National Institutes of Health, a Component of the US Dept. of Health & Human Services

US Government As Represented by the Secretary of the Army

The United States of America As Represented by the Department of Health

National Research Council of Canada

Scott & White Healthcare (swh)

Stephen H Leppla

John B Robbins

Rachel Schneerson

Robert H Purcell

Suzanne U Emerson

Zhaochun Chen

Mahtab Moayeri

Thomas H Bugge

Shi-Hui Liu

Joseph Shiloach

Craig P Webb

Nicholas S Duesbery

Joanna Kubler-Kielb

George Vande Woude

Naveen Arora

Fathy Majadly

Yogendra Singh

Darrell T Liu

Kurt Klimpel

Sarah Netzel-Arnett

Henning Birkedal-Hansen

Mary Jo Rosovitz

Jay A Berzofsky

Brad St Croix

Arthur E Frankel

Theresa J Goletz

Delia M Ramirez

Yunpeng Su

Andrei P Pomerantsev

Kurt R Klimpel

S Dana Hsu

George F Vande Woude

Evguenii Vinogradov

Peter J Nicholls

Kuang-Hua Chen

Christopher H Bachran

Alexander N Wein

Clinton Edward Leysath

Peter J Nichols

Damilola Daniel Phillips

Diane E Peters

Haijing Hu

Jie Liu

Disclosed is aprotective 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.

Modified anthrax toxin protective antigen

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.

Antibodies to tumor endothelial marker 8

The invention relates to a() in which more than one secreted protease is inactivated by genetic modification. Such a protease-deficienthas an improved ability to produce recombinant secreted proteins compared to other bacteria, particularly other. Improvements include production of intact (i.e., mature full-length) proteins, often at high yield. The disclosure provides athat 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 modifiedcomprising such genetic modification transformed with a recombinant molecule encoding a product, as well as methods to prepare and use such

Protease-deficient bacillus anthracis

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.

Monoclonal antibodies that neutralize anthrax protective antigen (PA) toxin

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.

Monoclonal antibodies that neutralize anthrax toxins

Disclosed is a protein comprising a cytolethal distending toxin subunit B (CdtB) conjugated or fused to atoxin 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.

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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.

Engineered anthrax lethal toxin for targeted delivery

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.

Mutated anthrax toxin protective antigen proteins that specifically target cells containing high amounts of cell-surface metalloproteinases or plasminogen activator receptors

Provided are immunogenic compositions and methods for eliciting an immune response againstand other bacteria that contain 3-methyl-3-hydroxybutyrate- or 3-hydroxybutryate-substituted saccharides. Conjugates of 3-methyl-3-hydroxybutyrate- or 3-hydroxybutryate-substituted saccharides elicit an effective immune response againstspores in mammalian hosts to which the conjugates are administered.

The invention relates to improved methods of producing and recoveringprotective antigen (PA), especially modified PA which is protease resistant, and to methods of using of these PAs or nucleic acids encoding these PAs for eliciting an immunogenic response in humans, including responses which provide protection against, or reduce the severity of,bacterial infections and which are useful to prevent and/or treat illnesses caused by, such as inhalation anthrax, cutaneous anthrax and gastrointestinal anthrax.

Growing community of inventors

Bethesda, MD, United States of America

Stephen H Leppla