IP Library › Granted Patent US 12,723,247
Granted Patent B2
US 12,723,247 · App. 17/579,655 · Granted Sep 1, 2026

Methods for inhibition of HAO1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression

Inventors: David V. Erbe (Arlington, MA); Tracy L McGregor (Cambridge, MA)
Assignee: Alnylam Pharmaceuticals, Inc.
C12N15/1137A61P13/12A61K9/0019A61K45/06C12N2310/14C12N2310/343C12N2310/346C12N2310/351C12N2320/35
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Quick Facts
Patent No.
US 12,723,247
App. No.
17/579,655
Granted
Sep 1, 2026
Kind
B2
Abstract

The invention relates methods of using RNAi agents to inhibit expression of HAO1 and methods of treating subjects having, e.g., PH1.

Claims (33)

1 . A method of treating a human subject having Primary Hyperoxaluria Type 1 (PH1), the method comprising

subcutaneously administering to the subject 3.0 mg per kg bodyweight or 6.0 mg per kg bodyweight of a double stranded ribonucleic acid (dsRNA) agent which inhibits the expression of hydroxyacid oxidase 1 (HAO1), or a salt thereof,

wherein the dsRNA agent, or a salt thereof, comprises a sense strand comprising the nucleotide sequence 5′-gsascuuuCfaUfCfCfuggaaauaua-3′ of SEQ ID NO: 14 and an antisense strand comprising the nucleotide sequence 5′-usAfsuauUfuCfCfaggaUfgAfaagucscsa-3′ of SEQ ID NO:15,

wherein a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U, respectively; Af, Cf, and Uf are 2′-fluoro A, C, and U, respectively; and s is a phosphorothioate linkage, and

wherein the 3′-end of the sense strand is conjugated to an N-acetylgalactosamine (GalNAc) 3 ligand which is

 thereby treating the human subject having PH1.

2 . A method of treating a human subject having Primary Hyperoxaluria Type 1 (PH1), the method comprising

subcutaneously administering to the subject 3.0 mg per kg bodyweight or 6.0 mg per kg bodyweight of a double stranded ribonucleic acid (dsRNA) agent which inhibits the expression of hydroxyacid oxidase 1 (HAO1), or a salt thereof,

wherein the dsRNA agent, or a salt thereof, comprises a sense strand consisting of the nucleotide sequence 5′-gsascuuuCfaUfCfCfuggaaauaua-3′ of SEQ ID NO:14 and an antisense strand consisting of the nucleotide sequence 5′-usAfsuauUfuCfCfaggaUfgAfaagucscsa-3′ of SEQ ID NO:15,

wherein a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U, respectively; Af, Cf, and Uf are 2′-fluoro A, C, and U, respectively; and s is a phosphorothioate linkage, and

wherein the 3′-end of the sense strand is conjugated to an N-acetylgalactosamine (GalNAc) 3 ligand which is

 thereby treating the human subject having PH1.

3 . The method of claim 1 , wherein the dsRNA agent, or a salt thereof, is administered to the subject in a dosing regimen that includes a loading phase followed by a maintenance phase.

4 . The method of claim 1 , wherein the dsRNA agent, or a salt thereof, is administered to the subject once a month.

5 . The method of claim 1 , wherein the dsRNA agent, or a salt thereof, is administered to the subject once a month for about three months.

6 . The method of claim 1 , wherein the dsRNA agent, or a salt thereof, is administered to the subject once every three months.

7 . The method of claim 2 , wherein the dsRNA agent, or a salt thereof, is administered to the subject once a month.

8 . The method of claim 2 , wherein the dsRNA agent, or a salt thereof, is administered to the subject once a month for about three months.

9 . The method of claim 2 , wherein the dsRNA agent, or a salt thereof, is administered to the subject once every three months.

10 . The method of claim 1 , wherein the subject is administered a 3 mg per kg bodyweight dose of the dsRNA agent, or a salt thereof, once a month.

11 . The method of claim 1 , wherein the subject is administered a 6 mg per kg bodyweight dose of the dsRNA agent, or a salt thereof, once a month.

12 . The method of claim 1 , wherein the subject is administered a 3 mg per kg bodyweight dose of the dsRNA agent, or a salt thereof, once every three months.

13 . The method of claim 1 , wherein the subject is administered a 6 mg per kg bodyweight dose of the dsRNA agent, or a salt thereof, once every three months.

14 . The method of claim 2 , wherein the subject is administered a 3 mg per kg bodyweight dose of the dsRNA agent, or a salt thereof, once a month.

15 . The method of claim 2 , wherein the subject is administered a 6 mg per kg bodyweight dose of the dsRNA agent, or a salt thereof, once a month.

16 . The method of claim 2 , wherein the subject is administered a 3 mg per kg bodyweight dose of the dsRNA agent, or a salt thereof, once every three months.

17 . The method of claim 2 , wherein the subject is administered a 6 mg per kg bodyweight dose of the dsRNA agent, or a salt thereof, once every three months.

18 . The method of claim 1 , wherein the dsRNA agent, or a salt thereof, is present in a pharmaceutical composition.

19 . The method of claim 17 , wherein the dsRNA agent, or a salt thereof, is present in a buffer solution.

20 . The method of claim 17 , wherein the dsRNA agent, or a salt thereof, is present in an unbuffered solution.

21 . The method of claim 2 , wherein the dsRNA agent, or a salt thereof, is present in a pharmaceutical composition.

22 . The method of claim 21 , wherein the dsRNA agent, or a salt thereof, is present in a buffer solution.

23 . The method of claim 21 , wherein the dsRNA agent, or a salt thereof, is present in an unbuffered solution.

Assignments (3)
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 May 17, 2022
From: ERBE, DAVID V.
To: ALNYLAM PHARMACEUTICALS, INC.
Reel/Frame 059927/0083 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 17, 2022
From: MCGREGOR, TRACY L.
To: ALNYLAM PHARMACEUTICALS, INC.
Reel/Frame 059927/0162 →
Continuity (6)
Continuation 16630800 · Jul 12, 2018
Provisional Application 62682020 · Jun 7, 2018
Provisional Application 62646285 · Mar 21, 2018
Provisional Application 62581565 · Nov 3, 2017
Provisional Application 62532176 · Jul 13, 2017
Related Publication 20220403394A1 · Dec 22, 2022
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