Abstract: The present invention relates to the treatment of pain and to compounds that modulate C-fibre activity. In particular, the present invention relates to the use of a lectin in the manufacture of a medicament for modulation of C-fibre neuron activity, and to lectin conjugates. The lectin conjugates comprise a lectin coupled to a peptide or protein, wherein the peptide or protein is substantially free of Clostridial neurotoxin enzyme activity. The present invention also concerns methods for manufacturing conjugates. The compounds and compositions described have particular application in the treatment of diseases of which C-fibre activity is a component. Such diseases include pain, inflamation, psoriasis and other C-fibre related conditions.

Abstract: Toxin derivatives are prepared by proteolytic treatment of holotoxin, and their toxicity is reduced by contacting the preparation with a ligand, which can be a metal or an antibody or another ligand. This ligand selectively binds to the toxin but not to the toxin derivative. Removing the ligand and toxin bound to the ligand further reduces toxicity. A second ligand is used to remove conjugates of the toxin and the first ligand. Compositions contain the purified derivative, optionally plus the toxin and the ligand.

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: A method of treating mucus hypersecretion, the causative factor in chronic obstructive pulmonary disease (COPD), asthma and other clinical conditions involving COPD, comprises administering a compound that inhibits exocytosis in mucus secreting cells or neurones that control or direct mucus secretion. Also described is a compound, for use in the treatment of hypersecretion of mucus, which inhibits mucus secretion by inhibiting mucus secretion by mucus secreting cells, and/or inhibiting neurotransmitter release from neuronal cells controlling or directing mucus secretion.

Abstract: Methods and compositions for the treatment of microbial infection, and in particular meningococcal disease, comprise a commensal Neisseria or an extract of a commensal Neisseria. Further methods and compositions comprise commensal Neisseria which express genes from virulent strains of Neisseria and/or heterologous gene products from non-neisserial sources. Such compositions are used in vaccine preparations for the treatment of microbial infection.

Abstract: Methods and compositions for the treatment of microbial infection, and in particular meningococcal disease, comprise a commensal Neisseria or an extract of a commensal Neisseria. Further methods and compositions comprise conimensal Neisseria which express genes from virulent strains of Neisseria and/or heterologous gene products from non-Neisserial sources. Such compositions are used in vaccine preparations for the treatment of microbial infection.

Abstract: The present invention provides a composition for treating a bacterial biofilm, comprising a first bacteriophage that is capable of infecting a bacterium within said biofilm, and a first polysaccharide lyase enzyme that is capable of degrading a polysaccharide within said biofilm. The composition preferably further comprises a pharmaceutically-acceptable antimicrobial agent, and may also include a DNase. Also provided are modified bacteriophages, methods of creating modified bacteriophages, use of said compositions and bacteriophage for treating biofilms, and methods for treating biofilms using the bacteriophages and compositions of the invention.

Abstract: A class of novel agents that are able to modify nociceptive afferent function is provided. The agents may inhibit the release of neurotransmitters from discrete populations of neurones and thereby reduce or preferably prevent the transmission of afferent pain signals from peripheral to central pain fibers. They comprise a galactose-binding lectin linked to a derivative of a clostridial neurotoxin. The derivative of the clostridial neurotoxin comprises the L-chain, or a fragment thereof, which includes the active proteolytic enzyme domain of the light (L) chain, linked to a molecule or domain with membrane translocating activity. The agents may be used in or as pharmaceuticals for the treatment of pain, particularly chronic pain.

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: In as assay, an analyte is specifically associated with a reporter adenylate kinase, ADP is added and then formation of ATP is monitored. Prior to addition of ADP, adenylate kinase other than reporter adenylate kinase is removed. Assay apparatus comprises a solid phase on which is immobilised the analyte or an antibody specific for the analyte, a reporter composition comprising a thermostable adenylate kinase coupled to an antibody specific for the analyte, and ADP plus associated reagents for conversion of ADP into ATP by thermostable adenylate kinase.

Abstract: A composition comprising Transferrin binding proteins A and B is described (TbpA and TbpB). The composition is suitable for use in vaccines and for treatment of Gram negative bacterial infection, particularly meningococcal infection, demonstrating a broad spectrum of protection to a number of different bacterial pathogens. Also described are compositions comprising Tbps and other components, such as neisserial outer membrane vesicles and Cu,Zn-Superoxide dismutase. Methods for preparation of these compositions and their uses in vaccination against disease are further provided.

Abstract: A transmissible spongiform encephalopathy (TSE) agent is inactivated by exposing the TSE agent to a thermostable proteolytic enzyme at elevated temperature and at acid or alkaline pH. Following this step, or separately, presence of TSE infectivity is detected by detection of dimers of prion protein.

Abstract: A method of treating mucus hypersecretion, the causative factor in chronic obstructive pulmonary disease (COPD), asthma and other clinical conditions involving COPD, comprises administering a compound that inhibits exocytosis in mucus secreting cells or neurones that control or direct mucus secretion. Also described is a compound, for use in the treatment of hypersecretion of mucus, which inhibits mucus secretion by inhibiting mucus secretion by mucus secreting cells, and/or inhibiting neurotransmitter release from neuronal cells controlling or directing mucus secretion.

Abstract: An agent for combating an intracellular microbial infection comprises a phage component and, associated therewith, a targeting moiety which directs the agent to a target cell and initiates delivery of the phage into the target cell. Once inside the target cell, the phage causes lysis of a microorganism residing within the target cell. A mycobacteriophage is combined with a targeting moiety of transferrin. Compositions comprising the agent, methods of preparing said agent, and use of said agent for combating intracellular infections are also provided.

Abstract: A method of treating mucus hypersecretion, the causative factor in chronic obstructive pulmonary disease (COPD), asthma and other clinical conditions involving COPD, comprises administering a compound that inhibits exocytosis in mucus secreting cells or neurones that control or direct mucus secretion. Also described is a compound, for use in the treatment of hypersecretion of mucus, which inhibits mucus secretion by inhibiting mucus secreting cells, and/or inhibiting neurotransmitter release from neuronal cells controlling or directing mucus secretion.