MEDICAMENT FOR TREATMENT OF LIVER CANCER

• US 20150079154A1
• Filed: 07/09/2012
• Published: 03/19/2015
• Est. Priority Date: 07/08/2011
• Status: Active Grant

• Current Assignee: Helmholtz Zentrum Fuer Infektionsforschung
• Original Assignee: Helmholtz-Zentrum FüR Umweltforschung GmbH - UFZ (Bundesrepublik Deutschland)
• Inventors: Zender, Lars, Rudalska, Ramona, Dauch, Daniel
• Granted Patent: US 10,441,577 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The invention provides a pharmaceutical composition comprising Sorafenib in combination with an inhibitor of a specific kinase inhibitor as a medicament for the treatment or prevention of liver cancer.

Claims

1. Pharmaceutical composition comprising Sorafenib and an inhibitor of the activity of Mapk14 for use as a medicament in the treatment or prevention of liver cancer.

2. Pharmaceutical composition according to claim 1, wherein the inhibitor of the activity of Mapk14 is an siRNA containing an oligonucleotide having a nucleotide sequence hybridizing under physiological conditions to the mRNA encoding Mapk14 of SEQ ID NO:

1365, SEQ ID NO;

1366, SEQ ID NO;

1367 or SEQ ID NO;

1368.

3. Pharmaceutical composition according to claim 2, wherein the oligonucleotide is selected from the group comprising SEQ ID NO:

1 to SEQ ID NO;

1364.

4. Pharmaceutical composition according to claim 2, wherein the oligonucleotide comprises first section in a nucleic acid construct which contains a second section which is reverse complementary to the first section.

5. Pharmaceutical composition according to claim 2, wherein the oligonucleotide is arranged under the control of a promoter in an expression cassette.

6. Pharmaceutical composition according to claim 2, wherein the oligonucleotide is contained in a liposome formulation and/or in a viral vector which is packaged in a viral particle or in a virus-like particle.

7. Pharmaceutical composition according to claim 1, wherein the inhibitor has an 1050 for Mapk14 of at maximum 30 nM.

8. Pharmaceutical composition according to claim 7, wherein the inhibitor is selected from the group consisting of the compounds of table 1 in the specification.

9. Pharmaceutical composition according to claim 1, wherein Sorafenib is contained in a formulation for administration separate from a formulation containing the inhibitor of the activity of Mapk14.

10. Pharmaceutical composition according to claim 1, wherein Sorafenib and the inhibitor of the activity of Mapk14 are contained in one composition.

11. Pharmaceutical combination for the treatment of or prevention of liver cancer comprising:

a pharmaceutical formulation comprising an inhibitor of the activity of Mapk14 and a separate pharmaceutical formulation comprising Sorafenib.

12. Pharmaceutical combination according to claim 11, wherein the pharmaceutical formulation comprising an inhibitor of the activity of Mapk14 is for administration separate from the administration of the pharmaceutical formulation comprising Sorafenib for the treatment or prevention of liver cancer for administration to a patient.

13. Pharmaceutical combination according to claim 11, wherein the inhibitor of the activity of Mapk14 is an siRNA containing an oligonucleotide having a nucleotide sequence hybridizing under physiological conditions to the mRNA encoding Mapk14 of SEQ ID NO:

1365, SEQ ID NO;

1366, SEQ ID NO;

1367 or SEQ ID NO;

1368.

14. Pharmaceutical combination according to claim 11, wherein the inhibitor is selected from the group consisting of the compounds of table 1 in the specification.

15. Method for treatment or prevention of liver cancer comprising administration of an inhibitor of the activity of Mapk14 in combination with Sorafenib.

16. Method according to claim 15, wherein the inhibitor of the activity of Mapk14 is an siRNA containing an oligonucleotide having a nucleotide sequence hybridizing under physiological conditions to the mRNA encoding Mapk14, the siRNA containing at least one of SEQ ID NO:

1 to SEQ ID NO;

1364, or an inhibitor which is a compound selected from the group consisting of the compounds of table 1 in the specification.