Probiodrug Ag

Vivoryon Therapeutics N.v.

Fraunhofer-gesellschaft Zur Foerderung Der Angewandten Forschung E.v.

Stephan Schilling

Hans-Ulrich Demuth

Jens-Ulrich Rahfeld

Ulrich Heiser

Andre Johannes Niestroj

Holger Cynis

Torsten Hoffmann

Mirko Buchholz

Martin Kleinschmidt

Kathrin Gans

Sonja Kampfer

Michael Wermann

Stephen D Gillies

Anke Piechotta

Anita Reisenauer-Schaupp

Birgit Koch

David Ruiz-Carillo

Milton T Stubbs

Christoph Parthier

Anett Stephan

Torsten Hoffman

Sigrid Graubner

Kristin Ebermann

Kathrin Gnoth

Michael Thormann

Andreas Treml

Daniel Ramsbeck

Michael Almstetter

Thore Hettmann

Robert Sommer

André Johannes Niestroj

Dagmar Schlenzig

Ulf-Torsten Gaertner

Antje Hamann

Daniel Friedrich

Astrid Kehlen

Reinhard Sedlmeier

Hans-Ulrich Dermuth

Wolfgang Jagla

Monique Haegele

André J Niestroj

Milton Stubbs

The present invention relates to novel hydroxamic acid derivatives as inhibitors of meprin β and/or α, pharmaceutical compositions comprising such compounds, methods for treatment or prophylaxis of diseases or conditions, especially such that are related to meprin β and/or α, and compounds and pharmaceutical compositions for use in such methods.

Inhibitors of meprin α and β

The invention relates to humanized and de-immunized antibodies that bind to an epitope at the N-terminus of pyroglutamated amyloid beta (Aβ N3pE) peptide and to preventive and therapeutic treatment of diseases and conditions that are related to accumulation and deposition of amyloid peptides, such as amyloidosis, a group of disorders and abnormalities associated with pyroglutamated amyloid peptide, like Alzheimer's disease, Down's syndrome, cerebral amyloid angiopathy and other related aspects. More specifically, it pertains to the use of monoclonal antibodies of the invention to bind pyroglutamated amyloid beta peptide in plasma, brain, and cerebrospinal fluid to prevent accumulation or to reverse deposition of Aβ N3pE within the brain and in various tissues in the periphery, and to alleviate amyloidosis. The present invention further pertains to diagnostic assays for the diagnosis of amyloidosis using the antibodies of the invention.

Humanized and de-immunized antibodies

The present invention can be included in the field of medicine. Specifically, the present invention provides antibodies and antigen-binding fragments thereof which can bind isoAsp7 amyloid &#x3b2; (A&#x3b2;) and a pharmaceutical composition comprising the antibodies or antigen-binding fragments thereof. IsoAsp7 A&#x3b2; can be found in plaques of Alzheimer's patients and is thus a suitable target for the treatment and/or prevention of A&#x3b2;-related diseases such as Alzheimer's disease. Thus, the antibodies, antigen-binding fragments thereof and the pharmaceutical composition comprising either can be used to treat and/or prevent neurodegenerative diseases. Further, the present invention provides hybridoma cell lines, the use of the antibodies or antigen-binding fragments thereof for the diagnosis and/or prognosis of a neurodegenerative disease and a method for detecting isoAsp7 A&#x3b2; in an isolated sample.

Anti-isoAsp7 amyloid &#x3b2; (A&#x3b2;) antibodies and uses thereof

The invention relates to humanized antibodies that bind to an epitope at the N-terminus of pyroglutamated amyloid beta (A&#x3b2; N3pE) peptide and to preventive and therapeutic treatment of diseases and conditions that are related to accumulation and deposition of amyloid peptides, such as amyloidosis, a group of disorders and abnormalities associated with pyroglutamated amyloid peptide, like Alzheimer's disease, Down's syndrome, cerebral amyloid angiopathy and other related aspects. More specifically, it pertains to the use of humanized monoclonal antibodies to bind pyroglutamated amyloid beta peptide in plasma, brain, and cerebrospinal fluid to prevent accumulation or to reverse deposition of A&#x3b3; N3pE within the brain and in various tissues in the periphery, and to alleviate amyloidosis. The present invention further pertains to diagnostic assays for the diagnosis of amyloidosis using the humanized antibodies of the invention.

Humanized antibodies

The invention relates to humanized antibodies that bind to an epitope at the N-terminus of pyroglutamated amyloid beta (A&#x3b2; N3pE) peptide and to preventive and therapeutic treatment of diseases and conditions that are related to accumulation and deposition of amyloid peptides, such as amyloidosis, a group of disorders and abnormalities associated with pyroglutamated amyloid peptide, like Alzheimer's disease, Down's syndrome, cerebral amyloid angiopathy and other related aspects. More specifically, it pertains to the use of humanized monoclonal antibodies to bind pyroglutamated amyloid beta peptide in plasma, brain, and cerebrospinal fluid to prevent accumulation or to reverse deposition of A&#x3b2; N3pE within the brain and in various tissues in the periphery, and to alleviate amyloidosis. The present invention further pertains to diagnostic assays for the diagnosis of amyloidosis using the humanized antibodies of the invention.

Diagnostic assays for the diagnosis of amyloidosis, in particular Alzheimer's disease, and related aspects. In particular, monoclonal antibodies and an antibody assay are provided.

Uses of antibodies directed against amyloid-&#x3b2;

Diagnostic antibody assay

The present invention provides a knock-out non-human animal, in particular a mouse carrying a Qpct knock-out mutation. The present invention additionally provides the respective cells and cell lines and methods and compositions for evaluating agents that affect Qpct, for use in compositions for the treatment of Qpct-related diseases.

Mouse carrying a knock-out mutation of the Qpct-gene

A knock-out non-human animal, in particular a mouse, carrying a QPCTL knock-out mutation. Additionally, respective cells and cell lines and methods and compositions for evaluating agents that affect QPCTL, for use in compositions for the treatment of QPCTL-related diseases are disclosed.

Mouse models carrying a knock-out mutation of the QPCTL-gene

Monoclonal antibodies which bind specifically to the proinflammatory cytokine pyroglutamate MCP-1 (MCP-1 N1pE).

Antibodies directed against pyroglutamate monocyte chemoattractant protein-1 (MCP-1 N1pE)

Diagnostic assays for the diagnosis of amyloidosis, in particular, Alzheimer's disease, and related aspects. In particular, monoclonal antibodies and an antibody assay are provided.

The present invention relates in general to an inhibitor of a glutaminyl peptide cyclotransferase-like protein (QPCTL), and the use thereof for the treatment and/or prevention of an inflammatory disease or disorder selected from the group consisting of (a) chronic and acute inflammations, e.g. rheumatoid arthritis, atherosclerosis, restenosis, pancreatitis; (b) other inflammatory diseases, e.g. neuropathic pain, graft rejection/graft failure/graft vasculopathy, HIV infections/AIDS, gestosis, tuberous sclerosis, Guillain-Barr&#xe9; syndrome, chronic inflammatory demyelinizing polyradiculoneuropathy and multiple sclerosis; (c) neuroinflammation; and (d) neurodegenerative diseases, e.g. mild cognitive impairment (MCI), Alzheimer's disease, neurodegeneration in Down Syndrome, Familial British Dementia, and Familial Danish Dementia, which may result from neuroinflammation.

Use of isoQC inhibitors in the treatment and prevention of inflammatory diseases or conditions

Novel crystal structures of human and murine glutaminyl cyclase (QC, EC 2.3.2.5), methods of preparing the crystals, as well as the use of said crystal structures for identifying inhibitors of human and murine glutaminyl cyclase.

Crystal structure of glutaminyl cyclase

Provided herein are methods for treating and preventing neurodegenerative disease in a mammal by administering an inhibitor of glutaminyl cyclase (QC). Neurodegenerative diseases treatable or preventable according to methods described herein include mild cognitive impairment (MCI), Alzheimer's disease, neurodegeneration in Down Syndrome, Familial British Dementia, and Familial Danish Dementia.

Method for prophylactic treatment of alzheimer's disease using inhibitors of glutaminyl cyclase and glutamate cyclases

Growing community of inventors

Halle/Saale, Germany

Stephan Schilling