Bioarctic Neuroscience Ab

Kabi Pharmacia Ab

Hemebiotech A/s

Bioartic Neuroscience Ab

Pär Gellerfors

Lars Lannfelt

Dag Sehlin

Martin Ingelsson

Frida Ekholm Pettersson

Joakim Bergström

Hillevi Englund

Jens Fogh

Linda Fryklund

Lars Nilsson

Anna Sknottner-Lundin

Methods of treating or delaying onset of a neurodegenerative disorder with &#x3b1;-synuclein pathology in an individual comprise administering an antibody which is produced from a stabilized soluble &#x3b1;-synuclein oligomer and capable of binding a stabilized soluble &#x3b1;-synuclein oligomer, the stabilized soluble &#x3b1;-synuclein oligomer having a lower formation rate to a non-soluble aggregated form than a non-stabilized soluble oligomer of the &#x3b1;-synuclein. The antibody has been collected from a non-human animal to which stabilized soluble &#x3b1;-synuclein oligomer had been administered or has been produced by hybridoma technology, phage display, ribosome display, mammalian cell display or bacterial display, and the disorder with &#x3b1;-synuclein pathology is characterized by deposition of Lewy bodies and Lewy neurites or is selected from the group consisting of Parkinson's disease (PD), dementia with Lewy bodies (DLB), the Lewy body variant of Alzheimer's disease, and multiple system atrophy (MSA).

Antibodies and vaccines for use in therapeutic and diagnostic methods for &#x3b1;-synuclein-related disorders

The invention relates to an isolated antibody, or fragment thereof, having high affinity for human A&#x3b2; protofibrils. The invention further relates to compositions that include the antibody, or a fragment thereof, and a pharmaceutically acceptable buffer. The invention further relates to a method of preventing or treating Alzheimer's disease, which includes the step of administering to a patient having or suspected of having Alzheimer's disease such an antibody, or fragment thereof or a composition that includes the antibody or a fragment thereof.

Protofibril selective antibodies and the use thereof

The invention relates to an isolated monoclonal antibody or antigen-binding fragment thereof that (a) binds (i) wild-type A&#x3b2; 42/40 protofibril comprising N-terminal truncated A&#x3b2; forms and (ii) A&#x3b2; 42/40 Arc protofibril comprising N-terminal truncated A&#x3b2; forms and (b) has no or little cross-reactivity to A&#x3b2; 42/40 monomers. The invention further relates to a method of using such an antibody to treat Alzheimer's disease.

Antibodies specific for soluble amyloid beta peptide protofibrils and uses thereof

A vaccine for delaying an onset of or for treatment of an &#x3b1;-synuclein-related disorder in an individual comprises a therapeutically effective amount of isolated stabilized soluble &#x3b1;-synuclein oligomer having a lower formation rate to a non-soluble aggregated form than a non-stabilized oligomer of the &#x3b1;-synuclein. An antibody for delaying an onset of or for treatment of an &#x3b1;-synuclein-related disorder in an individual binds soluble &#x3b1;-synuclein. Methods for delaying an onset of for treatment or for prevention of an &#x3b1;-synuclein-related disorder employ the vaccine or antibody. Methods of detecting &#x3b1;-synuclein oligomers employ the antibody.

The invention pertains to a method of measuring A&#x3b2; protofibrils in a sample. The method includes the steps of (a) providing a labeled monoclonal antibody or fragment thereof that binds wildtype A&#x3b2; 42/40 protofibril and A&#x3b2;42/40 Arc protofibril and has no or little cross-reactivity to A&#x3b2; 42/40 monomers with an agent that generates a measurable signal, (b) contacting said labeled antibody or fragment thereof with the fluid or tissue having or suspected of comprising A&#x3b2; protofibrils, and (c) measuring the amount of protofibrils bound to the antibody by measuring the signal generated by the agent.

The invention pertains to the development of antibodies that specifically bind amyloid beta protein (Abeta) in its protofibril conformation. The invention also comprises methods of using anti-Abeta protofibril antibodies to diagnose or treat Alzheimer's disease, Down's syndrome Lewybody dementia, vascular dementia, and other neurodegenerative disorders. Furthermore, the invention pertains to the use of anti-Abeta protofibril antibodies to screen and identify substances that will modulate protofibril activity or formation in vitro or in vivo. The invention also pertains to methods for synthesising pure Abeta protofibril antigens as well as to a method for stabilising Abeta protofibrils antigens as well as to a method for stabilising Abeta protofibrils.

The present invention pertains to the prevention, treatment and diagnosis of neurodegenerative diseases, in particular Alzheimer's disease, and other similar disease. More specifically to high affinity antibodies selective for amyloid beta protein (A&#x3b2;) in its protofibril conformation and of IgG class and IgG1 or IgG4 subclass or combinations thereof or mutations thereof, retaining high Fc receptor binding and low C1(C1q) binding, effective in clearance of A&#x3b2; protofibrils and with reduce risk of inflammation.

A transgenic non-human animal expressing at least one transgene including a DNA sequence encoding a heterologous Amyloid Precursor Protein (APP) including at least the Arctic mutation (E693G) and a further AD (Alzheimer's disease) pathogenic mutation or a further transgene affecting AD pathogenesis, which results in increased amounts of intracellular soluble A aggregates, including A peptides. The method of producing the transgenic animal, and methods of screening for therapeutic or diagnostic agents useful in treatment or diagnosis of Alzheimer's disease are also disclosed.

Transgenic mouse expressing arctic mutation E693G

A method for treatment or prophylaxis of disease caused by deficiency, in a subject, of an enzyme belonging to the heme biosynthetic pathway, the method comprising administering, to the subject, an effective amount of a catalyst which is an enzyme or an enzymatically equivalent part or analogue thereof. The disease is selected from the group consisting of acute intermittent porphyria (AIP), ALA deficiency porphyria (ADP), Porphyria cutanea tarda (PCT), Hereditary coproporphyria (HCP), Harderoporphyria (HDP), Variegata prophyria (VP), Congenital erthropoetic porphyria (CEP), Erythropoietic protoporphyria (EPP), and Hepatoerythropoietic porphyria (HEP). The catalyst is one or more enzymes selected from the group consisting of delta-aminolevulininic acid synthetase, delta-aminolevulinic acid dehydratase (ALAD), porphobilinogen deaminase (PBGD), uroporphyrinogen III cosythetase, uroporphyrinogen decarboxylase, coproporphyrinogen oxidase, protoporphyrinogen oxidase, and ferrochelatase, or an enzymatically equivalent part or analogue thereof. In addition the invention relates to the use of PBGD, to human recombinant PBGD and to a method of gene therapy. The invention also relates to an expression plasmid pExp1-M2-BB (Seq. ID No. 1) and to use of a DNA fragment, the EcoRI-Hind III linear fragment (seq. ID No. 2), used for transformation in the hemC disruption strategy for production of rhPBGD expressed in

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Lidingö, Sweden

Pär Gellerfors