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1. WO2010011890 - CANCER PEPTIDE THERAPEUTICS

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[ EN ]
AMENDED CLAIMS received by the International Bureau on 13 October 2010

CLAIMS:

1. A therapeutic composition for reducing cellular proliferation of malignant cells, the composition comprising a cell permeable peptide molecule comprising an amino acid sequence selected from the group consisting of LAIPEQEY, LGIAEQEY, LGIPAQEY, LGIPEAEY, LGIPEQAY, LGIAEAEY, LGIPEAAY, LGIAEQAY, LGIAEAAY.

2. The composition of claim 1, wherein the peptide molecule is a synthetic molecule.

3. The composition of claim 1, wherein the peptide molecule further comprises a cell permeable factor.

4. The composition of claim 3, wherein the cell permeable factor is a cell penetrating peptide selected from the group consisting of amino acid sequences RRRRRRR, RRRRRRRR, RRRRRRRRR, RRRRRRRRRR, RRRRRRRRRRR, RQIKIWFQNRRMKWKK, GRKKRRQRRRPPQ, GWTLNSAGYLLGKINLKALAALAKKIL, and GRKKRRQRRR.

5. The composition of claim 4, wherein the cell penetrating peptide is covalently linked or conjugated to the peptide molecule.

6. The composition of claim 4, where the cell penetrating peptide is recombinantly fused with the peptide molecule.

7. The composition of claim 4, wherein the cell penetrating peptide further comprises a spacer or a linker sequence.

8. The composition of claim 1, wherein the peptide molecule further comprises a nuclear localization sequence.

9. The composition of claim 1, wherein the peptide is protease resistant.

10. The composition of claim 1, wherein the peptide is a retro-inverso isomer.

11. The composition of claim 1 further comprises a chemotherapeutic agent.

12. The composition of claim 11, wherein the chemotherapeutic agent is a DNA damaging agent.

13. The composition of claim 12, wherein the DNA damaging agent is selected from the group consisting of doxorubicin, irinotecan, cyclophosphamide, chlorambucil, melphalan, methotrexate, cytarabine, fludarabine, 6-mercaptopurine, 5- fluorouracil, capecytabine, cisplatin, carboplatin, oxaliplatin, and a combination thereof.

14. The composition of claim 1, wherein the malignant cells express caPCNA isoform.

15. The composition of claim 14, wherein the malignant cells are selected from the group consisting of breast cancer, colon cancer, lung cancer, ovarian cancer, prostate cancer and leukemia.

16. The composition of claim 1 comprising a liposome.

17. The composition of claim 1, wherein the composition comprises a cell surface targeting factor.

18. The composition of claim 17, wherein the cell surface targeting factor is selected from the group consisting of HER2, estrogen receptor, progesterone receptor, EGFR.

19. Use of the therapeutic composition of claim 1 for reducing cellular proliferation of malignant cells comprising administering a therapeutically effective amount of the composition to contact the malignant cells.

20. The use of claim 19, wherein the composition is administered intravenously.

21. The use of claim 19, wherein the composition is delivered intratumorally.

22. The use of claim 19, wherein the composition comprises a cell permeable factor.

23. The use of claim 22, wherein the cell permeable factor is a cell penetrating peptide selected from the group consisting of amino acid sequences RRRRRRR, RRRRRRRR, RRRRRRRRR, RRRRRRRRRR, RRRRRRRRRRR, RQIKIWFQNRRMKWKK, GRKKRRQRRRPPQ, GWTLNSAGYLLGKINLKALAALAKKIL, and GRKKRRQRRR.

24. The use of claim 19 further comprises administering a chemotherapy agent.

25. The use of claim 24, wherein the chemo therapeutic agent is a DNA damaging agent.

26. The use of claim 25, wherein the DNA damaging agent is selected from the group consisting of doxorubicin, irinotecan, cyclophosphamide, chlorambucil, melphalan, methotrexate, cytarabine, fludarabine, 6-mercaptopurine, 5- fluorouracil, capecytabine, cisplatin, carboplatin, oxaliplatin, and a combination thereof.

27. The use of claim 19 further comprises administering radiotherapy.

28. The use of claim 27, wherein the radiotherapy is selected from the group consisting of beam radiation therapy and radio isotope therapy.

29. The use of claim 27 or 28, wherein the chemotherapy or radiotherapy is administered prior to or along with the administration of the composition.

30. Use of the therapeutic composition of claim 1 to sensitize or augment cancer cells for cancer therapy comprising administering a therapeutically effective amount of the composition and a chemotherapeutic agent or radiotherapy.

31. The use of claim 28, wherein the chemotherapeutic agent is a DNA damaging agent.

32. The use of claim 28, wherein the composition comprises a cell permeable factor.

33. The use of claim 30, wherein the cell permeable factor is a cell penetrating peptide selected from the group consisting of amino acid sequences RRRRRRR, RRRRRRRR, RRRRRRRRR, RRRRRRRRRR, RRRRRRRRRRR, RQIKIWFQNRRMKWKK, GRKKRRQRRRPPQ, and GWTLNSAGYLLGKINLKALAALAKKIL.

34. Use of the composition of claim 1 as a medicament for chemoprevention of cancer to prevent the transformation of the cells that express the cancer specific proliferating cell nuclear antigen (caPCNA) isoform to a malignant state or develop tumors.

35. The use of claim 34, wherein the chemopreventative agent is administered to an individual considered high-risk for a cancer type.

36. The method of claim 34, wherein the chemopreventative agent is administered to an individual with pre-cancerous cells.