Patents by Inventor Dale Boger

Dale Boger 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: 10975101
    Abstract: Synthetically-derived and previously inaccessible modifications of 20?-hydroxy-vinca derivative compounds such as vinblastine, vincristine or vindesine are disclosed that are a stunning 100-fold more active than the natural product (IC50's 50-75 pM vs 7 nM, HCT116), and are now accessible as a result of advances in the total synthesis of the natural product. Illustrative new ultra-potent vinblastines bind tubulin with much higher affinity and likely further disrupt the tubulin head-to-tail ?/? dimer-dimer interaction by virtue of the strategic placement of an added conformationally well-defined, rigid and extended C20?-urea along the adjacent protein-protein interface. Added molecular complexity was used to markedly enhance target binding and functional biological activity, and represents a general approach to improving the properties of other natural products targeting a protein-protein interaction.
    Type: Grant
    Filed: May 30, 2017
    Date of Patent: April 13, 2021
    Assignee: THE SCRIPPS RESEARCH INSTITUTE
    Inventor: Dale Boger
  • Patent number: 10934326
    Abstract: A C-terminus modification to a binding pocket-modified vancomycin introduces a quaternary ammonium salt that provides a binding pocket-modified vancomycin analog with a second mechanism of action that is independent of D-Ala-D-Ala/D-Ala-D-Lac binding. The modification disrupts cell wall integrity and induces cell wall permeability complementary to the glycopeptide inhibition of cell wall synthesis, and provides synergistic improvements in antimicrobial potency (200-fold) against vancomycin-resistant bacteria. Combining the C-terminus and binding pocket modifications with an orthogonal (4-chlorobiphenyl) methyl addition to the vancomycin disaccharide provides even more potent antimicrobial agents whose activity can be attributed to three independent and synergistic mechanisms of action, only one of which requires D-Ala-D-Ala/D-Ala-D-Lac binding.
    Type: Grant
    Filed: October 31, 2017
    Date of Patent: March 2, 2021
    Assignee: THE SCRIPPS RESEARCH INSTITUTE
    Inventor: Dale Boger
  • Publication number: 20200317696
    Abstract: Synthetically-derived and previously inaccessible modifications of 20?-hydroxy-vinca derivative compounds such as vinblastine, vincristine or vindesine are disclosed that are a stunning 100-fold more active than the natural product (IC50's 50-75 pM vs 7 nM, HCT116), and are now accessible as a result of advances in the total synthesis of the natural product. Illustrative new ultra-potent vinblastines bind tubulin with much higher affinity and likely further disrupt the tubulin head-to-tail ?/? dimer-dimer interaction by virtue of the strategic placement of an added conformationally well-defined, rigid and extended C20?-urea along the adjacent protein-protein interface. Added molecular complexity was used to markedly enhance target binding and functional biological activity, and represents a general approach to improving the properties of other natural products targeting a protein-protein interaction.
    Type: Application
    Filed: May 30, 2017
    Publication date: October 8, 2020
    Inventor: Dale Boger
  • Patent number: 10689381
    Abstract: A vinca alkaloid compound substituted at the 20?-position with a carboxamido group is disclosed. The carbonyl of the carboxamido group is bonded to a 20?-amino group and to a ring system that contains up to three 5-, 6- or 7-membered rings that are fused or otherwise bonded together. Each ring can be carbocyclic or heterocyclic, with a heterocyclic ring containing up to three hetero ring atoms that are the same or different and are selected from nitrogen, oxygen and sulfur. The ring system can include up to four substituent groups other than hydrogen that are discussed within. Methods of preparing the compounds are disclosed as are compositions for their use and methods of treatment using d compound. A particularly preferred compound has an activity in specified cancer cell growth inhibition assays that is the same or better than its parental, unsubstituted vinca compound and is not subject to Pgp-mediated efflux.
    Type: Grant
    Filed: August 1, 2018
    Date of Patent: June 23, 2020
    Assignee: The Scripps Research Institute
    Inventor: Dale Boger
  • Publication number: 20190119277
    Abstract: A vinca alkaloid compound substituted at the 20?-position with a carboxamido group is disclosed. The carbonyl of the carboxamido group is bonded to a 20?-amino group and to a ring system that contains up to three 5-, 6- or 7-membered rings that are fused or otherwise bonded together. Each ring can be carbocyclic or heterocyclic, with a heterocyclic ring containing up to three hetero ring atoms that are the same or different and are selected from nitrogen, oxygen and sulfur. The ring system can include up to four substituent groups other than hydrogen that are discussed within. Methods of preparing the compounds are disclosed as are compositions for their use and methods of treatment using d compound. A particularly preferred compound has an activity in specified cancer cell growth inhibition assays that is the same or better than its parental, unsubstituted vinca compound and is not subject to Pgp-mediated efflux.
    Type: Application
    Filed: August 1, 2018
    Publication date: April 25, 2019
    Inventor: Dale Boger
  • Patent number: 9918959
    Abstract: A TLR-independent adjuvant compound that corresponds in structure to Formula I, below, or its pharmaceutically acceptable salt is disclosed in which X, Y, Z, n, R1, R2, R3, R4 and W are defined within. Also disclosed are a method of its preparation and use, as well as a pharmaceutical composition containing the same.
    Type: Grant
    Filed: August 5, 2015
    Date of Patent: March 20, 2018
    Assignees: The Board of Regents of the University of Texas System, The Scripps Research Institute
    Inventors: Dale Boger, Bruce Beutler
  • Patent number: 9611271
    Abstract: A vinca alkaloid compound that is substituted at the 20?-position with a urea or thiourea group is disclosed. The urea's proximal nitrogen atom bonded to the 20?-position carbon atom is secondary, whereas the distal nitrogen atom can be unsubstituted only when the compound contains an optionally present 10?-fluoro substituent, and is otherwise preferably mono- or di-substituted. Methods of preparing the compounds are disclosed as are compositions for their use and methods of treatment using a compound.
    Type: Grant
    Filed: August 23, 2013
    Date of Patent: April 4, 2017
    Assignee: SCRIPPS RESEARCH INSTITUTE
    Inventor: Dale Boger
  • Patent number: 9586974
    Abstract: A group of cyclic N-acyl O-amino phenol CBI derivatives were synthesized and shown to be pro-drugs, subject to reductive activation by cleavage of a N-0 bond, effectively releasing the free drug in functional in vitro cellular assays for cytotoxic activity approaching the activity of the free drug, yet remain essentially stable to ex vivo DNA alkylation conditions. Assessment of the in vivo antitumor activity of a representative pro-drug indicates that a contemplated pro-drug approaches the potency and exceeds the efficacy of the free drug itself (CBI-indole2), indicating that the inactive pro-drugs not only effectively release the free drug in vivo, but that they offer additional advantages related to a controlled or targeted release in vivo.
    Type: Grant
    Filed: March 20, 2014
    Date of Patent: March 7, 2017
    Assignee: The Scripps Research Institute
    Inventor: Dale Boger
  • Publication number: 20150291610
    Abstract: A vinca alkaloid compound that is substituted at the 20?-position with a urea or thiourea group is disclosed. The urea's proximal nitrogen atom bonded to the 20?-position carbon atom is secondary, whereas the distal nitrogen atom can be unsubstituted only when the compound contains an optionally present 10?-fluoro substituent, and is otherwise preferably mono- or di-substituted. Methods of preparing the compounds are disclosed as are compositions for their use and methods of treatment using a compound.
    Type: Application
    Filed: August 23, 2013
    Publication date: October 15, 2015
    Inventor: Dale Boger
  • Patent number: 8377981
    Abstract: A unique class of N-acyl O-amino phenol prodrugs of CBI-TMI and CBI-indole2 were synthesized and shown to be prodrugs, subject to reductive activation by nucleophilic cleavage of a weak N—O bond, effectively releasing the free drug in functional cellular assays for cytotoxic activity approaching or matching the activity of the free drug, yet remain essentially stable to ex vivo DNA alkylation conditions. Most impressively, assessment of the in vivo antitumor activity of a representative O-(acylamino) prodrug, 8, indicate that they approach the potency and exceed the efficacy of the free drug itself (CBI-indole2), indicating that the inactive prodrugs not only effectively release the free drug in vivo, but that they offer additional advantages related to a controlled or targeted release in vivo.
    Type: Grant
    Filed: November 13, 2008
    Date of Patent: February 19, 2013
    Assignee: The Scripps Research Institute
    Inventor: Dale Boger
  • Publication number: 20110112163
    Abstract: A unique class of N-acyl O-amino phenol prodrugs of CBI-TMI and CBI-indole2 were synthesized and shown to be prodrugs, subject to reductive activation by nucleophilic cleavage of a weak N—O bond, effectively releasing the free drug in functional cellular assays for cytotoxic activity approaching or matching the activity of the free drug, yet remain essentially stable to ex vivo DNA alkylation conditions. Most impressively, assessment of the in vivo antitumor activity of a representative O-(acylamino) prodrug, 8, indicate that they approach the potency and exceed the efficacy of the free drug itself (CBI-indole2), indicating that the inactive prodrugs not only effectively release the free drug in vivo, but that they offer additional advantages related to a controlled or targeted release in vivo.
    Type: Application
    Filed: November 13, 2008
    Publication date: May 12, 2011
    Inventor: Dale Boger
  • Publication number: 20080096931
    Abstract: Certain oxadiazole ketone compounds are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity. Thus, the compounds may be administered to treat anxiety, pain, inflammation, sleep disorders, eating disorders, or movement disorders (such as MS).
    Type: Application
    Filed: October 19, 2007
    Publication date: April 24, 2008
    Applicant: The Scripps Research Institute
    Inventor: Dale Boger
  • Publication number: 20070203156
    Abstract: Certain oxazole ketone compounds are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity. Thus, the compounds may be administered to treat anxiety, pain, inflammation, sleep disorders, eating disorders, or movement disorders (such as MS).
    Type: Application
    Filed: February 20, 2007
    Publication date: August 30, 2007
    Applicant: The Scripps Research Institute
    Inventor: Dale Boger
  • Publication number: 20070173438
    Abstract: [?[CH2NH]PG4] glycopeptide antibiotic analogs are reengineered forms of glycopeptides that exhibit antimicrobial activity against both wild type and glycopeptide antibiotic resistant strains of microorganisms. For example, [?[CH2NH]Tpg4] vancomycin aglycon is a reengineered form of vancomycin that exhibits antimicrobial activity (MIC=31 ?g/mL) against both wild type and VanA resistant organism (E. faecalis BM4166). The VanA resistant organism achieves its resistance, upon glycopeptide antibiotic challenge, by remodeling its D-Ala-D-Ala peptidoglycan cell wall precursor to D-Ala-D-Lac. [?[CH2NH]PG4] glycopeptide antibiotic analogs have an altered glycopeptide backbone wherein the carbonyl of the fourth amino acid residue of the glycopeptide backbone has been replaced with a methylene. This alteration of the glycopeptide backbone imparts dual binding affinities for both D-Ala-D-Ala and D-Ala-D-Lac and dual antimicrobial activities for both wild type and resistant strains.
    Type: Application
    Filed: January 16, 2007
    Publication date: July 26, 2007
    Applicant: The Scripps Research Institute
    Inventor: Dale Boger
  • Publication number: 20070167377
    Abstract: Potent human inhibitors of human glycinamide ribonucleotide transformylase and of aminoimidazole carboxamide ribonucleotide transformylase are designed, synthesized, and characterized.
    Type: Application
    Filed: April 7, 2003
    Publication date: July 19, 2007
    Inventors: Dale Boger, Ian Wilson
  • Publication number: 20060211769
    Abstract: Angiogenesis, tumor growth, and metalloproteinase 2 (MMP2) interaction with integrin-?v?3 are inhibited by an inhibitor compound of formula: wherein G1 and G2 are each independently —NH—C(O)—O—(CH2)v—(C6H4)—X3; Y1 and Y2 are each independently —OH or C1-C4 alkoxy; X1 and X2 are each independently halo or C1-C4 alkoxy; X3 is fluoro, nitro, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 perfluoroalkyl; Z is —C?C—, —C6H4—, cis —CH?CH—, trans —CH?CH—, cis —CH2—CH?CH—CH2—, trans —CH2—CH?CH—CH2—, 1,4-naphthyl, cis-1,3-cyclohexyl, trans-1,3-cyclohexyl, cis-1,4-cyclohexyl, or trans-1,4-cyclohexyl; A is H or a covalent bond; m and n are each 1; t is an integer having a value of 0 or 1; p and r are each 2, and v is 1; with the proviso that when A is H, t is 0, and when A is a covalent bond, t is 1.
    Type: Application
    Filed: May 24, 2006
    Publication date: September 21, 2006
    Inventors: Dale Boger, David Cheresh
  • Publication number: 20060167271
    Abstract: A purified compound and its pharmaceutically acceptable salt that inhibits the binding between the integrin intracellular or cytoplasmic tail polypeptide and Paxillin, a pharmaceutical composition containing that compound or salt and a method of treating a biological function in an animal using that compound or salt are disclosed. The purified compound corresponds in structure to Formula I, wherein W1 and W2, X1, X2 and X3 and Y are defined within.
    Type: Application
    Filed: October 30, 2003
    Publication date: July 27, 2006
    Inventors: Mark Ginsberg, Dale Boger
  • Publication number: 20060111359
    Abstract: Improved competitive inhibitors of FAAH employ an ?-keto heterocyclic pharmacophore and a binding subunit having a ?-unsaturation. The ?-keto heterocyclic pharmacophore and a binding subunit are attached to one another, preferably by a hydrocarbon chain. The improvement lies in the use of a heterocyclic pharmacophore selected from oxazoles, oxadiazoles, thiazoles, and thiadiazoles that have alkyl or aryl substituents at their 4 and/or 5 positions. The improved competitive inhibitors of FAAH display enhanced activity over conventional competitive inhibitors of FAAH.
    Type: Application
    Filed: October 8, 2003
    Publication date: May 25, 2006
    Applicant: The Scripps Research Institute
    Inventor: Dale Boger
  • Publication number: 20060100212
    Abstract: Certain oxadiazole ketone compounds are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity. Thus, the compounds may be administered to treat anxiety, pain, inflammation, sleep disorders, eating disorders, or movement disorders (such as MS).
    Type: Application
    Filed: October 14, 2005
    Publication date: May 11, 2006
    Applicant: The Scripps Research Institute
    Inventor: Dale Boger
  • Publication number: 20050239785
    Abstract: Potent inhibitors of fatty acid amide hydrolase (FAAH) are constructed having Ki's below 200 pM and activities 102-103 times more potent than the corresponding trifluoromethyl ketones. The potent inhibitors combine several features, viz.: 1.) an ?-keto heterocylic head group; 2.) a hydrocarbon linkage unit employing an optimal C12-C8 chain length; and 3.) a phenyl or other ?-unsaturation corresponding to the arachidonyl ?8,9/?11,12 and/or oleyl ?9,10 positions. A preferred ?-keto heterocylic head group is ?-keto N4 oxazolopyridine, with incorporation of a second weakly basic nitrogen. Fatty acid amide hydrolase is an enzyme responsible for the degradation of oleamide (an endogenous sleep-inducing lipid) and anandamide (an endogenous ligand for cannabinoid receptors).
    Type: Application
    Filed: March 28, 2005
    Publication date: October 27, 2005
    Applicant: The Scripps Research Institute
    Inventor: Dale Boger