JPH11503918A - 免疫グロブリンの可変断片−治療又は獣医学上の目的のための使用 - Google Patents
免疫グロブリンの可変断片−治療又は獣医学上の目的のための使用Info
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. −決定された抗原で予め免疫されたラクダ科の動物の血液リンパ球又は他 の適切な細胞を、それらのmRNAを得るために処理し、 −得られたmRNAから開始してcDNAの第1の鎖を合成し、 −得られたcDNAを、少なくとも2種類の異なるプライマーオリゴヌクレオチ ドと、該cDNAに含まれる少なくとも2種類の相補性ヌクレオチド配列とのそ れらのハイブリダイゼーションを可能にする条件で接触させ、ここで、該プライ マーはヌクレオチド配列5’−GATGTGCAGCTGCAGGCGTCTG G(A/G)GGAGG−3’を有するBACKプライマー(back p1) 及びヌクレオチド配列5’−CGCCATCAAGGTACCGTTGA−3’ 又は5’−CGCCATCAAGGTACCAGTTGA−3’に応答するFO Rプライマー(for p1)を含み、 −該プライマーとハイブリダイズしたヌクレオチド配列の間に位置するDNA断 片を増幅させ、かつ −異なるサイズ順のバンドであって、 4本鎖免疫グロブリンの可変重鎖(VH)、CH1、ヒンジ及びCH2領域の 一部の増幅産物である750塩基対近辺のバンド、 ラクダ2本鎖免疫グロブリンIgG2の可変重鎖(VHH)、長ヒンジ、及びC H2の一部の増幅産物である620塩基対近辺のバンド、 ラクダ2本鎖免疫グロブリンIgG3の可変重鎖(VHH)、短ヒンジ、及びC H2の一部の増幅産物である550塩基対近辺のバンド を含むバンドに相当する増幅されたDNAを回収し、 −最も短い2つのバンドを、アガロースゲルから、例えばジーン・クリーン(G ene Clean)によって精製し、 −VHH断片をコードするヌクレオチド配列を含む増幅DNA断片を回収し、 −該増幅産物を、該増幅断片内及び/又はヌクレオチドプライマー内に標的部位 を有する制限酵素、例えばPstI及びBstEIIで消化し、 −消化された増幅DNA断片を回収し、 −該増幅DNA断片を、ファスミドベクター、例えばpHEN 4ベクターに、得られる組換えベクターがホスト細胞の形質転換に用いられる場 合に該増幅断片の発現が可能となる条件でライゲートし、 −決定された細菌ホスト細胞、例えば大腸菌細胞を得られた組換えファスミドベ クターで形質転換し、該細胞を選択培地において成長させてライブラリーを形成 し、 −適当な選択培地で培養した後に得られる組換えホスト細胞のライブラリーを、 バクテリオファージ、例えばM13K07バクテリオファージを用いて感染させ て組換えファージミドビリオンを得、 −該組換えホスト細胞を、組換えファスミドを有する組換えファージミドビリオ ン粒子、例えばM13ビリオン中にパッケージ化されているpHEN4ファスミ ドの分泌を可能にする条件でインキュベートし、 −該組換えファージミドビリオンを単離及び濃縮し、 −該ファージミドビリオンを、予め固定化されている関心のある抗原を用いる数 回のパニングに、該固定化抗原へのファージミドビリオンの吸着を可能にする条 件で供し、 −吸着したファージミドビリオンを溶離してそれらを適切な細 胞で成長させ、 −該細胞をヘルパーバクテリオファージに感染させることにより該ファージミド ビリオンを増幅させ、 −該ビリオンを回収し、例えばELISAにより、関心のある抗原に対する結合 活性についてそれらを試験し、 −適切な結合活性を有するファージミドビリオンを回収し、 −該ファスミドベクターに含まれ、かつ該ファージミドビリオンで適切な結合活 性を有するVHHアミノ酸配列として発現することが可能なヌクレオチド配列を単 離する、 方法によって得ることが可能なヌクレオチド配列によってコードされる、軽鎖を 欠く免疫グロブリンの重鎖の可変断片(VHH)。 2. 請求の範囲第1項に開示されるものに従う方法によって得ることができる ヌクレオチド配列によってコードされる、免疫グロブリンの重鎖の可変断片(VHH )であって、請求の範囲第1項の620塩基対及び550塩基対のPCR産物 の再増幅工程をそれぞれ以下のヌクレオチド配列を有するオリゴヌクレオチドプ ライマーを用いて行う可変断片。 3. 請求の範囲第1項に開示されるものに従う方法によって得ることができる ヌクレオチド配列によってコードされる、免疫グロブリンの重鎖の可変断片(VHH )であって、mRNAから得られるcDNAの増幅工程をそれぞれ以下のヌク レオチド配列を有するオリゴヌクレオチドプライマーを用いて行う可変断片。 4. ラクダ科の動物の血液リンパ球又は他の適切な細胞から得ることができる ヌクレオチド配列によってコードされる、請求の範囲第1項又は第2項のいずれ か1項による軽鎖を欠く免 疫グロブリンの重鎖の可変断片であって、該ラクダ科の動物が、それらの血液リ ンパ球又は他の適切な細胞の処理に先立って、決定された抗原で免疫されている 可変断片。 5. ラクダ科の動物の血液リンパ球又は他の適切な細胞から得ることができる ヌクレオチド配列によってコードされる、請求の範囲第1項ないし第4項のいず れか1項による免疫グロブリンの重鎖の可変断片であって、該ラクダ科の動物が 細菌の毒素又はそれに相当する類毒素である抗原で予め免疫されていることを特 徴とする可変断片。 6. ラクダ科の動物の血液リンパ球又は他の適切な細胞から得ることができる ヌクレオチド配列によってコードされる、請求の範囲第5項による免疫グロブリ ンの重鎖の可変断片であって、前記抗原がクロストリジウム・テタニの破傷風毒 素である可変断片。 7. 請求の範囲第5項によるヌクレオチド配列によってコードされる免疫グロ ブリンの重鎖の可変断片であって、前記抗原がクロストリジウム、特にはクロス トリジウム・ボツリヌムもしくはクロストリジウム・ペルフリンゲンス、スタフ ィロコッカス、シュードモナス、パスツレラ、エルシニア、バチルス・ アントラシス、ナイセリア、ビブリオ、特にはビブリオ・コレラ、腸内毒素大腸 菌、サルモネラ、赤痢菌、リステリアの細菌性毒素又は類毒素の中から選択され る細菌性毒素又は類毒素である可変断片。 8. ラクダ科の動物の血液リンパ球又は他の適切な細胞から得ることができる ヌクレオチド配列によってコードされる、請求の範囲第1項ないし第4項のいず れか1項による免疫グロブリンの重鎖の可変断片であって、該ラクダ科の動物が 動物の毒中に存在する抗原で免疫されている可変断片。 9. ヌクレオチド配列によってコードされる、請求の範囲第8項による免疫グ ロブリンの重鎖の可変断片であって、前記抗原がアネモネ、サンゴ、クラゲ、ク モ、ハチ、スズメバチ、サソリ、ビペリダエ、クロタリダエ、ラピダエ科に属す るものを含むヘビによって産生される毒素又は類毒素の中から選択される毒素又 は類毒素である可変断片。 10. 請求の範囲第1項ないし第9項のいずれか1項の方法によって得られる ヌクレオチド配列によってコードされる、重鎖免疫グロブリンの可変断片。 11. 以下のアミノ酸配列を有することを特徴とする免疫グ ロブリンの重鎖の可変断片。 (Glu/Asp)ValGlnLeuGlnAlaSerGlyGlyGly SerValGlnAlaGly(Gly/Gln)SerLeuArgLeu SerCysAla(Ala/Thr)SerGly(CDR1)Trp(Ph e /Tyr)ArgGlnAlaProGlyLysGlu(Arg/Cys)Glu (Gly/Leu)Val(Ser/Ala)(CDR2)Arg(Ph e/Leu)ThrIleSer(Arg/Leu/Gln)AspAsnAl aLysAsnThr(Val/Leu)TyrLeu(Gln/Leu)Me tAsnSerLeu(Lys/Glu)ProGluAspThrAla(V al/Met/Ile)TyrTyrCysAlaAla(CDR3)TrpG lyGlnGlyThrGlnValThrValSerSer又は (Glu/Asp)ValGlnLeuGlnAlaSerGlyGlyGly SerValGlnAlaGly(Gly/Gln)SerLeuArgLeu SerCysAla(Ala/Tlu)SerGly(Ala,Thr,Ser ,Ser/Tyr,Thr,Ile,Gly)(CDR1)Trp(P he /Tyr)ArgGlnAlaProGlyLysGlu(Arg/Cys )Glu(Gly/Leu)Val(Ser/Ala)(CDR2)Arg(P he/Leu)ThrIleSer(Arg/Leu/Gln)AspAsnA laLysAsnThr(Val/Leu)TyrLeu(Gln/Leu)M etAsnSerLeu(Lys/Glu)ProGluAspThrAla( Val/Met/Ile)TyrTyrCysAlaAla(CDR3)Trp GlyGlnGlyThrGlnValThrValSerSer (ここで、CDR1、CDR2及びCDR3はラクダ科の動物の免疫に用いられ る抗原の決定されたエピトープの認識をもたらす可変アミノ酸配列を表し、CD R1、CDR2及びCDR3配列は5ないし25個のアミノ酸残基を有し、好ま しくはCDR1は7ないし12個のアミノ酸残基を有し、CDR2は16ないし 21個のアミノ酸残基を有し、かつCDR3は7ないし25個のアミノ酸残基を 有する。) 12. 図15に示されるヌクレオチド配列のヌクレオチド400から始り、ヌ クレオチド479ないし495の間で終わる配列を含むヌクレオチド配列によっ てコードされるアミノ酸配 列。 13. 登録番号LMBP3247でBCCM/LMBPに寄託されている組換 えファスミドpHEN4−αTT2(WK6)中に存在するヌクレオチド配列に よってコードされる免疫グロブリンの重鎖の可変断片。 14. 以下のαTT1配列を含み、あるいは該配列に応答することを特徴とす る免疫グロブリンの重鎖の可変断片。 GluValGlnLeuGlnAlaSerGlyGlyGlySerVal GlnAlaGlyGlySerLeuArgLeuSerCysAlaAla SerGlyGlyGlnThrPheAspSerTyrAlaMetAla TrpPheArgGlnAlaProGlyLysGluCysGluLeu ValSerSerIleIleGlyAspAspAsnArgAsnTyr AlaAspSerValLysGlyArgPheThrIleSerArg AspAsnAlaLysAsnThrValTyrLeuGlnMetAsp ArgLeuAsnProGluAspThrAlaValTyrTyrCys AlaGlnLeuGlySerAlaArgSerAlaMetTyrCys AlaGlyGlnGly ThrGlnValThrValSerSer 15. 以下のαTT2アミノ酸配列を含み、あるいは該配列に応答することを 特徴とする免疫グロブリンの重鎖の可変断片。 GluValGlnLeuGlnAlaSerGlyGlyGlySerVal GlnAlaGlyGlySerLeuArgLeuSerCysThrAla AlaAsnTyrAlaPheAspSerLysThrValGlyTrp PheArgGlnValProGlyLysGluArgGluGlyVal AlaGlyIleSerSerGlyGlySerThrThrAlaTyr SerAspSerValLysGlyArgTyrThrValSerLeu GluAsnAlaLysAsnThrValTyrLeuLeuIleAsp AsnLeuGlnProGluAspThrAlaIleTyrTyrCys AlaGlyValSerGlyTrpArgGlyArgGlnTrpLeu LeuLeuAlaGluThrTyrArgPheTrpGlyGlnGly ThrGlnValThrValSerSer 16. 請求の範囲第1項ないし第15項のいずれか1項による軽鎖を欠く免疫 グロブリンの重鎖の可変断片であって、同じ 抗原特異性を有するVHH断片の少なくとも1つとさらに結合していることを特徴 とする、請求の範囲第1項ないし第15項のいずれか1項による免疫グロブリン の重鎖の可変断片。 17. 同じ特異性を有するVHH断片の二量体である、請求の範囲第16項によ る免疫グロブリンの可変断片の二価単特異的構築物。 18. 前記VHH断片が軽鎖を欠く免疫グロブリンのヒンジドメインのヒンジア ミノ酸配列で互いに結合している、請求の範囲第17項による二価単特異的構築 物。 19. 請求の範囲第1項ないし第15項のいずれか1項による軽鎖を欠く免疫 グロブリンの重鎖の可変断片であって、異なる抗原特異性を有するVHH断片の少 なくとも1つとさらに結合していることを特徴とする、請求の範囲第1項ないし 第15項のいずれか1項による免疫グロブリンの重鎖の可変断片。 20. 請求の範囲第19項による可変断片が、軽鎖を欠く免疫グロブリンのヒ ンジドメインのアミノ酸配列の一部であって、少なくとも該ヒンジドメインの末 端のシステイン残基をコードするコドンを欠く一部で互いに結合している多価多 特異的構築物。 21. 少なくとも2つの、異なる抗原及び/又はエピトープ特異性を有するVHH 断片を含む、請求の範囲第20項による多価多特異的構築物。 22. ヒンジドメインの配列が、図15の配列に示されるように、400位か ら始り、かつ489位ないし495位の間で終わるアミノ酸配列を含み、もしく はそれに相当する、請求の範囲第16項ないし第18項のいずれか1項による構 築物。 23. ヒンジド領域の一部の配列が、図15の配列に示されるように、400 位から始り、かつ479位ないし486位の間で終わるアミノ酸配列を含み、も しくはそれに相当する、請求の範囲第19項ないし第22項のいずれか1項によ る構築物。 24. 請求の範囲第1項ないし第6項又は第9項のいずれか1項による免疫可 変断片あるいは請求の範囲第17項、第18項、第20項ないし第23項のいず れか1項による構築物を生理学的に許容し得る担体及び/又は補助剤との混合状 態で含有していることを特徴とする医薬組成物。 25. 感染又はクロストリジウム、特にはクロストリジウム・ボツリヌムもし くはクロストリジウム・ペルフリンゲンス、スタフィロコッカス、シュードモナ ス、パスツレラ、エルシニア、 バチルス・アントラシス、ナイセリア、ビブリオ、特にはビブリオ・コレラ、腸 内毒素大腸菌、サルモネラ、赤痢菌、リステリア又はアネモネ、サンゴ、クラゲ 、クモ、ハチ、スズメバチ、サソリ、ビペリダエ、クロタリダエ、ラピダエ科に 属するものを含むヘビのもののような急性毒素による中毒の受動免疫化による治 療のための、請求の範囲第16項による医薬組成物。 26. 感染又はクロストリジウム、特にはクロストリジウム・ボツリヌムもし くはクロストリジウム・ペルフリンゲンス、スタフィロコッカス、シュードモナ ス、パスツレラ、エルシニア、バチルス・アントラシス、ナイセリア、ビブリオ 、特にはビブリオ・コレラ、腸内毒素大腸菌、サルモネラ、赤痢菌、リステリア 又はアネモネ、サンゴ、クラゲ、クモ、ハチ、スズメバチ、サソリ、ビペリダエ 、クロタリダエ、ラピダエ科に属するものを含むヘビのもののような毒素による 急性中毒の受動免疫化による治療に用いるための、請求の範囲第2項ないし第6 項又は第19項のいずれか1項による免疫グロブリン可変断片あるいは請求の範 囲第17項、第18項、第20項ないし第23項のいずれか1項による構築物。 27. −決定された抗原で予め免疫されたラクダ科の動物の 血液リンパ球又は他の適切な細胞を、それらのmRNAを得るために処理し、 −得られたmRNAから開始してcDNAの第1の鎖を合成し、 −得られたcDNAを、少なくとも2種類の異なるプライマーオリゴヌクレオチ ドと、該cDNAに含まれる少なくとも2種類の相補性ヌクレオチド配列とのそ れらのハイブリダイゼーションを可能にする条件で接触させ、ここで、該プライ マーはヌクレオチド配列5’−GATGTGCAGCTGCAGGCGTCTG G(A/G)GGAGG−3’を有するBACKプライマー(back p1) 及びヌクレオチド配列5’−CGCCATCAAGGTACCGTTGA−3’ 又は5’−CGCCATCAAGGTACCAGTTGA−3’に応答するFO Rプライマー(forp1)を含み、 −該プライマーとハイブリダイズしたヌクレオチド配列の間に位置するDNA断 片を増幅させ、かつ −異なるサイズ順のバンドであって、 4本鎖免疫グロブリンの可変重鎖(VH)、CH1、ヒンジ及びCH2領域の 一部の増幅産物である750塩基対近辺のバンド、 ラクダ2本鎖免疫グロブリンIgG2の可変重鎖(VHH)、長ヒンジ、及びC H2の一部の増幅産物である620塩基対近辺のバンド、 ラクダ2本鎖免疫グロブリンIgG3の可変重鎖(VHH)、短ヒンジ、及びC H2の一部の増幅産物である550塩基対近辺のバンド を含むバンドに相当する増幅されたDNAを回収し、 −620及び550塩基対の最も短い2つのバンドを、アガロースゲルから、例 えばジーン・クリーン(Gene Clean)によって精製し、 −VHH断片をコードするヌクレオチド配列を含む増幅DNA断片を回収し、 −該増幅産物を、該増幅断片内及び/又はヌクレオチドプライマー内に標的部位 を有する制限酵素、例えばPstI及びBstEIIで消化し、 −消化された増幅DNA断片を回収し、 −該増幅DNA断片を、ファスミドベクター、例えばpHEN4ベクターに、得 られる組換えベクターがホスト細胞の形質転換に用いられる場合に該増幅断片の 発現が可能となる条件でラ イゲートし、 −決定された細菌ホスト細胞、例えば大腸菌細胞を得られた組換えファスミドベ クターで形質転換し、該細胞を選択培地において成長させてライブラリーを形成 し、 −適当な選択培地で培養した後に得られる組換えホスト細胞のライブラリーを、 バクテリオファージ、例えばM13K07バクテリオファージを用いて感染させ て組換えファージミドビリオンを得、 −該バクテリオファージが吸着している組換えホスト細胞を回収し、 −該組換えホスト細胞を、組換えファスミドを有する組換えファージミドビリオ ン粒子、例えばM13ビリオン中にパッケージ化されているpHEN4ファスミ ドの分泌を可能にする条件でインキュベートし、 −該組換えファージミドビリオンを単離及び濃縮し、 −該ファージミドビリオンを、予め固定化されている関心のある抗原を用いる数 回のパニングに、該固定化抗原へのファージミドビリオンの吸着を可能にする条 件で供し、 −吸着したファージミドビリオンを溶離してそれらを適切な細 胞で成長させ、 −該細胞をヘルパーバクテリオファージに感染させることにより該ファージミド ビリオンを増幅させ、 −該ビリオンを回収し、例えばELISAにより、関心のある抗原に対する結合 活性についてそれらを試験し、 −適切な結合活性を有するファージミドビリオンを回収し、 −該ファスミドベクターに含まれ、かつ該ファージミドビリオンで適切な結合活 性を有するVHHアミノ酸配列として発現することが可能なヌクレオチド配列を単 離する、 方法によって得ることが可能な、免疫グロブリンの重鎖の可変断片(VHH)をコ ードするヌクレオチド配列。 28. クロストリジウム・テタニの破傷風毒素のエピトープに対する、軽鎖を 欠く免疫グロブリンの重鎖の可変断片VHHをコードするヌクレオチド配列であっ て、請求の範囲第14項又は第15項によるアミノ酸配列をコードすることを特 徴とするヌクレオチド配列。 29. クロストリジウム・テタニの破傷風毒素のエピトープに対する、軽鎖を 欠く免疫グロブリンの重鎖の可変断片VHHをコードするヌクレオチド配列であっ て、以下のヌクレオチド配 列のうちの1つを含むことを特徴とするヌクレオチド配列。 30. 図15のヌクレオチド配列のヌクレオチド440から始まり、かつヌク レオチド489ないしヌクレオチド495の間で終わるヌクレオチド配列、又は 請求の範囲第27項又は第28項のいずれか1項によるヌクレオチド配列との組 み合わせられている該ヌクレオチド配列。 31. 図15のヌクレオチド配列のヌクレオチド440から始り、かつヌクレ オチド479ないしヌクレオチド486の間で終わるヌクレオチド配列、又は請 求の範囲第27項又は第28項のいずれか1項によるヌクレオチド配列との組み 合わせられている該ヌクレオチド配列。 32. ホスト細胞における請求の範囲第28項ないし第31項のいずれか1項 によるヌクレオチド配列の発現産物。 33. 請求の範囲第20項ないし第23項のいずれか1項による構築物をコー ドするヌクレオチド配列。 34. 免疫グロブリンの重鎖の可変断片をコードする一価二特異的DNA構築 物の調製方法であって、 a)決定された抗原又はエピトープ特異性を有する可変VHH断片をコードする ヌクレオチド配列をリンカーヌクレオチド配列にライゲートしてVHH−リンカー 断片を形成する工程; b)VHH−リンカー断片をコードする形成されたヌクレオチド配列を、異なる 抗原及び/又はエピトープ特異性を有する別のVHH断片をコードするヌクレオチ ド配列にライゲートする工程; を包含し、 ここで、該リンカー配列はヒンジドメインの一部をコードするヌクレオチド配 列を含み、該ヒンジドメインは、特には該ヒンジドメイン内の最後のシステイン 残基間でのジスルフィド結合の形成によるVHH断片の二量体化の原因となるコド ンが欠失している方法。 35. 1以上の追加のライゲーション工程を含む請求の範囲第34項による方 法。 36. 前記ヒンジドメインの一部をコードする配列が、図15の配列上のヌク レオチド配列のヌクレオチド400から始り、かつヌクレオチド479ないし4 86の間のヌクレオチドの1つで終わるヌクレオチド配列を含み、もしくはそれ に相当する、請求の範囲第34項又は第35項による方法。
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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US9320792B2 (en) | 2002-11-08 | 2016-04-26 | Ablynx N.V. | Pulmonary administration of immunoglobulin single variable domains and constructs thereof |
US9371381B2 (en) | 2002-11-08 | 2016-06-21 | Ablynx, N.V. | Single domain antibodies directed against tumor necrosis factor-alpha and uses therefor |
JP2021516682A (ja) * | 2018-03-13 | 2021-07-08 | スミヴェット ビー.ブイ.Smivet B.V. | 破傷風神経毒素に結合する単一ドメイン抗体 |
Families Citing this family (343)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6765087B1 (en) | 1992-08-21 | 2004-07-20 | Vrije Universiteit Brussel | Immunoglobulins devoid of light chains |
EP0739981A1 (en) * | 1995-04-25 | 1996-10-30 | Vrije Universiteit Brussel | Variable fragments of immunoglobulins - use for therapeutic or veterinary purposes |
AU740043B2 (en) * | 1996-06-27 | 2001-10-25 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw | Recognition molecules interacting specifically with the active site or cleft of a target molecule |
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WO1999037681A2 (en) * | 1998-01-26 | 1999-07-29 | Unilever Plc | Method for producing antibody fragments |
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GB2398242B (en) * | 1999-09-10 | 2004-10-20 | Pasteur Institut | Bacillus anthracis strain |
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US7943129B2 (en) * | 2000-05-26 | 2011-05-17 | National Research Council Of Canada | Single-domain brain-targeting antibody fragments derived from llama antibodies |
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US7754208B2 (en) * | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
US7829084B2 (en) | 2001-01-17 | 2010-11-09 | Trubion Pharmaceuticals, Inc. | Binding constructs and methods for use thereof |
US20040058445A1 (en) * | 2001-04-26 | 2004-03-25 | Ledbetter Jeffrey Alan | Activation of tumor-reactive lymphocytes via antibodies or genes recognizing CD3 or 4-1BB |
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US20030219436A1 (en) * | 2002-03-15 | 2003-11-27 | Ledbetter Jeffrey A. | Compositions and methods to regulate an immune response using CD83 gene expressed in tumors and using soluble CD83-Ig fusion protein |
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US9321832B2 (en) | 2002-06-28 | 2016-04-26 | Domantis Limited | Ligand |
US20060228355A1 (en) | 2003-11-07 | 2006-10-12 | Toon Laeremans | Camelidae single domain antibodies vhh directed against epidermal growth factor receptor and uses therefor |
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US8105592B2 (en) | 2004-11-25 | 2012-01-31 | Vhsquared Limited | Heavy chain and single domain antibodies |
FR2879605B1 (fr) | 2004-12-16 | 2008-10-17 | Centre Nat Rech Scient Cnrse | Production de formats d'anticorps et applications immunologiques de ces formats |
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 |
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EP2007814A2 (en) | 2005-05-20 | 2008-12-31 | Ablynx N.V. | Single domain vhh antibodies against von willebrand factor |
US7875465B2 (en) * | 2005-05-31 | 2011-01-25 | Canon Kabushiki Kaisha | Target substance capturing molecule |
DK2298815T3 (en) | 2005-07-25 | 2015-06-15 | Emergent Product Dev Seattle | B-CELL REDUCTION USING CD37 SPECIFIC AND CD20 SPECIFIC BINDING MOLECULES |
BRPI0615547A2 (pt) * | 2005-08-19 | 2011-05-24 | Unilever Nv | produto alimentìcio, preparação farmacêutica, método de fabricação de produto alimentìcio, método de fabricação de preparação farmacêutica, uso do produto alimentìcio, usos da preparação farmacêutica, método de fornecimento de benefìcios à saúde do intestino e implementos de liberação para uso com produto alimentìcio |
US20100226920A1 (en) * | 2006-03-27 | 2010-09-09 | Ablynx N.V. | Medical delivery device for therapeutic proteins based on single domain antibodies |
BRPI0711119A2 (pt) | 2006-05-02 | 2011-08-30 | Actogenix Nv | administração microbiana de peptìdeos intestinais associados à obesidade |
SG172698A1 (en) | 2006-06-12 | 2011-07-28 | Trubion Pharmaceuticals Inc | Single-chain multivalent binding proteins with effector function |
US8703136B2 (en) | 2006-10-10 | 2014-04-22 | Regenesance B.V. | Complement inhibition for improved nerve regeneration |
AU2007336242B2 (en) | 2006-12-19 | 2012-08-30 | Ablynx N.V. | Amino acid sequences directed against GPCRs and polypeptides comprising the same for the treatment of GPCR-related diseases and disorders |
EP2102244A2 (en) | 2006-12-19 | 2009-09-23 | Ablynx N.V. | Amino acid sequences directed against a metalloproteinase from the adam family and polypeptides comprising the same for the treatment of adam-related diseases and disorders |
PL2308514T3 (pl) | 2007-03-23 | 2013-11-29 | To Bbb Holding B V | Koniugaty do ukierunkowanego dostarczania leku poprzez barierę krew-mózg |
CA2691940C (en) | 2007-07-03 | 2018-03-06 | Joost Alexander Kolkman | Methods for providing improved immunoglobulin sequences |
EP2217625B1 (en) | 2007-11-08 | 2021-08-04 | Precision Biologics, Inc. | Recombinant monoclonal antibodies and corresponding antigens for colon and pancreatic cancers |
US20110053865A1 (en) | 2007-11-27 | 2011-03-03 | Ablynx N.V. | Amino acid sequences directed against heterodimeric cytokines and/or their receptors and polypeptides comprising the same |
CA2713281C (en) | 2008-01-31 | 2019-10-15 | Dimiter S. Dimitrov | Engineered antibody constant domain molecules |
US20110091462A1 (en) | 2008-03-05 | 2011-04-21 | Ablynx N.V. | Novel antigen binding dimer-complexes, methods of making and uses thereof |
GB0809069D0 (en) | 2008-05-19 | 2008-06-25 | Univ Leuven Kath | Gene signatures |
US8557965B2 (en) | 2008-04-07 | 2013-10-15 | Ablynx N.V. | Single variable domains against notch pathway members |
ES2368700T3 (es) | 2008-04-11 | 2011-11-21 | Emergent Product Development Seattle, Llc | Agente inmunoterapéutico para cd37 y combinación con un agente quimioterapéutico bifuncional del mismo. |
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 |
GB0809474D0 (en) * | 2008-05-27 | 2008-07-02 | Prendergast Patrick T | Comosition and method for teh assay and treatment of anthrax |
WO2009150539A2 (en) * | 2008-06-10 | 2009-12-17 | Institut Pasteur | Variable domains of camelid heavy-chain antibodies directed against androctonus autralis hector toxins |
EP2362767B1 (en) | 2008-10-29 | 2017-12-06 | Ablynx N.V. | Formulations of single domain antigen binding molecules |
MX2011004558A (es) * | 2008-10-29 | 2011-06-01 | Wyeth Llc | Procedimientos para la purificacion de moleculas de union a antigeno de un unico dominio. |
US8465742B2 (en) | 2008-12-05 | 2013-06-18 | University Of Guelph | Anti-cobra toxin antibody fragments and method of producing a VHH library |
HUE042919T2 (hu) | 2008-12-19 | 2019-07-29 | Ablynx Nv | Genetikai immunizáció sejthez kapcsolódó antigének - például P2X7, CXCR7 vagy CXCR4 - elleni immunglobulinok elõállítására |
WO2010100135A1 (en) | 2009-03-05 | 2010-09-10 | Ablynx N.V. | Novel antigen binding dimer-complexes, methods of making/avoiding and uses thereof |
NZ595461A (en) | 2009-04-10 | 2013-01-25 | Ablynx Nv | Improved amino acid sequences directed against il-6r and polypeptides comprising the same for the treatment of il-6r related diseases and disorders |
EP3828201A1 (en) | 2009-04-30 | 2021-06-02 | Ablynx N.V. | Method for the production of domain antibodies |
WO2010139808A2 (en) | 2009-06-05 | 2010-12-09 | Ablynx Nv | IMPROVED AMINO ACID SEQUENCES DIRECTED AGAINST HUMAN RESPIRATORY SYNCYTIAL VIRUS (hRSV) AND POLYPEPTIDES COMPRISING THE SAME FOR THE PREVENTION AND/OR TREATMENT OF RESPIRATORY TRACT INFECTIONS |
ES2804450T3 (es) | 2009-07-10 | 2021-02-08 | Ablynx Nv | Método para la producción de dominios variables |
SG177763A1 (en) | 2009-07-28 | 2012-03-29 | Hoffmann La Roche | Non-invasive in vivo optical imaging method |
ES2567030T3 (es) | 2009-09-03 | 2016-04-19 | Cancer Research Technology Limited | Inhibidores de CLEC14A |
EP2473528B1 (en) | 2009-09-03 | 2014-12-03 | Ablynx N.V. | Stable formulations of polypeptides and uses thereof |
US20110195494A1 (en) | 2009-10-02 | 2011-08-11 | Boehringer Ingelheim International Gmbh | Dll4-binging molecules |
US20110172398A1 (en) | 2009-10-02 | 2011-07-14 | Boehringer Ingelheim International Gmbh | Bispecific binding molecules for anti-angiogenesis therapy |
WO2011045079A1 (en) | 2009-10-15 | 2011-04-21 | Intercell Ag | Hepatitis b virus specific human antibodies |
DK2491056T3 (da) | 2009-10-22 | 2021-10-25 | Univ Twente | Vhh til anvendelse i vævsreparation, organregenerering, organudskiftning og vævskonstruktion |
US9644022B2 (en) | 2009-11-30 | 2017-05-09 | Ablynx N.V. | Amino acid sequences directed against human respiratory syncytial virus (HRSV) and polypeptides comprising the same for the prevention and/or treatment of respiratory tract infections |
US8962807B2 (en) | 2009-12-14 | 2015-02-24 | Ablynx N.V. | Single variable domain antibodies against OX40L, constructs and therapeutic use |
WO2011083141A2 (en) | 2010-01-08 | 2011-07-14 | Ablynx Nv | Method for generation of immunoglobulin sequences by using lipoprotein particles |
EP2531523A1 (en) | 2010-02-05 | 2012-12-12 | Ablynx N.V. | Peptides capable of binding to serum albumin and compounds, constructs and polypeptides comprising the same |
US9120855B2 (en) | 2010-02-10 | 2015-09-01 | Novartis Ag | Biologic compounds directed against death receptor 5 |
EP3501499B1 (en) | 2010-02-11 | 2022-09-07 | Ablynx NV | Methods and compositions for the preparation of aerosols |
WO2011098518A2 (en) | 2010-02-11 | 2011-08-18 | Ablynx Nv | Delivery of immunoglobulin variable domains and constructs thereof |
SG183369A1 (en) | 2010-03-03 | 2012-09-27 | Boehringer Ingelheim Int | Biparatopic abeta binding polypeptides |
WO2011117423A1 (en) | 2010-03-26 | 2011-09-29 | Ablynx N.V. | Immunoglobulin single variable domains directed against cxcr7 |
AU2011231558B2 (en) | 2010-03-26 | 2016-08-11 | Westfaelische Wilhelms-Universitaet Muenster | Substitute therapy for glucocorticoids |
US9101674B2 (en) | 2010-03-29 | 2015-08-11 | Vib Vzw | Targeting and in vivo imaging of tumor-associated macrophages |
US9556273B2 (en) | 2010-03-29 | 2017-01-31 | Vib Vzw | Anti-macrophage mannose receptor single variable domains for targeting and in vivo imaging of tumor-associated macrophages |
BR112012028006A2 (pt) | 2010-05-07 | 2016-08-02 | Hoffmann La Roche | método de imuno-histoquímica (ihq), uso de um domínio de ligação, kit e domínio de ligação terapeuticamente ativo |
NZ603570A (en) | 2010-05-20 | 2014-12-24 | Ablynx Nv | Biological materials related to her3 |
WO2011161263A1 (en) | 2010-06-25 | 2011-12-29 | Ablynx Nv | Pharmaceutical compositions for cutaneous administration |
EP2601298B1 (en) | 2010-08-02 | 2016-11-30 | Regeneron Pharmaceuticals, Inc. | Mice that make binding proteins comprising vl domains |
US20120225081A1 (en) | 2010-09-03 | 2012-09-06 | Boehringer Ingelheim International Gmbh | Vegf-binding molecules |
US20120244141A1 (en) | 2010-09-28 | 2012-09-27 | Boehringer Ingelheim International Gmbh | Stratification of cancer patients for susceptibility to therapy with PTK2 inhibitors |
EP2621953B1 (en) | 2010-09-30 | 2017-04-05 | Ablynx N.V. | Biological materials related to c-met |
WO2012056000A1 (en) | 2010-10-29 | 2012-05-03 | Ablynx Nv | Method for the production of immunoglobulin single variable domains |
BR112013011003B1 (pt) | 2010-11-08 | 2021-12-07 | Novartis Ag | Polipeptídeo e seus usos, célula hospedeira transgênica de microrganismo, nanocorpo monovalente, bivalente, multivalente, biparatópico ou multiparatópico, e composição farmacêutica |
JP6385060B2 (ja) | 2011-03-07 | 2018-09-05 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 治療的に活性な抗体のインビボにおける選択 |
EP2683290B1 (en) | 2011-03-07 | 2018-11-07 | F.Hoffmann-La Roche Ag | Methods for in vivo testing of therapeutic antibodies |
AU2012234284B2 (en) | 2011-03-28 | 2015-10-08 | Ablynx Nv | Bispecific anti-CXCR7 immunoglobulin single variable domains |
PT2691415T (pt) | 2011-03-28 | 2018-10-19 | Ablynx Nv | Método para produção de formulações sólidas compreendendo domínios variáveis únicos de imunoglobulina |
US9527925B2 (en) | 2011-04-01 | 2016-12-27 | Boehringer Ingelheim International Gmbh | Bispecific binding molecules binding to VEGF and ANG2 |
US20130078247A1 (en) | 2011-04-01 | 2013-03-28 | Boehringer Ingelheim International Gmbh | Bispecific binding molecules binding to dii4 and ang2 |
UA117218C2 (uk) | 2011-05-05 | 2018-07-10 | Мерк Патент Гмбх | Поліпептид, спрямований проти il-17a, il-17f та/або il17-a/f |
US9534039B2 (en) | 2011-05-09 | 2017-01-03 | Ablynx N.V. | Method for the production of immunoglobulin single variable domains |
CN107936121B (zh) | 2011-05-16 | 2022-01-14 | 埃泰美德(香港)有限公司 | 多特异性fab融合蛋白及其使用方法 |
CA2835340A1 (en) | 2011-05-27 | 2012-12-06 | Ablynx Nv | Inhibition of bone resorption with rankl binding peptides |
US9580480B2 (en) | 2011-05-31 | 2017-02-28 | Massachusetts Institute Of Technology | Cell-directed synthesis of multifunctional nanopatterns and nanomaterials |
JP6324887B2 (ja) | 2011-06-23 | 2018-05-16 | アブリンクス エン.ヴェー. | 血清アルブミンに結合するタンパク質 |
CN104271598A (zh) | 2011-06-23 | 2015-01-07 | 埃博灵克斯股份有限公司 | 针对IgE的免疫球蛋白单可变结构域 |
WO2013041722A1 (en) | 2011-09-23 | 2013-03-28 | Ablynx Nv | Prolonged inhibition of interleukin-6 mediated signaling |
CN103889451B (zh) | 2011-09-30 | 2016-06-29 | 埃博灵克斯股份有限公司 | 与C-Met相关的生物物质 |
RU2739792C1 (ru) | 2011-11-30 | 2020-12-28 | Чугаи Сейяку Кабусики Кайся | Содержащий лекарственное средство переносчик в клетку для формирования иммунного комплекса |
CA2862979A1 (en) | 2012-01-09 | 2013-07-18 | The Scripps Research Institute | Humanized antibodies with ultralong cdr3s |
WO2013106485A2 (en) * | 2012-01-09 | 2013-07-18 | The Scripps Research Institute | Ultralong complementarity determining regions and uses thereof |
IL291571B1 (en) | 2012-02-27 | 2024-04-01 | Ablynx Nv | CX3CR1 binding polypeptides |
US9328174B2 (en) | 2012-05-09 | 2016-05-03 | Novartis Ag | Chemokine receptor binding polypeptides |
AU2013265665B2 (en) | 2012-05-24 | 2017-10-26 | Vib Vzw | Anti-macrophage mannose receptor single variable domains for targeting and in vivo imaging of tumor-associated macrophages |
TWI797443B (zh) | 2012-05-30 | 2023-04-01 | 日商中外製藥股份有限公司 | 抗原結合分子之篩選或製造方法 |
US11339208B1 (en) | 2012-05-31 | 2022-05-24 | United States Of America As Represented By The Secretary Of The Air Force | Camelidae single-domain antibodies against Yersinia pestis and methods of use |
WO2014087010A1 (en) | 2012-12-07 | 2014-06-12 | Ablynx N.V. | IMPROVED POLYPEPTIDES DIRECTED AGAINST IgE |
EP2943512A4 (en) | 2013-01-11 | 2016-06-01 | California Inst Biomedical Res | FUSION BOVINE ANTIBODIES |
CN112858672A (zh) | 2013-01-30 | 2021-05-28 | 弗拉芒区生物技术研究所 | 用于筛选和药物发现目的的新型嵌合多肽 |
ES2745772T3 (es) | 2013-02-05 | 2020-03-03 | Vib Vzw | Agentes de unión al receptor muscarínico de la acetilcolina y usos de los mismos |
WO2014122144A1 (en) | 2013-02-05 | 2014-08-14 | Engmab Ag | BISPECIFIC ANTIBODIES AGAINST CD3ε AND BCMA |
EP2762496A1 (en) | 2013-02-05 | 2014-08-06 | EngMab AG | Method for the selection of antibodies against BCMA |
US9617339B2 (en) | 2013-03-15 | 2017-04-11 | Vib Vzw | Method of imaging a cardiovascular disease with an anti-macrophage mannose receptor immunoglobulin single variable domain |
WO2014163101A1 (ja) | 2013-04-02 | 2014-10-09 | 中外製薬株式会社 | Fc領域改変体 |
EP2789630A1 (en) | 2013-04-09 | 2014-10-15 | EngMab AG | Bispecific antibodies against CD3e and ROR1 |
PT2992100T (pt) | 2013-04-29 | 2019-12-16 | Agrosavfe Nv | Composições agroquímicas compreendendo anticorpos que se ligam a esfingolípidos |
NL1040254C2 (en) | 2013-05-17 | 2014-11-24 | Ablynx Nv | Stable formulations of immunoglobulin single variable domains and uses thereof. |
EP3013356B1 (en) | 2013-06-27 | 2018-10-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Interleukin 15 (il-15) antagonists and uses thereof for the treatment of autoimmune diseases and inflammatory diseases |
US20160176943A1 (en) | 2013-07-05 | 2016-06-23 | Inserm (Insititut National De La Sante Et De La Recherche Medicale) | Novel alternative splice transcripts for mhc class i related chain alpha (mica) and uses thereof |
EP3022221B1 (en) | 2013-07-18 | 2021-09-15 | Taurus Biosciences, LLC | Humanized antibodies with ultralong complementarity determining regions |
CN104623637A (zh) | 2013-11-07 | 2015-05-20 | 健能隆医药技术(上海)有限公司 | Il-22二聚体在制备静脉注射药物中的应用 |
MX2016007312A (es) | 2013-12-04 | 2017-01-13 | Chugai Pharmaceutical Co Ltd | Moleculas de union al antigeno, cuya actividad de union al antigeno varia de acuerdo con la concentracion de los compuestos y bibliotecas de dichas moleculas. |
EP2883883A1 (en) | 2013-12-16 | 2015-06-17 | Cardio3 Biosciences S.A. | Therapeutic targets and agents useful in treating ischemia reperfusion injury |
CA2936728C (en) | 2014-01-30 | 2023-06-20 | Vib Vzw | Opioid receptor binding agents and uses thereof |
EP3895528A1 (en) | 2014-03-21 | 2021-10-20 | Regeneron Pharmaceuticals, Inc. | Non-human animals that make single domain binding proteins |
CN106164092A (zh) | 2014-03-21 | 2016-11-23 | 瑞泽恩制药公司 | 表现不同结合特征的vl抗原结合蛋白 |
NL2013661B1 (en) | 2014-10-21 | 2016-10-05 | Ablynx Nv | KV1.3 Binding immunoglobulins. |
EP3194976B1 (en) | 2014-07-22 | 2020-04-01 | Vib Vzw | Methods to select agents that stabilize protein complexes |
CN106573983B (zh) | 2014-07-29 | 2018-05-25 | 布鲁塞尔自由大学 | 用于在癌症的预防和/或治疗中使用的放射性标记的抗体片段 |
WO2016016329A1 (en) | 2014-07-29 | 2016-02-04 | Vrije Universiteit Brussel | Radio-labelled antibody fragments for use in the prognosis, diagnosis of cancer as well as for the prediction of cancer therapy response |
CA2963692A1 (en) | 2014-10-09 | 2016-04-14 | Engmab Ag | Bispecific antibodies against cd3epsilon and ror1 |
CA2966548A1 (en) | 2014-11-05 | 2016-05-12 | Agrosavfe Nv | Transgenic plant comprising a polynucleotide encoding a variable domain of heavy-chain antibody |
AU2015366284B2 (en) | 2014-12-19 | 2021-07-22 | Ablynx N.V. | Cysteine linked nanobody dimers |
GB201501004D0 (en) | 2015-01-21 | 2015-03-04 | Cancer Rec Tech Ltd | Inhibitors |
WO2016124568A1 (en) | 2015-02-03 | 2016-08-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-rho gtpase conformational single domain antibodies and uses thereof |
US20180022781A1 (en) | 2015-02-13 | 2018-01-25 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Polypeptides for engineering integrase chimeric proteins and their use in gene therapy |
WO2016135041A1 (en) | 2015-02-26 | 2016-09-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Fusion proteins and antibodies comprising thereof for promoting apoptosis |
CN107438622A (zh) | 2015-03-19 | 2017-12-05 | 瑞泽恩制药公司 | 选择结合抗原的轻链可变区的非人动物 |
CA2981096A1 (en) | 2015-03-31 | 2016-10-06 | Vhsquared Limited | Tnf-alpha binding polypeptides |
CA2981098A1 (en) * | 2015-03-31 | 2016-10-06 | Vhsquared Limited | Peptide construct having a protease-cleavable linker |
JP7163028B2 (ja) | 2015-05-13 | 2022-10-31 | アブリンクス エン.ヴェー. | Cd3反応性に基づくt細胞リクルートポリペプチド |
AU2016259792B2 (en) | 2015-05-13 | 2019-07-25 | Ablynx N.V. | T cell recruiting polypeptides based on TCR alpha/beta reactivity |
US10782304B2 (en) | 2015-06-24 | 2020-09-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for detecting protein-protein interactions |
US11298433B2 (en) | 2015-07-17 | 2022-04-12 | Vrije Universiteit Brussel | Radiolabelled antibody fragments for use in treating cancer |
EA036975B1 (ru) | 2015-08-03 | 2021-01-21 | Энгмаб Сарл | Моноклональные антитела против bcma |
CN105384825B (zh) | 2015-08-11 | 2018-06-01 | 南京传奇生物科技有限公司 | 一种基于单域抗体的双特异性嵌合抗原受体及其应用 |
CA2999138C (en) | 2015-09-21 | 2024-05-21 | Aptevo Research And Development Llc | Cd3 binding polypeptides |
NO2768984T3 (ja) | 2015-11-12 | 2018-06-09 | ||
HUE057241T2 (hu) | 2015-11-13 | 2022-04-28 | Ablynx Nv | Javított, szérumalbumint kötõ immunoglobulin variábilis domének |
JP7046804B2 (ja) | 2015-11-18 | 2022-04-04 | アブリンクス エン.ヴェー. | 改良された血清アルブミン結合剤 |
EP3377527A1 (en) | 2015-11-18 | 2018-09-26 | Merck Sharp & Dohme Corp. | Ctla4 binders |
CA3132021C (en) | 2015-11-18 | 2024-03-12 | Merck Sharp & Dohme Corp. | Pd1 and/or lag3 binders |
CN108473561B (zh) | 2015-11-27 | 2022-12-16 | 埃博灵克斯股份有限公司 | 抑制cd40l的多肽 |
KR20180081825A (ko) | 2015-12-04 | 2018-07-17 | 베링거 인겔하임 인터내셔날 게엠베하 | 종양 세포에서 wnt 신호 전달을 길항하는 바이파라토픽 폴리펩타이드 |
EP3411397A1 (en) | 2016-02-05 | 2018-12-12 | Orionis Biosciences NV | Cd8 binding agents |
CA3016849A1 (en) | 2016-03-07 | 2017-09-14 | Vib Vzw | Cd20 binding single domain antibodies |
CN109476756B (zh) | 2016-03-15 | 2022-05-31 | 埃泰美德(香港)有限公司 | 一种多特异性Fab融合蛋白及其用途 |
US20190120838A1 (en) | 2016-04-13 | 2019-04-25 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and kits for the rapid detection of the escherichia coli o25b-st131 clone |
US11510966B2 (en) | 2016-04-15 | 2022-11-29 | Evive Biotechnology (Shanghai) Ltd | Use of IL-22 in treating necrotizing enterocolitis |
WO2017182603A1 (en) | 2016-04-22 | 2017-10-26 | Université Libre de Bruxelles | A new biomarker expressed in pancreatic beta cells useful in imaging or targeting beta cells |
WO2017182605A1 (en) | 2016-04-22 | 2017-10-26 | Université Libre de Bruxelles | A new biomarker expressed in pancreatic beta cells useful in imaging or targeting beta cells |
US20190127447A1 (en) | 2016-05-02 | 2019-05-02 | Ablynx N.V. | Treatment of rsv infection |
US11753463B2 (en) | 2016-05-13 | 2023-09-12 | Orionis Biosciences BV | Therapeutic targeting of non-cellular structures |
WO2017202962A1 (en) | 2016-05-24 | 2017-11-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of non small cell lung cancer (nsclc) that coexists with chronic obstructive pulmonary disease (copd) |
WO2018007442A1 (en) | 2016-07-06 | 2018-01-11 | Ablynx N.V. | Treatment of il-6r related diseases |
WO2018014260A1 (en) | 2016-07-20 | 2018-01-25 | Nanjing Legend Biotech Co., Ltd. | Multispecific antigen binding proteins and methods of use thereof |
WO2018029182A1 (en) | 2016-08-08 | 2018-02-15 | Ablynx N.V. | Il-6r single variable domain antibodies for treatment of il-6r related diseases |
WO2018050833A1 (en) | 2016-09-15 | 2018-03-22 | Ablynx Nv | Immunoglobulin single variable domains directed against macrophage migration inhibitory factor |
WO2018060453A1 (en) | 2016-09-30 | 2018-04-05 | Vhsquared Limited | Compositions |
WO2018068201A1 (en) | 2016-10-11 | 2018-04-19 | Nanjing Legend Biotech Co., Ltd. | Single-domain antibodies and variants thereof against ctla-4 |
US11365257B2 (en) | 2016-10-21 | 2022-06-21 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods for promoting t cells response by administering an antagonist of human c-type lectin-like receptor 1 (CLEC-1) |
EP4295918A3 (en) | 2016-11-02 | 2024-03-20 | Bristol-Myers Squibb Company | Bispecific antibody against bcma and cd3 and an immunological drug for combined use in treating multiple myeloma |
EP3541846A1 (en) | 2016-11-16 | 2019-09-25 | Ablynx NV | T cell recruiting polypeptides capable of binding cd123 and tcr alpha/beta |
WO2018091720A1 (en) | 2016-11-21 | 2018-05-24 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the prophylactic treatment of metastases |
WO2018099968A1 (en) | 2016-11-29 | 2018-06-07 | Ablynx N.V. | Treatment of infection by respiratory syncytial virus (rsv) |
KR20230061582A (ko) | 2016-12-07 | 2023-05-08 | 아블린쓰 엔.브이. | 개선된 혈청 알부민 결합성 면역글로불린 단일 가변 도메인 |
AU2018209150A1 (en) | 2017-01-17 | 2019-07-25 | Ablynx Nv | Improved serum albumin binders |
KR20240013861A (ko) | 2017-01-17 | 2024-01-30 | 아블린쓰 엔.브이. | 개선된 혈청 알부민 결합제 |
US11384154B2 (en) | 2017-02-06 | 2022-07-12 | Orionis Biosciences BV | Targeted chimeric proteins and uses thereof |
EP3589725A1 (en) | 2017-02-28 | 2020-01-08 | Vib Vzw | Means and methods for oral protein delivery |
CN106929513A (zh) * | 2017-04-07 | 2017-07-07 | 东南大学 | mRNA编码的纳米抗体及其应用 |
CA3058290A1 (en) | 2017-04-18 | 2018-10-25 | Universite Libre De Bruxelles | Biomarkers and targets for proliferative diseases |
KR20200005635A (ko) | 2017-05-11 | 2020-01-15 | 브이아이비 브이지더블유 | 가변 면역글로불린 도메인의 글리코실화 |
EP3630816B1 (en) | 2017-05-31 | 2024-03-20 | Boehringer Ingelheim International GmbH | Polypeptides antagonizing wnt signaling in tumor cells |
EP3630817A1 (en) | 2017-06-02 | 2020-04-08 | Merck Patent GmbH | Polypeptides binding adamts5, mmp13 and aggrecan |
US20200190216A1 (en) | 2017-06-02 | 2020-06-18 | Merck Patent Gmbh | Mmp13 binding immunoglobulins |
MX2019014400A (es) | 2017-06-02 | 2020-02-10 | Merck Patent Gmbh | Inmunoglobulinas que se unen a adamts. |
EP3630818A1 (en) | 2017-06-02 | 2020-04-08 | Ablynx NV | Aggrecan binding immunoglobulins |
WO2019000223A1 (en) | 2017-06-27 | 2019-01-03 | Nanjing Legend Biotech Co., Ltd. | ENABLERS OF IMMUNE EFFECTOR CELLS OF CHIMERIC ANTIBODIES AND METHODS OF USE THEREOF |
JP2020532285A (ja) | 2017-07-11 | 2020-11-12 | アレクシオン ファーマシューティカルズ, インコーポレイテッド | 補体成分c5または血清アルブミンと結合するポリペプチドおよびその融合タンパク質 |
JP7241731B2 (ja) | 2017-07-19 | 2023-03-17 | フエー・イー・ベー・フエー・ゼツト・ウエー | 血清アルブミン結合剤 |
JP7330174B2 (ja) | 2017-09-20 | 2023-08-21 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | オートファジーをモジュレーションするための方法及び医薬組成物 |
CN111372950A (zh) | 2017-10-12 | 2020-07-03 | 免疫苏醒公司 | Vegfr-抗体轻链融合蛋白 |
JP7395471B2 (ja) | 2017-10-13 | 2023-12-11 | オーセ イミュノセラピューティクス | 改変抗SIRPa抗体及びその使用 |
CA3076791A1 (en) | 2017-10-31 | 2019-05-09 | Vib Vzw | Novel antigen-binding chimeric proteins and methods and uses thereof |
CA3082280A1 (en) | 2017-12-28 | 2019-07-04 | Nanjing Legend Biotech Co., Ltd. | Single-domain antibodies and variants thereof against tigit |
WO2019129211A1 (en) | 2017-12-28 | 2019-07-04 | Nanjing Legend Biotech Co., Ltd. | Antibodies and variants thereof against pd-l1 |
WO2019137541A1 (en) | 2018-01-15 | 2019-07-18 | Nanjing Legend Biotech Co., Ltd. | Single-domain antibodies and variants thereof against pd-1 |
EP3743096A1 (en) | 2018-01-25 | 2020-12-02 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antagonists of il-33 for use in methods for preventing ischemia reperfusion injury in an organ |
EP3749295A4 (en) | 2018-02-05 | 2022-04-27 | Orionis Biosciences, Inc. | FIBROBLAST BINDING AGENTS AND USES THEREOF |
WO2019155041A1 (en) | 2018-02-12 | 2019-08-15 | Vib Vzw | Gβγ COMPLEX ANTIBODIES AND USES THEREOF |
WO2019158512A1 (en) | 2018-02-13 | 2019-08-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the prognosis and the treatment of glioblastoma |
EP3758755A1 (en) | 2018-02-26 | 2021-01-06 | Ablynx N.V. | Improved nucleotide sequences encoding peptide linkers |
WO2019166622A1 (en) | 2018-03-01 | 2019-09-06 | Vrije Universiteit Brussel | Human pd-l1-binding immunoglobulins |
BR112020018908A2 (pt) | 2018-03-23 | 2021-01-26 | Université Libre de Bruxelles | moléculas de agonistas de sinalização de wnt |
WO2019185723A1 (en) | 2018-03-27 | 2019-10-03 | Umc Utrecht Holding B.V. | Targeted thrombolysis for treatment of microvascular thrombosis |
CN111886254B (zh) | 2018-03-30 | 2023-12-08 | 南京传奇生物科技有限公司 | 针对lag-3的单结构域抗体及其用途 |
WO2019193375A1 (en) | 2018-04-04 | 2019-10-10 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of fzd7 inhibitors for the treatment of retinal neovascularization |
WO2019207030A1 (en) | 2018-04-26 | 2019-10-31 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting a response with an immune checkpoint inhibitor in a patient suffering from a lung cancer |
TW202016151A (zh) | 2018-06-09 | 2020-05-01 | 德商百靈佳殷格翰國際股份有限公司 | 針對癌症治療之多特異性結合蛋白 |
GB2576914A (en) | 2018-09-06 | 2020-03-11 | Kymab Ltd | Antigen-binding molecules comprising unpaired variable domains produced in mammals |
WO2020064702A1 (en) | 2018-09-25 | 2020-04-02 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of antagonists of th17 cytokines for the treatment of bronchial remodeling in patients suffering from allergic asthma |
WO2020070062A1 (en) | 2018-10-01 | 2020-04-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of tim-3 inhibitors for the treatment of exacerbations in patients suffering from severe asthma |
EP3860653A1 (en) | 2018-10-05 | 2021-08-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and systems for controlling the agonistic properties of antibody variable domains by light |
EP3636657A1 (en) | 2018-10-08 | 2020-04-15 | Ablynx N.V. | Chromatography-free antibody purification method |
EP3877399A4 (en) | 2018-11-06 | 2022-10-19 | Alsatech, Inc. | CELL-BASED GENE THERAPY FOR NEURODEGENERATIVE DISEASES |
EP3894438A1 (en) | 2018-12-13 | 2021-10-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | New anti tau svqivykpv epitope single domain antibody |
CA3123338A1 (en) | 2018-12-21 | 2020-06-25 | Ose Immunotherapeutics | Bifunctional anti-pd-1/il-7 molecule |
KR20210107058A (ko) | 2018-12-21 | 2021-08-31 | 오제 이뮈노테라프틱스 | 인간 pd-1에 대항하는 이작용성 분자 |
SG11202106251UA (en) | 2018-12-21 | 2021-07-29 | Ose Immunotherapeutics | Bifunctional anti-pd-1/sirpa molecule |
BR112021013157A8 (pt) | 2019-01-03 | 2022-12-06 | Inst Nat Sante Rech Med | Usos de um inibidor de nrp-1, uso de uma combinação, uso de um anticorpo multiespecífico, método ex vivo para predizer, uso de um inibidor, anticorpo multiespecífico, população de células modificadas, método ex vivo de produção e uso de uma população de células t |
SG11202107606VA (en) | 2019-01-15 | 2021-08-30 | Inst Nat Sante Rech Med | Mutated interleukin-34 (il-34) polypeptides and uses thereof in therapy |
WO2020165374A1 (en) | 2019-02-14 | 2020-08-20 | Ose Immunotherapeutics | Bifunctional molecule comprising il-15ra |
JPWO2020189748A1 (ja) | 2019-03-19 | 2020-09-24 | ||
AU2020266750A1 (en) | 2019-04-29 | 2021-11-25 | Confo Therapeutics N.V. | Screening methods and assays for use with transmembrane proteins, in particular with GPCRS |
US20220289837A1 (en) | 2019-04-30 | 2022-09-15 | Vib Vzw | Cystic Fibrosis Transmembrane Conductance Regulator Stabilizing Agents |
EP3976067A1 (en) | 2019-05-28 | 2022-04-06 | Vib Vzw | Cd8+ t-cells lacking plexins and their application in cancer treatment |
WO2020239945A1 (en) | 2019-05-28 | 2020-12-03 | Vib Vzw | Cancer treatment by targeting plexins in the immune compartment |
WO2020245663A1 (en) | 2019-06-01 | 2020-12-10 | Institut Pasteur | Nanobody-based ns1 assay for the specific diagnosis of acute zika virus infection |
WO2020254619A1 (en) | 2019-06-20 | 2020-12-24 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti- protease nexin-1 conformational single domain antibodies and uses thereof |
CN114466864A (zh) | 2019-06-21 | 2022-05-10 | 索瑞索制药公司 | 多肽 |
CN114514243A (zh) | 2019-06-21 | 2022-05-17 | 索瑞索制药公司 | 多肽 |
AU2020295767A1 (en) | 2019-06-21 | 2022-02-17 | Sorriso Pharmaceuticals, Inc. | Compositions |
TW202128756A (zh) | 2019-10-02 | 2021-08-01 | 德商百靈佳殷格翰國際股份有限公司 | 用於癌症治療之多重專一性結合蛋白 |
WO2021078786A1 (en) | 2019-10-21 | 2021-04-29 | Vib Vzw | Nanodisc-specific antigen-binding chimeric proteins |
CA3160506A1 (en) | 2019-11-11 | 2021-05-20 | Ibi-Ag Innovative Bio Insecticides Ltd. | Insect control nanobodies and uses thereof |
WO2021105438A1 (en) | 2019-11-27 | 2021-06-03 | Vib Vzw | Positive allosteric modulators of the calcium-sensing receptor |
CA3159155A1 (en) | 2019-12-05 | 2021-06-10 | Ose Immunotherapeutics | Anti-clec-1a antibodies and antigen-binding fragment thereof |
MX2022006881A (es) | 2019-12-06 | 2022-07-11 | Ablynx Nv | Polipeptidos que comprenden dominios variables unicos de inmunoglobulina dirigidos a tnf alfa y ox40l. |
AU2020396204A1 (en) | 2019-12-06 | 2022-07-28 | Ablynx Nv | Polypeptides comprising immunoglobulin single variable domains targeting TNFα and IL-23 |
EP4072682A1 (en) | 2019-12-09 | 2022-10-19 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Antibodies having specificity to her4 and uses thereof |
CN114980974A (zh) | 2019-12-09 | 2022-08-30 | 艾伯霖克斯公司 | 含靶向il-13和tslp的免疫球蛋白单可变结构域的多肽 |
GB201918279D0 (en) | 2019-12-12 | 2020-01-29 | Vib Vzw | Glycosylated single chain immunoglobulin domains |
TW202136287A (zh) | 2019-12-17 | 2021-10-01 | 法商Ose免疫治療公司 | 包含il-7變體之雙官能分子 |
CA3165429A1 (en) | 2019-12-20 | 2021-06-24 | Vib Vzw | Nanobody exchange chromatography |
WO2021140205A1 (en) | 2020-01-10 | 2021-07-15 | Confo Therapeutics N.V. | Methods for generating antibodies and antibody fragments and libraries comprising same |
WO2021156490A2 (en) | 2020-02-06 | 2021-08-12 | Vib Vzw | Corona virus binders |
WO2021170540A1 (en) | 2020-02-25 | 2021-09-02 | Vib Vzw | Leucine-rich repeat kinase 2 allosteric modulators |
CA3169910A1 (en) | 2020-02-28 | 2021-09-02 | Shanghai Henlius Biotech, Inc. | Anti-cd137 constructs, multispecific antibody and uses thereof |
CA3169939A1 (en) | 2020-02-28 | 2021-09-02 | Jie Xue | Anti-cd137 construct and use thereof |
JP2023519967A (ja) | 2020-03-30 | 2023-05-15 | アブリンクス・エヌ・フェー | 多価免疫グロブリン単一可変ドメインの製造及び精製のための方法 |
WO2021198396A1 (en) | 2020-03-31 | 2021-10-07 | Biotalys NV | Anti-fungal polypeptides |
WO2021213435A1 (zh) | 2020-04-22 | 2021-10-28 | 迈威(上海)生物科技股份有限公司 | 一种靶向人程序性死亡配体1(pd-l1)的单可变域抗体及其衍生物 |
WO2021229104A1 (en) | 2020-05-15 | 2021-11-18 | Université de Liège | Anti-cd38 single-domain antibodies in disease monitoring and treatment |
EP3916088A1 (en) | 2020-05-28 | 2021-12-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Fusion proteins comprising the sars-cov-2 3clpro catalytic domain and their uses for screening anti-sars-cov-2 agents |
CN116529260A (zh) | 2020-06-02 | 2023-08-01 | 当康生物技术有限责任公司 | 抗cd93构建体及其用途 |
TW202210515A (zh) | 2020-06-02 | 2022-03-16 | 美商當康生物科技有限公司 | 抗cd39之構築體及其用途 |
KR20230025005A (ko) | 2020-06-17 | 2023-02-21 | 얀센 바이오테크 인코포레이티드 | 만능 줄기세포의 제조를 위한 재료 및 방법 |
WO2022002880A1 (en) | 2020-06-29 | 2022-01-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-protein s single-domain antibodies and polypeptides comprising thereof |
WO2022003156A1 (en) | 2020-07-02 | 2022-01-06 | Oncurious Nv | Ccr8 non-blocking binders |
EP4188550A1 (en) | 2020-07-29 | 2023-06-07 | Dynamicure Biotechnology LLC | Anti-cd93 constructs and uses thereof |
IL300173A (en) | 2020-07-31 | 2023-03-01 | Biotalys NV | expression host |
WO2022063947A1 (en) | 2020-09-24 | 2022-03-31 | Vib Vzw | Combination of p2y6 inhibitors and immune checkpoint inhibitors |
WO2022063957A1 (en) | 2020-09-24 | 2022-03-31 | Vib Vzw | Biomarker for anti-tumor therapy |
CA3195687A1 (en) | 2020-09-25 | 2022-03-31 | Ablynx Nv | Polypeptides comprising immunoglobulin single variable domains targeting il-13 and ox40l |
EP4228697A1 (en) | 2020-10-16 | 2023-08-23 | Invisishield Technologies Ltd. | Compositions for preventing or treating viral and other microbial infections |
WO2022117569A1 (en) | 2020-12-02 | 2022-06-09 | Oncurious Nv | A ccr8 antagonist antibody in combination with a lymphotoxin beta receptor agonist antibody in therapy against cancer |
JP2024508207A (ja) | 2020-12-02 | 2024-02-26 | ブイアイビー ブイゼットダブリュ | がんに対する組み合わせ治療におけるltbrアゴニスト |
EP4256067A2 (en) | 2020-12-04 | 2023-10-11 | Tidal Therapeutics, Inc. | Ionizable cationic lipids and lipid nanoparticles, and methods of synthesis and use thereof |
US20240067727A1 (en) | 2020-12-17 | 2024-02-29 | Ose Immunotherapeutics | Bifunctional anti-pd1/il-7 molecules |
KR20230123497A (ko) | 2020-12-18 | 2023-08-23 | 아블린쓰 엔.브이. | IL-6 및 TNF-α를 표적화하는 면역글로불린 단일 가변도메인을 포함하는 폴리펩티드 |
EP4263610A1 (en) | 2020-12-18 | 2023-10-25 | Ablynx N.V. | T cell recruiting polypeptides based on tcr alpha/beta reactivity |
MX2023007308A (es) | 2020-12-18 | 2023-07-04 | Ablynx Nv | Polipeptidos que comprenden dominios variables simples de inmunoglobulina dirigidos a glypican-3 y al receptor de celulas t. |
GB202020502D0 (en) | 2020-12-23 | 2021-02-03 | Vib Vzw | Antibody composistion for treatment of corona virus infection |
WO2022140797A1 (en) | 2020-12-23 | 2022-06-30 | Immunowake Inc. | Immunocytokines and uses thereof |
WO2022136647A1 (en) | 2020-12-24 | 2022-06-30 | Oncurious Nv | Human ccr8 binders |
WO2022136649A1 (en) | 2020-12-24 | 2022-06-30 | Oncurious Nv | Non-blocking human ccr8 binders |
EP4267621A1 (en) | 2020-12-24 | 2023-11-01 | Vib Vzw | Murine cross-reactive human ccr8 binders |
CN112920273B (zh) * | 2020-12-30 | 2022-07-01 | 中国人民解放军海军军医大学 | 抗水母毒素纳米抗体cozo32、制备方法及用途 |
US20240101717A1 (en) | 2021-01-22 | 2024-03-28 | Bionecure Therapeutics, Inc. | Anti-her-2/trop-2 constructs and uses thereof |
CN117794566A (zh) | 2021-02-05 | 2024-03-29 | Vib研究所 | 沙贝病毒结合剂 |
US20240101647A1 (en) | 2021-02-05 | 2024-03-28 | Vib Vzw | Sarbecovirus binders |
US20240130999A1 (en) | 2021-02-17 | 2024-04-25 | Vib Vzw | Inhibition of SLC4A4 in the Treatment of Cancer |
KR20220118963A (ko) | 2021-02-19 | 2022-08-26 | (주)샤페론 | Pd-l1 및 cd47에 대한 이중특이적 단일 도메인 항체 및 이의 용도 |
IL305301A (en) | 2021-02-19 | 2023-10-01 | Us Health | Single domain antibodies neutralizing SARS CoV-2 |
CA3211270A1 (en) | 2021-02-19 | 2022-08-25 | Vib Vzw | Cation-independent mannose-6-phosphate receptor binders |
KR20220118962A (ko) | 2021-02-19 | 2022-08-26 | (주)샤페론 | Pd-l1에 대한 단일 도메인 항체 및 이의 용도 |
EP4296282A1 (en) | 2021-02-19 | 2023-12-27 | SHAPERON Inc. | Single domain antibody against cd47 and use thereof |
AU2022232951A1 (en) | 2021-03-10 | 2023-10-19 | Immunowake Inc. | Immunomodulatory molecules and uses thereof |
WO2022199804A1 (en) | 2021-03-24 | 2022-09-29 | Vib Vzw | Nek6 inhibition to treat als and ftd |
EP4314049A1 (en) | 2021-03-25 | 2024-02-07 | Dynamicure Biotechnology LLC | Anti-igfbp7 constructs and uses thereof |
WO2022214652A1 (en) | 2021-04-09 | 2022-10-13 | Ose Immunotherapeutics | Scaffold for bifunctioanl molecules comprising pd-1 or cd28 and sirp binding domains |
IL307419A (en) | 2021-04-09 | 2023-12-01 | Ose Immunotherapeutics | A new scaffold for bifunctional molecules with improved properties |
WO2022242892A1 (en) | 2021-05-17 | 2022-11-24 | Université de Liège | Anti-cd38 single-domain antibodies in disease monitoring and treatment |
EP4355785A1 (en) | 2021-06-17 | 2024-04-24 | Amberstone Biosciences, Inc. | Anti-cd3 constructs and uses thereof |
WO2022269473A1 (en) | 2021-06-23 | 2022-12-29 | Janssen Biotech, Inc. | Materials and methods for hinge regions in functional exogenous receptors |
WO2022268993A1 (en) | 2021-06-23 | 2022-12-29 | Vib Vzw | Means and methods for selection of specific binders |
EP4365199A1 (en) | 2021-06-29 | 2024-05-08 | Shandong Simcere Biopharmaceutical Co., Ltd. | Cd16 antibody and use thereof |
CN116120449A (zh) * | 2021-07-09 | 2023-05-16 | 苏州晟济药业有限公司 | 抗体以及包含其的结合剂、免疫吸附材料及其应用 |
EP4377352A2 (en) | 2021-07-30 | 2024-06-05 | Vib Vzw | Cation-independent mannose-6-phosphate receptor binders for targeted protein degradation |
CN117751143A (zh) | 2021-07-30 | 2024-03-22 | 山东先声生物制药有限公司 | 抗pvrig/抗tigit双特异性抗体和应用 |
WO2023057601A1 (en) | 2021-10-06 | 2023-04-13 | Biotalys NV | Anti-fungal polypeptides |
WO2023083890A1 (en) | 2021-11-09 | 2023-05-19 | Ose Immunotherapeutics | Identification of clec-1 ligand and uses thereof |
WO2023089191A1 (en) | 2021-11-22 | 2023-05-25 | Ablynx N.V. | Obtaining sequence information for target multivalent immunoglobulin single variable domains |
WO2023098846A1 (zh) | 2021-12-03 | 2023-06-08 | 江苏先声药业有限公司 | 抗bcma纳米抗体及其应用 |
WO2023111266A1 (en) | 2021-12-17 | 2023-06-22 | Ablynx Nv | POLYPEPTIDES COMPRISING IMMUNOGLOBULIN SINGLE VARIABLE DOMAINS TARGETING TCRαβ, CD33 AND CD123 |
WO2023135198A1 (en) | 2022-01-12 | 2023-07-20 | Vib Vzw | Human ntcp binders for therapeutic use and liver-specific targeted delivery |
WO2023148291A1 (en) | 2022-02-02 | 2023-08-10 | Biotalys NV | Methods for genome editing |
WO2023148397A1 (en) | 2022-02-07 | 2023-08-10 | Vib Vzw | Engineered stabilizing aglycosylated fc-regions |
WO2023198848A1 (en) | 2022-04-13 | 2023-10-19 | Vib Vzw | An ltbr agonist in combination therapy against cancer |
WO2023198806A1 (en) | 2022-04-13 | 2023-10-19 | Ose Immunotherapeutics | New class of molecules for selective clearance of antibody |
WO2023198851A1 (en) | 2022-04-14 | 2023-10-19 | Institut National de la Santé et de la Recherche Médicale | Methods for controlling the tumor cell killing by light |
WO2023213751A1 (en) | 2022-05-02 | 2023-11-09 | Umc Utrecht Holding B.V | Single domain antibodies for the detection of plasmin-cleaved vwf |
WO2023217904A1 (en) | 2022-05-10 | 2023-11-16 | Institut National de la Santé et de la Recherche Médicale | Syncitin-1 fusion proteins and uses thereof for cargo delivery into target cells |
WO2023222825A1 (en) | 2022-05-18 | 2023-11-23 | Vib Vzw | Sarbecovirus spike s2 subunit binders |
WO2023232826A1 (en) | 2022-05-30 | 2023-12-07 | Ose Immunotherapeutics | Biomarkers of il7r modulator activity |
US20240002331A1 (en) | 2022-06-08 | 2024-01-04 | Tidal Therapeutics, Inc. | Ionizable cationic lipids and lipid nanoparticles, and methods of synthesis and use thereof |
US20240109965A1 (en) | 2022-06-14 | 2024-04-04 | Ablynx N.V. | Immunoglobulin single variable domains targeting t cell receptor |
EP4299125A1 (en) | 2022-06-30 | 2024-01-03 | Universite De Montpellier | Anti-mglur2 biparatopic nanobodies and uses thereof |
EP4299124A1 (en) | 2022-06-30 | 2024-01-03 | Universite De Montpellier | Anti-mglur2 nanobodies for use as biomolecule transporter |
WO2024008755A1 (en) | 2022-07-04 | 2024-01-11 | Vib Vzw | Blood-cerebrospinal fluid barrier crossing antibodies |
US20240117038A1 (en) | 2022-07-18 | 2024-04-11 | Ablynx N.V. | Cx3cr1-binding compounds, methods and uses thereof |
WO2024018426A1 (en) | 2022-07-22 | 2024-01-25 | Janssen Biotech, Inc. | Enhanced transfer of genetic instructions to effector immune cells |
US20240132624A1 (en) | 2022-07-27 | 2024-04-25 | Ablynx N.V. | Polypeptides binding to a specific epitope of the neonatal fc receptor |
WO2024028347A1 (en) | 2022-08-01 | 2024-02-08 | Ose Immunotherapeutics | Heterodimeric fc-clec-1 fusion molecule and uses thereof |
WO2024028386A1 (en) | 2022-08-02 | 2024-02-08 | Ose Immunotherapeutics | Multifunctional molecule directed against cd28 |
WO2024037633A2 (en) | 2022-08-19 | 2024-02-22 | Evive Biotechnology (Shanghai) Ltd | Formulations comprising g-csf and uses thereof |
WO2024068744A1 (en) | 2022-09-27 | 2024-04-04 | Vib Vzw | Antivirals against human parainfluenza virus |
WO2024068944A1 (en) | 2022-09-30 | 2024-04-04 | Sanofi | Anti-cd28 antibodies |
WO2024083843A1 (en) | 2022-10-18 | 2024-04-25 | Confo Therapeutics N.V. | Amino acid sequences directed against the melanocortin 4 receptor and polypeptides comprising the same for the treatment of mc4r-related diseases and disorders |
WO2024105091A1 (en) | 2022-11-15 | 2024-05-23 | Imec Vzw | Method and system for droplet manipulation |
WO2024126363A1 (en) | 2022-12-12 | 2024-06-20 | Institut National de la Santé et de la Recherche Médicale | Image-based high-content screening methods for identifying compounds targeting apicomplexan parasites |
WO2024126805A1 (en) | 2022-12-15 | 2024-06-20 | Aarhus Universitet | Synthetic activation of multimeric transmembrane receptors |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4689299A (en) * | 1982-09-30 | 1987-08-25 | University Of Rochester | Human monoclonal antibodies against bacterial toxins |
DK255887D0 (da) * | 1987-05-20 | 1987-05-20 | Claus Koch | Immunoassay |
US5919665A (en) * | 1989-10-31 | 1999-07-06 | Ophidian Pharmaceuticals, Inc. | Vaccine for clostridium botulinum neurotoxin |
US5719267A (en) * | 1989-10-31 | 1998-02-17 | Ophidian Pharmaceuticals Inc. | Clostridial toxin disease therapy |
US5124249A (en) * | 1989-11-28 | 1992-06-23 | Khan Rashid H | Method for evaluating protection to bee venom |
US6225447B1 (en) * | 1991-05-15 | 2001-05-01 | Cambridge Antibody Technology Ltd. | Methods for producing members of specific binding pairs |
DE4122599C2 (de) * | 1991-07-08 | 1993-11-11 | Deutsches Krebsforsch | Phagemid zum Screenen von Antikörpern |
AU4116793A (en) * | 1992-04-24 | 1993-11-29 | Board Of Regents, The University Of Texas System | Recombinant production of immunoglobulin-like domains in prokaryotic cells |
GB2270076A (en) | 1992-08-18 | 1994-03-02 | Univ Manchester | Human HSP 90 Epitopes |
US6005079A (en) * | 1992-08-21 | 1999-12-21 | Vrije Universiteit Brussels | Immunoglobulins devoid of light chains |
DE69330523T4 (de) * | 1992-08-21 | 2012-08-23 | Vrije Universiteit Brussel | Immunoglobuline ohne leichte ketten |
US6765087B1 (en) * | 1992-08-21 | 2004-07-20 | Vrije Universiteit Brussel | Immunoglobulins devoid of light chains |
US6838254B1 (en) * | 1993-04-29 | 2005-01-04 | Conopco, Inc. | Production of antibodies or (functionalized) fragments thereof derived from heavy chain immunoglobulins of camelidae |
US6103521A (en) * | 1995-02-06 | 2000-08-15 | Cell Genesys, Inc. | Multispecific chimeric receptors |
EP0739981A1 (en) * | 1995-04-25 | 1996-10-30 | Vrije Universiteit Brussel | Variable fragments of immunoglobulins - use for therapeutic or veterinary purposes |
US5989830A (en) * | 1995-10-16 | 1999-11-23 | Unilever Patent Holdings Bv | Bifunctional or bivalent antibody fragment analogue |
ATE535154T1 (de) * | 1998-03-12 | 2011-12-15 | Vhsquared Ltd | Produkten die inaktivierte hefen oder schimmel enthalten, die auf ihrer aussenoberfläche aktive antikörper haben |
US6610472B1 (en) * | 2000-10-31 | 2003-08-26 | Genetastix Corporation | Assembly and screening of highly complex and fully human antibody repertoire in yeast |
-
1995
- 1995-04-25 EP EP95400932A patent/EP0739981A1/en not_active Withdrawn
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1996
- 1996-04-25 EP EP06020795A patent/EP1816198A1/en not_active Withdrawn
- 1996-04-25 AT AT96913525T patent/ATE391179T1/de not_active IP Right Cessation
- 1996-04-25 AU AU56478/96A patent/AU5647896A/en not_active Abandoned
- 1996-04-25 JP JP53217196A patent/JP4394162B2/ja not_active Expired - Lifetime
- 1996-04-25 DE DE69637483T patent/DE69637483T2/de not_active Expired - Lifetime
- 1996-04-25 EP EP96913525A patent/EP0822985B1/en not_active Expired - Lifetime
- 1996-04-25 WO PCT/EP1996/001725 patent/WO1996034103A1/en active IP Right Grant
-
2002
- 2002-05-28 US US10/154,971 patent/US7655759B2/en not_active Expired - Fee Related
-
2006
- 2006-09-13 US US11/520,128 patent/US20070009512A1/en not_active Abandoned
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JP2011256169A (ja) * | 2002-11-08 | 2011-12-22 | Ablynx Nv | 治療用ポリペプチドの投与法およびそのためのポリペプチド |
US9243065B2 (en) | 2002-11-08 | 2016-01-26 | Ablynx N.V. | Polypeptide constructs including VHH directed against EGFR for intracellular delivery |
US9320792B2 (en) | 2002-11-08 | 2016-04-26 | Ablynx N.V. | Pulmonary administration of immunoglobulin single variable domains and constructs thereof |
US9371381B2 (en) | 2002-11-08 | 2016-06-21 | Ablynx, N.V. | Single domain antibodies directed against tumor necrosis factor-alpha and uses therefor |
US9725522B2 (en) | 2002-11-08 | 2017-08-08 | Ablynx N.V. | Pulmonary administration of immunoglobulin single variable domains and constructs thereof |
JP2021516682A (ja) * | 2018-03-13 | 2021-07-08 | スミヴェット ビー.ブイ.Smivet B.V. | 破傷風神経毒素に結合する単一ドメイン抗体 |
Also Published As
Publication number | Publication date |
---|---|
ATE391179T1 (de) | 2008-04-15 |
US20030088074A1 (en) | 2003-05-08 |
WO1996034103A1 (en) | 1996-10-31 |
DE69637483T2 (de) | 2009-08-06 |
DE69637483D1 (de) | 2008-05-15 |
EP1816198A1 (en) | 2007-08-08 |
US20070009512A1 (en) | 2007-01-11 |
JP4394162B2 (ja) | 2010-01-06 |
EP0822985A1 (en) | 1998-02-11 |
EP0739981A1 (en) | 1996-10-30 |
AU5647896A (en) | 1996-11-18 |
US7655759B2 (en) | 2010-02-02 |
EP0822985B1 (en) | 2008-04-02 |
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