Patents Assigned to BROAD INSTITUTE
  • Publication number: 20200199555
    Abstract: The present disclosure generally relates to systems, methods and compositions related to Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and components thereof. The present disclosure also relates to methods, systems, and compostions modified to reduce immunogenicity. Additionally, the present disclosure relates to methods for developing or designing CRISPR-Cas system based therapy or therapeutics.
    Type: Application
    Filed: December 5, 2019
    Publication date: June 25, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventor: Feng Zhang
  • Patent number: 10689691
    Abstract: The invention provides for systems, methods, compositions, and kits for the complete characterization of targeted nuclease specificity which necessitates techniques that can assess the full possibility space of off-target activity and genomic stability following genome editing. Also provided are the materials and techniques which enable the comprehensive genomic stability accompanying a range of cellular perturbations, including genome editing (ZFN, TALEN, CRISPR, and future technologies) and disease modeling among other applications.
    Type: Grant
    Filed: June 19, 2017
    Date of Patent: June 23, 2020
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Winston Yan, David A. Scott, Aaron Smargon, Mohammed Reza Mirzazadeh, Nicola Crosetto
  • Publication number: 20200190487
    Abstract: The present application provides systems, methods and compositions used for targeted gene modification, targeted insertion, perturbation of gene transcripts, nucleic acid editing. Novel nucleic acid targeting systems comprise components of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) systems and transposable elements.
    Type: Application
    Filed: December 17, 2019
    Publication date: June 18, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Jonathan Strecker, Alim Ladha
  • Publication number: 20200181210
    Abstract: The present invention relates to cyclic peptide structures possessing the ability to incorporate and deliver peptides of sizable length (e.g., peptides of twenty amino acid residues or more in length), while retaining properties of cyclic peptides and/or cyclotides, including, e.g., protease resistance, heat resistance, resistance to low pH, etc. Methods for preparing cyclic peptide compositions, assessing the extent of cyclization within a peptide population, as well as methods for using cyclic peptide compositions are also provided.
    Type: Application
    Filed: April 26, 2018
    Publication date: June 11, 2020
    Applicant: THE BROAD INSTITUTE, INC.
    Inventors: Robert Nicol, Ritika Dwivedi
  • Publication number: 20200181720
    Abstract: Provided herein is a nucleic acid detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind to corresponding target molecules; an RNA-based masking construct; and optionally, nucleic acid amplification reagents to amplify target RNA molecules in a sample. In another aspect, the embodiments provide a polypeptide detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind a trigger RNA, an RNA-based masking construct; and one or more detection aptamers comprising a masked RNA polymerase promoter binding site or a masked primer binding site. In some embodiments, the system may be used to detect viruses in samples.
    Type: Application
    Filed: March 15, 2018
    Publication date: June 11, 2020
    Applicants: 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, Pardis SABETI, Catherine Amanda FREIJE, Cameron MYHRVOLD
  • Publication number: 20200179534
    Abstract: The present disclosure provides compositions and methods for the treatment of PPARG activated cancer. For example, the present disclosure provides PPARG signaling modulators for the treatment of bladder cancer. In particular, therapeutic and/or prophylactic compositions and uses of PPARG inverse-agonists are described.
    Type: Application
    Filed: March 28, 2018
    Publication date: June 11, 2020
    Applicants: THE BROAD INSTITUTE, INC., DANA-FARBER CANCER INSTITUTE, INC
    Inventors: Jonathan Goldstein, Matthew Meyerson, Craig Strathdee
  • Publication number: 20200165594
    Abstract: The present invention offers a new approach for highly multiplexed, programmable antiviral therapies that directly target viral RNA, and can be flexibly adapted to target novel viruses or emerging outbreak pathogens. Class 2, type VI CRISPR system-based therapies can be used in combination with existing antiviral compounds for viruses where such compounds exist, either by increasing their efficacy or by preventing the evolution of specific drug resistance mutations. Perhaps most excitingly, if a virus evolves resistance to a specific guide RNA sequence, it is easy to switch to a different guide RNA sequence, or to design a new guide sequence to target the new mutation. Such approaches should prevent the widespread development of resistance to Class 2, type VI CRISPR system-based therapies.
    Type: Application
    Filed: July 6, 2018
    Publication date: May 28, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Jonathan S. Gootenberg, Omar O. Abudayyeh, Pardis Sabeti, Cameron Myhrvold, Catherine Amanda Freije
  • Patent number: 10654852
    Abstract: The present invention includes novel 3,6-diazabicyclo[3.1.1]heptane antibiotic compounds and any salts or solvates thereof. The present invention further includes methods of preparing such compounds, and methods of treating bacterial infection in a subject using such compounds.
    Type: Grant
    Filed: October 20, 2017
    Date of Patent: May 19, 2020
    Assignee: THE BROAD INSTITUTE, INC.
    Inventor: Joseph P. Vacca
  • Patent number: 10655173
    Abstract: The present invention relates to molecular microscopy or volumetric imaging by proximal unique molecular identifiers (“UID”) reaction (“VIPUR”) microscopy methods to record the cellular co-localization and/or spatial distributions of arbitrary nucleic acid sequences, or other biomolecules tagged with nucleic sequences. The method involves one or both of two DNA sequence-components such as an ?-UID, which may identify the targeted sequences-of-interest themselves and/or spatial beacons relative to which their distances are measured, and a- ?-UID, which labels ?-UID association events.
    Type: Grant
    Filed: October 17, 2014
    Date of Patent: May 19, 2020
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Joshua Asher Weinstein, Aviv Regev
  • Patent number: 10648020
    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: December 17, 2017
    Date of Patent: May 12, 2020
    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
  • Publication number: 20200123129
    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: October 25, 2017
    Publication date: April 23, 2020
    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: 10612088
    Abstract: A method for parallel sequencing target RNA from samples from multiple sources while maintaining source identification is provided. The method includes providing samples of RNA comprising target RNA from two or more sources; labeling, at the 3? end, the RNA from the two or more sources with a first nucleic acid adaptor that comprises a nucleic acid sequence that differentiates between the RNA from the two or more sources; reverse transcribing the two or more sources to create a single stranded DNA comprising the nucleic acid sequence that differentiates between the RNA from the two or more sources; amplifying the single stranded DNA to create DNA amplification products that comprise the nucleic acid sequence that differentiates between the RNA from the two or more sources; sequencing the DNA amplification products thereby parallel sequencing target RNA from samples from multiple sources while maintaining source identification.
    Type: Grant
    Filed: March 14, 2014
    Date of Patent: April 7, 2020
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Alexander A. Shishkin, Mitchell Guttman, Christine F. Surka, Eric S. Lander
  • Publication number: 20200095253
    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: Application
    Filed: March 20, 2018
    Publication date: March 26, 2020
    Applicants: THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: EAMON COMER, NOBUTAKA KATO, MARSHALL MORNINGSTAR, BRUNO MELILLO
  • Patent number: 10590473
    Abstract: Provided are systems, kits, and methods for the quantitative detection of single nucleotide polymorphisms or variants to identify malignant neoplasms. The methods include use of modified oligonucleotide blockers with peptide nucleic acid backbones that hybridize to and block logarithmic amplification of the wild-type alleles of a target, and incorporation of locked nucleic acids into probes that are complementary to a mutant allele of the target sequence to increase specificity. The methods include detection of variants in sequences with high GC content and/or low complexity, such as the TERT promoter, IDH1, BRAF, NRAS, GNAQ, GNA11 and H3F3 A gene variants. The methods include sensitive detection and staging of cancers with low cellularity, and can be used intraoperatively such as for glioma, or to detect cell-free circulating tumor DNA, such as for melanoma.
    Type: Grant
    Filed: December 22, 2015
    Date of Patent: March 17, 2020
    Assignees: THE BROAD INSTITUTE, INC., DANA-FARBER CANCER INSTITUTE, INC., THE GENERAL HOSPITAL CORPORATION
    Inventors: Matthew Meyerson, Ganesh M. Shankar, Joshua M. Francis, Daniel P. Cahill, Mikael L. Rinne
  • Publication number: 20200080112
    Abstract: Embodiments disclosed herein are directed to engineered CRISPR-Cas effector proteins that comprise at least one modification compared to an unmodified CRISPR-Cas effector protein that enhances binding of the of the CRISPR complex to the binding site and/or alters editing preference as compared to wild type. In certain example embodiments, the CRISPR-Cas effector protein is a Type V effector protein. In certain other example embodiments, the Type V effector protein is Cpf1. Embodiments disclosed herein are directed to viral vectors for delivery of CRISPR-Cas effector proteins, including Cpf1. In certain example embodiments, the vectors are designed so as to allow packaging of the CRISPR-Cas effector protein within a single vector. There is also an increased interest in the design of compact promoters for packing and thus expressing larger transgenes for targeted delivery and tissue-specificity.
    Type: Application
    Filed: August 17, 2017
    Publication date: March 12, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng ZHANG, David Arthur SCOTT, Winston Xia YAN, Sourav CHOUDHURY, Matthias HEIDENREICH
  • Patent number: 10577630
    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: December 16, 2015
    Date of Patent: March 3, 2020
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Le Cong, Fei Ran
  • Publication number: 20200062741
    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: Application
    Filed: February 1, 2018
    Publication date: February 27, 2020
    Applicants: 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: 20200018746
    Abstract: Described herein are tissue cultures and methods for culturing stem-cell derived neurons in three-dimensional culture. Also provided are methods for screening therapeutic agents, developing cell line models, identifying genes associated with a neurological disease, and identifying genes associated with neuronal cell phenotypes.
    Type: Application
    Filed: September 26, 2019
    Publication date: January 16, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Halil TEKIN, Feng ZHANG
  • Publication number: 20190375747
    Abstract: The present invention provides triazolone compounds 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: October 25, 2017
    Publication date: December 12, 2019
    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: 20190365770
    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: Application
    Filed: February 3, 2017
    Publication date: December 5, 2019
    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, PHILLIP LIENAU, ULRIKE SACK, MARTIN LANGE