JP6824735B2 - 抗C10orf54抗体およびその使用方法 - Google Patents
抗C10orf54抗体およびその使用方法 Download PDFInfo
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- JP6824735B2 JP6824735B2 JP2016518049A JP2016518049A JP6824735B2 JP 6824735 B2 JP6824735 B2 JP 6824735B2 JP 2016518049 A JP2016518049 A JP 2016518049A JP 2016518049 A JP2016518049 A JP 2016518049A JP 6824735 B2 JP6824735 B2 JP 6824735B2
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Description
本出願は、2014年1月31日に提出された米国特許仮出願第61/934,615号、および2013年6月6日に提出された米国特許仮出願第61/832,135号の優先権の恩典を主張するものであり、それの全内容はそれぞれ参照により本明細書に組み入れられる。
本開示は、全体として、抗C10orf54抗体を含む抗体-薬物コンジュゲートを含む該抗C10orf54抗体、およびそれらの使用方法に関する。
C10orft54は、311アミノ酸長であり、かつ、シグナル配列および1つのIgV様ドメインをその細胞内領域に含むI型1回膜貫通性タンパク質である。それは、B7タンパク質ファミリーのメンバーである可能性があり、B7-H1/PD-L1に対するおよそ24%の配列同一性を有する(Flajnik et al., Immunogenetic 64:571-590 (2012)(非特許文献1))。C10orf54のマウスオルソログは、T細胞活性化の免疫グロブリンV領域抑制因子(V-region Immunoglobulin-containing Suppressor of T Cell Activation)(VISTA;PD-L3としても公知)として公知である。VISTAはCD4陽性調節性T細胞(Treg)のライブラリーからクローニングされた(Wang et al., JEM 208(3):577-592 (2011)(非特許文献2))。VISTAは主に造血細胞上に発現され、VISTA発現は、骨髄性抗原提示細胞(APC)上およびT細胞上において高度に調節される(Wang et al., 前記(非特許文献2))。
第1局面において、本明細書において抗C10orf54抗体と称される、C10orf54ポリペプチド、C10orf54ポリペプチド断片、またはC10orf54エピトープを含むC10orf54と結合する抗体を、本明細書において提供する。さらに、式A-L-CTXのADCを含む、抗体-薬物コンジュゲート(ADC)として薬物とコンジュゲートされている抗C10orf54抗体を、本明細書において提供し、式中、Aは抗体であり、Lはリンカーであり、かつCTXは細胞毒素である。いくつかの態様において、抗C10orf54抗体は、C10orf54ポリペプチド、C10orf54ポリペプチド断片、またはC10orf54エピトープと結合するヒト化抗体である。ある態様において、抗C10orf54抗体は、本明細書に記載されるモノクローナル抗体175A、76E1もしくは141A、またはそのヒト化変異体の、VHドメイン、VLドメイン、VH CDR1、VH CDR2、VH CDR3、VL CDR1、VL CDR2、および/またはVL CDR3を含む。ある態様において、抗C10orf54抗体は、ヒト生殖細胞系免疫グロブリンアミノ酸配列またはその変異体のVH FR1、VH FR2、VH FR3、VH FR4、VL FR1、VL FR2、VL FR3、および/またはVL FR4をさらに含むことができる。
別途定義されない限り、本明細書において使用される全ての技術用語および科学用語は、当業者によって一般的に理解されるものと同一の意味を有する。全ての特許、出願、公開出願、および他の刊行物は、それらの全体が参照により組み入れられる。本明細書における用語について複数の定義が存在する場合は、特に指定のない限り、このセクションにおける定義が優先する。
のアミノ酸配列、および、SNP変異体を含む関連のポリペプチドを含む。C10orf54ポリペプチドは、シグナル配列(残基1〜32;Zhang et al., Protein Sci. 13:2819-2824 (2004)を参照のこと);免疫グロブリンドメイン-IgV様(残基33〜162);および膜貫通領域(残基195〜215)を含む、アミノ酸配列内にいくつかの別個の領域を含むことが示されたかまたは予想される。成熟C10orf54タンパク質は、SEQ ID NO: 1079のアミノ酸残基33〜311を含む。C10orf54タンパク質の細胞外ドメインは、SEQ ID NO: 1079のアミノ酸残基33〜194を含む。関連のポリペプチドには、対立遺伝子変異体(例えば、SNP変異体);スプライス変異体;断片;誘導体;置換、欠失、および挿入変異体;融合ポリペプチド;ならびに種間相同体が含まれ、好ましくは、これらは、C10orf54活性を保持しかつ/または抗C10orf54免疫反応を生じさせるのに十分である。当業者が認識するように、本明細書に提供される抗C10orf54抗体は、C10orf54ポリペプチド、ポリペプチド断片、抗原、および/またはエピトープと結合することができ、何故ならば、エピトープはより大きな抗原の一部であり、これはより大きなポリペプチド断片の一部であり、これは、同様に、より大きなポリペプチドの一部であるためである。C10orf54は、天然形態または性質が変えられた形態で存在することができる。本明細書に記載のC10ORF54ポリペプチドは、ヒトの各種の組織もしくは別の供給源といった種々の供給源から単離することもできるか、または組換え法もしくは合成法によって調製することもできる。「天然型配列C10ORF54ポリペプチド」には、天然由来のC10ORF54ポリペプチドに対応するものと同じアミノ酸配列を有するポリペプチドが含まれる。そのような天然型配列C10ORF54ポリペプチドは、自然界から単離することもできるか、または組換え手段もしくは合成手段によって生産することもできる。「天然型配列C10ORF54ポリペプチド」という用語は、特定のC10ORF54ポリペプチドの天然の切断型形態または分泌形態(例えば、細胞外ドメイン配列)、天然の変異体形態(例えば、選択的スプライス形態)、およびポリペプチドの天然の対立遺伝子変異体を明確に包含する。
C10orf54ポリペプチド、C10orf54ポリペプチド断片、またはC10orf54エピトープを含むC10orf54と結合する抗体を、本明細書において提供する。そのような抗体はヒト化抗C10orf54抗体を含む。C10orf54ポリペプチドと結合することから、本明細書に提供される抗C10orf54抗体を競合的に遮断する抗体(例えば、ヒト化抗C10orf54抗体)を、さらに提供する。本明細書に提供される抗C10orf54抗体(例えば、ヒト化抗C10orf54抗体)はまた、診断用物質、検出可能な物質、または治療用物質と、コンジュゲートされうるかまたは組換えで融合されうる(例えば、抗体-薬物コンジュゲート)。抗C10orf54抗体(例えば、ヒト化抗C10orf54抗体)を含む組成物を、さらに提供する。例えば、検出可能な物質は、検出可能なプローブでありうる。
いくつかの態様において、C10orf54ポリペプチド、C10orf54ポリペプチド断片、またはC10orf54エピトープを含むC10orf54と結合する抗体を、本明細書において提供する。いくつかの態様において、抗C10orf54抗体は、C10orf54ポリペプチド、C10orf54ポリペプチド断片、またはC10orf54エピトープを含むC10orf54と結合するヒト化抗体である。
のアミノ酸配列を有し、X1がRもしくはTであり、かつX2がYもしくはHである、VH CDR1;(2)
のアミノ酸配列を有し、X1がNもしくはSである、VH CDR2;および/または(3)
のアミノ酸配列を有し、xが任意のアミノ酸残基であり、X1がMもしくはFであり、かつX2がGもしくはDである、VH CDR3、を含むVH領域を含む。ある態様において、ヒト化抗C10orf54抗体は、(1)
のアミノ酸配列を有するVL CDR1;(2)KX1SNRFS(SEQ ID NO: 1152)のアミノ酸配列を有し、X1がVもしくはLである、VL CDR2;および/または(3)FQGSHX1PX2T(SEQ ID NO: 1153)のアミノ酸配列を有するVL CDR3、ここで、X1がVまたはFであり、X2がWまたはYである、を含むVL領域を含む。ある態様において、ヒト化抗C10orf54抗体は、(a)(1)
のアミノ酸配列を有し、X1がRもしくはTであり、X2がYもしくはHである、VH CDR1;(2)
のアミノ酸配列を有し、X1がNもしくはSである、VH CDR2;および/または(3)
のアミノ酸配列を有し、xが任意のアミノ酸残基であり、X1がMもしくはFであり、かつX2がGもしくはDである、VH CDR3、を含むVH領域;ならびに(b)(1)
のアミノ酸配列を有するVL CDR1;(2)KX1SNRFS(SEQ ID NO: 1152)のアミノ酸配列を有し、X1がVもしくはLである、VL CDR2;および/または(3)FQGSHX1PX2T(SEQ ID NO: 1153)のアミノ酸配列を有し、X1がVもしくはFであり、かつX2がWもしくはYである、VL CDR3、を含むVL領域を含む。
;または表5〜10に列挙されるVH CDR(SEQ ID NO:36、30、59〜62、33、37、101〜104、50、114、99、100、31、65〜74、83〜90、95、321、322、835〜842、34、847〜858、49、886〜894 1070〜1078、38、32、319、35、883〜885、1081、1086、1087、1092、1099、1104、1105、1110、1117、1122、1123、1128、1082、1088、1093、1098、1100、1106、1111、1116、1118、1124、1129、1134、1083、1089、1094、1101、1107、1112、1119、1125、および1130)、ならびにVL CDR(SEQ ID NO:45、253〜271、42、46、272〜275、40、843〜846、43、1045〜1048、47、41、44、1056〜1058、1084、1090、1095、1102、1108、1113、1120、1126、1131、1085、1096、1103、1114、1121、1132、1091、1097、1109、1115、1127、および1133)のそれらの任意の組み合わせを含む抗体を本明細書において提供する。
;または表5〜7に列挙されるVH FR(SEQ ID NO:51、105、55、115〜121、39、58、895〜902、52、106、56、122〜124、63、64、323〜326、53、107〜113、57、125〜251、96〜98、292〜318、327〜833、53、859〜882 903〜1030、54、または320)、およびVL FR(SEQ ID NO:75、252、79、277〜283、91、1031〜1037、1059〜1061、76、80、284、92、1038〜1044、1062〜1067、77、276、81、285〜291、93、1049〜1055、1068、1069、または78)のそれらの任意の組み合わせを含む抗体を本明細書において提供する。
いくつかの態様において、本明細書に提供される抗体は、診断用物質、検出可能な物質、もしくは治療用物質、または任意の他の分子と、コンジュゲートされているかまたは組換えで融合されている。コンジュゲートされたかまたは組換えで融合された抗体は、例えば、特定の療法の有効性を測定するなど、臨床試験手順の一部として、C10orf54媒介性疾患の発症、発生、進行、および/または重症度をモニタリングするかまたは予後予測するために有用でありうる。
いくつかの態様において、以下の式(Ia)および(Ib)の抗体-薬物コンジュゲートまたはその薬学的に許容される塩を含む、抗体-薬物コンジュゲートを本明細書において提供する。
式中、
Aは、抗体または抗体断片であり;
示されている2つのシステイン残基は、A中の開裂したシステイン-システインジスルフィド結合に由来し;
各XおよびX'は独立してO、S、NH、またはNR1であり、ここで、R1はC1〜6アルキルであり;
Waは、=N-、=CH-、=CHCH2-、=C(R2)-、または=CHCH(R2)-であり、Wbは、-NH-、-N(R1)-、-CH2-、-CH2-NH-、-CH2-N(R1)-、-CH2CH2-、-CH(R2)-、または-CH2CH(R2)-であり;ここで、R1およびR2は独立してC1〜6アルキルであり;
CTXは細胞毒素であり;
Rは任意の化学基であるか、またはRは存在せず;
各L1、L2、およびL3は独立してリンカーであり、該リンカーが、-O-、-C(O)-、-S-、-S(O)-、-S(O)2-、-NH-、-NCH3-、-(CH2)q-、-NH(CH2)2NH-、-OC(O)-、-CO2-、-NHCH2CH2C(O)-、-C(O)NHCH2CH2NH-、-NHCH2C(O)-、-NHC(O)-、-C(O)NH-、-NCH3C(O)-、-C(O)NCH3-、-(CH2CH2O)p、-(CH2CH2O)pCH2CH2-、-CH2CH2-(CH2CH2O)p-、-OCH(CH2O-)2、-(AA)r-、シクロペンタニル、シクロヘキサニル、非置換フェニレニル、および、1つまたは2つの置換基によって置換されたフェニレニルからなる群より選択され、該置換基が、ハロ、CF3-、CF3O-、CH3O-、-C(O)OH、-C(O)OC1〜3アルキル、-C(O)CH3、-CN、-NH-、-NH2、-O-、-OH、-NHCH3、-N(CH3)2、およびC1〜3アルキルからなる群より選択され;
a、b、およびcはそれぞれ独立して0、1、2、または3の整数であり、但しa、b、またはcのうちの少なくとも1つが1であり;
各kおよびk'は独立して0または1の整数であり;
各pは独立して1〜14の整数であり;
各qは独立して1〜12の整数であり;
各AAは独立して1つのアミノ酸であり;
各rは1〜12であり;
mは1〜4の整数であり;
nは1〜4の整数であり;かつ
結合は単結合または二重結合を表す。
本明細書に提供される抗体を1つまたは複数含有する治療用製剤は、所望の程度の純度を有する抗体と任意の生理学的に許容される担体、賦形剤または安定剤とを混合することによって、凍結乾燥製剤または水溶液の形態で、貯蔵用に調製することができる(Remington's Pharmaceutical Sciences (1990) Mack Publishing Co., Easton, PA)。許容される担体、賦形剤または安定剤は、使用される投与量および濃度でレシピエントに対して非毒性であり、緩衝剤、例えばホスフェート、シトレート、およびその他の有機酸;アスコルビン酸およびメチオニンを含む酸化防止剤;保存剤(例えば、塩化オクタデシルジメチルベンジルアンモニウム;塩化ヘキサメトニウム;塩化ベンザルコニウム、塩化ベンゼトニウム;フェノール、ブチルもしくはベンジルアルコール;アルキルパラベン、例えば、メチルもしくはプロピルパラベン;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;およびm-クレゾール);低分子量(約10残基未満)のポリペプチド;タンパク質、例えば血清アルブミン、ゼラチン、または免疫グロブリン;親水性ポリマー、例えばポリビニルピロリドン;アミノ酸、例えばグリシン、グルタミン、アスパラギン、ヒスチジン、アルギニン、またはリジン;グルコース、マンノース、またはデキストリンを含む、単糖類、二糖類、およびその他の炭水化物;キレート剤、例えばEDTA;糖類、例えば、スクロース、マンニトール、トレハロースまたはソルビトール;塩形成性対イオン、例えばナトリウム;金属複合体(例えば、Zn-タンパク質複合体);および/または非イオン性界面活性剤、例えばTWEEN(商標)、PLURONICS(商標)またはポリエチレングリコール(PEG)を含む。
さらに、疾患、例えばC10orf54媒介性疾患の、1つまたは複数の症状の予防、治療、および/または軽減において使用するための1つまたは複数の本明細書に提供される抗体を含む組成物を、本明細書において提供する。
C10orf54抗原と結合する、標識された本明細書に提供される抗体ならびにその誘導体および類似体は、C10orf54媒介性疾患を検出、診断、またはモニタリングするために診断目的で使用することができる。さらに、(a)C10orf54抗原と結合する1つまたは複数の本明細書に提供される抗体を使用して対象の細胞または組織試料中のC10orf54抗原の発現をアッセイする段階;ならびに(b)C10orf54抗原のレベルと、対照レベル、例えば、正常組織試料(例えば、C10orf54媒介性疾患を有さない患者由来、または疾患発症前の同じ患者由来)中のレベルとを比較する段階であって、C10orf54抗原の対照レベルと比較してのC10orf54抗原のアッセイされたレベルの増加がC10orf54媒介性疾患を示す、段階を含む、C10orf54媒介性疾患の検出のための方法を、本明細書において提供する。
抗原と結合する本明細書に提供される抗体は、抗体の合成について当技術分野で公知の任意の方法によって、特に、化学合成または組換え発現技術によって、生成することができる。本発明の実施は、別段の指示がない限り、分子生物学、微生物学、遺伝子分析、組換えDNA、有機化学、生化学、PCR、オリゴヌクレオチド合成および修飾、核酸ハイブリダイゼーション、ならびに当技術分野の技能内の関連分野における従来の技術を用いる。これらの技術は、本明細書に引用される参照文献に記載されており、文献において完全に説明されている。例えば、Maniatis et al. (1982) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press; Sambrook et al. (1989), Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor Laboratory Press; Sambrook et al. (2001) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Ausubel et al., Current Protocols in Molecular Biology, John Wiley & Sons (1987 and annual updates); Current Protocols in Immunology, John Wiley & Sons (1987 and annual updates) Gait (ed.) (1984) Oligonucleotide Synthesis: A Practical Approach, IRL Press; Eckstein (ed.) (1991) Oligonucleotides and Analogues: A Practical Approach, IRL Press; Birren et al. (eds.) (1999) Genome Analysis: A Laboratory Manual, Cold Spring Harbor Laboratory Pressを参照のこと。
さらに、C10orf54(例えば、C10orf54ポリペプチド、C10orf54ポリペプチド断片、C10orf54エピトープ)と結合する本明細書に提供される抗体をコードするヌクレオチド配列を含むポリヌクレオチドを、本明細書において提供する。さらに、本明細書に提供される抗体または改変抗体をコードするポリヌクレオチドへ、例えば上記に定義されるような、高ストリンジェンシー、中間または低ストリンジェンシーハイブリダイゼーション条件下でハイブリダイズするポリヌクレオチドを、本明細書において提供する。
C10orf54抗原と結合する本明細書に提供される抗体(例えば、本明細書に提供される完全長抗体、抗体の重鎖および/もしくは軽鎖、または単鎖抗体)の組換え発現は、抗体をコードするポリヌクレオチドを含有する発現ベクターの構築を必要とする。抗体分子、抗体の重鎖もしくは軽鎖、またはその断片(例えば、重鎖および/または軽鎖可変ドメインを含有するもの)をコードするポリヌクレオチドがいったん得られると、抗体分子の産生用のベクターを、当技術分野において周知の技法を使用して組換えDNA技術によって生成してもよい。したがって、抗体をコードするヌクレオチド配列を含有するポリヌクレオチドを発現させることによってタンパク質を調製するための方法を、本明細書に記載する。当業者に周知である方法を使用して、抗体コード配列ならびに適切な転写および翻訳制御シグナルを含有する発現ベクターを構築することができる。これらの方法としては、例えば、インビトロ組換えDNA技術、合成技術、およびインビボ遺伝子組換えが挙げられる。したがって、さらに、プロモーターに機能的に連結された、本明細書に提供される抗体分子、抗体の重鎖もしくは軽鎖、抗体の重鎖もしくは軽鎖可変ドメインまたはその断片、または重鎖もしくは軽鎖CDRをコードするヌクレオチド配列を含む複製可能ベクターを、本明細書において提供する。そのようなベクターは、抗体分子の定常領域をコードするヌクレオチド配列を含むことが可能であり(例えば、国際公報番号WO86/05807および同WO89/01036;ならびに米国特許第5,122,464号を参照のこと)、重鎖全体、軽鎖全体、または重鎖全体および軽鎖全体の両方を発現させるためのベクター中に、抗体の可変ドメインをクローン化しうる。
さらに、本明細書に提供される薬学的組成物に関する1つまたは複数の成分、例えば、1つまたは複数の本明細書に提供される抗体が充填された1つまたは複数の容器を含む薬学的パックまたはキットを、本明細書において提供する。薬剤または生物学的生成物の製造、使用、または販売を規制する政府機関によって定められた形式の通知が、このような容器に任意で付属され得、この通知は、ヒトへの投与に対する製造、使用または販売に関する政府機関による承認を表す。いくつかの態様において、キットは添付文書を含む。「添付文書」という用語は、治療用生成物の商品パッケージに通例含まれる説明書のことを指すために用いられ、そのような治療用生成物の使用に関する、指示、用法、投与量、投与、禁忌、および/または注意事項についての情報、ならびに使用説明書を含む。
AMLを有する患者由来の合計14個の新鮮な骨髄単核細胞(BMMC)をAllCellsから得、追加の16個の凍結患者試料をFred Hutchinson Cancer Research Center (FHCRC)から得た。対照として、健康なドナー由来の16個の新鮮なBMMC試料を分析した。個々のAML試料の質をモニタリングするために、AML芽細胞のヘマトキシリン-エオシン染色を行ったか、またはAMLマーカー発現を、フローサイトメトリー/FACS分析を用いてモニタリングした。試料単離の間の細胞生存度を最大限に維持するために、試料取り扱いを最適化した。細胞の完全性を損なわずに効率的な標識が可能となるように、AML試料に関して最適な標識時間を決定した。
抗C10orf54抗体を使用して、実施例1に記載されるように得られた23個の原発性および3個の正常BM-MNC試料を用いて、フローサイトメトリー研究を行い、AMLにおけるC10orf54の発現プロファイルを分析した。抗体をAF647またはAF488蛍光色素で標識した。細胞をカウントし、FACSバッファー:RPMI、4% HIFBS、0.02%NaN3中に再懸濁して、500000細胞/染色で使用した。抗体を室温で暗所にて15分間インキュベートし、次いで、MACSQuant (Miltenyl Biotec, Auburn, CA)機器で分析した。FLOWJO(TreeStar, Ashland, OR)ソフトウェアを用いてデータ解析を行った。抗C10orf54抗体76E1を用いてのFACS分析の結果を図2に示す。
iTAbプラットフォームを使用して、C10orf54に対する抗体を作製した。このシステムにおいて、ヒトタンパク質を安定発現するようにマウス腫瘍細胞株に形質導入し、次いで、これを同系マウスに皮下移植する。マウスを抗CD8抗体で処置して、体液性免疫反応をインタクトにしたまま、細胞媒介拒絶経路を除去した。この免疫処置後、脾細胞を採取し、不死化パートナー細胞と融合し、ハイブリドーマを作製する。これらのハイブリドーマ由来の抗体を、良好な結合特性を有する抗体の多様なパネルを同定するために設計されたマルチプルアッセイ法においてスクリーニングする。次いで、選択された抗体を以下のようにインビボ試験のために生成する。
実施例3に記載のように作製したマウス抗体を配列決定のために選択した。76E1、141Aおよび175Aと名付けられた選択したモノクローナル抗体を、以下のように2つの方法によってヒト化した。ヒト化の結果を図3〜8に示す。
抗C10orf54抗体を動物腫瘍モデルにおいて抗腫瘍活性について試験した。これらの研究のために、細胞株Kasumi-3(急性骨髄性白血病)をATCC(CRL-2725)から入手し、供給元のプロトコールに従って培養した。動物はTaconic (Hudson, NY)から入手した。抗C10orf54抗体を用いて動物腫瘍モデルにおいて研究を行った。
以下の例示的な一般スキームAに示すように、抗体-薬物コンジュゲート(ADC)を、C10orf54に対する抗体を用いて作製し、二次的ADCアッセイ法および直接的ADCアッセイ法において用いた。
マレイミドリンカー-薬物コンジュゲートの示されている結合は、抗体への可能性のある結合部位を示す。
MC-MMAFリンカー-薬物コンジュゲートの示されている結合は、抗体への可能性のある結合部位を示す。
代替的に、本開示の式(Ia)および(Ib)の抗体-薬物コンジュゲートは、それぞれ、以下のスキームCおよびDにおいて説明されるように、作製されうる。
Claims (17)
- 以下から選択される、C10orf54と結合し、腫瘍増殖阻害を誘導する単離された抗体:
a.i.それぞれアミノ酸配列SEQ ID NO.36、SEQ ID NO.37、およびSEQ ID NO.38を有するVH CDR1、VH CDR2、およびVH CDR3を含む重鎖可変(VH)領域、ならびに
ii.それぞれアミノ酸配列SEQ ID NO.45、SEQ ID NO.46、およびSEQ ID NO.47を有するVL CDR1、VL CDR2、およびVL CDR3を含む軽鎖可変(VL)領域
を含む抗体175A、ならびに
b.i.それぞれアミノ酸配列SEQ ID NO.33、SEQ ID NO.34、およびSEQ ID NO.35を有するVH CDR1、VH CDR2、およびVH CDR3を含む重鎖可変(VH)領域、ならびに
ii.それぞれアミノ酸配列SEQ ID NO.42、SEQ ID NO.43、およびSEQ ID NO.44を有するVL CDR1、VL CDR2、およびVL CDR3を含む軽鎖可変(VL)領域
を含む抗体141A。 - モノクローナル抗体である、請求項1に記載の抗体。
- 以下から選択される、請求項1または2のいずれか一項に記載の抗体:
a.i.アミノ酸配列SEQ ID NO.3を有するVH領域、および
ii.アミノ酸配列SEQ ID NO.6を有するVL領域
を含む抗体175A、ならびに
b.i.アミノ酸配列SEQ ID NO.2を有するVH領域、および
ii.アミノ酸配列SEQ ID NO.5を有するVL領域
を含む抗体141A。 - ヒト化されている、請求項1または2のいずれか一項に記載の抗体。
- 以下から選択される、請求項3に記載の抗体:
a.i.SEQ ID NO:20、21、22、および23からなる群より選択されるアミノ酸配列を有するVH 領域、および
ii.SEQ ID NO:28および29からなる群より選択されるアミノ酸配列を有するVL領域
を含む抗体175A、ならびに
b.i.SEQ ID NO:16、17、18、19からなる群より選択されるアミノ酸配列を有するVH 領域、および
ii.SEQ ID NO:26および27からなる群より選択されるアミノ酸配列を有するVL領域
を含む抗体141A。 - 前記抗体が、ヒト化抗体、モノクローナル抗体、組換え抗体、抗体と異種ポリペプチドとを含む融合タンパク質、抗原結合断片、Fab断片、F(ab’)2断片、単鎖Fv(scFv)、ダイアボディ、トリアボディ、またはミニボディである、請求項1〜4のいずれか一項に記載の抗体。
- 診断用物質、検出可能な物質、または治療用物質と、コンジュゲートされているかまたは組換えで融合されている、請求項1〜6のいずれか一項に記載の抗体。
- 請求項1〜6のいずれか一項に記載の抗体をコードする単離された核酸分子であって、該核酸分子は該抗体のVH領域およびVL領域をコードする核酸配列を含むかまたは該核酸配列からなる、核酸分子。
- 請求項8に記載の核酸分子を含む、ベクター。
- 請求項9に記載のベクターを含む、宿主細胞。
- 抗体の生成を促進する条件下で請求項10に記載の宿主細胞を培養する段階を含む、該抗体を生成する方法。
- 請求項1〜6のいずれか一項に記載の抗体と薬学的に許容される賦形剤を含む、薬学的組成物。
- 疾患に関する1つまたは複数の症状を治療、予防、または軽減するための、請求項12に記載の組成物。
- 前記疾患が癌である、請求項13に記載の組成物。
- 前記癌が白血病、膀胱癌、または線維肉腫である、請求項14に記載の組成物。
- 対象における免疫反応を調節するための、請求項12に記載の組成物。
- 腫瘍細胞を死滅させるための、請求項12に記載の組成物。
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Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8765432B2 (en) | 2009-12-18 | 2014-07-01 | Oligasis, Llc | Targeted drug phosphorylcholine polymer conjugates |
US10745467B2 (en) | 2010-03-26 | 2020-08-18 | The Trustees Of Dartmouth College | VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders |
US20150231215A1 (en) | 2012-06-22 | 2015-08-20 | Randolph J. Noelle | VISTA Antagonist and Methods of Use |
CA2884704C (en) | 2012-09-07 | 2023-04-04 | Randolph J. Noelle | Vista modulators for diagnosis and treatment of cancer |
CN105188766B (zh) | 2013-03-15 | 2019-07-12 | 瑞泽恩制药公司 | 生物活性分子、其偶联物及治疗用途 |
JP6608823B2 (ja) | 2013-08-26 | 2019-11-20 | レゲネロン ファーマシューティカルス,インコーポレーテッド | マクロライドジアステレオマーを含む医薬組成物、その合成方法、及び治療上の使用 |
WO2015035342A2 (en) | 2013-09-08 | 2015-03-12 | Oligasis Llc | Factor viii zwitterionic polymer conjugates |
US11014987B2 (en) | 2013-12-24 | 2021-05-25 | Janssen Pharmaceutics Nv | Anti-vista antibodies and fragments, uses thereof, and methods of identifying same |
HRP20220748T1 (hr) | 2013-12-24 | 2022-09-02 | Janssen Pharmaceutica Nv | Anti-vista antitijela i fragmenti |
EP3148592A2 (en) | 2014-06-02 | 2017-04-05 | Regeneron Pharmaceuticals, Inc. | Antibody-drug conjugates, their preparation and their therapeutic use |
US9840553B2 (en) | 2014-06-28 | 2017-12-12 | Kodiak Sciences Inc. | Dual PDGF/VEGF antagonists |
EP3207128B1 (en) | 2014-10-17 | 2022-07-27 | Kodiak Sciences Inc. | Butyrylcholinesterase zwitterionic polymer conjugates |
ES2834739T3 (es) * | 2014-12-11 | 2021-06-18 | Pf Medicament | Anticuerpos anti-C10orf54 y utilizaciones de los mismos |
DK3313882T3 (da) * | 2015-06-24 | 2020-05-11 | Janssen Pharmaceutica Nv | Anti-VISTA antistoffer og fragmenter |
MX2018006218A (es) | 2015-12-04 | 2018-09-05 | Seattle Genetics Inc | Conjugados de compuestos de tubulisina cuaternizada. |
US11793880B2 (en) | 2015-12-04 | 2023-10-24 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
AU2016381964B2 (en) | 2015-12-30 | 2024-02-15 | Kodiak Sciences Inc. | Antibodies and conjugates thereof |
EP3408271B1 (en) | 2016-01-25 | 2023-01-11 | Regeneron Pharmaceuticals, Inc. | Maytansinoid derivatives, conjugates thereof, and methods of use |
US10899836B2 (en) | 2016-02-12 | 2021-01-26 | Janssen Pharmaceutica Nv | Method of identifying anti-VISTA antibodies |
US20210017281A1 (en) | 2016-04-15 | 2021-01-21 | Immunext, Inc. | Anti-human vista antibodies and use thereof |
WO2018098352A2 (en) | 2016-11-22 | 2018-05-31 | Jun Oishi | Targeting kras induced immune checkpoint expression |
KR20230132603A (ko) | 2017-01-11 | 2023-09-15 | 브리스톨-마이어스 스큅 컴퍼니 | Psgl-1 길항제 및 그의 용도 |
JP7211961B2 (ja) | 2017-03-14 | 2023-01-24 | ファイヴ プライム セラピューティクス インク | 酸性pHでVISTAに結合する抗体 |
WO2018191548A2 (en) * | 2017-04-14 | 2018-10-18 | Kodiak Sciences Inc. | Complement factor d antagonist antibodies and conjugates thereof |
KR102225178B1 (ko) * | 2017-10-16 | 2021-03-10 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 항-타우 항체 및 그의 용도 |
CN112020516A (zh) * | 2018-03-13 | 2020-12-01 | 塔斯克疗法有限公司 | 用于肿瘤特异性细胞清除的抗-cd25 |
US20190300610A1 (en) * | 2018-03-29 | 2019-10-03 | Hummingbird Bioscience Pte. Ltd. | Vista antigen-binding molecules |
GB201814562D0 (en) | 2018-09-07 | 2018-10-24 | Hummingbird Bioscience Pte Ltd | Vista antigen-binding molecules |
WO2019209995A2 (en) | 2018-04-25 | 2019-10-31 | Precision Ibd, Inc. | Optimized anti-tl1a antibodies |
AU2019287765A1 (en) | 2018-06-15 | 2021-01-07 | Flagship Pioneering Innovations V, Inc. | Increasing immune activity through modulation of postcellular signaling factors |
MX2021000786A (es) | 2018-07-20 | 2021-06-15 | Pf Medicament | Receptor para supresor de ig del dominio v de activación de células t (vista). |
MA55805A (fr) | 2019-05-03 | 2022-03-09 | Flagship Pioneering Innovations V Inc | Métodes de modulation de l'activité immunitaire |
JP2022553640A (ja) | 2019-10-10 | 2022-12-26 | コディアック サイエンシーズ インコーポレイテッド | 眼障害を処置する方法 |
BR112022007720A2 (pt) | 2019-10-24 | 2022-08-23 | Prometheus Biosciences Inc | Anticorpos humanizados para ligante 1a tnf-like (tl1a) e seus usos |
WO2021127217A1 (en) | 2019-12-17 | 2021-06-24 | Flagship Pioneering Innovations V, Inc. | Combination anti-cancer therapies with inducers of iron-dependent cellular disassembly |
JP2023532339A (ja) | 2020-06-29 | 2023-07-27 | フラグシップ パイオニアリング イノベーションズ ブイ,インコーポレーテッド | サノトランスミッションを促進するためにエンジニアリングされたウイルス及び癌の処置におけるそれらの使用 |
WO2022212784A1 (en) | 2021-03-31 | 2022-10-06 | Flagship Pioneering Innovations V, Inc. | Thanotransmission polypeptides and their use in treating cancer |
EP4363059A1 (en) | 2021-06-29 | 2024-05-08 | Flagship Pioneering Innovations V, Inc. | Immune cells engineered to promote thanotransmission and uses thereof |
KR20240058149A (ko) | 2021-09-16 | 2024-05-03 | 허밍버드 바이오사이언스 피티이. 엘티디. | Vista 항원-결합 분자를 사용한 암의 치료 및 예방 |
WO2023046979A1 (en) | 2021-09-27 | 2023-03-30 | Hummingbird Bioscience Pte. Ltd. | Treatment and prevention of cancer using vista antigen-binding molecules |
WO2024062073A1 (en) | 2022-09-22 | 2024-03-28 | Hummingbird Bioscience Pte. Ltd. | Treatment and prevention of cancer using vista antigen-binding molecules |
WO2024077191A1 (en) | 2022-10-05 | 2024-04-11 | Flagship Pioneering Innovations V, Inc. | Nucleic acid molecules encoding trif and additionalpolypeptides and their use in treating cancer |
WO2024097877A1 (en) * | 2022-11-03 | 2024-05-10 | Baylor College Of Medicine | Anti-zp4 antibodies and chimeric antigen receptors and methods of use thereof |
WO2024121380A1 (en) | 2022-12-08 | 2024-06-13 | Pierre Fabre Medicament | Vaccinal composition and adjuvant |
Family Cites Families (234)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
US3710795A (en) | 1970-09-29 | 1973-01-16 | Alza Corp | Drug-delivery device with stretched, rate-controlling membrane |
GB1429184A (en) | 1972-04-20 | 1976-03-24 | Allen & Hanburys Ltd | Physically anti-inflammatory steroids for use in aerosols |
US4044126A (en) | 1972-04-20 | 1977-08-23 | Allen & Hanburys Limited | Steroidal aerosol compositions and process for the preparation thereof |
USRE28819E (en) | 1972-12-08 | 1976-05-18 | Syntex (U.S.A.) Inc. | Dialkylated glycol compositions and medicament preparations containing same |
DE2855919B1 (de) | 1978-12-23 | 1979-09-20 | Basf Farben & Fasern | Plastisole |
US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
US4410545A (en) | 1981-02-13 | 1983-10-18 | Syntex (U.S.A.) Inc. | Carbonate diester solutions of PGE-type compounds |
US4328245A (en) | 1981-02-13 | 1982-05-04 | Syntex (U.S.A.) Inc. | Carbonate diester solutions of PGE-type compounds |
US4358603A (en) | 1981-04-16 | 1982-11-09 | Syntex (U.S.A.) Inc. | Acetal stabilized prostaglandin compositions |
US4485045A (en) | 1981-07-06 | 1984-11-27 | Research Corporation | Synthetic phosphatidyl cholines useful in forming liposomes |
US4409239A (en) | 1982-01-21 | 1983-10-11 | Syntex (U.S.A.) Inc. | Propylene glycol diester solutions of PGE-type compounds |
EP0092918B1 (en) | 1982-04-22 | 1988-10-19 | Imperial Chemical Industries Plc | Continuous release formulations |
US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4544545A (en) | 1983-06-20 | 1985-10-01 | Trustees University Of Massachusetts | Liposomes containing modified cholesterol for organ targeting |
US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
US5128326A (en) | 1984-12-06 | 1992-07-07 | Biomatrix, Inc. | Drug delivery systems based on hyaluronans derivatives thereof and their salts and methods of producing same |
JP2532858B2 (ja) | 1985-04-01 | 1996-09-11 | セルテツク リミテツド | 形質転換したミエロ―マ細胞系 |
US4980286A (en) | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
WO1988007089A1 (en) | 1987-03-18 | 1988-09-22 | Medical Research Council | Altered antibodies |
US4880078A (en) | 1987-06-29 | 1989-11-14 | Honda Giken Kogyo Kabushiki Kaisha | Exhaust muffler |
GB8717430D0 (en) | 1987-07-23 | 1987-08-26 | Celltech Ltd | Recombinant dna product |
US5336603A (en) | 1987-10-02 | 1994-08-09 | Genentech, Inc. | CD4 adheson variants |
DE68921982T4 (de) | 1988-06-14 | 1996-04-25 | Cetus Oncology Corp | Kupplungsmittel und sterisch gehinderte, mit disulfid gebundene konjugate daraus. |
US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
EP1892296A1 (en) | 1988-09-02 | 2008-02-27 | Dyax Corporation | Generation and selection of recombinant varied binding proteins |
KR900005995A (ko) | 1988-10-31 | 1990-05-07 | 우메모또 요시마사 | 변형 인터류킨-2 및 그의 제조방법 |
US5734033A (en) | 1988-12-22 | 1998-03-31 | The Trustees Of The University Of Pennsylvania | Antisense oligonucleotides inhibiting human bcl-2 gene expression |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
EP0394827A1 (en) | 1989-04-26 | 1990-10-31 | F. Hoffmann-La Roche Ag | Chimaeric CD4-immunoglobulin polypeptides |
IE63847B1 (en) | 1989-05-05 | 1995-06-14 | Res Dev Foundation | A novel antibody delivery system for biological response modifiers |
US5112946A (en) | 1989-07-06 | 1992-05-12 | Repligen Corporation | Modified pf4 compositions and methods of use |
US5413923A (en) | 1989-07-25 | 1995-05-09 | Cell Genesys, Inc. | Homologous recombination for universal donor cells and chimeric mammalian hosts |
WO1991005548A1 (en) | 1989-10-10 | 1991-05-02 | Pitman-Moore, Inc. | Sustained release composition for macromolecular proteins |
US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
WO1991006570A1 (en) | 1989-10-25 | 1991-05-16 | The University Of Melbourne | HYBRID Fc RECEPTOR MOLECULES |
CA2071867A1 (en) | 1989-11-06 | 1991-05-07 | Edith Mathiowitz | Method for producing protein microspheres |
GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
US5585112A (en) | 1989-12-22 | 1996-12-17 | Imarx Pharmaceutical Corp. | Method of preparing gas and gaseous precursor-filled microspheres |
AU7247191A (en) | 1990-01-11 | 1991-08-05 | Molecular Affinities Corporation | Production of antibodies using gene libraries |
US5780225A (en) | 1990-01-12 | 1998-07-14 | Stratagene | Method for generating libaries of antibody genes comprising amplification of diverse antibody DNAs and methods for using these libraries for the production of diverse antigen combining molecules |
DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
US5314995A (en) | 1990-01-22 | 1994-05-24 | Oncogen | Therapeutic interleukin-2-antibody based fusion proteins |
WO1991014438A1 (en) | 1990-03-20 | 1991-10-03 | The Trustees Of Columbia University In The City Of New York | Chimeric antibodies with receptor binding ligands in place of their constant region |
IT1246382B (it) | 1990-04-17 | 1994-11-18 | Eurand Int | Metodo per la cessione mirata e controllata di farmaci nell'intestino e particolarmente nel colon |
US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
US5349053A (en) | 1990-06-01 | 1994-09-20 | Protein Design Labs, Inc. | Chimeric ligand/immunoglobulin molecules and their uses |
GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
KR100272077B1 (ko) | 1990-08-29 | 2000-11-15 | 젠팜인터내셔날,인코포레이티드 | 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물 |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5698426A (en) | 1990-09-28 | 1997-12-16 | Ixsys, Incorporated | Surface expression libraries of heteromeric receptors |
US5543390A (en) | 1990-11-01 | 1996-08-06 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education, Acting For And On Behalf Of The Oregon Health Sciences University | Covalent microparticle-drug conjugates for biological targeting |
JPH09506761A (ja) | 1990-11-09 | 1997-07-08 | ステファン ディー.ギリーズ | サイトカインの免疫複合体 |
CA2405246A1 (en) | 1990-12-03 | 1992-06-11 | Genentech, Inc. | Enrichment method for variant proteins with alterred binding properties |
DE69123241T2 (de) | 1990-12-14 | 1997-04-17 | Cell Genesys Inc | Chimärische ketten zur transduktion von rezeptorverbundenen signalwegen |
DE69233750D1 (de) | 1991-04-10 | 2009-01-02 | Scripps Research Inst | Bibliotheken heterodimerer Rezeptoren mittels Phagemiden |
CA2109528A1 (en) | 1991-05-01 | 1992-11-02 | Gregory A. Prince | A method for treating infectious respiratory diseases |
EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
CA2103059C (en) | 1991-06-14 | 2005-03-22 | Paul J. Carter | Method for making humanized antibodies |
US6800738B1 (en) | 1991-06-14 | 2004-10-05 | Genentech, Inc. | Method for making humanized antibodies |
JPH07503124A (ja) | 1991-06-14 | 1995-04-06 | ゾーマ・コーポレーション | 微生物によって生産される抗体断片とそれらの複合体 |
US5844095A (en) | 1991-06-27 | 1998-12-01 | Bristol-Myers Squibb Company | CTLA4 Ig fusion proteins |
US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
ES2341666T3 (es) | 1991-12-02 | 2010-06-24 | Medimmune Limited | Produccion de autoanticuerpos de repertorios de segmentos de anticue rpos expresados en la superficie de fagos. |
JP4157160B2 (ja) | 1991-12-13 | 2008-09-24 | ゾーマ テクノロジー リミテッド | 改変抗体可変領域の調製のための方法 |
US5824307A (en) | 1991-12-23 | 1998-10-20 | Medimmune, Inc. | Human-murine chimeric antibodies against respiratory syncytial virus |
US5622929A (en) | 1992-01-23 | 1997-04-22 | Bristol-Myers Squibb Company | Thioether conjugates |
US6271242B1 (en) | 1992-02-10 | 2001-08-07 | Bristol-Myers Squibb Co. | Method for treating cancer using a tyrosine protein kinase inhibitor |
GB9203459D0 (en) | 1992-02-19 | 1992-04-08 | Scotgen Ltd | Antibodies with germ-line variable regions |
US5912015A (en) | 1992-03-12 | 1999-06-15 | Alkermes Controlled Therapeutics, Inc. | Modulated release from biocompatible polymers |
US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
US6010715A (en) | 1992-04-01 | 2000-01-04 | Bertek, Inc. | Transdermal patch incorporating a polymer film incorporated with an active agent |
US5447851B1 (en) | 1992-04-02 | 1999-07-06 | Univ Texas System Board Of | Dna encoding a chimeric polypeptide comprising the extracellular domain of tnf receptor fused to igg vectors and host cells |
US6024975A (en) | 1992-04-08 | 2000-02-15 | Americare International Diagnostics, Inc. | Method of transdermally administering high molecular weight drugs with a polymer skin enhancer |
US6005079A (en) | 1992-08-21 | 1999-12-21 | Vrije Universiteit Brussels | Immunoglobulins devoid of light chains |
WO1994004678A1 (en) | 1992-08-21 | 1994-03-03 | Casterman Cecile | Immunoglobulins devoid of light chains |
US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
US5804187A (en) | 1992-11-16 | 1998-09-08 | Cancer Research Fund Of Contra Costa | Modified antibodies with human milk fat globule specificity |
US5441050A (en) | 1992-12-18 | 1995-08-15 | Neoprobe Corporation | Radiation responsive surgical instrument |
US5934272A (en) | 1993-01-29 | 1999-08-10 | Aradigm Corporation | Device and method of creating aerosolized mist of respiratory drug |
US6274552B1 (en) | 1993-03-18 | 2001-08-14 | Cytimmune Sciences, Inc. | Composition and method for delivery of biologically-active factors |
US5985307A (en) | 1993-04-14 | 1999-11-16 | Emory University | Device and method for non-occlusive localized drug delivery |
US5523092A (en) | 1993-04-14 | 1996-06-04 | Emory University | Device for local drug delivery and methods for using the same |
ES2162863T3 (es) | 1993-04-29 | 2002-01-16 | Unilever Nv | Produccion de anticuerpos o fragmentos (funcionalizados) de los mismos derivados de inmunoglobulinas de cadena pesada de camelidae. |
US5728868A (en) | 1993-07-15 | 1998-03-17 | Cancer Research Campaign Technology Limited | Prodrugs of protein tyrosine kinase inhibitors |
US6004534A (en) | 1993-07-23 | 1999-12-21 | Massachusetts Institute Of Technology | Targeted polymerized liposomes for improved drug delivery |
EP0733070A1 (en) | 1993-12-08 | 1996-09-25 | Genzyme Corporation | Process for generating specific antibodies |
US5925376C1 (en) | 1994-01-10 | 2001-03-20 | Madalene C Y Heng | Method for treating psoriasis using selected phosphorylase kinase inhibitor and additional compounds |
US5618709A (en) | 1994-01-14 | 1997-04-08 | University Of Pennsylvania | Antisense oligonucleotides specific for STK-1 and method for inhibiting expression of the STK-1 protein |
ATE243745T1 (de) | 1994-01-31 | 2003-07-15 | Univ Boston | Bibliotheken aus polyklonalen antikörpern |
US5834252A (en) | 1995-04-18 | 1998-11-10 | Glaxo Group Limited | End-complementary polymerase reaction |
US5605793A (en) | 1994-02-17 | 1997-02-25 | Affymax Technologies N.V. | Methods for in vitro recombination |
US5837458A (en) | 1994-02-17 | 1998-11-17 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
US5516637A (en) | 1994-06-10 | 1996-05-14 | Dade International Inc. | Method involving display of protein binding pairs on the surface of bacterial pili and bacteriophage |
CN1117155C (zh) | 1994-07-29 | 2003-08-06 | 史密丝克莱恩比彻姆有限公司 | 新型化合物 |
GB9415379D0 (en) | 1994-07-29 | 1994-09-21 | Smithkline Beecham Plc | Novel compounds |
US5759542A (en) | 1994-08-05 | 1998-06-02 | New England Deaconess Hospital Corporation | Compositions and methods for the delivery of drugs by platelets for the treatment of cardiovascular and other diseases |
US5911995A (en) | 1994-08-19 | 1999-06-15 | Regents Of The University Of Minnesota | EGF-genistein conjugates for the treatment of cancer |
US5587459A (en) | 1994-08-19 | 1996-12-24 | Regents Of The University Of Minnesota | Immunoconjugates comprising tyrosine kinase inhibitors |
US5660854A (en) | 1994-11-28 | 1997-08-26 | Haynes; Duncan H | Drug releasing surgical implant or dressing material |
ATE252894T1 (de) | 1995-01-05 | 2003-11-15 | Univ Michigan | Oberflächen-modifizierte nanopartikel und verfahren für ihre herstellung und verwendung |
US6030613A (en) | 1995-01-17 | 2000-02-29 | The Brigham And Women's Hospital, Inc. | Receptor specific transepithelial transport of therapeutics |
DE69627820T2 (de) | 1995-01-17 | 2004-04-08 | The Brigham And Women's Hospital Inc., Boston | Rezeptorspezifischer transepithelialer transport von immunogenen |
GB9501567D0 (en) | 1995-01-26 | 1995-03-15 | Pharmacia Spa | Hydrosoluble 3-arylidene-2-oxindole derivatives as tyrosine kinase inhibitors |
US5998596A (en) | 1995-04-04 | 1999-12-07 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibition of protein kinase activity by aptameric action of oligonucleotides |
US6019968A (en) | 1995-04-14 | 2000-02-01 | Inhale Therapeutic Systems, Inc. | Dispersible antibody compositions and methods for their preparation and use |
US5983134A (en) | 1995-04-23 | 1999-11-09 | Electromagnetic Bracing Systems Inc. | Electrophoretic cuff apparatus drug delivery system |
KR20050085971A (ko) | 1995-04-27 | 2005-08-29 | 아브게닉스, 인크. | 면역화된 제노마우스 유래의 인간 항체 |
AU2466895A (en) | 1995-04-28 | 1996-11-18 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
DE69636339T2 (de) | 1995-06-01 | 2007-07-19 | Kishimoto, Tadamitsu, Tondabayashi | Wachstumsinhibitor gegen leukämische zellen, der antisense-oligonukleotidderivate gegen das wilms-tumorgen enthält |
US6316652B1 (en) | 1995-06-06 | 2001-11-13 | Kosta Steliou | Drug mitochondrial targeting agents |
GB9515975D0 (en) | 1995-08-04 | 1995-10-04 | Zeneca Ltd | Chemical compounds |
US6167301A (en) | 1995-08-29 | 2000-12-26 | Flower; Ronald J. | Iontophoretic drug delivery device having high-efficiency DC-to-DC energy conversion circuit |
EP0850051A2 (en) | 1995-08-31 | 1998-07-01 | Alkermes Controlled Therapeutics, Inc. | Composition for sustained release of an agent |
US5863904A (en) | 1995-09-26 | 1999-01-26 | The University Of Michigan | Methods for treating cancers and restenosis with P21 |
GB9601081D0 (en) | 1995-10-06 | 1996-03-20 | Cambridge Antibody Tech | Specific binding members for human transforming growth factor beta;materials and methods |
US6039975A (en) | 1995-10-17 | 2000-03-21 | Hoffman-La Roche Inc. | Colon targeted delivery system |
US6127366A (en) | 1995-11-22 | 2000-10-03 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
ES2175137T3 (es) | 1995-12-08 | 2002-11-16 | Janssen Pharmaceutica Nv | Derivados de (imidazol-5-il)metil-2-quinolinona como inhibidores de laproteina farnesil-transferasa. |
US5723125A (en) | 1995-12-28 | 1998-03-03 | Tanox Biosystems, Inc. | Hybrid with interferon-alpha and an immunoglobulin Fc linked through a non-immunogenic peptide |
US5958769A (en) | 1996-01-18 | 1999-09-28 | Fred Hutchinson Cancer Research Center | Compositions and methods for mediating cell cycle progression |
JP2978435B2 (ja) | 1996-01-24 | 1999-11-15 | チッソ株式会社 | アクリロキシプロピルシランの製造方法 |
US6066738A (en) | 1996-01-30 | 2000-05-23 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
AU704087B2 (en) | 1996-01-30 | 1999-04-15 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
AU2063197A (en) | 1996-03-04 | 1997-09-22 | Massachusetts Institute Of Technology | Materials and methods for enhancing cellular internalization |
WO1997033899A1 (en) | 1996-03-14 | 1997-09-18 | Human Genome Sciences, Inc. | Apoptosis inducing molecule i |
CA2249195A1 (en) | 1996-03-18 | 1997-09-25 | Board Of Regents, The University Of Texas System | Immunoglobin-like domains with increased half lives |
EP0904278A4 (en) | 1996-03-22 | 1999-09-15 | Human Genome Sciences Inc | MOLECULE II INDUCER OF APOPTOSIS |
US6080870A (en) | 1996-04-03 | 2000-06-27 | Merck & Co., Inc. | Biaryl substituted imidazole compounds useful as farnesyl-protein transferase inhibitors |
US5891889A (en) | 1996-04-03 | 1999-04-06 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
US5883105A (en) | 1996-04-03 | 1999-03-16 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
US6063930A (en) | 1996-04-03 | 2000-05-16 | Merck & Co., Inc. | Substituted imidazole compounds useful as farnesyl-protein transferase inhibitors |
US6300501B1 (en) | 1996-05-22 | 2001-10-09 | Warner-Lambert Company | Histidine-(N-benzyl glycinamide) inhibitors of protein farnesyl transferase |
US5985309A (en) | 1996-05-24 | 1999-11-16 | Massachusetts Institute Of Technology | Preparation of particles for inhalation |
US5855913A (en) | 1997-01-16 | 1999-01-05 | Massachusetts Instite Of Technology | Particles incorporating surfactants for pulmonary drug delivery |
US5874064A (en) | 1996-05-24 | 1999-02-23 | Massachusetts Institute Of Technology | Aerodynamically light particles for pulmonary drug delivery |
TW345603B (en) | 1996-05-29 | 1998-11-21 | Gmundner Fertigteile Gmbh | A noise control device for tracks |
US5648239A (en) | 1996-06-21 | 1997-07-15 | Incyte Pharmaceuticals, Inc. | Human camp-dependent protein kinase inhibitor homolog |
CA2259222A1 (en) | 1996-06-27 | 1997-12-31 | Pfizer Inc. | Derivatives of 2-(2-oxo-ethylidene)-imidazolidin-4-one and their use as farnesyl protein transferase inhibitors |
CZ301044B6 (cs) | 1996-08-12 | 2009-10-21 | Mitsubishi Tanabe Pharma | Léciva obsahující amidové deriváty inhibující Rho kinázu |
US5985317A (en) | 1996-09-06 | 1999-11-16 | Theratech, Inc. | Pressure sensitive adhesive matrix patches for transdermal delivery of salts of pharmaceutical agents |
US6030982A (en) | 1996-09-13 | 2000-02-29 | Schering Corporationm | Compounds useful for inhibition of farnesyl protein transferase |
US5945429A (en) | 1996-09-13 | 1999-08-31 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
US6040305A (en) | 1996-09-13 | 2000-03-21 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
US5885834A (en) | 1996-09-30 | 1999-03-23 | Epstein; Paul M. | Antisense oligodeoxynucleotide against phosphodiesterase |
IL129242A0 (en) | 1996-10-01 | 2000-02-17 | Cima Labs Inc | Taste-masked microcapsule compositions and methods of manufacture |
US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
US6131570A (en) | 1998-06-30 | 2000-10-17 | Aradigm Corporation | Temperature controlling device for aerosol drug delivery |
EP2314625B1 (en) | 1996-12-03 | 2014-05-07 | Amgen Fremont Inc. | Transgenic mammals having human Ig loci including plural VH and Vkappa regions and antibodies produced therefrom |
US6013662A (en) | 1996-12-30 | 2000-01-11 | Rhone-Poulenc Rorer S.A. | Farnesyl transferase inhibitors, their preparation, the pharmaceutical compositions which contain them and their use in the preparation of medicaments |
US6093737A (en) | 1996-12-30 | 2000-07-25 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
US5939439A (en) | 1996-12-30 | 1999-08-17 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
ATE287257T1 (de) | 1997-01-16 | 2005-02-15 | Massachusetts Inst Technology | Zubereitung von partikelhaltigen arzneimitteln zur inhalation |
EP0975603A1 (en) | 1997-01-29 | 2000-02-02 | Zeneca Limited | Inhibitors of farnesyl protein transferase |
US5860957A (en) | 1997-02-07 | 1999-01-19 | Sarcos, Inc. | Multipathway electronically-controlled drug delivery system |
ZA981080B (en) | 1997-02-11 | 1998-08-12 | Warner Lambert Co | Bicyclic inhibitors of protein farnesyl transferase |
US20030175858A1 (en) * | 1997-03-07 | 2003-09-18 | Ruben Steven M. | 186 human secreted proteins |
TW591030B (en) | 1997-03-10 | 2004-06-11 | Janssen Pharmaceutica Nv | Farnesyl transferase inhibiting 1,8-annelated quinolinone derivatives substituted with N- or C-linked imidazoles |
US6120751A (en) | 1997-03-21 | 2000-09-19 | Imarx Pharmaceutical Corp. | Charged lipids and uses for the same |
US5994071A (en) | 1997-04-04 | 1999-11-30 | Albany Medical College | Assessment of prostate cancer |
US7227002B1 (en) | 1997-04-14 | 2007-06-05 | Micromet Ag | Human antibodies that bind human 17-A1/EpCAM tumor antigen |
US6060082A (en) | 1997-04-18 | 2000-05-09 | Massachusetts Institute Of Technology | Polymerized liposomes targeted to M cells and useful for oral or mucosal drug delivery |
US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
US6051582A (en) | 1997-06-17 | 2000-04-18 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
US6211193B1 (en) | 1997-06-17 | 2001-04-03 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
US6239140B1 (en) | 1997-06-17 | 2001-05-29 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
US6159984A (en) | 1997-06-17 | 2000-12-12 | Schering Corporation | Farnesyl protein transferase inhibitors |
US6225322B1 (en) | 1997-06-17 | 2001-05-01 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
US6228865B1 (en) | 1997-06-17 | 2001-05-08 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
HUP0003194A3 (en) | 1997-08-15 | 2003-03-28 | Cephalon Inc West Chester | Use of tyrosine kinase inhibitor in synergic pharmaceutical composition treating prostate cancer |
US5948433A (en) | 1997-08-21 | 1999-09-07 | Bertek, Inc. | Transdermal patch |
US5989463A (en) | 1997-09-24 | 1999-11-23 | Alkermes Controlled Therapeutics, Inc. | Methods for fabricating polymer-based controlled release devices |
US6103723A (en) | 1997-10-17 | 2000-08-15 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
WO1999020611A1 (en) | 1997-10-22 | 1999-04-29 | Zeneca Limited | Imidazole derivatives and their use as farnesyl protein transferase inhibitors |
JP2001520222A (ja) | 1997-10-22 | 2001-10-30 | ゼネカ・リミテッド | イミダゾール誘導体およびファルネシルタンパク質トランスフェラーゼインヒビターとしてのそれらの使用 |
SE512663C2 (sv) | 1997-10-23 | 2000-04-17 | Biogram Ab | Inkapslingsförfarande för aktiv substans i en bionedbrytbar polymer |
DE69839179T2 (de) | 1997-10-28 | 2009-02-19 | Bando Chemical Industries, Ltd., Kobe | Dermatologisches pflaster und verfahren zur herstellung seiner basisschicht |
KR20010031713A (ko) | 1997-11-03 | 2001-04-16 | 벤슨 로버트 에이치. | 맥관형성 및 종양 성장 억제제인 맥관 내피 세포 성장억제제 |
US6124465A (en) | 1997-11-25 | 2000-09-26 | Rhone-Poulenc S.A. | Farnesyl transferase inhibitors, their preparation, the pharmaceutical compositions which contain them and their use in the preparation of medicaments |
BR9815423A (pt) | 1997-11-28 | 2000-10-17 | Lg Chemical Ltd | Composto derivado de imidazol, processo para preparar um derivado de imidazol, e, composição farmacêutica. |
US6054466A (en) | 1997-12-04 | 2000-04-25 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
US6242196B1 (en) | 1997-12-11 | 2001-06-05 | Dana-Farber Cancer Institute | Methods and pharmaceutical compositions for inhibiting tumor cell growth |
US6335156B1 (en) | 1997-12-18 | 2002-01-01 | The Johns Hopkins University School Of Medicine | 14-3-3σ arrests the cell cycle |
US6210882B1 (en) | 1998-01-29 | 2001-04-03 | Mayo Foundation For Medical Education And Reseach | Rapid thermocycling for sample analysis |
ES2185307T3 (es) | 1998-02-02 | 2003-04-16 | Lg Chemical Ltd | Inhibidores de la farnesil transferasa que tienen una estructura piperidinica y procedimiento para su preparacion. |
PT1076663E (pt) | 1998-04-27 | 2004-06-30 | Warner Lambert Co | Derivados funcionalizados de alquilo e alcenilo de cadeia lateral de glicinamidas como inibidores de farnesil transferase |
US6048736A (en) | 1998-04-29 | 2000-04-11 | Kosak; Kenneth M. | Cyclodextrin polymers for carrying and releasing drugs |
JP2002518432A (ja) | 1998-06-24 | 2002-06-25 | アドバンスト インハレーション リサーチ,インコーポレイテッド | 吸入器から放出される大多孔性粒子 |
TR200003882T2 (tr) | 1998-07-06 | 2001-06-21 | Janssen Pharmaceutica N.V. | Artropatilerin tedavisi için farnesil protein transferaz inhibitörleri. |
US6034053A (en) | 1998-07-13 | 2000-03-07 | Wayne Hughes Institute | EGF-isoflavone conjugates for the prevention of restenosis |
US6362188B1 (en) | 1998-12-18 | 2002-03-26 | Schering Corporation | Farnesyl protein transferase inhibitors |
US6372747B1 (en) | 1998-12-18 | 2002-04-16 | Schering Corporation | Farnesyl protein transferase inhibitors |
FR2787327B1 (fr) | 1998-12-21 | 2003-01-17 | Aventis Pharma Sa | Compositions contenant des inhibiteurs de farnesyle transferase |
US6432959B1 (en) | 1998-12-23 | 2002-08-13 | Schering Corporation | Inhibitors of farnesyl-protein transferase |
ATE248170T1 (de) | 1999-01-11 | 2003-09-15 | Univ Princeton | Kinase-inhibitoren mit hoher affinität zur ziel detektion und ihre verwendung |
US6399633B1 (en) | 1999-02-01 | 2002-06-04 | Aventis Pharmaceuticals Inc. | Use of 4-H-1-benzopryan-4-one derivatives as inhibitors of smooth muscle cell proliferation |
US6245759B1 (en) | 1999-03-11 | 2001-06-12 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
US6271359B1 (en) | 1999-04-14 | 2001-08-07 | Musc Foundation For Research Development | Tissue-specific and pathogen-specific toxic agents and ribozymes |
US6143766A (en) | 1999-04-16 | 2000-11-07 | Warner-Lambert Company | Benzopyranone and quinolone inhibitors of ras farnesyl transferase |
US6256533B1 (en) | 1999-06-09 | 2001-07-03 | The Procter & Gamble Company | Apparatus and method for using an intracutaneous microneedle array |
US6458935B1 (en) | 1999-06-23 | 2002-10-01 | Merck & Co., Inc. | Radiolabeled farnesyl-protein transferase inhibitors |
ATE440111T1 (de) | 1999-11-29 | 2009-09-15 | Bac Ip B V | Immobilisierte antigenbindende moleküle aus einer domäne |
US6403581B1 (en) | 2000-01-19 | 2002-06-11 | American Cyanamid Company | Method of inhibition of farnesyl-protein transferase using substituted benz (cd) indol-2-imine and-amine derivatives |
US6261595B1 (en) | 2000-02-29 | 2001-07-17 | Zars, Inc. | Transdermal drug patch with attached pocket for controlled heating device |
JP2001273612A (ja) | 2000-03-28 | 2001-10-05 | Yamaha Corp | 磁気抵抗効果型磁気ヘッドおよびその製造方法ならびにこの磁気抵抗効果型磁気ヘッドを備えた磁気記録再生装置 |
US7365167B2 (en) | 2001-11-26 | 2008-04-29 | Cell Matrix, Inc. | Humanized collagen antibodies and related methods |
US6875433B2 (en) | 2002-08-23 | 2005-04-05 | The United States Of America As Represented By The Secretary Of The Army | Monoclonal antibodies and complementarity-determining regions binding to Ebola glycoprotein |
EP1633397A2 (en) | 2003-06-04 | 2006-03-15 | Eli Lilly And Company | Anti-ghrelin fab antibodies |
US20050042664A1 (en) | 2003-08-22 | 2005-02-24 | Medimmune, Inc. | Humanization of antibodies |
SI1725249T1 (sl) * | 2003-11-06 | 2014-04-30 | Seattle Genetics, Inc. | Spojine monometilvalina, sposobne konjugacije na ligande |
CA2572239C (en) * | 2004-06-24 | 2019-07-09 | Mayo Foundation For Medical Education And Research | B7-h5, a costimulatory polypeptide |
AU2006252733A1 (en) * | 2005-06-02 | 2006-12-07 | Astrazeneca Ab | Antibodies directed to CD20 and uses thereof |
JP5129143B2 (ja) | 2005-10-07 | 2013-01-23 | エグゼリクシス, インコーポレイテッド | Mekインヒビターおよびその使用方法 |
US8476451B2 (en) | 2007-07-20 | 2013-07-02 | The Regents Of The University Of California | Tubulysin D analogues |
HUE056313T2 (hu) | 2010-01-29 | 2022-02-28 | Chugai Pharmaceutical Co Ltd | Anti-DLL3 antitest |
MX342291B (es) | 2010-02-04 | 2016-09-23 | Toray Industries | Composicion farmaceutica para el tratamiento y/o prevencion del cancer. |
CN107098958B (zh) * | 2010-03-26 | 2021-11-05 | 达特茅斯大学理事会 | Vista调节性t细胞介体蛋白、vista结合剂及其用途 |
AU2011256290B2 (en) | 2010-05-17 | 2014-06-12 | The Board Of Regents Of The University Of Texas System | Rapid isolation of monoclonal antibodies from animals |
WO2012047427A2 (en) | 2010-08-31 | 2012-04-12 | The Regents Of The University Of California | Antibodies for botulinum neurotoxins |
CA2812865C (en) | 2010-10-07 | 2021-01-26 | Ac Immune S.A. | Phosphospecific antibodies recognising tau |
JP2014515740A (ja) | 2011-03-30 | 2014-07-03 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 抗凝固薬の解毒剤 |
JP6093360B2 (ja) | 2011-08-17 | 2017-03-08 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | インテグリンα−vβ−8と結合する抗体 |
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JP2019176863A (ja) | 2019-10-17 |
US10414823B2 (en) | 2019-09-17 |
CA2914369C (en) | 2023-02-14 |
JP2016527877A (ja) | 2016-09-15 |
WO2014197849A3 (en) | 2015-03-12 |
AU2014274660B2 (en) | 2019-05-16 |
SG10201708143QA (en) | 2017-11-29 |
WO2014197849A9 (en) | 2015-12-23 |
US20190031768A1 (en) | 2019-01-31 |
EP3003390A2 (en) | 2016-04-13 |
EP3003390B1 (en) | 2021-07-07 |
AU2014274660A1 (en) | 2015-12-24 |
US10100123B2 (en) | 2018-10-16 |
CA2914369A1 (en) | 2014-12-11 |
ZA201508896B (en) | 2019-06-26 |
EP3003390A4 (en) | 2017-01-18 |
US20190031767A1 (en) | 2019-01-31 |
NZ714765A (en) | 2021-12-24 |
US20200040102A1 (en) | 2020-02-06 |
US10421818B2 (en) | 2019-09-24 |
SG11201509982UA (ja) | 2016-04-28 |
ES2891755T3 (es) | 2022-01-31 |
WO2014197849A2 (en) | 2014-12-11 |
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