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:
Grant
Filed:
June 14, 2019
Date of Patent:
November 14, 2023
Assignee:
Dana-Farber Cancer Institute, Inc.
Inventors:
Nathanael S. Gray, Jaebong Jang, Pasi Janne, Jieun Son
Abstract: Disclosed are bispecific compounds (degraders) that target cereblon (CRBN) for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds as research tools and to reduce adverse side effects associated with a cereblon targeted therapy.
Type:
Application
Filed:
March 16, 2021
Publication date:
November 9, 2023
Applicant:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Nathanael S. Gray, Zhixiang He, Tinghu Zhang, Chelsea Powell, Eric S. Fischer, Jonathan Bushman, Guangyan Du
Abstract: Presently described are methods for enriching regions of a genome in a sample using ligation of fragmented genomic nucleic acid and amplification using repeat elements. The methods can be used for a number of applications, including genome-wide homopolymer indel detection, and enable increasing the amount of information obtained from a limited sample of genomic nucleic acid.
Abstract: A method for detecting oncogenic growth and viability, and/or degree of cellular transformation and/or identifying an agent that inhibits cellular transformation is disclosed. The method including: providing a cellular sample, such as a sample of cells obtained from a subject or a cell line; culturing the cellular sample in low attachment conditions; and detecting growth and7or cell viability of the sample, wherein increased growth relative and/or viability relative to a control or control level indicative of basal growth and/or viability indicates cellular transformation. In some embodiments, the method includes introducing a n expression vector into cells of the cellular sample, wherein the expression vector comprises a gene product expression sequence being tested for transformation ability. In some embodiments the cellular sample is contacted with a test agent and growth and/or cell viability of the sample is determined to determine if the agent inhibits transformation.
Type:
Grant
Filed:
March 24, 2016
Date of Patent:
November 7, 2023
Assignees:
THE BROAD INSTITUTE, INC., DANA FARBER CANCER INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE, MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventors:
Asaf Rotem, Kevin Struhl, Paul Blainey, Liyi Xu
Abstract: DCAF15 is a substrate recognition (adaptor) protein of E3 ubiquitin ligase. Disclosed herein are compounds that recruit ubiquitin ligase CRL4DCAF15, to a target RNA recognition motif (RRM), causing its degradation. Also disclosed herein are compositions and methods of use in treating associated disorders and diseases.
Type:
Grant
Filed:
January 24, 2019
Date of Patent:
November 7, 2023
Assignee:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Nathanael S. Gray, Eric Fischer, Hojong Yoon, Tinghu Zhang, Tyler Faust, Katherine Donovan, Quan Cai, Zhengnian Li
Abstract: Provided herein are bifunctional compounds that bind a target protein (e.g., a selected protein) and/or induce ubiquitination for degradation of the target protein. In particular, provided are compounds that bind a bromodomain or bromodomain-containing protein (e.g., BET proteins) or histone methyltransferases (HMTs, e.g., enhancer of zeste homolog 1 (EZH1), or FKBP12) and can promote its degradation by recruiting it to the ubiquitin receptor RPN13 (e.g., RA190), for proteasomal degradation. Also provided are pharmaceutical compositions comprising the bifunctional compounds, methods of treating and/or preventing diseases (e.g., proliferative diseases, cancers, benign neoplasms, pathological angiogenesis, inflammatory diseases, and autoimmune diseases) and musculoskeletal diseases, and methods of inducing the degradation of a target (e.g., a target protein) by recruiting it to the ubiquitin receptor RPN13 of the proteasome in a subject by administering a compound or composition described herein.
Type:
Grant
Filed:
February 22, 2019
Date of Patent:
October 31, 2023
Assignee:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Jun Qi, Lei Wu, Kenneth C. Anderson, Yan Song, Paul Park, Dharminder Chauhan
Abstract: The present application provides bifunctional compounds of Formula (X): or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for Bruton's tyrosine kinase (BTK). The present application also relates to methods for the targeted degradation of BTK through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to BTK which can be utilized in the treatment of disorders modulated by BTK.
Type:
Application
Filed:
June 27, 2023
Publication date:
October 26, 2023
Applicant:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Nathanael S. Gray, Dennis Dobrovolsky, Hai-Tsang Huang
Abstract: The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., HCK, BTK, LYN) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating diseases (e.g., proliferative diseases) in a subject in need thereof).
Type:
Application
Filed:
June 3, 2021
Publication date:
October 26, 2023
Applicant:
Dana-Farber Cancer Institute, Inc.
Inventors:
Nathanael S. Gray, Steven P. Treon, Sara Jean Buhrlage, Guang Yang, Jinhua Wang, Li Tan, Zachary R. Hunter
Abstract: The present invention relates to a homogeneous, time resolved, Förster resonance energy transfer (TR-FRET)-based method for detection of SARS-CoV-2, SARS CoV-1, and MERS-CoV antibodies in a patient fluid sample.
Type:
Application
Filed:
August 16, 2021
Publication date:
October 26, 2023
Applicants:
DANA-FARBER CANCER INSTITUTE, INC., THE GENERAL HOSPITAL CORPORATION, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Inventors:
Eric Fischer, Radoslaw Nowak, Hong Yue, Daan Overwijn, Ralph Mazitschek, Neil Connor Payne
Abstract: Disclosed are to compounds, compositions, and methods for treating diseases or conditions mediated by aberrant serine-arginine protein kinase (SRPK) 1 and SRPK2 activity.
Abstract: Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.
Type:
Grant
Filed:
August 25, 2020
Date of Patent:
October 17, 2023
Assignee:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Levi A. Garraway, Caroline Emery, Nikhil Wagle
Abstract: The present application relates to mass spectrometry methods for use in identifying proteins or other biomolecules which are bound irreversibly by test compounds.
Type:
Grant
Filed:
October 26, 2020
Date of Patent:
October 17, 2023
Assignee:
Dana-Farber Cancer Institute, Inc.
Inventors:
Jarrod A Marto, Scott B Ficarro, Guillaume Adelmant
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:
Grant
Filed:
August 11, 2021
Date of Patent:
October 17, 2023
Assignee:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Caroline Emery, Rajee Antony, Levi A. Garraway
Abstract: Disclosed are compounds with immunomodulatory 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 dysfunctional protein activity.
Type:
Application
Filed:
November 11, 2022
Publication date:
October 5, 2023
Applicant:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Nathanael Gray, Tinghu Zhang, Eric Fischer, Zhixiang He, Guangyan Du, Katherine Donovan, Radoslaw Nowak, Jing Ting Christine Yuan
Abstract: The present invention relates to compounds, compositions and methods for treating diseases or conditions mediated by proteins of the SWI/SNF chromatin-remodeling complex, including PB1.
Type:
Grant
Filed:
April 30, 2019
Date of Patent:
October 3, 2023
Assignee:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Eric Fischer, Nathanael Gray, Radoslaw Nowak, Katherine Donovan, Tinghu Zhang, Yao Liu
Abstract: The present invention provides dihydrooxydiazinone compounds of general formula (I) in which R1, R2, R3, and R4, 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:
Grant
Filed:
July 14, 2022
Date of Patent:
October 3, 2023
Assignees:
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, Christa Hegele-Hartung, Detlev Sülzle, Timothy A. Lewis, Heidi Greulich, Xiaoyun Wu, Matthew Meyerson, Alex Burgin
Abstract: The invention provides methods and compositions for inducing brown fat cell differentiation through modulation of both Prdm16 and C/EBP? activity and/or expression. Also provided are methods for preventing or treating obesity or an obesity related disorder in a subject through stimulation of both Prdm16 and C/EBP? expression and/or activity. Further provided are methods for identifying compounds that are capable of modulating both Prdm16 and C/EBP? expression and/or activity.
Abstract: Described and featured herein are antagonistic biparatopic antibodies that specifically bind and inhibit an FGF receptor (e.g., FGFR2) and methods of using such antibodies for the treatment of cancers, including Cholangiocarcinoma (CCAs).
Type:
Application
Filed:
June 2, 2021
Publication date:
September 21, 2023
Applicants:
The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc.
Inventors:
Saireudee CHATURANTABUT, William SELLERS