IP Library Granted Patent US 11,884,919
Granted Patent B2
US 11,884,919 · App. 17/475,305 · Granted Jan 30, 2024

Lipid formulated compositions and methods for inhibiting expression of serum amyloid a gene

Inventors: Antonin de Fougerolles (Brookline, MA); Tatiana Novobrantseva (Wellesley, MA); Gregory Hinkle (Plymouth, MA)
Assignee: Alnylam Pharmaceuticals, Inc.
C12N15/113A61K31/713C12N2310/11C12N2310/14C12N2310/321C12N2310/344C12N2310/3515
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Quick Facts
Patent No.
US 11,884,919
App. No.
17/475,305
Granted
Jan 30, 2024
Kind
B2
Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a Serum Amyloid A (SAA) gene, and methods of using the dsRNA to inhibit expression of SAA.

Claims (16)

1. A double-stranded ribonucleic acid (dsRNA), wherein said dsRNA comprises a sense strand and an antisense strand, wherein each of the sense strand and the antisense strand is 15-30 nucleotides in length, and wherein the antisense strand comprises a region of complementarity which is complementary to an mRNA encoding Serum amyloid A (SAA) and is complementary to at least 15 contiguous nucleotides of SEQ ID NO: 233.

2. The dsRNA of claim 1 , wherein the sense strand consists of the nucleotide sequence of SEQ ID NO: 233 and the antisense strand consists of SEQ ID NO: 234.

3. The dsRNA of claim 1 , wherein the sense strand consists of SEQ ID NO: 77 and the antisense strand consists of SEQ ID NO: 78.

4. The dsRNA of claim 1 , comprising at least one modified nucleotide.

5. The dsRNA of claim 1 , comprising at least one modified nucleotide selected from the group consisting of: a 2′- 0 -methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group, a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, a 2′-amino-modified nucleotide, a 2′-alkyl-modified nucleotide, a morpholino nucleotide, a phosphoramidate, a 2′-O-methylcytidine-5′-phosphate, a 2′-O-methyluridine-5′-phosphate, and a non-natural base comprising nucleotide.

6. The dsRNA of claim 1 , wherein each strand is 21 nucleotides in length.

7. The dsRNA of claim 1 , comprising a dTdT overhang on the 3′ end of each strand.

8. The dsRNA of claim 1 , wherein the region of complementarity is 19-21 nucleotides in length.

9. The dsRNA of claim 1 , wherein the dsRNA is conjugated to a ligand.

10. The dsRNA of claim 1 , wherein the dsRNA is formulated in a lipid formulation.

11. The dsRNA of claim 1 , wherein administration of the dsRNA to a cell results in 97% inhibition of SAA mRNA expression as measured by a real time PCR assay or 93% inhibition of SAA mRNA expression as measured by a branched DNA assay or 100% inhibition of SAA protein expression as measured by a ELISA assay compared to an siRNA control; or administration of the dsRNA to a mouse reduces SAA protein expression by about 80% compared to an siRNA control.

12. The dsRNA of claim 1 , wherein the dsRNA has an IC50 of less than 10 pM as measured by branched DNA assay.

13. A cell comprising the dsRNA of claim 1 .

14. A vector comprising a nucleotide sequence encoding at least one strand of the dsRNA of claim 1 .

15. A cell comprising the vector of claim 14 .

16. A pharmaceutical composition for inhibiting expression of an SAA gene comprising the dsRNA of claim 1 .

Assignments (2)
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 Sep 19, 2021
From: DE FOUGEROLLES, ANTONIN; NOVOBRANTSEVA, TATIANA; HINKLE, GREGORY
To: ALNYLAM PHARMACEUTICALS, INC.
Reel/Frame 057523/0094 →