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1. 发明申请

WO2018092020A1 DOSE AND REGIMEN FOR HDM2-P53 INTERACTION INHIBITORS 审中-公开
公开(公告)号：WO2018092020A1
公开(公告)日：2018-05-24
申请号：PCT/IB2017/057097
申请日：2017-11-14
申请人： NOVARTIS AG
发明人： FERRETTI, Stephane , GUERREIRO, Nelson , JEAY, Sebastien , JULLION, Astrid , MEILLE, Christophe , WUERTHNER, Jens
IPC分类号： A61K31/496 , A61K31/506 , A61K31/401 , A61K31/404 , A61K31/4418 , A61K31/4439 , A61K31/47 , A61P35/00
摘要： The present invention relates to HDM2-p53 interaction inhibitors for use in the treatment of cancer, wherein the drug is administered by a high dose intermittent dosing regimen. The present invention relates in particular to the HDM2-p53 interaction inhibitor HDM201 and the dosing regimen d1, d8 of a 4 week cycle.

2. 发明申请

WO2015198266A1 INTERMITTENT DOSING OF MDM2 INHIBITOR 审中-公开
标题翻译： MDM2抑制剂的间歇剂量
公开(公告)号：WO2015198266A1
公开(公告)日：2015-12-30
申请号：PCT/IB2015/054792
申请日：2015-06-25
申请人： NOVARTIS AG , FERRETTI, Stephane , JEAY, Sebastien
发明人： FERRETTI, Stephane , JEAY, Sebastien
IPC分类号： A61K31/402 , A61K31/404 , A61K31/4178 , A61K31/4418 , A61K31/4439 , A61K31/47 , A61K31/472 , A61K31/496 , A61P35/00
CPC分类号： A61K31/506 , A61K9/0019 , A61K31/402 , A61K31/404 , A61K31/4178 , A61K31/4418 , A61K31/4439 , A61K31/47 , A61K31/472 , A61K31/496 , A61K45/06
摘要： The present disclosure relates to mdm2 inhibitors for use in specific dosing schedules. It was found that if sufficiently potent or, in alternative, sufficiently high dose of a Mdm2 inhibitor is used, it can cause antineoplastic effect by triggering much longer lasting antiproliferative mechanism in cells. The long lasting effect can sustain for several weeks after a single dose, which eliminates the need for daily treatment and allows administering the Mdm2i intermittently. A treatment with the intermittent dosing schedule of a Mdm2 inhibitor can be combined with a daily treatment of the Mdm2i or with another pharmaceutically acceptable ingredient.
摘要翻译：本公开涉及用于特定给药方案的mdm2抑制剂。已经发现，如果使用足够强的或者替代地使用足够高剂量的Mdm2抑制剂，则可以通过在细胞中触发更持久的抗增殖机制而引起抗肿瘤作用。长期持续的效果可以在单次剂量后持续数周，这消除了日常治疗的需要并允许间歇地施用Mdm2i。使用Mdm2抑制剂间歇给药方案的治疗可以与Mdm2i的日常治疗或其他药学上可接受的成分组合。

3. 发明申请

WO2018178925A1 DOSE AND REGIMEN FOR AN HDM2-P53 INTERACTION INHIBITOR IN HEMATOLOGICAL TUMORS 审中-公开
公开(公告)号：WO2018178925A1
公开(公告)日：2018-10-04
申请号：PCT/IB2018/052187
申请日：2018-03-29
申请人： NOVARTIS AG
发明人： FERRETTI, Stephane , GUERREIRO, Nelson , JEAY, Sebastien , JULLION, Astrid , MEILLE, Christophe , WUERTHNER, Jens
IPC分类号： A61K31/506 , A61K45/06 , A61P35/02
摘要： The present invention relates to the HDM2-p53 interaction inhibitors (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one (HDM201), or a pharmaceutically acceptable non-covalent derivative thereof, for use in the treatment of patients with hematological tumors, wherein the drug is administered by an extended low dose dosing regimen.

4. 发明申请

WO2019180576A1 PHARMACEUTICAL COMBINATIONS 审中-公开
公开(公告)号：WO2019180576A1
公开(公告)日：2019-09-26
申请号：PCT/IB2019/052166
申请日：2019-03-18
申请人： NOVARTIS AG
发明人： FERRETTI, Stephane , GUERREIRO, Nelson , HALILOVIC, Ensar , JEAY, Sebastien , JULLION, Astrid , LIANG, Jinsheng , MEILLE, Christophe , WANG, Hui-Qin , WUERTHNER, Jens
IPC分类号： C07K16/28 , A61P35/00 , A61K31/496 , A61K39/00
摘要： The present invention relates to a pharmaceutical combination which comprises (a) at least one antibody molecule (e.g., humanized antibody molecules) that bind to Programmed Death 1 (PD-1), and (b) a HDM2-p53 interaction inhibitor, said combination for simultaneous, separate or sequential administration for use in the treatment of a proliferative disease, a pharmaceutical composition comprising such combination; a method of treating a subject having a proliferative disease comprising administration of said combination to a subject in need thereof; use of such combination for the treatment of proliferative disease; and a commercial package comprising such combination; said proliferative disease being a TP53 wildtype tumor, in particular TP53 wildtype renal cell carcinoma (RCC) or TP53 wildtype colorectal cancer (CRC).

5. 发明申请

WO2015097622A1 PHARMACEUTICAL COMBINATIONS 审中-公开
标题翻译：药物组合
公开(公告)号：WO2015097622A1
公开(公告)日：2015-07-02
申请号：PCT/IB2014/067141
申请日：2014-12-19
申请人： NOVARTIS AG , FERRETTI, Stephane , JEAY, Sebastien , HALILOVIC, Ensar , LI, Fang , WANG, Hui-qin
发明人： FERRETTI, Stephane , JEAY, Sebastien , HALILOVIC, Ensar , LI, Fang , WANG, Hui-qin
IPC分类号： A61K31/4188 , A61K31/505 , A61K31/519 , A61P35/00
CPC分类号： A61K31/519 , A61K31/4188 , A61K31/496 , A61K31/505 , A61K31/506 , A61K2300/00
摘要： The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-5 piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4- dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin- 2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the 10 disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.
摘要翻译：本公开涉及mdm2 / 4抑制剂的药物组合，即（S）-1-（4-氯 - 苯基）-7-异丙氧基-6-甲氧基-2-（4- {甲基 - [4-（4 - 甲基-3-氧代-5-哌嗪-1-基） - 反式 - 环己基甲基] - 氨基} - 苯基）-1,4-二氢-2H-异喹啉-3-酮或（S）-5-（5-氯 -1-甲基-2-氧代-1,2-二氢 - 吡啶-3-基）-6-（4-氯 - 苯基）-2-（2,4-二甲氧基 - 嘧啶-5-基）-1- 异丙基-5,6-二氢-1H-吡咯并[3,4-d]咪唑-4-酮和细胞周期蛋白依赖性激酶4/6（CDK4 / 6）抑制剂7-环戊基-2-（5-哌嗪-1-基 - 吡啶-2-基氨基）-7H-吡咯并[2,3-d]嘧啶-6-甲酸二甲基酰胺。此外，本公开涉及药物组合产品。本公开还涉及包含所述mdm2 / 4抑制剂或细胞周期蛋白依赖性激酶4/6（CDK4 / 6）抑制剂的相应药物制剂，用途和治疗方法。

6. 发明公开

EP3768717A1 PHARMACEUTICAL COMBINATIONS 审中-公开
公开(公告)号：EP3768717A1
公开(公告)日：2021-01-27
申请号：EP19719365.9
申请日：2019-03-18
申请人： Novartis AG
发明人： FERRETTI, Stephane , GUERREIRO, Nelson , HALILOVIC, Ensar , JEAY, Sebastien , JULLION, Astrid , LIANG, Jinsheng , MEILLE, Christophe , WANG, Hui-Qin , WUERTHNER, Jens
IPC分类号： C07K16/28 , A61P35/00 , A61K31/496 , A61K39/00

7. 发明公开

EP3160463A1 INTERMITTENT DOSING OF MDM2 INHIBITOR 有权
标题翻译： MDM2抑制剂的间歇给药
公开(公告)号：EP3160463A1
公开(公告)日：2017-05-03
申请号：EP15733926.8
申请日：2015-06-25
申请人： Novartis AG
发明人： FERRETTI, Stephane , JEAY, Sebastien
IPC分类号： A61K31/402 , A61K31/404 , A61K31/4178 , A61K31/4418 , A61K31/4439 , A61K31/47 , A61K31/472 , A61K31/496 , A61P35/00
摘要： The present disclosure relates to mdm2 inhibitors for use in specific dosing schedules. It was found that if sufficiently potent or, in alternative, sufficiently high dose of a Mdm2 inhibitor is used, it can cause antineoplastic effect by triggering much longer lasting antiproliferative mechanism in cells. The long lasting effect can sustain for several weeks after a single dose, which eliminates the need for daily treatment and allows administering the Mdm2i intermittently. A treatment with the intermittent dosing schedule of a Mdm2 inhibitor can be combined with a daily treatment of the Mdm2i or with another pharmaceutically acceptable ingredient.
摘要翻译：本公开涉及用于特定给药方案的mdm2抑制剂。发现如果使用足够有效或者使用足够高剂量的Mdm2抑制剂，则可以通过在细胞中引发更持久的抗增殖机制而引起抗肿瘤作用。长效持续的效果可以在单次剂量后维持数周，这消除了每日治疗的需要并且允许间歇地施用Mdm2i。具有Mdm2抑制剂的间歇给药方案的治疗可以与每日治疗Mdm2i或与另一种药学上可接受的成分组合。

8. 发明授权

EP3160463B1 INTERMITTENT DOSING OF MDM2 INHIBITOR 有权
公开(公告)号：EP3160463B1
公开(公告)日：2020-10-21
申请号：EP15733926.8
申请日：2015-06-25
申请人： Novartis AG
发明人： FERRETTI, Stephane , JEAY, Sebastien
IPC分类号： A61K31/402 , A61K31/404 , A61K31/4178 , A61K31/4418 , A61K31/4439 , A61K31/47 , A61K31/472 , A61K31/496 , A61P35/00

9. 发明公开

EP3086787A1 PHARMACEUTICAL COMBINATIONS 有权
标题翻译：药物组合
公开(公告)号：EP3086787A1
公开(公告)日：2016-11-02
申请号：EP14824115.1
申请日：2014-12-19
申请人： Novartis AG
发明人： FERRETTI, Stephane , JEAY, Sebastien , HALILOVIC, Ensar , LI, Fang , WANG, Hui-qin
IPC分类号： A61K31/4188 , A61K31/505 , A61K31/519 , A61P35/00
CPC分类号： A61K31/519 , A61K31/4188 , A61K31/496 , A61K31/505 , A61K31/506 , A61K2300/00
摘要： The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.
摘要翻译：本发明涉及mdm2 / 4抑制剂，即（S）-1-（4-氯 - 苯基）-7-异丙氧基-6-甲氧基-2-（4- {甲基 - [4-（4 - 甲基-3-氧代-5-哌嗪-1-基） - 反式 - 环己基甲基] - 氨基} - 苯基）-1,4-二氢-2H-异喹啉-3-酮或（S）-5-（5-氯 -1-甲基-2-氧代-1,2-二氢 - 吡啶-3-基）-6-（4-氯 - 苯基）-2-（2,4-二甲氧基 - 嘧啶-5-基）-1- 异丙基-5,6-二氢-1H-吡咯并[3,4-d]咪唑-4-酮和细胞周期蛋白依赖性激酶4/6（CDK4 / 6）抑制剂7-环戊基-2-（5-哌嗪-1 吡啶-2-基氨基）-7H-吡咯并[2,3-d]嘧啶-6-甲酸二甲基酰胺。此外，该公开涉及药物组合产品。本公开还涉及包含所述mdm2 / 4抑制剂或细胞周期蛋白依赖性激酶4/6（CDK4 / 6）抑制剂的相应药物制剂，用途和治疗方法。

10. 发明公开

EP3600326A1 DOSE AND REGIMEN FOR AN HDM2-P53 INTERACTION INHIBITOR IN HEMATOLOGICAL TUMORS 有权
公开(公告)号：EP3600326A1
公开(公告)日：2020-02-05
申请号：EP18718926.1
申请日：2018-03-29
申请人： Novartis AG
发明人： FERRETTI, Stephane , GUERREIRO, Nelson , JEAY, Sebastien , JULLION, Astrid , MEILLE, Christophe , WUERTHNER, Jens
IPC分类号： A61K31/506 , A61K45/06 , A61P35/02

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