	US 12,331,294 B2
	MicroRNA compounds and methods for modulating mir-21 activity
Balkrishen Bhat, Cambridge, MA (US)
Assigned to SANOFI, Paris (FR)
Filed by Sanofi, Paris (FR)
Filed on Aug. 18, 2021, as Appl. No. 17/405,482.
Application 17/405,482 is a division of application No. 16/751,402, filed on Jan. 24, 2020, abandoned.
Application 15/704,749 is a division of application No. 14/883,055, filed on Oct. 14, 2015, granted, now 9,790,496, issued on Oct. 17, 2017.
Application 16/751,402 is a continuation of application No. 16/586,216, filed on Sep. 27, 2019, abandoned.
Application 16/586,216 is a continuation of application No. 15/704,749, filed on Sep. 14, 2017, abandoned.
Application 14/883,055 is a continuation of application No. 14/111,976, granted, now 9,181,547, issued on Nov. 10, 2015, previously published as PCT/US2012/034880, filed on Apr. 25, 2012.
Claims priority of provisional application 61/565,779, filed on Dec. 1, 2011.
Claims priority of provisional application 61/478,767, filed on Apr. 25, 2011.
Prior Publication US 2022/0098583 A1, Mar. 31, 2022
Int. Cl. C12N 15/113 (2010.01)

CPC C12N 15/113 (2013.01) [C12N 2310/11 (2013.01); C12N 2310/113 (2013.01); C12N 2310/3231 (2013.01); C12N 2310/343 (2013.01); C12N 2310/35 (2013.01)]

14 Claims

1. A compound comprising a modified oligonucleotide consisting of 16 to 19 linked nucleosides, wherein the nucleobase sequence of the modified oligonucleotide is complementary to the nucleobase sequence of SEQ ID NO: 1, wherein;

(i) the modified oligonucleotide comprises at least 16 contiguous nucleosides of the following nucleoside pattern II in the 5′ to 3′ orientation:

N^M-N^B-N^Q-N^Q-N^B-(N^Q-N^Q-N^Q-N^B)₃-N^Q-N^Z

and wherein;

(a) N^Mis a 2′-O-methoxyethyl nucleoside;

each N^Bis an S-cEt nucleoside;

each N^Qis a 2′-O-methoxyethyl nucleoside; and

N^Zis a 2′-O-methoxyethyl nucleoside;

(b) N^Mis a 2′-O-methoxyethyl nucleoside;

each N^Bis an LNA nucleoside;

each N^Qis a β-D-deoxyribonucleoside; and

N^Zis a 2′-O-methoxyethyl nucleoside; or

each N^Bis an LNA nucleoside;

each N^Qis a β-D-deoxyribonucleoside; and

N^Zis an LNA nucleoside,

(ii) the modified oligonucleotide comprises one of the following nucleoside patterns in the 5′ to 3′ orientation:

(a) N^M-N^B-N^Q-N^Q-N^B-(N^Q-N^Q-N^Q-N^B)₃-N^Q-N^Z;

(b) N^B-N^Q-N^Q-N^B-(N^Q-N^Q-N^Q-N^B)₃-N^Q-N^Z;

(d) N^Q-N^B-(N^Q-N^Q-N^Q-N^B)₃-N^Q-N^Z,

and wherein;

N^Mis a 2′-O-methoxyethyl nucleoside;

each N^Bis an S-cEt nucleoside;

each N^Qis a β-D-deoxyribonucleoside; and

N^Zis an S-cEt nucleoside.