Patents Assigned to The Broad Institute
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Publication number: 20230027985Abstract: 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: ApplicationFiled: November 12, 2020Publication date: January 26, 2023Applicants: 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
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Publication number: 20230017200Abstract: 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: ApplicationFiled: July 11, 2022Publication date: January 19, 2023Applicants: 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
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Patent number: 11555031Abstract: 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: GrantFiled: March 19, 2018Date of Patent: January 17, 2023Assignees: 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
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Publication number: 20230009323Abstract: 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: ApplicationFiled: October 23, 2020Publication date: January 12, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard College, The University of Vermont and State Agriculture CollegeInventors: Eamon COMER, Bruno MELILLO, Christopher D. HUSTON
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Patent number: 11549149Abstract: 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: GrantFiled: January 23, 2018Date of Patent: January 10, 2023Assignee: The Broad Institute, Inc.Inventor: Edward F. Fritsch
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Publication number: 20230002745Abstract: 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: ApplicationFiled: January 23, 2020Publication date: January 5, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: Yongjoo Kim, David R. Liu, Kevin Tianmeng Zhao
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Patent number: 11535865Abstract: 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: GrantFiled: February 6, 2019Date of Patent: December 27, 2022Assignees: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: David Feldman, Avtar Singh, Paul Blainey
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Patent number: 11530440Abstract: 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: GrantFiled: November 4, 2019Date of Patent: December 20, 2022Assignees: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Paul Blainey, Liyi Xu
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Publication number: 20220396554Abstract: 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: ApplicationFiled: July 14, 2022Publication date: December 15, 2022Applicants: 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
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Publication number: 20220389395Abstract: 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: ApplicationFiled: October 29, 2019Publication date: December 8, 2022Applicants: The Broad Institute, Inc., President anf Fellows of Harvard CollegeInventors: David R. Liu, Yongjoo Kim
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Publication number: 20220380740Abstract: 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: ApplicationFiled: October 24, 2019Publication date: December 1, 2022Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Holly A. Rees
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Publication number: 20220378762Abstract: 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: ApplicationFiled: April 22, 2020Publication date: December 1, 2022Applicants: 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
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Patent number: 11498896Abstract: 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: GrantFiled: March 20, 2020Date of Patent: November 15, 2022Assignees: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Edward Holson, Florence Fevrier Wagner, Michel Weiwer, Edward Scolnick, Michelle Palmer, Luka Dordevic, Michael C. Lewis, Jennifer Q. Pan, Yan-Ling Zhang, Qihong Xu
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Publication number: 20220356469Abstract: 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: ApplicationFiled: March 31, 2021Publication date: November 10, 2022Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Andrew Vito Anzalone, James William Nelson
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Patent number: 11492358Abstract: 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: GrantFiled: February 26, 2021Date of Patent: November 8, 2022Assignees: The Broad Institute, Inc., Bayer Aktiengesellschaft, Bayer Pharma AktiengesellschaftInventors: 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
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Publication number: 20220340557Abstract: 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: ApplicationFiled: November 22, 2021Publication date: October 27, 2022Applicants: 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
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Patent number: 11478451Abstract: 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: GrantFiled: November 15, 2018Date of Patent: October 25, 2022Assignees: 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
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Publication number: 20220313650Abstract: Provided herein are methods for treating a neurodevelopmental disorder using a group II metabotropic glutamate receptor modulator.Type: ApplicationFiled: May 1, 2020Publication date: October 6, 2022Applicants: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Mario Arias Garcia, Guoping Fong, Zhanyan Fu
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Publication number: 20220315906Abstract: 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: ApplicationFiled: May 20, 2020Publication date: October 6, 2022Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Kevin Tianmeng Zhao, Tony P. Huang
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Patent number: 11459557Abstract: 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: GrantFiled: March 23, 2017Date of Patent: October 4, 2022Assignees: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Randall Jeffrey Platt, Feng Zhang, Ian Slaymaker