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Generated: August 23, 2019

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Claims for Patent: 6,087,172

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Summary for Patent: 6,087,172
Title: Ribozymes targeted to human IL-15 mRNA
Abstract:Enzymatic RNA molecules which cleave mRNA encoding IL-15, are provided. The constructs of the invention include regulatory regions for expression in cells, cell lines, or transgenic non-human animals. The ribozymes of the invention are directed against IL-15 mRNA and are useful in treating rheumatoid arthritis.
Inventor(s): Veerapaneni; Dange (San Diego, CA), Hamanaka; Shoji (Kanagawa, JP), Nozawa; Iwao (Tokyo, JP)
Assignee: Hisamitsu Pharmaceutical Co., Inc. (Saga, JP)
Application Number:08/962,503
Patent Claims:1. An isolated enzymatic RNA molecule which specifically cleaves human mRNA encoding interleukin-15 (IL-15).

2. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule is a hammerhead ribozyme.

3. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule is selected from the group consisting of a hairpin, hepatitis delta virus, group I intron, VS RNA, tetrahymena, and a RNAse P RNA motif.

4. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA comprises at least 5 bases complementary to said interleukin 15 (IL-15) mRNA.

5. The enzymatic RNA of claim 4, wherein said enzymatic RNA comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10.

6. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule comprises phosphorothioate or methyl phosphonate-linked analogues.

7. The enzymatic RNA molecule of claim 5, wherein said RNA molecule further comprises a stem loop structure.

8. The enzymatic RNA molecule of claim 5, wherein said enzymatic RNA molecule further comprises a 5' end modification.

9. The enzymatic RNA molecule of claim 8, wherein said 5' end modification is a 5' trimethylguanosine cap.

10. An expression vector comprising a nucleic acid encoding the enzymatic RNA molecule of claim 1.

11. The expression vector of claim 10, further comprising a promoter operably associated with the enzymatic RNA.

12. The expression vector of claim 10, wherein the enzymatic RNA molecule comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10, or any combination thereof.

13. A mammalian cell comprising an enzymatic RNA molecule of claim 1, wherein said cell is in vitro.

14. The cell of claim 14, wherein said cell is a human cell.

15. The cell of claim 15, wherein the enzymatic RNA molecule comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10, or any combination thereof.

16. A method for inhibiting IL-15 production in a cell in vitro, the method comprising: administering to the cell an amount of an enzymatic RNA molecule sufficient to cleave specifically mRNA encoding interleukin-15 (IL-15) thereby inhibiting IL-15 production.

17. The method of claim 16, further comprising administering an enzymatic RNA molecule which specifically cleaves TNF-.alpha..

18. The method of claim 16, wherein the enzymatic RNA molecule comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10, or any combination thereof.

19. A composition comprising:

a pharmaceutically acceptable carrier; and

an isolated enzymatic RNA molecule which specifically cleaves human mRNA encoding interleukin-15 (IL-15).

20. The composition of claim 19, wherein the enzymatic RNA molecule comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10, or any combination thereof.

Details for Patent 6,087,172

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Estimated Patent Expiration Status Orphan Source
Schering INTRON A interferon alfa-2b VIAL 103132 001 1986-06-04   Try a Free Trial Hisamitsu Pharmaceutical Co., Inc. (Saga, JP) 2037-11-19 RX search
Schering INTRON A interferon alfa-2b VIAL 103132 002 1986-06-04   Try a Free Trial Hisamitsu Pharmaceutical Co., Inc. (Saga, JP) 2037-11-19 RX search
Schering INTRON A interferon alfa-2b VIAL 103132 003 1986-06-04   Try a Free Trial Hisamitsu Pharmaceutical Co., Inc. (Saga, JP) 2037-11-19 RX search
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Number >Approval Date >Patent No. >Assignee >Estimated Patent Expiration >Status >Orphan >Source

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