JP2020506971A - ナチュラルキラー細胞の活性化のための多重特異性結合タンパク質およびがんを処置するためのその治療的使用 - Google Patents
ナチュラルキラー細胞の活性化のための多重特異性結合タンパク質およびがんを処置するためのその治療的使用 Download PDFInfo
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Abstract
Description
本出願は、2017年2月8日に出願された米国仮特許出願番号第62/456,535号に基づく利益および優先権を主張しており、この仮特許出願の全体の内容は、すべての目的のために本明細書中に参考として援用される。
本出願は、ASCIIフォーマットで電子提出された配列表を含み、その全体は、参照により本明細書に組み込まれている。前記ASCIIコピーは2018年2月6日に作成され、DFY−001PC_SL.txtという名称であり、71,169バイトのサイズである。
本発明は、腫瘍関連抗原、NKG2D受容体、およびCD16に結合する多重特異性結合タンパク質に関する。
がんは、この疾患を処置するための文献に報告されている十分な研究努力および科学進歩にもかかわらず、重大な健康問題であり続けている。最も頻繁に診断されるがんの中には、前立腺がん、乳がん、および肺がんが含まれる。前立腺がんは、男性におけるがんの最も一般的な形態である。乳がんは依然として女性における主要な死因である。これらのがんに対する現在の処置選択肢は、すべての患者に効果的というわけではなく、および/または実質的な有害副作用を有する可能性がある。他の種類のがんも、既存の治療選択肢を使用して処置することが依然として困難である。
NK細胞は、それらの表面における様々な活性化受容体および阻害受容体を介してシグナルに応答する。例えば、NK細胞が健康な自己細胞に遭遇すると、それらの活性は、キラー細胞免疫グロブリン様受容体(KIR)の活性化によって阻害される。あるいはNK細胞が外来細胞またはがん細胞に遭遇すると、それらは、それらの活性化受容体(例えば、NKG2D、NCR、DNAM1)を介して活性化される。NK細胞はまた、それらの表面におけるCD16受容体を介していくつかの免疫グロブリンの定常領域によって活性化される。活性化に対するNK細胞の全体的な感受性は、刺激シグナルおよび阻害シグナルの合計に依存する。
本発明は、がん細胞における腫瘍関連抗原ならびにナチュラルキラー細胞におけるNKG2D受容体およびCD16受容体に結合してナチュラルキラー細胞を活性化させる多重特異性結合タンパク質、かかる多重特異性結合タンパク質を含む医薬組成物、ならびに、がんの処置などのためにかかる多重特異性タンパク質および医薬組成物を使用する治療方法を提供する。かかるタンパク質は2種類以上のNK活性化受容体と会合することができ、天然リガンドのNKG2Dへの結合を阻止し得る。ある特定の実施形態では、タンパク質は、ヒトならびにげっ歯動物およびカニクイザルなどの他の種においてNK細胞を刺激し得る。本発明の様々な態様および実施形態を以下にさらに詳細に記載する。
本発明は、がん細胞における腫瘍関連抗原ならびにナチュラルキラー細胞におけるNKG2D受容体およびCD16受容体に結合してナチュラルキラー細胞を活性化させる多重特異性結合タンパク質、かかる多重特異性結合タンパク質を含む医薬組成物、ならびに、がんの処置などのためにかかる多重特異性タンパク質および医薬組成物を使用する治療方法を提供する。本発明の様々な態様を複数のセクションに分けて以下に記述する。しかしながら、1つの特定のセクションに記載される本発明の態様は、いずれかの特定のセクションに限定されるものではない。
I.タンパク質
II.TriNKETの特徴
III.治療用途
IV.併用療法
V.医薬組成物
(実施例1)
NKG2D結合ドメインはNKG2Dに結合する
NKG2D結合ドメインは精製した組換えNKG2Dに結合する
NKG2D結合ドメインはNKG2Dを発現する細胞に結合する
(実施例2)
NKG2D結合ドメインはNKG2Dへの天然リガンドの結合を阻止する
ULBP−6との競合
MICAとの競合
Rae−1デルタとの競合
(実施例3)
NKG2D結合ドメインクローンはNKG2Dを活性化させる
(実施例4)
NKG2D結合ドメインはNK細胞を活性化させる
初代ヒトNK細胞
初代マウスNK細胞
(実施例5)
NKG2D結合ドメインは標的腫瘍細胞の細胞傷害性を可能にする
(実施例6)
NKG2D抗体は高い熱安定性を示す
(実施例7)
多重特異性結合タンパク質はNK細胞を活性化させる能力の増強を示す
(実施例8)
多重特異性結合タンパク質は標的腫瘍細胞に対して増強した細胞傷害性を示す
初代ヒトNK細胞傷害性アッセイ
初代マウスNK細胞の細胞傷害性アッセイ
(実施例9)
多重特異性結合タンパク質はNKG2Dに結合する
EM−801重鎖可変ドメイン(配列番号82):
(実施例10)
多重特異性結合タンパク質はヒト腫瘍抗原に結合する
三重特異性結合タンパク質はCD33、HER2、CD20およびBCMAに結合する
(実施例11)
多重特異性結合タンパク質はNK細胞を活性化させる
初代ヒトNK細胞は、標的発現ヒトがん細胞株との共培養においてTriNKETによって活性化される
(実施例12)
三重特異性結合タンパク質は標的がん細胞の細胞傷害性を可能にする
(実施例13)
初代ヒトNK細胞活性化アッセイ
(実施例14)
細胞により発現されたヒトNKG2DへのTriNKET結合の評価
細胞により発現されたヒトがん抗原へのTriNKET結合の評価
ヒトHER2陽性がん細胞株の抗体結合能の決定
TriNKETによる初代NK細胞の活性化
初代ヒトNK細胞の細胞傷害性アッセイ
Cyto Tox96 LHD放出アッセイ:
DELFIA細胞傷害性アッセイ:
長期のヒトPBMC細胞傷害性アッセイ:
HER+がん細胞を標的とするTriNKETとSC2.2との比較
C57Bl/6マウスにおけるSC2.2血清半減期の評価
RMA/S−HER2皮下腫瘍に対するSC2.2のin vivo試験
TriNKETはヒトNKG2Dを発現する細胞に結合する
TriNKETはヒトがん抗原を発現する細胞に結合する
ヒトHER2陽性がん細胞株の抗体結合能
TriNKETは休止ヒトNK細胞およびIL−2活性化ヒトNK細胞の活性を増強する
TriNKETは休止ヒトNK細胞およびIL−2活性化ヒトNK細胞の細胞傷害性を増強する
TriNKETは表面発現が低い標的に対するNK細胞の細胞傷害性を増強する
FcRの発現が高いがんを処置する際のTriNKETの利点、または高レベルのFcRを有する腫瘍微小環境におけるTriNKETの利点
3つのAML細胞株におけるFcRγI(CD64)発現
TriNKETはFcRの表面発現が高い腫瘍細胞を標的とするのに有利である
TriNKETは、FcγRI発現にかかわらず、AML細胞株に対する有効性を示す
PBMC培養における正常な骨髄細胞および正常なB細胞の殺傷:TriNKETは、少ないオンターゲット・オフ腫瘍副作用によって、より良好な安全性プロファイルを提供する
TriNKETは長期の共培養においてSkBr−3腫瘍細胞のhPBMC殺傷を媒介する
初代ヒトPBMC細胞傷害性アッセイ
(実施例15)
in vitroでのmcFAE−C26.99 TriNKETの抗腫瘍効果
mcFAE−C26.99 TriNKETによって媒介されるNK細胞傷害性の増加
in vivoでのmcFAE−C26.99 TriNKETの抗腫瘍効果
(実施例17)
HER2陽性細胞に対する、TriNKET、モノクローナル抗体、または二重特異性抗体によって媒介される休止ヒトNK細胞の細胞傷害活性
モノクローナル抗体および二重特異性NK細胞エンゲージャーの組合せはTriNKET活性を再現しない:
参照による組み込み
等価物
Claims (24)
- (a)NKG2Dに結合する第1の抗原結合部位と、
(b)腫瘍関連抗原に結合する第2の抗原結合部位と、
(c)CD16に結合するに十分な抗体Fcドメインもしくはその一部分、またはCD16に結合する第3の抗原結合部位と
を含むタンパク質。 - 前記第1の抗原結合部位が、ヒト、非ヒト霊長類、およびげっ歯動物のNKG2Dに結合する、請求項1に記載のタンパク質。
- 前記第1の抗原結合部位が、重鎖可変ドメインおよび軽鎖可変ドメインを含む、請求項1または2に記載のタンパク質。
- 前記重鎖可変ドメインおよび前記軽鎖可変ドメインが、同じポリペプチド上に存在する、請求項3に記載のタンパク質。
- 前記第2の抗原結合部位も、重鎖可変ドメインおよび軽鎖可変ドメインを含む、請求項3または4に記載のタンパク質。
- 前記第1の抗原結合部位の前記軽鎖可変ドメインが、前記第2の抗原結合部位の前記軽鎖可変ドメインのアミノ酸配列と同一のアミノ酸配列を有する、請求項5に記載のタンパク質。
- 前記第1の抗原結合部位が、単一ドメイン抗体である、請求項1または2に記載のタンパク質。
- 前記単一ドメイン抗体が、VHH断片またはVNAR断片である、請求項7に記載のタンパク質。
- 前記第2の抗原結合部位が、単一ドメイン抗体である、請求項1から4または7から8のいずれか一項に記載のタンパク質。
- 前記第2の抗原結合部位が、VHH断片またはVNAR断片である、請求項9に記載のタンパク質。
- 前記第2の抗原結合部位が、重鎖可変ドメインおよび軽鎖可変ドメインを含む、請求項1、2、7または8に記載のタンパク質。
- 前記第1の抗原結合部位が、配列番号1と少なくとも90%同一の重鎖可変ドメインを含む、先行する請求項のいずれか一項に記載のタンパク質。
- 前記第1の抗原結合部位が、配列番号41と少なくとも90%同一の重鎖可変ドメインと、配列番号42と少なくとも90%同一の軽鎖可変ドメインとを含む、請求項1から11のいずれかに記載のタンパク質。
- 前記第1の抗原結合部位が、配列番号43と少なくとも90%同一の重鎖可変ドメインと、配列番号44と少なくとも90%同一の軽鎖可変ドメインとを含む、請求項1から11のいずれかに記載のタンパク質。
- 前記第1の抗原結合部位が、配列番号69と少なくとも90%同一の重鎖可変ドメインと、配列番号70と少なくとも90%同一の軽鎖可変ドメインとを含む、請求項1から11のいずれかに記載のタンパク質。
- 前記第1の抗原結合部位が、配列番号71と少なくとも90%同一の重鎖可変ドメインと、配列番号72と少なくとも90%同一の軽鎖可変ドメインとを含む、請求項1から11のいずれかに記載のタンパク質。
- 前記腫瘍関連抗原が、HER2、CD20、CD33、BCMA、EpCAM、CD2、CD19、CD30、CD38、CD40、CD52、CD70、EGFR/ERBB1、IGF1R、HER3/ERBB3、HER4/ERBB4、MUC1、cMET、SLAMF7、PSCA、MICA、MICB、TRAILR1、TRAILR2、MAGE−A3、B7.1、B7.2、CTLA4、およびPD1からなる群から選択される、先行する請求項のいずれか一項に記載のタンパク質。
- 前記タンパク質が、CD16に結合するに十分な抗体Fcドメインの一部分を含み、前記抗体Fcドメインが、ヒンジおよびCH2ドメインを含む、先行する請求項のいずれか一項に記載のタンパク質。
- ヒトIgG1抗体のアミノ酸234〜332と少なくとも90%同一のアミノ酸配列を含む、請求項1から17のいずれか一項に記載のタンパク質。
- 先行する請求項のいずれか一項に記載のタンパク質および薬学的に許容される担体を含む製剤。
- 請求項1から19のいずれか一項に記載のタンパク質をコードする1つまたは複数の核酸を含む細胞。
- 請求項1から19のいずれか一項に記載のタンパク質に腫瘍およびナチュラルキラー細胞を曝露することを含む、腫瘍細胞死を直接的または間接的に増強する方法。
- 請求項1から19のいずれか一項に記載のタンパク質または請求項20に記載の製剤を患者に投与することを含む、がんを処置する方法。
- 前記がんが、急性骨髄性白血病、急性骨髄単球性白血病、B細胞リンパ腫、膀胱がん、乳がん、大腸がん、びまん性大細胞型B細胞リンパ腫、食道がん、ユーイング肉腫、濾胞性リンパ腫、胃がん、消化管がん、消化管間質腫瘍、神経膠芽腫、頭頸部がん、黒色腫、中皮腫、多発性骨髄腫、骨髄異形成症候群、腎細胞癌、神経芽細胞腫、非小細胞肺がん、神経内分泌腫瘍、卵巣がん、および膵がん、前立腺がん、肉腫、小細胞肺がん、T細胞リンパ腫、精巣がん、胸腺癌、甲状腺がん、尿路上皮がん、骨髄由来抑制細胞が浸潤したがん、細胞外マトリックス沈着を伴うがん、高レベルの反応性間質を伴うがん、ならびに血管新生を伴うがんからなる群から選択される、請求項23に記載の方法。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022004805A1 (ja) | 2020-06-30 | 2022-01-06 | 株式会社ガイアバイオメディシン | Nk細胞と抗体との結合を安定化する方法、及びその利用 |
Families Citing this family (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2018219887A1 (en) | 2017-02-08 | 2019-08-22 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins for activation of natural killer cells and therapeutic uses thereof to treat cancer |
MA47465A (fr) * | 2017-02-10 | 2019-12-18 | Dragonfly Therapeutics Inc | Protéines fixant le bcma, le nkg2d et le cd16 |
WO2018152530A1 (en) * | 2017-02-20 | 2018-08-23 | Adimab, Llc | Proteins binding gd2, nkg2d and cd16 |
CA3054078A1 (en) * | 2017-02-20 | 2018-08-23 | Dragonfly Therapeutics, Inc. | Proteins binding cd33, nkg2d and cd16 |
KR20190120782A (ko) * | 2017-02-20 | 2019-10-24 | 드래곤플라이 쎄라퓨틱스, 인크. | Her2, nkg2d 및 cd16에 결합하는 단백질 |
MX2019014000A (es) * | 2017-05-23 | 2020-07-29 | Dragonfly Therapeutics Inc | Una proteína que se une a nkg2d, cd16 y un antígeno asociado a un tumor. |
CN111278460A (zh) * | 2017-05-23 | 2020-06-12 | 蜻蜓疗法股份有限公司 | 结合nkg2d、cd16和肿瘤相关抗原的蛋白质 |
CA3090236A1 (en) * | 2018-02-08 | 2019-08-15 | Dragonfly Therapeutics, Inc. | Combination therapy of cancer involving multi-specific binding proteins that activate natural killer cells |
AU2019218136A1 (en) | 2018-02-08 | 2020-08-13 | Dragonfly Therapeutics, Inc. | Antibody variable domains targeting the NKG2D receptor |
BR112020016939A2 (pt) * | 2018-02-20 | 2020-12-15 | Dragonfly Therapeutics, Inc. | Proteínas de ligação multiespecíficas que se ligam a cd33, nkg2d, e cd16 e métodos de uso |
CA3100234A1 (en) * | 2018-05-16 | 2019-11-21 | Dragonfly Therapeutics, Inc. | Protein binding nkg2d, cd16 and a fibroblast activation protein |
EA202091977A1 (ru) * | 2018-05-28 | 2021-02-09 | Драгонфлай Терапьютикс, Инк. | Мультиспецифические связывающие белки, которые связывают cd33, nkg2d и cd16, и способы применения |
BR112021002278A2 (pt) * | 2018-08-08 | 2021-07-20 | Dragonfly Therapeutics, Inc. | proteínas que ligam nkg2d, cd16 e um antígeno associado a tumor |
JP2022520978A (ja) * | 2019-02-18 | 2022-04-04 | クーリエ セラピューティクス インコーポレイテッド | オルソポックスウイルス主要組織適合性複合体(mhc)クラスi様タンパク質(omcp)と腫瘍特異的結合パートナーを用いた二重特異性融合タンパク質 |
AR119393A1 (es) | 2019-07-15 | 2021-12-15 | Hoffmann La Roche | Anticuerpos que se unen a nkg2d |
MX2023001555A (es) | 2020-08-05 | 2023-03-08 | Dragonfly Therapeutics Inc | Proteinas que se unen a nkg2d, cd16 y egfr. |
WO2022148853A1 (en) | 2021-01-11 | 2022-07-14 | F. Hoffmann-La Roche Ag | Immunoconjugates |
WO2023107956A1 (en) | 2021-12-08 | 2023-06-15 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16 and 5t4 |
CN116948029A (zh) * | 2022-04-20 | 2023-10-27 | 南京融捷康生物科技有限公司 | 一种包含IgG类Fc区变体的抗体及其用途 |
CN115058393B (zh) * | 2022-07-13 | 2024-05-24 | 北京鼎成肽源生物技术有限公司 | 一种包被刺激物、培养试剂盒和自然杀伤细胞的培养方法 |
WO2024035662A2 (en) | 2022-08-10 | 2024-02-15 | Merck Sharp & Dohme Llc | Proteins binding nkg2d, cd16, and ceacam5 |
WO2024056862A1 (en) | 2022-09-15 | 2024-03-21 | Avidicure Ip B.V. | Multispecific antigen binding proteins for tumor-targeting of nk cells and use thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011506406A (ja) * | 2007-12-14 | 2011-03-03 | ノボ・ノルデイスク・エー/エス | ヒトnkg2dに対する抗体とその使用 |
WO2013002362A1 (ja) * | 2011-06-30 | 2013-01-03 | 中外製薬株式会社 | ヘテロ二量化ポリペプチド |
JP2013500721A (ja) * | 2009-07-29 | 2013-01-10 | アボット・ラボラトリーズ | 二重可変ドメイン免疫グロブリンおよびその使用 |
Family Cites Families (273)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0366707A1 (en) | 1987-05-06 | 1990-05-09 | OOSTERWIJK, Egbert | Monoclonal antibodies to renal cell carcinoma |
JPH03503840A (ja) | 1988-01-15 | 1991-08-29 | セントコアー,インコーポレーテッド | 異種連結抗体およびその治療的使用 |
US5965132A (en) | 1992-03-05 | 1999-10-12 | Board Of Regents, The University Of Texas System | Methods and compositions for targeting the vasculature of solid tumors |
ES2193143T3 (es) | 1992-03-05 | 2003-11-01 | Univ Texas | Uso de inmunoconjugados para la diagnosis y/o terapia de tumores vascularizaos. |
US6036955A (en) | 1992-03-05 | 2000-03-14 | The Scripps Research Institute | Kits and methods for the specific coagulation of vasculature |
US5776427A (en) | 1992-03-05 | 1998-07-07 | Board Of Regents, The University Of Texas System | Methods for targeting the vasculature of solid tumors |
US7381803B1 (en) | 1992-03-27 | 2008-06-03 | Pdl Biopharma, Inc. | Humanized antibodies against CD3 |
US6129914A (en) | 1992-03-27 | 2000-10-10 | Protein Design Labs, Inc. | Bispecific antibody effective to treat B-cell lymphoma and cell line |
US5622701A (en) | 1994-06-14 | 1997-04-22 | Protein Design Labs, Inc. | Cross-reacting monoclonal antibodies specific for E- and P-selectin |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
DE69636015T2 (de) | 1995-05-03 | 2007-01-04 | Bioenhancementsments Ltd. | Bispezifische antikörper in denen die bindungsfähigkeit durch eine mittels licht spaltbare gruppe reversibel inhibiert wird |
DE19531346A1 (de) | 1995-08-25 | 1997-02-27 | Gsf Forschungszentrum Umwelt | Arzneimittel zur Immuntherapie, enthaltend Antikörper, die spezifisch das MHCII-Antigen eines zu behandelnden Patienten erkennen |
US7951917B1 (en) | 1997-05-02 | 2011-05-31 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
NZ507381A (en) | 1998-04-21 | 2003-12-19 | Micromet Ag | CD19xCD3 specific polypeptides and uses thereof |
US6572856B1 (en) | 1998-09-10 | 2003-06-03 | The University Of Virginia Patent Foundation | Methods for the prevention and treatment of cancer using anti-C3b(i) antibodies |
US6534633B1 (en) | 1998-10-21 | 2003-03-18 | Altor Bioscience Corporation | Polyspecific binding molecules and uses thereof |
US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
AU2001260153B2 (en) * | 2000-03-24 | 2006-08-17 | Micromet Ag | Multifunctional polypeptides comprising a binding site to an epitope of the NKG2D receptor complex |
JP2004511430A (ja) | 2000-05-24 | 2004-04-15 | イムクローン システムズ インコーポレイティド | 二重特異性免疫グロブリン様抗原結合蛋白および製造方法 |
US20040115198A1 (en) | 2001-02-28 | 2004-06-17 | Fred Hutchinson Cancer Research Center | Activation of lymphocyte populations expressing NKG2D using anti-NKG2D antibodies and ligand derivatives |
US20020193569A1 (en) | 2001-06-04 | 2002-12-19 | Idec Pharmaceuticals Corporation | Bispecific fusion protein and method of use for enhancing effector cell killing of target cells |
DE10156482A1 (de) | 2001-11-12 | 2003-05-28 | Gundram Jung | Bispezifisches Antikörper-Molekül |
CA2496419A1 (en) | 2002-08-19 | 2004-02-26 | Abgenix, Inc. | Antibodies directed to monocyte chemo-attractant protein-1 (mcp-1) and uses thereof |
US7820166B2 (en) | 2002-10-11 | 2010-10-26 | Micromet Ag | Potent T cell modulating molecules |
DE10261223A1 (de) | 2002-12-20 | 2004-07-08 | MedInnova Gesellschaft für medizinische Innovationen aus akademischer Forschung mbH | Steigerung der Immunantwort durch Substanzen, welche die Funktion von Natürlichen Killerzellen beeinflussen |
CA2515100A1 (en) | 2003-02-06 | 2004-08-19 | Micromet Ag | Trimeric polypeptide construct to induce an enduring t cell response |
US7666417B2 (en) | 2003-04-22 | 2010-02-23 | Fred Hutchinson Cancer Research Center | Methods and compositions for treating autoimmune diseases or conditions |
AU2004242846A1 (en) | 2003-05-31 | 2004-12-09 | Micromet Ag | Pharmaceutical compositions comprising bispecific anti-CD3, anti-CD19 antibody constructs for the treatment of B-cell related disorders |
CA2523716C (en) | 2003-05-31 | 2014-11-25 | Micromet Ag | Human anti-human cd3 binding molecules |
DK1648507T3 (en) | 2003-07-24 | 2017-05-01 | Innate Pharma Sa | PROCEDURES AND COMPOSITIONS FOR INCREASING THE EFFECTIVENESS OF THERAPEUTIC ANTIBODIES USING COMPOUNDS THAT POTENTATE NK CELLS |
HN2004000285A (es) | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
BRPI0415457A (pt) | 2003-10-16 | 2006-12-05 | Micromet Ag | constructo de ligação especìfico de cd3 citotoxicamente ativo, seu processo de produção, composição compreendendo o mesmo, seqüência de ácido nucléico, vetor, hospedeiro, seus usos na preparação de uma composição farmacêutica e kit compreendendo os mesmo |
US7235641B2 (en) | 2003-12-22 | 2007-06-26 | Micromet Ag | Bispecific antibodies |
US20110020273A1 (en) | 2005-04-06 | 2011-01-27 | Ibc Pharmaceuticals, Inc. | Bispecific Immunocytokine Dock-and-Lock (DNL) Complexes and Therapeutic Use Thereof |
JP4762158B2 (ja) | 2004-02-16 | 2011-08-31 | ミクロメット・アクチェンゲゼルシャフト | 低い免疫原性を有する結合分子 |
EA010374B1 (ru) | 2004-07-16 | 2008-08-29 | Микромет Аг | Полипептиды с повышенной экспрессией |
KR20070038557A (ko) | 2004-07-22 | 2007-04-10 | 제넨테크, 인크. | Her2 항체 조성물 |
JP2008514685A (ja) | 2004-10-01 | 2008-05-08 | メディジーン リミテッド | 治療剤に連結した、非天然型ジスルフィド鎖間結合を含有するt細胞レセプター |
DOP2006000029A (es) | 2005-02-07 | 2006-08-15 | Genentech Inc | Antibody variants and uses thereof. (variantes de un anticuerpo y usos de las mismas) |
EP3479844B1 (en) | 2005-04-15 | 2023-11-22 | MacroGenics, Inc. | Covalent diabodies and uses thereof |
US9284375B2 (en) | 2005-04-15 | 2016-03-15 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
US20070071759A1 (en) | 2005-06-29 | 2007-03-29 | University Of Miami | Antibody-immune cell ligand fusion protein for cancer therapy |
JP2009504787A (ja) | 2005-08-19 | 2009-02-05 | シーラス コーポレイション | 抗体によって媒介される免疫応答の増強 |
PE20071101A1 (es) | 2005-08-31 | 2007-12-21 | Amgen Inc | Polipeptidos y anticuerpos |
US8236308B2 (en) | 2005-10-11 | 2012-08-07 | Micromet Ag | Composition comprising cross-species-specific antibodies and uses thereof |
US9447185B2 (en) | 2005-10-14 | 2016-09-20 | Innate Pharma, S.A. | Compositions and methods for treating proliferative disorders |
WO2007048849A1 (en) | 2005-10-28 | 2007-05-03 | Novo Nordisk A/S | Fusion proteins that bind effector lymphocytes and target cells |
JP2009514528A (ja) | 2005-11-03 | 2009-04-09 | フレッド ハッチンソン キャンサー リサーチ センター | Nkg2d陽性cd4+細胞による免疫応答の負の免疫調節法 |
AU2006338562A1 (en) | 2005-11-03 | 2007-08-30 | Genentech, Inc. | Therapeutic anti-HER2 antibody fusion polypeptides |
AU2006326727A1 (en) | 2005-12-16 | 2007-06-21 | Amgen Research (Munich) Gmbh | Means and methods for the treatment of tumorous diseases |
EP1820513A1 (en) | 2006-02-15 | 2007-08-22 | Trion Pharma Gmbh | Destruction of tumor cells expressing low to medium levels of tumor associated target antigens by trifunctional bispecific antibodies |
NZ573646A (en) | 2006-06-12 | 2012-04-27 | Wyeth Llc | Single-chain multivalent binding proteins with effector function |
GB0614780D0 (en) | 2006-07-25 | 2006-09-06 | Ucb Sa | Biological products |
WO2008028946A2 (en) | 2006-09-07 | 2008-03-13 | Crucell Holland B.V. | Human binding molecules capable of neutralizing influenza virus h5n1 and uses thereof |
EP1900752A1 (en) | 2006-09-15 | 2008-03-19 | DOMPE' pha.r.ma s.p.a. | Human anti-folate receptor alpha antibodies and antibody fragments for the radioimmunotherapy of ovarian carcinoma |
BRPI0811857A2 (pt) | 2007-05-14 | 2014-10-21 | Biogen Idec Inc | Regiões fc (scfc) de cadeia simples, polipeptídeos de aglutinação que as compreendem e métodos relacionados. |
EP2014680A1 (en) | 2007-07-10 | 2009-01-14 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Recombinant, single-chain, trivalent tri-specific or bi-specific antibody derivatives |
WO2009013543A2 (en) | 2007-07-25 | 2009-01-29 | Astrazeneca Ab | Targeted binging agents directed to kdr and uses thereof - 035 |
JP2010536341A (ja) | 2007-08-15 | 2010-12-02 | アムニクス, インコーポレイテッド | 生物学的に活性なポリペプチドの特性を改変するための組成物および方法 |
JOP20080381B1 (ar) | 2007-08-23 | 2023-03-28 | Amgen Inc | بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9) |
CA2697193C (en) | 2007-09-14 | 2017-06-06 | Adimab, Inc. | Rationally designed, synthetic antibody libraries and uses therefor |
SI2235064T1 (sl) | 2008-01-07 | 2016-04-29 | Amgen Inc. | Metoda za izdelavo heterodimernih molekul - protitelesa fc z uporabo elektrostatičnih usmerjevalnih učinkov |
US20090226442A1 (en) | 2008-01-22 | 2009-09-10 | Biogen Idec Ma Inc. | RON antibodies and uses thereof |
EP2297208A4 (en) | 2008-06-03 | 2012-07-11 | Abbott Lab | DUAL VARIABLE DOMAIN IMMUNOGLOBULINS AND ITS USES |
US8067339B2 (en) | 2008-07-09 | 2011-11-29 | Merck Sharp & Dohme Corp. | Surface display of whole antibodies in eukaryotes |
US9273136B2 (en) | 2008-08-04 | 2016-03-01 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Fully human anti-human NKG2D monoclonal antibodies |
US20100124764A1 (en) | 2008-09-26 | 2010-05-20 | Wyeth | Single chain antibody library design |
DK2356270T3 (da) | 2008-11-07 | 2016-12-12 | Fabrus Llc | Kombinatoriske antistofbiblioteker og anvendelser deraf |
CA2747011C (en) | 2008-12-18 | 2018-06-19 | Dana-Farber Cancer Institute, Inc. | Nkg2d-fc for immunotherapy |
CN106432503B (zh) | 2008-12-19 | 2020-03-06 | 宏观基因有限公司 | 共价双抗体及其用途 |
EP2417159A1 (en) | 2009-04-07 | 2012-02-15 | Roche Glycart AG | Bispecific anti-erbb-3/anti-c-met antibodies |
WO2010132697A2 (en) | 2009-05-13 | 2010-11-18 | Genzyme Corporation | Methods and compositions for treatment |
WO2010144295A1 (en) | 2009-06-09 | 2010-12-16 | University Of Miami | Aptamer-targeted costimulatory ligand aptamer |
ES2536996T3 (es) | 2009-07-06 | 2015-06-01 | F. Hoffmann-La Roche Ag | Anticuerpos biespecíficos de unión a digoxigenina |
WO2011028952A1 (en) | 2009-09-02 | 2011-03-10 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
KR101679602B1 (ko) | 2009-09-11 | 2016-11-25 | 다카라 바이오 가부시키가이샤 | 내추럴킬러 세포의 제조방법 |
RS54655B2 (sr) | 2009-10-27 | 2021-04-29 | Amgen Res Munich Gmbh | Dozni režim za primenu cd19xcd3 bispecifičnog antitela |
WO2011057124A1 (en) | 2009-11-06 | 2011-05-12 | Transtarget, Inc. | Polyclonal bispecific antibody compositions and method of use |
EP2332994A1 (en) | 2009-12-09 | 2011-06-15 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Trispecific therapeutics against acute myeloid leukaemia |
EP2512600A2 (en) | 2009-12-18 | 2012-10-24 | Amgen Inc. | Wise binding agents and epitopes |
US8658765B2 (en) | 2009-12-31 | 2014-02-25 | Avidbiotics Corp. | Non-natural MIC proteins |
US8796420B2 (en) | 2009-12-31 | 2014-08-05 | Avidbiotics Corp. | Non-natural MIC proteins |
US8802091B2 (en) | 2010-03-04 | 2014-08-12 | Macrogenics, Inc. | Antibodies reactive with B7-H3 and uses thereof |
NZ602161A (en) | 2010-03-04 | 2014-12-24 | Macrogenics Inc | Antibodies reactive with b7-h3, immunologically active fragments thereof and uses thereof |
TWI653333B (zh) | 2010-04-01 | 2019-03-11 | 安進研究(慕尼黑)有限責任公司 | 跨物種專一性之PSMAxCD3雙專一性單鏈抗體 |
MX353144B (es) | 2010-04-20 | 2017-12-20 | Genmab As | Proteinas que contienen fc de anticuerpos heterodimericos y metodos para produccion de las mismas. |
EP2569337A1 (en) | 2010-05-14 | 2013-03-20 | Rinat Neuroscience Corp. | Heterodimeric proteins and methods for producing and purifying them |
DK3323830T3 (da) | 2010-06-19 | 2023-09-25 | Memorial Sloan Kettering Cancer Center | Anti-gd2 antibodies |
UY33492A (es) | 2010-07-09 | 2012-01-31 | Abbott Lab | Inmunoglobulinas con dominio variable dual y usos de las mismas |
DE102010039018B4 (de) | 2010-08-06 | 2013-02-28 | Technische Universität Dresden | Anti-La Antikörper und ihre Anwendung zum Immunotargeting |
CA2808154A1 (en) | 2010-08-13 | 2012-02-16 | Medimmmune Limited | Monomeric polypeptides comprising variant fc regions and methods of use |
CA2807278A1 (en) | 2010-08-24 | 2012-03-01 | F. Hoffmann - La Roche Ag | Bispecific antibodies comprising a disulfide stabilized - fv fragment |
TWI560199B (en) | 2010-08-31 | 2016-12-01 | Sanofi Sa | Peptide or peptide complex binding to α2 integrin and methods and uses involving the same |
WO2012032080A1 (en) | 2010-09-07 | 2012-03-15 | F-Star Biotechnologische Forschungs- Und Entwicklungsges.M.B.H | Stabilised human fc |
NZ607510A (en) | 2010-09-10 | 2014-10-31 | Apexigen Inc | Anti-il-1 beta antibodies and methods of use |
US20120263722A1 (en) | 2010-11-04 | 2012-10-18 | Abbott Laboratories | Dual Variable Domain Immunoglobulins and Uses Thereof |
CN103429620B (zh) | 2010-11-05 | 2018-03-06 | 酵活有限公司 | 在Fc结构域中具有突变的稳定异源二聚的抗体设计 |
US9518132B2 (en) | 2010-11-09 | 2016-12-13 | Altimab Therapeutics, Inc. | Protein complexes for antigen binding and methods of use |
WO2012088290A2 (en) | 2010-12-22 | 2012-06-28 | Abbott Laboratories | Tri-variable domain binding proteins and uses thereof |
BR112013021526B1 (pt) | 2011-02-25 | 2021-09-21 | Chugai Seiyaku Kabushiki Kaisha | Polipeptídio variante, métodos para manter ou diminuir as atividades de ligação a fcgriia (tipo r) e fcgriia (tipo h) e aumentar a atividade de ligação a fcgriib de um polipeptídio e para a supressão da produção de um anticorpo contra um polipeptídio compreendendo a região fc do anticorpo, métodos para a produção do referido polipeptídio com atividades de ligação mantidas ou diminuídas e aumentada e para a produção suprimida de um anticorpo, composição farmacêutica e uso de um polipeptídio |
EP2686345B1 (en) | 2011-03-16 | 2018-04-25 | Amgen Inc. | Fc variants |
SG10201602371VA (en) | 2011-03-25 | 2016-04-28 | Glenmark Pharmaceuticals Sa | Hetero-dimeric immunoglobulins |
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 |
NZ618016A (en) | 2011-05-21 | 2015-05-29 | Macrogenics Inc | Deimmunized serum-binding domains and their use for extending serum half-life |
WO2012162561A2 (en) | 2011-05-24 | 2012-11-29 | Zyngenia, Inc. | Multivalent and monovalent multispecific complexes and their uses |
US8852599B2 (en) | 2011-05-26 | 2014-10-07 | Bristol-Myers Squibb Company | Immunoconjugates, compositions for making them, and methods of making and use |
EP2723362A1 (en) | 2011-06-21 | 2014-04-30 | Innate Pharma | NKp46-MEDIATED NK CELL TUNING |
DE102011118022B4 (de) | 2011-06-30 | 2018-01-18 | Gemoab Monoclonals Gmbh | Antikörper gegen das Prostata-spezifische Stammzellenantigen und dessen Verwendung |
WO2013013700A1 (en) | 2011-07-22 | 2013-01-31 | Affimed Therapeutics Ag | Multivalent antigen-binding fv molecule |
US10040853B2 (en) | 2011-09-09 | 2018-08-07 | Fred Hutchinson Cancer Research Center | Methods and compositions involving NKG2D inhibitors and cancer |
JP6322411B2 (ja) | 2011-09-30 | 2018-05-09 | 中外製薬株式会社 | 複数の生理活性を有する抗原の消失を促進する抗原結合分子 |
US10024867B2 (en) | 2011-09-30 | 2018-07-17 | Chugai Seiyaku Kabushiki Kaisha | Ion concentration-dependent binding molecule library |
US9718893B2 (en) * | 2011-12-19 | 2017-08-01 | Synimmune Gmbh | Bispecific antibody molecule |
EP2809682B1 (en) | 2012-02-03 | 2020-04-08 | F.Hoffmann-La Roche Ag | Bispecific antibody molecules with antigen-transfected t-cells and their use in medicine |
MX363819B (es) | 2012-02-08 | 2019-04-03 | Igm Biosciences Inc | Uniones a cdim y sus usos. |
GB201203442D0 (en) | 2012-02-28 | 2012-04-11 | Univ Birmingham | Immunotherapeutic molecules and uses |
US9029510B2 (en) | 2012-03-30 | 2015-05-12 | Sorrento Therapeutics, Inc. | Fully human antibodies that bind to VEGFR2 and methods of use thereof |
ES2743399T3 (es) | 2012-04-20 | 2020-02-19 | Merus Nv | Métodos y medios para la producción de moléculas heterodiméricas similares a Ig |
US9163090B2 (en) | 2012-05-07 | 2015-10-20 | Cellerant Therapeutics, Inc. | Antibodies specific for CLL-1 |
RU2743463C2 (ru) | 2012-05-30 | 2021-02-18 | Чугаи Сейяку Кабусики Кайся | Специфичная к ткани-мишени антигенсвязывающая молекула |
JP6628966B2 (ja) | 2012-06-14 | 2020-01-15 | 中外製薬株式会社 | 改変されたFc領域を含む抗原結合分子 |
CA2877573A1 (en) | 2012-06-21 | 2013-12-27 | Sorrento Therapeutics, Inc. | Antigen binding proteins that bind c-met |
EP2867253B1 (en) | 2012-06-27 | 2016-09-14 | F. Hoffmann-La Roche AG | Method for selection and production of tailor-made highly selective and multi-specific targeting entities containing at least two different binding entities and uses thereof |
KR20150036606A (ko) | 2012-07-13 | 2015-04-07 | 자임워크스 인코포레이티드 | 항-cd3 구조체를 포함하는 이중특이적 비대칭 이형이합체 |
US20140072581A1 (en) | 2012-07-23 | 2014-03-13 | Zymeworks Inc. | Immunoglobulin Constructs Comprising Selective Pairing of the Light and Heavy Chains |
WO2014022540A1 (en) | 2012-08-02 | 2014-02-06 | Regeneron Pharmaceuticals, Inc. | Multivalent antigen-binding proteins |
CA2874864C (en) | 2012-08-14 | 2023-02-21 | Ibc Pharmaceuticals, Inc. | T-cell redirecting bispecific antibodies for treatment of disease |
EP3470431A1 (en) * | 2012-09-27 | 2019-04-17 | Merus N.V. | Bispecific igg antibodies as t cell engagers |
US9562110B2 (en) | 2012-11-21 | 2017-02-07 | Wuhan Yzy Biopharma Co., Ltd. | Bispecific antibody |
WO2014084607A1 (ko) | 2012-11-27 | 2014-06-05 | 아주대학교산학협력단 | 항체 중쇄불변부위의 이종이중체 고효율 형성을 유도하는 ch3 도메인 변이체 쌍, 이의 제조방법, 및 용도 |
KR20160007478A (ko) | 2013-01-10 | 2016-01-20 | 젠맵 비. 브이 | 인간 IgG1 Fc 영역 변이체 및 그의 용도 |
EP2943511B1 (en) | 2013-01-14 | 2019-08-07 | Xencor, Inc. | Novel heterodimeric proteins |
US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
EP2948475A2 (en) | 2013-01-23 | 2015-12-02 | AbbVie Inc. | Methods and compositions for modulating an immune response |
EP2953974B1 (en) | 2013-02-05 | 2017-12-20 | EngMab Sàrl | Bispecific antibodies against cd3epsilon and bcma |
JP2016509014A (ja) | 2013-02-08 | 2016-03-24 | ステムセントリックス, インコーポレイテッド | 新規の多特異的構成物 |
KR101833602B1 (ko) | 2013-02-26 | 2018-02-28 | 로슈 글리카트 아게 | 이중특이적 t 세포 활성화 항원 결합 분자 |
MX2015012709A (es) | 2013-03-14 | 2016-05-31 | Macrogenics Inc | Moleculas biespecificas que son inmunorreactivas con celulas efectoras inmunes que expresan un receptor activador y un antigeno expresado por una celula infectada por un virus y usos de las mismas. |
CA2903576C (en) | 2013-03-15 | 2021-06-08 | Nai-Kong V. Cheung | High affinity anti-gd2 antibodies |
AU2014232501C1 (en) | 2013-03-15 | 2021-04-22 | Xencor, Inc. | Heterodimeric proteins |
US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
WO2014165818A2 (en) | 2013-04-05 | 2014-10-09 | T Cell Therapeutics, Inc. | Compositions and methods for preventing and treating prostate cancer |
US10156574B2 (en) | 2013-04-29 | 2018-12-18 | Adimab, Llc | Polyspecificity reagents, methods for their preparation and use |
EP2994490A1 (en) | 2013-05-10 | 2016-03-16 | Numab AG | Bispecific constructs and their use in the treatment of various diseases |
WO2014198748A1 (en) | 2013-06-11 | 2014-12-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-her2 single domain antibodies, polypeptides comprising thereof and their use for treating cancer |
US9908944B2 (en) | 2013-07-15 | 2018-03-06 | Novo Nordisk A/S | Antibodies that bind urokinase plasminogen activator |
MY183503A (en) | 2013-07-16 | 2021-02-23 | Genentech Inc | Method of treating cancer using pd-1 axis binding antagonists and tigit inhibitors |
CA2918795A1 (en) | 2013-07-25 | 2015-01-29 | Cytomx Therapeutics, Inc. | Multispecific antibodies, multispecific activatable antibodies and methods of using the same |
ES2773306T3 (es) | 2013-09-16 | 2020-07-10 | Helmholtz Zentrum Muenchen Deutsches Forschungszentrum Gesundheit & Umwelt Gmbh | Polipéptidos bi o multiespecíficos de unión a antígenos de superficie de células efectoras inmunitarias y antígenos de VHB para tratar infecciones por VHB y estados asociados |
GB2518221A (en) | 2013-09-16 | 2015-03-18 | Sergej Michailovic Kiprijanov | Tetravalent antigen-binding protein molecule |
GB2519786A (en) | 2013-10-30 | 2015-05-06 | Sergej Michailovic Kiprijanov | Multivalent antigen-binding protein molecules |
ES2742224T3 (es) | 2013-11-07 | 2020-02-13 | Memorial Sloan Kettering Cancer Center | Anticuerpos biespecíficos anti-WT1/HLA |
DE102013019352A1 (de) | 2013-11-13 | 2015-09-17 | Elke Pogge Von Strandmann | Tri-spezifische rekombinante Antikörperderivate zur Behandlung von malignen Erkrankungen durch Aktivierung einer NK-Zell-basierten Immunantwort |
KR20160098328A (ko) | 2013-12-13 | 2016-08-18 | 제넨테크, 인크. | 항-cd33 항체 및 면역접합체 |
WO2015095412A1 (en) | 2013-12-19 | 2015-06-25 | Zhong Wang | Bispecific antibody with two single-domain antigen-binding fragments |
WO2015095539A1 (en) | 2013-12-20 | 2015-06-25 | Genentech, Inc. | Dual specific antibodies |
RU2016129517A (ru) | 2013-12-20 | 2018-01-25 | Ф. Хоффманн-Ля Рош Аг | Биспецифические антитела к her2 и способы применения |
AU2014373593B2 (en) | 2013-12-23 | 2020-07-16 | Zymeworks Bc Inc. | Antibodies comprising C-terminal light chain polypeptide extensions and conjugates and methods of use thereof |
ES2923641T3 (es) | 2013-12-30 | 2022-09-29 | Epimab Biotherapeutics Inc | Inmunoglobulina con Fabs en tándem y usos de la misma |
CA2936785A1 (en) | 2014-01-15 | 2015-07-23 | Zymeworks Inc. | Bi-specific cd3 and cd19 antigen-binding constructs |
RU2744046C2 (ru) | 2014-03-05 | 2021-03-02 | Отолус Лимитед | ХИМЕРНЫЙ АНТИГЕННЫЙ РЕЦЕПТОР (CAR) С АНТИГЕНСВЯЗЫВАЮЩИМИ ДОМЕНАМИ К КОНСТАНТНОЙ ОБЛАСТИ β Т-КЛЕТОЧНОГО РЕЦЕПТОРА |
WO2015153514A1 (en) | 2014-03-31 | 2015-10-08 | Genentech, Inc. | Combination therapy comprising anti-angiogenesis agents and ox40 binding agonists |
EP3126384B1 (en) | 2014-04-01 | 2020-12-02 | Adimab, LLC | Multispecific antibody analogs comprising a common light chain, and methods of their preparation and use |
UA117289C2 (uk) | 2014-04-02 | 2018-07-10 | Ф. Хоффманн-Ля Рош Аг | Мультиспецифічне антитіло |
PL3126383T3 (pl) | 2014-04-03 | 2019-08-30 | Igm Biosciences, Inc. | Zmodyfikowany łańcuch J |
WO2015157592A1 (en) | 2014-04-11 | 2015-10-15 | Medimmune, Llc | Bispecific her2 antibodies |
EP2930188A1 (en) | 2014-04-13 | 2015-10-14 | Affimed Therapeutics AG | Trifunctional antigen-binding molecule |
EP2942629A1 (en) | 2014-05-08 | 2015-11-11 | Universität Würzburg | Predictive markers for successful cancer immunotherapy |
TWI707872B (zh) | 2014-05-29 | 2020-10-21 | 美商宏觀基因股份有限公司 | 特異性結合多種癌症抗原的三特異性結合分子和其使用方法 |
GB201409558D0 (en) | 2014-05-29 | 2014-07-16 | Ucb Biopharma Sprl | Method |
CA2952727A1 (en) | 2014-06-27 | 2015-12-30 | Innate Pharma | Multispecific nkp46 binding proteins |
CA2952532A1 (en) | 2014-06-27 | 2015-12-30 | Innate Pharma | Multispecific antigen binding proteins |
WO2015197582A1 (en) | 2014-06-27 | 2015-12-30 | Innate Pharma | Monomeric multispecific antigen binding proteins |
AU2015283704A1 (en) | 2014-07-01 | 2016-12-15 | Pfizer Inc. | Bispecific heterodimeric diabodies and uses thereof |
US9777073B2 (en) | 2014-07-21 | 2017-10-03 | Wuhan Yzy Biopharma Co., Ltd. | Construction and application of bispecific antibody EpCAM×CD3 |
US10556964B2 (en) | 2014-07-21 | 2020-02-11 | Wuhan Yzy Biopharma Co., Ltd. | Bispecific antibody-mediated cancer therapy with cytokine-induced killer cell |
CN112481283A (zh) | 2014-07-21 | 2021-03-12 | 诺华股份有限公司 | 使用cd33嵌合抗原受体治疗癌症 |
JP6919118B2 (ja) | 2014-08-14 | 2021-08-18 | ノバルティス アーゲー | GFRα−4キメラ抗原受容体を用いる癌の治療 |
EP2985294A1 (en) | 2014-08-14 | 2016-02-17 | Deutsches Krebsforschungszentrum | Recombinant antibody molecule and its use for target cell restricted T cell activation |
JO3663B1 (ar) | 2014-08-19 | 2020-08-27 | Merck Sharp & Dohme | الأجسام المضادة لمضاد lag3 وأجزاء ربط الأنتيجين |
CN107106677A (zh) | 2014-08-28 | 2017-08-29 | 莱顿大学学术医院以Lumc的名义运作 | Cd94/nkg2a和/或cd94/nkg2b抗体、疫苗组合 |
EP2990416B1 (en) | 2014-08-29 | 2018-06-20 | GEMoaB Monoclonals GmbH | Universal chimeric antigen receptor expressing immune cells for targeting of diverse multiple antigens and method of manufacturing the same and use of the same for treatment of cancer, infections and autoimmune disorders |
AU2015342264B2 (en) | 2014-11-03 | 2021-08-12 | Merck Patent Gmbh | Methods for generating bispecific shark variable antibody domains and use thereof |
WO2016087416A1 (en) | 2014-12-03 | 2016-06-09 | F. Hoffmann-La Roche Ag | Multispecific antibodies |
HRP20220531T1 (hr) * | 2014-12-05 | 2022-06-10 | Xyphos Biosciences Inc. | Varijabilni fragmenti antitijela koji se umeću i modificirane a1-a2 domene nkg2d liganda |
CA2970255A1 (en) | 2014-12-17 | 2016-06-23 | Intrexon Corporation | Intercalated single-chain variable fragments |
AU2015366166B2 (en) | 2014-12-19 | 2021-08-05 | Chiome Bioscience, Inc | Fusion protein comprising three binding domains to 5T4 and CD3 |
CN114316061A (zh) | 2015-01-02 | 2022-04-12 | 武田药品工业株式会社 | 针对血浆激肽释放酶和因子xii的双特异性抗体 |
JP2018503399A (ja) | 2015-01-14 | 2018-02-08 | コンパス セラピューティクス リミテッド ライアビリティ カンパニー | 多特異性免疫調節抗原結合構築物 |
TW201627322A (zh) | 2015-01-26 | 2016-08-01 | 宏觀基因股份有限公司 | 抗-dr5抗體和包括其dr5-結合結構域的分子 |
CA2977350C (en) | 2015-02-20 | 2022-08-23 | Ohio State Innovation Foundation | Bivalent antibody directed against nkg2d and tumor associated antigens |
MA41613A (fr) | 2015-02-23 | 2018-01-02 | Abbvie Stemcentrx Llc | Récepteurs antigéniques chimériques anti-dll3 et procédés d'utilisation desdits récepteurs |
WO2016135041A1 (en) | 2015-02-26 | 2016-09-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Fusion proteins and antibodies comprising thereof for promoting apoptosis |
US11673957B2 (en) | 2015-03-10 | 2023-06-13 | Eureka Therapeutics, Inc. | Anti-ROR2 antibodies |
JP6726676B2 (ja) | 2015-03-16 | 2020-07-22 | ヘルムホルツ・ツェントルム・ミュンヒェン・ドイチェス・フォルシュンクスツェントルム・フューア・ゲズントハイト・ウント・ウムベルト(ゲーエムベーハー)Helmholtz Zentrum Muenchen Deutsches Forschungszentrum fuer Gesundheit und Umwelt (GmbH) | Hbv感染および関連症状を治療するための三重特異的結合分子 |
US20180208658A1 (en) | 2015-04-03 | 2018-07-26 | Eureka Therapeutics, Inc. | Constructs targeting afp peptide/mhc complexes and uses thereof |
CN107708720A (zh) | 2015-04-06 | 2018-02-16 | 苏伯多曼有限责任公司 | 含有从头结合结构域的多肽及其用途 |
PT3280441T (pt) | 2015-04-07 | 2021-11-30 | Alector Llc | Anticorpos anti-sortilina e métodos para a sua utilização |
IL290488B1 (en) | 2015-04-13 | 2024-03-01 | Pfizer | Therapeutic antibodies and their uses |
WO2016166139A1 (en) | 2015-04-14 | 2016-10-20 | Eberhard Karls Universität Tübingen | Bispecific fusion proteins for enhancing immune responses of lymphocytes against tumor cells |
JP2018524284A (ja) | 2015-05-18 | 2018-08-30 | ユーリカ セラピューティックス, インコーポレイテッド | 抗ror1抗体 |
EP3095792A1 (en) | 2015-05-19 | 2016-11-23 | Klinikum rechts der Isar der Technischen Universität München | T cell receptor with specificity for myeloperoxidase peptide and uses thereof |
WO2016191305A1 (en) | 2015-05-22 | 2016-12-01 | The Board Of Trustees Of The Leland Stanford Junior University | Btn3a ectodomain proteins and methods of use |
PE20180926A1 (es) | 2015-05-29 | 2018-06-08 | Bristol Myers Squibb Co | Anticuerpos contra el miembro 4 de la superfamilia del receptor del factor de necrosis tumoral (ox40) y sus usos |
US10144779B2 (en) | 2015-05-29 | 2018-12-04 | Agenus Inc. | Anti-CTLA-4 antibodies and methods of use thereof |
WO2016201389A2 (en) | 2015-06-12 | 2016-12-15 | Alector Llc | Anti-cd33 antibodies and methods of use thereof |
AU2016274989A1 (en) | 2015-06-12 | 2017-11-02 | Immunomedics, Inc. | Disease therapy with chimeric antigen receptor (car) constructs and t cells (car-t) or nk cells (car-nk) expressing car constructs |
WO2016207278A1 (en) | 2015-06-23 | 2016-12-29 | Innate Pharma | Multispecific nk engager proteins |
CA2990511A1 (en) | 2015-06-23 | 2016-12-29 | Innate Pharma | Multispecific antigen binding proteins |
MX2017015908A (es) | 2015-07-06 | 2018-03-15 | Ucb Biopharma Sprl | Anticuerpos de union a tau. |
US20180194861A1 (en) | 2015-07-10 | 2018-07-12 | Abbvie Inc. | IgM- or IgE-Modified Binding Proteins and Uses Thereof |
CA2991799A1 (en) | 2015-07-15 | 2017-01-19 | Zymeworks Inc. | Drug-conjugated bi-specific antigen-binding constructs |
AU2016293606A1 (en) | 2015-07-16 | 2018-02-08 | Cellerant Therapeutics, Inc. | Cysteine-substituted immunoglobulins |
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 |
AU2016322934A1 (en) | 2015-09-14 | 2018-04-12 | Compass Therapeutics Llc | Compositions and methods for treating cancer via antagonism of the CD155/TIGIT pathway and TGF-beta |
EP3356403A2 (en) | 2015-10-02 | 2018-08-08 | H. Hoffnabb-La Roche Ag | Bispecific antibodies specific for a costimulatory tnf receptor |
SG11201803567XA (en) | 2015-10-29 | 2018-05-30 | Alector Llc | Anti-siglec-9 antibodies and methods of use thereof |
CN116063574A (zh) | 2015-11-04 | 2023-05-05 | 希望之城公司 | 靶向her2的嵌合抗原受体 |
WO2017083545A1 (en) | 2015-11-10 | 2017-05-18 | Fred Hutchinson Cancer Research Center | Nkg2d decoys |
US20180327499A1 (en) | 2015-11-13 | 2018-11-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti- nkg2d single domain antibodies and uses thereof |
US11001629B2 (en) | 2015-12-28 | 2021-05-11 | Innate Pharma | Variable regions for NKp46 binding proteins |
AU2017207480A1 (en) | 2016-01-13 | 2018-08-02 | Compass Therapeutics Llc | Multispecific immunomodulatory antigen-binding constructs |
EP3851457A1 (en) | 2016-01-21 | 2021-07-21 | Novartis AG | Multispecific molecules targeting cll-1 |
WO2017142928A1 (en) | 2016-02-17 | 2017-08-24 | Macrogenics, Inc. | Ror1-binding molecules, and methods of use thereof |
JP2019510812A (ja) | 2016-02-26 | 2019-04-18 | イミュネクサス・ピーティーワイ・リミテッド | 多重特異性分子 |
JP7082604B2 (ja) | 2016-03-21 | 2022-06-08 | マレンゴ・セラピューティクス,インコーポレーテッド | 多重特異性および多機能性分子ならびにその使用 |
EP3432924A1 (en) | 2016-03-23 | 2019-01-30 | Novartis AG | Cell secreted minibodies and uses thereof |
KR102514317B1 (ko) | 2016-04-15 | 2023-03-27 | 마크로제닉스, 인크. | 신규 b7-h3-결합 분자, 그것의 항체 약물 콘쥬게이트 및 그것의 사용 방법 |
KR20180135460A (ko) | 2016-04-15 | 2018-12-20 | 자임워크스 인코포레이티드 | 면역치료제를 표적으로 하는 다중-특이적 항원-결합 작제물 |
GB201610044D0 (en) | 2016-06-08 | 2016-07-20 | Ucb Biopharma Sprl | Antibodies |
IL263542B1 (en) | 2016-06-14 | 2024-06-01 | Xencor Inc | Bispecific antibodies inhibit immunological checkpoint |
US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
CN105906722B (zh) | 2016-06-24 | 2020-02-07 | 安徽未名细胞治疗有限公司 | 一种Her2特异性嵌合抗原受体及其应用 |
EP3507307A4 (en) | 2016-09-01 | 2020-04-22 | Immunomab, Inc. | BISPECIFIC ANTIBODIES |
US20190225702A1 (en) | 2016-10-14 | 2019-07-25 | Harpoon Therapeutics, Inc. | Innate immune cell trispecific binding proteins and methods of use |
CN110267678A (zh) | 2016-10-29 | 2019-09-20 | 霍夫曼-拉罗奇有限公司 | 抗mic抗体和使用方法 |
AU2017363311A1 (en) | 2016-11-22 | 2019-06-13 | TCR2 Therapeutics Inc. | Compositions and methods for TCR reprogramming using fusion proteins |
JOP20190134A1 (ar) | 2016-12-23 | 2019-06-02 | Potenza Therapeutics Inc | بروتينات رابطة لمولد ضد مضادة لنيوروبيلين وطرق استخدامها |
US20200095327A1 (en) | 2017-02-08 | 2020-03-26 | Dragonfly Therapeutics, Inc. | Antibody heavy chain variable domains targeting the nkg2d receptor |
AU2018219887A1 (en) | 2017-02-08 | 2019-08-22 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins for activation of natural killer cells and therapeutic uses thereof to treat cancer |
US20200024353A1 (en) | 2017-02-10 | 2020-01-23 | Dragonfly Therapeutics, Inc. | Proteins binding psma, nkg2d and cd16 |
MA47465A (fr) | 2017-02-10 | 2019-12-18 | Dragonfly Therapeutics Inc | Protéines fixant le bcma, le nkg2d et le cd16 |
KR20190120782A (ko) | 2017-02-20 | 2019-10-24 | 드래곤플라이 쎄라퓨틱스, 인크. | Her2, nkg2d 및 cd16에 결합하는 단백질 |
WO2018152530A1 (en) | 2017-02-20 | 2018-08-23 | Adimab, Llc | Proteins binding gd2, nkg2d and cd16 |
CA3054078A1 (en) | 2017-02-20 | 2018-08-23 | Dragonfly Therapeutics, Inc. | Proteins binding cd33, nkg2d and cd16 |
SG11201907645PA (en) | 2017-02-20 | 2019-09-27 | Dragonfly Therapeutics Inc | Proteins binding cd123, nkg2d and cd16 |
CA3099179A1 (en) | 2017-02-27 | 2018-08-30 | Dragonfly Therapeutics, Inc. | Multispecific binding proteins targeting caix, ano1, mesothelin, trop2, cea, or claudin-18.2 |
WO2018201051A1 (en) | 2017-04-28 | 2018-11-01 | Novartis Ag | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
EP3630183A4 (en) | 2017-05-23 | 2021-03-03 | Dragonfly Therapeutics, Inc. | PROTEIN THAT BINDING NKG2D, CD16 AND ROR1 OR ROR2 |
CN111278460A (zh) | 2017-05-23 | 2020-06-12 | 蜻蜓疗法股份有限公司 | 结合nkg2d、cd16和肿瘤相关抗原的蛋白质 |
MX2019014000A (es) | 2017-05-23 | 2020-07-29 | Dragonfly Therapeutics Inc | Una proteína que se une a nkg2d, cd16 y un antígeno asociado a un tumor. |
SG11202000632QA (en) | 2017-07-31 | 2020-02-27 | Dragonfly Therapeutics Inc | Proteins binding nkg2d, cd16 and flt3 |
SG11201913969SA (en) | 2017-08-16 | 2020-01-30 | Dragonfly Therapeutics Inc | Proteins binding nkg2d, cd16, and egfr, hla-e ccr4, or pd-l1 |
US20200231679A1 (en) | 2017-08-23 | 2020-07-23 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16 and a tumor-associated antigen |
CN113004417A (zh) | 2017-09-07 | 2021-06-22 | 蜻蜓疗法股份有限公司 | 结合nkg2d、cd16和肿瘤相关抗原的蛋白质 |
WO2019055677A1 (en) | 2017-09-14 | 2019-03-21 | Dragonfly Therapeutics, Inc. | NKG2D, CD16, AND LIQUID-LIKE MOLECULE-1-LIKE PROTEINS (CLL-1) |
CA3090236A1 (en) | 2018-02-08 | 2019-08-15 | Dragonfly Therapeutics, Inc. | Combination therapy of cancer involving multi-specific binding proteins that activate natural killer cells |
AU2019218136A1 (en) | 2018-02-08 | 2020-08-13 | Dragonfly Therapeutics, Inc. | Antibody variable domains targeting the NKG2D receptor |
JP2021514206A (ja) | 2018-02-20 | 2021-06-10 | ドラゴンフライ セラピューティクス, インコーポレイテッド | Cd33を標的とする抗体可変ドメイン及びその使用 |
BR112020016939A2 (pt) | 2018-02-20 | 2020-12-15 | Dragonfly Therapeutics, Inc. | Proteínas de ligação multiespecíficas que se ligam a cd33, nkg2d, e cd16 e métodos de uso |
EP3773676A4 (en) | 2018-04-03 | 2022-05-18 | Dragonfly Therapeutics, Inc. | PROTEINS THAT BIND NKG2D, CD16 AND AN ANTIGEN ASSOCIATED WITH TUMORS, MDSCS AND/OR TAMS |
WO2019195408A1 (en) | 2018-04-03 | 2019-10-10 | Dragonfly Therapeutics, Inc. | Antibody variable domains targeting dll3, and use thereof |
EP3790585A4 (en) | 2018-05-07 | 2022-05-11 | Dragonfly Therapeutics, Inc. | NKG2D, CD16 AND TUMOR ASSOCIATED ANTIGEN BINDING PROTEIN |
CA3100234A1 (en) | 2018-05-16 | 2019-11-21 | Dragonfly Therapeutics, Inc. | Protein binding nkg2d, cd16 and a fibroblast activation protein |
EA202091977A1 (ru) | 2018-05-28 | 2021-02-09 | Драгонфлай Терапьютикс, Инк. | Мультиспецифические связывающие белки, которые связывают cd33, nkg2d и cd16, и способы применения |
EA202091888A1 (ru) | 2018-08-08 | 2020-10-23 | Драгонфлай Терапьютикс, Инк. | Вариабельные домены антител, нацеленные на рецептор nkg2d |
BR112021002278A2 (pt) | 2018-08-08 | 2021-07-20 | Dragonfly Therapeutics, Inc. | proteínas que ligam nkg2d, cd16 e um antígeno associado a tumor |
EP3870598A1 (en) | 2018-10-23 | 2021-09-01 | Dragonfly Therapeutics, Inc. | Heterodimeric fc-fused proteins |
JP2022520978A (ja) | 2019-02-18 | 2022-04-04 | クーリエ セラピューティクス インコーポレイテッド | オルソポックスウイルス主要組織適合性複合体(mhc)クラスi様タンパク質(omcp)と腫瘍特異的結合パートナーを用いた二重特異性融合タンパク質 |
EP3990476A1 (en) | 2019-06-25 | 2022-05-04 | Gilead Sciences, Inc. | Flt3l-fc fusion proteins and methods of use |
AR119393A1 (es) | 2019-07-15 | 2021-12-15 | Hoffmann La Roche | Anticuerpos que se unen a nkg2d |
JP2022546454A (ja) | 2019-08-30 | 2022-11-04 | ドラゴンフライ セラピューティクス, インコーポレイテッド | がん処置のためのher2、nkg2dおよびcd16に結合する多重特異性結合タンパク質の医薬製剤および投薬量レジメン |
WO2021226193A1 (en) | 2020-05-06 | 2021-11-11 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16 and clec12a |
-
2018
- 2018-02-08 AU AU2018219887A patent/AU2018219887A1/en active Pending
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-
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- 2019-08-06 IL IL268554A patent/IL268554A/en unknown
-
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- 2022-05-09 JP JP2022077006A patent/JP2022101709A/ja not_active Withdrawn
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- 2023-10-06 US US18/482,629 patent/US20240166753A1/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011506406A (ja) * | 2007-12-14 | 2011-03-03 | ノボ・ノルデイスク・エー/エス | ヒトnkg2dに対する抗体とその使用 |
JP2013500721A (ja) * | 2009-07-29 | 2013-01-10 | アボット・ラボラトリーズ | 二重可変ドメイン免疫グロブリンおよびその使用 |
WO2013002362A1 (ja) * | 2011-06-30 | 2013-01-03 | 中外製薬株式会社 | ヘテロ二量化ポリペプチド |
Non-Patent Citations (4)
Title |
---|
MEDCHEM NEWS, JPN6023014115, 2012, pages 25 - 29, ISSN: 0005031491 * |
NATURE, vol. 406, JPN6023014114, 2000, pages 267 - 273, ISSN: 0005031492 * |
がん免疫療法のメカニズム解明と臨床への展開 がんと免疫, vol. 1版, JPN6022033118, 2015, pages 23, ISSN: 0004844264 * |
ファルマシア, vol. 51, no. 5, JPN6021048876, 2015, pages 424 - 428, ISSN: 0004657200 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022004805A1 (ja) | 2020-06-30 | 2022-01-06 | 株式会社ガイアバイオメディシン | Nk細胞と抗体との結合を安定化する方法、及びその利用 |
KR20230030587A (ko) | 2020-06-30 | 2023-03-06 | 가부시키가이샤 가이아바이오메디신 | Nk 세포와 항체의 결합을 안정화시키는 방법, 및 그 이용 |
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US20240166753A1 (en) | 2024-05-23 |
CA3221995C (en) | 2024-05-28 |
CA3221995A1 (en) | 2018-08-16 |
AU2018219887A1 (en) | 2019-08-22 |
EP3579848A1 (en) | 2019-12-18 |
JP2022101709A (ja) | 2022-07-06 |
US20190359716A1 (en) | 2019-11-28 |
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RU2019128060A (ru) | 2021-03-09 |
US11834506B2 (en) | 2023-12-05 |
WO2018148445A1 (en) | 2018-08-16 |
KR20240023449A (ko) | 2024-02-21 |
BR112019016315A2 (pt) | 2020-03-31 |
EP3579848A4 (en) | 2021-03-03 |
SG11201907299XA (en) | 2019-09-27 |
CN110944651A (zh) | 2020-03-31 |
IL268554A (en) | 2019-09-26 |
MX2019009468A (es) | 2020-01-20 |
CA3053010A1 (en) | 2018-08-16 |
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