Medicament for preventing or treating tumors caused by human papilloma virus type 18

• US 20040101533A1
• Filed: 11/25/2003
• Published: 05/27/2004
• Est. Priority Date: 12/01/2000
• Status: Abandoned Application

• Current Assignee: Medigene AG
• Original Assignee: Medigene AG
• Inventors: Muller, Rainer, Herbst, Ruth, Gabelsberger, Josef, Nieland, John
• Application Number:
  US10/433,091
• Publication Number:
  US 20040101533A1
• Time in Patent Office: Days
• US Class Current: 424/186.1
• CPC Class Codes: A61K 2039/5258 Virus-like particles
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 2319/40 containing a tag for immunodetection, or an epitope for immunisation
• CPC Class Codes: C07K 2319/735 containing a domain for self-assembly, e.g. a viral coat protein (includes phage display)
• CPC Class Codes: C12N 15/62 DNA sequences coding for fusion proteins
• CPC Class Codes: C12N 2710/20022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/20034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

A medicament for the prevention or treatment of human papillomavirus type 18 (HPV-18)-specific tumor comprising at least one fusion protein of at least one L1 protein and at least one E protein of one or more HPV-18 and, where appropriate, suitable additives and/or excipients, characterized in that the fusion protein is an L1ΔCE7_x-y fusion protein, where x is an integer from 1 to 3 inclusive and y is an integer from 61 to 64, in particular 62 to 64, especially 62 or 64.

Claims

1. A medicament for the prevention or treatment of human papillomavirus type 18 (HPV-18)-specific tumor comprising at least one fusion protein of at least one L protein and at least one E protein of one or more HPV-18 and, where appropriate, suitable additives and/or excipients, characterized in that the fusion protein is an L1Δ

CE7_x-y fusion protein, where x is an integer from 1 to 3 inclusive and y is an integer from 61 to 64, in particular 62 to 64, especially 62 or 64.

2. The medicament as claimed in claim 1, characterized in that the fusion protein is a CVLP.

3. The medicament as claimed in claim 1 or 2, characterized in that the fusion protein comprises no foreign protein content or papillomavirus-nonspecific epitopes.

4. The medicament as claimed in claim 1 or 2, characterized in that the fusion protein comprises a foreign protein content or papillomavirus-nonspecific epitopes.

5. The medicament as claimed in any of claims 1 to 4, characterized in that the tumor is a laryngeal, cervical, penile, vulval or anal carcinoma.

6. The medicament as claimed in any of claims 1 to 4, characterized in that the medicament comprises no adjuvant.

7. The medicament as claimed in any of claims 1 to 6, characterized in that the additive or excipient is about 0.1 to about 3 M, preferably about 0.15 to about 1 M, in particular about 0.2M of a salt having a pH of about 7 to about 8, preferably of about 7.3 to 7.4, in particular of 7.4.

8. The medicament as claimed in claim 7, characterized in that the salt is an alkali metal or alkaline earth metal salt, preferably a halide or phosphate, in particular an alkali metal halide, especially NaCl and/or KC1.

9. The medicament as claimed in claim 7 or 8, characterized in that the pH is adjusted with a buffer, preferably with a phosphate buffer, Tris buffer, HEPES buffer or MOPS buffer.

10. The medicament as claimed in any of claims 1 to 9, characterized in that the L protein is a deleted L protein, preferably a deleted L1 and/or L2 protein.

11. The medicament as claimed in claim 10, characterized in that the L protein is a C-terminally deleted L protein, in particular a C-terminally deleted L1 protein.

12. The medicament as claimed in claim 10 or 11, characterized in that up to about 35 amino acids are deleted from the L protein, preferably about 15 to about 35 amino acids, in particular about 26-28 amino acids.

13. The medicament as claimed in any of claims 1 to 12, characterized in that the E protein is a deleted E protein, in particular a deleted E6 and/or E7 protein.

14. The medicament as claimed in claim 13, characterized in that the deleted E protein is a C-terminally deleted E protein, preferably a C-terminally deleted E7 protein.

15. The medicament as claimed in claim 13 or 14, characterized in that up to about 55 amino acids are deleted, preferably about 5 to about 55 amino acids, in particular about 40 to 51 amino acids, especially about 41 to 45 amino acids.

16. The medicament as claimed in claim 13, characterized in that the deleted E protein is an N-terminally deleted E protein, preferably an N-terminally deleted E7 protein.

17. The medicament as claimed in claim 12 or 15, characterized in that up to about 10 amino acids are deleted, preferably 1 to 2 amino acids.

18. The medicament as claimed in any of claims 1 to 17, characterized in that the fusion protein is in the form of a capsid and/or capsomere.

19. The medicament as claimed in any of claims 1 to 18 in the form of a solution for injection or infusion.

20. A method for producing a medicament as claimed in any of claims 1 to 19, characterized in that a cell comprising an expression vector which codes for said fusion protein is cultivated under suitable conditions, the expression product is isolated, and suitable additives and excipients are added where appropriate.

21. The method as claimed in claim 20, characterized in that the expression vector comprises no nucleic acid sequences which extend said fusion protein by further amino acids on expression.

22. The use of a fusion protein as set forth in any of claims 1 to 19 for producing a medicament on the one hand for the prevention of HPV-specific tumors, and on the other hand for the regression of already existing HPV-specific tumors.