CN112566661A - 喹啉衍生物与抗体的药物组合 - Google Patents
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Abstract
提供一种喹啉衍生物与抗体的药物组合，其包含免疫检查点抑制剂和酪氨酸激酶抑制剂，其中所述酪氨酸激酶抑制剂是式(I)的化合物或其药学上可接受的盐。药物组合显示具有良好的抗肺脏肿瘤和肝脏肿瘤活性。
Description
PCT国内申请，说明书已公开。
Claims (28)
- PCT国内申请，权利要求书已公开。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310003034.5A CN116077647A (zh) | 2018-07-18 | 2019-07-18 | 喹啉衍生物与抗体的药物组合 |
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810790198 | 2018-07-18 | ||
| CN2018107901986 | 2018-07-18 | ||
| CN2018113461733 | 2018-11-13 | ||
| CN201811346173 | 2018-11-13 | ||
| CN2019101495254 | 2019-02-28 | ||
| CN201910149525 | 2019-02-28 | ||
| PCT/CN2019/096540 WO2020015703A1 (zh) | 2018-07-18 | 2019-07-18 | 喹啉衍生物与抗体的药物组合 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN202310003034.5A Division CN116077647A (zh) | 2018-07-18 | 2019-07-18 | 喹啉衍生物与抗体的药物组合 |
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| CN112566661A true CN112566661A (zh) | 2021-03-26 |
| CN112566661B CN112566661B (zh) | 2024-02-02 |
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| CN202310003034.5A Pending CN116077647A (zh) | 2018-07-18 | 2019-07-18 | 喹啉衍生物与抗体的药物组合 |
| CN201980047782.5A Active CN112566661B (zh) | 2018-07-18 | 2019-07-18 | 喹啉衍生物与抗体的药物组合 |
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| CN202310003034.5A Pending CN116077647A (zh) | 2018-07-18 | 2019-07-18 | 喹啉衍生物与抗体的药物组合 |
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|---|---|
| US (1) | US20220160700A1 (zh) |
| EP (1) | EP3842070A4 (zh) |
| JP (1) | JP7455806B2 (zh) |
| KR (1) | KR20210034613A (zh) |
| CN (2) | CN116077647A (zh) |
| AU (1) | AU2019305857A1 (zh) |
| CA (1) | CA3106055A1 (zh) |
| WO (1) | WO2020015703A1 (zh) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20220175759A1 (en) * | 2019-03-15 | 2022-06-09 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Combined pharmaceutical composition for treating small cell lung cancer |
| WO2020233602A1 (zh) * | 2019-05-20 | 2020-11-26 | 正大天晴药业集团股份有限公司 | 用于联合治疗小细胞肺癌的喹啉衍生物 |
| EP4159238A1 (en) * | 2020-06-02 | 2023-04-05 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Combined pharmaceutical composition of c-met kinase inhibitor and anti-pd-l1 antibody |
| CN113925865A (zh) * | 2020-06-29 | 2022-01-14 | 上海市胸科医院 | 安罗替尼联合免疫检查点抑制剂治疗晚期肺癌的增效组合药物 |
| WO2023013700A1 (ja) * | 2021-08-04 | 2023-02-09 | 学校法人東海大学 | Ｔ細胞及び／又はｂ細胞の活性調節剤を含む併用剤 |
| KR20240046526A (ko) * | 2021-08-05 | 2024-04-09 | 치아타이 티안큉 파마수티컬 그룹 주식회사 | 소세포폐암 치료용 약학적 조성물 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106632674A (zh) * | 2015-10-30 | 2017-05-10 | 中山康方生物医药有限公司 | 一种抗pd-1单克隆抗体、其药物组合物及其用途 |
| CN106977602A (zh) * | 2016-08-23 | 2017-07-25 | 中山康方生物医药有限公司 | 一种抗 pd1 单克隆抗体、其药物组合物及其用途 |
| CN107771078A (zh) * | 2015-05-04 | 2018-03-06 | 爱德程医药有限公司 | 用于制备抗癌剂1‑((4‑(4‑氟‑2‑甲基‑1h‑吲哚‑5‑基氧基)‑6‑甲氧基喹啉‑7‑基氧基)甲基)环丙胺、其结晶形式和其盐的方法 |
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| US8148532B2 (en) | 2007-03-14 | 2012-04-03 | Guoqing Paul Chen | Spiro substituted compounds as angiogenesis inhibitors |
| US20160303231A1 (en) * | 2013-12-11 | 2016-10-20 | Robert Iannone | Treating cancer with a combination of a pd-1 antagonist and a vegfr inhibitor |
| PL3081576T3 (pl) | 2013-12-12 | 2020-03-31 | Shanghai Hengrui Pharmaceutical Co., Ltd. | Przeciwciało anty pd-1, jego fragment wiążący antygen i ich zastosowanie medyczne |
| KR20220127940A (ko) * | 2014-03-05 | 2022-09-20 | 브리스톨-마이어스 스큅 컴퍼니 | 항-pd-1 항체 및 또 다른 항암제의 조합물을 이용한 신장암의 치료 |
| CN107001326B (zh) | 2014-12-09 | 2020-05-05 | 正大天晴药业集团股份有限公司 | 抗非小细胞肺癌的喹啉衍生物 |
| JP2016196411A (ja) | 2015-03-04 | 2016-11-24 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍治療剤 |
| KR20240064733A (ko) | 2015-03-04 | 2024-05-13 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
| WO2017024465A1 (en) * | 2015-08-10 | 2017-02-16 | Innovent Biologics (Suzhou) Co., Ltd. | Pd-1 antibodies |
| TWI764943B (zh) | 2016-10-10 | 2022-05-21 | 大陸商蘇州盛迪亞生物醫藥有限公司 | 一種抗pd-1抗體和vegfr抑制劑聯合在製備治療癌症的藥物中的用途 |
| WO2020151759A1 (zh) * | 2019-01-25 | 2020-07-30 | 正大天晴药业集团股份有限公司 | 治疗肿瘤的联用药物组合物 |
| JP2022524761A (ja) * | 2019-03-07 | 2022-05-10 | アドヴェンチェン ファーマスーティカルズ，エルエルシー | 癌治療のための標準的な化学療法または免疫療法と組み合わせたカテケンチニブ（アンロチニブ）の順次使用 |
| US20220175759A1 (en) * | 2019-03-15 | 2022-06-09 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Combined pharmaceutical composition for treating small cell lung cancer |
| WO2020233602A1 (zh) * | 2019-05-20 | 2020-11-26 | 正大天晴药业集团股份有限公司 | 用于联合治疗小细胞肺癌的喹啉衍生物 |
| WO2020233723A1 (zh) * | 2019-05-23 | 2020-11-26 | 正大天晴药业集团股份有限公司 | 用于治疗头颈癌的喹啉衍生物 |
| CN113939315B (zh) * | 2019-05-30 | 2024-04-02 | 正大天晴药业集团南京顺欣制药有限公司 | 治疗黑色素瘤的联用药物组合物 |
| WO2020249018A1 (zh) * | 2019-06-10 | 2020-12-17 | 正大天晴药业集团南京顺欣制药有限公司 | 治疗驱动基因阳性肺癌的联用药物组合物 |
-
2019
- 2019-07-18 CN CN202310003034.5A patent/CN116077647A/zh active Pending
- 2019-07-18 KR KR1020217004238A patent/KR20210034613A/ko unknown
- 2019-07-18 EP EP19838501.5A patent/EP3842070A4/en active Pending
- 2019-07-18 WO PCT/CN2019/096540 patent/WO2020015703A1/zh active Application Filing
- 2019-07-18 CA CA3106055A patent/CA3106055A1/en active Pending
- 2019-07-18 CN CN201980047782.5A patent/CN112566661B/zh active Active
- 2019-07-18 AU AU2019305857A patent/AU2019305857A1/en active Pending
- 2019-07-18 JP JP2021502798A patent/JP7455806B2/ja active Active
- 2019-07-18 US US17/260,398 patent/US20220160700A1/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107771078A (zh) * | 2015-05-04 | 2018-03-06 | 爱德程医药有限公司 | 用于制备抗癌剂1‑((4‑(4‑氟‑2‑甲基‑1h‑吲哚‑5‑基氧基)‑6‑甲氧基喹啉‑7‑基氧基)甲基)环丙胺、其结晶形式和其盐的方法 |
| CN106632674A (zh) * | 2015-10-30 | 2017-05-10 | 中山康方生物医药有限公司 | 一种抗pd-1单克隆抗体、其药物组合物及其用途 |
| CN106977602A (zh) * | 2016-08-23 | 2017-07-25 | 中山康方生物医药有限公司 | 一种抗 pd1 单克隆抗体、其药物组合物及其用途 |
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| EP3842070A1 (en) | 2021-06-30 |
| CN116077647A (zh) | 2023-05-09 |
| JP7455806B2 (ja) | 2024-03-26 |
| JP2022512526A (ja) | 2022-02-07 |
| CN112566661B (zh) | 2024-02-02 |
| WO2020015703A9 (zh) | 2020-12-24 |
| KR20210034613A (ko) | 2021-03-30 |
| AU2019305857A1 (en) | 2021-02-18 |
| US20220160700A1 (en) | 2022-05-26 |
| CA3106055A1 (en) | 2020-01-23 |
| EP3842070A4 (en) | 2022-04-20 |
| WO2020015703A1 (zh) | 2020-01-23 |
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