Abstract: Biomarkers for the treatment of pathological conditions associated with the PI3K pathway, such as cancer, and methods of using inhibitors of upstream components of the PI3K pathway, such as PI3K-? inhibitors or AKT inhibitors, are described. In particular, there are described biomarkers for patient selection in the treatment of cancer, as well as methods of therapeutic treatment, diagnostic kits and methods of detection, wherein cancers that possess a mutation in an upstream component of the PI3K pathway (such as the PIK3CA gene and/or the AKT gene), and a wild-type MAP3K1 gene and MAP2K4 gene, are more likely to respond favourably to treatment with inhibitors of upstream components of the PI3K pathway.
Type:
Grant
Filed:
September 16, 2016
Date of Patent:
June 27, 2023
Assignee:
ASTRAZENECA AB
Inventors:
Alvaro Avivar Valderas, Francisco Humberto Cruzalegui, Kevin Hudson, Robert Kenneth McEwen
Abstract: The present disclosure relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.
Type:
Grant
Filed:
September 15, 2022
Date of Patent:
June 20, 2023
Assignee:
AstraZeneca AB
Inventors:
Hans Roland Lönn, Stephen Connolly, Steven Swallow, Staffan Po Karlsson, Carl-Johan Aurell, John Fritiof Pontén, Kevin James Doyle, Amanda Jane Van De Poël, Graham Peter Jones, David Wyn Watson, Jaqueline Anne Macritchie, Nicholas John Palmer
Abstract: The present disclosure relates to certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.
Type:
Grant
Filed:
September 10, 2022
Date of Patent:
June 13, 2023
Assignee:
AstraZeneca AB
Inventors:
Hans Roland Lönn, Stephen Connolly, Steven Swallow, Staffan Po Karlsson, Carl-Johan Aurell, John Fritiof Pontén, Kevin James Doyle, Amanda Jane Van De Poël, Graham Peter Jones, David Wyn Watson, Jaqueline Anne Macritchie, Nicholas John Palmer
Abstract: The present disclosure relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.
Type:
Grant
Filed:
September 16, 2022
Date of Patent:
June 13, 2023
Assignee:
AstraZeneca AB
Inventors:
Hans Roland Lönn, Stephen Connolly, Steven Swallow, Staffan Po Karlsson, Carl-Johan Aurell, John Fritiof Pontén, Kevin James Doyle, Amanda Jane Van De Poël, Graham Peter Jones, David Wyn Watson, Jaqueline Anne Macritchie, Nicholas John Palmer
Abstract: The specification generally relates to compounds of Formula (I), and pharmaceutically acceptable salts thereof, where A, U, V, W, X, Y, Z, R1, R2, R3, R4 and R5 have the meanings defined herein. Such compounds are modulators of RXFP1 and may be useful as therapeutic agents. The specification also relates to the use of such compounds to treat or prevent diseases and conditions including heart failure, heart failure with preserved ejection fraction, heart failure with mid-range ejection fraction, heart failure with reduced ejection fraction, chronic kidney disease and acute kidney injury. The specification further relates to compositions comprising such compounds, intermediates useful in processes for preparing such compounds, and processes for preparing such compounds using such intermediates.
Abstract: The present disclosure relates to certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.
Type:
Grant
Filed:
February 8, 2021
Date of Patent:
June 6, 2023
Assignee:
AstraZeneca AB
Inventors:
Hans Roland Lönn, Stephen Connolly, Steven Swallow, Staffan Po Karlsson, Carl-Johan Aurell, John Fritiof Pontén, Kevin James Doyle, Amanda Jane Van De Poël, Graham Peter Jones, David Wyn Watson, Jaqueline Anne Macritchie, Nicholas John Palmer
Abstract: The present disclosure relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.
Type:
Grant
Filed:
September 10, 2022
Date of Patent:
May 23, 2023
Assignee:
AstraZeneca AB
Inventors:
Hans Roland Lönn, Stephen Connolly, Steven Swallow, Staffan Po Karlsson, Carl-Johan Aurell, John Fritiof Pontén, Kevin James Doyle, Amanda Jane Van De Poël, Graham Peter Jones, David Wyn Watson, Jaqueline Anne Macritchie, Nicholas John Palmer
Abstract: The present disclosure relates to certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.
Type:
Grant
Filed:
September 10, 2022
Date of Patent:
May 23, 2023
Assignee:
AstraZeneca AB
Inventors:
Hans Roland Lönn, Stephen Connolly, Steven Swallow, Staffan P O Karlsson, Carl-Johan Aurell, John Fritiof Pontén, Kevin James Doyle, Amanda Jane Van De Poël, Graham Peter Jones, David Wyn Watson, Jaqueline Anne MacRitchie, Nicholas John Palmer
Abstract: The present disclosure relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.
Type:
Grant
Filed:
September 9, 2022
Date of Patent:
May 23, 2023
Assignee:
AstraZeneca AB
Inventors:
Hans Roland Lönn, Stephen Connolly, Steven Swallow, Staffan Po Karlsson, Carl-Johan Aurell, John Fritiof Pontén, Kevin James Doyle, Amanda Jane Van De Poël, Graham Peter Jones, David Wyn Watson, Jaqueline Anne Macritchie, Nicholas John Palmer
Abstract: The present disclosure relates to certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.
Type:
Grant
Filed:
September 10, 2022
Date of Patent:
May 23, 2023
Assignee:
AstraZeneca AB
Inventors:
Hans Roland Lönn, Stephen Connolly, Steven Swallow, Staffan Po Karlsson, Carl-Johan Aurell, John Fritiof Pontén, Kevin James Doyle, Amanda Jane Van De Poël, Graham Peter Jones, David Wyn Watson, Jaqueline Anne Macritchie, Nicholas John Palmer
Abstract: A method is provided for lowering blood pressure in a subject in need thereof by administering an angiotensin II receptor blocker pharmaceutical composition to a subject qualified for over-the-counter access to the angiotensin II receptor blocker pharmaceutical composition. In some embodiments, the angiotensin II receptor blocker pharmaceutical composition includes azilsartan medoxomil, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, or valsartan. In some embodiments, the angiotensin II receptor blocker pharmaceutical composition comprises an active ingredient that is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2?-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate or a pharmaceutically acceptable salt thereof.
Type:
Grant
Filed:
June 29, 2021
Date of Patent:
May 16, 2023
Assignee:
ASTRAZENECA UK LIMITED
Inventors:
Richard L. Skelly, Judy Firor, James Blasetto
Abstract: A method that provides a graphical indication of whether a patient will have cancer recurrence uses univariate and bivariate prognostic features that were generated as part of a minimal spanning tree (MST). The method determines the values of first and second features. A first value is measured by detecting objects in an image of tissue from the cancer patient stained with a protein-specific IHC biomarker. A second value is measured using objects marked with an mRNA-specific probe biomarker detected in the tissue. The first feature is the univariate prognostic feature for cancer recurrence in a cohort of cancer patients. A combination of the first and second features is the bivariate prognostic feature for cancer recurrence in the cohort. The first and second features are elements of the MST. Nodes of the MST represent the univariate features, edges represent the bivariate features, and edge weights represent prognostic significance of bivariate features.
Abstract: Described herein are triazalone compounds of Formula (I): and pharmaceutically acceptable salts thereof. Methods of making and using compounds of Formula (I) are also described. Compounds of Formula (I) and pharmaceutically acceptable salts thereof can be useful as adenosine receptor antagonists, for example in the treatment of diseases or conditions mediated by the adenosine receptor, such as cancer, movement disorders, or attention disorders.
Type:
Application
Filed:
March 25, 2021
Publication date:
May 11, 2023
Applicant:
ASTRAZENECA AB
Inventors:
Giles Albert Brown, Miles Stuart Congreve, Stephen Philippe Andrews, Jonathan Stephen Mason, Francesca Deflorian, Nigel Alan Swain
Abstract: Combinations of an apyrase and an annexin, including fusion proteins thereof, are synergistic antithrombotics that do not induce unwanted bleeding
Abstract: The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts thereof, where R1, R2, R3, R4 and R5 have any of the meanings defined herein. The specification also relates to the use of compounds of Formula (I) and salts thereof to treat or prevent ATM mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising substituted imidazo[4,5-c]quinolin-2-one compounds and pharmaceutically acceptable salts thereof; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; and intermediates useful in such manufacture.
Type:
Grant
Filed:
December 1, 2020
Date of Patent:
March 28, 2023
Assignee:
ASTRAZENECA AB
Inventors:
Bernard Christophe Barlaam, Kurt Gordon Pike, Andrew John Eatherton, Thomas Anthony Hunt
Abstract: The present disclosure relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.
Type:
Application
Filed:
September 15, 2022
Publication date:
March 2, 2023
Applicant:
AstraZeneca AB
Inventors:
Hans Roland LÖNN, Stephen CONNOLLY, Steven SWALLOW, Staffan PO KARLSSON, Carl-Johan AURELL, John Fritiof PONTÉN, Kevin James DOYLE, Amanda Jane VAN DE POËL, Graham Peter JONES, David Wyn WATSON, Jaqueline Anne MACRITCHIE, Nicholas John PALMER
Abstract: A convolutional neural network predicts which regions of a tissue slice would be stained by a first stain by training a model to identify those regions based only on tissue stained by a second stain. Thereafter the first stain need not be used to mark cancerous regions on other tissue slices that are stained with the second stain. The training slice is stained with a first immunohistochemical stain and a second counterstain. A target region of an image of the training slice is identified using image analysis based on the first stain. A set of parameters for associated mathematical operations are optimized to train the model to classify pixels of the image as belonging to the target region based on the second stain but not on the first stain. The trained parameters are stored in a database and applied to other images of tissue not stained with the first stain.
Abstract: The invention concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1, R2 and n have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use as anti-proliferative and/or cell-killing agents.
Type:
Application
Filed:
June 29, 2022
Publication date:
February 2, 2023
Applicant:
AstraZeneca AB
Inventors:
Robert Hugh Bradbury, Alfred Arthur Rabow, Michael James Waring, James Francis McCabe, Steven Christopher Glossop, Arshed Mahmood, Zoe Ann Cotter
Abstract: Disclosed are methods of treating cancer comprising administering to a subject in need thereof an effective amount of (3R)-4-[2-[4-[1-(3-Methoxy-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-4-piperidyl]phenoxy]ethyl]-1,3-dimethyl-piperazin-2-one or a pharmaceutically acceptable salt thereof and an effective amount of venetoclax or a pharmaceutically acceptable salt thereof.
Type:
Application
Filed:
October 12, 2020
Publication date:
January 26, 2023
Applicant:
AstraZeneca AB
Inventors:
Maureen Hattersley, Courtney Andersen, Huawei Raymond Chen