Bioarctic Neuroscience Ab

Other

Bioarctic Ab

Bioarctic Neruoscience Ab

Bioartic Neuroscience Ab

Lars Lannfelt

Pär Gellerfors

Eva Nordström

Alex Kasrayan

Monica Ekberg

Valentina Screpanti Sundquist

Mats Holmquist

Jan Näslund

Camilla Nilsberth

Dag Sehlin

Anita Campbell

Hillevi Englund

Frida Ekholm Pettersson

Martin Ingelsson

Joakim Bergström

Par Gellerfors

Lars Nilsson

Erik Rollman Waara

Greta Hultqvist

Stina Syvänen

Anita Westlind-Danielsson

Hans Basun

Karin Tegerstedt

Linda Söderberg

Jan Naslund

Eva Nordstroem

Linda Soederberg

Paer Gellerfors

The present invention relates to a brain delivery protein, comprising a target binding antibody which binds to a target in a mammalian brain; two carrier moieties, each of which being capable of monovalent interaction with a protein expressed on a blood brain barrier (BBB) endothelial cell, wherein each of said carrier moieties is linked to a C-terminal end of the target binding antibody. The present invention moreover relates to use of such brain delivery proteins in therapy or diagnosis or for research of e.g. neurodegenerative disorders, and other brain diseases.

Brain delivery protein

A method of preventing, alleviating or treating traumatic brain injury in an individual comprises administering to the individual a therapeutically effective and physiologically acceptable amount of an agent capable of reducing the amount of one or more aggregated forms of one or more peptides in the brain. An agent capable of reducing the amount of one or more aggregated forms of one or more peptides in the brain is suitable for use in preventing, alleviating or treating traumatic brain injury. A method for predication of the risk of an individual for complications after a traumatic brain injury comprises detecting one or more aggregated forms of one or more peptides prone to aggregate as a result of a traumatic brain injury event, in the brain of the individual, wherein an increased level of such aggregates in the brain indicates an increased risk for complications.

Method for treatment of traumatic brain injury targeting aggregated peptides

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

In an in vivo method for detecting &#x3b1;-synuclein protofibrils in human tissue, an antibody or fragment thereof is administered to a human. The antibody or fragment is labelled with a detectable label. A complex formed between the antibody or fragment and &#x3b1;-synuclein protofibrils in the human tissue is detected. The antibody or fragment has high affinity for human &#x3b1;-synuclein protofibrils and low affinity for &#x3b1;-synuclein monomers and has a combination of three specified variable heavy (VH) CDR sequences and three specified variable light (VL) CDR sequences.

Protofibril-binding antibodies and their use in therapeutic and diagnostic methods for parkinson's disease, dementia with lewy bodies and other &#x3b1;-synucleinopathies

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

Antibodies and fragments thereof have high affinity for human &#x3b1;-synuclein protofibrils and low binding of &#x3b1;-synuclein monomers, wherein the antibodies or fragments have specified Complementarity Determining Region (CDR) sequences. Compositions comprise such an antibody or fragment and methods of detecting &#x3b1;-synuclein protofibrils use such an antibody or fragment. In further embodiments, methods of preventing, delaying onset of or treating a neurodegenerative disorder with &#x3b1;-synuclein pathology comprise administering such an antibody or fragment, and such an antibody or fragment is used in the manufacture of a pharmaceutical composition for treatment of a neurodegenerative disorder with &#x3b1;-synuclein pathology. Such an antibody or fragment is used in the diagnosis or monitoring of the development of a neurodegenerative disorder with &#x3b1;-synuclein pathology, and in methods for reducing or inhibiting &#x3b1;-synuclein aggregation by administration of such an antibody or fragment.

Protofibril-binding antibodies and their use in therapeutic and diagnostic methods for Parkinson's disease, dementia with lewy bodies and other &#x3b1;-synucleinopathies

Protofibril-binding antibodies and their use in thereapeutic and diagnostic methods for parkinson's disease, dementia with lewy bodies and other alpha-synucleinopathies

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 relates to a purified antibody or fragment thereof that specifically binds an A&#x3b2; protofibril. The invention further relates to a composition that includes such antibodies. The invention also relates to using such antibodies and compositions for treating a patient having of suspected of having Alzheimer's disease.

Antibodies specific for amyloid beta protofibril

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.

Growing community of inventors

Stockholm, Sweden

Lars Lannfelt