公开(公告)号：US20180193346A1

公开(公告)日：2018-07-12

申请号：US15914479

申请日：2018-03-07

Applicant: Novartis AG

Inventor： Stephane Ferretti ,  Sebastien Jeay ,  Ensar Halilovic ,  Fang Li ,  Hui-Qin Wang

IPC: A61K31/519 ,  A61K31/506 ,  A61K31/496

CPC classification number: A61K31/519 ,  A61K31/4188 ,  A61K31/496 ,  A61K31/505 ,  A61K31/506 ,  A61K2300/00

Abstract: 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.

公开(公告)号：US20140038986A1

公开(公告)日：2014-02-06

申请号：US13950881

申请日：2013-07-25

Applicant: Novartis AG

Inventor： Swann Gaulis ,  Sebastien Jeay

IPC: C12Q1/68 ,  C07D401/12 ,  G01N33/68

CPC classification number: C12Q1/6886 ,  A61K31/496 ,  C07D401/12 ,  C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/136 ,  C12Q2600/156 ,  C12Q2600/158 ,  C12Y603/02019 ,  G01N33/5011 ,  G01N33/574 ,  G01N33/5748 ,  G01N33/57496 ,  G01N33/6875 ,  G01N2333/4704 ,  G01N2333/4748 ,  G01N2333/9015 ,  G01N2800/52

Abstract: The invention provides methods of monitoring differential gene expression of biomarkers to determine patient sensitivity to Human Double Minute inhibitors (MDM2i), methods of determining the sensitivity of a cell to an MDM2i by measuring biomarkers and methods of screening for candidate MDM2i.

Abstract translation: 本发明提供监测生物标志物的差异基因表达以确定患者对人双分钟抑制剂（MDM2i）的敏感性的方法，通过测量生物标志物和筛选候选MDM2i的方法来确定细胞对MDM2i的敏感性的方法。

公开(公告)号：US10220038B2

公开(公告)日：2019-03-05

申请号：US15914479

申请日：2018-03-07

Applicant: Novartis AG

Inventor： Stephane Ferretti ,  Sebastien Jeay ,  Ensar Halilovic ,  Fang Li ,  Hui-Qin Wang

IPC: A61K31/519 ,  A61K31/4188 ,  A61K31/505 ,  A61K31/496 ,  A61K31/506

Abstract: 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.

公开(公告)号：US20180015092A1

公开(公告)日：2018-01-18

申请号：US15683887

申请日：2017-08-23

Applicant: Novartis AG

Inventor： Stephane Ferretti ,  Sebastien Jeay ,  Ensar Halilovic ,  Fang Li ,  Hui-Qin Wang

IPC: A61K31/519 ,  A61K31/506 ,  A61K31/496

CPC classification number: A61K31/519 ,  A61K31/4188 ,  A61K31/496 ,  A61K31/505 ,  A61K31/506 ,  A61K2300/00

Abstract: 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.

公开(公告)号：US11419870B2

公开(公告)日：2022-08-23

申请号：US16898886

申请日：2020-06-11

Applicant: Novartis AG

Inventor： Stephane Ferretti ,  Sebastien Jeay

IPC: A61K31/506 ,  A61K31/402 ,  A61K31/404 ,  A61K31/4178 ,  A61K31/4418 ,  A61K31/4439 ,  A61K31/47 ,  A61K31/472 ,  A61K31/496 ,  A61K9/00 ,  A61K45/06

Abstract: 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.

公开(公告)号：US20190160069A1

公开(公告)日：2019-05-30

申请号：US16263517

申请日：2019-01-31

Applicant: Novartis AG

Inventor： Stephane Ferretti ,  Sebastien Jeay ,  Ensar Halilovic ,  Fang Li ,  Hui-Qin Wang

IPC: A61K31/519 ,  A61K31/506 ,  A61K31/4188 ,  A61K31/505 ,  A61K31/496

Abstract: 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.

公开(公告)号：US20170143723A1

公开(公告)日：2017-05-25

申请号：US15423855

申请日：2017-02-03

Applicant: Novartis AG

Inventor： Stephane Ferretti ,  Sebastien Jeay ,  Ensar Halilovic ,  Fang LI ,  Hui-Qin Wang

IPC: A61K31/519 ,  A61K31/496 ,  A61K31/506

CPC classification number: A61K31/519 ,  A61K31/4188 ,  A61K31/496 ,  A61K31/505 ,  A61K31/506 ,  A61K2300/00

Abstract: 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.

公开(公告)号：US10966978B2

公开(公告)日：2021-04-06

申请号：US16461005

申请日：2017-11-14

Applicant: Novartis AG

Inventor： Stephane Ferretti ,  Nelson Guerreiro ,  Sebastien Jeay ,  Astrid Jullion ,  Christophe Meille ,  Jens Wuerthner

IPC: A61K31/497 ,  A61K31/505 ,  A61K31/506 ,  A61P7/00 ,  A61P35/02 ,  A61K45/06 ,  A61K31/404 ,  A61K31/4418 ,  A61K31/4439 ,  A61P35/00 ,  A61K31/47 ,  A61K31/401 ,  A61K31/4152 ,  A61K31/496

Abstract: 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 HDM20I and the dosing regimen di, d8 of a 4 week cycle.

公开(公告)号：US20190298719A1

公开(公告)日：2019-10-03

申请号：US16461005

申请日：2017-11-14

Applicant: Novartis AG

Inventor： Stephane Ferretti ,  Nelson Guerreiro ,  Sebastien Jeay ,  Astrid Jullion ,  Christophe Meille ,  Jens Wuerthner

IPC: A61K31/506 ,  A61P7/00 ,  A61P35/02 ,  A61K45/06

Abstract: 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 HDM20I and the dosing regimen di, d8 of a 4 week cycle.

公开(公告)号：US09371568B2

公开(公告)日：2016-06-21

申请号：US13950881

申请日：2013-07-25

Applicant: Novartis AG

Inventor： Swann Gaulis ,  Sebastien Jeay

IPC: C12Q1/68 ,  C12Q1/00 ,  G01N33/53 ,  C07D401/12 ,  G01N33/68 ,  G01N33/574 ,  A61K31/496 ,  G01N33/50

CPC classification number: C12Q1/6886 ,  A61K31/496 ,  C07D401/12 ,  C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/136 ,  C12Q2600/156 ,  C12Q2600/158 ,  C12Y603/02019 ,  G01N33/5011 ,  G01N33/574 ,  G01N33/5748 ,  G01N33/57496 ,  G01N33/6875 ,  G01N2333/4704 ,  G01N2333/4748 ,  G01N2333/9015 ,  G01N2800/52

Abstract: The invention provides methods of monitoring differential gene expression of biomarkers to determine patient sensitivity to Human Double Minute inhibitors (MDM2i), methods of determining the sensitivity of a cell to an MDM2i by measuring biomarkers and methods of screening for candidate MDM2i.

Abstract translation: 本发明提供监测生物标志物差异基因表达以确定患者对人双分钟抑制剂（MDM2i）的敏感性的方法，通过测量生物标志物和筛选候选MDM2i的方法来确定细胞对MDM2i的敏感性的方法。