Ruprecht-karls-universitat Heidelberg

Other

Institut National De La Sante Et De La Recherche Medicale

Universitat Heidelberg

Ruprecht-karls-universität-heidelberg (rektorat)

Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Rechts

Cleeves, Volker

Urban, Stephan

Stephan Urban

Walter Mier

Uwe Haberkorn

Volker Cleeves

Ralf Kubitz

Philippe Gripon

Stefan Mehrle

Yi Ni

Philipp Uhl

Gert Fricker

Thomas Müller

Vasileios Askoxylakis

Florian Lempp

Frieder Helm

Thomas Mueller

The present invention relates to lipopeptide-based compounds for use in the diagnosis, prevention and/or treatment of a liver disease or condition, preferably liver involved metabolic diseases, as well as in the control or modification of the cholesterol level or cholesterol uptake and, thus, diagnosis, prevention and/or treatment of a cardiovascular disease. The present invention furthermore relates to an in vitro or in vivo assay or method for testing or measuring the NTCP-mediated transport of test compound(s). The present invention furthermore relates to a method for the diagnosis, prevention and/or treatment of a liver disease or condition, comprising administering a therapeutically effective amount of a lipopeptide-based compound to a patient. The present invention furthermore relates to a method for the diagnosis, prevention and/or treatment of a cardiovascular disease.

Lipopeptides for use in treating liver diseases and cardiovascular diseases

The present invention relates to a polypeptide and a nucleic acid encoding the polypeptide for use in a method of detecting the presence of hepatitis D virus (HDV) and/or of diagnosing an HDV infection and/or of monitoring the treatment of an HDV infection. The present invention further relates to an in vitro method, an immunographic test device as well as a kit. In particular, the present invention relates to a point of care diagnostic for HDV infections.

Method and means for the rapid detection of HDV infections

The present invention relates to cyclic NTCP targeting peptides which are preS-derived peptides of hepatitis B virus (HBV). The present invention further relates to pharmaceutical compositions comprising at least one cyclic peptide. The present invention further relates to medical uses of said cyclic peptides and the pharmaceutical compositions, such as in the diagnosis, prevention and/or treatment of a liver disease or condition, and/or in the inhibition of HBV and/or HDV infection. The present invention further relates to methods of diagnosis, prevention and/or treatment of a liver disease or condition and/or the inhibition of HBV and/or HDV infection.

Cyclic NTCP-targeting peptides and their uses as entry inhibitors

The present invention relates to liposomal compositions, comprising liposomes containing tetraether lipids (TELs), and further comprising the lipopeptide Myr-HBVpreS/2-48 (Myrcludex B) as part of said liposomes, as well as uses thereof for the prevention or treatment of hepatic disorders or diseases, and/or for the oral hepatic delivery of therapeutic and/or diagnostic agents.

Liposomal formulation for the oral hepatic delivery of drugs

The present invention relates to a novel Hepatitis B virus (HBV) and/or Hepatitis D virus (HDV) receptor and its use for the development of cells, cell lines and non-human animals that are susceptible to HBV and/or HDV infection and can be used for immunological studies and/or for the screening of drugs, post-entry restriction factors and host dependency factors. It further relates to the use of the receptor for the identification of compounds useful in the treatment of HBV and/or HDV infection.

Development of HBV-and/or HDV-susceptible cells, cell lines and non-human animals

The present invention relates to hydrophobic modified peptides for the specific delivery of compounds to the liver, preferably to hepatocytes, in vitro as well as in vivo. The present invention relates to pharmaceutical compositions comprising said hydrophobic modified peptide(s) and the compound(s) to be specifically delivered to the liver. The present invention furthermore relates to the use of the inventive hydrophobic modified peptides as well as to a method for the prevention and/or treatment of liver diseases or disorders.

Hydrophobic modified peptides and their use for liver specific targeting

The present invention relates to hydrophobic modified peptides for the specific delivery of labels to the liver, preferably to hepatocytes, in vitro as well as in vivo. The present invention relates to pharmaceutical compositions comprising said hydrophobic modified peptide(s) and the label(s) to be specifically delivered to the liver. The present invention furthermore relates to the diagnostic use of the inventive hydrophobic modified peptides as well as to a method for the diagnosis of liver diseases or disorders.

Hydrophobic modified peptides for liver specific diagnosis

The invention relates to a group of synthetic polypeptides, derived from the pre-S1 region of HBV, that efficiently interfere with early steps of an HBV infection. The peptides of the invention can be used in diagnostics for the detection of antigens and/or antibodies.

Hepatitis B virus pre-S1 derived synthetic polypeptides and uses thereof

The present invention relates to hydrophobic modified preS-derived peptides of hepatitis B virus (HBV) which are versatile vehicles for the specific delivery of compounds to the liver, preferably to hepatocytes, in vitro as well as in vivo. Any kind of compound, but in particular drugs, such as interferons, viral reverse transcriptase inhibitors or core assembly inhibitors, and/or labels can be specifically targeted to the liver and so be enriched in the liver. This liver targeting can further be used for the targeted diagnosis, prevention and/or treatment of liver diseases or disorders, such as hepatitis, malaria, hepatocellular carcinoma (HCC), as well as for the prevention of HAV, HBV, HCV and/or HDV infection. The present invention relates to pharmaceutical compositions comprising said hydrophobic modified preS-derived peptide(s) and the compound(s) to be specifically delivered to the liver. The present invention furthermore relates to a method for the combined treatment of a liver disease and the prevention of HAV, HBV, HCV and/or HDV infection. The present invention relates also to the use of the preS-derived peptides in gene therapy and the delivery of immunogenic epitopes for hepatocyte-mediated antigen presentation to activate liver-directed immunological responses.

Hydrophobic modified pres-derived peptides of hepatitis B virus (HBV) and their use as vehicles for the specific delivery of compounds to the liver

The present invention relates to hydrophobic modified preS-derived peptides of hepatitis B virus (HBV) which are derived from a HBV preS consensus sequence and are N-terminal preferably acylated and optional C-terminal modified. These hydrophobic modified preS-derived peptides of HBV are very effective HBV entry inhibitors as well as HDV entry inhibitors and are, thus, suitable for the inhibition of HBV and/or HDV infection, prevention of primary HBV and/or HDV infection as well as treatment of (chronic) hepatitis B and/or D. The present invention further relates to pharmaceutical and vaccine compositions comprising these hydrophobic modified preS-derived peptides of HBV.

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Neustadt/Weinstrasse, Germany

Stephan Urban