Hoffmann-la Roche Inc.

Arrowhead Madison, Inc.

Indiana University

Arrowhead Pharmaceuticals, Inc.

Roche Nimblegen, Inc.

F. Hoffmann-la Roche Ag

Arrowhead Research Corporation

Eric Argirios Kitas

Peter Mohr

David B Rozema

Philipp Hadwiger

David L Lewis

Torsten Hoffmann

Ingo Roehl

Darren H Wakefield

Hans Martin Mueller

Kerstin Jahn-Hofmann

Guenther Ott

Guido Galley

Hans Peter Wessel

Jon Asher Wolff

Roland Jakob-Roetne

Johannes Aebi

Paul Hebeisen

Henrietta Dehmlow

Andrei V Blokhin

Jeffrey Carlson

Jonathan D Benson

Jens-Uwe Peters

Alexander Flohr

Wolfgang Haap

Wolfgang Wostl

Daniel Bur

Alexander Chucholowski

Ulrike Obst

Linda Valis

Per-Ola Freskgard

Bernd Kuhn

Richard Dennis DiMarchi

Konrad H Bleicher

Cornelia Hertel

Thilo Enderle

Martin Graf

Rudolf E Minder

Sannah Jensen Zoffmann

Victor I Lyamichev

David L Smiley

Hans Peter Maerki

Holger Kuehne

Benoit Hornsperger

Annick Goergler

Jigar Patel

Michael Reutlinger

Eike Hoffmann

Sabine Wallbaum

Roberto Iacone

Bernd Michael Loeffler

Helmut Jacobsen

Marcel Gubler

Wilma Thuer

Denise Blum

Anish A Konkar

Armin Ruf

Ingo Röhl

Brigitte Schott

Jeremy Beauchamp

Torsten Hoffman

Sara Belli

Philipp Christoph Kohler

Kerstin Jahn-Hoffmann

Günther Ott

Jeffrey C Carlson

Linda Christine Valis

The present invention relates to dual-site BACE1 inhibitors, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

BACE1 inhibitor peptides

Provided herein are peptides having dual-site BACE1 inhibitory activity, useful for the treatment of, for example Alzheimer's disease and diabetes. One such peptide is a dual-site BACE1 inhibitor, or a pharmaceutically acceptable salt thereof, binding to both an enzymatic active site and an catalytic domain of the BACE enzyme, and an exosite inhibitory part is connected to an active-site inhibitory part of the dual site BACE1 inhibitor by a linker.

Dual-site BACE1 inhibitors

The invention provides novel compounds having the general formula (I) wherein R, R, R, R, R, R, R, Rand Rare as described herein, compositions including the compounds and methods of using the compounds.

Difluoroketamide derivatives

Peptides

Herein is reported a fusion polypeptide comprising i) one, two, three or four incretin receptor ligand polypeptides, and ii) one human immunoglobulin Fc-region, wherein at least one of the incretin receptor ligand polypeptides comprises an amino acid that is covalently conjugated to a lipid, and wherein each of the one, two, three or four incretin receptor ligand polypeptides is covalently conjugated by a peptide bond to a terminus of the human immunoglobulin Fc-region, whereby to each terminus of the human immunoglobulin Fc-region only a single incretin receptor ligand polypeptide is conjugated.

Lipidated incretin receptor ligand human immunoglobulin Fc-region fusion polypeptides

The invention provides novel compounds and conjugates of these compounds useful for the delivery of biologically active substances. Further novel design criteria for chemically stabilized siRNA particular useful when covalently attached to a delivery polymer to achieve in vivo mRNA knock down are disclosed therein.

Small molecule conjugates for intracellular delivery of biologically active compounds

Provided herein are glucagon analogs which exhibit potent activity at the GIP receptor, and, as such are contemplated for use in treating diabetes and obesity. In exemplary embodiments, the glucagon analog of the present disclosures exhibit an EC50 at the GIP receptor which is within the nanomolar or picomolar range.

Analogs of glucagon exhibiting GIP receptor activity

The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cell in vivo. The pharmacokinetic modulator improve in vivo targeting compared to the targeting ligand alone. Targeting ligand-pharmacokinetic modulator targeting moiety targeted RNAi polynucleotides can be administered in vivo alone or together with co-targeted delivery polymers.

Galactose cluster-pharmacokinetic modulator targeting moiety for siRNA

The invention provides use of novel compounds for delivery of nucleic acids, and conjugates of these compounds with nucleic acids. Further novel design criteria for chemically stabilized siRNA particular useful when covalently attached to said compounds and co-administered with a delivery polymer to achieve mRNA knock down in vivo are disclosed therein.

Small molecule conjugates for intracellular delivery of nucleic acids

The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted melittin delivery peptides. Delivery peptides provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery peptides.

Peptide-based in vivo siRNA delivery system

The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted delivery polymers. Delivery polymers provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery polymers.

Compositions for targeted delivery of siRNA

The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalently linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.

In vivo polynucleotide delivery conjugates having enzyme sensitive linkages

Growing community of inventors

Aesch, Switzerland

Eric Argirios Kitas