JP7459058B2 - Cd137/her2二重特異性物質とpd-1系阻害物質とを含む併用療法およびその使用法 - Google Patents
Cd137/her2二重特異性物質とpd-1系阻害物質とを含む併用療法およびその使用法 Download PDFInfo
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| JP2016508028A (ja) | 2012-11-30 | 2016-03-17 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | Pd−l1阻害剤併用療法を必要とする患者の同定 |
| JP2017507900A (ja) | 2013-12-17 | 2017-03-23 | ジェネンテック, インコーポレイテッド | Pd−1軸結合アンタゴニスト及び抗her2抗体を使用してher2陽性がんを治療する方法 |
| JP2018515085A (ja) | 2015-05-04 | 2018-06-14 | ピエリス ファーマシューティカルズ ゲーエムベーハー | 抗がん融合ポリペプチド |
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| RS54271B1 (sr) | 2005-07-01 | 2016-02-29 | E. R. Squibb & Sons, L.L.C. | Humana monoklonska antitela za ligand programirane smrti 1 (pd-l1) |
| NZ582150A (en) | 2007-06-18 | 2012-08-31 | Msd Oss Bv | Antibodies to human programmed death receptor pd-1 |
| WO2009114335A2 (en) | 2008-03-12 | 2009-09-17 | Merck & Co., Inc. | Pd-1 binding proteins |
| CN102203132A (zh) | 2008-08-25 | 2011-09-28 | 安普利穆尼股份有限公司 | Pd-1拮抗剂的组合物和使用方法 |
| HRP20170908T1 (hr) | 2008-12-09 | 2017-09-22 | F. Hoffmann - La Roche Ag | Protutijela anti-pd-l1 i njihova uporaba za poboljšanje funkcije t-stanice |
| WO2010089411A2 (en) | 2009-02-09 | 2010-08-12 | Universite De La Mediterranee | Pd-1 antibodies and pd-l1 antibodies and uses thereof |
| PT2504364T (pt) | 2009-11-24 | 2017-11-14 | Medimmune Ltd | Agentes de ligação direcionados contra b7-h1 |
| EP2545078A1 (en) | 2010-03-11 | 2013-01-16 | UCB Pharma, S.A. | Pd-1 antibody |
| CA2833636A1 (en) | 2011-04-20 | 2012-10-26 | Amplimmune, Inc. | Antibodies and other molecules that bind b7-h1 and pd-1 |
| EP2734551B1 (en) | 2011-07-24 | 2018-01-10 | Cure Tech Ltd. | Variants of humanized immunomodulatory monoclonal antibodies |
| RS61033B1 (sr) | 2011-11-28 | 2020-12-31 | Merck Patent Gmbh | Antitela na pd-l1 i njihova upotreba |
| US9676853B2 (en) | 2013-05-31 | 2017-06-13 | Sorrento Therapeutics, Inc. | Antigen binding proteins that bind PD-1 |
| SG11201601844TA (en) | 2013-09-13 | 2016-04-28 | Beigene Ltd | Anti-pd1 antibodies and their use as therapeutics and diagnostics |
| EP4285928A3 (en) | 2013-09-27 | 2024-03-13 | F. Hoffmann-La Roche AG | Anti-pdl1 antibody formulations |
| US10202454B2 (en) | 2013-10-25 | 2019-02-12 | Dana-Farber Cancer Institute, Inc. | Anti-PD-L1 monoclonal antibodies and fragments thereof |
| TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對pd-1的人類抗體 |
| KR102360693B1 (ko) | 2014-07-11 | 2022-02-08 | 벤타나 메디컬 시스템즈, 인코포레이티드 | 항-pd-l1 항체 및 이의 진단 용도 |
| EP3206711B1 (en) | 2014-10-14 | 2023-05-31 | Novartis AG | Antibody molecules to pd-l1 and uses thereof |
| CA2971734C (en) | 2014-12-22 | 2025-11-18 | Enumeral Biomedical Holdings Inc | Anti-pd-1 antibodies |
| GB201500319D0 (en) | 2015-01-09 | 2015-02-25 | Agency Science Tech & Res | Anti-PD-L1 antibodies |
| JP6432121B2 (ja) | 2016-03-04 | 2018-12-05 | シチュアン ケルン−バイオテック バイオファーマシューティカル カンパニー リミテッド | Pdl−1抗体、その医薬組成物及びその使用 |
-
2019
- 2019-08-27 CA CA3106881A patent/CA3106881A1/en active Pending
- 2019-08-27 KR KR1020217007565A patent/KR20210052468A/ko not_active Ceased
- 2019-08-27 AU AU2019328632A patent/AU2019328632A1/en not_active Abandoned
- 2019-08-27 WO PCT/EP2019/072754 patent/WO2020043683A1/en not_active Ceased
- 2019-08-27 JP JP2021510824A patent/JP7459058B2/ja active Active
- 2019-08-27 EP EP19756382.8A patent/EP3843849A1/en not_active Withdrawn
- 2019-08-27 US US17/271,149 patent/US20210246219A1/en not_active Abandoned
- 2019-08-27 CN CN201980071320.7A patent/CN112955221A/zh active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016508028A (ja) | 2012-11-30 | 2016-03-17 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | Pd−l1阻害剤併用療法を必要とする患者の同定 |
| JP2017507900A (ja) | 2013-12-17 | 2017-03-23 | ジェネンテック, インコーポレイテッド | Pd−1軸結合アンタゴニスト及び抗her2抗体を使用してher2陽性がんを治療する方法 |
| JP2018515085A (ja) | 2015-05-04 | 2018-06-14 | ピエリス ファーマシューティカルズ ゲーエムベーハー | 抗がん融合ポリペプチド |
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|---|---|
| US20210246219A1 (en) | 2021-08-12 |
| CN112955221A (zh) | 2021-06-11 |
| EP3843849A1 (en) | 2021-07-07 |
| AU2019328632A1 (en) | 2021-03-25 |
| CA3106881A1 (en) | 2020-03-05 |
| JP2021535149A (ja) | 2021-12-16 |
| WO2020043683A1 (en) | 2020-03-05 |
| KR20210052468A (ko) | 2021-05-10 |
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