Probiodrug Ag

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

Jens-Ulrich Rahfeld

Stephan Schilling

Hans-Ulrich Demuth

Martin Kleinschmidt

Holger Cynis

Sonja Kampfer

Kathrin Gans

Michael Wermann

Anke Piechotta

Anita Reisenauer-Schaupp

Christoph Parthier

Milton T Stubbs

David Ruiz-Carillo

Stephen D Gillies

Ulrich Heiser

Birgit Koch

Kristin Ebermann

Kathrin Gnoth

Torsten Hoffmann

Mirko Buchholz

Michael Thormann

Andreas Treml

Michael Almstetter

Robert Sommer

André Johannes Niestroj

Anett Stephan

Ulf-Torsten Gaertner

Antje Hamann

Sigrun Eick

Joachim Baer

Ingo Schulz

Hans-Ulrich Dermuth

Daniel Friedrich

Astrid Kehlen

Nadine Taudte

Jan Potempa

Monique Haegele

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 present invention relates to bacterial glutaminyl cyclases and inhibitors thereof for use in the treatment of periodontitis and related conditions, and provides a bacterial glutaminyl cyclase (bacQC); an antibody which recognizes the bacQC, a method for identifying an inhibitor of the bacQC; a compound according to Formula (I); a pharmaceutical composition comprising a bacQC inhibitor compound; a bacQC inhibitor compound and/or a pharmaceutical composition for use in a method for treatment of the human or animal body, for use in a method for therapy or prophylaxis of a bacterial infection, and for use in a method for therapy and/or prophylaxis of an acute, chronic or recurrent periodontal disease.

Bacterial glutaminyl cyclases and inhibitors thereof for use in the treatment of periodontitis

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

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

A crystal comprising human isoglutaminyl cyclase having a characterized space group of P1211 and unit cell dimensions of +/&#x2212;5% of a=126.51 &#x212b;, b=109.68 &#x212b;, c=159.53 &#x212b;, &#x3b1;=90.0&#xb0;, &#x3b2;=104.9&#xb0; and &#x3b3;=90.0&#xb0;.

Crystal structure of isoglutaminyl cyclase

Novel glutaminyl-peptide cyclotransferase-like proteins (QPCTLs), which are isoenzymes of glutaminyl cyclase (QC, EC 2.3.2.5), and to isolated nucleic acids coding for these isoenzymes, all of which are useful for the discovery of new therapeutic agents, for measuring cyclase activity, and for determining the inhibitory activity of compounds against these glutaminyl cyclase isoenzymes.

Screening method for enzyme inhibitors

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

A 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.

Growing community of inventors

Lieskau, Germany

Jens-Ulrich Rahfeld