Claims for Patent: 11,359,203

Summary for Patent: 11,359,203

Title:	Therapeutic inhibition of lactate dehydrogenase and agents therefor
Abstract:	This invention relates to compounds, compositions, and methods useful for reducing lactate dehydrogenase target RNA and protein levels via use of ds RNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.
Inventor(s):	Brown Bob D., Dudek Henryk T., Lai Cheng
Assignee:	Dicerna Pharmaceuticals, Inc.
Application Number:	US16918239
Patent Claims:	3. The dsNA of claim 2 , wherein the sense strand and antisense strand form a duplex and a hairpin such that the antisense strand comprises a two nucleotide overhang at its 3′ end.4. The dsNA of claim 2 , wherein the dsNA comprises a duplex of 25 to 35 base pairs in length.5. The dsNA of claim 3 , wherein the sense strand is 25 to 53 nucleotides in length.6. The dsNA of claim 3 , wherein the hairpin is a part of the sense strand.7. The dsNA of claim 3 , wherein the hairpin is a tetraloop.8. The dsNA of claim 7 , wherein the tetraloop comprises a single stranded loop having a sequence of GAAA.9. The dsNA of claim 7 , wherein the tetraloop is attached to a moiety selected from the group consisting of a GalNAc moiety claim 7 , a cholesterol moiety claim 7 , and a cholesterol targeting ligand.10. The dsNA of claim 8 , wherein the tetraloop is attached to a GalNAc moiety.11. The dsNA of claim 2 , wherein the dsNA comprises at least one phosphorothioate linkage.12. The dsNA of claim 3 , wherein the antisense strand is 22 nucleotides long.13. The dsNA of claim 2 , wherein the one or more modified nucleotides contains a 2′ modification.14. The dsNA of claim 13 , wherein the one or more modified nucleotides are selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide.15. The dsNA of claim 14 , wherein the dsNA comprises at least one 2′-fluoro nucleotide and at least one 2′-O-methyl nucleotide.16. The dsNA of claim 2 , wherein at least one modified nucleotide contains a methylphosphonate.19. A pharmaceutical composition comprising the dsNA of and a pharmaceutically acceptable carrier.20. A method for reducing expression of the lactate dehydrogenase (LDHA) gene in one or more tissues of a subject comprising administering to the subject the composition of .21. The method of claim 20 , wherein the subject has a lactate dehydrogenase knockdown treatable disease or disorder claim 20 , wherein the disease or disorder is chronic kidney disease or pyruvate dehydrogenase complex deficiency.22. The method of claim 21 , wherein the disease or disorder is selected from the group consisting of PH1 claim 21 , PH2 claim 21 , PH3 and idiopathic hyperoxaluria.23. The method of claim 22 , wherein the disease or disorder is PH1.24. The method of claim 20 , wherein the composition is administered in a lipid nanoparticle.25. The method of claim 20 , wherein the composition is administered with an excipient.26. The method of claim 20 , wherein the composition is administered subcutaneously to the subject.27. The method of claim 20 , wherein the one or more tissues comprise liver.28. The method of claim 20 , wherein said subject is human.