New York University

Einar M Sigurdsson

Thomas M Wisniewski

Blas Frangione

Ayodeji Asuni

Jorge Ghiso

Jose Alejandro Chabalgoity

Fernando Goni

Daniel H Turnbull

Youssef Zaim Wadghiri

Fernando R Goni

Marcin Sadowski

The present disclosure is directed to single domain antibodies that bind to tau and the use of these antibodies for the treatment and diagnosis of tauopathies. The present disclosure is also directed to polynucleotides encoding the tau single domain antibodies, therapeutic vectors comprising these polynucleotides and methods of administering these therapeutic vectors for the treatment of tauopathies.

Tau single domain antibodies

The present invention relates to antibody-based molecules that are capable of preferentially and selectively binding to the C-terminal di-phosphorylatedSer396/Ser404 Tau peptide as well as to theSer404 Tau peptide and the non-phosphorylated Tau peptide, but does not bind to theSer396 Tau peptide. Such antibody-based molecules are useful to detect pathological Tau protein conformer if present in a biological sample, especially in conjunction with the diagnosis and/or treatment of Alzheimer's disease or other Tauopathy, and thus provide a diagnostic for Alzheimer's disease and other Tau pathologies. The antibody-based molecules of the present invention also have particular utility as prophylactic and therapeutic molecules for the treatment and/or prevention of Alzheimer's disease and related tauopathies.

Antibodies binding to phospho-tau comprising phosphorylated Ser396 and Ser404 and methods of detecting thereof

The present disclosure is directed to single domain antibodies that bind to α-synuclein and the use of these antibodies for the treatment and diagnosis of α-synucleinopathies The present disclosure is also directed to polynucleotides encoding the α-synuclein single domain antibodies, therapeutic vectors comprising these polynucleotides and methods of administering these therapeutic vectors for the treatment of α-synucleinopathies.

Alpha-synuclein single domain antibodies

The present invention relates to antibody-based molecules (including single domain antibody fragment, scFv molecules, antibodies, antibody fragments, diabodies, and the epitope-binding domains thereof) that are capable of immunospecifically and selectively binding to the truncated Asp421 epitope of Tau. Such antibody-based molecules are useful to detect pathological Tau protein conformer if present in a biological sample, especially in conjunction with the diagnosis and/or treatment of Alzheimer's disease or other tauopathy, and thus provide a diagnostic for Alzheimer's disease and other Tau pathologies. The antibody-based molecules of the present invention have particular utility as diagnostic markers for, Alzheimer's disease and related tauopathies and as pharmaceutical compositions for the treatment of such conditions.

Antibody-based molecules specific for the truncated ASP421 epitope of Tau and their uses in the diagnosis and treatment of tauopathy

The present invention relates to methods and compositions for treating, preventing, and diagnosing Alzheimer's Disease or other tauopathies in a subject by administering an immunogenic tau peptide or an antibody recognizing the immunogenic tau epitope under conditions effective to treat, prevent, or diagnose Alzheimer's Disease or other tauopathies. Also disclosed are methods of promoting clearance of aggregates from the brain of the subject and of slowing progression of tau-pathology related behavioral phenotype in a subject.

Immunological targeting of pathological tau proteins

The present invention relates to antibody-based probes (including single domain antibody fragment, scFv molecules, antibodies, antibody fragments, diabodies, and the epitope-binding domains thereof) that are capable of immunospecifically and selectively binding to a phospho-serine-containing epitope of Tau, such as, for example, Tau-phospho-serine 396/404 peptide. Such imaging ligands are useful to detect pathological Tau protein conformer if present in a biological sample, especially in conjunction with the diagnosis of Alzheimer's disease or other tauopathy, and thus provide a diagnostic for Alzheimer's disease and other Tau pathologies. The scFv molecules of the present invention have utility as diagnostic markers for, Alzheimer's disease and related tauopathies and as pharmaceutical compositions for the treatment of such conditions.

Tau imaging ligands and their uses in the diagnosis and treatment of tauopathy

The present invention relates to antibody-based probes (including single domain antibody fragment, scFv molecules, antibodies, antibody fragments, diabodies, and the epitope-binding domains thereof) that are capable of immunospecifically and selectively binding to a phosphoserine-containing epitope of Tau, such as, for example, Tau-phospho-serine 396/404 peptide. Such imaging ligands are useful to detect pathological Tau protein conformer if present in a biological sample, especially in conjunction with the diagnosis of Alzheimer's disease or other tauopathy, and thus provide a diagnostic for Alzheimer's disease and other Tau pathologies. The scFv molecules of the present invention have utility as diagnostic markers for, Alzheimer's disease and related tauopathies and as pharmaceutical compositions for the treatment of such conditions.

The present invention relates to antibody-based molecules (including single domain antibody fragment, scFv molecules, antibodies, antibody fragments, diabodies, and the epitope-binding domains thereof) that are capable of immunospecifically and selectively binding to theSer404 Epitope of Tau. Such antibody-based molecules are useful to detect pathological Tau protein conformer if present in a biological sample, especially in conjunction with the diagnosis and/or treatment of Alzheimer's disease or other tauopathy, and thus provide a diagnostic for Alzheimer's disease and other Tau pathologies. The antibody-based molecules of the present invention have particular utility as diagnostic markers for, Alzheimer's disease and related tauopathies and as pharmaceutical compositions for the treatment of such conditions.

Antibody-based molecules selective for theSer404 epitope of Tau and their uses in the diagnosis and treatment of tauopathy

The present invention relates to methods of treating and preventing Alzheimer's Disease or other tauopathies in a subject by administering a tau protein, its immunogenic epitopes, or antibodies recognizing the tau protein or its immunogenic epitopes under conditions effective to treat or prevent Alzheimer's Disease of other tauopathies. Also disclosed are methods of promoting clearance of from the brain of the subject and of slowing progression of tangle-related behavioral phenotype in a subject.

Immunotherapy for clearing pathological tau conformers

Vaccines against prion disease eliciting a humoral immune response when administered mucosally are described. The vaccines comprise a prion protein, a prion protein fragment, or a non-amyloidogenic prion protein homolog and an adjuvant suitable for inducing a humoral immune response after mucosal administration. Suitable adjuvants include cholera toxin subunit B, heat-labile enterotoxin and aluminum hydroxide. Alternatively, the vaccine comprises a vector encoding a prion protein, fragment, or homolog in an attenuatedhost. The vaccines can be used to prevent or treat prion disease in humans and other mammals.

Mucosal immunization to prevent prion infection

Disclosed herein are methods for treating amyloid disease in humans by clearing amyloid peptides from one or more bodily fluids such as, e.g., blood, of a patient. In particular, the methods are based on the administration of compounds capable of binding to amyloid-beta (A&#x3b2;) or on dialysis of blood or plasma exchange in order to remove A&#x3b2; peptides from the blood circulation, and/or brain or other affected organs.

Method for treating amyloid disease

The present invention relates to methods of treating and preventing Alzheimer's Disease or other tauopathies in a subject by administering a tau protein, its immunogenic epitopes, or antibodies recognizing the tau protein or its immunogenic epitopes under conditions effective to treat or prevent Alzheimer's Disease of other tauopathies. Also disclosed are methods of promoting clearance of aggregates from the brain of the subject and of slowing progression of tangle-related behavioral phenotype in a subject.

Growing community of inventors

Scarsdale, NY, United States of America

Einar M Sigurdsson