Claims for Patent: 10,738,311

Summary for Patent: 10,738,311

Title:	Therapeutic inhibition of lactate dehydrogenase and agents therefor
Abstract:	This invention relates to compounds, compositions, and methods useful for reducing lactact 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:	US16355566
Patent Claims:	2. The method of claim 1 , wherein the subject has a lactate dehydrogenase knockdown treatable disease or disorder claim 1 , wherein the disease or disorder is chronic kidney disease or pyruvate dehydrogenase complex deficiency.3. The method of claim 2 , wherein the disease or disorder is selected from the group consisting of PH1 claim 2 , PH2 claim 2 , PH3 and idiopathic hyperoxaluria.4. The method of claim 1 , wherein the dsNA is administered in a lipid nanoparticle.5. The method of claim 1 , wherein the one or more tissues comprises liver.6. The method of claim 1 , wherein the sense strand and antisense strand form a duplex such that the antisense strand comprises a two nucleotide overhang at its 3′ end.7. The method of claim 1 , wherein the dsNA comprises a duplex of 19 to 25 base pairs in length.8. The method of claim 6 , wherein the sense strand is 25 to 53 nucleotides in length.9. The method of claim 6 , wherein the sense strand is 36 nucleotides in length and/or wherein the antisense strand is 22 nucleotides in length.10. The method of claim 1 , wherein the sense strand and the antisense strand are each in the range of 21 to 23 nucleotides in length.11. The method of claim 1 , wherein the sense strand is 21 nucleotides in length and the antisense strand is 23 nucleotides in length.12. The method of claim 11 , wherein the 3′ terminus of the sense strand and the 5′ terminus of the antisense strand form a blunt end.13. The method of claim 1 , wherein the sense strand comprises a tetraloop at its 3′ end.14. The method of claim 10 , wherein the sense strand comprises a tetraloop at its 3′ end.15. The method of claim 13 , wherein the tetraloop comprises a single stranded loop having a sequence of GAAA.16. The method of claim 1 , wherein the dsNA comprises at least one phosphorothioate linkage.17. The method of claim 15 , wherein the dsNA comprises at least one phosphorothioate linkage.18. The method of claim 1 , wherein the one or more modified nucleotides contains a 2′ modification.19. The method of claim 18 , wherein the one or more modified nucleotides are selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide.20. The method of claim 19 , wherein the dsNA comprises at least one 2′-fluoro nucleotide and at least one 2′-O-methyl nucleotide.21. The method of claim 1 , wherein the dsNA is attached to a moiety selected from the group consisting of a GalNAc moiety claim 1 , a cholesterol moiety claim 1 , and a cholesterol targeting ligand.22. The method of claim 19 , wherein the dsNA is attached to a GalNAc moiety.23. The method of claim 22 , wherein the dsNA is administered in a pharmaceutical composition claim 22 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.26. The method of claim 24 , wherein the nucleic acid is in a pharmaceutical composition claim 24 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.28. The method of claim 27 , wherein the complementary region of the antisense strand contains three claim 27 , two claim 27 , or one mismatched nucleotide residues relative to SEQ ID NO: 401.29. The method of claim 27 , wherein the sense strand and antisense strand form a duplex such that the antisense strand comprises a two nucleotide overhang at its 3′ end.30. The method of claim 27 , wherein the dsNA comprises a duplex of 19 to 25 base pairs in length.31. The method of claim 29 , wherein the sense strand is 25 to 53 nucleotides in length.32. The method of claim 29 , wherein the sense strand is 36 nucleotides in length and/or wherein the antisense strand is 22 nucleotides in length.33. The method of claim 27 , wherein the sense strand and the antisense strand are each in the range of 21 to 23 nucleotides in length.34. The method of claim 27 , wherein the sense strand is 21 nucleotides in length and the antisense strand is 23 nucleotides in length.35. The method of claim 34 , wherein the 3′ terminus of the sense strand and the 5′ terminus of the antisense strand form a blunt end.36. The method of claim 27 , wherein the sense strand comprises a tetraloop at its 3′ end.37. The method of claim 33 , wherein the sense strand comprises a tetraloop at its 3′ end.38. The method of claim 36 , wherein the tetraloop comprises a single stranded loop having a sequence of GAAA.39. The method of claim 3 , wherein the disease or disorder is PH1.