Syntaxin Limited

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Health Protection Agency

University of Georgia Research Foundation Inc

Microbiological Research Authority

Other

The Health Protection Agency Ipsen Limited

Microbiobiological Research Authority

Conrad Padraig Quinn

Keith Foster

John Andrew Chaddock

Clifford Charles Shone

Philip Marks

Patrick Stancombe

Jonathan Wayne

J Mark Sutton

Jan Pohl

Vera A Semenova

Pavel Svoboda

Bassam Hallis

Geert-Jan Boons

John Mark Sutton

Russell W Carlson

Patricia P Wilkins

Therese Buskas

Margreet A Wolfert

Benjamin Arthur James

Mahalakshmi Vasan

Elmar Kannenberg

Alok Mehta

Elke Saile

Jason Marc Goldstein

John R Barr

Anne E Boyer

Benjamin Arthur Frederick James

Dennis A Bagarozzi, Jr

Shannon Dalton

Jarad M Schiffer

John Robert Purkiss

Biswa Choudhury

Christine Leoff

Jana Rauvolfova

Charles Clifford Shone

John R Immunopharmacology Group Purkiss

John A Microbiological Res Authority Chaddock

Keith Alan Microbiological Res Authority Foster

Provided are antibodies capable of binding to a particular epitope or specifically binding to LF or LTx and enhancing the activity of the LF or LTx relative to the LF or LTx absent the antibody binding.

Regulating Bacillus anthracis lethal factor activity via an activating epitope region

Regions ofprotective antigen are provided representing epitopes recognized by antibodies in subjects that have acquired immunity toinfection. The recognition of these epitopes correlates with autoimmunity in a subject. Also provided are vaccines that include at least one of these epitopes that when administered to a subject provide improved acquired immunity.

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The present invention presents the isolation, characterization and synthesis of oligosaccharides of. Also presented are antibodies that bind to such saccharide moieties and various methods of use for such saccharide moieties and antibodies.

Anthrax carbohydrates, synthesis and uses thereof

Regions ofprotective antigen are provided representing sequences recognized by antibodies in subjects that have vaccine induced lethal toxin neutralizing anti-PA IgG responses. The recognition of these PA regions enhances the utility of anti-PA IgG reactivity as an immune correlate of protection against anthrax in a subject and increases predictive probability of survival. Also provided are vaccines that include at least one of these PA regions that when administered to a subject improve the predictive value of vaccine induced anti-PA IgG and TNA responses as immune correlates of protection against inhalation anthrax.

The present invention relates to treatment of disease by inhibition of cellular secretory processes, to agents and compositions therefor, and to manufacture of those agents and compositions. The present invention relates particularly, to treatment of disease dependent upon the exocytotic activity of endocrine cells, exocrine cells, inflammatory cells, cells of the immune system, cells of the cardiovascular system and bone cells.

Inhibition of secretion from non-neuronal cells

The present invention relates to treatment of mucus hypersecretion, to compositions therefore and manufacture of those compositions. The present invention relates particularly, though not exclusively, to the treatment of chronic bronchitis in chronic obstructive pulmonary disease (COPD), asthma and other clinical conditions involving COPD.

Treatment of mucus hypersecretion

One major problem in diagnosis methods presently available for anthrax is that these methods require several days to produce a result. The only existing treatment for anthrax requires administration soon after infection at a time when patients are exhibiting only mild flu-like symptoms. Thus, a patient may be days beyond the time when treatment would be effective by the time a diagnosis is made. The present invention reduces diagnosis time to as little as four hours providing same day identification of anthrax radically increasing the odds of delivering proper treatment and patient recovery. The rapid identification of anthrax lethal factor activity exhibited by the instant invention is also amenable to in vivo screening protocols for the discovery and development of anthrax vaccines and lethal factor inhibitors. The instant invention isolates and concentrates lethal factor and lethal toxin from nearly any biological sample. By capitalizing on the endopeptidase activity of lethal factor the present invention amplifies output signals producing reliable detection of picomolar concentrations of lethal factor. The instant invention involves novel purification and detection techniques and substrates for rapid, reproducible, and quantitative measurements of anthrax lethal factor in biological samples.

Detection of anthrax pathogenicity factors

A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.

Recombinant toxin fragments

Antigenic compositions are provided comprising a single chain polypeptide comprising first and second domains, wherein said first domain is a clostridial neurotoxin light chain or a fragment or a variant thereof and is capable of cleaving one or more vesicle or plasma membrane associated proteins essential to exocytosis; and said second domain is a clostridial neurotoxin heavy chain Hportion or a fragment or a variant thereof, wherein said second domain is capable of (i) translocating the polypeptide into a cell or (ii) increasing the solubility of the polypeptide compared to the solubility of the first domain on its own or (iii) both translocating the polypeptide into a cell and increasing the solubility of the polypeptide compared to the solubility of the first domain on its own; and wherein the second domain lacks a functional C-terminal part of a clostridial neurotoxin heavy chain designated Hthereby rendering the polypeptide incapable of binding to cell surface receptors that are the natural cell surface receptors to which native clostridial neurotoxin binds. Antibodies that bind to the polypeptides, and compositions comprising these antibodies, are also provided, as are DNA vaccines comprising polynucleotides that encode these polypeptides. The antigenic and antibody compositions, and the DNA vaccine compositions, can be used in methods of immunising against, or treating, clostridial neurotoxin poisoning in a subject by administering to that subject a therapeutically effective amount of the composition.

Growing community of inventors

Lilburn, GA, United States of America

Conrad Padraig Quinn