JP2018517888A - 循環trop−2陽性癌細胞の単離、検出、診断及び/または特徴付け - Google Patents
循環trop−2陽性癌細胞の単離、検出、診断及び/または特徴付け Download PDFInfo
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Abstract
【選択図】図1
Description
本出願は、2015年4月22日に出願された米国仮特許出願第62/151,169号の35USC119(e)に基づく利益を主張し、その文全体を参照により本明細書に援用する。
本出願は、EFS−Webを介してASCIIフォーマットで提出された、その全体が参照により本明細書に援用される配列表を含んでいる。2016年4月21日に作成された当該ASCIIコピーは、IMM359W01_SL.txtと称され、またサイズは44,906バイトである。
本発明は、好ましくは循環系由来のTrop−2+癌細胞を単離し、検出し、診断し、及び/または特徴付けるための方法及び組成物に関する。当該方法及び組成物は抗Trop−2抗体を利用するものであり、当該抗体は1価、2価または多価であってよい。好ましい実施形態において、抗Trop−2抗体は当該アッセイで利用される唯一の抗TAA(腫瘍関連抗原)捕捉抗体であり、これはTrop−2以外にはTAAに対する抗体混合物の使用を含まない。別の実施形態において、当該捕捉抗体は、抗Trop−2抗体または断片及び異なるTAAに対する第2の抗体または断片を含む二重特異性抗体であってよい。より好ましくは、当該抗体は、齧歯類類抗体、キメラ抗体、ヒト化抗体もしくはヒト抗体、またはその抗原結合断片である。癌細胞におけるTrop−2の発現は既知の技術を用いて評価することができ、これにはフローサイトメトリーまたは免疫組織化学により検出される抗Trop−2抗体の結合、及び定量的RT−PCRを含むが、これらに限定されない。循環腫瘍細胞(CTC)を単離及び/または検出するために開発された自動システム及び装置を、特許請求の範囲に記載された方法を実施することにおいて利用することができ、これにはMagSweeper装置(Illumina,Inc.,San Diego,CA)、LIQUIDBIOPSY(登録商標)システム(Cynvenio Biosystems,Inc.,Westlake Village,CA)、CELLSEARCH(登録商標)システム(Veridex LLC,Raritan,NJ)、GILUPI CELLCOLLECTOR(商標)(GILUPI GmbH,Potsdam,Germany)、APOSTREAM(登録商標)システム(Apocell,Houston,TX)、ONCOCEE(登録商標)マイクロ流体プラットフォーム(BioCept Laboratories,SanDiego,CA)、VerIFAST System(Casavant et al.,2013,Lab Chip 13:391−6;2014,Lab Chip 14:99−105)またはISOFLUX(商標)システム(Fluxion,South San Francisco,CA)が含まれるが、これらに限定されない。最も好ましくは、抗Trop−2抗体は、軽鎖CDR配列のCDR1(KASQDVSIAVA、配列番号1)、CDR2(SASYRYT、配列番号2)、及びCDR3(QQHYITPLT、配列番号3)、並びに重鎖CDR配列のCDR1(NYGMN、配列番号4)、CDR2(WINTYTGEPTYTDDFKG、配列番号5)及びCDR3(GGFGSSYWYFDV、配列番号6)を含むマウス抗体、キメラ抗体またはヒト化RS7(hRS7)抗体である。しかし、別の実施形態では、以下に述べるように、他の既知の抗Trop−2抗体を利用することができる。本方法及び組成物は、種々の転移性Trop−2発現癌、例えば乳癌(例えば、トリプルネガティブ乳癌)、卵巣癌、子宮頸癌、子宮内膜癌、肺癌、前立腺癌、結腸癌、直腸癌、胃癌、食道癌、膀胱癌、腎臓癌、膵臓癌、甲状腺癌、上皮癌、及び頭頸部癌の濃縮、単離、検出、診断及び/または特徴付けのために適用可能である。抗Trop−2抗体は、1以上の標識された検出抗体と組み合わせて利用されてよく、または少なくとも1つの診断薬との結合によって直接標識されてもよい。或いは、二重特異性抗体は、Trop−2についての1つの結合部位、及び標的とすることが可能な構築物(典型的には少なくとも1つの診断薬で標識された小さなペプチド)上のハプテンについての別の結合部位を含み得る。ある特定の代替実施形態においては、Trop−2+CTCの検出の後に、抗Trop−2抗体またはその断片を用いて、Trop−2+癌の治療的処置を行ってよい。好ましくは、この抗体または断片は、少なくとも1つの治療剤、例えば抗体、抗体断片、薬物、毒素、ヌクレアーゼ、ホルモン、免疫調節剤、アポトーシス促進剤、抗血管新生剤、ホウ素化合物、光活性剤もしくは色素または放射性同位体へ複合体化される。より好ましくは、当該治療剤はSN−38またはP2PDOXである。
Trop−2(ヒト栄養膜細胞表面マーカー)は、正常細胞及び悪性栄養膜細胞において最初に同定された細胞表面糖タンパク質である(Lipinski et al.,1981,Proc.Natl.Acad.Sci.USA 78:5147−50)。Trop−2は、殆どのヒト癌、特に上皮癌及び腺癌において高度に発現される一方、正常組織においては発現が低く制限されると報告されている(例えば、Cubas et al.,2010,Molec.Cancer 9:253;Stepan et al.,2011,J.Histochem.Cytochem.59:701−10;Varughese et al.,2011,Am.J.Obst.Gyn.205:567e−e7参照)。Trop−2の発現は、転移、腫瘍の攻撃性増加及び患者の生存低下と関連する(Cubas et al.,2010;Varughese et al.,2011)。Trop−2の病原性効果は、ERK 1/2 MAPK経路によって少なくとも部分的に媒介されることが報告されている(Cubas et al.,2010)。
別途特定しない限り、「a」または「an」は1以上を意味する。
CTCの単離及び/または検出のための主題の方法及び組成物は、Trop−2に結合する少なくとも1つの抗体またはその断片を利用するものであり、これには齧歯類抗体、キメラ抗体、ヒト抗体またはヒト化抗体が含まれる。特定の好ましい実施形態において、抗Trop−2抗体は、ヒト化RS7抗体(例えば、その全体を本明細書の一部として得援用する米国特許第7,238,785号参照)であることができ、これは軽鎖CDR配列のCDR1(KASQDVSIAVA、SEQ(配列番号1));CDR2(SASYRYT、配列番号2);及びCDR3(QQHYITPLT、配列番号3)、並びに重鎖CDR配列のCDR1(NYGMN、配列番号4);CDR2(WINTYTGEPTYTDDFKG、配列番号5);及びCDR3(GGFGSSYWYFDV、配列番号6)を備えている。
抗Trop−2抗体は、CTCの単離及び検出のための何れか既知の技術を使用して、Trop−2陽性CTCを濃縮、単離、検出及び/または診断するために利用することができる。多くのシステムが開発され、CTC検出のために商業的に入手可能である。多くは特異的な抗EpCAM抗体を使用して開発されたが、その代わりに、抗Trop−2抗体を利用するように組成及び方法を改変することができる。従って、Trop−2陽性CTCの単離及び検出は、そのような既知のシステム、または細胞単離及び検出の更に伝統的な方法を用いて実施することができる。そのような既知の技術の非限定的な例を以下に説明する。
実質的に任意の標的抗原、例えばTrop−2に対するモノクローナル抗体を調製するための技術は、当技術分野で周知である。例えば、Kohler and Milstein,Nature 256:495(1975)、及びColigan et al.(eds.),CURRENT PROTOCOLS IN IMMUNOLOGY,VOL.1,pages 2.5.1−2.6.7(John Wiley & Sons 1991)を参照されたい。簡単に言えば、モノクローナル抗体は、抗原を含む組成物をマウスに注射すること、脾臓を除去してBリンパ球を得ること、当該Bリンパ球をミエローマ細胞と融合させてハイブリドーマを産生すること、当該ハイブリドーマをクローニングすること、当該抗原に対する抗体を産生する陽性クローンを選択すること、当該抗原に対する抗体を産生するクローンを培養すること、及び当該ハイブリドーマ培養物から当該抗体を単離することによって得ることができる。
キメラ抗体は、ヒト抗体の可変領域が、例えば、マウス抗体の相補性決定領域(CDR)を含むマウス抗体の可変領域により置換されている組換えタンパク質である。キメラ抗体は、対象に投与された場合に減少した免疫原性及び増大した安定性を示す。マウス免疫グロブリン可変ドメインをクローニングするための一般的な技術は、例えば、Orlandi et al.,Proc. Nat’l Acad. Sci. USA 6:3833(1989).に開示されている。キメラ抗体を構築する技術は、当業者に周知である。一例として、Leung et al.,Hybridoma 13:469(1994)は、抗CD22モノクローナル抗体であるマウスLL2のVκ及びVHドメインをコードするDNA配列を、それぞれヒトκ及びIgG1定常領域ドメインと組み合わせることによってLL2キメラを製造した。
ヒト化MAbを産生する技術は、当技術分野で周知である(例えば、Jones et al.,Nature 321:522(1986),Riechmann et al.,Nature 332:323(1988),Verhoeyen et al.,Science 239:1534(1988),Carter et al.,Proc.Nat´l Acad.Sci.USA 89:4285(1992),Sandhu,Crit.Rev.Biotech.12:437(1992),及びSinger et al.,J.Immun.150:2844(1993)を参照されたい)。キメラまたはマウスモノクローナル抗体は、マウス免疫グロブリンにおける重鎖及び軽鎖の可変鎖由来マウスCDRを、ヒト抗体の対応する可変ドメインに移植することによってヒト化され得る。キメラモノクローナル抗体中のマウスフレームワーク領域(FR)もまた、ヒトFR配列で置換される。マウスCDRをヒトFRに単に移植するだけで、しばしば抗体親和性の低下または消失が生じるので、マウス抗体の本来の親和性を回復させるために追加の修飾が必要となる可能性がある。これは、そのエピトープに対して良好な結合親和性を有する抗体を得るために、FR領域中の1以上のヒト残基をそのマウス対応物で置換することにより達成できる。例えば、Tempest et al.,Biotechnology 9:266(1991)及びVerhoeyen et al.,Science 239:1534(1988)を参照されたい。好ましい置換残基には、CDR残基側鎖の1,2または3オングストローム以内に位置するか、CDR配列に隣接して位置するか、またはCDR残基と相互作用すると予測されるFR残基が含まれる。
コンビナトリアルアプローチ、またはヒト免疫グロブリン遺伝子座において形質転換されたトランスジェニック動物の何れかを用いて、完全なヒト抗体を産生する方法は当技術において知られている(例えば、Mancini et al.,2004,New Microbiol.27:315〜28;Conrad and Scheller,2005,Comb.Chem.High Throughput Screen.8:117〜26;Brekke and Loset,2003,Curr.Opin.Pharmacol.3:544〜50)。完全ヒト抗体はまた、遺伝子または染色体トランスフェクション法、ならびにファージディスプレイ技術によっても構築することができ、これらの技術は何れも当該技術において知られている。例えば、McCafferty et al.,Nature 348:552〜553(1990)を参照されたい。抗体が、例えばTrop−2陽性癌の検出後の腫瘍療法においてインビボで利用される場合、このような完全ヒト抗体は、キメラ抗体またはヒト化抗体よりも副作用が更に少なく、本質的に内因性のヒト抗体としてインビボで機能することが期待される。
上述のように、ある特定の代替実施形態において、抗Trop−2抗体は、循環Trop−2陽性腫瘍細胞の検出後に、Trop−2発現癌を治療するために使用される。幾つかの実施形態において、標的癌は、腫瘍療法の標的とされ得る1以上の追加の腫瘍関連抗原(TAA)を発現し得る。癌の治療のために使用され得る特定の抗体には、LL1(抗CD74)、LL2もしくはRFB4(抗CD22)、ベルツズマブ(hA20、抗CD20)、リツキシマブ(抗CD20)、及びオビヌツズマブ(GA101、抗CD20)、ランブロリズマブ(抗PD−1受容体)、ニボルマブ(抗PD−1受容体)、イピリムマブ(抗CTLA−4)、RS7(抗上皮糖タンパク質−1(EGP−1、Trop−2としても知られる))、PAM4もしくはKC4(両方とも抗ムチン)、MN−14(抗癌胎児性抗原(CEA、CD66eまたはCEACAM5としても知られる))、MN−15もしくはMN−3(抗CEACAM6)、Mu−9(抗結腸特異的抗原−p)、Immu31(抗アルファフェトプロテイン)、R1(抗IGF−1R)、A19(抗CD19)、TAG72(例えばCC49)、Tn、J591もしくはHuJ591(抗PSMA(前立腺特異的膜抗原))、AB−PG1−XG1−026(抗PSMA二量体)、D2/B(抗PSMA)、G250(抗炭酸脱水素酵素IX・MAb)、L243(抗HLA−DR)、アレムツズマブ(抗CD52)、ベバシツマブ(抗VEGF)、セツキシマブ(抗EGFR)、ゲムツズマブ(抗CD33)、イブリツモマブ・チウキセタン(ibritumomab tiuxetan:抗CD20);パニツムマブ(抗EGFR);トシツモマブ(抗CD20);PAM4(別名クリバツズマブ、抗ムチン)及びトラスツズマブ(抗ErbB2)が含まれるが、これらに限定されない。このような抗体は当該技術において知られている(例えば、米国特許番号5,686,072;5,874,540;6,107,090;6,183,744;6,306,393;6,653,104;6,730.300;6,899,864;6,926,893;6,962,702;7,074,403;7,230,084;7,238,785;7,238,786;7,256,004;7,282,567;7,300,655;7,312,318;7,585,491;7,612,180;7,642,239;及び米国特許出願公開番号20050271671;20060193865;20060210475;20070087001:これらの各々の実施例部分を参照により本明細書に援用する)。使用される特定の既知抗体には、hPAM4(米国特許第7,282,567号)、hA20(米国特許第7,251,164号)、hA19(米国特許第7,109,304号)、hIMMU−31(米国特許第7,300,655号)、hLL1(米国特許第7,312,318号)、hLL2(米国特許第7,074,403号)、hMu−9(米国特許第7,387,773号)、hL243(米国特許第7,612,180号)、hMN−14(米国特許第6,676,924号)、hMN−15(米国特許第7,541,440号)、hR1(米国特許出願第12/772,645号)、hRS7(米国特許第7,238,785号)、hMN−3(米国特許第7,541,440号)、AB−PG1−XG1−026(ATCC PTA−4405及びPTA−4406として寄託された米国特許出願第11/983,372号)、及びD2/B(WO 2009/130575)が含まれ、各引用された特許または出願のテキストは、図及び実施例の部分に関して参照により本明細書に援用する。
治療用抗体の免疫原性は、注入反応のリスク増大及び治療応答の持続時間低下に関連する(Baert et al.,2003,N Engl J Med 348:602−08)。治療用抗体が宿主において免疫応答を誘導する程度は、抗体のアロタイプによって部分的に決定され得る(Stickler et al.,2011,Genes and Immunity 12:213−21)。抗体アロタイプは、抗体の定常領域配列における特定の位置でのアミノ酸配列変化に関連する。重鎖γ型定常領域を含むIgG抗体のアロタイプをGmアロタイプと命名する(1976,J Immunol 117:1056−59)。
ナノボディは、サイズが約12〜15kDa(約110アミノ酸長)の単一ドメイン抗体である。ナノボディは、フルサイズ抗体と同様に標的抗原に選択的に結合することができ、抗原に対して同様の親和性を有する。しかしながら、そのサイズが遥かに小さいため、固形腫瘍へのより良好な浸透が可能である可能性がある。より小さいサイズはまた、ナノボディの安定性に寄与し、これはフルサイズの抗体よりも極端なpH及び温度に対してより耐性である(Van Der Linden et al.,1999,Biochim Biophys Act 1431:37−46)。単一ドメイン抗体は、元々は、ラクダ科動物(ラクダ、アルパカ、ラマ)が軽鎖を持たない完全に機能的な抗体を有するとの発見(例えば、Hamsen et al.,2007,Appl Microbiol Biotechnol 77:13−22))に続いて開発された。重鎖抗体は、単一可変ドメイン(VHH)及び2つの定常ドメイン(CH2及びCH3)からなっている。抗体と同様に、ナノボディは、多価及び/または二重特異性の構築物として開発及び使用され得る。癌及び他の疾患における潜在的な臨床的用途を有する、IL−6R、vWF、TNF、RSV、RANKL、IL−17A&F、及びIgEのような種々の標的抗原を標的とするヒト化形態のナノボディ(例えばABLYNX(登録商標)、Ghent、ベルギー)が商業的開発の最中である。(例えば、Saerens et al.,2008,Curr Opin Pharmacol 8:600−8;Muyldermans,2013,Ann Rev Biochem 82:775−97;Ibanez et al.,2011,J Infect Dis 203:1063−72)。
抗体断片は、F(ab´)2、Fab´、F(ab)2、Fab、Fv、sFv、scFvのような、抗体の抗原結合性部分である。特異的エピトープを認識する抗体断片は、既知の技術によって生成できる。例えば、F(ab´)2断片は、抗体分子のペプシン消化によって製造し得る。これら及び他の方法は、例えば、Goldenbergによって、米国特許第4,036,945号及び同第4,331,647号及びそれに含まれる参照文献に記載されている。また、Nisonoff et al.,Arch Biochem.Biophys.89:230(1960);Porter,Biochem.J.73:119(1959),Edelman et al.,in METHODS IN ENZYMOLOGY VOL.1,page 422(Academic Press 1967), and Coligan at pages 2.8.1−2.8.10および2.10.−2.10.4を参照されたい。或いは、望ましい特異性を備えたモノクローナルFab´断片の迅速かつ容易な同定を可能にするために、Fab´発現ライブラリーを構築することができる(Huse et al.,1989,Science,246:1274−1281)
キメラまたはヒト化抗体の製造のような種々の技術は、抗体のクローニング及び構築の手順を含み得る。対象となる抗体の抗原結合性VK(可変軽鎖)及びVH(可変重鎖)配列は、RT−PCR、5´−RACE及びcDNAライブラリースクリーニングのような、種々の分子クローニング手順によって得ることができる。マウスMAbを発現する細胞由来のMAbにおけるV遺伝子は、PCR増幅によってクローニングされ、配列決定することができる。それらの真正性を確認するために、クローン化されたVL及びVH遺伝子は、Orlandi et al.,(Proc.Natl.Acad.Sci.,USA,86:3833(1989))が記載したように、細胞培養においてキメラAbとして発現することができる。次いで、V遺伝子配列に基づき、Leung et al.(Mol.Immunol.,32:1413(1995))が記載したようにして、ヒト化MAbを設計及び構築することができる。
ある特定の代替実施形態では、抗Trop−2抗体またはその断片を、例えばハプテン結合性抗体またはその断片、例えば抗HSGまたは抗In−DTPA抗体と同時投与することができる。そのような二重特異性抗体は、インビボでTrop−2陽性腫瘍に対して診断剤及び/または治療剤を投与するための、プレターゲッティング技術において使用することができる。他の実施形態において、二重特異性抗体または多重特異性抗体は、抗癌療法のために直接的に利用され得る。
二重特異性または多重特異性の抗体または構築物は、DOCK−AND−LOCK(登録商標)技術(例えば、米国特許第7,550,143号;第7,521,056号;第7,534,866;第7,527,787号、及び第7,666,400号参照、各々の実施例の節を参照により本明細書に援用する)を用いて製造することができる。一般に、この技術は、cAMP依存性プロテインキナーゼ(PKA)の調節(R)サブユニットの二量体化およびドッキングドメイン(DDD)配列と、様々なAKAPタンパク質の何れかに由来するアンカードメイン(AD)配列の間に生じる特異的かつ高親和性の結合相互作用を利用する(Baillie et al.,FEBS Letters.2005;579:3264.Wong and Scott,Nat.Rev.Mol.Cell Biol.2004;5:959)。DDD及びADペプチドは、任意のタンパク質、ペプチドまたは他の分子に対して、好ましくはADまたはDDD配列を含む融合タンパク質として結合され得る。DDD配列は自発的に二量体化してAD配列に結合するので、この技術は、DDDまたはAD配列に結合され得る何れかの選択された分子間での複合体の形成を可能にする。
異なるタイプのDNL(登録商標)構築物について、異なるADまたはDDD配列を利用することができる。例示的なDDD及びAD配列を以下に示す。
DDD1
SHIQIPPGLTELLQGYTVEVLRQQPPDLVEFAVEYFTRLREARA(配列番号9)
DDD2
CGHIQIPPGLTELLQGYTVEVLRQQPPDLVEFAVEYFTRLREARA(配列番号10)
AD1
QIEYLAKQIVDNAIQQA(配列番号11)
AD2
CGQIEYLAKQIVDNAIQQAGC(配列番号12)
DDD3
SLRECELYVQKHNIQALLKDSIVQLCTARPERPMAFLREYFERLEKEEAK(配列番号13)
DDD3C
MSCGGSLRECELYVQKHNIQALLKDSIVQLCTARPERPMAFLREYFERLEKEEAK(配列番号14)
AD3
CGFEELAWKIAKMIWSDVFQQGC(配列番号15)
PKA RIα
SLRECELYVQKHNIQALLKDVSIVQLCTARPERPMAFLREYFEKLEKEEAK(配列番号16)
PKA RIβ
SLKGCELYVQLHGIQQVLKDCIVHLCISKPERPMKFLREHFEKLEKEENRQILA(配列番号17)
PKA RIIα
SHIQIPPGLTELLQGYTVEVGQQPPDLVDFAVEYFTRLREARRQ(配列番号18)
PKA RIIβ
SIEIPAGLTELLQGFTVEVLRHQPADLLEFALQHFTRLQQENER(配列番号19)
THIQIPPGLTELLQGYTVEVLRQQPPDLVEFAVEYFTRLREARA(配列番号20)
SKIQIPPGLTELLQGYTVEVLRQQPPDLVEFAVEYFTRLREARA(配列番号21)
SRIQIPPGLTELLQGYTVEVLRQQPPDLVEFAVEYFTRLREARA(配列番号22)
SHINIPPGLTELLQGYTVEVLRQQPPDLVEFAVEYFTRLREARA(配列番号23)
SHIQIPPALTELLQGYTVEVLRQQPPDLVEFAVEYFTRLREARA(配列番号24)
SHIQIPPGLSELLQGYTVEVLRQQPPDLVEFAVEYFTRLREARA(配列番号25)
SHIQIPPGLTDLLQGYTVEVLRQQPPDLVEFAVEYFTRLREARA(配列番号26)
SHIQIPPGLTELLNGYTVEVLRQQPPDLVEFAVEYFTRLREARA(配列番号27)
SHIQIPPGLTELLQAYTVEVLRQQPPDLVEFAVEYFTRLREARA(配列番号28)
SHIQIPPGLTELLQGYSVEVLRQQPPDLVEFAVEYFTRLREARA(配列番号29)
SHIQIPPGLTELLQGYTVDVLRQQPPDLVEFAVEYFTRLREARA(配列番号30)
SHIQIPPGLTELLQGYTVEVLKQQPPDLVEFAVEYFTRLREARA(配列番号31)
SHIQIPPGLTELLQGYTVEVLRNQPPDLVEFAVEYFTRLREARA(配列番号32)
SHIQIPPGLTELLQGYTVEVLRQNPPDLVEFAVEYFTRLREARA(配列番号33)
SHIQIPPGLTELLQGYTVEVLRQQPPELVEFAVEYFTRLREARA(配列番号34)
SHIQIPPGLTELLQGYTVEVLRQQPPDLVDFAVEYFTRLREARA(配列番号35)
SHIQIPPGLTELLQGYTVEVLRQQPPDLVEFLVEYFTRLREARA(配列番号36)
SHIQIPPGLTELLQGYTVEVLRQQPPDLVEFIVEYFTRLREARA(配列番号37)
SHIQIPPGLTELLQGYTVEVLRQQPPDLVEFVVEYFTRLREARA(配列番号38)
SHIQIPPGLTELLQGYTVEVLRQQPPDLVEFAVDYFTRLREARA(配列番号39)
NIEYLAKQIVDNAIQQA(配列番号40)
QLEYLAKQIVDNAIQQA(配列番号41)
QVEYLAKQIVDNAIQQA(配列番号42)
QIDYLAKQIVDNAIQQA(配列番号43)
QIEFLAKQIVDNAIQQA(配列番号44)
QIETLAKQIVDNAIQQA(配列番号45)
QIESLAKQIVDNAIQQA(配列番号46)
QIEYIAKQIVDNAIQQA(配列番号47)
QIEYVAKQIVDNAIQQA(配列番号48)
QIEYLARQIVDNAIQQA(配列番号49)
QIEYLAKNIVDNAIQQA(配列番号50)
QIEYLAKQIVENAIQQA(配列番号51)
QIEYLAKQIVDQAIQQA(配列番号52)
QIEYLAKQIVDNAINQA(配列番号53)
QIEYLAKQIVDNAIQNA(配列番号54)
QIEYLAKQIVDNAIQQL(配列番号55)
QIEYLAKQIVDNAIQQI(配列番号56)
QIEYLAKQIVDNAIQQV(配列番号57)
<RII特異的AKAP>
AKAP−KL
PLEYQAGLLVQNAIQQAI(配列番号62)
AKAP79
LLIETASSLVKNAIQLSI(配列番号63)
AKAP−Lbc
LIEEAASRIVDAVIEQVK(配列番号64)
<RI特異的AKAP>
AKAPce
ALYQFADRFSELVISEAL(配列番号65)
RIAD
LEQVANQLADQIIKEAT(配列番号66)
PV38
FEELAWKIAKMIWSDVF(配列番号67)
<二重特異性AKAP>
AKAP7
ELVRLSKRLVENAVLKAV(配列番号68)
MAP2D
TAEEVSARIVQVVTAEAV(配列番号69)
DAKAP1
QIKQAAFQLISQVILEAT(配列番号70)
DAKAP2
LAWKIAKMIVSDVMQQ(配列番号71)
Ht31
DLIEEAASRIVDAVIEQVKAAGAY(配列番号72)
RIAD
LEQYANQLADQIIKEATE(配列番号73)
PV−38
FEELAWKIAKMIWSDVFQQC(配列番号74)
ある特定の代替的実施形態において、DNL(登録商標)構築物は代替的に構築された抗体または抗体断片を用いて形成され得るものであり、ここではAD部分が重鎖上におけるFcのC末端の代わりに、カッパ軽鎖のC末端(Ck)に結合し得る。代替的に形成されたDNL(登録商標)構築物は、2012年6月1日に出願された米国仮特許出願第61/654,310号、2012年6月20日に出願された第61/662,086号、2012年7月19日に出願された第61/673,553号、2012年8月13日に出願された第61/682,531号に記載されており、それら各々は、参照により本明細書に援用する。軽鎖複合体化DNL(登録商標)構築物は、インビトロでの向上したFc−エフェクター機能活性及び改善された薬物動態、インビボでの安定性及び抗リンパ腫活性を示す(Rossi et al.,2013,Bioconjug Chem 24:63−71)。
別の実施形態において、開示される方法及び組成物は、1以上の置換アミノ酸残基を有するタンパク質またはペプチドの製造及び使用を含み得る。例えば、DNL(登録商標)構築物を作製するために使用されるDDD及び/またはAD配列は、上で述べたようにして改変され得る。
二重特異性抗体または多重特異性抗体は、プレターゲッティング技術において有用であり得る。この場合、1以上の診断薬及び/または治療薬を、1以上のハプテンを含む標的化可能な構築物に複合体化させることができる。当該ハプテンは、腫瘍関連抗原または他の疾患関連抗原にも結合する二重特異性または多重特異性抗体の少なくとも1つのアームによって認識される。この場合、当該治療剤は、当該標的化可能な構築物の結合を介して当該抗体に間接的に結合する。このプロセスは、プレターゲッティングと称される。
ある特定の実施形態において、プレターゲッティングに使用するための1以上の治療剤または診断剤で標識された標的化可能な構築物ペプチドは、標的化可能な構築物ペプチドのための1以上の結合部位、及び疾患または状態に関連する標的抗原のための1以上の結合部位を備えた二重特異性抗体に結合するように選択することができる。二重特異性抗体はプレターゲッティング技術において使用することができ、ここでは抗体が最初に対象に投与され得る。二重特異性抗体が標的抗原に結合するために、及び未結合の抗体が循環系から消失するために、十分な時間が許容され得る。次に、標識されたペプチドのような標的化可能な構築物を対象に投与し、当該二重特異性抗体に結合させ、罹患した細胞または組織に局在させることができる。
様々な実施形態は、1以上の診断薬または治療薬に結合した抗Trop−2抗体またはその抗原結合性断片を備えた免疫複合体の使用を含み得る。幾つかの実施形態において、薬物または他の作用物質は、担体部分を介して抗体またはその断片に結合され得る。担体部分は、例えば還元されたSH基及び/または炭水化物側鎖に結合することができる。担体成分は、ジスルフィド結合形成を介して、還元された抗体成分のヒンジ領域に結合することができる。或いは、このような薬剤は、N−スクシニル3−(2−ピリジルジチオ)プロピオネート(SPDP)のようなヘテロ二官能性架橋剤を用いて結合させることができる(Yu et al.,Int.J.Cancer 56:244(1994))。そのような複合体化のための一般的な技術は、当技術において周知である。例えば、Wong,CHEMISTRY OF PROTEIN CONJUGATION AND CROSS−LINKING(CRC Press 1991);Upeslacis et al.,“Modification of Antibodies by Chemical Methods,”in MONOCLONAL ANTIBODIES:PRINCIPLES AND APPLICATIONS,Birch et al.(eds.),pages187−230(Wiley−Liss,Inc.1995);Price,“Production and Characterization of Synthetic Peptide−Derived Antibodies,”in MONOCLONAL ANTIBODIES:PRODUCTION,ENGINEERING AND CLINICAL APPLICATION,Ritter et al.(eds.),pages60−84(Cambridge University Press 1995)を参照されたい。或いは、担体部分は、抗体のFc領域における糖鎖部分を介して結合させることができる。
診断剤は、検出抗体を標識するために、またはCTCを直接標識するために使用され得る任意の検出可能な物質を含むことができ、好ましくは、放射性核種、放射線造影剤、常磁性イオン、金属、蛍光標識、化学発光標識、超音波造影剤及び光活性剤からなる群から選択される。そのような診断薬は周知であり、斯かる既知の診断薬の何れをも使用することができる。診断剤の非限定的な例には、110In、111In、177Lu、18F、52Fe、62Cu、64Cu、67Cu、67Ga、68Ga、86Y、90Y、89Zr、94mTc、94Tc、99mTc、120I、123I、124I、125I、131I、154−158Gd、32P、11C、13N、15O、186Re、188Re、51Mn、52mMn、55Co、72As、75Br、76Br、82mRb、83Sr、または他のガンマ放出体、ベータ放出体もしくはポジトロン放出体のような放射性核種が含まれ得る。使用される常磁性イオンには、クロム(III)、マンガン(II)、鉄(III)、鉄(II)、コバルト(II)、ニッケル(II)、銅(II)、ネオジム(III)、サマリウム(III)、イッテルビウム(III)、ガドリニウム(III)、バナジウム(II)、テルビウム(III)、ジスプロシウム(III)、ホルミウム(III)またはエルビウム(III)が含まれ得る。金属造影剤には、ランタン(III)、金(III)、鉛(II)またはビスマス(III)が含まれ得る。超音波造影剤には、ガス充填リポソームのようなリポソームが含まれ得る。放射線不透過性診断薬は、化合物、バリウム化合物、ガリウム化合物、及びタリウム化合物から選択することができる。
多種多様な治療試薬を、抗Trop−2または他の抗TAA抗体と同時にまたは順次投与することができる。或いは、このような薬剤、例えば、薬物、毒素、オリゴヌクレオチド、免疫調節剤、ホルモン、ホルモンアンタゴニスト、酵素、酵素阻害剤、放射性核種、血管新生阻害剤等は、抗体に複合体化することができる。治療剤には、例えば、ビンカアルカロイド等の細胞毒性薬物、ドキソルビシン等のアントラサイクリン、2−PDoxもしくはpro−2−PDox、ゲムシタビン、エピポドフィロトキシン、タキサン、代謝拮抗剤、アルキル化剤、抗生物質、SN−38、COX−2阻害剤、抗有糸分裂剤、抗血管新生剤及びアポトーシス促進剤、特にドキソルビシン、メソトレキセート、タキソール、CPT−11、カンプトテカン、プロテオソーム阻害剤、mTOR阻害剤、HDAC阻害剤、チロシンキナーゼ阻害剤ーおよび他のものが含まれる。他の有用な抗癌細胞毒性薬には、ナイトロジェンマスタード、アルキルスルホネート、ニトロソウレア、トリアゼン、葉酸類似体、COX−2阻害剤、代謝拮抗剤、ピリミジン類似体、プリン類似体、白金配位錯体、mTOR阻害剤、チロシンキナーゼ阻害剤、プロテオソーム阻害剤、HDAC阻害剤、カンプトテシン、ホルモン等が含まれる。適切な細胞傷害剤は、REMINGTON‘S PHARMACEUTICAL SCIENCES,19th Ed.(Mack Publishing Co.1995)、およびGOODMAN AND GILMAN’S THE PHARMACOLOGICAL BAISIS OF THERAPEUTICS,7th Ed.(MacMillan Publishing Co.1985)、並びにこれらの改訂版を含む刊行物に記載されている。実験薬物等の他の適切な細胞毒性物質は、当業者に既知である。好ましい実施形態において、カンプトテシンおよびSN−38のようなの関連化合物の複合体は、抗Trop−2抗体または他の抗TAA抗体に複合体化され得る。別の好ましい実施形態において、ゲムシタビンは、SN−38−hRS7および/または90Y−hPAM4と複合体化させて対象に投与される。
治療用抗体をインビボで投与する場合、適切な投与経路には、経口、非経口、直腸、経粘膜、腸内投与、髄内、髄腔内、直接的な脳室内、静脈内、硝子体内、腔内、腹腔内、腫瘍内注射が含まれるが、これ等に限定されない。好ましい投与経路は非経口、より好ましくは静脈内投与である。或いは、化合物を全身的ではなく局所的に、例えば、固形腫瘍または血液腫瘍への化合物の直接注射により投与することができる。
種々の実施形態は、患者においてTrop−2陽性CTCを検出するのに適した構成要素を含むキットに関する。例示的キットは、本明細書に記載の少なくとも1つの抗Trop−2抗体を含み得る。ある特定の実施形態において、抗体は、少なくとも1つの診断薬に複合体化され得る。別の実施形態では、Trop−2陽性CTCに結合する第2の抗体を含めることができる。当該第2の抗体は、Trop−2の異なるエピトープまたは異なるTAAに結合し、少なくとも1つの診断薬で標識することができる。ある特定の実施形態において、抗Trop−2抗体またはその抗原結合性断片は、抗体の滅菌液体製剤または凍結乾燥調製物を含有するプレフィルドシリンジまたはプレフィルドバイアルの形態で提供され得る(例えば、Kivitz et al.,Clin.Ther.2006,28:1619−29)。
ヒトTrop−2に対する2つの異なるマウスモノクローナル抗体が得られた。最初のもの、162−46.2が、ローラーボトルで増殖させたハイブリドーマ(ATCC、HB−187)から精製された。第2の抗体であるMAB650は、R&Dシステムズ(Minneapolis,MN)から購入した。結合の比較のために、Trop−2陽性ヒト胃癌のNCI−N87を標的として使用した。結合アッセイの前日に、細胞(1.5×105/ウェル)を96ウェルプレートに播種した。翌朝、162−46.2、MAB650、及びマウスRS7(0.03〜66nM)(図示せず)を用いて、用量/応答曲線を作成した。これらの一次抗体を細胞と共に1.5時間4℃でインキュベートした。ウェルを洗浄し、抗マウスHRP二次抗体を全てのウェルに4℃で1時間加えた。ウェルを再度洗浄し、続いて発光基質を添加する。Envisionプレートリーダーを用いてプレートを読み取り、値を相対発光単位として報告する。
10人の健常なドナー及び20人の転移性乳癌患者それぞれから、10mLの血液試料を採取し、CELLSAVE(商標)防腐チューブ(Jassen Diagnostics LLC,Raritan,NJ)に分注する。試料を室温で保存し、採血から72時間以内に処理する(Allard et al.,2004,Clin Cancer Res,10:6897)。或いは、10mLの血液試料をCYTOCHEX(登録商標)採血管(Streck,Omaha,NE)に引き込み、室温で維持し、7日以内に処理する(Ng et al.,2012 J Immunol Methods,385:79)。血液はまた、10mLのK2EDTA VACUTARNER(登録商標)(BD,Waltham,MA)の中に抜き取り、採血の4時間以内にLIQUIDBIOPSY(登録商標)固定剤(Cynvenio Biosystems,Westlake Village,CA)で固定し、室温で保存し、固定の96時間以内に処理することができる。
何れも高レベルのTrop−2を発現するSK−BR−3細胞及びBxPC−3細胞を、それらの指定培地で培養し、トリプシンを用いて回収する。得られた細胞懸濁液の生存率及び細胞数を、Guava EASYCYTE(商標)フローサイトメーターによって評価する。当該細胞懸濁液は、生存率が90%を超える場合にのみ使用される。正常血清に添加された細胞の数は、mL当たり1〜100である。中程度のレベルのTrop−2を発現する癌細胞、例えばMCF−7、LoVo、及びLS174T、低レベルのTrop−2を発現する癌細胞、例えばHT−29、またはTrop−2について陰性である癌細胞、例えばA549及びH460はまた、血液試料に添加するために使用することができる。
上皮癌細胞を添加した血液試料を、ビオチン化トリFab・hRS7(上記のDNL(登録商標)技術により調製されたビオチン−E1/3)及びストレプトアビジンで被覆した強膜流体(FF−SV)と共にインキュベートして、上皮細胞を免疫磁気的に濃縮する。簡単に言えば、既知数の添加されたBxPC−3またはSK−BR−3を含有する7.5mLの血液試料を6mLの緩衝液と混合し、800×gで10分間遠心分離する。血漿及び緩衝液層を除去した後、ビオチン−E1/3及びFF−SVを添加し、1時間インキュベートする。続いて、磁気分離した後、未標識細胞を標識細胞から除去する。その後、ビオチン−El/3で標識された細胞を、更なる洗浄及び遠心分離でFF−SVから脱離させ、DAPI、PE−抗CK18及びAPC−抗CD45で標識した後にフローサイトメトリーによって分析する。CD45を欠失し且つサイトケラチン(CK8、CK18、CK19)を発現しない有核細胞は、一般にCTCsと定義される(Swaby & Cristofanilli,2011,BMC Medicine,9:43)。
Stott et al.(2010,PNAS,107:18392)に記載されているように、上皮癌細胞を添加した血液試料を、アビジンで化学修飾した微小渦発生ヘリンボーンチップ(HP−Chip)中でビオチン−E1/3と共にインキュベートするか、或いは、より好ましくは、ビオチン−E1/3と1時間インキュベートした後、Lu et al.(2013,Methods,64:144)が記載するようにして、ストレプトアビジンで官能化したNanoVelcroチップに添加する。未結合細胞を洗い流した後、実施例3に記載したようにして、結合した細胞をCTCについて分析する。
BxPC−3を添加した血液試料中の赤血球を塩化アンモニウムで溶解し、遠心分離する。細胞ペレットを回収し、FITC標識したE1/3と共にインキュベートする。次いで、懸濁液中の生細胞をポリリジン処理スライドに塗布し、レーザースキャニングサイトメーターで分析する(Pachmann et al.,2005,Breast Cancer Res,7:R975)。或いは、赤血球の溶解後に集めた細胞ペレットを、FITC標識アビジンの存在下に、ビオチン化E1/3及び1つ以上の他のビオチン化DNL(登録商標)複合体を含むカクテルと共にインキュベートする。次いで懸濁液中の生細胞をレーザー走査サイトメーターで分析する。
高レベルのTrop−2及びEGFRを発現するBxPC−3細胞を添加した血液試料を、実施例4に記載したように、(E1)−225と命名されたビオチン化二重特異性Tri−Fab、及びストレプトアビジンでコーティングされた磁性流体(FF−SV)と共にインキュベートする。(E1)−225は、CH1−DDD2−Fab−hRS7をCH1−AD2−Fab−c225に結合させて、それぞれTrop−2及びEGFRに対する二価及び一価の結合を与えることにより生成される。単一特異性のhRS7またはc225(セツキシマブ)のみを使用した濃縮と比較した場合、二重特異性(E1)−225は、CD45陽性白血球の汚染が少なく、血液試料中に添加されたBxPC−3をより多く捕捉することができる。
リキッドバイオプシー(登録商標)装置(カタログ番号A28188)、リキッドバイオプシー(登録商標)血液採取キット(カタログ番号A28171)及びリキッドバイオプシー試薬及び消耗品キット(カタログ番号A28186、A28187)を、Life Technologies,ThermoFisher(グランドアイランド、NY)から入手した。リキッドバイオプシー(登録商標)キットには、血液試料を処理するためのバッファー、試薬、バイアル、溶出チューブ、及びフローセルのほか、試料の未冷蔵出荷(96時間窓)を可能にする全血試料の安定化プロトコールが含まれている。
精製マウス抗ヒトTrop−2抗体を、BD Pharmingen(San Jose,CA)から購入したクローン162−46から調製する。この抗Trop−2抗体を、実施例7に記載されるようにしてビオチン化する。IMAG(商標)磁性粒子(ストレプトアビジン粒子プラス−DM)及びBD IMAG(商標)細胞分離磁石は、BD Biosciences(San Jose,CA)から購入する。K2EDTA(カタログ番号366643)でスプレーコートされた10mLのプラスチック製全血チューブもまたBDから購入する。
CELLSEARCH(登録商標)システム及び循環腫瘍細胞キットを、Veridex LLC(Raritan,NJ)から入手する。NSCLCが疑われる65歳の男性から7.5mLの血液試料を採取し、CellSaveチューブ(Veridex LLC)中に保存する。抗Trop−2・hRS7抗体を、CELLSEARCH(登録商標)キットと共に提供される抗EpCAM抗体の代わりに用いる。血液試料を、抗Trop−2抗体に複合体化させた磁性ナノ粒子と混合する。細胞を蛍光標識抗CD45及び抗CK抗体で染色し、細胞核をDAPI核色素で蛍光標識する。強力な磁場をCELLSEARCH(登録商標)システムで生成させ、磁気ナノ粒子に結合した細胞を分離するために使用し、次いで、上記実施例7に記載したようにして、Trop−2のコピー数を決定するためにFISHにより分析する。結果は、1細胞当たり4コピーのTrop−2を備えた循環Trop−2+腫瘍細胞の存在を示す。CTCにおけるTrop−2の高いコピー数の存在は、当該患者が抗Trop−2抗体による治療のための良好な候補であることを示す。
Casavant et al.(2013、Lab Chip 13:391−6;2014,Lab Chip 14:99−105)において開示されたVerlFASTシステムを用いて、TNBCにおけるTrop−2+CTCを検出する。7.5mLの血液試料を、TNBCが疑われる一連の患者または対照の正常個体から採取し、CellSaveチューブ(Veridex LLC)の中に保存する。ビオチン化抗Trop−2・hRS7抗体を、Casavant et al.(2013、Lab Chip 13:391−6)に開示されたようにして調製する。当該血液試料を、ビオチン化抗Trop−2抗体及びストレプトアビジンに複合体化されたPMP(Casavantら、2013、Lab Chip 13:391−6)と混合し、CTCを、VerlFASTプラットフォーム及び手持ち型磁石を用いて分離する。細胞を腫瘍マーカーについて染色し、細胞核をDAPI核色素で蛍光標識する。その結果は、TNBCを持つ個体の血液試料中における循環Trop−2+腫瘍細胞の存在を示す。
概要
本実施例は、IMMU−132(サシツズマブ・ゴビベカン)、即ち、pH感受性リンカーによりSN−38に複合体化された内在化ヒト化hRS7抗Trop−2抗体の抗体−薬物複合体(ADC)を用いた、第I相臨床試験及び進行中の拡大第II相試験の結果を報告する(平均薬物−抗体比=7.6)。Trop−2は、を伴って、多くのヒト癌腫によって、高い密度(約1×105)、頻度及び特異性で発現され、限定された正常組織発現を示すI型膜貫通の、カルシウム形質導入タンパク質である。Capan−1ヒト膵臓腫瘍異種移植片を有するヌードマウスでの前臨床試験により、IMMU−132は、最大耐容性のイリノテカン療法(示されていない)から誘導されるよりも、136倍多いSN−38を腫瘍に送達できることが明らかになった。
2つのELISA法を用いて、IgG(抗hRS7イディオタイプ抗体での捕捉)及び完全な複合体(抗−RS−38IgG/抗hRS7イディオタイプ抗体を備えたプローブでの捕捉)のクリアランスを測定した。SN−38をHPLCで測定した。複合体からのSN−38の徐放を反映して、全IMMU−132画分(インタクトコンジュゲート)は、IgG(図示せず)よりも速く消失した。SN−38(非結合及び総)のHPLC測定は、血清中のSN−38の>95%がIgGに結合したことを示した。低濃度のSN−38Gは、IgGに結合したSN−38がグルコロニド化から保護されることを示唆している。複合体およびSN−38についてのHPLCのELISA比較は、両方の重複を明らかにし、ELISAがSN−38クリアランスをモニターするための代用であることを示唆している。
以前の3つの治療法の中央値を有する種々の転移性癌を有する合計69人の患者(第I相における25人の患者を含む)が報告された。8人の患者は臨床的進行を有し、CT評価の前に離脱した。13人のCT評価可能な膵臓癌患者が別々に報告された。PDC患者の中央値TTP(進行までの時間)は、以前の最後の治療についての中央値8週間のTTPと比較して、11.9週(範囲2〜21.4週)であった。
Claims (52)
- 循環Trop−2+腫瘍細胞を単離し、検出し、または特徴付ける方法であって、
a)Trop−2+癌を有する疑いのある対象由来の血液に、抗Trop−2抗体またはその抗原結合性断片を露出させることと、
b)前記抗Trop−2抗体またはその断片を、前記Trop−2+循環腫瘍細胞(CTC)に結合させることと、
c)前記抗Trop−2抗体またはその断片に結合した前記CTCを検出すること
を含む前記方法。 - 請求項1に記載の方法であって、更に、前記CTCを濃縮または単離することを含む前記方法。
- 請求項1に記載の方法であって、前記抗Trop−2抗体またはその断片が磁気ナノ粒子に結合される前記方法。
- 請求項3に記載の方法であって、更に、磁場を用いて前記磁性ナノ粒子に結合したCTCを正常細胞から分離することを含む前記方法。
- 請求項1に記載の方法であって、前記抗Trop−2抗体またはその断片が、軽鎖CDR配列のCDR1(KASQDVSIAVA、配列番号1)、CDR2(SASYRYT、配列番号2)、及びCDR3(QQHYITPLT、配列番号3)、並びに重鎖CDR配列のCDR1(NYGMN、配列番号4)、CDR2(WINTYTGEPTYTDDFKG、配列番号5)及びCDR3(GGFGSSYWYFDV、配列番号6)を含むRS7抗体である前記方法。
- 請求項1に記載の方法であって、前記抗Trop−2抗体が、マウスRS7、hRS7、MAB650、K5−70、K5−107、K5−116−2−1、T6−16、T5−86、BR110、AR47A6.4.2、3E9、6G11、7E6、15E2、18B1、PD08019、PD08020、PD08021、77220、KM4097、KM4590、A1、A4、162−25.3、162−46.2、およびPr1E11からなる群から選択される前記方法。
- 請求項1に記載の方法であって、前記抗Trop−2抗体が、マウス抗体、キメラ抗体、ヒト化抗体またはヒト抗体である前記方法。
- 請求項1に記載の方法であって、前記抗Trop−2抗体が、放射性同位元素、色素、造影剤、発光剤、化学発光剤、蛍光剤、及び増強剤からなる群から選択される少なくとも1つの診断剤に結合される前記方法。
- 請求項1に記載の方法であって、更に、腫瘍関連抗原に結合する第2の抗体またはその抗原結合性断片に前記CTCを露出させることを含み、ここで前記第2の抗体またはその断片は、放射性同位体、色素、造影剤、発光剤、化学発光剤、蛍光剤、及び増強剤からなる群から選択される少なくとも1つの診断剤に結合される前記方法。
- 請求項9に記載の方法であって、前記TAAが、炭酸脱水素酵素IX、B7、CCL19、CCL21、CSAp、HER−2/neu、BrE3、CD1、CD1a、CD2、CD3、CD4、CD5、CD8、CD11A、CD14、CD15、CD16、CD18、CD19、CD20、CD21、CD22、CD23、CD25、CD29、CD30、CD32b、CD33、CD37、CD38、CD40、CD40L、CD44、CD45、CD46、CD47、CD52、CD54、CD55、CD59、CD64、CD67、CD70、CD74、CD79a、CD80、CD83、CD95、CD126、CD133、CD138、CD147、CD154、CEACAM5、CEACAM6、CTLA−4,アルファ−フェトプロテイン(AFP)、VEGF、ED−Bフィブロネクチン、EGP−1(Trop−2)、EGP−2、EGF受容体、ErbB2、ErbB3、ファクターH、Flt−1、Flt−3、葉酸受容体、Ga733,GRO−β、HMGB−1、低酸素誘導因子HM1.24、HER−2/neu、ヒストンH2B、ヒストンH3、ヒストンH4、インスリン様成長因子、IFN−γ、IFN−α、IFN−β、IFN−λ、IL−2R、IL−4R、IL−6R、IL−13R、IL−15R、IL−17R、IL−18R、IL−2、IL−6、IL−8、IL−12、IL−15、IL−17、IL−18、IL−25、IP−10、IGF−1R、Ia、HM1.24、ガングリオシド、HCG、HLA−DR、CD66a−d、MAGE、mCRP、MCP−1、MIP−1A、MIP−1B、マクロファージ遊走阻害因子(MIF)、MUC1、MUC2、MUC3、MUC4、MUC5ac、胎盤成長因子、PSA(前立腺特異的抗原)、PSMA、PD−1受容体、PD−L1、NCA−95、NCA−90、A3、A33、Ep−CAM、KS−1、Le(y)、メソテリン、S100、テネイシン、TAC、Tn抗原、トーマス−フリーデンライヒ抗原、腫瘍壊死抗原、腫瘍血管新生抗原、TNF−α、TRAIL受容体R1、TRAIL受容体R2、VEGFR、RANTES、T101、補体因子C3、C3a、C3b、C5a、C5、及び発癌遺伝子産物からなる群から選択される前記方法。
- 請求項9に記載の方法であって、前記第2の抗体またはその断片が、Trop−2、EpCAM、サイトケラチン(CK)及びCD45からなる群から選択されるTAAに結合する、前記方法。
- 請求項1に記載の方法であって、前記CTCが、蛍光顕微鏡法、FISH(蛍光in−situハイブリダイゼーション)、免疫組織化学、FACS(蛍光活性化された細胞の選別)、フローサイトメトリー、マイクロ流体アッセイ、及びRT−PCRからなる群から選択される方法により検出される前記方法。
- 請求項1に記載の方法であって、更に、蛍光標識抗体により、上皮癌マーカーについて前記CTCを分析することを含む前記方法。
- 請求項13に記載の方法であって、前記CTCが、FISH(蛍光インサイチューハイブリダイゼーション)により上皮癌マーカーについて分析される前記方法。
- 請求項1に記載の方法であって、更に、RT−PCRにより上皮癌マーカーについてCTCを分析することを含む前記方法。
- 請求項9に記載の方法であって、前記抗Trop−2抗体がRS7抗体であり、前記第2抗体が、RS7とは異なるエピトープに結合する抗Trop−2抗体である前記方法。
- 請求項1に記載の方法であって、前記Trop−2+癌が、膵臓癌、トリプルネガティブ乳癌、転移性結腸直腸癌、HER+、ER+、プロゲステロン+乳癌、転移性非小細胞肺癌(NSCLC)、転移性膵臓癌、転移性食道癌、転移性尿路上皮癌、転移性腎細胞癌、転移性胃癌、転移性前立腺癌及び転移性小細胞肺癌を含む転移性Trop−2陽性癌からなる群から選択される前記方法。
- 請求項1に記載の方法であって、前記抗Trop−2抗体またはその断片が、エクスビボで血液試料に露出される前記方法。
- 請求項1に記載の方法であって、前記抗Trop−2抗体またはその断片が、インビボで血液試料に露出される前記方法。
- 請求項1に記載の方法であって、前記Trop−2+CTCの存在は転移性癌のための診断に役立つ前記方法。
- 請求項1に記載の方法であって、前記対象がヒト対象である前記方法。
- 循環腫瘍細胞を単離、検出または特徴付けする方法であって、。
a)(i)抗Trop−2抗体またはその抗原結合性断片、及び(ii)抗TAA抗体またはその抗原結合性断片を具備する二重特異性抗体を、Trop−2+癌を有することが疑われる対象からの血液に露出させることと、
b)前記二重特異性抗体を循環腫瘍細胞(CTC)に結合させることと、
c)前記二重特異性抗体に結合したCTCを検出すること
を含む前記方法。 - 請求項22に記載の方法であって、前記TAAが、炭酸脱水素酵素IX、B7、CCL19、CCL21、CSAp、HER−2/neu、BrE3、CD1、CD1a、CD2、CD3、CD4、CD5、CD8、CD11A、CD14、CD15、CD16、CD18、CD19、CD20、CD21、CD22、CD23、CD25、CD29、CD30、CD32b、CD33、CD37、CD38、CD40、CD40L、CD44、CD45、CD46、CD47、CD52、CD54、CD55、CD59、CD64、CD67、CD70、CD74、CD79a、CD80、CD83、CD95、CD126、CD133、CD138、CD147、CD154、CEACAM5、CEACAM6、CTLA−4,アルファ−フェトプロテイン(AFP)、VEGF、ED−Bフィブロネクチン、EGP−1(Trop−2)、EGP−2、EGF受容体、ErbB2、ErbB3、ファクターH、Flt−1、Flt−3、葉酸受容体、Ga733,GRO−β、HMGB−1、低酸素誘導因子HM1.24、HER−2/neu、ヒストンH2B、ヒストンH3、ヒストンH4、インスリン様成長因子、IFN−γ、IFN−α、IFN−β、IFN−λ、IL−2R、IL−4R、IL−6R、IL−13R、IL−15R、IL−17R、IL−18R、IL−2、IL−6、IL−8、IL−12、IL−15、IL−17、IL−18、IL−25、IP−10、IGF−1R、Ia、HM1.24、ガングリオシド、HCG、HLA−DR、CD66a−d、MAGE、mCRP、MCP−1、MIP−1A、MIP−1B、マクロファージ遊走阻害因子(MIF)、MUC1、MUC2、MUC3、MUC4、MUC5ac、胎盤成長因子、PSA(前立腺特異的抗原)、PSMA、PD−1受容体、PD−L1、NCA−95、NCA−90、A3、A33、Ep−CAM、KS−1、Le(y)、メソテリン、S100、テネイシン、TAC、Tn抗原、トーマス−フリーデンライヒ抗原、腫瘍壊死抗原、腫瘍血管新生抗原、TNF−α、TRAIL受容体R1、TRAIL受容体R2、VEGFR、RANTES、T101、補体因子C3、C3a、C3b、C5a、C5、及び発癌遺伝子産物からなる群から選択される前記方法。
- 請求項22に記載の方法であって、前記TAAは、CEACAM5、MUC5ac、CD74、HLA−DR、CSAp、AFP(アルファ−フェトプロテイン)、HER2、ビメンチン、EGFR、IGF−1R、PD−L1及びPD−L2からなる群から選択される前記方法。
- 請求項22に記載の方法であって、前記抗TAA抗体は、MN−14(抗−CEACAM5)、PAM4(抗−MUC5ac)、LL1(抗−CD74)、L243(抗−HLA−DR)、Mu−9(抗−CSAp)、IMMU31(抗−AFP)、トラスツズマブ(抗−HER2)、セツキシマブ(抗−EGFR)、パニツムマブ(抗−EGFR)、R1(抗−IGF−1R)からなる群から選択される前記方法。
- 請求項1に記載の方法であって、更に、前記CTCを濃縮または単離することを含む前記方法。
- 請求項22に記載の方法であって、前記二重特異性抗体が磁気ナノ粒子に結合される前記方法。
- 請求項27に記載の方法であって、更に、磁場を用いて前記磁性ナノ粒子に結合したCTCを正常細胞から分離することを含む前記方法。
- 請求項22に記載の方法であって、前記抗Trop−2抗体またはその断片が、軽鎖CDR配列のCDR1(KASQDVSIAVA、配列番号1)、CDR2(SASYRYT、配列番号2)、及びCDR3(QQHYITPLT、配列番号3)、並びに重鎖CDR配列のCDR1(NYGMN、配列番号4)、CDR2(WINTYTGEPTYTDDFKG、配列番号5)及びCDR3(GGFGSSYWYFDV、配列番号6)を含むRS7抗体である前記方法。
- 請求項22に記載の方法であって、前記抗Trop−2抗体が、マウスRS7、hRS7、MAB650、K5−70、K5−107、K5−116−2−1、T6−16、T5−86、BR110、AR47A6.4.2、3E9、6G11、7E6、15E2、18B1、PD08019、PD08020、PD08021、77220、KM4097、KM4590、A1、A4、162−25.3、162−46.2、およびPr1E11からなる群から選択される前記方法。
- 請求項22に記載の方法であって、前記二重特異性抗体が、放射性同位元素、色素、造影剤、発光剤、化学発光剤、蛍光剤、及び増強剤からなる群から選択される少なくとも1つの診断剤に結合される前記方法。
- 請求項22に記載の方法であって、前記CTCが、蛍光顕微鏡法、FISH(蛍光インサイチューハイブリダイゼーション)、免疫組織化学、FACS(蛍光活性化された細胞選別)、フローサイトメトリー、マイクロ流体アッセイ、及びRT−PCRからなる群から選択される方法により検出される前記方法。
- 請求項22に記載の方法であって、前記Trop−2+癌が、膵臓癌、トリプルネガティブ乳癌、転移性結腸直腸癌、HER+、ER+、プロゲステロン+乳癌、転移性非小細胞肺癌(NSCLC)、転移性膵臓癌、転移性食道癌、転移性尿路上皮癌、転移性腎細胞癌、転移性胃癌、転移性前立腺癌及び転移性小細胞肺癌を含む転移性Trop−2陽性癌からなる群から選択される前記方法。
- 請求項22に記載の方法であって、前記二重特異性抗体が、エクスビボで血液試料に露出される前記方法。
- 請求項22に記載の方法であって、前記二重特異性抗体が、インビボで血液試料に露出される前記方法。
- 請求項1に記載の方法であって、の存在が転移性癌のための診断に役立つ前記方法。
- 請求項22に記載の方法であって、前記対象がヒト対象である前記方法。
- Trop−2+腫瘍を治療する方法であって、。
a)抗Trop−2抗体またはその抗原結合性断片を、Trop−2+癌を有することが疑われる対象からの血液に露出させることと、
b)前記抗Trop−2抗体またはその抗原結合性断片を、Trop−2+循環腫瘍細胞(CTC)に結合させることと、
c)前記抗Trop−2抗体またはその断片に結合したCTCを検出することと、
d)前記対象を、少なくとも1つの治療剤に複合体化された抗Trop−2抗体で治療すること
を含む前記方法。 - 請求項38に記載の方法であって、更に、前記CTCにおけるTrop−2のコピー数を分析することを含む前記方法。
- 請求項39に記載の方法であって、高コピー数のTrop−2を有するTrop−2+CTC存在が治療用抗Trop−2抗体に対する応答を予測し、ここでの高コピー数とは細胞当たり3以上である前記方法。
- 請求項38に記載の方法であって、更に、循環系におけるTrop−2+CTCの存在をモニタリングして、治療用抗Trop−2抗体に対する腫瘍の応答を決定することを含む前記方法。
- 請求項38に記載の方法であって、前記治療剤が、抗体、抗体断片、薬物、毒素、ホルモン、免疫調節物質、アポトーシス促進剤、抗血管新生剤、ホウ素化合物、光活性剤及び放射性核種からなる群から選択される前記方法。
- 請求項42に記載の方法であって、前記薬物は、アントラサイクリン、カンプトテシン、チューブリン阻害剤、メイタンシノイド、カリケアマイシン、アウリスタチン、ナイトロジェンマスタード、エチレンイミン誘導体、アルキルスルホネート、ニトロソ尿素、トリアゼン、葉酸類似体、タキサン、COX−2阻害剤、ピリミジン類似体、プリン類似体、抗生物質、酵素阻害剤、エピポドフィロトキシン、白金配位錯体、ビンカアルカロイド、置換尿素、メチルヒドラジン誘導体、副腎皮質抑制剤、ホルモンアンタゴニスト、代謝拮抗物質、アルキル化剤、有糸分裂阻害剤、抗血管新生剤、チロシンキナーゼ阻害剤、mTOR阻害剤、熱ショックタンパク質(HSP90)阻害剤、プロテオソーム阻害剤、HDAC阻害剤、及びアポトーシス促進剤からなる群から選択される前記方法。
- 請求項42に記載の方法であって、前記薬物は、5−フルオロウラシル、アファチニブ、アプリジン、アザリビン、アナストロゾール、アントラサイクリン、アキシチニブ、AVL−101、AVL−291、ベンダムスチン、ブレオマイシン、ボルテゾミブ、ボスチニブ、ブリオスタチン−1、ブスルファン、カリケアマイシン、カンプトテシン、カルボプラチン、10−ヒドロキシカンプトテシン、カルムスチン、セレコキシブ、クロラムブシル、シスプラチン、COX−2阻害剤、イリノテカン(CPT−11)、SN−38、カルボプラチン、クラドリビン、カンプトテカン、クリゾチニブ、シクロホスファミド、シタラビン、ダカルバジン、ダサチニブ、ディナシクリブ(dinaciclib)、ドセタキセル、ダクチノマイシン、ダウノルビシン、DM1、DM3、DM4、ドキソルビシン、2−ピロリノドキソルビシン(2−PDox)、2−PDoxのプロドラッグ形態(pro−2−PDox)、シアノ−モルホリノドキソルビシン、ドキソルビシングルクロニド、エンドスタチン、エピルビシングルクロニド、エルロチニブ、エストラムスチン、エピドフィロトキシン(epidophyllotoxin)、エルロチニブ、エンチノスタット、エストロゲン受容体結合剤、エトポシド(VP16)、エトポシドグルクロニド、リン酸エトポシド、エキセメスタン、フィンゴリモド、フロクスウリジン(FUdR)、3´,5´−O−ジオレオイル−FudR(FUdR−dO)、フルダラビン、フルタミド、ファルネシル−タンパク質トランスフェラーゼ阻害剤、フラボピリドール、フォスタマチニブ(fostamatinib)、ガネテスピブ(ganetespib)、GDC−0834、GS−1101、ゲフィチニ、ゲムシタビン、ヒドロキシ尿素、イブルチニブ、イダルビシン、イデラリシブ、イフォスファミド、イマチニブ、ラパチニブ、レノリダミド(lenolidamide)、ロイコボリン、LFM−A13、ロムスチン、メクロレタミン、メルファラン、メルカプトプリン、6−メルカプトプリン、メソトレキセート、ミトキサントロン、ミトラマイシン、マイトマイシン、ミトタン、モノメチルオーリスタチンF(MMAF)、モノメチルオーリスタチンD(MMAD)、モノメチルオーリスタチンE(MMAE)、ナベルビン、ネラチニブ、ニロチニブ、ニトロソ尿素、オラパリブ、プリコマイシン(plicomycin)、プロカルバジン、パクリタキセル、PCI−32765、ペントスタチン、PSI−341、ラロキシフェン、セムスチン、SN−38、ソラフェニブ、ストレプトゾシン、SU11248、スニチニブ、タモキシフェン、テマゾロミド(temazolomide)、トランスプラチナ、サリドマイド、チオグアニン、チオテパ、テニポシド、トポテカン、ウラシルマスタード、バタラニブ、ビノレルビン、ビンブラスチン、ビンクリスチン、ビンカアルカロイド、及びZD1839からなる群から選択される前記方法。
- 請求項42に記載の方法であって、前記薬物が、SN−38、pro−2−ピロリノドキソルビシン(pro−2−PDox)、パクリタキセル、カリケマイシン、DM1、DM3、DM4、MMAE、MMAD、及びMMAFからなる群から選択される前記方法。
- 請求項38に記載の方法であって、前記癌は少なくとも1つの抗癌療法での治療に対して抵抗性である前記方法。
- 請求項38に記載の方法であって、前記癌が膵臓癌である前記方法。
- 請求項42に記載の方法であって、前記放射性核種が、11C、13N、15O、32P、33P、47Sc、51Cr、57Co、58Co、59Fe、62Cu、67Cu、67Ga、67Ga、75Br、75Se、75Se、76Br、77As、77Br、80mBr、89Sr、90Y、95Ru、97Ru、99Mo、99mTc、103mRh、103Ru、105Rh、105Ru、107Hg、109Pd、109Pt、111Ag、111In、113mIn、119Sb、121mTe、122mTe、125I、125mTe、126I、131I、133I、142Pr、143Pr、149Pm、152Dy、153Sm、161Ho、161Tb、165Tm、166Dy、166Ho、167Tm、168Tm、169Er、169Yb、177Lu、186Re、188Re、189mOs、189Re、192Ir、194Ir、197Pt、198Au、199Au、199Au、201Tl、203Hg、211At、211Bi、211Pb、212Bi、212Pb、213Bi、215Po、217At、219Rn、221Fr、223Ra、224Ac、225Ac、255Fm、及び227Thからなる群から選択される前記方法。
- 請求項42に記載の方法であって、前記毒素が、リシン、アブリン、アルファトキシン、サポリン、リボヌクレアーゼ(RNase)、DNaseI、ブドウ球菌エンテロトキシン−A、ヤマゴボウ抗ウイルスタンパク質、ゲロニン、ジフテリア毒素、シュードモナス(Pseudomonas)外毒素およびシュードモナス内毒素からなる群から選択される前記方法。
- 請求項42に記載の方法であって、前記免疫調節物質が、サイトカイン、幹細胞成長因子、リンホトキシン、造血因子、コロニー刺激因子(CSF)、インターフェロン(IFN)、インターロイキン、エリスロポエチン及びトロンボポエチンからなる群から選択される前記方法。
- 請求項50に記載の方法であって、前記サイトカインが、ヒト成長ホルモン、N−メチオニルヒト成長ホルモン、ウシ成長ホルモン、副甲状腺ホルモン、チロキシン、インスリン、プロインスリン、リラキシン、プロリラキシン、卵胞刺激ホルモン(FSH)、甲状腺刺激ホルモン(TSH)、黄体形成ホルモン(LH)、肝臓成長因子、プロスタグランジン、線維芽細胞成長因子、プロラクチン、胎盤ラクトゲン、OBタンパク質、腫瘍壊死因子α、腫瘍壊死因子β、ミュラー管阻害物質、マウスゴナドトロピン関連ペプチド、インヒビン、アクチビン、血管内皮増殖因子、インテグリン、トロンボポエチン(TPO)、NGF−β、血小板成長因子、TGF−α、TGF−β、インスリン様増殖因子−I、インスリン様成長因子−II、エリスロポエチン(EPO)、骨誘導因子、インターフェロン−α、インターフェロン−β、インターフェロン−γ、マクロファージ−CSF(M−CSF)、IL−1、IL−1α、IL−2、IL−3、IL−4、IL−5、IL−6、IL−7、IL−8、IL−9、IL−10、IL−11、IL−12、IL−13、IL−14、IL−15、IL−16、IL−17、IL−18、IL−21、IL−25、LIF、FLT−3、アンジオスタチン、トロンボスポンジン、エンドスタチン、腫瘍壊死因子及びリンホトキシンからなる群から選択される前記方法。
- 請求項1に記載の方法であって、前記抗Trop−2抗体またはその断片が、軽鎖CDR配列のCDR1(KASQDVSIAVA、配列番号1)、CDR2(SASYRYT、配列番号2)及びCDR3(QQHYITPLT、配列番号3)、並びに重鎖CDR配列のCDR1(NYGMN、配列番号4)、CDR2(WINTYTGEPTYTDDFKG、配列番号5)及びCDR3(GGFGSSYWYFDV、配列番号6)を備えた抗Trop−2抗体と同じエピトープに結合する前記方法。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050153309A1 (en) | 2003-12-22 | 2005-07-14 | David Hoon | Method and apparatus for in vivo surveillance of circulating biological components |
CA2968330A1 (en) * | 2014-12-04 | 2016-06-09 | Abruzzo Theranostic S.R.L. | Humanized anti-trop-2 monoclonal antibodies and uses thereof |
JP6746845B2 (ja) * | 2015-04-22 | 2020-08-26 | イミューノメディクス、インコーポレイテッドImmunomedics, Inc. | 循環trop−2陽性癌細胞の単離、検出、診断及び/または特徴付け |
ITUB20155701A1 (it) * | 2015-11-19 | 2017-05-19 | Saverio Alberti | Uso di Trop-2 circolante sierico come nuovo biomarcatore tumorale |
US11160542B2 (en) | 2016-06-09 | 2021-11-02 | Haimachek, Inc. | Collector for detection and reversible capturing of cells from body fluids in vivo |
WO2018009916A1 (en) | 2016-07-07 | 2018-01-11 | The Board Of Trustees Of The Leland Stanford Junior University | Antibody adjuvant conjugates |
CN110392580A (zh) * | 2017-02-24 | 2019-10-29 | 免疫医疗公司 | 用靶向trop-2的拓扑异构酶-i抑制性抗体-药物缀合物(adc)治疗小细胞肺癌(sclc) |
CN107058226A (zh) * | 2017-04-01 | 2017-08-18 | 云南赫斯提雅生物科技有限公司 | 准确快速捕获循环肿瘤细胞的方法 |
CN107356744B (zh) * | 2017-07-13 | 2020-10-27 | 珠海圣美生物诊断技术有限公司 | 一种循环肿瘤细胞分选和/或富集的方法及其试剂盒 |
CN107446050A (zh) * | 2017-08-11 | 2017-12-08 | 百奥泰生物科技(广州)有限公司 | Trop2阳性疾病治疗的化合物及方法 |
CN107918013A (zh) * | 2017-09-25 | 2018-04-17 | 浙江天科高新技术发展有限公司 | 化学发光酶免测定循环肿瘤细胞中K‑Ras蛋白的方法及试剂盒 |
CN108398560A (zh) * | 2017-12-28 | 2018-08-14 | 兰州大学 | 一种cd133质谱流式抗体、制备方法及应用 |
CN108264548B (zh) * | 2018-03-26 | 2021-02-09 | 中国科学院水生生物研究所 | 鳜鱼伽玛干扰素相关因子及其重组蛋白和应用 |
CN109100504B (zh) * | 2018-06-25 | 2020-09-22 | 武汉大学 | 一种血小板-白细胞混合膜包被免疫磁珠及其制备方法与应用 |
CN109053862A (zh) * | 2018-08-07 | 2018-12-21 | 复旦大学附属肿瘤医院 | 靶向PD-L1的多肽衍生物及其99mTc配合物的制备和应用 |
JP7462615B2 (ja) * | 2018-09-25 | 2024-04-05 | ユニバーシティ・オブ・テクノロジー・シドニー | アナライトの定量 |
CN111100839B (zh) * | 2018-10-29 | 2024-03-08 | 猎源(上海)生物医药科技有限公司 | EGFR/Vimentin/叶酸免疫脂质体磁球、制备方法及试剂盒 |
CN109540859B (zh) * | 2018-11-27 | 2021-02-09 | 上海交通大学 | 一种水体中抗生素的分析和含量预测方法 |
US12006345B2 (en) | 2019-02-21 | 2024-06-11 | Xencor, Inc. | Untargeted and targeted IL-10 Fc-fusion proteins |
CN109946230B (zh) * | 2019-02-26 | 2022-04-15 | 山东师范大学 | 一种用于ctc高通量单细胞表型分析的微流控装置 |
WO2020190725A1 (en) | 2019-03-15 | 2020-09-24 | Bolt Biotherapeutics, Inc. | Immunoconjugates targeting her2 |
WO2020191092A1 (en) * | 2019-03-19 | 2020-09-24 | Cspc Dophen Corporation | Anti-trophoblast cell surface antigen 2 (trop2) antibodies and antibody drug conjugates comprising same |
AU2020257528A1 (en) * | 2019-04-15 | 2021-10-28 | Targinta Ab | Integrin alpha10 and aggressive cancer forms |
WO2020228604A1 (zh) * | 2019-05-10 | 2020-11-19 | 江苏豪森药业集团有限公司 | 抗trop-2抗体、其抗原结合片段及其医药用途 |
EP3999186A1 (en) * | 2019-07-17 | 2022-05-25 | BioInvent International AB | Antibody combinations for treatment of cancer in specific patients |
WO2021067403A1 (en) * | 2019-10-01 | 2021-04-08 | Immunomedics, Inc. | Biomarkers for antibody-drug conjugate monotherapy or combination therapy |
CN110776649B (zh) * | 2019-11-11 | 2021-10-26 | 重庆师范大学 | 含蒽基的镉-有机超分子聚合物及其制备方法与应用 |
CN111141906A (zh) * | 2020-01-06 | 2020-05-12 | 中南大学湘雅医院 | 一种小细胞肺癌患者外周血循环肿瘤细胞及pd-l1的检测试剂盒 |
CN111826351B (zh) * | 2020-03-13 | 2023-10-03 | 武汉大学深圳研究院 | 一种基于磁性分离法富集循环肿瘤细胞的磁性红细胞团簇 |
WO2021190480A1 (zh) * | 2020-03-24 | 2021-09-30 | 上海翰森生物医药科技有限公司 | 抗体-药物偶联物及其医药用途 |
CN115996756A (zh) | 2020-05-08 | 2023-04-21 | 博尔特生物治疗药物有限公司 | 弹性蛋白酶底物肽连接子免疫缀合物及其用途 |
CN111647561B (zh) * | 2020-05-28 | 2022-12-20 | 大连理工大学 | 纳米抗体在细胞特异性捕获和细胞释放中的应用 |
BR112022025947A2 (pt) * | 2020-06-22 | 2023-03-14 | Baili Bio Chengdu Pharmaceutical Co Ltd | Anticorpo anti-trop2, sequência de ácidos nucleicos, rna, vetor de expressão, hospedeiro, conjugado imune e usos do anticorpo |
IL300316A (en) | 2020-08-13 | 2023-04-01 | Bolt Biotherapeutics Inc | Immune conjugates of pyrazolozapines and their uses |
CA3194725A1 (en) * | 2020-10-14 | 2022-04-21 | Dongjie MAO | Anti-trop-2 antibody, antigen-binding fragment thereof or mutant thereof, and medical use thereof |
IT202000031838A1 (it) * | 2020-12-22 | 2022-06-22 | Saverio Alberti | Piattaforma per ottenere anticorpi monoclonali diretti contro antigeni processati tumore-specifici |
CN117769439A (zh) | 2021-03-26 | 2024-03-26 | 博尔特生物治疗药物有限公司 | 2-氨基-4-甲酰胺-苯并氮杂卓免疫缀合物及其用途 |
EP4313161A1 (en) | 2021-03-26 | 2024-02-07 | Bolt Biotherapeutics, Inc. | 2-amino-4-carboxamide-benzazepine immunoconjugates, and uses thereof |
WO2023143343A1 (en) * | 2022-01-26 | 2023-08-03 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Anti-her2/trop2 antibodies and uses thereof |
CN117607441B (zh) * | 2024-01-23 | 2024-04-12 | 杭州华得森生物技术有限公司 | 一种循环肿瘤细胞trop-2免疫显色检测试剂 |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007525642A (ja) * | 2003-02-27 | 2007-09-06 | イムニベスト・コーポレイション | 循環腫瘍細胞(ctc):転移癌患者における増悪までの時間、生存および療法に対する応答の早期評価 |
CN101363046A (zh) * | 2008-08-29 | 2009-02-11 | 芮屈生物技术(上海)有限公司 | 一种广谱性癌症原位杂交检测试剂盒及其检测方法和应用 |
JP2009539097A (ja) * | 2006-06-02 | 2009-11-12 | ファイザー・プロダクツ・インク | 循環腫瘍細胞アッセイ |
JP2011515109A (ja) * | 2008-03-25 | 2011-05-19 | ベリデックス・エルエルシー | FISH法を用いた循環腫瘍細胞中のIGF1R/Chr15を検出するための方法 |
JP2012503483A (ja) * | 2008-09-25 | 2012-02-09 | サヴェリオ・アルベルティ | サイクリンd1−trop2キメラの発現を抑制することができるオリゴヌクレオチド配列、および医療分野におけるその使用 |
JP2012522217A (ja) * | 2009-03-24 | 2012-09-20 | バイオセプト インコーポレイティッド | 細胞の捕捉および解析のデバイスおよび方法 |
WO2015002975A1 (en) * | 2013-07-05 | 2015-01-08 | University Of Washington Through Its Center For Commercialization | Methods, compositions and systems for microfluidic assays |
WO2015028489A1 (en) * | 2013-08-27 | 2015-03-05 | Gilupi Gmbh | Diagnostic device for the detection of disease related target structures |
WO2015047510A1 (en) * | 2013-09-27 | 2015-04-02 | Immunomedics, Inc. | Anti-trop-2 antibody-drug conjugates and uses thereof |
JP2016536330A (ja) * | 2013-08-30 | 2016-11-24 | イミュノジェン, インコーポレイテッド | 葉酸受容体1の検出用の抗体及びアッセイ |
Family Cites Families (303)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1541435A (en) | 1975-02-04 | 1979-02-28 | Searle & Co | Immunological materials |
US4036945A (en) | 1976-05-03 | 1977-07-19 | The Massachusetts General Hospital | Composition and method for determining the size and location of myocardial infarcts |
US4200690A (en) | 1976-12-16 | 1980-04-29 | Millipore Corporation | Immunoassay with membrane immobilized antibody |
US4331647A (en) | 1980-03-03 | 1982-05-25 | Goldenberg Milton David | Tumor localization and therapy with labeled antibody fragments specific to tumor-associated markers |
US5204095A (en) | 1980-04-09 | 1993-04-20 | National Research Development Corporation | Monoclonal antibodies against hepatitis B virus |
US4359457A (en) | 1980-09-30 | 1982-11-16 | Neville Jr David M | Anti Thy 1.2 monoclonal antibody-ricin hybrid utilized as a tumor suppressant |
US4554101A (en) | 1981-01-09 | 1985-11-19 | New York Blood Center, Inc. | Identification and preparation of epitopes on antigens and allergens on the basis of hydrophilicity |
US4925922A (en) | 1983-02-22 | 1990-05-15 | Xoma Corporation | Potentiation of cytotoxic conjugates |
US4916213A (en) | 1983-02-22 | 1990-04-10 | Xoma Corporation | Ribosomal inhibiting protein-immunoglobulin conjugates with specificity for tumor cell surface antigens, and mixtures thereof |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4624846A (en) | 1983-07-29 | 1986-11-25 | Immunomedics, Inc. | Method for enhancing target specificity of antibody localization and clearance of non-target diagnostic and therapeutic principles |
US5672347A (en) | 1984-07-05 | 1997-09-30 | Genentech, Inc. | Tumor necrosis factor antagonists and their use |
US4824659A (en) | 1985-06-07 | 1989-04-25 | Immunomedics, Inc. | Antibody conjugates |
US5525338A (en) | 1992-08-21 | 1996-06-11 | Immunomedics, Inc. | Detection and therapy of lesions with biotin/avidin conjugates |
US5776093A (en) | 1985-07-05 | 1998-07-07 | Immunomedics, Inc. | Method for imaging and treating organs and tissues |
US4918163A (en) | 1985-09-27 | 1990-04-17 | Pfizer Inc. | Monoclonal antibodies specific for lipid-A determinants of gram negative bacteria |
US5618920A (en) | 1985-11-01 | 1997-04-08 | Xoma Corporation | Modular assembly of antibody genes, antibodies prepared thereby and use |
US5057313A (en) | 1986-02-25 | 1991-10-15 | The Center For Molecular Medicine And Immunology | Diagnostic and therapeutic antibody conjugates |
US4699784A (en) | 1986-02-25 | 1987-10-13 | Center For Molecular Medicine & Immunology | Tumoricidal methotrexate-antibody conjugate |
US6861511B1 (en) | 1986-06-04 | 2005-03-01 | Bayer Corporation | Detection and quantification of neu related proteins in the biological fluids of humans |
US4863713A (en) | 1986-06-23 | 1989-09-05 | The Board Of Trustees Of Leland Stanford Jr. Univ. | Method and system for administering therapeutic and diagnostic agents |
US4997913A (en) | 1986-06-30 | 1991-03-05 | Oncogen | pH-sensitive immunoconjugates and methods for their use in tumor therapy |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
US4704692A (en) | 1986-09-02 | 1987-11-03 | Ladner Robert C | Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides |
US5567610A (en) | 1986-09-04 | 1996-10-22 | Bioinvent International Ab | Method of producing human monoclonal antibodies and kit therefor |
FR2604092B1 (fr) | 1986-09-19 | 1990-04-13 | Immunotech Sa | Immunoreactifs destines a cibler les cellules animales pour leur visualisation ou leur destruction in vivo |
US6893625B1 (en) | 1986-10-27 | 2005-05-17 | Royalty Pharma Finance Trust | Chimeric antibody with specificity to human B cell surface antigen |
CA1320905C (en) | 1986-11-06 | 1993-08-03 | Joseph M. Cummins | Treatment of immuno-resistant disease |
US4932412A (en) | 1986-12-18 | 1990-06-12 | Immunomedics, Inc. | Intraoperative and endoscopic tumor detection and therapy |
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 |
WO1988007553A1 (en) | 1987-03-26 | 1988-10-06 | Teijin Limited | Process for preparing antibody complex |
US4981979A (en) | 1987-09-10 | 1991-01-01 | Neorx Corporation | Immunoconjugates joined by thioether bonds having reduced toxicity and improved selectivity |
US6511665B1 (en) | 1987-11-25 | 2003-01-28 | Immunex Corporation | Antibodies to interleukin-1 receptors |
IL106992A (en) | 1988-02-11 | 1994-06-24 | Bristol Myers Squibb Co | Noble hydrazonic history of anthracycline and methods for their preparation |
US5112954A (en) | 1988-02-26 | 1992-05-12 | Neorx Corporation | Method of enhancing the effect of cytotoxic agents |
US4861579A (en) | 1988-03-17 | 1989-08-29 | American Cyanamid Company | Suppression of B-lymphocytes in mammals by administration of anti-B-lymphocyte antibodies |
US6362325B1 (en) | 1988-11-07 | 2002-03-26 | Advanced Research And Technology Institute, Inc. | Murine 4-1BB gene |
US6352694B1 (en) | 1994-06-03 | 2002-03-05 | Genetics Institute, Inc. | Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells |
US5571714A (en) | 1988-12-22 | 1996-11-05 | Celtrix Pharmaceuticals, Inc. | Monoclonal antibodies which bind both transforming growth factors β1 and β2 and methods of use |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
GB8903021D0 (en) | 1989-02-10 | 1989-03-30 | Celltech Ltd | Chemical compounds |
US5134075A (en) | 1989-02-17 | 1992-07-28 | Oncogen Limited Partnership | Monoclonal antibody to novel antigen associated with human tumors |
US5171665A (en) | 1989-04-17 | 1992-12-15 | Oncogen | Monoclonal antibody to novel antigen associated with human tumors |
JPH02283294A (ja) | 1989-04-24 | 1990-11-20 | Sumitomo Chem Co Ltd | ヒトモノクローナル抗体 |
US6432402B1 (en) | 1989-05-25 | 2002-08-13 | Sloan-Kettering Institute For Cancer Research | Anti-idiotypic antibody which induces an immune response against a glycosphingolipid and use thereof |
EP0432249B1 (en) | 1989-06-02 | 1996-09-25 | The Johns Hopkins University School Of Medicine | Monoclonal antibodies against leukocyte adhesion receptor beta-chain, methods of producing these antibodies and use therefore |
US5800992A (en) | 1989-06-07 | 1998-09-01 | Fodor; Stephen P.A. | Method of detecting nucleic acids |
US5332567A (en) | 1989-08-24 | 1994-07-26 | Immunomedics | Detection and treatment of infections with immunoconjugates |
KR0162259B1 (ko) | 1989-12-05 | 1998-12-01 | 아미 펙터 | 감염성 병변 및 염증성 병변을 검출 및 치료하기 위한 키메라 항체 |
SG46445A1 (en) | 1990-01-26 | 1998-02-20 | Immunomedics Inc | Vaccines against cancer and infectious diseases |
WO1991013974A1 (en) | 1990-03-14 | 1991-09-19 | The Biomembrane Institute | Monoclonal antibody and immunoconjugates for the treatment and detection of b cell disorders |
US7041293B1 (en) | 1990-04-03 | 2006-05-09 | Genentech, Inc. | HIV env antibodies |
US5229275A (en) | 1990-04-26 | 1993-07-20 | Akzo N.V. | In-vitro method for producing antigen-specific human monoclonal antibodies |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
GB9020075D0 (en) | 1990-09-14 | 1990-10-24 | Filler Aaron G | Contrast agents for magnetic resonance imaging of axonal transport |
US5679640A (en) | 1991-02-12 | 1997-10-21 | Cytel Corporation | Immunosuppressant peptides |
JP3105629B2 (ja) | 1991-04-23 | 2000-11-06 | サングスタット メディカル コーポレイション | 特異的結合ペアのメンバーの細胞活性調節接合体 |
IE922437A1 (en) | 1991-07-25 | 1993-01-27 | Idec Pharma Corp | Recombinant antibodies for human therapy |
CA2116774C (en) | 1991-09-19 | 2003-11-11 | Paul J. Carter | Expression in e. coli antibody fragments having at least a cysteine present as a free thiol. use for the production of bifunctional f(ab') 2 antibodies |
US6764681B2 (en) | 1991-10-07 | 2004-07-20 | Biogen, Inc. | Method of prophylaxis or treatment of antigen presenting cell driven skin conditions using inhibitors of the CD2/LFA-3 interaction |
US5854416A (en) | 1991-11-14 | 1998-12-29 | The United States Of America As Represented By The Department Of Health And Human Services | Streptococcus pneumoniae 37-KDA surface adhesin a protein and nucleic acids coding therefor |
US5474771A (en) | 1991-11-15 | 1995-12-12 | The Trustees Of Columbia University In The City Of New York | Murine monoclonal antibody (5c8) recognizes a human glycoprotein on the surface of T-lymphocytes, compositions containing same |
US5622929A (en) | 1992-01-23 | 1997-04-22 | Bristol-Myers Squibb Company | Thioether conjugates |
CA2128700A1 (en) | 1992-01-29 | 1993-08-05 | Keiji Koda | Carcinoma associated antigen (sk1) and monoclonal antibodies against sk1, methods of producing these antibodies and use therefor |
US5965132A (en) | 1992-03-05 | 1999-10-12 | Board Of Regents, The University Of Texas System | Methods and compositions for targeting the vasculature of solid tumors |
EP0671920B1 (en) | 1992-03-09 | 2003-12-10 | San Diego Regional Cancer Center | An anti-idiotypic antibody and its use in diagnosis and in therapy in hiv-related disease |
US6129914A (en) | 1992-03-27 | 2000-10-10 | Protein Design Labs, Inc. | Bispecific antibody effective to treat B-cell lymphoma and cell line |
DE69322860T2 (de) | 1992-04-03 | 1999-07-01 | Genentech Inc | Antikörper gegen alpha v beta 3 integrin |
US6096289A (en) | 1992-05-06 | 2000-08-01 | Immunomedics, Inc. | Intraoperative, intravascular, and endoscopic tumor and lesion detection, biopsy and therapy |
ATE194916T1 (de) | 1992-05-06 | 2000-08-15 | Immunomedics Inc | Intraoperative, intravaskulare und endoskopische bestimmung und behandlung von verletzungen und tumoren |
WO1993023556A1 (en) | 1992-05-08 | 1993-11-25 | Genentech, Inc. | Antibodies to leukemia inhibitory factor |
US5686072A (en) | 1992-06-17 | 1997-11-11 | Board Of Regents, The University Of Texas | Epitope-specific monoclonal antibodies and immunotoxins and uses thereof |
US5397703A (en) | 1992-07-09 | 1995-03-14 | Cetus Oncology Corporation | Method for generation of antibodies to cell surface molecules |
CA2149329C (en) | 1992-11-13 | 2008-07-15 | Darrell R. Anderson | Therapeutic application of chimeric and radiolabeled antibodies to human b lymphocyte restricted differentiation antigen for treatment of b cell lymphoma |
DE69411154T2 (de) | 1993-02-22 | 1998-10-22 | Alza Corp | Mittel zur oralen gabe von wirkstoffen |
US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
CA2163107C (en) | 1993-05-17 | 2001-04-17 | David Milton Goldenberg | Improved detection and therapy of lesions with biotin/avidin-metal chelating protein conjugates |
US5484892A (en) | 1993-05-21 | 1996-01-16 | Dana-Farber Cancer Institute, Inc. | Monoclonal antibodies that block ligand binding to the CD22 receptor in mature B cells |
AU695124B2 (en) | 1993-05-28 | 1998-08-06 | Scripps Research Institute, The | Methods and compositions for inhibiting CD14 mediated cell activation |
US6180377B1 (en) | 1993-06-16 | 2001-01-30 | Celltech Therapeutics Limited | Humanized antibodies |
US5565215A (en) | 1993-07-23 | 1996-10-15 | Massachusettes Institute Of Technology | Biodegradable injectable particles for imaging |
US6084067A (en) | 1993-07-26 | 2000-07-04 | Dana-Farber Cancer Institute | CTLA4/CD28 ligands and uses therefor |
UA40577C2 (uk) | 1993-08-02 | 2001-08-15 | Мерк Патент Гмбх | Біспецифічна молекула, що використовується для лізису пухлинних клітин, спосіб її одержання, моноклональне антитіло (варіанти), фармацевтичний препарат, фармацевтичний набір (варіанти), спосіб видалення пухлинних клітин |
US5417972A (en) | 1993-08-02 | 1995-05-23 | The Board Of Trustees Of The Leland Stanford Junior University | Method of killing B-cells in a complement independent and an ADCC independent manner using antibodies which specifically bind CDIM |
GB9316989D0 (en) | 1993-08-16 | 1993-09-29 | Lynxvale Ltd | Binding molecules |
US6468531B1 (en) | 1993-09-09 | 2002-10-22 | Duke University | Method of promoting cellular function |
WO1995009917A1 (en) | 1993-10-07 | 1995-04-13 | The Regents Of The University Of California | Genetically engineered bispecific tetravalent antibodies |
US5824701A (en) | 1993-10-20 | 1998-10-20 | Enzon, Inc. | Taxane-based prodrugs |
AU1289795A (en) | 1993-11-19 | 1995-06-06 | Baylor College Of Medicine | Monoclonal antibodies specific for human interleukin-5 |
US5443953A (en) | 1993-12-08 | 1995-08-22 | Immunomedics, Inc. | Preparation and use of immunoconjugates |
US6432404B1 (en) | 1993-12-23 | 2002-08-13 | Icos Corporation | Methods of inhibiting locomotor damage following spinal cord injury with α D-specific antibodies |
US5922572A (en) | 1994-01-25 | 1999-07-13 | Human Genome Sciences, Inc. | Polynucleotides encoding haemopoietic maturation factor |
US5639725A (en) | 1994-04-26 | 1997-06-17 | Children's Hospital Medical Center Corp. | Angiostatin protein |
US6074642A (en) | 1994-05-02 | 2000-06-13 | Alexion Pharmaceuticals, Inc. | Use of antibodies specific to human complement component C5 for the treatment of glomerulonephritis |
US6100389A (en) | 1995-04-21 | 2000-08-08 | Human Genome Sciences, Inc. | Polynucleotides encoding a human chemotactic protein |
US5798100A (en) | 1994-07-06 | 1998-08-25 | Immunomedics, Inc. | Multi-stage cascade boosting vaccine |
US6303769B1 (en) | 1994-07-08 | 2001-10-16 | Immunex Corporation | Lerk-5 dna |
US5686578A (en) | 1994-08-05 | 1997-11-11 | Immunomedics, Inc. | Polyspecific immunoconjugates and antibody composites for targeting the multidrug resistant phenotype |
US8771694B2 (en) | 1994-08-12 | 2014-07-08 | Immunomedics, Inc. | Immunoconjugates and humanized antibodies specific for B-cell lymphoma and leukemia cells |
AU3272695A (en) | 1994-08-12 | 1996-03-07 | Immunomedics Inc. | Immunoconjugates and humanized antibodies specific for b-cell lymphoma and leukemia cells |
US5587459A (en) | 1994-08-19 | 1996-12-24 | Regents Of The University Of Minnesota | Immunoconjugates comprising tyrosine kinase inhibitors |
US6174995B1 (en) | 1994-08-23 | 2001-01-16 | Haodong Li | Human chemokines, CKβ4 and CKβ10/MCP-4 |
US6458349B1 (en) | 1995-06-02 | 2002-10-01 | Human Genome Sciences, Inc. | Chemokine β-4 polypeptides |
US6709653B1 (en) | 1994-09-16 | 2004-03-23 | Human Genome Sciences, Inc. | Antibodies specific for human inositol monophosphatase H1 |
US5874540A (en) | 1994-10-05 | 1999-02-23 | Immunomedics, Inc. | CDR-grafted type III anti-CEA humanized mouse monoclonal antibodies |
US5750370A (en) | 1995-06-06 | 1998-05-12 | Human Genome Sciences, Inc. | Nucleic acid encoding human endothlein-bombesin receptor and method of producing the receptor |
US6538121B1 (en) | 1994-11-01 | 2003-03-25 | Human Genome Sciences, Inc. | Interleukin-1 β converting enzyme like apoptosis protease-3 and 4 |
US5677136A (en) | 1994-11-14 | 1997-10-14 | Systemix, Inc. | Methods of obtaining compositions enriched for hematopoietic stem cells, compositions derived therefrom and methods of use thereof |
US6521227B1 (en) | 1999-11-18 | 2003-02-18 | Peter L. Hudson | Polynucleotides encoding prostatic growth factor and process for producing prostatic growth factor polypeptides |
US6537764B1 (en) | 1995-01-19 | 2003-03-25 | Children's Medical Center Corporation | Method of identifying inhibitors of C—C chemokine receptor 3 |
US5786204A (en) | 1995-01-20 | 1998-07-28 | Human Genome Sciences, Inc. | Human prostatic specific reductase |
US6312691B1 (en) | 1996-01-26 | 2001-11-06 | Jeffrey L. Browning | Lymphotoxin-α/β complexes and anti-lympotoxin-β receptor antibodies as anti-tumor agents |
US6949244B1 (en) | 1995-12-20 | 2005-09-27 | The Board Of Trustees Of The University Of Kentucky | Murine monoclonal anti-idiotype antibody 11D10 and methods of use thereof |
US5798554A (en) | 1995-02-24 | 1998-08-25 | Consorzio Per La Ricerca Sulla Microelettronica Nel Mezzogiorno | MOS-technology power device integrated structure and manufacturing process thereof |
US5783404A (en) | 1995-04-13 | 1998-07-21 | Amgen Inc. | Methods and compositions for determining HER-2/neu expression using monoclonal antibodies |
US6319668B1 (en) | 1995-04-25 | 2001-11-20 | Discovery Partners International | Method for tagging and screening molecules |
AUPO591797A0 (en) | 1997-03-27 | 1997-04-24 | Commonwealth Scientific And Industrial Research Organisation | High avidity polyvalent and polyspecific reagents |
US5686292A (en) | 1995-06-02 | 1997-11-11 | Genentech, Inc. | Hepatocyte growth factor receptor antagonist antibodies and uses thereof |
US5773252A (en) | 1995-06-05 | 1998-06-30 | Human Genome Sciences, Inc. | Fibroblast growth factor 15 |
US6605441B1 (en) | 1995-06-05 | 2003-08-12 | Human Genome Sciences, Inc. | Antibodies against fibroblast growth factor 11 |
US5773292A (en) | 1995-06-05 | 1998-06-30 | Cornell University | Antibodies binding portions, and probes recognizing an antigen of prostate epithelial cells but not antigens circulating in the blood |
AU6223296A (en) | 1995-06-07 | 1996-12-30 | Novartis Ag | Methods for obtaining compositions enriched for hematopoieti c stem cells and antibodies for use therein |
US5840854A (en) | 1995-10-19 | 1998-11-24 | Bristol-Myers Squibb Company | Monoclonal antibody BR110 and uses thereof |
US6340459B1 (en) | 1995-12-01 | 2002-01-22 | The Trustees Of Columbia University In The City Of New York | Therapeutic applications for the anti-T-BAM (CD40-L) monoclonal antibody 5C8 in the treatment of reperfusion injury in non-transplant recipients |
US5783186A (en) | 1995-12-05 | 1998-07-21 | Amgen Inc. | Antibody-induced apoptosis |
US6441025B2 (en) | 1996-03-12 | 2002-08-27 | Pg-Txl Company, L.P. | Water soluble paclitaxel derivatives |
US5945309A (en) | 1996-03-19 | 1999-08-31 | Human Genome Sciences, Inc. | Cytostatin III nucleic acids encoding |
DE69734109T2 (de) | 1996-03-20 | 2006-06-29 | Immunomedics, Inc. | Humanisierung von anti-carcinoembryonalen Antigen anti-idiotypischen Antikörper und dessen Verwendung als Tumorvakzin und zur Markierung |
AU705063B2 (en) | 1996-03-20 | 1999-05-13 | Immunomedics Inc. | Glycosylated humanized B-cell specific antibodies |
FR2746398B1 (fr) | 1996-03-21 | 1998-04-30 | Bio Merieux | Anticorps specifique de staphylococcus aureaus, et utilisations |
US6174992B1 (en) | 1997-03-21 | 2001-01-16 | Human Genome Sciences, Inc. | Human endometrial specific steroid-binding factor I, II and III |
US6962981B1 (en) | 1996-03-25 | 2005-11-08 | Medarex, Inc. | Monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen |
US6004780A (en) | 1996-03-26 | 1999-12-21 | Human Genome Sciences, Inc. | Growth factor HTTER36 |
US6110463A (en) | 1996-03-29 | 2000-08-29 | North Carolina State University | Anti-Cryptosporidium parvum preparations |
US6066617A (en) | 1996-04-03 | 2000-05-23 | Human Genome Sciences, Inc. | Human cystatin F |
CA2253904A1 (en) | 1996-05-03 | 1997-11-13 | Immunomedics, Inc. | Targeted combination immunotherapy of cancer |
US7011812B1 (en) | 1996-05-03 | 2006-03-14 | Immunomedics, Inc. | Targeted combination immunotherapy of cancer and infectious diseases |
US6136311A (en) | 1996-05-06 | 2000-10-24 | Cornell Research Foundation, Inc. | Treatment and diagnosis of cancer |
US6107090A (en) | 1996-05-06 | 2000-08-22 | Cornell Research Foundation, Inc. | Treatment and diagnosis of prostate cancer with antibodies to extracellur PSMA domains |
EP0938334A4 (en) | 1996-07-26 | 2004-12-15 | Smithkline Beecham Corp | IMPROVED METHOD FOR TREATING IMMUNE-MEDIATED SYSTEMIC DISEASES |
US6558669B1 (en) | 1996-08-28 | 2003-05-06 | Immunomedics, Inc. | Stable radioiodine conjugates and methods for their synthesis |
DE69735547T2 (de) | 1996-09-03 | 2007-03-08 | Kaneka Corp. | Verfahren zur induzierung von immunsupprimierten zellen und vorrichtung zu deren kultivierung |
WO1998012227A1 (en) | 1996-09-19 | 1998-03-26 | Diagnocure Inc. | Recombinant single chain antibodies directed against the gp54 cancer marker, composition comprising same and use thereof |
DE19640207A1 (de) | 1996-09-30 | 1998-04-02 | Bayer Ag | Glycokonjugate von modifizierten Camptothecin-Derivaten (A- oder B-Ring-Verknüpfung) |
EP0956304B1 (en) | 1996-10-09 | 2004-12-15 | Canterbury Health Limited | Dendritic cell-specific antibodies |
US6056973A (en) | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
US6653104B2 (en) | 1996-10-17 | 2003-11-25 | Immunomedics, Inc. | Immunotoxins, comprising an internalizing antibody, directed against malignant and normal cells |
DK0932417T3 (da) | 1996-10-17 | 2003-04-14 | Immunomedics Inc | Non-antigent toxinkonjugat og fusionsprotein af internaliserende receptorsystem |
US6812327B1 (en) | 1996-10-25 | 2004-11-02 | Human Genome Sciences, Inc. | Neutrokine-alpha polypeptides |
US6528625B1 (en) | 1996-10-28 | 2003-03-04 | Millennium Pharmaceuticals, Inc. | Anti-CCR5 antibodies and kits comprising same |
US6043348A (en) | 1996-11-13 | 2000-03-28 | Lawman; Michael J. P. | Antibody recognizing a small subset of human hematopoietic cells |
US6455040B1 (en) | 1997-01-14 | 2002-09-24 | Human Genome Sciences, Inc. | Tumor necrosis factor receptor 5 |
EP0988385A2 (en) | 1997-01-21 | 2000-03-29 | Human Genome Sciences | Tace-like and matrilysin-like polypeptides |
US6605699B1 (en) | 1997-01-21 | 2003-08-12 | Human Genome Sciences, Inc. | Galectin-11 polypeptides |
DE69837806T3 (de) | 1997-01-28 | 2012-01-05 | Human Genome Sciences, Inc. | "death-domain"-enthaltender rezeptor 4 (dr4), ein mitglied der tnf-rezeptor superfamilie, welcher an trail (apo-2l) bindet |
ATE427966T1 (de) | 1997-02-11 | 2009-04-15 | Immunomedics Inc | Stimulation einer immunantwort durch antikírper, welche mit dem alpha-galaktosylepitop markiert sind |
US7122636B1 (en) | 1997-02-21 | 2006-10-17 | Genentech, Inc. | Antibody fragment-polymer conjugates and uses of same |
JP2001523956A (ja) | 1997-03-03 | 2001-11-27 | ブリストル−マイヤーズ・スクイブ・カンパニー | ヒトcd6に対するモノクローナル抗体 |
US6919433B2 (en) | 1997-03-14 | 2005-07-19 | Human Genome Sciences, Inc. | Antibodies to protein HPMBQ91 |
US6951924B2 (en) | 1997-03-14 | 2005-10-04 | Human Genome Sciences, Inc. | Antibodies against secreted protein HTEBYII |
US6872568B1 (en) | 1997-03-17 | 2005-03-29 | Human Genome Sciences, Inc. | Death domain containing receptor 5 antibodies |
US6183744B1 (en) | 1997-03-24 | 2001-02-06 | Immunomedics, Inc. | Immunotherapy of B-cell malignancies using anti-CD22 antibodies |
US6306393B1 (en) | 1997-03-24 | 2001-10-23 | Immunomedics, Inc. | Immunotherapy of B-cell malignancies using anti-CD22 antibodies |
AU745823B2 (en) | 1997-05-02 | 2002-04-11 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Immunotoxins, comprising an onc protein, directed against malignant cells |
US6284474B1 (en) | 1998-04-23 | 2001-09-04 | The Regents Of The University Of California | Detection and diagnosis of conditions associated with lung injury |
US6372217B1 (en) | 1997-06-03 | 2002-04-16 | Regents Of The University Of Minnesota | Methods for the treatment of CD7+ viral infection with TXU-7-PAP |
US6545130B2 (en) | 1997-06-04 | 2003-04-08 | Albert Einstein College Of Medicine Of Yeshiva University | Monoclonal antibodies to mycobacterium tuberculosis and a modified ELISA assay |
US6358508B1 (en) | 1997-06-11 | 2002-03-19 | Human Genome Sciences, Inc. | Antibodies to human tumor necrosis factor receptor TR9 |
US6368596B1 (en) | 1997-07-08 | 2002-04-09 | Board Of Regents, The University Of Texas System | Compositions and methods for homoconjugates of antibodies which induce growth arrest or apoptosis of tumor cells |
US6165440A (en) | 1997-07-09 | 2000-12-26 | Board Of Regents, The University Of Texas System | Radiation and nanoparticles for enhancement of drug delivery in solid tumors |
DE69837095T2 (de) | 1997-09-03 | 2007-11-22 | Immunomedics, Inc. | Fluorierung von proteinen und peptiden für positronemissionstomographie |
IL134578A0 (en) | 1997-09-18 | 2001-04-30 | Genentech Inc | DcR3 POLYPEPTIDE, A TNFR HOMOLOG |
US6689607B2 (en) | 1997-10-21 | 2004-02-10 | Human Genome Sciences, Inc. | Human tumor, necrosis factor receptor-like proteins TR11, TR11SV1 and TR11SV2 |
US6953675B2 (en) | 1997-11-06 | 2005-10-11 | Immunomedics, Inc. | Landscaped antibodies and antibody fragments for clinical use |
US6355244B1 (en) | 1997-11-17 | 2002-03-12 | University Of Kentucky Research Foundation | Methods and compositions for the treatment of psoriasis |
US6610833B1 (en) | 1997-11-24 | 2003-08-26 | The Institute For Human Genetics And Biochemistry | Monoclonal human natural antibodies |
WO1999033878A1 (fr) | 1997-12-25 | 1999-07-08 | Japan Tobacco Inc. | Anticorps monoclonal contre le facteur de croissance du tissu conjonctif et ses mises en applications medicales |
US6051228A (en) | 1998-02-19 | 2000-04-18 | Bristol-Myers Squibb Co. | Antibodies against human CD40 |
US6956107B2 (en) | 1998-02-20 | 2005-10-18 | Tanox, Inc. | Inhibitors of complement activation |
US6861227B2 (en) | 1998-03-19 | 2005-03-01 | Human Genome Sciences, Inc. | Antibodies to cytokine receptor common gamma chain like |
US7112324B1 (en) | 1998-04-21 | 2006-09-26 | Micromet Ag | CD 19×CD3 specific polypeptides and uses thereof |
US6200765B1 (en) | 1998-05-04 | 2001-03-13 | Pacific Northwest Cancer Foundation | Non-invasive methods to detect prostate cancer |
US6071490A (en) | 1998-05-07 | 2000-06-06 | Immunomedics, Inc. | Position emission tomography using gallium-68 chelates |
JP2002515460A (ja) | 1998-05-20 | 2002-05-28 | イムノメディクス, インコーポレイテッド | 二重特異性抗hlaクラスii不変鎖x抗病原体抗体を使用した治療 |
CA2328504A1 (en) | 1998-06-15 | 1999-12-23 | Altarex Corp. | Immunotherapeutic composition and method for the treatment of prostate cancer |
US7387779B2 (en) | 1998-06-17 | 2008-06-17 | Beth Israel Deaconess Medical Center | Anti-angiogenic proteins and fragments and methods of use thereof |
US7387772B1 (en) | 1999-06-22 | 2008-06-17 | Immunimedics, Inc. | Chimeric, human and humanized anti-CSAP monoclonal antibodies |
US6528269B1 (en) | 1998-06-22 | 2003-03-04 | Case Western Reserve University | Immunological agents specific for prion protein (PRP) |
CA2335364C (en) | 1998-06-22 | 2010-05-04 | Immunomedics, Inc. | Use of bi-specific antibodies for pre-targeting diagnosis and therapy |
US7052872B1 (en) | 1999-06-22 | 2006-05-30 | Immunomedics, Inc. | Bi-specific antibodies for pre-targeting diagnosis and therapy |
US6962702B2 (en) | 1998-06-22 | 2005-11-08 | Immunomedics Inc. | Production and use of novel peptide-based agents for use with bi-specific antibodies |
US7405320B2 (en) | 1998-06-22 | 2008-07-29 | Immunomedics, Inc. | Therapeutic and diagnostic conjugates for use with multispecific antibodies |
US7138103B2 (en) | 1998-06-22 | 2006-11-21 | Immunomedics, Inc. | Use of bi-specific antibodies for pre-targeting diagnosis and therapy |
US6312689B1 (en) | 1998-07-23 | 2001-11-06 | Millennium Pharmaceuticals, Inc. | Anti-CCR2 antibodies and methods of use therefor |
AUPP525198A0 (en) | 1998-08-13 | 1998-09-03 | Medvet Science Pty. Ltd. | Monoclonal antibody inhibitor of GM-CSF, IL-3 and IL-5 and other cytokines and uses thereof |
US6572856B1 (en) | 1998-09-10 | 2003-06-03 | The University Of Virginia Patent Foundation | Methods for the prevention and treatment of cancer using anti-C3b(i) antibodies |
US6818749B1 (en) | 1998-10-31 | 2004-11-16 | The United States Of America As Represented By The Department Of Health And Human Services | Variants of humanized anti carcinoma monoclonal antibody cc49 |
JP2002528140A (ja) | 1998-11-05 | 2002-09-03 | ザ ボード オブ トラスティーズ オブ リーランド スタンフォード ジュニア ユニバーシティ | ヒトpan−hcvヒトモノクローナル抗体 |
EP1135498B1 (en) | 1998-11-18 | 2008-01-23 | Genentech, Inc. | Antibody variants with higher binding affinity compared to parent antibodies |
US6201104B1 (en) | 1998-12-04 | 2001-03-13 | Entremed, Inc. | Angiogenesis—inhibiting protein binding peptides and proteins and methods of use |
ES2259247T3 (es) | 1998-12-21 | 2006-09-16 | Ludwig Institute For Cancer Research | Anticuerpos frente a vegf-d truncado y sus usos. |
US6444790B1 (en) | 1998-12-23 | 2002-09-03 | Human Genome Sciences, Inc. | Peptidoglycan recognition proteins |
US6682736B1 (en) | 1998-12-23 | 2004-01-27 | Abgenix, Inc. | Human monoclonal antibodies to CTLA-4 |
US6488930B1 (en) | 1999-01-15 | 2002-12-03 | Millennium Pharmaceuticals, Inc. | Anti-CCR4 antibodies and methods of use therefor |
JP2002543044A (ja) | 1999-03-01 | 2002-12-17 | ジェネンテック・インコーポレーテッド | 癌の治療及び診断のための抗体 |
US6379698B1 (en) | 1999-04-06 | 2002-04-30 | Isis Pharmaceuticals, Inc. | Fusogenic lipids and vesicles |
EP1179541B1 (en) | 1999-04-28 | 2004-06-16 | Board Of Regents, The University Of Texas System | Compositions and methods for cancer treatment by selectively inhibiting VEGF |
US7820161B1 (en) | 1999-05-07 | 2010-10-26 | Biogen Idec, Inc. | Treatment of autoimmune diseases |
US8119101B2 (en) | 1999-05-10 | 2012-02-21 | The Ohio State University | Anti-CD74 immunoconjugates and methods of use |
US7527787B2 (en) | 2005-10-19 | 2009-05-05 | Ibc Pharmaceuticals, Inc. | Multivalent immunoglobulin-based bioactive assemblies |
US7534866B2 (en) | 2005-10-19 | 2009-05-19 | Ibc Pharmaceuticals, Inc. | Methods and compositions for generating bioactive assemblies of increased complexity and uses |
US7666400B2 (en) | 2005-04-06 | 2010-02-23 | Ibc Pharmaceuticals, Inc. | PEGylation by the dock and lock (DNL) technique |
US7550143B2 (en) | 2005-04-06 | 2009-06-23 | Ibc Pharmaceuticals, Inc. | Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses |
GB9911569D0 (en) | 1999-05-18 | 1999-07-21 | Oxford Biomedica Ltd | Antibodies |
US6946129B1 (en) | 1999-06-08 | 2005-09-20 | Seattle Genetics, Inc. | Recombinant anti-CD40 antibody and uses thereof |
DE19926154A1 (de) | 1999-06-09 | 2000-12-14 | Ktb Tumorforschungs Gmbh | Verfahren zur Herstellung einer injizierbaren Arzneimittelzubereitung |
DE05075555T1 (de) | 1999-06-09 | 2007-02-08 | Immunomedics, Inc. | Immuntherapie von Autoimmunerkrankungen durch die Verwendung von B-Zell-spezifischen Antikörpern |
US20020002270A1 (en) | 1999-06-16 | 2002-01-03 | Raymond P. Zinkowski | Purified antigen for alzheimer's disease, and methods of obtaining and using same |
AU5625500A (en) | 1999-06-18 | 2001-01-09 | Emory University | Huntington disease cellular model: stably transfected pc12 cells expressing mutant huntingtin |
US6964854B1 (en) | 1999-07-13 | 2005-11-15 | Science & Technology Corporation | Compositions and methods useful for the diagnosis and treatment of heparin induced thrombocytopenia/thrombosis |
US6693176B1 (en) | 1999-07-23 | 2004-02-17 | University Of Massachusetts | Antitumor antibodies, proteins, and uses thereof |
US6376654B1 (en) | 1999-08-13 | 2002-04-23 | Molecular Discoveries, Llc | Myeloma cell and ovarian cancer cell surface glycoproteins, antibodies thereto, and uses thereof |
US6716966B1 (en) | 1999-08-18 | 2004-04-06 | Altarex Corp. | Therapeutic binding agents against MUC-1 antigen and methods for their use |
WO2001016183A1 (en) | 1999-08-30 | 2001-03-08 | U.S. Army Medical Research Institute Of Infectious Diseases | Monoclonal antibodies and vaccines against epitopes on the ebola virus glycoprotein |
EP1229934B1 (en) | 1999-10-01 | 2014-03-05 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
US6824780B1 (en) | 1999-10-29 | 2004-11-30 | Genentech, Inc. | Anti-tumor antibody compositions and methods of use |
US6835370B2 (en) | 1999-11-08 | 2004-12-28 | Rhode Island Hospital | Diagnosis and treatment of malignant neoplasms |
US20030031670A1 (en) | 1999-11-08 | 2003-02-13 | Jack R. Wands | Diagnosis and treatment of malignant neoplasms |
US6994852B1 (en) | 1999-11-12 | 2006-02-07 | Temple University-Of The Commonwealth System Of Higher Education | Inhibition of angiogenesis by antibodies against high molecular weight kininogen domain 5 |
US6994976B1 (en) | 1999-11-19 | 2006-02-07 | Tittle Thomas V | Tr3-specific binding agents and methods for their use |
US6319675B1 (en) | 1999-11-24 | 2001-11-20 | Millennium Pharmaceuticals, Inc. | Methods for detecting and/or identifying agents which bind and/or modulate function of “bonzo” chemokine receptor |
US6530944B2 (en) | 2000-02-08 | 2003-03-11 | Rice University | Optically-active nanoparticles for use in therapeutic and diagnostic methods |
US6835549B2 (en) | 2000-02-24 | 2004-12-28 | University Of Medicine & Dentistry Of New Jersey | Immunoassay method for the diagnosis of gastric intestinal metaplasia associated with gastric carcinoma |
AU2001249410A1 (en) | 2000-03-23 | 2001-10-03 | Tanox, Inc. | Anti-c2/c2a inhibitors of complement activation |
CA2408549A1 (en) | 2000-05-11 | 2001-11-15 | Altarex Corp. | Therapeutic method and composition utilizing antigen-antibody complexation and presentation by dendritic cells |
EP1292619B1 (en) | 2000-06-06 | 2008-02-06 | Bristol-Myers Squibb Company | B7-related nucleic acids and polypeptides and their uses for immunomodulation |
DE10034607A1 (de) | 2000-07-20 | 2002-02-07 | Gundram Jung | Multispezifisches Reagenz zur selektiven Stimulierung von Zelloberflächenrezeptoren |
US6939547B2 (en) | 2000-07-31 | 2005-09-06 | The United States Of America As Represented By The Department Of Health And Human Services | Specific binding agents for KSHV vIL-6 that neutralize a biological activity |
US7060802B1 (en) | 2000-09-18 | 2006-06-13 | The Trustees Of Columbia University In The City Of New York | Tumor-associated marker |
ATE464374T1 (de) | 2000-10-02 | 2010-04-15 | Oklahoma Med Res Found | Assay zum schnellen nachweis vom humanen aktivierten protein c und hochspezifischer monoklonaler antikörper dagegen |
ATE449791T1 (de) | 2000-10-10 | 2009-12-15 | Genentech Inc | Inhibierung von c5 komplement-aktivierung für die behandlung und vorbeugung von xeno-transplantat oder akute vaskuläre abstossung |
US20030133972A1 (en) | 2000-10-11 | 2003-07-17 | Targesome, Inc. | Targeted multivalent macromolecules |
JP2004531217A (ja) | 2001-01-05 | 2004-10-14 | ファイザー・インク | インスリン様成長因子i受容体に対する抗体 |
US6743898B2 (en) | 2001-03-15 | 2004-06-01 | Ochsner Clinic Foundation | Monoclonal antibodies that suppress B cell growth and/or differentiation |
EP1372741B1 (en) | 2001-03-30 | 2006-08-09 | University of Massachusetts | Morpholino imaging and therapy |
US6824778B2 (en) | 2001-04-23 | 2004-11-30 | The United States Of America As Represented By The Secretary Of The Army | Prophylactic and therapeutic monoclonal antibodies |
US6962813B2 (en) | 2001-05-21 | 2005-11-08 | The Brigham And Women's Hospital, Inc. | P. aeruginosa mucoid exopolysaccharide specific binding peptides |
NZ513418A (en) | 2001-08-07 | 2004-04-30 | Univ Massey | Vaccine comprising proteins from mycobacterium paratuberculosis |
US7049060B2 (en) | 2001-11-05 | 2006-05-23 | Ortho-Clinical Diagnostics, Inc. | HCV anti-core monoclonal antibodies |
US6716821B2 (en) | 2001-12-21 | 2004-04-06 | Immunogen Inc. | Cytotoxic agents bearing a reactive polyethylene glycol moiety, cytotoxic conjugates comprising polyethylene glycol linking groups, and methods of making and using the same |
RU2004122702A (ru) | 2001-12-26 | 2005-04-20 | Иммуномедикс, Инк. (Us) | Способы получения полиспецифичных, поливалентных средств из vh и vl доменов |
CN100522999C (zh) | 2002-02-14 | 2009-08-05 | 免疫医疗公司 | 抗cd20抗体及其融合蛋白和使用方法 |
US7591994B2 (en) | 2002-12-13 | 2009-09-22 | Immunomedics, Inc. | Camptothecin-binding moiety conjugates |
US7585491B2 (en) | 2002-12-13 | 2009-09-08 | Immunomedics, Inc. | Immunoconjugates with an intracellularly-cleavable linkage |
US8877901B2 (en) | 2002-12-13 | 2014-11-04 | Immunomedics, Inc. | Camptothecin-binding moiety conjugates |
JP4354280B2 (ja) | 2002-03-01 | 2009-10-28 | イミューノメディクス、インコーポレイテッド | Rs7抗体 |
DE60333732D1 (de) | 2002-03-01 | 2010-09-23 | Immunomedics Inc | Internalisierung von anti cd74 monoklonalen antikörpern und deren verwendungen |
FR2840532B1 (fr) | 2002-06-11 | 2005-05-06 | Ethypharm Sa | Nanocapsules lipidiques furtives, procede de preparation et utilisation comme vecteur de principes(s) actif(s) |
ES2524767T3 (es) | 2002-06-14 | 2014-12-12 | Immunomedics, Inc. | Anticuerpo monoclonal humanizado HPAM4 |
EP1521775B1 (en) | 2002-06-14 | 2015-09-09 | Immunomedics, Inc. | Monoclonal antibody pam4 and its use for diagnosis and therapy of pancreatic cancer |
AU2003248982B2 (en) | 2002-08-01 | 2009-12-10 | Immunomedics, Inc. | Alpha-fetoprotein immu31 antibodies and fusion proteins and methods of use thereof |
US7541440B2 (en) | 2002-09-30 | 2009-06-02 | Immunomedics, Inc. | Chimeric, human and humanized anti-granulocyte antibodies and methods of use |
US8420086B2 (en) | 2002-12-13 | 2013-04-16 | Immunomedics, Inc. | Camptothecin conjugates of anti-CD22 antibodies for treatment of B cell diseases |
US20040202666A1 (en) | 2003-01-24 | 2004-10-14 | Immunomedics, Inc. | Anti-cancer anthracycline drug-antibody conjugates |
CA2510267A1 (en) | 2003-01-28 | 2004-08-12 | Schering Corporation | Antibodies specific for plasmacytoid dendritic cells |
WO2004074434A2 (en) | 2003-01-31 | 2004-09-02 | Immunomedics, Inc. | Methods and compositions for administering therapeutic and diagnostic agents |
CA2534639C (en) | 2003-07-31 | 2013-07-30 | Immunomedics, Inc. | Anti-cd19 antibodies |
CA2543127A1 (en) | 2003-10-31 | 2005-05-12 | The Regents Of The University Of California | Primate prokineticin and prokineticin receptor polypeptides, related compositions and methods |
EP2962699A3 (en) | 2003-12-01 | 2016-04-06 | Immunomedics Inc. | Improved method for preparing conjugates of proteins and chelating agents |
US8551480B2 (en) | 2004-02-13 | 2013-10-08 | Immunomedics, Inc. | Compositions and methods of use of immunotoxins comprising ranpirnase (Rap) show potent cytotoxic activity |
US7531327B2 (en) | 2004-07-23 | 2009-05-12 | Immunomedics, Inc. | Methods and compositions for increasing longevity and protein yield from a cell culture |
US7608425B2 (en) | 2004-07-23 | 2009-10-27 | Immunomedics, Inc. | Methods for protein expression in mammalian cells in serum-free medium |
US7537930B2 (en) | 2004-07-23 | 2009-05-26 | Immunomedics, Inc. | Mammalian cell lines for increasing longevity and protein yield from a cell culture |
WO2006047419A2 (en) | 2004-10-25 | 2006-05-04 | Intezyne Technologies, Incorporated | Heterobifunctional poly(ethylene glycol) and uses thereof |
US7251164B2 (en) | 2004-11-10 | 2007-07-31 | Innovative Silicon S.A. | Circuitry for and method of improving statistical distribution of integrated circuits |
SI1836500T1 (sl) | 2005-01-14 | 2010-11-30 | Ablynx Nv | Postopki in testi za razlikovanje med različnimioblikami bolezni in motenj ki so označene s trombocitopenijo in ali s spontano interakcijo med von Willebrandovim faktorjem vWF in krvnimi ploščicami |
ES2665422T3 (es) | 2005-03-03 | 2018-04-25 | Immunomedics Inc. | Anticuerpos L243 humanizados |
US8349332B2 (en) | 2005-04-06 | 2013-01-08 | Ibc Pharmaceuticals, Inc. | Multiple signaling pathways induced by hexavalent, monospecific and bispecific antibodies for enhanced toxicity to B-cell lymphomas and other diseases |
JP5011277B2 (ja) | 2005-04-06 | 2012-08-29 | アイビーシー・ファーマシューティカルズ・インコーポレーテッド | ホモダイマー、ホモテトラマーまたはダイマーのダイマーのからなる安定に連結された複合体を発生させるための方法および使用 |
LT2949668T (lt) | 2005-05-18 | 2019-11-11 | Ablynx Nv | Pagerinti nanokūnai tm prieš navikų nekrozės faktorių alfa |
EP2007814A2 (en) | 2005-05-20 | 2008-12-31 | Ablynx N.V. | Single domain vhh antibodies against von willebrand factor |
CN101534865A (zh) | 2005-10-19 | 2009-09-16 | Ibc药品公司 | 生物活性装配体的制备方法及其用途 |
US7420040B2 (en) | 2006-02-24 | 2008-09-02 | Arius Research Inc. | Cytotoxicity mediation of cells evidencing surface expression of TROP-2 |
EP2007386B1 (en) | 2006-04-19 | 2012-08-22 | Bionumerik Pharmaceuticals, Inc. | Camptothecin-analog with a novel, flipped lactone-stable, e-ring and methods for making and using same |
US7940926B2 (en) | 2006-06-08 | 2011-05-10 | Novell, Inc. | Cooperative encoding of data by pluralities of parties |
CA2666599A1 (en) | 2006-08-18 | 2008-02-21 | Ablynx N.V. | Amino acid sequences directed against il-6r and polypeptides comprising the same for the treatment of diseases and disorders associated with il-6-mediated signalling |
NZ581097A (en) | 2007-05-24 | 2012-03-30 | Ablynx Nv | Amino acid sequences directed against rank-l and polypeptides comprising the same for the treatment of bone diseases and disorders |
US8557965B2 (en) | 2008-04-07 | 2013-10-15 | Ablynx N.V. | Single variable domains against notch pathway members |
JP2011516603A (ja) | 2008-04-17 | 2011-05-26 | アブリンクス エン.ヴェー. | 血清タンパク質と結合することが可能なペプチド、並びにこれを含む化合物、構築物及びポリペプチド |
ITTO20080313A1 (it) | 2008-04-22 | 2009-10-23 | Marco Colombatti | Anticorpo monoclonale isolato o suo frammento legante l'antigene specifico di membrana della prostata, suoi coniugati e suoi usi |
US8715662B2 (en) | 2009-02-05 | 2014-05-06 | Oncoxx Biotech S.R.L. | Anti-trop-2 monoclonal antibodies and uses thereof in the treatment and diagnosis of tumors |
HUE060624T2 (hu) | 2009-02-13 | 2023-04-28 | Immunomedics Inc | Sejten belüli hasítható kötést tartalmazó immunkonjugátumok |
BR112012005594A2 (pt) | 2009-09-15 | 2015-09-08 | Cerulean Pharma Inc | tratamento de câncer |
NZ702053A (en) | 2010-05-17 | 2016-01-29 | Livtech Inc | Anti-human trop-2 antibody having antitumor activity in vivo |
WO2011155579A1 (ja) | 2010-06-10 | 2011-12-15 | 北海道公立大学法人札幌医科大学 | 抗Trop-2抗体 |
DK2694111T3 (en) | 2011-04-01 | 2016-10-10 | Wyeth Llc | Antibody pharmaceutical conjugates |
JP6024025B2 (ja) | 2011-05-02 | 2016-11-09 | イミューノメディクス、インコーポレイテッドImmunomedics, Inc. | 少容量投与用のアロタイプ選択抗体の限外濾過濃縮 |
RU2014116406A (ru) | 2011-11-11 | 2015-12-20 | Ринат Ньюросайенс Корп. | Антитела, специфичные к trop-2, и их применения |
ES2819573T3 (es) | 2012-12-13 | 2021-04-16 | Immunomedics Inc | Método para producir inmunoconjugados de anticuerpo-SN-38 con un enlazador CL2A |
KR20230078823A (ko) | 2012-12-13 | 2023-06-02 | 이뮤노메딕스, 인코오포레이티드 | 개선된 효능 및 감소된 독성을 위한 항체 및 sn-38의 면역컨쥬게이트의 투약 |
WO2014124227A1 (en) | 2013-02-07 | 2014-08-14 | Immunomedics, Inc. | Pro-drug form (p2pdox) of the highly potent 2-pyrrolinodoxorubicin conjugated to antibodies for targeted therapy of cancer |
EP3004888A1 (en) | 2013-05-31 | 2016-04-13 | Nektar Therapeutics | Method for predicting and evaluating responsiveness to cancer treatment with dna-damaging chemotherapeutic agents |
JP6746845B2 (ja) * | 2015-04-22 | 2020-08-26 | イミューノメディクス、インコーポレイテッドImmunomedics, Inc. | 循環trop−2陽性癌細胞の単離、検出、診断及び/または特徴付け |
-
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- 2016-04-22 WO PCT/US2016/028765 patent/WO2016172427A1/en unknown
-
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-
2019
- 2019-08-22 US US16/548,445 patent/US20190369103A1/en not_active Abandoned
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007525642A (ja) * | 2003-02-27 | 2007-09-06 | イムニベスト・コーポレイション | 循環腫瘍細胞(ctc):転移癌患者における増悪までの時間、生存および療法に対する応答の早期評価 |
JP2009539097A (ja) * | 2006-06-02 | 2009-11-12 | ファイザー・プロダクツ・インク | 循環腫瘍細胞アッセイ |
JP2011515109A (ja) * | 2008-03-25 | 2011-05-19 | ベリデックス・エルエルシー | FISH法を用いた循環腫瘍細胞中のIGF1R/Chr15を検出するための方法 |
CN101363046A (zh) * | 2008-08-29 | 2009-02-11 | 芮屈生物技术(上海)有限公司 | 一种广谱性癌症原位杂交检测试剂盒及其检测方法和应用 |
JP2012503483A (ja) * | 2008-09-25 | 2012-02-09 | サヴェリオ・アルベルティ | サイクリンd1−trop2キメラの発現を抑制することができるオリゴヌクレオチド配列、および医療分野におけるその使用 |
JP2012522217A (ja) * | 2009-03-24 | 2012-09-20 | バイオセプト インコーポレイティッド | 細胞の捕捉および解析のデバイスおよび方法 |
WO2015002975A1 (en) * | 2013-07-05 | 2015-01-08 | University Of Washington Through Its Center For Commercialization | Methods, compositions and systems for microfluidic assays |
WO2015028489A1 (en) * | 2013-08-27 | 2015-03-05 | Gilupi Gmbh | Diagnostic device for the detection of disease related target structures |
JP2016536330A (ja) * | 2013-08-30 | 2016-11-24 | イミュノジェン, インコーポレイテッド | 葉酸受容体1の検出用の抗体及びアッセイ |
WO2015047510A1 (en) * | 2013-09-27 | 2015-04-02 | Immunomedics, Inc. | Anti-trop-2 antibody-drug conjugates and uses thereof |
Non-Patent Citations (5)
Title |
---|
"Detection and Isolation of Circulating Tumor Cells in Urologic Cancers", NEOPLASIA, vol. 6, 4, JPN6019051509, 2004, pages 302 - 309, ISSN: 0004299971 * |
"Detection of EpCAM-Negative and Cytokeratin-Negative Circulating Tumor Cells", JOURNAL OF ONCOLOGY, vol. 2011, JPN6019051505, 2011, pages 252361, ISSN: 0004247524 * |
"Gene Copy Number Analysis by Fluorescence in Situ Hybridization", METHODS: A COMPANION TO METHODS IN ENZYMOLOGY, vol. 9, JPN6019051511, 1996, pages 113 - 121, ISSN: 0004299972 * |
"High expression of TROP2 correlates with poor prognosis in pancreatic cancer", BRITISH JOURNAL OF CANCER, vol. 99, JPN6019051503, 2008, pages 1290 - 1295, ISSN: 0004247523 * |
"Multimarker Analysis of Circulating Tumor Cells in Peripheral Blood of Metastatic Breast Cancer", BREAST CARE, vol. 7, JPN6019051507, 2012, pages 7 - 12, ISSN: 0004247525 * |
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US20190369103A1 (en) | 2019-12-05 |
AU2016252771B2 (en) | 2021-12-16 |
WO2016172427A1 (en) | 2016-10-27 |
EP3286224A4 (en) | 2018-11-14 |
CN107428837A (zh) | 2017-12-01 |
JP6746845B2 (ja) | 2020-08-26 |
US9797907B2 (en) | 2017-10-24 |
US20160313339A1 (en) | 2016-10-27 |
US10436788B2 (en) | 2019-10-08 |
EP3286224A1 (en) | 2018-02-28 |
AU2016252771A1 (en) | 2017-08-10 |
US20180149657A1 (en) | 2018-05-31 |
CA2981543A1 (en) | 2016-10-27 |
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