Variants of human papilloma virus antigens

• US 6,306,397 B1
• Filed: 07/23/1999
• Issued: 10/23/2001
• Est. Priority Date: 12/20/1994
• Status: Expired due to Term

• Current Assignee: CSL Limited, The University of Queensland
• Original Assignee: CSL Limited, The University of Queensland
• Inventors: Frazer, Ian, Cox, John Cooper, Webb, Elizabeth Ann, Edwards, Stirling John
• Primary Examiner(s): SALIMI, ALI REZA
• Application Number:
  US09/359,382
• Time in Patent Office: 823 Days
• Field of Search: 424/192.1, 424/199.1, 424/204.1, 424/186.1, 435/320.1, 435/235.1, 435/69.1, 435/69.7, 536/23.72, 536/23.1, 536/24.3, 530/350
• US Class Current: 424/192.1
• 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 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 2710/20022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Abstract

Variants of human papilloma virus (HPV) E6 and E7 proteins able to elicit a humoral and/or cellular immune response against HPV in a host animal but not being cell-transforming in the host animal are disclosed, and are useful in treatment or prevention of diseases or conditions involving HPV.

Claims

1. An isolated variant human papillomavirus (HPV) protein able to elicit an immune response against HPV in a host animal but not being cell-transforming in said host animal, wherein said variant protein comprises a fusion protein comprising a first HPV E6 protein selected from the group consisting of full length E6 protein and non-full length deletion mutants thereof, and a second HPV E6 protein selected from the group consisting of full length E6 protein and non-full length deletion mutants thereof, and optionally a linker linking said first and second proteins.

3. An isolated variant HPV protein according to claim 1, wherein said first and second proteins are selected from different HPV genotypes.

4. An isolated variant HPV protein according to claim 1, wherein said protein further comprises a foreign protein or peptide fused or otherwise coupled to one or both of said first and second proteins.

5. An isolated variant HPV protein according to claim 4, wherein the foreign protein or peptide is selected from the group consisting of (i) proteins or peptides to assist in purification of the fusion protein or (ii) proteins or peptides to enhance the immunogenicity of the fusion protein.

6. An isolated variant HPV protein according to claim 1, which comprises a fusion protein comprising a first full length E6 protein fused to a second full length E6 protein.

8. An isolated variant HPV protein according to claim 1, comprising a first non-full length deletion mutant of the E6 protein fused to a second non-full length deletion mutant of the E6 protein.

10. An isolated variant HPV protein according to claim 1, wherein each deletion mutant of the E6 or E7 protein comprises at least 50% of the full length sequence of the protein.

11. An isolated variant HPV protein according to claim 10, wherein each deletion mutant of the E6 or E7 protein comprises at least 60% of the full length sequence of the protein.

12. An isolated variant HPV protein according to claim 11, wherein each deletion mutant of the E6 or E7 protein comprises at least the N-terminal 60% of the full length sequence of the protein.

13. An isolated variant HPV protein according to claim 11, wherein each deletion mutant of the E6 or E7 protein comprises at least the C-terminal 60% of the full length sequence of the protein.

14. An isolated variant HPV protein according to claim 1, wherein said linker consists of from 1 to 50 amino acid residues.

15. An isolated variant HPV protein according to claim 14, wherein said linker consists of from 1 to 20 amino acid residues.

16. An isolated variant HPV protein according to claim 15, wherein said linker consists of from 1 to 5 amino acid residues.

17. An isolated variant HPV protein according to claim 1, wherein said first and second HPV proteins are selected from the group consisting of HPV-16, HPV-18, HPV-6 and HPV-11 genotypes.

18. An isolated variant HPV protein according to claim 17, wherein said first and second HPV proteins are selected from the group consisting of HPV-16 and HPV-18 genotypes.

19. A composition for use in eliciting an immune response against HPV in a host animal, said composition comprising an isolated variant HPV protein according to claim 1, together with a pharmaceutically acceptable carrier and/or diluent.

20. A composition according to claim 19, further comprising an adjuvant.

21. A method for eliciting an immune response against HPV in a host animal, which method comprises administering to the host animal an effective amount of an isolated variant HPV protein according to claim 1.

22. A method according to claim 21, wherein said variant HPV protein is administered in a composition together with a pharmaceutically acceptable carrier and/or diluent.

23. A method according to claim 22, wherein said composition further comprises an adjuvant.

24. A method according to claim 21, wherein said host animal is a human.

27. An isolated variant HPV protein according to claim 3, wherein said protein further comprises a foreign protein or peptide fused or otherwise coupled to one or both of said first and second proteins.

2. An isolated variant human papillomavirus (HPV) protein able to elicit an immune response against HPV in a host animal but not being cell-transforming in said host animal, wherein said variant protein comprises a fusion protein comprising a first HPV E7 protein selected from the group consisting of full length E7 protein and non-full length deletion mutants thereof, and a second HPV E7 protein selected from the group consisting of full length E7 protein and non-full length deletion mutants thereof, and optionally a linker linking said first and second proteins.

7. An isolated variant HPV protein according to claim 2, which comprises a fusion protein comprising a first full length E7 protein fused to a second full length E7 protein.

9. An isolated variant HPV protein according to claim 2, comprising a first non-full length deletion mutant of the E7 protein fused to a second non-full length deletion mutant of the E7 protein.

25. An isolated variant HPV protein according to claim 2, wherein said first and second proteins are selected from different HPV genotypes.

26. An isolated variant HPV protein according to claim 2, wherein said protein further comprises a foreign protein or peptide fused or otherwise coupled to one or both of said first and second proteins.

28. An isolated variant HPV protein according to claim 2, wherein each deletion mutant of the E6 or E7 protein comprises at least 50% of the full length sequence of the protein.

29. An isolated variant HPV protein according to claim 2, wherein said linker consists of from 1 to 50 amino acid residues.

30. An isolated variant HPV protein according to claim 2, wherein said first and second HPV proteins are selected from the group consisting of HPV-16, HPV-18, HPV-6 and HPV-11 genotypes.

31. A composition for use in eliciting an immune response against HPV in a host animal, said composition comprising an isolated variant HPV protein according to claim 2, together with a pharmaceutically acceptable carrier and/or diluent.

32. A method for eliciting an immune response against HPV in a host animal, which method comprises administering to the host animal an effective amount of an isolated variant HPV protein according to claim 2.

33. An isolated variant human papillomavirus (HPV) protein able to elicit an immune response against HPV in a host animal but not being cell-transforming in said host animal, wherein said variant protein is either:

(a) a fusion protein comprising a first HPV E6 protein selected from the group consisting of full length E6 protein and non-full length deletion mutants thereof, and a second HPV E6 protein selected from the group consisting of full length E6 protein and non-full length deletion mutants thereof, and optionally a linker linking said first and second HPV E6 proteins, or

(b) a fusion protein comprising a first HPV E7 protein selected from the group consisting of full length E7 protein and non-full length deletion mutants thereof, and a second HPV E7 protein selected from the group consisting of full length E7 protein and non-full length deletion mutants thereof, and optionally a linker linking said first and second HPV E7 proteins.