	US 11,781,137 B2
	Variant RNAi
Lisa M. Stanek, Natick, MA (US); Adam Palermo, Boston, MA (US); Brenda Richards, Hopkinton, MA (US); Sergio Pablo Sardi, Newton, MA (US); Catherine O′Riordan, Bridgewater, NJ (US); and Antonius Song, Dublin, CA (US)
Assigned to Genzyme Corporation, Cambridge, MA (US)
Filed by Genzyme Corporation, Cambridge, MA (US)
Filed on Jul. 28, 2020, as Appl. No. 16/941,303.
Application 16/941,303 is a division of application No. 16/566,565, filed on Sep. 10, 2019, granted, now 10,760,079.
Application 16/566,565 is a division of application No. 15/549,895, granted, now 10,450,563, issued on Oct. 22, 2019, previously published as PCT/US2016/017207, filed on Feb. 9, 2016.
Claims priority of provisional application 62/114,578, filed on Feb. 10, 2015.
Prior Publication US 2021/0047641 A1, Feb. 18, 2021
Int. Cl. C07H 21/04 (2006.01); C12N 15/113 (2010.01)

CPC C12N 15/113 (2013.01) [C12N 2310/14 (2013.01); C12N 2310/531 (2013.01); C12N 2310/533 (2013.01)]

31 Claims

1. A method for inhibiting or reducing the expression of a polypeptide in a mammal disease comprising administering to the mammal the RNAi comprising a first strand and a second strand, wherein

a) the first strand and the second strand form a duplex;

b) the first strand comprises a guide region of at least 19 bases, wherein the guide region comprises a seed region comprising bases 1-N of the guide strand, wherein N=7 or N=8;

c) the second strand comprises a non-guide region of at least 19 bases, wherein the non-guide region comprises a bulge sequence opposite of any one or more of bases 2-(N+2) of the guide region in the duplex; and

(d) wherein the first strand and the second strand are linked by means of RNA linker capable of forming a loop structure.