Longhorn Vaccines and Diagnostics, LLC

Biosynexus, Inc.

The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc.

US Government As Represented by the Secretary of the Army

Altor Bioscience Corporation

Other

Sunol Molecular Corporation

Richard F Schuman

Gerald Walter Fischer

Jeffrey R Stinson

Hing C Wong

Andrew Lees

Luke T Daum

Clara Jebet Sei

James J Mond

Frederick J Cassels

Simon J Foster

John Fitzgerald Kokai-Kun

Jeffrey L Stinson

The present invention is directed to compositions and methods for preventing and/or treating diseases and disorders of patients caused by non-Staphylococcal microorganisms. In particular, compositions and methods contain lysostaphin, altered forms of lysostaphin as compared to wild-type, and synergistic combinations of lysostaphin plus additional conventional treatments such as other enzyme, antibiotic and/or antibody treatment. The invention is also directed to detecting and identifying altered forms of lysostaphin that possess increased efficacy against infections as compared to wild-type lysostaphin, and forms that generate a minimal or no immune response in a patient. The invention is also directed to method of manufacturing lysostaphin and altered forms of lysostaphin, and compositions that direct the lysostaphin to the site of the infection such as aerosolized nanoparticles.

Multimodal antimicrobial therapy

The invention is directed to compositions and methods for stimulating, enhancing or modulating the immune system of a patient before or after infection by a pathogen, and in particular multidrug resistant (MDR) MTB and extremely drug resistant (XDR) MTB. Compositions of the invention contain non-naturally occurring antigens that generate an effective cellular and/or humoral immune response to MTB and/or antibodies that are specifically reactive to MTB antigens. The greater activity of the immune system generated by a vaccine of the invention increases generation of memory T cells that provide for a greater and/or extended response to an MTB infection. Responses involve an increased generation of antibodies that enhance immunity against MTB infection and promote an enhanced phagocytic response. Monoclonal antibodies produced by the non-naturally occurring antigens enhance phagocytosis and killing of mycobacteria by phagocytic cells, enhance clearance of MTB from the blood and modulate immunity and cytokine responses.

Antibodies that modulate immunity to drug resistant and latent MTB infections

The invention is directed to compositions and methods for stimulating, enhancing or modulating the immune system of a patient before or after infection by a pathogen, and in particular MTB. Compositions of the invention contain non-naturally occurring antigens that generate an effective cellular and/or humoral immune response to MTB and/or antibodies that are specifically reactive to MTB antigens. The greater activity of the immune system generated by a vaccine of the invention increases generation of memory T cells that provide for a greater and/or extended response to an MTB infection. Responses involve an increased generation of antibodies that enhance immunity against MTB infection and promote an enhanced phagocytic response. Monoclonal antibodies produced by the non-naturally occurring antigens enhance phagocytosis and killing of mycobacteria by phagocytic cells, enhance clearance of MTB from the blood and modulate immunity and cytokine responses.

Monoclonal antibodies that modulate immunity to MTB and enhance immune clearance

The present invention encompasses monoclonal and chimeric antibodies that bind to lipoteichoic acid of Gram positive bacteria. The antibodies also bind to whole bacteria and enhance phagocytosis and killing of the bacteria in vitro and enhance protection from lethal infection in vivo. The mouse monoclonal antibody has been humanized and the resulting chimeric antibody provides a previously unknown means to diagnose, prevent and/or treat infections caused by gram positive bacteria bearing lipoteichoic acid. This invention also encompasses a peptide mimic of the lipoteichoic acid epitope binding site defined by the monoclonal antibody. This epitope or epitope peptide mimic identifies other antibodies that may bind to the lipoteichoic acid epitope. Moreover, the epitope or epitope peptide mimic provides a valuable substrate for the generation of vaccines or other therapeutics.

Opsonic and protective monoclonal and chimeric antibodies specific for lipoteichoic acid of gram posiive bacteria

Polynucleotides encoding humanized and chimeric antibodies specific for lipoteichoic acid of gram positive bacteria

The present invention encompasses monoclonal antibodies that bind to lipoteichoic acid (LTA) of Gram positive bacteria. The antibodies also bind to whole bacteria and enhance phagocytosis and killing of the bacteria in vitro. The invention also provides antibodies having human sequences (chimeric, humanized and human antibodies). The invention also sets forth the variable regions of three antibodies within the invention and presents the striking homology between them.

Nucleic acids encoding opsonic monoclonal and chimeric antibodies specific for lipoteichoic acid of gram positive bacteria

A monoclonal antibody to a consensus peptide of the formula: The monoclonal antibody of the invention binds exclusively to the sequence SAVALTYS (SEQ ID NO:2) and has use as a diagnostic and for prophylaxis against illness arising fromwhich produce the CS4-CFA/I family of proteins and for treatment of disease arising therefrom.

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Humanized and chimeric antibodies specific for lipoteichoic acid of GRAM positive bacteria

Opsonic monoclonal and chimeric antibodies specific for lipoteichoic acid of Gram positive bacteria

The present invention encompasses protective monoclonal antibodies that bind to peptidoglycan of Gram-positive bacteria. The antibodies also bind to whole bacteria and enhance phagocytosis and killing of the bacteria in vitro and block nasal colonization by Gram-positive bacteria in vivo. The invention also provides human, humanized and chimeric antibodies. The invention also sets forth the heavy chain and light chain variable regions of an antibody within the invention.

Multifunctional monoclonal antibodies directed to peptidoglycan of gram-positive bacteria

A monoclonal antibody to a consensus peptide of the formula: The monoclonal antibody of the invention binds exclusively to the sequence SAVALTYS (SEQ ID NO. 2) and has use as a diagnostic and for prophylaxis against illness arising fromwhich produce the CS4-CFA/I family of proteins and for treatment of disease arising therefrom.

Growing community of inventors

Gaithersburg, MD, United States of America

Richard F Schuman