JP2022095888A - エンドセリン受容体ベータサブタイプに対する抗体 - Google Patents
エンドセリン受容体ベータサブタイプに対する抗体 Download PDFInfo
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Abstract
Description
- CDR1(以下CDR1Hという)、CDR2(以下CDR2Hという)及びCDR3(以下CDR3Hという)を含む重鎖可変領域であって、CDR1H、CDR2H及びCDR3Hのアミノ酸配列で形成される順序で並べられた配置が、以下のアミノ酸配列:GYTFISYWIDPDSGGTAREGDYAWFAY(配列番号1)と少なくとも80%の同一性を示す、重鎖可変領域、及び
- CDR1(以下CDR1Lという)、CDR2(以下CDR2Lという)及びCDR3(以下CDR3Lという)を含む軽鎖可変領域であって、CDR1L、CDR2L及びCDR3Lのアミノ酸配列で形成される順序で並べられた配置が、以下のアミノ酸配列:QSIVHSNGNTYKVSFQGSHVPWT(配列番号2)と少なくとも80%の同一性を示す、軽鎖可変領域
を含む抗体に関する。
i1)
- アミノ酸配列がGYTFISYW(配列番号5)であるCDR1H、
- アミノ酸配列がIDPDSGGT(配列番号10)であるCDR2H、及び
- アミノ酸配列がAREGDYAWFAY(配列番号15)であるCDR3H
を含む重鎖可変領域、
又は
ii1)
- アミノ酸配列がGYTFTSYW(配列番号7)であるCDR1H、
- アミノ酸配列がIDPDSGGT(配列番号10)であるCDR2H、及び
- アミノ酸配列がVREGWDAWFVY(配列番号17)であるCDR3H
を含む重鎖可変領域、
又は
iii1)
- アミノ酸配列がGYTFTSYW(配列番号7)であるCDR1H、
- アミノ酸配列がIDPNSGGT(配列番号12)であるCDR2H、及び
- アミノ酸配列がAREGEFAWFAY(配列番号19)であるCDR3H
を含む重鎖可変領域
を含む。
QVQLQQPGAALVKPGASVKLSCKASGYTFISYWMLWVKQRPGRGLEWIGRIDPDSGGTKYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCAREGDYAWFAYWGQGTLVPVSA (配列番号31)
と少なくとも80%の同一性を示す。
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGRGLEWIGRIDPDSGGTKYNEKFKSKATLTVDKPSNTANMQLSSLTSEDSAVYYCVREGWDAWFVYWGQGTLLTVSA (配列番号33)
に対応する、すなわちそれからなる。
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWIHWVNQRPGRGLEWIGRIDPNSGGTKYNEKFKSKATLTVDKTSSTAYMQFSSLTSEDSAVYYCAREGEFAWFAYWGQGTLVTVSA (配列番号35)
に対応する、すなわちそれからなる。
i2)
- アミノ酸配列がQSIVHSNGNTY(配列番号22)であるCDR1L、
- アミノ酸配列がKVSであるCDR2L、
- アミノ酸配列がFQGSHVPWT(配列番号27)であるCDR3L
を含む軽鎖可変領域、
又は
ii2)
- アミノ酸配列がQSIVHSNGNTY(配列番号22)であるCDR1L、
- アミノ酸配列がKVFであるCDR2L、
- アミノ酸配列がFQGSHVPLT(配列番号29)であるCDR3L
を含む軽鎖可変領域、
又は
iii2)
- アミノ酸配列がQNIVHSNGYTY(配列番号24)であるCDR1L、
- アミノ酸配列がKVSであるCDR2L、
- アミノ酸配列がFQGSHVPLT(配列番号29)であるCDR3L
を含む軽鎖可変領域
を含む。
DVLMTQTPLSLPVSLGDQASISCRSSQSIVHSNGNTYLEWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGGGTKLEIK (配列番号37)
と少なくとも80%の同一性を示す。
DVLMTQTPLSLPVSLGDQASISCRSSQSIVHSNGNTYLEWYLQKPGQSPKLLIYKVFNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPLTFGAGTKLELKR (配列番号39)
に対応する、すなわちそれからなる。
DVLMTQTPLSLPVSLGDQASISCRSSQNIVHSNGYTYLEWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPLTFGSGTKLEIKR (配列番号41)
に対応する、すなわちそれからなる。
α)先に定義された抗体をコードするポリヌクレオチド、
β)(α)で定義されたポリヌクレオチドに相補的なポリヌクレオチド、
γ)高ストリンジェンシー条件下で(α)及び(β)で定義されたポリヌクレオチドとハイブリダイズ可能な少なくとも18ヌクレオチドのポリヌクレオチド
から選択される、単離されたポリヌクレオチドにも関する。
GGC TAC ACC TTC ATC AGC TAC TGG (配列番号4)及び
GGC TAC ACC TTC ACC AGC TAC TGG (配列番号6)
から選択されるCDR1Hをコードする少なくとも1つのヌクレオチド配列を含む。
ATT GAT CCT GAT AGN1 GGT GGT ACT(式中、N1はC又はTのいずれかを表す) (配列番号9)及び
ATT GAT CCT AAT AGT GGT GGC ACT (配列番号11)
から選択されるCDR2Hをコードする少なくとも1つのヌクレオチド配列を含む。
GCA AGA GAA GGG GAT TAC GCC TGG TTT GCT TAC (配列番号14);
GTA AGA GAA GGG TGG GAC GCC TGG TTT GTT TAC (配列番号16)及び
GCA AGA GAG GGG GAA TTC GCC TGG TTT GCT TAC (配列番号18)
から選択されるCDR3Hをコードする少なくとも1つのヌクレオチド配列を含む。
CAG AGC ATT GTA CAT AGT AAT GGA AAC ACC TAT (配列番号21)及び
CAG AAC ATT GTC CAT AGT AAT GGA TAC ACC TAT (配列番号23)
から選択されるCDR1Lをコードする少なくとも1つのヌクレオチド配列を含む。
AAA GTT TCC及び
AAA GTT TTC
から選択されるCDR2Lをコードする少なくとも1つのヌクレオチド配列を含む。
TTT CAA GGT TCA CAT GTT CCG TGG ACG (配列番号26)及び
TTT CAA GGT TCA CAT GTT CCN2 CTC ACG(式中、N2はG又はTのいずれかを表す) (配列番号28)
から選択されるCDR3Lをコードする少なくとも1つのヌクレオチド配列を含む。
(i1')配列番号4、配列番号9(式中、N1はCを表す)、及び配列番号14、のヌクレオチド配列、
(ii1')配列番号6、配列番号9(式中、N1はTを表す)、及び配列番号16、のヌクレオチド配列、並びに
(iii1')配列番号6、配列番号11(式中、N1はTを表す)、及び配列番号18、のヌクレオチド配列
のうちの1つに対応する少なくとも3つのヌクレオチド配列を含む。
CAGGTCCAACTGCAGCAGCCTGGGGCTGCGCTTGTGAAGCCTGGGGCTTCAGTGAAGCTGTCCTGCAAGGCTTCTGGCTACACCTTCATCAGCTACTGGATGCTCTGGGTGAAGCAGAGGCCTGGACGAGGCCTTGAGTGGATTGGAAGGATTGATCCTGATAGCGGTGGTACTAAGTACAATGAGAAGTTCAAGAGCAAGGCCACACTGACTGTAGACAAATCCTCCAGCACAGCCTACATGCAGCTCAGCAGCCTGACATCTGAGGACTCTGCGGTCTATTATTGTGCAAGAGAAGGGGATTACGCCTGGTTTGCTTACTGGGGCCAAGGGACTCTGGTCCCTGTCTCTGCA (配列番号30)
と少なくとも80%の同一性を有する少なくとも1つのヌクレオチド配列を含む。
CAGGTCCAACTGCAGCAGCCTGGGGCTGAGCTTGTGAAGCCTGGGGCTTCAGTGAAGCTGTCCTGCAAGGCTTCTGGCTACACCTTCACCAGCTACTGGATGCACTGGGTGAAGCAGAGGCCTGGACGAGGCCTTGAGTGGATTGGAAGGATTGATCCTGATAGTGGTGGTACTAAATACAATGAGAAGTTCAAGAGCAAGGCCACACTGACTGTAGACAAACCCTCCAACACAGCCAACATGCAGCTCAGCAGCCTGACATCTGAAGACTCTGCGGTCTATTATTGTGTAAGAGAAGGGTGGGACGCCTGGTTTGTTTACTGGGGCCAAGGGACTCTGCTCACTGTCTCTGCA (配列番号32)
を含む。
CAGGTCCAACTGCAGCAGCCTGGGGCTGAACTTGTGAAGCCTGGGGCTTCAGTGAAGCTGTCCTGCAAGGCTTCTGGCTACACCTTCACCAGCTACTGGATACACTGGGTAAATCAGAGGCCTGGACGAGGCCTTGAGTGGATTGGAAGGATTGATCCTAATAGTGGTGGCACTAAGTACAATGAGAAGTTCAAGAGTAAGGCCACACTGACTGTAGACAAAACCTCCAGCACAGCCTACATGCAGTTCAGCAGCCTGACATCTGAGGACTCTGCGGTCTATTATTGTGCAAGAGAGGGGGAATTCGCCTGGTTTGCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCA (配列番号34)
を含む。
(i2')配列番号21、AAAGTTTCC、及び配列番号26のヌクレオチド配列、
(ii2')配列番号21、AAAGTTTTC、及び配列番号28(式中、N2はGを表す)のヌクレオチド配列、並びに
(iii2')配列番号23、AAAGTTTCC、及び配列番号28(式中、N2はTを表す)のヌクレオチド配列
のうちの1つに対応する少なくとも3つのヌクレオチド配列を含む。
GATGTTTTGATGACCCAAACTCCACTCTCCCTGCCTGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGCAGATCTAGTCAGAGCATTGTACATAGTAATGGAAACACCTATTTAGAATGGTACCTGCAGAAACCAGGCCAGTCTCCAAAGCTCCTGATCTACAAAGTTTCCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATTACTGCTTTCAAGGTTCACATGTTCCGTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA (配列番号36)
と少なくとも80%の同一性を有する少なくとも1つのヌクレオチド配列を含む。
GATGTTTTGATGACCCAAACTCCACTCTCCCTGCCTGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGCAGATCTAGTCAGAGCATTGTACATAGTAATGGAAACACCTATTTAGAATGGTACTTGCAGAAACCAGGCCAGTCTCCAAAGCTCCTGATCTACAAAGTTTTCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATTACTGCTTTCAAGGTTCACATGTTCCGCTCACGTTCGGTGCTGGGACCAAGCTGGAGCTGAAACGG (配列番号38)
を含む。
GATGTTTTGATGACCCAAACTCCACTCTCCCTGCCTGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGCAGATCTAGTCAGAACATTGTCCATAGTAATGGATACACCTATTTAGAATGGTACCTGCAGAAACCAGGCCAGTCTCCAAAGCTCCTGATCTACAAAGTTTCCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATTACTGCTTTCAAGGTTCACATGTTCCTCTCACGTTCGGCTCGGGGACAAAGTTGGAAATAAAACGG (配列番号40)
を含む。
a)本発明による宿主生物、特に単細胞宿主生物を培養培地中で適切な条件下で培養すること、
b)前記培養宿主生物の培養培地又は前記培養宿主生物から前記抗体を回収すること
を含む。
a1)生物学的試料を本発明による化合物と接触させること、
b1)前記化合物と前記エンドセリン受容体サブタイプBとの間の可能性のある複合体を検出すること
で構成される方法に関する。
a1')対象の生物学的試料を本発明による化合物と接触させる工程、
b1')容易に検出可能な基によって放出されたシグナルを検出する工程、及び
c1')工程(b1')で検出されたシグナルに基づいて、前記対象におけるがんの存在又は非存在を判定する工程
を含む。
I.1.免疫化
本発明者らの研究室で開発されたいわゆる「遺伝子免疫化」戦略は、ETB-Rを過剰発現する細胞の注射として、DNA注射とタンパク質追加免疫とを組み合わせることで構成される(Allardら、2011、「Electroporation-aided DNA immunisation generates polyclonal antibodies against the native conformation of human endothelin B receptor」、DNA and Cell Biology、30巻、727~737頁)。
得られたハイブリドーマを、最初に、陰性対照として無関係の受容体NK1を発現するCHO細胞(CHO-WT)と共に、ETB-Rを安定に発現するCHO細胞に対するELISAによってスクリーニングした。
Rendomab-B49、Rendomab-B41及びRendomab-B36を精製後、それらの生化学的特性の特徴付けを行った。
III.1.プロトコール
細胞をニューロスフェア(懸濁培養)又はポリDリジン/ラミニンで覆われたスライドガラスに接着させて培養する。次いで細胞を4%パラホルムアルデヒド溶液により室温で15分間結合させ、次いでPBS(SigmaAldrich社)で2回洗浄する。非特異的部位をブロックし、PBS溶液+5%ロバ血清+0.1%Tritonによって、30分間、細胞を透過性にする。
Rendomab-B49、Rendomab-B41及びRendomab-B36のナノモル範囲に近い親和性、及びヒトエンドセリン受容体サブタイプBに対するそれらの排他的特異性を図1に示す。
Rendomab-B1の重鎖及び軽鎖をコードする核の前駆体のクローニングは、キット「Gene-Elute/総RNA」(Sigma社)及び「RACE-PCR」(Invitrogen社)を用いて行った。
V.1.材料及び方法
ETB-R表面でのRendomab-B49、Rendomab-B41及びRendomab-B36によって認識されるエピトープのマッピングは、MontpellierにあるUMR3145「SysDiag」CNRS/BioRad社(Dr. Claude Granier)内で開発されたプロトコールと連携して及びそれに従って「Pep-スキャン」技術によって行われた。ヒトエンドセリン受容体サブタイプBの配列は、以下のアミノ酸配列:
MQPPPSLCGRALVALVLACGLSRIWGEERGFPPDRATPLLQTAEIMTPPTKTLWPKGSNASLARSLAPAEVPKGDRTAGSPPRTISPPPCQGPIEIKETFKYINTVVSCLVFVLGIIGNSTLLRIIYKNKCMRNGPNILIASLALGDLLHIVIDIPINVYKLLAEDWPFGAEMCKLVPFIQKASVGITVLSLCALSIDRYRAVASWSRIKGIGVPKWTAVEIVLIWVVSVVLAVPEAIGFDIITMDYKGSYLRICLLHPVQKTAFMQFYKTAKDWWLFSFYFCLPLAITAFFYTLMTCEMLRKKSGMQIALNDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTLYNQNDPNRCELLSFLLVLDYIGINMASLNSCINPIALYLVSKRFKNCFKSCLCCWCQSFEEKQSLEEKQSCLKFKANDHGYDNFRSSNKYSSS (配列番号42)
を示す。
- エタノール浴中で膜を加湿する。
- 25mlのTBS緩衝液(50mMトリス、150mM NaCl、pH7.4)中、室温で10分間撹拌しながら3回洗浄する。
- 25mlの飽和緩衝液(TBS、5%脱脂乳粉末、0.1%Tween20)を用いて室温で30分間撹拌しながら膜を飽和させる。
- 最終濃度1μg/mlのRendomab-B49抗体を含有する25mlの飽和緩衝液と4℃で一晩撹拌しながらインキュベートする。
- TBS緩衝液で3回短時間洗浄し(30秒)、次いで25mlのTBST緩衝液(TBST=TBS+0.1%Tween20)で10分間撹拌しながら3回洗浄する。
- 1/5,000に希釈したヤギ抗マウス二次抗体を含有する25mlの飽和緩衝液と室温で30分間撹拌しながらインキュベートする。
- TBS緩衝液で3回短時間洗浄し(30秒)、次いで25mlのTBST緩衝液で10分間撹拌しながら3回洗浄する、
- Pierce(Pierce ECL Plus Western Blotting Ref:32132)からの顕示溶液中に5分間浸漬し、BioRad社のシステムChemiDoc(商標)による自動モードでのシグナル取得によって膜を顕示させる。
Rendomab-B49のエピトープ分析の結果を図8に示す。高強度でハイブリダイズするペプチド配列は、C5、C6、C7、C8、C9及びC10ペプチドである(図8A)。
Claims (20)
- エンドセリン受容体サブタイプBに対する抗体であって、
- CDR1(以下CDR1Hという)、CDR2(以下CDR2Hという)及びCDR3(以下CDR3Hという)を含む重鎖可変領域であって、CDR1H、CDR2H及びCDR3Hのアミノ酸配列で形成される順序で並べられた配置が、以下のアミノ酸配列:GYTFISYWIDPDSGGTAREGDYAWFAY(配列番号1)と少なくとも80%の同一性を示す、重鎖可変領域、及び
- CDR1(以下CDR1Lという)、CDR2(以下CDR2Lという)及びCDR3(以下CDR3Lという)を含む軽鎖可変領域であって、CDR1L、CDR2L及びCDR3Lのアミノ酸配列で形成される順序で並べられた配置が、以下のアミノ酸配列:QSIVHSNGNTYKVSFQGSHVPWT(配列番号2)と少なくとも80%の同一性を示す、軽鎖可変領域
を含む、抗体、そのフラグメント又は誘導体。 - i1)
- アミノ酸配列がGYTFISYW(配列番号5)であるCDR1H、
- アミノ酸配列がIDPDSGGT(配列番号10)であるCDR2H、及び
- アミノ酸配列がAREGDYAWFAY(配列番号15)であるCDR3H
を含む重鎖可変領域、
又は
ii1)
- アミノ酸配列がGYTFTSYW(配列番号7)であるCDR1H、
- アミノ酸配列がIDPDSGGT(配列番号10)であるCDR2H、及び
- アミノ酸配列がVREGWDAWFVY(配列番号17)であるCDR3H
を含む重鎖可変領域、
又は
iii1)
- アミノ酸配列がGYTFTSYW(配列番号7)であるCDR1H、
- アミノ酸配列がIDPNSGGT(配列番号12)であるCDR2H、及び
- アミノ酸配列がAREGEFAWFAY(配列番号19)であるCDR3H
を含む重鎖可変領域
を含む、請求項1に記載の抗体。 - アミノ酸配列が以下の配列:
QVQLQQPGAALVKPGASVKLSCKASGYTFISYWMLWVKQRPGRGLEWIGRIDPDSGGTKYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCAREGDYAWFAYWGQGTLVPVSA (配列番号31)
と少なくとも80%の同一性を示す重鎖可変領域を含む、請求項1又は2に記載の抗体。 - i2)
- アミノ酸配列がQSIVHSNGNTY(配列番号22)であるCDR1L、
- アミノ酸配列がKVSであるCDR2L、
- アミノ酸配列がFQGSHVPWT(配列番号27)であるCDR3L
を含む軽鎖可変領域、
又は
ii2)
- アミノ酸配列がQSIVHSNGNTY(配列番号22)であるCDR1L、
- アミノ酸配列がKVFであるCDR2L、
- アミノ酸配列がFQGSHVPLT(配列番号29)であるCDR3L
を含む軽鎖可変領域、
又は
iii2)
- アミノ酸配列がQNIVHSNGYTY(配列番号24)であるCDR1L、
- アミノ酸配列がKVSであるCDR2L、
- アミノ酸配列がFQGSHVPLT(配列番号29)であるCDR3L
を含む軽鎖可変領域
を含む、請求項1から3のいずれか一項に記載の抗体。 - アミノ酸配列が以下の配列:
DVLMTQTPLSLPVSLGDQASISCRSSQSIVHSNGNTYLEWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGGGTKLEIK (配列番号37)
と少なくとも80%の同一性を示す軽鎖可変領域を含む、請求項1から4のいずれか一項に記載の抗体。 - IgG1/カッパ型又はIgG3/カッパ型免疫グロブリンである、請求項1から5のいずれか一項に記載の抗体。
- モノクローナルである、請求項1から6のいずれか一項に記載の抗体。
- 2016年5月19日に受託番号CNCM I-5084でCNCMに寄託されたハイブリドーマ、2016年6月7日に受託番号CNCM I-5104でCNCMに寄託されたハイブリドーマ及び2016年6月7日に受託番号CNCM I-5103でCNCMに寄託されたハイブリドーマから選択されるハイブリドーマから得られたモノクローナルマウス抗体である、請求項1から7のいずれか一項に記載の抗体。
- キメラ抗体である、請求項1から8のいずれか一項に記載の抗体。
- ヒト化抗体である、請求項1から9のいずれか一項に記載の抗体。
- 2016年5月19日に受託番号CNCM I-5084でCNCMに寄託されたハイブリドーマ、2016年6月7日に受託番号CNCM I-5104でCNCMに寄託されたハイブリドーマ及び2016年6月7日に受託番号CNCM I-5103でCNCMに寄託されたハイブリドーマから選択されるハイブリドーマ。
- 以下の異なるポリヌクレオチド:
α)請求項1から10のいずれか一項で定義された抗体をコードするポリヌクレオチド、
β)(α)で定義されたポリヌクレオチドに相補的なポリヌクレオチド、
γ)高ストリンジェンシー条件下で(α)及び(β)で定義されたポリヌクレオチドとハイブリダイズ可能な少なくとも18ヌクレオチドのポリヌクレオチド
から選択される、単離されたポリヌクレオチド。 - 請求項12に記載の少なくとも1つのポリヌクレオチドを含有するクローニング及び/又は発現ベクター。
- 請求項12に記載のポリヌクレオチド又は請求項13に記載のベクターによって形質転換された又はそれを含む宿主生物。
- 細胞毒性基、容易に検出可能な基、又はエフェクター基からなる群から選択される要素と結合した、請求項1から10のいずれか一項に記載の抗体を含む化合物。
- 医薬で使用するための、請求項1から10のいずれか一項に記載の抗体、請求項12に記載のポリヌクレオチド又は請求項15に記載の化合物。
- 活性成分として、請求項1から10のいずれか一項に記載の抗体、請求項12に記載のポリヌクレオチド又は請求項15に記載の化合物、及び薬学的に許容されるビヒクルを含む医薬組成物。
- エンドセリン、及びエンドセリン受容体サブタイプBのようなその受容体の少なくとも1つを含む軸の直接的な又は別の生理的経路が付随する機能不全が関与する障害又は状態の治療及び/又は予防における使用のための、請求項1から10のいずれか一項に記載の抗体、請求項12に記載のポリヌクレオチド、請求項15に記載の化合物又は請求項17に記載の医薬組成物。
- 前記障害又は前記状態が、がんである、請求項18に記載の使用のための抗体、ポリヌクレオチド、化合物又は医薬組成物。
- インビトロで膠芽腫のようながんを診断する方法であって、
a1')対象から採取した生物学的試料を請求項15に記載の化合物と接触させる工程、
b1')容易に検出可能な基によって放出されたシグナルを検出する工程、及び
c1')工程(b1')で検出されたシグナルに基づいて、前記対象におけるがんの存在又は非存在を判定する工程
を含む方法。
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FR1655915A FR3053042B1 (fr) | 2016-06-24 | 2016-06-24 | Anticorps dirige contre le sous-type b des recepteurs aux endothelines et ses utilisations |
FR1655915 | 2016-06-24 | ||
PCT/EP2017/065442 WO2017220739A1 (en) | 2016-06-24 | 2017-06-22 | Antibody directed against the endothelin receptor beta sub-type |
JP2018567052A JP2019528041A (ja) | 2016-06-24 | 2017-06-22 | エンドセリン受容体ベータサブタイプに対する抗体 |
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JP2022066434A Pending JP2022095888A (ja) | 2016-06-24 | 2022-04-13 | エンドセリン受容体ベータサブタイプに対する抗体 |
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EP (1) | EP3458480B1 (ja) |
JP (2) | JP2019528041A (ja) |
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CN116444653B (zh) * | 2023-03-09 | 2024-03-15 | 中国农业科学院上海兽医研究所(中国动物卫生与流行病学中心上海分中心) | 一株阻断性非洲猪瘟病毒单克隆抗体杂交瘤细胞株的制备与应用 |
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US20070292409A1 (en) * | 2004-06-17 | 2007-12-20 | The Regents Of The University Of California | Methods and Compositions for Producing Insulin Sensitization |
US20100003240A1 (en) * | 1999-05-04 | 2010-01-07 | New York University | Cancer treatment with endothelin receptor antagonists |
JP2012111706A (ja) * | 2010-11-24 | 2012-06-14 | Sekisui Chem Co Ltd | モノクローナル抗体、並びに、ハイブリドーマ |
JP2014532648A (ja) * | 2011-10-28 | 2014-12-08 | ジェネンテック, インコーポレイテッド | メラノーマ治療の治療の組み合わせ及び方法 |
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US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
FR2965810B1 (fr) * | 2010-10-06 | 2012-12-28 | Commissariat Energie Atomique | Anticorps antagoniste du sous-type b des recepteurs aux endothelines et ses utilisations |
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US20100003240A1 (en) * | 1999-05-04 | 2010-01-07 | New York University | Cancer treatment with endothelin receptor antagonists |
US20070292409A1 (en) * | 2004-06-17 | 2007-12-20 | The Regents Of The University Of California | Methods and Compositions for Producing Insulin Sensitization |
JP2012111706A (ja) * | 2010-11-24 | 2012-06-14 | Sekisui Chem Co Ltd | モノクローナル抗体、並びに、ハイブリドーマ |
JP2014532648A (ja) * | 2011-10-28 | 2014-12-08 | ジェネンテック, インコーポレイテッド | メラノーマ治療の治療の組み合わせ及び方法 |
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EP3458480B1 (en) | 2021-01-27 |
FR3053042A1 (fr) | 2017-12-29 |
HUE053695T2 (hu) | 2021-07-28 |
EP3458480A1 (en) | 2019-03-27 |
JP2019528041A (ja) | 2019-10-10 |
PT3458480T (pt) | 2021-04-28 |
ES2865300T3 (es) | 2021-10-15 |
PL3458480T3 (pl) | 2021-09-20 |
WO2017220739A1 (en) | 2017-12-28 |
DK3458480T3 (da) | 2021-04-19 |
FR3053042B1 (fr) | 2018-08-10 |
US20190185574A1 (en) | 2019-06-20 |
US11312780B2 (en) | 2022-04-26 |
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