KR102426765B1 - Cd137에 대한 신규한 이중특이성 폴리펩타이드 - Google Patents
Cd137에 대한 신규한 이중특이성 폴리펩타이드 Download PDFInfo
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| PCT/EP2017/059656 WO2017182672A1 (en) | 2016-04-22 | 2017-04-24 | Novel bispecific polypeptides against cd137 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024117781A1 (ko) * | 2022-11-29 | 2024-06-06 | (주) 테라베스트 | Cd137 세포외 도메인을 포함하는 융합단백질, 이를 발현하는 면역세포 및 이의 용도 |
Families Citing this family (75)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10532106B2 (en) | 2014-10-29 | 2020-01-14 | Bicyclerd Limited | Bicyclic peptide ligands specific for MT1-MMP |
| CA3025345A1 (en) | 2016-05-27 | 2017-11-30 | Abbvie Biotherapeutics Inc. | Bispecific binding proteins binding an immunomodulatory protein and a tumor antigen |
| US11214618B2 (en) | 2016-06-20 | 2022-01-04 | F-Star Therapeutics Limited | LAG-3 binding members |
| US11214620B2 (en) | 2016-06-20 | 2022-01-04 | F-Star Therapeutics Limited | Binding molecules binding PD-L1 and LAG-3 |
| UA128304C2 (uk) | 2016-07-14 | 2024-06-05 | Ґенмаб А/С | Мультиспецифічне антитіло до cd40 і cd137 |
| GB201612520D0 (en) | 2016-07-19 | 2016-08-31 | F-Star Beta Ltd | Binding molecules |
| CN117510643A (zh) * | 2016-09-23 | 2024-02-06 | 美勒斯公司 | 调节细胞表达的生物活性的结合分子 |
| MY200973A (en) | 2017-04-11 | 2024-01-26 | Inhibrx Inc | Multispecific Polypeptide Constructs Having Constrained Cd3 Binding And Methods Of Using The Same |
| BR112019017241A2 (pt) | 2017-04-13 | 2020-04-14 | Agenus Inc | anticorpos anti-cd137 e métodos de uso dos mesmos |
| CA3070272A1 (en) | 2017-07-20 | 2019-01-24 | Aptevo Research And Development Llc | Antigen binding proteins binding to 5t4 and 4-1bb and related compositions and methods |
| JP7290013B2 (ja) | 2017-08-04 | 2023-06-13 | ジェンマブ エー／エス | Ｐｄ－ｌ１およびｃｄ１３７に結合する結合物質ならびにその使用 |
| CN111183147B (zh) | 2017-08-04 | 2024-07-05 | 拜斯科技术开发有限公司 | Cd137特异性的双环肽配体 |
| CN111683968B (zh) | 2017-11-13 | 2024-07-05 | 克雷森多生物制剂有限公司 | 结合至cd137和psma的分子 |
| TWI825046B (zh) | 2017-12-19 | 2023-12-11 | 英商拜西可泰克斯有限公司 | Epha2特用之雙環胜肽配位基 |
| CN111741976B (zh) | 2017-12-19 | 2024-09-17 | 英沃克斯制药有限公司 | 包括pd-l1抗原结合位点的fc结合片段 |
| CN109970865B (zh) * | 2017-12-28 | 2022-10-04 | 上海细胞治疗研究院 | 一种cd137双向激活共刺激分子受体及其用途 |
| JP2021514953A (ja) | 2018-02-23 | 2021-06-17 | バイスクルテクス・リミテッド | 多量体二環式ペプチドリガンド |
| EP3765493A2 (en) | 2018-03-12 | 2021-01-20 | Genmab A/S | Antibodies |
| KR20200139236A (ko) * | 2018-04-04 | 2020-12-11 | 바이사이클티엑스 리미티드 | 헤테로탠덤 비사이클릭 펩티드 복합체 |
| IL323061A (en) | 2018-04-11 | 2025-10-01 | Inhibrx Biosciences Inc | Multispecific polypeptide constructs with forced CD3 binding and related methods and uses |
| US12168691B2 (en) | 2018-05-31 | 2024-12-17 | Board Of Regents, The University Of Texas System | VHS format bi-specific antibodies specific for HER2 and VEGF and use thereof |
| JP7557377B2 (ja) | 2018-06-06 | 2024-09-27 | レアダルティス、ソシエダッド リミターダ | 三量体ポリペプチド複合体およびその使用 |
| GB201810316D0 (en) | 2018-06-22 | 2018-08-08 | Bicyclerd Ltd | Peptide ligands for binding to EphA2 |
| US11180531B2 (en) | 2018-06-22 | 2021-11-23 | Bicycletx Limited | Bicyclic peptide ligands specific for Nectin-4 |
| GB201811408D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | CD137 Binding Molecules |
| CA3106048A1 (en) | 2018-07-12 | 2020-01-16 | F-Star Beta Limited | Antibody molecules that bind cd137 and ox40 |
| GB201811450D0 (en) * | 2018-07-12 | 2018-08-29 | F Star Delta Ltd | Mesothelin and CD137 binding molecules |
| GB201811403D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Antibody molecules |
| GB201811415D0 (en) * | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Anti-Mesothelin Anti bodies |
| GB201811410D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | OX40 Binding molecules |
| CN112423845B (zh) | 2018-07-12 | 2024-07-30 | F-星治疗有限公司 | 结合pd-l1和cd137的抗体分子 |
| GB201811404D0 (en) * | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Anti-CD137 Antibodies |
| CN112789294A (zh) | 2018-07-24 | 2021-05-11 | 印希比股份有限公司 | 含有受限cd3结合结构域和受体结合区的多特异性多肽构建体及其使用方法 |
| CA3113539A1 (en) * | 2018-10-10 | 2020-04-16 | Zymeworks Inc. | Antibody constructs binding 4-1bb and tumor-associated antigens and uses thereof |
| TW202506736A (zh) * | 2018-10-11 | 2025-02-16 | 美商因荷布瑞克斯生物科學公司 | 5t4單域抗體及其治療性組合物 |
| WO2020083277A1 (zh) * | 2018-10-22 | 2020-04-30 | 上海一宸医药科技有限公司 | 一种双特异性抗体 |
| BR112021010402A2 (pt) | 2018-11-30 | 2021-08-24 | Abl Bio Inc. | Anticorpos biespecíficos anti-pd-l1/anti-4-1bb e uso dos mesmos |
| GB201820325D0 (en) | 2018-12-13 | 2019-01-30 | Bicyclerd Ltd | Bicyclic peptide ligands specific for psma |
| GB201820288D0 (en) | 2018-12-13 | 2019-01-30 | Bicycle Tx Ltd | Bicycle peptide ligaands specific for MT1-MMP |
| GB201820295D0 (en) | 2018-12-13 | 2019-01-30 | Bicyclerd Ltd | Bicyclic peptide ligands specific for MT1-MMP |
| EP3898681A2 (en) * | 2018-12-17 | 2021-10-27 | Alligator Bioscience AB | Polypeptides |
| GB201820556D0 (en) * | 2018-12-17 | 2019-01-30 | Alligator Bioscience Ab | Novel polypeptides |
| US20220064325A1 (en) * | 2018-12-17 | 2022-03-03 | Alligator Bioscience Ab | Novel polypeptides |
| EP3897725A4 (en) * | 2018-12-21 | 2022-11-30 | Actinium Pharmaceuticals, Inc. | COMBINATION OF RADIOIMMUNOTHERAPY AND IMMUNOTHERAPY IN THE TREATMENT OF CANCER |
| WO2020128526A1 (en) | 2018-12-21 | 2020-06-25 | Bicycletx Limited | Bicyclic peptide ligands specific for pd-l1 |
| TWI793395B (zh) * | 2019-01-25 | 2023-02-21 | 大陸商信達生物製藥（蘇州）有限公司 | 結合ｐｄ-ｌ１和ｏｘ４０的雙特異性抗體 |
| GB201905100D0 (en) * | 2019-04-10 | 2019-05-22 | Antibody Innovation Ltd | Polypeptides and methods of use |
| CN113811541A (zh) | 2019-05-09 | 2021-12-17 | 拜斯科技术开发有限公司 | Ox40特异性的双环肽配体 |
| CN114450306B (zh) * | 2019-07-26 | 2024-04-05 | Abl生物公司 | 抗egfr/抗4-1bb双特异性抗体及其用途 |
| WO2021020846A1 (en) | 2019-07-26 | 2021-02-04 | Abl Bio Inc. | Anti-her2/anti-4-1bb bispecific antibody and use thereof |
| TWI862640B (zh) | 2019-07-30 | 2024-11-21 | 英商拜西可泰克斯有限公司 | 異質雙環肽複合物 |
| CN112592404B (zh) * | 2019-09-20 | 2023-07-25 | 上海交通大学医学院 | 抗体活性改造及其筛选方法 |
| PL4464721T3 (pl) * | 2019-10-03 | 2025-08-25 | Bicycletx Limited | Heterotandemowe kompleksy peptydów bicyklicznych |
| EP3816185A1 (en) | 2019-11-04 | 2021-05-05 | Numab Therapeutics AG | Multispecific antibody directed against pd-l1 and a tumor-associated antigen |
| WO2021101346A1 (en) * | 2019-11-21 | 2021-05-27 | Dong-A St Co., Ltd. | Anti-ror1/anti-4-1bb bispecific antibodies and uses thereof |
| US20230048361A1 (en) | 2019-12-31 | 2023-02-16 | Kahr Medical Ltd. | Methods of culturing t cells and uses of same |
| WO2021137231A1 (en) | 2019-12-31 | 2021-07-08 | Kahr Medical Ltd. | Methods of culturing t cells with a 4-1bbl fusion polypeptide and uses of same |
| JP2023509516A (ja) | 2020-01-07 | 2023-03-08 | ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | がん治療のための改良型ヒトメチルチオアデノシン／アデノシン枯渇酵素変種 |
| CN115151573A (zh) * | 2020-02-28 | 2022-10-04 | 上海复宏汉霖生物技术股份有限公司 | 抗cd137构建体、多特异性抗体及其用途 |
| JP7702961B6 (ja) * | 2020-02-28 | 2025-07-17 | 上海復宏漢霖生物技術股▲フン▼有限公司 | 抗ｃｄ１３７コンストラクト、多重特異性抗体及びその使用 |
| CA3146977A1 (en) * | 2020-04-15 | 2021-10-21 | Zymeworks Inc. | Antibody constructs binding 4-1bb and folate receptor alpha and uses thereof |
| WO2021236658A1 (en) | 2020-05-19 | 2021-11-25 | Boehringer Ingelheim International Gmbh | Binding molecules for the treatment of cancer |
| US20230242658A1 (en) * | 2020-06-30 | 2023-08-03 | Nona Biosciences (Suzhou) Co., Ltd. | 4-1bb-binding protein and use thereof |
| KR20230042524A (ko) | 2020-08-07 | 2023-03-28 | 주식회사 유틸렉스 | 항-her2 / 항-4-1bb 이중특이적 항체 및 이의 용도 |
| JP2023547507A (ja) * | 2020-11-03 | 2023-11-10 | ドイチェス クレブスフォルシュンクスツェントルム スチフトゥング デス エッフェントリヒェン レヒツ | 標的細胞限定的で共刺激性の二重特異性かつ２価の抗ｃｄ２８抗体 |
| JP2024504388A (ja) * | 2021-01-25 | 2024-01-31 | ユーハン・コーポレイション | 抗４－１ｂｂ／抗ｈｅｒ２二重特異性抗体の精製方法 |
| CN118234750A (zh) * | 2021-09-02 | 2024-06-21 | 纪念斯隆-凯特琳癌症中心 | 抗cd33抗体和其用途 |
| US20240417482A1 (en) * | 2021-10-12 | 2024-12-19 | Concept To Medicine Biotech Co., Ltd. | Single-domain 4-1bb antibodies |
| WO2023174521A1 (en) * | 2022-03-15 | 2023-09-21 | Genmab A/S | Binding agents binding to epcam and cd137 |
| WO2024051752A1 (en) * | 2022-09-06 | 2024-03-14 | I-Mab Biopharma Co., Ltd. | Multispecific constructs and uses thereof |
| WO2024061364A1 (zh) * | 2022-09-22 | 2024-03-28 | 成都盛世君联生物技术有限公司 | 一种抗4-1bb纳米抗体及其制备和应用 |
| TW202426503A (zh) * | 2022-10-19 | 2024-07-01 | 日商安斯泰來製藥股份有限公司 | 癌症治療中與ｐｄ－１訊息抑制劑組合之抗ｃｌｄｎ４－抗ｃｄ１３７雙特異性抗體的用途 |
| WO2024143643A1 (ko) * | 2022-12-30 | 2024-07-04 | 앱클론(주) | Cd137에 특이적으로 결합하는 어피바디 및 이의 용도 |
| WO2025035107A2 (en) * | 2023-08-09 | 2025-02-13 | Curadh Mtr, Inc. | Trophoblast glycoprotein antibody compositions and methods of use |
| WO2025056180A1 (en) * | 2023-09-15 | 2025-03-20 | BioNTech SE | Methods of treatment using agents binding to epcam and cd137 in combination with pd-1 axis binding antagonists |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014116846A2 (en) * | 2013-01-23 | 2014-07-31 | Abbvie, Inc. | Methods and compositions for modulating an immune response |
| WO2015156268A1 (ja) * | 2014-04-07 | 2015-10-15 | 中外製薬株式会社 | 免疫活性化抗原結合分子 |
| US20150307620A1 (en) * | 2014-04-16 | 2015-10-29 | University Of Connecticut | Linked immunotherapeutic agonists that costimulate multiple pathways |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| SE459005B (sv) | 1985-07-12 | 1989-05-29 | Aake Rikard Lindahl | Saett att framstaella sfaeriska polymerpartiklar |
| CA2192782C (en) | 1995-12-15 | 2008-10-14 | Nobuyuki Takechi | Production of microspheres |
| ATE411342T1 (de) * | 1999-11-18 | 2008-10-15 | Oxford Biomedica Ltd | Scfv antikörper gegen krankheiten-assoziierte moleküle |
| BR0108001A (pt) * | 2000-02-01 | 2004-01-06 | Tanox Inc | Moléculas ativadoras de apc com ligação para cd-40 |
| DK1272647T3 (en) | 2000-04-11 | 2014-12-15 | Genentech Inc | Multivalent antibodies and uses thereof |
| TW200616662A (en) | 2004-09-10 | 2006-06-01 | Wyeth Corp | Humanized anti-5t4 antibodies and anti-5t4 antibody/calicheamicin conjugates |
| US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
| PL2663580T3 (pl) * | 2011-01-10 | 2017-08-31 | Ct Atlantic Ltd. | Terapia skojarzona obejmująca przeciwciała wiążące antygen związany z nowotworem |
| KR20160044598A (ko) | 2011-03-29 | 2016-04-25 | 로슈 글리카트 아게 | 항체 Fc 변이체 |
| WO2013026839A1 (en) | 2011-08-23 | 2013-02-28 | Roche Glycart Ag | Bispecific antibodies specific for t-cell activating antigens and a tumor antigen and methods of use |
| WO2013041687A1 (en) * | 2011-09-23 | 2013-03-28 | Amgen Research (Munich) Gmbh | Bispecific binding molecules for 5t4 and cd3 |
| CN112546231A (zh) * | 2014-07-09 | 2021-03-26 | 博笛生物科技有限公司 | 用于治疗癌症的联合治疗组合物和联合治疗方法 |
| HRP20191824T1 (hr) * | 2015-01-08 | 2020-01-24 | BioNTech SE | Agonistička sredstva za vezivanje tnf receptora |
| 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 |
| RU2017142008A (ru) * | 2015-05-21 | 2019-06-24 | Эллигейтор Биосайенс Аб | Новые полипептиды |
| EP3585431A4 (en) * | 2017-02-24 | 2020-12-16 | MacroGenics, Inc. | BISPECIFIC BINDING MOLECULES CAPABLE OF BINDING TO CD137 AND TUMOR ANTIGENS, AND THEIR USES |
| CA3070272A1 (en) | 2017-07-20 | 2019-01-24 | Aptevo Research And Development Llc | Antigen binding proteins binding to 5t4 and 4-1bb and related compositions and methods |
-
2017
- 2017-04-24 KR KR1020187030680A patent/KR102426765B1/ko active Active
- 2017-04-24 RU RU2018139339A patent/RU2018139339A/ru unknown
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-
2021
- 2021-09-23 US US17/482,708 patent/US12173082B2/en active Active
- 2021-11-26 JP JP2021192091A patent/JP2022058338A/ja active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014116846A2 (en) * | 2013-01-23 | 2014-07-31 | Abbvie, Inc. | Methods and compositions for modulating an immune response |
| WO2015156268A1 (ja) * | 2014-04-07 | 2015-10-15 | 中外製薬株式会社 | 免疫活性化抗原結合分子 |
| US20150307620A1 (en) * | 2014-04-16 | 2015-10-29 | University Of Connecticut | Linked immunotherapeutic agonists that costimulate multiple pathways |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024117781A1 (ko) * | 2022-11-29 | 2024-06-06 | (주) 테라베스트 | Cd137 세포외 도메인을 포함하는 융합단백질, 이를 발현하는 면역세포 및 이의 용도 |
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| IL262482A (en) | 2018-12-31 |
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| JP2019523630A (ja) | 2019-08-29 |
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