Patents Assigned to The Broad Institute
  • Patent number: 11180492
    Abstract: The present disclosure provides compounds of Formula (I?), Formula (II), and Formula (III). The compounds described herein may useful in treating and/or preventing protozoan infections in a subject in need thereof, treating and/or preventing trypanosomal infections (e.g., Trypanosoma cruzi (T. cruzi) or Trypanosoma brucei infections) and/or plasmodial infections in a subject in need thereof, treating and/or preventing diseases in a subject in need thereof (e.g., Chagas disease, malaria, and/or sleeping sickness), and may be useful in treating and/or preventing infectious diseases in a subject in need thereof. Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including a compound described herein.
    Type: Grant
    Filed: January 17, 2017
    Date of Patent: November 23, 2021
    Assignees: University of Central Florida Research Foundation, Inc., The Regents of the University of California, Memorial Sloan-Kettering Cancer Center, The Broad Institute, Inc.
    Inventors: Derek Shieh Tan, Corinne N. Foley, Gustavo Moura-Letts, James McKerrow, Sivaraman Dandapani, Rahul Edwankar, Alyssa Verano, Debopam Chakrabarti, Bracken Roberts
  • Patent number: 11180751
    Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA or RNA-targeting systems comprising a novel DNA or RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.
    Type: Grant
    Filed: December 14, 2017
    Date of Patent: November 23, 2021
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College, Rutgers, the State University of New Jersey, The United States of America, as represented by the Secretary, Department of Health and Human Services, Skolkovo Institute of Science and Technology
    Inventors: Eugene Koonin, Feng Zhang, Yuri I. Wolf, Sergey Shmakov, Konstantin Severinov, Ekaterina Semenova, Leonid Minakhin, Kira S. Makarova, Silvana Konermann, Julia Joung, Jonathan S. Gootenberg, Omar O. Abudayyeh
  • Patent number: 11174515
    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. 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: Grant
    Filed: March 15, 2018
    Date of Patent: November 16, 2021
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College
    Inventors: Omar Abudayyeh, James Joseph Collins, Jonathan Gootenberg, Feng Zhang, Eric S. Lander, Aviv Regev
  • Patent number: 11149267
    Abstract: The present invention generally relates to libraries, kits, methods, applications and screens used in functional genomics that focus on gene function in a cell and that may use vector systems and other aspects related to Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas systems and components thereof. The present invention also relates to rules for making potent single guide RNAs (sgRNAs) for use in CRISPR-Cas systems. Provided are genomic libraries and genome wide libraries, kits, methods of knocking out in parallel every gene in the genome, methods of selecting individual cell knock outs that survive under a selective pressure, methods of identifying the genetic basis of one or more medical symptoms exhibited by a patient, and methods for designing a genome-scale sgRNA library.
    Type: Grant
    Filed: April 28, 2016
    Date of Patent: October 19, 2021
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research
    Inventors: Tim Wang, David Sabatini, Eric Lander
  • Patent number: 11149259
    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. In particular the present invention comprehends the engineering of optimized modular CRISPR-Cas enzyme systems.
    Type: Grant
    Filed: July 1, 2019
    Date of Patent: October 19, 2021
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Feng Zhang, Bernd Zetsche
  • Patent number: 11142522
    Abstract: The present invention features improved compounds, especially the compound having the structure (1). Compositions and methods of identifying patients having cancer using biomarkers (e.g., PDE3A, PDE3B, SLFN12 and/or CREB3L1) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention.
    Type: Grant
    Filed: February 1, 2018
    Date of Patent: October 12, 2021
    Assignees: The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., Bayer Aktiengesellschaft, Bayer Pharma Aktiengesellschaft
    Inventors: Timothy A. Lewis, Xiaoyun Wu, Heidi Greulich, Matthew Meyerson, Manuel Ellermann, Philip Lienau, Knut Eis, Antje Margret Wengner, Charlotte Christine Kopitz, Martin Lange
  • Publication number: 20210292794
    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: Application
    Filed: May 17, 2021
    Publication date: September 23, 2021
    Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College
    Inventors: Feng ZHANG, Chie-yu LIN, Fei RAN
  • Patent number: 11124796
    Abstract: The invention involves inducing 3-50 or more mutations (e.g., any whole number between 3 and 50 of mutations, with it noted that in some embodiments there can be up to 16 different RNA(s), e.g., sgRNAs each having its own a promoter, in a vector, such as AAV, and that when each sgRNA does not have its own promoter, there can be twice to thrice that amount of different RNA(s), e.g., sgRNAs, e.g., 32 or even 48 different guides delivered by one vector) in transgenic Cas9 eukaryotes to model genetic disease, e.g. cancer. The invention comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate a genetic disease or a condition, e.g., cancer.
    Type: Grant
    Filed: March 23, 2017
    Date of Patent: September 21, 2021
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Phillip A. Sharp, Feng Zhang, Randall Jeffrey Platt, Sidi Chen
  • Publication number: 20210277370
    Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences especially for use as to nucleotide repeat disorders. Provided are delivery systems and tissues or organ which are targeted as sites for delivery especially for use as to nucleotide repeat disorders. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex or system especially for use as to nucleotide repeat disorders, as well as methods for the design and of such. Also provided are methods of directing CRISPR complex or system formation in eukaryotic cells especially for use as to nucleotide repeat disorders including with consideration of specificity for target recognition and avoidance of toxicity and editing or modifying a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.
    Type: Application
    Filed: December 1, 2020
    Publication date: September 9, 2021
    Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, University of Iowa Research Foundation
    Inventors: Beverly Davidson, Chie-Yu Lin, Edgardo Rodriguez, Feng Zhang
  • Publication number: 20210277482
    Abstract: The invention provides methods and devices for determining molecular signatures in a cancer that predict response to a MARPK pathway inhibitor and methods of use of such signatures.
    Type: Application
    Filed: March 16, 2021
    Publication date: September 9, 2021
    Applicants: The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc.
    Inventors: Cory M. Johannessen, David J. Konieczkowski, Levi A. Garraway
  • Publication number: 20210277371
    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. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems. In particular the present invention comprehends engineered new guide architectures to be used in optimized CRISPR-Cas enzyme systems.
    Type: Application
    Filed: December 16, 2020
    Publication date: September 9, 2021
    Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College
    Inventors: Fei RAN, Feng ZHANG
  • Publication number: 20210269831
    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: Application
    Filed: April 30, 2021
    Publication date: September 2, 2021
    Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Feng ZHANG, Randall Jeffrey PLATT, Guoping FENG, Yang ZHOU
  • Patent number: 11104937
    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: Grant
    Filed: March 15, 2018
    Date of Patent: August 31, 2021
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College, The General Hospital Corporation
    Inventors: Omar Abudayyeh, James Joseph Collins, Jonathan Gootenberg, Feng Zhang, Eric S. Lander, Roby Bhattacharyya, Deborah Hung
  • Patent number: 11072816
    Abstract: The application relates to proteome analysis in single cells. Specifically, disclosed are high throughput methods of detecting proteins in single cells using barcoding, aptamers and single cell sequencing. Solid supports used in recording the cell-of-origin of target proteins and target proteins expressed in the cell-of-origin are disclosed. Additionally, methods of detecting proteins and mRNA in single cells are disclosed. Additionally, methods of detecting protein interactions are disclosed. Additionally, methods of detecting post translationally modified proteins in single cells are disclosed. The application also relates to solid supports or beads and methods of producing said solid supports or beads for use in the described methods.
    Type: Grant
    Filed: May 3, 2018
    Date of Patent: July 27, 2021
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Jellert Gaublomme, Aviv Regev
  • Patent number: 11060115
    Abstract: The invention 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 CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.
    Type: Grant
    Filed: April 7, 2017
    Date of Patent: July 13, 2021
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College, Rutgers, the State University of New Jersey, Skolkovo Institute of Science and Technology, The United States of America, as represented by the Secretary, Department of Health and Human Services
    Inventors: Konstantin Severinov, Feng Zhang, Yuri I. Wolf, Sergey Shmakov, Ekaterina Semenova, Leonid Minakhin, Kira S. Makarova, Eugene Koonin, Silvana Konermann, Julia Joung, Jonathan S. Gootenberg, Omar O. Abudayyeh, Eric S. Lander
  • Patent number: 11052080
    Abstract: The present invention provides compounds of formula I, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting kinase (e.g., GSK3 (e.g., GSK3? or GSK3?) or CK1) activity. The present invention further provides methods of using the compounds described herein for treating kinase-mediated disorders, such as neurological diseases, psychiatric disorders, metabolic disorders, and cancer.
    Type: Grant
    Filed: November 21, 2018
    Date of Patent: July 6, 2021
    Assignees: The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., The General Hospital Corporation
    Inventors: Florence Fevrier Wagner, Jennifer Q. Pan, Sivaraman Dandapani, Andrew Germain, Edward Holson, Benito Munoz, Partha P. Nag, Michael C. Lewis, Stephen J. Haggarty, Joshua A. Bishop, Kimberly Stegmaier, Michel Weiwer, Versha Banerji
  • Publication number: 20210198330
    Abstract: Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. The disclosure provides fusion proteins of nucleic acid programmable DNA binding proteins (napDNAbp), e.g., Cas9 or variants thereof, and nucleic acid editing proteins such as cytidine deaminase domains (e.g., novel cytidine deaminases generated by ancestral sequence reconstruction), and adenosine deaminases that deaminate adenine in DNA. Aspects of the disclosure relate to fusion proteins (e.g., base editors) that have improved expression and/or localize efficiently to the nucleus. In some embodiments, base editors are codon optimized for expression in mammalian cells. In some embodiments, base editors include multiple nuclear localization sequences (e.g., bipartite NLSs), e.g., at least two NLSs.
    Type: Application
    Filed: May 23, 2019
    Publication date: July 1, 2021
    Applicants: The Broad Institute, Inc., President and Fellows of Harvard College
    Inventors: David R. Liu, Luke W. Koblan, Christopher Gerard Wilson, Jordan Leigh Doman
  • Patent number: 11046952
    Abstract: Embodiments disclosed herein are directed to a new genetic perturbation and screening method that combines advantages of pooled perturbation with imaging assays for complex phenotypes. Specifically, the method may be used to screen pooled genomic perturbations to identify phenotypes and to identify perturbed genes at the single-cell level using optical barcodes. A major advantage offered by this approach is the ability to screen for any cellular phenotype that can be identified by high-resolution microscopy—including live-cell phenotypes, protein localization, or highly multiplexed expression profile and mRNA localization by RNA-FISH—in conjunction with a large array of genetic perturbations applied as a pool in a single test volume.
    Type: Grant
    Filed: March 16, 2016
    Date of Patent: June 29, 2021
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Paul Blainey, David Feldman
  • Patent number: 11021740
    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: Grant
    Filed: March 15, 2018
    Date of Patent: June 1, 2021
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College
    Inventors: Omar Abudayyeh, James Joseph Collins, Jonathan Gootenberg, Feng Zhang, Eric S. Lander
  • Publication number: 20210147425
    Abstract: The present disclosure provides compounds of Formula (I), (II), and (III). The provided compounds are able to bind C protein kinases (e.g., SIK) and may be useful in modulating (e.g., inhibiting) the activity of a protein kinase (e.g., SIK, (e.g., SIK1, SIK2, or SIK3)) in a subject or cell. The provided compounds may be useful in treating or preventing a disease (e.g., proliferative disease, musculoskeletal disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, or metabolic disorder) in a subject in need thereof. Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.
    Type: Application
    Filed: November 20, 2020
    Publication date: May 20, 2021
    Applicants: The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., The General Hospital Corporation
    Inventors: Nathanael S. Gray, Yanke Liang, Hwan Geun Choi, Thomas Sundberg, Alykhan Shamji, Ramnik Xavier, David E. Fisher, Nisma Mujahid