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CN105816855A - 用于诱发单核细胞免疫应答的重组lag-3或其衍生物的应用 - Google Patents

用于诱发单核细胞免疫应答的重组lag-3或其衍生物的应用 Download PDF

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CN105816855A
CN105816855A CN201610221687.0A CN201610221687A CN105816855A CN 105816855 A CN105816855 A CN 105816855A CN 201610221687 A CN201610221687 A CN 201610221687A CN 105816855 A CN105816855 A CN 105816855A
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弗雷德里克·特里贝尔
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Abstract

本申请涉及用于诱发单核细胞免疫应答的重组LAG?3或其衍生物的应用。本发明涉及重组LAG?3或其衍生物的应用，以促进单核细胞介导的免疫应答，特别是诱发血液中单核细胞数量的增加。该发现用于治疗感染性疾病或癌症的新型治疗试剂的开发。

Description

用于诱发单核细胞免疫应答的重组LAG-3或其衍生物的应用
本申请是申请日为2008年10月3日、申请号为“200880117476.6”、发明名称为“用于诱发单核细胞免疫应答的重组LAG-3或其衍生物的应用”的中国专利申请的分案申请，原申请是国际申请PCT/IB2008/002653的中国国家阶段申请。
技术领域
本发明涉及重组LAG-3或其衍生物的应用以促进单核细胞介导的免疫应答。
本发明使血液中单核细胞的数量增加。
本发明发现了多种应用，特别是在癌症免疫治疗中的新型治疗试剂的开发应用。
参考文献参见随附在说明书后面方括号[]中的参考文献。
背景技术
在人CD4+和CD8+活化的T细胞中以及在活化的NK细胞中表达的淋巴细胞活化基因3(hlag-3)编码503个氨基酸1型膜蛋白(LAG-3)以及四个细胞外免疫球蛋白超家族(IgSF)结构域[1]。克隆了小鼠淋巴细胞活化基因3(mlag-3)并且发现与hlag-3有大约70％的同源性，在细胞质内的氨基酸链中具有相同的富含脯氨酸结构。
正如MHC II类的天然高度亲和配体描述的，LAG-3(CD223)已知在体外诱导单核细胞衍生的树突状细胞的成熟，并且在体内用作免疫治疗佐剂诱导CD41型辅助性T细胞反应和CD8T细胞反应[2]。关于LAG-3和其用作免疫刺激剂的进一步信息可在TRIEBELE等人[1]、TRIEBEL等人[3]以及HUARD等人[4]的著作中找到。
可溶性LAG-3的一些形式能够与MHC II类分子结合并且能够诱导树突状细胞成熟并迁移至次级淋巴器官，在次级淋巴器官中它们能够启动导致肿瘤排斥的原态CD4-辅助和CD8细胞毒性T细胞[5]。
最近，重组可溶性人LAG-3Ig融合蛋白显示在先天性免疫应答和获得性免疫应答中均能激活大范围的效应器细胞，例如诱导单核细胞-巨噬细胞分泌细胞因子/趋化因子[6]。
单核细胞由来自称为成单核细胞的造血干细胞前体的骨髓生成。它们在血液中构成了3％-8％之间的白细胞。单核细胞在血流中循环约24小时(8小时的半衰期)，随后通常进入全身组织中。在组织中，单核细胞成熟为巨噬细胞、上皮状细胞或抗原提呈细胞(APCs，例如树突状细胞)。单核细胞负责体内外来物质的吞噬(吸收)。单核细胞能够使用中间(调理作用)蛋白例如包被病原体的抗体或补体，以及通过经识别病原体的模式识别受体直接与病原体结合，从而进行吞噬作用。单核细胞还能够通过抗体杀死感染的宿主细胞，称为抗体依赖性细胞介导的细胞毒性(ADCC)。由于它们的分泌作用和吞噬作用特性，单核细胞-巨噬细胞存在于非特异性和特异性免疫应答中。
膜标记物的研究允许识别单核细胞群体，无论是成熟的或未成熟的、营养缺陷的或非营养缺陷的。存在于单核细胞膜(成熟的或未成熟的)上的分子几乎总是非特异性的而是与以下活性相对应：
-IgG的Fc片段的受体(CD16、CD32、CD64)，
-IgE的Fc片段的受体(CD23)，
-补体片段的受体(CD11b，CD21/CD35)，
-白细胞粘附蛋白(CD11a，CD11c)，
-促进与革兰氏细菌的LPS结合的蛋白(CD14)，
-具有酪氨酸磷酸酶活性的蛋白(CD45)。
发明内容
目前，本发明的发明人完全意外地发现了当接种至高度恶性的肿瘤患者时人LAG-3或其衍生物，例如转移性乳腺癌(MBC)或转移性肾透明细胞癌(MRCC)患者体内时诱导单核细胞依赖性的强效免疫力。
所述诱导的免疫力通过血液中单核细胞计数的显著增加表现自身。
该结果通过多次将LAG-3或其衍生物施入接受免疫治疗或化学免疫治疗的患者体内的方式来获得。
该结果相当令人吃惊，因为在与单核细胞结合和单核细胞活化之后的单核细胞扩增是非预期的。事实上，单核细胞是结束分化的造血细胞并且不能增殖。它们能够作为单核细胞或在不同细胞因子的影响下朝着巨噬细胞或树突状细胞分化而停留在血液里，直至它们死亡。因此，可以相信在不受以下理论的限制下涉及的作用机理可以是针对存在于骨髓中的造血前体细胞(在前单核细胞阶段之前)的增殖信号，或者是成熟循环单核细胞的半衰期或停留时间的增加。
因此，本发明涉及在制备用于治疗感染性疾病或癌症的诱导单核细胞数量增加的药物中诱发单核细胞介导的免疫应答的重组LAG-3或其衍生物的应用。
从本发明意义上而言，“LAG-3的衍生物”是指LAG-3的突变体、变型或片段，假设它们保持与MHC II类分子结合的LAG-3的能力。
因此，可使用LAG-3的以下形式：
-全部LAG-3蛋白；
-由四个免疫球蛋白细胞外结构域中的至少一个所组成的其可溶性多肽片段，即在法国专利申请FR9000126中公开的、由从LAG-3序列的第23位氨基酸延伸至第448位氨基酸的细胞外区域组成的LAG-3的可溶性部分；
-基本上由所有的第一个和第二个结构域组成的LAG-3的片段；
-基本上由所有的第一个和第二个结构域或者所有四个结构域组成的LAG-3的片段，例如在WO95/30750中定义的；
-可溶性LAG-3的突变形式或者包含D1和D2细胞外结构域并且由以下位点的氨基酸置换组成的其片段：
*在以下位点之一的氨基酸置换：
73位，ARG被GLU置换；
75位，ARG被ALA或GLU置换；
76位，ARG被GLU置换；
或者两个或多个这些置换的组合；
*在以下位点之一的氨基酸置换：
30位，ASP被ALA置换；
56位，HIS被ALA置换；
77位，TYR被PHE置换；
88位，ARG被ALA置换；
103位，ARG被ALA置换；
109位，ASP被GLU置换；
115位，ARG被ALA置换；
或者54位和66位之间包含的区域的缺失；
或者两个或多个这些置换的组合。
HUARD等人(Proc.Natl.Acad.Sci.USA，11：5744-5749，1997)描述了这些突变体。
-由含D1、D2和D3的可溶性52kDa蛋白组成的LAG-3的生理变型。
-重组可溶性人LAG-3Ig融合蛋白(IMP321)，一种在采用质粒转染的中国仓鼠卵巢细胞中生产的200kDa二聚体，该质粒编码与人IgGlFc融合的hLAG-3的细胞外结构域。
从本发明意义上而言，“药物”是指有效多剂量的重组LAG-3蛋白或其衍生物。
从本发明意义上而言，“有效多剂量的重组LAG-3蛋白或其衍生物”是指允许每一至几周施用一剂重组LAG-3蛋白或其衍生物，持续至少12周，优选地持续至少24周，由13天±2天停药间隔期所隔开的制剂。优选地，施药为每两周方案。
从本发明意义上而言，“一剂重组LAG-3蛋白或其衍生物”是指允许一次施药在0.25～30mg范围内，优选地1～6.25mg，更优选地6～30mg，例如，向体重指数(体重/身高2)在18～30kg/m2范围内的患者根据需要施用大约1.25mg的重组LAG-3蛋白或其衍生物。
通过将它们进行全身性接种例如作为皮下、肌肉或静脉注射，优选地作为皮下注射，以游离形式例如以溶液形式施用重组LAG-3蛋白或其衍生物。
所述重组LAG-3蛋白或其衍生物还可以进行配制，以便允许与具有抗癌或抗感染疾病免疫治疗或化学治疗特性的化合物一起施用。
从本发明意义上而言，“与化合物一起施用”是指在施用所述化合物之前、过程中或者之后施用重组LAG-3蛋白或其衍生物。
从本发明意义上而言，“具有抗癌或抗感染疾病化学治疗特性的化合物”是指，例如选自紫杉醇类(紫杉醇和多西紫杉醇)、吉西他滨和蒽环类(阿霉素)的化疗试剂或者抗病毒试剂例如利巴韦林。
在本发明的具体实施例中，在第一次施用具有抗癌或抗感染疾病化学治疗特性的细胞毒性化合物之后，给患者施用重组LAG-3蛋白或其衍生物。
优选地，在施用具有抗癌或抗感染疾病化学治疗特性的细胞毒性化合物之后12～96小时，给患者施用重组LAG-3蛋白或其衍生物。
在另一实施例中，在第一次施用具有抗癌或抗感染疾病化学治疗特性的细胞毒性化合物之后一或两天，给患者施用重组LAG-3蛋白或其衍生物。
在本发明的另一具体实施例中，同时、单独或序贯地施用重组LAG-3蛋白或其衍生物和具有抗癌或抗感染疾病化学治疗特性的细胞毒性化合物。
优选地，在本发明的该具体实施例中，施用重组LAG-3蛋白或其衍生物至少6次，例如7次、10次，12次或更多。
优选地，在本发明的该具体实施例中，按照每两周方案施用重组LAG-3蛋白或其衍生物。
优选地，以包含0.25～30mg之间的剂量，最终以包含6～30mg之间的剂量、最终以包含8～25mg之间的剂量、最终以包含介于12～20mg之间的剂量施用重组LAG-3蛋白或其衍生物。
从本发明意义上而言，“具有抗癌或抗感染疾病化学治疗特性的化合物”也指，例如选自由通过ADCC(抗体依赖性细胞毒性)杀死肿瘤细胞的治疗抗体的化合物组成的组，以及其混合物，优选地选自由利妥昔单抗、西妥昔单抗、依决洛单抗和曲妥珠单抗组成的组。
在本发明的具有实施例中，将重组LAG-3蛋白或其衍生物同时、单独或序贯地施予患者。
优选地，在本发明的具有实施例中，重组LAG-3蛋白或其衍生物与治疗抗体在同一天施用。
本发明还涉及试剂盒，即包含用于同时、单独或序贯使用的重组LAG-3蛋白或其衍生物与治疗抗体的组合制剂。
优选地，该试剂盒包含重组LAG-3蛋白或其衍生物和选自由利妥昔单抗、西妥昔单抗、依决洛单抗和曲妥珠单抗组成的组的治疗抗体。
优选地，本发明的试剂盒包含重组LAG-3蛋白或其衍生物和利妥昔单抗。
本发明的试剂盒中，由于两种组分之间的协同细胞毒性作用，重组LAG-3蛋白或其衍生物和治疗抗体形成功能统一体。这种效应是一种新的联合效应，因为在单独施用两种组分时不产生与作为组合制剂施用时相同的效应。
本发明还涉及试剂盒，即包含重组LAG-3蛋白或其衍生物和具有抗癌或抗感染疾病化学治疗特性的组合制剂，用于同时、单独或序贯使用。
优选地，本发明的试剂盒包含重组LAG-3蛋白或其衍生物和选自由紫杉醇类(紫杉醇和多西紫杉醇)、吉西他滨和蒽环类(阿霉素)组成的组的具有抗癌或抗感染疾病化学治疗特性的化合物。
本发明还涉及用于治疗涉及单核细胞介导的免疫应答的病理状态的方法，包括根据患者的需要，向其施用如上定义的药物。
从本发明意义上而言，“涉及单核细胞介导的免疫应答的病理状态”是指病毒感染性疾病、寄生感染性疾病、细菌感染性疾病、以及癌症。
通过以下给出的非限制性实例，本发明的其他优点对于本领域的技术人员来说也可以是显而易见的，并通过附图示出。
附图说明
图1表示来自转移性乳腺癌患者的PBMC中单核细胞(即CD14+CD45+细胞)的荧光激活细胞分选(FACS)分析。
图2表示来自转移性乳腺癌患者的新鲜全血中单核细胞(即CD14+CD45+细胞)的荧光激活细胞分选(FACS)分析。
图3表示来自转移性肾细胞癌患者的新鲜全血中单核细胞(即CD14+CD45+细胞)的荧光激活细胞分选(FACS)分析。
图4表示来自转移性乳腺癌患者的新鲜全血中单核细胞(即CD14+CD45+细胞)的荧光激活细胞分选(FACS)分析。
图5表示在转移性肾细胞癌患者血浆中通过ELISA法测定的IMP321的药代动力学曲线。
图6表示用利妥昔单抗和/或IMP321在不同条件下培养的PBMC的流式细胞仪分析。
具体实施方式
实施例1：使用低IMP321剂量在转移性乳腺癌(MBC)患者中单核细胞的增加
接受已知诱导肿瘤细胞吞噬作用的5例MBC患者，在每两周一次的化学治疗之后1-2天分别接受一剂皮下注射IMP321，剂量为0.25mg，持续24周，通过14天的停药间隔期隔开。
在最后一次注射IMP321(即，观察产品的持续性免疫调节效应)后14天、在3个月(第85天)和6个月(第170天)采集每例患者的血液样品置于肝素锂采血管(Vacutainer；BDBiosciences)中。使用LeucoSep管(Greiner Bio-One)在Ficoll-Paque梯度(Pharmacia)上分离PBMC，并立即使用。
在所述新鲜PBMC样品(因为单核细胞对冷冻敏感)中，通过荧光激活细胞分选(FACS)法分析单核细胞数量的增加，并与在IMP321施用(第1天)之前采集的基于新鲜PBMC样品进行的单核细胞计数进行比较。
结果见图1。
结果表明，在这种低IMP321剂量临床方案下，单核细胞计数平均增加2.5倍(在3个月，第85天)和3.5倍(在6个月，第170天)。
为了证实上述结果，采用了更加直接和很可能更加准确的方法，该方法通过首先测定采用稀释的荧光微珠进行分析的血液的准确体积并且随后计数存在于该全血量中的门控CD45+(白细胞)中的CD14+细胞(即单核细胞)的数量在体外直接定量全血细胞中单核细胞的数量(即未事先在Ficoll梯度上纯化的PBMC)。
结果见图2。
结果表明，当以低剂量(0.25mg)给予IMP321持续很长的时间，即6个月，注射12次时，单核细胞计数在第170天平均增加44倍(在第85天为2.8倍)，表明靶向的MHC II+类单核细胞样造血细胞的强而直接的刺激作用。
实施例2：使用高IMP321剂量在转移性肾透明细胞癌(MRCC)患者中单核细胞的增加3例MRCC患者分别接受一次皮下注射IMP321，剂量为6.25mg，每两周一次，持续12周，通过14天的停药间隔期隔开。
采用如上所述的方法，在最后一次注射IMP321之后14天(即，观察产品的持续性免疫调节效应)、在2个月(第57天)和3个月(第85天)，采集每例患者的血液样品，并立即使用。
在新鲜血液样品中(因为单核细胞对冷冻敏感)，通过FACS分析CD14+CD45+细胞的扩增，并与基于在施用IMP321(第1天)之前采集的新鲜血液样品进行的单核细胞计数进行比较。
结果见图3。
结果表明，采用该种高IMP321剂量临床方案，单核细胞计数平均增加2倍(在3个月，第85天)，在该临床方案中，患者仅接受6次注射。
实施例3：在接受紫杉醇和IMP321剂量的转移性乳腺癌患者中单核细胞的增加
在28天疗程的第1、8和15天接受作为转移性乳腺癌6个疗程紫杉醇(静脉注射给予80mg/m2)的一线化疗的患者，在每个28疗程的第2和16天接受皮下注射IMP3211-30mg。或者在第3或17天施用IMP321。
因此，每例患者接受了每周1次紫杉醇和12次皮下注射IMP321的标准6个月疗程，在每两周方案中施用紫杉醇后1至2天给予每次注射。
与第1天比较，在最后一次注射后14天，在3个月(第85天)和6个月(第170天)通过荧光激活细胞分选(FACS)法分析每微升新鲜血液中绝对单核细胞计数的增加。
在注射低剂量IMP321(1.25mg)的患者中获得的结果见图4。
这些数据表明，在大多数患者(如果不是全部)中1.25mg的剂量(图4)诱导血液中单核细胞亚群库的扩增。
预计IMP321的最佳剂量方案将是介于6和30mg/注射之间。
基于在转移性肾细胞癌患者中获得的药代动力学数据结果(图5)，这些剂量已经表明是安全的并且给出可接受的全身暴露量。在接受大于6mg的IMP321剂量注射的患者中，在皮下注射后至少24小时可获得高于1ng/ml的IMP321的血液浓度(图5)。
实施例4：接受吉西他滨和IMP321剂量的晚期胰腺癌患者的治疗
在28天疗程的第1、8和15天接受作为晚期胰腺癌6个疗程标准吉西他滨(30分钟内静脉注射1mg/m2)的一线化疗的患者(或者不符合外科手术移除肿瘤的患者)，在每个28疗程的第2和16天另外接受6至30mg皮下注射IMP321。或者，在第3或17天施用IMP321。
因此，每例患者接受了吉西他滨和12次皮下注射IMP321的标准6个月疗程，在每两周方案中吉西他滨施用后1至2天给予每次注射。
如实施例1所述的方法，通过荧光激活细胞分选(FACS)法分析单核细胞的数量。
实施例5：通过低剂量IMP321诱导利妥昔单抗介导的ADCC的增加
首先，将PBMC与IL-2(100U/ml)，含或不含IMP321(浓度为0μg/ml、0.03μg/ml或0.1μg/ml)一起孵育40个小时。然后，在靶细胞(即人CD20+Raji B细胞)存在下，将PBMC与增加浓度的利妥昔单抗(0、0.5和5μg/ml)一起孵育。
首先采用CFSE(羧基荧光素琥珀酰亚胺酯)标记Raji细胞，在添加0、0.5和5μg/ml的利妥昔单抗的培养基中孵育并与效应器细胞以效应器-靶细胞25∶1的比率，在37℃下共培养6小时。
然后，将细胞与7-AAD(7-氨基-放线菌素-D)一起在冰上孵育15min并通过流式细胞仪进行分析以确定死亡的CFSE+7-AAD+Raji靶细胞的百分比(即细胞毒性％)。
结果见图6。
增加利妥昔单抗的浓度增加了细胞毒性的百分比，清楚地表明剂量依赖性ADCC活性。
当添加0.03或0.1μg/ml IMP321时，细胞毒性的比例大大提高。例如，在0.1μg/mlIMP321存在下，采用0.5μg/ml利妥昔单抗观察到30％的细胞毒性，该30％细胞毒性高于在缺乏IMP321时采用5μg/ml利妥昔单抗获得的25％细胞毒性值。
因此，添加0.1μg/ml IMP321可能具有10-15倍的利妥昔单抗活性，因为当添加低剂量IMP321(0.1μg/ml)时采用小于10倍的抗体获得优良的细胞毒性。
这些数据显示利妥昔单抗和IMP321之间的协同作用。
以下内容对应于原申请的权利要求书：
1.一种在制备用于治疗感染性疾病或癌症的诱导单核细胞数量增加的药物中诱发单核细胞介导的免疫应答的重组LAG-3或其衍生物的用途。
2.根据权利要求1的用途，其中，所述药物由有效剂量的重组LAG-3蛋白或其衍生物组成。
3.根据权利要求2的用途，其中，配制所述剂量的重组LAG-3蛋白或其衍生物以便允许每1至几周施用一剂量，持续至少12周，优选地持续至少24周，通过13天±2天停药间隔期隔开。
4.根据权利要求2或3的用途，其中，配制所述剂量的重组LAG-3蛋白或其衍生物以便允许向体重指数(体重/身高2)在18～30kg/m2范围内的患者根据其需要皮下或静脉施用范围为0.25～30mg，优选地为6～30mg的重组LAG-3蛋白或其衍生物。
5.根据权利要求2～4中任一项的用途，其中，配制所述剂量的重组LAG-3蛋白或其衍生物以便允许与具有抗癌或者抗感染疾病免疫治疗或者化学治疗特性的化合物一起施用。
6.根据权利要求5的用途，其中，重组LAG-3蛋白或其衍生物的剂量包含0.25～30mg，优选地6～30mg的所述重组LAG-3蛋白或其衍生物。
7.根据权利要求5或6的用途，其中，所述化合物选自化疗试剂。
8.根据权利要求7的用途，其中，所述化疗试剂选自由例如紫杉醇和多西紫杉醇的紫杉醇类，例如阿霉素的蒽环类，以及吉西他滨组成的组。
9.根据权利要求5或6的用途，其中，所述化合物选自由通过ADCC(抗体-依赖性细胞-介导的细胞毒性)杀死肿瘤细胞的治疗抗体、以及其混合物组成的组。
10.根据权利要求9的用途，其中，所述治疗抗体选自由利妥昔单抗、西妥昔单抗、依决洛单抗和曲妥珠单抗组成的组。
11.试剂盒，包含重组LAG-3蛋白或其衍生物和如权利要求9或10中所述的治疗抗体，用于同时、单独或序贯使用。
12.试剂盒，包含重组LAG-3蛋白或其衍生物和如权利要求7或8中所述的具有抗癌化学治疗特性的化合物，用于同时、单独或序贯使用。
参考文献
[1]TRIEBEL et al.，J.Exp.Med.，171：1393-1405，1990
[2]BRIGNONE et al.，J.Immune Based Ther Immunotherapies，5：5，2007
[3]TRIEBEL et al.，Trends Immunol.，24：619-622，2003
[4]HUARD et al.，Proc.Natl.Acad.Sci.USA，94：5744-5749，1997
[5]PRIGENT et al.，Eur.J.Immunol.，29：3867-3876，1999
[6]BRIGNONE et al.，J.Immunol.，179：4202-4211，2007

Claims (23)

1.制剂，其包含有效多剂量的诱发单核细胞介导之免疫应答的重组LAG-3蛋白或其衍生物。
2.根据权利要求1所述的制剂，其中每个剂量的重组LAG-3蛋白或衍生物包含0.25-30mg摩尔当量的重组可溶性人LAG-3Ig融合蛋白IMP321。
3.根据权利要求1所述的制剂，其中每个剂量的重组LAG-3蛋白或衍生物包含6-30mg摩尔当量的重组可溶性人LAG-3Ig融合蛋白IMP321。
4.根据任一前述权利要求所述的制剂，其中配制所述有效多剂量的重组LAG-3蛋白或其衍生物以便允许每1至几周施用一剂量，持续至少12周，优选地持续至少24周，通过13天±2天停药间隔期隔开。
5.根据任一前述权利要求所述的制剂，其中配制每一剂量重组LAG-3蛋白或其衍生物以便允许皮下或静脉施用。
6.根据任一前述权利要求所述的制剂，其中所述重组LAG-3蛋白或其衍生物是指重组可溶性人LAG-3Ig融合蛋白。
7.诱发单核细胞介导之免疫应答的重组LAG-3蛋白或其衍生物与具有抗癌或抗感染疾病免疫治疗或化学治疗特性的化合物的组合制剂在制备用于感染性疾病或者癌症治疗的诱导单核细胞数量增加的药物中的用途，其中配制由有效多剂量的重组LAG-3蛋白或其衍生物组成的药物，以便允许在施用具有抗癌或者抗感染性疾病的免疫治疗或者化学治疗特性的化合物之前/过程中/之后施用。
8.根据权利要求7所述的用途，其中每个剂量的重组LAG-3蛋白或衍生物包含0.25-30mg摩尔当量的重组可溶性人LAG-3Ig融合蛋白IMP321。
9.根据权利要求7所述的用途，其中每个剂量的重组LAG-3蛋白或衍生物包含6-30mg摩尔当量的重组可溶性人LAG-3Ig融合蛋白IMP321。
10.根据权利要求7至9中任一项所述的用途，其中所述化合物选自化疗试剂。
11.根据权利要求10所述的用途，其中所述化疗试剂选自紫杉醇类、蒽环类、以及吉西他滨。
12.根据权利要求11所述的用途，其中所述紫杉醇类为紫杉醇或多西紫杉醇。
13.根据权利要求11所述的用途，其中所述蒽环类为阿霉素。
14.根据权利要求7至9中任一项所述的用途，其中所述化合物选自通过ADCC(抗体-依赖性细胞-介导的细胞毒性)杀死肿瘤细胞的治疗抗体、以及其混合物。
15.根据权利要求14所述的用途，其中所述治疗抗体选自利妥昔单抗、西妥昔单抗、依决洛单抗和曲妥珠单抗。
16.根据权利要求7至15中任一项所述的用途，其中所述重组LAG-3蛋白或其衍生物是指重组可溶性人LAG-3Ig融合蛋白。
17.试剂盒，其包含重组LAG-3蛋白或其衍生物和化疗试剂，用于同时、单独或序贯使用。
18.根据权利要求17所述的试剂盒，其中所述化疗试剂选自紫杉醇类、蒽环类、以及吉西他滨。
19.根据权利要求18所述的试剂盒，其中所述紫杉醇类为紫杉醇或多西紫杉醇。
20.根据权利要求18所述的试剂盒，其中所述蒽环类为阿霉素。
21.试剂盒，其包含重组LAG-3蛋白或其衍生物和治疗抗体，用于同时、单独或序贯使用，其中所述治疗抗体选自通过ADCC(抗体-依赖性细胞-介导的细胞毒性)杀死肿瘤细胞的治疗抗体、以及其混合物。
22.根据权利要求21所述的试剂盒，其中所述治疗抗体选自利妥昔单抗、西妥昔单抗、依决洛单抗和曲妥珠单抗。
23.根据权利要求17至22中任一项所述的试剂盒，其中所述重组LAG-3蛋白或其衍生物是指重组可溶性人LAG-3Ig融合蛋白。
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110950966A (zh) * 2019-12-13 2020-04-03 启辰生生物科技(珠海)有限公司 融合蛋白、编码核酸和细胞及用途
US10954246B2 (en) 2017-04-13 2021-03-23 Taizhou Eoc Pharma Co., Ltd. Compound of EOC315 Mod.I crystal form and preparation method thereof

Families Citing this family (365)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2044949A1 (en) * 2007-10-05 2009-04-08 Immutep Use of recombinant lag-3 or the derivatives thereof for eliciting monocyte immune response
PT3409278T (pt) 2011-07-21 2020-12-18 Sumitomo Dainippon Pharma Oncology Inc Inibidores de proteína cinase heterocíclicos
CN106211758B (zh) 2013-04-09 2021-03-23 北京强新生物科技有限公司 2-乙酰基萘并[2,3-b]呋喃-4,9-二酮用于治疗癌症的用途
AU2014296887A1 (en) 2013-08-02 2016-01-28 Aduro Biotech Holdings, Europe B.V. Combining CD27 agonists and immune checkpoint inhibition for immune stimulation
GB201322626D0 (en) * 2013-12-19 2014-02-05 Immutep S A Combined preparations for the treatment of cancer
LT3087071T (lt) 2013-12-24 2018-11-12 Bristol-Myers Squibb Company Tricikliniai junginiai kaip priešvėžiniai agentai
JOP20200094A1 (ar) 2014-01-24 2017-06-16 Dana Farber Cancer Inst Inc جزيئات جسم مضاد لـ pd-1 واستخداماتها
RS59853B1 (sr) 2014-03-14 2020-02-28 Novartis Ag Molekuli anti-lag-3 antitela i njihove upotrebe
RU2016149812A (ru) 2014-06-06 2018-07-17 Флексус Байосайенсиз, Инк. Иммунорегулирующие средства
RS59643B1 (sr) 2014-06-06 2020-01-31 Bristol Myers Squibb Co Antitela na glukokortikoidom indukovani receptor faktora nekroze tumora (gitr) i njihova primena
JO3663B1 (ar) 2014-08-19 2020-08-27 Merck Sharp & Dohme الأجسام المضادة لمضاد lag3 وأجزاء ربط الأنتيجين
BR112017008575B1 (pt) 2014-10-29 2021-07-13 Bicyclerd Limited Ligantes de peptídeos bicíclicos específicos a mt1-mmp, conjugado de fármaco, processo para preparação de um conjugado de fármaco e composição farmacêutica
US11242319B2 (en) 2014-11-05 2022-02-08 Flexus Biosciences, Inc. Immunoregulatory agents
AR102537A1 (es) 2014-11-05 2017-03-08 Flexus Biosciences Inc Agentes inmunomoduladores
UY36390A (es) 2014-11-05 2016-06-01 Flexus Biosciences Inc Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido), sus métodos de síntesis y composiciones farmacéuticas que los contienen
TW201630907A (zh) 2014-12-22 2016-09-01 必治妥美雅史谷比公司 ＴＧＦβＲ拮抗劑
GB201500374D0 (en) * 2015-01-09 2015-02-25 Immutep S A Combined preparations for the treatment of cancer
MA41463A (fr) * 2015-02-03 2017-12-12 Anaptysbio Inc Anticorps dirigés contre le gène d'activation 3 des lymphocytes (lag-3)
WO2016127052A1 (en) 2015-02-05 2016-08-11 Bristol-Myers Squibb Company Cxcl11 and smica as predictive biomarkers for efficacy of anti-ctla4 immunotherapy
WO2016140884A1 (en) 2015-03-02 2016-09-09 Rigel Pharmaceuticals, Inc. TGF-β INHIBITORS
US20180133327A1 (en) 2015-03-16 2018-05-17 Amal Therapeutics Sa Cell Penetrating Peptides and Complexes Comprising the Same
US10399933B2 (en) 2015-04-03 2019-09-03 Bristol-Myers Squibb Company Inhibitors of indoleamine-2,3-dioxygenase for the treatment of cancer
TW201642897A (zh) 2015-04-08 2016-12-16 Ｆ 星生物科技有限公司 Ｈｅｒ２結合劑治療
CN107709365A (zh) 2015-04-13 2018-02-16 戊瑞治疗有限公司 癌症组合疗法
CA2984975A1 (en) 2015-05-06 2016-11-10 Snipr Technologies Limited Altering microbial populations & modifying microbiota
US10683290B2 (en) 2015-05-11 2020-06-16 Bristol-Myers Squibb Company Tricyclic compounds as anticancer agents
US9725449B2 (en) 2015-05-12 2017-08-08 Bristol-Myers Squibb Company Tricyclic compounds as anticancer agents
EP3307740B1 (en) 2015-05-12 2019-12-18 Bristol-Myers Squibb Company 5h-pyrido[3,2-b]indole compounds as anticancer agents
TR201911032T4 (tr) 2015-05-18 2019-08-21 Tolero Pharmaceuticals Inc Artırılmış biyoyararlanıma sahip alvocıdıb ön ilaçları.
PT3303396T (pt) 2015-05-29 2023-01-30 Bristol Myers Squibb Co Anticorpos contra ox40 e utilizações dos mesmos
TW201717935A (zh) 2015-06-03 2017-06-01 波士頓生醫公司 用於治療癌症的組成物和方法
EP3328861A1 (en) 2015-07-28 2018-06-06 Bristol-Myers Squibb Company Tgf beta receptor antagonists
WO2017035118A1 (en) 2015-08-25 2017-03-02 Bristol-Myers Squibb Company Tgf beta receptor antagonists
MY205096A (en) 2015-09-02 2024-10-01 Immutep Sas Anti-lag-3 antibodies
US10265379B2 (en) * 2015-09-16 2019-04-23 Annabelle Rodriguez Oquendo Use of recombinant lymphocyte activation gene-3 as a companion therapeutic for patients at risk for cardiovascular disease and other chronic inflammatory diseases
US10149887B2 (en) 2015-10-23 2018-12-11 Canbas Co., Ltd. Peptides and peptidomimetics in combination with t cell activating and/or checkpoint inhibiting agents for cancer treatment
MX2018005517A (es) 2015-11-02 2018-11-09 Five Prime Therapeutics Inc Polipeptidos del dominio extracelular de cd80 y su uso en el tratamiento del cancer.
WO2017079746A2 (en) 2015-11-07 2017-05-11 Multivir Inc. Methods and compositions comprising tumor suppressor gene therapy and immune checkpoint blockade for the treatment of cancer
EA201891121A1 (ru) 2015-11-19 2018-12-28 Бристол-Майерс Сквибб Компани Антитела к глюкокортикоид-индуцированному рецептору фактора некроза опухоли (gitr) и их применения
TWI791422B (zh) 2015-11-23 2023-02-11 美商戊瑞治療有限公司 用於癌症治療之單獨fgfr2抑制劑或與免疫刺激劑組合
EP3390406A1 (en) 2015-12-15 2018-10-24 Bristol-Myers Squibb Company Cxcr4 receptor antagonists
US11045547B2 (en) 2015-12-16 2021-06-29 Merck Sharp & Dohme Corp. Anti-LAG3 antibodies and antigen-binding fragments
RU2748378C2 (ru) 2016-03-16 2021-05-25 Амаль Терапьютикс Са Комбинация модулятора иммунных контрольных точек и комплекса, содержащего проникающий в клетку пептид, карго-молекулу и пептидный агонист tlr, для применения в медицине
WO2017184619A2 (en) 2016-04-18 2017-10-26 Celldex Therapeutics, Inc. Agonistic antibodies that bind human cd40 and uses thereof
CN109414421A (zh) 2016-05-04 2019-03-01 百时美施贵宝公司 吲哚胺2,3-双加氧酶的抑制剂及其使用方法
JP2019519485A (ja) 2016-05-04 2019-07-11 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ インドールアミン２，３−ジオキシゲナーゼ阻害剤およびその使用方法
US10323004B2 (en) 2016-05-04 2019-06-18 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
US10696648B2 (en) 2016-05-04 2020-06-30 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
KR20190004742A (ko) 2016-05-04 2019-01-14 브리스톨-마이어스 스큅 컴퍼니 인돌아민 2,3-디옥시게나제의 억제제 및 그의 사용 방법
GB201609811D0 (en) 2016-06-05 2016-07-20 Snipr Technologies Ltd Methods, cells, systems, arrays, RNA and kits
WO2018013818A2 (en) 2016-07-14 2018-01-18 Bristol-Myers Squibb Company Antibodies against tim3 and uses thereof
US20190292179A1 (en) 2016-07-21 2019-09-26 Bristol-Myers Squibb Company TGF Beta RECEPTOR ANTAGONISTS
WO2018039518A1 (en) 2016-08-26 2018-03-01 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
JP7346291B2 (ja) 2016-09-21 2023-09-19 アマル セラピューティクス エスエー 癌を治療するための細胞透過性ペプチド、マルチエピトープ、及びｔｌｒペプチドアゴニストを含む融合体
WO2018064165A2 (en) 2016-09-27 2018-04-05 Board Of Regents, The University Of Texas System Methods for enhancing immune checkpoint blockade therapy by modulating the microbiome
KR102661905B1 (ko) 2016-10-12 2024-04-29 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 Tusc2 면역요법을 위한 방법 및 조성물
US10660909B2 (en) 2016-11-17 2020-05-26 Syntrix Biosystems Inc. Method for treating cancer using chemokine antagonists
WO2018094275A1 (en) 2016-11-18 2018-05-24 Tolero Pharmaceuticals, Inc. Alvocidib prodrugs and their use as protein kinase inhibitors
US11299469B2 (en) 2016-11-29 2022-04-12 Sumitomo Dainippon Pharma Oncology, Inc. Naphthofuran derivatives, preparation, and methods of use thereof
WO2018099539A1 (en) 2016-11-29 2018-06-07 Horst Lindhofer Combination of t-cell redirecting multifunctional antibodies with immune checkpoint modulators and uses thereof
JP2020510624A (ja) 2016-12-12 2020-04-09 マルチビア インコーポレイテッド がんおよび感染性疾患の治療および予防のための、ウイルス遺伝子治療および免疫チェックポイント阻害剤を含む方法および組成物
CN108204958A (zh) * 2016-12-19 2018-06-26 伊缪泰普有限公司 结合测定
WO2018132279A1 (en) 2017-01-05 2018-07-19 Bristol-Myers Squibb Company Tgf beta receptor antagonists
EP3570844B1 (en) 2017-01-20 2023-09-06 Arcus Biosciences, Inc. Azolopyrimidine for the treatment of cancer-related disorders
EP3601353A1 (en) 2017-03-31 2020-02-05 Five Prime Therapeutics, Inc. Combination therapy for cancer using anti-gitr antibodies
CA3060516A1 (en) 2017-04-21 2018-10-25 Sillajen, Inc. Oncolytic vaccinia virus and checkpoint inhibitor combination therapy
EP3612030B1 (en) 2017-04-21 2025-12-24 Ikena Oncology, Inc. Indole ahr inhibitors and uses thereof
MX2019012849A (es) 2017-04-28 2019-11-28 Five Prime Therapeutics Inc Metodos de tratamiento con polipeptidos del dominio extracelular del cd80.
AR111651A1 (es) 2017-04-28 2019-08-07 Novartis Ag Conjugados de anticuerpos que comprenden agonistas del receptor de tipo toll y terapias de combinación
WO2018209049A1 (en) 2017-05-12 2018-11-15 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
JP2020520923A (ja) 2017-05-17 2020-07-16 ボストン バイオメディカル， インコーポレイテッド がんを処置するための方法
EP3634417B1 (en) 2017-05-17 2023-07-12 Arcus Biosciences, Inc. Quinazoline-pyrazole derivatives for the treatment of cancer-related disorders
BR112019025352A8 (pt) 2017-05-29 2022-12-13 Gamamabs Pharma Inibidor de imunossupressão associada ao câncer
WO2018222722A2 (en) 2017-05-30 2018-12-06 Bristol-Myers Squibb Company Compositions comprising an anti-lag-3 antibody or an anti-lag-3 antibody and an anti-pd-1 or anti-pd-l1 antibody
WO2018222711A2 (en) 2017-05-30 2018-12-06 Bristol-Myers Squibb Company Compositions comprising a combination of an anti-lag-3 antibody, a pd-1 pathway inhibitor, and an immunotherapeutic agent
SMT202300418T1 (it) 2017-05-30 2024-01-10 Bristol Myers Squibb Co Trattamento di tumori positivi per lag-3
WO2018229715A1 (en) 2017-06-16 2018-12-20 Novartis Ag Compositions comprising anti-cd32b antibodies and methods of use thereof
WO2018237157A1 (en) 2017-06-22 2018-12-27 Novartis Ag CD73 BINDING ANTIBODY MOLECULES AND USES THEREOF
AU2018287519B2 (en) 2017-06-22 2021-07-22 Novartis Ag IL-1beta binding antibodies for use in treating cancer
WO2018235056A1 (en) 2017-06-22 2018-12-27 Novartis Ag Il-1beta binding antibodies for use in treating cancer
JP2020525483A (ja) 2017-06-27 2020-08-27 ノバルティス アーゲー 抗ｔｉｍ−３抗体のための投与レジメンおよびその使用
CN111093651B (zh) 2017-06-30 2023-06-06 百时美施贵宝公司 Ido抑制剂的无定形和结晶形式
JP2020527572A (ja) 2017-07-20 2020-09-10 ノバルティス アーゲー 抗ｌａｇ−３抗体の投薬量レジメンおよびその使用
JP7186764B2 (ja) 2017-07-28 2022-12-09 ブリストル－マイヤーズ スクイブ カンパニー 抗癌剤としての環状ジヌクレオチド
US11261214B2 (en) 2017-08-04 2022-03-01 Bicycletx Limited Bicyclic peptide ligand specific for CD137
EP3668496A4 (en) 2017-08-17 2021-07-14 Ikena Oncology, Inc. AHR INHIBITORS AND THEIR USES
ES2904317T3 (es) 2017-08-31 2022-04-04 Bristol Myers Squibb Co Dinucleótidos cíclicos como agentes anticancerosos
JP7209697B2 (ja) 2017-08-31 2023-01-20 ブリストル－マイヤーズ スクイブ カンパニー 抗癌剤としての環状ジヌクレオチド
CN111032672B (zh) 2017-08-31 2024-09-13 百时美施贵宝公司 作为抗癌剂的环二核苷酸
US11497756B2 (en) 2017-09-12 2022-11-15 Sumitomo Pharma Oncology, Inc. Treatment regimen for cancers that are insensitive to BCL-2 inhibitors using the MCL-1 inhibitor alvocidib
MX2020003190A (es) 2017-09-22 2020-11-11 Kymera Therapeutics Inc Degradadores de proteinas y usos de los mismos.
EP3684366A4 (en) 2017-09-22 2021-09-08 Kymera Therapeutics, Inc. Crbn ligands and uses thereof
WO2019074822A1 (en) 2017-10-09 2019-04-18 Bristol-Myers Squibb Company INDOLEAMINE 2,3-DIOXYGENASE INHIBITORS AND METHODS OF USE
WO2019074824A1 (en) 2017-10-09 2019-04-18 Bristol-Myers Squibb Company INDOLEAMINE 2,3-DIOXYGENASE INHIBITORS AND METHODS OF USE
EP3694867B1 (en) 2017-10-10 2025-12-24 Bristol-Myers Squibb Company Cyclic dinucleotides as anticancer agents
WO2019075090A1 (en) 2017-10-10 2019-04-18 Tilos Therapeutics, Inc. ANTI-LAP ANTIBODIES AND USES THEREOF
US11427610B2 (en) 2017-10-16 2022-08-30 Bristol-Myers Squibb Company Cyclic dinucleotides as anticancer agents
EP3700933A1 (en) 2017-10-25 2020-09-02 Novartis AG Antibodies targeting cd32b and methods of use thereof
EP3704159A1 (en) 2017-11-01 2020-09-09 Bristol-Myers Squibb Company Immunostimulatory agonistic antibodies for use in treating cancer
WO2019090198A1 (en) 2017-11-06 2019-05-09 Bristol-Myers Squibb Company Isofuranone compounds useful as hpk1 inhibitors
WO2019099838A1 (en) 2017-11-16 2019-05-23 Novartis Ag Combination therapies
TW201925782A (zh) 2017-11-30 2019-07-01 瑞士商諾華公司 靶向bcma之嵌合抗原受體及其用途
IL315310A (en) 2017-12-26 2024-10-01 Kymera Therapeutics Inc Irak degraders and uses thereof
US11447449B2 (en) 2018-01-05 2022-09-20 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
CN112218651A (zh) 2018-01-08 2021-01-12 诺华公司 用于与嵌合抗原受体疗法组合的免疫增强rna
EP3737675A4 (en) 2018-01-12 2022-01-05 Kymera Therapeutics, Inc. Crbn ligands and uses thereof
EP3737666A4 (en) 2018-01-12 2022-01-05 Kymera Therapeutics, Inc. PROTEIN DEGRADATION AGENTS AND ASSOCIATED USES
JP7358361B2 (ja) 2018-01-12 2023-10-10 ブリストル－マイヤーズ スクイブ カンパニー Ｔｉｍ３に対する抗体およびその使用
US10988477B2 (en) 2018-01-29 2021-04-27 Merck Patent Gmbh GCN2 inhibitors and uses thereof
MX2020007797A (es) 2018-01-29 2020-09-18 Merck Patent Gmbh Inhibidores de la cinasa 2 de control general no desrepresible (gcn2) y usos de los mismos.
AU2019215031B2 (en) 2018-01-31 2025-10-09 Novartis Ag Combination therapy using a chimeric antigen receptor
US10519187B2 (en) 2018-02-13 2019-12-31 Bristol-Myers Squibb Company Cyclic dinucleotides as anticancer agents
WO2019160956A1 (en) 2018-02-13 2019-08-22 Novartis Ag Chimeric antigen receptor therapy in combination with il-15r and il15
AU2019222747B2 (en) 2018-02-16 2024-09-05 Arcus Biosciences, Inc. Dosing with an azolopyrimidine compound
US12090142B2 (en) 2018-02-22 2024-09-17 Board Of Regents, The University Of Texas System Combination therapy for the treatment of cancer
CA3091775A1 (en) 2018-02-23 2019-08-29 Bicycletx Limited Multimeric bicyclic peptide ligands
WO2019165315A1 (en) 2018-02-23 2019-08-29 Syntrix Biosystems Inc. Method for treating cancer using chemokine antagonists alone or in combination
SG11202008113RA (en) 2018-03-05 2020-09-29 Arcus Biosciences Inc Arginase inhibitors
KR20200130362A (ko) 2018-03-08 2020-11-18 브리스톨-마이어스 스큅 컴퍼니 항암제로서의 시클릭 디뉴클레오티드
AU2019322487B2 (en) 2018-03-19 2024-04-18 Multivir Inc. Methods and compositions comprising tumor suppressor gene therapy and CD122/CD132 agonists for the treatment of cancer
WO2019183040A1 (en) 2018-03-21 2019-09-26 Five Prime Therapeutics, Inc. ANTIBODIES BINDING TO VISTA AT ACIDIC pH
BR112020019418A2 (pt) 2018-03-25 2021-02-17 Snipr Biome Aps. tratamento e prevenção de infecções microbianas
US10760075B2 (en) 2018-04-30 2020-09-01 Snipr Biome Aps Treating and preventing microbial infections
US20210147547A1 (en) 2018-04-13 2021-05-20 Novartis Ag Dosage Regimens For Anti-Pd-L1 Antibodies And Uses Thereof
AU2019255196A1 (en) 2018-04-16 2020-11-12 Arrys Therapeutics, Inc. EP4 inhibitors and use thereof
WO2019213340A1 (en) 2018-05-03 2019-11-07 Bristol-Myers Squibb Company Uracil derivatives as mer-axl inhibitors
UY38247A (es) 2018-05-30 2019-12-31 Novartis Ag Anticuerpos frente a entpd2, terapias de combinación y métodos de uso de los anticuerpos y las terapias de combinación
WO2019232244A2 (en) 2018-05-31 2019-12-05 Novartis Ag Antibody molecules to cd73 and uses thereof
IL317554A (en) 2018-06-01 2025-02-01 Novartis Ag Anti-BCMA binding molecules and their uses
IL279489B2 (en) 2018-06-22 2025-10-01 Bicycletx Ltd Bicyclic peptide ligands specific for nectin-4, a drug conjugate containing the peptide ligands and a pharmaceutical composition containing the drug conjugate
FI3814348T3 (fi) 2018-06-27 2023-09-22 Bristol Myers Squibb Co Substituoituja naftyridinoniyhdisteitä, jotka ovat käyttökelpoisia t-solun aktivoijina
LT3814347T (lt) 2018-06-27 2023-07-10 Bristol-Myers Squibb Company Naftiridinono junginiai naudotini kaip t ląstelių aktyvatoriai
US12454520B2 (en) 2018-07-06 2025-10-28 Kymera Therapeutics, Inc. Protein degraders and uses thereof
US11292792B2 (en) 2018-07-06 2022-04-05 Kymera Therapeutics, Inc. Tricyclic CRBN ligands and uses thereof
PE20211604A1 (es) 2018-07-09 2021-08-23 Five Prime Therapeutics Inc Anticuerpos de union a ilt4
AR116109A1 (es) 2018-07-10 2021-03-31 Novartis Ag Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos
LT3820573T (lt) 2018-07-10 2023-11-10 Novartis Ag 3-(5-hidroksi-1-oksoizoindolin-2-il)piperidin-2,6-diono dariniai ir jų naudojimas gydyti nuo ikaros šeimos cinko pirštų 2 (ikzf2) priklausomas ligas
AU2019301120A1 (en) 2018-07-11 2021-02-25 Bristol-Myers Squibb Company Antibodies binding to VISTA at acidic pH
CN113015523B (zh) 2018-07-18 2024-07-16 艾库斯生物科学有限公司 偶氮嘧啶化合物的固体形式
AU2019306628B2 (en) 2018-07-20 2024-11-14 Surface Oncology, LLC Anti-CD112R compositions and methods
US12145927B2 (en) 2018-07-23 2024-11-19 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
WO2020023355A1 (en) 2018-07-23 2020-01-30 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
WO2020021465A1 (en) 2018-07-25 2020-01-30 Advanced Accelerator Applications (Italy) S.R.L. Method of treatment of neuroendocrine tumors
CA3107660A1 (en) 2018-07-26 2020-01-30 Bristol-Myers Squibb Company Lag-3 combination therapy for the treatment of cancer
US11253525B2 (en) 2018-08-29 2022-02-22 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
US10959986B2 (en) 2018-08-29 2021-03-30 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase and methods of their use
JP2022500499A (ja) 2018-09-07 2022-01-04 ピク セラピューティクス， インコーポレイテッド Ｅｉｆ４ｅ阻害剤およびその使用
WO2020076969A2 (en) 2018-10-10 2020-04-16 Tilos Therapeutics, Inc. Anti-lap antibody variants and uses thereof
HRP20241325T1 (hr) 2018-10-19 2024-12-20 Bristol-Myers Squibb Company Kombinirana terapija za melanom
EP3873532A1 (en) 2018-10-31 2021-09-08 Novartis AG Dc-sign antibody drug conjugates
UY38476A (es) 2018-11-16 2020-06-30 Arcus Biosciences Inc Inhibidores de arg1 y/o arg2
BR112021010484A2 (pt) 2018-11-30 2021-08-24 Kymera Therapeutics, Inc. Degradadores de irak e usos dos mesmos
JP2022511029A (ja) 2018-12-04 2022-01-28 スミトモ ダイニッポン ファーマ オンコロジー， インコーポレイテッド がんの処置のための薬剤としての使用のためのｃｄｋ９インヒビターおよびその多形
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
CN113271945A (zh) 2018-12-20 2021-08-17 诺华股份有限公司 包含3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物的给药方案和药物组合
EP3670659A1 (en) 2018-12-20 2020-06-24 Abivax Biomarkers, and uses in treatment of viral infections, inflammations, or cancer
WO2020128637A1 (en) 2018-12-21 2020-06-25 Novartis Ag Use of il-1 binding antibodies in the treatment of a msi-h cancer
CN113474045A (zh) 2018-12-21 2021-10-01 拜斯科技术开发有限公司 Pd-l1特异性的双环肽配体
US20200369762A1 (en) 2018-12-21 2020-11-26 Novartis Ag Use of il-1beta binding antibodies
EP3897613A1 (en) 2018-12-21 2021-10-27 Novartis AG Use of il-1beta binding antibodies
AU2019409139A1 (en) 2018-12-21 2021-06-03 Novartis Ag Use of IL-1β binding antibodies
CA3127502A1 (en) 2019-02-12 2020-08-20 Sumitomo Dainippon Pharma Oncology, Inc. Formulations comprising heterocyclic protein kinase inhibitors
MX2021009763A (es) 2019-02-15 2021-09-08 Novartis Ag Derivados de 3-(1-oxo-5-(piperidin-4-il)isoindolin-2-il)piperidina -2,6-diona y usos de los mismos.
MX2021009764A (es) 2019-02-15 2021-09-08 Novartis Ag Derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona sustituidos y usos de los mismos.
EP3937964A4 (en) 2019-03-12 2022-11-16 Arcus Biosciences, Inc. TREATMENT OF ONCOGENE-DRIVEN CANCERS
US20220152179A1 (en) 2019-03-19 2022-05-19 Fundació Privada Institut D'investigació Oncològica De Vall Hebron Combination therapy with omomyc and an antibody binding pd-1 or ctla-4 for the treatment of cancer
JP2022525149A (ja) 2019-03-20 2022-05-11 スミトモ ダイニッポン ファーマ オンコロジー， インコーポレイテッド ベネトクラクスが失敗した急性骨髄性白血病（ａｍｌ）の処置
CN113747895A (zh) 2019-03-22 2021-12-03 大日本住友制药肿瘤公司 包含pkm2调节剂的组合物和用其治疗的方法
WO2020205527A1 (en) 2019-03-29 2020-10-08 Arcus Biosciences, Inc. Treatment of cancer utilizing an identified adenosine fingerprint
WO2020201753A1 (en) 2019-04-02 2020-10-08 Bicycletx Limited Bicycle toxin conjugates and uses thereof
CA3135802A1 (en) 2019-04-05 2020-10-08 Kymera Therapeutics, Inc. Stat degraders and uses thereof
GB201906118D0 (en) 2019-05-01 2019-06-12 Immutep S A Anti-LAG-3 binding molecules
US20230295087A1 (en) 2019-05-13 2023-09-21 Bristol-Myers Squibb Company AGONISTS OF ROR GAMMAt
US12012374B2 (en) 2019-05-13 2024-06-18 Bristol-Myers Squibb Company Agonists of ROR GAMMAt
KR20220016155A (ko) 2019-05-30 2022-02-08 브리스톨-마이어스 스큅 컴퍼니 면역-종양학 (i-o) 요법에 적합한 대상체를 확인하는 방법
US20220233691A1 (en) 2019-05-30 2022-07-28 Bristol-Myers Squibb Company Cell localization signature and combination therapy
WO2020243563A1 (en) 2019-05-30 2020-12-03 Bristol-Myers Squibb Company Multi-tumor gene signatures for suitability to immuno-oncology therapy
AU2020282759A1 (en) 2019-05-31 2021-12-23 Ikena Oncology, Inc. TEAD inhibitors and uses thereof
US12521438B2 (en) 2019-06-10 2026-01-13 Kymera Therapeutics, Inc. SMARCA degraders and uses thereof
JP2022539208A (ja) 2019-07-03 2022-09-07 スミトモ ファーマ オンコロジー， インコーポレイテッド チロシンキナーゼ非受容体１（ｔｎｋ１）阻害剤およびその使用
CN110320352A (zh) * 2019-07-25 2019-10-11 上海轩锋生物科技有限公司 基于抗体依赖的细胞介导细胞毒性的抗体效价检测方法
WO2021026179A1 (en) 2019-08-06 2021-02-11 Bristol-Myers Squibb Company AGONISTS OF ROR GAMMAt
WO2021024020A1 (en) 2019-08-06 2021-02-11 Astellas Pharma Inc. Combination therapy involving antibodies against claudin 18.2 and immune checkpoint inhibitors for treatment of cancer
AR119821A1 (es) 2019-08-28 2022-01-12 Bristol Myers Squibb Co Compuestos de piridopirimidinonilo sustituidos útiles como activadores de células t
AU2020347274A1 (en) 2019-09-13 2022-03-31 Nimbus Saturn, Inc. HPK1 antagonists and uses thereof
WO2021053559A1 (en) 2019-09-18 2021-03-25 Novartis Ag Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies
MX2022003204A (es) 2019-09-19 2022-04-18 Bristol Myers Squibb Co Anticuerpos de union al supresor de activacion de linfocitos t que contiene inmunoglobulina con dominio v (vista) a ph acido.
CA3153777A1 (en) 2019-09-22 2021-03-25 Bristol-Myers Squibb Company Quantitative spatial profiling for lag-3 antagonist therapy
IL292347A (en) 2019-10-21 2022-06-01 Novartis Ag Combination treatments with ventoclax and tim-3 inhibitors
BR112022007179A2 (pt) 2019-10-21 2022-08-23 Novartis Ag Inibidores de tim-3 e usos dos mesmos
WO2021092221A1 (en) 2019-11-06 2021-05-14 Bristol-Myers Squibb Company Methods of identifying a subject with a tumor suitable for a checkpoint inhibitor therapy
WO2021092220A1 (en) 2019-11-06 2021-05-14 Bristol-Myers Squibb Company Methods of identifying a subject with a tumor suitable for a checkpoint inhibitor therapy
BR112022008191A2 (pt) 2019-11-08 2022-07-12 Bristol Myers Squibb Co Terapia com antagonista de lag-3 para melanoma
US11548870B2 (en) 2019-11-19 2023-01-10 Bristol-Myers Squibb Company Compounds useful as inhibitors of helios protein
CA3159317A1 (en) 2019-11-26 2021-06-03 Alfredo C. Castro Polymorphic carbazole derivatives and uses thereof
US12527783B2 (en) 2019-11-26 2026-01-20 Bristol-Myers Squibb Company Salts/cocrystals of (R)-N-(4-chlorophenyl-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide
WO2021113644A1 (en) 2019-12-05 2021-06-10 Multivir Inc. Combinations comprising a cd8+ t cell enhancer, an immune checkpoint inhibitor and radiotherapy for targeted and abscopal effects for the treatment of cancer
WO2021127283A2 (en) 2019-12-17 2021-06-24 Kymera Therapeutics, Inc. Irak degraders and uses thereof
CN115052627A (zh) 2019-12-17 2022-09-13 凯麦拉医疗公司 Irak降解剂和其用途
JP2023507190A (ja) 2019-12-20 2023-02-21 ノバルティス アーゲー 増殖性疾患を治療するための抗ＴＧＦβ抗体及びチェックポイント阻害薬の使用
EP4081308A4 (en) 2019-12-23 2024-01-24 Kymera Therapeutics, Inc. SMARCA DEGRADERS AND USES THEREOF
CN114846015B (zh) 2019-12-23 2024-07-30 百时美施贵宝公司 用作t细胞激活剂的经取代的杂芳基化合物
EP4081516B1 (en) 2019-12-23 2025-07-30 Bristol-Myers Squibb Company Substituted quinazolinyl compounds useful as t cell activators
AU2020412698A1 (en) 2019-12-23 2022-08-18 Bristol-Myers Squibb Company Substituted piperazine derivatives useful as T cell activators
AR120823A1 (es) 2019-12-23 2022-03-23 Bristol Myers Squibb Co Compuestos bicíclicos sustituidos útiles como activadores de células t
WO2021133748A1 (en) 2019-12-23 2021-07-01 Bristol-Myers Squibb Company Substituted quinolinonyl piperazine compounds useful as t cell activators
US20230045791A1 (en) 2020-01-06 2023-02-16 Hifibio (Hk) Limited Anti-tnfr2 antibody and uses thereof
AU2021205143A1 (en) 2020-01-07 2022-07-28 Hifibio, Inc. Anti-Galectin-9 antibody and uses thereof
US11534441B2 (en) 2020-01-15 2022-12-27 Blueprint Medicines Corporation MAP4K1 inhibitors
WO2021144657A1 (en) 2020-01-17 2021-07-22 Novartis Ag Combination comprising a tim-3 inhibitor and a hypomethylating agent for use in treating myelodysplastic syndrome or chronic myelomonocytic leukemia
KR20220139915A (ko) 2020-02-06 2022-10-17 브리스톨-마이어스 스큅 컴퍼니 Il-10 및 그의 용도
MX2022010944A (es) 2020-03-03 2022-11-09 Pic Therapeutics Inc Inhibidores del factor de iniciacion de traduccion eucariotica 4e (eif4e) y sus usos.
CA3171258A1 (en) 2020-03-19 2021-09-23 Nan JI Mdm2 degraders and uses thereof
JP7474861B2 (ja) 2020-03-19 2024-04-25 アーカス バイオサイエンシーズ，インコーポレーテッド Ｈｉｆ－２アルファの阻害剤としてのテトラリン化合物及びテトラヒドロキノリン化合物
TW202140441A (zh) 2020-03-23 2021-11-01 美商必治妥美雅史谷比公司 經取代之側氧基異吲哚啉化合物
WO2021207449A1 (en) 2020-04-09 2021-10-14 Merck Sharp & Dohme Corp. Affinity matured anti-lap antibodies and uses thereof
WO2021239292A1 (en) 2020-05-28 2021-12-02 Immutep S.A.S. Treatment of cancer
JP7776448B2 (ja) 2020-06-02 2025-11-26 アーカス バイオサイエンシズ インコーポレイティド Ｔｉｇｉｔに対する抗体
EP4162037A1 (en) 2020-06-03 2023-04-12 MV Biotherapeutics SA Combination of an atp-hydrolyzing enzyme and an immune checkpoint modulator and uses thereof
US20230250110A1 (en) 2020-06-03 2023-08-10 Kymera Therapeutics, Inc. Deuterated irak degraders and uses thereof
TW202210483A (zh) 2020-06-03 2022-03-16 美商凱麥拉醫療公司 Irak降解劑之結晶型
WO2021258010A1 (en) 2020-06-19 2021-12-23 Gossamer Bio Services, Inc. Oxime compounds useful as t cell activators
EP4168007A1 (en) 2020-06-23 2023-04-26 Novartis AG Dosing regimen comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives
AU2021306613A1 (en) 2020-07-07 2023-02-02 BioNTech SE Therapeutic RNA for HPV-positive cancer
CA3187255A1 (en) 2020-07-30 2022-02-03 Duncan Walker Methods of treating mutant lymphomas
EP4188549A1 (en) 2020-08-03 2023-06-07 Novartis AG Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
CA3188996A1 (en) 2020-08-10 2022-02-17 Tengfei XIAO Compositions and methods for treating autoimmune diseases and cancers by targeting igsf8
KR20230074721A (ko) 2020-08-17 2023-05-31 바이사이클티엑스 리미티드 Nectin-4에 특이적인 이환 콘쥬게이트 및 이의 용도
KR20230058442A (ko) 2020-08-28 2023-05-03 브리스톨-마이어스 스큅 컴퍼니 간세포성 암종에 대한 lag-3 길항제 요법
EP4204453A1 (en) 2020-08-31 2023-07-05 Bristol-Myers Squibb Company Cell localization signature and immunotherapy
US20230321285A1 (en) 2020-08-31 2023-10-12 Advanced Accelerator Applications International Sa Method of treating psma-expressing cancers
WO2022043558A1 (en) 2020-08-31 2022-03-03 Advanced Accelerator Applications International Sa Method of treating psma-expressing cancers
KR20230069956A (ko) 2020-09-14 2023-05-19 베링거 인겔하임 인터내셔날 게엠베하 이종 프라임 부스트 백신
US20230416382A1 (en) 2020-10-14 2023-12-28 Five Prime Therapeutics, Inc. Anti-c-c chemokine receptor 8 (ccr8) antibodies and methods of use thereof
IL301907A (en) 2020-10-23 2023-06-01 Bristol Myers Squibb Co Lag-3 antagonist therapy for lung cancer
AU2021373366A1 (en) 2020-11-06 2023-06-01 Novartis Ag Cd19 binding molecules and uses thereof
WO2022120353A1 (en) 2020-12-02 2022-06-09 Ikena Oncology, Inc. Tead inhibitors and uses thereof
AU2021392040A1 (en) 2020-12-02 2023-06-29 Ikena Oncology, Inc. Tead inhibitors and uses thereof
WO2022120179A1 (en) 2020-12-03 2022-06-09 Bristol-Myers Squibb Company Multi-tumor gene signatures and uses thereof
TW202237119A (zh) 2020-12-10 2022-10-01 美商住友製藥腫瘤公司 Ａｌｋ﹘５抑制劑和彼之用途
CA3202330A1 (en) 2020-12-16 2022-06-23 Anthony Casarez Compounds useful as t cell activators
TW202245808A (zh) 2020-12-21 2022-12-01 德商拜恩迪克公司 用於治療癌症之治療性ｒｎａ
WO2022135666A1 (en) 2020-12-21 2022-06-30 BioNTech SE Treatment schedule for cytokine proteins
WO2022135667A1 (en) 2020-12-21 2022-06-30 BioNTech SE Therapeutic rna for treating cancer
US20220233689A1 (en) 2020-12-28 2022-07-28 Bristol-Myers Squibb Company Methods of treating tumors
US20220233693A1 (en) 2020-12-28 2022-07-28 Bristol-Myers Squibb Company Antibody Compositions and Methods of Use Thereof
CN116867758A (zh) 2020-12-30 2023-10-10 凯麦拉医疗公司 Irak降解剂和其用途
US20250186539A2 (en) 2021-01-11 2025-06-12 Bicycletx Limited Methods for treating cancer
CA3210196A1 (en) 2021-01-29 2022-08-04 Board Of Regents, The University Of Texas System Methods of treating cancer with kinase inhibitors
AU2022215844A1 (en) 2021-02-02 2023-09-14 Liminal Biosciences Limited Gpr84 antagonists and uses thereof
MX2023009060A (es) 2021-02-02 2023-09-29 Liminal Biosciences Ltd Antagonistas de gpr84 y usos de estos.
US20240109899A1 (en) 2021-02-04 2024-04-04 Bristol-Myers Squibb Company Benzofuran compounds as sting agonists
JP2024506909A (ja) 2021-02-12 2024-02-15 ニンバス サターン， インコーポレイテッド Ｈｐｋ１アンタゴニスト及びその使用
EP4291558A1 (en) 2021-02-12 2023-12-20 F. Hoffmann-La Roche AG Bicyclic tetrahydroazepine derivatives for the treatment of cancer
CA3207380A1 (en) 2021-02-15 2022-08-18 Haojing RONG Irak4 degraders and uses thereof
AU2022220043A1 (en) 2021-02-15 2023-08-31 Kymera Therapeutics, Inc. Irak4 degraders and uses thereof
US11926625B2 (en) 2021-03-05 2024-03-12 Nimbus Saturn, Inc. HPK1 antagonists and uses thereof
EP4305041A1 (en) 2021-03-08 2024-01-17 Blueprint Medicines Corporation Map4k1 inhibitors
US11918582B2 (en) 2021-03-15 2024-03-05 Rapt Therapeutics, Inc. Pyrazole pyrimidine compounds and uses thereof
EP4313127A1 (en) 2021-03-29 2024-02-07 Juno Therapeutics, Inc. Methods for dosing and treatment with a combination of a checkpoint inhibitor therapy and a car t cell therapy
WO2022213062A1 (en) 2021-03-29 2022-10-06 Nimbus Saturn, Inc. Hpk1 antagonists and uses thereof
JP2024515545A (ja) 2021-04-05 2024-04-10 ブリストル－マイヤーズ スクイブ カンパニー がん治療のためのピリジニル置換オキソイソインドリン化合物
PE20231941A1 (es) 2021-04-06 2023-12-05 Bristol Myers Squibb Co Compuestos de oxoisoindolina sustituidos con piridinilo
TW202304979A (zh) 2021-04-07 2023-02-01 瑞士商諾華公司 抗ＴＧＦβ抗體及其他治療劑用於治療增殖性疾病之用途
AU2022253474A1 (en) 2021-04-08 2023-11-16 Board Of Regents, The University Of Texas System Compounds and methods for theranostic targeting of parp activity
BR112023020781A2 (pt) 2021-04-09 2023-12-19 Nimbus Clio Inc Moduladores de cbl-b e usos dos mesmos
MX2023012060A (es) 2021-04-13 2024-01-22 Nuvalent Inc Heterociclos con sustitucion amino para tratar canceres con mutaciones de egfr.
IL307673A (en) 2021-04-16 2023-12-01 Ikena Oncology Inc MEK inhibitors and their use
IL308314A (en) 2021-05-07 2024-01-01 Kymera Therapeutics Inc CDK2 compounds and their uses
US20240285740A1 (en) 2021-05-12 2024-08-29 Dana-Farber Cancer Institute, Inc. Compositions and methods for treating cancer
AR125874A1 (es) 2021-05-18 2023-08-23 Novartis Ag Terapias de combinación
JP2024521712A (ja) 2021-05-21 2024-06-04 アーカス バイオサイエンシーズ，インコーポレーテッド Ａｘｌ阻害化合物
WO2022246177A1 (en) 2021-05-21 2022-11-24 Arcus Biosciences, Inc. Axl compounds
GB202108718D0 (en) 2021-06-18 2021-08-04 Immutep Sas Triple combination therapy
EP4370552A1 (en) 2021-07-13 2024-05-22 BioNTech SE Multispecific binding agents against cd40 and cd137 in combination therapy for cancer
TW202321237A (zh) 2021-07-14 2023-06-01 美商纜圖藥品公司 Ｍａｐ４ｋ１抑制劑
WO2023288264A1 (en) 2021-07-15 2023-01-19 Blueprint Medicines Corporation Map4k1 inhibitors
WO2023028235A1 (en) 2021-08-25 2023-03-02 PIC Therapeutics, Inc. Eif4e inhibitors and uses thereof
CN118019739A (zh) 2021-08-25 2024-05-10 皮克医疗公司 Eif4e抑制剂及其用途
TW202333802A (zh) 2021-10-11 2023-09-01 德商拜恩迪克公司 用於肺癌之治療性rna(二)
WO2023076556A1 (en) 2021-10-29 2023-05-04 Kymera Therapeutics, Inc. Irak4 degraders and synthesis thereof
IL309227A (en) 2021-10-29 2024-02-01 Bristol Myers Squibb Co LAG-3 antagonist therapy for hematological cancer
IL312348A (en) 2021-10-29 2024-06-01 Arcus Biosciences Inc HIF-2ALPHA inhibitors and methods of using it
WO2023114984A1 (en) 2021-12-17 2023-06-22 Ikena Oncology, Inc. Tead inhibitors and uses thereof
WO2023122778A1 (en) 2021-12-22 2023-06-29 Gossamer Bio Services, Inc. Pyridazinone derivatives useful as t cell activators
WO2023122772A1 (en) 2021-12-22 2023-06-29 Gossamer Bio Services, Inc. Oxime derivatives useful as t cell activators
WO2023122777A1 (en) 2021-12-22 2023-06-29 Gossamer Bio Services, Inc. Oxime derivatives useful as t cell activators
US20250215076A1 (en) 2022-01-26 2025-07-03 Bristol-Myers Squibb Company Combination therapy for hepatocellular carcinoma
WO2023147594A2 (en) 2022-01-31 2023-08-03 Kymera Therapeutics, Inc. Irak degraders and uses thereof
EP4472963A1 (en) 2022-02-01 2024-12-11 Arvinas Operations, Inc. Dgk targeting compounds and uses thereof
US20250368714A1 (en) 2022-02-11 2025-12-04 Immutep S.A.S. Treatment of cancer
MX2024010310A (es) 2022-02-25 2024-08-28 Bristol Myers Squibb Co Terapia de combinacion para carcinoma colorrectal.
WO2023168404A1 (en) 2022-03-04 2023-09-07 Bristol-Myers Squibb Company Methods of treating a tumor
WO2023170606A1 (en) 2022-03-08 2023-09-14 Alentis Therapeutics Ag Use of anti-claudin-1 antibodies to increase t cell availability
WO2023173057A1 (en) 2022-03-10 2023-09-14 Ikena Oncology, Inc. Mek inhibitors and uses thereof
WO2023173053A1 (en) 2022-03-10 2023-09-14 Ikena Oncology, Inc. Mek inhibitors and uses thereof
IL314346A (en) 2022-03-15 2024-09-01 Compugen Ltd Antibodies antagonistic to IL-18BP and their use in monotherapy and combination therapy in cancer treatment
KR20240159621A (ko) 2022-03-18 2024-11-05 브리스톨-마이어스 스큅 컴퍼니 폴리펩티드를 단리하는 방법
WO2023211889A1 (en) 2022-04-25 2023-11-02 Ikena Oncology, Inc. Polymorphic compounds and uses thereof
WO2023214325A1 (en) 2022-05-05 2023-11-09 Novartis Ag Pyrazolopyrimidine derivatives and uses thereof as tet2 inhibitors
KR20250040894A (ko) 2022-05-25 2025-03-25 이케나 온콜로지, 인코포레이티드 Mek 억제제 및 이의 용도
JP2025518785A (ja) 2022-06-02 2025-06-19 ブリストル－マイヤーズ スクイブ カンパニー 抗体組成物及びその使用方法
US11873296B2 (en) 2022-06-07 2024-01-16 Verastem, Inc. Solid forms of a dual RAF/MEK inhibitor
CN114942217A (zh) * 2022-06-13 2022-08-26 南京怀锡医疗科技有限公司 用于临床感染性疾病诊断的中性粒细胞感染指数测定方法
GB202209518D0 (en) 2022-06-29 2022-08-10 Snipr Biome Aps Treating & preventing E coli infections
EP4554680A1 (en) 2022-07-15 2025-05-21 Arcus Biosciences, Inc. Inhibitors of hpk1 and methods of use thereof
US20260028336A1 (en) 2022-07-20 2026-01-29 Arcus Biosciences, Inc. Cbl-b inhibitors and methods of use thereof
AU2023317742A1 (en) 2022-08-02 2025-03-20 Liminal Biosciences Limited Substituted pyridone gpr84 antagonists and uses thereof
WO2024028364A1 (en) 2022-08-02 2024-02-08 Liminal Biosciences Limited Aryl-triazolyl and related gpr84 antagonists and uses thereof
EP4565568A1 (en) 2022-08-02 2025-06-11 Liminal Biosciences Limited Heteroaryl carboxamide and related gpr84 antagonists and uses thereof
CN119654312A (zh) 2022-08-08 2025-03-18 百时美施贵宝公司 用作t细胞活化剂的取代的四唑基化合物
WO2024036101A1 (en) 2022-08-09 2024-02-15 Bristol-Myers Squibb Company Tertiary amine substituted bicyclic compounds useful as t cell activators
EP4568958A1 (en) 2022-08-11 2025-06-18 F. Hoffmann-La Roche AG Bicyclic tetrahydrothiazepine derivatives
TW202417439A (zh) 2022-08-11 2024-05-01 瑞士商赫孚孟拉羅股份公司 雙環四氫噻吖呯衍生物
WO2024033389A1 (en) 2022-08-11 2024-02-15 F. Hoffmann-La Roche Ag Bicyclic tetrahydrothiazepine derivatives
TW202417001A (zh) 2022-08-11 2024-05-01 瑞士商赫孚孟拉羅股份公司 雙環四氫吖呯衍生物
AU2023341373A1 (en) 2022-09-14 2025-03-06 Arcus Biosciences, Inc. Dispersions of etrumadenant
WO2024081385A1 (en) 2022-10-14 2024-04-18 Arcus Biosciences, Inc. Hpk1 inhibitors and methods of use thereof
KR20250080902A (ko) 2022-10-20 2025-06-05 아르커스 바이오사이언시즈 인코포레이티드 Cd73 화합물의 동결건조된 제형
CN120390652A (zh) 2022-12-01 2025-07-29 免疫医疗有限公司 用于治疗癌症的包含抗pd-l1抗体和抗cd73抗体的组合疗法
CN120418289A (zh) 2022-12-14 2025-08-01 安斯泰来制药欧洲有限公司 结合cldn18.2和cd3的双特异性结合剂与免疫检查点抑制剂的联合疗法
KR20250123912A (ko) 2022-12-21 2025-08-18 브리스톨-마이어스 스큅 컴퍼니 폐암에 대한 병용 요법
WO2024137865A1 (en) 2022-12-22 2024-06-27 Gossamer Bio Services, Inc. Compounds useful as t cell activators
AU2024225483A1 (en) 2023-02-23 2025-08-28 Imcheck Therapeutics Combination of btn3a activating antibody and immune checkpoint inhibitors
WO2024196952A1 (en) 2023-03-20 2024-09-26 Bristol-Myers Squibb Company Tumor subtype assessment for cancer therapy
US20240425497A1 (en) 2023-05-05 2024-12-26 Arcus Biosciences, Inc. Cbl-b Inhibitors and Methods of Use Thereof
TW202500139A (zh) 2023-05-08 2025-01-01 美商必治妥美雅史谷比公司 經取代之苯基㗁唑酮化合物
TW202509014A (zh) 2023-05-10 2025-03-01 美商纜圖藥品公司 ＧＳＫ３α抑制劑及其使用方法
WO2024243502A1 (en) 2023-05-25 2024-11-28 Arcus Biosciences, Inc. Cbl-b inhibitors and methods of use thereof
WO2024249540A1 (en) 2023-05-31 2024-12-05 Bristol-Myers Squibb Company Substituted oxazolone compound for decreasing levels of ikzf1-4 proteins
AU2024281414A1 (en) 2023-06-02 2025-12-11 Arcus Biosciences, Inc. Biomarkers for predicting cancer treatment efficacy
AU2024285766A1 (en) 2023-06-07 2026-01-08 Bristol-Myers Squibb Company Spirocyclic substituted oxoisoindolinyl piperidine-2,6-dione compound
WO2024263853A1 (en) 2023-06-23 2024-12-26 Bristol-Myers Squibb Company Substituted oxoisoindolinyl piperidine-2,6-dione compound as anticancer agent
IL321489A (en) 2023-06-23 2025-08-01 Kymera Therapeutics Inc IRAQ joints and their uses
TW202515608A (zh) 2023-06-26 2025-04-16 以色列商坎布根有限公司 Ｉｌ—１８ｂｐ拮抗抗體及其於癌症治療之單一療法及組合療法的用途
WO2025030002A2 (en) 2023-08-02 2025-02-06 Arvinas Operations, Inc. Dgk targeting compounds and uses thereof
WO2025038763A1 (en) 2023-08-15 2025-02-20 Bristol-Myers Squibb Company Ceramic hydroxyapatite chromatography flow through method
WO2025038857A1 (en) 2023-08-16 2025-02-20 Arcus Biosciences, Inc. TETRALINS TARGETING MUTANT HIF-2α
WO2025064197A1 (en) 2023-09-02 2025-03-27 Bristol-Myers Squibb Company Substituted azetidinyl oxoisoindolinyl piperidine-2,6-dione compounds
AR133696A1 (es) 2023-09-02 2025-10-22 Bristol Myers Squibb Co Compuestos de fenil oxooxazolil piperidinadiona sustituida
WO2025054339A1 (en) 2023-09-08 2025-03-13 Arcus Biosciences, Inc. Triazolopyridine compounds as inhibitors of kit
JP7808733B2 (ja) 2023-09-13 2026-01-29 ブリストル－マイヤーズ スクイブ カンパニー 置換オキソイソインドリニルピペリジン－２，６－ジオン化合物
WO2025072330A1 (en) 2023-09-26 2025-04-03 Arcus Biosciences, Inc. Kit inhibitor compounds and methods of use thereof
TW202517260A (zh) 2023-10-06 2025-05-01 美商阿克思生物科學有限公司 Ｃｂｌ—ｂ抑制劑及其使用方法
WO2025096494A1 (en) 2023-10-31 2025-05-08 Bristol-Myers Squibb Company Ubiquitin specific processing protease 1 (usp1) compounds
US20250145590A1 (en) 2023-10-31 2025-05-08 Bristol-Myers Squibb Company Ubiquitin specific processing protease 1 (usp1) compounds
WO2025096488A1 (en) 2023-10-31 2025-05-08 Bristol-Myers Squibb Company Ubiquitin specific processing protease 1 (usp1) compounds
WO2025096505A1 (en) 2023-10-31 2025-05-08 Bristol-Myers Squibb Company Ubiquitin specific processing protease 1 (usp1) compounds
WO2025096487A1 (en) 2023-10-31 2025-05-08 Bristol-Myers Squibb Company Ubiquitin specific processing protease 1 (usp1) compounds
WO2025096490A1 (en) 2023-10-31 2025-05-08 Bristol-Myers Squibb Company Ubiquitin specific processing protease 1 (usp1) compounds
WO2025096489A1 (en) 2023-10-31 2025-05-08 Bristol-Myers Squibb Company Ubiquitin specific processing protease 1 (usp1) compounds
US12384773B2 (en) 2023-11-02 2025-08-12 Arcus Biosciences, Inc. Thiazole compounds and methods of use thereof
WO2025121445A1 (en) 2023-12-08 2025-06-12 Astellas Pharma Inc. Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and agents stabilizing or increasing expression of cldn18.2
WO2025120866A1 (en) 2023-12-08 2025-06-12 Astellas Pharma Inc. Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and agents stabilizing or increasing expression of cldn18.2
WO2025120867A1 (en) 2023-12-08 2025-06-12 Astellas Pharma Inc. Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and anti-vegfr2 antibodies
US20250230173A1 (en) 2023-12-20 2025-07-17 Arcus Biosciences, Inc. Salt forms of an axl inhibitor
US20250215087A1 (en) 2023-12-29 2025-07-03 Bristol-Myers Squibb Company Combination therapy of kras inhibitor and treg depleting agent
WO2025184208A1 (en) 2024-02-27 2025-09-04 Bristol-Myers Squibb Company Anti-ceacam5 antibodies and uses thereof
EP4658320A1 (en) 2024-02-27 2025-12-10 Bristol-Myers Squibb Company Anti-ceacam5 antibody drug conjugates
WO2025193759A1 (en) 2024-03-12 2025-09-18 Gilead Sciences, Inc. Solid forms of an azolopyrimidine compound
WO2025226767A1 (en) 2024-04-24 2025-10-30 Bristol-Myers Squibb Company Substituted 3-(5-(6-aminopyridin-2-yl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione compounds for use in the treatment of cancer
WO2025245489A1 (en) 2024-05-24 2025-11-27 Bristol-Myers Squibb Company Treatment of tumors in subjects having fgl-1 positive samples
WO2026006759A1 (en) 2024-06-28 2026-01-02 Arcus Biosciences, Inc. Pharmaceutical compositions, dosage forms, and methods of making and using same

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1265149A (zh) * 1997-07-25 2000-08-30 古斯塔夫鲁西研究院 Mhc－11－类配体作为疫苗佐剂以及lag－3用于癌症治疗的应用

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1341281C (en) * 1986-07-09 2001-08-07 Hubert J.P. Schoemaker Immunotherapy of tumor with monoclonal antibody against the 17-1a antigen
US5785973A (en) * 1988-02-01 1998-07-28 Praxis Biologics, Inc. Synthetic peptides representing a T-cell epitope as a carrier molecule for conjugate vaccines
EP0628570A1 (en) * 1989-02-17 1994-12-14 Chiron Mimotopes Pty. Ltd. Method for the use and synthesis of peptides
US5976877A (en) 1990-01-08 1999-11-02 Institut National De La Sante Et De La Recherche Medicale (Inserm) Proteins produced by human lymphocytes DNA sequence encoding these proteins and their pharmaceutical and biological uses
FR2656800B1 (fr) 1990-01-08 1992-05-15 Roussy Inst Gustave Nouvelles proteines produits par les lymphocytes humains, sequence d'adn codant pour ces proteines et applications pharmaceutiques et biologiques.
US7294712B2 (en) 1990-06-04 2007-11-13 Aventis Pharma S.A. Nucleotide sequences coding for variable regions of β chains of human T lymphocyte receptors, corresponding peptide segments and the diagnostic and therapeutic uses
US6596536B1 (en) 1991-02-08 2003-07-22 Aventis Pharma S.A. Nucleotide sequences coding for variable regions of the alpha chains of human T lymphocyte receptors, corresponding peptide segments and the diagnostic and therapeutic uses
CA2079879C (fr) 1991-02-08 2007-11-06 Thierry Hercend Sequences nucleotidiques codant pour des regions variables de chaines alpha des recepteurs des lymphocytes humains ainsi que leurs applications
AU660306B2 (en) 1991-02-12 1995-06-22 Roussel-Uclaf Nucleotidic sequences coding for variable regions of beta chains of human T lymphocyte receptors, corresponding peptidic segments and diagnostic and therapeutic applications
CA2189657C (fr) 1994-05-06 2002-03-12 Florence Faure Fractions polypeptidiques solubles de la proteine lag-3; procede de production; composition therapeutique; anticorps anti-idiotype
JPH11507535A (ja) * 1995-06-07 1999-07-06 イムクローン システムズ インコーポレイテッド 腫瘍の成長を抑制する抗体および抗体フラグメント類
US5840839A (en) * 1996-02-09 1998-11-24 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Alternative open reading frame DNA of a normal gene and a novel human cancer antigen encoded therein
US6277368B1 (en) * 1996-07-25 2001-08-21 The Regents Of The University Of California Cancer immunotherapy using autologous tumor cells combined with cells expressing a membrane cytokine
AU728911B2 (en) * 1996-11-28 2001-01-18 Institut Gustave Roussy Mutants of the LAG-3 proteins, products for the expression of these mutants and use
PT941329E (pt) * 1996-11-29 2004-11-30 Applied Research Systems Metodo para prevenir a rejeicao de enxertos em transplantacao e para produzir uma celula-hospedeiro para terapia genetica universal utilizando activacao de linfocitos (lag-3)
FR2777890B1 (fr) 1998-04-22 2000-12-29 Roussy Inst Gustave Composes peptidiques d'hsp70 utiles dans l'immunotherapie du cancer
FR2795415B1 (fr) 1999-06-28 2003-09-05 Roussy Inst Gustave Compose peptidique derive d'une orf decalee du gene ice
AT409086B (de) 1999-11-16 2002-05-27 Igeneon Krebs Immuntherapie Neue verwendung von antikörpern als impfstoffe
CA2406949A1 (fr) 2000-04-26 2001-11-01 Roger Kravtzoff Utilisation de vecteurs particulaires dans l'immunomodulation
US7517526B2 (en) * 2000-06-29 2009-04-14 Merck Patent Gmbh Enhancement of antibody-cytokine fusion protein mediated immune responses by combined treatment with immunocytokine uptake enhancing agents
EP1295895B1 (en) 2001-09-19 2011-08-10 Institut Gustave Roussy Peptides and proteins binding to glu-pro motifs, therapeutical compositions containing the same and applications thereof
MXPA06003977A (es) * 2003-10-10 2006-06-27 Powderject Vaccines Inc Metodo.
FR2868781B1 (fr) 2004-04-13 2008-02-22 Immutep Composition de vaccin comprenant un ligand cmh de classe ii couple a un antigene, procede de preparation et utilisations
JP2006124383A (ja) 2004-09-30 2006-05-18 Kobayashi Pharmaceut Co Ltd 樹状細胞活性化剤
JP2006141346A (ja) 2004-11-24 2006-06-08 Kobayashi Pharmaceut Co Ltd 樹状細胞活性化剤
EP1928495A2 (en) * 2005-08-19 2008-06-11 Cerus Corporation Antibody-mediated enhancement of immune response
PT2170959E (pt) 2007-06-18 2014-01-07 Merck Sharp & Dohme Anticorpos para o receptor humano de morte programada pd-1
US8425897B2 (en) 2007-08-30 2013-04-23 Immutep S.A. Compositions containing LAG-3 and cells that secrete GM-CSF and methods of use
EP2044949A1 (en) * 2007-10-05 2009-04-08 Immutep Use of recombinant lag-3 or the derivatives thereof for eliciting monocyte immune response
EA037351B8 (ru) 2012-05-15 2021-04-29 Бристол-Майерс Сквибб Компани Способ лечения злокачественных опухолей с использованием комбинации антител против pd-1 и ctla-4
GB201322626D0 (en) * 2013-12-19 2014-02-05 Immutep S A Combined preparations for the treatment of cancer
GB201500374D0 (en) * 2015-01-09 2015-02-25 Immutep S A Combined preparations for the treatment of cancer

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1265149A (zh) * 1997-07-25 2000-08-30 古斯塔夫鲁西研究院 Mhc－11－类配体作为疫苗佐剂以及lag－3用于癌症治疗的应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHIARA CASATI, ET AL.: "Soluble Human LAG-3 Molecule Amplifies the In vitro Generation of Type 1 Tumor-Specific Immunity", 《CANCER RESEARCH》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10954246B2 (en) 2017-04-13 2021-03-23 Taizhou Eoc Pharma Co., Ltd. Compound of EOC315 Mod.I crystal form and preparation method thereof
CN110950966A (zh) * 2019-12-13 2020-04-03 启辰生生物科技(珠海)有限公司 融合蛋白、编码核酸和细胞及用途

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