Abstract: The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.
Type:
Grant
Filed:
December 5, 2019
Date of Patent:
April 5, 2022
Assignee:
Vertex Pharmaceuticals Incorporated
Inventors:
Patricia Hurter, William Rowe, Christopher R. Young, Adriana Costache, Patrick R. Connelly, Mariusz Krawiec, Yuchuan Gong, Yushi Feng, Martin Trudeau
Abstract: Disclosed herein are compositions and methods related to differentiation of stem cells into pancreatic endocrine cells. In some aspects, the methods provided herein relate to generation of pancreatic ? cell, ? cell, ? cells, and EC cells in vitro. In some aspects, the disclosure provides pharmaceutical compositions including the cells generated according to the methods disclosed herein, as well as methods of treatment making use thereof.
Abstract: Materials and methods for treating a patient with hemoglobinopathy, both ex vivo and in vivo and materials and methods for deleting at least a portion of a human beta globin locus on chromosome 11 in a human cell by genome editing and thereby increasing the production of fetal hemoglobin (HbF).
Abstract: Compound I of the formula (formula) A pharmaceutically acceptable salt of Compound I. Pharmaceutical compositions containing at least Compound I and methods of treating cystic fibrosis comprising administering at least Compound I. Pharmaceutical compositions containing a pharmaceutically acceptable salt of at least Compound I and methods of treating cystic fibrosis comprising administering a pharmaceutically acceptable salt of at least Compound I.
Type:
Grant
Filed:
June 8, 2018
Date of Patent:
February 22, 2022
Assignee:
Vertex Pharmaceuticals Incorporated
Inventors:
Weichao George Chen, Eric L. Haseltine, Samuel Moskowitz, Sarah Robertson, David Waltz
Abstract: A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a diluent, a disintegrant, a surfactant, a binder, a glidant and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Methods for treating a patient in need thereof include administering an oral pharmaceutical formulation of Compound 1 to the patient.
Type:
Application
Filed:
May 28, 2021
Publication date:
February 3, 2022
Applicant:
Vertex Pharmaceuticals Incorporated
Inventors:
Marinus Jacobus VERWIJS, Rossitza Gueorguieva ALARGOVA, Ritu Rohit KAUSHIK, Irina Nikolaevna KADIYALA, Christopher YOUNG
Abstract: Described herein are highly efficient gene-editing systems comprising a nuclease, a guide RNA, and/or a donor template and uses thereof for editing a cystic fibrosis transmembrane regulator (CFTR) gene either in vitro or in vivo.
Abstract: The invention relates to compounds of formula I or pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels: (I). The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders, including pain.
Type:
Grant
Filed:
July 18, 2014
Date of Patent:
December 21, 2021
Assignee:
VERTEX PHARMACEUTICALS INCORPORATED
Inventors:
Sara Sabina Hadida-Ruah, Corey Anderson, Andreas P. Termin, Brian Richard Bear, Vijayalaksmi Arumugam, Paul Krenitsky, James Philip Johnson
Abstract: Compounds of Formula I: pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed.
Type:
Grant
Filed:
December 4, 2019
Date of Patent:
November 30, 2021
Assignee:
Vertex Pharmaceuticals Incorporated
Inventors:
Timothy Alcacio, Minson Baek, Peter Grootenhuis, Sara Sabina Hadida Ruah, Robert M. Hughes, Ali Keshavarz-Shokri, Rachel McAuley-Aoki, Jason McCartney, Mark Thomas Miller, Fredrick Van Goor, Beili Zhang, Corey Anderson, Thomas Cleveland, Bryan A. Frieman, Haripada Khatuya, Pramod Virupax Joshi, Paul John Krenitsky, Vito Melillo, Fabrice Jean Denis Pierre, Andreas P. Termin, Johnny Uy, Jinglan Zhou, Alexander Russell Abela, Brett Bradley Busch, Prasuna Paraselli
Abstract: The disclosure provides to CRISPR/Cas systems and compositions which target the dystrophin gene. Also provided are methods for using the CRISPR/Cas systems, vectors and compositions in methods for genome engineering to correct a mutant dystrophin gene, and for treating Duchenne muscular dystrophy.
Type:
Application
Filed:
November 9, 2018
Publication date:
November 25, 2021
Applicant:
Vertex Pharmaceuticals Incorporated
Inventors:
Seshidhar Reddy Police, Song Chou, Thomas James Cradick, Robert Ng, Yanfei Yang
Abstract: A pharmaceutical composition comprising Compound I: Methods of treating cystic fibrosis comprising administering one or more of such pharmaceutical compositions to a patient.
Type:
Grant
Filed:
February 4, 2019
Date of Patent:
November 23, 2021
Assignee:
Vertex Pharmaceuticals Incorporated
Inventors:
Cathy Chu, Varsha Dhamankar, Eleni Dokou, Eric L. Haseltine, Samuel Moskowitz, Sarah Robertson, David Waltz, Weichao George Chen
Abstract: The present invention relates to methods of treating cancer in a patient by administering a compound useful as an inhibitor of ATR protein kinase in combination with a compound useful as an inhibitor of Chk1 protein kinase. The aforementioned combination displays a surprising synergistic effect in treating cancer despite the targeted protein kinases being within the same biological pathway. Moreover, the present invention also relates to methods of treating cancer by administering a compound useful as an inhibitor of ATR protein kinase; administering a compound useful as an inhibitor of Chk1 protein kinase; as well as administering a DNA damaging agent to a patient. The compounds utilized in this invention are represented by formula I and formula II: wherein the variables are as defined herein.
Abstract: The present invention relates to solid forms of (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide (Compound 1) in substantially crystalline form (Form A) or amorphous form, pharmaceutical compositions thereof, and methods of treatment therewith.
Type:
Application
Filed:
November 25, 2020
Publication date:
November 4, 2021
Applicant:
Vertex Pharmaceuticals Incorporated
Inventors:
Ali Keshavarz-Shokri, Beili Zhang, Tim Edward Alcacio, Elaine Chungmin Lee, Yuegang Zhang, Mariusz Krawiec
Abstract: Crystalline Forms of Compound I: and pharmaceutically acceptable salts thereof are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed.
Type:
Grant
Filed:
March 25, 2020
Date of Patent:
October 26, 2021
Assignee:
Vertex Pharmaceuticals Incorporated
Inventors:
Varsha Dhamankar, Kirk Raymond Dinehart, Eleni Dokou, Lori Ann Ferris, Nishanth Gopinathan, Katie McCarty, Catherine Metzler, Beili Zhang, Samuel Moskowitz, Sarah Robertson, David Waltz, Eric L. Haseltine, Weichao George Chen
Abstract: The present invention relates to pharmaceutical compositions containing a solid dispersion of N-[2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide including formulations of the solid dispersions into powders, granules and mini-tablets, methods for manufacturing and processing the powders, granules and mini-tablets, and methods for treating cystic fibrosis employing the pharmaceutical composition.
Type:
Grant
Filed:
March 12, 2019
Date of Patent:
October 19, 2021
Assignee:
Vertex Pharmaceuticals Incorporated
Inventors:
Eleni Dokou, Shahla Jamzad, John P. Caesar, Jr., Majed Fawaz, Laura Das, Chong-Hui Gu, Patricia Nell Hurter, Meghna Jai Israni, Meghan M. Johnston, Dragutin Knezic, Andrew G. Kuzmission, Hongren Wang
Abstract: The present application provides materials and methods for treating hemoglobinopathies. More specifically, the application provides methods for producing progenitor cells that are genetically modified via genome editing to increase the production of fetal hemoglobin (HbF), as well as modified progenitor cells (including, for example, CD34+ human hematopoietic stem cells) producing increased levels of HbF, and methods of using such cells for treating hemoglobinopathies such as sickle cell anemia and ?-thalassemia.
Abstract: The present invention features compositions comprising a plurality of therapeutic agents wherein the presence of one therapeutic agent enhances the properties of at least one other therapeutic agent. In one embodiment, the therapeutic agents are cystic fibrosis transmembrane conductance regulators (CFTR) such as a CFTR corrector or CFTR potentiator for the treatment of CFTR mediated diseases such as cystic fibrosis. Methods and kits thereof are also disclosed.
Type:
Application
Filed:
March 17, 2021
Publication date:
October 7, 2021
Applicant:
Vertex Pharmaceuticals Incorporated
Inventors:
Brian Dean Phenix, Laurent Jean-Claude Bagnol, Geoffrey Glen Brodeur, Sachin Chandran, Eleni Dokou, Lori Ann Ferris, Dragutin Knezic, Katie Lynn McCarty, Ales Medek, Sara A. Waggener
Abstract: Methods of editing a target genomic region(s), methods of repairing of a DNA break via a HDR pathway, methods of inhibiting or suppressing repair of a DNA break via a NHEJ pathway, and methods of modifying expression of a gene(s) or protein(s) comprise administering to one or more cells that include one or more target genomic regions, a genome editing system and a DNA protein-kinase (DNAPK) inhibitor disclosed herein. Kits and compositions for editing a target gene comprise a genome editing system and a DNAPK inhibitor disclosed herein.
Type:
Grant
Filed:
July 13, 2017
Date of Patent:
September 21, 2021
Assignee:
Vertex Pharmaceuticals Incorporated
Inventors:
Norzehan Abdul-Manan, David A. Newsome, Jacque Zwahlen
Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: or a pharmaceutically acceptable salt, wherein the variables are as devined herein. Moreover, The compounds of this invention have formula I-A: or a pharmaceutically acceptable salt, wherein the variables are as defined herein.
Type:
Grant
Filed:
August 6, 2019
Date of Patent:
September 14, 2021
Assignee:
VERTEX PHARMACEUTICALS INCORPORATED
Inventors:
Nadia Ahmad, Dean Boyall, Jean-Damien Charrier, Chris Davis, Rebecca Davis, Steven Durrant, Gorka Etxebarria I Jardi, Damien Fraysse, Juan-Miguel Jimenez, David Kay, Ronald Knegtel, Donald Middleton, Michael O'Donnell, Maninder Panesar, Francoise Pierard, Joanne Pinder, David Shaw, Pierre-Henri Storck, John Studley, Heather Twin
Abstract: Described herein are methods of treating a proliferative disease in a subject by administering a DNA-damaging agent and between about 8 and about 48 hours later administering to the subject a DNA-PK inhibitor. Exemplary DNA-PK inhibitors are represented by Formula (B-I): and by pharmaceutically acceptable salts thereof, wherein R1, Q, Ring A, and Ring B are as defined herein.
Type:
Grant
Filed:
September 27, 2017
Date of Patent:
September 7, 2021
Assignee:
VERTEX PHARMACEUTICALS INCORPORATED
Inventors:
Diane M. Boucher, Shawn M. Hillier, Wanjung Tsai, Brian Hare, William Markland, David A. Newsome, Marina S. Penney