Bibliographic Details
| Title: |
COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF IKK-B GENE |
| Document Number: |
20080108584 |
| Publication Date: |
May 8, 2008 |
| Appl. No: |
11/751283 |
| Application Filed: |
May 21, 2007 |
| Abstract: |
The invention relates to a doable-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the IKK-B gene, comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the IKK-B gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases, caused by the expression or activation of the IKK-B gene using the pharmaceutical composition; and methods for inhibiting the expression of the IKK-B gene in a cell. |
| Inventors: |
DE FOUGEROLLES, ANTONIN (Brookline, MA, US); SPRAGUE, ANDREW (Haverhill, MA, US); HARBORTH, JENS (Boston, MA, US); BELVISI, MARIA GABRIELLA (Liverpool, GB); BIRRELL, MARK ANDREW (Essex, GB); HARDAKER, ELIZABETH LOUISE (London, GB); CATLEY, MATTHEW COPELAND (London, GB) |
| Claim: |
1. A double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a human IKK-B gene in a cell, wherein said dsRNA comprises at least two sequences that are complementary to each other and wherein a sense strand comprises a first sequence and an antisense strand comprises a second sequence comprising a region of complementarity which is substantially complementary to at least a part of a mRNA encoding IKK-B, and wherein said region of complementarity is less than 30 nucleotides in length and wherein said dsRNA, upon contact with a cell expressing said IKK-B, inhibits expression of said IKK-B gene by at least 25%. |
| Claim: |
2. The dsRNA of claim 1, wherein said first sequence is selected from the group consisting of Tables 1.4 and 6 and said second sequence is selected from the group consisting of Tables L4 and 6. |
| Claim: |
3. The dsRNA of claim 1, wherein said dsRNA comprises at least one modified nucleotide. |
| Claim: |
4. The dsRNA of claim 2, wherein said dsRNA comprises at least one modified nucleotide. |
| Claim: |
5. The dsRNA of claims 3 or 4, wherein said modified nucleotide is chosen from the group of: a 2′-O-methyl modified nucleotide, a nucleotide comprising a 5-phosphorothioate group, and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group. |
| Claim: |
6. The dsRNA of claims 3 or 4, wherein said modified nucleotide is chosen from the group of: a 2′-deoxy-2′-fluoro modified nucleotide, a Z-deoxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide. 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and anon-natural base comprising nucleotide. |
| Claim: |
7. The dsRNA of claims 3 or 4, wherein said first sequence is selected from the group consisting of Tables 1, 4 and 6 and said second sequence is selected from the group consisting of Tables 1, 4 and 6. |
| Claim: |
8. The dsRNA of claims 6 or 7, wherein said first sequence is selected from the group consisting of Tables 1, 4 and 6 and said second sequence is selected from the group consisting of Tables 1, 4 and 6. |
| Claim: |
9. A cell comprising the dsRNA of claim 1. |
| Claim: |
10. A pharmaceutical composition for inhibiting the expression of the IKK-B gene in an organism, comprising a dsRNA and a pharmaceutically acceptable carrier, wherein the dsRNA comprises at least two sequences that are complementary to each other and wherein a sense strand comprises a first sequence and an antisense strand comprises a second sequence comprising a region of complementarity which is substantially complementary to at least a part of a mRNA encoding IKK-B, and wherein said region of complementarity is less than 30 nucleotides in length and wherein said dsRNA, upon contact with a cell expressing said IKK-B, inhibits expression of said IKK-B gene by at least 25%, or preferably by at least 40%. |
| Claim: |
11. The pharmaceutical composition of claim 10, wherein said first sequence of said dsRNA is selected from the group consisting of Tables 1, 4 and 6 and said second sequence of said dsRNA is selected from the group consisting of Tables 1, 4 and 6. |
| Claim: |
12. The pharmaceutical composition of claim 10, wherein said first sequence of said dsRNA is selected from the group consisting of Tables 1, 4 and 6 and said second sequence of said dsRNA is selected from the group consisting of Tables 1, 4 and 6. |
| Claim: |
13. A method for inhibiting the expression of the IKK-B gene in a cell, the method comprising: (a) introducing into the cell a double-stranded ribonucleic acid (dsRNA), wherein the dsRNA comprises at least two sequences that are complementary to each other and wherein a sense strand comprises a first sequence and an antisense strand comprises a second sequence comprising a region of complementarity which is substantially complementary to at least a part of a mRNA encoding IKK-B, and wherein said region of complementarity is less than 30 nucleotides in length and wherein said dsRNA, upon contact with a cell expressing said IKK-B, inhibits expression of said IKK-B gene by at least 25%, or preferably by at least 40%; and (b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of the IKK-B gene, thereby inhibiting expression of the IKK-B gene in the cell. |
| Claim: |
14. A method of treating, preventing or managing inflammation comprising administering to a patient in need of such treatment, prevention or management a therapeutically or prophylactically effective amount of a dsRNA, wherein the dsRNA comprises at least two sequences that are complementary to each other and wherein a sense strand comprises a first sequence and an antisense strand comprises a second sequence comprising a region of complementarity which is substantially complementary to at least a part of a mRNA encoding IKK-B, and wherein said region of complementarity is less than 30 nucleotides in length and wherein said dsRNA, upon contact with a cell expressing said IKK-B, inhibits expression of said IKK-B gene by at least 25%, or preferably by at least 40%. |
| Claim: |
15. A vector for inhibiting the expression of the IKK-B gene in a cell, said vector comprising a regulatory sequence operably linked to a nucleotide sequence that encodes at least one strand of a dsRNA, wherein one of the strands of said dsRNA is substantially complementary to at least a part of a mRNA encoding IKK-B and wherein said dsRNA is less than 30 base pairs in length and wherein said dsRNA, upon contact with a cell expressing said IKK-B, Inhibits the expression of said IKK-B gene by at least 25%, or preferably by at least 40%. |
| Claim: |
16. A cell comprising the vector of claim 15. |
| Current U.S. Class: |
514044/000 |
| Current International Class: |
61; 61; 07; 12; 12 |
| Accession Number: |
edspap.20080108584 |
| Database: |
USPTO Patent Applications |
