Abstract: Compounds of Formula I: and salts thereof in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification, are inhibitors of Trk kinases and are useful in the treatment of diseases which can be treated with a Trk kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.
Type:
Grant
Filed:
April 8, 2019
Date of Patent:
September 1, 2020
Assignee:
Array BioPharma Inc.
Inventors:
Shelley Allen, Steven W. Andrews, Kevin Ronald Condroski, Julia Haas, Lily Huang, Yutong Jiang, Timothy Kercher, Jeongbeob Seo
Abstract: In some embodiments, provided herein is a process for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof, as disclosed herein.
Type:
Grant
Filed:
October 10, 2018
Date of Patent:
August 18, 2020
Assignees:
Loxo Oncology Inc., Array Biopharma Inc.
Inventors:
Charles Todd Eary, Stacey Spencer, Zack Crane, Katelyn Chando, Sylvie Asselin, Weidong Liu, Mike Welch, Adam Cook, Gabrielle R. Kolakowski, Andrew T. Metcalf, David A. Moreno, Tony P. Tang
Abstract: The present invention relates to processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound.
Type:
Grant
Filed:
July 16, 2019
Date of Patent:
August 4, 2020
Assignee:
Array BioPharma Inc.
Inventors:
Christoph Max Krell, Marian Misun, Daniel Andreas Niederer, Werner Heinz Pachinger, Marie-Christine Wolf, Daniel Zimmermann, Weidong Liu, Peter J. Stengel, Paul Nichols
Abstract: Compounds of Formula I: and stereoisomers and pharmaceutically acceptable salts and solvates thereof in which R1, R2, R3 and R4 have the meanings given in the specification, are inhibitors of one or more JAK kinases and are useful in the treatment of JAK kinase-associated diseases and disorders, such as autoimmune diseases, inflammatory diseases, rejection of transplanted organs, tissues and cells, as well as hematologic disorders and malignancies and their co-morbidities.
Inventors:
Shelley Allen, Mark Laurence Boys, Mark J. Chicarelli, Jay Bradford Fell, John P. Fischer, John Gaudino, Erik James Hicken, Ronald Jay Hinklin, Christopher F. Kraser, Ellen Laird, John E. Robinson, Tony P. Tang, Laurence E. Burgess, Robert Andrew Rieger, Jed Pheneger, Yoshitaka Satoh, Katerina Leftheris, Raj K. Raheja, Brydon L. Bennett
Abstract: Provided herein are methods of treating a subject having a cancer, methods of selecting a treatment for a subject having a cancer, methods of selecting a subject having a cancer for a treatment that does not include a Trk inhibitor, methods of determining the likelihood that a subject having a cancer will have a positive response to a treatment with a Trk inhibitor, methods of predicting the efficacy of a Trk inhibitor in a subject having cancer, methods of determining a subject's risk for developing a Trk inhibitor-resistant cancer, and methods of determining the presence of a Trk inhibitor-resistant cancer in a subject, based on the detection of a cell from a sample from the subject that has at least one of the point mutations in NTRK1 and/or NTRK2 and/or NTRK3.
Type:
Grant
Filed:
October 26, 2016
Date of Patent:
July 28, 2020
Assignees:
Loxo Oncology, Inc., Array BioPharma, Inc.
Inventors:
Nisha Nanda, Joshua H. Bilenker, James F. Blake, Gabrielle R. Kolakowski, Barbara J. Brandhuber, Steven W. Andrews
Abstract: Provided herein are compounds of the Formula I: or pharmaceutically acceptable salts thereof, wherein X1, X2, X3, R1, R2, R3, R4, R5, R6 and R7 are as defined herein, which are inhibitors of one or more TAM kinases and/or c-Met kinase, and are useful in the treatment and prevention of diseases which can be treated with a TAM kinase inhibitor and/or a c-Met kinase inhibitor.
Type:
Application
Filed:
January 2, 2020
Publication date:
July 9, 2020
Applicant:
Array BioPharma Inc.
Inventors:
Adam Cook, Ronald Jay Hinklin, Oren T. McNulty
Abstract: The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.
Type:
Grant
Filed:
November 14, 2018
Date of Patent:
June 23, 2020
Assignees:
Mirati Therapeutics, Inc., Array Biopharma Inc.
Inventors:
James F. Blake, Laurence E. Burgess, Mark Joseph Chicarelli, James Gail Christensen, Adam Cook, Jay Bradford Fell, John P. Fischer, Matthew Arnold Marx, Macedonio J. Mejia, Pavel Savechenkov, Guy P. A. Vigers, Christopher Ronald Smith, Martha E. Rodriguez
Abstract: Methods for inhibiting a ROS1 kinase with compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R2, R2a, R3, R3a, and Z are as defined herein. The compounds and methods provided herein are useful in the treatment of cancer (e.g., ROS1-associated cancers as defined herein).
Type:
Grant
Filed:
November 26, 2018
Date of Patent:
June 23, 2020
Assignee:
Array BioPharma Inc.
Inventors:
Steven W. Andrews, James F. Blake, Julia Haas, Gabrielle R. Kolakowski
Abstract: Compounds of Formula I: and pharmaceutically acceptable salts thereof in which R1, R2, R3, R4, R5 and R6 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of fibrosis, bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases, pain and burns in a mammal.
Type:
Grant
Filed:
September 27, 2017
Date of Patent:
June 2, 2020
Assignee:
Array BioPharma Inc.
Inventors:
Mark Laurence Boys, Robert Kirk DeLisle, Erik James Hicken, April L. Kennedy, David A. Mareska, Fredrik P. Marmsäter, Mark C. Munson, Brad Newhouse, Bryson Rast, James P. Rizzi, Martha E. Rodriguez, George T. Topalov, Qian Zhao
Abstract: Provided herein are methods of treating a subject having a cancer, methods of selecting a treatment for a subject having a cancer, methods of selecting a subject having a cancer for a treatment that does not include a Trk inhibitor, methods of determining the likelihood that a subject having a cancer will have a positive response to a treatment with a Trk inhibitor, methods of predicting the efficacy of a Trk inhibitor in a subject having cancer, methods of determining a subject's risk for developing a Trk inhibitor-resistant cancer, and methods of determining the presence of a Trk inhibitor-resistant cancer in a subject, based on the detection of a cell from a sample from the subject that has at least one of the point mutations in NTRK1 and/or NTRK2 and/or NTRK3.
Type:
Grant
Filed:
October 16, 2017
Date of Patent:
May 19, 2020
Assignees:
Loxo Oncology, Inc., Array Biopharma, Inc.
Inventors:
Nisha Nanda, Joshua H. Bilenker, James F. Blake, Gabrielle R. Kolakowski, Barbara J. Brandhuber, Steven W. Andrews
Abstract: The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.
Type:
Grant
Filed:
May 14, 2019
Date of Patent:
May 12, 2020
Assignees:
MIRATI THERAPEUTICS, INC., ARRAY BIOPHARMA INC.
Inventors:
Matthew Arnold Marx, Thomas P. Bobinski, Aaron Craig Burns, John Gaudino, Julia Haas, John Michael Ketcham, John David Lawson, Brad Newhouse, Spencer Pajk, Christopher Ronald Smith, Tony P. Tang
Abstract: Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, R2, R2a, R3, R3a, and Z are as defined herein, are inhibitors of Trk kinases and are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.
Type:
Grant
Filed:
February 20, 2018
Date of Patent:
May 12, 2020
Assignee:
Array BioPharma Inc.
Inventors:
Steven W. Andrews, Kevin Ronald Condroski, Julia Haas, Yutong Jiang, Gabrielle R. Kolakowski, Jeongbeob Seo, Hong-Woon Yang, Qian Zhao
Abstract: The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.
Type:
Grant
Filed:
October 29, 2018
Date of Patent:
April 28, 2020
Assignees:
Mirati Therapeutics, Inc., Array BioPharma Inc.
Inventors:
James F. Blake, Laurence E. Burgess, Mark Joseph Chicarelli, James Gail Christensen, Jay Bradford Fell, John P. Fischer, John J. Gaudino, Erik James Hicken, Ronald Jay Hinklin, Matthew Randolf Lee, Matthew Arnold Marx, Macedonio J. Mejia, Martha E. Rodriguez, Pavel Savechenkov, Tony P. Tang, Guy P. A. Vigers, Henry J. Zecca
Abstract: Methods for treating a disease or disorder selected from pain, cancer, inflammation, neurodegenerative disease, Typanosoma cruzi infection and osteolytic disease in a mammal, which comprise administering to said mammal a therapeutically effective amount of a compound of Formula I in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification.
Type:
Grant
Filed:
July 2, 2018
Date of Patent:
March 17, 2020
Assignee:
Array BioPharma Inc.
Inventors:
Steven W. Andrews, Julia Haas, Yutong Jiang, Gan Zhang
Abstract: Provided herein are compound of Formula I-IV and pharmaceutically acceptable salts thereof which exhibit rearranged during transfection (RET) kinase inhibition. In particular, provided herein are novel crystalline forms of 4-(6-(4-((6-methoxypyridin-3-yl)methyl)piperazin-1-yl)pyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (Formula I), 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (Formula II), 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-(6-methoxynicotinoyl)-3,6-diazabicyclo[3.1.
Type:
Grant
Filed:
October 10, 2018
Date of Patent:
March 10, 2020
Assignee:
Array Biopharma Inc.
Inventors:
Andrew T. Metcalf, David Fry, Elizabeth A. McFaddin, Gabrielle R. Kolakowski, Julia Haas, Tony P. Tang, Yutong Jiang
Abstract: The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of B-Raf.
Type:
Grant
Filed:
November 20, 2017
Date of Patent:
March 3, 2020
Assignee:
Array BioPharma Inc.
Inventors:
Shenlin Huang, Xianming Jin, Zuosheng Liu, Daniel Poon, John Tellew, Yongqin Wan, Xing Wang, Yongping Xie
Abstract: The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of B-Raf.
Type:
Grant
Filed:
November 20, 2017
Date of Patent:
February 25, 2020
Assignee:
Array BioPharma Inc.
Inventors:
Shenlin Huang, Xianming Jin, Zuosheng Liu, Daniel Poon, John Tellew, Yongqin Wan, Xing Wang, Yongping Xie
Abstract: This invention relates to solid oral pharmaceutical formulations of (S)-methyl (1-((4-(3-(5-chloro-2-fluoro-3-(methylsulfonamido)phenyl)-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)propan-2-yl)carbamate (COMPOUND A) and the use of these formulations for treating proliferative diseases, such as solid tumor diseases.
Type:
Grant
Filed:
March 14, 2018
Date of Patent:
February 18, 2020
Assignee:
Array BioPharma Inc.
Inventors:
Daya Verma, Yogita Krishnamachari, Xiaohong Shen, Hanchen Lee, Ping Li, Rajinder Singh, LayChoo Tan
Abstract: Reversing resistance to a B-Raf inhibitor for the treatment of a proliferative disease by obtaining a tumor sample from the patient and testing it for genetic alterations in a panel of genes comprising BRAF, CRAF, CCND1, CDK4, HER2, IGF-1R, cMET, FGFR1, FGFR2, FGFR3 EGFR, MAP2K1, MAP2K2, NRAS, KRAS HRAS, PTEN, PIK3CA, and P16 and administering a drug combination therapy comprising the B-Raf inhibitor and a second inhibitor which overcomes resistance to the B-Raf inhibitor, which second inhibitor is selected based on genetic alterations discovered in the tumor sample.
Type:
Grant
Filed:
January 19, 2018
Date of Patent:
February 4, 2020
Assignee:
Array BioPharma Inc.
Inventors:
Giordano Caponigro, Darrin Stuart, Laure De Parseval
Abstract: Compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof are provided, which are useful for the treatment of hyperproliferative, pain and inflammatory diseases. Methods of using compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
Type:
Grant
Filed:
June 16, 2017
Date of Patent:
December 31, 2019
Assignees:
Array BioPharma Inc., Genentech, Inc.
Inventors:
James F. Blake, Mark Joseph Chicarelli, Rustam Ferdinand Garrey, John Gaudino, Jonas Grina, David A. Moreno, Peter J. Mohr, Li Ren, Jacob Schwarz, Huifen Chen, Kirk Robarge, Aihe Zhou