JP2017518366A - Pd−l1抗体及びその使用 - Google Patents
Pd−l1抗体及びその使用 Download PDFInfo
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Abstract
Description
本出願は、内容全体が参照により本明細書に援用される、2014年5月29日出願の米国特許出願公開第62/004572号及び2014年10月28日出願の米国特許出願公開第62/069420号の利益を主張する。
発明の分野
本開示は、新規のPD−L1抗体及び生物学的試料中のPD−L1ポリペプチドを検出するための、その使用方法に関する。PD−L1抗体は、PD−L1関連の医学的状態を有すると診断された対象における特定の治療剤の有効性を評価するのにも有用である。
以下の説明は、読者の理解を助けるために提供される。提供されている情報又は引用参照文献のいずれも、先行技術とは認められない。
抗体及び抗体断片
抗体の一般的な構造は、当該技術分野で知られており、ここでは簡単に要約する。免疫グロブリンモノマーは、ジスルフィド結合で連結された二の重鎖と二の軽鎖とを含む。各重鎖は、それがジスルフィド結合を介して直接結合している軽鎖の一つと対になっている。各重鎖は、定常領域(抗体のアイソタイプによって異なる)と可変領域とを含む。可変領域は、CDRH1、CDRH2、及びCDRH3と称され、フレームワーク領域内に維持される三つの超可変領域(すなわち相補性決定領域)を含む。各軽鎖は、定常領域と可変領域とを含み、可変領域は重鎖の可変領域に類似の様式でフレームワーク領域によって維持される三つの超可変領域(CDRL1、CDRL2、及びCDRL3と称される)を含む。
(a) LC免疫グロブリン可変ドメイン配列は、SP263、J45H2L4又はJ27H6L4のLC可変ドメインのCDRと少なくとも85%同一である一又は複数のCDRを含む;
(b) HC免疫グロブリン可変ドメイン配列は、SP263、J45H2L4又はJ27H6L4のHC可変ドメインのCDRと少なくとも85%同一である一又は複数のCDRを含む;
(c) LC免疫グロブリン可変ドメイン配列は、SP263、J45H2L4又はJ27H6L4のLC可変ドメインと少なくとも85%同一である;
(d) HC免疫グロブリン可変ドメイン配列は、SP263、J45H2L4又はJ27H6L4のHC可変ドメインと少なくとも85%同一である;及び
(e) 抗体は、SP263、J45H2L4又はJ27H6L4によって結合されたエピトープと重複するエピトープに結合する。
1) 塩基性側鎖を有するアミノ酸:リジン、アルギニン、ヒスチジン
2) 酸性側鎖を有するアミノ酸:アスパラギン酸、グルタミン酸
3) 非荷電極性側鎖を有するアミノ酸:アスパラギン、グルタミン、セリン、スレオニン、チロシン
4) 非極性側鎖を有するアミノ酸:グリシン、アラニン、バリン、ロイシン、イソロイシン、プロリン、フェニルアラニン、メチオニン、トリプトファン、システイン
APTKAPDVFPIISGCRHPKDNSPVVLACLITGYHPTSVTVTWYMGTQSQPQRTFPEIQRRDSYYMTSSQLSTPLQQWRQGEYKCVVQHTASKSKKEIFRWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGRGGEEKKKEKEKEEQEERETKTPECPSHTQPLGVYLLTPAVQDLWLRDKATFTCFVVGSDLKDAHLTWEVAGKVPTGGVEEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTLNHPSLPPQRLMALREPAAQAPVKLSLNLLASSDPPEAASWLLCEVSGFSPPNILLMWLEDQREVNTSGFAPARPPPQPGSTTFWAWSVLRVPAPPSPQPATYTCVVSHEDSRTLLNASRSLEVSYVTDHGPMK
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDISVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
ASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTCNVNHKPSNTKVDKRVELKTPLGDTTHTCPRCPEPKSCDTPPPCPRCPEPKSCDTPPPCPRCPEPKSCDTPPPCPRCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVDGVEVHNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSDGSFFLYSKLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSLSLSPGK
GSASAPTLFPLVSCENSPSDTSSVAVGCLAQDFLPDSITLSWKYKNNSDISSTRGFPSVLRGGKYAATSQVLLPSKDVMQGTDEHVVCKVQHPNGNKEKNVPLPVIAELPPKVSVFVPPRDGFFGNPRKSKLICQATGFSPRQIQVSWLREGKQVGSGVTTDQVQAEAKESGPTTYKVTSTLTIKESDWLGQSMFTCRVDHRGLTFQQNASSMCVPDQDTAIRVFAIPPSFASIFLTKSTKLTCLVTDLTTYDSVTISWTRQNGEAVKTHTNISESHPNATFSAVGEASICEDDWNSGERFTCTVTHTDLPSPLKQTISRPKGVALHRPDVYLLPPAREQLNLRESATITCLVTGFSPADVFVQWMQRGQPLSPEKYVTSAPMPEPQAPGRYFAHSILTVSEEEWNTGETYTCVAHEALPNRVTERTVDKSTGKPTLYNVSLVMSDTAGTCY
ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
ASPTSPKVFPLSLCSTQPDGNVVIACLVQGFFPQEPLSVTWSESGQGVTARNFPPSQDASGDLYTTSSQLTLPATQCLAGKSVTCHVKHYTNPSQDVTVPCPVPSTPPTPSPSTPPTPSPSCCHPRLSLHRPALEDLLLGSEANLTCTLTGLRDASGVTFTWTPSSGKSAVQGPPERDLCGCYSVSSVLPGCAEPWNHGKTFTCTAAYPESKTPLTATLSKSGNTFRPEVHLLPPPSEELALNELVTLTCLARGFSPKDVLVRWLQGSQELPREKYLTWASRQEPSQGTTTFAVTSILRVAAEDWKKGDTFSCMVGHEALPLAFTQKTIDRLAGKPTHVNVSVVMAEVDGTCY
ASPTSPKVFPLSLDSTPQDGNVVVACLVQGFFPQEPLSVTWSESGQNVTARNFPPSQDASGDLYTTSSQLTLPATQCPDGKSVTCHVKHYTNPSQDVTVPCPVPPPPPCCHPRLSLHRPALEDLLLGSEANLTCTLTGLRDASGATFTWTPSSGKSAVQGPPERDLCGCYSVSSVLPGCAQPWNHGETFTCTAAHPELKTPLTANITKSGNTFRPEVHLLPPPSEELALNELVTLTCLARGFSPKDVLVRWLQGSQELPREKYLTWASRQEPSQGTTTFAVTSILRVAAEDWKKGDTFSCMVGHEALPLAFTQKTIDRMAGKPTHVNVSVVMAEVDGTCY
TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
抗体、その製造及び使用は、よく知られており、例えばHarlow, E. and Lane, D.,Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1999に開示されている。抗体は、当該技術分野で既知の標準的な方法を用いて生成されうる。抗体の例は、抗体のモノクローナル、一本鎖、及び機能的断片を含む(ただしこれらに限定されない)。
概略本開示の抗体は、PD−L1ポリペプチドの局在化及び/又は定量化に関する当該技術分野で既知の方法において(例えば適切な生理学的試料中のPD−L1ポリペプチドのレベルの測定における使用のため、診断方法における使用のため、ポリペプチドの画像化における使用のため等)有用である。本開示の抗体は、アフィニティークロマトグラフィー又は免疫沈降などの標準的な技術によってPD−L1ポリペプチドを単離する際に有用である。本開示のPD−L1抗体は、生物学的試料、例えば哺乳動物の血清又は細胞及び宿主系において発現される組換え産生PD−L1ポリペプチド由来の天然PD−L1ポリペプチドの精製を容易にすることができる。さらに、ポリペプチドの発現の量及びパターンを評価するために、PD−L1抗体を用いて(例えば、血漿、細胞溶解物又は細胞上清中の)PD−L1ポリペプチドを検出することができる。例えば所与の治療レジメンの有効性を決定するために、臨床試験手順の一部として本開示のPD−L1抗体を用いて、組織中のPD−L1レベルを診断的にモニターすることができる。検出は、本開示のPD−L1抗体を検出可能な物質とカップリング(すなわち物理的に連結)させることにより促進されうる。
本明細書に記載されるように、本開示は、PD−L1の発現レベルを決定するための診断方法を提供する。一つの特定の態様において、本開示は、このような方法を実施するためのキット、並びに組織の収集及び/又はスクリーニングの実施及び/又は結果の分析などの本開示の方法を実施するための説明書を提供する。
図1は、ウサギ宿主を使用してPD−L1モノクローナル抗体を作製するために用られる全体的な手順を示す。抗PD−L1ウサギモノクローナル一次抗体は、ヒトPD−L1のアミノ酸残基272〜290に相当する配列CGIQDTNSKKQSDTHLEET(配列番号1)に対して向けられた。したがって、得られた抗体は、E1L3N(登録商標)抗PD−L1抗体(マサチューセッツ州のCell Signaling Technology)に非常に類似しているヒトPD−L1のC末端細胞質領域を標的とすることになる。
軽鎖CDR2配列は、LASTLAS(配列番号12)である。
QSLEESGGRLVTPGTPLTLTCTASGFSLSNHAISWVRQAPGKGLEWIGTINSDTHTYYATWPKGRFTISKTSSTTVDLKMTSPTTEDTATYFCARRIFSSSNIWGPGTLVTVSS(配列番号2)
AIVMTQTSSPVSAVVGGTVAINCQASQSIYNNNWLSWFQQKPGQPPKLLIYLASTLASGVPSRFKGSGSGTQFTLTISDVVCDDAATYYCIGGESSNNDGIAFGGGTEVVVK(配列番号3)
QSLEESGGRLVTPGTPLTLTCTASGFSLSSNAISWVRQAPGKGLEWIGTINSDSHIYSATWAKGRFTISKTSTAVDLKMTSPTTEDTATYFCAGRLFSSTNIWGPGTLVTVSS(配列番号4)
VMTQTSSPVSAAVGGTVTINCQASQSIYKDNWLSWFQQKPGQPPKLLIYLASTLASGVPSRFKGSGSGTQFTLTISDVVCDDAATYYCLGGESSSDDGIAFGGGTEVVVK(配列番号5)
QSLEESGGRLVTPGTPLTLTCTVSGFSLSSHAISWVRQAPGKGLEWIGTINSDSHTYYATWAKGRFTSSKTSTTVDLKLTSPTTEDTATYFCARRIFSSSNIWGPGTLVTVSS(配列番号6)
VMTQTSSPVSAAVGGTVTINCQASQSIYNNNWLSWFQQKPGQPPKLLIYLASTLASGVPSRFKGSGSGTQSTLTISDVVCDDAATYYCIGGESSNTDGIAFGGGTEVVVE(配列番号7)
ウサギ抗ヒトPD−L1モノクローナル抗体SP263、J45H2L4、及びJ27H6L4をホルマリン固定パラフィン包埋(FFPE)組織試料に適用し、これらの抗体の染色パターンを評価した。組織試料は、胎盤(陽性対照)、胃(陰性対照)及び結腸を含む。標準CC1細胞コンディショニング及び標準Opt iView DAB検出プロトコールを用い、BenchMark Ultra(Ventana Medical System)で免疫組織化学を実施した。各一次抗体を0.9μg/mlで16分間インキュベートした。
ウェスタンブロット分析を用いて、生物学的試料中のSP263抗PD−L1抗体の結合特異性を評価した。NIH H820肺腺癌細胞株(陽性対照)、HEK293細胞株、Calu−3肺腺癌細胞株(陰性対照)、ZR75−1ヒト乳癌細胞株(陰性対照)、MCF7ヒト乳癌細胞株(陰性対照)、及びT47Dヒト乳癌細胞株(陰性対照)からの細胞溶解物を、SDS−PAGEにより分画し、標準的技術を用いてSP263抗PD−L1抗体でウェスタンブロッティングに供した(OptiView DAB検出プロトコール参照)。
E1L3N(登録商標)抗体(マサチューセッツ州のCell Signaling Technology)は、その改良された結合特性(特異性および感受性)が認められており、それにより生物学的試料(例えば組織生検)中のヒトPD−L1ポリペプチドの検出を助ける、市販のウサギ抗ヒトPD−L1モノクローナル抗体である。http://www.cellsignal.com/contents/science-cancer-research/pivotal-tumor-immunology-targets-pd-l1/pd-li-signalingを参照のこと。SP263及びE1L3N(登録商標)抗体はいずれも、ヒトPD−L1のC末端領域付近のエピトープを標的とし、したがってPD−L1の細胞内ドメインに結合する。
FFPE胎盤、扁桃、子宮頸部扁平上皮癌、ホジキンリンパ腫、膵臓腺癌、前立腺腺癌、皮膚扁平上皮癌、及び非小細胞肺がん(NSCLC)組織試料に、SP263抗PD−L1抗体(0.44μg/ml)を適用した。免疫組織化学を、Opt iView検出キットとともに標準CC1細胞コンディショニングを用い、BenchMark Ultra(Ventana Medical System)で実施した。E1L3N(登録商標)抗体での対応するIHC実験は、製造業者のプロトコールに従って行った。
特に定義がない限り、本明細書で使用されるすべての技術用語及び科学用語は、本開示が属する技術分野の当業者によって一般に理解されるものと同一の意味を持つ。
Claims (34)
- 重鎖(HC)免疫グロブリン可変ドメイン配列と軽鎖(LC)免疫グロブリン可変ドメイン配列とを含む単離された抗体であって、アミノ酸配列CGIQDTNSKKQSDTHLEET(配列番号1)を含むヒトPD−L1のエピトープに結合し、かつ/又は少なくとも1.5x10−11Mの半数効果濃度(EC50)を有する抗体。
- (a) HCがCDR3コンセンサス配列RX1FSSX2NI(配列番号10)を含み、ここでX1はI又Lであり、X2はS又はTであり;又は
(b) LCがCDR3コンセンサス配列X3GGESSX4X5DGIA(配列番号13)を含み、ここでX3はL又はIであり、X4はN又はSであり、かつX5はN、T又はDであり;又は
(c) HCがCDR3コンセンサス配列RX1FSSX2NI(配列番号10)を含み、ここでX1はI又はLであり、X2はS又はTであり、かつLCがCDR3コンセンサス配列X3GGESSX4X5DGIA(配列番号13)を含み、ここでX3はL又はIであり、X4はN又はSであり、X5はN、T又はDである、
請求項1に記載の抗体。 - HCがCDR2コンセンサス配列TINSDX6HX7YX8ATWX9KG(配列番号9)をさらに含み、ここでX6はT又はSであり、X7はT又はIであり、X8はY又はSであり、X9はP又はAである、請求項1又は2に記載の抗体。
- HCがCDR1コンセンサス配列X10X11AIS(配列番号8)をさらに含み、ここでX10はN又はSであり、X11はH又はNである、請求項1から3のいずれか一項に記載の抗体。
- LCがCDR2配列LASTLAS(配列番号12)をさらに含む、請求項1から4のいずれか一項に記載の抗体。
- LCがCDR1コンセンサス配列QASQSIYX12X13NWLS(配列番号11)をさらに含み、ここでX12はN又はKであり、X13はN又はDである、請求項1から5のいずれか一項に記載の抗体。
- HCが、
(a) アミノ酸配列NHAIS(配列番号14)を含むHC CDR1;及び/若しくは
(b) アミノ酸配列TINSDTHTYYATWPKG(配列番号15)を含むHC CDR2;及び/又は
(c) アミノ酸配列RIFSSSNI(配列番号16)を含むHC CDR3
を含み;かつ/又は
LCが、
(a) アミノ酸配列QASQSIYNNNWLS(配列番号17)を含むLC CDR1;及び/若しくは
(b) アミノ酸配列LASTLAS(配列番号12)を含むLC CDR2;及び/若しくは
(c) アミノ酸配列IGGESSNNDGIA(配列番号18)を含むLC CDR3
を含む、請求項1から6のいずれか一項に記載の抗体。 - HCが、
(a) アミノ酸配列SNAIS(配列番号19)を含むHC CDR1;及び/若しくは
(b) アミノ酸配列TINSDSHIYSATWAKG(配列番号20)を含むHC CDR2;及び/若しくは
(c) アミノ酸配列RLFSSTNI(配列番号21)を含むHC CDR3
を含み;かつ/又は
LCが、
(a) アミノ酸配列QASQSIYKDNWLS(配列番号22)を含むLC CDR1;及び/若しくは
(b) アミノ酸配列LASTLAS(配列番号12)を含むLC CDR2;及び/若しくは
(c) アミノ酸配列LGGESSSDDGIA(配列番号23)を含むLC CDR3
を含む、請求項1から6のいずれか一項に記載の抗体。 - HCが、
(a) アミノ酸配列SHAIS(配列番号24)を含むHC CDR1;及び/若しくは
(b) アミノ酸配列TINSDSHTYYATWAKG(配列番号25)を含むHC CDR2; 及び/若しくは
(c) アミノ酸配列RIFSSSNI(配列番号16)を含むHC CDR3
を含み;かつ/又は
LCが、
(a) アミノ酸配列QASQSIYNNNWLS(配列番号17)を含むLC CDR1;及び/若しくは
(b) アミノ酸配列LASTLAS(配列番号12)を含むLC CDR2;及び/若しくは
(c) アミノ酸配列IGGESSNTDGIA(配列番号26)を含むLC CDR3
を含む、請求項1から6のいずれか一項に記載の抗体。 - HC免疫グロブリン可変ドメイン配列が配列番号2、配列番号4又は配列番号6のアミノ酸配列を含む、請求項1から9のいずれか一項に記載の抗体。
- LC免疫グロブリン可変ドメイン配列が配列番号3、配列番号5又は配列番号7のアミノ酸配列を含む、請求項1から9のいずれか一項に記載の抗体。
- HC免疫グロブリン可変ドメイン配列が配列番号2、配列番号4又は配列番号6のアミノ酸配列を含み、かつLC免疫グロブリン可変ドメイン配列が配列番号3、配列番号5又は配列番号7のアミノ酸配列を含む、請求項1から9のいずれか一項に記載の抗体。
- 抗体がモノクローナル抗体、キメラ抗体又はヒト化抗体である、請求項1から12のいずれか一項に記載の抗体。
- 抗原結合断片がFab、F(ab’)2、Fab’、scFv、及びFvからなる群より選択される、請求項1から13のいずれか一項に記載の抗体の抗原結合断片。
- 配列番号1を含むペプチドに結合する、請求項1から13のいずれか一項に記載の抗体又は請求項14に記載の抗原結合断片を含む組成物。
- ペプチドがPD−L1タンパク質である、請求項15に記載の組成物。
- ペプチドが細胞と結合している、請求項15又は16に記載の組成物。
- ペプチドが固体支持体に結合している、請求項15又は16に記載の組成物。
- ペプチドが溶液中に配置されている、請求項15又は16に記載の組成物。
- ペプチドがマトリックスと結合している、請求項15又は16に記載の組成物。
- 生物学的試料中のPD−L1を検出する方法であって、試料を請求項1から13のいずれか一項に記載の抗体又は請求項14に記載の抗原結合断片と接触させることと、抗体又は抗原結合断片のPD−L1への結合により形成される複合体を検出することとを含む、方法。
- 試料が細胞又は組織試料を含む、請求項21に記載の方法。
- 試料ががんに罹患していると診断されるか、罹患していることが疑われるか、又は罹患するリスクがある対象から得られる、請求項21に記載の方法。
- がんが膀胱移行細胞癌、肺腺癌、乳管癌、ホジキンリンパ腫、膵臓腺癌、前立腺腺癌、子宮頸部扁平上皮癌、皮膚扁平上皮癌、及び非小細胞肺がんからなる群より選択される、請求項23に記載の方法。
- 検出が免疫組織化学(IHC)、ウェスタンブロッティング、フローサイトメトリー又はELISAのうちの一又は複数を含む、請求項21から24のいずれか一項に記載の方法。
- 対象から単離された試料中の病的細胞を検出する方法であって、
(a)生物学的試料中のPD−L1に結合する、請求項1から14のいずれか一項に記載の抗体又は抗原結合断片により形成された複合体を検出することによって、対象からの該試料中のPD−L1のレベルを検出すること;及び
(b) 工程(a)で観察されたPD−L1のレベルを対照生物学的試料中で観察されたPD−L1のレベルと比較すること
を含み、
PD−L1のレベルが対照生物学的試料中で観察されたレベルと比較して上昇している場合に病的細胞が検出され、PD−L1レベルが対照生物学的試料中で観察されたレベルと比較して上昇していない場合には検出されない、
方法。 - 対象の生物学的試料が肺、腎臓、膀胱、乳房、膵臓、前立腺、子宮頸部又は皮膚から単離された一又は複数の試料を含む、請求項26に記載の方法。
- 検出が免疫組織化学(IHC)、ウェスタンブロッティング、フローサイトメトリー又はELISAのうちの一又は複数を含む、請求項26又は27に記載の方法。
- 生物学的試料を対象から単離することをさらに含む、請求項26から28のいずれか一項に記載の方法。
- 対象が哺乳動物である、請求項29に記載の方法。
- 哺乳動物がネズミ、ネコ、イヌ、ヒツジ、ウシ、サル、及びヒトの群から選択される、請求項30に記載の方法。
- PD−L1特異的抗体又は抗原結合断片であって、請求項1から12のいずれか一項に記載の抗体と同じエピトープ特異性有する抗体又は抗原結合断片。
- 請求項1から13のいずれか一項に記載の抗体又は請求項14に記載の抗原結合断片及び使用説明書を含む、PD−L1を検出するためのキット。
- 腫瘍試料中のPD−L1を検出する方法であって、
(a)重鎖(HC)免疫グロブリン可変ドメイン配列及び軽鎖(LC)免疫グロブリン可変ドメイン配列を含む抗体又は抗体の抗原結合断片と試料を接触させることであって、ここで抗体はアミノ酸配列CGIQDTNSKKQSDTHLEET(配列番号1)を含むヒトPD−L1のエピトープに結合し、かつ/又は少なくとも1.5x10−11Mの半数効果濃度(EC50)を有し、
HCは
(i) アミノ酸配列NHAIS(配列番号14)を含むHC CDR1;
(ii) アミノ酸配列TINSDTHTYYATWPKG(配列番号15)を含むHC CDR2;及び
(iii) アミノ酸配列RIFSSSNI(配列番号16)を含むHC CDR3を含み;かつ
LCは
(i) アミノ酸配列QASQSIYNNNWLS(配列番号17)を含むLC CDR1;
(ii) アミノ酸配列LASTLAS(配列番号12)を含むLC CDR2;及び
(iii) アミノ酸配列IGGESSNNDGIA(配列番号18)を含むLC CDR3)を含むこと;並びに
(b) 抗体又は抗原結合断片のPD−L1への結合により形成された複合体を検出すること
を含む、方法。
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US20150346208A1 (en) | 2015-12-03 |
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US10775383B2 (en) | 2020-09-15 |
ES2753360T3 (es) | 2020-04-08 |
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