Small-mer compositions and methods of use

• US 20050203044A1
• Filed: 01/26/2005
• Published: 09/15/2005
• Est. Priority Date: 08/08/2002
• Status: Abandoned Application

• Current Assignee: Sirna Therapeutics, Inc. (Alnylam Pharmaceuticals Incorporated)
• Original Assignee: Sirna Therapeutics, Inc. (Alnylam Pharmaceuticals Incorporated)
• Inventors: Zinnen, Shawn
• Application Number:
  US11/043,673
• Publication Number:
  US 20050203044A1
• Time in Patent Office: Days
• US Class Current: 514/44.A
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical

Abstract

The present invention concerns small-mer compositions and methods useful in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to small-mer compositions capable of inhibiting viral replication, useful in treating diseases and conditions related to viral infection, and/or capable of inhibiting cellular proliferation, useful in treating diseases and conditions related to cellular proliferation.

Claims

1. A small-mer molecule having anti-HIV activity, wherein said small-mer comprises about 3 to about 6 nucleotides.

3. The small-mer molecule of claim 1, wherein said small-mer molecule is adapted for use to treat HIV infection.

6. The small-mer molecule of claim 1, wherein said small-mer molecule comprises one or more internucleotide linkages having Formula I:

8. The small-mer molecule of claim 1, wherein said small-mer comprises one or more nucleotides or non-nucleotides having Formula II:

10. A composition comprising the small-mer of claim 1 and a pharmaceutically acceptable carrier or diluent.

12. A method for generating a small-mer with improved antiviral activity comprising:

(a) providing the small-mer of claim 1 as a scaffold for additional nucleotides and/or non-nucleotides, (b) generating a library of small-mers by extending the length of the scaffold using all possible nucleotide and/or non-nucleotide combinations for a fixed additional small-mer length, and (c) assaying the small-mer molecule of (b) under conditions suitable for isolating a small-mer having improved antiviral activity.

14. The method of claim 12, wherein the fixed additional length is about 1 to about 10 additional nucleotides and/or non-nucleotides.

16. The small-mer of claim 1 or claim 2 comprising a 5′

-cap, 3′

-cap, or a 5′ and

3′

-cap moiety.

17. The small-mer of claim 1 or claim 2 comprising one or more abasic moiety.

18. The small-mer of claim 16, wherein said 5′

-cap is an inverted abasic moiety.

19. The small-mer of claim 16, wherein said 3′

-cap is an inverted abasic moiety.

20. The small-mer of claim 16, wherein said 5′

-cap and said 3′

-cap is an inverted abasic moiety.

2. A small-mer molecule having anti-proliferative activity, wherein said small-mer comprises about 3 to about 6 nucleotides.

4. The small-mer molecule of claim 2, wherein said small-mer molecule is adapted for use to treat cancer.

7. The small-mer molecule of claim 2, wherein said small-mer molecule comprises one or more internucleotide linkages having Formula I:

9. The small-mer molecule of claim 2, wherein said small-mer comprises one or more nucleotides or non-nucleotides having Formula II:

11. A composition comprising the small-mer of claim 2 and a pharmaceutically acceptable carrier or diluent.

13. A method generating a small-mer with improved antiproliferative activity comprising:

(a) providing the small-mer of claim 2 as a scaffold for additional nucleotides and/or non-nucleotides, (b) generating a library of small-mers by extending the length of the scaffold using all possible nucleotide and/or non-nucleotide combinations for a fixed additional small-mer length, and (c) assaying the small-mer molecule of (b) under conditions suitable for isolating a small-mer having improved antiproliferative activity.

15. The method of claim 13, wherein the fixed additional length is about 1 to about 10 additional nucleotides and/or non-nucleotides.

5. A small-mer molecule having any of SEQ ID NOs. 1-182.