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Last Updated: March 28, 2024

Claims for Patent: 7,638,620


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Summary for Patent: 7,638,620
Title:Antisense IAP nucleobase oligomers and uses thereof
Abstract: The present invention features nucleobase oligomers that hybridize to IAP polynucleotides, and methods for using them to enhance apoptosis and treat proliferative diseases.
Inventor(s): LaCasse; Eric (Ottawa, CA), McManus; Daniel (Ottawa, CA), Durkin; Jonathan P. (Ottawa, CA)
Assignee: Aegera Therapeutics, Inc. (Verdun, Quebec, unknown)
Application Number:11/448,862
Patent Claims:1. A substantially pure nucleobase oligomer of up to 30 nucleobases in length, said nucleobase oligomer comprising 5'-NGCACCCNGGANACCANNN-3' (SEQ ID NO: 151), wherein "N" is "T" or "U".

2. The nucleobase oligomer of claim 1, wherein said nucleobase oligomer consists essentially of 5'-NGCACCCNGGANACCANNN-3' (SEQ ID NO: 151), wherein "N" is "T" or "U".

3. The nucleobase oligomer of claim 2, wherein said nucleobase oligomer consists of 5'-NGCACCCNGGANACCANNN-3' (SEQ ID NO: 151), wherein "N" is "T" or "U".

4. The nucleobase oligomer of claim 1, wherein said nucleobase oligomer is an oligonucleotide that comprises at least one modified linkage.

5. The nucleobase oligomer of claim 4, wherein said modified linkage is selected from the group consisting of phosphorothioate, methylphosphonate, phosphotriester, phosphorodithioate, and phosphoselenate linkages.

6. The nucleobase oligomer of claim 1, wherein said nucleobase oligomer comprises at least one modified sugar moiety.

7. The nucleobase oligomer of claim 6, wherein said modified sugar moiety is a 2'-O-methyl group or a 2'-O-methoxyethyl group.

8. The nucleobase oligomer of claim 1, wherein said nucleobase oligomer comprises at least one modified nucleobase.

9. The nucleobase oligomer of claim 8 wherein said modified nucleobase is 5-methyl cytosine.

10. The nucleobase oligomer of claim 1, wherein said nucleobase oligomer is a chimeric nucleobase oligomer.

11. The nucleobase oligomer of claim 10, wherein said nucleobase oligomer comprises DNA residues linked together by phosphorothioate linkages, said DNA residues flanked on each side by at least one 2'-O-methyl or 2'-O-methoxyethyl RNA residue.

12. The nucleobase oligomer of claim 11, wherein said DNA residues are flanked on each side by at least three 2'-O-methyl or 2'-O-methoxyethyl RNA residues.

13. The nucleobase oligomer of claim 12, wherein said DNA residues are flanked on each side by four 2'-O-methyl or 2'-O-methoxyethyl RNA residues.

14. The nucleobase oligomer of claim 11, wherein said RNA residues are linked together by phosphorothioate linkages, and said RNA residues are linked to said DNA residues by phosphorothioate linkages.

15. The nucleobase oligomer of claim 10, wherein said nucleobase oligomer comprises DNA residues linked together by phosphodiester linkages, said DNA residues flanked on each side by at least two 2'-O-methyl or 2'-O-methoxyethyl RNA residues linked together by phosphorothioate linkages.

16. The nucleobase oligomer of claim 15, wherein said DNA residues are flanked on each side by at least three 2'-O-methyl or 2'-O-methoxyethyl RNA residues.

17. The nucleobase oligomer of claim 1, said nucleobase oligomer comprising eleven DNA residues flanked on each side by four 2'-O-methyl RNA residues, said nucleobase oligomer consisting of 5'-UGCACCCTGGATACCAUUU-3' (SEQ ID NO: 151), said residues linked together by phosphorothioate linkages.

18. The nucleobase oligomer of claim 1, wherein said nucleobase oligomer inhibits the expression of a XIAP in a cell.

19. A pharmaceutical composition comprising (i) the nucleobase oligomer of claim 15; and (ii) a pharmaceutically acceptable carrier.

20. The pharmaceutical composition of claim 19, further comprising a colloidal dispersion system.

21. A catalytic RNA molecule capable of cleaving XIAP, HIAP1, or HIAP2 mRNA, the binding arms of which comprise 5'-UGCACCCUGGAUACCAUUU-3' (SEQ ID NO: 151).

22. The catalytic RNA molecule of claim 21, wherein said RNA molecule is in a hammerhead motif.

23. The catalytic RNA molecule of claim 22, wherein said RNA molecule is in a hairpin, hepatitis delta virus, group 1 intron, VS RNA or RNAseP RNA motif.

24. An expression vector comprising a nucleic acid encoding a catalytic RNA molecule, the binding arms of which comprise 5'-UGCACCCUGGAUACCAUUU-3' (SEQ ID NO: 151), said nucleic acid positioned for expression in a mammalian cell.

25. A double-stranded RNA molecule comprising between 21 and 29 nucleobases, said RNA molecule comprising 5'-UGCACCCUGGAUACCAUUU-3' (SEQ ID NO: 151).

26. A double-stranded RNA molecule comprising between 50 and 70 nucleobases, said RNA molecule comprising a first domain of between 21 and 29 nucleobases that comprises 5'-UGCACCCUGGAUACCAUUU-3' (SEQ ID NO: 151); a second domain complementary to said first domain; and a loop domain situated between said first and said second domains.

27. An expression vector comprising a nucleic acid molecule encoding a double stranded RNA molecule comprising between 50 and 70 nucleobases, said RNA molecule comprising a first domain of between 21 and 29 nucleobases that comprises 5'-UGCACCCUGGAUACCAUUU-3' (SEQ ID NO:151); a second domain complementary to said first domain; and a loop domain situated between said first and said second domains, said nucleic acid molecule positioned for expression in a mammalian cell.

28. An oligonucleotide consisting of 5'-NGCACCCNGGANACCANNN-3' (SEQ ID NO: 151), wherein "N" is "T" or "U".

29. The pharmaceutical composition of claim 19, further comprising a chemotherapeutic agent.

30. The pharmaceutical composition of claim 29, wherein the chemotherapeutic agent is doxorubicin, vinorelbine, etoposide, paclitaxel, or cisplatin.

31. The nucleobase oligomer of claim 1 comprising 5'-UGCACCCTGGATACCAUUU-3' (SEQ ID NO: 151).

32. The nucleobase oligomer of claim 1 consisting essentially of 5'-UGCACCCTGGATACCAUUU-3' (SEQ ID NO: 151).

33. The nucleobase oligomer of claim 1 consisting of 5'-UGCACCCTGGATACCAUUU-3' (SEQ ID NO: 151).

Details for Patent 7,638,620

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 06/04/1986 ⤷  Try a Trial 2022-03-27
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 ⤷  Try a Trial 2022-03-27
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b Injection 103132 ⤷  Try a Trial 2022-03-27
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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