Patents Assigned to THE BROAD INSTITUTE, INC.
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Publication number: 20230405015Abstract: The present invention provides a method of treatment of sarcoma comprising administering to a patient in need thereof a compound of general formula (I), in which R1, R2, R3, and R4, are as defined herein, alone or in pharmaceutical compositions or combinations comprising said compounds as a sole agent or in combination with other active ingredients.Type: ApplicationFiled: August 31, 2023Publication date: December 21, 2023Applicants: Bayer Aktiengesellschaft, The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc.Inventors: Martin LANGE, Stefan KAULFUSS, Charlotte Christine KOPITZ, Heidi GREULICH, Xiaoyun WU, Matthew MEYERSON
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Publication number: 20230399662Abstract: 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: ApplicationFiled: June 30, 2023Publication date: December 14, 2023Applicants: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventor: Feng ZHANG
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Patent number: 11840711Abstract: 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: GrantFiled: April 11, 2018Date of Patent: December 12, 2023Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGYInventors: Feng Zhang, David Benjamin Turitz Cox
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Patent number: 11841371Abstract: The application relates to methods and systems for proteomics and spatial mapping of biomolecules using a next generation sequencing readout to decipher biomolecular and cellular interaction networks. Specifically, disclosed are antenna networks generated by conjugating DNA antennas to proteins. The antennas carry a unique antenna identifier (UAI) sequence that can provide spatial location of the network, as well as biomolecules by transfer of the UAI to reporter oligonucleotides associated with other antennas and biomolecules. The methods and systems are also applicable to single cells.Type: GrantFiled: March 13, 2019Date of Patent: December 12, 2023Assignees: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Aviv Regev, Jellert Gaublomme
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Patent number: 11840495Abstract: The present disclosure relates to compositions and methods related to bicyclo[2.2.1] heptanamine-containing compounds and salts.Type: GrantFiled: December 23, 2021Date of Patent: December 12, 2023Assignees: The Broad Institute, Inc., Instituto Carlos Slim de la Salud, A.C., Brigham and Women's Hospital, Inc.Inventors: Brian T. Chamberlain, David Kornfilt, Florence F. Wagner, Maria Alimova, Anna Greka, Joseph Growney
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Patent number: 11834718Abstract: The present invention relates to methods of determining a cancer treatment prognosis for a subject in need thereof by evaluating epigenetic and genetic changes within a tumor sample from the subject. The present invention further provides methods of treating cancer in a subject by evaluating epigenetic and genetic changes within a tumor sample from the subject. In addition, the present invention provides methods of screening test agents to identify agents that decrease tumor cell plasticity.Type: GrantFiled: September 10, 2020Date of Patent: December 5, 2023Assignees: The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., The General Hospital Corporation, President and Fellows of Harvard CollegeInventors: Mark Kendell Clement, Gad Getz, Dan-Avi Landau, Alexander Meissner, Catherine Ju-Ying Wu
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Publication number: 20230383289Abstract: Compositions and methods are provided herein 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 compositions include 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. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap which is synthesized by the polymerase of the fusion protein and which becomes incorporated into the target DNA molecule.Type: ApplicationFiled: May 31, 2023Publication date: November 30, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Andrew Vito Anzalone, James William Nelson
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Publication number: 20230374527Abstract: The invention provides for 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 eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.Type: ApplicationFiled: April 13, 2023Publication date: November 23, 2023Applicants: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventor: Feng Zhang
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Publication number: 20230374550Abstract: 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: ApplicationFiled: February 6, 2023Publication date: November 23, 2023Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard CollegeInventors: Feng ZHANG, Patrick HSU, Chie-yu LIN, Fei RAN
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Publication number: 20230365950Abstract: 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 SIN CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing SIN 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: ApplicationFiled: February 8, 2023Publication date: November 16, 2023Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, University of Iowa Research FoundationInventors: Feng ZHANG, Beverly DAVIDSON, Chie-Yu LIN, Edgardo RODRIGUEZ
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Publication number: 20230365524Abstract: 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 and prophylaxis of diseases, in particular hyperproliferative disorders, as a sole agent or in combination with other active ingredients.Type: ApplicationFiled: April 20, 2023Publication date: November 16, 2023Applicants: Bayer Aktiengesellschaft, Bayer Pharma Aktiengesellschaft, The Broad Institute, Inc., President and Fellows of Harvard College, The General Hospital CorporationInventors: 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
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Patent number: 11814687Abstract: The present invention features methods for characterizing mutational profiles in patients with bladder cancer.Type: GrantFiled: August 7, 2020Date of Patent: November 14, 2023Assignees: The Broad Institute, Inc., The General Hospital Corporation, Baylor College of Medicine, The Brigham and Women's Hospital, Inc., Northwestern University, The Johns Hopkins University, United States Government as represented by the U.S. Department of Veterans AffairsInventors: Jaegil Kim, Gad Getz, Seth Paul Lerner, David Kwiatkowski, Joshua Meeks, Joaquim Bellmunt, David McConkey
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Publication number: 20230357766Abstract: The disclosure provides modified pegRNAs comprising one or more appended nucleotide structural motifs which increase the editing efficiency during prime editing, increase half-life in vivo, and increase lifespan in a cell. Modifications include, but are not limited to, an aptamer (e.g., prequeosim-1 riboswitch aptamer or “evopreQi-1”) or a variant thereof, a pseudoknot (the MMLV viral genome pseudoknot or “Mpknot-1”) or a variant thereof, a tRNA (e.g., the modified tRNA used by MMLV as a primer for reverse transcription) or a variant thereof, or a G-quadruplex or a variant thereof. The disclosure further provides prime editor complexes comprising the modified pegRNAs and having improved characteristics and/or performance, including stability, improved cellular lifespan, and improved editing efficiency.Type: ApplicationFiled: September 24, 2021Publication date: November 9, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, James William Nelson, Peyton Barksdale Randolph, Andrew Vito Anzalone, Simon Shen, Kelcee Everette, Peter J. Chen
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Patent number: 11807895Abstract: A method for detecting oncogenic growth and viability, and/or degree of cellular transformation and/or identifying an agent that inhibits cellular transformation is disclosed. The method including: providing a cellular sample, such as a sample of cells obtained from a subject or a cell line; culturing the cellular sample in low attachment conditions; and detecting growth and7or cell viability of the sample, wherein increased growth relative and/or viability relative to a control or control level indicative of basal growth and/or viability indicates cellular transformation. In some embodiments, the method includes introducing a n expression vector into cells of the cellular sample, wherein the expression vector comprises a gene product expression sequence being tested for transformation ability. In some embodiments the cellular sample is contacted with a test agent and growth and/or cell viability of the sample is determined to determine if the agent inhibits transformation.Type: GrantFiled: March 24, 2016Date of Patent: November 7, 2023Assignees: THE BROAD INSTITUTE, INC., DANA FARBER CANCER INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE, MASSACHUSETTS INSTITUTE OF TECHNOLOGYInventors: Asaf Rotem, Kevin Struhl, Paul Blainey, Liyi Xu
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Patent number: 11806372Abstract: This application provides for methods of treatment for IBD, especially in subjects who have R. gnavus species or R. gnavus group IBD strains as a component of their microbiome. The application also provides for methods of diagnosing IBD, as well as kits for use in the claimed methods.Type: GrantFiled: April 20, 2018Date of Patent: November 7, 2023Assignees: The Broad Institute, Inc., The General Hospital Corporation, President and Fellows of Harvard CollegeInventors: Andrew Brantley Hall, Ramnik Xavier, Curtis Huttenhower, Moran Yassour, Hera Vlamakis
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Patent number: 11810649Abstract: Embodiments disclosed herein provide methods for identifying new CRISPR loci and effectors, as well as different CRISPR loci combinations found in various organisms. Class-II CRISPR systems contain single-gene effectors that have been engineered for transformative biological discovery and biomedical applications. Discovery of additional single-gene or multi-component CRISPR effectors may enhance existing CRISPR applications, such as precision genome engineering. Comprehensive characterization of CRISPR-loci may identify novel functional roles of CRISPR loci enabling new tools for biomedicine and biological discovery. CRISPR loci have enormous feature complexity, but classification of CRISPR loci has been focused on a small fraction of highly abundant features. Increased genome sequencing has enhanced the sampling of this feature complexity.Type: GrantFiled: August 17, 2017Date of Patent: November 7, 2023Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGYInventors: Feng Zhang, David Arthur Scott
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Publication number: 20230340505Abstract: The invention provides for 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 eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.Type: ApplicationFiled: March 29, 2023Publication date: October 26, 2023Applicants: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventor: Feng Zhang
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Publication number: 20230340467Abstract: Compositions and methods are provided herein 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 compositions include 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. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap which is synthesized by the polymerase of the fusion protein and which becomes incorporated into the target DNA molecule.Type: ApplicationFiled: May 31, 2023Publication date: October 26, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Andrew Vito Anzalone, James William Nelson
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Publication number: 20230340466Abstract: Compositions and methods are provided herein 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 compositions include 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. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap which is synthesized by the polymerase of the fusion protein and which becomes incoporated into the target DNA molecule.Type: ApplicationFiled: May 31, 2023Publication date: October 26, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Andrew Vito Anzalone, James William Nelson
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Publication number: 20230340465Abstract: Compositions and methods are provided herein 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 compositions include 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. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap which is synthesized by the polymerase of the fusion protein and which becomes incorporated into the target DNA molecule.Type: ApplicationFiled: May 31, 2023Publication date: October 26, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Andrew Vito Anzalone, James William Nelson