Patents Assigned to Whitehead Institute for Biomedical Research
  • Patent number: 11225469
    Abstract: The present invention provides compounds of Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, pro-drugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I), (II) or (III) for treating diseases associated with the over-expression of phosphoglycerate dehydrogenase (PHGDH) in a subject, such as proliferative diseases (e.g., cancers (e.g., breast cancer, ER negative breast cancer, melanoma, cervical cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the activity of PHGDH or inhibit the serine biosynthetic pathway, or both.
    Type: Grant
    Filed: January 15, 2016
    Date of Patent: January 18, 2022
    Assignees: Whitehead Institute for Biomedical Research, Dana-Farber Cancer Institute, Inc., The United States of America, as represented by the Secretary, Department of Health and Human Services
    Inventors: David M. Sabatini, Michael Pacold, Matthew B. Boxer, Jason M. Rohde, Kyle R. Brimacombe, Min Shen, Ganesha Bantukallu, Li Liu
  • Publication number: 20220002769
    Abstract: Disclosed are methods, compositions, proteins, nucleic acids, cells, vectors, compounds, reagents, and systems for the preparation of kavalactones, flavokavains, and kavalactone and flavokavain biosynthetic intermediates using enzymes expressed in heterologous host cells, such as microorganisms or plants, or using in vitro enzymatic reactions. This invention also provides for the expression of the enzymes by recombinant cell lines and vectors. Furthermore, the enzymes can be components of constructs such as fusion proteins. The kavalactones produced can be utilized to treat anxiety disorder, insomnia, and other psychological and neurological disorders. The flavokavains produced can be utilized to treat various cancers including colon, bladder, and breast cancers.
    Type: Application
    Filed: March 3, 2021
    Publication date: January 6, 2022
    Applicant: Whitehead Institute for Biomedical Research
    Inventors: Tomás Pluskal, Jing-Ke Weng
  • Publication number: 20220002768
    Abstract: Disclosed are methods, compositions, proteins, nucleic acids, cells, vectors, compounds, reagents, and systems for the preparation of kavalactones, flavokavains, and kavalactone and flavokavain biosynthetic intermediates using enzymes expressed in heterologous host cells, such as microorganisms or plants, or using in vitro enzymatic reactions. This invention also provides for the expression of the enzymes by recombinant cell lines and vectors. Furthermore, the enzymes can be components of constructs such as fusion proteins. The kavalactones produced can be utilized to treat anxiety disorder, insomnia, and other psychological and neurological disorders. The flavokavains produced can be utilized to treat various cancers including colon, bladder, and breast cancers.
    Type: Application
    Filed: March 3, 2021
    Publication date: January 6, 2022
    Applicant: Whitehead Institute for Biomedical Research
    Inventors: Tomás Pluskal, Jing-Ke Weng
  • Patent number: 11208653
    Abstract: Methods and compositions for increasing RNAi efficiency through single nucleotide mismatches.
    Type: Grant
    Filed: April 27, 2017
    Date of Patent: December 28, 2021
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Grace Chen, David Bartel, Hazel Sive
  • Publication number: 20210353566
    Abstract: The invention relates to methods of using choline supplementation for treating APOE4-related disorders. In particular the methods are accomplished by administering choline treatment paradigms to re-establish lipid homeostasis in APOE4 carriers.
    Type: Application
    Filed: May 12, 2021
    Publication date: November 18, 2021
    Applicants: Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research
    Inventors: Li-Huei Tsai, Yuan-Ta Lin, Julia Bonner, Priyanka Narayan, Grzegorz Sienski
  • Patent number: 11149267
    Abstract: The present invention generally relates to libraries, kits, methods, applications and screens used in functional genomics that focus on gene function in a cell and that may use vector systems and other aspects related to Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas systems and components thereof. The present invention also relates to rules for making potent single guide RNAs (sgRNAs) for use in CRISPR-Cas systems. Provided are genomic libraries and genome wide libraries, kits, methods of knocking out in parallel every gene in the genome, methods of selecting individual cell knock outs that survive under a selective pressure, methods of identifying the genetic basis of one or more medical symptoms exhibited by a patient, and methods for designing a genome-scale sgRNA library.
    Type: Grant
    Filed: April 28, 2016
    Date of Patent: October 19, 2021
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research
    Inventors: Tim Wang, David Sabatini, Eric Lander
  • Patent number: 11136548
    Abstract: Described herein are cell culture media useful for the differentiation of human pluripotent stem cells into microglia. The methods described herein relate to in vitro generation of expandable, bankable, microglial cells by directed differentiation from human pluripotent stem cells (induced or embryonic). Using only defined cell culture media, differentiation of pluripotent stem cells is directed down a mesodermal path, in a rapid and scalable fashion, to generate cells adopting signatures of their in vivo counterparts, including gene expression, protein marker expression and functionality.
    Type: Grant
    Filed: June 24, 2016
    Date of Patent: October 5, 2021
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Julien Muffat, Yun Li, Rudolf Jaenisch
  • Patent number: 11092608
    Abstract: The invention relates to methods of identifying compounds that modulate mTORC1 activity in a cell by modulating the activity of CASTOR1, as well as to the use of such identified compounds in the modulation of mTORC1 and the treatment of diseases and conditions characterized by aberrant mTORC1 activity.
    Type: Grant
    Filed: December 28, 2016
    Date of Patent: August 17, 2021
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: David M. Sabatini, Lynne Chantranupong, Robert A. Saxton, Steven P. Gygi, Melanie P. Gygi
  • Patent number: 11092602
    Abstract: In some aspects, the disclosure provides methods of modulating the level of proteasome inhibitor resistance of a cell, the methods comprising manipulating the level of expression or activity of a subunit of the 19S proteasome in the cell. In some aspects, cells in which the level of a 19S subunit is modulated, e.g., reduced, are provided. In some aspects, methods of identifying agents that reduce proteasome inhibitor resistance are provided. In some aspects, methods of classifying cancers according to predicted proteasome inhibitor resistance are provided. In some aspects, methods of killing or inhibiting proliferation of cancer cells, e.g., proteasome inhibitor resistant cancer cells, are provided. In some aspects, methods of treating cancer, e.g., proteasome inhibitor resistant cancer, are provided.
    Type: Grant
    Filed: July 6, 2016
    Date of Patent: August 17, 2021
    Assignees: Whitehead Institute for Biomedical Research, The Brigham and Women's Hospital, Inc.
    Inventors: Peter Tsvetkov, Sandro Santagata, Susan Lindquist
  • Publication number: 20210230538
    Abstract: The present disclosure provides compounds of any one of Formulae (A) to (L). The present disclosure also provides compositions, uses, and methods that include or involve a compound described herein, a serine/threonine-protein kinase B-Raf (BRAF) inhibitor, an epidermal growth factor receptor (EGFR) inhibitor, a vascular endothelial growth factor 1 (VEGFR1) inhibitor, a fibroblast growth factor receptor 1 (FGFR1) inhibitor, or a combination thereof. The compounds, compositions, uses, and methods are useful in changing the pluripotency state of a vertebrate cell to a more nave state.
    Type: Application
    Filed: October 15, 2020
    Publication date: July 29, 2021
    Applicants: Whitehead Institute for Biomedical Research, Dana-Farber Cancer Institute, Inc.
    Inventors: Thorold W. Theunissen, Nathanael S. Gray, Rudolf Jaenisch
  • Patent number: 11047848
    Abstract: In some aspects, a cross-species platform useful for drug discovery in neurodegenerative diseases is described.
    Type: Grant
    Filed: March 17, 2014
    Date of Patent: June 29, 2021
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Susan L. Lindquist, Vikram Khurana, Chee-Yeun Chung
  • Patent number: 11041161
    Abstract: Metabolic flux biosensors are provided herein, as are related compositions and methods useful for, inter alia, identifying factors which increase the production of metabolites and/or end products of metabolic pathways, and for the production of inter alia, metabolites and/or end products of metabolic pathways.
    Type: Grant
    Filed: January 8, 2015
    Date of Patent: June 22, 2021
    Assignees: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
    Inventors: Jose Luis Avalos, Gerald Fink, Gregory Stephanopoulos
  • Patent number: 11028185
    Abstract: Methods and reagents for the installation of click chemistry handles on target proteins are provided, as well as modified proteins comprising click chemistry handles. Further, chimeric proteins, for example, bi-specific antibodies, that comprise two proteins conjugated via click chemistry, as well as methods for their generation and use are disclosed herein.
    Type: Grant
    Filed: September 24, 2018
    Date of Patent: June 8, 2021
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Hidde L. Ploegh, Martin D. Witte, Nicholas C. Yoder
  • Patent number: 10941429
    Abstract: Disclosed are methods, compositions, proteins, nucleic acids, cells, vectors, compounds, reagents, and systems for the preparation of kavalactones, flavokavains, and kavalactone and flavokavain biosynthetic intermediates using enzymes expressed in heterologous host cells, such as microorganisms or plants, or using in vitro enzymatic reactions. This invention also provides for the expression of the enzymes by recombinant cell lines and vectors. Furthermore, the enzymes can be components of constructs such as fusion proteins. The kavalactones produced can be utilized to treat anxiety disorder, insomnia, and other psychological and neurological disorders. The flavokavains produced can be utilized to treat various cancers including colon, bladder, and breast cancers.
    Type: Grant
    Filed: January 16, 2019
    Date of Patent: March 9, 2021
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Tomás Pluskal, Jing-Ke Weng
  • Publication number: 20200384137
    Abstract: The present invention, in some aspects, provides methods, reagents, compositions, and kits for the radiolabeling of proteins, for example, of proteins useful for positron emission tomography (PET) or single-photon emission computed tomography (SPECT) (e.g., for diagnostic and therapeutic applications), using sortase-mediated transpeptidation reactions. Some aspects of this invention provide methods for the conjugation of an agent, for example, a radioactive agent or molecule to diagnostic or therapeutic peptides or proteins. Compositions comprising sortagged, radiolabeled proteins as well as reagents for generating radiolabeled proteins are also provided. Kits comprising reagents useful for the generation of radiolabeled proteins are provided, as are precursor proteins that comprise a sortase recognition motif.
    Type: Application
    Filed: January 8, 2020
    Publication date: December 10, 2020
    Applicants: Whitehead Institute for Biomedical Research, The General Hospital Corporation
    Inventors: Mohammad Rashidian, Hidde L. Ploegh, Ralph Weissleder, Edmund J. Keliher
  • Publication number: 20200375996
    Abstract: A method for treating neurodegenerative disease in a subject in need thereof by administering to the subject an effective amount of a Nedd4 activator as described herein.
    Type: Application
    Filed: December 14, 2016
    Publication date: December 3, 2020
    Applicants: D.E. Shaw Research, LLC, WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH
    Inventors: Yibing SHAN, Venkat MYSORE, Susan LINDQUIST, Dan TARDIFF, Srividya CHANDRAMOULI
  • Patent number: 10745744
    Abstract: The disclosed Hi-C protocol can identify genomic loci that are spatially co-located in vivo. These spatial co-locations may include, but are not limited to, intrachromosomal interactions and/or interchromosomal interactions. Hi-C techniques may be applied to many different scales of interest. For example, on a large scale, Hi-C techniques can be used to identify long-range interactions between distant genomic loci.
    Type: Grant
    Filed: June 15, 2017
    Date of Patent: August 18, 2020
    Assignees: University of Massachusetts, Massachusetts Institute of Technology, President and Fellows of Harvard College, Whitehead Institute for Biomedical Research
    Inventors: Job Dekker, Erez Lieberman Aiden, Nynke Van Berkum, Andreas Gnirke, Eric Lander, Chad Nusbaum, Louise Williams, Alexandre Melnikov, Georgia Giannoukos
  • Publication number: 20200206269
    Abstract: Multi-step methods for the in vitro production of enucleated red blood cells and the enucleated red blood cells thus prepared are provided. Such enucleated red blood cells may express fusion proteins comprising an antigen binding protein which allows the red blood cell to bind a toxin or an antigen of a pathogen. Also described herein are methods for neutralizing a toxin or pathogen in a subject by administering enucleated red blood cells that express any of the fusion proteins provided herein.
    Type: Application
    Filed: August 22, 2018
    Publication date: July 2, 2020
    Applicants: Whitehead Institute for Biomedical Research, Trustees of Tufts College
    Inventors: Harvey Lodish, Nai-Jia Huang, Novalia Pishesha, Hidde L. Ploegh, Charles Shoemaker
  • Patent number: 10633656
    Abstract: Double-stranded RNA (dsRNA) induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using a Drosophila in vitro system, we demonstrate that 19-23 nt short RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs (siRNAs) are generated by an RNase III-like processing reaction from long dsRNA. Chemically synthesized siRNA duplexes with overhanging 3? ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNP complex.
    Type: Grant
    Filed: December 22, 2016
    Date of Patent: April 28, 2020
    Assignees: MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN E.V., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, Whitehead Institute for Biomedical Research, UNIVERSITY OF MASSACHUSETTS
    Inventors: Thomas Tuschl, Sayda Mahgoub Elbashir, Winfried Lendeckel
  • Publication number: 20200085817
    Abstract: Potassium chloride cotransporter-2 (KCC2) plays a critical role in brain function, and deficiency in KCC2 has been linked to neurological diseases, psychiatric disorders, and central nervous system injuries. In particular, Rett syndrome (RTT), a severe neurodevelopmental disorder caused by mutations in the X-linked gene Methyl CpG binding Protein 2 (MECP2), has been linked to deficits in KCC2. The disclosure reports the use of CRISPR/Cas9 genome-editing technology to generate stem cell-derived, genetically defined KCC2 reporter human neurons for large-scale compound screening. This screening platform has been utilized to identify a number of small molecule compounds that are capable of enhancing KCC2 expression in both wild-type and RTT neurons, as well as organotypical brain slices cultured from wild-type mice.
    Type: Application
    Filed: May 22, 2018
    Publication date: March 19, 2020
    Applicant: Whitehead Institute for Biomedical Research
    Inventors: Rudolf Jaenisch, Xin Tang