D-gen Limited

E.i. Dupont De Nemours and Company

University College London

Medical Research Council

Imperial College of Science, Technology and Medicine

Electrophoretics Limited

John Collinge

Graham Stuart Jackson

Vincent Brian Croud

Anthony R Clarke

Andrew J Nicoll

Malcolm Andrew Ward

Helen Louise Byers

James Campbell

Nicola Louise Leeds

Emma McGregor

Jules Arthur Westbrook

Simon Hawke

Jonathan David Frank Wadsworth

Julie Ann Edgeworth

David Thornley

Jules Westbrook

The invention relates to a ligand capable of binding PrP at a site within amino acid residues 131 to 153 of PrP, for use in treatment or prevention of impaired synaptic plasticity. The invention also relates to a ligand capable of binding PrP at a site within amino acid residues 131 to 153 of PrP, for use in treatment or prevention of toxicity of A&#x3b2; oligomers. The invention also relates to a ligand capable of binding PrP at a site within amino acid residues 131 to 153 of PrP, for use in treatment or prevention of Alzheimer's Disease. The invention also relates to methods of medical treatment.

Prion protein antibodies for the treatment of Alzheimer's disease

The invention relates to a method for detection of abnormal PrP in a sample of blood or urine, said method comprising: (a) diluting the sample with buffer to comprise final concentrations of (i) 10 mM to 500 mM buffer agent; (ii) 1% to 10% w/v bovine serum albumin; and (iii) 1% to 8% w/v CHAPS; (b) adding steel particles and incubating to allow PrP binding; (c) washing the steel particles to remove diluted sample; and (d) detecting abnormal PrP captured on the steel particles using antibody capable of binding said abnormal PrP. The invention also provides compositions and kits.

Assay for prions

The invention relates to a method of diagnosis of vCJD in a diagnostic sample of a valid body tissue taken from a human subject, which comprises detecting an increased concentration of a protein in the diagnostic sample, compared with a sample of a control human subject, the protein being: beta-actin (SwissProt Acc. No. P60709), apolipoprotein A-IV precursor (SwissProt Acc. No. P06727); haptoglobin beta-chain consisting of residues 162-406 (SwissProt Acc. No. P00738); haemoglobin beta chain (SwissProt Acc. No. P02023); or alpha-1-antitrypsin (SwissProt Acc. No. P01009); or a decreased concentration of a protein in the diagnostic sample, compared with a sample of a control, normal human subject, the protein being plasma protease (C1) inhibitor precursor (SwissProt Acc. No. P05155); complement component 1, s sub-component (SwissProt Acc. No. P09871); butyrylcholinesterase precursor (SwissProt Acc. No. P06276); complement component C4B (SwissProt Acc. No. P01028); lumican (SwissProt Acc. No. P51884); alpha-fibrinogen precursor (SwissProt Acc. No. P02671); IGHG4 protein (Swiss Prot Acc. No. Q8TC63) or immunoglobulin lambda heavy chain. Other marker proteins are also disclosed.

Diagnosis of neurodegenerative diseases

The invention relates to compositions and methods for prion degradation, decontamination or disinfection. The composition comprises an oxidizing agent, one or more proteases and a surfactant such as an ionic surfactant/detergent. The method comprises contacting a prion contaminated entity with a prion-degrading composition comprising an effective amount of an oxidizing agent, an effective amount of at least one protease, and an effective amount of a surfactant. The components of the composition may be contacted with a prion-contaminated entity sequentially or simultaneously using an aqueous composition. Typically at least two different proteases are used for optimal efficacy. Preferably the oxidizing agent comprises peracetyl ions or a source thereof. The invention also relates to kits comprising the various reagents.

Compositions and methods for prion decontamination

The present invention relates to a method of making a &#x3b2;-form of a prion protein which preferably has more &#x3b2;-sheet than &#x3b1;-helix structure and is soluble in the absence of a denaturant and/or is non-aggregated and exhibits partial resistance to digestion with proteinase K. The invention also relates to use of the &#x3b2;-form in medicine, especially for raising antibodies useful in the treatment and/or diagnosis of prion diseases. The invention also relates to methods of screening for compounds which are capable of inhibiting and/or reversing the conversion of the native &#x3b1;-form of a prion protein to a &#x3b2;-form, and to uses of identified compounds in medicine.

Biological materials and methods useful in the diagnosis and treatment of diseases

The invention relates to the use of an agent such as an antibody capable of reacting with PrP in the prevention of prion replication in a subject, in the treatment or prevention of prion infection, in the treatment or prevention of neuropathology associated with prion infection or in the preparation of a medicament for the treatment or prevention of prion disease. Furthermore, the invention relates to methods of treatment of prion disease, methods of inhibiting prion replication and antibodies for use in such methods.

Prion inhibition

The present invention relates to a method for typing a sample of a prion or spongiform encephalopathy disease, a kit suitable for use in such a typing method, a method for identifying infection in an animal and/or tissue of bovine spongiform encephalopathy (BSE), a method for assessing and/or predicting the susceptibility of an animal to BSE, a kit for use in such an assessment and/or prediction method, a method for the treatment of a prion disease, and compounds suitable for such a method.

Typing and diagnosis of spongiform encephalopathy

The invention relates to methods and materials for use in the typing, diagnosis, prevention and/or treatment of prion disease.

Method to type prion proteins

The present invention relates to a method of making a &bgr;-form of a prion protein which preferably has more &bgr;-sheet than &agr;-helix structure and is soluble in the absence of a denaturant and/or is non-aggregated and exhibits partial resistance to digestion with proteinase K. The invention also relates to use of the &bgr;-form in medicine, especially for raising antibodies useful in the treatment and/or diagnosis of prion diseases. The invention also relates to methods of screening for compounds which are capable of inhibiting and/or reversing the conversion of the native &agr;-form of a prion protein to a &bgr;-form, and to uses of identified compounds in medicine.

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London, United Kingdom

John Collinge