Abstract: A method for treating chronic pancreatitis and diabetes type II in a patient in need thereof comprises administering botulinum toxin to the patient. The botulinum toxin may be administered by subcutaneous or intradermal injection. The subcutaneous or intradermal injection may be administered to and/or around the vicinity of a trigeminal nerve, a cervical nerve, a thoracic nerve, a lumbar nerve, a sacral nerve, or a combination thereof.

Abstract: This invention describes a novel agent for the targeted control of a mammalian cell activity, in particular the agent is used to control the interaction of particular cell types with their external environment. The agent has applications as a pharmaceutical for the treatment of a variety of disorders. An agent according to the invention comprises three Domains B, T and E linked together in the following manner: Domain B-Domain T-Domain E where Domain B is the Binding Domain which binds the agent to a Binding Site on the cell which undergoes endocytosis to produce an endosome, Domain T is the Translocation Domain which translocates the agent (with or without the Binding Site) from within the endosome across the endosomal membrane into the cytosol of the cell, Domain E is the Effector Domain which inhibits the ability of the Recyclable Membrane Vesicles to transport the Integral Membrane Proteins to the surface of the cell.

Abstract: The present invention relates to methods and compositions of modified variants of diphtheria toxin (DT) that reduce binding to vascular endothelium or vascular endothelial cells, and therefore, reduce the incidence of Vascular Leak Syndrome. One aspect of the present invention relates to a polypeptide toxophore from a modified DT, wherein the mutation is the substitution or deletion at least one amino acid residue at the amino acid residues 6-8, 28-30 or 289-291 of native DT. Another aspect of the present invention relates to a fusion protein which comprises a modified DT and a non-DT fragment. Another aspect of the present invention relates to the use of modified DT for the treatment of cancer.

Abstract: The present invention relates to nucleic acids and polypeptides encoded thereby, whose expression is modulated in brain microvascular endothelial cells undergoing early dynamic inflammation-induced changes in blood-brain barrier functionality. Such polypeptides are referred to as lipopolysaccharide-sensitive (LPSS) polypeptides herein. These nucleic acids and polypeptides may be useful in methods for controlling blood-brain barrier properties in mammals in need of such biological effects. This includes the diagnosis and treatment of disturbances in the blood-brain/retina barrier, brain (including the eye) disorders, as well as peripheral vascular disorders. Additionally, the invention relates to the use of anti-LPSS polypeptide antibodies or ligands as diagnostic probes, as blood-brain barrier targeting agents or as therapeutic agents as well as the use of ligands or modulators of expression, activation or bioactivity of LPSS polypeptides as diagnostic probes, therapeutic agents or drug delivery enhancers.

Abstract: Combination vaccines for treating or preventing Neisseria meningitidis infection are described. The vaccines include Neisseria meningitidis serogroup B proteoliposomic vesicles and Neissera meningitidis serogroup C conjugated oligosaccharides.

Abstract: This invention describes a novel agent for the targeted control of a mammalian cell activity, in particular the agent is used to control the interaction of particular cell types with their external environment. The agent has applications as a pharmaceutical for the treatment of a variety of disorders. An agent according to the invention comprises three Domains B, T and E linked together in the following manner: Domain B-Domain T-Domain E where Domain B is the Binding Domain which binds the agent to a Binding Site on the cell which undergoes endocytosis to produce an endosome, Domain T is the Translocation Domain which translocates the agent (with or without the Binding Site) from within the endosome across the endosomal membrane into the cytosol of the cell, Domain E is the Effector Domain which inhibits the ability of the Recyclable Membrane Vesicles to transport the Integral Membrane Proteins to the surface of the cell.

Abstract: This invention describes a novel agent for the targeted control of a mammalian cell activity, in particular the agent is used to control the interaction of particular cell types with their external environment. The agent has applications as a pharmaceutical for the treatment of a variety of disorders. An agent according to the invention comprises three Domains B, T and E linked together in the following manner: Domain B-Domain T-Domain E where Domain B is the Binding Domain which binds the agent to a Binding Site on the cell which undergoes endocytosis to produce an endosome, Domain T is the Translocation Domain which translocates the agent (with or without the Binding Site) from within the endosome across the endosomal membrane into the cytosol of the cell, Domain E is the Effector Domain which inhibits the ability of the Recyclable Membrane Vesicles to transport the Integral Membrane Proteins to the surface of the cell.

Abstract: The invention relates to polypeptide carrier proteins that comprise at least five CD4+ T cell epitopes, for conjugation to capsular polysaccharides. The carrier proteins are useful as components of vaccines that can elicit a T-cell dependent immune response. These vaccines are particularly useful to confer protection against infection from encapsulated bacteria in infants between the ages of 3 months and about 2 years.

Abstract: The present invention relates to a hybrid bacterial toxin subunit, to a hybrid bipartite bacterial toxin and to nucleic acid molecules comprising a nucleotide sequence encoding such bacterial toxins. Furthermore, the invention relates to vaccines comprising bacterial toxins and to their use in vaccines. Finally, the invention relates to methods for the preparation of such vaccines and to the use of such bacterial toxins for the manufacture of such vaccines.

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: Mucosal DTPa vaccines, especially intranasal vaccines, comprising (a) a diphtheria antigen, a tetanus antigen and an acellular pertussis antigen, and (b) a detoxified mutant of cholera toxin (CT) or E. coli heat labile toxin (LT). Component (b) acts as a mucosal adjuvant. The acellular pertussis antigen preferably comprises pertussis holotoxin (PT) and filamentous haemagglutinin (FHA) and, optionally, pertactin. The mucosally-delivered combined DTPa formulation is capable of generating a level of protection against B. pertussis infection equivalent to that observed by alum-adjuvanted parenteral administration.

Abstract: The present invention relates to a method of producing recombinant modified Staphylococcal toxin having improved stability, comprising the steps of preparing a modified toxin in which a specific amino acid sequence is substituted and a vector for expressing the modified toxin, and culturing E. coli transformed with the vector, and a use thereof for the vaccine.

Abstract: The present invention pertains generally to novel Neisseria meningitidis serogroup B glycoconjugates. More particularly, the invention pertains to glycoconjugates formed from a Neisseria meningitidis serogroup B capsular oligosaccharide derivative (MenB OS derivative) in which sialic acid residue N-acetyl groups are replaced with N-acyl groups. The invention also pertains to vaccine formulations containing the glycoconjugates, methods of making the vaccine formulations, and methods of using the vaccine formulations to treat or prevent Neisseria meningitidis serogroup B or E. coli K1 disease in a mammalian subject.

Abstract: A non-toxic mucosal adjuvant is provided which may be admixed with further antigens to provide a vaccine administrable to mucosal surfaces in organisms including man. Preferably, the non-toxic mucosal adjuvant is a detoxified mutant of a bacterial ADP-ribosylating toxin, optionally comprising one or more amino acid additions, deletions or substitutions.

Abstract: The invention relates to an agent specific for peripheral sensory afferents. The agent may inhibit the transmission of signals between a primary sensory afferent and a projection neutron by controlling the release of at least one neurotransmitter or neuromodulator from the primary sensory afferent. The agent may be used in or as a pharmaceutical for the treatment of pain, particularly chronic pain.

Abstract: The invention relates to polyepitope carrier proteins that comprise at least five CD4+ T cell epitopes, for conjugation to capsular polysaccharides. The carrier proteins are use useful as components of vaccines that can elicit a T-cell dependent immune response. These vaccines arm particularly useful to confer protection against infection from encapsulated bacteria in infants between the ages of 3 months and about 2 years.

Abstract: This invention is directed to mutant SPE-C toxins or fragments thereof, vaccine and pharmaceutical compositions, and methods of using the vaccine and pharmaceutical compositions. The preferred SPE-C toxin has at least one amino acid change and is substantially non-lethal compared with the wild type SPE-C toxin. The mutant SPE-C toxins can form vaccine compositions useful to protect animals against the biological activities of wild type SPE-C toxin.

Abstract: Provided are compositions and methods useful for modulating the activity of autoinducer synthase catalysts. A method for identifing modulators of the autoinducer synthesis reaction is also provided. Such modulators are useful for controlling bacterial growth and can be used for therapeutic treatment of bacterial infections particularly in immunocompromised subjects. They are also useful in treating disease states associated with autoinducer synthesis and biofilm development.

Abstract: The present invention relates to transformed plants and plant cells comprising DNA molecules encoding Bacillus thuringiensis proteins with insecticidal activity. The invention relates more particularly to transformed plants and plant cells comprising DNA molecules encoding the protease resistant toxins BTS02618Aa or BTS02618Ab, as well as to methods of rendering plants or plant cells resistant to insects using these DNA molecules.

Abstract: The invention encompasses a method for treating hyperinsulinemic type 2 diabetes by local administration of a neurotoxin, such as a botulinum toxin, into the pancreas, thereby reducing insulin secretion from a B cell, and a method for treating hypoinsulinemic type 2 diabetes by local administration of a neurotoxin, such as a botulinum toxin, into a sympathetic ganglion, thereby reducing an inhibitory effect upon insulin secretion.

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.

Abstract: The subject invention concerns novel Bacillus thuringiensis strains containing parasporal proteins with pesticidal properties against whitefly, aphid, jassid, and possibly other sucking insects of agronomic importance, and peptide sequences to these proteins that can be used to obtain structural genes. The spores or crystals of these microbes, or mutants thereof, are useful to control hymenopteran pests in various environments. The genes of the invention can be used to transform various hosts wherein the novel toxic proteins can be expressed.

Abstract: A vaccine for immunizing animals against diseases caused by microorganisms producing an osteolytic toxin comprising an immunologically effective amount of a recombinant, immunogenic, detoxified Pasteurella multocida toxin or toxin analog, the vaccine being encoded by a nucleotide sequence coding for a Pasteurella multocida toxin or toxin analog which is inserted in an expression vector capable of replicating in a suitable host microorganism in which the said sequence may be expressed. Optionally, the produced toxin or toxin analog is subjected to posttranscriptional modifications to provide the detoxified toxin or toxin analog. Alternatively, the nucleotide sequence may be modified prior to insertion into the expression vector so as to provide the toxin or toxin analog in a detoxified form.

Abstract: Compositions and methods of oral delivery of an antigen or therapeutic agent to the general circulation using a modified botulinum toxin which is capable of translocating from the gut to the general circulation but which is altered to be nontoxic are provided.

Abstract: The present invention is directed towards a novel composition which is a genetically distinct mutant of E. coli heat-labile enterotoxin (LT). Specifically, the mutant LT designated LT(R192G/L211A) is modified by two amino acid substitutions, i.e., the arginine at amino acid position 192 is replaced by glycine and the leucine at amino acid position 211 is replaced by alanine. The invention relates to compositions and methods for use of the novel double mutant of LT as an adjuvant.

Abstract: The invention relates to an agent specific for peripheral sensory afferents. The agent may inhibit the transmission of signals between a primary sensory afferent and a projection neuron by controlling the release of at least one neurotransmitter or neuromodulator from the primary sensory afferent. The agent may be used in or as a pharmaceutical for the treatment of pain, particularly chronic pain.

Abstract: An improved Bacillus thuringiensis (B.t.) delta-endotoxin is created by the modification of the gene encoding the toxin. The toxicity of a B.t. toxin was improved by replacing the native protoxin segment with an alternate protoxin segment by constructing a chimeric toxin gene.

Abstract: Immunological active polypeptides with no or reduced toxicity useful for the preparation of an antipertussis vaccine. Method for the preparation of said polypeptides which comprises, cultivating a microorganism transformed with a hybrid plasmid including the gene/s which codes for at least one of said polypeptides in a suitable medium and recovering the desired polypeptide from the cells or from the culture medium.

Abstract: Immunologically active polypeptides with no or reduced toxicity useful for the preparation of an antipertussis vaccine. Method for the preparation of said polypeptides which comprises, cultivating a microorganism transformed with a hybrid plasmid including the gene/s which codes for at least one of said polypeptides in a suitable medium and recovering the desired polypeptide from the cells or from the culture medium.

Abstract: New proteins and subunit antigens from P. haemolytica for use in stimulating immunity against respiratory diseases such as pneumonia, including shipping fever pneumonia, are disclosed. The subunit antigens include immunogenic amino acid sequences of P. haemolytica fimbrial protein, P. haemolytica plasmin receptor protein, and P. haemolytica 50K outer membrane protein and P. haemolytica leukotoxin. The antigens can be used in a vaccine composition, either alone or in combination. Also disclosed are methods of vaccination as well as methods of making the subunit antigens employed in the vaccines.

Abstract: The invention consists of modified Clostridium neurotoxin compounds, pharmaceutical compositions containing such compounds and methods for preparing such compounds. In particular, the compounds of the invention are purified Clostridium botulinum and Clostridium tetani neurotoxins in which the tyrosine residues have been modified to have a negative charge (e.g., by covalent attachment of a phosphate or sulphate thereto) or in which the tyrosine residues have been substituted with amino acids having a negative charge (e.g., glutamate, aspartate, or negatively charged, non-natural amino acids). Toxins having phosphorylated tyrosine residues in both the light and heavy chains of the toxins are preferred. Methods for enzymatic and chemical modification of tyrosine residues in purified Clostridium neurotoxins are provided.

Abstract: This invention relates to the production and use of recombinant Pseudomonas-derived toxins modified to increase their toxicity and potency in therapy. More particularly, the invention relates to certain deletions in domain II of the amino acid sequence of Pseudomonas exotoxin the domain which relates to the toxin's natural proteolytic processing.

Abstract: A potent and specific immunotoxin is prepared by coupling an inactivated diphtheria toxin to a binding moiety such as a monoclonal antibody or transferrin. The immunotoxins are specific for human tumors and leukemias and are indistinguishable in cell toxicity from that of the native toxin linked to the binding domain without the toxicity to other cells. The immunotoxin is useful in treating graft versus host disease as well as selectively killing tumor cells, such as medulloblastoma and glioblastoma cells.

Abstract: The development of subunits and subunit analogs of the cholera exotoxin by recombinant DNA techniques provides vaccine products that can retain their biological activity and immunogenicity, and can confer protection against disease challenge. Genetically-engineered modifications of the subunits result in products that retain immunogenicity, yet are reduced in, or are essentially free of, enzymatic activity associated with toxin reactogenicity.

Abstract: Potent and specific immunotoxins are prepared by conjugation of moieties binding to receptors on the surface of tumor cells to a mutant diphtheria toxin having A-chain translocation activity, but lacking membrane-binding activity. The immunotoxins are used to treat primary tumors of neurologic origin, metastatic tumors of small cell lung carcinoma or breast carcinoma origin, leptomeningeal leukemia and leptomeningeal carcinomatosis. The preferred route of administration of the immunotoxin is to a compartment of the body containing cerebrospinal fluid.

Abstract: A DNA encoding an immunologically cross-reactive form of diphtheria toxin Fragment A, wherein the codons corresponding to Val-147 and Glu-148 of naturally-occurring diphtheria toxin are deleted from the DNA.

Abstract: An immunogenic conjugate which is the reductive amination product of an immunogenic capsular polymer fragment having at least one reducing group and derived from a bacterial capsular polymer of a bacterial pathogen, and a bacterial toxin or toxoid. The invention also relates to methods for the preparation of the conjugates, a vaccine containing the conjugates which elicits effective levels of anti-capsular polymer antibodies in humans. Also disclosed are methods for inducing active immunization against systemic infection in young mammals caused by bacterial pathogens comprising the administration of an immunogenic amount of the above-described conjugate. In a preferred embodiment, the capsular polymer fragment prior to conjugation has at least one aldehyde group at each end of the fragment. The final conjugate made with such capsular polymers has a lattice or network structure, and provides extremely high levels of anti-capsular polymer antibodies in infants.

Abstract: A potent and specific immunotoxin is prepared by coupling a binding-site inactivated diphtheria toxin (CRM 107) to a new binding moiety consisting of transferrin or a monoclonal antibody against the human transferrin receptor. These immunotoxins are tumor specific and lack the nonspecific toxicity produced by the binding activity of the native toxin. The immunotoxin is useful in treating primary brain tumors, metastatic tumors to the brain, CSF-borne tumors, leptomeningeal leukemia and leptomeningeal carcinomatosis.