JP7090347B2 - メソテリン結合タンパク質 - Google Patents
メソテリン結合タンパク質 Download PDFInfo
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- JP7090347B2 JP7090347B2 JP2019562603A JP2019562603A JP7090347B2 JP 7090347 B2 JP7090347 B2 JP 7090347B2 JP 2019562603 A JP2019562603 A JP 2019562603A JP 2019562603 A JP2019562603 A JP 2019562603A JP 7090347 B2 JP7090347 B2 JP 7090347B2
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- msln
- binding protein
- mesothelin
- sequence
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/734—Complement-dependent cytotoxicity [CDC]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Description
本出願は、各々が全体において参照により本明細書に組み込まれている、2017年5月12日出願の米国仮特許出願62/505,719号及び2018年4月13日出願の米国仮特許出願62/657,417号の利益を主張するものである。
本出願は、ASCIIフォーマットで電子的に提出され、参照によって本明細書に組み込まれる配列表を含んでいる。2018年5月11日に作成された上記のASCIIのコピーは、47517-719_601_SL.txtのファイル名であり、145,039バイトのサイズである。
本明細書で言及される刊行物、特許、及び特許出願は全て、あたかも個々の刊行物、特許、又は特許出願がそれぞれ参照により組み込まれるべく具体的且つ個々に指示されるかのように、及び、その全体にわたって、同程度まで参照により本明細書に組み込まれる。
f1-r1-f2-r2-f3-r3-f4
式中、r1は、SEQ ID NO:51と同一である、又はこれに対して1つ以上のアミノ酸残基置換を含んでおり;r2は、SEQ ID NO:52と同一である、又はこれに対して1つ以上のアミノ酸残基置換を含んでおり;及びr3は、SEQ ID NO:53と同一である、又はこれに対して1つ以上のアミノ酸残基置換を含んでおり;及びここで、f1、f2、f3、及びf4はフレームワーク残基である。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質は、SEQ ID NO:1-29、30-40、58、及び60-62から成る群から選択された配列に少なくとも80%同一の配列を含む。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質は、該結合タンパク質のヒト化を結果としてもたらす1つ以上の修飾を含む。幾つかの実施形態において、修飾は、アミノ酸残基の置換、付加、又は欠失を含む。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質は、111~124のアミノ酸を含む。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質は、非ヒトソース由来のVHHドメインを含む。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質はラマVHHドメインを含む。幾つかの実施形態において、前記エピトープは、SEQ ID NO:57のアミノ酸残基296-390を含む領域I、SEQ ID NO:57のアミノ酸残基391-486を含む領域II、又はSEQ ID NO:57のアミノ酸残基487-598を含む領域IIIに位置する。
f1-r1-f2-r2-f3-r3-f4
式中、r1は、SEQ ID NO:54と同一である、又はこれに対して1つ以上のアミノ酸残基置換を含んでおり;r2は、SEQ ID NO:55と同一である、又はこれに対して1つ以上のアミノ酸残基置換を含んでおり;及びr3は、SEQ ID NO:56と同一である、又はこれに対して1つ以上のアミノ酸残基置換を含んでおり;及びここで、f1、f2、f3、及びf4はフレームワーク残基である。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質は、SEQ ID NO:30-40、58、及び60-62から成る群から選択された配列に少なくとも80%同一の配列を含む。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質は、111~119のアミノ酸を含む。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質は、非ヒトソース由来のVHHドメインを含む。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質はラマVHHドメインを含む。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質は、SEQ ID NO:57として明記される配列を含むヒトメソテリンタンパク質に結合する。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質はメソテリンのエピトープに結合し、前記エピトープは、SEQ ID NO:57のアミノ酸残基296-390を含む領域I、SEQ ID NO:57のアミノ酸残基391-486を含む領域II、又はSEQ ID NO:57のアミノ酸残基487-598を含む領域IIIに位置する。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質は、キメラ抗体又はヒト化抗体である。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質は単一ドメイン抗体である。幾つかの実施形態において、前記単一ドメインメソテリン結合タンパク質はヒト化単一ドメイン抗体である。
本明細書で使用される用語は、特定の事例のみを記載することを目的としており、本発明を制限することを意図していない。本明細書で使用されるように、単数形「a」、「an」、及び「the」は、文脈が他に明白に示していない限り、同様に複数形を含むように意図される。更に、用語「含んでいる(including)」、「含む(includes)」、「有している(having)」、「有する(has)」、「含んだ(with)」、又はそれらの変異形が発明を実施するための形態及び/又は請求項の何れかで使用される程度には、上記のような用語は「含んでいる(comprising)」という用語と同様の洋式で包括的であることが意図されている。
MSLN結合タンパク質
本開示のMSLN結合タンパク質、例えば抗MSLN単一ドメイン抗体は、特定の例において、キメラ抗原受容体(CAR)へと組み込むことができる。操作された免疫エフェクター細胞、例えばT細胞又はNK細胞は、本明細書に記載されるような抗MSLN単一ドメイン抗体を含むCARを発現するために使用され得る。一実施形態において、本明細書に記載されるような抗MSLN単一ドメイン抗体を含むCARは、ヒンジ領域を介して膜貫通ドメインに、及び更には共刺激ドメイン、例えばOX40、CD27、CD28、CD5、ICAM-1、LFA-1(CD11a/CD18)、ICOS(CD278)、又は4-1BBから得られる機能的シグナル伝達ドメインに接続される。幾つかの実施形態において、CARは、4-1BB及び/又はCD3ゼータなどの細胞内シグナル伝達ドメインをコードする配列を更に含む。
特定の実施形態において、本開示のMSLN結合タンパク質は、メソテリンを発現する腫瘍細胞を有する被験体に投与すると、インビボで腫瘍細胞の成長を減少する。腫瘍細胞の成長の減少の測定は、当該技術分野で周知の複数の異なる方法によって判定され得る。非限定的な実施例は、腫瘍寸法の直接測定、切除した腫瘤の測定及び対照被験体との比較、解析の向上のために同位体又は発光分子(例えばルシフェラーゼ)を使用する又は使用しない画像処理技術(例えばCT又はMRI)を介した測定などを含む。特異的な実施形態において、本開示の抗原結合剤の投与は結果として、対照の抗原結合剤と比較して、腫瘍成長の少なくとも約10%、20%、30%、40%、50%、60%、70%、80%、90%、又は100%の腫瘍細胞のインビボ成長の減少をもたらし、腫瘍の完全寛解及び消失を示す。更なる実施形態において、本開示の抗原結合剤の投与は結果として、対照の抗原結合剤と比較して、約50-100%、約75-100%、又は約90%-100%の腫瘍細胞のインビボ成長の減少をもたらす。更なる実施形態において、本開示の抗原結合剤の投与は結果として、対照の抗原結合剤と比較して、約50-60%、約70-80%、約80-90%、又は約90%-100%の腫瘍細胞のインビボ成長の減少をもたらす。
本明細書に記載されるMSLN結合タンパク質は、(i)アミノ酸が遺伝子コードによってコードされるものではないアミノ酸残基で置換され、(ii)成熟ポリペプチドがポリエチレングリコールなどの別の化合物と融合され、又は、(iii)追加のアミノ酸が、リーダー配列、分泌配列、或いは免疫原ドメインを遮断するための及び/又はタンパク質の精製のための配列などのタンパク質に融合される、誘導体又はアナログを包含する。
幾つかの実施形態において、本明細書に記載されるMSLN結合タンパク質をコードするポリヌクレオチド分子も提供される。幾つかの実施形態において、ポリヌクレオチド分子はDNA構築物として提供される。他の実施形態において、ポリヌクレオチド分子はメッセンジャーRNA転写産物として提供される。
幾つかの実施形態において、本明細書に記載されるMSLN結合タンパク質、MSLN結合タンパク質のポリペプチドをコードするポリヌクレオチドを含むベクター、或いはこのベクター及び少なくとも1つの薬学的に許容可能な担体によって形質転換された宿主細胞を含む、医薬組成物も提供される。用語「薬学的に許容可能な担体」としては、限定されないが、成分の生物学的活性の有効性に干渉せず、且つ、投与される患者にとって毒性ではない任意の担体が挙げられる。適切な医薬担体の例は当該技術分野で周知であり、リン酸緩衝生理食塩水、水、油/水エマルジョンなどのエマルジョン、様々なタイプの湿潤剤、無菌液などを含む。こうした担体は、従来の方法によって製剤することができ、適切な投与量で被験体に投与可能である。好ましくは、組成物は無菌である。これらの組成物は、防腐剤、乳化剤、及び分散剤などのアジュバントを更に含み得る。微生物の作用の予防は、様々な抗菌剤及び抗真菌剤の包含によって確保され得る。更なる実施形態は、凍結乾燥形態で包装される、或いは水性媒体に包装される、抗MSLN単一ドメイン抗体又はその抗原結合性フラグメントなどの、上記結合タンパク質の1つ以上を提供する。
本明細書にはまた、幾つかの実施形態において、本明細書に記載されるようなMSLN結合タンパク質の投与を含む、個体の免疫系を刺激するための方法と使用が提供される。幾つかの例において、本明細書に記載されるMSLN結合タンパク質の投与は、標的抗原を発現する細胞への細胞毒性を引き起こす、及び/又は持続させる。幾つかの例において、細胞は、癌細胞、ウイルス感染細胞、細菌感染細胞、自己反応性のT又はB細胞、損傷を受けた赤血球、動脈プラーク、或いは繊維症の組織である。
ロニック酸;パナキシトリオール;パノミフェン;パラバクチン;パゼリプチン;ペガスパルガーゼ;ペルデシン;ペントサンポリサルフェートナトリウム;ペントスタチン;ペントロゾール;ペルフルブロン;ペルフォスファミド;ペリルアルコール;フェナジノマイシン;酢酸フェニル;ホスファターゼ阻害剤;ピシバニール;塩酸ピロカルピン;ピラルビシン;ピリトレキシム;プラセチンA;プラセチンB;プラスミノゲンアクチベータインヒビター;白金複合体;白金化合物;白金トリアミン複合体;ポルフィマーナトリウム;ポルフィロマイシン;プレドニゾン;プロピルビス-アクリドン;プロスタグランジンJ2;プロテアソーム阻害剤;タンパク質Aベースの免疫モジュレータ;プロテインキナーゼC阻害剤;プロテインキナーゼC阻害剤、微細藻類;チロシンホスファターゼタンパク質阻害剤;プリンヌクレオシドホスホリラーゼ阻害剤;プルプリン;ピラゾロアクリジン;ピリドキシル化したヘモグロビン・ポリオキシエチレン抱合体;rafアンタゴニスト;ラルチトレキセド;ラモセトロン;rasファルネシルタンパク質トランスフェラーゼ阻害剤;ras阻害剤;ras-GAP阻害剤;脱メチル化レティプチン;レニウムRe 186エチドロネート;リゾキシン;リボザイム;RIIレチンアミド;ログレチミド;ロヒツキン;ロムルチド;ロキニメックス;ラビジノンB1;ラボキシル;サフィンゴル;セイントピン;SarCNU;サルコフィトールA;サルグラモスチム;Sdi 1模倣物;セムスチン;セネスセンス由来の阻害剤1;センスオリゴヌクレオチド;シグナル伝達阻害剤;シグナル伝達モジュレータ;一本鎖抗原結合タンパク質;シゾフィラン;ソブゾキサン;ナトリウムボロカプテート;フェニル酢酸ナトリウム;サルバロル;ソマトメジン結合タンパク質;ソナーミン;スパルフォシック酸;スピカマイシンD;スピロマスチン;スプレノペンチン;スポンジスタチン1;スクワラミン;幹細胞阻害剤;幹細胞分割阻害剤;スティピアミド;ストロメリシン阻害剤;サルフィノジン;超活性血管作用性小腸ペプチドアンタゴニスト;サラディスタ;スラミン;スウェインソニン;合成グリコサミノグリカン;タリムスチン;タモキシフェンメチオジド;タウロマスチン;タザロテン;テコガランナトリウム;テガフール;テルラピリウム;テロメラーゼ阻害剤;テモポルフィン;テモゾロミド;テニポシド;テトラクロロデカオキシド;テトラゾミン;サリブラスチン;チオコラリン;トロンボポイエチン;トロンボポイエチン模倣物;チマルファジン;チモポイエチン受容体アゴニスト;チモトリナン;甲状腺刺激ホルモン;スズエチルエチオプロプリン;チラパザミン;チタノセン二塩化物;トプセンチン;トレミフェン;全能性幹細胞因子;翻訳阻害剤;トレチノイン;トリアセチルウリジン;トリシビリン;トリメトレキサート;トリプトレリン;トロピセトロン;テュロステリド;チロシンキナーゼ阻害剤;チルホスチン;UBC阻害剤;ウベニメクス;尿生殖洞由来の成長阻害因子;ウロキナーゼ受容体アンタゴニスト;バプレオチド;バリオリンB;ベクターシステム、赤血球遺伝子治療薬;ベラレゾール;ベラミン;アメリカツリスガラ;ベルテポルフィン;ビノレルビン;ビンザルチン;Vitaxin(登録商標);ボロゾール;ザノテロン;ゼニプラチン;ジラスコルブ;及びジノスタチンスチマラマー。追加の抗癌剤は5-フルオロウラシル及びロイコボリンである。サリドマイド及びトポイソメラーゼ阻害剤を利用する方法での使用時、これらの2つの薬剤は特に有用である。幾つかの実施形態において、本開示の抗MSLNの単一ドメイン結合タンパク質は、ゲムシタビンと組み合わせて使用される。
本開示の他の実施形態に従い、インビトロ又はインビボでメソテリンの発現を検出するためのキットが提供される。キットは、前述のMSLN結合タンパク質(例えば、標識された抗MSLN単一ドメイン抗体又はその抗原結合フラグメント)、及びラベルを検出するための1つ以上の化合物を含む。幾つかの実施形態において、ラベルは、蛍光ラベル、酵素ラベル、放射性ラベル、核磁気共鳴活性ラベル、発光ラベル、及び発色団ラベルから成る群から選択される。
典型的な抗MSLN単一ドメイン抗体配列を、Expi293細胞(Invitrogen)へとトランスフェクトする。トランスフェクトされたExpi293細胞からの調整培地中の典型的な抗MSLN抗体の量を、プロテインAチップを備えたOctet器機を使用し、且つ標準曲線として対照抗MSLN抗体を使用して、定量する。
本開示に係るMSLN結合タンパク質を含むMSLN標的三重特異性分子の配列を、リーダー配列が先行し6xヒスチジンタグが後続する、哺乳動物発現ベクターpCDNA 3.4(Invitrogen)へとクローン化した。Expi293F細胞(Life Technologies A14527)を、Expi 293培地中の0.2~8×1e6細胞/mL間でOptimum Growth Flasks(Thomson)の懸濁液において維持した。精製されたプラスミドDNAを、Expi293 Expression System Kit(Life Technologies A14635)プロトコルに従ってExpi293細胞へとトランスフェクトし、トランスフェクション後4-6日間維持した。トランスフェクトされたExpi293細胞からの、調製培地中の試験されている典型的な三重特異性タンパク質の量を、プロテインAチップを備えたOctet器機を使用し、且つ標準曲線に対して対照の三重特異性タンパク質を使用して、定量した。
この研究は、本開示の典型的な抗体として配列修飾又は置換を持たない比較対象のラマ抗MSLN抗体と比較して、ADCCを媒介する本開示の典型的な抗MSLN単一ドメイン抗体の能力を判定することを対象とする。両方の抗体は、追加の免疫グロブリンドメインを含む多重ドメインタンパク質として発現される。
ドナーを白血球泳動し(leukophoresed)、NK細胞を、Milteni AutoMacs Proの負選択システムを使用して細胞精製群によりleukopackから単離する。NK細胞をロッカー(rocker)上で4℃で一晩保持し、その後洗浄し、計数して、ADCCアッセイでの使用のために完全RPMIにおいて4×106細胞/mLで再懸濁する。
癌細胞に対する、本開示に係る典型的な抗MSLN単一ドメイン抗体の抗腫瘍活性を評価するために、補体のソースとしてヒト血清の存在下でのA431/H9及びNCI-H226細胞モデルの細胞毒性活性を試験する。典型的な抗MSLN単一ドメイン抗体を、追加の免疫グロブリンドメインを含む多重ドメインタンパク質として発現する。本開示の典型的な抗MSLN単一ドメイン抗体を含む多重ドメインタンパク質が、A431/H9の約40%、及びNCI-H226中皮腫細胞株の30%よりも多くを死滅させることにより強力なCDC活性を及ぼし、メソテリン陰性A431細胞株に対して活性を示さないことを、確認する。本開示の典型的な抗体として配列修飾又は置換を有していない、比較対象のラマ抗MSLN抗体は、同じ濃度で活性を示さない。
ヒトT細胞依存性細胞毒性(TDCC)アッセイを使用して、T細胞が腫瘍細胞を死滅させるよう導く、三重特異性分子を含むT細胞エンゲージャー(engagers)の能力を測定した(Nazarian et al. 2015. J Biomol Screen. 20:519-27)。このアッセイに使用されるCaov3細胞を操作し、ルシフェラーゼを発現させた。5つの異なる健康なドナー(ドナー02、ドナー86、ドナー41、ドナー81、及びドナー34)からのT細胞及び標的癌細胞Caov3を共に混合し、MSLN結合ドメイン(MH6T)を含む様々な量のMSLN標的三重特異性抗原結合タンパク質(SEQ ID NO:58)を加え、混合物を37℃で48時間インキュベートした。Caov3細胞及びT細胞も、GFPを標的とする対照三重特異性分子、GFP TriTAC(SEQ ID NO:59)により37℃で48時間インキュベートした。48時間後、残る生存可能な腫瘍細胞を、発光アッセイによって定量した。
このアッセイにおいて、健康なドナーのT細胞を、MSLNを発現する標的癌細胞(Caov3細胞、Caov4細胞、OVCAR3細胞、及びOVCAR8細胞)、又はMSLNを発現しない標的癌細胞(NCI-H510A細胞、MDAPCa2b細胞)でインキュベートした。この研究に使用される標的細胞の各々を操作し、ルシフェラーゼを発現させた。MH6T(SEQ ID NO:58)ドメインを含む様々な量のMSLN標的三重特異性抗原結合性のタンパク質を、上述のT細胞と標的癌細胞の混合物に加えた。混合物を37℃で48時間インキュベートした。48時間後、残る生存可能な標的癌細胞を、発光アッセイによって定量した。
このアッセイにおいて、カニクイザルドナーからの末梢血単核球(PBMC;T細胞はPBMCの構成要素である)を、MSLNを発現する細胞(CaOV3細胞及びOVCAR3細胞)と混合し、様々な量のMSLN標的三重特異性抗原結合タンパク質(MH6Tドメイン、SEQ ID NO:58を含む)を混合物に加え、37℃で48時間インキュベートした。並行して、カニクイザルPBMC及びMSLN発現細胞の混合物を、上述のように、37℃で48時間、GFPを標的とする様々な量の対照TriTAC分子GFP TriTAC(SEQ ID NO:59)でインキュベートした。このアッセイに使用される標的癌細胞を操作し、ルシフェラーゼを発現させた。48時間後、残る生存可能な標的細胞を、発光アッセイによって定量した。
この試験の目標は、(MH6Tドメイン;SEQ ID NO:58を含む)MSLN標的三重特異性抗原結合タンパク質が、T細胞にMSLN発現細胞を死滅させるよう導くタンパク質の能力に影響を与えたかどうかを評価することであった。この研究に使用されるNCI-H2052中皮腫細胞を操作し、ルシフェラーゼを発現させた。健康なドナーのT細胞及びMSLN発現細胞(NCI-H2052)を組み合わせ、(MH6Tドメインを含む)様々な量のMSLN標的三重特異性抗原結合タンパク質を混合物に加えた。混合物をHSAの存在下又は不在下で、37℃で48時間インキュベートした。NCI-H2052細胞及びT細胞の混合物も、HSAの存在下で、GFPを標的とする対照三重特異性分子、GFP TriTAC(SEQ ID NO:59)により37℃で48時間インキュベートした。48時間後、残る生存可能な標的細胞を、発光アッセイによって定量した。
このアッセイに使用される標的癌細胞CaOv4を操作し、ルシフェラーゼを発現させた。このアッセイにおいて、4つの異なる健康なドナー(ドナー02、ドナー86、ドナー35、及びドナー81)からのT細胞及びCaov4細胞を共に混合し、(MH6Tドメイン;SEQ ID NO:58を含む)様々な量のMSLN標的三重特異性抗原結合タンパク質を加え、混合物を37℃で48時間インキュベートした。Caov4細胞及びT細胞も、GFPを標的とする対照三重特異性分子、GFP TriTAC(SEQ ID NO:59)により37℃で48時間インキュベートした。発光アッセイを使用して標的癌細胞の生存率を測定する前に、TDCCアッセイからの調整培地を48時間で集めた。調整培地中のTNF-αの濃度を、AlphaLISAアッセイキット(Perkin Elmer)を使用して測定した。
このアッセイに使用されるOVCAR8細胞を操作し、ルシフェラーゼを発現させた。このアッセイにおいて、4つの異なる健康なドナー(ドナー02、ドナー86、ドナー35、及びドナー81)からのT細胞及びOVCAR8細胞を共に混合し、(MH6Tドメイン;SEQ ID NO:58を含む)様々な量のMSLN標的三重特異性抗原結合タンパク質を加え、混合物を37℃で48時間インキュベートした。OVCAR8細胞及びT細胞も、GFPを標的とする対照三重特異性分子、GFP TriTAC(SEQ ID NO:59)により37℃で48時間インキュベートした。48時間後、T細胞を集め、T細胞上でのCD69発現をフローサイトメトリーによって測定した。
この研究のために、MSLNを発現する特定の標的癌細胞(Caov3細胞、CaOV4細胞、OVCAR3細胞、及びOVCAR8細胞)及びMSLNを発現しない特定の癌細胞(MDAPCa2b細胞及びNCI-H510A細胞)を、MSLN標的三重特異性抗原結合タンパク質(MH6Tドメイン;SEQ ID NO:58を含む)又は対照GFP TriTAC分子(SEQ ID NO:59)でインキュベートした。インキュベーションの後、細胞を洗浄し、未結合のMH6T又はGFP TriTAC分子を取り除き、Alexa Fluor 647に抱合されるTriTAC分子中の抗アルブミンドメインを認識できる二次抗体で更にインキュベートした。(MH6Tドメインを含む)MSLN標的三重特異性抗原結合タンパク質の結合、又はMSLN発現又は非MSLN発現細胞へのGFP TriTACの結合を、フローサイトメトリーによって測定した。
この研究のために、4つの健康なドナーからのT細胞を、陰性対照として、(MH6Tドメイン;SEQ ID NO:58を含む)MSLN標的三重特異性抗原結合タンパク質又は緩衝液でインキュベートした。インキュベーションの後、細胞を洗浄し、未結合の(MH6Tドメインを含む)MSLN標的三重特異性抗原結合タンパク質を取り除き、(MH6Tドメインを含む)MSLN標的三重特異性抗原結合タンパク質中の抗アルブミンドメインを認識できる、Alexa Fluor 647を抱合した二次抗体で更にインキュベートした。結合をフローサイトメトリーによって測定した。
この研究のために、107のNCI-H292細胞及び107のヒトPBMCを、NCGマウスの2つの群(群ごとに8匹のマウス)において共に皮下移植した。5日後、1つの群のマウスに、(MH6Tドメイン;SEQ ID NO:58を含む)MSLN標的三重特異性抗原結合タンパク質を、10日間毎日(5-14日目)、0.25mg/kgの投与量で注入し;他の群のマウスにはビヒクル対照を注入した。腫瘍堆積を数日毎に測定し、36日目に試験を終了した。図11に示されるように、ビヒクル対照を注入されたマウスと比較して腫瘍成長の有意な阻害を、(MH6Tドメインを含む)MSLN標的三重特異性抗原結合タンパク質を注入されたマウスにおいて観察した。
この研究のために、2匹のカニクイザルに、10mg/kgの投与量の(MH6Tドメイン;SEQ ID NO:58を含む)MSLN標的三重特異性抗原結合タンパク質を静脈内注入し、血清サンプルを注入後の様々な時点で集めた。血清中の(MH6Tドメインを含む)MSLN標的三重特異性抗原結合タンパク質の量を、電気化学発光(electrochemiluminescient)アッセイにおいて、(MH6Tドメインを含む)MSLN標的三重特異性抗原結合タンパク質を認識する抗イディオタイプ抗体を使用して測定した。図12は、様々な時点での血清の(MH6Tドメインを含む)MSLN標的三重特異性抗原結合タンパク質レベルのプロットを示す。その後、データを使用して、表VIIに提供されるように(MH6Tドメインを含む)MSLN標的三重特異性抗原結合タンパク質の薬物動態特性を算出した。
Claims (18)
- 以下の式を含む、単一ドメインメソテリン結合タンパク質であって、
f1-r1-f2-r2-f3-r3-f4
式中、r1はCDR1であり、r2はCDR2であり、及びr3はCDR3であり、ならびに、f1、f2、f3、及びf4はフレームワーク残基であり、ならびに、
(i)CDR1は配列GSTFSIRAMR(SEQ ID NO:88、及び96-98の何れか1つ)であり、CDR2は配列VIYGSSTYYADAVKGRFT(SEQ ID NO:127、及び135-137の何れか1つ)であり、及びCDR3は配列DTIGTARDY(SEQ ID NO:166、及び174-176の何れか1つ)であり、
(ii)CDR1は配列GRTSTIDTMY(SEQ ID NO:89、及び99-101の何れか1つ)であり、CDR2は配列YVTSRGTSNVADSVKGRFT(SEQ ID NO:128、及び138-140の何れか1つ)であり、及びCDR3は配列RTTSYPVDF(SEQ ID NO:167、及び177-179の何れか1つ)であり、
(iii)CDR1は配列GSTSSINTMY(SEQ ID NO:82、86、90、及び93-95の何れか1つ)であり、CDR2は配列FISSGGSTNVRDSVKGRFT(SEQ ID NO:132-134の何れか1つ)であり、及びCDR3は配列YIPYGGTLHDF(SEQ ID NO:164、168、及び171-173の何れか1つ)であり、
(iv)CDR1は配列GGDWSANFMY(SEQ ID NO:54、及び91-92の何れか1つ)であり、CDR2は配列RISGRGVVDYVESVKGRFT(SEQ ID NO:130、又は131)であり、及びCDR3は配列ASY(SEQ ID NO:169又は170)であり、又は、
(v)CDR1は配列GSTFRIRVMR(SEQ ID NO:79)であり、CDR2は配列VISGSSTYYADSVKGRFT(SEQ ID NO:118)であり、及びCDR3は配列DDSGIARDY(SEQ ID NO:157)である、
単一ドメインメソテリン結合タンパク質。 - 前記単一ドメインメソテリン結合タンパク質はメソテリンのエピトープに結合し、前記エピトープは、SEQ ID NO:57のアミノ酸残基296-390を含む領域I、SEQ ID NO:57のアミノ酸残基391-486を含む領域II、又はSEQ ID NO:57のアミノ酸残基487-598を含む領域IIIに位置する、ことを特徴とする請求項1に記載の単一ドメインメソテリン結合タンパク質。
- 前記単一ドメインメソテリン結合タンパク質は、SEQ ID NO:17、26、27、32-40、58、及び60-62の何れか1つのアミノ酸配列を含む、ことを特徴とする請求項1に記載の単一ドメインメソテリン結合タンパク質。
- f1は、SEQ ID NO:196、205、及び208-218の何れか1つの配列を含む、ことを特徴とする請求項1に記載の単一ドメインメソテリン結合タンパク質。
- f2は、SEQ ID NO:235、244、及び247-257の何れか1つの配列を含む、ことを特徴とする請求項1に記載の単一ドメインメソテリン結合タンパク質。
- f3は、SEQ ID NO:274、283、及び286-296の何れか1つの配列を含む、ことを特徴とする請求項1に記載の単一ドメインメソテリン結合タンパク質。
- f4は、SEQ ID NO:313、322、及び325-335の何れか1つの配列を含む、ことを特徴とする請求項1に記載の単一ドメインメソテリン結合タンパク質。
- SEQ ID NO:17、26、27、32-40、58、及び60-62の何れか1つのアミノ酸配列を含む、単一ドメインメソテリン結合タンパク質。
- 必要とする被験体において、メソテリンを発現する増殖性疾患又は腫瘍疾患の処置あるいは改善に使用される、ことを特徴とする請求項1に記載の単一ドメインメソテリン結合タンパク質を含む医薬組成物。
- 前記単一ドメインメソテリン結合タンパク質が最大10mg/kgの用量で、前記被験体への投与のために製剤化される、ことを特徴とする請求項9に記載の医薬組成物。
- 前記医薬組成物は、週に1回、週に2回、隔日、又は3週間に1回の、前記被験体への投与のために製剤化される、ことを特徴とする請求項10に記載の医薬組成物。
- 前記被験体はヒトである、ことを特徴とする請求項11に記載の医薬組成物。
- 前記単一ドメインメソテリン結合タンパク質は、薬剤と組み合わせて、前記被験体への投与のために製剤化される、ことを特徴とする請求項9に記載の医薬組成物。
- 前記単一ドメインメソテリン結合タンパク質は、メソテリンを発現する腫瘍細胞に選択的に結合する、ことを特徴とする請求項9に記載の医薬組成物。
- 前記単一ドメインメソテリン結合タンパク質は、メソテリンを発現する腫瘍細胞のT細胞死滅を媒介する、ことを特徴とする請求項14に記載の医薬組成物。
- 前記腫瘍疾患は固形腫瘍疾患を含む、ことを特徴とする請求項15に記載の医薬組成物。
- 前記固形腫瘍疾患は、中皮腫、肺癌、胃癌、卵巣癌、又は三種陰性乳癌を含む、ことを特徴とする請求項16に記載の医薬組成物。
- 前記固形腫瘍疾患は転移性である、ことを特徴とする請求項17に記載の医薬組成物。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016187594A1 (en) | 2015-05-21 | 2016-11-24 | Harpoon Therapeutics, Inc. | Trispecific binding proteins and methods of use |
WO2017201488A1 (en) | 2016-05-20 | 2017-11-23 | Harpoon Therapeutics, Inc. | Single domain serum albumin binding protein |
US10544221B2 (en) | 2016-05-20 | 2020-01-28 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
US11623958B2 (en) | 2016-05-20 | 2023-04-11 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
ES2875959T3 (es) | 2016-10-07 | 2021-11-11 | Tcr2 Therapeutics Inc | Composiciones y métodos para reprogramación de receptores de linfocitos T mediante el uso de proteínas de fusión |
WO2018098354A1 (en) | 2016-11-23 | 2018-05-31 | Harpoon Therapeutics, Inc. | Prostate specific membrane antigen binding protein |
EP3544629A4 (en) | 2016-11-23 | 2020-06-17 | Harpoon Therapeutics, Inc. | TRISPECIFIC PROTEINS CIBLANG PSMA AND METHODS OF USE |
US11535668B2 (en) | 2017-02-28 | 2022-12-27 | Harpoon Therapeutics, Inc. | Inducible monovalent antigen binding protein |
US10730954B2 (en) | 2017-05-12 | 2020-08-04 | Harpoon Therapeutics, Inc. | MSLN targeting trispecific proteins and methods of use |
US20200270362A1 (en) * | 2017-05-12 | 2020-08-27 | Harpoon Therapeutics, Inc. | Msln targeting trispecific proteins and methods of use |
CN113896792A (zh) | 2017-05-12 | 2022-01-07 | 哈普恩治疗公司 | 间皮素结合蛋白质 |
MX2020003856A (es) | 2017-10-13 | 2020-08-13 | Harpoon Therapeutics Inc | Proteinas de union a antigenos de maduracion de celulas b. |
MX2020003915A (es) | 2017-10-13 | 2020-10-08 | Harpoon Therapeutics Inc | Proteinas trispecificas y metodos de uso. |
CA3114038A1 (en) | 2018-09-25 | 2020-04-02 | Harpoon Therapeutics, Inc. | Dll3 binding proteins and methods of use |
WO2020146182A1 (en) * | 2019-01-08 | 2020-07-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Cross-species single domain antibodies targeting mesothelin for treating solid tumors |
CN113508134A (zh) * | 2019-02-22 | 2021-10-15 | 安维达生物科技公司 | 白蛋白结合抗体及其用途 |
KR20220008866A (ko) * | 2019-05-14 | 2022-01-21 | 하푼 테라퓨틱스, 인크. | EpCAM 결합 단백질 및 사용 방법 |
TW202128961A (zh) | 2019-11-20 | 2021-08-01 | 美商安維塔生物科學股份有限公司 | 細胞激素融合蛋白及其醫藥組合物及治療應用 |
EP4106806A1 (en) | 2020-02-21 | 2022-12-28 | Harpoon Therapeutics, Inc. | Flt3 binding proteins and methods of use |
AU2022279862B2 (en) | 2021-05-26 | 2024-02-29 | Cellengene Inc | Chimeric antigen receptor comprising anti-mesothelin scfv, and use thereof |
TW202317625A (zh) | 2021-06-17 | 2023-05-01 | 德商百靈佳殷格翰國際股份有限公司 | 新穎三特異性結合分子 |
WO2023153711A1 (ko) * | 2022-02-10 | 2023-08-17 | 경북대학교 산학협력단 | 메소세린에 결합하는 펩타이드 및 이의 용도 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016500655A (ja) | 2012-09-27 | 2016-01-14 | ザ・ユナイテッド・ステイツ・オブ・アメリカ・アズ・リ | メソテリン抗体および強力な抗腫瘍活性を惹起するための方法 |
WO2018067993A1 (en) | 2016-10-07 | 2018-04-12 | TCR2 Therapeutics Inc. | Compositions and methods for t-cell receptors reprogramming using fusion proteins |
Family Cites Families (369)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR901228A (fr) | 1943-01-16 | 1945-07-20 | Deutsche Edelstahlwerke Ag | Système d'aimant à entrefer annulaire |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4943533A (en) | 1984-03-01 | 1990-07-24 | The Regents Of The University Of California | Hybrid cell lines that produce monoclonal antibodies to epidermal growth factor receptor |
US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US6303121B1 (en) | 1992-07-30 | 2001-10-16 | Advanced Research And Technology | Method of using human receptor protein 4-1BB |
US6355476B1 (en) | 1988-11-07 | 2002-03-12 | Advanced Research And Technologyinc | Nucleic acid encoding MIP-1α Lymphokine |
US6362325B1 (en) | 1988-11-07 | 2002-03-26 | Advanced Research And Technology Institute, Inc. | Murine 4-1BB gene |
US6905680B2 (en) | 1988-11-23 | 2005-06-14 | Genetics Institute, Inc. | Methods of treating HIV infected subjects |
US6534055B1 (en) | 1988-11-23 | 2003-03-18 | Genetics Institute, Inc. | Methods for selectively stimulating proliferation of T cells |
US5858358A (en) | 1992-04-07 | 1999-01-12 | The United States Of America As Represented By The Secretary Of The Navy | Methods for selectively stimulating proliferation of T cells |
US6352694B1 (en) | 1994-06-03 | 2002-03-05 | Genetics Institute, Inc. | Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
US5399346A (en) | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
US5585362A (en) | 1989-08-22 | 1996-12-17 | The Regents Of The University Of Michigan | Adenovirus vectors for gene therapy |
US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
US5061620A (en) | 1990-03-30 | 1991-10-29 | Systemix, Inc. | Human hematopoietic stem cell |
EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
US5199942A (en) | 1991-06-07 | 1993-04-06 | Immunex Corporation | Method for improving autologous transplantation |
LU91067I2 (fr) | 1991-06-14 | 2004-04-02 | Genentech Inc | Trastuzumab et ses variantes et dérivés immuno chimiques y compris les immotoxines |
US5851795A (en) | 1991-06-27 | 1998-12-22 | Bristol-Myers Squibb Company | Soluble CTLA4 molecules and uses thereof |
ES2136092T3 (es) | 1991-09-23 | 1999-11-16 | Medical Res Council | Procedimientos para la produccion de anticuerpos humanizados. |
AU2764792A (en) | 1991-10-04 | 1993-05-03 | Iit Research Institute | Conversion of plastic waste to useful oils |
GB9125768D0 (en) | 1991-12-04 | 1992-02-05 | Hale Geoffrey | Therapeutic method |
JP4157160B2 (ja) | 1991-12-13 | 2008-09-24 | ゾーマ テクノロジー リミテッド | 改変抗体可変領域の調製のための方法 |
ES2162823T5 (es) | 1992-08-21 | 2010-08-09 | Vrije Universiteit Brussel | Inmunoglobulinas desprovistas de cadenas ligeras. |
US6005079A (en) | 1992-08-21 | 1999-12-21 | Vrije Universiteit Brussels | Immunoglobulins devoid of light chains |
US5350674A (en) | 1992-09-04 | 1994-09-27 | Becton, Dickinson And Company | Intrinsic factor - horse peroxidase conjugates and a method for increasing the stability thereof |
US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
EP1005870B1 (en) | 1992-11-13 | 2009-01-21 | Biogen Idec Inc. | Therapeutic application of chimeric antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma |
AU2071695A (en) | 1994-03-17 | 1995-10-03 | Merck Patent Gmbh | Anti-EGFR single-chain FVS and anti-EGFR antibodies |
US7175843B2 (en) | 1994-06-03 | 2007-02-13 | Genetics Institute, Llc | Methods for selectively stimulating proliferation of T cells |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
US7067318B2 (en) | 1995-06-07 | 2006-06-27 | The Regents Of The University Of Michigan | Methods for transfecting T cells |
US6692964B1 (en) | 1995-05-04 | 2004-02-17 | The United States Of America As Represented By The Secretary Of The Navy | Methods for transfecting T cells |
US5773292A (en) | 1995-06-05 | 1998-06-30 | Cornell University | Antibodies binding portions, and probes recognizing an antigen of prostate epithelial cells but not antigens circulating in the blood |
US7060808B1 (en) | 1995-06-07 | 2006-06-13 | Imclone Systems Incorporated | Humanized anti-EGF receptor monoclonal antibody |
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 |
US6051227A (en) | 1995-07-25 | 2000-04-18 | The Regents Of The University Of California, Office Of Technology Transfer | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling |
US6107090A (en) | 1996-05-06 | 2000-08-22 | Cornell Research Foundation, Inc. | Treatment and diagnosis of prostate cancer with antibodies to extracellur PSMA domains |
US6136311A (en) | 1996-05-06 | 2000-10-24 | Cornell Research Foundation, Inc. | Treatment and diagnosis of cancer |
DK0826696T3 (da) | 1996-09-03 | 2002-09-23 | Gsf Forschungszentrum Umwelt | Anvendelse af bi- og trispecifikke antistoffer til inducering af en tumorimmunitet |
WO1998016249A1 (en) | 1996-10-11 | 1998-04-23 | Bristol-Myers Squibb Company | Methods and compositions for immunomodulation |
AU2152299A (en) | 1997-10-27 | 1999-05-24 | Unilever Plc | Multivalent antigen-binding proteins |
AU3596599A (en) | 1998-01-26 | 1999-08-09 | Unilever Plc | Method for producing antibody fragments |
HUP9900956A2 (hu) | 1998-04-09 | 2002-04-29 | Aventis Pharma Deutschland Gmbh. | Egyláncú, több antigéntkötőhely kialakítására képes molekulák, előállításuk és alkalmazásuk |
EE05627B1 (et) | 1998-12-23 | 2013-02-15 | Pfizer Inc. | CTLA-4 vastased inimese monoklonaalsed antikehad |
ATE276359T1 (de) | 1999-01-19 | 2004-10-15 | Unilever Nv | Verfahren zur herstellung von antikörperfragmenten |
HU228477B1 (en) | 1999-08-23 | 2013-03-28 | Dana Farber Cancer Inst Inc | Pd-1, a receptor for b7-4, and uses therefor |
CN1371416B (zh) | 1999-08-24 | 2012-10-10 | 梅达里克斯公司 | 人ctla-4抗体及其应用 |
US7605238B2 (en) | 1999-08-24 | 2009-10-20 | Medarex, Inc. | Human CTLA-4 antibodies and their uses |
CA2388298C (en) | 1999-10-28 | 2013-05-14 | Seyedhossein Aharinejad | The use of csf-1 inhibitors |
US6326193B1 (en) | 1999-11-05 | 2001-12-04 | Cambria Biosciences, Llc | Insect control agent |
US20060228364A1 (en) | 1999-12-24 | 2006-10-12 | Genentech, Inc. | Serum albumin binding peptides for tumor targeting |
WO2001054732A1 (en) | 2000-01-27 | 2001-08-02 | Genetics Institute, Llc. | Antibodies against ctla4 (cd152), conjugates comprising same, and uses thereof |
US6797514B2 (en) | 2000-02-24 | 2004-09-28 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
US7572631B2 (en) | 2000-02-24 | 2009-08-11 | Invitrogen Corporation | Activation and expansion of T cells |
US6867041B2 (en) | 2000-02-24 | 2005-03-15 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
ATE373078T1 (de) | 2000-02-24 | 2007-09-15 | Xcyte Therapies Inc | Gleichzeitige stimulation und konzentration von zellen |
AU2001268855A1 (en) | 2000-05-26 | 2001-12-03 | National Research Council Of Canada | Single-domain antigen-binding antibody fragments derived from llama antibodies |
AU2001275474A1 (en) | 2000-06-12 | 2001-12-24 | Akkadix Corporation | Materials and methods for the control of nematodes |
GB0100621D0 (en) | 2001-01-10 | 2001-02-21 | Vernalis Res Ltd | Chemical compounds VI |
CN1294148C (zh) | 2001-04-11 | 2007-01-10 | 中国科学院遗传与发育生物学研究所 | 环状单链三特异抗体 |
GB0110029D0 (en) | 2001-04-24 | 2001-06-13 | Grosveld Frank | Transgenic animal |
CN1195779C (zh) | 2001-05-24 | 2005-04-06 | 中国科学院遗传与发育生物学研究所 | 抗人卵巢癌抗人cd3双特异性抗体 |
US7666414B2 (en) | 2001-06-01 | 2010-02-23 | Cornell Research Foundation, Inc. | Methods for treating prostate cancer using modified antibodies to prostate-specific membrane antigen |
IL159225A0 (en) | 2001-06-13 | 2004-06-01 | Genmab As | Human monoclonal antibodies to epidermal growth factor receptor (egfr) |
US7595378B2 (en) | 2001-06-13 | 2009-09-29 | Genmab A/S | Human monoclonal antibodies to epidermal growth factor receptor (EGFR) |
EP1433793A4 (en) | 2001-09-13 | 2006-01-25 | Inst Antibodies Co Ltd | METHOD FOR CREATING A CAMEL ANTIBODY LIBRARY |
US20050215472A1 (en) | 2001-10-23 | 2005-09-29 | Psma Development Company, Llc | PSMA formulations and uses thereof |
ES2606537T3 (es) | 2001-10-23 | 2017-03-24 | Psma Development Company L.L.C. | Anticuerpos contra PSMA |
JP2005289809A (ja) | 2001-10-24 | 2005-10-20 | Vlaams Interuniversitair Inst Voor Biotechnologie Vzw (Vib Vzw) | 突然変異重鎖抗体 |
US7745140B2 (en) | 2002-01-03 | 2010-06-29 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an engineered multivalent signaling platform as a research tool |
JP2005518789A (ja) | 2002-01-28 | 2005-06-30 | メダレックス, インク. | 前立腺特異性膜抗原(psma)に対するヒトモノクローナル抗体 |
US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
SI1507556T1 (sl) | 2002-05-02 | 2016-10-28 | Wyeth Holdings Llc | Konjugati kaliheamicinski derivat-nosilec |
DK1517921T3 (da) | 2002-06-28 | 2006-10-09 | Domantis Ltd | Immunglobulin-enkeltvariable antigen-bindende domæner og dobbeltspecifikke konstruktioner deraf |
US9321832B2 (en) | 2002-06-28 | 2016-04-26 | Domantis Limited | Ligand |
US6887673B2 (en) | 2002-07-30 | 2005-05-03 | Bristol-Myers Squibb Company | Humanized antibodies against human 4-1BB |
NZ581541A (en) | 2002-10-17 | 2011-07-29 | Genmab As | Human monoclonal antibodies against CD20 |
ZA200503075B (en) | 2002-11-07 | 2006-09-27 | Immunogen Inc | Anti-CD33 antibodies and method for treatment of acute myeloid leukemia using the same |
AU2003283860B2 (en) | 2002-11-07 | 2009-09-17 | Erasmus Universiteit Rotterdam | Fret probes and methods for detecting interacting molecules |
US9320792B2 (en) | 2002-11-08 | 2016-04-26 | Ablynx N.V. | Pulmonary administration of immunoglobulin single variable domains and constructs thereof |
EP1558646A2 (en) | 2002-11-08 | 2005-08-03 | Ablynx N.V. | Single domain antibodies directed against interferon- gamma and uses thereof |
EP2316852B1 (en) | 2002-11-08 | 2014-03-05 | Ablynx N.V. | Stabilized single domain antibodies |
ES2466716T3 (es) | 2002-11-08 | 2014-06-11 | Ablynx N.V. | Anticuerpos de un solo dominio estabilizados |
GB0228210D0 (en) | 2002-12-03 | 2003-01-08 | Babraham Inst | Single chain antibodies |
CN103833854B (zh) | 2002-12-16 | 2017-12-12 | 健泰科生物技术公司 | 免疫球蛋白变体及其用途 |
WO2004056875A1 (en) | 2002-12-23 | 2004-07-08 | Wyeth | Antibodies against pd-1 and uses therefor |
ATE455127T1 (de) | 2003-05-31 | 2010-01-15 | Micromet Ag | Humane anti-humane cd3-bindungsmoleküle |
AU2004255216B2 (en) | 2003-07-01 | 2010-08-19 | Immunomedics, Inc. | Multivalent carriers of bi-specific antibodies |
CN103467602B (zh) | 2003-07-02 | 2018-04-10 | 依奈特制药公司 | 用于调节nk细胞活性的组合物和方法 |
CN104645327A (zh) | 2003-07-24 | 2015-05-27 | 依奈特制药公司 | 使用nk细胞增效化合物提高治疗性抗体功效的方法和组合物 |
EP2272566A3 (en) | 2003-08-18 | 2013-01-02 | MedImmune, LLC | Humanisation of antibodies |
US20050042664A1 (en) | 2003-08-22 | 2005-02-24 | Medimmune, Inc. | Humanization of antibodies |
US7288638B2 (en) | 2003-10-10 | 2007-10-30 | Bristol-Myers Squibb Company | Fully human antibodies against human 4-1BB |
CN100376599C (zh) | 2004-04-01 | 2008-03-26 | 北京安波特基因工程技术有限公司 | 基因工程重组抗cea抗cd3抗cd28线性单链三特异抗体 |
AU2005250408B2 (en) | 2004-05-27 | 2010-09-23 | The Trustees Of The University Of Pennsylvania | Novel artificial antigen presenting cells and uses therefor |
KR20070039911A (ko) | 2004-06-01 | 2007-04-13 | 도만티스 리미티드 | 증강된 혈청 반감기를 가지는 이특이성 융합 항체 |
JP2008512352A (ja) | 2004-07-17 | 2008-04-24 | イムクローン システムズ インコーポレイティド | 新規な四価の二重特異性抗体 |
US20080069772A1 (en) | 2004-08-26 | 2008-03-20 | Eberhard-Karls-Universitaet Tuebingen Universitaetsklinikum | Treatment of transformed or infected biological cells |
EP1634603A1 (de) | 2004-08-26 | 2006-03-15 | Eberhard-Karls-Universität Tübingen Universitätsklinikum | Behandlung von transformierten oder infizierten biologischen Zellen |
FR2879605B1 (fr) | 2004-12-16 | 2008-10-17 | Centre Nat Rech Scient Cnrse | Production de formats d'anticorps et applications immunologiques de ces formats |
KR20130105885A (ko) | 2005-01-05 | 2013-09-26 | 에프-스타 비오테크놀로기쉐 포르슝스 운드 엔트비클룽스게스.엠.베.하. | 상보성 결정부위와 다른 분자의 부위에서 처리된 결합성을 갖는 합성 면역글로불린 영역 |
EP3072522B1 (en) | 2005-01-06 | 2019-04-24 | Novo Nordisk A/S | Anti-kir combination treatments and methods |
JP5295568B2 (ja) | 2005-01-06 | 2013-09-18 | ノヴォ ノルディスク アー/エス | Kir結合剤およびその使用方法 |
DK1866339T3 (da) | 2005-03-25 | 2013-09-02 | Gitr Inc | GTR-bindende molekyler og anvendelser heraf |
US7833979B2 (en) | 2005-04-22 | 2010-11-16 | Amgen Inc. | Toxin peptide therapeutic agents |
US20060252096A1 (en) | 2005-04-26 | 2006-11-09 | Glycofi, Inc. | Single chain antibody with cleavable linker |
CA2607147C (en) | 2005-05-09 | 2018-07-17 | Ono Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1 (pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics |
PL1888640T3 (pl) | 2005-05-18 | 2012-08-31 | Ablynx Nv | Ulepszone nanociała skierowane przeciwko czynnikowi martwicy nowotworów typu alfa |
PT2444424T (pt) | 2005-05-20 | 2018-11-09 | Ablynx Nv | Nanocorpos tm aperfeiçoados para o tratamento de distúrbios mediados por agregação |
EP1726650A1 (en) | 2005-05-27 | 2006-11-29 | Universitätsklinikum Freiburg | Monoclonal antibodies and single chain antibody fragments against cell-surface prostate specific membrane antigen |
JP5252635B2 (ja) | 2005-07-01 | 2013-07-31 | 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 |
MY169746A (en) | 2005-08-19 | 2019-05-14 | Abbvie Inc | Dual variable domain immunoglobulin and uses thereof |
JP5686953B2 (ja) | 2005-10-11 | 2015-03-18 | アムゲン リサーチ (ミュンヘン) ゲーエムベーハー | 交差種特異的(cross−species−specific)抗体を含む組成物および該組成物の使用 |
EP1934260B1 (en) | 2005-10-14 | 2017-05-17 | Innate Pharma | Compositions and methods for treating proliferative disorders |
GB0521991D0 (en) | 2005-10-28 | 2005-12-07 | Univ Dundee | Siglec-9 binding agents |
CA2629095A1 (en) | 2005-11-12 | 2007-05-24 | Eli Lily And Company | Anti-egfr antibodies |
US8623356B2 (en) | 2005-11-29 | 2014-01-07 | The University Of Sydney | Demibodies: dimerization-activated therapeutic agents |
US7498142B2 (en) | 2006-01-31 | 2009-03-03 | Yeda Research And Development Co., Ltd. | Methods of identifying combinations of antibodies with an improved anti-tumor activity and compositions and methods using the antibodies |
WO2007115230A2 (en) | 2006-03-30 | 2007-10-11 | University Of Medicine And Dentistry Of New Jersey | A strategy for homo- or hetero-dimerization of various proteins in solutions and in cells |
WO2007113648A2 (en) | 2006-04-05 | 2007-10-11 | Pfizer Products Inc. | Ctla4 antibody combination therapy |
US20070269422A1 (en) | 2006-05-17 | 2007-11-22 | Ablynx N.V. | Serum albumin binding proteins with long half-lives |
WO2008020079A1 (en) | 2006-08-18 | 2008-02-21 | Ablynx N.V. | Amino acid sequences directed against il-6r and polypeptides comprising the same for the treatment of deseases and disorders associated with il-6-mediated signalling |
US20100113339A1 (en) | 2006-09-08 | 2010-05-06 | Ablynx N. V. | Serum albumin binding proteins with long half-lives |
US20100166734A1 (en) | 2006-12-20 | 2010-07-01 | Edward Dolk | Oral delivery of polypeptides |
US20100189723A1 (en) | 2007-01-11 | 2010-07-29 | Peter Andreas Nicolai Reumert Wagtmann | Anti-kir antibodies, formulations, and uses thereof |
TR201816277T4 (tr) | 2007-04-03 | 2018-11-21 | Amgen Res Munich Gmbh | Çapraz-tür-spesifik bağlama alanı. |
JP2008278814A (ja) | 2007-05-11 | 2008-11-20 | Igaku Seibutsugaku Kenkyusho:Kk | アゴニスティック抗ヒトgitr抗体による免疫制御の解除とその応用 |
KR101264473B1 (ko) | 2007-05-24 | 2013-05-29 | 아블린쓰 엔.브이. | Rank-l에 대한 아미노산 서열, 및 이를 포함하는 골 질환 및 장애 치료용 폴리펩티드 |
CN104945508B (zh) | 2007-06-18 | 2019-02-22 | 默沙东有限责任公司 | 针对人程序性死亡受体pd-1的抗体 |
EP2014680A1 (en) | 2007-07-10 | 2009-01-14 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Recombinant, single-chain, trivalent tri-specific or bi-specific antibody derivatives |
CA2693677C (en) | 2007-07-12 | 2018-02-13 | Tolerx, Inc. | Combination therapies employing gitr binding molecules |
EP2487190A3 (en) | 2007-07-13 | 2012-11-14 | Bac Ip B.V. | Single-domain antigen-binding proteins that bind mammalian IgG |
WO2009025846A2 (en) | 2007-08-22 | 2009-02-26 | The Regents Of The University Of California | Activatable binding polypeptides and methods of identification and use thereof |
EP2195342A1 (en) | 2007-09-07 | 2010-06-16 | Ablynx N.V. | Binding molecules with multiple binding sites, compositions comprising the same and uses thereof |
ES2622460T3 (es) | 2007-09-26 | 2017-07-06 | Ucb Biopharma Sprl | Fusiones de anticuerpos con doble especificidad |
JP5774312B2 (ja) | 2008-01-24 | 2015-09-09 | ノボ・ノルデイスク・エー/エス | ヒト化抗ヒトnkg2aモノクローナル抗体 |
CN104548091A (zh) | 2008-02-11 | 2015-04-29 | 治疗科技公司 | 用于肿瘤治疗的单克隆抗体 |
US8168757B2 (en) | 2008-03-12 | 2012-05-01 | Merck Sharp & Dohme Corp. | PD-1 binding proteins |
EP3424526A1 (en) | 2008-06-05 | 2019-01-09 | Ablynx NV | Immunoglobulin single variable domains binding to the g envelope protein of rabies virus and uses thereof for the treatment and prevention of rabies |
US20100122358A1 (en) * | 2008-06-06 | 2010-05-13 | Crescendo Biologics Limited | H-Chain-only antibodies |
NZ590667A (en) | 2008-07-02 | 2013-01-25 | Emergent Product Dev Seattle | Tgf-b antagonist multi-target binding proteins |
US8444976B2 (en) | 2008-07-02 | 2013-05-21 | Argen-X B.V. | Antigen binding polypeptides |
DE102008036127A1 (de) | 2008-08-01 | 2010-02-04 | Emitec Gesellschaft Für Emissionstechnologie Mbh | Verfahren zum Betrieb einer Abgasanlage mit Lambda-Regelung |
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 |
EP2350129B1 (en) | 2008-08-25 | 2015-06-10 | Amplimmune, Inc. | Compositions of pd-1 antagonists and methods of use |
BRPI0917891A2 (pt) | 2008-08-25 | 2015-11-24 | Amplimmune Inc | antagonistas de pd-1 e métodos de utilização dos mesmos |
PT2352763E (pt) | 2008-10-01 | 2016-06-02 | Amgen Res (Munich) Gmbh | Anticorpos biespecíficos de cadeia única com especificidade para antigénios-alvo com elevado peso molecular |
WO2010037838A2 (en) | 2008-10-01 | 2010-04-08 | Micromet Ag | Cross-species-specific single domain bispecific single chain antibody |
CA2738565C (en) | 2008-10-01 | 2023-10-10 | Micromet Ag | Cross-species-specific psmaxcd3 bispecific single chain antibody |
US9327022B2 (en) | 2008-10-14 | 2016-05-03 | National Research Council Of Canada | BSA-specific antibodies |
US8709411B2 (en) | 2008-12-05 | 2014-04-29 | Novo Nordisk A/S | Combination therapy to enhance NK cell mediated cytotoxicity |
WO2010077643A1 (en) | 2008-12-08 | 2010-07-08 | Tegopharm Corporation | Masking ligands for reversible inhibition of multivalent compounds |
LT4209510T (lt) | 2008-12-09 | 2024-03-12 | F. Hoffmann-La Roche Ag | Anti-pd-l1 antikūnai ir jų panaudojimas t ląstelių funkcijos pagerinimui |
EP3543256A1 (en) | 2009-01-12 | 2019-09-25 | Cytomx Therapeutics Inc. | Modified antibody compositions, methods of making and using thereof |
EP2210902A1 (en) | 2009-01-14 | 2010-07-28 | TcL Pharma | Recombinant monovalent antibodies |
EP2393835B1 (en) | 2009-02-09 | 2017-04-05 | Université d'Aix-Marseille | Pd-1 antibodies and pd-l1 antibodies and uses thereof |
EP2772269A3 (en) | 2009-03-05 | 2015-01-14 | Abbvie Inc. | IL-17 binding proteins |
CN102574924A (zh) | 2009-09-03 | 2012-07-11 | 先灵公司 | 抗-gitr抗体 |
US20110195494A1 (en) | 2009-10-02 | 2011-08-11 | Boehringer Ingelheim International Gmbh | Dll4-binging molecules |
WO2011051327A2 (en) | 2009-10-30 | 2011-05-05 | Novartis Ag | Small antibody-like single chain proteins |
EP2504028A4 (en) | 2009-11-24 | 2014-04-09 | Amplimmune Inc | SIMULTANEOUS INHIBITION OF PD-L1 / PD-L2 |
RU2016105962A (ru) | 2009-12-04 | 2018-11-23 | Дженентек, Инк. | Мультиспецифические антитела, аналоги антител, композиции и способы |
EP2332994A1 (en) | 2009-12-09 | 2011-06-15 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Trispecific therapeutics against acute myeloid leukaemia |
RS58693B1 (sr) | 2009-12-10 | 2019-06-28 | Hoffmann La Roche | Antitela koja poželjno vezuju ekstracelularni domen 4 humanog csf1r, i njihova primena |
WO2011090762A1 (en) | 2009-12-29 | 2011-07-28 | Emergent Product Development Seattle, Llc | Heterodimer binding proteins and uses thereof |
GB2476681B (en) | 2010-01-04 | 2012-04-04 | Argen X Bv | Humanized camelid VH, VK and VL immunoglobulin domains |
KR101656548B1 (ko) | 2010-03-05 | 2016-09-09 | 에프. 호프만-라 로슈 아게 | 인간 csf-1r에 대한 항체 및 이의 용도 |
EP2542588A1 (en) | 2010-03-05 | 2013-01-09 | F. Hoffmann-La Roche AG | Antibodies against human csf-1r and uses thereof |
EP2550529B1 (en) | 2010-03-23 | 2021-11-17 | Iogenetics, LLC. | Bioinformatic processes for determination of peptide binding |
US8937164B2 (en) | 2010-03-26 | 2015-01-20 | Ablynx N.V. | Biological materials related to CXCR7 |
US9556273B2 (en) | 2010-03-29 | 2017-01-31 | Vib Vzw | Anti-macrophage mannose receptor single variable domains for targeting and in vivo imaging of tumor-associated macrophages |
TWI713942B (zh) | 2010-05-04 | 2020-12-21 | 美商戊瑞治療有限公司 | 與集落刺激因子1受體(csf1r)結合之抗體類 |
TWI629483B (zh) | 2010-06-11 | 2018-07-11 | 協和醱酵麒麟有限公司 | anti-TIM-3 antibody |
WO2012009568A2 (en) | 2010-07-16 | 2012-01-19 | Adimab, Llc | Antibody libraries |
CA2807664A1 (en) | 2010-08-12 | 2012-02-16 | Theraclone Sciences, Inc. | Anti-hemagglutinin antibody compositions and methods of use thereof |
CA2807269A1 (en) | 2010-08-24 | 2012-03-01 | Roche Glycart Ag | Activatable bispecific antibodies |
WO2012025530A1 (en) | 2010-08-24 | 2012-03-01 | F. Hoffmann-La Roche Ag | Bispecific antibodies comprising a disulfide stabilized - fv fragment |
WO2012042026A1 (en) | 2010-09-30 | 2012-04-05 | Ablynx Nv | Biological materials related to c-met |
WO2012066058A1 (en) | 2010-11-16 | 2012-05-24 | Boehringer Ingelheim International Gmbh | Agents and methods for treating diseases that correlate with bcma expression |
AR083957A1 (es) | 2010-11-22 | 2013-04-10 | Innate Pharma Sa | Tratamiento para modular las celulas nk y metodos para tratar malignidad hematologica |
CA2828940C (en) | 2011-03-10 | 2024-04-16 | Provectus Pharmaceuticals, Inc. | Combination of local and systemic immunomodulative therapies for enhanced treatment of cancer |
CN103547592A (zh) | 2011-03-30 | 2014-01-29 | 埃博灵克斯股份有限公司 | 使用针对TNFα的单结构域抗体治疗免疫病症的方法 |
PL2694549T3 (pl) | 2011-04-08 | 2019-01-31 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeryczne receptory antygenowe anty-wariant III receptora czynnika wzrostu naskórka i ich zastosowanie do leczenia raka |
CA2833636A1 (en) | 2011-04-20 | 2012-10-26 | Amplimmune, Inc. | Antibodies and other molecules that bind b7-h1 and pd-1 |
CN107936121B (zh) | 2011-05-16 | 2022-01-14 | 埃泰美德(香港)有限公司 | 多特异性fab融合蛋白及其使用方法 |
MX347514B (es) | 2011-05-25 | 2017-04-28 | Innate Pharma Sa | Anticuerpos anti-receptores tipo inmunoglobulina citoliticos (kir) para el tratamiento de trastornos inflamatorios. |
DK3415531T3 (da) | 2011-05-27 | 2023-09-18 | Glaxo Group Ltd | Bcma (cd269/tnfrsf17)-bindende proteiner |
HUE047238T2 (hu) | 2011-06-23 | 2020-04-28 | Ablynx Nv | Szérumalbuminhoz kötõdõ fehérjék |
WO2013006490A2 (en) | 2011-07-01 | 2013-01-10 | Cellerant Therapeutics, Inc. | Antibodies that specifically bind to tim3 |
UA117901C2 (uk) | 2011-07-06 | 2018-10-25 | Ґенмаб Б.В. | Спосіб посилення ефекторної функції вихідного поліпептиду, його варіанти та їх застосування |
EP2753644A1 (en) | 2011-09-09 | 2014-07-16 | Universiteit Utrecht Holding B.V. | Broadly neutralizing vhh against hiv-1 |
US20130108641A1 (en) | 2011-09-14 | 2013-05-02 | Sanofi | Anti-gitr antibodies |
WO2013041730A1 (en) | 2011-09-23 | 2013-03-28 | Universität Stuttgart Please note that the status of the person identified in Box 1 changed from Applicant for all designated States except US to Applicant for all designated States. | Serum half-life extension using immunoglobulin binding domains |
JP6219287B2 (ja) | 2011-09-30 | 2017-10-25 | アブリンクス エン.ヴェー. | c−Metに関連する生物学的物質 |
TWI679212B (zh) | 2011-11-15 | 2019-12-11 | 美商安進股份有限公司 | 針對bcma之e3以及cd3的結合分子 |
AU2012344260B2 (en) | 2011-11-28 | 2017-09-07 | Merck Patent Gmbh | Anti-PD-L1 antibodies and uses thereof |
RU2658603C2 (ru) | 2011-12-15 | 2018-06-21 | Ф.Хоффманн-Ля Рош Аг | Антитела против человеческого csf-1r и их применения |
BR112014014181A2 (pt) | 2011-12-16 | 2017-06-13 | Oncology Inst Of Southern Switzerland | combinação de ozogamicina inotuzumab e torisel para o tratamento de câncer |
CN108034006A (zh) | 2012-01-13 | 2018-05-15 | 乌利班-马克西姆利安大学 | 双抗原诱导的双功能互补作用 |
AU2013201422B2 (en) | 2012-01-23 | 2015-04-09 | Ablynx Nv | Sequences directed against hepatocyte growth factor (HFG) and polypeptides comprising the same for the treatment of cancers and/or tumors |
RU2014136332A (ru) | 2012-02-06 | 2016-03-27 | Дженентек, Инк. | Композиции и способы применения ингибиторов csf1r |
MX2014010183A (es) | 2012-02-22 | 2015-03-20 | Univ Pennsylvania | Composiciones y metodos para generar una poblacion persistente de celulas t utiles para el tratamiento de cancer. |
ES2812849T3 (es) | 2012-02-24 | 2021-03-18 | Abbvie Stemcentrx Llc | Anticuerpos anti-DLL3 y procedimientos de utilización de los mismos |
GB201203442D0 (en) | 2012-02-28 | 2012-04-11 | Univ Birmingham | Immunotherapeutic molecules and uses |
ES2680151T3 (es) | 2012-03-01 | 2018-09-04 | Amgen Research (Munich) Gmbh | Moléculas de unión de polipéptidos de larga duración |
AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
CN107266574A (zh) | 2012-03-30 | 2017-10-20 | 拜尔健康护理有限责任公司 | 蛋白酶调节的抗体 |
SG10201608307WA (en) | 2012-04-20 | 2016-11-29 | Emergent Product Dev Seattle | Cd3 binding polypeptides |
CA2871445C (en) | 2012-05-11 | 2020-07-07 | Five Prime Therapeutics, Inc. | Methods of treating conditions with antibodies that bind colony stimulating factor 1 receptor (csf1r) |
CA2873402C (en) | 2012-05-15 | 2023-10-24 | Bristol-Myers Squibb Company | Cancer immunotherapy by disrupting pd-1/pd-l1 signaling |
KR101566538B1 (ko) | 2012-06-08 | 2015-11-05 | 국립암센터 | 신규한 Th17 세포 전환용 에피토프 및 이의 용도 |
US9856314B2 (en) | 2012-06-22 | 2018-01-02 | Cytomx Therapeutics, Inc. | Activatable antibodies having non-binding steric moieties and methods of using the same |
WO2014004549A2 (en) | 2012-06-27 | 2014-01-03 | Amgen Inc. | Anti-mesothelin binding proteins |
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 |
CN112587658A (zh) | 2012-07-18 | 2021-04-02 | 博笛生物科技有限公司 | 癌症的靶向免疫治疗 |
WO2014036357A1 (en) | 2012-08-31 | 2014-03-06 | Five Prime Therapeutics, Inc. | Methods of treating conditions with antibodies that bind colony stimulating factor 1 receptor (csf1r) |
CN104583236A (zh) | 2012-08-31 | 2015-04-29 | 阿尔金-X有限公司 | 高度多样的组合抗体文库 |
KR101963231B1 (ko) | 2012-09-11 | 2019-03-28 | 삼성전자주식회사 | 이중특이 항체의 제작을 위한 단백질 복합체 및 이를 이용한 이중특이 항체 제조 방법 |
JOP20200236A1 (ar) | 2012-09-21 | 2017-06-16 | Regeneron Pharma | الأجسام المضادة لمضاد cd3 وجزيئات ربط الأنتيجين ثنائية التحديد التي تربط cd3 وcd20 واستخداماتها |
SG10201702421TA (en) | 2012-10-02 | 2017-05-30 | Bristol Myers Squibb Co | Combination of anti-kir antibodies and anti-pd-1 antibodies to treat cancer |
HUE058790T2 (hu) | 2012-12-17 | 2022-09-28 | Pf Argentum Ip Holdings Llc | CD47+ beteg sejtek kezelése SIRP-alfa-Fc fúziókkal |
JO3519B1 (ar) | 2013-01-25 | 2020-07-05 | Amgen Inc | تركيبات أجسام مضادة لأجل cdh19 و cd3 |
KR20150121715A (ko) | 2013-02-28 | 2015-10-29 | 더 유니버시티 코트 오브 더 유니버시티 오브 에딘버그 | Csf1 치료제 |
ES2681948T3 (es) | 2013-03-05 | 2018-09-17 | Baylor College Of Medicine | Células de acoplamiento para inmunoterapia |
WO2014160030A2 (en) | 2013-03-13 | 2014-10-02 | Health Research, Inc. | Compositions and methods for use of recombinant t cell receptors for direct recognition of tumor antigen |
EP3721902A1 (en) | 2013-03-14 | 2020-10-14 | The Scripps Research Institute | Targeting agent antibody conjugates and uses thereof |
WO2014159915A1 (en) | 2013-03-14 | 2014-10-02 | The Board Of Regents Of The University Of Texas System | Her3 specific monoclonal antibodies for diagnostic and therapeutic use |
US20140302037A1 (en) | 2013-03-15 | 2014-10-09 | Amgen Inc. | BISPECIFIC-Fc MOLECULES |
LT2970449T (lt) | 2013-03-15 | 2019-11-25 | Amgen Res Munich Gmbh | Viengrandės surišančios molekulės, apimančios n galo abp |
AR095502A1 (es) | 2013-03-15 | 2015-10-21 | Bayer Healthcare Llc | Anticuerpos profármaco contra el inhibidor de la vía del factor tisular |
US11634502B2 (en) | 2013-03-15 | 2023-04-25 | Amgen Inc. | Heterodimeric bispecific antibodies |
CN105722859B (zh) | 2013-07-25 | 2021-05-07 | 西托姆克斯治疗公司 | 多特异性抗体、多特异性可活化抗体及其使用方法 |
KR102362609B1 (ko) | 2013-08-01 | 2022-02-11 | 위니베르시트카솔리끄드루뱅 | 항garp 단백질 항체와 그 용도 |
AR097306A1 (es) | 2013-08-20 | 2016-03-02 | Merck Sharp & Dohme | Modulación de la inmunidad tumoral |
TW201605896A (zh) | 2013-08-30 | 2016-02-16 | 安美基股份有限公司 | Gitr抗原結合蛋白 |
CN112457403B (zh) | 2013-09-13 | 2022-11-29 | 广州百济神州生物制药有限公司 | 抗pd1抗体及其作为治疗剂与诊断剂的用途 |
AU2014323523B2 (en) | 2013-09-20 | 2020-02-20 | Bristol-Myers Squibb Company | Combination of anti-LAG-3 antibodies and anti-PD-1 antibodies to treat tumors |
CN107041146A (zh) | 2013-09-24 | 2017-08-11 | 华盛顿大学商业化中心 | 桥粒芯糖蛋白2(dsg2)结合蛋白质及其用途 |
US20160251440A1 (en) | 2013-09-26 | 2016-09-01 | Ablynx N.V. | Bispecific nanobodies |
US9126984B2 (en) | 2013-11-08 | 2015-09-08 | Iteos Therapeutics | 4-(indol-3-yl)-pyrazole derivatives, pharmaceutical compositions and methods for use |
US20160263087A1 (en) | 2013-11-08 | 2016-09-15 | Iteos Therapeutics | Novel 4-(indol-3-yl)-pyrazole derivatives, pharmaceutical compositions and methods for use |
WO2015082499A2 (en) | 2013-12-03 | 2015-06-11 | Iomet Pharma Ltd | Pharmaceutical compound |
JP6706578B2 (ja) | 2013-12-30 | 2020-06-10 | エピムアブ バイオセラピューティクス インコーポレイテッド | タンデム型Fab免疫グロブリン及びその使用 |
JP2017505346A (ja) | 2014-02-12 | 2017-02-16 | アイティーオス セラペウティクス | 新規な3−(インドール−3−イル)−ピリジン誘導体、医薬組成物、および使用方法 |
JP2017507983A (ja) | 2014-03-18 | 2017-03-23 | アイティーオス セラペウティクス | 新規な3−インドール置換誘導体、医薬組成物、および使用方法 |
JP6682498B2 (ja) | 2014-03-24 | 2020-04-15 | キャンサー・リサーチ・テクノロジー・リミテッドCancer Research Technology Limited | アゴニストまたはアンタゴニスト性を誘発する修飾されたIgG2ドメインを含む修飾された抗体及びその使用 |
WO2015146437A1 (ja) | 2014-03-25 | 2015-10-01 | 国立大学法人東北大学 | 高機能性IgG2型二重特異性抗体 |
UA117289C2 (uk) | 2014-04-02 | 2018-07-10 | Ф. Хоффманн-Ля Рош Аг | Мультиспецифічне антитіло |
JP6554117B2 (ja) | 2014-04-04 | 2019-07-31 | イオメット ファーマ リミテッド | 医療で使用されるインドール誘導体 |
ES2962694T3 (es) | 2014-05-02 | 2024-03-20 | Momenta Pharmaceuticals Inc | Composiciones y procedimientos relacionados con construcciones de Fc manipuladas |
MD20160118A2 (ro) | 2014-05-15 | 2017-04-30 | Iteos Therapeutics | Derivaţi ai pirolidin-2,5-dionei, compoziţii farmaceutice şi metode de utilizare ca inhibitori ai IDO1 |
IL293212B2 (en) | 2014-05-28 | 2023-12-01 | Memorial Sloan Kettering Cancer Center | Anti-GITR antibodies and methods of using them |
KR20220025917A (ko) | 2014-05-29 | 2022-03-03 | 마크로제닉스, 인크. | 삼중-특이적 결합 분자 및 그것의 사용 방법 |
KR101923326B1 (ko) | 2014-06-06 | 2018-11-29 | 브리스톨-마이어스 스큅 컴퍼니 | 글루코코르티코이드-유도 종양 괴사 인자 수용체 (gitr)에 대한 항체 및 그의 용도 |
GB201412659D0 (en) | 2014-07-16 | 2014-08-27 | Ucb Biopharma Sprl | Molecules |
AR101669A1 (es) | 2014-07-31 | 2017-01-04 | Amgen Res (Munich) Gmbh | Constructos de anticuerpos para cdh19 y cd3 |
US20170275373A1 (en) | 2014-07-31 | 2017-09-28 | Amgen Research (Munich) Gmbh | Bispecific single chain antibody construct with enhanced tissue distribution |
GB201414730D0 (en) | 2014-08-19 | 2014-10-01 | Tpp Global Dev Ltd | Pharmaceutical compound |
EP3186282A1 (en) | 2014-08-28 | 2017-07-05 | Academisch Ziekenhuis Leiden h.o.d.n. LUMC | Cd94/nkg2a and/or cd94/nkg2b antibody, vaccine combinations |
SG11201701599UA (en) | 2014-09-05 | 2017-03-30 | Janssen Pharmaceutica Nv | Cd123 binding agents and uses thereof |
CN105471609B (zh) | 2014-09-05 | 2019-04-05 | 华为技术有限公司 | 一种用于配置业务的方法和装置 |
CA2957351A1 (en) | 2014-09-10 | 2016-03-17 | Innate Pharma | Cross reactive siglec antibodies |
JP2017538660A (ja) | 2014-09-16 | 2017-12-28 | イナート・ファルマ・ソシエテ・アノニムInnate Pharma Pharma S.A. | 抗nkg2a抗体を使用した治療計画 |
WO2016046778A2 (en) | 2014-09-25 | 2016-03-31 | Amgen Inc | Protease-activatable bispecific proteins |
JP2017531430A (ja) | 2014-10-07 | 2017-10-26 | セレクティスCellectis | Carによって誘導される免疫細胞の活性を調節するための方法 |
CA2965741C (en) | 2014-11-03 | 2022-05-17 | Iomet Pharma Ltd | Pharmaceutical compound |
GB201419579D0 (en) | 2014-11-03 | 2014-12-17 | Iomet Pharma Ltd | Pharmaceutical compound |
CN107001472B (zh) | 2014-11-10 | 2020-12-11 | 免疫医疗有限公司 | 对cd73具有特异性的结合分子及其用途 |
JP2017536830A (ja) | 2014-11-26 | 2017-12-14 | ゼンコー・インコーポレイテッドXencor、 Inc. | Cd3及びcd38に結合するヘテロ二量体抗体 |
EP3029068A1 (en) | 2014-12-03 | 2016-06-08 | EngMab AG | Bispecific antibodies against CD3epsilon and BCMA for use in the treatment of diseases |
WO2016094602A1 (en) | 2014-12-10 | 2016-06-16 | Tufts University | Vhh based binding antibodies for anthrax and botulinum toxins and methods of making and using therefor |
WO2016105450A2 (en) | 2014-12-22 | 2016-06-30 | Xencor, Inc. | Trispecific antibodies |
WO2016125017A1 (en) | 2015-02-03 | 2016-08-11 | Universite Catholique De Louvain | Anti-garp protein and uses thereof |
KR20170107562A (ko) | 2015-02-05 | 2017-09-25 | 얀센 백신스 앤드 프리벤션 비.브이. | 인플루엔자 적혈구응집소에 대한 결합 분자 및 이의 용도 |
EP3256495A4 (en) | 2015-02-11 | 2018-09-19 | Aptevo Research and Development LLC | Compositions and methods for combination therapy with prostate-specific membrane antigen binding proteins |
CN115350275A (zh) | 2015-02-19 | 2022-11-18 | 康姆普根有限公司 | 抗pvrig抗体和使用方法 |
DK3259597T3 (da) | 2015-02-19 | 2022-05-09 | Compugen Ltd | Pvrig-polypeptider og fremgangsmåder til behandling |
WO2016147144A1 (en) | 2015-03-17 | 2016-09-22 | Pfizer Inc. | Novel 3-indol substituted derivatives, pharmaceutical compositions and methods for use |
CN114644689A (zh) | 2015-04-22 | 2022-06-21 | 农业生物群落股份有限公司 | 杀虫基因和使用方法 |
EP3778640A1 (en) | 2015-05-01 | 2021-02-17 | Genentech, Inc. | Masked anti-cd3 antibodies and methods of use |
WO2016180982A1 (en) | 2015-05-13 | 2016-11-17 | Ablynx N.V. | T cell recruiting polypeptides based on cd3 reactivity |
JP6841754B2 (ja) | 2015-05-13 | 2021-03-10 | 中外製薬株式会社 | 多重抗原結合分子融合体、医薬組成物、線状エピトープの同定方法、および多重抗原結合分子融合体の製造方法 |
TW201705955A (zh) | 2015-05-14 | 2017-02-16 | 輝瑞大藥廠 | 包含吡咯啶-2,5-二酮ido1抑制劑及抗-pd1/抗-pd-l1抗體之組合療法 |
WO2016187594A1 (en) | 2015-05-21 | 2016-11-24 | Harpoon Therapeutics, Inc. | Trispecific binding proteins and methods of use |
WO2016187101A2 (en) | 2015-05-21 | 2016-11-24 | Full Spectrum Genetics, Inc. | Method of improving characteristics of proteins |
BR112017025929A2 (pt) | 2015-06-03 | 2018-08-14 | Agbiome Inc | genes pesticidas e métodos de uso |
WO2016210447A1 (en) | 2015-06-26 | 2016-12-29 | University Of Southern California | Masking chimeric antigen receptor t cells for tumor-specific activation |
GB201511790D0 (en) | 2015-07-06 | 2015-08-19 | Iomet Pharma Ltd | Pharmaceutical compound |
TWI796283B (zh) * | 2015-07-31 | 2023-03-21 | 德商安美基研究(慕尼黑)公司 | Msln及cd3抗體構築體 |
TW202346349A (zh) | 2015-07-31 | 2023-12-01 | 德商安美基研究(慕尼黑)公司 | Dll3及cd3抗體構築體 |
TWI829617B (zh) | 2015-07-31 | 2024-01-21 | 德商安美基研究(慕尼黑)公司 | Flt3及cd3抗體構築體 |
EP3331913A1 (en) | 2015-08-07 | 2018-06-13 | Novartis AG | Treatment of cancer using chimeric cd3 receptor proteins |
CA2994917A1 (en) | 2015-08-10 | 2017-02-16 | Pfizer Inc. | 3-indol substituted derivatives, pharmaceutical compositions and methods for use |
CN105384825B (zh) | 2015-08-11 | 2018-06-01 | 南京传奇生物科技有限公司 | 一种基于单域抗体的双特异性嵌合抗原受体及其应用 |
WO2017025698A1 (en) | 2015-08-11 | 2017-02-16 | Queen Mary University Of London | Bispecific, cleavable antibodies |
EP3337824B1 (en) | 2015-08-17 | 2020-06-03 | Janssen Pharmaceutica NV | Anti-bcma antibodies, bispecific antigen binding molecules that bind bcma and cd3, and uses thereof |
CN106519037B (zh) | 2015-09-11 | 2019-07-23 | 科济生物医药(上海)有限公司 | 可活化的嵌合受体 |
IL302932A (en) | 2015-09-24 | 2023-07-01 | Daiichi Sankyo Co Ltd | Antibodies against GARP, nucleotides encoding them, and vectors, cells and preparations containing them, methods for their preparation and uses thereof |
CA3003458A1 (en) | 2015-10-29 | 2017-05-04 | Alector Llc | Anti-siglec-9 antibodies and methods of use thereof |
US20180320133A1 (en) | 2015-11-05 | 2018-11-08 | City Of Hope | Methods for preparing cells for adoptive t cell therapy |
EP3377103B1 (en) | 2015-11-19 | 2021-03-17 | Revitope Limited | Functional antibody fragment complementation for a two-components system for redirected killing of unwanted cells |
US20190023786A1 (en) | 2016-01-12 | 2019-01-24 | Palleon Pharmaceuticals Inc. | Use of siglec-7 or siglec-9 antibodies for the treatment of cancer |
US9624185B1 (en) | 2016-01-20 | 2017-04-18 | Yong Xu | Method for preparing IDO inhibitor epacadostat |
EP3411380A4 (en) | 2016-02-03 | 2020-01-22 | Youhealth Biotech, Limited | COMPOUNDS FOR THE TREATMENT OF EYE DISORDERS OR DISEASES |
CN105968201A (zh) | 2016-02-03 | 2016-09-28 | 南昌大学 | 针对***特异性膜抗原的单域重链抗体 |
DK3411402T3 (da) | 2016-02-03 | 2022-02-07 | Amgen Res Munich Gmbh | Bcma- og cd3-bispecifikke t-celle-engagerende antistofkonstruktioner |
CN105968204B (zh) | 2016-02-03 | 2020-01-21 | 中国人民解放军第三军医大学第一附属医院 | 一种抗***特异性膜抗原的单域重链抗体 |
SG11201807548SA (en) | 2016-03-08 | 2018-09-27 | Maverick Therapeutics Inc | Inducible binding proteins and methods of use |
JP7034489B2 (ja) | 2016-03-15 | 2022-03-14 | アイタブメッド (エイチケイ) リミテッド | 多重特異性Fab融合タンパクおよびその使用 |
WO2017161206A1 (en) | 2016-03-16 | 2017-09-21 | Halozyme, Inc. | Conjugates containing conditionally active antibodies or antigen-binding fragments thereof, and methods of use |
US11046782B2 (en) | 2016-03-30 | 2021-06-29 | Musc Foundation For Research Development | Methods for treatment and diagnosis of cancer by targeting glycoprotein A repetitions predominant (GARP) and for providing effective immunotherapy alone or in combination |
WO2017201488A1 (en) | 2016-05-20 | 2017-11-23 | Harpoon Therapeutics, Inc. | Single domain serum albumin binding protein |
US10544221B2 (en) | 2016-05-20 | 2020-01-28 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
EP3464365A1 (en) | 2016-06-01 | 2019-04-10 | Xencor, Inc. | Bispecific antibodies that bind cd123 and cd3 |
WO2018017864A2 (en) | 2016-07-20 | 2018-01-25 | Oncomed Pharmaceuticals, Inc. | Pvrig-binding agents and uses thereof |
US20190309092A1 (en) | 2016-07-21 | 2019-10-10 | Development Center For Biotechnology | Modified antigen-binding fab fragments and antigen-binding molecules comprising the same |
US11242376B2 (en) | 2016-08-02 | 2022-02-08 | TCR2 Therapeutics Inc. | Compositions and methods for TCR reprogramming using fusion proteins |
MX2019001471A (es) | 2016-08-05 | 2019-10-30 | Allakos Inc | Anticuerpos anti-siglec-7 para el tratamiento del cancer. |
EP3496751B1 (en) | 2016-08-08 | 2022-10-19 | Acetylon Pharmaceuticals Inc. | Pharmaceutical combinations of histone deacetylase 6 inhibitors and cd20 inhibitory antibodies and uses thereof |
SI3347379T1 (sl) | 2016-08-17 | 2020-04-30 | Compugen Ltd. | ANTI-TIGIT protitelesa, ANTI-PVRIG protitelesa in njihove kombinacije |
WO2018071777A1 (en) | 2016-10-14 | 2018-04-19 | Harpoon Therapeutics, Inc. | Innate immune cell trispecific binding proteins and methods of use |
JP2019537438A (ja) | 2016-11-01 | 2019-12-26 | アナプティスバイオ インコーポレイティッド | Tim−3(t細胞イムノグロブリンおよびムチンタンパク質3)に対する抗体 |
EP3535295A1 (en) | 2016-11-02 | 2019-09-11 | EngMab Sàrl | Bispecific antibody against bcma and cd3 and an immunological drug for combined use in treating multiple myeloma |
WO2018098354A1 (en) | 2016-11-23 | 2018-05-31 | Harpoon Therapeutics, Inc. | Prostate specific membrane antigen binding protein |
EP3544629A4 (en) | 2016-11-23 | 2020-06-17 | Harpoon Therapeutics, Inc. | TRISPECIFIC PROTEINS CIBLANG PSMA AND METHODS OF USE |
WO2018106529A1 (en) | 2016-12-08 | 2018-06-14 | Eli Lilly And Company | Anti-tim-3 antibodies for combination with anti-pd-l1 antibodies |
JOP20190133A1 (ar) | 2016-12-08 | 2019-06-02 | Innovent Biologics Suzhou Co Ltd | أجسام مضادة لـ Tim-3 لمزجها بأجسام مضادة لـ PD-1 |
BR112019011988A2 (pt) | 2016-12-13 | 2019-11-05 | Astellas Pharma Inc | anticorpo anti-cd73 humana |
WO2018136725A1 (en) | 2017-01-19 | 2018-07-26 | Harpoon Therapeutics, Inc. | Innate immune cell inducible binding proteins and methods of use |
AU2018209012A1 (en) | 2017-01-23 | 2019-09-12 | Crage Medical Co., Limited | BCMA-targeting antibody and use thereof |
WO2018160671A1 (en) | 2017-02-28 | 2018-09-07 | Harpoon Therapeutics, Inc. | Targeted checkpoint inhibitors and methods of use |
US11535668B2 (en) | 2017-02-28 | 2022-12-27 | Harpoon Therapeutics, Inc. | Inducible monovalent antigen binding protein |
AU2018231127A1 (en) | 2017-03-09 | 2019-09-19 | Cytomx Therapeutics, Inc. | CD147 antibodies, activatable CD147 antibodies, and methods of making and use thereof |
EP3619234A4 (en) | 2017-05-03 | 2021-05-26 | Harpoon Therapeutics, Inc. | COMPOSITIONS AND METHODS FOR ADOPTIVE CELL THERAPIES |
US10730954B2 (en) | 2017-05-12 | 2020-08-04 | Harpoon Therapeutics, Inc. | MSLN targeting trispecific proteins and methods of use |
CN113896792A (zh) | 2017-05-12 | 2022-01-07 | 哈普恩治疗公司 | 间皮素结合蛋白质 |
CN111247167A (zh) | 2017-06-02 | 2020-06-05 | 辉瑞公司 | Flt3的特异性抗体及其用途 |
WO2018232020A1 (en) * | 2017-06-13 | 2018-12-20 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
CA3066514A1 (en) | 2017-07-10 | 2019-01-17 | Innate Pharma | Siglec-9-neutralizing antibodies |
AU2018298673A1 (en) | 2017-07-10 | 2019-12-19 | Innate Pharma | Combination therapy using antibody to human Siglec-9 and antibody to human NKG2A for treating cancer |
SG11202000499RA (en) | 2017-08-01 | 2020-02-27 | Medimmune Llc | Bcma monoclonal antibody-drug conjugate |
JP2019052752A (ja) | 2017-09-15 | 2019-04-04 | 日本電産株式会社 | 変速機及びアクチュエータ |
MX2020003856A (es) | 2017-10-13 | 2020-08-13 | Harpoon Therapeutics Inc | Proteinas de union a antigenos de maduracion de celulas b. |
MX2020003915A (es) | 2017-10-13 | 2020-10-08 | Harpoon Therapeutics Inc | Proteinas trispecificas y metodos de uso. |
WO2019089848A1 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Methods associated with tumor burden for assessing response to a cell therapy |
WO2019136305A1 (en) | 2018-01-04 | 2019-07-11 | Neumedicines Inc. | Cell-based and immune checkpoint inhibitor therapies combined with il-12 for treating cancer |
AU2019271138A1 (en) | 2018-05-14 | 2021-01-07 | Harpoon Therapeutics, Inc. | Binding moiety for conditional activation of immunoglobulin molecules |
US20210269530A1 (en) | 2018-05-14 | 2021-09-02 | Harpoon Therapeutics, Inc. | Conditionally activated binding protein comprising a sterically occluded target binding domain |
US20210284728A1 (en) | 2018-05-14 | 2021-09-16 | Harpoon Therapeutics, Inc. | Dual binding moiety |
CR20200571A (es) | 2018-06-01 | 2021-01-18 | Novartis Ag | Moléculas de únion contra bcma y usos de las mismas |
CN113166266A (zh) | 2018-06-18 | 2021-07-23 | 安维塔生物科学股份有限公司 | 抗间皮素构建体及其用途 |
CN113226324A (zh) | 2018-09-11 | 2021-08-06 | Iteos比利时公司 | 作为a2a抑制剂的硫代氨基甲酸酯衍生物、其药物组合物以及与抗癌剂的组合 |
US20210355219A1 (en) | 2018-09-21 | 2021-11-18 | Harpoon Therapeutics, Inc. | Conditionally activated target-binding molecules |
WO2020060593A1 (en) | 2018-09-21 | 2020-03-26 | Harpoon Therapeutics, Inc. | Conditionally active receptors |
US20220017626A1 (en) | 2018-09-21 | 2022-01-20 | Harpoon Therapeutics, Inc. | Egfr binding proteins and methods of use |
CA3114038A1 (en) | 2018-09-25 | 2020-04-02 | Harpoon Therapeutics, Inc. | Dll3 binding proteins and methods of use |
JP2022512971A (ja) | 2018-11-08 | 2022-02-07 | ジュノー セラピューティクス インコーポレイテッド | 処置およびt細胞調節のための方法および併用 |
CN109593786A (zh) | 2019-01-09 | 2019-04-09 | 上海怡豪生物科技有限公司 | 联合EpCAM和MSLN单链抗体的双靶点CAR载体及其构建方法和在乳腺癌应用 |
KR20220008866A (ko) | 2019-05-14 | 2022-01-21 | 하푼 테라퓨틱스, 인크. | EpCAM 결합 단백질 및 사용 방법 |
WO2021097060A1 (en) | 2019-11-13 | 2021-05-20 | Harpoon Therapeutics, Inc. | Pro immune modulating molecule comprising a clustering moiety |
EP4106806A1 (en) | 2020-02-21 | 2022-12-28 | Harpoon Therapeutics, Inc. | Flt3 binding proteins and methods of use |
WO2021231434A1 (en) | 2020-05-12 | 2021-11-18 | Harpoon Therapeutics, Inc. | Psma targeting tritacs and methods of use |
WO2022098909A1 (en) | 2020-11-06 | 2022-05-12 | Harpoon Therapeutics, Inc. | Epcam targeting trispecific protein for treatment of cancer |
-
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016500655A (ja) | 2012-09-27 | 2016-01-14 | ザ・ユナイテッド・ステイツ・オブ・アメリカ・アズ・リ | メソテリン抗体および強力な抗腫瘍活性を惹起するための方法 |
WO2018067993A1 (en) | 2016-10-07 | 2018-04-12 | TCR2 Therapeutics Inc. | Compositions and methods for t-cell receptors reprogramming using fusion proteins |
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