Patents Assigned to BROAD INSTITUTE
  • Publication number: 20210207203
    Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide robust CRISPR-based nucleic acid amplification methods and systems. Embodiments disclosed herein can amplify both double-stranded and single-stranded nucleic acid targets. Moreover, the embodiments disclosed herein can be combined with various detection platforms, for example, CRISPR-SHERLOCK, to achieve detection and diagnostic with attomolar sensitivity. 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: June 26, 2019
    Publication date: July 8, 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
  • Publication number: 20210188846
    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: Application
    Filed: January 28, 2021
    Publication date: June 24, 2021
    Applicants: BAYER AKTIENGESELLSCHAFT, BAYER PHARMA AKTIENGELLSCHAFT, 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 MUELLER, Sherif El SHEIKH, Han Jie ZHOU, Changjia ZHAO, David B. SYKES, Steven James FERRARA, Kery LIU, Simon Anthony HERBERT, Claudia MERZ, Michael NIEHUES, Carl Friedrich NISING, Martina SCHÄFER, Katja ZIMMERMANN, Jörg KNÄBLEIN, Kai THEDE, Thomas FAUPEL
  • Publication number: 20210188805
    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: Application
    Filed: August 18, 2020
    Publication date: June 24, 2021
    Applicants: BAYER AKTIENGESELLSCHAFT, BAYER PHARMA AKTIENGELLSCHAFT, 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, Han Jie ZHOU, Changjia ZHAO, David B. SYKES, Steven James FERRARA, Kery LIU, Michael KRÖBER, Claudia MERZ, Michael NIEHUES, Martina SCHÄFER, Katja ZIMMERMANN, Carl Friedrich NISING
  • Patent number: 11041173
    Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.
    Type: Grant
    Filed: November 11, 2016
    Date of Patent: June 22, 2021
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Randall Jeffrey Platt, Guoping Feng, Yang Zhou
  • Publication number: 20210169827
    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: Application
    Filed: January 28, 2021
    Publication date: June 10, 2021
    Applicants: THE BROAD INSTITUTE, INC., THE BRIGHAM & WOMEN'S HOSPITAL, INC., DANA-FARBER CANCER INSTITUTE, 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
  • Publication number: 20210166783
    Abstract: Disclosed here is a method of identifying novel CRISPR effectors, comprising: identifying sequences in a genomic or metagenomic database encoding a CRISPR array; identifying one or more Open Reading Frames (ORFs) in said selected sequences within 10 kb of the CRISPR array; discarding all loci encoding proteins which are assigned to known CRISPR-Cas subtypes and, optionally, all loci encoding a protein of less than 700 amino acids; and identifying putative novel CRISPR effectors, and optionally classifying them based on structure analysis.
    Type: Application
    Filed: August 16, 2017
    Publication date: June 3, 2021
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY, THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH
    Inventors: Sergey SHMAKOV, Kira S. MAKAROVA, Yuri I. WOLF, Aaron SMARGON, Neena PYZOCHA, David COX, Winston YAN, David SCOTT, Konstantin SEVERINOV, Feng ZHANG, Eugene V. KOONIN
  • Publication number: 20210163944
    Abstract: The disclosure provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered RNA-targeting systems comprising a novel RNA-targeting Cas12b effector protein and at least one targeting nucleic acid component like a guide RNA or crRNA.
    Type: Application
    Filed: August 7, 2019
    Publication date: June 3, 2021
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Jonathan Strecker, Ian Slaymaker, Sara Jones
  • Publication number: 20210147831
    Abstract: The invention provides a cell library for use in detecting protein expression comprising a plurality of cells, wherein each cell comprises a polynucleotide sequence encoding a detectable marker integrated into the genome of the cell in frame with a protein coding gene selected from a set of target genes, wherein the library comprises more than one cell tagged at each target gene, as well as a cell library for use in detecting protein interactions between a protein of interest and a set of target proteins and a cell library for use in detecting protein modifications. The invention also provides methods of constructing a cell library for use in proteomics, as well as methods for sequencing integration sites of a donor sequence inserted into the genome of a cell. Also provided are systems for analysis of proteins in a cell and kits comprising vectors for tagging a population of cells and for performing proteomics studies.
    Type: Application
    Filed: April 26, 2019
    Publication date: May 20, 2021
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Jonathan Leo Schmid-Burgk, Veit Hornung
  • Publication number: 20210147799
    Abstract: Described herein are engineered antigen presenting cells that can be capable of modulating a target T-cell in a T-cell antigen specific manner. In some embodiments, the engineered APCs can include a modified antigen presentation pathway. Also described herein are methods of making and using the engineered antigen presenting cells.
    Type: Application
    Filed: November 9, 2020
    Publication date: May 20, 2021
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Blake Lash, Daniel Strebinger
  • Publication number: 20210147915
    Abstract: Provided herein are methods and systems for detecting a target nucleic acid sequence. The method comprises contacting an oligonucleotide comprising the target nucleic acid sequence with a transposon complex; inserting one or more T7 RNA promoters into the oligonucleotide using the transposase; and (c) amplifying the target nucleic acid sequence. The transposon complex may comprise a transposase and a transposon sequence comprising one or more T7 RNA promoters. The target nucleic sequence may be amplified by generating RNA oligonucleotides comprising the target nucleic acid sequence via transcription from the inserted one or more T7 RNA promoters. The amplified target nucleic acid may be detected using a CRISPR Cas13-based detection system.
    Type: Application
    Filed: June 26, 2019
    Publication date: May 20, 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
  • Patent number: 11008588
    Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in prokaryotic and eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity.
    Type: Grant
    Filed: December 17, 2015
    Date of Patent: May 18, 2021
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Chie-yu Lin, Fei Ran
  • Publication number: 20210130800
    Abstract: The present disclosure provides for systems, methods, and compositions for targeting and editing nucleic acids. In particular, the present disclosure provides non-naturally occurring or engineered RNA-targeting systems comprising a RNA-targeting Cas13 protein, at least one guide molecule, and at least one adenosine deaminase protein or catalytic domain thereof.
    Type: Application
    Filed: October 23, 2018
    Publication date: May 6, 2021
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Jonathan Gootenberg, David Benjamin Turitz Cox, Omar Abudayyeh, Ian Slaymaker
  • Publication number: 20210130833
    Abstract: Engineered systems comprising components of defense systems identified in prokaryotes are provided.
    Type: Application
    Filed: October 30, 2020
    Publication date: May 6, 2021
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Linyi Gao
  • Publication number: 20210123040
    Abstract: The present disclosure relates to compositions and methods for assessing relative macromolecule abundance (e.g., RNA expression levels) in a spatially-defined manner across a tissue sample, specifically providing deep transcriptomic coverage at high-resolution across multiple locations assessed across the tissue sample.
    Type: Application
    Filed: May 1, 2019
    Publication date: April 29, 2021
    Applicants: THE GENERAL HOSPITAL CORPORATION, THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Evan Macosko, Fei Chen, Sam Rodriques, Robert Stickels, Carly Martin
  • Patent number: 10982278
    Abstract: The present disclosure generally relates to methods and compositions of linking, amplifying, and sequencing nucleic acid molecules. Also disclosed is the use of 5?-5?linked oligonucleotides for linking nucleic acid molecules for sequencing of the ends of long nucleic acid template molecules, or for sequencing polymorphism or different target genes or different RNAs simultaneously.
    Type: Grant
    Filed: April 26, 2018
    Date of Patent: April 20, 2021
    Assignee: THE BROAD INSTITUTE, INC.
    Inventors: Xiaofeng Xin, Robert Nicol
  • Patent number: 10982291
    Abstract: The specification relates generally to methods of detecting, diagnosing, and/or identifying pathogens, e.g., infectious disease pathogens and determining their drug sensitivity and appropriate methods of treatment. This invention also relates generally to methods of monitoring pathogen infection in individual subjects as well as larger populations of subjects.
    Type: Grant
    Filed: July 13, 2018
    Date of Patent: April 20, 2021
    Assignees: THE BROAD INSTITUTE, INC., THE GENERAL HOSPITAL CORPORATION
    Inventors: James Gomez, Deborah Hung, Amy Barczak
  • Patent number: 10981167
    Abstract: Embodiments disclosed herein are directed to microfluidic devices that allow for scalable on-chip screening of combinatorial libraries and methods of use thereof. Droplets comprising individual molecular species to be screened are loaded onto the microfluidic device. The droplets are labeled by methods known in the art, including but not limited to barcoding, such that the molecular species in each droplet can be uniquely identified. The device randomly sorts the droplets into individual microwells of an array of microwells designed to hold a certain number of individual droplets in order to derive combinations of the various molecular species. The paired droplets are then merged in parallel to form merged droplets in each microwell, thereby avoiding issues associated with single stream merging. Each microwell is then scanned, e.g., using microscopy, such as high content imaging microscopy, to detect the optical labels, thereby identifying the combination of molecular species in each microwell.
    Type: Grant
    Filed: March 18, 2016
    Date of Patent: April 20, 2021
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Paul Blainey, Anthony Kulesa, Jared Kehe
  • Publication number: 20210108267
    Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect broth DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. 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: December 20, 2018
    Publication date: April 15, 2021
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Bernd Zetsche, Jonathan Gootenberg, Omar Abudayyeh
  • Patent number: 10968216
    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: October 25, 2017
    Date of Patent: April 6, 2021
    Assignees: BAYER AKTIENGESELLSCHAFT, BAYER PHARMA AKTIENGESELLSCHAFT, 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 Mueller, Sherif El Sheikh, Han Jie Zhou, Changjia Zhao, David B. Sykes, Steven James Ferrara, Kery Liu, Simon Anthony Herbert, Claudia Merz, Michael Niehues, Carl Friedrich Nising, Martina Schäfer, Katja Zimmermann, Jörg Knäblein, Kai Thede, Thomas Faupel
  • Patent number: 10966986
    Abstract: The present invention features improved Compounds, especially (I) 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: Grant
    Filed: February 3, 2017
    Date of Patent: April 6, 2021
    Assignees: 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