公开(公告)号：US20210147354A1

公开(公告)日：2021-05-20

申请号：US16891898

申请日：2020-06-03

Applicant: Novartis AG

Inventor： Hubert BORELL ,  Anne GARDIN ,  Yi JIN ,  Eric LEGANGNEUX ,  Mike UFER

IPC: C07D205/04 ,  C12Q1/6883 ,  G01N33/50 ,  G01N33/569

Abstract: The invention provides a method of assessing the appropriate therapeutic dose of 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid to administer to a patient in need thereof, comprising the steps of: (i) testing whether or not the patient has the poor metabolizer genotype; and (ii) if the patient does not have the poor metaboliser genotype, administering 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof, to the patient at the standard therapeutic dose; and (iii) if the patient does have the poor metaboliser genotype, either (a) administering 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof, to the patient at a therapeutic dose below that of the standard therapeutic dose; or (b) not administering 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof, to the patient.

公开(公告)号：US20210069150A1

公开(公告)日：2021-03-11

申请号：US16898071

申请日：2020-06-10

Applicant: NOVARTIS AG

Inventor： Bruno GALLI ,  Jean-Marie GLANTZMANN ,  Arnaud GRANDEURY ,  Klaus-Peter MOLL ,  Martin MUELLER- ZSIGMONDY ,  Karsten PUTZBACH ,  Dirk SPICKERMANN ,  Hubert THOMA ,  Mike UFER

IPC: A61K31/404 ,  A61K9/28 ,  A61K9/20 ,  A61K31/4045 ,  A61J3/02 ,  A61J3/10 ,  A61K9/16 ,  A61K9/50 ,  A61K47/38

Abstract: Drug products in the form of modified release formulations comprising the drug substance (−)-(3aR,4S,7aR)-4-Hydroxy-4m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester (AFQ056), as well as processes for making such drug products are provided. The drug products are useful in treating patients with Parkinson's disease and exhibiting L-dopa induced dyskinesia.

公开(公告)号：US20240270688A1

公开(公告)日：2024-08-15

申请号：US18630271

申请日：2024-04-09

Applicant: Novartis AG

Inventor： Hubert BORELL ,  Anne GARDIN ,  Yi JIN ,  Eric LEGANGNEUX ,  Mike UFER

IPC: C07D205/04 ,  C12Q1/6883 ,  G01N33/50 ,  G01N33/569

CPC classification number: C07D205/04 ,  C12Q1/6883 ,  G01N33/5094 ,  G01N33/56972 ,  C12Q2600/106 ,  C12Q2600/156 ,  G01N2800/52

Abstract: The invention provides a method of assessing the appropriate therapeutic dose of 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid to administer to a patient in need thereof, comprising the steps of:



(i) testing whether or not the patient has the poor metabolizer genotype; and
(ii) if the patient does not have the poor metaboliser genotype, administering 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof, to the patient at the standard therapeutic dose; and
(iii) if the patient does have the poor metaboliser genotype, either

(a) administering 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof, to the patient at a therapeutic dose below that of the standard therapeutic dose; or
(b) not administering 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof, to the patient.

公开(公告)号：US20190135744A1

公开(公告)日：2019-05-09

申请号：US16136630

申请日：2018-09-20

Applicant: Novartis AG

Inventor： Hubert BORELL ,  Anne GARDIN ,  Yi JIN ,  Eric LEGANGNEUX ,  Mike UFER

IPC: C07D205/04 ,  G01N33/50 ,  G01N33/569 ,  C12Q1/6883

Abstract: The invention provides a method of assessing the appropriate therapeutic dose of 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid to administer to a patient in need thereof, comprising the steps of: (i) testing whether or not the patient has the poor metabolizer genotype; and (ii) if the patient does not have the poor metaboliser genotype, administering 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof, to the patient at the standard therapeutic dose; and (iii) if the patient does have the poor metaboliser genotype, either (a) administering 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof, to the patient at a therapeutic dose below that of the standard therapeutic dose; or (b) not administering 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof, to the patient.

公开(公告)号：US20170320820A1

公开(公告)日：2017-11-09

申请号：US15605277

申请日：2017-05-25

Applicant: Novartis AG

Inventor： Hubert Borell ,  Anne GARDIN ,  Yi JIN ,  Eric LEGANGNEUX ,  Mike UFER

IPC: C07D205/04 ,  C12Q1/68 ,  G01N33/569 ,  G01N33/50

CPC classification number: C07D205/04 ,  C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/156 ,  G01N33/5094 ,  G01N33/56972 ,  G01N2800/52

Abstract: The invention provides a method of assessing the appropriate therapeutic dose of 1-{4-[1-(4-cyclohexyl-3-trifluoromethyi-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid to administer to a patient in need thereof, comprising the steps of: (i) testing whether or not the patient has the poor metabolizer genotype; and (ii) if the patient does not have the poor metaboliser genotype, administering 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof, to the patient at the standard therapeutic dose; and (iii) if the patient does have the poor metaboliser genotype, either (a) administering 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof, to the patient at a therapeutic dose below that of the standard therapeutic dose; or (b) not administering 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid, or a pharmaceutically acceptable salt thereof, to the patient.

公开(公告)号：US20230355582A1

公开(公告)日：2023-11-09

申请号：US18355618

申请日：2023-07-20

Applicant: NOVARTIS AG

Inventor： Bruno GALLI ,  Jean-Marie GLANTZMANN ,  Arnaud GRANDEURY ,  Klaus-Peter MOLL ,  Martin MUELLER-ZSIGMONDY ,  Karsten PUTZBACH ,  Dirk SPICKERMANN ,  Hubert THOMA ,  Mike UFER

IPC: A61K31/404 ,  A61K9/28 ,  A61K9/20 ,  A61K31/4045 ,  A61J3/02 ,  A61J3/10 ,  A61K9/16 ,  A61K9/50 ,  A61K47/38

CPC classification number: A61K31/404 ,  A61K9/28 ,  A61K9/2004 ,  A61K31/4045 ,  A61J3/02 ,  A61J3/10 ,  A61K9/1652 ,  A61K9/1682 ,  A61K9/2072 ,  A61K9/50 ,  A61K9/5089 ,  A61K47/38

Abstract: Drug products in the form of modified release formulations comprising the drug substance (-)-(3aR,45,7aR)-4-Hydroxy-4m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester (AFQ056), as well as processes for making such drug products are provided. The drug products are useful in treating patients with Parkinson's disease and exhibiting L-dopa induced dyskinesia.