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11/27/08 - USPTO Class 514 | 1 views | #20080293662 | Prev - Next | About this Page

Rnai modulation of the bcr-abl fusion gene and uses thereof

Title: Rnai modulation of the bcr-abl fusion gene and uses thereof

Brief Patent Description - Full Patent Description - Patent Claims

The Patent Description & Claims data below is from USPTO Patent Application 20080293662, Rnai modulation of the bcr-abl fusion gene and uses thereof.

1. An iRNA agent comprising an antisense strand which differs at no more than 1, 2, or 3 nucleotides from a sequence of 15 or more contiguous nucleotides of one of the group consisting of SEQ ID Nos:23, 24, 25, 26, 27, and 28.

2. The iRNA agent of claim 1, wherein the antisense strand comprises at least 15 contiguous nucleotides of one of the group consisting of SEQ ID Nos:23, 24, 25, 26, 27, and 28.

3. The iRNA agent of claim 1, further comprising a sense strand which differs at no more than 1, 2, or 3 nucleotides from a sequence of 15 or more contiguous nucleotides of one of the group consisting of SEQ ID Nos:1, 5, 11, 13, 15, and 19.

4. The iRNA agent of claim 1, further comprising a sense strand having a sequence of 15 contiguous nucleotides of one of the group consisting of SEQ ID Nos:1, 5, 11, 13, 15, and 19.

5. The iRNA agent of claim 1, wherein the agent is agent no. 3, agent no. 4 or agent no. 5.

6. The iRNA agent of claim 1, wherein the sense strand comprises at least 15 contiguous nucleotides of the sense sequences of agent nos. 3, 4 or 5, and the antisense strand comprises at least 15 contiguous nucleotides of the antisense sequences of agent nos. 3, 4 or 5, respectively.

7. The iRNA agent of claim 1, wherein the iRNA agent significantly reduces the amount of BCR-ABL fusion protein levels present in cultured human cells after incubation with the agent compared to cells which have not been incubated with the agent, wherein the cells are 32Dp210/e14a2, 32Dp210-T3151, 32Dp210-H396P, 32Dp210/e13a2, 32Dp190/e1a2, M07p210/e14a2, K562, MEG-01, or SUP-B15, or wherein the cells have been isolated from a leukemic patient.

8. The iRNA agent of claim 1, wherein the antisense RNA strand is 30 or fewer nucleotides in length, and the duplex region of the iRNA agent is 15-30 nucleotide pairs in length.

9. The iRNA agent of claim 1, comprising a modification that causes the iRNA agent to have increased stability in a biological sample.

10. The iRNA agent of claim 9, comprising a phosphorothioate or a 2′-modified nucleotide.

11. The iRNA agent of claim 10, comprising at least one 5′-uridine-adenine-3′ (5′-ua-3′) dinucleotide wherein the uridine is a 2′-modified nucleotide; at least one 5′-uridine-guanine-3′ (5′-ug-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide; at least one 5′-cytidine-adenine-3′ (5′-ca-3′) dinucleotide, wherein the 5′-cytidine is a 2′-modified nucleotide; or at least one 5′-uridine-uridine-3′ (5′-uu-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide.

12. The iRNA agent of claim 10, wherein the 2′-modified nucleotide comprises a modification selected from the group consisting of: 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O—N-methylacetamido (2′-O-NMA).

13. The iRNA agent of claim 1, further comprising a nucleotide overhang comprising 1 to 4 unpaired nucleotides.

14. The iRNA agent of claim 13, wherein the nucleotide overhang comprises 2 or 3 unpaired nucleotides.

15. The iRNA agent of claim 13, wherein the nucleotide overhang is at the 3′-end of the antisense strand of the iRNA agent.

16. The iRNA agent of claim 1, further comprising a ligand.

17. The iRNA agent of claim 16, wherein the ligand is conjugated to the 3′-end of the sense strand of the iRNA agent.

18. A pharmaceutical composition, comprising: an iRNA agent of claim 1, and a pharmaceutically acceptable carrier.

19. A method of reducing the amount of BCR-ABL RNA in a cell of a subject, comprising contacting the cell with an iRNA agent of claim 1.

20. A method of making an iRNA agent of claim 1, the method comprising synthesis of the iRNA agent, wherein the sense and antisense strands comprise at least one modification that stabilizes the iRNA agent against nucleolytic degradation.

21. A method of treating a human having or at risk for developing a proliferative disorder comprising administering an iRNA agent of claim 1, wherein the iRNA agent comprises a sense strand having at least 15 contiguous nucleotides of the sense strand sequences of the iRNA agents of agent numbers 1, 2, 3, 4, 5, or 6, and an antisense strand having at least 15 contiguous nucleotides of the antisense sequences of the iRNA agents of agent numbers, 1, 2, 3, 4, 5, or 6.

22. The method of claim 21, wherein the sense strand of the iRNA agent comprises at least 15 contiguous nucleotides of the sense sequence of agent nos. 3, 4 or 5, and the antisense strand of the iRNA agent comprises at least 15 contiguous nucleotides of the antisense sequence of agent nos. 3, 4 or 5, respectively.

23. The method of claim 22, wherein the sense strand of the iRNA agent comprises at least 15 contiguous nucleotides of the sense sequence of agent nos. 3 or 4, and the antisense strand of the iRNA agent comprises at least 15 contiguous nucleotides of the antisense sequence of agent nos. 3 or 4, respectively, and wherein the proliferative disorder is a Chronic Myeloid Leukemia.

24. The method of claim 22, wherein the sense strand of the iRNA agent comprises at least 15 contiguous nucleotides of the sense sequence of agent no. 5, and the antisense strand of the iRNA agent comprises at least 15 contiguous nucleotides of the antisense sequence of agent no. 5, and the proliferative disorder is a Ph+ acute lymphoblastic leukemia.

25. The method of claim 21, wherein the iRNA agent is administered in an amount sufficient to reduce the level of BCR-ABL RNA in a cell or tissue of the human.

Brief Patent Description - Full Patent Description - Patent Claims

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Patent Applications in related categories:

20090291906 - Oligomeric compounds and compositions for use in modulation of small non-coding rnas - Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment ...

20090291907 - Oligomeric compounds and compositions for use in modulation of small non-coding rnas - Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment ...

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