Composition for treating prostate cancer (PCa)

Patent metadata

Field	Value
Publication number	US-9402887-B2
Application number	US-201313759542-A
Country	US
Kind code	B2
Filing date	Feb 5, 2013
Priority date	Oct 9, 2007
Publication date	Aug 2, 2016
Grant date	Aug 2, 2016

Abstract

The present invention relates to an active (immunostimulatory) composition comprising at least one RNA, preferably an mRNA, encoding at least two (preferably different) antigens capable of eliciting an (adaptive) immune response in a mammal wherein the antigens are selected from the group consisting of PSA (Prostate-Specific Antigen), PSMA (Prostate-Specific Membrane Antigen), PSCA (Prostate Stem Cell Antigen), and STEAP (Six Transmembrane Epithelial Antigen of the Prostate). The invention furthermore relates to a vaccine comprising an active (immunostimulatory) composition, and to the use of the active (immunostimulatory) composition (for the preparation of a vaccine) and/or of the vaccine for eliciting an (adaptive) immune response for the treatment of prostate cancer (PCa), preferably of neoadjuvant and/or hormone-refractory prostate cancers, and diseases or disorders related thereto. Finally, the invention relates to kits, particularly to kits of parts, containing the active (immunostimulatory) composition and/or the vaccine.

First claim

The invention claimed is:

1. A kit comprising at least four different immunostimulatory compositions, wherein the at least four different immunostimulatory compositions are:
(a) an immunostimulatory composition comprising an isolated STEAP (Six Transmembrane Epithelial Antigen of the Prostate) antigen coding RNA complexed with protamine;
(b) an immunostimulatory composition comprising an isolated PSA (Prostate-Specific Antigen) antigen coding RNA complexed with protamine;
(c) an immunostimulatory composition comprising an isolated PSMA (Prostate-Specific Membrane Antigen) antigen coding RNA complexed with protamine; and
(d) an immunostimulatory composition comprising an isolated PSCA (Prostate Stem Cell Antigen) antigen coding RNA complexed with protamine.

2. The kit according to claim 1 , further comprising an immunostimulatory composition comprising an isolated PAP (Prostatic Acid Phosphatase) antigen coding RNA complexed with protamine.

3. The kit according to claim 1 , wherein the antigen coding RNA of said at least four different immunostimulatory compositions comprises a length of 250 to 20000 nucleotides.

4. The kit according to claim 1 , wherein at least one of the at least four different immunostimulatory compositions comprises RNA that is mRNA.

5. The kit according to claim 1 , wherein at least one of the at least four different immunostimulatory compositions comprises RNA that is monocistronic RNA.

6. The kit according to claim 5 , wherein the antigen coding RNA of said at least four different immunostimulatory compositions is monocistronic RNA.

7. The kit according to claim 4 , wherein the mRNA comprises a G/C content of the antigen coding region that is increased compared to the G/C content of a wild-type RNA encoding the antigen.

8. The kit according to claim 4 , wherein the mRNA comprises an A/U content in the environment of the ribosome binding site that is increased compared with the A/U content of a wild-type RNA encoding the antigen.

9. The kit according to claim 4 , wherein the mRNA comprises a 5′ cap structure; a poly(A) tail; a poly(C) tail and/or a globin 3′ untranslated region (3′ UTR).

10. The kit according to claim 1 , wherein at least one of said at least four different immunostimulatory compositions comprises at least one adjuvant.

11. The kit according to claim 1 , wherein at least one of said at least four different immunostimulatory compositions comprises a pharmaceutically acceptable carrier.

12. The kit according to claim 4 , wherein at least one of said at least four different immunostimulatory compositions comprises mRNA that does not comprise the sequence GAACAAG.

13. The kit according to claim 4 , wherein the mRNA comprises a 3′UTR that does not comprise an AU-rich sequence.

14. The kit according to claim 1 , wherein at least one of said at least four different immunostimulatory compositions comprises RNA that comprises a globin 3′ UTR.

15. The kit according to claim 1 ,
wherein each of said at least four different immunostimulatory compositions comprises isolated mRNA complexed with protamine and wherein each of said at least four different immunostimulatory compositions comprises mRNA comprising a 5′ cap structure, a poly(A) tail, a globin 3′ UTR, and a G/C content of the coding region, which is increased compared to the G/C content of wild-type RNA encoding the antigen.

16. The kit according to claim 2 ,
wherein each of said different immunostimulatory compositions comprises isolated mRNA complexed with protamine and wherein each of said different immunostimulatory compositions comprises mRNA comprising a 5′ cap structure, a poly(A) tail, a globin 3′ UTR, and a G/C content of the antigen coding region, which is increased compared to the G/C content of wild-type RNA encoding the antigen.

17. The kit according to claim 11 , wherein the pharmaceutically acceptable carrier comprises Ringer-Lactate.

18. A method of treating a subject having prostate cancer (PCa) comprising administering an effective amount of the at least four different immunostimulatory compositions of a kit according to claim 1 to the subject.

19. The method according to claim 18 , wherein the PCa is selected from a neoadjuvant prostate cancer and a hormone-refractory prostate cancer.

20. A method of treating a subject having PCa comprising administering an effective amount of said different immunostimulatory compositions of a kit according to claim 2 to the subject.

21. A kit comprising at least four different immunostimulatory compositions, wherein the at least four different immunostimulatory compositions are:
(a) an immunostimulatory composition comprising an isolated STEAP antigen coding RNA comprising a globin 3′ UTR;
(b) an immunostimulatory composition comprising an isolated PSA antigen coding RNA comprising a globin 3′ UTR;
(c) an immunostimulatory composition comprising an isolated PSMA antigen coding RNA comprising a globin 3′ UTR; and
(d) an immunostimulatory composition comprising an isolated PSCA antigen coding RNA comprising a globin 3′ UTR.

22. The kit according to claim 21 , further comprising an immunostimulatory composition comprising an isolated PAP antigen coding RNA comprising a globin 3′ UTR.

23. The kit according to claim 21 , wherein at least one of said at least four different immunostimulatory compositions comprises RNA that is mRNA.

24. The kit according to claim 21 , wherein at least one of said at least four different immunostimulatory compositions comprises RNA that is monocistronic RNA.

25. The kit according to claim 21 , wherein the antigen coding RNA of said at least four different immunostimulatory compositions is monocistronic RNA.

26. The kit according to claim 23 , wherein the mRNA comprises a G/C content of the antigen coding region that is increased compared to the G/C content of a wild-type RNA encoding the antigen.

27. The kit according to claim 23 , wherein the mRNA comprises an A/U content in the environment of the ribosome binding site that is increased compared with the A/U content of a wild-type RNA encoding the antigen.

28. The kit according to claim 23 , wherein the mRNA comprises a 5 ′ cap structure; a poly(A) tail; and/or a poly(C) tail.

29. The kit according to claim 21 , wherein at least one of said at least four different immunostimulatory compositions comprises RNA that is complexed with one or more polycationic molecules.

30. The kit according to claim 29 , wherein the one or more polycationic molecules comprise protamine.

31. The kit according to claim 21 , wherein at least one of said at least four different immunostimulatory compositions comprises at least one adjuvant.

32. The kit according to claim 21 , wherein at least one of said at least four different immunostimulatory compositions comprises a pharmaceutically acceptable carrier.

33. A method of treating a subject having PCa comprising administering an effective amount of said at least four different immunostimulatory compositions of a kit according to claim 21 to the subject.

34. A method of treating a subject having PCa comprising administering an effective amount of said different immunostimulatory compositions of a kit according to claim 22 to the subject.

35. A kit comprising at least f

Assignees

• Curevac Ag

Inventors

• Probst Jochen
• Hoerr Ingmar
• Lander Thomas

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title

• A61K2039/575

  humoral response · CPC title

• A61K39/39

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title