JP2020180135A - 抗pd−l1抗体およびその使用 - Google Patents
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Abstract
Description
「1」または「一」という語句のエンティティは、1または複数のエンティティを指すことに留意されたい。例えば、「1つの抗体」は、1または複数の抗体を表すものと理解されるべきである。したがって、本明細書においては、「1」(または「一」)、「1または複数」、「少なくとも1つ」という語句は、交換可能に使用できる。
本開示は、ヒトPD−L1タンパク質への高親和性を有する抗PD−L1抗体を提供する。試験対象の抗体は、強力な結合および阻害活性を示したので、治療および診断の用途に有用である。
[表1 CDR領域の配列]
[表2 アミノ酸類似性マトリクス]
PD−L1は免疫チェックポイント分子であり、腫瘍抗原でもある。腫瘍抗原標的分子として、PD−L1に特異的な抗体または抗原結合断片を、免疫細胞に特異的な第2の抗原結合断片と組み合わせることで、二重特異性抗体を生成することができる。
また、本開示は、本開示の抗体、変異型、または、誘導体をコードする、単離ポリヌクレオチドまたは核酸分子(例えば、配列識別番号34−60、112および114)を提供する。本開示のポリヌクレオチドは、同一のポリヌクレオチド分子上で、または、別個のポリヌクレオチド分子上で、抗原結合ポリペプチド、その変異型または誘導体の重鎖および軽鎖可変領域の全体をコードし得る。加えて、本開示のポリヌクレオチドは、同一のポリヌクレオチド分子上で、または、別個のポリヌクレオチド分子上で、抗原結合ポリペプチド、その変異型または誘導体の重鎖および軽鎖可変領域の一部をコードし得る。
本明細書において説明されるように、本開示の抗体、変異型または誘導体は、特定の治療および診断方法において使用され得る。
更なる実施形態において、本開示の組成物は、抗腫瘍剤、抗ウイルス剤、抗菌剤もしくは抗生物質製剤、または、抗真菌剤と組み合わせて投与される。本技術分野において知られている、これらの製剤のいずれかは、本開示の組成物において投与され得る。
実験例において示されるように、本開示の抗体は、感染の治療に有用となり得る免疫反応を活性化できる。
[表4 感染症および関連する微生物感染源]
PD−L1の過剰発現は、特定の腫瘍試料において観察され、PD−L1過剰発現細胞を有する患者は、本開示の抗PD−L1抗体を用いる治療に反応する可能性がある。従って、本開示の抗体は、診断および予後の目的のために使用することもできる。
また、本開示は、医薬組成物を提供する。そのような組成物は、有効量の抗体、および、許容可能な担体を含む。いくつかの実施形態において、組成物は更に、第2の抗癌剤(例えば、免疫チェックポイント阻害剤)を含む。
[例1:ヒトPD−L1に対するヒトモノクローナル抗体の生成]
抗ヒトPD−L1マウスモノクローナル抗体は、ハイブリドーマ技術を使用して生成される。
[表5 HL1210−3可変領域配列]
ハイブリドーマクローンHL1210−3の結合活性を評価するために、このクローンから精製されたmAbに対してELISA試験を行った。簡単に説明すると、0.1μg/mlのヒトPD−L1−Fcタンパク質のPBS溶液をウェルあたり100μl加えてマイクロタイタープレートをコーティングし、4℃で一晩放置した後に、ウェルあたり100μlの5%BSAを用いてブロックした。0.2μg/mlから開始するHL1210−3抗体の3倍希釈を各ウェルに加え、室温で1〜2時間培養した。PBS/Tweenを用いてプレートを洗浄し、次に、ホースラディッシュペルオキシダーゼ(HRP)と結合させたヤギ抗マウスIgG抗体と室温で1時間培養した。洗浄後、TMB基質を用いてプレートを現像し、分光光度計によってOD 450〜630nmで解析した。図1に示されるように、HL1210−3は、高い活性(EC50=5.539ng/ml)で、ヒトPD−L1と結合できる。
[組換えヒトPD−L1の使用による受容体遮断アッセイ]
組換えヒトPD−L1の受容体PD−1への結合に対する、HL1210−3マウスmAbの遮断効果を評価するために、ELISAベースの受容体遮断アッセイを利用した。簡単に説明すると、1μg/mlのヒトPD−L1−Fcタンパク質のPBS溶液をウェルあたり100μl加えてマイクロタイタープレートをコーティングし、4℃で一晩放置した後に、ウェルあたり100μlの5%BSAを用いてブロックした。50μlのビオチン標識ヒトPD−1−Fcタンパク質、および、50μlで2μg/mlから開始するHL1210−3抗体の3倍希釈物を各ウェルに加え、37℃で1時間培養した。PBS/Tweenを用いてプレートを洗浄し、次に、ストレプトアビジン−HRPを用いて37℃で1時間培養した。洗浄後、TMB基質を用いてプレートを現像し、分光光度計によってOD 450〜630nmで解析した。図2に示されるように、HL1210−3は、ヒトPD1に対するヒトPD−L1の結合をIC50=0.7835nMで効率的に阻害できる。
哺乳類細胞上で発現するヒトPD−L1の受容体PD−1への結合に対する、HL1210−3マウスmAbの遮断効果を評価するために、FACSベース受容体遮断アッセイを使用した。簡潔に説明すると、まず、20μg/mlから開始する3倍段階希釈HL1210−3マウスmAbを用いて、PDL1−CHOK1細胞を室温で1時間培養した。FACSバッファ(PBS+2% FBS)による洗浄後、ビオチン標識huPD−1を各ウェルに加え、室温で1時間培養した。次に、ストレプトアビジン−PEを各ウェルに加え、FACSバッファを用いて、0.5時間の後洗浄を2回行った。PEの平均蛍光強度(MFI)をFACSAriaIIIによって評価した。図3に示されるように、HL1210−3抗体は、哺乳類細胞上で発現するPD−L1に対するPD−1の結合を非常に効率的に阻害できる(IC50は2.56nM、92.6%の最高阻害率)。
阻害率(%)=(1−試験抗体のMFI/対照担体のMFI)×100%
HL1210−3マウスmAbの作用を評価するために、混合リンパ球反応の環境において、ヒトT細胞の応答を調べた。ヒトDCを、GM−CSFおよびIL−4の存在下で、CD14+単球から7日間にわたって分化させた。次に、別のドナーから単離されたCD4+T細胞を、DCおよび抗PD−L1遮断抗体の希釈系列を用いて共培養した。接種後5日目に、IFNγ生成について、培養上清のアッセイを行った。その結果、HL1210−3抗体は、用量依存的に、IFNγの生成を促進できることが示された。このことは、抗PD−L1抗体がヒトT細胞応答を促進できることを示唆している(図4)。
捕捉方法を使用して、BIACORETM(登録商標)を用いて、組換えPD−L1タンパク質(ヒトPD−L1−his taq)に対するHL1210−3抗体結合を試験した。CM5チップ上にコーティングされた抗マウスFc抗体を使用して、HL1210−3マウスmAbを捕集された。捕集された抗体に対して、ヒトPD−L1−his taqタンパク質の希釈系列を25μg/mlの流速で3分間注入した。抗原を900秒間にわたって解離させた。すべての実験は、Biacore T200(登録商標)上で実行した。データ分析は、Biacore T200(登録商標)評価ソフトウェアを使用して実行した。結果を図5および下の表6に示す。
[表6 組換えヒトPD−L1に対するHL1210−3の結合速度]
mAb HL1210−3可変領域遺伝子を利用してヒト化mAbを作成した。このプロセスの第1段階において、mAb HL1210−3のVHおよびVKのアミノ酸配列をヒトIg遺伝子配列の利用可能なデータベースと比較して、全体の一致率が最高のヒト生殖細胞系Ig遺伝子配列を発見した。軽鎖については、最も近いヒトのマッチは、O18/Jk2およびKV1−39*01/KJ2*04遺伝子である。重鎖については、最も近いヒトのマッチは、VH3−21遺伝子である。一致率が高いことから、VH3−11、VH3−23、VH3−7*01およびVH3−48遺伝子も選択された。
[表8 ヒト化抗体配列(太字はCDRを示す)]
[表9 VHおよびVL領域を有するヒト化抗体]
[組換えヒトPD−L1の結合特性]
抗原結合活性を評価するために、ヒト化抗体に対してELISA試験を行った。簡単に説明すると、0.1μg/mlのヒトPD−L1−Fcタンパク質のPBS溶液をウェルあたり100μl加えてマイクロタイタープレートをコーティングし、4℃で一晩放置した後に、100μl/ウェルの5%BSAを用いてブロックした。10μg/mlから開始するヒト化抗体の5倍希釈物を各ウェルに加え、室温で1〜2時間培養した。PBS/Tweenを用いてプレートを洗浄し、次に、ホースラディッシュペルオキシダーゼ(HRP)と結合させたヤギ抗マウスIgG抗体と室温で1時間培養した。洗浄後、TMB基質を用いてプレートを現像し、分光光度計によってOD 450〜630nmで解析した。図6に示されるように、すべてのヒト化抗体は、キメラ抗体に接触するヒトPD−L1に対する同等の結合効力を示す。
抗原結合特性を評価するために、哺乳動物細胞で発現させたPD−L1との結合について、FACSによってヒト化抗体を解析した。簡単に説明すると、まず、2μg/から開始するヒト化抗体の5倍段階希釈物を用いて、PDL1−CHOK1細胞を室温で1時間培養した。FACSバッファ(PBS+2%FBS)による洗浄後、Alexa488−抗ヒトIgG抗体を各ウェルに加え、室温で1時間培養した。FACSAriaIIIによって、Alexa488のMFIを評価した。図7に示されるように、すべてのヒト化抗体は、哺乳類細胞で発現されるPD−L1に対して、キメラ抗体と同等に非常に効率的に結合できる。
[表10 ヒト化抗体の親和性順位]
捕捉方法を使用して、BIACORETM(登録商標)を用いて、組換えPD−L1タンパク質(ヒトPD−L1−his taq)に対するヒト化抗体結合を試験した。CM5チップ上にコーティングされた抗マウスFc抗体を使用して、HL1210−3マウスmAbを捕集された。捕集された抗体に対して、ヒトPD−L1−his taqタンパク質の希釈系列を25μg/mlの流速で3分間注入した。抗原を900秒間にわたって解離させた。すべての実験は、Biacore T200(登録商標)上で実行した。データ分析は、Biacore T200(登録商標)評価ソフトウェアを使用して実行し、下の表11に示されている。
[表11 Biacoreによる親和性]
huPD−L1、マウスPD−L1、ラットPD−L1、アカゲザルPD−L1に対するヒト化抗体の結合を評価するために、抗体に対してELISA試験を実行した。簡単に説明すると、1μg/mlのヒト、マウス、ラットおよびアカゲザルPD−L1−Fcタンパク質のPBS溶液をウェルあたり100μl加えてマイクロタイタープレートをコーティングし、4℃で一晩放置した後に、100μl/ウェルの5% BSAを用いてブロックした。1μg/mlから開始するヒト化抗体の3倍希釈を各ウェルに加え、室温で1〜2時間培養した。PBS/Tweenを用いてプレートを洗浄し、次に、ホースラディッシュペルオキシダーゼ(HRP)と結合させたヤギ抗マウスIgG抗体と室温で1時間培養した。洗浄後、TMB基質を用いてプレートを現像し、分光光度計によってOD 450〜630nmで解析した。Hu1210−41抗体は、低い親和性でアカゲザルPD−L1に結合でき、ラットおよびマウスPD−L1には結合できない(図8)。
ヒトB7ファミリーおよび他の免疫チェックポイントに対する、ヒト化抗PD−L1抗体の結合を評価するために、ELISAによって、B7−H1(PD−L1)、B7−DC、B7−1、B7−2、B7−H2、PD−1、CD28、CTLA4、ICOSおよびBTLAへの結合について抗体を評価した。図9に示されるように、Hu1210−41抗体は、B7−H1(PD−L1)のみに特異的に結合できる。
[細胞ベースの受容体遮断アッセイ]
哺乳類細胞上で発現するヒトPD−L1の受容体PD−1への結合に対する、ヒト化抗体の遮断効果を評価するために、FACSベース受容体遮断アッセイを利用した。簡潔に説明すると、まず、20μg/mlから開始する3倍段階希釈HL1210−3マウスmAbを用いて、PDL1−CHOK1細胞を室温で1時間培養した。FACSバッファ(PBS+2% FBS)による洗浄後、ビオチン標識huPD−1を各ウェルに加え、室温で1時間培養した。次に、ストレプトアビジン−PEを各ウェルに加え、FACSバッファを用いて、0.5時間の2回後洗浄を行った。PEの平均蛍光強度(MFI)をFACSAriaIIIによって評価した。
阻害率(%)=(1−試験抗体のMFI/対照担体のMFI)×100%
[表12 PD−1受容体遮断アッセイ]
ヒトPD−L1について、2つの受容体、すなわち、PD−1およびB7−1がある。これら2つのタンパク質に対するヒト化PD−L1抗体の遮断特性を調査するために、ここでは、タンパク質ベースの受容体遮断アッセイを利用した。簡単に説明すると、1μg/mlのヒトPD−L1−Fcタンパク質のPBS溶液をウェルあたり100μl加えてマイクロタイタープレートをコーティングし、4℃で一晩放置した後に、ウェルあたり200μlの5%BSAを用いてブロックし、37℃で2時間放置した。50μlのビオチン標識ヒトPD−1−FcまたはB7‐1vタンパク質、および、100nM、50μlから開始するPD−L1抗体の5倍希釈物を各ウェルに加え、37℃で1時間培養した。PBS/Tweenを用いてプレートを洗浄し、次に、ストレプトアビジン−HRPを用いて37℃で1時間培養した。洗浄後、TMB基質を用いてプレートを現像し、分光光度計によってOD 450nmで解析した。図10および11に示されるように、Hu1210−41は、ヒトPD1およびB7−1に対するヒトPD−L1n結合を効率的に阻害できる。
[混合リンパ球反応アッセイ]
ヒト化抗体のインビトロ機能を評価するために混合リンパ球反応の環境において、ヒトT細胞の応答を調べた。ヒトDCを、GM−CSFおよびIL−4の存在下で、CD14+単球から7日間にわたって分化させた。次に、別のドナーから単離されたCD4+T細胞を、DCおよび抗PD−L1遮断抗体の希釈系列を用いて共培養した。接種後5日目に、IL−2およびIFNγ生成について、培養上清のアッセイを行った。この結果は、Hu1210−8、Hu1210−9、Hu1210−16およびHu1210−17抗体が用量依存的に、IL−2およびIFNγの生成を促進できることを示し、抗PD−L1抗体がヒトT細胞応答を促進できることを示唆する。
ヒト化抗体のインビトロ機能を評価するために、ヒトT細胞の応答をCMVリコールアッセイにおいて調べた。段階希釈されたヒト化抗体の存在下で、1μg/mlのCMV抗原を用いて、ヒトPBMCを刺激した。図12および13に示されるように、Hu1210−40、Hu1210−41およびHu1210−17は、用量依存的に、IFNγの生成を促進できる。
ヒト肺腺癌細胞株HCC827に由来する細胞は、NOD scid gamma(NSG)マウスに移植される。NSGマウスは、NOD scid gammaが欠損した、かつ、もっとも免疫不全のマウスであるため、ヒト腫瘍細胞およびPBMC移植のレシピエントとして理想的である。移植後10日目に、腫瘍を有するマウスの中にヒトPBMCを移植する。移植後約20日目に、腫瘍体積が100〜150mm3に到達すると、1日おきに5mg/kgのPD−L1抗体がマウスに投与される。腫瘍体積は、抗体投与と併せて、1日おきにモニタリングされる。図14に示されるように、Hu1210−31は、5mg/kgで、腫瘍増殖を30%阻害できる。Hu1210−41抗体は、用量依存的に腫瘍増殖を阻害でき、一方、腫瘍重量も、Hu1210−41抗体によって用量依存的に抑制される(図15)。
CDR領域またはフレームワーク領域における特定のアミノ酸残基を変更することにより、抗体の活性および/または安定性が更に改善される得る、または、保持され得ることが考えられた。計算ツール(VectorNTI、www.ebi.ac.uk/tools/msa/clustalo/で入手可能)を用いて、構造、配座、機能の特性に関連して、変異型を試験した。可能性を示したもの(CDR領域内)を下の表に列挙する。
[表13 ヒト化抗体への組み入れに好適なVHおよびVL CDRおよび変異型]
本試験は、本開示の抗体に対するPD−L1の結合に関与するアミノ酸残基を同定するために実行された。
Claims (50)
- 単離された抗体または抗体断片であって、ヒトプログラム細胞死リガンド1(PD−L1)タンパク質への特異性を有し、配列識別番号1のVH CDR1、配列識別番号2のVH CDR2、配列識別番号3のVH CDR3、配列識別番号4のVL CDR1、配列識別番号5のVL CDR2、および、配列識別番号6のVL CDR3を含む抗体または抗体断片。
- 重鎖定常領域、軽鎖定常領域、Fc領域、または、それらの組み合わせを更に含む、請求項1に記載の抗体または抗体断片。
- 前記軽鎖定常領域はカッパまたはラムダ鎖定常領域である、請求項2に記載の抗体または抗体断片。
- 前記抗体または抗体断片は、IgG、IgM、IgA、IgEまたはIgDのアイソタイプである、請求項1に記載の抗体または抗体断片。
- 前記アイソタイプは、IgG1、IgG2、IgG3またはIgG4である、請求項4に記載の抗体または抗体断片。
- 前記抗体または抗体断片は、キメラ抗体、ヒト化抗体、または、完全ヒト型抗体である、請求項1から5のいずれか一項に記載の抗体または抗体断片。
- 前記抗体または抗体断片はヒト化抗体である、請求項6に記載の抗体または抗体断片。
- Kabatナンバリングによる、
(a)位置44のSer、
(b)位置49のAla、
(c)位置53のAla、
(d)位置91のIle、
(e)位置1のGlu、
(f)位置37のVal、
(g)位置40のThr、
(h)位置53のVal、
(i)位置54のGlu、
(j)位置77のAsn、
(k)位置94のArg、および、
(l)位置108のThr、ならびに、
それらの組み合わせ
から成る群から選択される1または複数のアミノ酸残基を含む重鎖可変領域を含む、請求項6に記載の抗体または抗体断片。 - Kabatナンバリングによる、(a)位置44のSer、(b)位置49のAla、(c)位置53のAla、および/または、(d)位置91のIle、および、それらの組み合わせを含む重鎖可変領域を含む、請求項7に記載の抗体または抗体断片。
- Kabatナンバリングによる、
(a)位置22のSer、
(b)位置42のGln、
(c)位置43のSer、
(d)位置60のAsp、および、
(e)位置63のThr、ならびに、
それらの組み合わせ
から成る群から選択される1または複数のアミノ酸残基を含む軽鎖可変領域を含む、請求項6に記載の抗体または抗体断片。 - 配列識別番号7‐26から成る群から選択されるアミノ酸配列、または、配列識別番号7‐26から成る群から選択されるアミノ酸配列と少なくとも90%の配列同一性を有するペプチドを含む重鎖可変領域を含む、請求項1から10のいずれか一項に記載の抗体または抗体断片。
- 配列識別番号27‐33から成る群から選択されるアミノ酸配列、または、配列識別番号27‐33から成る群から選択されるアミノ酸配列と少なくとも90%の配列同一性を有するペプチドを含む軽鎖可変領域を含む、請求項1から11のいずれか一項に記載の抗体または抗体断片。
- 配列識別番号20のアミノ酸配列を含む重鎖可変領域と、配列識別番号28のアミノ酸配列を含む軽鎖可変領域とを含む、請求項1に記載の抗体または抗体断片。
- 単離された抗体または抗体断片であって、前記抗体または抗体断片は、ヒトプログラム細胞死リガンド1タンパク質(PD−L1タンパク質)の免疫グロブリンCドメイン(IgCドメイン)に特異的に結合でき、前記IgCドメインは、アミノ酸残基133‐225から成る、抗体または抗体断片。
- 前記PD−L1タンパク質のアミノ酸残基Y134、K162またはN183のうち少なくとも1つに結合できる、請求項14に記載の抗体または抗体断片。
- 前記PD−L1タンパク質のアミノ酸残基Y134、K162およびN183に結合できる、請求項14に記載の抗体または抗体断片。
- 前記PD−L1タンパク質の免疫グロブリンVドメイン(IgVドメイン)に結合しない前記抗体または抗体断片であって、前記IgVドメインはアミノ酸残基19‐127から成る、請求項14に記載の抗体または抗体断片。
- 前記抗体または抗体断片は、キメラ抗体、ヒト化抗体、または、完全ヒト型抗体である、請求項14から17のいずれか一項に記載の抗体または抗体断片。
- 前記抗体または抗体断片はヒト化抗体である、請求項1に記載の抗体または抗体断片。
- 請求項1から19のいずれか一項に記載の抗体または抗体断片と、薬学的に許容可能な担体とを含む組成物。
- 請求項1から19のいずれか一項に記載の抗体または抗体断片をコードする1または複数のポリヌクレオチドを含む単離細胞。
- 治療を必要とする患者の癌または感染を治療する方法であって、請求項1から19のいずれか一項に記載の抗体または抗体断片の有効量を前記患者に投与する段階を備える方法。
- 前記癌は固形腫瘍である、請求項22に記載の方法。
- 前記癌は、膀胱癌、肝臓癌、結腸癌、直腸癌、子宮内膜癌、白血病、リンパ腫、膵臓癌、小細胞肺癌、非小細胞肺癌、乳癌、尿道癌、頭頸部癌、胃腸癌、胃癌、食道癌、卵巣癌、腎癌、悪性黒色腫、前立腺癌、および、甲状腺癌から成る群から選択される、請求項22に記載の方法。
- 前記患者に第2の癌治療剤を投与する段階を更に備える、請求項22に記載の方法。
- 前記感染は、ウイルス感染、細菌感染、真菌感染、または、寄生虫感染である、請求項22に記載の方法。
- 治療を必要とする患者の癌または感染を治療する方法であって、
(a)請求項1から19のいずれか一項に記載の抗体または抗体断片を用いて、インビトロで細胞を処理する段階と、
(b)処理された前記細胞を前記患者に投与する段階と
を備える方法。 - 段階(a)の前に、前記細胞を個人から単離する段階を更に備える、請求項27に記載の方法。
- 前記細胞は前記患者から単離される、請求項28に記載の方法。
- 前記細胞は、前記患者とは異なるドナー個人から単離される、請求項29に記載の方法。
- 前記細胞はT細胞である、請求項27から30のいずれか一項に記載の方法。
- 前記T細胞は、腫瘍浸潤Tリンパ球、CD4+T細胞、CD8+T細胞、または、それらの組み合わせである、請求項31に記載の方法。
- 試料におけるPD−L1の発現を検出する方法であって、
前記抗体または抗体断片が前記PD−L1に結合する条件下で、請求項1から19のいずれか一項にに記載の抗体または抗体断片に前記試料を接触させる段階と、
前記試料におけるPD−L1の発現を示す前記結合を検出する段階と
を備える方法。 - 前記試料は、腫瘍細胞、腫瘍組織、感染組織または血液試料を含む、請求項33に記載の方法。
- 単離された抗体または抗体断片であって、ヒトPD−L1タンパク質への特異性を有し、
(a)配列識別番号1のVH CDR1、または、配列識別番号1の位置1、2もしくは5において、単一置換、欠失もしくは挿入を有する、配列識別番号1の変異型、
(b)配列識別番号2のVH CDR2、または、配列識別番号2の位置7、8、14もしくは15において、単一置換、欠失もしくは挿入を有する、配列識別番号2の変異型、
(c)配列識別番号3のVH CDR3、または、配列識別番号3の位置1、2、3、4、5もしくは6において、単一置換、欠失もしくは挿入を有する、配列識別番号3の変異型、
(d)配列識別番号4のVL CDR1、または、配列識別番号4の位置3において、単一置換、欠失もしくは挿入を有する配列識別番号4の変異型、
(e)配列識別番号5のVL CDR2、または、配列識別番号5の位置1、2、3、4、5もしくは6において、単一置換、欠失もしくは挿入を有する、配列識別番号5の変異型、および、
(f)配列識別番号6のVL CDR3、または、配列識別番号6の位置11もしくは2において、単一置換、欠失もしくは挿入を有する、配列識別番号6の変異型
を含む抗体または抗体断片。 - 前記配列識別番号1の変異型は、配列識別番号61‐67から成る群から選択される、請求項35に記載の抗体または抗体断片。
- 前記配列識別番号2の変異型は、配列識別番号68‐77から成る群から選択される、請求項35に記載の抗体または抗体断片。
- 前記配列識別番号3の変異型は、配列識別番号78‐90から成る群から選択される、請求項35に記載の抗体または抗体断片。
- 前記配列識別番号4の変異型は、配列識別番号91‐92から成る群から選択される、請求項35に記載の抗体または抗体断片。
- 前記配列識別番号5の変異型は、配列識別番号93‐105から成る群から選択される、請求項35に記載の抗体または抗体断片。
- 前記配列識別番号6の変異型は、配列識別番号106‐111から成る群から選択される、請求項35に記載の抗体または抗体断片。
- 重鎖定常領域、軽鎖定常領域、Fc領域、または、それらの組み合わせを更に備える、請求項35から41のいずれか一項に記載の抗体または抗体断片。
- 前記抗体または抗体断片はキメラ抗体、ヒト化抗体、または、完全ヒト型抗体である、請求項35から41のいずれか一項に記載の抗体または抗体断片。
- Kabatナンバリングによる、
(a)位置44のSer、
(b)位置49のAla、
(c)位置53のAla、
(d)位置91のIle、
(e)位置1のGlu、
(f)位置37のVal、
(g)位置40のThr、
(h)位置53のVal、
(i)位置54のGlu、
(j)位置77のAsn、
(k)位置94のArg、および、
(l)位置108のThr、ならびに、
それらの組み合わせ
から成る群から選択される1または複数のアミノ酸残基を含む重鎖可変領域を含む、請求項43に記載の抗体または抗体断片。 - Kabatナンバリングによる、(a)位置44のSer、(b)位置49のAla、(c)位置53のAla、および/または、(d)位置91のIle、ならびに、それらの組み合わせを含む重鎖可変領域を含む、請求項43に記載の抗体または抗体断片。
- Kabatナンバリングによる、
(a)位置22のSer、
(b)位置42のGln、
(c)位置43のSer、
(d)位置60のAsp、および、
(e)位置63のThr、ならびに、
それらの組み合わせ
から成る群から選択される1または複数のアミノ酸残基を含む軽鎖可変領域を含む請求項43に記載の抗体または抗体断片。 - 請求項1から19または35から46のいずれか一項に記載の抗体断片と、免疫細胞上の分子への特異性を有する第2の抗原結合断片とを含む、単離された二重特異性抗体。
- 前記分子は、PD−1、CTLA−4、LAG−3、CD28、CD122、4‐1BB、TIM3、OX−40、OX40L、CD40、CD40L、LIGHT、ICOS、ICOSL、GITR、GITRL、TIGIT、CD27、VISTA、B7H3、B7H4、HEVM、BTLA、KIRおよびCD47から成る群から選択される、請求項47に記載の二重特異性抗体。
- 前記抗体断片、および、前記第2の抗原結合断片は、Fab断片、一本鎖可変断片(scFv)または単一ドメイン抗体から各々独立に選択される、請求項47に記載の二重特異性抗体。
- Fc断片を更に含む、請求項47に記載の二重特異性抗体。
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Families Citing this family (48)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
BR112017019559B1 (pt) | 2015-03-13 | 2020-08-04 | Cytomx Therapeutics, Inc | Anticorpos anti-pdl1, anticorpos anti-pdl1 ativáveis, e métodos de uso destes |
CA3027209C (en) * | 2016-06-13 | 2022-08-16 | I-Mab | Anti-pd-l1 antibodies and uses thereof |
CN107488229B (zh) * | 2016-06-13 | 2020-11-17 | 天境生物科技(上海)有限公司 | Pd-l1抗体及其用途 |
US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
WO2018083248A1 (en) | 2016-11-03 | 2018-05-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
WO2018189382A1 (en) | 2017-04-14 | 2018-10-18 | Solstice Biologics, Ltd. | Immunomodulating polynucleotides, antibody conjugates thereof, and methods of their use |
KR20200016899A (ko) | 2017-06-01 | 2020-02-17 | 싸이톰스 테라퓨틱스, 인크. | 활성화가능 항-pdl1 항체, 및 이의 이용 방법 |
JP7145895B2 (ja) * | 2017-09-01 | 2022-10-03 | 四川科倫博泰生物医薬股▲フン▼有限公司 | 組換え二重特異性抗体 |
JP7163399B2 (ja) * | 2017-11-20 | 2022-10-31 | 泰州▲邁▼博太科▲薬▼▲業▼有限公司 | Cd47とpd-l1を標的にする二重機能の融合タンパク質 |
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 |
CN109970857B (zh) | 2017-12-27 | 2022-09-30 | 信达生物制药(苏州)有限公司 | 抗pd-l1抗体及其用途 |
KR102311838B1 (ko) * | 2017-12-27 | 2021-10-14 | 주식회사 파멥신 | 항-pd-l1 항체 및 이의 용도 |
CN111542543B (zh) * | 2017-12-28 | 2023-12-22 | 南京传奇生物科技有限公司 | 针对pd-l1的抗体及其变体 |
CA3082280A1 (en) * | 2017-12-28 | 2019-07-04 | Nanjing Legend Biotech Co., Ltd. | Single-domain antibodies and variants thereof against tigit |
EP3568417A4 (en) | 2018-01-25 | 2020-07-15 | I-Mab Biopharma US Limited | ANTI-PD-L1 ANTIBODIES AND IL-7 FUSIONS |
EP3758735B1 (en) | 2018-02-28 | 2023-12-13 | AP Biosciences, Inc. | Bifunctional proteins combining checkpoint blockade for targeted therapy |
CN117362436A (zh) * | 2018-03-29 | 2024-01-09 | 桂林三金药业股份有限公司 | 抗pd-l1抗体及其用途 |
MX2020007842A (es) * | 2018-03-29 | 2020-09-25 | I Mab Biopharma Us Ltd | Anticuerpos anti-pd-l1 y usos de los mismos. |
EP3778635A4 (en) * | 2018-04-09 | 2022-01-26 | Origincell Therapeutics Co., Ltd. | ANTI-PD-L1 ANTIBODIES AND ITS USE |
WO2019227490A1 (en) * | 2018-06-01 | 2019-12-05 | Tayu Huaxia Biotech Medical Group Co., Ltd. | Compositions and methods for imaging |
JP2021525806A (ja) * | 2018-06-01 | 2021-09-27 | タユー ファシャ バイオテック メディカル グループ カンパニー, リミテッド | 疾患または状態を処置するための組成物およびそれらの使用 |
WO2020005869A2 (en) * | 2018-06-25 | 2020-01-02 | Duke University | Compositions and methods for the treatment of cancer characterized with pcsk9 expression |
WO2020004984A1 (ko) * | 2018-06-29 | 2020-01-02 | 국민대학교 산학협력단 | Pd-1과 결합력이 증가된 pd-l1 변이체 |
WO2020020307A1 (en) | 2018-07-25 | 2020-01-30 | I-Mab Biopharma Co., Ltd. | Anti-cd73 anti-pd-l1 bispecific antibodies |
HRP20230590T2 (hr) * | 2018-07-31 | 2024-02-16 | Pieris Pharmaceuticals Gmbh | Novi fuzijski protein specifičan za cd137 i pd-l1 |
CN116063519A (zh) * | 2018-08-20 | 2023-05-05 | 北京强新生物科技有限公司 | 新型癌症免疫治疗抗体组合物 |
CN109232740B (zh) * | 2018-08-20 | 2022-05-10 | 中国科学院微生物研究所 | 一种抗pd-l1抗体及其在抗肿瘤治疗中的应用 |
CN110678484B (zh) * | 2018-08-21 | 2022-12-27 | 天境生物科技(杭州)有限公司 | 抗pd-l1/抗lag3双特异性抗体及其用途 |
US20220363763A1 (en) * | 2018-08-21 | 2022-11-17 | Abl Bio Inc. | Anti-pd-l1/anti-lag3 bispecific antibodies and uses thereof |
CN108997499B (zh) * | 2018-09-12 | 2020-07-31 | 首都医科大学附属北京胸科医院 | 一种抗人pd-l1抗体及其应用 |
CN109053891B (zh) * | 2018-09-17 | 2021-12-21 | 苏州泓迅生物科技股份有限公司 | 一种抗pd-l1抗体及其制备方法和应用 |
AU2019379576A1 (en) | 2018-11-13 | 2021-06-03 | Compass Therapeutics Llc | Multispecific binding constructs against checkpoint molecules and uses thereof |
PE20211778A1 (es) | 2018-11-30 | 2021-09-08 | Abl Bio Inc | Anticuerpos biespecificos anti-pd-l1/anti-4-1bb y usos de los mismos |
EP3891182A4 (en) * | 2018-12-03 | 2022-08-17 | Immuneonco Biopharmaceuticals (Shanghai) Co., Ltd | RECOMBINATION PROTEIN TARGETING PD-L1 AND VEGF |
WO2020192709A1 (en) * | 2019-03-27 | 2020-10-01 | Wuxi Biologics (Shanghai) Co., Ltd. | Novel bispecific polypeptide complexes |
JP2022530496A (ja) * | 2019-04-26 | 2022-06-29 | ウーシー バイオロジクス アイルランド リミテッド | Pd-1およびlag-3に対する二重特異性抗体 |
CN111606995B (zh) * | 2019-06-04 | 2021-02-12 | 优睿赛思(武汉)生物科技有限公司 | 抗人pd-l1单克隆抗体及其应用 |
CN110330550B (zh) * | 2019-08-02 | 2021-04-13 | 郑州大学 | PD-L1-IgV的亲和肽及其应用 |
CA3157516A1 (en) * | 2019-11-08 | 2021-05-14 | Xinyan Zhao | Anti-human programmed cell death ligand-1 (pd-l1) antibody and use thereof |
WO2021097800A1 (en) * | 2019-11-22 | 2021-05-27 | Abl Bio Inc. | Anti-pd-l1/anti-b7-h3 multispecific antibodies and uses thereof |
CN115427458A (zh) | 2020-02-28 | 2022-12-02 | 塔拉克治疗公司 | 转谷氨酰胺酶介导的缀合 |
WO2021226984A1 (zh) * | 2020-05-15 | 2021-11-18 | 三生国健药业(上海)股份有限公司 | 一种抗pd-1和pd-l1的四价双特异性抗体 |
CN111551733A (zh) * | 2020-05-29 | 2020-08-18 | 武汉大学 | 定量检测免疫细胞来源细胞外囊泡pd-1含量的方法、elisa试剂盒及使用方法 |
IL300666A (en) | 2020-08-19 | 2023-04-01 | Xencor Inc | ANTI–CD28 COMPOSITIONS |
WO2022068775A1 (zh) * | 2020-09-29 | 2022-04-07 | 锋宏生物医药科技(昆山)有限公司 | 抗pd-l1抗体及其用途 |
WO2022148414A1 (zh) * | 2021-01-08 | 2022-07-14 | 北京韩美药品有限公司 | 特异性结合pd-l1的抗体及其抗原结合片段 |
TW202346366A (zh) * | 2022-04-02 | 2023-12-01 | 大陸商和鉑醫藥(上海)有限責任公司 | 標靶pd-l1和cd40的抗原結合蛋白及其製備和應用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008544755A (ja) * | 2005-07-01 | 2008-12-11 | メダレックス インコーポレーティッド | プログラム死リガンド1(pd−l1)に対するヒトモノクローナル抗体 |
JP2016504336A (ja) * | 2012-12-21 | 2016-02-12 | メルク・シャープ・アンド・ドーム・コーポレーションMerck Sharp & Dohme Corp. | ヒトプログラム死リガンド1(pd−l1)に結合する抗体 |
Family Cites Families (88)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4694778A (en) | 1984-05-04 | 1987-09-22 | Anicon, Inc. | Chemical vapor deposition wafer boat |
US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
US4980286A (en) | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
US5892019A (en) | 1987-07-15 | 1999-04-06 | The United States Of America, As Represented By The Department Of Health And Human Services | Production of a single-gene-encoded immunoglobulin |
US4965288A (en) | 1988-02-25 | 1990-10-23 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
US5021456A (en) | 1988-02-25 | 1991-06-04 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
US5252608A (en) | 1988-02-25 | 1993-10-12 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
US5182297A (en) | 1988-02-25 | 1993-01-26 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
US5059714A (en) | 1988-02-25 | 1991-10-22 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
US4943593A (en) | 1988-02-25 | 1990-07-24 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
US5120764A (en) | 1988-11-01 | 1992-06-09 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5413923A (en) | 1989-07-25 | 1995-05-09 | Cell Genesys, Inc. | Homologous recombination for universal donor cells and chimeric mammalian hosts |
US4997854A (en) | 1989-08-25 | 1991-03-05 | Trustees Of Boston University | Anti-fibrotic agents and methods for inhibiting the activity of lysyl oxidase in-situ using adjacently positioned diamine analogue substrates |
GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
AU633698B2 (en) | 1990-01-12 | 1993-02-04 | Amgen Fremont Inc. | Generation of xenogeneic antibodies |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for 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 |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
WO1992003918A1 (en) | 1990-08-29 | 1992-03-19 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
IE922437A1 (en) | 1991-07-25 | 1993-01-27 | Idec Pharma Corp | Recombinant antibodies for human therapy |
US5756096A (en) | 1991-07-25 | 1998-05-26 | Idec Pharmaceuticals Corporation | Recombinant antibodies for human therapy |
US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
US6130364A (en) | 1995-03-29 | 2000-10-10 | Abgenix, Inc. | Production of antibodies using Cre-mediated site-specific recombination |
EP1978033A3 (en) | 1995-04-27 | 2008-12-24 | Amgen Fremont Inc. | Human antibodies derived from immunized xenomice |
CA2219486A1 (en) | 1995-04-28 | 1996-10-31 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US6420140B1 (en) | 1996-10-11 | 2002-07-16 | Abgenix, Inc. | Production of multimeric protein by cell fusion method |
US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
CA2616914C (en) | 1996-12-03 | 2012-05-29 | Abgenix, Inc. | Egfr-binding antibody |
CZ294425B6 (cs) | 1997-04-14 | 2005-01-12 | Micromet Ag | Způsob výroby anti-humánního antigenového receptoru, anti-humánní antigenový receptor, řetězec VH a VL, souprava pro selekci anti-humánních antigenových receptorů a farmaceutická kompozice, obsahující uvedený receptor |
US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
ES2258817T3 (es) | 1997-05-21 | 2006-09-01 | Biovation Limited | Metodo para la produccion de proteinas no inmunogenas. |
US6190370B1 (en) | 1997-07-25 | 2001-02-20 | Arrow International, Inc. | Devices, systems and methods for determining proper placement of epidural catheters |
EP1051432B1 (en) | 1998-12-08 | 2007-01-24 | Biovation Limited | Method for reducing immunogenicity of proteins |
FR2828206B1 (fr) | 2001-08-03 | 2004-09-24 | Centre Nat Rech Scient | Utilisation d'inhibiteurs des lysyl oxydases pour la culture cellulaire et le genie tissulaire |
ES2605792T3 (es) | 2004-05-13 | 2017-03-16 | Icos Corporation | Quinazolinona usada como inhibidor de la fosfatidilinositol 3-quinasa delta humana |
US20090142345A1 (en) | 2005-03-15 | 2009-06-04 | Takeda Pharmaceutical Company Limited | Prophylactic/therapeutic agent for cancer |
US7331637B2 (en) | 2005-11-11 | 2008-02-19 | Hayes Lemmerz International, Inc. | Dual mountable cast commercial vehicle wheels with spokes |
AU2008266951B2 (en) * | 2007-06-18 | 2013-12-12 | Merck Sharp & Dohme B.V. | Antibodies to human programmed death receptor PD-1 |
HUE025283T2 (en) | 2007-08-02 | 2016-03-29 | Gilead Biologics Inc | LOX and LOX2 inhibitors and their use |
US8652843B2 (en) | 2008-08-12 | 2014-02-18 | Oncomed Pharmaceuticals, Inc. | DDR1-binding agents and methods of use thereof |
KR101050829B1 (ko) * | 2008-10-02 | 2011-07-20 | 서울대학교산학협력단 | 항 pd-1 항체 또는 항 pd-l1 항체를 포함하는 항암제 |
US8450321B2 (en) | 2008-12-08 | 2013-05-28 | Gilead Connecticut, Inc. | 6-(1H-indazol-6-yl)-N-[4-(morpholin-4-yl)phenyl]imidazo-[1,2-A]pyrazin-8-amine, or a pharmaceutically acceptable salt thereof, as a SYK inhibitor |
CN108997498A (zh) * | 2008-12-09 | 2018-12-14 | 霍夫曼-拉罗奇有限公司 | 抗-pd-l1抗体及它们用于增强t细胞功能的用途 |
TWI625121B (zh) | 2009-07-13 | 2018-06-01 | 基利科學股份有限公司 | 調節細胞凋亡信號之激酶的抑制劑 |
AU2011212830B2 (en) | 2010-02-04 | 2014-05-22 | Gilead Biologics, Inc. | Antibodies that bind to lysyl oxidase-like 2 (LOXL2) and methods of use therefor |
JP5878538B2 (ja) | 2010-08-27 | 2016-03-08 | ギリアド バイオロジクス, インク.Gilead Biologics, Inc. | マトリクスメタロプロティナーゼ9に対する抗体 |
AU2012282116B2 (en) * | 2011-07-11 | 2016-07-07 | Ichnos Sciences SA | Antibodies that bind to OX40 and their uses |
EP2749572A4 (en) | 2011-08-23 | 2015-04-01 | Chugai Pharmaceutical Co Ltd | NEW ANTI-DDR1 ANTIBODY WITH ANTITUMORACTIVITY |
GB201115529D0 (en) | 2011-09-08 | 2011-10-26 | Imp Innovations Ltd | Antibodies, uses and methods |
WO2013052699A2 (en) | 2011-10-04 | 2013-04-11 | Gilead Calistoga Llc | Novel quinoxaline inhibitors of pi3k |
KR101981873B1 (ko) | 2011-11-28 | 2019-05-23 | 메르크 파텐트 게엠베하 | 항-pd-l1 항체 및 그의 용도 |
UY34573A (es) | 2012-01-27 | 2013-06-28 | Gilead Sciences Inc | Inhibidor de la quinasa que regula la señal de la apoptosis |
WO2013116562A1 (en) | 2012-02-03 | 2013-08-08 | Gilead Calistoga Llc | Compositions and methods of treating a disease with (s)-4 amino-6-((1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile |
TW201427995A (zh) | 2012-09-24 | 2014-07-16 | Gilead Sciences Inc | 抗ddr1抗體 |
TW201441216A (zh) | 2012-12-21 | 2014-11-01 | Gilead Calistoga Llc | 肌醇磷酯3-激酶的抑制劑 |
AU2013364070B2 (en) | 2012-12-21 | 2016-10-27 | Gilead Calistoga Llc | Isoquinolinone or quinazolinone phosphatidylinositol 3-kinase inhibitors |
MX347988B (es) | 2013-06-14 | 2017-05-19 | Gilead Sciences Inc | Inhibidores de fosfatidilinositol 3-cinasa. |
AU2014339900B2 (en) * | 2013-10-25 | 2019-10-24 | Dana-Farber Cancer Institute, Inc. | Anti-PD-L1 monoclonal antibodies and fragments thereof |
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 |
US10280223B2 (en) * | 2014-07-09 | 2019-05-07 | Nippon Zenyaku Kogyo Co., Ltd. | Anti-canine PD-1 antibody or anti-canine PD-L1 antibody |
HRP20220738T1 (hr) * | 2014-08-11 | 2022-08-19 | Acerta Pharma B.V. | Terapijske kombinacije inhibitora btk, inhibitora pd-1 i/ili inhibitora pd-l1 |
EP4245376A3 (en) | 2014-10-14 | 2023-12-13 | Novartis AG | Antibody molecules to pd-l1 and uses thereof |
AR105654A1 (es) | 2015-08-24 | 2017-10-25 | Lilly Co Eli | Anticuerpos pd-l1 (ligando 1 de muerte celular programada) |
WO2017087547A1 (en) * | 2015-11-17 | 2017-05-26 | Oncomed Pharmaceuticals, Inc. | Pd-l1-binding agents and uses thereof |
CN105566496B (zh) * | 2015-11-26 | 2019-04-02 | 大庆东竺明生物技术有限公司 | 阻断人程序性死亡因子1(pd-1)功能的单克隆抗体及其编码基因和应用 |
PL3386541T3 (pl) | 2015-12-07 | 2021-04-06 | Merck Patent Gmbh | Wodna formulacja farmaceutyczna zawierającą przeciwciało anty-pd-1 awelumab |
CN105461808B (zh) * | 2015-12-24 | 2019-03-19 | 长春金赛药业股份有限公司 | 单克隆抗体及其应用 |
EP3943508B1 (en) * | 2016-03-29 | 2024-01-10 | Board Of Regents, The University Of Texas System | Dual function antibodies specific to glycosylated pd-l1 and methods of use thereof |
EP3448428A4 (en) | 2016-04-25 | 2019-11-27 | Medimmune, LLC | COMPOSITIONS COMPRISING ANTI-PD-L1 AND ANTI-CTLA-4 ANTIBODY CO-FORMULATION |
CA3027209C (en) * | 2016-06-13 | 2022-08-16 | I-Mab | Anti-pd-l1 antibodies and uses thereof |
CN107488229B (zh) * | 2016-06-13 | 2020-11-17 | 天境生物科技(上海)有限公司 | Pd-l1抗体及其用途 |
MX2020007842A (es) * | 2018-03-29 | 2020-09-25 | I Mab Biopharma Us Ltd | Anticuerpos anti-pd-l1 y usos de los mismos. |
US20220363763A1 (en) * | 2018-08-21 | 2022-11-17 | Abl Bio Inc. | Anti-pd-l1/anti-lag3 bispecific antibodies and uses thereof |
PE20211778A1 (es) * | 2018-11-30 | 2021-09-08 | Abl Bio Inc | Anticuerpos biespecificos anti-pd-l1/anti-4-1bb y usos de los mismos |
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008544755A (ja) * | 2005-07-01 | 2008-12-11 | メダレックス インコーポレーティッド | プログラム死リガンド1(pd−l1)に対するヒトモノクローナル抗体 |
JP2016504336A (ja) * | 2012-12-21 | 2016-02-12 | メルク・シャープ・アンド・ドーム・コーポレーションMerck Sharp & Dohme Corp. | ヒトプログラム死リガンド1(pd−l1)に結合する抗体 |
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