Patents by Inventor Nathanael S. Gray

Nathanael S. Gray has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Publication number: 20230002397
    Abstract: Disclosed are compounds and pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers thereof that may cause degradation of various proteins e.g., IKZF2 (Helios). Also disclosed are pharmaceutical compositions containing same, and methods of making and using the compounds to treat diseases and disorders associated with Helios and which may benefit from Helios degradation.
    Type: Application
    Filed: October 29, 2020
    Publication date: January 5, 2023
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, Hu Liu, Tinghu Zhang, Lyn Howard Jones, Jianwei Che
  • Patent number: 11542251
    Abstract: The present invention relates to heterobifunctional compounds (degraders), compositions and methods for treating diseases or conditions mediated by Interleukin Receptor-Associated Kinases (IRAKs).
    Type: Grant
    Filed: February 13, 2019
    Date of Patent: January 3, 2023
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, John Hatcher
  • Publication number: 20220411404
    Abstract: The disclosure relates to compounds that act as allosteric inhibitors of epidermal growth factor receptor (EGFR); pharmaceutical compositions comprising the compounds; and methods of treating or preventing kinase-mediated disorders, including cancer and other proliferation diseases.
    Type: Application
    Filed: May 10, 2022
    Publication date: December 29, 2022
    Inventors: David A. Scott, David Heppner, Thomas Gero, Courtney A. Cullis, Ciric To, Shih-Chung Huang, Yongbo Hu, Steve Stroud, Tyler Beyett, Michael Eck, Nathanael S. Gray
  • Publication number: 20220409731
    Abstract: Disclosed are bispecific compounds (degraders) that target ALK for degradation.
    Type: Application
    Filed: September 26, 2019
    Publication date: December 29, 2022
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, John M. Hatcher, Chelsea E. Powell, Pasi A. Janne
  • Publication number: 20220402869
    Abstract: Provided herein are compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, compositions, and mixtures thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing diseases (e.g., proliferative diseases (e.g., cancers, such as carcinoma, sarcoma, lung cancer, thyroid cancer, skin cancer, ovarian cancer, colorectal cancer, prostate cancer, pancreatic cancer, esophageal cancer, liver cancer, breast cancer)) in a subject. Provided are methods of inhibiting a TEAD transcription factors (e.g., TEAD1, TEAD2, TEAD3, TEAD4) in a subject.
    Type: Application
    Filed: October 15, 2019
    Publication date: December 22, 2022
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Yao Liu, Mengyang Fan, Yang Gao
  • Publication number: 20220395509
    Abstract: Provided herein are methods of treating diseases (e.g., proliferative disease (e.g., cancer (e.g., breast cancer, colon cancer, testicular cancer, CNS cancer, stomach cancer, lymphoma (e.g., B-cell lymphoma (e.g., lymphoplasmacytic lymphoma (e.g., IgM secreting lymphoplasmacytic lymphoma (i.e., Waldenstrom's Macroglobulinemia), non-IgM secreting lymphoplasmacytic lymphoma)), diffuse large B-cell lymphoma (e.g., activated B-cell-like (ABC)-DLBCL, germinal center B-cell-like (GBC)-DLBCL), follicular lymphoma, marginal zone B-cell lymphoma, small lymphocytic lymphoma, mantle cell lymphoma), and leukemia (e.g., chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia, myelogenous leukemia (e.g., chronic myelogenous leukemia, acute myelogenous leukemia))))) comprising administering to the subject in need thereof a therapeutically effective amount of Compound (I). Further provided are methods for treating disease resistant to treatment with BTK inhibitors (e.g., ibmtinib).
    Type: Application
    Filed: October 7, 2020
    Publication date: December 15, 2022
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Steven P. Treon, Guang Yang, Jinhua Wang, Li Tan, Nathanael S. Gray, Sara Jean Buhrlage
  • Publication number: 20220378919
    Abstract: Disclosed are bispecific compounds (degraders) that target ERK5 for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat cancer and inflammatory diseases.
    Type: Application
    Filed: September 24, 2020
    Publication date: December 1, 2022
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, Jinhua Wang, Fleur Marcia Ferguson, Jie Jiang, Inchul You
  • Publication number: 20220378757
    Abstract: The disclosure relates to a compound of Formula (I), which acts as an allosteric inhibitor of epidermal growth factor receptor (EGFR); pharmaceutical compositions comprising the compound; and methods of treating or preventing kinase-mediated disorders, including cancer and other proliferation diseases.
    Type: Application
    Filed: June 19, 2020
    Publication date: December 1, 2022
    Inventors: Courtney A. Cullis, Krista E. Gipson, Yongbo Hu, Shih-Chung Huang, Nathanael S. Gray, David A. Scott, Thomas Gero, David Heppner, Tyler Beyett, Ciric To, Michael Eck
  • Publication number: 20220372017
    Abstract: Provided herein are bifunctional compounds with a moiety (e.g., lenalidomide, thalidomide) that is a binder of an E3 ubiquitin ligase (e.g., Cereblon) and another moiety that is a binder of a kinase (e.g., HCK, BTK) to induce degradation of the kinase (e.g., HCK, BTK). Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases (e.g., non-Hodgkin's lymphoma, Burkitt's lymphoma, Waldenstrom macroglobulinemia, MYD88-mutated Waldenstrom macroglobulinemia, activated B-cell diffuse large B-cell lymphoma, leukemia)), inflammatory disease, or other diseases associated with MYD88 mutations). Provided also are methods of inducing the degradation of a kinase (e.g., HCK, BTK) in a cell in a biological sample or subject by administering the bifunctional compound or composition described herein.
    Type: Application
    Filed: June 24, 2020
    Publication date: November 24, 2022
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, Steven P. Treon, Jinhua Wang, Guang Yang, Sara Jean Buhrlage, Li Tan
  • Patent number: 11505560
    Abstract: Disclosed are heterobifunctional compounds that effectuate selective degradation of a target protein, and which include a targeting ligand that binds a target protein and at least one other protein, a ligand that binds an E3 ubiquitin ligase or a component of E3 ubiquitin ligase, and a specificity modulating linker that links the first ligand and the second ligand. Pharmaceutical compositions containing the compounds, and methods of using and making the compounds are also disclosed.
    Type: Grant
    Filed: October 19, 2018
    Date of Patent: November 22, 2022
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Radoslaw P. Nowak, Eric S. Fischer, Nathanael S. Gray, Tinghu Zhang, Zhixiang He, Brian Groendyke
  • Publication number: 20220305016
    Abstract: The present disclosure provides methods of treating and/or preventing osteoporosis using salt-inducible kinase (SIK) inhibitors. Also provided are methods of using SIK inhibitors for increasing the function of osteocytes, increasing the number of osteoblasts, increasing the activity of osteoblasts, inhibiting the resorption of a bone, decreasing the number of osteoclasts, inhibiting the activity of osteoclasts, increasing the mass of a bone, down-regulating the expression of the gene SOST, and/or inhibiting the activity of sclerostin. The SIK inhibitors may be combined with Src inhibitors or CSF I R inhibitors. Exemplary SIK inhibitors include the compounds of the formula: (I), (II), (III), (IV), (V) or (VI).
    Type: Application
    Filed: January 21, 2022
    Publication date: September 29, 2022
    Applicants: The General Hospital Corporation, The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc.
    Inventors: Marc Wein, Henry Kronenberg, Thomas Sundberg, Ramnik Xavier, Nathanael S. Gray, Yanke Liang, Hwan Geun Choi, Alykhan Shamji
  • Patent number: 11447467
    Abstract: The application relates to a compound of Formula (I) which modulate the amount of STK4, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease or disorder associated with the modulation of STK4.
    Type: Grant
    Filed: December 13, 2018
    Date of Patent: September 20, 2022
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Sara Buhrlage, Kenneth C. Anderson, Teru Hideshima, Nathanael S. Gray, Xiaoxi Liu
  • Publication number: 20220281874
    Abstract: The present disclosure provides compounds of Formula (I), (II-1), (II-2), (II-3), or (II-4). The compounds of the present disclosure may be inhibitors of kinases (e.g., a cyclin-dependent kinase (CDK) (e.g., CDK7)). In some embodiments, the compounds disclosed herein are selective for inhibiting the activity of a kinase (e.g., CDK7) over certain other kinases (e.g., CDK2, CDK9, CDK12). In certain embodiments, the compounds do not bind or inhibit a 5-hydroxytryptamine (5-HT) receptor. Also provided are pharmaceutical compositions, kits, methods of use, and uses that involve the compounds disclosed herein. In some embodiments, the compounds are useful in inhibiting the activity of a kinase, inhibiting the growth of a cell, inducing apoptosis of a cell, treating a disease, and/or preventing a disease (e.g., proliferative disease, cystic fibrosis).
    Type: Application
    Filed: July 22, 2020
    Publication date: September 8, 2022
    Applicant: Dana-Farber Cancer Institure, Inc.
    Inventors: Tinghu Zhang, Nicholas Paul Kwiatkowski, Nathanael S. Gray, Zhixiang He, Yanke Liang
  • Publication number: 20220280649
    Abstract: Disclosed are bispecific compounds (degraders) that target CDK7 for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat disease.
    Type: Application
    Filed: August 4, 2020
    Publication date: September 8, 2022
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, Guangyan Du, Tinghu Zhang, Zhixiang He, Nicholas Kwiatkowski, Jie Jiang
  • Publication number: 20220267294
    Abstract: Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof. Also disclosed herein are methods of using the compounds of Formula (I) in the treatment of certain diseases (e.g., cancer).
    Type: Application
    Filed: June 18, 2020
    Publication date: August 25, 2022
    Inventors: Nathanael S. Gray, Guangyan Du, Tinghu Zhang, Nathaniel Henning, Suman Rao, Kenneth Westover, Deepak Gurbani
  • Publication number: 20220242865
    Abstract: The present invention provides novel compounds of Formula (I), (II), or (III), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g.
    Type: Application
    Filed: April 7, 2022
    Publication date: August 4, 2022
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Nicholas Paul Kwiatkowski
  • Publication number: 20220233545
    Abstract: The disclosure relates to compounds that act as an allosteric inhibitors of epidermal growth factor receptor (EGFR); pharmaceutical compositions comprising the compounds; and methods of treating or preventing kinase-mediated disorders, including cancer and other proliferation diseases.
    Type: Application
    Filed: June 19, 2020
    Publication date: July 28, 2022
    Inventors: Nathanael S. Gray, David A. Scott, Thomas Gero, Michael Eck, David Heppner, Tyler Beyett, Ciric To
  • Publication number: 20220227734
    Abstract: Provided herein are bifunctional compounds with a moiety (e.g., lenalidomide, thalidomide) that is a binder of an E3 ubiquitin ligase (e.g., Cereblon) and another moiety that is a binder of a target protein (e.g., kinase (e.g., CDK (e.g., CDK9 and/or CDK12))) to induce degradation of the target protein CDK9 and/or CDK12. Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases, such as cancers (e.g., ovarian cancer, breast cancer, or prostate cancer))). Provided also are methods of inducing the degradation of the target protein (e.g., kinase (e.g., CDK (e.g., CDK9 and/or CDK12))), and methods of inducing apoptosis in a cell in a biological sample or subject by administering the bifunctional compound or composition described herein.
    Type: Application
    Filed: April 23, 2020
    Publication date: July 21, 2022
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Jianwei Che, Nathanael S. Gray, Tinghu Zhang, Baishan Jiang, Yang Gao, Nicholas Paul Kwiatkowski
  • Publication number: 20220213067
    Abstract: The present invention provides novel compounds of Formulae (I?) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g.
    Type: Application
    Filed: March 7, 2022
    Publication date: July 7, 2022
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Baishan Jiang, Nicholas Paul Kwiatkowski
  • Publication number: 20220204515
    Abstract: Disclosed are compounds that possess inhibitory activity against LRRK2. Also disclosed are pharmaceutical compositions containing the compounds and methods of using the compounds to treat neurodegenerative diseases and disorders such as Parkinson's disease and brain cancer (e.g., gliomas and glioblastomas).
    Type: Application
    Filed: May 15, 2020
    Publication date: June 30, 2022
    Applicants: DANA-FARBER CANCER INSTITUTE, INC., VORONOI INC.
    Inventors: Nathanael S. Gray, John Hatcher, Jieun Choi, Sun-Hwa Lee, Hwangeun Choi, Eunhwa Ko, Yeonsil Kim, Daekwon Kim, Namdoo Kim, Jungbeom Son