Patents Assigned to THE BROAD INSTITUTE, INC.
-
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
-
Patent number: 11795452Abstract: 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 a 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: GrantFiled: May 23, 2022Date of Patent: October 24, 2023Assignees: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Andrew Vito Anzalone
-
Patent number: 11793787Abstract: The subject matter disclosed herein is generally directed to modulating anti-tumor T cell immunity by modulating steroidogenesis. Steroidogenesis may be modulated with inhibitors of enzymes that synthesize glucocorticoids in a tumor. The inhibitor may target Cyp11a1. The inhibitor may be metyrapone. The invention further relates to modulating immune states, such as CD8 T cell immune states, in vivo, ex vivo and in vitro. The invention further relates to diagnostic and screening methods.Type: GrantFiled: October 7, 2020Date of Patent: October 24, 2023Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, The Brigham and Women's Hospital, Inc.Inventors: Ana Carrizosa Anderson, Asaf Madi, Nandini Acharya, Vijay K. Kuchroo, Aviv Regev
-
Patent number: 11795443Abstract: The disclosure provides methods and compositions for treating blood diseases/disorders, such as sickle cell disease, hemochromatosis, hemophilia, and beta-thalassemia. For example the disclosure provides therapeutic guide RNAs that target the promotor of HBG1/2 to generate point mutations that increase expression of fetal hemoglobin. As another example, the disclosure provides therapeutic guide RNAs that target mutations in HBB, Factor VIII, and HFE to treat sickle cell disease, beta-thalassemia, hemophilia and hemochromatosis. The disclosure also provides fusion proteins comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA. In some embodiments, the fusion proteins are in complex with nucleic acids, such as guide RNAs (gRNAs), which target the fusion proteins to a DNA sequence (e.g., an HBG1 or HBG2 protmoter sequence, or an HFE, GBB, or F8 gene sequence).Type: GrantFiled: October 16, 2018Date of Patent: October 24, 2023Assignees: The Broad Institute, Inc., President and Fellows of Harvard College, Beam Therapeutics, Inc.Inventors: David R. Liu, Nicole Marie Gaudelli, Michael S. Packer, Gregory Newby
-
Publication number: 20230332144Abstract: 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 a 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 24, 2023Publication date: October 19, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Andrew Vito Anzalone, Gregory Newby, Kelcee Everette
-
Patent number: 11787797Abstract: 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: GrantFiled: January 28, 2021Date of Patent: October 17, 2023Assignees: 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 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
-
Patent number: 11785925Abstract: The present invention features a knock-in mouse comprising a mutation in an endogenous CRBN locus and methods of use thereof.Type: GrantFiled: May 10, 2019Date of Patent: October 17, 2023Assignees: THE BROAD INSTITUTE, INC., THE BRIGHAM AND WOMEN'S HOSPITAL, INC.Inventors: Benjamin Levine Ebert, Jan Krönke, Steven A. Carr, Namrata D. Udeshi, Emma Fink
-
Patent number: 11788083Abstract: 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: June 19, 2017Date of Patent: October 17, 2023Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard CollegeInventors: Feng Zhang, Omar O. Abudayyeh, Jonathan Gootenberg, Eric S. Lander
-
Patent number: 11788135Abstract: As described below, disclosed herein are methods of analyzing DNA methylation in cell-free DNA (cfDNA) and genomic DNA (gDNA) from sequencing data.Type: GrantFiled: August 4, 2017Date of Patent: October 17, 2023Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGYInventors: Yaping Liu, Manolis Kellis, Viktor Adalsteinsson, Zhizhuo Zhang
-
Patent number: 11788063Abstract: The present invention features assays for co-culturing primary cells while maintaining key biological activities specific to the primary cells. The invention is based, at least in part, on the discovery that compositions and methods for primary cells in a high-throughput co-culture platform, image analysis for distinguishing cells in co-cultures and assays that are suitable for screening of agents in epithelial cells, such as hepatocytes.Type: GrantFiled: August 27, 2020Date of Patent: October 17, 2023Assignees: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Sangeeta Bhatia, Jing Shan, Anne Carpenter Van Dyk, David Logan, Nathan Ross
-
Patent number: 11781172Abstract: 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: GrantFiled: April 30, 2019Date of Patent: October 10, 2023Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Feng Zhang, Bernd Zetsche, Jonathan S. Gootenberg, Omar O. Abudayyeh, Ian Slaymaker
-
Patent number: 11773412Abstract: 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: June 24, 2022Date of Patent: October 3, 2023Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College, Rutgers, the State University of New Jersey, Skolkovo Institute of Science and Technology, The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Konstantin Severinov, Feng Zhang, Yuri I. Wolf, Sergey Shmakov, Ekaterina Semenova, Leonid Minakhin, Kira S. Makarova, Eugene Koonin, Silvana Konermann, Julia Joung, Jonathan S. Gootenberg, Omar O. Abudayyeh, Eric S. Lander
-
Patent number: 11773070Abstract: 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: GrantFiled: July 14, 2022Date of Patent: October 3, 2023Assignees: 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: 11773432Abstract: 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: GrantFiled: December 17, 2021Date of Patent: October 3, 2023Assignees: THE BROAD INSTITUTE INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Feng Zhang, Bernd Zetsche, Johnathan S. Gootenberg, Omar O. Abudayyeh, Ian Slaymaker
-
Patent number: 11767534Abstract: The invention provides methods for determining the activity of a plurality of nucleic acid regulatory elements. These methods may facilitate, e.g., the systematic reverse engineering, and optimization of mammalian cis-regulatory elements at high resolution and at a large scale. The method may include integration of multiplexed DNA synthesis and sequencing technologies to generate and quantify the transcriptional regulatory activity of e.g., thousands of arbitrary DNA sequences in parallel in cell-based as says (e.g., mammalian cell based assays).Type: GrantFiled: May 4, 2012Date of Patent: September 26, 2023Assignee: THE BROAD INSTITUTE, INC.Inventors: Tarjei Mikkelsen, Andreas Gnirke, Alexandre Melnikov, Eric S. Lander, Li Wang, Xiaolan Zhang
-
Publication number: 20230295308Abstract: Described and featured herein are antagonistic biparatopic antibodies that specifically bind and inhibit an FGF receptor (e.g., FGFR2) and methods of using such antibodies for the treatment of cancers, including Cholangiocarcinoma (CCAs).Type: ApplicationFiled: June 2, 2021Publication date: September 21, 2023Applicants: The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc.Inventors: Saireudee CHATURANTABUT, William SELLERS
-
Publication number: 20230287510Abstract: As described below, the present invention features compositions, panels of biomarkers, and methods for characterizing chronic lymphocytic leukemia (CLL) for prognosis and selection of a subject for a treatment and/or inclusion in a clinical trial.Type: ApplicationFiled: August 9, 2021Publication date: September 14, 2023Applicants: The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., The General Hospital Corporation, President and Fellows of Harvard CollegeInventors: Catherine J. WU, Gad GETZ, Binyamin A. KNISBACHER, Ziao LIN, Cynthia K. HAHN
-
Publication number: 20230287373Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRJSPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CR.ISPR-Cas enzyme systems. In particular the present invention comprehends engineered new guide architectures and enzymes to be used in optimized Staphylococcus aureus CRISPR-Cas enzyme systems.Type: ApplicationFiled: January 26, 2023Publication date: September 14, 2023Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College, University of TokyoInventors: Feng ZHANG, Winston YAN, Osamu NUREKI, Kaijie ZHENG, Le CONG, Hiroshi NISHIMASU, Fei RAN, Yinqing LI
-
Publication number: 20230290467Abstract: The invention features methods that are useful for treatment of a patient at increased risk for infection and for selecting a patient for treatment for an infection. In various embodiments, the infection is coronavirus disease 2019 (COVID-19), sepsis, or other respiratory infections.Type: ApplicationFiled: March 14, 2023Publication date: September 14, 2023Applicants: The Broad Institute, Inc., The United States of America, as represented by the Secretary, Department of Health and Human Servic, Yale University, The General Hospital CorporationInventors: Pradeep NATARAJAN, Giulio GENOVESE, Seyedeh Maryam ZEKAVAT, Mitchell J. MACHIELA, Shu-Hong LIN
-
Publication number: 20230279018Abstract: The invention provides agents that inhibit L-Phe in cytoplasmic phenylalanine tRNA-synthetase (cFRS), methods for identifying them, compositions comprising such agents, and therapeutic methods of using such agents.Type: ApplicationFiled: March 22, 2023Publication date: September 7, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard College, Eisai R&D Management Co., LTD.Inventors: Eamon COMER, Bruno MELILLO, Francis G. FANG, Branko MITASEV