Mixture comprising an inhibitor or suppresor of a gene and a molecule binding to an expression product of that gene

• US 20030186906A1
• Filed: 10/31/2002
• Published: 10/02/2003
• Est. Priority Date: 03/11/2000
• Status: Abandoned Application

• Current Assignee: Biognostik Gesellschaft Fur Biomolekulare Diagnostik MbH
• Original Assignee: Biognostik Gesellschaft Fur Biomolekulare Diagnostik MbH
• Inventors: Schlingensiepen, Reimar, Schlingensiepen, Karl-Hermann
• Application Number:
  US10/220,033
• Publication Number:
  US 20030186906A1
• Time in Patent Office: Days
• US Class Current: 514/44
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C12N 15/1136 against growth factors, growth regulators, cytokines, lymphokines or hormones
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/315 Phosphorothioates

Abstract

A mixture comprising at least one inhibitor or suppressor of the expression of a gene and at least one molecule binding to an expression product of said gene.

Claims

1. A mixture comprising at least one inhibitor or suppressor of the expression of a gene and at least one molecule inhibiting functional activity of an expression product of said gene.

2. The mixture of claim 1 wherein the at least one inhibitor or suppressor is a nucleic acid molecule or a derivative thereof.

3. The mixture of claim 2 wherein the nucleic acid molecule is an oligonucleotide, an antisense oligonucleotide and/or a ribozyme molecule.

4. The mixture of claim 3 wherein the oligonucleotide, the antisense oligonucleotide and/or the ribozyme molecule is integrated into a DNA delivery system comprising viral and/or non-viral vectors together with lipids selected from the group of anionic lipids, cationic lipids, non-cationic lipids and mixtures thereof.

5. The mixture of claim 3 wherein the antisense oligonucleotide and/or ribozyme molecule is modified at one or more of the sugar moieties, the bases and/or the internucleotide linkages and/or by coupling the antisense and/or ribozyme molecule to an enhancer of uptake and/or inhibitory activity.

6. The mixture of claim 2 wherein the oligonucleotide has any one of the nucleotide sequences Seq. Id. No 1 to 17.

7. The mixture of claim 1, wherein the at least one inhibitor or supressor is a peptide and/or a protein.

8. The mixture of any one of claims 1 to 7 wherein the at least one molecule binding to the expression product of the gene is an antibody, antibody fragment, such as a F_ab fragment, single chain antibody or combinations thereof.

9. The mixture according to claim 8 wherein the antibody, antibody fragment, such as a F_ab fragment, single chain antibody or combinations thereof is derived by screening antibody libraries and testing the expression products for binding to an expression product of the gene.

10. The mixture of any one of claims 1 to 7 wherein the at least one molecule binding to an expression product of the gene is a peptide and/or protein.

11. The mixture according to claim 10 wherein the peptide and/or protein is derived by screening an expression library and testing the expression products for binding to an expression product of the gene or is derived by screening randomly synthesised peptides and/or proteins for binding to an expression product of the gene.

12. The mixture according to claim 1, wherein the molecule or factor binding to an expression product of the gene is a low molecular weight molecule.

13. The mixture according to claim 12 wherein the low molecular weight molecule inhibitor is derived using combinatorial chemistry and testing the products for binding to an expression product of the gene.

14. The mixture according to claim 1, wherein the molecule binding to an expression product of the gene is a DNA or RNA molecule or a derivative thereof including aptamers and/or spiegelmers.

15. The mixture according to claims 3 and 8 wherein the at least one inhibitor or suppressor of the expression of a gene is an antisense oligonucleotide and the at least one molecule inhibiting functional activity of an expression product of said gene as an antibody.

16. The mixture of any one of claims 1 to 15 wherein the gene is a gene selected from the group consisting of TGF-β

, erbB-2, MIA, c-jun, junB, c-fos, VCAM, NF-kappaB p65, NF-kappa B p50, ICAM, VEGF and NF-kB 2.

18. A medicament comprising the mixture of any one of claims 1 to 16.

19. Use of the mixture according to claims 1 to 16 for the preparation of a medicament for treating tumors, immune disorders, or improving organ or cell transplantation or cell expansion.

20. Use according to claim 18 wherein inhibition of tumor growth, improvement of organ or cell transplantation, cell expansion, enhancement or inhibition of immune response is enhanced in a supra-additive manner.

17. Oligonucleotides having the sequences Seq. ID. No 1 to 17.

21. A method for reducing a functional activity of a gene product in a biological system comprising treatment of the biological system simultaneously or successively with at least one inhibitor or suppressor of the expression of a gene and at least one molecule inhibiting functional activity of an expression product of said gene.

22. The method of claim 21, wherein the biological system is a cell, a cell culture, an organ or an organism.

23. The method of claim 21, wherein the biological system is a patient suffering from the functional activity of a gene product.