Patents by Inventor Dennis Buckley

Dennis Buckley has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 10730862
    Abstract: The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins that are degraded and/or otherwise inhibited by bifunctional compounds of the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand that binds to the ubiquitin ligase and on the other end a moiety that binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds of the present invention, consistent with the degradation/inhibition of targeted polypeptides.
    Type: Grant
    Filed: January 11, 2013
    Date of Patent: August 4, 2020
    Assignees: Yale University, Glaxosmithkline Intellectual Property Development, Cambridge Enterprise Limited University of Cambridge
    Inventors: Craig M. Crews, Dennis Buckley, Alessio Ciulli, William Jorgensen, Peter C. Gareiss, Inge Van Molle, Jeffrey Gustafson, Hyun-Seop Tae, Julien Michel, Denton Wade Hoyer, Anke G. Roth, John David Harling, Ian Edward David Smith, Afjal Hussain Miah, Sebastien Andre Campos, Joelle Le
  • Publication number: 20200216454
    Abstract: The invention provides bifunctional compounds which act as protein degradation inducing moieties for a HER family protein, such as Her3. The invention also provides methods for the targeted degradation of a HER family protein through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to the HER family protein which can be utilized in the treatment of disorders modulated by a HER family protein.
    Type: Application
    Filed: December 29, 2016
    Publication date: July 9, 2020
    Inventors: Nathanael S. GRAY, James BRADNER, Pasi JANNE, Jaebong JANG, Dennis BUCKLEY, Dennis DOBROVOLSKY
  • Patent number: 10702504
    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 tripartite motif-containing 24 (TRIM24). The present application also relates to methods for the targeted degradation of TRIM24 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to TRIM24 which can be utilized in the treatment of disorders modulated by TRIM24.
    Type: Grant
    Filed: June 23, 2017
    Date of Patent: July 7, 2020
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: James Bradner, Dennis Buckley, Lara Gechijian
  • Publication number: 20200199150
    Abstract: The present invention provides compounds and pharmaceutically compositions thereof. The compounds and compositions 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: Application
    Filed: September 9, 2016
    Publication date: June 25, 2020
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: James E. Bradner, Jun Qi, Minoru Tanaka, Dennis Buckley
  • Patent number: 10669253
    Abstract: The present application provides bifunctional compounds which act as SMARCA2 and Ras protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of SMARCA2 and Ras through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to SMARCA2 or Ras.
    Type: Grant
    Filed: October 22, 2018
    Date of Patent: June 2, 2020
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: James Bradner, Dennis Buckley, Georg Winter
  • Publication number: 20190374657
    Abstract: The present invention provides a means to modulate gene expression in vivo in a manner that avoids problems associated with CRISPR endogenous protein knock-out or knock-in strategies and strategies that provide for correction, or alteration, of single nucleotides. The invention includes inserting into the genome a nucleotide encoding a heterobifunctional compound targeting protein (dTAG) in-frame with the nucleotide sequence of a gene encoding an endogenously expressed protein of interest which, upon expression, produces an endogenous protein-dTAG hybrid protein. This allows for targeted protein degradation of the dTAG and the fused endogenous protein using a heterobifunctional compound.
    Type: Application
    Filed: February 8, 2018
    Publication date: December 12, 2019
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Dennis Buckley, Georg Winter, Andrew J. Phillips, Timothy P. Heffernan, James Bradner, Justin Roberts, Behnam Nabet
  • Publication number: 20190374528
    Abstract: The present application provides bifunctional compounds of Formula (I): or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for protein kinases (e.g., Bcr-Abl). The present application also relates to methods for the targeted degradation of one or more protein kinases through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to one or more protein kinases which can be utilized in the treatment of disorders modulated by protein kinases.
    Type: Application
    Filed: November 10, 2017
    Publication date: December 12, 2019
    Inventors: Nathanael S. GRAY, James BRADNER, Li TAN, Hai-Tsang HUANG, Dennis BUCKLEY, Georg WINTER, Mette Ishoey ROSENBAUM
  • Publication number: 20190365875
    Abstract: This invention is in the area of compositions and methods for regulating chimeric antigen receptor immune effector cell, for example T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation.
    Type: Application
    Filed: February 8, 2018
    Publication date: December 5, 2019
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: James Bradner, Justin Roberts, Behnam Nabet, Georg Winter, Andrew J. Phillips, Timothy P. Heffernan, Dennis Buckley
  • Patent number: 10464925
    Abstract: The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof.
    Type: Grant
    Filed: January 5, 2018
    Date of Patent: November 5, 2019
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: James Bradner, Dennis Buckley, Georg Winter
  • Publication number: 20190314374
    Abstract: The present invention relates to methods, compositions and kits for treatment of ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA). In some embodiments, the invention relates to the use of novel classes of compounds, i.e. inhibitors of RSK (p90S6K); inhibitors of p70S6K; and inhibitors of rps6, to treat ribosomal disorders and ribosomopathies. In some embodiments, the invention relates to the use of specific Chk2 inhibitors and to the use of specific phenothiazine derivatives to treat ribosomal disorders and ribosomopathies, e.g. DBA.
    Type: Application
    Filed: July 13, 2017
    Publication date: October 17, 2019
    Applicants: The Children's Medical Center Corporation, Dana-Faber Cancer Institute, Inc.
    Inventors: James BRADNER, Jun QI, Dennis BUCKLEY, Leonard I. ZON, Elizabeth MACARI
  • Publication number: 20190263823
    Abstract: The present application provides bifunctional compounds of Formula (X): or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for protein kinases. The present application also relates to methods for the targeted degradation of one or more protein kinases through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to one or more protein kinases which can be utilized in the treatment of disorders modulated by protein kinases.
    Type: Application
    Filed: November 22, 2017
    Publication date: August 29, 2019
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: James BRADNER, Dennis BUCKLEY, Mette Ishoey ROSENBAUM, Georg WINTER
  • Publication number: 20190247509
    Abstract: The present application provides bifunctional compounds of Formula (I): or Targeting Ligand or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for bromodomain-containing protein 9 (BRD9). The present application also provides methods for the targeted degradation of BRD9 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to BRD9 which can be utilized in the treatment of disorders modulated by BRD9.
    Type: Application
    Filed: June 23, 2017
    Publication date: August 15, 2019
    Inventors: Dennis BUCKLEY, James BRADNER, David Ian REMILLARD
  • Publication number: 20190209535
    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 tripartite motif-containing 24 (TRIM24). The present application also relates to methods for the targeted degradation of TRIM24 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to TRIM24 which can be utilized in the treatment of disorders modulated by TRIM24.
    Type: Application
    Filed: June 23, 2017
    Publication date: July 11, 2019
    Inventors: James BRADNER, Dennis BUCKLEY, Lara GECHIJIAN
  • Patent number: 10308653
    Abstract: The present disclosure provides compounds of Formula (I), and pharmaceutically compositions thereof. Compounds of Formula (I) have been found to bind bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits of 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, neurological diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.
    Type: Grant
    Filed: February 7, 2017
    Date of Patent: June 4, 2019
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: James E. Bradner, Dennis Buckley
  • Publication number: 20190151457
    Abstract: The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof.
    Type: Application
    Filed: January 31, 2019
    Publication date: May 23, 2019
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: James Bradner, Dennis Buckley, Georg Winter
  • Publication number: 20190127359
    Abstract: The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.
    Type: Application
    Filed: December 18, 2018
    Publication date: May 2, 2019
    Inventors: CRAIG M. CREWS, DENNIS BUCKLEY, ALESSIO CIULLI, WILLIAM L. JORGENSEN, PETER C. GAREISS, INGE VAN MOLLE, JEFFREY GUSTAFSON, HYUN-SEOP TAE, JULIEN MICHEL, DENTON WADE HOYER, ANKE G. ROTH, JOHN DAVID HARLING, IAN EDWARD DAVID SMITH, AFJAL HUSSAIN MIAH, SEBASTIEN ANDRE CAMPOS, JOELLE LE
  • Patent number: 10239888
    Abstract: The present application provides bifunctional compounds of Formula I or II: or an enantiomer, diastereomer, or stereoisomer, or a pharmaceutically acceptable salt thereof, which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds of Formula (I) or (II) that link a mutant cereblon-binding moiety to a ligand that is capable of binding to a targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof. The present application also relates to polynucleotides or polypeptides of a mutant cereblon and methods of use thereof.
    Type: Grant
    Filed: July 25, 2018
    Date of Patent: March 26, 2019
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: James Bradner, Mette Ishoey, Dennis Buckley, Joshiawa Paulk, Marc Andrew Cohen, Rhamy Zeid
  • Publication number: 20190071415
    Abstract: The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof.
    Type: Application
    Filed: October 22, 2018
    Publication date: March 7, 2019
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: James Bradner, Dennis Buckley, Georg Winter
  • Publication number: 20180327419
    Abstract: The present application provides bifunctional compounds of Formula I or II: or an enantiomer, diastereomer, or stereoisomer, or a pharmaceutically acceptable salt thereof, which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds of Formula (I) or (II) that link a mutant cereblon-binding moiety to a ligand that is capable of binding to a targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof. The present application also relates to polynucleotides or polypeptides of a mutant cereblon and methods of use thereof.
    Type: Application
    Filed: July 25, 2018
    Publication date: November 15, 2018
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: James Bradner, Mette Ishoey, Dennis Buckley, Joshiawa Paulk, Marc Andrew Cohen, Rhamy Zeid
  • Patent number: 10125114
    Abstract: The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof.
    Type: Grant
    Filed: June 23, 2017
    Date of Patent: November 13, 2018
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: James Bradner, Dennis Buckley, Georg Winter