Patents Assigned to Whitehead Institute
  • Patent number: 11377466
    Abstract: Provided herein are analogs of the natural product icariin represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. The analogs can be used to modulate (e.g., inhibit, such as by competitive inhibition) PDE5 and thereby treat a wide range of PDE5-mediated diseases, including cardiovascular, gastrointestinal, pulmonary, musculoskeletal, neurological and reproductive diseases. Also provided herein are compositions and methods including compounds of Structural Formula (I).
    Type: Grant
    Filed: August 7, 2019
    Date of Patent: July 5, 2022
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Yasmin Chau, Fu-Shuang Li, Jing-Ke Weng
  • Patent number: 11371019
    Abstract: A population of early-stage burst-forming unit-eryhtoid (BFU-E) cells characterized by low expression of the Type III Transforming Growth Factor ? Receptor (TGFRPIII) and uses thereof for producing red blood cells in vitro, genotoxicity analysis of chemicals, drug sensitivity assessment, and drug development. Also described herein are methods for producing the population of early-stage BFU-E cells and methods for producing red blood cells.
    Type: Grant
    Filed: March 3, 2017
    Date of Patent: June 28, 2022
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Harvey Lodish, Xiaofei Gao, Hsiang-Ying Lee
  • Patent number: 11331313
    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: Grant
    Filed: May 22, 2018
    Date of Patent: May 17, 2022
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Rudolf Jaenisch, Xin Tang
  • Patent number: 11326209
    Abstract: The present invention relates to a cell based genomic Recorded Accumulative Memory (geRAM) system (also referred to herein as Genomically Encoded Memory (GEM)) for recoding data (i.e., changes in nucleic acid sequences in cellular DNA in response to physical and/or chemical signal(s)) from the cellular environment.
    Type: Grant
    Filed: November 7, 2014
    Date of Patent: May 10, 2022
    Assignees: Massachusetts Institute of Technology, Whitehead Institute of Biomedical Research
    Inventors: Joseph M. Jacobson, Noah Jakimo, Naama Kanarek, David Sabatini
  • Patent number: 11319591
    Abstract: Disclosed are methods for identifying the core regulatory circuitry or cell identity program of a cell or tissue, and related methods of diagnoses, screening, and treatment involving the core regulatory circuitry and/or cell identity programs identified using the methods.
    Type: Grant
    Filed: December 23, 2016
    Date of Patent: May 3, 2022
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Violaine Saint-Andre, Brian J. Abraham, Zi Peng Fan, Tong Ihn Lee, Richard A. Young
  • Patent number: 11266695
    Abstract: 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 a sortaggable surface protein, which allows for surface modification in the presence of a sortase. Also described herein are surface modified enucleated red blood cells, e.g., conjugated with an agent of interest such as a peptide, a detectable label, or a chemotherapeutic agent, and uses thereof in delivering the agent to a subject.
    Type: Grant
    Filed: March 23, 2018
    Date of Patent: March 8, 2022
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Harvey Lodish, Hidde L. Ploegh, Hsiang-Ying Sherry Lee, Jiahai Shi, Lenka Hoffman, Novalia Pishesha
  • Patent number: 11261453
    Abstract: Disclosed are yeast cells expressing a polypeptide comprising a signal sequence and a human ApoE protein. In some embodiments the polypeptide comprises ApoE2. In some embodiments the polypeptide comprises ApoE3. In some embodiments the polypeptide comprises ApoE4. Also disclosed are methods of screening yeast cells to identify compounds that prevent or suppress Apo-induced toxicity. Compounds identified by such screens can be used to treat or prevent neurodegenerative disorders such as Alzheimer's disease. Also disclosed are methods of screening yeast cells to identify genetic suppressors or enhancers of ApoE-induced toxicity. Also disclosed are genetic suppressors or enhancers of ApoE-induced toxicity identified using the methods, and human homologs thereof. Also disclosed are methods of identifying compounds that modulate expression or activity of genetic modifiers of ApoE-induced toxicity.
    Type: Grant
    Filed: September 11, 2015
    Date of Patent: March 1, 2022
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Susan L. Lindquist, Priyanka Narayan
  • 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: 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
  • 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
  • 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