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:
November 29, 2023
Publication date:
July 25, 2024
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
Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions by modulating (e.g., reducing) the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C.
Type:
Application
Filed:
December 22, 2021
Publication date:
July 25, 2024
Applicants:
DANA-FARBER CANCER INSTITUTE, INC., CORNELL UNIVERSITY
Inventors:
Nathanael S. Gray, Tinghu Zhang, Lewis C. Cantley, Sindhu Carmen Sivakumaren, Theresa Manz, Eric Wang, Wenzhi Ji, Eric S. Fischer, Katherine Donovan
Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treat diseases or conditions mediated by aberrant activity of at least one class IIa histone deacetylase (HDAC4/5/7/9).
Type:
Application
Filed:
May 2, 2022
Publication date:
July 25, 2024
Applicant:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Eric S. Fischer, Yuan Xiong, Katherine Donovan
Abstract: Disclosed are degraders, pharmaceutical compositions containing them, and methods of making and using the degraders to treat diseases and disorders characterized by dysregulated or dysfunctional protein activity that can be targeted by cereblon.
Abstract: The present disclosure provides methods of treating a disease in a subject in need thereof (e.g., proliferative diseases (e.g., cancer (e.g., multiple myeloma))) comprising administering to a subject in need thereof an effective amount of an immunomodulatory drug (e.g., pomalidomide, thalidomide, lenalidomide, iberdomide). The disclosed IMiDs may increase the activity of a kinase (e.g., Zap-70). Also provided are kits comprising the disclosed IMiDs.
Abstract: Disclosed are compounds and pharmaceutically acceptable salts and stereoisomers thereof that may bind to CRBN complex and 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 characterized or mediated by the presence of a protein, and hence would benefit from degradation of said protein.
Type:
Application
Filed:
April 28, 2022
Publication date:
July 4, 2024
Applicant:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Tinghu Zhang, Lyn Howard Jones, Hu Liu, Jianwei Che
Abstract: The present invention provides chimeric antigen receptor cells specific for carbonic anhydrase IX (CAIX) and methods of using same for treatment of CAIX expressing cancers such as renal cell carcinoma.
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:
October 5, 2021
Date of Patent:
July 2, 2024
Assignees:
THE BROAD INSTITUTE, INC., DANA-FARBER CANCER INSTITUTE, INC., THE BRIGHAM & WOMEN'S HOSPITAL, INC., Instituto Carlos Slim de la Salud, A.C.
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 provides a means to modulate gene expression in vivo in a manner that avoids problems associated with CRISPR endogenous protein knock-out or knock-in strategies and strategies that provide for correction, or alteration, of single nucleotides. The invention includes inserting into the genome a nucleotide encoding a heterobifunctional compound targeting protein (dTAG) in-frame with the nucleotide sequence of a gene encoding an endogenously expressed protein of interest which, upon expression, produces an endogenous protein-dTAG hybrid protein. This allows for targeted protein degradation of the dTAG and the fused endogenous protein using a heterobifunctional compound.
Type:
Grant
Filed:
February 8, 2018
Date of Patent:
July 2, 2024
Assignee:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Dennis Buckley, Georg Winter, Andrew J. Phillips, Timothy P. Heffernan, James Bradner, Justin Roberts, Behnam Nabet
Abstract: Disclosed are compounds and pharmaceutically acceptable salts and stereoisomers thereof that are suitable for diagnosis and the treatment of diseases and disorders characterized by, associate with or which exhibit tissue hypoxia, such as, for example, solid tumors. Also disclosed are pharmaceutical compositions containing same, and methods of making and using the compounds.
Type:
Application
Filed:
March 24, 2022
Publication date:
June 27, 2024
Applicant:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Justin Kim, Dahye Kang, Sheldon T. Cheung
Abstract: Systems and methods for capturing cells of interest from a larger group of cells are provided. In some embodiments, the cells are held within cell culture media inside a chamber during laser dissection.
Type:
Grant
Filed:
March 22, 2019
Date of Patent:
June 25, 2024
Assignees:
DANA-FARBER CANCER INSTITUTE, INC., THE BROAD INSTITUTE, INC.
Abstract: Provided are methods and compositions for treating cancer in a subject in need thereof. One of the top gene products in glioblastoma multiforme (GBM) is KLRB1 (also known as CD161), a C-type lectin protein that binds to CLEC2D. Binding of CLEC2D to the KLRB1 receptor inhibits the cytotoxic function of NK cells as well as cytokine secretion. KLRB1 is only expressed by small subpopulations of human blood T cells, and consequently little is known about the function of this receptor in T cells. However, preliminary data demonstrate that KLRB1 expression is induced in T cells within the GBM microenvironment. In an exemplary embodiment, a method is provided comprising administering an agent capable of blocking the interaction of KLRB1 with its ligand. The agent may comprise an antibody or fragment thereof, which may bind KLRB1 or CLEC2D.
Type:
Grant
Filed:
November 13, 2018
Date of Patent:
June 25, 2024
Assignees:
The Broad Institute, Inc., Massachusetts Institute of Technology, The General Hospital Corporation, Dana-Farber Cancer Institute, Inc.
Inventors:
Mario Suva, Kai Wucherpfennig, Aviv Regev, Itay Tirosh, Nathan D. Mathewson
Abstract: Disclosed are compounds which inhibit Pin1 activity, methods of making the compounds, pharmaceutical compositions containing the compounds, and methods of using the compounds to treat diseases or disorders characterized or mediated by dysregulated Pin1 activity.
Type:
Application
Filed:
March 18, 2022
Publication date:
June 20, 2024
Applicants:
DANA-FARBER CANCER INSTITUTE, INC., YEDA RESEARCH AND DEVLOPMENT CO. LTD.
Inventors:
Inchul You, Nathanael S. Gray, Tinghu Zhang, Sirano Dhe-Paganon, Nir London, Christian Dubiella
Abstract: Methods and compositions for cancer immunotherapy are provided. The methods involve the use of a chimeric molecule (e.g., fusion protein) comprising a dimeric NKG2D portion and an Fc portion, which binds one or more NKG2D ligands. In some embodiments, the molecule further comprises a drug moiety (e.g., an IL15/Ra moiety). 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:
November 10, 2023
Publication date:
June 13, 2024
Applicant:
Dana-Farber Cancer Institute, Inc.
Inventors:
Glenn Dranoff, Ryan Sullivan, Matthew Vanneman
Abstract: The present invention is based, in part, on methods for modulating regulatory T cells, regulatory B cells, and immune responses using modulators of the APRIL-TACI interaction.
Abstract: The present invention provides dihydropyridazinone compounds of general formula (I) in which R1, R2 and R3 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative diseases, as a sole agent or in combination with other active ingredients.
Type:
Application
Filed:
December 28, 2023
Publication date:
June 6, 2024
Applicants:
Bayer Aktiengesellschaft, Bayer Pharma Aktiengesellschaft, The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc.
Inventors:
Manuel ELLERMANN, Stefan Nikolaus GRADL, Charlotte Christine KOPITZ, Martin LANGE, Adrian TERSTEEGEN, Philip LIENAU, Detlev SÜLZLE, Timothy LEWIS, Heidi GREULICH, Xiaoyun WU, Matthew MEYERSON
Abstract: The invention features compositions and methods for the treatment and prevention of peroxisomal diseases (e.g., neonatal adrenoleukodystrophy and Zellweger syndrome), including in a subject selected as having increased levels of metallothionein polypeptides. The invention also provides compositions and methods for identifying a subject having a peroxisomal disease involving detecting metallothionein polypeptides or polynucleotides.
Type:
Grant
Filed:
January 16, 2018
Date of Patent:
June 4, 2024
Assignees:
Children's Medical Center Corporation, Ospedale San Raffaele S.R.L., Dana-Farber Cancer Institute, Inc., Fondazione Telethon
Abstract: Provided herein are compounds that interrupt the function of SALL4. Also described are pharmaceutical compositions and medical uses of these compounds.
Type:
Grant
Filed:
November 1, 2022
Date of Patent:
June 4, 2024
Assignees:
DANA-FARBER CANCER INSTITUTE, INC., THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
Abstract: The present invention comprises compositions, methods, and devices for enhancing an endogenous immune response against a cancer. Devices and methods provide therapeutic immunity to subjects against cancer.
Type:
Grant
Filed:
May 18, 2020
Date of Patent:
June 4, 2024
Assignees:
President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.
Inventors:
Omar Abdel-Rahman Ali, David J. Mooney, Glenn Dranoff
Abstract: The present invention provides compounds of any one of Formulae (A), (I-11), (II), and (V) (e.g., compounds of Formula (A-1)-(A-18)), and methods for treating Waldenström's macroglobulinemia (WM) and other B cell neoplasm in a subject using the compounds. The methods comprise administering to a subject in need thereof an effective amount of the compounds. Also provided are methods to treat B cell neoplasms using the compounds in combination with inhibitors of Bruton's tyrosine kinase (BTK), interleukin-1 receptor-associated kinase 1 (IRAK1), interleukin-1 receptor-associated kinase 4 (IRAK4), bone marrow on X chromosome kinase (BMX), phosphoinositide 3-kinase (PI3K), transforming growth factor b-activated kinase-1 (TAK1), and/or a Src family kinase.
Type:
Grant
Filed:
November 24, 2021
Date of Patent:
July 2, 2024
Assignee:
Dana-Farber Cancer Institute, Inc.
Inventors:
Steven P. Treon, Sara Jean Buhrlage, Nathanael S. Gray, Li Tan, Guang Yang