Patents Assigned to THE BROAD INSTITUTE, INC.
  • METHODS AND COMPOSITIONS FOR EDITING NUCLEOTIDE SEQUENCES METHODS AND COMPOSITIONS FOR EDITING NUCLEOTIDE SEQUENCES
    Publication number: 20220356469
    Abstract: The present disclosure provides compositions and methods for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The nucleotide change can include a single-nucleotide change (e.g., any transition or any transversion), an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA.
    Type: Application
    Filed: March 31, 2021
    Publication date: November 10, 2022
    Applicants: The Broad Institute, Inc., President and Fellows of Harvard College
    Inventors: David R. Liu, Andrew Vito Anzalone, James William Nelson
  • Macrocyclic indole derivatives
    Patent number: 11492358
    Abstract: The present invention relates to macrocyclic indole derivatives of general formula (I) in which R1, R2, R3, R4, R5, R6, A and L 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: February 26, 2021
    Date of Patent: November 8, 2022
    Assignees: The Broad Institute, Inc., Bayer Aktiengesellschaft, Bayer Pharma Aktiengesellschaft
    Inventors: Sarah Anna Liesa Johannes, Philipp Buchgraber, Ulrich Klar, Clara Christ, Kai Thede, Joachim Kuhnke, Manfred Moewes, Knut Eis, Amaury Ernesto Fernandez-Montalvan, Nicolas Werbeck, Ursula Mönning, Philip Lienau, Ulrike Sack, Arne Scholz, Michael H. Serrano-Wu, Christopher Lemke, David McKinney, Mark Fitzgerald, Christopher Nasveschuk, Kiel Lazarski, Steven James Ferrara, Laura Furst, Guo Wei, Patrick Ryan McCarren
  • Compositions and methods for targeting cancer-specific sequence variations
    Patent number: 11492670
    Abstract: The present invention relates to compositions and methods for targeting cancer-specific DNA sequences, such as copy number amplifications and other types of cancer-specific sequence variations, such as cancer-specific polymorphisms, insertions, or deletions. The present invention provides hereto sequence-specific DNA targeting agents targeting a sequence within the amplified DNA region or a sequence otherwise specific for a cancer cell compared to a non-cancer cell. The invention further relates to methods for treating cancer, comprising administering such sequence-specific DNA targeting agents. The invention further relates to methods for preparing sequence-specific DNA targeting agent, as well as screening methods using the DNA targeting agents.
    Type: Grant
    Filed: October 20, 2016
    Date of Patent: November 8, 2022
    Assignees: THE BROAD INSTITUTE INC., DANA-FARBER CANCER INSTITUTE, INC., INSTITUTO CARLOS SLIM DE LA SALUD, A.C.
    Inventors: William C. Hahn, Andrew Aguirre, April Cook, Glenn Cowley, Robin Meyers, David E. Root, Aviad Tsherniak, Barbara Weir, Francisca Vazquez
  • PROGRAMMABLE POLYNUCLEOTIDE EDITORS FOR ENHANCED HOMOLOGOUS RECOMBINATION
    Publication number: 20220340936
    Abstract: An engineered system for modulating a nucleic acid molecule. In some examples, the system comprises a programmable inducer of DNA damage; one or more functional domain such as a reverse transcriptase domain, topoisomerase domain and/or polymerase domain; a recombination enhancer domain; and an RNA template encoding a donor polynucleotide and capable of forming a complex with the RT domain.
    Type: Application
    Filed: September 28, 2020
    Publication date: October 27, 2022
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Jonathan Schmid-Burgk, Suchita Nety
  • ANTI-PARASITIC COMPOUNDS AND USES THEREOF
    Publication number: 20220340557
    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: Application
    Filed: November 22, 2021
    Publication date: October 27, 2022
    Applicants: Memorial Sloan-Kettering Cancer Center, The Regents of the University of California, University of Central Florida Research Foundation, Inc., 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
  • RAPID PREDICTION OF DRUG RESPONSIVENESS
    Publication number: 20220340976
    Abstract: The present disclosure relates to compositions and methods for rapid prediction, based upon early single cell transcriptomic assessment of a biopsied sample obtained from a subject, of whether a subject will be responsive to a drug.
    Type: Application
    Filed: September 1, 2020
    Publication date: October 27, 2022
    Applicants: THE BROAD INSTITUTE, INC., DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Andrew J. Aguirre, Francisca Vazquez, Aviad Tsherniak, James McFarland, Brenton Paolella
  • Macrocyclic chlorine substituted indole derivatives
    Patent number: 11478451
    Abstract: The present invention relates to macrocyclic indole derivatives of general formula (I): in which R1, R2, R3, R4, R5, R6, A and L 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: November 15, 2018
    Date of Patent: October 25, 2022
    Assignees: Bayer Aktiengesellschaft, Bayer Pharma Aktiengesellschaft, The Broad Institute, Inc.
    Inventors: Kai Thede, Anne Mengel, Clara Christ, Joachim Kuhnke, Sarah Anna Liesa Johannes, Philipp Buchgraber, Ulrich Klar, Ulrike Rauh, Stefan Kaulfuss, Amaury Ernesto Fernandez-Montalvan, Nicolas Werbeck, Ursula Moenning, Katrin Nowak-Reppel, Chris Lemke, Michael H. Serrano-Wu, David McKinney, Mark Fitzgerald, Christopher Nasveschuk, Kiel Lazarski, Steven J. Ferrara, Laura Furst, Guo Wei, Patrick R. McCarren, Rebecca Ann Harvey, Daniel Payne, Thomas Pesnot, Craig Wilson
  • Methods for genome characterization
    Patent number: 11479878
    Abstract: The invention provides methods of using low coverage sequencing to assess the relative fraction of tumor versus normal DNA in a sample, and to assess copy number alterations present in the sample.
    Type: Grant
    Filed: March 16, 2017
    Date of Patent: October 25, 2022
    Assignees: DANA-FARBER CANCER INSTITUTE, INC., THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Gavin Ha, Viktor Adalsteinsson, Samuel Freeman
  • CRISPR EFFECTOR SYSTEM BASED MULTIPLEX CANCER DIAGNOSTICS
    Publication number: 20220333208
    Abstract: Systems and methods for rapid diagnostics related to the use of CRISPR effector systems and optimized guide sequences, including multiplex lateral flow diagnostic devices and methods of use, including for detection of cancer markers, are provided.
    Type: Application
    Filed: September 3, 2020
    Publication date: October 20, 2022
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Jonathan Gootenberg, Omar Abudayyeh, Jeremy Koob, Rahul Vedula, Coleman Lindsley, Feng Zhang
  • Compositions and methods for detecting and treating diabetes
    Patent number: 11471462
    Abstract: The invention features compositions and methods that are useful for increasing the level or activity of SLC16A11 in a subject, there by treating or preventing type 2 diabetes in the subject.
    Type: Grant
    Filed: June 27, 2017
    Date of Patent: October 18, 2022
    Assignees: THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Eitan Hoch, Suzanne Beth Rosenberg Jacobs, Victor Rusu, Liping Zhao, Jose M. Mercader Bigas
  • CRISPR EFFECTOR SYSTEM BASED CORONAVIRUS DIAGNOSTICS
    Publication number: 20220325334
    Abstract: Systems and methods for rapid diagnostics related to the use of CRISPR effector systems and optimized guide sequences for detection of coronavirus, including multiplex lateral flow diagnostic devices and methods of use, are provided.
    Type: Application
    Filed: April 27, 2022
    Publication date: October 13, 2022
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Jonathan Gootenberg, Omar Abudayyeh, Julia Joung, Alim Ladha, Han Altae-Tran, Guilhem Faure
  • HETEROLOGOUS RIBOSOME GENERATION, ASSESSMENT AND COMPOSITIONS THEREOF
    Publication number: 20220315934
    Abstract: The present disclosure relates to compositions and methods that enable enhanced monitoring and improvement of heterologous ribosome activity within a host cell. Specifically, the instant disclosure provides a reporter system that allows for improved monitoring of heterologous ribosome activity in a host cell, via engineering of both heterologous rRNA operon sequences and reporter operon sequences. New transgenic organisms harboring heterologous ribosome operons are also provided, as are methods for identifying agents capable of targeting heterologous ribosomes (e.g., ribosomes of pathogenic organisms, optionally selectively as compared to ribosomes of, e.g., commensal organisms) within a host cell.
    Type: Application
    Filed: July 14, 2020
    Publication date: October 6, 2022
    Applicant: THE BROAD INSTITUTE, INC.
    Inventors: Ahmed H. Badran, Natalie Kolber
  • METHODS FOR TREATING NEURODEVELOPMENTAL DISORDERS
    Publication number: 20220313650
    Abstract: Provided herein are methods for treating a neurodevelopmental disorder using a group II metabotropic glutamate receptor modulator.
    Type: Application
    Filed: May 1, 2020
    Publication date: October 6, 2022
    Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Mario Arias Garcia, Guoping Fong, Zhanyan Fu
  • BASE EDITORS WITH DIVERSIFIED TARGETING SCOPE
    Publication number: 20220315906
    Abstract: The present disclosure provides improved adenosine base editors (ABE) that have an expanded range of PAM sequence recognition capability (i.e., recognition of non-canonical ?5-NGG-?3 PAM sequence). In addition, the present disclosure provides improved cytidine base editors (CBE) and adenosine base editors (ABE) comprising circular permutant variants of Cas9 (CP-Cas9) with an increased window of base editing within the protospacer sequence (e.g., from about 4-5 nucleotides to up to about 8-9 nucleotides) and even outside of the protospacer sequence.
    Type: Application
    Filed: May 20, 2020
    Publication date: October 6, 2022
    Applicants: The Broad Institute, Inc., President and Fellows of Harvard College
    Inventors: David R. Liu, Kevin Tianmeng Zhao, Tony P. Huang
  • Use and production of CHD8+/? transgenic animals with behavioral phenotypes characteristic of autism spectrum disorder
    Patent number: 11459557
    Abstract: Methods and compositions for inducing a plurality of mutations in transgenic Cas9 eukaryotes to model a neuronal disease or disorder. The invention further 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., autism, autism-spectrum disease or disorder, obsessive-compulsive disorder, or psychiatric disorders.
    Type: Grant
    Filed: March 23, 2017
    Date of Patent: October 4, 2022
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Randall Jeffrey Platt, Feng Zhang, Ian Slaymaker
  • IN SILICO DISCOVERY OF EFFECTIVE ANTIMICROBIALS
    Publication number: 20220310198
    Abstract: The present disclosure relates to antimicrobial compositions, particularly to antibiotic compositions; to methods for identification of antimicrobial compositions involving in silico prediction of antimicrobial activity; and to use of antimicrobial compositions and methods.
    Type: Application
    Filed: September 9, 2020
    Publication date: September 29, 2022
    Applicants: MASSACHUSETTS INSTITUTE OF TECHOLOGY, THE BROAD INSTITUTE, INC.
    Inventors: James Collins, Regina Barzilay, Jonathan Stokes, Ian Andrews, Daniel Collins
  • USES OF SALT-INDUCIBLE KINASE (SIK) INHIBITORS FOR TREATING OSTEOPOROSIS
    Publication number: 20220305016
    Abstract: The present disclosure provides methods of treating and/or preventing osteoporosis using salt-inducible kinase (SIK) inhibitors. Also provided are methods of using SIK inhibitors for increasing the function of osteocytes, increasing the number of osteoblasts, increasing the activity of osteoblasts, inhibiting the resorption of a bone, decreasing the number of osteoclasts, inhibiting the activity of osteoclasts, increasing the mass of a bone, down-regulating the expression of the gene SOST, and/or inhibiting the activity of sclerostin. The SIK inhibitors may be combined with Src inhibitors or CSF I R inhibitors. Exemplary SIK inhibitors include the compounds of the formula: (I), (II), (III), (IV), (V) or (VI).
    Type: Application
    Filed: January 21, 2022
    Publication date: September 29, 2022
    Applicants: The General Hospital Corporation, The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc.
    Inventors: Marc Wein, Henry Kronenberg, Thomas Sundberg, Ramnik Xavier, Nathanael S. Gray, Yanke Liang, Hwan Geun Choi, Alykhan Shamji
  • ADENINE BASE EDITORS WITH REDUCED OFF-TARGET EFFECTS
    Publication number: 20220307003
    Abstract: The present disclosure provides novel adenine base editors that retain ability to edit DNA efficiently but show greatly reduced off-target effects, such as reduced RNA editing activity, as well as lower off-target DNA editing activity and reduced indel by product formation. Also provided are base editing methods comprising contacting a nucleic acid molecule with an adenine base editor and a guide RNA that has complementarity to a target sequence. Further provided are complexes comprising a guide RNA bound to a base editor provided herein; and kits and pharmaceutical compositions for the administration of adenine base editor variants to a host cell.
    Type: Application
    Filed: April 16, 2020
    Publication date: September 29, 2022
    Applicants: The Broad Institute, Inc., President and Fellows of Harvard College
    Inventors: David R. Liu, Holly A. Rees
  • Crispr effector system based coronavirus diagnostics
    Patent number: 11453907
    Abstract: Systems and methods for rapid diagnostics related to the use of CRISPR effector systems and optimized guide sequences for detection of coronavirus, including multiplex lateral flow diagnostic devices and methods of use, are provided.
    Type: Grant
    Filed: June 5, 2020
    Date of Patent: September 27, 2022
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Jonathan Gootenberg, Omar Abudayyeh, Julia Joung, Alim Ladha, Han Altae-Tran, Guilhem Faure
  • Combination therapy with neoantigen vaccine
    Patent number: 11452768
    Abstract: The present invention relates to neoplasia vaccine or immunogenic composition administered in combination with other agents, such as checkpoint blockade inhibitors for the treatment or prevention of neoplasia in a subject.
    Type: Grant
    Filed: December 19, 2014
    Date of Patent: September 27, 2022
    Assignees: The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., The General Hospital Corporation
    Inventors: Nir Hacohen, Catherine J. Wu, Edward F. Fritsch