Patents by Inventor Terrence R. Burke, Jr.
Terrence R. Burke, Jr. 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).
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Patent number: 10905769Abstract: The description provides novel compounds that may serve as anticancer therapeutics. The compounds of the description bind to polo-like kinases through the polo-box domain. The peptide derivatives of the description have achieved improved efficacy in biochemical assays against Plk1. Exemplary compounds of the description include macrocyclic peptidomimetics with high affinity and selectivity for polo-like kinases, which may provide the basis for a new genre of anticancer therapeutics. Other exemplary compounds of the description include bi-valent compounds with that bind to polo-like kinases through both kinase domain and polo-box domain simultaneously by incorporating additional moieties that target Plk1 kinase domain, which significantly enhances affinitity relative and may provide the basis for a new genre of anticancer therapeutics. The description also provides methods of use, methods of preparation, compositions, and kits thereof.Type: GrantFiled: May 11, 2018Date of Patent: February 2, 2021Assignee: The United States of America, as represented by the Secretary, Department of Health & Human ServicesInventors: Terrence R. Burke, Jr., David T. Hymel, Kohei Tsuji
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Patent number: 10266565Abstract: Novel compounds are provided that bind to polo-like kinases through the polo-box domain. In certain embodiments, the novel compounds are PEGylated peptides. The PEGylated peptides in accordance with the invention demonstrate high PBD-binding affinity. In certain embodiments, the PEGylated peptides have also achieved activities in whole cell systems. The invention also provides compounds that bind polo-like kinases through the polo-box domain and possess reduced anionic charge. Further provided are methods of design and/or synthesis of the PEGylated peptides and methods of use thereof. The invention provides methods of use of the compounds and methods of synthesis of the compounds.Type: GrantFiled: April 12, 2012Date of Patent: April 23, 2019Assignee: The United States of America, as represented by the Secretary, Department of Health & Human ServicesInventors: Terrence R. Burke, Jr., Fa Liu, Kyung S. Lee, Jung-Eun Park
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Patent number: 10208035Abstract: A method of inhibiting drug-resistant HIV-1 integrase in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or ester thereof, having a structure of: wherein X is N, C(OH), or CH; Y is H or OH; each of Z1-Z5 is independently H or halogen; R4 is H, OH, NH2, NHR8, NR8R9 or R8; R5, R6, and R7 is each independently H, halogen, OR8, R8, NHR8, NR8R9, CO2R8, CONR8R9, SO2NR8R9, or R5 and R6 together with the carbon atoms to which R5 and R6 are attached form an optionally-substituted carbocycle or optionally-substituted heterocycle; and R8 and R9 is each independently H, optionally-substituted alkyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted cycloalkylene, optionally-substituted heterocycle, optionally-substituted amide, optionally-substituted ester, or R8 and R9 together with the nitrogen tType: GrantFiled: May 8, 2017Date of Patent: February 19, 2019Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Xue Zhi Zhao, Steven Smith, Mathieu Metifiot, Barry Johnson, Christophe Marchand, Stephen H. Hughes, Yves Pommier, Terrence R. Burke, Jr.
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Publication number: 20180296686Abstract: The description provides novel compounds that may serve as anticancer therapeutics. The compounds of the description bind to polo-like kinases through the polo-box domain. The peptide derivatives of the description have achieved improved efficacy in biochemical assays against Plk1. Exemplary compounds of the description include macrocyclic peptidomimetics with high affinity and selectivity for polo-like kinases, which may provide the basis for a new genre of anticancer therapeutics. Other exemplary compounds of the description include bi-valent compounds with that bind to polo-like kinases through both kinase domain and polo-box domain simultaneously by incorporating additional moieties that target Plk1 kinase domain, which significantly enhances affinitity relative and may provide the basis for a new genre of anticancer therapeutics. The description also provides methods of use, methods of preparation, compositions, and kits thereof.Type: ApplicationFiled: May 11, 2018Publication date: October 18, 2018Inventors: Terrence R. Burke, JR., David T. Hymel, Kohei Tsuji
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Patent number: 10047122Abstract: The invention provides novel compounds that may serve as anticancer therapeutics. The compounds of the invention bind to polo-like kinases through the polo-box domain. In certain embodiments, the compounds of the invention are POM-protected peptide derivatives. The use of cationic bis-alkyl his residues in combination with a mono POM-protected phophoryl group results in a peptide possessing an overall neutral charge. The peptide derivatives of the invention have achieved both good efficacy and an enhanced bioavailability. The invention also provides methods of use, compositions, and kits thereof. Further, the invention provides a novel method of design and/or synthesis of phosphoryl-derived peptide derivatives useful as therapeutic agents.Type: GrantFiled: March 14, 2014Date of Patent: August 14, 2018Assignee: The United States of America, as represented by the Secretary, Department of Health & Human ServicesInventors: Wenjian Qian, Jung Eun Park, Christopher C. Lai, James A. Kelley, Kyung S. Lee, Terrence R. Burke, Jr.
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Publication number: 20170305904Abstract: A method of inhibiting drug-resistant HIV-1 integrase in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or ester thereof, having a structure of: wherein X is N, C(OH), or CH; Y is H or OH; each of Z1-Z5 is independently H or halogen; R4 is H, OH, NH2, NHR8, NR8R9 or R8; R5, R6, and R7 is each independently H, halogen, OR8, R8, NHR8, NR8R9, CO2R8, CONR8R9, SO2NR8R9, or R5 and R6 together with the carbon atoms to which R5 and R6 are attached form an optionally-substituted carbocycle or optionally-substituted heterocycle; and R8 and R9 is each independently H, optionally-substituted alkyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted cycloalkylene, optionally-substituted heterocycle, optionally-substituted amide, optionally-substituted ester, or R8 and R9 together with the nitrogen tType: ApplicationFiled: May 8, 2017Publication date: October 26, 2017Applicant: The United States of America, as represented by the Secretary, Department of Health and Human ServInventors: Xue Zhi Zhao, Steven Smith, Mathieu Metifiot, Barry Johnson, Christophe Marchand, Stephen H. Hughes, Yves Pommier, Terrence R. Burke, JR.
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Patent number: 9676771Abstract: A method of inhibiting drug-resistant HIV-1 integrase in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or ester thereof, having a structure of: wherein X is N, C(OH), or CH; Y is H or OH; each of Z1-Z5 is independently H or halogen; R4 is H, OH, NH2, NHR8, NR8R9 or R8; R5, R6, and R7 is each independently H, halogen, OR8, R8, NHR8, NR8R9, CO2R8, CONR8R9, SO2NR8R9, or R5 and R6 together with the carbon atoms to which R5 and R6 are attached form an optionally-substituted carbocycle or optionally-substituted heterocycle; and R8 and R9 is each independently H, optionally-substituted alkyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted cycloalkylene, optionally-substituted heterocycle, optionally-substituted amide, optionally-substituted ester, or R8 and R9 together with the nitrogen tType: GrantFiled: May 13, 2014Date of Patent: June 13, 2017Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Xue Zhi Zhao, Steven Smith, Mathieu Metifiot, Barry Johnson, Christophe Marchand, Stephen H. Hughes, Yves Pommier, Terrence R. Burke, Jr.
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Publication number: 20160083382Abstract: A method of inhibiting drug-resistant HIV-1 integrase in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or ester thereof, having a structure of: wherein X is N, C(OH), or CH; Y is H or OH; each of Z1-Z5 is independently H or halogen; R4 is H, OH, NH2, NHR8, NR8R9 or R8; R5, R6, and R7 is each independently H, halogen, OR8, R8, NHR8, NR8R9, CO2R8, CONR8R9, SO2NR8R9, or R5 and R6 together with the carbon atoms to which R5 and R6 are attached form an optionally-substituted carbocycle or optionally-substituted heterocycle; and R8 and R9 is each independently H, optionally-substituted alkyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted cycloalkylene, optionally-substituted heterocycle, optionally-substituted amide, optionally-substituted ester, or R8 and R9 together with the nitrogen tType: ApplicationFiled: May 13, 2014Publication date: March 24, 2016Applicant: The United States of American, as represented by the Sec, Dept. of Health and Human ServicesInventors: Xue Zhi Zhao, Steven Smith, Mathieu Metifiot, Barry Johnson, Christophe Marchand, Stephen H. Hughes, Yves Pommier, Terrence R. Burke, Jr.
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Publication number: 20160039872Abstract: The invention provides novel compounds that may serve as anticancer therapeutics. The compounds of the invention bind to polo-like kinases through the polo-box domain. In certain embodiments, the compounds of the invention are POM-protected peptide derivatives. The use of cationic bis-alkyl his residues in combination with a mono POM-protected pho-phoryl group results in a peptide possessing an overall neutral charge. The peptide derivatives of the invention have achieved both good efficacy and an enhanced bioavailability. The invention also provides methods of use, compositions, and kits thereof. Further, the invention provides a novel method of design and/or synthesis of phosphoryl-derived peptide derivatives useful as therapeutic agents.Type: ApplicationFiled: March 14, 2014Publication date: February 11, 2016Inventors: Wenjian Qian, Jung Eun Park, Christopher C. Lai, James A. Kelley, Kyung S. Lee, Terrence R. Burke, JR.
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Patent number: 9175038Abstract: Found in various eukaryotic organisms, polo-like kinases (collectively, Plks) are a conserved subfamily of Ser/Thr protein kinases that play critical roles in cell proliferation. Provided herein are compounds that specifically inhibit the activity of Plks, specifically Plk1. Further provided herein are methods for use of the compounds for the treatment of hyperproliferative disorders, particularly cancer. Also provided are uses of the compounds for the preparation of a medicament.Type: GrantFiled: May 17, 2010Date of Patent: November 3, 2015Assignee: The United States of America, as represented by the Secretary, Department of Health & Human ServicesInventors: Terrence R. Burke, Jr., Fa Liu, Kyung S. Lee, Jung-Eun Park
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Publication number: 20150104383Abstract: The invention provides methods and compositions employing hybrid molecules of a synthetic molecule and antibody or antibody fragment comprising a selenocysteine residue, wherein the synthetic molecule is covalently linked to the antibody or antibody fragment at the selenocysteine residue. The invention also provides a composition comprising a hybrid molecule as described above and a pharmaceutically acceptable carrier. The invention further provides for methods of making the hybrid molecules, and methods of using the hybrid molecule described above to inhibit cell surface receptor binding.Type: ApplicationFiled: December 22, 2014Publication date: April 16, 2015Inventors: Christoph Rader, Thomas Hofer, Terrence R. Burke, JR., Joshua Thomas
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Publication number: 20140142044Abstract: Novel compounds are provided that bind to polo-like kinases through the polo-box domain. In certain embodiments, the novel compounds are PEGylated peptides. The PEGylated peptides in accordance with the invention demonstrate high PBD-binding affinity. In certain embodiments, the PEGylated peptides have also achieved activities in whole cell systems. The invention also provides compounds that bind polo-like kinases through the polo-box domain and possess reduced anionic charge. Further provided are methods of design and/or synthesis of the PEGylated peptides and methods of use thereof. The invention provides methods of use of the compounds and methods of synthesis of the compounds. The compounds of the invention have potential therapeutic activity in view of their binding and inhibitory activities towards Plk1. They are based on the amino acid sequence PLHSpT (phosphorylated Thr). The PEG moiety, when present, is covalently attached at the N-terminus.Type: ApplicationFiled: April 12, 2012Publication date: May 22, 2014Applicant: The United States of America, as represented by the Secretary, Department of Health & Human ServicInventors: Terrence R. Burke, JR., Wenjian Qian, Fa Liu, Kyung S. Lee, Jung-Eun Park
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Publication number: 20120065146Abstract: Found in various eukaryotic organisms, polo-like kinases (collectively, Plks) are a conserved subfamily of Ser/Thr protein kinases that play critical roles in cell proliferation. Provided herein are compounds that specifically inhibit the activity of Plks, specifically Plk1. Further provided herein are methods for use of the compounds for the treatment of hyperproliferative disorders, particularly cancer. Also provided are uses of the compounds for the preparation of a medicament.Type: ApplicationFiled: May 17, 2010Publication date: March 15, 2012Applicant: Government of the United States of America, as Represented by the Secretary, Department of HealthInventors: Terrence R. Burke, JR., Fa Liu, Kyung S. Lee, Jung-Eun Park
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Patent number: 7871981Abstract: Disclosed are methods of inhibiting cell motility, for example, by inhibiting the binding between an intracellular transducer and a receptor protein tyrosine kinase, and more particularly by inhibiting hepatocyte growth factor (HGF) induced cell motility. The present invention also provides a method of inhibiting angiogenesis. The methods of the present invention employ peptides such as phosphotyrosyl mimetics. Also disclosed are methods of preventing and/or treating diseases, disorders, states, or conditions such as cancer, particularly metastatic cancer, for example, melanoma or prostate cancer, comprising administering to a mammal of interest one or more peptides of the present invention. Also disclosed are methods of blocking blocks HGF, VEGF, or bFGF-stimulated migration, cell proliferation, and formation of capillary-like structures.Type: GrantFiled: September 22, 2006Date of Patent: January 18, 2011Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Donald P Bottaro, Alessio Giubellino, Safiye N Atabey, Jesus V Soriano, Diane E Breckenridge, Terrence R Burke, Jr.
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Patent number: 7825216Abstract: The present invention provides phenylalanine derivatives that inhibit SH2 domain binding with a phosphoprotein. These derivatives include compounds of the formula: W—Y-(AA)n-Z wherein n is 0 to 15; Y is a phenylalanyl radical having a phenyl ring, an amine end, and a carboxyl end, the phenyl ring having one or more substituents, e.g., hydroxyl, carboxyl, formyl, carboxyalkyl, carboxyalkyloxy, dicarboxyalkyl, dicarboxyalkyloxy, dicarboxyhaloalkyl, dicarboxyhaloalkyloxy, and phosphonoalkyl, or phosphonohaloalkyl; W is a moiety attached to the nitrogen of Y and is, e.g.Type: GrantFiled: May 16, 2007Date of Patent: November 2, 2010Assignees: The United States of America as represented by the Department of Health and Human Services, Georgetown UniversityInventors: Terrence R. Burke, Jr., Yang Gao, Zhu-jun Yao, Dajun Yang
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Patent number: 7767645Abstract: Disclosed are compounds represented by the formula: or a pharmaceutically acceptable salt or isomer thereof, wherein R1-R6 are as defined in the specification. These compounds are targeted for use as inhibitors of SH2 domain binding with a phosphoprotein, and are contemplated for use in a number of diseases including cancer. Also disclosed are pharmaceutical compositions comprising a compound of the invention and a pharmaceutically acceptable carrier.Type: GrantFiled: October 31, 2007Date of Patent: August 3, 2010Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Terrence R. Burke, Jr., Zhen-Dan Shi, Sang-Uk Kang
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Patent number: 7425537Abstract: Disclosed are compounds for SH2 domain binding inhibition, for example, a compound of formula (I), wherein R1 is a lipophile; R2, in combination with the phenyl ring, is a phenylphosphate mimic group or a protected phenylphosphate mimic group; R3 is hydrogen, azido, amino, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, or alkylcarbonylamino, wherein the alkyl portion of R3 may be optionally substituted with a substituent selected from the group consisting of halo, hydroxy, carboxyl, amino, aminoalkyl, alkyl, alkoxy, and keto; R6 is a linker; AA is an amino acid; and n is 1 to 6; or a salt thereof. The conformationally compounds provide enhanced binding affinity with SH2 domain protein. Also disclosed are a pharmaceutical compositions and a method for inhibiting an SH2 domain from binding with a phosphoprotein.Type: GrantFiled: June 26, 2003Date of Patent: September 16, 2008Assignee: The United States of America as represented by the Secretary of the Department of Health and Human ServicesInventors: Terrence R Burke, Jr., Chang-Qing Wei, Zhen-Dan Shi, Yang Gao
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Patent number: 7226991Abstract: Disclosed herein are phenylalanine derivative compounds of the following formula W—Y—(AA)n—Z wherein Y is a phenylalanyl radical, AA is an amino acid, n is an integer of 1 to 15, and substituent variables W and Z are as described herein. The compounds can be used to inhibit SH2 binding with phosphoproteins, and to inhibit proliferation of tumor cells.Type: GrantFiled: March 23, 2000Date of Patent: June 5, 2007Assignees: United States of America, represented by the Secretary, Department of Health and Human Services, Georgetown UniversityInventors: Terrence R. Burke, Jr., Yang Gao, Zhu-jun Yao, Dajun Yang
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Patent number: 7132392Abstract: Disclosed are methods of inhibiting cell motility, for example, by inhibiting the binding between an intracellular transducer and a receptor protein tyrosine kinase, and more particularly by inhibiting hepatocyte growth factor (HGF) induced cell motility. The present invention also provides a method of inhibiting angiogenesis. The methods of the present invention employ peptides such as phosphotyrosyl mimetics. The present invention further provides methods of preventing and/or treating diseases, disorders, states, or conditions such as cancer, particularly metastatic cancer comprising administering to a mammal of interest one or more peptides of the present invention.Type: GrantFiled: October 20, 2000Date of Patent: November 7, 2006Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Donald P. Bottaro, Safiye N. Atabey, Jesus V. Soriano, Diane E. Breckenridge, Zhu-Jun Yao, Yang Gao, Terrence R. Burke, Jr.
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Patent number: 6977241Abstract: Disclosed are compounds for SH2 domain binding inhibition. For example, disclosed is a compound of formula (I) wherein R1 is a lipophile; R2, in combination with the phenyl ring, forms a phenylphosphate mimic group or a protected phenylphosphate mimic group; R3 is hydrogen, azido, amino, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, or alkylcarbonylamino, wherein the alkyl portion of R3 may be optionally substituted with a substituent selected from the group consisting of halo, hydroxy, carboxyl, amino, aminoalkyl, alkyl, alkoxy, and keto; R6 is a linker; AA is an amino acid; and n is 1 to 6; or a salt thereof. Also disclosed are a pharmaceutical composition, a method for inhibiting an SH2 domain from binding with a phosphoprotein and a method of treating breast cancer.Type: GrantFiled: August 22, 2001Date of Patent: December 20, 2005Assignee: The United States of America as represented by the Department of Health & Human ServicesInventors: Terrence R. Burke, Jr., Chang-Qing Wei, Johannes H. Voigt, Yang Gao