Patents Assigned to Dana-Farber Cancer Institute, Inc.
  • Publication number: 20200253981
    Abstract: The present disclosure provides methods of increasing skin pigmentation in a subject in need thereof using salt-inducible kinase (SIK) inhibitors, such as macrocyclic compounds of Formula (I), bicyclic urea compounds of Formula (II), (III), and (IV), and compounds of Formula (V), (VI), (VI-A), or (VII). Also provided are pharmaceutical compositions, methods, and uses that include or involve a compound described herein.
    Type: Application
    Filed: February 28, 2018
    Publication date: August 13, 2020
    Applicants: The General Hospital Corporation, Dana-Farber Cancer Institute, Inc.
    Inventors: David E. Fisher, Nisma Mujahid, Ryo Murakami, Nathanael S. Gray, Yanke Liang, Hwan Geun Choi
  • Publication number: 20200255422
    Abstract: The application relates to a compound of Formula (I): which modulates the activity of TRIM33, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which TRIM33 plays a role.
    Type: Application
    Filed: April 27, 2018
    Publication date: August 13, 2020
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Jun QI, Cheng-kui PEI
  • Patent number: 10739333
    Abstract: In various aspects the invention provides methods of predicting sensitivity of a cancer cell to a therapeutic agent by contacting a test cell population BH3 domain peptide; measuring the amount of BH3 domain peptide induced mitochondrial outer membrane permeabilization in the test cell population; and comparing the amount of BH3 domain peptide induced mitochondrial outer membrane permeabilization in the test cell population to a control cell population that has not been contacted with the therapeutic agent. An increase in mitochondrial membrane permeabilization in the test cell population compared to the control cell population indicates the cell is sensitive to the therapeutic agent.
    Type: Grant
    Filed: September 18, 2014
    Date of Patent: August 11, 2020
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: Jeremy Ryan, Anthony Letai
  • Patent number: 10730860
    Abstract: The present invention provides compounds of Formula (II) (e.g., compounds of Formula (I)), and pharmaceutically compositions thereof. Compounds of Formula (II) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.
    Type: Grant
    Filed: November 2, 2018
    Date of Patent: August 4, 2020
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: James E. Bradner, Jun Qi, Minoru Tanaka
  • Patent number: 10723753
    Abstract: Described herein are compounds of Formulae (I)-(II), and pharmaceutically acceptable salts, and pharmaceutical compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases such as cancers (e.g., lung cancer, large bowel cancer, pancreas cancer, biliary tract cancer, or endometrial cancer), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases in a subject.
    Type: Grant
    Filed: March 13, 2014
    Date of Patent: July 28, 2020
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael Gray, Sang Min Lim, Hwan Geun Choi, Kenneth Dale Westover, Matthew Meyerson
  • Publication number: 20200230135
    Abstract: The present invention relates to a combination of a signal transducer and activator of transcription 3 (STAT3) activity inhibitor; and an immune checkpoint inhibitor for use in treating or preventing the hyperproliferative disorder in a subject. Preferably, the STA3 activity inhibitor is pyrimethamine or atovaquone, and the immune checkpoint inhibitor is an anti-PD1 antibody. Preferably, the hyperproliferative disorder is a glioma or a glioblastoma.
    Type: Application
    Filed: July 27, 2018
    Publication date: July 23, 2020
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: David FRANK, Darwin YE
  • Patent number: 10717992
    Abstract: The invention provides compositions and methods for regulating thermogenesis and muscle inflammation through modulation of Metrnl and/or Metrn activity and/or expression. Also provided are methods for preventing or treating metabolic disorders and muscle inflammation disorders in a subject through modulation of Metrnl and/or Metrn activity and/or expression. Further provided are methods for identifying compounds that are capable of treating metabolic disorders and muscle inflammation disorders by modulating Metrnl and/or Metrn activity and/or expression.
    Type: Grant
    Filed: January 21, 2014
    Date of Patent: July 21, 2020
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: Bruce M. Spiegelman, Rajesh R. Rao, Jonathan Z. Long
  • Patent number: 10716828
    Abstract: The invention provides composition and therapeutic, methods for modulating homeostatic pathways that are useful in treatment, and prevention of diabetes, diabetes associated disorders, metabolic disorders and cancer.
    Type: Grant
    Filed: May 2, 2008
    Date of Patent: July 21, 2020
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: Nika N. Danial, Loren D. Walensky, Gregory Bird, Susan R. Korsmeyer
  • Publication number: 20200223926
    Abstract: PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In addition, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist.
    Type: Application
    Filed: August 23, 2019
    Publication date: July 16, 2020
    Applicants: Emory University, Dana-Farber Cancer Institute, Inc., President and Fellows of Harvard College
    Inventors: Rafi Ahmed, Rama Amara, Gordon Freeman, Arlene Sharpe, Daniel Barber, E. John Wherry, Sang-Jun Ha
  • Patent number: 10710978
    Abstract: The application relates to compounds of Formula (I?): which modulate the activity of a kinase (e.g., STK4), a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease or disorder associated with the modulation of a kinase, such as STK4.
    Type: Grant
    Filed: March 31, 2016
    Date of Patent: July 14, 2020
    Assignees: DANA-FARBER CANCER INSTITUTE, INC., FONDAZIONE CENTRO SAN RAFFAELE
    Inventors: Nathanael S. Gray, Sara Buhrlage, Kenneth Anderson, Francesca Cottini, Giovanni Tonon
  • Patent number: 10711036
    Abstract: Provided herein are compounds of Formula (I) and pharmaceutical compositions thereof, which may be useful as MALT1 inhibitors. Also provided are for the treatment of proliferative disorders (e.g., cancer (e.g., non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, MALT lymphoma), benign neoplasm, a disease associated with angiogenesis, an autoimmune disease, an inflammatory disease, an autoinflammatory disease) by administering a compound of Formula (I).
    Type: Grant
    Filed: August 26, 2016
    Date of Patent: July 14, 2020
    Assignees: Cornell University, Dana-Farber Cancer Institute, Inc., Children's Medical Center Corporation
    Inventors: Nathanael S. Gray, David A. Scott, John Hatcher, Spandan Chennamadhavuni, Ari M. Melnick, Lorena Fontan Gabas, Hao Wu, Qi Qiao, Guangyan Du
  • Publication number: 20200215038
    Abstract: Embodiments of the present invention are directed to methods for treatment of melanoma using an inhibitor of dihydroorotate dehydrogenase (DHODH) and to combination therapies that involve administering to a subject an inhibitor of oncogenic BRAF (e.g. BRAF(V600E)), as well as an inhibitor of dihydroorotate dehydrogenase (DHODH). Assays for identifying compounds useful for the treatment of melanoma are also provided. The methods comprise screening for compounds or agents that inhibit neural crest progenitor formation in a zebra fish model of melanoma.
    Type: Application
    Filed: August 27, 2019
    Publication date: July 9, 2020
    Applicants: CHILDREN'S MEDICAL CENTER CORPORATION, DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Leonard ZON, Richard M. White
  • Patent number: 10703785
    Abstract: The invention provides structurally-constrained peptides by hydrocarbon stapling of a BCL9 HD2 helix for use as a therapeutic agent. The invention further provides methods and kits for use of the structurally-constrained peptide of the instant invention. The invention is based, at least in part, on the results provided herein demonstrating that hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, possess superior pharmacokinetic properties compared to the corresponding unmodified peptides, and are highly effective in binding to ?-catenin in vitro, in cellulo, and in vivo, disrupting the BCL-9/?-catenin interaction, and thereby interfering with deregulated Wnt/?-catenin signaling for therapeutic benefit in a variety of human diseases including human cancer.
    Type: Grant
    Filed: April 16, 2012
    Date of Patent: July 7, 2020
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Loren D. Walensky, Ruben Carrasco, Gregory H. Bird
  • Patent number: 10702504
    Abstract: The present application provides bifunctional compounds of Formula Ia or Ib: or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for tripartite motif-containing 24 (TRIM24). The present application also relates to methods for the targeted degradation of TRIM24 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to TRIM24 which can be utilized in the treatment of disorders modulated by TRIM24.
    Type: Grant
    Filed: June 23, 2017
    Date of Patent: July 7, 2020
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: James Bradner, Dennis Buckley, Lara Gechijian
  • Patent number: 10702527
    Abstract: The present disclosure provides combination therapy of a transcription inhibitor and a kinase inhibitor. The combination of the transcription inhibitor and the kinase inhibitor may be useful in treating and/or preventing in a subject a proliferative disease, such as proliferative a disease that is resistant to the transcription inhibitor alone or the kinase inhibitor alone. In certain embodiments, the proliferative disease is a cancer. The combination of the transcription inhibitor and the kinase inhibitor is expected to be synergistic.
    Type: Grant
    Filed: June 10, 2016
    Date of Patent: July 7, 2020
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: Peter Hammerman, Kwok-kin Wong, Nathanael S. Gray
  • Publication number: 20200209239
    Abstract: Light-generating fusion proteins having a ligand binding site and a light-generating polypeptide moiety and their use as diagnostics, in drug screening and discovery, and as therapeutics, are disclosed. The light-generating fusion protein has a feature where the bioluminescence of the polypeptide moiety changes upon binding of a ligand at the ligand binding site. The ligand may be, for example, an enzyme present in an environment only under certain conditions, e.g., ubiquitin ligase in a hypoxic state, such that the light-generating fusion protein is “turned on” only under such conditions.
    Type: Application
    Filed: June 6, 2019
    Publication date: July 2, 2020
    Applicant: Dana Farber Cancer Institute, Inc.
    Inventors: William G. KAELIN, JR., Mircea Ivan
  • Patent number: 10695346
    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: Grant
    Filed: June 24, 2016
    Date of Patent: June 30, 2020
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang
  • Publication number: 20200199150
    Abstract: The present invention provides compounds and pharmaceutically compositions thereof. The compounds and compositions are binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.
    Type: Application
    Filed: September 9, 2016
    Publication date: June 25, 2020
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: James E. Bradner, Jun Qi, Minoru Tanaka, Dennis Buckley
  • Publication number: 20200199683
    Abstract: Methods for evaluating and treating Waldenstrom's macroglobulinemia are provided.
    Type: Application
    Filed: November 14, 2019
    Publication date: June 25, 2020
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Steven P. Treon, Zachary Hunter
  • Patent number: 10689366
    Abstract: Provided herein are bifunctional compounds that inhibit MALT1 and/or promote targeted ubiquitination for the degradation of MALT1. In particular, provided are compounds that can bind MALT1, a protein whose activity is responsible for constitutive NF-KB signaling in certain cancers (e.g., activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL)), and can assist in its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon, VHL), which can ubiquitinate MALT1, marking it for proteasome degradation. Also provided are pharmaceutical compositions comprising the bifunctional compounds, methods of treating cancer with the bifunctional compounds, methods of promoting the degradation of MALT1, and methods of binding E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.
    Type: Grant
    Filed: October 31, 2017
    Date of Patent: June 23, 2020
    Assignees: Cornell University, Dana-Farber Cancer Institute, Inc.
    Inventors: Ari M. Melnick, Lorena Fontan Gabas, Nathanael S. Gray, David A. Scott, John Hatcher, Guangyan Du