JP2018126149A - リンパ球活性化遺伝子−3(lag−3)へ結合する抗体の最適化およびその使用 - Google Patents
リンパ球活性化遺伝子−3(lag−3)へ結合する抗体の最適化およびその使用 Download PDFInfo
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Abstract
【解決手段】ヒトLAG−3への高アフィニティー結合、および物理的(すなわち、熱的および化学的)安定性を維持している部位特異的変異を誘発させた抗体。該抗体をコードする核酸分子、発現ベクター、宿主細胞および該抗体を発現するための方法、ならびに該抗体を含む免疫複合体、二重特異性分子および医薬組成物。LAG−3を検出するための方法、ならびに抗LAG−3抗体を使用して、免疫応答を刺激して処置するための方法。
【選択図】なし
Description
治療抗体は、医薬産業の最も急速に成長している分野の一つである。効力(すなわち、活性)を維持するため、および免疫原性を最小限にするために、抗体および他のタンパク質薬物は、製造および保存中に、物理化学的分解から保護されなければならない。実際に、抗体治療薬の開発における主な困難の一つは、対象に投与するときの起こり得る免疫原性応答であり、これは、迅速なクリアランスを引き起こし得るか、またはアナフィラキシーショックを含む生命に関わる副作用を誘発さえし得る。種々の因子、例えば、その生理化学特性(例えば、純度、安定性または溶解性)、臨床的因子(例えば、用量、投与経路、疾患の不均一性、または患者特性)、および他の薬剤との同時処置が、抗体の免疫原性に影響する(Swannら (2008) Curr Opinion Immuol 20:493-499)。
本発明は、LAG−3(例えば、ヒトLAG−3)に結合し、以前に記載されている抗LAG−3抗体と比較して、最適化された物理的安定性を有する単離されたモノクローナル抗体(例えば、ヒトモノクローナル抗体)を提供する。特に、本発明は、修飾されていない抗体と比較して、有意に改善された熱および化学安定性を示す抗体25F7(US 2011/0150892 A1)の修飾された形態に関する。具体的には、抗体25F7の重鎖CDR2ドメインの重要な結合領域を改変することにより、修飾された抗体は、有意に高い物理的および熱安定性、低下した脱アミド、高い熱可逆性、および低い凝集を示すことが示された。同時に、修飾された抗体が、ヒトLAG−3への修飾されていない抗体と同じ高い結合アフィニティーおよび修飾されていない抗体の機能活性を維持する、例えば、LAG−3の主要組織適合性(MHC)クラスII分子への結合を阻害する、および抗原特異的T細胞応答を刺激する能力を維持することが予想外に観察された。修飾された抗体の結合/生物学的活性の安定性および維持における組み合わせられた実質的な増加は、特に抗体機能に対するCDR領域の重要性(criticality)を考慮すると、驚くべきことであった。
(a)サルLAG−3へ結合する;
(b)マウスLAG−3へ結合しない;
(c)LAG−3の主要組織適合性(MHC)クラスII分子への結合を阻害する;および
(d)免疫応答、特に抗原特異的T細胞応答を刺激する
をさらに示す。
本明細書をさらに容易に理解するために、特定の用語を最初に定義する。さらなる定義は詳細な説明中に記載されている。
本発明の抗体は、ヒトLAG−3に特異的に結合し、以前に記載されている抗LAG−3抗体と比較して、特に抗体25F7(LAG3.1)と比較して、最適化された安定性を有する。この最適化は、減少した脱アミド(例えば、増加した化学安定性)および増加した熱リフォールディング(例えば、増加した物理的安定性)を含むが、ヒトLAG−3への高アフィニティー結合を維持している。
本発明の好ましい抗体は、以下および実施例に記載されるように構造的および化学的に特徴付けられるヒトモノクローナル抗体LAG3.5である。LAG3.5のVHアミノ酸配列は、配列番号:12(図2A)に示される。LAG3.5のVLアミノ酸配列は、配列番号:14(図2B)に示される。
(a)アミノ酸配列配列番号:12を含む重鎖可変領域(すなわち、LAG3.5のVH);および
(b)アミノ酸配列配列番号:14を含む軽鎖可変領域(すなわち、LAG3.5のVL)または別の抗−LAG3抗体のVL(すなわち、LAG3.5と異なる);
を含み、ヒトLAG−3に特異的に結合する。
(a)アミノ酸配列配列番号:12を含む重鎖可変領域のCDR1、CDR2およびCDR3領域(すなわち、LAG3.5のCDR配列、それぞれ配列番号:15、16および17);および
(b)アミノ酸配列配列番号:14を含む軽鎖可変領域のCDR1、CDR2およびCDR3領域(すなわち、LAG3.5のCDR配列、それぞれ配列番号:18、19および20)または別の抗−LAG3抗体のCDR(すなわち、LAG3.5と異なる);
を含み、ヒトLAG−3に特異的に結合する。
他の態様において、本発明の抗体は、1つ以上の保存的修飾により、LAG3.5のものと異なるCDR1、CDR2およびCDR3配列の重鎖および/または軽鎖可変領域配列を含む。好ましい態様において、しかしながら、VHCDR2の残基54および56は、それぞれ、アルギニンおよびセリンとして残る(すなわち、変異されない)。特定の保存的配列修飾は、抗原結合を取り除くことなく作ることができることが、当分野で理解されている。例えば、Brummellら (1993) Biochem 32:1180-8; de Wildtら (1997) Prot. Eng. 10:835-41; Komissarovら (1997) J. Biol. Chem. 272:26864-26870; Hallら (1992) J. Immunol. 149:1605-12; Kelley and O'Connell (1993) Biochem. 32:6862-35; Adib-Conquyら (1998) Int. Immunol. 10:341-6およびBeersら (2000) Clin. Can. Res. 6:2835-43、参照。したがって、1つの態様において、抗体は、CDR1、CDR2およびCDR3配列を含む重鎖可変領域および/またはCDR1、CDR2およびCDR3配列を含む軽鎖可変領域を含み:
(a)重鎖可変領域CDR1配列は、配列番号:15、および/または位置54および56以外でその保存的修飾を含み;そして/または
(b)重鎖可変領域CDR3配列は、配列番号:17、およびその保存的修飾を含み;および/または
(c)軽鎖可変領域CDR1、および/またはCDR2、および/またはCDR3配列は、配列番号:18、および/または、配列番号:19および/または配列番号:20、および/またはそれらの保存的修飾を含み;そして
(d)抗体はヒトLAG−3に特異的に結合する。
本発明の抗体は、修飾された抗体を操作するように、出発物質としてLAG3.5の1つ以上のVHおよび/またはVL配列を有する抗体を使用して調製することができる。抗体を、1つまたは両方の可変領域(すなわち、VHおよび/またはVL)内、例えば、1つ以上のCDR領域および/または1つ以上のフレームワーク領域内の1つ以上の残基を修飾することにより操作することができる。さらに、または、あるいは、抗体を、例えば、抗体のエフェクター機能を改変するために、定常領域内の残基を修飾することにより操作することができる。
本発明の抗体は、異なるクラスを検出および/または区別するために、種々の物理的特性により特徴付けることができる。
他の局面において、本発明は、本発明の抗体の重鎖および/または軽鎖可変領域、またはCDRをコードする核酸分子を提供する。核酸は、完全な細胞で、細胞溶解物で、または部分的に精製された、もしくは実質的に純粋な形態で存在してよい。核酸は、アルカリ/SDS処理、CsCl結合、カラムクロマトグラフィー、アガロースゲル電気泳動およびその他当分野で既知の技術を含む標準技術により、他の細胞成分または他の汚染物質、例えば、他の細胞性核酸またはタンパク質から精製されたとき、「単離された」または「実質的に純粋」である。Ausubelら, ed. (1987) Current Protocols in Molecular Biology, Greene Publishing and Wiley Interscience, New York、参照。本発明の核酸は、例えば、DNAまたはRNAであってよく、イントロン配列を含んでいても含まなくてもよい。好ましい態様において、核酸はcDNA分子である。
本発明のモノクローナル抗体(mAb)は、Kohler and Milstein (1975) Nature 256: 495の標準体細胞ハイブリダイゼーション(ハイブリドーマ)技術を使用して、生産することができる。モノクローナル抗体を生産するための他の態様は、Bリンパ球のウイルスまたは発癌性形質転換およびファージディスプレイ技術を含む。キメラまたはヒト化抗体も当分野で知られている。例えば、米国特許第4,816,567;5,225,539;5,530,101;5,585,089;5,693,762および6,180,370、参照(これらの内容を出典明示によりその全体を明確に本明細書に包含させる)。
本発明の1つの態様において、ヒトIgマウスは、LAG−3抗原、組換えLAG−3タンパク質またはLAG−3タンパク質を発現する細胞の精製または濃縮された調製物にて免疫化される。例えば、Lonbergら (1994)、上記; Fishwildら (1996)、上記;PCT公開WO98/24884またはWO01/14424、参照(これらの内容を出典明示によりその全体を本明細書に包含させる)。好ましい態様において、6−16週齢マウスを5−50μgのLAG−3タンパク質にて免疫化する。あるいは、非−LAG−3ポリペプチドに融合したLAG−3の部分を使用する。
本発明のヒトモノクローナル抗体を生産するハイブリドーマを調製するため、免疫マウスから脾細胞および/またはリンパ節細胞を単離し、適当な不死化細胞系、例えば、マウス骨髄腫細胞系に融合することができる。得られたハイブリドーマを抗原特異的抗体の生成に関してスクリーニングすることができる。ハイブリドーマの作製は当分野で知られている。例えば、Harlow and Lane (1988) Antibodies, A Laboratory Manual, Cold Spring Harbor Publications, New York、参照。
本発明の抗体はまた、例えば、当分野で既知である組換えDNA技術および遺伝子トランスフェクション法の組合せを使用して、宿主細胞トランスフェクトーマにおいて調製することができる(例えば、Morrison, S. (1985) Science 229:1202)。1つの態様において、標準分子生物学技術により得られる部分的または全長軽鎖および重鎖をコードするDNAは、遺伝子が転写および翻訳調節配列に作動可能に連結されるように、1つ以上の発現ベクターに挿入される。これに関して、「作動可能に連結」なる用語は、抗体遺伝子が、ベクター内の転写および翻訳コントロール配列が抗体遺伝子の転写および翻訳を調節する意図された機能を果たすように、ベクターに結合されることを意味することを意図する。
本発明の抗体は、免疫複合体、例えば、抗体−薬物複合体(ADC)を形成するために治療剤とコンジュゲートさせることができる。適当な治療剤は、代謝拮抗剤、アルキル化剤、DNA副溝結合剤、DNA挿入剤、DNA架橋剤、ヒストンデアセチラーゼ阻害剤、核外輸送阻害剤、プロテアソーム阻害剤、トポイソメラーゼIもしくはII阻害剤、熱ショックタンパク質阻害剤、チロシンキナーゼ阻害剤、抗生物質および抗有糸分裂剤を含む。ADCにおいて、抗体および治療剤は、好ましくは、開裂可能なリンカー、例えば、ペプチジル、ジスルフィドまたはヒドラゾンリンカーを介してコンジュゲートされる。さらに好ましくは、リンカーは、ペプチジルリンカー、例えば、Val−Cit、Ala−Val、Val−Ala−Val、Lys−Lys、Pro−Val−Gly−Val−Val(配列番号:39)、Ala−Asn−Val、Val−Leu−Lys、Ala−Ala−Asn、Cit−Cit、Val−Lys、Lys、Cit、SerまたはGluである。ADCは、米国特許第7,087,600;6,989,452;および7,129,261号;PCT公開WO02/096910;WO07/038658;WO07/051081;WO07/059404;WO08/083312;およびWO08/103693;米国特許公開20060024317;20060004081;および20060247295に記載されているとおりに製造することができる(これらの記載を出典明示により本明細書に包含させる)。
他の局面において、本発明は、少なくとも1つの他の機能分子、例えば、他のペプチドまたはタンパク質(例えば、受容体に対する他の抗体またはリガンド)と連結している本発明の1つ以上の抗体を含む二重特異性分子を特徴とし、少なくとも2つの異なる結合部位または標的分子に結合する二重特異性分子を産生する。したがって、本明細書において使用される「二重特異性分子」は3つ以上の特異性を有する分子を含む。好ましい態様において、二重特異性分子は、LAG−3に対する第1の結合特異性およびLAG−3を発現する標的細胞を殺すことができる細胞毒性エフェクター細胞を補充するトリガー分子に対する第2の結合特異性を含む。適当なトリガー分子の例はCD64、CD89、CD16およびCD3である。例えば、Kuferら, TRENDS in Biotechnology, 22 (5), 238-244 (2004)、参照。
他の局面において、本明細書は、製剤化された1つ以上の本発明の抗体を薬学的に許容される担体と共に含む医薬組成物を提供する。該組成物は、所望により1つ以上のさらなる薬学的に活性な成分、例えば、別の抗体または薬物を含んでもよい。本発明の医薬組成物はまた、抗LAG−3抗体がワクチンに対する免疫応答を増強するように、例えば、他の免疫刺激剤、抗癌剤、抗ウイルス剤またはワクチンと併用療法において投与することができる。
本発明の抗体(組成物、二重特異性および免疫複合体)は、例えば、LAG−3の検出またはLAG−3の遮断(Blockade)による免疫応答の増強に関する、多数のインビトロおよびインビボにおける有用性を有する。好ましい態様において、抗体はヒト抗体である。このような抗体は、種々の状態における免疫を増強するために、インビトロまたはエキソビボにおいて培養中の細胞、または、例えば、インビボにおいてヒト対象に投与することができる。したがって、1つの局面において、本発明は、対象における免疫応答が修飾されるように、本発明の抗体またはその抗原結合部分を対象に投与することを含む、対象における免疫応答を修飾する方法を提供する。好ましくは、応答は増強されるか、刺激されるか、または上方制御される。
抗体によるLAG−3の遮断は、患者における癌細胞に対する免疫応答を増強することができる。1つの局面において、本発明は、癌性腫瘍の増殖が阻害されるように、抗LAG−3抗体を使用するインビボにおける対象の処置に関する。抗LAG−3抗体は、癌性腫瘍の増殖を阻害するために単独で使用することができる。あるいは、抗LAG−3抗体は、以下に記載されているように、他の免疫原、標準癌処置または他の抗体と共に使用することができる。
本発明の他の方法は、特定の毒素または病原体に暴露されている患者を処置するために使用される。したがって、本発明の他の局面は、対象が感染病を処置されるように、抗LAG−3抗体またはその抗原結合部分を対象に投与することを含む対象における感染病を処置する方法を提供する。好ましくは、抗体はヒト抗−ヒトLAG−3抗体(本明細書に記載されているヒト抗LAG−3抗体のいずれかのような)である。さらに、またはあるいは、抗体はキメラまたはヒト化抗体であり得る。
抗−LAG−3抗体は自己免疫応答を誘導および増幅し得る。実際に、腫瘍細胞およびペプチドワクチンを使用する抗腫瘍応答の誘導は、多数の抗腫瘍応答が抗−自己反応性に関連することを示す(van Elsasら (2001) J. Exp. Med. 194:481-489; Overwijkら (1999) Proc. Natl. Acad. Sci. U.S.A. 96: 2982-2987; Hurwitz, (2000) supra; Rosenberg & White (1996) J. Immunother Emphasis Tumor Immunol 19 (1): 81-4)。したがって、疾患処置に関するこれらの自己タンパク質に対する免疫応答を効率的に発生させるようにワクチンプロトコールを考案するために、種々の自己タンパク質と共に抗−LAG−3遮断を使用することを考えることができる。例えば、アルツハイマー病は脳においてアミロイド沈着におけるAβペプチドの不適当な蓄積に関する;アミロイドに対する抗体反応は、これらのアミロイド沈着を明らかにすることができる(Schenkら, (1999) Nature 400: 173-177)。
抗−LAG−3抗体は、抗LAG−3抗体と興味ある抗原(例えば、ワクチン)の共投与により、抗原特異的免疫応答を刺激するために使用することができる。したがって、別の局面において、本発明は、対象における抗原に対する免疫応答が増強されるように、(i)抗原;および(ii)抗LAG−3抗体またはその抗原結合部分を対象に投与することを含む、対象における抗原に対する免疫応答を増強する方法を提供する。好ましくは、抗体はヒト抗−ヒトLAG−3抗体(本明細書に記載されているヒト抗LAG−3抗体のいずれかのような)である。さらに、またはあるいは、抗体はキメラまたはヒト化抗体であり得る。抗原は、例えば、腫瘍抗原、ウイルス抗原、細菌抗原または病原体由来の抗原であり得る。このような抗原の非限定的な例は、上記のセクションにおいて記載されているもの、例えば、上記腫瘍抗原(または腫瘍ワクチン)、または上記ウイルス、細菌もしくは他の病原体由来の抗原を含む。
他の局面において、本発明は、本発明の抗LAG−3抗体(またはその抗原結合部分)を、免疫応答を刺激し、それによりさらに対象における免疫応答を増強、刺激または上方制御するために有効である1つ以上のさらなる抗体と共投与する、併用療法の方法を提供する。1つの態様において、本発明は、例えば、腫瘍増殖を阻害するか、または抗−ウイルス応答を刺激するために、対象における免疫応答を刺激するように、抗LAG−3抗体および1つ以上のさらなる免疫刺激抗体、例えば、抗PD−1抗体、抗PD−L1抗体および/または抗CTLA−4抗体を対象に投与することを含む、対象における免疫応答を刺激する方法を提供する。他の態様において、対象は抗LAG−3抗体および抗PD−1抗体を投与される。さらに別の態様において、対象は抗LAG−3抗体および抗PD−L1抗体を投与される。さらに他の態様において、対象は抗LAG−3抗体および抗CTLA−4抗体を投与される。1つの態様において、抗LAG−3抗体はヒト抗体、例えば、本明細書の抗体である。あるいは、抗LAG−3抗体は、例えば、キメラまたはヒト化抗体(例えば、マウス抗−LAG−3mAbから調製される)であり得る。他の態様において、少なくとも1つのさらなる免疫刺激抗体(例えば、抗PD−1、抗PD−L1および/または抗CTLA−4抗体)はヒト抗体である。あるいは、少なくとも1つのさらなる免疫刺激抗体は、例えば、キメラまたはヒト化抗体(例えば、マウス抗PD−1、抗PD−L1および/または抗CTLA−4抗体から調製される)であり得る。
LAG3.1と本明細書において称される以前に記載されている抗LAG−3抗体である25F7抗体変異体を、分解の起こり得る部位に対する抗体のアミノ酸配列を最初に分析することにより、作製した。LAG3.1 VH領域の部位特異的突然変異誘発の発現を、QuikChange II XL(登録商標)部位特異的突然変異誘発キット(Agilent Technologies)を使用して行った。次に、改変されたVH領域を、ヒトIgG4−S228P定常領域を含むUCOE(登録商標)(EMD Millipore)ベクターにサブクローニングした。種々の重鎖ベクターを、CHO−S細胞にLAG3.1カッパ鎖を発現するベクターとそれぞれ共トランスフェクトし、安定なプールを発現のために選択した。
1.活性化ヒトCD4 + T細胞結合
抗体変異体が活性化ヒトT細胞の表面上で天然ヒトLAG−3に結合する能力を試験するために、正常健常ドナー末梢血単核細胞を、溶液中でそれぞれ5μg/mLおよび3μg/mLで存在する抗−CD3(eBioscience、Cat #16−0037−85)および抗−CD28(BD Bioscience、Cat # 555725)抗体の組合せで、2x10e6細胞/mLの密度で15cm組織培養プレートにおいて刺激した。刺激の3日後に、細胞を回収し、1xPFAEバッファー(1xPBS+2% FBS、0.02% アジ化ナトリウム、2mM Na EDTA)で1X洗浄し、染色のために1xPFAEバッファーに再懸濁した。
変異体の熱安定性および熱変性を、Microcal VP−DSCを使用して試験した。具体的には、それぞれの変異体をPBS(Mediatech cat # 21−040−CV lot # 21040139)に希釈した。サンプルの最終濃度は、PBSへの希釈後に250μg/mLであった。サンプルを74℃に合わせ(scanned)、25℃に冷却し、74℃に再加熱した。PBSバッファーをブランクコントロールとして使用した。データをNon−2−状態モデルに合わせ、曲線適合をOriginソフトウェアにより実施した。
変異体もまた、以下のプロトコールにしたがって、標準サイズ排除HPLC(SEC−HPLC)を使用してタンパク質凝集の尺度として安定性について試験した:抗体試験サンプルをリン酸緩衝生理食塩水(PBS)で1.0mg/mlに希釈し、10uLをHPLC(Waters、model 2795)に適用した。0.1M リン酸ナトリウム、0.15M 塩化ナトリウム、0.1M 硫酸ナトリウム、pH7.2の移動相を使用するゲル濾過カラム(TOSOH Bioscience、TSKgel G3000 SWxl、7.8mmx300mm、product #08541)において、分離を成し遂げた。分析物を、280nmでのUV吸光度をモニタリングすることにより検出し、抗体ピーク面積パーセント組成をEmpowerソフトウェアを使用して決定した。表4に示されるとおり、LAG3.5は、LAG3.1と比較して、実質的に減少した凝集を示した。
上記試験に基づいて、その修飾されていない形態(LAG3.1)と比較して、その有意に改善された物理化学的安定性、特に、構造リフォールディング(熱可逆性)に対するその高い能力を考慮して、抗体変異体LAG3.5をさらなる分析のために選択した。この分析は、(a)加速ストレス、(b)次に、12週リアルタイム安定性評価の2工程アプローチを含んだ。具体的には、LAG3.5を、40℃で5日間pH8.0、50mM 重炭酸アンモニウムにおいて1.0mg/mlでインキュベートした。5日後に、修飾の程度、ならびに活性および安定性に対する効果を分析した。次に、LAG3.5変異体を、12週間PBSにおけるリアルタイム安定性に付し、次に分析した。これらの試験の結果は、以下に記載される。
図7(および表5)に示されるとおり、抗原結合における変化は、5日後に観察されなかった。図10AおよびBにおいても示されるとおり、LAG3.5は、12週後に抗原結合または物理的安定性における変化を示さなかった。特に、LAG3.5は、4℃および40℃の両方で全12週にわたって、LAG3.8よりも高いアフィニティーを維持する。
質量分析によるペプチドマッピングを、LAG3.1と比較してのLAG3.5の化学/分子安定性を分析するために使用した。具体的には、精製された抗体を還元し、アルキル化し、透析し、トリプシン(Promega Cat. V5111)およびGluC(Roche Cat. 11047817001)で消化した。消化物を、ナノ−LC MSMS質量分析(Thermo Fisher LTQ Orbitrap)により分析した。
熱可逆性は、PBSおよびpH8.0で測定した。両方の条件下で、LAG3.5は、再び、LAG3.1と比較して、約2倍のリフォールディングのレベルを示した。具体的には、表6−8に示されるとおり、LAG3.5は、PBSにおいてLAG3.1に対する18%と比較して、43%のリフォールディングを示した。LAG3.5もまた、pH8.0でLAG3.1に対する29%リフォールディングと比較して、48%リフォールディングを示した。
電荷不均一性を評価するために、変異体は、LAG3.1と比較して、pI5.5およびpI10.0の標準マーカーで等電点分画電気泳動(IEF)を使用して分析した。簡潔には、抗体溶液を、pI3−10マーカー(SERVA、Cat# 39212)と共に、1mmの厚さのIEF pI3−7の予め作られたゲル(Invitrogen、Cat# EC6648BOX)上に付した。電気泳動法を、IEF 3−7 Cathodeバッファー(Invitrogen、Cat# LC5370)およびIEF Anodeバッファー(Invitrogen、Cat# LC5300)を使用して行い、1時間100V定数、1時間200V定数、および30分間500V定数の順に電流を加えた。IEFゲルをCoomassieブルーで染色し、タンパク質バンドを検出し、メタノール−酢酸溶液で脱染色した。次に、IEFゲルを、ImageQuant TLソフトウェアにより分析した。この分析に基づいて(データは示していない)、LAG3.5は、LAG3.1と比較して、有意に低い不均一性を示した。
溶解性を評価するために、変異体は、以下のプロトコールにしたがって標準疎水性相互作用クロマトグラフィー(HIC−HPLC)を使用して分析した:50uLの2M 硫酸アンモニウムを1mg/mlで50uLの抗体試験サンプルに加えた。次に、80uLの試験サンプルを、HICカラム(TOSOH Bioscience、Ether−5PW TSK−gel、7.5mm x 75mm、product #07573)に一列に接続されたHPLC(Waters、model 2795)に適用した。50分にわたって100% バッファーA(2M 硫酸アンモニウム、0.1M リン酸ナトリウム、pH7.0)から100% バッファーB(0.1M リン酸ナトリウム、pH7.0)の勾配で1.0ml/分の流速で、サンプルを溶離した。抗体を280nmでのUV吸光度をモニタリングすることにより検出し、データをEmpowerソフトウェアを使用して分析した。図9に示されるとおり、LAG3.5の親水性は、硫酸アンモニウムの高い濃度で溶解性を示した。
LAG3.5の活性を、抗原特異的マウスT細胞ハイブリドーマ(3A9)を利用した機能アッセイの手段により決定した。ハイブリドーマ3A9は、ニワトリ卵白リゾチーム(HEL48−62)からのペプチドに特異的なT細胞受容体を発現し、ペプチドパルスMHC適合抗原提示細胞(LK35.2)と共培養したとき、IL−2を分泌する。huLAG−3−FcがMHCクラスII−ポジティブマウスB細胞系に結合することができるため、3A9系におけるhuLAG−3の発現は、マウス提示系上のクラスIIとの関与を介して阻害効果を発揮することができた。3A9親のペプチド応答プロフィールとMHC適合抗原提示細胞と共培養されたヒトLAG−3−形質導入3A9細胞のものとの比較は、ヒトLAG−3の発現がコントロール3A9細胞と比較してペプチド応答性を阻害することを証明した。この阻害は、LAG3.5を使用するLAG−3遮断により逆転された。したがって、LAG−3介在阻害の遮断は、LAG3.5について証明された。
初代T細胞におけるLAG3.5の機能活性を、スーパー抗原SEBによって刺激されたヒトPBMC培養物を使用して評価した。全PBMCを18人のヒトドナーの血液から単離し、2つのアッセイフォーマット:(i)固定された量の抗体(20μg/mL)およびSEBの連続希釈物、または(ii)固定された量のSEB(85ng/mL)および抗体の連続希釈物のいずれかにおいて72時間刺激した。分泌されたIL−2を、T細胞活性の測定のために、ELISAによりモニタリングした。抗体抗PD−1抗体およびIpilimumabをポジティブコントロールとして使用し、抗−PD−1または抗−CTLA−4と組み合わせてのLAG3.5の活性もドナーのサブセットに対して評価した。
Claims (40)
- 重鎖および軽鎖可変領域を含む、ヒトLAG−3に結合する単離されたモノクローナル抗体またはその抗原結合部分であって、該重鎖可変領域は、配列番号:12の重鎖可変領域からのCDR1、CDR2およびCDR3領域を含む、単離されたモノクローナル抗体またはその抗原結合部分。
- 重鎖CDR1、CDR2およびCDR3領域が、それぞれ配列番号:15、16および17のアミノ酸配列を含む、請求項1に記載の抗体またはその抗原結合部分。
- 軽鎖可変領域が、配列番号:14の軽鎖可変領域からのCDR1、CDR2およびCDR3領域を含む、請求項1に記載の抗体またはその抗原結合部分。
- 軽鎖CDR1、CDR2およびCDR3領域が、それぞれ配列番号:18、19および20のアミノ酸配列を含む、請求項3に記載の抗体またはその抗原結合部分。
- 重鎖可変領域が、配列番号:12のアミノ酸配列を含む、請求項1または3に記載の抗体またはその抗原結合部分。
- 軽鎖可変領域が、配列番号:14のアミノ酸配列を含む、請求項1から5のいずれかに記載の抗体またはその抗原結合部分。
- それぞれ配列番号:15、16、17、および配列番号:18、19および20のアミノ酸配列を含む重鎖および軽鎖CDR1、CDR2およびCDR3領域を含む、ヒトLAG−3に結合する単離されたモノクローナル抗体またはその抗原結合部分。
- それぞれ配列番号:12および14のアミノ酸配列を含む重鎖および軽鎖可変領域を含む、ヒトLAG−3に結合する単離されたモノクローナル抗体またはその抗原結合部分。
- 以下の特性の1つまたは組合せ:
(a)サルLAG−3へ結合する;
(b)マウスLAG−3へ結合しない;
(c)LAG−3の主要組織適合性(MHC)クラスII分子へ結合する;
(d)LAG−3の主要組織適合性(MHC)クラスII分子への結合を阻害する;または
(e)免疫応答を刺激する
を示す、請求項1から8のいずれかに記載の抗体またはその抗原結合部分。 - 抗原特異的T細胞応答においてインターロイキン−2(IL−2)生産を刺激する、請求項1から9のいずれかに記載の抗体またはその抗原結合部分。
- 抗腫瘍免疫応答を刺激する、請求項1から10のいずれかに記載の抗体またはその抗原結合部分。
- アミノ酸配列PGHPLAPG(配列番号:21)を含むヒトLAG−3のエピトープに結合する、請求項1から11のいずれかに記載の抗体またはその抗原結合部分。
- アミノ酸配列HPAAPSSW(配列番号:22)またはPAAPSSWG(配列番号:23)を含むヒトLAG−3のエピトープに結合する、請求項1から12のいずれかに記載の抗体またはその抗原結合部分。
- 0.27x10−9M以下のKDにてヒトLAG−3に結合する、請求項1から13のいずれかに記載の抗体またはその抗原結合部分。
- ヒト、ヒト化またはキメラ抗体である、請求項1から14のいずれかに記載の抗体またはその抗原結合部分。
- IgG1、IgG2またはIgG4アイソタイプである、請求項1から15のいずれかに記載の抗体またはその抗原結合部分。
- 抗体フラグメントまたは一本鎖抗体である、請求項1から16のいずれかに記載の抗体またはその抗原結合部分。
- 請求項1から17のいずれかに記載の抗体またはその抗原結合部分、および第2の抗体またはその抗原結合部分を含む、二重特異性分子。
- 治療剤に連結した、請求項1から17のいずれかに記載の抗体またはその抗原結合部分を含む、免疫複合体。
- 治療剤が、細胞毒素または放射性同位体である、請求項19に記載の免疫複合体。
- 請求項1から17のいずれかに記載の抗体またはその抗原結合部分、請求項18に記載の二重特異性分子、または請求項19または20に記載の免疫複合体、および薬学的に許容される担体を含む組成物。
- 抗癌剤をさらに含む、請求項21に記載の組成物。
- 該剤が抗体または化学療法剤である、請求項22に記載の組成物。
- 請求項1−8のいずれかに記載の抗体またはその抗原結合部分の重鎖および/または軽鎖可変領域をコードする単離された核酸。
- 請求項24に記載の核酸を含む発現ベクター。
- 請求項25に記載の発現ベクターを含む宿主細胞。
- 請求項26に記載の宿主細胞において抗体を発現させ、宿主細胞から抗体を単離することを含む、抗LAG−3抗体を製造するための方法。
- 対象における免疫応答が刺激されるように、請求項1−17のいずれかに記載の抗体またはその抗原結合部分、請求項18に記載の二重特異性分子、または請求項19または20に記載の免疫複合体を対象に投与することを含む、対象における免疫応答を刺激する方法。
- 対象が腫瘍を有する対象であり、腫瘍に対する免疫応答が刺激される、請求項28に記載の方法。
- 対象がウイルスを有する対象であり、ウイルスに対する免疫応答が刺激される、請求項28に記載の方法。
- 抗原特異的T細胞応答が刺激されるように、免疫応答が抗原特異的T細胞応答である、請求項28に記載の方法。
- 抗原特異的T細胞によるインターロイキン−2生産が刺激される、請求項31に記載の方法。
- 腫瘍の増殖が対象において阻害されるように、請求項1−17のいずれかに記載の抗体またはその抗原結合部分、請求項18に記載の二重特異性分子、または請求項19または20に記載の免疫複合体を対象に投与することを含む、対象における腫瘍細胞の増殖を阻害するための方法。
- ウイルス感染が対象において処置されるように、請求項1−17のいずれかに記載の抗体またはその抗原結合部分、請求項18に記載の二重特異性分子、または請求項19または20に記載の免疫複合体を対象に投与することを含む、対象におけるウイルス感染を処置するための方法。
- 少なくとも1つのさらなる免疫刺激抗体の投与をさらに含む、請求項30に記載の方法。
- 少なくとも1つのさらなる免疫刺激抗体が抗PD−1抗体である、請求項35に記載の方法。
- 少なくとも1つのさらなる免疫刺激抗体が抗PD−L1抗体である、請求項36に記載の方法。
- 少なくとも1つのさらなる免疫刺激抗体が抗−CTLA−4抗体である、請求項36に記載の方法。
- 対象における免疫応答、所望により抗原特異的T細胞応答を刺激するため、または腫瘍細胞の増殖を阻害するため、またはウイルス感染を処置するための、請求項1−17のいずれかに記載の抗体またはその抗原結合部分、請求項18に記載の二重特異性分子、または請求項19または20に記載の免疫複合体の使用。
- 対象における免疫応答、所望により抗原特異的T細胞応答を刺激するため、または腫瘍細胞の増殖を阻害するため、またはウイルス感染を処置するための薬物の製造のための、請求項1−17のいずれかに記載の抗体またはその抗原結合部分、請求項18に記載の二重特異性分子、または請求項19または20に記載の免疫複合体の使用。
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Families Citing this family (460)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101213297B (zh) * | 2005-05-09 | 2013-02-13 | 小野药品工业株式会社 | 程序性死亡-1(pd-1)的人单克隆抗体及单独使用或与其它免疫治疗剂联合使用抗pd-1抗体来治疗癌症的方法 |
KR101411165B1 (ko) * | 2005-07-01 | 2014-06-25 | 메다렉스, 엘.엘.시. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날항체 |
AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
SI3702371T1 (sl) | 2009-03-25 | 2023-01-31 | Genentech, Inc. | Protitelesa proti FGFR3 in postopki za uporabo le-teh |
ES2671748T3 (es) | 2011-07-21 | 2018-06-08 | Tolero Pharmaceuticals, Inc. | Inhibidores heterocíclicos de proteína quinasas |
AR091649A1 (es) | 2012-07-02 | 2015-02-18 | Bristol Myers Squibb Co | Optimizacion de anticuerpos que se fijan al gen de activacion de linfocitos 3 (lag-3) y sus usos |
JP6224739B2 (ja) * | 2013-03-15 | 2017-11-01 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | 抗lag−3結合タンパク質 |
RU2015147696A (ru) | 2013-04-09 | 2017-05-12 | Бостон Байомедикал, Инк. | Способы лечения злокачественной опухоли |
BR122023024195A2 (pt) * | 2013-09-20 | 2023-12-26 | Bristol-Myers Squibb Company | Usos de anticorpos anti-lag-3 e anticorpos anti-pd-1 |
EP3049442A4 (en) | 2013-09-26 | 2017-06-28 | Costim Pharmaceuticals Inc. | Methods for treating hematologic cancers |
WO2015066413A1 (en) | 2013-11-01 | 2015-05-07 | Novartis Ag | Oxazolidinone hydroxamic acid compounds for the treatment of bacterial infections |
LT3081576T (lt) | 2013-12-12 | 2019-10-25 | Shanghai hengrui pharmaceutical co ltd | Pd-1 antikūnas, antigeną surišantis jo fragmentas ir jų medicininis pritaikomumas |
TWI726544B (zh) | 2013-12-24 | 2021-05-01 | 美商必治妥美雅史谷比公司 | 作為抗癌劑之新穎三環化合物 |
JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
TWI680138B (zh) * | 2014-01-23 | 2019-12-21 | 美商再生元醫藥公司 | 抗pd-l1之人類抗體 |
JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
CA2937503A1 (en) * | 2014-01-28 | 2015-08-06 | Bristol-Myers Squibb Company | Anti-lag-3 antibodies to treat hematological malignancies |
EP3099709B1 (en) | 2014-01-31 | 2019-12-25 | AIMM Therapeutics B.V. | Means and methods for producing stable antibodies |
JOP20200096A1 (ar) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | جزيئات جسم مضاد لـ tim-3 واستخداماتها |
US10519237B2 (en) | 2014-03-12 | 2019-12-31 | Yeda Research And Development Co. Ltd | Reducing systemic regulatory T cell levels or activity for treatment of disease and injury of the CNS |
US9394365B1 (en) | 2014-03-12 | 2016-07-19 | Yeda Research And Development Co., Ltd | Reducing systemic regulatory T cell levels or activity for treatment of alzheimer's disease |
KR102248804B1 (ko) | 2014-03-12 | 2021-05-11 | 예다 리서치 앤드 디벨럽먼트 캄파니 리미티드 | Cns의 질환 및 손상을 치료하기 위한 전신적 조절 t 세포 수준 또는 활성의 감소 |
US10618963B2 (en) | 2014-03-12 | 2020-04-14 | Yeda Research And Development Co. Ltd | Reducing systemic regulatory T cell levels or activity for treatment of disease and injury of the CNS |
US20150259420A1 (en) | 2014-03-14 | 2015-09-17 | Novartis Ag | Antibody molecules to lag-3 and uses thereof |
CN106164072B (zh) | 2014-03-24 | 2019-10-01 | 诺华股份有限公司 | 用于治疗细菌感染的单环内酰胺有机化合物 |
WO2015188085A1 (en) | 2014-06-06 | 2015-12-10 | Flexus Biosciences, Inc. | Immunoregulatory agents |
SI3151921T1 (sl) | 2014-06-06 | 2019-12-31 | Bristol-Myers Squibb Company | Protitelesa proti z glukortikoidom induciranim receptorjem za faktor nekroze tumorja(GITR) in njihova uporaba |
TWI693232B (zh) * | 2014-06-26 | 2020-05-11 | 美商宏觀基因股份有限公司 | 與pd-1和lag-3具有免疫反應性的共價結合的雙抗體和其使用方法 |
JP2017523213A (ja) | 2014-08-06 | 2017-08-17 | ノバルティス アーゲー | 抗菌薬としてのキノロン誘導体 |
JO3663B1 (ar) * | 2014-08-19 | 2020-08-27 | Merck Sharp & Dohme | الأجسام المضادة لمضاد lag3 وأجزاء ربط الأنتيجين |
WO2016040882A1 (en) | 2014-09-13 | 2016-03-17 | Novartis Ag | Combination therapies of egfr inhibitors |
EP3200775B1 (en) | 2014-10-03 | 2019-11-20 | Novartis AG | Combination therapies |
MA41044A (fr) | 2014-10-08 | 2017-08-15 | Novartis Ag | Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer |
BR112017007379A2 (pt) | 2014-10-14 | 2017-12-19 | Dana Farber Cancer Inst Inc | moléculas de anticorpo para pd-l1 e usos das mesmas |
CA2964276A1 (en) | 2014-11-05 | 2016-05-12 | Flexus Biosciences, Inc. | Immunoregulatory agents |
UY36390A (es) | 2014-11-05 | 2016-06-01 | Flexus Biosciences Inc | Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido), sus métodos de síntesis y composiciones farmacéuticas que los contienen |
AR102537A1 (es) | 2014-11-05 | 2017-03-08 | Flexus Biosciences Inc | Agentes inmunomoduladores |
HUE050596T2 (hu) | 2014-11-21 | 2020-12-28 | Bristol Myers Squibb Co | Antitestek CD73 ellen és azok felhasználásai |
WO2016094639A1 (en) * | 2014-12-10 | 2016-06-16 | Wisconsin Alumni Research Foundation | Mini-intronic plasmid dna vaccines in combination with lag3 blockade |
PT3233843T (pt) | 2014-12-16 | 2019-11-26 | Novartis Ag | Compostos de ácido isoxazol hidroxámico como inibidores de lxpc |
WO2016100882A1 (en) | 2014-12-19 | 2016-06-23 | Novartis Ag | Combination therapies |
TW201630907A (zh) | 2014-12-22 | 2016-09-01 | 必治妥美雅史谷比公司 | TGFβR拮抗劑 |
AU2015369683C1 (en) | 2014-12-23 | 2024-06-20 | Bristol-Myers Squibb Company | Antibodies to TIGIT |
ES2929532T3 (es) * | 2015-01-29 | 2022-11-30 | Univ Pennsylvania | Combinaciones de inhibidores de puntos de control y vacunas y su uso en inmunoterapia |
MA41463A (fr) * | 2015-02-03 | 2017-12-12 | Anaptysbio Inc | Anticorps dirigés contre le gène d'activation 3 des lymphocytes (lag-3) |
WO2016127052A1 (en) | 2015-02-05 | 2016-08-11 | Bristol-Myers Squibb Company | Cxcl11 and smica as predictive biomarkers for efficacy of anti-ctla4 immunotherapy |
BR112017017700A2 (pt) * | 2015-02-19 | 2018-07-31 | Bioclin Therapeutics Inc | métodos, composições e kits para tratamento do câncer |
MY186133A (en) | 2015-03-02 | 2021-06-24 | Rigel Pharmaceuticals Inc | Tgf-? inhibitors |
WO2016145102A1 (en) | 2015-03-10 | 2016-09-15 | Aduro Biotech, Inc. | Compositions and methods for activating "stimulator of interferon gene" -dependent signalling |
JP2018516238A (ja) | 2015-04-03 | 2018-06-21 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 癌の治療のためのインドールアミン−2,3−ジオキシゲナーゼの阻害剤およびそれらの使用方法 |
MX2017013178A (es) | 2015-04-13 | 2018-03-01 | Five Prime Therapeutics Inc | Terapia de combinacion para cancer. |
EP3283107B1 (en) | 2015-04-17 | 2020-05-27 | Bristol-Myers Squibb Company | Compositions comprising a combination of ipilimumab and nivolumab |
US10683290B2 (en) | 2015-05-11 | 2020-06-16 | Bristol-Myers Squibb Company | Tricyclic compounds as anticancer agents |
ES2770349T3 (es) | 2015-05-12 | 2020-07-01 | Bristol Myers Squibb Co | Compuestos de 5H-pirido[3,2-b]indol como agentes antineoplásicos |
US9725449B2 (en) | 2015-05-12 | 2017-08-08 | Bristol-Myers Squibb Company | Tricyclic compounds as anticancer agents |
HRP20230060T1 (hr) | 2015-05-29 | 2023-03-17 | Bristol-Myers Squibb Company | Antitijela protiv ox40 i njihova primjena |
CN113603784A (zh) | 2015-05-29 | 2021-11-05 | 艾吉纳斯公司 | 抗-ctla-4抗体及其使用方法 |
AU2016271475A1 (en) | 2015-06-03 | 2017-12-21 | Boston Biomedical, Inc. | Compositions comprising a cancer stemness inhibitor and an immunotherapeutic agent for use in treating cancer |
EA039293B1 (ru) * | 2015-06-05 | 2021-12-30 | Мерк Шарп И Доум Корп. | Антитела против lag3 и антигенсвязывающие фрагменты |
TWI773646B (zh) | 2015-06-08 | 2022-08-11 | 美商宏觀基因股份有限公司 | 結合lag-3的分子和其使用方法 |
BR112017028353A2 (pt) | 2015-06-29 | 2018-09-04 | The Rockfeller University | anticorpos para cd40 com atividade agonista melhorada |
EP3744340A3 (en) | 2015-07-16 | 2021-03-03 | Biokine Therapeutics Ltd. | Compositions and methods for treating cancer |
AR105444A1 (es) * | 2015-07-22 | 2017-10-04 | Sorrento Therapeutics Inc | Anticuerpos terapéuticos que se unen a la proteína codificada por el gen de activación de linfocitos 3 (lag3) |
WO2017019757A1 (en) | 2015-07-28 | 2017-02-02 | Bristol-Myers Squibb Company | Tgf beta receptor antagonists |
EP3328418A1 (en) | 2015-07-29 | 2018-06-06 | Novartis AG | Combination therapies comprising antibody molecules to pd-1 |
PL3317301T3 (pl) | 2015-07-29 | 2021-11-15 | Novartis Ag | Terapie skojarzone zawierające cząsteczki przeciwciał przeciw lag-3 |
EP3316902A1 (en) | 2015-07-29 | 2018-05-09 | Novartis AG | Combination therapies comprising antibody molecules to tim-3 |
GEP20227419B (en) | 2015-07-30 | 2022-10-10 | Macrogenics Inc | Pd-1-binding molecules and methods of use thereof |
US20180250303A1 (en) | 2015-08-25 | 2018-09-06 | Bristol-Myers Squibb Company | Tgf beta receptor antagonists |
PT3344654T (pt) | 2015-09-02 | 2021-01-26 | Immutep Sas | Anticorpos anti-lag-3 |
US10981991B2 (en) * | 2015-09-29 | 2021-04-20 | Shanghai Zhangjiang Biotechnology Co., Ltd. | PD-1 antibodies and uses thereof |
MY192202A (en) | 2015-10-02 | 2022-08-06 | Hoffmann La Roche | Bispecific antibodies specific for pd1 and tim3 |
TWI756187B (zh) | 2015-10-09 | 2022-03-01 | 美商再生元醫藥公司 | 抗lag3抗體及其用途 |
US10149887B2 (en) | 2015-10-23 | 2018-12-11 | Canbas Co., Ltd. | Peptides and peptidomimetics in combination with t cell activating and/or checkpoint inhibiting agents for cancer treatment |
JP2018534930A (ja) | 2015-10-30 | 2018-11-29 | ジェネンテック, インコーポレイテッド | 抗d因子抗体及びコンジュゲート |
AU2016350701B2 (en) | 2015-11-02 | 2021-08-19 | Five Prime Therapeutics, Inc. | CD80 extracellular domain polypeptides and their use in cancer treatment |
WO2017083224A1 (en) | 2015-11-09 | 2017-05-18 | Bristol-Myers Squibb Company | Methods to manipulate quality attributes of polypeptides produced in cho cells |
JP6945456B2 (ja) * | 2015-11-13 | 2021-10-06 | マクロジェニクス,インコーポレーテッド | Lag‐3結合分子及びその使用方法 |
MX2018006245A (es) * | 2015-11-18 | 2018-08-01 | Merck Sharp & Dohme | Proteinas de union a pd1 y/o lag3. |
MX2018006072A (es) | 2015-11-19 | 2018-08-01 | Squibb Bristol Myers Co | Anticuerpos contra receptor de factor de necrosis de tumor inducido por glucocorticoides (gitr) y usos de los mismos. |
US10306874B2 (en) * | 2015-11-20 | 2019-06-04 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized lymphocyte-activation gene 3 |
TWI791422B (zh) | 2015-11-23 | 2023-02-11 | 美商戊瑞治療有限公司 | 用於癌症治療之單獨fgfr2抑制劑或與免疫刺激劑組合 |
BR112018011781A2 (pt) | 2015-12-14 | 2018-12-04 | Macrogenics Inc | molécula biespecífica possuindo um ou mais sítios de ligação a epítopo capazes de ligação imunoespecífica a (um) epítopo(s) de pd-1 e um ou mais sítios de ligação a epítopo capazes de ligação imunoespecífica a (um) epítopo(s) de ctla-4, e composição farmacêutica |
CN108602829A (zh) | 2015-12-15 | 2018-09-28 | 百时美施贵宝公司 | Cxcr4受体拮抗剂 |
AU2016371639A1 (en) | 2015-12-16 | 2018-06-28 | Merck Sharp & Dohme Llc | Anti-LAG3 antibodies and antigen-binding fragments |
CN108495651A (zh) | 2015-12-17 | 2018-09-04 | 诺华股份有限公司 | 抗pd-1的抗体分子及其用途 |
JP2019506844A (ja) | 2015-12-18 | 2019-03-14 | ノバルティス アーゲー | CD32bを標的とする抗体およびその使用方法 |
CN108473569B (zh) | 2016-01-11 | 2022-11-22 | 苏黎世大学 | 针对人白介素-2的免疫刺激性人源化单克隆抗体及其融合蛋白 |
JOP20170045B1 (ar) | 2016-02-19 | 2021-08-17 | Novartis Ag | مركبات بيريدون رباعية الحلقة كمضادات فيروسية |
US20190284293A1 (en) | 2016-03-04 | 2019-09-19 | Bristol-Myers Squibb Company | Combination therapy with anti-cd73 antibodies |
EP3423489A1 (en) * | 2016-03-04 | 2019-01-09 | The Rockefeller University | Antibodies to cd40 with enhanced agonist activity |
WO2017163186A1 (en) | 2016-03-24 | 2017-09-28 | Novartis Ag | Alkynyl nucleoside analogs as inhibitors of human rhinovirus |
CN109789195A (zh) | 2016-04-13 | 2019-05-21 | 维维雅生物技术公司 | 离体bite激活的t细胞 |
CN109071665B (zh) | 2016-04-18 | 2022-11-01 | 塞德斯医疗公司 | 结合人cd40的激动性抗体及其用途 |
US10696648B2 (en) | 2016-05-04 | 2020-06-30 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
KR20190003687A (ko) | 2016-05-04 | 2019-01-09 | 브리스톨-마이어스 스큅 컴퍼니 | 인돌아민 2,3-디옥시게나제의 억제제 및 그의 사용 방법 |
US11066383B2 (en) | 2016-05-04 | 2021-07-20 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
EP3452029A4 (en) | 2016-05-04 | 2019-10-30 | Bristol-Myers Squibb Company | INDOLEAMINE 2,3-DIOXYGENASE INHIBITORS AND METHODS OF USE |
KR20190004743A (ko) | 2016-05-04 | 2019-01-14 | 브리스톨-마이어스 스큅 컴퍼니 | 인돌아민 2,3-디옥시게나제의 억제제 및 그의 사용 방법 |
EP3458478B1 (en) | 2016-05-18 | 2021-01-06 | Boehringer Ingelheim International GmbH | Anti pd-1 and anti-lag3 antibodies for cancer treatment |
US11623958B2 (en) | 2016-05-20 | 2023-04-11 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
LT4019019T (lt) | 2016-05-20 | 2024-06-25 | Biohaven Therapeutics Ltd. | Riluzolo, riluzolo provaistų arba riluzolo analogų naudojimas kartu su imunoterapijos rūšimis vėžio formų gydymui |
CA3029813A1 (en) | 2016-06-13 | 2017-12-21 | Torque Therapeutics, Inc. | Methods and compositions for promoting immune cell function |
BR112018074983A2 (pt) | 2016-06-14 | 2019-03-12 | Novartis Ag | forma cristalina de (r)-4-(5-ciclopropiletinil)isoxazol-3-il)-n-hidróxi-2-metil-2-(metilsulfonil)butanamida como um agente antibacteriano |
WO2017216685A1 (en) | 2016-06-16 | 2017-12-21 | Novartis Ag | Pentacyclic pyridone compounds as antivirals |
WO2017216686A1 (en) | 2016-06-16 | 2017-12-21 | Novartis Ag | 8,9-fused 2-oxo-6,7-dihydropyrido-isoquinoline compounds as antivirals |
CN109311993B (zh) | 2016-06-20 | 2022-12-20 | F-星治疗有限公司 | Lag-3结合元件 |
KR102379464B1 (ko) | 2016-06-20 | 2022-03-29 | 키맵 리미티드 | 항-pd-l1 항체 |
AU2017283181A1 (en) | 2016-06-20 | 2019-01-03 | F-Star Therapeutics Limited | Binding molecules binding PD-L1 and LAG-3 |
EP3476399B1 (en) | 2016-06-23 | 2022-04-20 | Jiangsu Hengrui Medicine Co. Ltd. | Lag-3 antibody, antigen-binding fragment thereof, and pharmaceutical application thereof |
CA3028718A1 (en) | 2016-06-24 | 2017-12-28 | Infinity Pharmaceuticals, Inc. | Combination therapies |
US11098077B2 (en) | 2016-07-05 | 2021-08-24 | Chinook Therapeutics, Inc. | Locked nucleic acid cyclic dinucleotide compounds and uses thereof |
US20190233534A1 (en) | 2016-07-14 | 2019-08-01 | Fred Hutchinson Cancer Research Center | Multiple bi-specific binding domain constructs with different epitope binding to treat cancer |
TWI780057B (zh) | 2016-07-14 | 2022-10-11 | 美商必治妥美雅史谷比公司 | 針對tim3之抗體及其用途 |
GB201612520D0 (en) | 2016-07-19 | 2016-08-31 | F-Star Beta Ltd | Binding molecules |
US20190292179A1 (en) | 2016-07-21 | 2019-09-26 | Bristol-Myers Squibb Company | TGF Beta RECEPTOR ANTAGONISTS |
CA3033904A1 (en) * | 2016-08-15 | 2018-02-22 | National University Corporation Hokkaido University | Anti-lag-3 antibody |
KR20190040990A (ko) | 2016-08-26 | 2019-04-19 | 브리스톨-마이어스 스큅 컴퍼니 | 인돌아민 2,3-디옥시게나제의 억제제 및 그의 사용 방법 |
WO2018047109A1 (en) | 2016-09-09 | 2018-03-15 | Novartis Ag | Polycyclic pyridone compounds as antivirals |
CA3036564A1 (en) | 2016-09-23 | 2018-03-29 | Elstar Therapeutics, Inc. | Multispecific antibody molecules comprising lambda and kappa light chains |
JOP20190061A1 (ar) | 2016-09-28 | 2019-03-26 | Novartis Ag | مثبطات بيتا-لاكتاماز |
MX2019003683A (es) | 2016-10-11 | 2019-08-22 | Agenus Inc | Anticuerpos anti gen 3 de activación linfocítica (lag 3 ) y métodos para usarlos. |
SG10201912940WA (en) * | 2016-10-13 | 2020-02-27 | Symphogen As | Anti-lag-3 antibodies and compositions |
WO2018073753A1 (en) | 2016-10-18 | 2018-04-26 | Novartis Ag | Fused tetracyclic pyridone compounds as antivirals |
US10660909B2 (en) | 2016-11-17 | 2020-05-26 | Syntrix Biosystems Inc. | Method for treating cancer using chemokine antagonists |
WO2018094275A1 (en) | 2016-11-18 | 2018-05-24 | Tolero Pharmaceuticals, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
US11299469B2 (en) | 2016-11-29 | 2022-04-12 | Sumitomo Dainippon Pharma Oncology, Inc. | Naphthofuran derivatives, preparation, and methods of use thereof |
MD3551660T2 (ro) | 2016-12-07 | 2024-03-31 | Agenus Inc | Anticorpi anti-CTLA-4 și procedee de utilizare a acestora |
US10961239B2 (en) | 2017-01-05 | 2021-03-30 | Bristol-Myers Squibb Company | TGF beta receptor antagonists |
UA126863C2 (uk) | 2017-01-20 | 2023-02-15 | Аркус Байосайєнсіз, Інк. | Азолопіримідини для лікування ракових захворювань |
KR20240058959A (ko) | 2017-02-10 | 2024-05-07 | 리제너론 파마슈티칼스 인코포레이티드 | 면역-pet 이미지화를 위한 방사선 라벨링된 항-lag3 항체 |
US20200291089A1 (en) | 2017-02-16 | 2020-09-17 | Elstar Therapeutics, Inc. | Multifunctional molecules comprising a trimeric ligand and uses thereof |
CN109475617B (zh) * | 2017-02-22 | 2022-05-17 | 天境生物科技(杭州)有限公司 | 抗lag-3抗体及其应用 |
KR20190133213A (ko) | 2017-03-31 | 2019-12-02 | 브리스톨-마이어스 스큅 컴퍼니 | 종양을 치료하는 방법 |
CN110709420A (zh) | 2017-03-31 | 2020-01-17 | 戊瑞治疗有限公司 | 使用抗gitr抗体的癌症组合疗法 |
BR112019017329A2 (pt) | 2017-04-03 | 2020-04-14 | Hoffmann La Roche | imunoconjugados, um ou mais polinucleotídeos e vetores, métodos para a produção de um imunoconjugado, tratamento de uma doença e para a estimulação do sistema imunológico, composição, uso do imunoconjugado, invenção e usos da composição |
CN110392698B (zh) | 2017-04-05 | 2022-01-25 | 豪夫迈·罗氏有限公司 | 抗lag3抗体 |
MA49042A (fr) | 2017-04-05 | 2020-02-12 | Symphogen As | Polythérapies ciblant pd-1, tim-3 et lag-3 |
US11285207B2 (en) | 2017-04-05 | 2022-03-29 | Hoffmann-La Roche Inc. | Bispecific antibodies specifically binding to PD1 and LAG3 |
TWI788340B (zh) | 2017-04-07 | 2023-01-01 | 美商必治妥美雅史谷比公司 | 抗icos促效劑抗體及其用途 |
CA3058944A1 (en) | 2017-04-19 | 2018-10-25 | Elstar Therapeutics, Inc. | Multispecific molecules and uses thereof |
JP7232244B2 (ja) | 2017-04-21 | 2023-03-08 | イケナ オンコロジー, インコーポレイテッド | インドールahr阻害剤およびその使用 |
WO2018200430A1 (en) | 2017-04-26 | 2018-11-01 | Bristol-Myers Squibb Company | Methods of antibody production that minimize disulfide bond reduction |
AU2018256934B2 (en) * | 2017-04-27 | 2021-10-14 | Anaptysbio, Inc. | Antibody agents directed against Lymphocyte Activation Gene-3 (LAG-3) and uses thereof |
AR111419A1 (es) | 2017-04-27 | 2019-07-10 | Novartis Ag | Compuestos fusionados de indazol piridona como antivirales |
UY37695A (es) | 2017-04-28 | 2018-11-30 | Novartis Ag | Compuesto dinucleótido cíclico bis 2’-5’-rr-(3’f-a)(3’f-a) y usos del mismo |
AR111651A1 (es) | 2017-04-28 | 2019-08-07 | Novartis Ag | Conjugados de anticuerpos que comprenden agonistas del receptor de tipo toll y terapias de combinación |
WO2018201047A1 (en) | 2017-04-28 | 2018-11-01 | Elstar Therapeutics, Inc. | Multispecific molecules comprising a non-immunoglobulin heterodimerization domain and uses thereof |
AU2018258661A1 (en) | 2017-04-28 | 2019-10-17 | Five Prime Therapeutics, Inc. | Methods of treatment with CD80 extracellular domain polypeptides |
AR111658A1 (es) | 2017-05-05 | 2019-08-07 | Novartis Ag | 2-quinolinonas tricíclicas como agentes antibacteriales |
US11339218B2 (en) | 2017-05-10 | 2022-05-24 | Zhejiang Shimai Pharmaceutical Co., Ltd. | Human monoclonal antibodies against LAG3 and uses thereof |
WO2018209049A1 (en) | 2017-05-12 | 2018-11-15 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
BR112019023855B1 (pt) | 2017-05-12 | 2021-11-30 | Harpoon Therapeutics, Inc | Proteínas de ligação à mesotelina |
PL3634417T3 (pl) | 2017-05-17 | 2023-09-25 | Arcus Biosciences, Inc. | Pochodne chinazolino-pirazolowe do leczenia chorób związanych z nowotworem |
CA3062656A1 (en) | 2017-05-17 | 2018-11-22 | Boston Biomedical, Inc. | Methods for treating cancer |
CA3065304A1 (en) * | 2017-05-30 | 2018-12-06 | Bristol-Myers Squibb Company | Compositions comprising an anti-lag-3 antibody or an anti-lag-3 antibody and an anti-pd-1 or anti-pd-l1 antibody |
AU2018277559A1 (en) * | 2017-05-30 | 2019-10-17 | Bristol-Myers Squibb Company | Compositions comprising a combination of an anti-LAG-3 antibody, a PD-1 pathway inhibitor, and an immunotherapeutic agent |
HUE065242T2 (hu) | 2017-05-30 | 2024-05-28 | Bristol Myers Squibb Co | LAG-3-pozitív tumorok kezelése |
JP2020522254A (ja) | 2017-05-31 | 2020-07-30 | エルスター セラピューティクス, インコーポレイテッド | 骨髄増殖性白血病(mpl)タンパク質に結合する多特異性分子およびその使用 |
WO2018223004A1 (en) | 2017-06-01 | 2018-12-06 | Xencor, Inc. | Bispecific antibodies that bind cd20 and cd3 |
EP3630839A1 (en) | 2017-06-01 | 2020-04-08 | Xencor, Inc. | Bispecific antibodies that bind cd 123 cd3 |
WO2018229715A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Compositions comprising anti-cd32b antibodies and methods of use thereof |
WO2018235056A1 (en) | 2017-06-22 | 2018-12-27 | Novartis Ag | IL-1BETA BINDING ANTIBODIES FOR USE IN THE TREATMENT OF CANCER |
EP3642240A1 (en) | 2017-06-22 | 2020-04-29 | Novartis AG | Antibody molecules to cd73 and uses thereof |
CN118307674A (zh) | 2017-06-22 | 2024-07-09 | 诺华股份有限公司 | 针对cd73的抗体分子及其用途 |
JP2020524694A (ja) | 2017-06-22 | 2020-08-20 | ノバルティス アーゲー | がんの処置における使用のためのIL−1β結合性抗体 |
EP3645037A1 (en) | 2017-06-27 | 2020-05-06 | Novartis AG | Dosage regimens for anti-tim-3 antibodies and uses thereof |
KR102630575B1 (ko) | 2017-06-30 | 2024-01-29 | 브리스톨-마이어스 스큅 컴퍼니 | Ido 억제제의 무정형 및 결정질 형태 |
US10844121B2 (en) * | 2017-07-13 | 2020-11-24 | Nanjing Leads Biolabs Co., Ltd | Antibodies binding LAG-3 and uses thereof |
KR20200031659A (ko) | 2017-07-20 | 2020-03-24 | 노파르티스 아게 | 항-lag-3 항체의 투여 요법 및 그의 용도 |
KR20200032180A (ko) | 2017-07-28 | 2020-03-25 | 브리스톨-마이어스 스큅 컴퍼니 | 항암제로서의 시클릭 디뉴클레오티드 |
WO2019035938A1 (en) | 2017-08-16 | 2019-02-21 | Elstar Therapeutics, Inc. | MULTISPECIFIC MOLECULES BINDING TO BCMA AND USES THEREOF |
US10696650B2 (en) | 2017-08-17 | 2020-06-30 | Ikena Oncology, Inc. | AHR inhibitors and uses thereof |
CN111372934B (zh) | 2017-08-18 | 2024-04-26 | 科瑞华生物技术有限公司 | Tg02的多晶型形式 |
KR20200042937A (ko) * | 2017-08-30 | 2020-04-24 | 페인스 테라퓨틱스 인코포레이티드 | 항-lag-3 항체 및 이의 용도 |
WO2019046500A1 (en) | 2017-08-31 | 2019-03-07 | Bristol-Myers Squibb Company | CYCLIC DINUCLEOTIDES AS ANTICANCER AGENTS |
KR102651946B1 (ko) | 2017-08-31 | 2024-03-26 | 브리스톨-마이어스 스큅 컴퍼니 | 항암제로서의 시클릭 디뉴클레오티드 |
KR20200039796A (ko) | 2017-08-31 | 2020-04-16 | 브리스톨-마이어스 스큅 컴퍼니 | 항암제로서의 시클릭 디뉴클레오티드 |
WO2019055579A1 (en) | 2017-09-12 | 2019-03-21 | Tolero Pharmaceuticals, Inc. | TREATMENT REGIME FOR CANCERS THAT ARE INSENSITIVE TO BCL-2 INHIBITORS USING THE MCL-1 ALVOCIDIB INHIBITOR |
JP7366031B2 (ja) | 2017-09-22 | 2023-10-20 | カイメラ セラピューティクス, インコーポレイテッド | タンパク質分解剤およびそれらの使用 |
WO2019060693A1 (en) | 2017-09-22 | 2019-03-28 | Kymera Therapeutics, Inc. | CRBN LIGANDS AND USES THEREOF |
US20200262917A1 (en) * | 2017-10-05 | 2020-08-20 | Daiichi Sankyo Company, Limited | Composition for cytotoxic t cell depletion |
US11203592B2 (en) | 2017-10-09 | 2021-12-21 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
WO2019074822A1 (en) | 2017-10-09 | 2019-04-18 | Bristol-Myers Squibb Company | INDOLEAMINE 2,3-DIOXYGENASE INHIBITORS AND METHODS OF USE |
CN111344297B (zh) | 2017-10-10 | 2023-10-20 | 百时美施贵宝公司 | 作为抗癌剂的环二核苷酸 |
WO2019075090A1 (en) | 2017-10-10 | 2019-04-18 | Tilos Therapeutics, Inc. | ANTI-LAP ANTIBODIES AND USES THEREOF |
AU2018346955A1 (en) | 2017-10-13 | 2020-04-30 | Harpoon Therapeutics, Inc. | B cell maturation antigen binding proteins |
US20200239577A1 (en) | 2017-10-15 | 2020-07-30 | Bristol-Myers Squibb Company | Methods of treating tumor |
JP7254821B2 (ja) | 2017-10-16 | 2023-04-10 | ブリストル-マイヤーズ スクイブ カンパニー | 抗がん剤としての環状ジヌクレオチド |
WO2019077062A1 (en) | 2017-10-18 | 2019-04-25 | Vivia Biotech, S.L. | C-CELLS ACTIVATED BY BIT |
WO2019081983A1 (en) | 2017-10-25 | 2019-05-02 | Novartis Ag | CD32B TARGETING ANTIBODIES AND METHODS OF USE |
KR20200074214A (ko) | 2017-11-01 | 2020-06-24 | 브리스톨-마이어스 스큅 컴퍼니 | 암을 치료하는데 사용하기 위한 면역자극 효능작용 항체 |
JP7167146B2 (ja) | 2017-11-06 | 2022-11-08 | ブリストル-マイヤーズ スクイブ カンパニー | Hpk1阻害剤として有用なイソフラノン化合物 |
WO2019099838A1 (en) | 2017-11-16 | 2019-05-23 | Novartis Ag | Combination therapies |
CN111315749A (zh) | 2017-11-17 | 2020-06-19 | 诺华股份有限公司 | 新颖的二氢异噁唑化合物及其在治疗乙型肝炎中的用途 |
TW201925782A (zh) | 2017-11-30 | 2019-07-01 | 瑞士商諾華公司 | 靶向bcma之嵌合抗原受體及其用途 |
US20200377571A1 (en) | 2017-12-08 | 2020-12-03 | Elstar Therapeutics, Inc. | Multispecific molecules and uses thereof |
EP3728316A1 (en) | 2017-12-19 | 2020-10-28 | F-Star Beta Limited | Fc binding fragments comprising a pd-l1 antigen-binding site |
WO2019123285A1 (en) | 2017-12-20 | 2019-06-27 | Novartis Ag | Fused tricyclic pyrazolo-dihydropyrazinyl-pyridone compounds as antivirals |
CN111356476B (zh) | 2017-12-22 | 2023-03-10 | 江苏恒瑞医药股份有限公司 | Lag-3抗体药物组合物及其用途 |
JP2021508703A (ja) | 2017-12-26 | 2021-03-11 | カイメラ セラピューティクス, インコーポレイテッド | Irak分解剤およびそれらの使用 |
WO2019129137A1 (zh) | 2017-12-27 | 2019-07-04 | 信达生物制药(苏州)有限公司 | 抗lag-3抗体及其用途 |
WO2019129136A1 (zh) | 2017-12-27 | 2019-07-04 | 信达生物制药(苏州)有限公司 | 抗pd-l1抗体及其用途 |
CN115925943A (zh) | 2017-12-27 | 2023-04-07 | 信达生物制药(苏州)有限公司 | 抗pd-l1抗体及其用途 |
JP7284759B2 (ja) | 2017-12-27 | 2023-05-31 | ブリストル-マイヤーズ スクイブ カンパニー | 抗cd40抗体およびその使用 |
CN109970856B (zh) | 2017-12-27 | 2022-08-23 | 信达生物制药(苏州)有限公司 | 抗lag-3抗体及其用途 |
US11447449B2 (en) | 2018-01-05 | 2022-09-20 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
EP3737408A1 (en) | 2018-01-08 | 2020-11-18 | Novartis AG | Immune-enhancing rnas for combination with chimeric antigen receptor therapy |
WO2019140387A1 (en) | 2018-01-12 | 2019-07-18 | Kymera Therapeutics, Inc. | Crbn ligands and uses thereof |
KR20200108870A (ko) | 2018-01-12 | 2020-09-21 | 브리스톨-마이어스 스큅 컴퍼니 | Tim3에 대한 항체 및 그의 용도 |
EP3737666A4 (en) | 2018-01-12 | 2022-01-05 | Kymera Therapeutics, Inc. | PROTEIN DEGRADANTS AND USES THEREOF |
CN111542546B (zh) * | 2018-01-18 | 2022-08-16 | 四川科伦博泰生物医药股份有限公司 | 抗lag-3抗体及其用途 |
CA3089762A1 (en) | 2018-01-29 | 2019-08-01 | Merck Patent Gmbh | Gcn2 inhibitors and uses thereof |
WO2019148136A1 (en) | 2018-01-29 | 2019-08-01 | Merck Patent Gmbh | Gcn2 inhibitors and uses thereof |
CN111630063A (zh) | 2018-01-31 | 2020-09-04 | 豪夫迈·罗氏有限公司 | 稳定化的免疫球蛋白结构域 |
EP3746480A1 (en) | 2018-01-31 | 2020-12-09 | F. Hoffmann-La Roche AG | Bispecific antibodies comprising an antigen-binding site binding to lag3 |
AU2019215031A1 (en) | 2018-01-31 | 2020-08-20 | Novartis Ag | Combination therapy using a chimeric antigen receptor |
US10519187B2 (en) | 2018-02-13 | 2019-12-31 | Bristol-Myers Squibb Company | Cyclic dinucleotides as anticancer agents |
US20200399383A1 (en) | 2018-02-13 | 2020-12-24 | Novartis Ag | Chimeric antigen receptor therapy in combination with il-15r and il15 |
WO2019165315A1 (en) | 2018-02-23 | 2019-08-29 | Syntrix Biosystems Inc. | Method for treating cancer using chemokine antagonists alone or in combination |
JP2021514982A (ja) | 2018-02-28 | 2021-06-17 | ノバルティス アーゲー | インドール−2−カルボニル化合物及びb型肝炎治療のためのそれらの使用 |
EP3762397B1 (en) | 2018-03-08 | 2024-05-01 | Bristol-Myers Squibb Company | Cyclic dinucleotides as anticancer agents |
US20210009711A1 (en) | 2018-03-14 | 2021-01-14 | Elstar Therapeutics, Inc. | Multifunctional molecules and uses thereof |
US20210238280A1 (en) | 2018-03-14 | 2021-08-05 | Elstar Therapeutics, Inc. | Multifunctional molecules that bind to calreticulin and uses thereof |
JP7438180B2 (ja) * | 2018-03-20 | 2024-02-26 | ウーシー バイオロジクス アイルランド リミテッド | 新規抗lag-3抗体ポリペプチド |
CA3092589A1 (en) | 2018-03-21 | 2019-09-26 | Five Prime Therapeutics, Inc. | Antibodies binding to vista at acidic ph |
MX2020009861A (es) | 2018-03-23 | 2020-10-08 | Bristol Myers Squibb Co | Anticuerpos contra el complejo principal de histocompatibilidad relacionado con las cadenas a y b clase i (mica) y/o (micb) y sus usos. |
WO2019191676A1 (en) | 2018-03-30 | 2019-10-03 | Bristol-Myers Squibb Company | Methods of treating tumor |
EP3778639A4 (en) | 2018-04-02 | 2021-06-09 | Mab-Venture Biopharm Co., Ltd. | ANTIBODIES BINDING TO LYMPHOCYTAIR ACTIVATION GENE 3 (LAG-3) AND ITS USE |
CN110343178B (zh) * | 2018-04-03 | 2022-07-22 | 上海开拓者生物医药有限公司 | 抗人lag-3单克隆抗体及其应用 |
US20210147547A1 (en) | 2018-04-13 | 2021-05-20 | Novartis Ag | Dosage Regimens For Anti-Pd-L1 Antibodies And Uses Thereof |
JP2021522211A (ja) | 2018-04-16 | 2021-08-30 | アリーズ セラピューティクス, インコーポレイテッド | Ep4阻害剤およびその使用 |
AU2019255744A1 (en) | 2018-04-18 | 2020-11-26 | Xencor, Inc. | IL-15/IL-15Ra heterodimeric Fc fusion proteins and uses thereof |
AU2019256539A1 (en) | 2018-04-18 | 2020-11-26 | Xencor, Inc. | PD-1 targeted heterodimeric fusion proteins containing IL-15/IL-15Ra Fc-fusion proteins and PD-1 antigen binding domains and uses thereof |
WO2019213340A1 (en) | 2018-05-03 | 2019-11-07 | Bristol-Myers Squibb Company | Uracil derivatives as mer-axl inhibitors |
AR126019A1 (es) | 2018-05-30 | 2023-09-06 | Novartis Ag | Anticuerpos frente a entpd2, terapias de combinación y métodos de uso de los anticuerpos y las terapias de combinación |
WO2019232244A2 (en) | 2018-05-31 | 2019-12-05 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
WO2019232528A1 (en) | 2018-06-01 | 2019-12-05 | Xencor, Inc. | Dosing of a bispecific antibody that bind cd123 and cd3 |
JP7398396B2 (ja) | 2018-06-01 | 2023-12-14 | ノバルティス アーゲー | Bcmaに対する結合分子及びその使用 |
EP3802922B1 (en) | 2018-06-11 | 2023-04-26 | Yale University | Novel immune checkpoint inhibitors |
CN110606892B (zh) * | 2018-06-14 | 2023-09-26 | 华博生物医药技术(上海)有限公司 | 一种高亲和力高生物活性的lag-3抗体及其应用 |
CN110615840A (zh) * | 2018-06-19 | 2019-12-27 | 信达生物制药(苏州)有限公司 | 全人源的抗lag-3抗体及其应用 |
US11180531B2 (en) | 2018-06-22 | 2021-11-23 | Bicycletx Limited | Bicyclic peptide ligands specific for Nectin-4 |
DK3814347T3 (da) | 2018-06-27 | 2023-08-07 | Bristol Myers Squibb Co | Naphthyridinonforbindelse, der er nyttige som t-celleaktivatorer |
RS64641B1 (sr) | 2018-06-27 | 2023-10-31 | Bristol Myers Squibb Co | Supstituisana jedinjenja naftiridinona korisna kao aktivatori t ćelija |
WO2020005003A1 (ko) | 2018-06-29 | 2020-01-02 | 주식회사 와이바이오로직스 | Lag-3에 특이적으로 결합하는 단클론항체 및 이의 용도 |
US11845797B2 (en) | 2018-07-03 | 2023-12-19 | Marengo Therapeutics, Inc. | Anti-TCR antibody molecules and uses thereof |
US11292792B2 (en) | 2018-07-06 | 2022-04-05 | Kymera Therapeutics, Inc. | Tricyclic CRBN ligands and uses thereof |
EP3820904A2 (en) | 2018-07-09 | 2021-05-19 | Five Prime Therapeutics, Inc. | Antibodies binding to ilt4 |
AR116109A1 (es) | 2018-07-10 | 2021-03-31 | Novartis Ag | Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos |
FI3820573T3 (fi) | 2018-07-10 | 2023-11-01 | Novartis Ag | 3-(5-hydroksi-1-oksoisoindolin-2-yyli)piperidiini-2,6-dionijohdannaisia ja niiden käyttö ikaros-perheen sinkkisormi 2 (ikzf2) -riippuvaisten sairauksien hoidossa |
SG11202100102VA (en) | 2018-07-11 | 2021-02-25 | Five Prime Therapeutics Inc | Antibodies binding to vista at acidic ph |
MX2021000745A (es) | 2018-07-20 | 2021-03-26 | Surface Oncology Inc | Composiciones anti-cd112r y metodos. |
US20210299126A1 (en) | 2018-07-23 | 2021-09-30 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
US20210355113A1 (en) | 2018-07-23 | 2021-11-18 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
WO2020021465A1 (en) | 2018-07-25 | 2020-01-30 | Advanced Accelerator Applications (Italy) S.R.L. | Method of treatment of neuroendocrine tumors |
EP3826660A1 (en) * | 2018-07-26 | 2021-06-02 | Bristol-Myers Squibb Company | Lag-3 combination therapy for the treatment of cancer |
CN110172099B (zh) * | 2018-08-16 | 2020-03-03 | 上海健信生物医药科技有限公司 | 抗lag-3人源化单克隆抗体分子,抗原结合片段及其医药用途 |
US10959986B2 (en) | 2018-08-29 | 2021-03-30 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
US11253525B2 (en) | 2018-08-29 | 2022-02-22 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
EP3846793B1 (en) | 2018-09-07 | 2024-01-24 | PIC Therapeutics, Inc. | Eif4e inhibitors and uses thereof |
KR20230170813A (ko) | 2018-09-12 | 2023-12-19 | 노파르티스 아게 | 항바이러스 피리도피라진디온 화합물 |
AU2019344875B2 (en) | 2018-09-21 | 2021-12-23 | Innovent Biologics (Suzhou) Co., Ltd. | Novel interleukin 2 and use thereof |
JP7512210B2 (ja) | 2018-09-21 | 2024-07-08 | イノベント バイオロジックス (スウツォウ) カンパニー,リミテッド | 新規インターロイキン2およびその使用 |
CA3114038A1 (en) | 2018-09-25 | 2020-04-02 | Harpoon Therapeutics, Inc. | Dll3 binding proteins and methods of use |
CN113164777A (zh) | 2018-09-27 | 2021-07-23 | 马伦戈治疗公司 | Csf1r/ccr2多特异性抗体 |
KR20210068473A (ko) | 2018-09-29 | 2021-06-09 | 노파르티스 아게 | Shp2 활성 억제용 화합물의 제조 방법 |
AU2019355971A1 (en) | 2018-10-03 | 2021-05-06 | Xencor, Inc. | IL-12 heterodimeric Fc-fusion proteins |
EP3863722A2 (en) | 2018-10-10 | 2021-08-18 | Tilos Theapeutics, Inc. | Anti-lap antibody variants and uses thereof |
CN113423734A (zh) | 2018-10-12 | 2021-09-21 | Xencor股份有限公司 | 靶向PD-1的IL-15/IL-15RαFC融合蛋白及其在联合疗法中的应用 |
JP2022512750A (ja) * | 2018-10-19 | 2022-02-07 | ブリストル-マイヤーズ スクイブ カンパニー | 黒色腫に対する併用療法 |
EP3873532A1 (en) | 2018-10-31 | 2021-09-08 | Novartis AG | Dc-sign antibody drug conjugates |
WO2020102501A1 (en) | 2018-11-16 | 2020-05-22 | Bristol-Myers Squibb Company | Anti-nkg2a antibodies and uses thereof |
KR20210111252A (ko) | 2018-11-30 | 2021-09-10 | 카이메라 쎄라퓨틱스 인코포레이티드 | Irak 분해제 및 이의 용도 |
US11034710B2 (en) | 2018-12-04 | 2021-06-15 | Sumitomo Dainippon Pharma Oncology, Inc. | CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer |
BR112021011874A2 (pt) | 2018-12-20 | 2021-09-08 | Novartis Ag | Regime de dosagem e combinação farmacêutica compreendendo derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona |
EP3897853A1 (en) | 2018-12-20 | 2021-10-27 | Xencor, Inc. | Targeted heterodimeric fc fusion proteins containing il-15/il-15ra and nkg2d antigen binding domains |
EP3670659A1 (en) | 2018-12-20 | 2020-06-24 | Abivax | Biomarkers, and uses in treatment of viral infections, inflammations, or cancer |
US20220025036A1 (en) | 2018-12-21 | 2022-01-27 | Novartis Ag | Use of il-1beta binding antibodies |
US20220056123A1 (en) | 2018-12-21 | 2022-02-24 | Novartis Ag | Use of il-1beta binding antibodies |
BR112021012066A2 (pt) | 2018-12-21 | 2021-11-03 | Onxeo | Novas moléculas de ácido nucleico conjugadas e seus usos |
WO2020128637A1 (en) | 2018-12-21 | 2020-06-25 | Novartis Ag | Use of il-1 binding antibodies in the treatment of a msi-h cancer |
SG11202104699TA (en) | 2018-12-21 | 2021-07-29 | Novartis Ag | Use of il-1 beta antibodies in the treatment or prevention of myelodysplastic syndrome |
CA3127502A1 (en) | 2019-02-12 | 2020-08-20 | Sumitomo Dainippon Pharma Oncology, Inc. | Formulations comprising heterocyclic protein kinase inhibitors |
CN113329792B (zh) | 2019-02-15 | 2024-06-28 | 诺华股份有限公司 | 取代的3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途 |
CN113490528A (zh) | 2019-02-15 | 2021-10-08 | 诺华股份有限公司 | 3-(1-氧代-5-(哌啶-4-基)异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途 |
CN111620949A (zh) | 2019-02-28 | 2020-09-04 | 三生国健药业(上海)股份有限公司 | 结合人lag-3的抗体、其制备方法和用途 |
AU2020242284A1 (en) | 2019-03-19 | 2021-09-16 | Fundació Privada Institut D'investigació Oncològica De Vall Hebron | Combination therapy for the treatment of cancer |
US11793802B2 (en) | 2019-03-20 | 2023-10-24 | Sumitomo Pharma Oncology, Inc. | Treatment of acute myeloid leukemia (AML) with venetoclax failure |
US11712433B2 (en) | 2019-03-22 | 2023-08-01 | Sumitomo Pharma Oncology, Inc. | Compositions comprising PKM2 modulators and methods of treatment using the same |
SG11202110449YA (en) | 2019-03-26 | 2021-10-28 | Univ Michigan Regents | Small molecule degraders of stat3 |
WO2020205467A1 (en) | 2019-03-29 | 2020-10-08 | The Regents Of The University Of Michigan | Stat3 protein degraders |
US20220184222A1 (en) | 2019-04-02 | 2022-06-16 | Bicycletx Limited | Bicycle toxin conjugates and uses thereof |
WO2020206424A1 (en) | 2019-04-05 | 2020-10-08 | Kymera Therapeutics, Inc. | Stat degraders and uses thereof |
EP3725370A1 (en) | 2019-04-19 | 2020-10-21 | ImmunoBrain Checkpoint, Inc. | Modified anti-pd-l1 antibodies and methods and uses for treating a neurodegenerative disease |
WO2020231713A1 (en) | 2019-05-13 | 2020-11-19 | Bristol-Myers Squibb Company | AGONISTS OF ROR GAMMAt |
US20230295087A1 (en) | 2019-05-13 | 2023-09-21 | Bristol-Myers Squibb Company | AGONISTS OF ROR GAMMAt |
CN113825527A (zh) | 2019-05-13 | 2021-12-21 | 瑞泽恩制药公司 | 用于在治疗癌症中增强效力的pd-1抑制剂和lag-3抑制剂的组合 |
US20220233691A1 (en) | 2019-05-30 | 2022-07-28 | Bristol-Myers Squibb Company | Cell localization signature and combination therapy |
KR20220016155A (ko) | 2019-05-30 | 2022-02-08 | 브리스톨-마이어스 스큅 컴퍼니 | 면역-종양학 (i-o) 요법에 적합한 대상체를 확인하는 방법 |
EP3976831A1 (en) | 2019-05-30 | 2022-04-06 | Bristol-Myers Squibb Company | Multi-tumor gene signatures for suitability to immuno-oncology therapy |
CN114502540A (zh) | 2019-05-31 | 2022-05-13 | 医肯纳肿瘤学公司 | Tead抑制剂和其用途 |
CN114269715A (zh) | 2019-06-12 | 2022-04-01 | 范德比尔特大学 | 作为氨基酸转运抑制剂的二苄基胺 |
JP2022536419A (ja) | 2019-06-12 | 2022-08-16 | ヴァンダービルト ユニバーシティー | アミノ酸輸送阻害剤及びその使用 |
US20220251188A1 (en) * | 2019-06-24 | 2022-08-11 | Innovent Biologics (Suzhou) Co., Ltd. | Formulation comprising anti-lag-3 antibody, method for preparing same and use thereof |
EP3994132A1 (en) | 2019-07-03 | 2022-05-11 | Sumitomo Dainippon Pharma Oncology, Inc. | Tyrosine kinase non-receptor 1 (tnk1) inhibitors and uses thereof |
IT201900011676A1 (it) | 2019-07-12 | 2021-01-12 | St Superiore Di Sanita | Anticorpo ricombinante umano contro il recettore di membrana LAG3, suoi usi medici e diagnostici. |
EP3999510A1 (en) | 2019-07-16 | 2022-05-25 | The Regents Of The University Of Michigan | Imidazopyrimidines as eed inhibitors and the use thereof |
US20220306630A1 (en) | 2019-08-06 | 2022-09-29 | Bristol-Myers Squibb Company | AGONISTS OF ROR GAMMAt |
WO2021024020A1 (en) | 2019-08-06 | 2021-02-11 | Astellas Pharma Inc. | Combination therapy involving antibodies against claudin 18.2 and immune checkpoint inhibitors for treatment of cancer |
US20220388978A1 (en) | 2019-08-27 | 2022-12-08 | Regents Of The University Of Michigan | Cereblon e3 ligase inhibitors |
AR119821A1 (es) | 2019-08-28 | 2022-01-12 | Bristol Myers Squibb Co | Compuestos de piridopirimidinonilo sustituidos útiles como activadores de células t |
MX2022002877A (es) | 2019-09-13 | 2022-08-08 | Nimbus Saturn Inc | Antagonistas de cinasa progenitora hematopoyetica 1 (hpk1) y sus usos. |
JP2022548881A (ja) | 2019-09-18 | 2022-11-22 | ノバルティス アーゲー | Entpd2抗体、組合せ療法並びに抗体及び組合せ療法を使用する方法 |
EP4031575A1 (en) | 2019-09-19 | 2022-07-27 | Bristol-Myers Squibb Company | Antibodies binding to vista at acidic ph |
CA3155010A1 (en) | 2019-09-19 | 2021-03-25 | The Regents Of The Universtiy Of Michigan | Spirocyclic androgen receptor protein degraders |
JP2022549273A (ja) | 2019-09-22 | 2022-11-24 | ブリストル-マイヤーズ スクイブ カンパニー | Lag-3アンタゴニスト治療のための定量的空間プロファイリング |
US11667613B2 (en) | 2019-09-26 | 2023-06-06 | Novartis Ag | Antiviral pyrazolopyridinone compounds |
AU2020358979A1 (en) | 2019-10-03 | 2022-04-21 | Xencor, Inc. | Targeted IL-12 heterodimeric Fc-fusion proteins |
US20220356248A1 (en) * | 2019-10-09 | 2022-11-10 | Stcube & Co | Antibodies specific to glycosylated lag3 and methods of use thereof |
TW202128757A (zh) | 2019-10-11 | 2021-08-01 | 美商建南德克公司 | 具有改善之特性的 PD-1 標靶 IL-15/IL-15Rα FC 融合蛋白 |
MX2022004766A (es) | 2019-10-21 | 2022-05-16 | Novartis Ag | Terapias combinadas con venetoclax e inhibidores de tim-3. |
JP2022553306A (ja) | 2019-10-21 | 2022-12-22 | ノバルティス アーゲー | Tim-3阻害剤およびその使用 |
EP4054591A1 (en) | 2019-11-04 | 2022-09-14 | Astrazeneca AB | Combination therapy for treating cancer |
US20220411499A1 (en) | 2019-11-08 | 2022-12-29 | Bristol-Myers Squibb Company | LAG-3 Antagonist Therapy for Melanoma |
JP2023503052A (ja) | 2019-11-19 | 2023-01-26 | ブリストル-マイヤーズ スクイブ カンパニー | Heliosタンパク質の阻害剤として有用な化合物 |
CN115279764A (zh) | 2019-11-26 | 2022-11-01 | 医肯纳肿瘤学公司 | 多晶型咔唑衍生物及其用途 |
AU2020393854A1 (en) | 2019-11-26 | 2022-06-09 | Bristol-Myers Squibb Company | Salts/cocrystals of (R)-N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide |
TW202136251A (zh) | 2019-12-17 | 2021-10-01 | 美商凱麥拉醫療公司 | Irak降解劑及其用途 |
EP4076524A4 (en) | 2019-12-17 | 2023-11-29 | Kymera Therapeutics, Inc. | IRAQ DEGRADERS AND USES THEREOF |
CA3165399A1 (en) | 2019-12-20 | 2021-06-24 | Novartis Ag | Uses of anti-tgf-beta antibodies and checkpoint inhibitors for the treatment of proliferative diseases |
AR120823A1 (es) | 2019-12-23 | 2022-03-23 | Bristol Myers Squibb Co | Compuestos bicíclicos sustituidos útiles como activadores de células t |
CA3162992A1 (en) | 2019-12-23 | 2021-07-01 | Louis S. Chupak | Substituted quinolinonyl piperazine compounds useful as t cell activators |
KR20220120624A (ko) | 2019-12-23 | 2022-08-30 | 브리스톨-마이어스 스큅 컴퍼니 | T 세포 활성화제로서 유용한 치환된 피페라진 유도체 |
BR112022012410A2 (pt) | 2019-12-23 | 2022-08-30 | Kymera Therapeutics Inc | Degradadores smarca e usos dos mesmos |
JP2023508054A (ja) | 2019-12-23 | 2023-02-28 | ブリストル-マイヤーズ スクイブ カンパニー | T細胞アクティベーターとして有用な置換ヘテロアリール化合物 |
WO2021133751A1 (en) | 2019-12-23 | 2021-07-01 | Bristol-Myers Squibb Company | Substituted quinazolinyl compounds useful as t cell activators |
EP4084821A4 (en) | 2020-01-03 | 2024-04-24 | Marengo Therapeutics, Inc. | CD33-BINDING MULTIFUNCTIONAL MOLECULES AND THEIR USES |
WO2021141907A1 (en) | 2020-01-06 | 2021-07-15 | Hifibio (Hong Kong) Limited | Anti-tnfr2 antibody and uses thereof |
IL294466A (en) | 2020-01-07 | 2022-09-01 | Hifibio Hk Ltd | Anti-galectin-9 antibody and uses thereof |
JP2023510918A (ja) | 2020-01-15 | 2023-03-15 | ブループリント メディシンズ コーポレイション | Map4k1阻害剤 |
MX2022008763A (es) | 2020-01-17 | 2022-07-27 | Novartis Ag | Combinacion que comprende un inhibidor de tim-3 y un agente hipometilante para usarse en el tratamiento del sindrome mielodisplasico o leucemia mielomonocitica cronica. |
CN111205371B (zh) * | 2020-01-22 | 2022-03-29 | 北京吉尔麦迪生物医药科技有限公司 | 一种抗淋巴细胞激活基因3的抗体及应用 |
WO2021171264A1 (en) | 2020-02-28 | 2021-09-02 | Novartis Ag | Dosing of a bispecific antibody that binds cd123 and cd3 |
EP4114529A1 (en) | 2020-03-03 | 2023-01-11 | PIC Therapeutics, Inc. | Eif4e inhibitors and uses thereof |
JP2023516459A (ja) | 2020-03-09 | 2023-04-19 | ブリストル-マイヤーズ スクイブ カンパニー | 増強されたアゴニスト活性を有するcd40に対する抗体 |
MX2022011534A (es) | 2020-03-19 | 2022-10-13 | Arcus Biosciences Inc | Compuestos de tetralina y tetrahidroquinolina como inhibidores de hif-2alfa. |
IL296451A (en) | 2020-03-19 | 2022-11-01 | Kymera Therapeutics Inc | mdm2 joints and their uses |
TW202140441A (zh) | 2020-03-23 | 2021-11-01 | 美商必治妥美雅史谷比公司 | 經取代之側氧基異吲哚啉化合物 |
WO2021195481A1 (en) | 2020-03-26 | 2021-09-30 | The Regents Of The University Of Michigan | Small molecule stat protein degraders |
WO2021207449A1 (en) | 2020-04-09 | 2021-10-14 | Merck Sharp & Dohme Corp. | Affinity matured anti-lap antibodies and uses thereof |
WO2021231732A1 (en) | 2020-05-15 | 2021-11-18 | Bristol-Myers Squibb Company | Antibodies to garp |
PE20231078A1 (es) | 2020-06-02 | 2023-07-17 | Arcus Biosciences Inc | Anticuerpos anti-tigit |
TW202210483A (zh) | 2020-06-03 | 2022-03-16 | 美商凱麥拉醫療公司 | Irak降解劑之結晶型 |
AR122644A1 (es) | 2020-06-19 | 2022-09-28 | Onxeo | Nuevas moléculas de ácido nucleico conjugado y sus usos |
WO2021258010A1 (en) | 2020-06-19 | 2021-12-23 | Gossamer Bio Services, Inc. | Oxime compounds useful as t cell activators |
CA3182346A1 (en) | 2020-06-23 | 2021-12-30 | Novartis Ag | Dosing regimen comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives |
CN116234568A (zh) | 2020-07-07 | 2023-06-06 | 生物技术公司 | 用于hpv阳性癌症的治疗性rna |
US20230257365A1 (en) | 2020-07-10 | 2023-08-17 | The Regents Of The University Of Michigan | Small molecule androgen receptor protein degraders |
WO2022011205A1 (en) | 2020-07-10 | 2022-01-13 | The Regents Of The University Of Michigan | Androgen receptor protein degraders |
KR20230044480A (ko) | 2020-07-30 | 2023-04-04 | 카이메라 쎄라퓨틱스 인코포레이티드 | 돌연변이 림프종의 치료 방법 |
US20230271940A1 (en) | 2020-08-03 | 2023-08-31 | Novartis Ag | Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
AU2021325225A1 (en) | 2020-08-10 | 2023-03-23 | Gv20 Therapeutics Llc | Compositions and methods for treating autoimmune diseases and cancers by targeting IGSF8 |
WO2022036079A1 (en) | 2020-08-13 | 2022-02-17 | Bristol-Myers Squibb Company | Methods of redirecting of il-2 to target cells of interest |
AU2021327130A1 (en) | 2020-08-17 | 2023-03-02 | Bicycletx Limited | Bicycle conjugates specific for Nectin-4 and uses thereof |
AU2021333779A1 (en) | 2020-08-26 | 2023-04-13 | Marengo Therapeutics, Inc. | Methods of detecting TRBC1 or TRBC2 |
WO2022047189A1 (en) | 2020-08-28 | 2022-03-03 | Bristol-Myers Squibb Company | Lag-3 antagonist therapy for hepatocellular carcinoma |
EP4204021A1 (en) | 2020-08-31 | 2023-07-05 | Advanced Accelerator Applications International S.A. | Method of treating psma-expressing cancers |
US20230338587A1 (en) | 2020-08-31 | 2023-10-26 | Advanced Accelerator Applications International Sa | Method of treating psma-expressing cancers |
JP2023538955A (ja) | 2020-08-31 | 2023-09-12 | ブリストル-マイヤーズ スクイブ カンパニー | 細胞局在シグネチャーおよび免疫療法 |
WO2022081718A1 (en) | 2020-10-14 | 2022-04-21 | Five Prime Therapeutics, Inc. | Anti-c-c chemokine receptor 8 (ccr8) antibodies and methods of use thereof |
WO2022087402A1 (en) | 2020-10-23 | 2022-04-28 | Bristol-Myers Squibb Company | Lag-3 antagonist therapy for lung cancer |
EP4240491A1 (en) | 2020-11-06 | 2023-09-13 | Novartis AG | Cd19 binding molecules and uses thereof |
US20240018248A1 (en) | 2020-12-02 | 2024-01-18 | Vib Vzw | An ltbr agonist in combination therapy against cancer |
IL303376A (en) | 2020-12-02 | 2023-08-01 | Ikena Oncology Inc | TEAD inhibitors and their uses |
WO2022120353A1 (en) | 2020-12-02 | 2022-06-09 | Ikena Oncology, Inc. | Tead inhibitors and uses thereof |
WO2022120179A1 (en) | 2020-12-03 | 2022-06-09 | Bristol-Myers Squibb Company | Multi-tumor gene signatures and uses thereof |
WO2022125497A1 (en) | 2020-12-08 | 2022-06-16 | Infinity Pharmaceuticals, Inc. | Eganelisib for use in the treatment of pd-l1 negative cancer |
CN114621344B (zh) * | 2020-12-10 | 2022-08-30 | 北京东方百泰生物科技股份有限公司 | 一种抗lag-3单克隆抗体的纯化方法 |
TW202237119A (zh) | 2020-12-10 | 2022-10-01 | 美商住友製藥腫瘤公司 | Alk﹘5抑制劑和彼之用途 |
WO2022133083A1 (en) | 2020-12-16 | 2022-06-23 | Gossamer Bio Services, Inc. | Compounds useful as t cell activators |
WO2022135667A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Therapeutic rna for treating cancer |
TW202245808A (zh) | 2020-12-21 | 2022-12-01 | 德商拜恩迪克公司 | 用於治療癌症之治療性rna |
WO2022135666A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Treatment schedule for cytokine proteins |
US20220233689A1 (en) | 2020-12-28 | 2022-07-28 | Bristol-Myers Squibb Company | Methods of treating tumors |
JP2024503265A (ja) | 2020-12-28 | 2024-01-25 | ブリストル-マイヤーズ スクイブ カンパニー | 抗体組成物およびその使用の方法 |
EP4274597A1 (en) | 2021-01-11 | 2023-11-15 | BicycleTX Limited | Methods for treating cancer |
EP4284919A1 (en) | 2021-01-29 | 2023-12-06 | Iovance Biotherapeutics, Inc. | Methods of making modified tumor infiltrating lymphocytes and their use in adoptive cell therapy |
BR112023015590A2 (pt) | 2021-02-02 | 2023-10-17 | Liminal Biosciences Ltd | Antagonistas de gpr84 e usos dos mesmos |
MX2023009059A (es) | 2021-02-02 | 2023-09-15 | Liminal Biosciences Ltd | Antagonistas de gpr84 y usos de estos. |
US20240109899A1 (en) | 2021-02-04 | 2024-04-04 | Bristol-Myers Squibb Company | Benzofuran compounds as sting agonists |
PE20231505A1 (es) | 2021-02-12 | 2023-09-26 | Hoffmann La Roche | Derivados de tetrahidroazepina biciclicos para el tratamiento del cancer |
CA3207380A1 (en) | 2021-02-15 | 2022-08-18 | Haojing RONG | Irak4 degraders and uses thereof |
WO2022187423A1 (en) | 2021-03-03 | 2022-09-09 | The Regents Of The University Of Michigan | Cereblon ligands |
US20240190874A1 (en) | 2021-03-03 | 2024-06-13 | The Regents Of The University Of Michigan | Small molecule degraders of androgen receptor |
US11926625B2 (en) | 2021-03-05 | 2024-03-12 | Nimbus Saturn, Inc. | HPK1 antagonists and uses thereof |
WO2022192145A1 (en) | 2021-03-08 | 2022-09-15 | Blueprint Medicines Corporation | Map4k1 inhibitors |
US11918582B2 (en) | 2021-03-15 | 2024-03-05 | Rapt Therapeutics, Inc. | Pyrazole pyrimidine compounds and uses thereof |
BR112023019847A2 (pt) | 2021-03-29 | 2023-11-07 | Juno Therapeutics Inc | Métodos para dosagem e tratamento com uma combinação de uma terapia com inibidor de ponto de verificação e uma terapia com célula t car |
JP2024514530A (ja) | 2021-04-02 | 2024-04-02 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 切断型cdcp1に対する抗体およびその使用 |
KR20230167067A (ko) | 2021-04-05 | 2023-12-07 | 브리스톨-마이어스 스큅 컴퍼니 | 암의 치료를 위한 피리디닐 치환된 옥소이소인돌린 화합물 |
WO2022216644A1 (en) | 2021-04-06 | 2022-10-13 | Bristol-Myers Squibb Company | Pyridinyl substituted oxoisoindoline compounds |
TW202304979A (zh) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | 抗TGFβ抗體及其他治療劑用於治療增殖性疾病之用途 |
BR112023020832A2 (pt) | 2021-04-08 | 2023-12-19 | Marengo Therapeutics Inc | Moléculas multifuncionais ligadas a tcr e seus usos |
CA3213079A1 (en) | 2021-04-13 | 2022-10-20 | Kristin Lynne ANDREWS | Amino-substituted heterocycles for treating cancers with egfr mutations |
KR20230172548A (ko) | 2021-04-16 | 2023-12-22 | 이케나 온콜로지, 인코포레이티드 | Mek 억제제 및 이의 용도 |
WO2022240741A1 (en) | 2021-05-12 | 2022-11-17 | Dana-Farber Cancer Institute, Inc. | Lag3 and gal3 inhibitory agents, xbp1, cs1, and cd138 peptides, and methods of use thereof |
AR125874A1 (es) | 2021-05-18 | 2023-08-23 | Novartis Ag | Terapias de combinación |
WO2022246179A1 (en) | 2021-05-21 | 2022-11-24 | Arcus Biosciences, Inc. | Axl inhibitor compounds |
JP2024521706A (ja) | 2021-05-21 | 2024-06-04 | アーカス バイオサイエンシーズ,インコーポレーテッド | Axl化合物 |
IL309831A (en) | 2021-07-13 | 2024-02-01 | BioNTech SE | Multispecific binding agents against CD40 and CD137 in combined cancer therapy |
CN117940438A (zh) | 2021-07-14 | 2024-04-26 | 缆图药品公司 | 作为map4k1抑制剂的杂环化合物 |
WO2023288264A1 (en) | 2021-07-15 | 2023-01-19 | Blueprint Medicines Corporation | Map4k1 inhibitors |
WO2023028238A1 (en) | 2021-08-25 | 2023-03-02 | PIC Therapeutics, Inc. | Eif4e inhibitors and uses thereof |
CN118103368A (zh) | 2021-08-25 | 2024-05-28 | 皮克医疗公司 | Eif4e抑制剂及其用途 |
AU2022341239A1 (en) | 2021-09-08 | 2024-03-21 | Redona Therapeutics, Inc. | Papd5 and/or papd7 inhibiting 4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives |
CN115873116A (zh) * | 2021-09-29 | 2023-03-31 | 中山康方生物医药有限公司 | 抗lag3抗体、药物组合物及用途 |
TW202333802A (zh) | 2021-10-11 | 2023-09-01 | 德商拜恩迪克公司 | 用於肺癌之治療性rna(二) |
US20230159466A1 (en) | 2021-10-29 | 2023-05-25 | Arcus Biosciences, Inc. | Inhibitors of hif-2alpha and methods of use thereof |
CN118176214A (zh) | 2021-10-29 | 2024-06-11 | 百时美施贵宝公司 | 血液癌症的lag-3拮抗剂疗法 |
AU2022409713A1 (en) | 2021-12-16 | 2024-06-20 | Valerio Therapeutics | New conjugated nucleic acid molecules and their uses |
WO2023114984A1 (en) | 2021-12-17 | 2023-06-22 | Ikena Oncology, Inc. | Tead inhibitors and uses thereof |
WO2023122772A1 (en) | 2021-12-22 | 2023-06-29 | Gossamer Bio Services, Inc. | Oxime derivatives useful as t cell activators |
WO2023122778A1 (en) | 2021-12-22 | 2023-06-29 | Gossamer Bio Services, Inc. | Pyridazinone derivatives useful as t cell activators |
WO2023122777A1 (en) | 2021-12-22 | 2023-06-29 | Gossamer Bio Services, Inc. | Oxime derivatives useful as t cell activators |
WO2023147371A1 (en) | 2022-01-26 | 2023-08-03 | Bristol-Myers Squibb Company | Combination therapy for hepatocellular carcinoma |
WO2023147488A1 (en) | 2022-01-28 | 2023-08-03 | Iovance Biotherapeutics, Inc. | Cytokine associated tumor infiltrating lymphocytes compositions and methods |
WO2023150186A1 (en) | 2022-02-01 | 2023-08-10 | Arvinas Operations, Inc. | Dgk targeting compounds and uses thereof |
TW202342474A (zh) | 2022-02-14 | 2023-11-01 | 美商基利科學股份有限公司 | 抗病毒吡唑并吡啶酮化合物 |
WO2023164638A1 (en) | 2022-02-25 | 2023-08-31 | Bristol-Myers Squibb Company | Combination therapy for colorectal carcinoma |
WO2023173053A1 (en) | 2022-03-10 | 2023-09-14 | Ikena Oncology, Inc. | Mek inhibitors and uses thereof |
WO2023173057A1 (en) | 2022-03-10 | 2023-09-14 | Ikena Oncology, Inc. | Mek inhibitors and uses thereof |
WO2023178192A1 (en) | 2022-03-15 | 2023-09-21 | Compugen Ltd. | Il-18bp antagonist antibodies and their use in monotherapy and combination therapy in the treatment of cancer |
WO2023178329A1 (en) | 2022-03-18 | 2023-09-21 | Bristol-Myers Squibb Company | Methods of isolating polypeptides |
WO2023211889A1 (en) | 2022-04-25 | 2023-11-02 | Ikena Oncology, Inc. | Polymorphic compounds and uses thereof |
WO2023214325A1 (en) | 2022-05-05 | 2023-11-09 | Novartis Ag | Pyrazolopyrimidine derivatives and uses thereof as tet2 inhibitors |
CN114874324B (zh) * | 2022-05-13 | 2023-02-03 | 苏州旭光科星抗体生物科技有限公司 | 一种检测可溶性lag-3蛋白含量的酶联免疫检测试剂盒及应用 |
TW202404581A (zh) | 2022-05-25 | 2024-02-01 | 美商醫肯納腫瘤學公司 | Mek抑制劑及其用途 |
WO2023235847A1 (en) | 2022-06-02 | 2023-12-07 | Bristol-Myers Squibb Company | Antibody compositions and methods of use thereof |
WO2024015251A1 (en) | 2022-07-15 | 2024-01-18 | Arcus Biosciences, Inc. | Inhibitors of hpk1 and methods of use thereof |
WO2024020034A1 (en) | 2022-07-20 | 2024-01-25 | Arcus Biosciences, Inc. | Cbl-b inhibitors and methods of use thereof |
WO2024028363A1 (en) | 2022-08-02 | 2024-02-08 | Liminal Biosciences Limited | Heteroaryl carboxamide and related gpr84 antagonists and uses thereof |
WO2024028365A1 (en) | 2022-08-02 | 2024-02-08 | Liminal Biosciences Limited | Substituted pyridone gpr84 antagonists and uses thereof |
TW202415650A (zh) | 2022-08-02 | 2024-04-16 | 英商利米那生物科技有限公司 | 芳基-三唑基及相關gpr84拮抗劑及其用途 |
WO2024036100A1 (en) | 2022-08-08 | 2024-02-15 | Bristol-Myers Squibb Company | Substituted tetrazolyl compounds useful as t cell activators |
WO2024036101A1 (en) | 2022-08-09 | 2024-02-15 | Bristol-Myers Squibb Company | Tertiary amine substituted bicyclic compounds useful as t cell activators |
WO2024033457A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024033389A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024033458A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydroazepine derivatives |
WO2024033388A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024059142A1 (en) | 2022-09-14 | 2024-03-21 | Arcus Biosciences, Inc. | Dispersions of etrumadenant |
WO2024081385A1 (en) | 2022-10-14 | 2024-04-18 | Arcus Biosciences, Inc. | Hpk1 inhibitors and methods of use thereof |
WO2024086718A1 (en) | 2022-10-20 | 2024-04-25 | Arcus Biosciences, Inc. | Lyophilized formulations of cd73 compounds |
WO2024089417A1 (en) | 2022-10-24 | 2024-05-02 | Memorial Sloan-Kettering Cancer Center | Tumour stratification for responsiveness to an immune checkpoint inhibitor |
WO2024089418A1 (en) | 2022-10-24 | 2024-05-02 | Cancer Research Technology Limited | Tumour sensitisation to checkpoint inhibitors with redox status modifier |
US20240208961A1 (en) | 2022-11-22 | 2024-06-27 | PIC Therapeutics, Inc. | Eif4e inhibitors and uses thereof |
WO2024126457A1 (en) | 2022-12-14 | 2024-06-20 | Astellas Pharma Europe Bv | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and immune checkpoint inhibitors |
WO2024137776A1 (en) | 2022-12-21 | 2024-06-27 | Bristol-Myers Squibb Company | Combination therapy for lung cancer |
WO2024137865A1 (en) | 2022-12-22 | 2024-06-27 | Gossamer Bio Services, Inc. | Compounds useful as t cell activators |
CN115819595B (zh) * | 2023-01-03 | 2023-05-16 | 上海百英生物科技股份有限公司 | 一种抗lag3纳米抗体及其制备方法与应用 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001523958A (ja) * | 1997-03-21 | 2001-11-27 | ブライハム アンド ウィミンズ ホスピタル,インコーポレイテッド | 免疫療法のctla−4結合ペプチド |
JP2006340714A (ja) * | 2005-05-09 | 2006-12-21 | Ono Pharmaceut Co Ltd | ProgrammedDeath1(PD−1)に対するヒトモノクローナル抗体および抗PD−1抗体単独または他の免疫療法と併用した癌治療方法 |
JP2011097943A (ja) * | 2003-12-10 | 2011-05-19 | Medarex Inc | インターフェロンα抗体及びその使用 |
JP2012500006A (ja) * | 2008-08-11 | 2012-01-05 | メダレックス インコーポレーティッド | リンパ球活性化遺伝子−3(lag−3)へ結合するヒト抗体およびその使用 |
WO2012009442A2 (en) * | 2010-07-14 | 2012-01-19 | Merck Sharp & Dohme Corp. | Anti-addl monoclonal antibody and uses thereof |
Family Cites Families (155)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1081681A (en) | 1910-08-31 | 1913-12-16 | Otis Elevator Co | Alternating-current-motor control. |
US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US5179017A (en) | 1980-02-25 | 1993-01-12 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US4634665A (en) | 1980-02-25 | 1987-01-06 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US4475196A (en) | 1981-03-06 | 1984-10-02 | Zor Clair G | Instrument for locating faults in aircraft passenger reading light and attendant call control system |
US4447233A (en) | 1981-04-10 | 1984-05-08 | Parker-Hannifin Corporation | Medication infusion pump |
US4439196A (en) | 1982-03-18 | 1984-03-27 | Merck & Co., Inc. | Osmotic drug delivery system |
US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
US4447224A (en) | 1982-09-20 | 1984-05-08 | Infusaid Corporation | Variable flow implantable infusion apparatus |
US4487603A (en) | 1982-11-26 | 1984-12-11 | Cordis Corporation | Implantable microinfusion pump system |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4486194A (en) | 1983-06-08 | 1984-12-04 | James Ferrara | Therapeutic device for administering medicaments through the skin |
EP0154316B1 (en) | 1984-03-06 | 1989-09-13 | Takeda Chemical Industries, Ltd. | Chemically modified lymphokine and production thereof |
US4596556A (en) | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
US5374548A (en) | 1986-05-02 | 1994-12-20 | Genentech, Inc. | Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor |
MX9203291A (es) | 1985-06-26 | 1992-08-01 | Liposome Co Inc | Metodo para acoplamiento de liposomas. |
GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
WO1988007089A1 (en) | 1987-03-18 | 1988-09-22 | Medical Research Council | Altered antibodies |
US4790824A (en) | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
US4941880A (en) | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
GB8717430D0 (en) | 1987-07-23 | 1987-08-26 | Celltech Ltd | Recombinant dna product |
US5677425A (en) | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
GB8809129D0 (en) | 1988-04-18 | 1988-05-18 | Celltech Ltd | Recombinant dna methods vectors and host cells |
US5476996A (en) | 1988-06-14 | 1995-12-19 | Lidak Pharmaceuticals | Human immune system in non-human animal |
US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
CA2006596C (en) | 1988-12-22 | 2000-09-05 | Rika Ishikawa | Chemically-modified g-csf |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5108921A (en) | 1989-04-03 | 1992-04-28 | Purdue Research Foundation | Method for enhanced transmembrane transport of exogenous molecules |
US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
US5312335A (en) | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
US5976877A (en) | 1990-01-08 | 1999-11-02 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Proteins produced by human lymphocytes DNA sequence encoding these proteins and their pharmaceutical and biological uses |
FR2656800B1 (fr) | 1990-01-08 | 1992-05-15 | Roussy Inst Gustave | Nouvelles proteines produits par les lymphocytes humains, sequence d'adn codant pour ces proteines et applications pharmaceutiques et biologiques. |
US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
US6172197B1 (en) | 1991-07-10 | 2001-01-09 | Medical Research Council | Methods for producing members of specific binding pairs |
US6255458B1 (en) | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
KR100272077B1 (ko) | 1990-08-29 | 2000-11-15 | 젠팜인터내셔날,인코포레이티드 | 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물 |
US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic 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 |
US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
GB9108652D0 (en) | 1991-04-23 | 1991-06-12 | Antisoma Ltd | Immunoreactive compounds |
ES2341666T3 (es) | 1991-12-02 | 2010-06-24 | Medimmune Limited | Produccion de autoanticuerpos de repertorios de segmentos de anticue rpos expresados en la superficie de fagos. |
CA2124967C (en) | 1991-12-17 | 2008-04-08 | Nils Lonberg | Transgenic non-human animals capable of producing heterologous antibodies |
US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
EP0640094A1 (en) | 1992-04-24 | 1995-03-01 | The Board Of Regents, The University Of Texas System | Recombinant production of immunoglobulin-like domains in prokaryotic cells |
US5383851A (en) | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
DK0671927T3 (da) | 1992-09-16 | 2003-04-22 | Us Gov Health & Human Serv | Neutraliserende humane monoklonale antistoffer mod respiratorisk syncytialvirus |
JP3919830B2 (ja) | 1992-11-28 | 2007-05-30 | 財団法人化学及血清療法研究所 | 抗ネコヘルペスウイルス−1組換え抗体および該抗体をコードする遺伝子断片 |
EP0754225A4 (en) | 1993-04-26 | 2001-01-31 | Genpharm Int | HETEROLOGIC ANTIBODY-PRODUCING TRANSGENIC NON-HUMAN ANIMALS |
AU691811B2 (en) | 1993-06-16 | 1998-05-28 | Celltech Therapeutics Limited | Antibodies |
AU1866895A (en) | 1994-01-04 | 1995-08-01 | Scripps Research Institute, The | Human monoclonal antibodies to herpes simplex virus and methods therefor |
ATE352617T1 (de) | 1994-05-06 | 2007-02-15 | Roussy Inst Gustave | Lösliche polypeptidfraktionen des lag-3-proteins; verfahren zur herstellung; therapeutische zusamensetzung; antiidiotypischer antikörper |
US6121022A (en) | 1995-04-14 | 2000-09-19 | Genentech, Inc. | Altered polypeptides with increased half-life |
US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
US6410690B1 (en) | 1995-06-07 | 2002-06-25 | Medarex, Inc. | Therapeutic compounds comprised of anti-Fc receptor antibodies |
AU701375B2 (en) | 1995-07-21 | 1999-01-28 | Institut Gustave Roussy | Methods for detecting, identifying, isolating, and selectively labelling and targeting Th1 lymphocytes by means of the LAG-3 protein |
US5811097A (en) | 1995-07-25 | 1998-09-22 | The Regents Of The University Of California | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling |
US6090382A (en) | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
AU2071597A (en) | 1996-03-07 | 1997-09-22 | Eastman Chemical Company | Near infrared fluorescent security thermal transfer printing and marking ribbons |
US5922845A (en) | 1996-07-11 | 1999-07-13 | Medarex, Inc. | Therapeutic multispecific compounds comprised of anti-Fcα receptor antibodies |
WO1998023741A1 (fr) | 1996-11-28 | 1998-06-04 | Institut Gustave Roussy | Mutants de la proteine lag-3, leur expression et utilisation |
EA003772B1 (ru) | 1996-11-29 | 2003-08-28 | Апплайд Резеч Системз Арс Холдинг Н.В. | Средство для обеспечения защиты трансплантата от отторжения иммунной системой хозяина на основе штамма генетически сконструированных эукариотических клеток, содержащих днк, кодирующую трансмембранный белок lag-3 |
US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
JP2002512624A (ja) | 1997-05-21 | 2002-04-23 | バイオベーション リミテッド | 非免疫原性タンパク質の製造方法 |
EP0900841A1 (en) | 1997-06-18 | 1999-03-10 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | LAG-3 splice variants |
US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
ATE458007T1 (de) | 1998-04-20 | 2010-03-15 | Glycart Biotechnology Ag | Glykosylierungs-engineering von antikörpern zur verbesserung der antikörperabhängigen zellvermittelten zytotoxizität |
GB9814383D0 (en) | 1998-07-02 | 1998-09-02 | Cambridge Antibody Tech | Improvements relating to antibodies |
US6951646B1 (en) | 1998-07-21 | 2005-10-04 | Genmab A/S | Anti hepatitis C virus antibody and uses thereof |
EA006972B1 (ru) | 1998-12-23 | 2006-06-30 | Пфайзер Инк. | Моноклональное антитело человека к ctla-4 и способы его применения |
ES2694002T3 (es) | 1999-01-15 | 2018-12-17 | Genentech, Inc. | Polipéptido que comprende una región Fc de IgG1 humana variante |
US6914128B1 (en) | 1999-03-25 | 2005-07-05 | Abbott Gmbh & Co. Kg | Human antibodies that bind human IL-12 and methods for producing |
CA2704600C (en) | 1999-04-09 | 2016-10-25 | Kyowa Hakko Kirin Co., Ltd. | A method for producing antibodies with increased adcc activity |
GB9911569D0 (en) | 1999-05-18 | 1999-07-21 | Oxford Biomedica Ltd | Antibodies |
JP4896327B2 (ja) | 1999-08-23 | 2012-03-14 | ダナ−ファーバー キャンサー インスティテュート,インコーポレイテッド | Pd−1、b7−4の受容体、およびその使用 |
US7605238B2 (en) | 1999-08-24 | 2009-10-20 | Medarex, Inc. | Human CTLA-4 antibodies and their uses |
EP1792991A1 (en) | 1999-08-24 | 2007-06-06 | Medarex, Inc. | Human CTLA-4 antibodies and their uses |
US6794132B2 (en) | 1999-10-02 | 2004-09-21 | Biosite, Inc. | Human antibodies |
EP2281843B1 (en) | 2000-06-16 | 2016-10-12 | Human Genome Sciences, Inc. | Antibodies that immunospecifically bind to BLyS |
US6818216B2 (en) | 2000-11-28 | 2004-11-16 | Medimmune, Inc. | Anti-RSV antibodies |
US7041870B2 (en) | 2000-11-30 | 2006-05-09 | Medarex, Inc. | Transgenic transchromosomal rodents for making human antibodies |
CN1277843C (zh) | 2001-02-22 | 2006-10-04 | 巴斯德研究院 | 分枝杆菌比较基因组学作为鉴定分枝杆菌病的诊断、预防或治疗靶的工具 |
US20020146753A1 (en) | 2001-04-06 | 2002-10-10 | Henrik Ditzel | Autoantibodies to glucose-6-phosphate isomerase and their participation in autoimmune disease |
CN100448992C (zh) | 2001-05-11 | 2009-01-07 | 麒麟医药株式会社 | 含人抗体λ轻链基因的人类人工染色体 |
MXPA03011094A (es) | 2001-05-31 | 2004-12-06 | Medarex Inc | Citotoxinas, profarmacos, ligadores, y estabilizadores utiles para ello. |
EP1295895B1 (en) | 2001-09-19 | 2011-08-10 | Institut Gustave Roussy | Peptides and proteins binding to glu-pro motifs, therapeutical compositions containing the same and applications thereof |
DE60234369D1 (de) | 2001-09-19 | 2009-12-24 | Alexion Pharma Inc | Manipulierte matrizen und ihre verwendung bei der single-primer-amplifikation |
HUP0600342A3 (en) | 2001-10-25 | 2011-03-28 | Genentech Inc | Glycoprotein compositions |
WO2003072035A2 (en) | 2002-02-22 | 2003-09-04 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
BR0309145A (pt) | 2002-04-09 | 2005-02-01 | Kyowa Hakko Kogyo Kk | Células das quais o genoma é modificado |
CA2481507A1 (en) | 2002-04-16 | 2003-10-30 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
ES2654064T3 (es) | 2002-07-03 | 2024-03-13 | Ono Pharmaceutical Co | Composiciones inmunopotenciadoras que comprenden anticuerpos anti-PD-L1 |
EP2322203A3 (en) | 2002-10-29 | 2011-07-27 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
WO2005035732A2 (en) | 2003-02-19 | 2005-04-21 | Dyax Corporation | Papp-a ligands |
SI1897548T1 (sl) | 2003-02-28 | 2013-12-31 | The Johns Hopkins University | Regulacija celic T |
CA2541360A1 (en) | 2003-10-08 | 2005-04-21 | Bradley T. Messmer | Methods and compositions for diagnosis and treatment of b cell chronic lymphocytic leukemia |
ES2403055T3 (es) | 2004-04-13 | 2013-05-13 | F. Hoffmann-La Roche Ag | Anticuerpos anti-P-selectina |
WO2005103081A2 (en) | 2004-04-20 | 2005-11-03 | Genmab A/S | Human monoclonal antibodies against cd20 |
RU2402548C2 (ru) | 2004-05-19 | 2010-10-27 | Медарекс, Инк. | Химические линкеры и их конъюгаты |
AU2005244980B2 (en) | 2004-05-19 | 2011-09-15 | E. R. Squibb & Sons, L.L.C. | Chemical linkers and conjugates thereof |
CA2574062A1 (en) | 2004-07-20 | 2006-01-26 | Symphogen A/S | Anti-rhesus d recombinant polyclonal antibody and methods of manufacture |
WO2006017538A2 (en) | 2004-08-03 | 2006-02-16 | Dyax Corp. | Hk1-binding proteins |
WO2006029219A2 (en) | 2004-09-08 | 2006-03-16 | Ohio State University Research Foundation | Human monoclonal anti-ctla4 antibodies in cancer treatment |
KR20070083899A (ko) | 2004-10-01 | 2007-08-24 | 메다렉스, 인코포레이티드 | Cd30 양성 림프종의 치료 방법 |
AU2005295038B2 (en) | 2004-10-06 | 2012-05-17 | Mayo Foundation For Medical Education And Research | B7-H1 and methods of diagnosis, prognosis, and treatment of cancer |
EP1851251A2 (en) | 2005-02-18 | 2007-11-07 | Medarex, Inc. | Monoclonal antibodies against prostate specific membrane antigen (psma) lacking in fucosyl residues |
AU2006227879A1 (en) | 2005-03-23 | 2006-09-28 | Pfizer Products Inc. | Therapy of prostate cancer with CTLA4 antibodies and hormonal therapy |
US7714016B2 (en) | 2005-04-08 | 2010-05-11 | Medarex, Inc. | Cytotoxic compounds and conjugates with cleavable substrates |
KR101411165B1 (ko) | 2005-07-01 | 2014-06-25 | 메다렉스, 엘.엘.시. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날항체 |
JP5290756B2 (ja) | 2005-09-26 | 2013-09-18 | メダレックス インコーポレイテッド | 抗体−薬剤コンジュゲート及びその使用 |
US7847105B2 (en) | 2005-10-26 | 2010-12-07 | Medarex, Inc. | Methods and compounds for preparing CC-1065 analogs |
EP2465870A1 (en) | 2005-11-07 | 2012-06-20 | Genentech, Inc. | Binding polypeptides with diversified and consensus VH/VL hypervariable sequences |
WO2007059404A2 (en) | 2005-11-10 | 2007-05-24 | Medarex, Inc. | Duocarmycin derivatives as novel cytotoxic compounds and conjugates |
JP2009518320A (ja) | 2005-12-05 | 2009-05-07 | シュムフォウエン アクティーゼルスカブ | 抗オルトポックスウイルス組換えポリクローナル抗体 |
EP2078732B1 (en) | 2006-07-10 | 2015-09-16 | Fujita Health University | Method of identifying a candidate diagnostic or therapeutic antibody using flow cytometry |
WO2008073160A2 (en) | 2006-08-17 | 2008-06-19 | The Trustees Of Columbia University In The City Of New York | Methods for converting or inducing protective immunity |
EP2059535B1 (en) | 2006-08-18 | 2013-11-06 | Novartis AG | Prlr-specific antibody and uses thereof |
CL2007003622A1 (es) | 2006-12-13 | 2009-08-07 | Medarex Inc | Anticuerpo monoclonal humano anti-cd19; composicion que lo comprende; y metodo de inhibicion del crecimiento de celulas tumorales. |
TWI412367B (zh) | 2006-12-28 | 2013-10-21 | Medarex Llc | 化學鏈接劑與可裂解基質以及其之綴合物 |
KR20090122439A (ko) | 2007-02-21 | 2009-11-30 | 메다렉스, 인코포레이티드 | 단일 아미노산을 갖는 화학적 링커 및 이의 접합체 |
EP2077859A4 (en) | 2007-03-30 | 2010-11-24 | Medimmune Llc | ANTIBODY FORMULATION |
EP1987839A1 (en) | 2007-04-30 | 2008-11-05 | I.N.S.E.R.M. Institut National de la Sante et de la Recherche Medicale | Cytotoxic anti-LAG-3 monoclonal antibody and its use in the treatment or prevention of organ transplant rejection and autoimmune disease |
KR101586617B1 (ko) | 2007-06-18 | 2016-01-20 | 머크 샤프 앤 도메 비.브이. | 사람 프로그램된 사멸 수용체 pd-1에 대한 항체 |
WO2009014708A2 (en) | 2007-07-23 | 2009-01-29 | Cell Genesys, Inc. | Pd-1 antibodies in combination with a cytokine-secreting cell and methods of use thereof |
PL2201100T3 (pl) | 2007-09-14 | 2016-10-31 | Wzmacnianie zdolności ludzkich komórek prezentujących antygen do stymulacji komórek T i ich zastosowanie w szczepieniu | |
EA018396B1 (ru) | 2007-10-01 | 2013-07-30 | Бристоль-Мейерз Сквибб Компани | Антитела человека, которые связывают мезотелин, и применение таких антител |
WO2009073533A2 (en) | 2007-11-30 | 2009-06-11 | Medarex, Inc. | Anti-b7h4 monoclonal antibody-drug conjugate and methods of use |
CL2008003527A1 (es) | 2007-11-30 | 2009-10-09 | Medarex Inc | Conjugado de anticuerpo o porcion de union de antigeno del mismo, que se une a la proteina tirosina quinasa 7 (ptk-7/cck4); composicion que lo comprende; acido nulceico cidificante del anticuerpo; vector y celula huesped; uso del conjugado para tratar o prevenir una enfermedad de celulas tumorales que expresan ptk7 |
NZ591130A (en) | 2008-08-25 | 2012-09-28 | Amplimmune Inc | Compositions comprising a PD-1 antagonists and cyclophosphamide and methods of use thereof |
CN102203125A (zh) | 2008-08-25 | 2011-09-28 | 安普利穆尼股份有限公司 | Pd-1拮抗剂及其使用方法 |
PE20120341A1 (es) | 2008-12-09 | 2012-04-24 | Genentech Inc | Anticuerpos anti-pd-l1 y su uso para mejorar la funcion de celulas t |
CN105440133A (zh) * | 2009-07-15 | 2016-03-30 | Aimm医疗股份公司 | 革兰氏阳性细菌特异性结合化合物 |
MX343747B (es) | 2009-11-24 | 2016-11-22 | Medimmune Ltd | Agentes de union diana contra b7-h1. |
WO2012054438A1 (en) * | 2010-10-22 | 2012-04-26 | Schering Corporation | Anti-pcsk9 |
BR122022015975B1 (pt) | 2012-05-15 | 2024-01-02 | Bristol-Myers Squibb Company | Anticorpos monoclonais, kit para o tratamento de um indivíduo afligido com um câncer, processo para medir pd-l1 membranoso em células tumorais isoladas e uso do anticorpo ou uma porção que se liga ao antígeno do mesmo |
AR091649A1 (es) * | 2012-07-02 | 2015-02-18 | Bristol Myers Squibb Co | Optimizacion de anticuerpos que se fijan al gen de activacion de linfocitos 3 (lag-3) y sus usos |
JP6224739B2 (ja) | 2013-03-15 | 2017-11-01 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | 抗lag−3結合タンパク質 |
EP3027210A1 (en) | 2013-08-02 | 2016-06-08 | Aduro Biotech Holdings, Europe B.V. | Combining cd27 agonists and immune checkpoint inhibition for immune stimulation |
BR122023024195A2 (pt) | 2013-09-20 | 2023-12-26 | Bristol-Myers Squibb Company | Usos de anticorpos anti-lag-3 e anticorpos anti-pd-1 |
CA2937503A1 (en) | 2014-01-28 | 2015-08-06 | Bristol-Myers Squibb Company | Anti-lag-3 antibodies to treat hematological malignancies |
EP3283107B1 (en) | 2015-04-17 | 2020-05-27 | Bristol-Myers Squibb Company | Compositions comprising a combination of ipilimumab and nivolumab |
TWI756187B (zh) | 2015-10-09 | 2022-03-01 | 美商再生元醫藥公司 | 抗lag3抗體及其用途 |
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001523958A (ja) * | 1997-03-21 | 2001-11-27 | ブライハム アンド ウィミンズ ホスピタル,インコーポレイテッド | 免疫療法のctla−4結合ペプチド |
JP2011097943A (ja) * | 2003-12-10 | 2011-05-19 | Medarex Inc | インターフェロンα抗体及びその使用 |
JP2006340714A (ja) * | 2005-05-09 | 2006-12-21 | Ono Pharmaceut Co Ltd | ProgrammedDeath1(PD−1)に対するヒトモノクローナル抗体および抗PD−1抗体単独または他の免疫療法と併用した癌治療方法 |
JP2012500006A (ja) * | 2008-08-11 | 2012-01-05 | メダレックス インコーポレーティッド | リンパ球活性化遺伝子−3(lag−3)へ結合するヒト抗体およびその使用 |
WO2012009442A2 (en) * | 2010-07-14 | 2012-01-19 | Merck Sharp & Dohme Corp. | Anti-addl monoclonal antibody and uses thereof |
Non-Patent Citations (2)
Title |
---|
HARRIS RJ ET AL, J CHROMATOGR B BIOMED SCI APPL., vol. 752, JPN6017007286, March 2001 (2001-03-01), pages 233 - 245, ISSN: 0004133759 * |
VLASAK J ET AL, ANAL BIOCHEM., vol. 392, no. 2, JPN6017007287, September 2009 (2009-09-01), pages 145 - 154, ISSN: 0004133760 * |
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