IP Library Granted Patent US 7,759,320
Granted Patent B2
US 7,759,320 · App. 12/055,295 · Granted Jul 20, 2010

Compositions and methods for inhibiting expression of a gene from the Ebola

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Quick Facts
Patent No.
US 7,759,320
App. No.
12/055,295
Granted
Jul 20, 2010
Kind
B2
Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a gene from the Ebola virus.

Claims (23)

1. A double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a gene in the Ebola virus 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, wherein said first sequence is identical to the first 19 nucleotides of SEQ ID NO:9 (UGAUGAAGAUUAAGAAAAA), and an antisense strand comprises a second sequence, wherein said second sequence is identical to the first 19 nucleotides of SEQ ID NO: 10 (UUUUUCUUAAUCUUCAUCA), and wherein said sense strand and said antisense strand are each between 19 and 24 nucleotides in length.

2. The dsRNA of claim 1 , wherein said dsRNA comprises at least one modified nucleotide.

3. The dsRNA of claim 2 , wherein said modified nucleotide is chosen from the group of: a 2′- 0 -methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group.

4. The dsRNA of claim 2 , wherein said modified nucleotide is chosen from the group of: a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide.

5. The dsRNA of claim 3 , wherein said sense strand consists of SEQ ID NO: 159 and wherein said antisense strand consists of SEQ ID NO: 160.

6. The dsRNA of claim 2 , wherein said sense strand consists of SEQ ID NO: 1027 and wherein said antisense strand consists of SEQ ID NO: 1028.

7. A cell comprising the dsRNA of claim 1 .

8. A pharmaceutical composition for inhibiting the expression of a gene from an Ebola virus in an organism, comprising a dsRNA of claim 1 and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8 , wherein said sense strand consists of SEQ ID NO: 159 and wherein said antisense strand consists of SEQ ID NO: 160.

10. The-pharmaceutical composition of claim 8 , wherein said sense strand consists of SEQ ID NO: 1027 and wherein said antisense strand consists of SEQ ID NO: 1028.

11. A method for inhibiting the expression of a gene from an Ebola virus in a cell, the method comprising:

(a) introducing into the cell a double-stranded ribonucleic acid (dsRNA) of claim 1 ; and

(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of a gene from the Ebola virus, thereby inhibiting expression of a gene from the Ebola virus in the cell.

12. A method of treating or managing pathological processes mediated by Ebola expression comprising administering to a patient in need of such treatment or management a therapeutically effective amount of a dsRNA of claim 1 .

13. A vector for inhibiting the expression of a gene from the Ebola virus in a cell, said vector comprising a regulatory sequence operably linked to a nucleotide sequence that encodes the dsRNA of claim 1 .

14. A cell comprising the vector of claim 13 .

15. The dsRNA of claim 1 , wherein said dsRNA, upon contact with a cell infected with Ebola virus, inhibits expression of a gene from the virus by at least 40%.

16. The dsRNA of claim 1 , wherein said antisense strand comprises a region of complementarity to at least a part of Ebola VP35 mRNA, wherein said region of complementarity is between 19 and 24 nucleotides in length.

17. The vector of claim 13 , wherein said dsRNA, upon contact with a cell infected with Ebola virus, inhibits expression of a gene from the virus by at least 40%.

18. A method of increasing life-span of a subject infected with an Ebola virus, comprising administering to the subject a dsRNA of claim 1 in an amount sufficient to increase the life-span of the subject.

19. A method of decreasing viral titre in a subject infected with an Ebola virus, comprising administering to the subject a dsRNA of claim 1 in an amount sufficient to decrease viral titre in the subject.

20. A method of sustaining platelet count in a subject infected with an Ebola virus, comprising administering to the subject a dsRNA of claim 1 in an amount sufficient to sustain platelet count.

21. The method of claim 20 , wherein the lymphocyte count of the subject is also sustained.

Assignments (6)
SECURITY INTEREST Recorded Oct 1, 2025
From: ALNYLAM PHARMACEUTICALS, INC.; SIRNA THERAPEUTICS, INC.
To: BANK OF AMERICA, N.A.
Reel/Frame 072996/0337 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 1, 2009
From: BAVARI, SINA; WARFIELD, KELLY LYN
To: THE GOVERNMENT OF THE U.S., REPRESENTED BY THE SECRETARY OF THE ARMY
Reel/Frame 023314/0675 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 14, 2009
From: TAN, PAMELA
To: ALNYLAM EUROPE AG
Reel/Frame 023224/0712 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 14, 2009
From: ALNYLAM EUROPE AG
To: ALNYLAM PHARMACEUTICALS, INC.
Reel/Frame 023224/0733 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 14, 2009
From: BAVARI, SINA; WARFIELD, KELLY LYN
To: SECRETARY OF THE ARMY
Reel/Frame 023224/0818 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 16, 2008
From: BORODOVSKY, ANNA; NOVOBRANTSEVA, TATIANA; DE FOUGEROLLES, ANTONIN
To: ALNYLAM PHARMACEUTICALS, INC.
Reel/Frame 021989/0285 →