Abstract: This invention relates to stable formulations of multiple antibodies comprising a plurality of antibodies and an effective amount of a succinate buffer wherein the pH of the formulation is between about 4.5 and about 7.0.

Abstract: 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.

Abstract: Antibodies for binding epitopes of BoNT/A and hybridomas which produce such antibodies are described. The antibodies of the present invention can be used in a method for detecting BoNT/A in a sample and/or in a method for purifying BoNT/A from an impure solution. In addition, the antibodies can be used for passive immunization against BoNT/A intoxication or as intoxication therapy. Another aspect of the invention is a kit for detecting BoNT/A in a sample.

Abstract: A device that includes a scaffold composition and a bioactive composition with the bioactive composition being incorporated therein or thereon, or diffusing from the scaffold composition such that the scaffold composition and/or a bioactive composition captures and eliminates undesirable cells from the body a mammalian subject. The devices mediate active recruitment, sequestration, and removal or elimination of undesirable cells from their host.

Abstract: Provided herein is a means which is effective for botulism diseases and the prevention of the botulism diseases. Specifically provided is a plurality of human anti-botulinum toxin type-A antibodies having different epitopes from one another. Also specifically provided is a composition for neutralizing botulinum toxin type-A, which comprises a combination of two or more of the antibodies and which has a high neutralizing activity.

Abstract: This invention relates to a novel hybridoma strategy that uses CD27+ B cells cultured in vitro to induce IgM to IgG class switch prior to fusion with a fusion partner. Hybridomas resulting from the fusion between CD27+ B cells and a fusion partner cell line and antibodies secreted from the hybridomas are included in the invention.

Abstract: Small-molecule inhibitors of Botulinum toxin, including BoNTA, BoNTD and BoNTE are provided, as well as methods of using the inhibitors.

Abstract: This invention provides antibodies that specifically bind to botulinum neurotoxin type A (BoNT/A) and/or botulinum neurotoxin type B (BoNT/B) and the epitopes bound by those antibodies. The antibodies and derivatives thereof and/or other antibodies that specifically bind to the neutralizing epitopes provided herein can be used to neutralize botulinum neurotoxin and are therefore also useful in the treatment of botulism. Also included in the invention are diagnostic and therapeutic assays directed to botulinum neurotoxins.

Abstract: This invention provides antibodies that specifically bind to and typically neutralize botulinum neurotoxins (e.g., BoNT/A, BoNT/B, BoNT/E, etc.) and the epitopes bound by those antibodies. The antibodies and derivatives thereof and/or other antibodies that specifically bind to the neutralizing epitopes provided herein can be used to neutralize botulinum neurotoxin and are therefore also useful in the treatment of botulism.

Abstract: This invention provides botulinum antitoxin compositions and methods of production, and methods of treating animals and humans prophylactically and also those suspected of having contacted botulism toxin. The botulinum antitoxin is prepared by inoculating an animal with a monovalent botulinum toxoid and toxin. The animal's plasma is collected and purified at a high pH by affinity chromatography. The resulting monovalent immunoglobulins are de-speciated by digestion with pepsin. Monovalent antitoxins for all seven botulinum serotypes are then combined to produce a high titered heptavalent botulinum antitoxin composition.

Abstract: 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 HN portion 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 HC thereby rendering the polypeptide incapable of binding to cell surface receptors that are the natural cell sur

Abstract: A chemical conjugate for treating a nerve cell related disorder is provided. This conjugate includes an active or inactive Clostridial toxin having specificity for a target nerve cell. The toxin is conjugated to a drug or other bioactive molecule without affecting the toxin's ability to enter the target nerve cell.

Abstract: Pharmaceutical compositions, each consisting of a cell-permeable fusion protein conjugate of a polypeptidic cell-membrane transport moiety and a Clostridium botulinum C3 exotransferase unit, or a functional analog thereof, are provided. The compositions are useful to prevent or inhibit uncontrolled proliferation, spreading, and migration of a metastatic neoplastic cell of a cancer in a mammal. The compositions can each effect or arrest combination of two or more of tumor cell proliferation, migration, angiogenesis, and metalloproteinase secretion.

Abstract: 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 HN portion 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 HC thereby rendering the polypeptide incapable of binding to cell surface receptors that are the natural cell sur

Abstract: A method is provided for improving the solubility of proteins, for example, bacterial toxins. In one embodiment, solubility is improved by introducing point mutations that replace cysteine residues capable of forming intermolecular disulfide bonds with other amino acid residues that do not form such bonds. By abrogating the ability of the cysteine residues to form inter-molecular disulfide bonds, aggregation of the protein is reduced, thereby improving the solubility of the protein. In another embodiment, solubility of the protein is improved by producing truncated forms of the protein that express the LHN domain and a fragment of the Hc domain. Proteins made according to the method of the invention are useful, for example, as immunodiagnostic agents and vaccine components.

Abstract: The present invention is concerned with compounds, medicaments and treatments for Clostridium difficile infection, together with novel isolated antibodies and their use in same. The present invention is also concerned with the treatment and prophylaxis of E. faecium and E. faecalis infection and provides medicaments and treatments for same.

Abstract: This invention provides antibodies that specifically bind to and neutralize botulinum neurotoxin type A (BoNT/A) and the epitopes bound by those antibodies. The antibodies and derivatives thereof and/or other antibodies that specifically bind to the neutralizing epitopes provided herein can be used to neutralize botulinum neurotoxin and are therefore also useful in the treatment of botulism.

Abstract: A composition for treating a subject is provided. The composition includes dimeric or polymeric secretory IgM therapeutic. Formulating agents are mixed with the dimeric or polymeric secretory IgM to yield a dosing form of a capsule, tablet, and a suppository. A process for manufacturing a medicament for the treatment of C. difficile associated disease in a human is also provided that the modification of pentameric or hexameric IgM with secretory component to form a pentameric or hexameric secretory IgM therapeutic. The pentameric or hexameric secretory IgM therapeutic is then mixed with formulating agents to create a capsule, tablet, or suppository dosing form. The therapeutic is amenable to enrobement directly through microencapsulation or the dosing form is coated with an enteric coating. A method of C. difficile treatment with the therapeutic is also provided that is amenable to supplementation with concurrent or prior antibiotic administration.

Abstract: This invention provides identification and characterization of racemases and epimerases and definition of protein signatures of those racemases and epimerases. This invention also provides identification of nucleic acid molecules encoding a peptide consisting of a motif characteristic of the protein signatures, and to the peptides consisting of these motifs. Antibodies specific for the peptides and to immune complexes of these antibodies with the peptides are also provided. Further, the invention relates to methods and kits for detecting racemases and epimerases using the nucleic acid molecules of the invention, as well as the peptides consisting of the motifs and antibodies to these peptides.

Abstract: This invention provides antibodies that specifically bind to and neutralize botulinum neurotoxin type A (BoNT/A) and the epitopes bound by those antibodies. The antibodies and derivatives thereof and/or other antibodies that specifically bind to the neutralizing epitopes provided herein can be used to neutralize botulinum neurotoxin and are therefore also useful in the treatment of botulism.

Abstract: 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.

Abstract: The invention relates to monoclonal antibodies capable of recognizing and neutralizing epitopes from the ligand domain, the translocation domain or the catalytic domain of the enterotoxin (toxin A) and cytotoxin (toxin B) from Clostridium difficile, as well as their production and therapeutic and prophylactic applications to diseases caused by said toxins.

Abstract: The invention provides active and passive immunization methods for preventing and treating Clostridium difficile infection, which involve percutaneous administration of C. difficile toxin-neutralizing polyclonal immune globulin, C. difficile toxoids, or combinations thereof. Also provided by the invention are C. difficile toxoids, C. difficile toxin-neutralizing polyclonal immune globulin, and methods of identifying subjects that produce C. difficile toxin-neutralizing polyclonal immune globulin.

Abstract: Anthrax bio-terrorism is a poor man's nuclear bomb with devastating effects on the freedom and economy of any nation. No nation is immune. Urgently, there is a need for life saving technology that can be readily available and deployed in real time. Polystyrene sulfonate is the answer. It is life saving and will help in the development of next generation superior vaccines.

Abstract: Disclosed herein is a multicomponent low dose vaccine comprising a safe and immunogenically effective combination of a protective antigen component or components of clostridial organism, a protective antigen component of a non-clostridial organism and an adjuvant.

Abstract: Treating humans and animals intoxicated with a bacterial toxin by administration of antitoxin. Avian antitoxin in an aqueous solution in therapeutic amount that is orally administrable.

Abstract: The invention provides active and passive immunization methods for preventing and treating Clostridium difficile infection, which involve percutaneous administration of C. difficile toxin-neutralizing polyclonal immune globulin, C. difficile toxoids, or combinations thereof. Also provided by the invention are C. difficile toxoids, C. difficile toxin-neutralizing polyclonal immune globulin, and methods of identifying subjects that produce C. difficile toxin-neutralizing polyclonal immune globulin.

Abstract: The invention relates to monoclonal antibodies capable of recognizing and neutralizing epitopes from the ligand domain, the translocation domain or the catalytic domain of the enterotoxin (toxin A) and cytotoxin (toxin B) from Clostridium difficile, as well as their production and therapeutical and prophylactic applications to diseases due to the toxins.

Abstract: Treating humans and animals intoxicated with a bacterial toxin by administration of antitoxin. Avian antitoxin in an aqueous solution in therapeutic amount that is orally administrable.

Abstract: The present invention relates to a method of inhibiting a toxin in an animal, such as a human, by administering to the animal a therapeutically effective amount of a polymer having a plurality of pendant acid functional groups which are directly attached to the polymer backbone or attached to the polymer backbone by a spacer group. The spacer group can have a length in the range from 0 to about 20 atoms. The toxin is, typically, an exotoxin secreted by a pathogenic microorganism, such as a bacterium.

Abstract: The present invention relates to a method of inhibiting a toxin in an animal, such as a human, by administering to the animal a therapeutically effective amount of a polymer having a plurality of pendant acid functional groups which are directly attached to the polymer backbone or attached to the polymer backbone by a spacer group. The spacer group can have a length in the range from 0 to about 20 atoms. The toxin is, typically, an exotoxin secreted by a pathogenic microorganism, such as a bacterium.

Abstract: A polypeptide has first and second domains which enable the polypeptide to be translocated into a target cell or which increase the solubility of the polypeptide, or both, and further enable the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis. 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.

Abstract: A method for treating hypothyroidism by local administration of a neurotoxin, such as a botulinum toxin, to a thyroid, thereby reducing an inhibitory effect upon thyroid hormone secretion. A method for treating hyperthyroidism by local administration of a neurotoxin, such as a botulinum toxin, to a sympathetic ganglion which innervates the thyroid, thereby reducing a stimulatory effect upon thyroid hormone secretion. Methods for treating calcium metabolism disorders by local administration of a neurotoxin to modulate calcitonin secretion are also disclosed.

Abstract: The invention provides active and passive immunization methods for preventing and treating Clostridium difficile infection, which involve percutaneous administration of C. difficile toxin-neutralizing polyclonal immune globulin, C. difficile toxoids, or combinations thereof. Also provided by the invention are C. difficile toxoids, C. difficile toxin-neutralizing polyclonal immune globulin, and methods of identifying subjects that produce C. difficile toxin-neutralizing polyclonal immune globulin.

Abstract: The present investion provides vaccines capable of protecting a vaccinated recipient from the morbidity and mortality associated with C. difficile infection. These vaccines are produced with portions of C. difficile Toxin A, or Toxin B, or both. These portions of Toxins A and B may be fusion proteins with at least one non-toxin protein sequence, and may also be soluble and substantially endotoxin-free. These vaccines are useful for administration to humans and other animals at risk of exposure to C. difficile toxins.

Abstract: The invention provides active and passive immunization methods for preventing and treating Clostridium difficile infection, which involve percutaneous administration of C. difficile toxin-neutralizing polyclonal immune globulin, C. difficile toxoids, or combinations thereof. Also provided by the invention are C. difficile toxoids, C. difficile toxin-neutralizing polyclonal immune globulin, and methods of identifying subjects that produce C. difficile toxin-neutralizing polyclonal immune globulin.

Abstract: A chemical conjugate for treating a nerve cell related disorder is provided. The conjugate includes an active or inactive Clostridial toxin having specificity for a target nerve cell. The toxin is conjugated to a drug or other bioactive molecule without affecting the toxin's ability to enter the target nerve cell.