Patents by Inventor Stephen H. Leppla

Stephen H. Leppla 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: 10835593
    Abstract: Disclosed is a Bacillus anthracis protective antigen (PA) comprising a PA amino acid sequence, wherein one or more of amino acid residues I207, I210, E654, I656, R659, M662, Y681, and L687, as defined by reference to SEQ ID NO: 1, are, independently, substituted, with the proviso that amino acid residue I207 is not substituted with alanine and amino acid residue I210 is not substituted with alanine. Related compositions, nucleic acids, recombinant expression vectors, host cells, populations of cells, methods of treating or preventing cancer in a mammal, and methods of inhibiting the growth of a target cell are also disclosed.
    Type: Grant
    Filed: August 25, 2016
    Date of Patent: November 17, 2020
    Assignee: The United States of America as represented by the Secretary Department of Health and Human Services
    Inventors: Shi-Hui Liu, Stephen H. Leppla, Thomas H. Bugge, Alexander N. Wein, Diane E. Peters, Jie Liu, Kuang-Hua Chen
  • Publication number: 20190144527
    Abstract: The present invention relates to monoclonal antibodies that bind or neutralize anthrax protective antigen (PA) toxin. The invention provides such antibodies, fragments of such antibodies retaining anthrax PA toxin-binding ability, fully human or humanized antibodies retaining anthrax PA toxin-binding ability, and pharmaceutical compositions including such antibodies. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. Additionally, the invention provides for prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention.
    Type: Application
    Filed: January 21, 2019
    Publication date: May 16, 2019
    Inventors: Zhaochun CHEN, Stephen H. LEPPLA, Mahtab MOAYERI, Suzanne U. EMERSON, Robert H. PURCELL
  • Patent number: 10273548
    Abstract: The invention relates to a Bacillus anthracis (B. anthracis) in which more than one secreted protease is inactivated by genetic modification. Such a protease-deficient B. anthracis has an improved ability to produce recombinant secreted proteins compared to other bacteria, particularly other Bacillus. Improvements include production of intact (i.e., mature full-length) proteins, often at high yield. The disclosure provides a B. anthracis that comprises a genetic modification that inactivates a protease of the M4 family of metalloproteases and a genetic modification that inactivates a protease of the M6 family of metalloproteases. Also provided is a modified B. anthracis comprising such genetic modification transformed with a recombinant molecule encoding a product, as well as methods to prepare and use such B. anthracis.
    Type: Grant
    Filed: December 14, 2016
    Date of Patent: April 30, 2019
    Assignee: The Unites States of America, as represented by the Secretary, Dept. of Health and Human Services
    Inventors: Andrei P. Pomerantsev, Stephen H. Leppla
  • Patent number: 10273299
    Abstract: The present invention is directed to particular antibodies and fragments thereof that find use in the detection, prevention and treatment of diseases and disorders associated with abnormal angiogenesis. In particular, these antibodies detect tumor endothelial marker 8 (TEM8) in its native and cell-surface expressed form. Also disclosed are improved methods for producing monoclonal antibodies, as well as pharmaceutical compositions and kits.
    Type: Grant
    Filed: April 4, 2016
    Date of Patent: April 30, 2019
    Assignee: The United States of America, as Represented by the Secretary, Department of Health and Human Services
    Inventors: Arthur E. Frankel, Yunpeng Su, Brad St. Croix, Stephen H. Leppla
  • Patent number: 10227395
    Abstract: The present invention relates to monoclonal antibodies that bind or neutralize anthrax protective antigen (PA) toxin. The invention provides such antibodies, fragments of such antibodies retaining anthrax PA toxin-binding ability, fully human or humanized antibodies retaining anthrax PA toxin-binding ability, and pharmaceutical compositions including such antibodies. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. Additionally, the invention provides for prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention.
    Type: Grant
    Filed: February 14, 2014
    Date of Patent: March 12, 2019
    Assignee: The United States of America, as represented by the Secretary, Dept. of Health and Human Services
    Inventors: Zhaochun Chen, Stephen H. Leppla, Mahtab Moayeri, Suzanne U. Emerson, Robert H. Purcell
  • Publication number: 20180250376
    Abstract: Disclosed is a Bacillus anthracis protective antigen (PA) comprising a PA amino acid sequence, wherein one or more of amino acid residues I207, I210, E654, I656, R659, M662, Y681, and L687, as defined by reference to SEQ ID NO: 1, are, independently, substituted, with the proviso that amino acid residue I207 is not substituted with alanine and amino acid residue I210 is not substituted with alanine. Related compositions, nucleic acids, recombinant expression vectors, host cells, populations of cells, methods of treating or preventing cancer in a mammal, and methods of inhibiting the growth of a target cell are also disclosed.
    Type: Application
    Filed: August 25, 2016
    Publication date: September 6, 2018
    Applicant: The United States of America as represented by the Secretary Department of Health and Human Services
    Inventors: Shi-Hui Liu, Stephen H. Leppla, Thomas H. Bugge, Alexander N. Wein, Diane E. Peters, Jie Liu, Kuang-Hua Chen
  • Patent number: 10053503
    Abstract: The present invention relates to monoclonal antibodies that bind or neutralize anthrax lethal factor (LF), edema factor (EF), and/or protective antigen (PA). The invention provides such antibodies, fragments of such antibodies retaining anthrax toxin-binding ability, fully human or humanized antibodies retaining anthrax toxin-binding ability, and pharmaceutical compositions including such antibodies. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. Additionally, the invention provides for prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention.
    Type: Grant
    Filed: January 20, 2017
    Date of Patent: August 21, 2018
    Assignee: The United States of America, as represented by the Secretary, Department of Health and Human Services
    Inventors: Zhaochun Chen, Robert H. Purcell, Suzanne U. Emerson, Stephen H. Leppla, Mahtab Moayeri
  • Publication number: 20180111981
    Abstract: The present invention relates to monoclonal antibodies that bind or neutralize anthrax lethal factor (LF), edema factor (EF), and/or protective antigen (PA). The invention provides such antibodies, fragments of such antibodies retaining anthrax toxin-binding ability, fully human or humanized antibodies retaining anthrax toxin-binding ability, and pharmaceutical compositions including such antibodies. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. Additionally, the invention provides for prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention.
    Type: Application
    Filed: January 20, 2017
    Publication date: April 26, 2018
    Inventors: Zhaochun CHEN, Robert H. PURCELL, Suzanne U. EMERSON, Stephen H. LEPPLA, Mahtab MOAYERI
  • Patent number: 9890369
    Abstract: Disclosed is a protein comprising a cytolethal distending toxin subunit B (CdtB) conjugated or fused to a Bacillus anthracis toxin lethal factor (LF) or a functional portion of LF. Related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, methods of treating or preventing cancer, and methods of inhibiting the growth of a target cell are also disclosed.
    Type: Grant
    Filed: June 19, 2014
    Date of Patent: February 13, 2018
    Assignee: The United States of America, as represented by the Secretary, Department of Health and Human Services
    Inventors: Christopher H. Bachran, Stephen H. Leppla
  • Patent number: 9730993
    Abstract: The present invention provides methods and systems for targeted delivery of a compound to a target cell that over-expresses two different proteinases. Specifically, two different modified protective antigen proteins, each comprising a cleavage site recognized by a distinct proteinase in place of the native proteinase cleavage site recognized by furin, are administered in combination with a compound that contains a protective antigen binding site. Upon cleavage by the two proteinases the two modified protective antigen proteins form a hetero-oligomer, allowing the compound to bind to the hetero-oligomer and subsequently to be translocated into the target cell.
    Type: Grant
    Filed: August 22, 2013
    Date of Patent: August 15, 2017
    Assignee: The United States of America, as Represented by the Secretary, Department of Health and Human Services
    Inventors: Clinton Edward Leysath, Stephen H Leppla, Damilola Daniel Phillips
  • Publication number: 20170145525
    Abstract: The invention relates to a Bacillus anthracis (B. anthracis) in which more than one secreted protease is inactivated by genetic modification. Such a protease-deficient B. anthracis has an improved ability to produce recombinant secreted proteins compared to other bacteria, particularly other Bacillus. Improvements include production of intact (i.e., mature full-length) proteins, often at high yield. The disclosure provides a B. anthracis that comprises a genetic modification that inactivates a protease of the M4 family of metalloproteases and a genetic modification that inactivates a protease of the M6 family of metalloproteases. Also provided is a modified B. anthracis comprising such genetic modification transformed with a recombinant molecule encoding a product, as well as methods to prepare and use such B. anthracis.
    Type: Application
    Filed: December 14, 2016
    Publication date: May 25, 2017
    Inventors: Andrei P. POMERANTSEV, Stephen H. LEPPLA
  • Patent number: 9580492
    Abstract: The present invention relates to monoclonal antibodies that bind or neutralize anthrax lethal factor (LF), edema factor (EF), and/or protective antigen (PA). The invention provides such antibodies, fragments of such antibodies retaining anthrax toxin-binding ability, fully human or humanized antibodies retaining anthrax toxin-binding ability, and pharmaceutical compositions including such antibodies. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. Additionally, the invention provides for prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention.
    Type: Grant
    Filed: January 13, 2015
    Date of Patent: February 28, 2017
    Assignee: The United States of America, as represented by the Secretary, Department of Health and Human Services
    Inventors: Zhaochun Chen, Robert H. Purcell, Suzanne U. Emerson, Stephen H. Leppla, Mahtab Moayeri
  • Patent number: 9555064
    Abstract: The invention relates to a Bacillus anthracis (B. anthracis) in which more than one secreted protease is inactivated by genetic modification. Such a protease-deficient B. anthracis has an improved ability to produce recombinant secreted proteins compared to other bacteria, particularly other Bacillus. Improvements include production of intact (i.e., mature full-length) proteins, often at high yield. The disclosure provides a B. anthracis that comprises a genetic modification that inactivates a protease of the M4 family of metalloproteases and a genetic modification that inactivates a protease of the M6 family of metalloproteases. Also provided is a modified B. anthracis comprising such genetic modification transformed with a recombinant molecule encoding a product, as well as methods to prepare and use such B. anthracis.
    Type: Grant
    Filed: August 2, 2012
    Date of Patent: January 31, 2017
    Assignee: The United States of America, as represented by the Secretary Dept. of Health and Human Services
    Inventors: Andrei P. Pomerantsev, Stephen H. Leppla
  • Publication number: 20160319016
    Abstract: The present invention is directed to particular antibodies and fragments thereof that find use in the detection, prevention and treatment of diseases and disorders associated with abnormal angiogenesis. In particular, these antibodies detect tumor endothelial marker 8 (TEM8) in its native and cell-surface expressed form. Also disclosed are improved methods for producing monoclonal antibodies, as well as pharmaceutical compositions and kits.
    Type: Application
    Filed: April 4, 2016
    Publication date: November 3, 2016
    Applicants: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERV
    Inventors: Arthur E. FRANKEL, Yunpeng SU, Brad ST.CROIX, Stephen H. LEPPLA
  • Patent number: 9403872
    Abstract: The present invention provides methods of specifically targeting compounds to cells overexpressing matrix metalloproteinases, plasminogen activators, or plasminogen activator receptors, by administering a compound and a mutant protective antigen protein comprising a matrix metalloproteinase or a plasminogen activator-recognized cleavage site in place of the native protective antigen furin-recognized cleavage site, wherein the mutant protective antigen is cleaved by a matrix metalloproteinase or a plasminogen activator overexpressed by the cell, thereby translocating into the cell a compound comprising a lethal factor polypeptide comprising a protective antigen binding site.
    Type: Grant
    Filed: June 24, 2014
    Date of Patent: August 2, 2016
    Assignee: THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES, NATIONAL INSTITUTES OF HEALTH
    Inventors: Stephen H. Leppla, Shi-Hui Liu, Sarah Netzel-Arnett, Henning Birkedal-Hansen, Thomas Bugge
  • Publication number: 20160200803
    Abstract: The present invention relates to monoclonal antibodies that bind or neutralize anthrax lethal factor (LF), edema factor (EF), and/or protective antigen (PA). The invention provides such antibodies, fragments of such antibodies retaining anthrax toxin-binding ability, fully human or humanized antibodies retaining anthrax toxin-binding ability, and pharmaceutical compositions including such antibodies. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. Additionally, the invention provides for prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention.
    Type: Application
    Filed: January 13, 2015
    Publication date: July 14, 2016
    Inventors: Zhaochun CHEN, Robert H. PURCELL, Suzanne U. EMERSON, Stephen H. LEPPLA, Mahtab MOAYERI
  • Publication number: 20160145590
    Abstract: Disclosed is a protein comprising a cytolethal distending toxin subunit B (CdtB) conjugated or fused to a Bacillus anthracis toxin lethal factor (LF) or a functional portion of LF. Related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, methods of treating or preventing cancer, and methods of inhibiting the growth of a target cell are also disclosed.
    Type: Application
    Filed: June 19, 2014
    Publication date: May 26, 2016
    Applicants: DEPARTMENT OF HEALTH AND HUMAN SERVICES
    Inventors: Christopher H. Bachran, Stephen H. Leppla
  • Patent number: 9309322
    Abstract: The present invention is directed to particular antibodies and fragments thereof that find use in the detection, prevention and treatment of diseases and disorders associated with abnormal angiogenesis. In particular, these antibodies detect tumor endothelial marker 8 (TEM8) in its native and cell-surface expressed form. Also disclosed are improved methods for producing monoclonal antibodies, as well as pharmaceutical compositions and kits.
    Type: Grant
    Filed: November 14, 2011
    Date of Patent: April 12, 2016
    Assignee: Scott & White Healthcare (SWH)
    Inventors: Arthur E. Frankel, Yunpeng Su, Brad St. Croix, Stephen H. Leppla
  • Publication number: 20150224184
    Abstract: The present invention provides methods and systems for targeted delivery of a compound to a target cell that overexpresses two different proteinases. Specifically, two different modified protective antigen proteins, each comprising a cleavage site recognized by a distinct proteinase in place of the native proteinase cleavage site recognized by furin, are administered in combination with a compound that contains a protective antigen binding site. Upon cleavage by the two proteinases the two modified protective antigen proteins form a hetero-oligomer, allowing the compound to bind to the hetero-oligomer and subsequently to be translocated into the target cell.
    Type: Application
    Filed: August 22, 2013
    Publication date: August 13, 2015
    Inventors: Clinton Edward Leysath, Stephen H. Leppla, Damilola Daniel Phillips
  • Publication number: 20150093412
    Abstract: Provided are immunogenic compositions and methods for eliciting an immune response against B. anthracis and other bacteria that contain 3-methyl-3-hydroxybutyrate- or 3-hydroxybutyrate-substituted saccharides. Conjugates of 3-methyl-3-hydroxybutyrate- or 3-hydroxybutyrate-substituted saccharides elicit an effective immune response against B. anthracis spores in mammalian hosts to which the conjugates are administered.
    Type: Application
    Filed: December 8, 2014
    Publication date: April 2, 2015
    Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Serv, National Research Council of Canada
    Inventors: Joanna Kubler-Kielb, Evguenii Vinogradov, Rachel Schneerson, Haijing Hu, Stephen H. Leppla, John B. Robbins