Abstract: The embodiments disclosed herein utilize RNA targeting effectors to provide a robust CRISPR-based diagnostic for hemorrhagic fever virus applications. Embodiments disclosed herein can differentiate between hemorrhagic fever viruses that present with similar symptoms, as well as between strains of a hemorrhagic fever virus.
Type:
Application
Filed:
October 3, 2019
Publication date:
December 23, 2021
Applicants:
THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Inventors:
Pardis Sabeti, Cameron Myhrvold, Catherine Amanda Freije, Anna Elizabeth Lachenauer, Kayla Grace Barnes
Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect both DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences, and includes detection by colorimetric and/or fluorescence shifts. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.
Type:
Application
Filed:
January 29, 2019
Publication date:
December 2, 2021
Applicants:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Inventors:
Feng Zhang, Jonathan Gootenberg, Omar Abudayyeh
Abstract: The present disclosure features methods for identifying pateints having a hyperproliferative disease, disorder, or condition responsive to phosphodiesterase 3 (PDE3) and schlafen family member 12 (SLFN12) complex formation. The hyperproliferative disease, disorder, or condition may be cancer in a patient including glioblastoma, melanoma, ovarian cancer, cervical cancer, sarcoma, or hematopoietic cancers, such as acute myeloid leukemia. Those responsive diseases, disorders, or conditions may be identified using the biomarker AIP and/or TRRAP in combination with those biomarkers pertinent to phosphodieseterase 3 and schlafen family member 12 complexes which may be formed by PDE3 modulation with certain active compounds. Expression of combinations of these biomarkers have been shown to correlate with active compound (e.g., PDE3 modulator, PDE3A modulator, PDE3B modulator) sensitivity.
Abstract: The disclosure relates to methods for increasing the speed and efficiency of computational genomics. In particular, the disclosure relates to methods of scaling computational genomics by using one or more specialized architectures for highly parallelized computations, such as graphics processing units (GPUs), tensor processing units (TPUs), and field programmable gate arrays (FPGAs), and the like, to compute the computational genomics calculations.
Type:
Application
Filed:
October 15, 2019
Publication date:
November 18, 2021
Applicants:
THE BROAD INSTITUTE, INC., THE GENERAL HOSPITAL CORPORATION, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Abstract: The present invention includes name compounds of general formula (I): (I) in which R1, R2, R3 and R4 are as defined herein, methods for their preparation, pharmaceutical compositions and combinations comprising said compounds, and their use for the treatment of hyperproliferative diseases.
Type:
Application
Filed:
July 30, 2021
Publication date:
November 18, 2021
Applicants:
BAYER AKTIENGESELLSCHAFT, THE BROAD INSTITUTE, INC.
Inventors:
Stefan Nikolaus GRADL, Manuel ELLERMANN, Philip LIENAU, Charlotte Christine KOPITZ, Martin LANGE, Adrian TERSTEEGEN, Detlev SÜLZLE, Timothy A. LEWIS, Heidi GREULICH, Xiaoyun WU
Abstract: Provided herein are compounds useful for the treatment of various parasitic diseases. These compounds, as well as pharmaceutically acceptable salts thereof may be formulated in pharmaceutical compostions, veterinary compositions and may be used in methods of treatment and/or prophylaxis of diseases spread by parasites, including malaria and cryptosporidiosis.
Type:
Grant
Filed:
March 20, 2018
Date of Patent:
November 16, 2021
Assignees:
THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Inventors:
Eamon Comer, Nobutaka Kato, Marshall Morningstar, Bruno Melillo
Abstract: In one aspect, the invention features a method for identifying a drug-modulated polypeptide substrate of cereblon (CRBN). In another aspect, the invention features a method of identifying a polypeptide target of a modulator of CRBN. In yet another aspect, the invention provides methods of monitoring or characterizing the sensitivity of a subject to a modulator of CRBN.
Type:
Grant
Filed:
September 9, 2016
Date of Patent:
November 9, 2021
Assignees:
THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE, THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
Inventors:
Tarjei Mikkelsen, Benjamin Levine Ebert, Quinlan Sievers
Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system.
Type:
Grant
Filed:
June 2, 2016
Date of Patent:
October 26, 2021
Assignees:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, UNIVERSITY OF TOKYO
Abstract: The present invention relates to compositions which may comprise a non-naturally occurring or engineered artificial transcription factor, wherein the transcription factor may comprise a sequence specific DNA binding domain, a sliding domain, and one or more linkers, wherein the DNA binding domain and the sliding domain are operably connected by the one or more linkers, and uses thereof. Methods involving the use of a non-naturally occurring or engineered artificial transcription factors and pharmaceutical compositions, methods for treating cancer, a degenerative disease, a genetic disease or an infectious disease as well as diagnostic methods are also contemplated by the present invention.
Type:
Application
Filed:
October 13, 2020
Publication date:
September 30, 2021
Applicants:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventors:
Paul Blainey, Anthony Kulesa, Kan Xiong
Abstract: The present invention provides triazolone compounds of general formula (I): in which R1, R2, R3, R4 and R5 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 disorders, as a sole agent or in combination with other active ingredients.
Type:
Grant
Filed:
August 18, 2020
Date of Patent:
September 28, 2021
Assignees:
BAYER AKTIENGELLSCHAFT, BAYER PHARMA AKTIEGELLSCHAFT, THE BROAD INSTITUTE INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE, THE GENERAL HOSPITAL CORPORATION
Inventors:
Stefan Nikolaus Gradl, Duy Nguyen, Knut Eis, Judith Günther, Timo Stellfeld, Andreas Janzer, Sven Christian, Thomas Müller, Sherif El Sheikh, David B. Sykes, Steven James Ferrara, Michael Kröber, Claudia Merz, Michael Niehues, Martina Schäfer, Katja Zimmermann, Carl Friedrich Nising
Abstract: The present invention provides methods and compositions based on a non-naturally occurring nucleic acid construct encoding a fusion protein for quantitating levels of secretion in a single cell which may comprise a protein sequence which may comprise a cytoplasmic domain, a transmembrane domain and a vesicular domain, wherein the vesicular domain may comprise a protein tag sequence, wherein upon expression of the fusion protein by a cell, the fusion protein localizes to the membrane of a secretory vesicle such that the protein tag localizes to the lumen of the secretory vesicle, and wherein the protein tag binds to a cell-impermeable marker, whereby upon secretion of the contents of the secretory vesicle, the protein tag is exposed to the cell-impermeable marker, the fusion protein is recycled back into the cell, and the single cell becomes labeled with the marker relative to the amount of secretion.
Type:
Application
Filed:
April 17, 2018
Publication date:
September 23, 2021
Applicants:
THE GENERAL HOSPITAL CORPORATION, THE BROAD INSTITUTE, INC.
Inventors:
Sean Burns, Jason Wright, Thomas Sundberg
Abstract: The present invention relates to a relationship between microbial metagenomic structure and function and clinical remission with anti-integrin therapy induction; longitudinal trajectory of changes in the microbiome with maintenance treatment; and a comprehensive predictive model incorporating clinical and microbiome-related data to accurately classify treatment response.
Type:
Application
Filed:
May 9, 2018
Publication date:
September 9, 2021
Applicants:
THE BROAD INSTITUTE, INC., THE GENERAL HOSPITAL CORPORATION
Inventors:
ASHWIN N. ANANTHAKRISHNAN, CHENGWEI LUO, VIJAY YAJNIK, RAMNIK J. XAVIER
Abstract: The invention provides compositions and methods for treating cardiac dysfunction, particularly cachexia-associated or RAGE-associated cardiac dysfunction, using an anti-RAGE agent. The invention also provides compositions and methods for identifying therapeutic agents useful for disrupting (slowing, reducing, reversing, or preventing). The methods comprise designing or identifying agents that bind to functional sites identified on the RAGE polypeptide, wherein binding of agents to the functional site(s) inhibit RAGE-mediated cachetogenic signaling.
Type:
Grant
Filed:
December 13, 2016
Date of Patent:
September 7, 2021
Assignees:
THE BROAD INSTITUTE, INC., DANA-FARBER CANCER INSTITUTE, INC.
Abstract: Provided herein are methods and systems for amplifying and/or detecting target double-stranded or single-stranded nucleic acids. The methods comprise combining a sample comprising the target nucleic acid with an amplification reaction mixture, amplifying the target nucleic acid, and further amplifying the target nucleic acid by repeated opening, unwinding, annealing and extension under isothermal conditions. The amplification reaction mixture may include an amplification CRISPR system, a helicase, a primer pair, and a polymerase. The amplification CRISPR system may comprise a first and second CRISPR/Cas complex, the first and second CRISPR/Cas complex may comprise a first CRISPR/Cas enzyme and a first guide molecule that guides the first CRISPR/Cas complex to a first strand of the target nucleic acid; the second CRISPR/Cas complex may comprise a second CRISPR/Cas enzyme and a second guide molecule that guides the second CRISPR/Cas complex to a second strand of the target nucleic acid.
Type:
Application
Filed:
June 26, 2019
Publication date:
September 2, 2021
Applicants:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Inventors:
Feng Zhang, Max Kellner, Jonathan Gootenberg, Omar Abudayyeh
Abstract: The present invention includes methods of treating patients with acute myeloid leukemia across a range of genetic subtypes with DHODH inhibitors, such as 6-fluoro-2-(2?-fluoro-[1,1?-biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid).
Type:
Grant
Filed:
August 29, 2016
Date of Patent:
August 24, 2021
Assignees:
THE BROAD INSTITUTE, INC., THE GENERAL HOSPITAL CORPORATION, PRESIDENT AND FELLOWS OF HARVARD COLLEGE, BAYER PHARMA AKTIENGESELLSCHAFT
Inventors:
David B. Sykes, David Scadden, Timothy A. Lewis, Andreas Janzer, Hanna Meyer, Detlef Stöckigt
Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.
Type:
Grant
Filed:
July 27, 2018
Date of Patent:
August 17, 2021
Assignees:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Inventors:
Feng Zhang, Bernd Zetsche, Jonathan S. Gootenberg, Omar O. Abudayyeh, Ian Slaymaker
Abstract: The present invention features improved compounds, especially methods of identifying patients having cancer using biomarkers (e.g., PDE3A, SLFN12 and/or CREB3L1) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., Compounds 1-6 disclosed herein).
Type:
Application
Filed:
January 28, 2021
Publication date:
August 5, 2021
Applicants:
BAYER PHARMA AKTIENGESELLSCHAFT, THE BROAD INSTITUTE, INC., DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
TIMOTHY A. LEWIS, ALEX BURGIN, MONICA SCHENONE, XIAOYUN WU, HEIDI GREULICH, MATTHEW MEYERSON, LUC DE WAAL, ANTJE MARGRET WENGNER, KNUT EIS, PHILIP LIENAU, ULRIKE SACK, MARTIN LANGE
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:
Grant
Filed:
April 5, 2017
Date of Patent:
August 3, 2021
Assignees:
DANA-FARBER CANCER INSTITUTE, INC., BROAD INSTITUTE, INC.
Abstract: The invention provides markers indicative of pre-cachexia, compositions and methods for identifying patients with a molecular signature indicative of pre-cachexia; a culture system that reproduces the cachetic process in cells in vitro, which facilitates the screening and identification of therapeutic agents useful for disrupting (slowing, reducing, reversing, or preventing) the progression of pre-cachexia to refractory cachexia; as well as therapeutic agents identified using the culture system of the invention.
Type:
Grant
Filed:
December 21, 2018
Date of Patent:
July 13, 2021
Assignees:
THE BROAD INSTITUTE, INC., DANA-FARBER CANCER INSTITUTE, INC.