Patents Assigned to Dana-Farber Cancer Institute
  • Publication number: 20210008147
    Abstract: Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.
    Type: Application
    Filed: August 25, 2020
    Publication date: January 14, 2021
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Levi A. Garraway, Caroline Emery, Nikhil Wagle
  • Publication number: 20210008048
    Abstract: Provided are drug delivery compositions and devices useful for the treatment and/or prevention of cancer and metastatic tumors. For example, a drug delivery composition and/or device is provided that comprises a biodegradable scaffold or biomaterial comprising one or more agents that inhibit one or more proinflammatory pathways, such as one or more immune responses mediated by a p38 mitogen-activated protein kinase (MAPK) pathway. In some embodiments, a drug delivery composition and/or device may further comprise one or more agents that activate the innate immune system (e.g., STING agonists) and/or the adaptive immune system (e.g., anti-PD-1 antibodies). In some embodiments, a drug delivery composition and/or device may include a cytokine (e.g., IL-15 superagonist). In some embodiments, a drug delivery composition and/or device can be administered to a tumor resection site (e.g., a void volume resulting from a tumor resection).
    Type: Application
    Filed: March 20, 2019
    Publication date: January 14, 2021
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventor: Michael Solomon Goldberg
  • Publication number: 20210002336
    Abstract: The invention provides structurally-constrained peptides by hydrocarbon stapling of a BCL9 HD2 helix for use as a therapeutic agent. The invention further provides methods and kits for use of the structurally-constrained peptide of the instant invention. The invention is based, at least in part, on the results provided herein demonstrating that hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, possess superior pharmacokinetic properties compared to the corresponding unmodified peptides, and are highly effective in binding to ?-catenin in vitro, in cellulo, and in vivo, disrupting the BCL-9/?-catenin interaction, and thereby interfering with deregulated Wnt/?-catenin signaling for therapeutic benefit in a variety of human diseases including human cancer.
    Type: Application
    Filed: May 18, 2020
    Publication date: January 7, 2021
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Loren D. Walensky, Ruben Carrasco, Gregory H. Bird
  • Patent number: 10881668
    Abstract: The present invention provides compounds of Formula (I), and pharmaceutically compositions thereof. Compounds of Formula (I) are binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.
    Type: Grant
    Filed: September 9, 2016
    Date of Patent: January 5, 2021
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: James E. Bradner, Jun Qi, Minoru Tanaka
  • Publication number: 20200407371
    Abstract: Provided herein are bifunctional compounds that bind a target protein (e.g., a selected protein) and/or induce ubiquitination for degradation of the target protein. In particular, provided are compounds that bind a bromodomain or bromodomain-containing protein (e.g., BET proteins) or histone methyltransferases (HMTs, e.g., enhancer of zeste homolog 1 (EZH1), or FKBP12) and can promote its degradation by recruiting it to the ubiquitin receptor RPN13 (e.g., RA190), for proteasomal degradation. Also provided are pharmaceutical compositions comprising the bifunctional compounds, methods of treating and/or preventing diseases (e.g., proliferative diseases, cancers, benign neoplasms, pathological angiogenesis, inflammatory diseases, and autoimmune diseases) and musculoskeletal diseases, and methods of inducing the degradation of a target (e.g., a target protein) by recruiting it to the ubiquitin receptor RPN13 of the proteasome in a subject by administering a compound or composition described herein.
    Type: Application
    Filed: February 22, 2019
    Publication date: December 31, 2020
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Jun Qi, Lei Wu, Kenneth C. Anderson, Yan Song, Paul Park, Dharminder Chauhan
  • Patent number: 10875844
    Abstract: Provided herein are small molecule inhibitors of maternal embryonic leucine zipper kinase (MELK) having the structure of formula (I), wherein X and R1-R3 are defined in the specification. The compounds are useful for treating cancer and other conditions or diseases associated with aberrant MELK expression. Also provided herein are pharmaceutical compositions comprising a compound of formula (I) and a pharmaceutically acceptable carrier. The invention also provides methods of treating cancers associated with over-expression of MELK.
    Type: Grant
    Filed: March 4, 2016
    Date of Patent: December 29, 2020
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael Gray, Tinghu Zhang, Hai-Tsang Huang, Yubao Wang, Jean Zhao, Hwan Geun Choi
  • Patent number: 10876971
    Abstract: Provided herein are, inter alia, barcode probes comprised of transiently or stably fluorescently labeled nucleic acid nanostructures that are fully addressable and able to be read using standard fluorescent microscope and methods of use thereof including methods of use as detectable labels for probes.
    Type: Grant
    Filed: June 14, 2018
    Date of Patent: December 29, 2020
    Assignees: President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.
    Inventors: Chenxiang Lin, Chao Li, William M. Shih, Peng Yin, Ralf Jungmann
  • Patent number: 10876120
    Abstract: 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: Grant
    Filed: April 3, 2018
    Date of Patent: December 29, 2020
    Assignees: DANA-FARBER CANCER INSTITUTE, INC, THE GENERAL HOSPITAL CORPORATION
    Inventors: Kai W. Wucherpfennig, Glenn Dranoff, Penghui Zhou, Donald Shaffer, Nir Hacohen, Harvey I. Cantor, Diana Alvarez Arias
  • Publication number: 20200399573
    Abstract: Provided herein are methods for culturing patient-derived tumor cell spheroids in a three-dimensional microfluidic device. The method comprises mincing primary tumor sample in a medium supplemented with serum; treating the minced primary tumor sample with a composition comprising an enzyme; collecting tumor spheroids having a diameter of 10 ?m to 500 ?m from the enzyme treated sample; suspending the tumor spheroids in biocompatible gel; and culturing the tumor spheroids in a three dimensional microfluidic device. Methods for identifying an agent for treating cancer and microfluidic devices that allow for the simultaneous exposure of the cultured patient-derived primary tumor cell spheroids to a treatment of choice and to control treatment are also provided.
    Type: Application
    Filed: October 2, 2019
    Publication date: December 24, 2020
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: David Barbie, Amir Aref, Thanh Barbie, Russell W. Jenkins, Kwok-kin Wong
  • Publication number: 20200399224
    Abstract: Provided herein are compounds useful for the treatment of various proliferative diseases. These compounds, as well as pharmaceutically acceptable salts thereof may be formulated in pharmaceutical compositions, and may be used in methods of treatment and/or prophylaxis of proliferative diseases, including cancer, and more specifically, pancreatic cancer.
    Type: Application
    Filed: September 4, 2020
    Publication date: December 24, 2020
    Applicants: The Broad Insitute, Inc., Dana-Farber Cancer Institute, Inc., President and Fellows Of Harvard College
    Inventors: Srivatsan Raghavan, Bruce Hua, Shubhroz Gill, Stuart Schreiber, William Hahn, Paul Clemons, Raymond Ng, Partha Nag
  • Patent number: 10870636
    Abstract: The application relates to a compound having Formula (I): which modulates the activity of EGFR, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which EGFR plays a role.
    Type: Grant
    Filed: March 1, 2019
    Date of Patent: December 22, 2020
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, Pasi Janne, Hwan Geun Choi, Jaebong Jang
  • Patent number: 10870705
    Abstract: The present invention provides chimeric antigen receptor cells specific for carbonic anhydrase IX (CAIX) and methods of using same for treatment of CAIX expressing cancers such as renal cell carcinoma.
    Type: Grant
    Filed: December 21, 2015
    Date of Patent: December 22, 2020
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventor: Wayne A. Marasco
  • Patent number: 10870651
    Abstract: The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g.
    Type: Grant
    Filed: December 23, 2015
    Date of Patent: December 22, 2020
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Yanke Liang, Tinghu Zhang, Nicholas Paul Kwiatkowski
  • Patent number: 10870694
    Abstract: The present invention comprises methods of using a humanized monoclonal antibody that binds to the human immunoglobulin heavy chain variable region germline gene VH1-69 to treat B-cell disorders.
    Type: Grant
    Filed: September 5, 2017
    Date of Patent: December 22, 2020
    Assignee: Dana Farber Cancer Institute, Inc.
    Inventor: Wayne A. Marasco
  • Publication number: 20200392533
    Abstract: Disclosed are methods of modifying the genome of HSPCs in vivo by introducing an AAV into a subject transducing a sequence targeting nuclease. In some aspects, the method can be utilized to ascertain causal links between CHIP mutations and age-associated disease. In other aspects, the method can be utilized to treat Sickle cell disease (SCD) and ?-thalassemia.
    Type: Application
    Filed: April 11, 2018
    Publication date: December 17, 2020
    Applicants: President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc., Dana-Farber Cancer Institute, Inc.
    Inventors: Amy J. Wagers, Leo Wang, Jill Goldstein
  • Patent number: 10865205
    Abstract: The present application provides bifunctional compounds of Formula (Ia) or (Ib): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 8 (CDK8). The present application also relates to methods for the targeted degradation of CDK8 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK8 which can be utilized in the treatment of disorders modulated by CDK8.
    Type: Grant
    Filed: April 21, 2017
    Date of Patent: December 15, 2020
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Calla M. Olson, Yanke Liang, Nicholas Kwiatkowski
  • Patent number: 10865204
    Abstract: The present application provides bifunctional compounds of Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 4 (CDK4) and/or cyclin-dependent kinase 6 (CDK6). The present application also relates to methods for the targeted degradation of CDK4 and/or CDK6 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK4 and/or CDK6 which can be utilized in the treatment of disorders modulated by CDK4 and/or CDK6.
    Type: Grant
    Filed: April 21, 2017
    Date of Patent: December 15, 2020
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Calla M. Olson, Yanke Liang, Nicholas Kwiatkowski, Baishan Jiang, Eric Wang
  • Patent number: 10865232
    Abstract: Methods and compositions for cancer immunotherapy are provided. The methods involve the use of a chimeric molecule (e.g., fusion protein) comprising a dimeric NKG2D portion and an Fc portion, which binds one or more NKG2D ligands. In some embodiments, the molecule further comprises a drug moiety (e.g., an IL15/Ra moiety). The methods disclosed herein are useful for the treatment of cancer that is associated with abnormal expression of one or more NKG2D ligands.
    Type: Grant
    Filed: November 11, 2016
    Date of Patent: December 15, 2020
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: Glenn Dranoff, Ryan Sullivan, Matthew Vanneman
  • Patent number: 10865252
    Abstract: The present embodiments provide for compositions and methods that regulate microRNA-binding protein-mediated miRNA biogensis; for example Lin28-mediated biogenesis of let-7; and in particular Lin28A-recruited 3? terminal uridylyl transferase (TUTase) uridylation of pre-let-7. A particular embodiment provide compositions and methods for screening for agents that inhibit TUTase-dependent Lin28A-mediated repression of let-7 miRNA.
    Type: Grant
    Filed: March 6, 2018
    Date of Patent: December 15, 2020
    Assignees: Dana-Farber Cancer Institute, Inc., Children's Medical Center Corporation
    Inventors: Richard I. Gregory, Elena Piskounova, Dimitrios Iliopoulos
  • Patent number: 10865233
    Abstract: Methods for cancer immunotherapy are provided. The methods involve the use of a chimeric molecule (e.g., fusion protein) comprising an NKG2D portion and an Fc portion, which binds one or more NKG2D ligands. The methods disclosed herein are useful for the treatment of cancer that is associated with abnormal expression of one or more NKG2D ligands.
    Type: Grant
    Filed: December 18, 2009
    Date of Patent: December 15, 2020
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: Glenn Dranoff, Matthew Vanneman, Gordon Freeman