JP2013521772A - pH依存性の抗原結合を有する抗体 - Google Patents
pH依存性の抗原結合を有する抗体 Download PDFInfo
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- JP2013521772A JP2013521772A JP2012556634A JP2012556634A JP2013521772A JP 2013521772 A JP2013521772 A JP 2013521772A JP 2012556634 A JP2012556634 A JP 2012556634A JP 2012556634 A JP2012556634 A JP 2012556634A JP 2013521772 A JP2013521772 A JP 2013521772A
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Images
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- C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
- C07K16/4283—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig
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Abstract
【図1】
Description
本発明の実施は、別段の指示がない限り、分子生物学(組換え技術を含む)、微生物学、細胞生物学、生化学、および免疫学の従来の技術を採用し、これらは当技術分野の技術の範囲内である。このような技術は、Molecular Cloning:A Laboratlry Manual、第2版(Sambrookら、1989)Cold Spring Harbor Press;Oligonucleotide Synthesis(M.J.Gait編、1984);Methods in Molecular Biology、Humana Press;Cell Biology:A Laboratory Notebook(J.E.Cellis編、1998)Academic Press;Animal Cell Culture(R.I.Freshney編、1987);Introduction to Cell and Tissue Culture(J.P.MatherおよびP.E.Roberts、1998)Plenum Press;Cell and Tissue Culture:Laboratory Procedures(A.Doyle、J.B.Griffiths、およびD.G.Newell編、1993〜1998)J.Wiley and Sons;Methods in Enzymology(Academic Press,Inc.);Handbook of Experimental Immunology(D.M.WeirおよびC.C.Blackwell編);Gene Transfer Vectors for Mammalian Cells(J.M.MillerおよびM.P.Calos編、1987);Current Protocols in Molecular Biology(F.M.Ausubelら編、1987);PCR:The Polymerase Chain Reaction(Mullisら編、1994);Current Protocols in Immunology(J.E.Coliganら編、1991);Short Protocols in Molecular Biology(Wiley and Sons、1999);Immunobiology(C.A.JanewayおよびP.Travers、1997);Antibodies(P.Finch、1997);Antibodies:a practical approach(D.Catty.編、IRL Press、1988〜1989);Monoclonal antibodies:a practical approach(P.ShepherdおよびC.Dean編、Oxford University Press、2000);Using antibodies:a laboratory manual(E.HarlowおよびD.Lane(Cold Spring Harbor Laboratory Press、1999);The Antibodies(M.ZanettiおよびJ.D.Capra編、Harwood Academic Publishers、1995)などの文献において完全に説明されている。
「抗体」は、免疫グロブリン分子の可変領域に位置する少なくとも1つの抗原認識部位を介して、糖質、ポリヌクレオチド、脂質、ポリペプチドなどの標的に特異的結合し得る、免疫グロブリン分子である。本明細書において用いられる場合、この用語は、無傷のポリクローナル抗体またはモノクローナル抗体だけではなく、あらゆるその抗原結合断片(すなわち、「抗原結合部分」)またはその一本鎖、抗体を包含する融合タンパク質、および抗原認識部位を包含する免疫グロブリン分子のあらゆる他の修飾された立体構造を包含し、これには、例えば、限定はしないが、一本鎖(scFv)抗体およびドメイン抗体(例えば、ヒト、ラクダ、またはサメのドメイン抗体)、マキシボディ、ミニボディ、イントラボディ、ダイアボディ、トリアボディ、テトラボディ、vNAR、およびビスscFvが含まれる(例えば、HollingerおよびHudson、Nature Biotech 23:1126〜1136、2005を参照されたい)。抗体には、あらゆるクラス、例えばIgG、IgA、またはIgM(またはそのサブクラス)の抗体が含まれ、抗体は、いずれかの特定のクラスのものである必要はない。抗体の重鎖の定常ドメインのアミノ酸配列に応じて、免疫グロブリンを異なるクラスに割り当てることができる。5つの主要なクラスの免疫グロブリン、すなわちIgA、IgD、IgE、IgG、およびIgMが存在し、これらのいくつかは、さらにサブクラス(アイソタイプ)、例えば、IgG1、IgG2、IgG3、IgG4、IgA1、およびIgA2に分けることができる。異なるクラスの免疫グロブリンに対応する重鎖定常ドメインは、それぞれ、アルファ、デルタ、イプシロン、ガンマ、およびミューと呼ばれる。異なるクラスの免疫グロブリンのサブユニット構造および三次元立体配置は周知である。
pH依存性のPCSK9アンタゴニスト抗体に関する1つの態様において、本発明は、効果的な量の、循環PCSK9に拮抗するpH依存性のPCSK9アンタゴニスト抗体を個体に投与するステップを包含する、個体における高コレステロール血症、および/または脂質異常症、アテローム性動脈硬化症、CVD、もしくは冠動脈性心疾患の少なくとも1つの症候を治療または予防するための方法を提供する。
本発明において有用な抗体は、モノクローナル抗体、ポリクローナル抗体、抗体断片(例えば、Fab、Fab’、F(ab’)2、Fv、Fcなど)、キメラ抗体、二重特異的抗体、ヘテロコンジュゲート抗体、一本鎖(ScFv)、その突然変異体、抗体部分を包含する融合タンパク質(例えば、ドメイン抗体)、ヒト抗体、ヒト化抗体、ならびに、抗体のグリコシル化変異体、抗体のアミノ酸配列変異体、および共有結合によって修飾された抗体を含む、所要の特異性を有する抗原認識部位を包含する免疫グロブリン分子のあらゆる他の修飾された立体構造を包含し得る。抗体は、マウス、ラット、ヒト、またはあらゆる他のものに由来し得る(キメラ抗体またはヒト化抗体を含む)。
本発明の方法において用いられる組成物は、効果的な量のpH依存性の抗体、または、本明細書において記載されているpH依存性の抗体に由来するポリペプチドを包含する。このような組成物の例、およびこれらを製剤する方法もまた、先の節および以下に記載されている。1つの実施形態において、組成物は、1つまたは複数のpH依存性の抗体を包含する。他の実施形態において、pH依存性の抗体は、ヒトPCSK9を認識する。さらに他の実施形態において、pH依存性の抗体はヒト化されている。さらに他の実施形態において、pH依存性の抗体は、抗体介在性の溶解またはADCCなどの望ましくないまたは好ましくない免疫応答を引き起こさない定常領域を包含する。他の実施形態において、pH依存性の抗体は、抗体の1つまたは複数のCDR(1つまたは複数)(例えば、1個、2個、3個、4個、5個、またはいくつかの実施形態においては6個全てのCDR)を包含する。いくつかの実施形態において、pH依存性の抗体はヒト抗体である。
本発明はまた、本方法において用いるためのキットを提供する。本発明のキットには、本明細書において記載されているpH依存性の抗体(ヒト化抗体など)またはペプチドを包含する1つまたは複数の容器と、本明細書において記載されているあらゆる本発明の方法に従った使用のための指示とが含まれる。通常、これらの指示は、上記に記載された治療的治療のためのpH依存性の抗体の投与の説明を包含する。
本発明の抗体を発現させるために、VH領域およびVL領域をコードするDNA断片をまず、上記の方法のいずれかを用いて得ることができる。様々な修飾、例えば、突然変異、欠失、および/または付加をまた、当業者に知られている標準的な方法を用いてDNA配列内に導入することができる。例えば、突然変異生成は、標準的な方法、例えば、突然変異したヌクレオチドをPCRプライマー内に組み込んでPCR産物が所望の突然変異または部位特異的突然変異生成を含むようにする、PCR介在性の突然変異生成を用いて実施することができる。
代表的な本発明の抗体、5L1721H23_6L3および5L1721H23_6L3H3の重鎖および軽鎖のDNAは、2009年12月22日にAmerican Type Culture Collection(ATCC)に寄託され(ブダペスト条約の条件のもとで)、表2に示す受託番号を割り当てられた。このように寄託されたプラスミドの、公衆にとっての利用性に対するすべての制限は、本発明の明細書の特許が発行されることで変更不可能に取り除かれる。5L1721H23_6L3の重鎖および軽鎖についての抗体参照番号は、それぞれ、UC−H5H23およびUC−H5L1721−6L3である。5L1721H23_6L3H3の重鎖および軽鎖についての抗体参照番号は、それぞれ、UC−H5H23−6H3およびUC−H5L1721−6L3である。
コンピュータモデリングを用いて、pH依存性の抗原結合を有する抗体が、抗体の半減期、PCSK9血清濃度が低下する期間に影響し得るかどうかを予測した。このモデリングの目的で、以下の仮定を行った:血液中1uM用量の抗体;21日の(非pH依存性の)抗体の半減期;100日の刺激付与期間;pH依存性の抗体では、Kon=1e5/M/s、中性pHでのKoff=KD×Kon、pH依存性の結合は、酸性のエンドソームにおけるKoffの増大としてモデリングされる;酸性pHでのKoff=R×中性pHでのKoff。
ヒスチジンスキャン突然変異生成を、モノクローナル抗体h5A10(5A10 huフレームとしても知られている)の全CDRについて行った。この抗体は、マウスモノクローナル抗体5A10(5A10.B8としても知られている)に由来するが、ヒトフレームワーク領域を有する。開始鋳型として用いられるh5A10抗体の配列を以下に示す(CDRは太字である)。
軽鎖可変領域:
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQRYSTPRTFGQGTKLEIK(配列番号1)
重鎖可変領域:
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGEINPSGGRTNYNEKFKSRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARERPLYAMDYWGQGTTVTVSS(配列番号2)
5L1721H23_6L3および5L1721H23_6L3H3の軽鎖可変領域:
DIQMTQSPSSLSASVGDRVTITCKASQDVHTAVAWYQQKPGKAPKLLIYHASYRYTGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQRYSLWRTFGQGTKLEIK(配列番号3)
重鎖可変領域5L1721H23_6L3:
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGEIHPSGGRTNYNEKFKSRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARERPLYAMDY WGQGTTVTVSS(配列番号4)
重鎖可変領域5L1721H23_6L3H3:
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGEIHPSGGRTNYNEKFKSRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARERPLYASDL WGQGTTVTVSS(配列番号5)
5L1721H23_6L3および5L1721H23_6L3H3の軽鎖可変領域(カッパ)
gatatccagatgacacagtccccatcctccctgtctgcctctgtgggcgaccgcgtcaccatcacctgcaaggcctctcaggatgtgcatactgctgtagcctggtatcagcagaagccaggcaaagccccaaaactgctgatctaccatgcatcctaccgctacactggtgtcccatcacgcttcagtggcagtggctctggtacagatttcaccttcaccattagcagcctgcaaccagaagatattgccacttattactgccagcaacgttatagtctgtggcgcacgttcggtcaaggcaccaagctggagatcaaa(配列番号23)
5L1721H23_6L3H3の重鎖可変領域
caggtgcagctggtgcagtctggtgctgaggtgaagaagcctggcgcttccgtgaaggtttcctgcaaagcatctggttacacctttaccagctactatatgcactgggtgcgccaagcccctggtcaaggcctggagtggatgggcgagattcatcctagcggcggtcgtactaactacaatgagaagttcaagagccgcgtgactatgactcgcgatacctccaccagcactgtctacatggaactgagctctctgcgctctgaggacactgctgtgtattactgtgcccgcgagcgccccctgtatgctagcgacctgtggggccagggtaccacggtcaccgtctcctca(配列番号24)
A.pH依存性PCSK9結合アンタゴニスト抗体は、マウスにおいて、延長した時間にわたり、血清コレステロールを低下させる
pH依存性PCSK9結合アンタゴニスト抗体が、非pH依存性の抗体と比較して、延長した期間にわたりコレステロールレベルをインビボで低下させ得るかどうかを決定するために、酸感受性抗体5L1721H23_6H3および5L1721H23_6L3H3ならびに非酸性感受性抗体h5A10(10mg/kgでのみ投与する)および5A10.B8の経時的な効果を、1、3、または10mg/kgでマウスに注入した場合の血清コレステロールについて試験した。4つの抗体全ては、中性pH(PH7.4)で、マウスPCSK9に対して5〜14nMの類似の結合親和性を有する。抗体5L1721H23_6H3および5L1721H23_6L3H3は、pH5.5で、それぞれ117nMおよび408nMの低減した親和性を有するが、h5A10および5A10.B8は、pH5.5で、7.4でのKD(5.2nM)に類似したKDを有する。6から7週齢のオスC57/bl6マウスを、12時間の明/暗サイクルで維持し、7日目に採血しておよそ70μlの血清を回収した。アンタゴニストPCSK9抗体、およびいかなる既知の哺乳動物タンパク質にも結合しない対照のアイソタイプ適合モノクローナル抗体を、オスの7週齢のC57/bl6マウスにIV注入し、血清試料を、注入後5日目、12日目、19日目、26日目、61日目、および75日目に回収した。全ての血清試料を、Ace Alera機器(Alfa Wassermann、West Caldwell、NJ)で、総コレステロール、トリグリセリド、HDLコレステロールについて分析し、LDLコレステロールレベルを、Friedewaldの式を用いて計算した。図7は、PCSK9アンタゴニスト抗体を注入した後の、総コレステロールレベルの迅速かつ用量依存的な減少を示す。マウスにおけるLDLコレステロールレベルは、確実に測定および計算するには低すぎた。10mg/kgの用量では、4つの抗体全ては、5日目および12日目に、HDLコレステロールを35〜40%低下させたが、5L1721H23_6H3および5L1721H23_6L3H3を注入された動物は61日目まで回復せず、h5A10および5A10.B8を注入された動物は、それぞれ26日目および33日目にベースラインレベルまで回復した。
抗体の血清濃度を、実施例bにおいて記載されているものと同一の研究で決定して、PH感受性の抗PCSK9抗体が延長した抗体半減期をもたらすかどうかを決定した。h5A10および5A10.B6などの正常な抗PCSK9抗体は、抗体/抗原複合体のPCSK9介在性の分解に起因して、他の可溶性抗原に結合する抗体と比較して、用量依存的な短い半減期を有する。図8Aにおいて示されるように、pH依存性の結合特性は、抗体の分解を低減させ、抗PCSK9抗体5L1721H23_6H3および5L1721H23_6L3H3の半減期を延長させた。5L1721H23_6H3および5L1721H23_6L3H3の引き延ばされたPKが抗体のPCSK9介在性のクリアランスの低下により生じたということをさらに実証するために、類似の経時的研究をPCSKノックアウトマウスにおいて行った。pH感受性抗体と非感受性抗体との間の血清抗体濃度および低減速度の差は、3mg/kgのヒトPCSK9をマウスに注入するまで顕著ではなかった。この注入の後、非pH感受性のPCSK9抗体は、pH感受性の抗体および陰性対照抗体と比較して分解の増大を示した(図8B)。これらの結果は、pH依存性PCSK9結合PCSK9抗体の分解の観察された減少が、PCSK9からの抗体の解離、つまりPCSK9介在性の分解からの抗体の救出によって生じることを示す。
図9Bは、パーセント対照であるカニクイザルの血清LDLコレステロールレベルに対する、PH感受性の抗PCSK9アンタゴニスト抗体5L1721H23_6H3および5L1721H23_6L3H3ならびに非感受性の抗PCSK抗体L1L3の効果を説明するものである。抗体(それぞれ1.5mg/kg)を、0日目にメスのカニクイザルにi.v.ボーラス注入を介して投与した。LDLコレステロールは、3つ全ての抗体で処理した群において、日目までにベースラインの50%まで低減した。LDLコレステロールレベルは、非pH感受性の抗体を投与した後10日目までにベースラインに戻ったが、LDLコレステロールは、pH感受性の抗体で処理したサルにおいては、21日目まで抑制されたままであった。HDLレベルは、抗体治療の結果、基本的に不変のまま維持された(図9A)。図10は、pH感受性の抗PCSK9抗体の半減期が非pH感受性のL1L3と比較して延長したことを示す。
コンピュータモデリングを用いて、その包括的な抗原に対するpH依存性の結合を有する抗体が抗体の半減期および/または抗原の量もしくは血清濃度を低下させる期間に影響し得るかどうかを予測した。このモデリングの目的で、以下の仮定を行った:1)抗体;血液中1uM用量の抗体;21日の抗体半減期;2)100日の刺激付与;抗体の結合およびpH依存性の結合;Kon=1e5/M/s;中性pHでのKoff=KD×Kon;pH依存性の結合は、酸性のエンドソームにおけるKoffの増大としてモデリングされる;酸性pHでのKoff=R×中性pHでのKoff。
ヒスチジン置換を、以下の軽鎖可変領域(VL)および重鎖可変領域(VH)のアミノ酸配列(CDRは太字である)を有する抗IgE抗体5.948−H100Yにおける、下線を引かれた残基の位置で行った。
VL
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHRNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPPATFGGGTKVEIK(配列番号25)
VH
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMDPNSGNTGYAQKFQGRVTMTRNTSISTAYMELSSLRSEDTAVYYCARGYYDSDGYYSFSGMDVWGQGTTVTVSS(配列番号26)
ATCC PTA−10548
ATCC PTA−10549
Claims (31)
- pH6.0よりもpH7.4で高い親和性で抗原に特異的に結合する、pH依存性の結合を有する抗体であって、pH6.0/pH7.4および25℃でのKD比率および/またはkoff比率が、2、3、4、8、10、16、またはそれ以上を超えるか、またはこの間の範囲であり、前記抗体が、pH7.4で前記抗原に対する類似の親和性を有するが2未満であるpH6.0/pH7.4での比較KD比率および/またはkoff比率を有する、pH依存性の結合を有さない抗体と比較して、前記抗原に曝露された場合にインビボでの低減した血漿クリアランスを有する、抗体。
- pH6.0よりもpH7.4で高い親和性で抗原に特異的に結合する、pH依存性の結合を有する抗体であって、pH6.0/pH7.4および25℃でのKD比率および/またはkoff比率が、2、3、4、8、10、16、またはそれ以上を超えるか、またはこの間の範囲であり、前記抗原が、膜に結合しており、かつインビボで可溶性であり、前記抗体が、pH7.4で前記抗原に対する類似の親和性を有するが2未満であるpH6.0/pH7.4での比較KD比率および/またはkoff比率を有する抗体と比較して、細胞膜受容体への増大した局在化を仲介する、抗体。
- 抗原がインターロイキン−6受容体ではない、請求項1または2に記載の抗体。
- 抗原が、非シグナル伝達デコイである可溶性受容体である、請求項2に記載の抗体。
- pH依存性の結合を有する前記抗体が、抗体薬剤コンジュゲートであり、抗体依存性細胞介在性細胞傷害作用(ADCC)および/または補体依存性細胞傷害作用(CDC)を仲介する、請求項2に記載の抗体。
- pH6.0よりもpH7.4で高い親和性で抗原に特異的に結合する、pH依存性の結合を有する抗体であって、pH6.0/pH7.4および25℃でのKD比率および/またはkoff比率が2、3、4、8、10、16、またはそれ以上を超えるか、またはこの間の範囲であり、pH7.4で前記抗原に対する類似の親和性を有するが2未満であるpH6.0/pH7.4での比較KD比率および/またはkoff比率を有する、pH依存性の結合を有さない抗体と比較して、前記抗体に曝露された場合に、抗体に結合していない抗原のインビボでの量の減少が引き延ばされる、抗体。
- pH6.0よりもpH7.4で高い親和性で抗原に特異的に結合する、pH依存性の結合を有する抗体であって、pH6.0/pH7.4および25℃でのKD比率および/またはkoff比率が2、3、4、8、10、16、またはそれ以上を超えるか、またはこの間の範囲であり、pH7.4で前記抗原に対する類似の親和性を有するが2未満であるpH6.0/pH7.4での比較KD比率および/またはkoff比率を有する、pH依存性の結合を有さない抗体と比較して、抗体に結合している抗原のインビボでの量が減少する、抗体。
- pH6.0よりもpH7.4で高い親和性で抗原に特異的に結合する、pH依存性の結合を有するアゴニスト抗体であって、pH6.0/pH7.4および25℃でのKD比率および/またはkoff比率が2、3、4、8、10、16、またはそれ以上を超えるか、またはこの間の範囲であり、前記抗原が受容体であり、前記受容体が、pH7.4で前記受容体に対する類似の親和性を有するが2未満であるpH6.0/pH7.4での比較KD比率および/またはkoff比率を有する抗体と比較して、前記抗体に曝露された場合にインビボでの低減したクリアランスを有する、抗体。
- pH6.0/pH7.4でのKD比率またはkoff比率が、20、30、40、または100以上を超えるか、またはこの間の範囲である、請求項1から8のいずれかに記載の抗体。
- pH7.4での抗原への抗体の結合が、約0.01nMから約100nMのKDを有する、請求項1から9のいずれかに記載の抗体。
- pH7.4での抗原への抗体の結合が、約0.1nMから約10nMのKDを有する、請求項10に記載の抗体。
- pH7.4での抗原への抗体の結合が、約1×10E−4s−1から約1×10E−1s−1のkoffを有する、請求項1から11のいずれかに記載の抗体。
- pH7.4での抗原への抗体の結合が、約1×10E−3s−1から約1×10E−1s−1のkoffを有する、請求項12に記載の抗体。
- 抗原がPCSK9である、請求項1に記載の抗体。
- 抗原が、IgE、C5、またはDKK1であり、KDが、1.0nMから約10nMの間または1.0nMから約100nMの間の範囲である、請求項6に記載の抗体。
- 治療用抗体で患者を治療するための間隔投与を延長する方法および/または治療用量を減少させる方法であって、治療上効果的な量の請求項1から15のいずれかに記載の抗体を前記患者に投与するステップを包含し、前記抗体が、pH7.4で類似の親和性を有するが2未満であるpH6.0/7.4でのKD比率および/またはkoff比率を有する抗体と比較して、延長された薬力学的効果および/または半減期を有する、方法。
- pH依存的に抗体結合親和性を調節することによって引き延ばされた半減期および/または薬力学的効果を有する抗体を作製する方法であって、抗体抗原結合が、2、3、4、8、10、16、またはそれ以上を超えるか、またはこの間の範囲であるpH6.0/pH7.4でのKD比率および/またはkoff比率を有するように、pKaに影響する微小環境を最適化する抗体CDRのヒスチジン残基または他の残基を選択するステップを包含する方法。
- pKaに影響する微小環境を最適化するCDR残基または他の残基においてヒスチジンに富む抗体ライブラリー。
- 抗体に突然変異を誘発して、少なくとも100nMのpH7.4でのKDを有する抗体親和性を達成するステップをさらに包含する、請求項17に記載の方法。
- PCSK9に特異的に結合し、配列番号4もしくは配列番号5で示されるVHアミノ酸配列の重鎖可変領域(VH)相補性決定領域1(CDR1)、VH CDR2、およびVH CDR3を包含する、単離された抗体、またはCDR1、CDR2、および/もしくはCDR3に1個、2個、3個、もしくはそれ以上の保存的なアミノ酸置換を有するその変異体。
- 配列番号3で示されるVLアミノ酸配列の軽鎖可変領域(VL)CDR1、CDR2、およびCDR3をさらに包含する、請求項20に記載の単離された抗体、またはCDR1、CDR2、および/もしくはCDR3に1個、2個、3個、もしくはそれ以上の保存的なアミノ酸置換を有するその変異体。
- VH CDR1が配列番号6で示されるアミノ酸配列を有し、VH CDR2が配列番号7で示されるアミノ酸配列を有し、VH CDR3が列番号8または9で示されるアミノ酸配列を有し、VL CDR1が配列番号10で示されるアミノ酸配列を有し、VL CDR2が配列番号11で示されるアミノ酸配列を有し、VL CDR3が、配列番号12で示されるアミノ酸配列を有する、請求項21に記載の単離された抗体、または、CDR1、CDR2、および/もしくはCDR3に1個、2個、3個、もしくはそれ以上の保存的なアミノ酸置換を有するその変異体。
- VH CDR3が配列番号9のアミノ酸配列を有する、請求項22に記載の単離された抗体、または、CDR1、CDR2、および/もしくはCDR3に1個、2個、3個、もしくはそれ以上の保存的なアミノ酸置換を有するその変異体。
- VH領域が配列番号4または配列番号5を包含し、VL領域が配列番号3を包含する、請求項23に記載の単離された抗体。
- VH領域が配列番号5を包含する、請求項24に記載の単離された抗体。
- ATCCに寄託され、ATCC受託番号PTA−10547またはPTA−10548および/またはPTA−10549を有するプラスミドによってコードされている、抗体またはその抗原結合部分。
- 治療上効果的な量の請求項1から26のいずれかに記載の抗体を包含する医薬組成物。
- 請求項1から26のいずれかに記載の抗体を組換えにより産生する宿主細胞。
- 請求項1から26のいずれかに記載の抗体をコードする単離された核酸。
- ATCCに寄託され、ATCC受託番号PTA−10547またはPTA−10548および/またはPTA−10549を有する、単離されたプラスミド。
- それを必要とする対象の血液におけるLDLコレステロールのレベルを低減させるための方法であって、治療上効果的な量の請求項1から26に記載の抗体を前記対象に投与するステップを包含する方法。
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---|---|---|---|---|
ES2592271T3 (es) | 2005-03-31 | 2016-11-29 | Chugai Seiyaku Kabushiki Kaisha | Métodos de producción de polipéptidos mediante la regulación de la asociación de los polipéptidos |
WO2007114325A1 (ja) | 2006-03-31 | 2007-10-11 | Chugai Seiyaku Kabushiki Kaisha | 二重特異性抗体を精製するための抗体改変方法 |
US20130072665A1 (en) * | 2007-08-23 | 2013-03-21 | Simon Mark Jackson | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (pcsk9) |
JOP20080381B1 (ar) | 2007-08-23 | 2023-03-28 | Amgen Inc | بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9) |
MX342551B (es) | 2007-09-26 | 2016-10-04 | Chugai Pharmaceutical Co Ltd | Region constante de anticuerpo modificada. |
US20110129459A1 (en) | 2007-12-05 | 2011-06-02 | Chugai Seiyaku Kabushiki Kaisha | Anti-nr10 antibody and use thereof |
TWI440469B (zh) | 2008-09-26 | 2014-06-11 | Chugai Pharmaceutical Co Ltd | Improved antibody molecules |
JO3672B1 (ar) | 2008-12-15 | 2020-08-27 | Regeneron Pharma | أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9). |
US20130064834A1 (en) | 2008-12-15 | 2013-03-14 | Regeneron Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia using antibodies to pcsk9 |
JP5787446B2 (ja) | 2009-03-19 | 2015-09-30 | 中外製薬株式会社 | 抗体定常領域改変体 |
JP5717624B2 (ja) | 2009-03-19 | 2015-05-13 | 中外製薬株式会社 | 抗体定常領域改変体 |
KR20120024763A (ko) | 2009-05-15 | 2012-03-14 | 추가이 세이야쿠 가부시키가이샤 | 항axl 항체 |
EP2481752B1 (en) | 2009-09-24 | 2016-11-09 | Chugai Seiyaku Kabushiki Kaisha | Modified antibody constant regions |
WO2011108714A1 (ja) | 2010-03-04 | 2011-09-09 | 中外製薬株式会社 | 抗体定常領域改変体 |
TWI667346B (zh) | 2010-03-30 | 2019-08-01 | 中外製藥股份有限公司 | 促進抗原消失之具有經修飾的FcRn親和力之抗體 |
PT2644698T (pt) | 2010-11-17 | 2018-01-31 | Chugai Pharmaceutical Co Ltd | Molécula multiespecífica de ligação ao antigénio com uma função alternativa à função do fator viii de coagulação do sangue |
RU2721279C2 (ru) | 2011-01-28 | 2020-05-18 | Санофи Байотекнолоджи | Антитела человека к pcsk9 для применения в способах лечения конкретных групп индивидуумов |
EP3138581B1 (en) | 2011-03-17 | 2019-01-02 | The University of Birmingham | Re-directed immunotherapy |
EP2731623A1 (en) * | 2011-07-14 | 2014-05-21 | Pfizer Inc | Treatment with anti-pcsk9 antibodies |
AR087305A1 (es) | 2011-07-28 | 2014-03-12 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit |
JP6158813B2 (ja) | 2011-09-16 | 2017-07-05 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | プロタンパク質転換酵素サブチリシンケキシン−9(PCSK9)の阻害剤を投与することによってリポタンパク質(a)レベルを低下させる方法 |
AR087715A1 (es) | 2011-09-16 | 2014-04-09 | Lilly Co Eli | Anticuerpos anti pcsk9 y usos de los mismos |
CA3186007A1 (en) * | 2011-09-30 | 2013-04-04 | Chugai Seiyaku Kabushiki Kaisha | Ion concentration-dependent binding molecule library |
CA2850322C (en) | 2011-09-30 | 2023-10-10 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule inducing immune response to target antigen |
TW201817745A (zh) | 2011-09-30 | 2018-05-16 | 日商中外製藥股份有限公司 | 具有促進抗原清除之FcRn結合域的治療性抗原結合分子 |
JP6635655B2 (ja) | 2011-12-08 | 2020-01-29 | アムジエン・インコーポレーテツド | ヒトlcat抗原結合タンパク質および治療法におけるそれらの使用 |
LT2825037T (lt) * | 2012-03-16 | 2019-08-12 | Regeneron Pharmaceuticals, Inc. | Graužikai, ekspresuojantys ph jautrias imunoglobulino sekas |
RS57118B1 (sr) * | 2012-03-16 | 2018-06-29 | Regeneron Pharma | Antitela sa lakim lancem konstruisanim sa histidinom i genetički modifikovani glodari za generisanje istih |
RU2014141536A (ru) | 2012-03-16 | 2016-05-10 | Регенерон Фармасьютикалз, Инк. | Мыши, которые продуцируют антигенсвязывающие белки с зависимыми от величины ph характеристиками связывания |
US20140013456A1 (en) | 2012-03-16 | 2014-01-09 | Regeneron Pharmaceuticals, Inc. | Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same |
US9255154B2 (en) | 2012-05-08 | 2016-02-09 | Alderbio Holdings, Llc | Anti-PCSK9 antibodies and use thereof |
EP2852840B1 (en) * | 2012-05-23 | 2019-10-09 | F.Hoffmann-La Roche Ag | Selection method for therapeutic agents |
WO2013188855A1 (en) | 2012-06-15 | 2013-12-19 | Genentech, Inc. | Anti-pcsk9 antibodies, formulations, dosing, and methods of use |
TWI596115B (zh) * | 2012-08-13 | 2017-08-21 | 再生元醫藥公司 | 具有pH-依賴性結合特性之抗-PCSK9抗體 |
RU2729831C2 (ru) | 2012-08-24 | 2020-08-12 | Чугаи Сейяку Кабусики Кайся | ВАРИАНТЫ FcγRIIB-СПЕЦИФИЧЕСКОЙ Fc-ОБЛАСТИ |
JP6774164B2 (ja) | 2012-08-24 | 2020-10-21 | 中外製薬株式会社 | マウスFcγRII特異的Fc抗体 |
WO2014047222A2 (en) * | 2012-09-19 | 2014-03-27 | Abbvie Biotherapeutics Inc. | Methods for identifying antibodies with reduced immunogenicity |
EP2922590B1 (en) | 2012-11-21 | 2020-02-05 | Amgen Inc. | Drug delivery device |
US10766960B2 (en) | 2012-12-27 | 2020-09-08 | Chugai Seiyaku Kabushiki Kaisha | Heterodimerized polypeptide |
WO2014107739A1 (en) * | 2013-01-07 | 2014-07-10 | Eleven Biotherapeutics, Inc. | Antibodies against pcsk9 |
ES2736052T3 (es) * | 2013-02-20 | 2019-12-23 | Regeneron Pharma | Ratones que expresan co-receptores humanizados de células T |
EP2958937B1 (en) * | 2013-02-22 | 2018-08-15 | Regeneron Pharmaceuticals, Inc. | Mice expressing humanized major histocompatibility complex |
CN105208855B (zh) * | 2013-03-11 | 2018-04-27 | 瑞泽恩制药公司 | 表达嵌合的主要组织相容性复合物(mhc)ii类分子的转基因小鼠 |
EP3593839A1 (en) | 2013-03-15 | 2020-01-15 | Amgen Inc. | Drug cassette |
US20160009818A1 (en) * | 2013-03-15 | 2016-01-14 | Bayer Healthcare Llc | Anti-TFPI Antibody Variants with Differential Binding Across pH Range For Improved Pharmacokinetics |
TWI580451B (zh) | 2013-03-15 | 2017-05-01 | 安美基公司 | 用於注射器之匣盒及使用具有自動注射器及匣盒之自動注射器設備之方法 |
LT2976117T (lt) | 2013-03-22 | 2021-02-25 | Amgen Inc. | Purkštuvas ir surinkimo būdas |
US10111953B2 (en) | 2013-05-30 | 2018-10-30 | Regeneron Pharmaceuticals, Inc. | Methods for reducing remnant cholesterol and other lipoprotein fractions by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9) |
EP2862877A1 (en) | 2013-10-18 | 2015-04-22 | Sanofi | Methods for inhibiting atherosclerosis by administering an inhibitor of PCSK9 |
CA2914721A1 (en) | 2013-06-07 | 2014-12-11 | Regeneron Pharmaceuticals, Inc. | Methods for inhibiting atherosclerosis by administering an inhibitor of pcsk9 |
AR096890A1 (es) * | 2013-07-12 | 2016-02-03 | Hanmi Pharm Ind Co Ltd | Conjugando fc de inmunoglobulina, que mantiene la afinidad de unión del fragmento fc de la inmunoglobulina a fcrn |
ES2738679T3 (es) * | 2013-09-18 | 2020-01-24 | Regeneron Pharma | Anticuerpos de cadena ligera diseñados genéticamente con histidina y animales no humanos modificados genéticamente para generar los mismos |
SG11201602261VA (en) | 2013-09-27 | 2016-04-28 | Chugai Pharmaceutical Co Ltd | Method for producing polypeptide heteromultimer |
WO2015061389A1 (en) | 2013-10-24 | 2015-04-30 | Amgen Inc. | Drug delivery system with temperature-sensitive control |
AU2014340171B2 (en) | 2013-10-24 | 2019-05-30 | Amgen Inc. | Injector and method of assembly |
WO2015073494A1 (en) | 2013-11-12 | 2015-05-21 | Sanofi | Dosing regimens for use with pcsk9 inhibitors |
US9914769B2 (en) | 2014-07-15 | 2018-03-13 | Kymab Limited | Precision medicine for cholesterol treatment |
US9051378B1 (en) | 2014-07-15 | 2015-06-09 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US8945560B1 (en) | 2014-07-15 | 2015-02-03 | Kymab Limited | Method of treating rheumatoid arthritis using antibody to IL6R |
US8986694B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Targeting human nav1.7 variants for treatment of pain |
US9023359B1 (en) | 2014-07-15 | 2015-05-05 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US8992927B1 (en) | 2014-07-15 | 2015-03-31 | Kymab Limited | Targeting human NAV1.7 variants for treatment of pain |
US8980273B1 (en) | 2014-07-15 | 2015-03-17 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
US9067998B1 (en) | 2014-07-15 | 2015-06-30 | Kymab Limited | Targeting PD-1 variants for treatment of cancer |
US9045548B1 (en) | 2014-07-15 | 2015-06-02 | Kymab Limited | Precision Medicine by targeting rare human PCSK9 variants for cholesterol treatment |
US8883157B1 (en) | 2013-12-17 | 2014-11-11 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
US8986691B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
US9034332B1 (en) | 2014-07-15 | 2015-05-19 | Kymab Limited | Precision medicine by targeting rare human PCSK9 variants for cholesterol treatment |
DE202014010499U1 (de) | 2013-12-17 | 2015-10-20 | Kymab Limited | Targeting von humaner PCSK9 zur Cholesterinbehandlung |
US9017678B1 (en) | 2014-07-15 | 2015-04-28 | Kymab Limited | Method of treating rheumatoid arthritis using antibody to IL6R |
US9045545B1 (en) | 2014-07-15 | 2015-06-02 | Kymab Limited | Precision medicine by targeting PD-L1 variants for treatment of cancer |
WO2015119906A1 (en) | 2014-02-05 | 2015-08-13 | Amgen Inc. | Drug delivery system with electromagnetic field generator |
MX2016009858A (es) | 2014-02-21 | 2017-01-26 | Medimmune Llc | Fusiones anti proteína convertasa subtilisina/kexina tipo 9 (anti-pcsk9)n péptido 1 similar a glucagón (glp-1) y métodos de uso. |
GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
MX2016012667A (es) * | 2014-03-28 | 2017-01-09 | Opko Diagnostics Llc | Composiciones y metodos relacionados con el diagnostico de cancer de prostata. |
CA3193070A1 (en) | 2014-05-07 | 2015-11-12 | Amgen Inc. | Autoinjector with shock reducing elements |
WO2015175375A1 (en) | 2014-05-13 | 2015-11-19 | Short Jay M | Conditionally active biological proteins |
JP6817074B2 (ja) | 2014-06-03 | 2021-01-20 | アムジエン・インコーポレーテツド | 制御可能な薬物送達システム及び使用方法 |
CN106459192B (zh) * | 2014-06-30 | 2021-08-03 | 默克专利股份公司 | 具有pH依赖性抗原结合的抗TNFa抗体 |
DE202015008974U1 (de) | 2014-07-15 | 2016-06-30 | Kymab Limited | Targeting von humaner PCSK9 zur Cholesterinbehandlung |
US9150660B1 (en) | 2014-07-15 | 2015-10-06 | Kymab Limited | Precision Medicine by targeting human NAV1.8 variants for treatment of pain |
EP3332790A1 (en) | 2014-07-15 | 2018-06-13 | Kymab Limited | Antibodies for use in treating conditions related to specific pcsk9 variants in specific patients populations |
DE202015009002U1 (de) | 2014-07-15 | 2016-08-18 | Kymab Limited | Targeting von humaner PCSK9 zur Cholesterinbehandlung |
US9139648B1 (en) | 2014-07-15 | 2015-09-22 | Kymab Limited | Precision medicine by targeting human NAV1.9 variants for treatment of pain |
AU2015289613B2 (en) | 2014-07-16 | 2021-07-01 | Regeneron Pharmaceuticals, Inc. | Methods for treating patients with heterozygous familial hypercholesterolemia (heFH) |
WO2016023916A1 (en) | 2014-08-12 | 2016-02-18 | Kymab Limited | Treatment of disease using ligand binding to targets of interest |
MA40764A (fr) | 2014-09-26 | 2017-08-01 | Chugai Pharmaceutical Co Ltd | Agent thérapeutique induisant une cytotoxicité |
MX2021014323A (es) | 2014-10-14 | 2023-02-02 | Amgen Inc | Dispositivo de inyección de fármaco con indicadores visuales y audibles. |
WO2016071701A1 (en) | 2014-11-07 | 2016-05-12 | Kymab Limited | Treatment of disease using ligand binding to targets of interest |
KR20160069363A (ko) | 2014-12-08 | 2016-06-16 | 삼성전자주식회사 | 항체 선별 방법 |
SG11201700841QA (en) | 2014-12-19 | 2017-03-30 | Chugai Pharmaceutical Co Ltd | Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use |
EP3233163B1 (en) | 2014-12-19 | 2021-10-13 | Amgen Inc. | Drug delivery device with proximity sensor |
US11357916B2 (en) | 2014-12-19 | 2022-06-14 | Amgen Inc. | Drug delivery device with live button or user interface field |
CN114773469A (zh) | 2015-02-05 | 2022-07-22 | 中外制药株式会社 | 包含离子浓度依赖性的抗原结合结构域的抗体,fc区变体,il-8-结合抗体及其应用 |
CA3069716C (en) | 2015-02-17 | 2021-11-09 | Amgen Inc. | Drug delivery device with vacuum assisted securement and/or feedback |
EP3981450A1 (en) | 2015-02-27 | 2022-04-13 | Amgen, Inc | Drug delivery device having a needle guard mechanism with a tunable threshold of resistance to needle guard movement |
JP6130983B2 (ja) | 2015-02-27 | 2017-05-17 | 中外製薬株式会社 | Il−6関連疾患治療用組成物 |
ES2867798T3 (es) | 2015-03-27 | 2021-10-20 | Opko Diagnostics Llc | Estándares del antígeno prostático y usos de estos |
WO2016159213A1 (ja) | 2015-04-01 | 2016-10-06 | 中外製薬株式会社 | ポリペプチド異種多量体の製造方法 |
WO2016191659A1 (en) * | 2015-05-28 | 2016-12-01 | Bio-Rad Laboratories, Inc. | Affinity ligands and methods relating thereto |
JP2018523684A (ja) | 2015-08-18 | 2018-08-23 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | リポタンパク質アフェレーシスを受けている高脂血症の患者を治療するための抗pcsk9阻害抗体 |
WO2017039786A1 (en) | 2015-09-02 | 2017-03-09 | Amgen Inc. | Syringe assembly adapter for a syringe |
JP7082568B2 (ja) | 2015-12-09 | 2022-06-08 | アムジエン・インコーポレーテツド | 信号伝達キャップ付き自動注射器 |
WO2017104783A1 (en) * | 2015-12-18 | 2017-06-22 | Chugai Seiyaku Kabushiki Kaisha | Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use |
KR102467124B1 (ko) * | 2015-12-18 | 2022-11-15 | 추가이 세이야쿠 가부시키가이샤 | 항-c5 항체 및 사용 방법 |
US11359009B2 (en) | 2015-12-25 | 2022-06-14 | Chugai Seiyaku Kabushiki Kaisha | Anti-myostatin antibodies and methods of use |
CA3004288A1 (en) | 2015-12-28 | 2017-07-06 | Nobuyuki Tanaka | Method for promoting efficiency of purification of fc region-containing polypeptide |
JP7032662B2 (ja) | 2015-12-31 | 2022-03-09 | ジエンス ヘンルイ メデイシンカンパニー リミテッド | Pcsk9抗体、その抗原結合フラグメント及び医薬用途 |
WO2017118307A1 (zh) | 2016-01-05 | 2017-07-13 | 江苏恒瑞医药股份有限公司 | Pcsk9抗体、其抗原结合片段及其医药用途 |
WO2017120178A1 (en) | 2016-01-06 | 2017-07-13 | Amgen Inc. | Auto-injector with signaling electronics |
RU2746754C2 (ru) | 2016-03-14 | 2021-04-20 | Чугаи Сейяку Кабусики Кайся | Индуцирующее повреждение клеток терапевтическое лекарственное средство, предназначенное для противораковой терапии |
EP3721922B1 (en) | 2016-03-15 | 2022-05-04 | Amgen Inc. | Reducing probability of glass breakage in drug delivery devices |
EP3443012A4 (en) * | 2016-04-15 | 2019-09-11 | Bioatla, LLC | ANTI-AXL ANTIBODIES, ANTIBODY FRAGMENTS AND ITS IMMUNOCONJUGATES AND USES THEREOF |
US11541168B2 (en) | 2016-04-29 | 2023-01-03 | Amgen Inc. | Drug delivery device with messaging label |
US11389588B2 (en) | 2016-05-02 | 2022-07-19 | Amgen Inc. | Syringe adapter and guide for filling an on-body injector |
CA3018426A1 (en) | 2016-05-13 | 2017-11-16 | Amgen Inc. | Vial sleeve assembly |
WO2017200989A1 (en) | 2016-05-16 | 2017-11-23 | Amgen Inc. | Data encryption in medical devices with limited computational capability |
EP3465124A1 (en) | 2016-06-03 | 2019-04-10 | Amgen Inc. | Impact testing apparatuses and methods for drug delivery devices |
MY187848A (en) * | 2016-06-17 | 2021-10-26 | Chugai Pharmaceutical Co Ltd | Anti-c5 antibodies and methods of use |
EP3478342A1 (en) | 2016-07-01 | 2019-05-08 | Amgen Inc. | Drug delivery device having minimized risk of component fracture upon impact events |
EP3481864A1 (en) | 2016-07-08 | 2019-05-15 | Staten Biotechnology B.V. | Anti-apoc3 antibodies and methods of use thereof |
WO2018034784A1 (en) | 2016-08-17 | 2018-02-22 | Amgen Inc. | Drug delivery device with placement detection |
US20200261643A1 (en) | 2016-10-25 | 2020-08-20 | Amgen Inc. | On-body injector |
WO2018083248A1 (en) | 2016-11-03 | 2018-05-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
JP2020518240A (ja) | 2017-01-17 | 2020-06-25 | ザ テキサス エー アンド エム ユニバーシティー システム | 標的細胞のエンドリソソーム区画へのカーゴ分子の送達の向上のためのエンドリソソーム標的化コンジュゲート |
AU2018210301A1 (en) | 2017-01-17 | 2019-08-01 | Amgen Inc. | Injection devices and related methods of use and assembly |
SG10201908697XA (en) | 2017-01-31 | 2019-10-30 | Chugai Pharmaceutical Co Ltd | A pharmaceutical composition for use in the treatment or prevention of a c5-related disease and a method for treating or preventing a c5-related disease |
EP3582829A1 (en) | 2017-02-17 | 2019-12-25 | Amgen Inc. | Insertion mechanism for drug delivery device |
MX2019009625A (es) | 2017-02-17 | 2019-10-09 | Amgen Inc | Dispositivo de administracion de farmacos con trayectoria de flujo de fluido esteril y metodo relacionado de ensamblaje. |
CA3050927A1 (en) | 2017-03-06 | 2018-09-13 | Brian Stonecipher | Drug delivery device with activation prevention feature |
CA3052482A1 (en) | 2017-03-07 | 2018-09-13 | Amgen Inc. | Needle insertion by overpressure |
IL303449B1 (en) | 2017-03-09 | 2024-04-01 | Amgen Inc | Insertion mechanism for a drug delivery device |
MA49886A (fr) | 2017-03-16 | 2020-06-24 | Medimmune Ltd | Anticorps anti-par2 et leurs utilisations |
CN114588404A (zh) | 2017-03-28 | 2022-06-07 | 美国安进公司 | 柱塞杆和注射器组件系统以及方法 |
JP7185884B2 (ja) | 2017-05-02 | 2022-12-08 | 国立研究開発法人国立精神・神経医療研究センター | Il-6及び好中球の関連する疾患の治療効果の予測及び判定方法 |
AU2018280054B2 (en) | 2017-06-08 | 2023-07-13 | Amgen Inc. | Syringe assembly for a drug delivery device and method of assembly |
AU2018282077B2 (en) | 2017-06-08 | 2023-11-23 | Amgen Inc. | Torque driven drug delivery device |
AU2018288604B2 (en) | 2017-06-22 | 2023-12-21 | Amgen Inc. | Device activation impact/shock reduction |
MX2019015479A (es) | 2017-06-23 | 2020-02-20 | Amgen Inc | Dispositivo electronico de administracion de farmacos con tapa accionada por un conjunto de conmutador. |
WO2019014014A1 (en) | 2017-07-14 | 2019-01-17 | Amgen Inc. | NEEDLE INSERTION-RETRACTING SYSTEM HAVING DOUBLE TORSION SPRING SYSTEM |
JP2020527376A (ja) | 2017-07-21 | 2020-09-10 | アムジエン・インコーポレーテツド | 薬物容器のためのガス透過性シーリング部材及び組立方法 |
JP7242562B2 (ja) | 2017-07-25 | 2023-03-20 | アムジエン・インコーポレーテツド | 容器アクセスシステムを有する薬物送達デバイス及び関連する組立方法 |
EP3658203B1 (en) | 2017-07-25 | 2022-08-31 | Amgen Inc. | Drug delivery device with gear module and related method of assembly |
SI3658184T1 (sl) | 2017-07-27 | 2024-01-31 | Alexion Pharmaceuticals, Inc., | Formulacije z visoko koncentracijo protiteles proti-C5 |
MA49838A (fr) | 2017-08-09 | 2020-06-17 | Amgen Inc | Systèm de administration de médicaments avec pression hydraulique-pneumatique de chambre |
US11077246B2 (en) | 2017-08-18 | 2021-08-03 | Amgen Inc. | Wearable injector with sterile adhesive patch |
US11103636B2 (en) | 2017-08-22 | 2021-08-31 | Amgen Inc. | Needle insertion mechanism for drug delivery device |
US11759565B2 (en) | 2017-10-04 | 2023-09-19 | Amgen Inc. | Flow adapter for drug delivery device |
EP4257164A3 (en) | 2017-10-06 | 2024-01-17 | Amgen Inc. | Drug delivery device with interlock assembly and related method of assembly |
US11464903B2 (en) | 2017-10-09 | 2022-10-11 | Amgen Inc. | Drug delivery device with drive assembly and related method of assembly |
JP7039694B2 (ja) | 2017-10-31 | 2022-03-22 | スターテン・バイオテクノロジー・ベー・フェー | 抗apoc3抗体およびその使用方法 |
US10538583B2 (en) | 2017-10-31 | 2020-01-21 | Staten Biotechnology B.V. | Anti-APOC3 antibodies and compositions thereof |
WO2019090086A1 (en) | 2017-11-03 | 2019-05-09 | Amgen Inc. | Systems and approaches for sterilizing a drug delivery device |
MA50553A (fr) | 2017-11-06 | 2020-09-16 | Amgen Inc | Dispositif d'administration de médicament avec détection de positionnement et de débit |
MA50569A (fr) | 2017-11-06 | 2020-09-16 | Amgen Inc | Ensembles de remplissage-finition et procédés associés |
JP7247174B2 (ja) | 2017-11-10 | 2023-03-28 | アムジエン・インコーポレーテツド | 薬物送達デバイスのプランジャ |
AU2018368340B2 (en) | 2017-11-16 | 2024-03-07 | Amgen Inc. | Door latch mechanism for drug delivery device |
MA50903A (fr) | 2017-11-16 | 2021-05-12 | Amgen Inc | Auto-injecteur avec détection de décrochage et de point d'extrémité |
US10835685B2 (en) | 2018-05-30 | 2020-11-17 | Amgen Inc. | Thermal spring release mechanism for a drug delivery device |
US11083840B2 (en) | 2018-06-01 | 2021-08-10 | Amgen Inc. | Modular fluid path assemblies for drug delivery devices |
CA3103681A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Delivery devices for administering drugs |
WO2020023220A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Hybrid drug delivery devices with tacky skin attachment portion and related method of preparation |
US20210228815A1 (en) | 2018-07-24 | 2021-07-29 | Amgen Inc. | Hybrid drug delivery devices with grip portion |
MA53375A (fr) | 2018-07-24 | 2021-06-02 | Amgen Inc | Dispositifs d'administration pour l'administration de médicaments |
MA53320A (fr) | 2018-07-31 | 2021-11-03 | Amgen Inc | Ensemble de trajet de fluide pour dispositif d'administration de médicament |
CN112512563A (zh) | 2018-08-01 | 2021-03-16 | 中外制药株式会社 | 用于治疗或预防c5相关疾病的药物组合物和治疗或预防c5相关疾病的方法 |
US20210346601A1 (en) | 2018-09-24 | 2021-11-11 | Amgen Inc. | Interventional dosing systems and methods |
WO2020068476A1 (en) | 2018-09-28 | 2020-04-02 | Amgen Inc. | Muscle wire escapement activation assembly for a drug delivery device |
AR116679A1 (es) | 2018-10-02 | 2021-06-02 | Amgen Inc | Sistemas de inyección para la administración de fármacos con transmisión de fuerza interna |
US20210338936A1 (en) | 2018-10-05 | 2021-11-04 | Amgen Inc. | Drug delivery device having dose indicator |
EP3866890A1 (en) | 2018-10-15 | 2021-08-25 | Amgen Inc. | Drug delivery device having damping mechanism |
CA3109988A1 (en) | 2018-10-15 | 2020-04-23 | Amgen Inc. | Platform assembly process for drug delivery device |
WO2020091981A1 (en) | 2018-11-01 | 2020-05-07 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
EP3873567A1 (en) | 2018-11-01 | 2021-09-08 | Amgen Inc. | Drug delivery devices with partial needle retraction |
WO2020091956A1 (en) | 2018-11-01 | 2020-05-07 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
EP3903102B1 (en) * | 2018-12-30 | 2023-04-12 | F. Hoffmann-La Roche AG | Ph-gradient spr-based binding assay |
MX2021012557A (es) | 2019-04-24 | 2021-11-12 | Amgen Inc | Conjuntos y metodos de verificacion de esterilizacion de jeringuillas. |
WO2020236670A1 (en) | 2019-05-17 | 2020-11-26 | Regeneron Pharmaceuticals, Inc. | Genome-based methods for reducing cardiovascular risk |
AU2020287165A1 (en) * | 2019-06-06 | 2022-02-03 | Mythic Therapeutics, Inc. | Antigen-binding protein constructs and uses thereof |
EP3980130A1 (en) * | 2019-06-06 | 2022-04-13 | Mythic Therapeutics, Inc. | Antigen-binding protein constructs and uses thereof |
WO2020247873A1 (en) * | 2019-06-07 | 2020-12-10 | Mythic Therapeutics, Inc. | Antigen-binding protein constructs and uses thereof |
US20220288219A1 (en) * | 2019-07-08 | 2022-09-15 | Mythic Therapeutics, Inc. | Antigen-binding protein constructs and uses thereof |
US20230018417A1 (en) | 2019-07-26 | 2023-01-19 | Shire Human Genetic Therapies, Inc. | Recombinant Heme Oxygenase-1 (HO-1) for the Treatment of Sickle Cell Disease |
JP2022543771A (ja) * | 2019-07-30 | 2022-10-14 | ミシック セラピューティクス インコーポレイテッド | 抗原結合タンパク質構築物及びその使用 |
US20220273887A1 (en) | 2019-08-23 | 2022-09-01 | Amgen Inc. | Drug delivery device with configurable needle shield engagement components and related methods |
US20220348679A1 (en) * | 2019-10-04 | 2022-11-03 | Mythic Therapeutics, Inc. | Antigen-binding protein constructs and uses thereof |
BR112022021450A2 (pt) | 2020-04-24 | 2022-12-27 | Millennium Pharm Inc | O cd19 ou fragmento de ligação, método de tratamento de um câncer, composição farmacêutica, ácido nucleico, vetor, e, célula isolada |
CN114716560B (zh) * | 2021-01-04 | 2024-02-02 | 中国医学科学院基础医学研究所 | 一种人乳头瘤病毒18型嵌合蛋白及其用途 |
CN117425673A (zh) | 2021-04-09 | 2024-01-19 | 武田药品工业株式会社 | 靶向补体因子d的抗体和其用途 |
CN117580860A (zh) | 2021-04-26 | 2024-02-20 | 米伦纽姆医药公司 | 抗adgre2抗体及其用途 |
CA3216770A1 (en) | 2021-04-26 | 2022-11-03 | Tomoki Yoshihara | Anti-clec12a antibodies and uses thereof |
CA3217207A1 (en) | 2021-05-21 | 2022-11-24 | Amgen Inc. | Method of optimizing a filling recipe for a drug container |
WO2023068382A2 (en) | 2021-10-20 | 2023-04-27 | Takeda Pharmaceutical Company Limited | Compositions targeting bcma and methods of use thereof |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007520494A (ja) * | 2004-02-03 | 2007-07-26 | 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 | 溶血性疾患の処置方法 |
WO2009026558A1 (en) * | 2007-08-23 | 2009-02-26 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (pcsk9) |
JP2009055902A (ja) * | 1997-07-02 | 2009-03-19 | Genentech Inc | 改良抗IgE抗体及びポリペプチドの改良方法 |
JP2009523421A (ja) * | 2006-01-13 | 2009-06-25 | ノバルティス アクチエンゲゼルシャフト | Dickkopf−1および/または−4に対する抗体の組成物および製造法その使用方法 |
WO2009125825A1 (ja) * | 2008-04-11 | 2009-10-15 | 中外製薬株式会社 | 複数分子の抗原に繰り返し結合する抗原結合分子 |
Family Cites Families (92)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
FR2413974A1 (fr) | 1978-01-06 | 1979-08-03 | David Bernard | Sechoir pour feuilles imprimees par serigraphie |
US4485045A (en) | 1981-07-06 | 1984-11-27 | Research Corporation | Synthetic phosphatidyl cholines useful in forming liposomes |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4544545A (en) | 1983-06-20 | 1985-10-01 | Trustees University Of Massachusetts | Liposomes containing modified cholesterol for organ targeting |
US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
US4754065A (en) | 1984-12-18 | 1988-06-28 | Cetus Corporation | Precursor to nucleic acid probe |
US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
US4777127A (en) | 1985-09-30 | 1988-10-11 | Labsystems Oy | Human retrovirus-related products and methods of diagnosing and treating conditions associated with said retrovirus |
GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
US4800159A (en) | 1986-02-07 | 1989-01-24 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences |
GB8702816D0 (en) | 1987-02-07 | 1987-03-11 | Al Sumidaie A M K | Obtaining retrovirus-containing fraction |
US5219740A (en) | 1987-02-13 | 1993-06-15 | Fred Hutchinson Cancer Research Center | Retroviral gene transfer into diploid fibroblasts for gene therapy |
US5422120A (en) | 1988-05-30 | 1995-06-06 | Depotech Corporation | Heterovesicular liposomes |
AP129A (en) | 1988-06-03 | 1991-04-17 | Smithkline Biologicals S A | Expression of retrovirus gag protein eukaryotic cells |
GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
US5047335A (en) | 1988-12-21 | 1991-09-10 | The Regents Of The University Of Calif. | Process for controlling intracellular glycosylation of proteins |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
EP0454781B1 (en) | 1989-01-23 | 1998-12-16 | Chiron Corporation | Recombinant cells for therapies of infection and hyperproliferative disorders and preparation thereof |
CA2489769A1 (en) | 1989-03-21 | 1990-10-04 | Philip L. Felgner | Expression of exogenous polynucleotide sequences in a vertebrate |
US6673776B1 (en) | 1989-03-21 | 2004-01-06 | Vical Incorporated | Expression of exogenous polynucleotide sequences in a vertebrate, mammal, fish, bird or human |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
EP0479909B1 (en) | 1989-06-29 | 1996-10-30 | Medarex, Inc. | Bispecific reagents for aids therapy |
EP1001032A3 (en) | 1989-08-18 | 2005-02-23 | Chiron Corporation | Recombinant retroviruses delivering vector constructs to target cells |
US5585362A (en) | 1989-08-22 | 1996-12-17 | The Regents Of The University Of Michigan | Adenovirus vectors for gene therapy |
US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
NZ237464A (en) | 1990-03-21 | 1995-02-24 | Depotech Corp | Liposomes with at least two separate chambers encapsulating two separate biologically active substances |
US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
ATE158021T1 (de) | 1990-08-29 | 1997-09-15 | Genpharm Int | Produktion und nützung nicht-menschliche transgentiere zur produktion heterologe antikörper |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
ATE164395T1 (de) | 1990-12-03 | 1998-04-15 | Genentech Inc | Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften |
US5278299A (en) | 1991-03-18 | 1994-01-11 | Scripps Clinic And Research Foundation | Method and composition for synthesizing sialylated glycosyl compounds |
EP0586505A1 (en) | 1991-05-14 | 1994-03-16 | Repligen Corporation | Heteroconjugate antibodies for treatment of hiv infection |
EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
GB9115364D0 (en) | 1991-07-16 | 1991-08-28 | Wellcome Found | Antibody |
CA2115742A1 (en) | 1991-08-20 | 1993-03-04 | Ronald G. Crystal | Adenovirus mediated transfer of genes to the gastrointestinal tract |
AU669124B2 (en) | 1991-09-18 | 1996-05-30 | Kyowa Hakko Kirin Co., Ltd. | Process for producing humanized chimera antibody |
DE69229477T2 (de) | 1991-09-23 | 1999-12-09 | Cambridge Antibody Tech | Methoden zur Herstellung humanisierter Antikörper |
US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
WO1993010218A1 (en) | 1991-11-14 | 1993-05-27 | The United States Government As Represented By The Secretary Of The Department Of Health And Human Services | Vectors including foreign genes and negative selective markers |
AU3144193A (en) | 1991-11-21 | 1993-06-15 | Board Of Trustees Of The Leland Stanford Junior University | Controlling degradation of glycoprotein oligosaccharides by extracellular glycosisases |
GB9125623D0 (en) | 1991-12-02 | 1992-01-29 | Dynal As | Cell modification |
US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
FR2688514A1 (fr) | 1992-03-16 | 1993-09-17 | Centre Nat Rech Scient | Adenovirus recombinants defectifs exprimant des cytokines et medicaments antitumoraux les contenant. |
US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
WO1993025234A1 (en) | 1992-06-08 | 1993-12-23 | The Regents Of The University Of California | Methods and compositions for targeting specific tissue |
EP0644946A4 (en) | 1992-06-10 | 1997-03-12 | Us Health | VECTOR PARTICLES RESISTANT TO HUMAN SERUM INACTIVATION. |
GB2269175A (en) | 1992-07-31 | 1994-02-02 | Imperial College | Retroviral vectors |
CA2140280A1 (en) | 1992-08-17 | 1994-03-03 | Avi J. Ashkenazi | Bispecific immunoadhesins |
US6210671B1 (en) | 1992-12-01 | 2001-04-03 | Protein Design Labs, Inc. | Humanized antibodies reactive with L-selectin |
JPH08503855A (ja) | 1992-12-03 | 1996-04-30 | ジェンザイム・コーポレイション | 嚢胞性線維症に対する遺伝子治療 |
US5981568A (en) | 1993-01-28 | 1999-11-09 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
EP0695169B1 (en) | 1993-04-22 | 2002-11-20 | SkyePharma Inc. | Multivesicular cyclodextrin liposomes encapsulating pharmacologic compounds and methods for their use |
US6180377B1 (en) | 1993-06-16 | 2001-01-30 | Celltech Therapeutics Limited | Humanized antibodies |
DE69434486T2 (de) | 1993-06-24 | 2006-07-06 | Advec Inc. | Adenovirus vektoren für gentherapie |
EP0814154B1 (en) | 1993-09-15 | 2009-07-29 | Novartis Vaccines and Diagnostics, Inc. | Recombinant alphavirus vectors |
US6015686A (en) | 1993-09-15 | 2000-01-18 | Chiron Viagene, Inc. | Eukaryotic layered vector initiation systems |
ATE314482T1 (de) | 1993-10-25 | 2006-01-15 | Canji Inc | Rekombinante adenoviren-vektor und verfahren zur verwendung |
ES2149955T3 (es) | 1993-11-16 | 2000-11-16 | Skyepharma Inc | Vesiculas con liberacion controlada de sustancias activas. |
IL107742A0 (en) | 1993-11-24 | 1994-02-27 | Yeda Res & Dev | Chemically-modified binding proteins |
US6436908B1 (en) | 1995-05-30 | 2002-08-20 | Duke University | Use of exogenous β-adrenergic receptor and β-adrenergic receptor kinase gene constructs to enhance myocardial function |
AU2585395A (en) | 1994-05-09 | 1995-11-29 | Chiron Corporation | Retroviral vectors having a reduced recombination rate |
WO1996017072A2 (en) | 1994-11-30 | 1996-06-06 | Chiron Viagene, Inc. | Recombinant alphavirus vectors |
US6326155B1 (en) | 1995-03-20 | 2001-12-04 | Dyax Corp. | Engineering affinity ligands for macromolecules |
US6265150B1 (en) | 1995-06-07 | 2001-07-24 | Becton Dickinson & Company | Phage antibodies |
DE69739286D1 (de) | 1996-05-06 | 2009-04-16 | Oxford Biomedica Ltd | Rekombinationsunfähige retrovirale vektoren |
WO1999018792A1 (en) | 1997-10-10 | 1999-04-22 | Johns Hopkins University | Gene delivery compositions and methods |
GB9809951D0 (en) | 1998-05-08 | 1998-07-08 | Univ Cambridge Tech | Binding molecules |
CA2341029A1 (en) | 1998-08-17 | 2000-02-24 | Abgenix, Inc. | Generation of modified molecules with increased serum half-lives |
CA2364484A1 (en) | 1999-03-09 | 2000-09-14 | University Of Southern California | Method of promoting myocyte proliferation and myocardial tissue repair |
US6236155B1 (en) * | 1999-04-12 | 2001-05-22 | Osram Sylvania Inc. | High chromium second anode button for cathode ray tube |
US6849425B1 (en) | 1999-10-14 | 2005-02-01 | Ixsys, Inc. | Methods of optimizing antibody variable region binding affinity |
DK1317537T3 (da) * | 2000-09-08 | 2007-04-30 | Massachusetts Inst Technology | Sammensætninger og fremgangsmåder med G-CSF analoger |
CN1305905C (zh) | 2002-03-22 | 2007-03-21 | Aprogen株式会社 | 人源化抗体及其制备方法 |
CA2921578C (en) | 2002-12-24 | 2017-02-14 | Rinat Neuroscience Corp. | Anti-ngf antibodies and methods using same |
AU2005285347A1 (en) * | 2004-08-19 | 2006-03-23 | Genentech, Inc. | Polypeptide variants with altered effector function |
EP1871417B1 (en) | 2005-04-15 | 2013-09-11 | Precision Biologics, Inc. | Recombinant monoclonal antibodies and corresponding antigens for colon and pancreatic cancers |
EP4001409A1 (en) * | 2006-03-31 | 2022-05-25 | Chugai Seiyaku Kabushiki Kaisha | Methods for controlling blood pharmacokinetics of antibodies |
US20100040610A1 (en) * | 2006-11-07 | 2010-02-18 | Ayesha Sitlani | Antagonists of pcsk9 |
CN101636179B (zh) * | 2006-11-07 | 2012-10-10 | 默沙东公司 | Pcsk9拮抗剂 |
JP2009069095A (ja) | 2007-09-18 | 2009-04-02 | Daiwa House Ind Co Ltd | コンクリート中性化サンプル抽出装置および中性化測定方法 |
CN101874042B9 (zh) * | 2007-09-26 | 2019-01-01 | 中外制药株式会社 | 利用cdr的氨基酸取代来改变抗体等电点的方法 |
BRPI0817250A2 (pt) * | 2007-09-26 | 2014-06-17 | Chugai Pharmaceutical Co Ltd | Anticorpo anti-receptor da il-6. |
WO2009041062A1 (ja) * | 2007-09-28 | 2009-04-02 | Chugai Seiyaku Kabushiki Kaisha | 血漿中動態が改善されたグリピカン3抗体 |
JO3672B1 (ar) * | 2008-12-15 | 2020-08-27 | Regeneron Pharma | أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9). |
RU2565809C2 (ru) | 2009-03-19 | 2015-10-20 | Чугаи Сейяку Кабусики Кайся | Фармацевтический состав, содержащий молекулы антител с улучшенными свойствами |
-
2011
- 2011-03-09 JP JP2012556634A patent/JP5932670B2/ja not_active Expired - Fee Related
- 2011-03-09 SA SA111320266A patent/SA111320266B1/ar unknown
- 2011-03-09 SG SG10201507722QA patent/SG10201507722QA/en unknown
- 2011-03-09 WO PCT/IB2011/050989 patent/WO2011111007A2/en active Application Filing
- 2011-03-09 KR KR1020127026478A patent/KR20120138241A/ko active IP Right Grant
- 2011-03-09 KR KR20147033744A patent/KR20150002894A/ko not_active Application Discontinuation
- 2011-03-09 EP EP11711682A patent/EP2545079A2/en not_active Withdrawn
- 2011-03-09 BR BR112012022917A patent/BR112012022917A2/pt not_active IP Right Cessation
- 2011-03-09 PE PE2012001540A patent/PE20130393A1/es not_active Application Discontinuation
- 2011-03-09 CA CA2792740A patent/CA2792740A1/en not_active Abandoned
- 2011-03-09 CN CN201510430943.2A patent/CN105218674A/zh active Pending
- 2011-03-09 NZ NZ602220A patent/NZ602220A/en not_active IP Right Cessation
- 2011-03-09 RU RU2012137490/15A patent/RU2570729C2/ru not_active IP Right Cessation
- 2011-03-09 AU AU2011225716A patent/AU2011225716A1/en not_active Abandoned
- 2011-03-09 SG SG2012064994A patent/SG183867A1/en unknown
- 2011-03-09 CN CN201180019465.6A patent/CN102844332B/zh not_active Expired - Fee Related
- 2011-03-09 MX MX2012010481A patent/MX2012010481A/es not_active Application Discontinuation
- 2011-03-10 US US13/045,345 patent/US9029515B2/en active Active
- 2011-03-11 AR ARP110100789A patent/AR080511A1/es unknown
-
2012
- 2012-09-11 CO CO12155949A patent/CO6592103A2/es unknown
- 2012-09-26 ZA ZA2012/07211A patent/ZA201207211B/en unknown
-
2015
- 2015-04-03 US US14/677,983 patent/US20150266974A1/en not_active Abandoned
-
2019
- 2019-03-08 US US16/296,852 patent/US20200024366A1/en not_active Abandoned
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009055902A (ja) * | 1997-07-02 | 2009-03-19 | Genentech Inc | 改良抗IgE抗体及びポリペプチドの改良方法 |
JP2007520494A (ja) * | 2004-02-03 | 2007-07-26 | 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 | 溶血性疾患の処置方法 |
JP2009523421A (ja) * | 2006-01-13 | 2009-06-25 | ノバルティス アクチエンゲゼルシャフト | Dickkopf−1および/または−4に対する抗体の組成物および製造法その使用方法 |
WO2009026558A1 (en) * | 2007-08-23 | 2009-02-26 | Amgen Inc. | Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (pcsk9) |
WO2009125825A1 (ja) * | 2008-04-11 | 2009-10-15 | 中外製薬株式会社 | 複数分子の抗原に繰り返し結合する抗原結合分子 |
Cited By (36)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11046784B2 (en) | 2006-03-31 | 2021-06-29 | Chugai Seiyaku Kabushiki Kaisha | Methods for controlling blood pharmacokinetics of antibodies |
US9828429B2 (en) | 2007-09-26 | 2017-11-28 | Chugai Seiyaku Kabushiki Kaisha | Method of modifying isoelectric point of antibody via amino acid substitution in CDR |
US11248053B2 (en) | 2007-09-26 | 2022-02-15 | Chugai Seiyaku Kabushiki Kaisha | Method of modifying isoelectric point of antibody via amino acid substitution in CDR |
US10472623B2 (en) | 2008-04-11 | 2019-11-12 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding two or more antigen molecules repeatedly |
US11371039B2 (en) | 2008-04-11 | 2022-06-28 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly |
US11359194B2 (en) | 2008-04-11 | 2022-06-14 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding two or more antigen molecules repeatedly |
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US11891434B2 (en) | 2010-11-30 | 2024-02-06 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to plurality of antigen molecules repeatedly |
US11718678B2 (en) | 2011-02-25 | 2023-08-08 | Chugai Seiyaku Kabushiki Kaisha | Method for altering plasma retention and immunogenicity of antigen-binding molecule |
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RU2570729C2 (ru) | 2015-12-10 |
AR080511A1 (es) | 2012-04-11 |
CN102844332A (zh) | 2012-12-26 |
WO2011111007A3 (en) | 2011-12-01 |
KR20120138241A (ko) | 2012-12-24 |
US20200024366A1 (en) | 2020-01-23 |
AU2011225716A1 (en) | 2012-09-27 |
CA2792740A1 (en) | 2011-09-15 |
CN102844332B (zh) | 2015-08-19 |
EP2545079A2 (en) | 2013-01-16 |
WO2011111007A2 (en) | 2011-09-15 |
KR20150002894A (ko) | 2015-01-07 |
BR112012022917A2 (pt) | 2017-01-10 |
PE20130393A1 (es) | 2013-04-07 |
US20110229489A1 (en) | 2011-09-22 |
JP5932670B2 (ja) | 2016-06-08 |
RU2012137490A (ru) | 2014-05-10 |
US9029515B2 (en) | 2015-05-12 |
CN105218674A (zh) | 2016-01-06 |
CO6592103A2 (es) | 2013-01-02 |
SA111320266B1 (ar) | 2015-06-21 |
US20150266974A1 (en) | 2015-09-24 |
SG10201507722QA (en) | 2015-10-29 |
ZA201207211B (en) | 2014-06-25 |
MX2012010481A (es) | 2012-10-09 |
NZ602220A (en) | 2014-10-31 |
SG183867A1 (en) | 2012-10-30 |
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