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).
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Patent number: 10835593Abstract: 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: GrantFiled: August 25, 2016Date of Patent: November 17, 2020Assignee: The United States of America as represented by the Secretary Department of Health and Human ServicesInventors: Shi-Hui Liu, Stephen H. Leppla, Thomas H. Bugge, Alexander N. Wein, Diane E. Peters, Jie Liu, Kuang-Hua Chen
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Publication number: 20190144527Abstract: 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: ApplicationFiled: January 21, 2019Publication date: May 16, 2019Inventors: Zhaochun CHEN, Stephen H. LEPPLA, Mahtab MOAYERI, Suzanne U. EMERSON, Robert H. PURCELL
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Patent number: 10273548Abstract: 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: GrantFiled: December 14, 2016Date of Patent: April 30, 2019Assignee: The Unites States of America, as represented by the Secretary, Dept. of Health and Human ServicesInventors: Andrei P. Pomerantsev, Stephen H. Leppla
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Patent number: 10273299Abstract: 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: GrantFiled: April 4, 2016Date of Patent: April 30, 2019Assignee: The United States of America, as Represented by the Secretary, Department of Health and Human ServicesInventors: Arthur E. Frankel, Yunpeng Su, Brad St. Croix, Stephen H. Leppla
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Patent number: 10227395Abstract: 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: GrantFiled: February 14, 2014Date of Patent: March 12, 2019Assignee: The United States of America, as represented by the Secretary, Dept. of Health and Human ServicesInventors: Zhaochun Chen, Stephen H. Leppla, Mahtab Moayeri, Suzanne U. Emerson, Robert H. Purcell
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Publication number: 20180250376Abstract: 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: ApplicationFiled: August 25, 2016Publication date: September 6, 2018Applicant: The United States of America as represented by the Secretary Department of Health and Human ServicesInventors: Shi-Hui Liu, Stephen H. Leppla, Thomas H. Bugge, Alexander N. Wein, Diane E. Peters, Jie Liu, Kuang-Hua Chen
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Patent number: 10053503Abstract: 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: GrantFiled: January 20, 2017Date of Patent: August 21, 2018Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Zhaochun Chen, Robert H. Purcell, Suzanne U. Emerson, Stephen H. Leppla, Mahtab Moayeri
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Publication number: 20180111981Abstract: 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: ApplicationFiled: January 20, 2017Publication date: April 26, 2018Inventors: Zhaochun CHEN, Robert H. PURCELL, Suzanne U. EMERSON, Stephen H. LEPPLA, Mahtab MOAYERI
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Patent number: 9890369Abstract: 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: GrantFiled: June 19, 2014Date of Patent: February 13, 2018Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Christopher H. Bachran, Stephen H. Leppla
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Patent number: 9730993Abstract: 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: GrantFiled: August 22, 2013Date of Patent: August 15, 2017Assignee: The United States of America, as Represented by the Secretary, Department of Health and Human ServicesInventors: Clinton Edward Leysath, Stephen H Leppla, Damilola Daniel Phillips
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Publication number: 20170145525Abstract: 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: ApplicationFiled: December 14, 2016Publication date: May 25, 2017Inventors: Andrei P. POMERANTSEV, Stephen H. LEPPLA
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Patent number: 9580492Abstract: 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: GrantFiled: January 13, 2015Date of Patent: February 28, 2017Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Zhaochun Chen, Robert H. Purcell, Suzanne U. Emerson, Stephen H. Leppla, Mahtab Moayeri
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Patent number: 9555064Abstract: 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: GrantFiled: August 2, 2012Date of Patent: January 31, 2017Assignee: The United States of America, as represented by the Secretary Dept. of Health and Human ServicesInventors: Andrei P. Pomerantsev, Stephen H. Leppla
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Publication number: 20160319016Abstract: 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: ApplicationFiled: April 4, 2016Publication date: November 3, 2016Applicants: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVInventors: Arthur E. FRANKEL, Yunpeng SU, Brad ST.CROIX, Stephen H. LEPPLA
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Patent number: 9403872Abstract: 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: GrantFiled: June 24, 2014Date of Patent: August 2, 2016Assignee: THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES, NATIONAL INSTITUTES OF HEALTHInventors: Stephen H. Leppla, Shi-Hui Liu, Sarah Netzel-Arnett, Henning Birkedal-Hansen, Thomas Bugge
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Publication number: 20160200803Abstract: 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: ApplicationFiled: January 13, 2015Publication date: July 14, 2016Inventors: Zhaochun CHEN, Robert H. PURCELL, Suzanne U. EMERSON, Stephen H. LEPPLA, Mahtab MOAYERI
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Publication number: 20160145590Abstract: 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: ApplicationFiled: June 19, 2014Publication date: May 26, 2016Applicants: DEPARTMENT OF HEALTH AND HUMAN SERVICESInventors: Christopher H. Bachran, Stephen H. Leppla
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Patent number: 9309322Abstract: 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: GrantFiled: November 14, 2011Date of Patent: April 12, 2016Assignee: Scott & White Healthcare (SWH)Inventors: Arthur E. Frankel, Yunpeng Su, Brad St. Croix, Stephen H. Leppla
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Publication number: 20150224184Abstract: 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: ApplicationFiled: August 22, 2013Publication date: August 13, 2015Inventors: Clinton Edward Leysath, Stephen H. Leppla, Damilola Daniel Phillips
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Publication number: 20150093412Abstract: 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: ApplicationFiled: December 8, 2014Publication date: April 2, 2015Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Serv, National Research Council of CanadaInventors: Joanna Kubler-Kielb, Evguenii Vinogradov, Rachel Schneerson, Haijing Hu, Stephen H. Leppla, John B. Robbins