公开(公告)号：US10724102B2

公开(公告)日：2020-07-28

申请号：US15335378

申请日：2016-10-26

Applicant: Loxo Oncology, Inc. ,  Array BioPharma, Inc.

Inventor： Nisha Nanda ,  Joshua H. Bilenker ,  James F. Blake ,  Gabrielle R. Kolakowski ,  Barbara J. Brandhuber ,  Steven W. Andrews

IPC: C12Q1/6886 ,  A61K31/5025 ,  A61K31/519 ,  G01N33/574

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.

公开(公告)号：US10688100B2

公开(公告)日：2020-06-23

申请号：US16199875

申请日：2018-11-26

Applicant: Array BioPharma Inc.

Inventor： Steven W. Andrews ,  James F. Blake ,  Julia Haas ,  Gabrielle R. Kolakowski

IPC: A61K31/529 ,  A61K31/519 ,  A61K45/06 ,  G01N33/574 ,  A61P35/00 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/675

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).

公开(公告)号：US20200171002A1

公开(公告)日：2020-06-04

申请号：US16512823

申请日：2019-07-16

Applicant: Array BioPharma Inc.

Inventor： Christoph Max Krell ,  Marian Misun ,  Daniel Andreas Niederer ,  Werner Heinz Pachinger ,  Marie-Christine Wolf ,  Daniel Zimmermann ,  Weidong Liu ,  Peter J. Stengel ,  Paul Nichols

IPC: A61K31/4184 ,  A61K45/06 ,  A61K9/20 ,  A61K9/00 ,  C07D235/08 ,  A61K47/12 ,  A61K47/02 ,  C30B29/54 ,  C30B7/08 ,  C07D235/06 ,  A61K47/38 ,  A61K47/26

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.

公开(公告)号：US10584124B2

公开(公告)日：2020-03-10

申请号：US16156880

申请日：2018-10-10

Applicant: Array BioPharma Inc.

Inventor： Andrew T. Metcalf ,  David Fry ,  Elizabeth A. McFaddin ,  Gabrielle R. Kolakowski ,  Julia Haas ,  Tony P. Tang ,  Yutong Jiang

IPC: C07D471/08 ,  A61P35/00 ,  A61K9/00 ,  C07D471/04

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[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (Formula III), 6-(2-hydroxy-2-methylpropoxy)-4-(6-(4-hydroxy-4-(pyridin-2-ylmethyl)piperidin-1-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (Formula IV), and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the compounds, processes for making the compounds, and the use of the compounds in therapy. More particularly, the application relates to novel crystalline forms of Formula I-IV and pharmaceutically acceptable salts thereof useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including RET-associated diseases and disorders.

公开(公告)号：US10519126B2

公开(公告)日：2019-12-31

申请号：US15625297

申请日：2017-06-16

Applicant: Array BioPharma Inc. ,  Genentech, Inc.

Inventor： 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

IPC: C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  A61K31/506 ,  A61K45/06 ,  C07F9/6558 ,  C07D403/04 ,  A61K31/513 ,  A61K31/53 ,  A61K31/444

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.

公开(公告)号：US20190270743A1

公开(公告)日：2019-09-05

申请号：US16412091

申请日：2019-05-14

Applicant: Mirati Therapeutics, Inc. ,  Array BioPharma Inc.

Inventor： 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

IPC: C07D471/04 ,  C07D519/00 ,  A61P35/00

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.

公开(公告)号：US20190255051A1

公开(公告)日：2019-08-22

申请号：US16402068

申请日：2019-05-02

Applicant: Array BioPharma Inc.

Inventor： Patrice A. Lee ,  Shannon L. Winski ,  Kevin Koch

IPC: A61K31/517 ,  A61P35/00 ,  A61P35/04 ,  A61K45/06 ,  A61K31/337 ,  A61K31/7068

Abstract: Compounds for the treatment of brain cancer are provided herein. Pharmaceutical compositions comprised of those compounds for the treatment of brain cancer are also provided herein.

公开(公告)号：US10370727B2

公开(公告)日：2019-08-06

申请号：US15785174

申请日：2017-10-16

Applicant: Loxo Oncology, Inc. ,  Array BioPharma, Inc.

Inventor： Nisha Nanda ,  Joshua H. Bilenker ,  James F. Blake ,  Gabrielle R. Kolakowski ,  Barbara J. Brandhuber ,  Steven W. Andrews

IPC: C12Q1/6886 ,  A61K31/5025 ,  A61K31/519 ,  G01N33/574

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 the point mutations in NTRK1 and/or NTRK2 and/or NTRK3.

公开(公告)号：US20190211017A1

公开(公告)日：2019-07-11

申请号：US16044653

申请日：2018-07-25

Applicant: Array BioPharma Inc.

Inventor： Julia Haas ,  Steven W. Andrews ,  Yutong Jiang ,  Gan Zhang

IPC: C07D487/04 ,  A61K31/519 ,  A61P29/00 ,  A61K31/5377 ,  C07D471/04 ,  A61K45/06 ,  A61K9/00 ,  C07D519/00

Abstract: Compounds useful in the synthesis of compounds for treating pain, cancer, inflammation, neurodegenerative disease or Typanosoma cruzi infection in a mammal.

公开(公告)号：US20190151322A1

公开(公告)日：2019-05-23

申请号：US16199818

申请日：2018-11-26

Applicant: Array BioPharma Inc.

Inventor： Steven W. Andrews ,  James F. Blake ,  Julia Haas ,  Gabrielle R. Kolakowski

IPC: A61K31/529 ,  A61K31/496 ,  A61K31/675 ,  A61K31/4545 ,  A61P35/00

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).