Patents Assigned to The Broad Institute
  • Publication number: 20230027985
    Abstract: The application relates to substituted hydantoinamides of formula (I) as ADAMTS7 antagonists, to processes for their preparation, their use alone or in combination for the treatment or prophylaxis of diseases, in particular of cardiovascular diseases, including atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), arterial occlusive disease or restenosis after angioplasty. R1 is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, 5- to 6-membered heteroaryl or phenyl; R2 is hydrogen or alkyl; A is 5-membered heteroaryl; Z is 6- to 10-membered aryl or 5- to 10-membered heteroaryl; all groups being optionally substituted.
    Type: Application
    Filed: November 12, 2020
    Publication date: January 26, 2023
    Applicants: Bayer Aktiengesellschaft, The Broad Institute, Inc.
    Inventors: Daniel MEIBOM, Yolanda CANCHO GRANDE, Pierre WASNAIRE, Sarah Anna Liesa JOHANNES, Niels LINDNER, Kristin BEYER, Till FREUDENBERGER, Damian BROCKSCHNIEDER, Ilka MATHAR, Jürgen KLAR, Dmitry ZUBOV, Dzianis MENSHYKAU, Tanja KRAINZ, Eric STEFAN, Bryan MACDONALD, Yi XING, Nadine ELOWE, Guzman SANCHEZ
  • Publication number: 20230017200
    Abstract: The present invention provides dihydrooxydiazinone compounds of general formula (I): in which R1, R2, R3, and R4, 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 diseases, as a sole agent or in combination with other active ingredients.
    Type: Application
    Filed: July 11, 2022
    Publication date: January 19, 2023
    Applicants: Bayer Aktiengesellschaft, Bayer Pharma Aktiengesellschaft, The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc.
    Inventors: Manuel ELLERMANN, Stefan Nikolaus GRADL, Charlotte Christine KOPITZ, Martin LANGE, Adrian TERSTEEGEN, Philip LIENAU, Christa HEGELE-HARTUNG, Detlev SÜLZLE, Timothy A. LEWIS, Heidi GREULICH, Xiaoyun WU, Matthew MEYERSON, Alex BURGIN
  • Patent number: 11555031
    Abstract: Disclosed herein are methods for inducing insulin secretion in a glucose-dependent manner and compounds for use in these methods. The compounds may have the structure of formula I(a): wherein the substituents are as described in the description; or a pharmaceutically acceptable form thereof.
    Type: Grant
    Filed: March 19, 2018
    Date of Patent: January 17, 2023
    Assignees: The Broad Institute, Inc., The General Hospital Corporation, Instituto Carlos Slim de la Salud, A.C.
    Inventors: Sean M. Burns, Bridget K. Wagner, Amedeo Vetere
  • Publication number: 20230009323
    Abstract: Cryptosporidium is a leading contributor to early childhood mortality, and fully effective treatment for this important infectious disease is lacking. A bicyclic azetidine compound series is disclosed having potent in vitro activity against all C. parvum isolates tested, comparable potencies against C. hominis and C. parvum, and cured cryptosporidiosis in highly susceptible immunosuppressed mice with once-daily dosing.
    Type: Application
    Filed: October 23, 2020
    Publication date: January 12, 2023
    Applicants: The Broad Institute, Inc., President and Fellows of Harvard College, The University of Vermont and State Agriculture College
    Inventors: Eamon COMER, Bruno MELILLO, Christopher D. HUSTON
  • Patent number: 11549149
    Abstract: In one aspect, the invention features a combination of oligonucleotides comprising a forward primer oligonucleotide and a blocking oligonucleotide. The forward primer oligonucleotide has a 3? end region, where the 3? end region includes a portion complementary to a mutation positioned in a region within a polynucleotide. The blocking oligonucleotide contains a blocking moiety and has a 5? end region, where the 5? end region includes a portion complementary to a wild-type sequence of the region corresponding to the position of the mutation. In other aspects, the invention provides kits including the combination of primer oligonucleotides and methods of using the oligonucleotides to detect a mutation in a polynucleotide.
    Type: Grant
    Filed: January 23, 2018
    Date of Patent: January 10, 2023
    Assignee: The Broad Institute, Inc.
    Inventor: Edward F. Fritsch
  • Publication number: 20230002745
    Abstract: Provided herein are compositions, systems, and methods for delivering an effector protein into a cell. The present disclosure, in some aspects, provide novel proteins delivering an effector protein into a cell. The novel proteins are supernegatively charged proteins derived from highly anionic proteins identified from the proteome (e.g., human proteome). The novel protein tags can be associated (e.g., covalently or nocovalently) with the protein to be delivered to facilitate delivery of the effector protein into a cell.
    Type: Application
    Filed: January 23, 2020
    Publication date: January 5, 2023
    Applicants: The Broad Institute, Inc., President and Fellows of Harvard College
    Inventors: Yongjoo Kim, David R. Liu, Kevin Tianmeng Zhao
  • Patent number: 11535865
    Abstract: The subject matter disclosed herein is generally directed to methods and compositions for stable transduction of target cells with libraries of genetic elements. The invention reduces intermolecular recombination between library elements and integration of multiple genetic elements.
    Type: Grant
    Filed: February 6, 2019
    Date of Patent: December 27, 2022
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: David Feldman, Avtar Singh, Paul Blainey
  • Patent number: 11530440
    Abstract: The present invention relates to methods of quantifying, amplifying, or preparing nucleic acid molecules, where the methods involve contacting a sample to be tested with nucleic acid molecule amplification reaction components and a label to form a reaction sample. The methods further involve partitioning the reaction sample into droplets or a gel and allowing nucleic acid molecule amplification to occur.
    Type: Grant
    Filed: November 4, 2019
    Date of Patent: December 20, 2022
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Paul Blainey, Liyi Xu
  • Publication number: 20220396554
    Abstract: The present invention provides dihydrooxydiazinone compounds of general formula (I) in which R1, R2, R3, and R4, 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 diseases, as a sole agent or in combination with other active ingredients.
    Type: Application
    Filed: July 14, 2022
    Publication date: December 15, 2022
    Applicants: Bayer Aktiengesellschaft, Bayer Pharma Aktiengesellschaft, The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc.
    Inventors: Manuel ELLERMANN, Stefan Nikolaus GRADL, Charlotte Christine KOPITZ, Martin LANGE, Adrian TERSTEEGEN, Philip LIENAU, Christa HEGELE-HARTUNG, Detlev SÜLZLE, Timothy A. LEWIS, Heidi GREULICH, Xiaoyun WU, Matthew MEYERSON, Alex BURGIN
  • Publication number: 20220389395
    Abstract: Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids or the modification of nucleic acids or proteins, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of nucleic acid programmable DNA binding proteins e.g., GeoCas9 or variants thereof, and effector domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing or protein modification are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of a GeoCas9 and effector domains, are provided.
    Type: Application
    Filed: October 29, 2019
    Publication date: December 8, 2022
    Applicants: The Broad Institute, Inc., President anf Fellows of Harvard College
    Inventors: David R. Liu, Yongjoo Kim
  • Publication number: 20220380740
    Abstract: The invention provides an improved genome editing construct which is capable of editing a target sequence in an HDR-dependent manner (i.e., “HDR-dependent genome editors”) with increased efficiency and reduced indel formation and which does not require a dividing cell. In particular, the instant specification provides a new fusion protein comprising a nucleic acid programmable DNA binding protein (napDNAbp) (e.g., Cas9) with a nickase activity and a single-stranded DNA binding protein (e.g., Rad51) which edits a target DNA in an HDR-dependent manner with greater efficiency (e.g., increased rate of induced HDR) and/or with a lower rate or occurrence of indel formation.
    Type: Application
    Filed: October 24, 2019
    Publication date: December 1, 2022
    Applicants: The Broad Institute, Inc., President and Fellows of Harvard College
    Inventors: David R. Liu, Holly A. Rees
  • Publication number: 20220378762
    Abstract: Compounds of formula (I) for use in the treatment or prophylaxis of a disease, which is a hyperproliferative disease and/or a disorder responsive to induction of cell death, selected from a haematological tumour, a solid tumour and/or metastases thereof, said tumour harbouring a mutant EGFR with exon 19 or 21 mutations, and their use as pharmaceuticals.
    Type: Application
    Filed: April 22, 2020
    Publication date: December 1, 2022
    Applicants: Bayer Aktiengesellschaft, The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc.
    Inventors: Franziska SIEGEL, Daniel KORR, Jens SCHRÖDER, Stephan SIEGEL, Heidi GREULICH, Bethany KAPLAN, Matthew MEYERSON
  • Patent number: 11498896
    Abstract: The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity.
    Type: Grant
    Filed: March 20, 2020
    Date of Patent: November 15, 2022
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Edward Holson, Florence Fevrier Wagner, Michel Weiwer, Edward Scolnick, Michelle Palmer, Luka Dordevic, Michael C. Lewis, Jennifer Q. Pan, Yan-Ling Zhang, Qihong Xu
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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