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: 20220017510
    Abstract: The present application provides bifunctional compounds of Formula (I): which act as protein degradation inducing moieties for EGFR and/or a mutant thereof. The present application also describes methods for the targeted degradation of EGFR and/or a mutant thereof through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to EGFR and/or a mutant thereof which can be utilized in the treatment of disorders modulated by EGFR or a mutant thereof.
    Type: Application
    Filed: September 27, 2021
    Publication date: January 20, 2022
    Inventors: NATHANAEL S. GRAY, JAEBONG JANG, DRIES DE CLERCQ, MICHAEL ECK, PASI JANNE
  • Patent number: 11186574
    Abstract: The application relates to a compound having Formula X: which modulates the activity of HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, plays a role.
    Type: Grant
    Filed: August 31, 2018
    Date of Patent: November 30, 2021
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: John M. Hatcher, Nathanael S. Gray, Jaebong Jang, Dries De Clercq, Pasi Janne, Jamie A. Saxon, Michael Eck, David A. Scott, Alyssa Verano
  • Publication number: 20210361774
    Abstract: Disclosed are bifunctional compounds (degraders) that target LRKK2 for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the degraders to treat neurodegenerative diseases and disorders such as Parkinson's disease and brain cancer (e.g., gliomas and glioblastomas).
    Type: Application
    Filed: October 16, 2019
    Publication date: November 25, 2021
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, John Hatcher
  • Publication number: 20210355119
    Abstract: The application relates to a compound having Formula I which modulates the activity of HER2 and/or a mutant thereof, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which HER2 and/or a mutant thereof plays a role.
    Type: Application
    Filed: June 14, 2019
    Publication date: November 18, 2021
    Inventors: NATHANAEL S. GRAY, JAEBONG JANG, PASI JANNE, JIEUN SON
  • Publication number: 20210347772
    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 diseases and disorders including neurodegenerative diseases and disorders such as Parkinson's disease, and brain cancer (e.g., gliomas and glioblastomas).
    Type: Application
    Filed: October 16, 2019
    Publication date: November 11, 2021
    Applicants: DANA-FARBER CANCER INSTITUTE, INC., VORONOI INC.
    Inventors: Nathanael S. Gray, John Hatcher, Jieun Choi, Hwanguen Choi, Eunhwa Ko, Namdoo Kim
  • Publication number: 20210346395
    Abstract: The application relates to compounds, or pharmaceutically acceptable salts, hydrates, solvates, or stereoisomers thereof, which modulate the activity of EGFR, a pharmaceutical composition comprising said compounds, and methods of treating or preventing a disease in which EGFR plays a role.
    Type: Application
    Filed: June 21, 2019
    Publication date: November 11, 2021
    Inventors: NATHANAEL S. GRAY, JAEBONG JANG, DRIES DE CLERCQ, DAVID A. SCOTT
  • Publication number: 20210338825
    Abstract: Disclosed are bifunctional compounds (degraders) that target hepatitis C virus (HCV) NS3/4A for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat HCV infection and HCV-associated diseases or disorders.
    Type: Application
    Filed: September 26, 2019
    Publication date: November 4, 2021
    Applicants: DANA-FARBER CANCER INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Nathanael S. Gray, Tinghu Zhang, Priscilla Yang, Melissanne De Wispelaere, Guangyan Du
  • Publication number: 20210340140
    Abstract: The present application provides bifunctional compounds, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 4 (CDK4) and/or cyclin-dependent kinase 6 (CDK6).
    Type: Application
    Filed: July 23, 2019
    Publication date: November 4, 2021
    Inventors: NATHANAEL S. GRAY, BAISHAN JIANG, TINGHU ZHANG, ERIC WANG, NICHOLAS KWIATKOWSKI, YANKE LIANG, CALLA M. OLSON
  • Publication number: 20210340102
    Abstract: The application relates to a compound of Formula (I): which modulates the activity of ALK or SRPK, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which ALK or SRPK plays a role.
    Type: Application
    Filed: June 15, 2021
    Publication date: November 4, 2021
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: John Hatcher, Nathanael S. Gray, Hwangeun Choi, Pasi Janne, Tinghu Zhang
  • Publication number: 20210332024
    Abstract: Disclosed herein are compounds comprising an electrophilic moiety and rigid moiety for use in modulating an activity of Pin1. The rigid moiety comprises at least one functional group that is capable of forming hydrogen bonds with hydrogen atoms, wherein the electrophilic moiety and the rigid moiety are arranged such that the electrophilic moiety is capable of covalently binding to the Cys113 residue of Pin1, and the rigid moiety is capable of forming hydrogen bonds with the Gln131 and His 157 residues of Pin1. Further disclosed are novel compounds having Formula Id: wherein the dashed line, W, X, Y, Z, Ra-Rc, R1, R2, L1, L2 and n are as defined herein, and libraries comprising such compounds. Further disclosed are methods of identifying a compound capable of modulating an activity of Pin1, by screening a library of compounds.
    Type: Application
    Filed: July 8, 2021
    Publication date: October 28, 2021
    Applicants: Yeda Research and Development Co. Ltd., Dana-Farber Cancer Institute, Inc., Beth Israel Deaconess Medical Center, Inc.
    Inventors: Nir LONDON, Daniel ZAIDMAN, Christian DUBIELLA, Nathanael S. GRAY, Benika Joan PINCH, Kun Ping LU, Alfred Thomas LOOK, Shuning HE, Xiao Zhen ZHOU, Xiaolan LIAN
  • Patent number: 11155556
    Abstract: The present invention relates to use of pyrimido-diazepinone compounds that are able to modulate protein kinases such as PI3K-? and PI3K-?, which are members of the Class I Type IA and Class I Type IB family of phosphatidylinositol-4,5-bisphosphate 3-kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.
    Type: Grant
    Filed: April 7, 2017
    Date of Patent: October 26, 2021
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Fleur M. Ferguson, Jean Zhao, Jing Ni
  • Publication number: 20210317105
    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: November 22, 2017
    Publication date: October 14, 2021
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Baishan Jiang, Nicholas Paul Kwiatkowski
  • Publication number: 20210315894
    Abstract: The present invention provides novel compounds of Formula (I), 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 or preventing proliferative diseases (e.g., cancers (e.g., lung cancer, breast cancer, leukemia, lymphoma, melanoma, multiple myeloma, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma), benign neoplasms, 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 (e.g. a protein kinase (e.g. a cyclin-dependent kinase (CDK) (e.g. CDK7, CDK12, or CDK13) or a lipid kinase such as a phosphatidylinositol-5-phosphate 4-kinase (PIP4K) (e.g.
    Type: Application
    Filed: June 11, 2020
    Publication date: October 14, 2021
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang
  • Patent number: 11142507
    Abstract: The present invention provides novel compounds of Formulae (I?), (I), (II?), 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: Grant
    Filed: September 9, 2016
    Date of Patent: October 12, 2021
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Nicholas Paul Kwiatkowski, Mingfeng Hao
  • Publication number: 20210300911
    Abstract: The present invention provides novel compounds according to Formula (I): where Ring A, Ring B, X, L1, L2, RA, RC, RD, RE, m, n, and p are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of human diseases associated with kinase activity, for example, proliferative diseases, neurodegenerative diseases, metabolic disorders, inflammatory diseases, and cardiovascular diseases.
    Type: Application
    Filed: February 26, 2021
    Publication date: September 30, 2021
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang
  • Publication number: 20210292299
    Abstract: Provided herein are compounds of Formula (I?) or (I), 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 diseases (e.g., proliferative diseases (e.g., cancers (e.g., carcinoma); lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, ovarian cancer, colon cancer, colorectal cancer)), metabolic disorders (e.g., diabetes), autoimmune diseases, and neurological diseases (e.g., Alzheimer's disease, gliosis, spinal cord injury)) in a subject, as well as for male contraception (e.g., reducing or inhibiting spermatogenesis, or reducing the rate of male fertility in a healthy fertile male subject). Provided are methods of inhibiting a CDK (e.g., CDK14, CDK15, CDK16, CDK17, CDK18) in a subject.
    Type: Application
    Filed: June 24, 2019
    Publication date: September 23, 2021
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Fleur M. Ferguson, Zainab M. Doctor
  • Publication number: 20210276996
    Abstract: Disclosed are bifunctional compounds, pharmaceutical compositions containing them, and methods of making and using them to treat diseases and disorders characterized by aberrant protein activity wherein the protein is targeted for degradation by KEAP1 and the Cul3-based E3-ubiquitin ligase complex.
    Type: Application
    Filed: July 18, 2019
    Publication date: September 9, 2021
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Eric Fischer, Guangyan Du, Nozhat Safaee, Nathaniel Henning, Katherine Donovan
  • Publication number: 20210261551
    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: February 3, 2020
    Publication date: August 26, 2021
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Nicholas Paul Kwiatkowski
  • Publication number: 20210230538
    Abstract: The present disclosure provides compounds of any one of Formulae (A) to (L). The present disclosure also provides compositions, uses, and methods that include or involve a compound described herein, a serine/threonine-protein kinase B-Raf (BRAF) inhibitor, an epidermal growth factor receptor (EGFR) inhibitor, a vascular endothelial growth factor 1 (VEGFR1) inhibitor, a fibroblast growth factor receptor 1 (FGFR1) inhibitor, or a combination thereof. The compounds, compositions, uses, and methods are useful in changing the pluripotency state of a vertebrate cell to a more nave state.
    Type: Application
    Filed: October 15, 2020
    Publication date: July 29, 2021
    Applicants: Whitehead Institute for Biomedical Research, Dana-Farber Cancer Institute, Inc.
    Inventors: Thorold W. Theunissen, Nathanael S. Gray, Rudolf Jaenisch
  • Publication number: 20210230144
    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: Application
    Filed: February 13, 2019
    Publication date: July 29, 2021
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, John Hatcher