Abstract: Disclosed are bifunctional compounds (degraders) that target HAT EP300 for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat disease.
Abstract: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers, particularly cancers that exhibit arm-level loss of chromosome 16q, focal copy loss of 16q13 and/or low expression of metallothionein proteins, such as certain uterine, ovarian, gastroesophageal and lung cancers. Three known drugs, disulfiram, elesclomol and thiram, as well as certain disulfiram metabolites, are specifically provided for killing cancer cells characterized by arm-level loss of chromosome 16q, focal copy loss of 16q13 and/or low expression of metallothioneins. The instant disclosure therefore provides for selecting and/or administering disulfiram, elesclomol and thiram and/or active metabolites or derivatives of disulfiram, elesclomol and thiram as a therapeutic agent(s) to target a cancer cell and/or subject having or at risk of developing a cancer. Methods and compositions for therapies that include such compounds are also provided.
Type:
Application
Filed:
November 13, 2019
Publication date:
January 13, 2022
Applicants:
THE BROAD INSTITUTE, INC., DANA-FARBER CANCER INSTITUTE, INC., INSTITUTO CARLOS SLIM DE LA SALUD, A.C.
Inventors:
Steven CORSELLO, Ryan SPANGLER, Rohith NAGARI, Todd GOLUB
Abstract: The present invention relates to methods, compositions and kits for treatment of ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA). In some embodiments, the invention relates to the use of novel classes of compounds, i.e. inhibitors of RSK (p90S6K); inhibitors of p70S6K; and inhibitors of rps6, to treat ribosomal disorders and ribosomopathies. In some embodiments, the invention relates to the use of specific Chk2 inhibitors and to the use of specific phenothiazine derivatives to treat ribosomal disorders and ribosomopathies, e.g. DBA.
Type:
Application
Filed:
February 12, 2021
Publication date:
January 13, 2022
Applicants:
THE CHILDREN'S MEDICAL CENTER CORPORATION, DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
James BRADNER, Jun QI, Dennis BUCKLEY, Leonard I. ZON, Elizabeth MACARI
Abstract: The present disclosure provides a method for treating a subject afflicted with Waldenström's macroglobulinemia (WM) comprising administering to the subject a therapeutically effective amount of an antibody or an antigen-binding portion thereof that specifically binds to a CXCR4 receptor expressed on the surface of a WM cell. The disclosure also provides a therapeutic regimen for treating a patient afflicted with C1013G/CXCR4-associated WM.
Type:
Grant
Filed:
February 8, 2019
Date of Patent:
January 11, 2022
Assignees:
BRISTOL-MYERS SQUIBB COMPANY, DANA-FARBER CANCER INSTITUTE, Inc.
Inventors:
Irene M. Ghobrial, Aldo M. Roccaro, Josephine M. Cardarelli, Antonio Sacco
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 BCL9/?-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:
May 18, 2020
Date of Patent:
January 11, 2022
Assignee:
Dana-Farber Cancer Institute, Inc.
Inventors:
Loren D. Walensky, Ruben Carrasco, Gregory H. Bird
Abstract: Methods for cancer immunotherapy are provided. The methods involve the use of a chimeric molecule (e.g., fusion protein) comprising an NKG2D portion and an Fc portion, which binds one or more NKG2D ligands. The methods disclosed herein are useful for the treatment of cancer that is associated with abnormal expression of one or more NKG2D ligands.
Type:
Application
Filed:
April 2, 2021
Publication date:
January 6, 2022
Applicant:
Dana-Farber Cancer Institute, Inc.
Inventors:
Glenn Dranoff, Matthew Vanneman, Gordon Freeman
Abstract: Provided herein are methods and kits for determining the presence or absence of certain microRNA biomarkers in a blood sample of a female patient. The microRNA biomarkers are associated with ovarian cancer. Also provided are methods for screening a female subject for the presence or absence of certain microRNA biomarkers, as well as methods for treating a female subject having an ovarian cancer.
Type:
Grant
Filed:
January 9, 2018
Date of Patent:
January 4, 2022
Assignees:
DANA-FARBER CANCER INSTITUTE, INC., THE BRIGHAM AND WOMEN'S HOSPITAL, INC., MEDICAL UNIVERSITY OF LODZ
Inventors:
Dipanjan Chowdhury, Kevin M. Elias, Wojciech Fendler, Konrad Stawiski
Abstract: The disclosure provides materials and methods related to using biomarkers for prediction of duration of response to prostate cancer treatment and for treating prostate cancer.
Type:
Grant
Filed:
March 12, 2019
Date of Patent:
January 4, 2022
Assignee:
Dana-Farber Cancer Institute, Inc.
Inventors:
Philip W. Kantoff, Ming Yang, Gwo-Shu Mary Lee, Tong Sun, Wanling Xie
Abstract: Provided herein, in some embodiments, are methods for detecting a level of asparaginase (ASNS) in a sample obtained from a subject having or at risk for stomach cancer or liver cancer, and methods of treating the subject.
Type:
Application
Filed:
November 13, 2019
Publication date:
December 30, 2021
Applicants:
The Broad Institute, Inc., President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.
Abstract: A method of identifying a subject having cancer who is likely to benefit from treatment with a combination therapy with a RAF inhibitor and a second inhibitor is provided. A method of treating cancer in a subject in need thereof is also provided and includes administering to the subject an effective amount of a RAF inhibitor and an effective amount of a second inhibitor, wherein the second inhibitor is a MEK inhibitor, a CRAF inhibitor, a CrkL inhibitor or a TPL2/COT inhibitor. A method of identifying a kinase target that confers resistance to a first inhibitor is also provided.
Type:
Application
Filed:
June 24, 2021
Publication date:
December 30, 2021
Applicants:
DANA-FARBER CANCER INSTITUTE, INC., BROAD INSTITUTE, INC.
Abstract: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of proteinopathies, particularly MUC1-associated kidney disease (ADTKD-MUC1 or MKD), Retinitis Pigmentosa (e.g., due to rhodopsin mutations), autosomal dominant tubulo-interstitial kidney disease due to UMOD mutation(s) (ADTKD-UMOD), and other forms of toxic proteinopathies resulting from mutant protein accumulation in the ER or other secretory pathway compartments and/or vesicles, among others. The disclosure also identifies and provides TMED9-binding agents as capable of treating or preventing proteinopathies of the secretory pathway, and further provides methods for identifying additional TMED9-binding agents.
Type:
Grant
Filed:
January 28, 2021
Date of Patent:
December 28, 2021
Assignees:
The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., The Brigham and Women's Hospital, Inc.
Inventors:
Anna Greka, Moran Dvela-Levitt, Maria Alimova, Eric Lander, Todd R. Golub, Florence Wagner, Brian Chamberlain, Valeria Padovano, Joseph Growney
Abstract: The present invention is based, in part, on the identification of methods of modulating PD-1 expression and/or activity in regulatory T cells (Tregs) to thereby regulate effector immune responses in effector T cells (Teffs).
Type:
Grant
Filed:
October 14, 2016
Date of Patent:
December 28, 2021
Assignees:
President and Fellows of Harvard College, The Brigham and Women's Hospital, Inc., Dana-Farber Cancer Institute, Inc.
Inventors:
Arlene H. Sharpe, Gordon J. Freeman, Loise M. Francisco, Peter T. Sage, Sun J. Lee, Scott B. Lovitch, Vikram R. Juneja, Catherine L. Tan
Abstract: The present invention features improved methods of identifying patients having cancer (e.g., melanoma, adenocarcinoma, lung, cervical, liver or breast cancer) using biomarkers (e.g., PDE3A, SLFN12) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., DNMDP, zardaverine, and anagrelide).
Type:
Grant
Filed:
August 12, 2016
Date of Patent:
December 28, 2021
Assignees:
The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., Bayer Pharma Aktiengesellschaft
Inventors:
Luc De Waal, Matthew Meyerson, Heidi Greulich, Monica Schenone, Alex Burgin, Xiaoyun Wu, Ulrike Sack
Abstract: The present invention provides compounds of Formula (I), and pharmaceutically compositions thereof. Compounds of Formula (I) 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, 2020
Publication date:
December 23, 2021
Applicant:
Dana-Farber Cancer Institute, Inc.
Inventors:
James E. Bradner, Jun Qi, Minoru Tanaka
Abstract: Nucleic acids and proteins having a mutant C-RAF sequence, and methods of identifying patients having cancer who are likely to benefit from a combination therapy and methods of treatment are provided.
Type:
Application
Filed:
August 11, 2021
Publication date:
December 16, 2021
Applicant:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Caroline Emery, Rajee Antony, Levi A. Garraway
Abstract: The present invention relates to screening methods for identification of agents (e.g., small molecules) that modulate cytotoxic T lymphocyte antigen-specific target (e.g., tumor) cell killing, as well as to uses of compounds identified thereby as immunomodulatory, including use of EGFR inhibitors as immunomodulatory agents.
Type:
Application
Filed:
July 9, 2018
Publication date:
December 9, 2021
Applicant:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Patrick H. LIZOTTE, Paul T. KIRSCHMEIER, Mark BITTINGER, Nathanael GRAY