Claims for Patent: 11,446,380

Summary for Patent: 11,446,380

Title:	Compositions and methods for inhibition of HAO1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression
Abstract:	The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the HAO1 gene, and methods of using such RNAi agents to inhibit expression of HAO1 and methods of treating subjects having, e.g., PH1.
Inventor(s):	Querbes; William (Boston, MA), Fitzgerald; Kevin (Brookline, MA), Bettencourt; Brian (Groton, MA), Liebow; Abigail (Somerville, MA), Erbe; David V. (Arlington, MA)
Assignee:	Alnylam Pharmaceuticals, Inc. (Cambridge, MA)
Application Number:	16/673,863
Patent Claims:	1. A double stranded RNAi agent, or salt thereof, that inhibits expression of HAO1 in a cell, comprising a sense strand and an antisense strand forming a double stranded region, wherein the sense strand comprises the nucleotide sequence of 5'-gsascuuuCfaUfCfCfuggaaauauaL96-3' (SEQ ID NO:213) and the antisense strand comprises the nucleotide sequence 5'-usAfsuauUfuCfCfaggaUfgAfaagucscsa-3' (SEQ ID NO:330), wherein a, g, c, and u are 2'-O-methyl (2'-OMe) modified A, G, C, and U nucleotides, respectively; Af, Gf, Cf, and Uf are 2' fluoro A, G, C, and U modified nucleotides, respectively; s is a phosphorothioate linkage; and L96 is N-[tris(GalNAc-alkyl)-amidodecanoyl)]-4-hydroxyprolinol. 2. A pharmaceutical composition comprising the double stranded RNAi agent of claim 1. 3. An isolated cell containing the double stranded RNAi agent of claim 1. 4. A double stranded RNAi agent, or salt thereof, that inhibits expression of HAO1 in a cell, comprising a sense strand and an antisense strand forming a double stranded region, wherein the sense strand comprises the nucleotide sequence of 5'-gsascuuuCfaUfCfCfuggaaauaua-3' (SEQ ID NO:213) and the antisense strand comprises the nucleotide sequence 5'-usAfsuauUfuCfCfaggaUfgAfaagucscsa-3' (SEQ ID NO:330), wherein a, g, c, and u are 2'-O-methyl (2'-OMe) modified A, G, C, and U nucleotides, respectively; Af, Gf, Cf, and Uf are 2' fluoro A, G, C, and U modified nucleotides, respectively; and s is a phosphorothioate linkage, wherein a ligand is conjugated to the 3' end of the sense strand as shown in the following schematic ##STR00009## wherein X is O. 5. A pharmaceutical composition comprising the double stranded RNAi agent of claim 4. 6. An isolated cell containing the double stranded RNAi agent of claim 4. 7. The pharmaceutical composition of claim 2, wherein the double stranded RNAi agent is present in an unbuffered solution. 8. The pharmaceutical composition of claim 7, wherein the unbuffered solution is water. 9. The pharmaceutical composition of claim 6, wherein the unbuffered solution is saline. 10. The pharmaceutical composition of claim 2, wherein the double stranded RNAi agent is present in a buffer solution. 11. The pharmaceutical composition of claim 10 wherein the buffer solution comprises acetate, citrate, prolamine, carbonate, or phosphate or any combination thereof. 12. The pharmaceutical composition of claim 5, wherein the double stranded RNAi agent is present in an unbuffered solution. 13. The pharmaceutical composition of claim 12, wherein the unbuffered solution is water. 14. The pharmaceutical composition of claim 12, wherein the unbuffered solution is saline. 15. The pharmaceutical composition of claim 5, wherein the double stranded RNAi agent is present in a buffer solution. 16. The pharmaceutical composition of claim 15 wherein the buffer solution comprises acetate, citrate, prolamine, carbonate, or phosphate or any combination thereof.