JP7273732B2 - ５－ブロモ－２，６－ジ（１ｈ－ピラゾール－１－イル）ピリミジン－４－アミン及び新たな塩の結晶形 - Google Patents
５－ブロモ－２，６－ジ（１ｈ－ピラゾール－１－イル）ピリミジン－４－アミン及び新たな塩の結晶形 Download PDFInfo
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| JP2013512251A (ja) | 2009-11-24 | 2013-04-11 | アンプリミューン、インコーポレーテッド | Ｐｄ−ｌ１／ｐｄ−ｌ２の同時阻害 |
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| 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 |
| HRP20210122T1 (hr) | 2013-05-02 | 2021-04-16 | Anaptysbio, Inc. | Protutijela usmjerena protiv programirane smrti-1 (pd-1) |
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| TWI693232B (zh) | 2014-06-26 | 2020-05-11 | 美商宏觀基因股份有限公司 | 與pd-1和lag-3具有免疫反應性的共價結合的雙抗體和其使用方法 |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017025918A1 (en) | 2015-08-11 | 2017-02-16 | Novartis Ag | 5-bromo-2,6-di-(lh-pyrazol-l-yl)pyrimidin-4-amine for use in the treatment of cancer |
Non-Patent Citations (3)
| Title |
|---|
| Stephen BYRN et al.，Pharmaceutical Solids: A Strategic Approach to Regulatory Considerations，Pharmaceutical Research，1995年07月，Vol.12, No.7，p.945-954 |
| 平山令明，有機化合物結晶作製ハンドブック，2008年，p.17-23,37-40,45-51,57-65 |
| 芦澤一英，医薬品の多形現象と晶析の科学，2002年09月20日，p.273,278,305-17 |
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