US 11,702,659 B2
Optimized anti-FLT1 oligonucleotide compounds for treatment of preeclampsia and other angiogenic disorders
Anastasia Khvorova, Westborough, MA (US); Vignesh Narayan Hariharan, Natick, MA (US); Sarah Davis, Wellesley, MA (US); Annabelle Biscans, Cambridge, MA (US); and Ananth Karumanchi, Chestnut Hill, MA (US)
Assigned to UNIVERSITY OF MASSACHUSETTS, Boston, MA (US); and BETH ISRAEL DEACONESS MEDICAL CENTER, INC., Boston, MA (US)
Filed by University of Massachusetts, Boston, MA (US); and Beth Israel Deaconess Medical Center, Inc., Boston, MA (US)
Filed on Jun. 22, 2022, as Appl. No. 17/846,526.
Claims priority of provisional application 63/214,224, filed on Jun. 23, 2021.
Prior Publication US 2023/0078622 A1, Mar. 16, 2023
Int. Cl. C07H 21/04 (2006.01); C12N 15/113 (2010.01); A61P 7/00 (2006.01)
CPC C12N 15/113 (2013.01) [A61P 7/00 (2018.01); C12N 2310/11 (2013.01); C12N 2310/315 (2013.01); C12N 2310/321 (2013.01); C12N 2310/322 (2013.01); C12N 2310/344 (2013.01); C12N 2310/346 (2013.01); C12N 2320/32 (2013.01)] 30 Claims
 
1. A double stranded RNA (dsRNA), wherein said dsRNA comprises an antisense strand and a sense strand, each strand with a 5′ end and a 3′ end, wherein:
(1) the antisense strand comprises (mU)#(fA)#(mA)(fA)(fU)(fU)(mU)(fG)(mG)(fA)(mG)(fA)(mU)(fC)#(mC)#(fG)#(mA)#(mG)#(mA)#(fG)#(mA) (SEQ ID NO: 12) or a salt thereof; and
(2) the sense strand comprises (mC)#(mG)#(mG)(fA)(mU)(fC)(mU)(fC)(mC)(fA)(mA)(mA)(mU)(fU)#(mU)#(mA) (SEQ ID NO: 13) or a salt thereof,
wherein “m” corresponds to a 2′-O-methyl modification, “f” corresponds to a 2′-fluoro modification, “#” corresponds to a phosphorothioate internucleotide linkage.