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1. WO2000024885 - AGENT ANTISENS p53 ET PROCEDE ASSOCIE

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[ EN ]

IT IS CLAIMED:

1. A method of treating a disease state characterized by p53 induction in a mammalian subject, comprising administering to the subject, in a suitable pharmaceutical carrier, a pharmaceutically effective amount of an antisense agent having the base sequence SEQ ID NO: 1 , identified as 5' -TCA GTC TGA GTC AGG CCC-3, or the base sequence SEQ ID NO:2, identified as 5'-CCC TGC TCC CCC CTG GCT CC-3',
wherein the antisense agent is a moφholino oligonucleotide, a peptide nucleic acid, a 2'-0-allyl or 2'-0-alkyl modified oligonucleotide, a N3' -- P5' phosphoramidate oligonucleotide, or a C-5-propyne pyrimidine-modified oligonucleotide.

2. The method of claim 1 , wherein the antisense agent is a moφholino oligonucleotide.

3. The method of claim 2, wherein the moφholino oligonucleotide comprises moφholino subunits joined by phosphorodiamidate backbone linkages.

4. The method of claim 1, wherein the oligonucleotide is a C-5-propyne pyrimidine-modified oligonucleotide.

5. The method of claim 1, wherein the antisense agent has the sequence SEQ ID NO: 1.

6. The method of claim 1, wherein the antisense agent has the sequence SEQ ID NO: 2.

7. The method of claim 1, wherein said subject is a human subject.

8. The method of claim 1, wherein said disease state is cancer.

9. The method of claim 8, further comprising treating said subject with an agent effective to increase radical oxygen species at the cellular level.

10. The method of claim 9, wherein said agent is selected from a radiosensitizing agent, ionizing radiation, a hyperbaric oxygen environment, and a chemotherapeutic agent which increases radical oxygen species at the cellular level.

11. The method of claim 10, wherein said chemotherapeutic agent is an anthracycline or anthraquinone.
12. The method of claim 8, further comprising treating said subject with an agent effective to interfere with progression from the G2 phase to the M phase of the cell cycle.

13. The method of claim 12, wherein said agent is selected from the group consisting of a phosphokinase C (PKC) inhibitor, bis(chloroethyl)nitrosourea (BCNU), pentoxi-ylline, silymarin, staurosporine, phenylahistin, paclitaxel, retinoic acid, flavopiridol, methyl-2,5-dihydrocinnamate, herboxidiene, 9-nitrocamptothecin, maitotoxin, apigenin, nocodazole, and colcemid.

14. The method of claim 1, wherein said disease state results from an ischemic or ischemic/reperfusive injury.

15. A composition for use in treating a disease state characterized by p53 induction in a subject, comprising
an antisense agent having a base sequence selected from the group consisting of SEQ ID NO:l, identified as 5'-TCA GTC TGA GTC AGG CCC-3' , and SEQ ID NO:2, identified as 5'-CCC TGC TCC CCC CTG GCT CC-3',
wherein the antisense agent is a moφholino oligonucleotide, a peptide nucleic acid, a 2'-0-allyl or 2'-0-alkyl modified oligonucleotide, a N3' -> P5' phosphoramidate oligonucleotide, or a C-5-propyne pyrimidine-modified oligonucleotide, and
a suitable pharmaceutical carrier.

16. The composition of claim 15, wherein the antisense agent is a moφholino oligonucleotide.

17. The composition of claim 16, wherein the moφholino oligonucleotide comprises moφholino subunits joined by phosphorodiamidate backbone linkages.

18. The composition of claim 15, wherein the oligonucleotide is a C-5-propyne pyrimidine-modified oligonucleotide.

19. The composition of claim 15, wherein the antisense agent has the sequence SEQ ID NO: 1.

20. The composition of claim 15, wherein the antisense agent has the sequence SEQ ID NO: 2.

21. An oligonucleotide having a base sequence selected from the group consisting of SEQ

ID NO: l, identified as 5'-TCA GTC TGA GTC AGG CCC-3', and SEQ ID NO:2, identified as 5' -CCC TGC TCC CCC CTG GCT CC-3',
wherein the oligonucleotide is selected from the group consisting of a moφholino
oligonucleotide, a peptide nucleic acid, a 2'-0-allyl or 2'-0-alkyl modified oligonucleotide, and a N3' - P5' phosphoramidate oligonucleotide.

22. An oligonucleotide as recited in claim 21, having the base sequence SEQ ID NO: 1.

23. An oligonucleotide as recited in claim 21, having the base sequence SEQ ID NO: 2.

24. An oligonucleotide as recited in claim 23, wherein the oligonucleotide is a moφholino oligonucleotide.

25. A moφholino oligonucleotide as recited in claim 24, which comprises moφholino subunits joined by phosphorodiamidate backbone linkages.

26. An oligonucleotide as recited in claim 23, wherein the oligonucleotide is a moφholino oligonucleotide.

27. The moφholino oligonucleotide of claim 26, which comprises moφholino subunits joined by phosphorodiamidate backbone linkages.

28. An oligonucleotide having a base sequence selected from the group consisting of SEQ

ID NO: l, identified as 5'-TCA GTC TGA GTC AGG CCC-3', and SEQ ID NO:2, identified as 5' -CCC TGC TCC CCC CTG GCT CC-3',
wherein the oligonucleotide is a C-5-propyne pyrimidine-modified oligonucleotide.

29. An oligonucleotide as recited in claim 28, having the base sequence SEQ ID NO: 1.

30. An oligonucleotide as recited in claim 28, having the base sequence SEQ ID NO: 2.