Claims for Patent: 11,261,447

Summary for Patent: 11,261,447

Title:	Methods for inhibition of HAO1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression
Abstract:	The invention relates methods of using RNAi agents to inhibit expression of HAO1 and methods of treating subjects having, e.g., PH1.
Inventor(s):	Erbe; David V. (Arlington, MA), McGregor; Tracy L. (Cambridge, MA)
Assignee:	Alnylam Pharmaceuticals, Inc. (Cambridge, MA)
Application Number:	16/630,800
Patent Claims:	1. A method of treating a human subject having Primary Hyperoxaluria Type 1 (PH1), the method comprising, in a loading phase, subcutaneously administering to the subject three monthly doses of 3 mg ALN-GO1 per kg bodyweight of the subject, thereby treating the subject; wherein ALN-GO1 comprises gsascuuuCfaUfCfCfuggaaauauaL96 (SEQ ID NO:14) and usAfsuauUfuCfCfaggaUfgAfaagucscsa (SEQ ID NO: 15); wherein, c, u, g, and a are 2'-O-methyl ribonucleotides; Af, Cf, and Uf are 2'-fluoro ribonucleotides; s is a phosphorothioate linkage; and L96 is N-[tris(GaINAc-alkyl)-amidodecanoyl)]-4-hydroxyprolinol Hyp-(GaINAc-alkyl).sub.3. 2. A method of treating a human subject having Primary Hyperoxaluria Type 1 (PH1), the method comprising subcutaneously administering to the subject quarterly doses of 3.0 mg ALN-GO1 per kg bodyweight of the subject, thereby treating the subject. 3. The method of claim 1, wherein a urinary oxalate excretion of the subject is reduced by at least 50% after treatment compared to before treatment. 4. The method of claim 1, wherein a plasma glycolate level of the subject is increased and sustained until at least day 75 after treatment compared to before treatment. 5. The method of claim 1, wherein a GO (Glycolate Oxidase) enzyme of the subject is inhibited by at least 90% after treatment compared to before treatment. 6. The method of claim 2, wherein a urinary oxalate excretion of the subject is reduced by at least 50% after treatment compared to before treatment. 7. The method of claim 2, wherein a plasma glycolate level of the subject is increased and sustained until at least day 75 after treatment compared to before treatment. 8. The method of claim 2, wherein a GO enzyme of the subject is inhibited by at least 90% after treatment compared to before treatment. 9. The method of claim 1, further comprising determining the urinary oxalate excretion in the subject before and after treatment. 10. The method of claim 2, further comprising determining the urinary oxalate excretion in the subject before and after treatment. 11. The method of claim 1, wherein the subject has a urinary oxalate excretion of.gtoreq.0.70 mmol/24h/1.73m.sup.2before treatment. 12. The method of claim 2, wherein the subject has a urinary oxalate excretion of.gtoreq.0.70 mmol/24h/1.73m.sup.2before treatment. 13. The method of claim 1, wherein the subject has an eGFR (estimated glomerular filtration rate) of >45ml/min/1.73m{circumflex over ( )}2 before treatment. 14. The method of claim 2, wherein the subject has an eGFR of >45ml/min/1.73mm{circumflex over ( )}2 before treatment. 15. The method of claim 1, wherein the subject has end stage renal disease (ESRD). before treatment. 16. The method of claim 2, wherein the subject has end stage renal disease (ESRD). before treatment. 17. The method of claim 1, further comprising identifying a mutation in a AGT1 gene of the subject. 18. The method of claim 2, further comprising identifying a mutation in a AGT1 gene of the subject.