Patents Assigned to The Massachusetts General Hospital
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Publication number: 20240091213Abstract: Provided herein are bifunctional compounds that bind tau protein and/or promote targeted ubiquitination for the degradation of tau protein. In particular, provided are compounds that can bind tau protein, a protein whose aggregation is implicated in a variety of neurodegenerative disease (e.g., tauopathies), and can promote its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon), which can ubiquitinate tau protein, marking it for proteasomal degradation. Also provided are radiolabeled forms of the bifunctional compounds, pharmaceutical compositions comprising the bifunctional compounds, methods of detecting and/or diagnosing neurological disorders, methods of detecting and/or diagnosing pathological aggregation of tau protein (e.g., in the central nervous system), methods of treating and/or preventing neurological disorders, and methods of promoting the degradation of tau protein by E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.Type: ApplicationFiled: May 23, 2023Publication date: March 21, 2024Applicants: DANA-FARBER CANCER INSTITUTE, INC., THE GENERAL HOSPITAL CORPORATION d/b/a MASSACHUSETTS GENERAL HOSPITALInventors: Nathanael S. Gray, Stephen J. Haggarty, Quan Cai, Tinghu Zhang, Maria Catarina Telo Baptista Lima da Silva, Fleur M. Ferguson
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Patent number: 11885802Abstract: Methods and compositions are described for the diagnosis of primary biliary cirrhosis. Novel autoantigens are described for use in assays which employ test samples from individuals.Type: GrantFiled: March 24, 2017Date of Patent: January 30, 2024Assignees: AMBERGEN, INC., MASSACHUSETTS GENERAL HOSPITALInventors: Mark J. Lim, Heather P. Ostendorff, Kenneth J. Rothschild, Donald B. Bloch
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Publication number: 20230383298Abstract: The present disclosure provides, in part, methods of discovering immunotherapy targets in vivo, therapeutic compositions (e.g., shRNA, immunoresponsive cells expressing shRNA and/or a chimeric antigen receptors (CAR)), and methods of use thereof.Type: ApplicationFiled: January 3, 2023Publication date: November 30, 2023Applicants: Dana-Farber Cancer Institute, Inc., The General Hospital Corporation d/b/a Massachusetts General HospitalInventors: Kai W. Wucherpfennig, Glenn Dranoff, Penghui Zhou, Donald Shaffer, Nir Hacohen, Harvey I. Cantor, Diana Alvarez Arias
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Publication number: 20230201299Abstract: The disclosure relates to methods for treating a subject suffering from a burn injury or associated complications by administering to the subject an effective amount of an aromatic-cationic peptide. For example, a burn injury may be associated with distant pathophysiological effects, such as hypermetabolism, skeletal muscle dysfunction, and organ damage. The disclosure also relates to methods for protecting a subject from a burn injury by administering an effective amount of an aromatic-cationic peptide to a subject at risk of a burn injury.Type: ApplicationFiled: August 2, 2022Publication date: June 29, 2023Applicant: The General Hospital Corporation d/b/a Massachusetts General HospitalInventors: Ronald G. Tompkins, A. Aria Tzika, Yong-Ming Yu, Laurence Rahme, Jeevendra A. Martyn
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Publication number: 20230101412Abstract: A method of inhibiting inflammation with milk oligosaccharides or glycoconjugates containing the oligosaccharides.Type: ApplicationFiled: May 4, 2022Publication date: March 30, 2023Applicants: Children's Hospital Medical Center, The General Hospital Corporation d/b/a Massachusetts General Hospital, Instituto Nacional de Ciencias Medicas Y NutricionInventors: Ardythe L. Morrow, David S. Newburg, Guillermo M. Ruiz-Palacios
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Publication number: 20220160702Abstract: The present invention provides compounds of formula I, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting kinase (e.g., GSK3 (e.g., GSK3? or GSK3?) or CK1) activity. The present invention further provides methods of using the compounds described herein for treating kinase-mediated disorders, such as neurological diseases, psychiatric disorders, metabolic disorders, and cancer.Type: ApplicationFiled: June 10, 2021Publication date: May 26, 2022Applicants: The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., The General Hospital Corporation d/b/a Massachusetts General HospitalInventors: Florence Fevrier Wagner, Jennifer Q. Pan, Sivaraman Dandapani, Andrew Germain, Edward Holson, Benito Munoz, Partha P. Nag, Michael C. Lewis, Stephen J. Haggarty, Joshua A. Bishop, Kimberly Stegmaier, Michel Weiwer, Versha Banerji
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Publication number: 20220064151Abstract: The present invention provides compounds of Formulae (A), (B), (C), and (D), pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, pharmaceutical compositions thereof, and kits thereof. The present invention further provides methods of using the compounds to treat or prevent neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, ALS (amyotrophic lateral sclerosis), traumatic brain injury, ischemic brain injury, stroke, frontal temporal dementia, Pick's disease, corticobasal degeneration, supra cerebral palsy, prion diseases (e.g., Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, Fatal Familial Insomnia, and Kuru), Nieman Pick type C, spinal cerebellar ataxia, spinal muscular dystrophy, ataxia telangiectasia, hippocampal sclerosis, Cockayne syndrome, Werner syndrome, xeroderma pigmentosaum, and Bloom syndrome.Type: ApplicationFiled: August 9, 2021Publication date: March 3, 2022Applicants: Massachusetts Institute of Technology, The General Hospital Corporation d/b/a Massachusetts General HospitalInventors: Li-Huei Tsai, Ling Pan, Stephen J. Haggarty, Debasis Patnaik
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Publication number: 20210388444Abstract: The invention provides novel FUS/TLS nucleic acids and proteins that comprise one or more genetic markers (for example, single nucleotide polymorphisms) and methods of use thereof including methods relating to the diagnosis of ALS or other related motor neuron disease by virtue of the presence of the mutant FUS/TLS sequence(s).Type: ApplicationFiled: May 20, 2021Publication date: December 16, 2021Applicant: The General Hospital Corporation d/b/a Massachusetts General HospitalInventors: Thomas J. Kwiatkowski, JR., Robert H. Brown, JR.
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Publication number: 20210283155Abstract: A method of inhibiting inflammation with milk oligosaccharides or glycoconjugates containing the oligosaccharides.Type: ApplicationFiled: May 28, 2021Publication date: September 16, 2021Applicants: Children's Hospital Medical Center, The General Hospital Corporation d/b/a Massachusetts General Hospital, Instituto Nacional de Ciencias Medicas Y NutricionInventors: Ardythe L. Morrow, David S. Newburg, Guillermo M. Ruiz-Palacios
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Publication number: 20210171429Abstract: The present invention relates to polyhydroxylated benzophenone compounds useful in the treatment of neurodegenerative, neurological, psychiatric, and cognitive diseases, in particular those associated with a deficiency in HDAC1 deacetylase activity.Type: ApplicationFiled: December 9, 2020Publication date: June 10, 2021Applicants: Massachusetts Institute of Technology, The General Hospital Corporation d/b/a Massachusetts General HospitalInventors: Li-Huei Tsai, Stephen J. Haggarty, Debasis Patnaik, Ping-Chieh Pao
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Publication number: 20210154184Abstract: Provided herein are bifunctional compounds that bind tau protein and/or promote targeted ubiquitination for the degradation of tau protein. In particular, provided are compounds that can bind tau protein, a protein whose aggregation is implicated in a variety of neurodegenerative disease (e.g., tauopathies), and can promote its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon), which can ubiquitinate tau protein, marking it for proteasomal degradation. Also provided are radiolabeled forms of the bifunctional compounds, pharmaceutical compositions comprising the bifunctional compounds, methods of detecting and/or diagnosing neurological disorders, methods of detecting and/or diagnosing pathological aggregation of tau protein (e.g., in the central nervous system), methods of treating and/or preventing neurological disorders, and methods of promoting the degradation of tau protein by E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.Type: ApplicationFiled: July 12, 2018Publication date: May 27, 2021Applicants: Dana-Farber Cancer Institute, Inc., The General Hospital Corporation D/B/A Massachusetts General HospitalInventors: Nathanael S. Gray, Stephen J. Haggarty, Quan Cai, Tinghu Zhang, Maria Catarina Telo Baptista Lima da Silva, Fleur M. Ferguson
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Publication number: 20210139914Abstract: The present disclosure provides, in part, methods of discovering immunotherapy targets in vivo, therapeutic compositions (e.g., shRNA, immunoresponsive cells expressing shRNA and/or a chimeric antigen receptors (CAR)), and methods of use thereof.Type: ApplicationFiled: November 24, 2020Publication date: May 13, 2021Applicants: Dana-Farber Cancer Institute, Inc., The General Hospital Corporation d/b/a Massachusetts General HospitalInventors: Kai W. Wucherpfennig, Glenn Dranoff, Penghui Zhou, Donald Shaffer, Nir Hacohen, Harvey I. Cantor, Diana Alvarez Arias
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Publication number: 20210102203Abstract: Aspects of the invention provide single stranded oligonucleotides for activating or enhancing expression of MECP2. Further aspects provide compositions and kits comprising single stranded oligonucleotides for activating or enhancing expression of MECP2. Methods for modulating expression of MECP2 using the single stranded oligonucleotides are also provided. Further aspects of the invention provide methods for selecting a candidate oligonucleotide for activating or enhancing expression of MECP2.Type: ApplicationFiled: May 18, 2020Publication date: April 8, 2021Applicants: Translate Bio MA, Inc., The General Hospital Corporation d/b/a Massachusetts General HospitalInventors: Arthur M. Krieg, Romesh R. Subramanian, James McSwiggen, Jeannie T. Lee
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Publication number: 20210040499Abstract: Disclosed herein are populations of microvesicles containing or otherwise associated with viral particles, methods of producing these purified populations, and methods of using these purified populations in a variety of diagnostic, therapeutic and/or prophylactic indications.Type: ApplicationFiled: June 23, 2020Publication date: February 11, 2021Applicant: THE GENERAL HOSPITAL CORPORATION d/b/a Massachusetts General HospitalInventors: Johan Karl Olov Skog, Casey Maguire
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Publication number: 20200338087Abstract: The present disclosure provides methods of treating and/or preventing inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) using salt-inducible kinase (SIK) inhibitors, such as macrocyclic SIK inhibitors of Formula (I), imidazolyl SIK inhibitors of Formula (II), and urea and carbamate SIK inhibitors of Formula (III-A) (e.g., urea and carbamate STK inhibitors of Formula (III)).Type: ApplicationFiled: April 19, 2019Publication date: October 29, 2020Applicants: Dana-Farber Cancer Institute, Inc., The Broad Institute, Inc., President and Fellows of Harvard College, The General Hospital Corporation d/b/a Massachusetts General HospitalInventors: Alykhan Shamji, Thomas Sundberg, Nathanael S. Gray, Ramnik Xavier, Stuart L. Schreiber, Hwan Geun Choi, Yanke Liang
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Publication number: 20200323945Abstract: The disclosure relates to methods for treating a subject suffering from a burn injury or associated complications by administering to the subject an effective amount of an aromatic-cationic peptide. For example, a burn injury may be associated with distant pathophysiological effects, such as hypermetabolism, skeletal muscle dysfunction, and organ damage. The disclosure also relates to methods for protecting a subject from a burn injury by administering an effective amount of an aromatic-cationic peptide to a subject at risk of a burn injury.Type: ApplicationFiled: April 6, 2020Publication date: October 15, 2020Applicant: The General Hospital Corporation d/b/a Massachusetts General HospitalInventors: Ronald G. Tompkins, A. Aria Tzika, Yong-Ming Yu, Laurence Rahme, Jeevendra A. Martyn
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Publication number: 20200312426Abstract: Embodiments of the present invention provide materials and methods for performing phenotype-based chemical screens. Embodiments disclosed herein pertain to the use of a battery of high-throughput zebrafish behavioral assays to generate behavioral profiles. In accordance with these embodiments, responses to various chemical compounds with known and unknown biological functions can be used to generate behavioral profiles. Embodiments also involve generating behavioral profiles based on genetic mutations or environmental perturbations. Establishing databases of behavioral profiles facilitates identification of novel chemicals that phenocopy effects of therapeutic agents and/or that modulate genetic or environmental behavioral profiles, thereby providing a basis for not only assessing the properties of known chemical compounds but also for developing novel treatments for human diseases.Type: ApplicationFiled: March 6, 2020Publication date: October 1, 2020Applicants: NemaMetrix, Inc, The General Hospital Corportation, dba Massachusetts General HospitalInventors: David Kokel, Randall T. Peterson, Giancarlo Bruni, Andrea Velenich
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Patent number: 10595794Abstract: An animal, specimen, or imaging phantom is imaged in precise increments over at least 360 degrees. The animal, specimen, or imaging phantom is supported within a subject holder. The subject holder has an elongated portion or tube for holding securely the animal, specimen or imaging phantom. The subject holder is connected to an actuator motor driver. The actuator motor driver causes the subject holder to rotate at the precise increments, and an image of the animal, specimen, or imaging phantom is captured at each increment. The subject holder limits movement of the subject being imaged at each increment.Type: GrantFiled: July 9, 2015Date of Patent: March 24, 2020Assignees: AUBURN UNIVERSITY, MASSACHUSETTS GENERAL HOSPITALInventors: Peter Panizzi, Andrew D. Brannen, Robert D. Arnold, Matthias Nahrendorf
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Publication number: 20200087236Abstract: The present invention relates to polyhydroxylated benzophenone compounds useful in the treatment of neurodegenerative, neurological, psychiatric, and cognitive diseases, in particular those associated with a deficiency in HDAC1 deacetylase activity.Type: ApplicationFiled: June 15, 2018Publication date: March 19, 2020Applicant: The General Hospital Corporation d/b/a Massachusetts General HospitalInventors: Li-Huei TSAI, Stephen J. HAGGARTY, Debasis PATNAIK, Ping-Chieh PAO
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Publication number: 20190343842Abstract: The present disclosure provides methods of treating and/or preventing inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) using salt-inducible kinase (SIK) inhibitors, such as macrocyclic SIK inhibitors of Formula (I), imidazolyl SIK inhibitors of Formula (II), and urea and carbamate SIK inhibitors of Formula (III-A) (e.g., urea and carbamate STK inhibitors of Formula (III)).Type: ApplicationFiled: April 19, 2019Publication date: November 14, 2019Applicants: Dana-Farber Cancer Institute, Inc., The Broad Institute, Inc., President and Fellows of Harvard College, The General Hospital Corporation d/b/a Massachusetts General HospitalInventors: Alykhan Shamji, Thomas Sundberg, Nathanael S. Gray, Ramnik Xavier, Stuart L. Schreiber, Hwan Geun Choi, Yanke Liang