982006B2 (en) | 2018-04-04 | 2021-04-20 | Xencor, Inc. | Heterodimeric antibodies that bind fibroblast activation protein |
US11505595B2 (en) | 2018-04-18 | 2022-11-22 | Xencor, Inc. | TIM-3 targeted heterodimeric fusion proteins containing IL-15/IL-15RA Fc-fusion proteins and TIM-3 antigen binding domains |
JP2021521784A (ja) | 2018-04-18 | 2021-08-30 | ゼンコア インコーポレイテッド | IL−15/IL−15RaFc融合タンパク質とPD−1抗原結合ドメインを含むPD−1標的化ヘテロダイマー融合タンパク質およびそれらの使用 |
CN113195534A (zh) | 2018-04-18 | 2021-07-30 | Xencor股份有限公司 | 包含il-15/il-15ra fc融合蛋白和lag-3抗原结合结构域的靶向lag-3的异源二聚体融合蛋白 |
TW202016151A (zh) | 2018-06-09 | 2020-05-01 | 德商百靈佳殷格翰國際股份有限公司 | 針對癌症治療之多特異性結合蛋白 |
SG11202013138RA (en) | 2018-07-02 | 2021-01-28 | Amgen Inc | Anti-steap1 antigen-binding protein |
WO2020072821A2 (en) | 2018-10-03 | 2020-04-09 | Xencor, Inc. | Il-12 heterodimeric fc-fusion proteins |
US11377477B2 (en) | 2018-10-12 | 2022-07-05 | Xencor, Inc. | PD-1 targeted IL-15/IL-15RALPHA fc fusion proteins and uses in combination therapies thereof |
SG11202109406TA (en) | 2019-03-01 | 2021-09-29 | Xencor Inc | Heterodimeric antibodies that bind enpp3 and cd3 |
SG11202110986YA (en) | 2019-04-10 | 2021-11-29 | Chugai Pharmaceutical Co Ltd | Method for purifying fc region-modified antibody |
US11512122B2 (en) | 2019-05-17 | 2022-11-29 | Xencor, Inc. | IL-7-FC-fusion proteins |
US20210102002A1 (en) | 2019-08-06 | 2021-04-08 | Xencor, Inc. | HETERODIMERIC IgG-LIKE BISPECIFIC ANTIBODIES |
KR20220113791A (ko) | 2019-12-18 | 2022-08-16 | 에프. 호프만-라 로슈 아게 | 이중특이적 항-ccl2 항체 |
US20230058982A1 (en) | 2019-12-27 | 2023-02-23 | Chugai Seiyaku Kabushiki Kaisha | Anti-ctla-4 antibody and use thereof |
US20220106403A1 (en) | 2020-05-14 | 2022-04-07 | Xencor, Inc. | Heterodimeric antibodies that bind msln and cd3 |
WO2021231976A1 (en) | 2020-05-14 | 2021-11-18 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (psma) and cd3 |
IL300666A (en) | 2020-08-19 | 2023-04-01 | Xencor Inc | ANTI–CD28 COMPOSITIONS |
WO2022044248A1 (ja) | 2020-08-28 | 2022-03-03 | 中外製薬株式会社 | ヘテロ二量体Fcポリペプチド |
US20220135684A1 (en) | 2020-10-14 | 2022-05-05 | Xencor, Inc. | Bispecific antibodies that bind pd-l1 and cd28 |
CN117157319A (zh) | 2021-03-09 | 2023-12-01 | Xencor股份有限公司 | 结合cd3和cldn6的异二聚抗体 |
JP2024509274A (ja) | 2021-03-10 | 2024-02-29 | ゼンコア インコーポレイテッド | Cd3及びgpc3に結合するヘテロ二量体抗体 |
EP4355775A1 (en) | 2021-06-18 | 2024-04-24 | F. Hoffmann-La Roche AG | Bispecific anti-ccl2 antibodies |
IL309115A (en) | 2021-06-25 | 2024-02-01 | Chugai Pharmaceutical Co Ltd | Anti-CTLA-4 antibodies |
TW202311291A (zh) | 2021-06-25 | 2023-03-16 | 日商中外製藥股份有限公司 | 抗ctla-4抗體的用途 |
US20230146665A1 (en) | 2021-07-27 | 2023-05-11 | Xencor, Inc. | Il-18-fc fusion proteins |
WO2023028612A2 (en) | 2021-08-27 | 2023-03-02 | Board Of Regents, The University Of Texas System | Anti-tslpr (crlf2) antibodies |
CN118043356A (zh) | 2021-09-27 | 2024-05-14 | Xencor股份有限公司 | B细胞成熟抗原(bcma)结合结构域组合物 |
WO2023086772A1 (en) | 2021-11-12 | 2023-05-19 | Xencor, Inc. | Bispecific antibodies that bind to b7h3 and nkg2d |
WO2023164510A1 (en) | 2022-02-23 | 2023-08-31 | Xencor, Inc. | Anti-cd28 x anti-psma antibodies |
WO2023164627A1 (en) | 2022-02-24 | 2023-08-31 | Xencor, Inc. | Anti-cd28 x anti-msln antibodies |
WO2023164640A1 (en) | 2022-02-24 | 2023-08-31 | Xencor, Inc. | Anti-cd28 x anti-trop2 antibodies |
US20240025968A1 (en) | 2022-04-07 | 2024-01-25 | Xencor, Inc. | LAG-3 TARGETED HETERODIMERIC FUSION PROTEINS CONTAINING IL-15/IL-15RA Fc-FUSION PROTEINS AND LAG-3 ANTIGEN BINDING DOMAINS |
WO2023201309A1 (en) | 2022-04-13 | 2023-10-19 | Xencor, Inc. | Antibodies that bind pd-l1, pd-l2 and/or cd28 |
WO2024092038A2 (en) | 2022-10-25 | 2024-05-02 | Ablexis, Llc | Anti-cd3 antibodies |
WO2024102636A1 (en) | 2022-11-07 | 2024-05-16 | Xencor, Inc. | Bispecific antibodies that bind to b7h3 and mica/b |
US20240166705A1 (en) | 2022-11-07 | 2024-05-23 | Xencor, Inc. | Il18-fc fusion proteins |
WO2024107731A2 (en) | 2022-11-14 | 2024-05-23 | Ablexis, Llc | Anti-pd-l1 antibodies |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009041613A1 (ja) * | 2007-09-26 | 2009-04-02 | Chugai Seiyaku Kabushiki Kaisha | 抗体定常領域改変体 |
WO2009041643A1 (ja) * | 2007-09-26 | 2009-04-02 | Chugai Seiyaku Kabushiki Kaisha | Cdrのアミノ酸置換により抗体の等電点を改変する方法 |
WO2009041062A1 (ja) * | 2007-09-28 | 2009-04-02 | Chugai Seiyaku Kabushiki Kaisha | 血漿中動態が改善されたグリピカン3抗体 |
WO2009086320A1 (en) * | 2007-12-26 | 2009-07-09 | Xencor, Inc | Fc variants with altered binding to fcrn |
Family Cites Families (290)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
CU22545A1 (es) | 1994-11-18 | 1999-03-31 | Centro Inmunologia Molecular | Obtención de un anticuerpo quimérico y humanizado contra el receptor del factor de crecimiento epidérmico para uso diagnóstico y terapéutico |
US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
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 |
US4364935A (en) | 1979-12-04 | 1982-12-21 | Ortho Pharmaceutical Corporation | Monoclonal antibody to a human prothymocyte antigen and methods of preparing same |
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 |
US4753894A (en) | 1984-02-08 | 1988-06-28 | Cetus Corporation | Monoclonal anti-human breast cancer antibodies |
US4943533A (en) | 1984-03-01 | 1990-07-24 | The Regents Of The University Of California | Hybrid cell lines that produce monoclonal antibodies to epidermal growth factor receptor |
US4970198A (en) | 1985-10-17 | 1990-11-13 | American Cyanamid Company | Antitumor antibiotics (LL-E33288 complex) |
DE3675588D1 (de) | 1985-06-19 | 1990-12-20 | Ajinomoto Kk | Haemoglobin, das an ein poly(alkenylenoxid) gebunden ist. |
JPS63502716A (ja) | 1986-03-07 | 1988-10-13 | マサチューセッツ・インステチュート・オブ・テクノロジー | 糖タンパク安定性の強化方法 |
DE3783588T2 (de) | 1986-04-17 | 1993-06-09 | Kyowa Hakko Kogyo Kk | Neue verbindungen dc-88a und dc-89a1 und deren herstellungsverfahren. |
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 |
IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
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 |
US5770701A (en) | 1987-10-30 | 1998-06-23 | American Cyanamid Company | Process for preparing targeted forms of methyltrithio antitumor agents |
US5053394A (en) | 1988-09-21 | 1991-10-01 | American Cyanamid Company | Targeted forms of methyltrithio antitumor agents |
WO1989006692A1 (en) | 1988-01-12 | 1989-07-27 | Genentech, Inc. | Method of treating tumor cells by inhibiting growth factor receptor function |
IL89220A (en) | 1988-02-11 | 1994-02-27 | Bristol Myers Squibb Co | Immunoconjugates of anthracycline, their production and pharmaceutical preparations containing them |
US5084468A (en) | 1988-08-11 | 1992-01-28 | Kyowa Hakko Kogyo Co., Ltd. | Dc-88a derivatives |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
JP2598116B2 (ja) | 1988-12-28 | 1997-04-09 | 協和醗酵工業株式会社 | 新規物質dc113 |
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 |
CA2026147C (en) | 1989-10-25 | 2006-02-07 | Ravi J. Chari | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
IE911537A1 (en) | 1990-05-07 | 1991-11-20 | Scripps Clinic Res | Intermediates in the formation of the calicheamicin and¹esperamicin oligosaccharides |
US5968509A (en) | 1990-10-05 | 1999-10-19 | Btp International Limited | Antibodies with binding affinity for the CD3 antigen |
SK281142B6 (sk) | 1991-03-06 | 2000-12-11 | Merck Patent Gesellschaft Mit Beschr�Nkter Haftung | Humanizovaná monoklonálna protilátka, expresné vektory a farmaceutický prostriedok |
WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
EP1400536A1 (en) | 1991-06-14 | 2004-03-24 | 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 |
GB9206422D0 (en) | 1992-03-24 | 1992-05-06 | Bolt Sarah L | Antibody preparation |
CA2076465C (en) | 1992-03-25 | 2002-11-26 | Ravi V. J. Chari | Cell binding agent conjugates of analogues and derivatives of cc-1065 |
ZA932522B (en) | 1992-04-10 | 1993-12-20 | Res Dev Foundation | Immunotoxins directed against c-erbB-2(HER/neu) related surface antigens |
US6329507B1 (en) | 1992-08-21 | 2001-12-11 | The Dow Chemical Company | Dimer and multimer forms of single chain polypeptides |
US5736137A (en) | 1992-11-13 | 1998-04-07 | Idec Pharmaceuticals Corporation | Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma |
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 |
US5837242A (en) | 1992-12-04 | 1998-11-17 | Medical Research Council | Multivalent and multispecific binding proteins, their manufacture and use |
SG55079A1 (en) | 1992-12-11 | 1998-12-21 | Dow Chemical Co | Multivalent single chain antibodies |
US5780588A (en) | 1993-01-26 | 1998-07-14 | Arizona Board Of Regents | Elucidation and synthesis of selected pentapeptides |
US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
ES2233928T3 (es) | 1993-10-01 | 2005-06-16 | Teikoku Hormone Mfg. Co., Ltd. | Derivados de dolastatina. |
GB9401182D0 (en) | 1994-01-21 | 1994-03-16 | Inst Of Cancer The Research | Antibodies to EGF receptor and their antitumour effect |
WO1995029179A1 (fr) | 1994-04-22 | 1995-11-02 | Kyowa Hakko Kogyo Co., Ltd. | Derive de dc-89 |
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 |
US5945311A (en) | 1994-06-03 | 1999-08-31 | GSF--Forschungszentrumfur Umweltund Gesundheit | Method for producing heterologous bi-specific antibodies |
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 |
US5541087A (en) | 1994-09-14 | 1996-07-30 | Fuji Immunopharmaceuticals Corporation | Expression and export technology of proteins as immunofusins |
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 |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
US5739277A (en) * | 1995-04-14 | 1998-04-14 | Genentech Inc. | Altered polypeptides with increased half-life |
US5714586A (en) | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
AU6267896A (en) | 1995-06-07 | 1996-12-30 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth oftumors |
US5712374A (en) | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
US7696338B2 (en) | 1995-10-30 | 2010-04-13 | The United States Of America As Represented By The Department Of Health And Human Services | Immunotoxin fusion proteins and means for expression thereof |
PT871490E (pt) | 1995-12-22 | 2003-07-31 | Bristol Myers Squibb Co | Ligantes de hidrazona ramificada |
ES2246069T3 (es) | 1997-05-02 | 2006-02-01 | Genentech, Inc. | Procedimiento de preparacion de anticuerpos multiespecificos que tienen componentes comunes y multimericos. |
US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
EP1049787B1 (en) | 1998-01-23 | 2004-11-24 | Vlaams Interuniversitair Instituut voor Biotechnologie | Multipurpose antibody derivatives |
PT1071700E (pt) | 1998-04-20 | 2010-04-23 | Glycart Biotechnology Ag | Modificação por glicosilação de anticorpos para melhorar a citotoxicidade celular dependente de anticorpos |
NZ507381A (en) | 1998-04-21 | 2003-12-19 | Micromet Ag | CD19xCD3 specific polypeptides and uses thereof |
US6455677B1 (en) | 1998-04-30 | 2002-09-24 | Boehringer Ingelheim International Gmbh | FAPα-specific antibody with improved producibility |
DE69942148D1 (de) | 1998-06-22 | 2010-04-29 | Immunomedics Inc | Gebrauch von bispezifischen antikörpern in diagnose und therapie |
GB9815909D0 (en) | 1998-07-21 | 1998-09-16 | Btg Int Ltd | Antibody preparation |
US6723538B2 (en) | 1999-03-11 | 2004-04-20 | Micromet Ag | Bispecific antibody and chemokine receptor constructs |
ES2571230T3 (es) | 1999-04-09 | 2016-05-24 | Kyowa Hakko Kirin Co Ltd | Procedimiento para controlar la actividad de una molécula inmunofuncional |
US6939545B2 (en) | 1999-04-28 | 2005-09-06 | Genetics Institute, Llc | Composition and method for treating inflammatory disorders |
US7303749B1 (en) | 1999-10-01 | 2007-12-04 | Immunogen Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
EP2289549A3 (en) | 1999-10-01 | 2011-06-15 | Immunogen, Inc. | Immunoconjugates for treating cancer |
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 |
US6716410B1 (en) | 1999-10-26 | 2004-04-06 | The Regents Of The University Of California | Reagents and methods for diagnosing, imaging and treating atherosclerotic disease |
UA77157C2 (en) | 2000-02-25 | 2006-11-15 | Polypeptide anti-egfrviii scfvs with improved cytotoxicity and output, molecule of nucleic acid, that codes the indicated polypeptide, and method of cell destructure with using of this polypeptide | |
US20010035606A1 (en) | 2000-03-28 | 2001-11-01 | Schoen Alan H. | Set of blocks for packing a cube |
AU5943201A (en) | 2000-05-03 | 2001-11-12 | Amgen Inc | Modified peptides as therapeutic agents |
AU2001258567A1 (en) | 2000-05-19 | 2001-11-26 | Scancell Limited | Humanised antibodies to the epidermal growth factor receptor |
JP2004511430A (ja) | 2000-05-24 | 2004-04-15 | イムクローン システムズ インコーポレイティド | 二重特異性免疫グロブリン様抗原結合蛋白および製造方法 |
AU2001283496A1 (en) | 2000-07-25 | 2002-02-05 | Immunomedics, Inc. | Multivalent target binding protein |
US6333410B1 (en) | 2000-08-18 | 2001-12-25 | Immunogen, Inc. | Process for the preparation and purification of thiol-containing maytansinoids |
DE10043437A1 (de) | 2000-09-04 | 2002-03-28 | Horst Lindhofer | Verwendung von trifunktionellen bispezifischen und trispezifischen Antikörpern zur Behandlung von malignem Aszites |
MXPA00009407A (es) | 2000-09-26 | 2004-12-08 | Mexicano Inst Petrol | Procedimiento para la preparacion de un catalizador monometalico de tipo zeolitico para la obtencion de gasolinas de alto octando mediante reformacion de naftas. |
CN102311986B (zh) | 2000-10-06 | 2015-08-19 | 协和发酵麒麟株式会社 | 产生抗体组合物的细胞 |
EP1333032A4 (en) | 2000-10-06 | 2005-03-16 | Kyowa Hakko Kogyo Kk | METHOD FOR PURIFYING ANTIBODIES |
US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
WO2002062850A2 (en) | 2001-02-02 | 2002-08-15 | Millennium Pharmaceuticals, Inc. | Hybrid antibodies and uses thereof |
EP1243276A1 (en) | 2001-03-23 | 2002-09-25 | Franciscus Marinus Hendrikus De Groot | Elongated and multiple spacers containing activatible prodrugs |
AU2002307037B2 (en) | 2001-04-02 | 2008-08-07 | Biogen Idec Inc. | Recombinant antibodies coexpressed with GnTIII |
US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
MXPA03011094A (es) | 2001-05-31 | 2004-12-06 | Medarex Inc | Citotoxinas, profarmacos, ligadores, y estabilizadores utiles para ello. |
US6441163B1 (en) | 2001-05-31 | 2002-08-27 | Immunogen, Inc. | Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents |
CA2450285C (en) | 2001-06-13 | 2016-08-02 | Genmab A/S | Human monoclonal antibodies to epidermal growth factor receptor (egfr) |
CA2452058A1 (en) | 2001-06-26 | 2003-01-09 | Imclone Systems Incorporated | Bispecific antibodies that bind to vegf receptors |
AU2002337935B2 (en) | 2001-10-25 | 2008-05-01 | Genentech, Inc. | Glycoprotein compositions |
US20080219974A1 (en) | 2002-03-01 | 2008-09-11 | Bernett Matthew J | Optimized antibodies that target hm1.24 |
US8188231B2 (en) | 2002-09-27 | 2012-05-29 | Xencor, Inc. | Optimized FC variants |
US7332580B2 (en) | 2002-04-05 | 2008-02-19 | The Regents Of The University Of California | Bispecific single chain Fv antibody molecules and methods of use thereof |
WO2004010957A2 (en) | 2002-07-31 | 2004-02-05 | Seattle Genetics, Inc. | Drug conjugates and their use for treating cancer, an autoimmune disease or an infectious disease |
US8946387B2 (en) | 2002-08-14 | 2015-02-03 | Macrogenics, Inc. | FcγRIIB specific antibodies and methods of use thereof |
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 |
US7820166B2 (en) | 2002-10-11 | 2010-10-26 | Micromet Ag | Potent T cell modulating molecules |
AU2003282624A1 (en) | 2002-11-14 | 2004-06-03 | Syntarga B.V. | Prodrugs built as multiple self-elimination-release spacers |
KR101329843B1 (ko) | 2002-11-15 | 2013-11-14 | 젠맵 에이/에스 | Cd25에 대한 인간 모노클로날 항체 |
BRPI0316779B1 (pt) | 2002-12-16 | 2020-04-28 | Genentech Inc | anticorpo humanizado que liga cd20 humano, composição, artigo manufaturado, método de indução da apoptose, método de tratamento de câncer cd20 positivo, métodos de tratamento de doenças autoimunes, ácidos nucléicos isolados, vetores de expressão, células hospedeiras, método para a produção de um anticorpo 2h7 humanizado, polipeptídeo isolado, formulação líquida, método de tratamento de artrite reumatóide (ra) e anticorpos de ligação de cd20 humanizados |
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 |
LT3524611T (lt) | 2003-05-20 | 2021-04-12 | Immunogen, Inc. | Patobulinti citotoksiniai agentai, apimantys naujus maitansinoidus |
US7276497B2 (en) | 2003-05-20 | 2007-10-02 | Immunogen Inc. | Cytotoxic agents comprising new maytansinoids |
KR20060015602A (ko) | 2003-05-31 | 2006-02-17 | 마이크로메트 에이지 | EpCAM 에 대한 이중 특이성 항체를 포함하는약학조성물 |
AU2004242846A1 (en) | 2003-05-31 | 2004-12-09 | Micromet Ag | Pharmaceutical compositions comprising bispecific anti-CD3, anti-CD19 antibody constructs for the treatment of B-cell related disorders |
US7888134B2 (en) | 2003-06-05 | 2011-02-15 | Oakland University | Immunosensors: scFv-linker design for surface immobilization |
US20060134105A1 (en) | 2004-10-21 | 2006-06-22 | Xencor, Inc. | IgG immunoglobulin variants with optimized effector function |
US20150071948A1 (en) | 2003-09-26 | 2015-03-12 | Gregory Alan Lazar | Novel immunoglobulin variants |
US20050176028A1 (en) | 2003-10-16 | 2005-08-11 | Robert Hofmeister | Deimmunized binding molecules to CD3 |
BR122018071808B8 (pt) | 2003-11-06 | 2020-06-30 | Seattle Genetics Inc | conjugado |
US20050142133A1 (en) | 2003-12-03 | 2005-06-30 | Xencor, Inc. | Optimized proteins that target the epidermal growth factor receptor |
CA2548817A1 (en) | 2003-12-04 | 2005-06-23 | Xencor, Inc. | Methods of generating variant proteins with increased host string content and compositions thereof |
PT1718677E (pt) | 2003-12-19 | 2012-07-18 | Genentech Inc | Fragmentos de anticorpo monovalentes úteis como agentes terapêuticos |
US7235641B2 (en) | 2003-12-22 | 2007-06-26 | Micromet Ag | Bispecific antibodies |
EP1737890A2 (en) * | 2004-03-24 | 2007-01-03 | Xencor, Inc. | Immunoglobulin variants outside the fc region |
US7691962B2 (en) | 2004-05-19 | 2010-04-06 | Medarex, Inc. | Chemical linkers and conjugates thereof |
US7517903B2 (en) | 2004-05-19 | 2009-04-14 | Medarex, Inc. | Cytotoxic compounds and conjugates |
MXPA06014075A (es) | 2004-06-03 | 2007-03-15 | Novimmune Sa | Anticuerpos anti-cd3 y metodos de uso de los mismos. |
US20060018897A1 (en) | 2004-06-28 | 2006-01-26 | Transtarget Inc. | Bispecific antibodies |
EP1786918A4 (en) | 2004-07-17 | 2009-02-11 | Imclone Systems Inc | NEW BISPECIFIC ANTIBODY TETRAVALENT |
ZA200701783B (en) | 2004-09-02 | 2009-10-28 | Genentech Inc | Anti-Fc-gamma RIIB receptor antibody and uses therefor |
CA2580141C (en) | 2004-09-23 | 2013-12-10 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
BRPI0516011A (pt) | 2004-09-24 | 2008-08-19 | Amgen Inc | moléculas fc modificadas |
US8367805B2 (en) | 2004-11-12 | 2013-02-05 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US8066989B2 (en) | 2004-11-30 | 2011-11-29 | Trion Pharma Gmbh | Method of treating tumor growth and metastasis by using trifunctional antibodies to reduce the risk for GvHD in allogeneic antitumor cell therapy |
KR101404512B1 (ko) | 2005-01-05 | 2015-01-29 | 에프-스타 비오테크놀로기쉐 포르슝스 운드 엔트비클룽스게스.엠.베.하. | 상보성 결정부위와 다른 분자의 부위에서 처리된 결합성을갖는 합성 면역글로불린 영역 |
US8716451B2 (en) | 2005-01-12 | 2014-05-06 | Kyowa Hakko Kirin Co., Ltd | Stabilized human IgG2 and IgG3 antibodies |
TWI671403B (zh) | 2005-03-31 | 2019-09-11 | 中外製藥股份有限公司 | 控制組裝之多肽的製造方法 |
US7714016B2 (en) | 2005-04-08 | 2010-05-11 | Medarex, Inc. | Cytotoxic compounds and conjugates with cleavable substrates |
US9284375B2 (en) | 2005-04-15 | 2016-03-15 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
US8309690B2 (en) | 2005-07-01 | 2012-11-13 | Medimmune, Llc | Integrated approach for generating multidomain protein therapeutics |
DE602006020577D1 (de) | 2005-07-01 | 2011-04-21 | Dako Denmark As | Monomere und polymere linker zur konjugierung von biologischen molekülen und anderen stoffen |
UA97469C2 (uk) | 2005-07-25 | 2012-02-27 | Емерджент Продакт Дівелопмент Сіетл, Елелсі | Гуманізована специфічна до cd37 зв'язувальна молекула імуноглобуліну |
AU2006272597A1 (en) | 2005-07-25 | 2007-02-01 | Emergent Product Development Seattle Llc | Single dose use of CD20-specific binding molecules |
US8158590B2 (en) | 2005-08-05 | 2012-04-17 | Syntarga B.V. | Triazole-containing releasable linkers, conjugates thereof, and methods of preparation |
US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
WO2007041635A2 (en) | 2005-10-03 | 2007-04-12 | Xencor, Inc. | Fc variants with optimized fc receptor binding properties |
US8236308B2 (en) | 2005-10-11 | 2012-08-07 | Micromet Ag | Composition comprising cross-species-specific antibodies and uses thereof |
AU2006304387A1 (en) | 2005-10-14 | 2007-04-26 | Medimmune, Llc | Cell display of antibody libraries |
WO2007047829A2 (en) | 2005-10-19 | 2007-04-26 | Laboratoires Serono S.A. | Novel heterodimeric proteins and uses thereof |
AR056142A1 (es) | 2005-10-21 | 2007-09-19 | Amgen Inc | Metodos para generar el anticuerpo igg monovalente |
CA2627190A1 (en) | 2005-11-10 | 2007-05-24 | Medarex, Inc. | Duocarmycin derivatives as novel cytotoxic compounds and conjugates |
EP1957541A2 (en) | 2005-11-21 | 2008-08-20 | Laboratoires Serono SA | Compositions and methods of producing hybrid antigen binding molecules and uses thereof |
MX2008008046A (es) | 2005-12-21 | 2009-03-04 | Micromet Ag | Moleculas de epha2-bite y usos de las mismas. |
CN101415679A (zh) | 2006-02-02 | 2009-04-22 | 辛塔佳有限公司 | 水溶性cc-1065类似物及其缀合物 |
EP1820513A1 (en) | 2006-02-15 | 2007-08-22 | Trion Pharma Gmbh | Destruction of tumor cells expressing low to medium levels of tumor associated target antigens by trifunctional bispecific antibodies |
EP1829895A1 (en) | 2006-03-03 | 2007-09-05 | f-star Biotechnologische Forschungs- und Entwicklungsges.m.b.H. | Bispecific molecule binding TLR9 and CD32 and comprising a T cell epitope for treatment of allergies |
NZ591252A (en) | 2006-03-17 | 2012-06-29 | Biogen Idec Inc | Methods of designing antibody or antigen binding fragments thereof with substituted non-covarying amino acids |
PT1999154E (pt) | 2006-03-24 | 2013-01-24 | Merck Patent Gmbh | Domínios proteicos heterodiméricos modificados |
WO2007114325A1 (ja) | 2006-03-31 | 2007-10-11 | Chugai Seiyaku Kabushiki Kaisha | 二重特異性抗体を精製するための抗体改変方法 |
US11046784B2 (en) | 2006-03-31 | 2021-06-29 | Chugai Seiyaku Kabushiki Kaisha | Methods for controlling blood pharmacokinetics of antibodies |
CA2647282A1 (en) | 2006-04-05 | 2007-10-11 | Pfizer Products Inc. | Ctla4 antibody combination therapy |
WO2007147901A1 (en) | 2006-06-22 | 2007-12-27 | Novo Nordisk A/S | Production of bispecific antibodies |
AT503902B1 (de) | 2006-07-05 | 2008-06-15 | F Star Biotech Forsch & Entw | Verfahren zur manipulation von immunglobulinen |
AT503861B1 (de) | 2006-07-05 | 2008-06-15 | F Star Biotech Forsch & Entw | Verfahren zur manipulation von t-zell-rezeptoren |
AT503889B1 (de) | 2006-07-05 | 2011-12-15 | Star Biotechnologische Forschungs Und Entwicklungsges M B H F | Multivalente immunglobuline |
JP5473603B2 (ja) | 2006-10-02 | 2014-04-16 | シー レーン バイオテクノロジーズ, エルエルシー | 多様な合成ペプチドおよびポリペプチドライブラリーの設計および構築 |
JP5779350B2 (ja) | 2007-03-27 | 2015-09-16 | シー レーン バイオテクノロジーズ, エルエルシー | 抗体代替軽鎖配列を含む構築物およびライブラリー |
EP1975178A1 (en) | 2007-03-30 | 2008-10-01 | f-star Biotechnologische Forschungs- und Entwicklungsges.m.b.H. | Transcytotic modular antibody |
MX2009010611A (es) | 2007-04-03 | 2010-03-26 | Micromet Ag | Enlazadores biespecificos, especificos para especies. |
BRPI0809594A2 (pt) | 2007-04-03 | 2019-08-27 | Micromet Ag | polipeptídeo, seqüência de ácido nucléico, vetor, hospedeiro, processo para a produção de um polipeptídeo, composição farmacêutica, uso de um polipeptídeo, método para prevenção, tratamento ou melhora de uma doença, em um indivíduo com necessidade do mesmo, kit, método para a identificação de um polipeptídeo(s) |
WO2008124858A2 (en) | 2007-04-11 | 2008-10-23 | F-Star Biotechnologische Forschungs- Und Entwicklungsges. M.B.H. | Targeted receptor |
BRPI0811857A2 (pt) | 2007-05-14 | 2014-10-21 | Biogen Idec Inc | Regiões fc (scfc) de cadeia simples, polipeptídeos de aglutinação que as compreendem e métodos relacionados. |
EP2708557A1 (en) | 2007-05-30 | 2014-03-19 | Xencor, Inc. | Method and compositions for inhibiting CD32B expressing cells |
US20100267934A1 (en) | 2007-05-31 | 2010-10-21 | Genmab A/S | Stable igg4 antibodies |
WO2008156713A2 (en) | 2007-06-12 | 2008-12-24 | Wyeth | Anti-cd20 therapeutic compositions and methods |
EP3241842B1 (en) | 2007-06-26 | 2024-01-31 | F-star Therapeutics Limited | Display of binding agents |
WO2009017394A1 (en) | 2007-08-01 | 2009-02-05 | Syntarga B.V. | Substituted cc-1065 analogs and their conjugates |
EP2187971A2 (en) | 2007-08-01 | 2010-05-26 | The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services | A fold-back diabody diphtheria toxin immunotoxin and methods of use |
KR20100052545A (ko) | 2007-08-28 | 2010-05-19 | 바이오겐 아이덱 엠에이 인코포레이티드 | Igf―1r의 다중 에피토프에 결합하는 조성물 |
EP2033657A1 (de) | 2007-09-04 | 2009-03-11 | Trion Pharma Gmbh | Intraoperative trifunktionale Antikörper-Applikation zur Prophylaxe intraperitonealer Tumorzelldissemination |
JP5963341B2 (ja) | 2007-09-14 | 2016-08-10 | アムジエン・インコーポレーテツド | 均質な抗体集団 |
EP2535349A1 (en) | 2007-09-26 | 2012-12-19 | UCB Pharma S.A. | Dual specificity antibody fusions |
SI2235064T1 (sl) | 2008-01-07 | 2016-04-29 | Amgen Inc. | Metoda za izdelavo heterodimernih molekul - protitelesa fc z uporabo elektrostatičnih usmerjevalnih učinkov |
WO2009106096A1 (en) | 2008-02-27 | 2009-09-03 | Fresenius Biotech Gmbh | Treatment of resistant tumors with trifunctional antibodies |
NZ603059A (en) | 2008-04-11 | 2014-07-25 | Emergent Product Dev Seattle | Cd37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof |
CA2723197C (en) | 2008-05-02 | 2017-09-19 | Seattle Genetics, Inc. | Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation |
NZ589434A (en) | 2008-06-03 | 2012-11-30 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
WO2010028796A1 (en) | 2008-09-10 | 2010-03-18 | F. Hoffmann-La Roche Ag | Trispecific hexavalent antibodies |
US20170247470A9 (en) | 2008-09-17 | 2017-08-31 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
EP2331578B1 (en) | 2008-09-17 | 2014-06-04 | Xencor, Inc. | Novel compositions and methods for treating ige-mediated disorders |
KR20110047255A (ko) | 2008-09-26 | 2011-05-06 | 로슈 글리카트 아게 | 이중특이적 항-egfr/항-igf-1r 항체 |
DK2352763T4 (da) | 2008-10-01 | 2022-10-17 | Amgen Res Munich Gmbh | Bispecifikke enkeltkædede antistoffer med specificitet for højmolekylære målantigener |
BRPI0919841A2 (pt) | 2008-10-01 | 2014-11-18 | Micromet Ag | Anticorpo de cadeia unica biespecifico de psmaxcd3, especifico de especies cruzadas |
CA2738545A1 (en) | 2008-10-01 | 2010-04-08 | Micromet Ag | Cross-species-specific pscaxcd3, cd19xcd3, c-metxcd3, endosialinxcd3, epcamxcd3, igf-1rxcd3 or fapalpha xcd3 bispecific single chain antibody |
EP2352765B1 (en) | 2008-10-01 | 2018-01-03 | Amgen Research (Munich) GmbH | Cross-species-specific single domain bispecific single chain antibody |
CA2740098A1 (en) | 2008-10-10 | 2010-04-15 | Valerie Odegard | Tcr complex immunotherapeutics |
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 |
JP2012515556A (ja) | 2009-01-23 | 2012-07-12 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | 低下したエフェクタ機能を有する安定化Fcポリペプチドおよび使用方法 |
EP2403874A1 (en) | 2009-03-06 | 2012-01-11 | Genentech, Inc. | Antibody formulation |
EP2233500A1 (en) | 2009-03-20 | 2010-09-29 | LFB Biotechnologies | Optimized Fc variants |
BRPI1014089A2 (pt) | 2009-04-02 | 2016-04-19 | Roche Glycart Ag | anticorpos multiespecíficos que compreendem anticorpos de comprimento completo e fragmentos fab de cadeia simples |
EP2417159A1 (en) | 2009-04-07 | 2012-02-15 | Roche Glycart AG | Bispecific anti-erbb-3/anti-c-met antibodies |
AU2010233995A1 (en) | 2009-04-07 | 2011-09-08 | Roche Glycart Ag | Bispecific anti-ErbB-2/anti-c-Met antibodies |
JP5616428B2 (ja) | 2009-04-07 | 2014-10-29 | ロシュ グリクアート アクチェンゲゼルシャフト | 三価の二重特異性抗体 |
EP2241576A1 (en) | 2009-04-17 | 2010-10-20 | Trion Pharma Gmbh | Use of trifunctional bispecific antibodies for the treatment of tumors associated with CD133+/EpCAM+ cancer stem cells |
CN101531718B (zh) * | 2009-04-22 | 2011-11-02 | 中国人民解放军南京军区军事医学研究所 | 抗VEGFR-2抗体嵌合Fab抗体片段及其制备方法、应用 |
CA2764729C (en) | 2009-06-26 | 2019-04-02 | Sea Lane Biotechnologies, Llc | Expression of surrogate light chains |
CN102471378B (zh) | 2009-06-26 | 2014-04-02 | 瑞泽恩制药公司 | 容易地分离的具有天然免疫球蛋白形式的双特异性抗体 |
MX2011013455A (es) | 2009-07-08 | 2012-02-13 | Amgen Inc | Diseño de moleculas de fc de anticuerpo estables y libres de agregacion a traves del diseño de la interfase del dominio de ch3. |
WO2011028952A1 (en) | 2009-09-02 | 2011-03-10 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
DE102009045006A1 (de) | 2009-09-25 | 2011-04-14 | Technische Universität Dresden | Anti-CD33 Antikörper und ihre Anwendung zum Immunotargeting bei der Behandlung von CD33-assoziierten Erkrankungen |
JP2013511281A (ja) | 2009-11-23 | 2013-04-04 | アムジェン インコーポレイテッド | 単量体抗体Fc |
EP2504028A4 (en) | 2009-11-24 | 2014-04-09 | Amplimmune Inc | SIMULTANEOUS INHIBITION OF PD-L1 / PD-L2 |
EA201890907A1 (ru) | 2009-11-30 | 2020-04-30 | Янссен Байотек, Инк. | МУТИРОВАННЫЕ Fc АНТИТЕЛА С УСТРАНЕННЫМИ ЭФФЕКТОРНЫМИ ФУНКЦИЯМИ |
MX2012007497A (es) | 2009-12-25 | 2012-08-01 | Chugai Pharmaceutical Co Ltd | Metodo para modificacion de polipeptidos para purificar multimeros de polipeptido. |
US20130129723A1 (en) | 2009-12-29 | 2013-05-23 | Emergent Product Development Seattle, Llc | Heterodimer Binding Proteins and Uses Thereof |
PT2519543T (pt) | 2009-12-29 | 2016-10-07 | Emergent Product Dev Seattle | Proteínas de ligação de heterodímero e suas utilizações |
EP2552957A4 (en) | 2010-03-29 | 2013-11-20 | Zymeworks Inc | ANTIBODIES HAVING ENHANCED OR DELETED EFFECTIVE FUNCTION |
MX353144B (es) | 2010-04-20 | 2017-12-20 | Genmab As | Proteinas que contienen fc de anticuerpos heterodimericos y metodos para produccion de las mismas. |
TWI586806B (zh) | 2010-04-23 | 2017-06-11 | 建南德克公司 | 異多聚體蛋白質之製造 |
EP2569337A1 (en) | 2010-05-14 | 2013-03-20 | Rinat Neuroscience Corp. | Heterodimeric proteins and methods for producing and purifying them |
EP2580243B1 (en) | 2010-06-09 | 2019-10-16 | Genmab A/S | Antibodies against human cd38 |
AU2011283694B2 (en) | 2010-07-29 | 2017-04-13 | Xencor, Inc. | Antibodies with modified isoelectric points |
JP5964300B2 (ja) | 2010-08-02 | 2016-08-03 | マクロジェニクス,インコーポレーテッド | 共有結合型ダイアボディおよびその使用 |
WO2012032080A1 (en) | 2010-09-07 | 2012-03-15 | F-Star Biotechnologische Forschungs- Und Entwicklungsges.M.B.H | Stabilised human fc |
CN103429620B (zh) | 2010-11-05 | 2018-03-06 | 酵活有限公司 | 在Fc结构域中具有突变的稳定异源二聚的抗体设计 |
HUE055284T2 (hu) | 2011-02-10 | 2021-11-29 | Roche Glycart Ag | Mutáns interleukin-2 polipeptidek |
CN103732628B (zh) | 2011-03-03 | 2017-06-23 | 酵活有限公司 | 多价杂多聚体骨架设计和构建体 |
AU2012229251A1 (en) | 2011-03-11 | 2013-09-12 | Amgen Inc. | Method of correlated mutational analysis to improve therapeutic antibodies |
EP2686345B1 (en) | 2011-03-16 | 2018-04-25 | Amgen Inc. | Fc variants |
SG10201602371VA (en) | 2011-03-25 | 2016-04-28 | Glenmark Pharmaceuticals Sa | Hetero-dimeric immunoglobulins |
TWI622597B (zh) | 2011-03-28 | 2018-05-01 | 賽諾菲公司 | 具有交叉結合區定向之雙重可變區類抗體結合蛋白 |
MX354359B (es) | 2011-03-29 | 2018-02-28 | Roche Glycart Ag | Variantes de fragmento cristalizable (fc) de los anticuerpos. |
EA201892619A1 (ru) | 2011-04-29 | 2019-04-30 | Роше Гликарт Аг | Иммуноконъюгаты, содержащие мутантные полипептиды интерлейкина-2 |
KR20190105112A (ko) | 2011-05-21 | 2019-09-11 | 마크로제닉스, 인크. | 사람 및 비-사람 cd3에 결합할 수 있는 cd3-결합 분자 |
KR20140028013A (ko) | 2011-05-25 | 2014-03-07 | 머크 샤프 앤드 돔 코포레이션 | 개선된 특성을 갖는 Fc-함유 폴리펩티드를 제조하는 방법 |
WO2013006544A1 (en) | 2011-07-06 | 2013-01-10 | Medimmune, Llc | Methods for making multimeric polypeptides |
CA2842860A1 (en) | 2011-07-28 | 2013-01-31 | Sea Lane Biotechnologies, Llc | Sur-binding proteins |
WO2013022855A1 (en) | 2011-08-05 | 2013-02-14 | Xencor, Inc. | Antibodies with modified isoelectric points and immunofiltering |
JP6339015B2 (ja) | 2011-08-23 | 2018-06-06 | ロシュ グリクアート アーゲー | 二重特異性t細胞活性化抗原結合分子 |
EP2748197A2 (en) | 2011-08-26 | 2014-07-02 | Merrimack Pharmaceuticals, Inc. | Tandem fc bispecific antibodies |
JP6322411B2 (ja) | 2011-09-30 | 2018-05-09 | 中外製薬株式会社 | 複数の生理活性を有する抗原の消失を促進する抗原結合分子 |
DK2766392T3 (da) | 2011-10-10 | 2019-10-07 | Xencor Inc | Fremgangsmåde til oprensning af antistoffer |
US10851178B2 (en) | 2011-10-10 | 2020-12-01 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
WO2013056851A2 (en) | 2011-10-20 | 2013-04-25 | Esbatech - A Novartis Company Llc | Stable multiple antigen-binding antibody |
CA2853230C (en) | 2011-10-31 | 2021-11-23 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule having regulated conjugation between heavy-chain and light-chain |
PT2773671T (pt) | 2011-11-04 | 2021-12-14 | Zymeworks Inc | Geração de anticorpo heterodimérico estável com mutações no domínio fc |
ES2710916T3 (es) | 2011-12-22 | 2019-04-29 | I2 Pharmaceuticals Inc | Proteínas de unión sustitutas |
US20160046693A1 (en) | 2012-02-24 | 2016-02-18 | Chugai Seiyaku Kabushiki Kaisha | Antigen-Binding Molecule for Promoting Disappearance of Antigen via Fc gamma RIIB |
ES2743399T3 (es) | 2012-04-20 | 2020-02-19 | Merus Nv | Métodos y medios para la producción de moléculas heterodiméricas similares a Ig |
ES2856272T3 (es) | 2012-05-30 | 2021-09-27 | Chugai Pharmaceutical Co Ltd | Molécula de unión a antígenos para eliminar antígenos agregados |
US9499634B2 (en) | 2012-06-25 | 2016-11-22 | Zymeworks Inc. | Process and methods for efficient manufacturing of highly pure asymmetric antibodies in mammalian cells |
KR20150036606A (ko) | 2012-07-13 | 2015-04-07 | 자임워크스 인코포레이티드 | 항-cd3 구조체를 포함하는 이중특이적 비대칭 이형이합체 |
US20140072581A1 (en) | 2012-07-23 | 2014-03-13 | Zymeworks Inc. | Immunoglobulin Constructs Comprising Selective Pairing of the Light and Heavy Chains |
US9562110B2 (en) | 2012-11-21 | 2017-02-07 | Wuhan Yzy Biopharma Co., Ltd. | Bispecific antibody |
WO2014100490A1 (en) | 2012-12-19 | 2014-06-26 | Adimab, Llc | Multivalent antibody analogs, and methods of their preparation and use |
US10131710B2 (en) | 2013-01-14 | 2018-11-20 | Xencor, Inc. | Optimized antibody variable regions |
US9701759B2 (en) | 2013-01-14 | 2017-07-11 | Xencor, Inc. | Heterodimeric proteins |
US9605084B2 (en) | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
EP2943511B1 (en) | 2013-01-14 | 2019-08-07 | Xencor, Inc. | Novel heterodimeric proteins |
US10487155B2 (en) | 2013-01-14 | 2019-11-26 | Xencor, Inc. | Heterodimeric proteins |
US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
EP2945969A1 (en) | 2013-01-15 | 2015-11-25 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
CN113045660B (zh) | 2013-03-13 | 2023-09-01 | 伊麦吉纳博公司 | 与cd8的抗原结合构建体 |
WO2014145907A1 (en) | 2013-03-15 | 2014-09-18 | Xencor, Inc. | Targeting t cells with heterodimeric proteins |
US10106624B2 (en) | 2013-03-15 | 2018-10-23 | Xencor, Inc. | Heterodimeric proteins |
US10519242B2 (en) | 2013-03-15 | 2019-12-31 | Xencor, Inc. | Targeting regulatory T cells with heterodimeric proteins |
US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
AU2014232501C1 (en) | 2013-03-15 | 2021-04-22 | Xencor, Inc. | Heterodimeric proteins |
US9493563B2 (en) | 2013-11-04 | 2016-11-15 | Glenmark Pharmaceuticals S.A. | Production of T cell retargeting hetero-dimeric immunoglobulins |
SG10202008629XA (en) | 2014-03-28 | 2020-10-29 | Xencor Inc | Bispecific antibodies that bind to cd38 and cd3 |
AU2015292326A1 (en) | 2014-07-24 | 2017-02-23 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
JP2017536830A (ja) | 2014-11-26 | 2017-12-14 | ゼンコー・インコーポレイテッドXencor、 Inc. | Cd3及びcd38に結合するヘテロ二量体抗体 |
IL252480B2 (en) | 2014-11-26 | 2023-12-01 | Xencor Inc | Heterodimeric antibodies that bind CD3 and tumor antigens |
WO2016086186A2 (en) | 2014-11-26 | 2016-06-02 | Xencor, Inc. | Heterodimeric antibodies including binding to cd8 |
EP3237449A2 (en) | 2014-12-22 | 2017-11-01 | Xencor, Inc. | Trispecific antibodies |
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 |
-
2011
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- 2014-01-27 US US14/165,487 patent/US9605061B2/en active Active
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- 2017-02-27 US US15/444,087 patent/US20170174757A1/en not_active Abandoned
- 2017-07-12 AU AU2017204797A patent/AU2017204797B2/en not_active Ceased
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009041613A1 (ja) * | 2007-09-26 | 2009-04-02 | Chugai Seiyaku Kabushiki Kaisha | 抗体定常領域改変体 |
WO2009041643A1 (ja) * | 2007-09-26 | 2009-04-02 | Chugai Seiyaku Kabushiki Kaisha | Cdrのアミノ酸置換により抗体の等電点を改変する方法 |
WO2009041062A1 (ja) * | 2007-09-28 | 2009-04-02 | Chugai Seiyaku Kabushiki Kaisha | 血漿中動態が改善されたグリピカン3抗体 |
WO2009086320A1 (en) * | 2007-12-26 | 2009-07-09 | Xencor, Inc | Fc variants with altered binding to fcrn |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2021119173A (ja) * | 2014-06-06 | 2021-08-12 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | グルココルチコイド誘導腫瘍壊死因子受容体(gitr)に対する抗体およびその使用 |
JP7320555B2 (ja) | 2014-06-06 | 2023-08-03 | ブリストル-マイヤーズ スクイブ カンパニー | グルココルチコイド誘導腫瘍壊死因子受容体(gitr)に対する抗体およびその使用 |
JP2017525335A (ja) * | 2014-06-12 | 2017-09-07 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | FcRn相互作用が変更された抗体を選択するための方法 |
JP2019508013A (ja) * | 2015-11-19 | 2019-03-28 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | グルココルチコイド誘発腫瘍壊死因子受容体(gitr)に対する抗体およびその使用 |
JP2021534194A (ja) * | 2018-08-21 | 2021-12-09 | バイオアトラ インコーポレイテッド | pH選択性を有する条件的活性型タンパク質 |
WO2022220275A1 (ja) * | 2021-04-15 | 2022-10-20 | 中外製薬株式会社 | 抗C1s抗体 |
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JP5953303B2 (ja) | 2016-07-20 |
US9605061B2 (en) | 2017-03-28 |
WO2012016227A2 (en) | 2012-02-02 |
AU2017204797B2 (en) | 2019-11-21 |
EP2598530A2 (en) | 2013-06-05 |
US20140249297A1 (en) | 2014-09-04 |
EP3029066A2 (en) | 2016-06-08 |
CN105585630B (zh) | 2020-09-15 |
CN103052649A (zh) | 2013-04-17 |
EP3029066B1 (en) | 2019-02-20 |
US8637641B2 (en) | 2014-01-28 |
US20120028304A1 (en) | 2012-02-02 |
CA2806252C (en) | 2019-05-14 |
US20170174757A1 (en) | 2017-06-22 |
CN105585630A (zh) | 2016-05-18 |
CA2806252A1 (en) | 2012-02-02 |
AU2017204797A1 (en) | 2017-07-27 |
AU2011283694A1 (en) | 2013-02-28 |
EP3029066A3 (en) | 2016-09-14 |
AU2011283694B2 (en) | 2017-04-13 |
WO2012016227A3 (en) | 2012-05-03 |
DK3029066T3 (da) | 2019-05-20 |
IL224441B (en) | 2021-12-01 |
CN103052649B (zh) | 2015-12-16 |
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